Episodes Archives - Cardionerds

Join Thomas Jefferson University FITs, Drs. Sean Dikdan, Rachel Debenham and Harsh Doshi, as well as Cardionerds, Dan Ambinder and Karan Desai, on this incredible story of a young man who presented with ventricular arrhythmias and cardiogenic shock. The TJU Cardionerds expertly walk us through a rare diagnosis, his course over several years and his ultimate treatment with heart transplantation. From the evaluation of cardiogenic shock to the role of endomyocardial biopsy to facing inequities in organ allocation, there are learning pearls for every listener!  

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A 35 year old healthy male presents with cardiogenic shock and new heart failure with reduced ejection fraction. He has ventricular instability and is diagnosed with giant cell myocarditis by endomyocardial biopsy. His course over several years includes LVAD bridge to heart transplantation. He then has a recurrence of giant cell myocarditis in the transplanted heart which is successfully treated with high dose immunosuppression. 

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A. ECG, B. CXR

• CardioNerds Myocarditis, updated 1.20.21

1. Giant cell myocarditis (GCM is a rare – and often fatal – cause of acute myocarditis. A hallmark of GCM is the presence of multinucleated giant cells; however, these may take 1-2 weeks to appear and can also be seen in sarcoidosis.
2. Most etiologies of fulminant myocarditis do not have bradyarrhythmias as a prominent feature, and their presence should increase the suspicion for sarcoidosis, Chagas disease, or GCM.
3. While non-specific, a clue to the diagnosis of GCM amongst other causes of myocarditis could be rapid clinical deterioration with minimal response to guideline directed therapy, including a lack of spontaneous recovery on mechanical support which more commonly occurs in fulminant lymphocytic myocarditis.
4. Mechanical support is typically needed in the management of GCM, either as a bridge to transplantation or recovery.
5. GCM can recur in the transplanted heart. This happens in up to 25% of transplant patients and warrants aggressive immunosuppression which usually is sufficient to ensure disease remission.

1. What is Giant Cell myocarditis (GCM)?
   • Giant cell myocarditis (GCM) is an extremely rare – and often fatal – cause of acute non-infectious myocarditis. The pathophysiology of GCM is poorly understood, but thought to be a T-cell mediated autoimmune process leading to diffuse or multifocal inflammatory infiltrate, including lymphocytes with multinucleated giant cells (note multinucleated giant cells are not exclusive to GCM and can be seen in sarcoidosis as well). It has been estimated to occur at a rate of 0.13 cases per 100,000 people (one in a million).
   • It typically affects the myocardium in isolation and may not have any extracardiac manifestations, presenting with rapid hemodynamic deterioration, ventricular arrhythmias, and at times bradyarrhythmias.  The rate of death or cardiac transplantation has been estimated at 89%, with a median survival of 5.5 months from the onset of symptoms to the time of death or transplantation.
     
2. When should you be suspicious of GCM?
   • The classic presentation is in a middle-aged Caucasian male who develops acute or subacute nonischemic cardiomyopathy (NICM) with clinical heart failure that progressively worsens. These patients often develop cardiogenic shock or arrhythmic instability – including both ventricular arrhythmia and conduction delays/heart block. See our prior episodes on the basics of building a clinical suspicion for myocarditis and the differential diagnosis (Episodes 29-33).
   • While non-specific, a clue to the diagnosis of GCM amongst other causes of myocarditis should be rapid clinical deterioration with minimal response to guideline directed therapy, including a lack of spontaneous recovery on mechanical support which more commonly occurs in fulminant lymphocytic myocarditis. Furthermore, bradyarrhythmias are less common in myocarditis and should raise the suspicion for GCM, sarcoidosis or Chagas disease.
     
3. How is GCM diagnosed?
   • Definitive diagnosis of GCM requires endomyocardial biopsy (EMB). Similar to other rare forms of myocarditis like sarcoidosis or eosinophilic myocarditis, GCM requires pathology for diagnosis. Typically, a Class I indication (based on a joint statement 2007 statement from the AHA/ACC/ESC) for performing an EMB are (1) unexplained acute cardiomyopathywith < 2 weeks duration that is associated with hemodynamic compromise or  (2) unexplained cardiomyopathy between 2 weeks’ to 3 months’ duration associated with a dilated LV and new bradyarrhythmia, new ventricular arrhythmias or lack of response to GDMT within 1 to 2 weeks of initial diagnosis. 
   • The specific pathology will naturally include multinucleated Giant cells, but it will also include a high count of CD3 cells and usually a higher CD8 to CD4 ratio. The characteristic giant cells make typically take 1-2 weeks to appear and thus EMB in the first few days of the illness may render a false negative. Furthermore, because myocardial involvement in GCM can be patchy, repeat biopsy may be needed if the clinical suspicion remains high. Finally, multinucleated cells can also be seen in sarcoidosis; however, granulomas and fibrosis tend to be more striking features in cardiac sarcoid.
   • MRI can aid the diagnosis of GCM, however, many of these patients are too unstable to undergo MRI. When an MRI is able to be obtained, it will generally show diffuse abnormalities in T1 and T2 imaging and mapping.
     
4. How is GCM treated?
   • In addition to GDMT as tolerated, treatment includes multi-drug immunosuppression that typically involve some combination of cyclosporine, azathioprine, and high dose steroids. Antithymocyte immunoglobulin and the T-cell specific monoclonal antibody, muromonab, have been used as well. Even after treating the underlying myocarditis with aggressive immunosuppression, ventricular arrhythmias may persist.
   • Mechanical circulatory support (MCS) is often needed as a bridge to heart transplantation or recovery. Options typically include intra-aortic balloon pump (IABP), IMPELLA (both RV and/or LV support devices), LVAD, RVAD, and ECMO. In patients with fulminant myocarditis, our goal is to maintain tissue perfusion while ensuring that we reduce LV workload and LVEDP. For this reason, peripheral VA ECMO alone is generally not used as it can increase afterload.
   • IABP is typically not useful in a patient with a rapid and severe decrease in cardiac output, as it offers an additional 0.5L to 1 L/min of support. In this patient, LVAD and RVAD support were pursued. Surgical RVAD implantation involves cannulation of the right atrium or RV as well as pulmonary artery and is connected to an extracorporeal centrifugal flow pump. Another option for percutaneous RV support is a novel axial-flow pump. This device utilizes a catheter-mounted microaxial flow pump with the inflow just below the right atrium-inferior vena cava junction and the outflow into the pulmonary artery after insertion via the femoral vein due to the design of the system, internal jugular placement and ambulation are not possible.
5. What are the expected outcomes in patients with GCM?
   • Outcomes are generally poor without a heart transplant. With transplantation, however, 5-year survival is estimated at around 71%, which is similar to transplant survival rates in patients of other disease. Of note, GCM can recur in the transplanted heart. This happens in up to 25% of transplant patients. Recurrence warrants aggressive immunosuppression which is typically sufficient for disease remission.

References

1. Ammirati E, Cipriani M, Moro C, Raineri C, Pini D, Sormani P, Mantovani R, Varrenti M, Pedrotti P, Conca C, Mafrici A, Grosu A, Briguglia D, Guglielmetto S, Perego GB, Colombo S, Caico SI, Giannattasio C, Maestroni A, Carubelli V, Metra M, Lombardi C, Campodonico J, Agostoni P, Peretto G, Scelsi L, Turco A, Di Tano G, Campana C, Belloni A, Morandi F, Mortara A, Cirò A, Senni M, Gavazzi A, Frigerio M, Oliva F, Camici PG; Registro Lombardo delle Miocarditi. Clinical Presentation and Outcome in a Contemporary Cohort of Patients With Acute Myocarditis: Multicenter Lombardy Registry. Circulation. 2018 Sep 11;138(11):1088-1099. doi: 10.1161/CIRCULATIONAHA.118.035319. PMID: 29764898.

2. Heymans S, Eriksson U, Lehtonen J, Cooper LT Jr. The quest for new approaches in myocarditis and inflammatory cardiomyopathy. J Am Coll Cardiol. 2016;68:2348-2364.

3. Rosenstein ED, Zucker MJ, Kramer N. Giant cell myocarditis: most fatal of autoimmune diseases. Semin Arthritis Rheum. 2000 Aug;30(1):1-16.

4. Cooper LT Jr, Berry GJ, Shabetai R. Idiopathic giant-cell myocarditis–natural history and treatment. Multicenter Giant Cell Myocarditis Study Group Investigators. N Engl J Med. 1997 Jun 26;336(26):1860-6.

5. Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U, Levine GN, Narula J, Starling RC, Towbin J, Virmani R; American Heart Association; American College of Cardiology; European Society of Cardiology. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Circulation. 2007 Nov 6;116(19):2216-33.

6. Kociol, R. D. et al. (2020). Recognition and Initial Management of Fulminant Myocarditis. Circulation, 141, E69-E92.

7. Kandolin R, Lehtonen J, Salmenkivi K, Räisänen-Sokolowski A, Lommi J, Kupari M. Diagnosis, treatment, and outcome of giant-cell myocarditis in the era of combined immunosuppression. Circ Heart Fail. 2013 Jan;6(1):15-22.

8. Tschöpe C, Van Linthout S, Klein O, et al. Mechanical Unloading by Fulminant Myocarditis: LV-IMPELLA, ECMELLA, BI-PELLA, and PROPELLA Concepts. J Cardiovasc Transl Res. 2019;12(2):116-123.

9. Kirklin JK, Naftel DC. Mechanical circulatory support: registering a therapy in evolution. Circ Heart Fail. 2008;1(3):200-205.

10. Kapur NK, Esposito ML, Bader Y, et al. Mechanical Circulatory Support Devices for Acute Right Ventricular Failure. Circulation. 2017 Jul;136(3):314-326.

11. Toennes, B; Garan, A. Percutaneous Right Ventricular Support Devices for Right Ventricular Failure Mar 01, 2016. ACC journal expert analysis. 

12. Patil NP, Mohite PN, Sabashnikov A, et al. Preoperative predictors and outcomes of right ventricular assist device implantation after continuous-flow left ventricular assist device implantation. J Thorac Cardiovasc Surg. 2015;150(6):1651-1658.

13. Cooper LT Jr, ElAmm C. Giant cell myocarditis: diagnosis and treatment. Herz. 2012;37:632-636

14. Scott RL, Ratliff NB, Starling RC, Young JB. Recurrence of giant cell myocarditis in cardiac allograft. J Heart Lung Transplant. 2001;20:375-380

15. Patel PM, Saxena A, Wood CT, O’Malley TJ, Maynes EJ, Entwistle JWC, Massey HT, Pirlamarla PR, Alvarez RJ, Cooper LT, Rame JE, Tchantchaleishvili V. Outcomes of Mechanical Circulatory Support for Giant Cell Myocarditis: A Systematic Review. J Clin Med. 2020 Dec 1;9(12):3905.

• Gurleen Kaur
• Karan Desai, MD
• Amit Goyal, MD
• Daniel Ambinder, MD

CardioNerds (Amit Goyal & Karan Desai) join Dr. Alex Pipilas (FIT, Boston University) and Dr. Danny Pipilas (FIT, MGH) for in Boston, MA. Adult congenital heart disease expert Dr. Keri Shafer (Brigham and Women’s Hospital) provides the E-CPR expert segment. They discuss a case of heart failure secondary to sinus venosus defect with partial anomalous pulmonary venous return.

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A 78-year-old woman with atrial fibrillation and heart failure with preserved ejection fraction presented with recurrent dyspnea and volume overload. A transthoracic echocardiogram demonstrated severe right ventricular enlargement and dysfunction. A CT pulmonary angiogram demonstrated partial anomalous pulmonary venous return and a transesophageal echocardiogram revealed a sinus venosus defect with left to right shunting. A right heart catheterization with oximetry saturation (“shunt run”) demonstrated pulmonary hypertension and a large left to right shunt (Qp/Qs ~ 3). She was referred for cardiac surgery and underwent repair of the sinus venosus defect and baffling of the anomalous pulmonary venous flow to the left atrium.

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A. CXR, B. ECG, C. TR Velocity

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1. It is critical to determine whether there is more to a diagnosis of heart failure with a preserved ejection fraction. Utilize all available clinical data and risk calculators to determine if there are more appropriate diagnoses causing the patients symptoms, especially when certain aspects of the presentation does not add up.
   
2. Right ventricular failure may be related to pressure overload (i.e., pulmonary hypertension, PV stenosis), volume overload (i.e., tricuspid regurgitation, left to right shunt lesions), or primary myocardial process (i.e., ischemia, infiltration, ARVC). In cases of severe right ventricular enlargement and dysfunction without apparent cause, look for a left to right shunt lesion (i.e., VSD, ASD, PAPVR). Sometimes further imaging (TEE, cardiac CT, cardiac MRI) is necessary to detect these lesions if not visualized on TTE.
   
3. Left to right shunts can be quantified in the cardiac catheterization laboratory by measuring oxygen saturation in each chamber and detecting an O2 “step up” (increase in oxygen saturation from one chamber to the next). Large left to right shunts are quantified using the Fick principle and comparing the ratio of pulmonary blood flow (Qp) to systemic blood flow (Qs).
   
4. Large left-to-right shunts can cause right ventricular volume overload and pulmonary hypertension. Patients often present with signs and symptoms of right ventricular failure including shortness of breath, exercise intolerance, volume overload, atrial arrhythmias, and recurrent heart failure. Some may develop right-to-left shunting and possible paradoxical embolism.
   
5. ACC/AHA guidelines recommend closure of a sinus venosus defect if the PA systolic pressure is < 50% systemic pressures AND PVR is <1/3 of SVR. It is a Class III recommendation (potentially harmful) to close a defect if PA systolic pressure is >2/3 of systemic systolic pressure and/or PVR >2/3 SVR.

About ACHD – “As we go through this physiology, I just want to remind all of the listeners out there that you have the opportunity to apply the knowledge you have from medical school about physiology to the adult human heart. You can’t make assumptions as we sometimes do in the setting of normal cardiac anatomy. We really need to think about the compliances of the downstream structures and where is the blood flow.” – Keri Shafer, MD

1. What are features and causes of RV failure?

• The clinical symptoms of right ventricular failure include fatigue, dyspnea, lower extremity edema, elevated JVP, early satiety, and abdominal swelling. Although there is overlap between the symptoms of right ventricular failure and left ventricular failure, in isolated right ventricular failure orthopnea, paroxysmal nocturnal dyspnea, and pulmonary edema are typically absent.
• It is convenient to break down the etiologies of right heart failure into “buckets”. Specifically, volume overload, pressure overload, and primary cardiomyopathic processes. Causes of right ventricular volume overload include valvular disease (tricuspid regurgitation, pulmonic insufficiency) and left-to-right shunts (ASD, VSD, sinus venosus defect, coronary sinus defect, PAPVR). Causes of right ventricular pressure overload, or excessive afterload, include pulmonary arterial hypertension, pulmonary embolism and chronic thromboembolic pulmonary hypertension, pulmonic stenosis, chronic hypoxemia, and longstanding elevated left atrial pressure causing group 2 PH (mitral regurgitation/stenosis, HFrEF, HFpEF). Cardiomyopathic processes include cardiac amyloidosis, right ventricular myocardial infarction, post-transplant right ventricular dysfunction, and arrhythmogenic right ventricular cardiomyopathy. Also, keep in mind that these disease processes often overlap.

2. What is partial anomalous pulmonary venous return (PAPVR)?

• Normally, the four pulmonary veins return oxygenated blood to the left atrium.
• Partial anomalous pulmonary venous return is a spectrum of congenital heart defects when one or more (but not all) of the pulmonary veins return oxygenated blood from the lungs to the systemic venous system (typically the SVC, IVC, or RA).
• The most common PAPVRs are LUPV (left upper pulmonary vein) à ascending vertical vein à innominate vein or RUPV à SVC. The latter is often associated with a concurrent sinus venosus defect connecting the RA and LA.
• Scimitar syndrome is a subtype of PAPVR in which part or all of the blood from the right lung is returned into the IVC. On chest X-ray, the outline of the anomalous drainage and associated congestion gives the appearance of a scimitar.

3. What is a sinus venosus defect? What is the sinus venosus?

• Early in development, the atria are one single chamber. The sinus venosus is the posterior entryway for blood returning to this primitive atrium.
• Eventually, the sinus venosus closes and moves rightward due to hemodynamic shifts during development.
• In adults, the sinus venous becomes the smooth posterior wall of the adult right atrium called the sinus venarum and is separated from the anterior wall of the RA by the cristae terminalis.
• If a persistent channel through the sinus venosus remains into adulthood, it can result in an intra-cardiac shunt. This is termed a sinus venosus defect and accounts for 10-15% of all inter-atrial shunts.
• Typically, this shunt is left-to-right and may lead to right ventricular volume overload, dysfunction and pulmonary hypertension. Some patients may develop right-to-left shunting or paradoxical embolism. Arrhythmias are an important complication.
• As above, sinus venosus defects are associated with PAPVR with RUPV à SVC.
• NOTE: a sinus venosus defect is NOT a defect in the atrial septum and so is not an “ASD”. Rather it is a defect connecting either the SVC-RA junction (more common) or the IVC-RA junction to the LA. The former is associated with a RUPV PAPVR and the latter is associated with a RLPV PAPVR.

4. What are the imaging modalities that are used to identify sinus venosus defects?

• Sinus venosus defects are poorly visualized on transthoracic echocardiography (TTE).
• If there is clinical suspicion for an inter-atrial shunt not visualized on TTE, then a transesophageal echocardiogram (TTE) should be performed. Additional imaging modalities include cross-sectional imaging with cardiac CT or cardiac MRI, which may also identify the presence of concomitant PAPVR.
• In cases of RV dilation and dysfunction without know etiology, evaluation for sinus venosus defect +/- PAPVR should be pursued.

5. What is the role for right heart catheterization in characterizing shunt defects?

• A right heart catheterization is useful for multiple reasons.
• Intracardiac pressure measurements serve as a surrogate for volume status.
• One can also obtain oxygen saturation in each cardiac chamber to identify the presence of a “step up”, or unexpected increase in oxygen saturation, which signifies a left-to-right shunt. To simplify, a left-to-right shunt is when oxygenated blood from the systemic circulation (left) inappropriately mixes with the pulmonary circulation (right), increasing the oxygen concentration. This can occur via anomalous pulmonary veins, defects at the atrial or ventricular level, or sometimes systemic arterio-venous fistulas.
• To obtain pressure measurements, a balloon-tipped catheter (Swann-Ganz catheter, PA catheter) is inserted through a vein and advanced through the heart and “wedged” in the pulmonary artery to estimate left atrial pressure. Normal pressure measurements are as follows (in mmHg): Right atrium < 8, right ventricle 25/5 (systolic/end diastolic pressure), pulmonary artery 25/15 (systolic/diastolic), and pulmonary capillary wedge pressure 8-12. Cardiac output can also be measured by thermodilution and via the Fick principle.
• In our case, the patient’s pressure measurements were: RA 20, RV 72/24, PA 68/36 (47), PCWP 26.
• As the catheter is passed through the great vessels and cardiac chambers and into the pulmonary artery, small amounts of blood can be sent for oximetry. Blood can be taken from the proximal and distal SVC, proximal and distal IVC, right atrium (low, mid, high), RV, PA and aorta. Taking multiple samples in each chamber are only necessary when the level of a suspected shunt is unknown. A left to right shunt is detected by an oximetry “step up” where oxygenated blood from the systemic circulation blood mixes with deoxygenated blood from the venous circulation.
• An oxygen saturation step up of >7% is considered significant at the level of the great veins and RA while a step up of >5% is considered significant at levels distal to the RA.
• For intra-cardiac shunts, the degree of left to right shunting can be quantified by calculating the ratio of pulmonary blood flow (Qp; oxygen consumption divided by the difference in AV oxygen content across the lungs) to systemic blood flow (Qs; oxygen consumption divided by the difference in the arteriovenous oxygen content across the systemic circulation). This ratio is calculated using the Fick principle for cardiac output, and by making a few assumptions.

• Because intra-cardiac shunts will affect the mixed venous (pulmonary artery oxygen saturation), a systemic mixed venous saturation needs to be calculated to estimate “pre-shunt” mixed venous O2. This is defined by Flamm’s formula: (3*SVC +IVC)/4
  • We also assume that oxygen consumption, hemoglobin concentration and atmospheric pressure are constant. This allows for many of the terms in the complex calculation to cancel out, leaving only the oximetry saturations.
  • Ultimately, the simplified equation for Qp/Qs becomes the difference in saturation across the systemic circulation (Ao – calculated mixed venous) divided by the difference across the pulmonic circulation (PV sat – PA sat).
  • Practically, the pulmonary venous saturation cannot be obtained without transeptal puncture or retrograde catheterization through the left sided valves. In the absence of a significant R to L shunt, we expect systemic arterial saturation and pulmonary venous saturation to be the same, and thus the pulmonary venous saturation is often replaced by systemic arterial saturation in this equation.
• Small shunts are defined by Qp/Qs <1.5. These are often asymptomatic and generally do not need to be treated. Large shunts are defined by Qp/Qs >2 and often require closure.
• Our patient’s saturations were as follows: SVC 50%, IVC 43%, RA 77%, PA 79%, Ao 94%.
  • The calculated mixed venous saturation is then 48.25% ((3*50% + 1*43%) / 4 = 48.25%).
  • Finally, her Qp/Qs = (94 – 48.25)/(94-79) = 3.1.
• When we walk through this equation with our patient’s data, her Qp/Qs is 3.1, meaning that for every 1 L of cardiac output through the systemic circulation, 3.1 L are going through the pulmonary circulation.

6. What are the indications and contraindications to correction of sinus venosus defects and PAPVR?

• According to the 2018 ACC/AHA guidelines, in adults with a primum ASD, sinus venous defect or coronary sinus defect causing impaired functional capacity, right atrial and/or right ventricular enlargement and net left to right shunt sufficiently large to cause physiological sequelae (Qp/Qs >1.5:1) – without cyanosis at rest or during exercise – should be referred for surgical repair unless precluded by comorbidities.
•  It is important to evaluate for pulmonary hypertension, as the recommendations differ based on the degree of concomitant pHTN.
• Surgical correction is:
  • Class I (B-NR) if the systolic PA pressure is less than 50% of the systemic pressure and the PVR is less than one third of the SVR.
  • Class III, or potentially harmful, (C-LD) if the PA systolic pressure is greater than 2/3 of the systemic systolic pressure or if the PVR is greater than 2/3 of the SVR and/or if there exists a right to left shunt.
• Those with PA systolic pressures between 50% and 2/3 systemic pressures and PVRs between 1/3 and 2/3 should be considered for repair on a case-by-case basis (Class IIb, our patient in this case).

References

Stout KK, Daniels CJ, Aboulhosn JA, et al. 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(14). doi:10.1161/cir.0000000000000603. https://www.ahajournals.org/doi/10.1161/CIR.0000000000000603

De Faria Yeh D, Bhatt AB, Gaggin HK, Januzzi JL. Adult Congenital Heart Disease. In: MGH Cardiology Board Review. 2nd ed. Cham: Springer International Publishing; 2021:387-420. https://www.springer.com/gp/book/9783030457914

Askari AT, Messerli AW. In: Cardiovascular Hemodynamics An Introductory Guide. Cham: Springer International Publishing; 2019. https://www.springer.com/gp/book/9783030191306

• Karan Desai, MD
• Amit Goyal, MD
• Daniel Ambinder, MD

CardioNerds (Amit Goyal and Daniel Ambinder) join Dr. Bryan Smith (Advanced Heart Failure and Transplant Cardiologist at the University of Chicago) and Dr. Shirlene Obuobi (rising cardiology fellow, CardioNerds ambassador for the University of Chicago, and creator of ShirlyWhirl, M.D.) They discuss the story of a patient with end stage heart failure due to peripartum cardiomyopathy that highlights racial disparities in healthcare and advanced heart failure. They emphasize the importance of providing mentorship for Black and Indigenous People of Color (BIPOC) and share personal stories of their journey to Cardiology. Dr. Andi Shahu joins us to read his AHA blog titled “Let’s Ban the Phrase “Social Issues”: Social Justice and Advanced Heart Failure Therapies”. Audio editing by CardioNerds Academy intern, Pace Wetstein.

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“One of the reasons why I went into Heart Failure is because I connected a lot with these young patients, a lot of these young black men and black women who were terrified of the hospital. As a resident and a fellow I would go talk to them and really understand their fears and where they are coming from. I think a lot of times these patients can be labeled as ‘noncompliant,’ or ‘withdrawn,’ or ‘aggressive,’ but a lot of times you just have to understand where they’re coming from. And I really found that just sitting down to talk to them, and to get to know them, I was able to help get them better, or a lot of them went on to get VADs or transplant. And, to be perfectly honest, I’m in touch with a lot of these patients who I met as a fellow who…I feel are part of my life….You have to meet patients where they are. Meaning you need to text them, interact with them on social media, and really connect with them in a way they understand.” Dr. Bryan Smith (12:10)

“Being black in America means not getting the benefit of doubt. …I can’t help but wonder if unconscious bias among providers is imposing…unreasonable scrutiny on patients of color.” Shirlene (21:15)

“There are many different ways to combat [racial] disparities. As a Heart Failure physician we have these multidisciplinary meetings where we discuss patients for transplant. And I think it’s…important to highlight to our providers that how we discuss patients really matters. Language definitely matters. Heart failure is art in addition to science. …Sometimes when discussing these patients…charged words are used, like ‘withdrawn,’ or ‘aggressive,’ or ‘ghetto’ even. And it’s all coded, racist language. …Part of our responsibility is to educate everyone with implicit bias training….and to make sure we’re able to advocate for patients in the right way.” Dr. Bryan Smith (22:30)

“I’ve felt like I’ve been paying the minority tax…which is doing the necessary but unpaid and frequently seldom recognized labor of mentorship, community engagement, etc, and also of being hyper visible and acting as a symbol…” – Shirlene (24:52)

“It’s really easy when patients are in the hospital to think of them only as patients and forget that they’re people too, and that people are complex, they have complex emotions, they have reactions to things, sometimes those reactions aren’t necessarily what we would think are appropriate for their medical situation, but they’re what make us human.” – Shirlene (9:50)

1. What are some of the racial disparities in diagnosis and outcomes of peri-partum cardiomyopathy, and what are some factors that might be contributing to those disparities?

• CVD disease is the leading cause of pregnancy-associated mortality in the US. Black and American Indian/ Alaskan Native women are 3-4x more likely to die from a pregnancy-related cause than white women. (1,2)
• The incidence of peripartum cardiomyopathy (PPCM) is 4x higher in black women than in white women. Black women may make up to 40% of the cases. (3,4)
• Black women with PPCM have lower LVEF at the time of diagnosis, lower rates of recovery of LVEF, higher incidence of mortality and need for LVAD/ transplant. (1,2)
• Studies looking for genetic reasons for this disparity have come up short.
• Black women are more likely to have comorbid conditions (i.e., gestational HTN, preeclampsia).

2. What is it like taking care of younger patients with LVEF, especially young black patients?

• Working in Advanced Heart Failure gives cardiologists the opportunity to work with younger patients due to the prevalence of CMs that present at younger ages.
• Younger patients tend to feel more invincible, and to have more distrust of the medical system.
• It is important to get to know these patients, meet them where they are, and communicate with them in ways they understand (text, social media).  

3. How can we help to break the black patients’ distrust in the medical system?

• Understand the history: medicine has historically excluded and abused black patients. (ie. the Tuskegee study withheld treatment from black sharecroppers, gynecological surgery experimentations on black slave women, a legacy of segregation, etc.)
• Listen to our patients and try to meet them where they are.
• Understand the social determinants of health (SDOH) that may influence their ability to “adhere” to therapy/ appointments (i.e., difficulty finding childcare, employment restrictions)
• Partner with community initiatives (i.e., Urban Health Initiative at University of Chicago)
• Hire and train members of the community to work in the hospital!
• Invest in Pipeline programs and mentorship.

4. Why is diversity in the medicine important?

• Concordance of race between providers and patients improves trust, quality of care, and improves patient outcomes! (5)
• Black patients are less likely to be referred for catheterization, AICDs, etc., despite our best efforts to provide equitable care.
• Language is important! Consider the use of coded language and racially disparate expectations for patients when discussing issues such as transplant candidacy.
• Recruit physicians who are interested in disparities research, and make research into disparities a basis for promotion.

5. How do we engage the rest of the cardiology community to be invested in the recruitment and mentorship of underrepresented minorities in medicine (URiMs)?

• URiMs frequently pay the “minority tax,” or the necessary but unpaid and seldom recognized labor of mentorship, community engagement, etc. That can be a heavy load to carry, especially considering only 5% of cardiology fellows identify as being Black.
• “You can’t really be what you can’t see” – there’s a responsibility that URMs have in cardiology to be visible to inspire future generations.
• However, mentorship of URiMs should not be limited to only URiM faculty. Centers should try to recruit and establish a culture that values diversity.
• Diversity shouldn’t be limited to just attributes like race/ gender, but also in interest. Without diversity of thought, you may not have adequate mentorship and community engagement.

Show notes updated as of 3.2.2021

The CardioNerds Narratives in Cardiology series features cardiovascular faculty representing diverse backgrounds, subspecialties, career stages, and career paths. Discussing why these faculty chose careers in cardiology and their passion for their work are essential components to inspiring interest in the field.

Each talk will feature a cardiology faculty from an underrepresented group, within at least one of several domains: gender, race, ethnicity, religion, national origin, international graduate status, disadvantaged backgrounds, etc.

Featured faculty will also represent a variety of practice settings, academic ranks, subspecialties (e.g. clinical cardiology, interventional cardiology, electrophysiology, etc), and career paths (e.g. division chief, journal editor, society leadership, industry consultant, etc).

Faculty will be interviewed by fellows-in-training for a two-part discussion that will focus on:

1) Faculty’s content area of expertise
2) Faculty’s personal and professional narrative

As part of their narrative, faculty  will discuss their unique path to cardiology and their current professional role with particular attention to challenges, successes, and advice for junior trainees. Specific topics will be guided by values relevant to trainees, including issues related to mentorship, work-life integration, and family planning.

To help guide this important initiative, the CardioNerds Narratives Council was founded to provide mentorship and guidance in producing the Narratives series with regards to guests and content. The CardioNerds Narratives Council members include: Dr. Pamela Douglas, Dr. Nosheen Reza, Dr. Martha Gulati, Dr. Quinn Capers, IV, Dr. Ann Marie Navar, Dr. Ki Park, Dr. Bob Harrington, Dr. Sharonne Hayes, and Dr. Michelle Albert.

The Narratives Council includes three FIT advisors who will lead the CardioNerds’ diversity and inclusion efforts, including the current project: Dr. Zarina Sharalaya, Dr. Norrisa Haynes, and Dr. Pablo Sanchez.

Dr. Bryan Smith is an Advanced Heart Failure and Transplant Cardiologist at University of Chicago. Dr. Smith completed his medical school training, residency and Cardiology fellowship at University of Chicago, then traversed Lake Shore Drive to complete his advanced HF fellowship at Northwestern. At University of Chicago, he serves as the director of the hemodynamic Cath lab, on the Chicago board for AHA, and as a faculty mentor for SNMA (Student National Medical Association.) Dr. Smith’s interests lie in community-based interventions for heart failure management and racial disparities, and he is the face of several mentorship programs, including the Heart and Vascular Mentoring program here in Chicago.

Shirlene Obuobi, M.D. is a current PGY3 IM resident and rising cardiology fellow. Born in Accra, Ghana and bred in Chicago, Hot Springs, Arkansas, and The Woodlands, Texas, Shirlene completed her medical school training at University of Chicago Pritzker School of Medicine, and has remained at the University ever since. She is passionate about narrative medicine, health equity, and health disparities, and espouses these passions via her medical comic platform, ShirlyWhirl, M.D. Outside of medicine, she also loves to write. Within Cardiology, she is most interested in Prevention, but is remaining open minded.

Dr. Andi Shahu is a resident physician in the Osler Medical Residency in Internal Medicine at Johns Hopkins Hospital in Baltimore, MD. He will begin General Cardiology fellowship in July 2021 at Yale University. He is interested in the intersection between cardiovascular outcomes, health equity and health policy. You can follow him on Twitter @andishahu. 

1. Irizarry OC, Levine LD, Lewey J, et al. Comparison of Clinical Characteristics and Outcomes of Peripartum Cardiomyopathy Between African American and Non-African American Women. JAMA Cardiol. 2017;2(11):1256-1260. doi:10.1001/jamacardio.2017.3574  (https://jamanetwork.com/journals/jamacardiology/fullarticle/2657313)
2. DeFilippis EM, Truby LK, Garan AR, et al. Sex-Related Differences in Use and Outcomes of Left Ventricular Assist Devices as Bridge to Transplantation. JACC Heart Fail. 2019;7(3):250-257. doi:10.1016/j.jchf.2019.01.008  https://pubmed.ncbi.nlm.nih.gov/30819381/
3. Arany Z, Elkayam U. Peripartum Cardiomyopathy. Circulation. 2016;133(14):1397-1409. doi:10.1161/CIRCULATIONAHA.115.020491 (https://pubmed.ncbi.nlm.nih.gov/27045128/)
4. Lewey J, Levine LD, Elovitz MA, Irizarry OC, Arany Z. Importance of Early Diagnosis in Peripartum Cardiomyopathy. Hypertension. 2020;75(1):91-97. doi:10.1161/HYPERTENSIONAHA.119.13291 (https://pubmed.ncbi.nlm.nih.gov/31707840/0)
5. Jetty A, Jabbarpour Y, Pollack J, Huerto R, Woo S, Petterson S. Patient-Physician Racial Concordance Associated with Improved Healthcare Use and Lower Healthcare Expenditures in Minority Populations [published online ahead of print, 2021 Jan 5]. J Racial Ethn Health Disparities. 2021;10.1007/s40615-020-00930-4. doi:10.1007/s40615-020-00930-4 (https://pubmed.ncbi.nlm.nih.gov/33403653/)
6. Takeshita J, Wang S, Loren AW, et al. Association of Racial/Ethnic and Gender Concordance Between Patients and Physicians With Patient Experience Ratings. JAMA Netw Open. 2020;3(11):e2024583. Published 2020 Nov 2. doi:10.1001/jamanetworkopen.2020.24583 (https://pubmed.ncbi.nlm.nih.gov/33165609/)

• Amit Goyal, MD
• Daniel Ambinder, MD
• Pace Wetstein

CardioNerd Amit Goyal is joined by Dr. Erika Hutt (Cleveland Clinic general cardiology fellow), Dr. Aldo Schenone (Brigham and Women’s advanced cardiovascular imaging fellow), and Dr. Wael Jaber (Cleveland Clinic cardiovascular imaging staff and co-founder of Cardiac Imaging Agora) to discuss nuclear and complimentary multimodality cardiovascular imaging for the evaluation of abnormal coronary anatomy including anomalous coronary arteries and myocardial bridges. Show notes were created by Dr. Hussain Khalid (University of Florida general cardiology fellow and CardioNerds Academy fellow in House Thomas). To learn more about multimodality cardiovascular imaging, check out Cardiac Imaging Agora!

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Five Take Home Pearls

1. Anomalous coronaries are present in 1-6% of the general population and predominantly involve origins of the right coronary artery (RCA). Anomalous origination of the left coronary artery from the right sinus, although less common, is consistently associated with sudden cardiac death, especially if there is an intramural course. Sudden cardiac death can occur due to several proposed mechanisms: (1) intramural segments pass between the aorta and pulmonary artery making them susceptible to compression as the great vessels dilate during strenuous exercise; (2) an acute angle takeoff of the anomalous coronary can create a “slit-like” ostium making it vulnerable to closure. Anomalous left circumflex arteries are virtually always benign because the path taken behind the great vessels to reach the lateral wall prevents vessel compression.
2. Myocardial bridging (MB) is a congenital anomaly in which a segment of the coronary artery (most commonly, the mid-left anterior descending artery [LAD]) takes an intramuscular course and is “tunneled” under a “bridge” of overlying myocardium. In the vast majority of cases, these are benign. However, a MB >2 mm in depth, >20 mm in length, and a vessel that is totally encased under the myocardium are more likely to be of clinical significance, especially if there is myocardial oxygen supply-demand mismatch such as with tachycardia (reduced diastolic filling time), decreased transmural perfusion gradient (e.g. in myocardial hypertrophy and/or diastolic dysfunction), and endothelial dysfunction resulting in vasospasm.
3. PET offers many benefits over SPECT in functional assessment of MB including the ability to acquire images at peak stress when using dobutamine stress-PET, enhanced spatial resolution, and quantification of absolute myocardial blood flow. For pharmacologic stress in evaluation of MB, we should preferentially use dobutamine over vasodilator stress. Its inotropic and chronotropic effects enhance systolic compression of the vessel, better targeting the pathological mechanisms in pearl 2 above that predispose a MB to being clinically significant.
4. CCTA can help better define the anatomy of MB as well as anomalous origination of the coronary artery from the opposite sinus (ACAOS), help with risk stratification, and assist with surgical planning.
5. Instantaneous wave-free ratio (iFR) measures intracoronary pressure of MB during the diastolic “wave-free” period – the period in the cardiac cycle when microvascular resistance is stable and minimized allowing the highest blood flow. This allows a more accurate assessment of a functionally significant dynamic stenosis than fractional flow reserve (FFR) – which can be falsely normal due to systolic overshooting.

Detailed Show Notes

1. What are some examples of abnormal coronary anatomies and how often do they lead to clinical events?
   • Abnormal coronary anatomy can relate to the origin (e.g. anomalous origination of coronary artery from the opposite sinus [ACAOS]), course (e.g. myocardial bridging [MB]), intrinsic properties (e.g. aneurysm or hypoplasia), or termination (e.g. fistula) of the coronary artery. In this episode and in these notes, we examine MB and ACAOS in more detail. For an excellent case discussion of anomalous left coronary artery from the pulmonary artery (ALCAPA) by the team from Massachusetts General Hospital, listen to CardioNerds Podcast Episode 81!
   • MB –Myocardial Bridging
     • MB is a congenital anomaly in which a segment of the coronary artery (most commonly, the mid-left anterior descending artery [LAD]) takes an intramuscular course and is “tunneled” under a “bridge” of overlying myocardium.
     • MB was originally identified at autopsy by Reyman in his dissertation, “Disertatio de vasis cordis propriis “ in 1737. In the largest subsequent autopsy study by Risse et al. involving 1056 patients, MB was demonstrated in 26% of patients.
     • Because it is so prevalent, it is difficult to determine its clinical significance. In most patients, MB is an incidental finding with an excellent survival rate (97% at 5 years); however, there are associations with myocardial ischemia, infarction, stress cardiomyopathy, arrhythmia, and sudden cardiac death (SCD).
     • MB can generally be classified into two subtypes: a “superficial” variant which represents 75% of cases and a “deep” variant in which the LAD deviates towards the right ventricle (RV) and dives into the intraventricular septum. The overlying muscle bundle in the deep variant is typically at an oblique or transverse angle resulting in twisting of the tunneled segment and more commonly compromised coronary flow.
     • One of the longest MB usually occurs in association with ACAOS! In this case, the left coronary artery comes off the right coronary cusp. The Left Main (LM) is around 3-4x longer in this instance and dives into the interventricular septum and takes a trans-septal course behind the pulmonary artery before emerging on the other side.
     • There is increased prevalence in certain patient populations: hypertrophic cardiomyopathy (HCM), patients with spontaneous coronary artery dissection (SCAD) +/- fibromuscular dysplasia (FMD), and heart transplant recipients
   • ACAOS – anomalous origination of coronary artery from the opposite sinus
     • Anomalous coronaries are present in 1-6% of the general population and predominantly involve the origin of the right coronary artery (RCA)
     • Anomalous origination of the left coronary artery from the right sinus, although less common, is consistently related to SCD. Separate studies have shown the incidence of SCD may be as high as 23% or 59% of cases in athletes under the age of 20 years.
     • In a large Armed Forces Institute of Pathology (AFIP) study of 6.3 million military recruits, the autopsies of recruits who suffered nontraumatic deaths over a 25-year period were reviewed and ACAOS was found to be the most common cause. It accounted for 33% (64 of 126) of nontraumatic deaths and all cases involved a left coronary artery with an interarterial course.

1. What features predispose MB or ACAOS to become clinically significant? What is the pathophysiology behind development of ischemia in those with clinically significant MB or ACAOS?
   • MB – myocardial bridging
     • Given the majority of MB is benign, correlating MB  as causative in myocardial ischemia and its consequences has been a diagnostic challenge.
     • In systole, the portion of the artery that is tunneled under the MB (bridge segment) is compressed. This can manifest clinically as angina, acute coronary syndrome, left ventricular (LV) dysfunction, arrhythmias, and SCD. However, the majority of myocardial perfusion occurs in diastole which is why MB is usually benign. Nonetheless, certain conditions in patients with MB can set up an oxygen supply-demand mismatch severe enough to lead to myocardial ischemia:
       • Exercise-related stress  leads to tachycardia which can decrease diastolic filling time for the coronary arteries and lead to more of the cardiac cycle to be spent in systole
       • Myocardial hypertrophy and diastolic dysfunction can affect the transmural perfusion gradient increasing supply-demand mismatch. Furthermore, LV hypertrophy can compress the microvasculature and reduce the microvascular reserve.
       • Endothelial dysfunction (driven by metabolic changes secondary to hypoxia) can contribute to coronary compression and lead to the development of accelerated atherosclerosis and/or coronary vasospasm (leading to compression of the epicardial coronary artery throughout the cardiac cycle, not just during systole)
       • There has been a recognized multiplier-effect described by Klues et al. in which the greater the degree of systolic narrowing of the MB, the greater the reduction in diastolic vessel diameter. This is also associated with increased retrograde flow in the coronary artery (which not only reduces perfusion but can introduce shear wall stress and predispose to plaque formation) and reduced flow reserve.
       • Myocardial ischemia can also occur due to “branch steal.” The LAD may have septal perforators that arise from the tunneled segment. When there is compression of the vessel under the MB, there can be “steal” from these septal branches due to the Venturi effect. The septal branches are essentially depressurized because as the vessel narrows, velocity increases but the fluid (coronary blood flow) exerts less pressure. Thus, mild to moderate MB severity typically demonstrates septal ischemia (due to branch steal) rather than distal ischemia downstream from the compression.
       • The vessel segment proximal to the bridge appears to develop atherosclerosis at increased rates approaching 90% — likely as the sequela of shear stress. In contrast, the tunneled segment of the artery is usually spared of atherosclerosis because:
         1. The intima is significantly thinner with a higher prevalence of contractile cells (thought to be negatively associated with development of atherosclerotic lesions)
         1. There is a lack of foam cells (lipid-laden macrophages that are important components of atherosclerosis)
         1. There is reduced expression of known vasoactive agents such as nitric oxide synthase, endothelin-1, and angiotensin-converting enzyme
   • ACAOS – anomalous origination of coronary artery from the opposite sinus
     • The mechanism of ischemia for ACAOS with an interarterial course (between the pulmonary artery and the aorta) and specifically an intramural course has not fully been determined. An intramural course refers to the proximal part of the epicardial coronary artery being contained within the aortic wall and sharing the aortic wall media without a separating adventitia. There are several proposed mechanisms for why this anatomic setup can lead to myocardial ischemia.
       • Compression of the vessel between the aorta and the pulmonary artery during intense exercise as the great vessels dilate
         1. The pulmonary artery likely needs to be enlarged secondary to concomitant pulmonary hypertension for this to occur
         1. An anomalous left circumflex is almost never clinically significant because the path it takes behind the great vessels to reach the lateral wall means the vessel is not exposed to compression!
       • Anacute angle takeoff of the coronary artery, which shares a common wall with the aorta, can result in a significantly narrowed coronary artery ostium (e.g., “slit-like”). This is even further narrowed during exercise when the great vessels expand.
       • Marked narrowing of the intramural segment due to hypoplasia of the intramural segment

1. What is the role of nuclear imaging in the evaluation of MB or ACAOS?

• MB – myocardial bridging
  • In general, nuclear imaging evaluation of MB has had mixed results, and available studies generally have smaller sample sizes and most are retrospective. Prior studies — predominantly involving exercise SPECT — have shown that reversible ischemia may be present in patients with MB and systolic compression of the vessel >50% or >75%. However, other studies in similar populations have shown that reversible ischemia was not inducible in patients with MB with similar degrees of systolic compression of the vessel. There are very few studies available assessing the utility of PET stress testing in patients with MB. One prior study demonstrated that PET stress testing revealed decreased myocardial perfusion reserve in patients with MB, although this was with adenosine rather than dobutamine stress (more on this below).
  • In patients who are symptomatic and have full encasement of the epicardial artery or a deep course seen on coronary CTA, it is reasonable to pursue functional testing, either noninvasive or invasive. Otherwise, we shouldn’t pursue functional testing as the overwhelming majority of MB are benign.
  • Rest/Stress myocardial perfusion imaging with PET has certain advantages over SPECT:
    • Improved spatial resolution
    • Ability to acquire stress images at peak stress if using dobutamine (versus lag time with SPECT)
    • Absolute myocardial blood flow quantification with PET (not available with SPECT where perfusion is relative)
    • With PET we can use either Rubidium-82 (half-life = 76 sec) or N-13 Ammonia (half-life = 10 min) as tracers to assess myocardial perfusion. If using dobutamine as the stress agent, either tracer can be injected at peak stress for the stress imaging. However, if we are using exercise as the stress agent, the patient must be transferred from the treadmill to the camera for stress image acquisition. Because of the time it takes to transfer, Rb-82 cannot be used for exercise PET; it’s half-life is so short (76 sec), it will be gone by the time images are acquired! Therefore, if using exercise PET, you must use N-13 Ammonia PET.
  • When picking a stress agent, remember the goal is to look for significant mechanical compression that leads to coronary ischemia. Therefore, a vasodilator (e.g., adenosine or regadenoson) would be inappropriate. Rather we need to increase chronotropy and inotropy to simulate mechanical compression and can use either dobutamine or exercise.
    • NOTE – If the patient has a resting significant mid ventricular or left ventricular outflow gradient (as occasionally seen in HCM) and/or is pacer-dependent, dobutamine and exercise may increase the LVOT gradient and compromise hemodynamics. Rather, consider rapid atrial pacing or other pharmacologic stress in these patients.
  • Dobutamine or exercise echocardiography are alternatives to nuclear imaging.
    • Since MB is often studied in younger patients and since younger patients generally have rapid heart rate recovery, if using exercise as a stressor, consider supine bicycle rather than treadmill so that stress TTE images may be acquired prior to HR recovery for increased sensitivity.
• ACAOS – anomalous origination of coronary artery from the opposite sinus
  • The 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease state that in patients w/ ACAOS with either left coronary artery arising from the right sinus or right coronary artery arising from the left sinus, ischemic symptoms or ischemia during functional testing is a Class I indication for surgery.
  • After identification of ACAOS, it is reasonable to consider functional testing with nuclear imaging, however the sensitivity of this approach is not yet known. Also, the intense physical exertion that usually results in SCD in these patients is usually not achieve with standard stress tests, so the sensitivity of these tests are difficult to judge. The risks/benefits of functional nuclear imaging should be addressed with patients  in shared decision making with the patient.
  • A number of case reports have described inducible ischemia on myocardial perfusion imaging in patients with ACAOS. This may provide additional justification for surgical intervention.
    • Dr. Wael Jaber (our excellent podcast expert guest on this episode!) as part of the group with Cremer et al. demonstrated in a retrospective study of 27 patients with anomalous take-off of the RCA from the left coronary sinus (AAORCA) that patients with typical angina and exertional dyspnea had a significantly higher rate of demonstrable ischemia on an exercise N13-ammonia positron emission tomography (PET) protocol compared to patients without symptoms. The large majority (11/12) of the patients who underwent surgery had demonstrable ischemia on the above protocol. There were no deaths at 245 days in either the conservative management group or those who underwent surgery. Evidence of ischemia on exercise N13-ammonia positron emission tomography (PET) protocol in patients with may identify patients with AAORCA who would benefit from surgical vs. conservative management.

1. What is the role of coronary CTA (CCTA) in the evaluation of MB or ACAOS?

• Cross-sectional imaging with CCTA is crucial in the assessment of MB and ACAOS for both identifying the abnormality and risk stratification.
• MB – myocardial bridging
  • CCTA has increased the detection of MB from ~5% on invasive coronary angiography to ~21% – much closer to what has been identified on autopsy studies.
  • CCTA can help risk stratify by:
    • Quantifying the depth (>2mm considered clinically significant)
    • Quantifying the length (>20 mm considered clinically significant)
    • Observing the degree of encasement (more fully encased considered clinically significant)
    • Detect concurrent atherosclerosis (particularly proximal to the MB)
    • If there are high risk features and corrective surgery is planned, the anatomical information provided by the CCTA is useful for surgical planning.  NOTE – If depth >5 mm and/or length >25 mm, CABG is preferred over myotomy as risks of myotomy is considerable in these circumstances!
• ACAOS – anomalous origination of coronary artery from the opposite sinus
  • CCTA is endorsed by the European Society of Cardiology (ESC) as the first-line diagnostic imaging in known or suspected coronary artery anomalies. The American Heart Association (AHA) Committee on Cardiovascular Imaging provides a IIa recommendation for CCTA or MRI in the evaluation of anomalous coronary arteries.
  • CCTA can help risk stratify patients by identifying anatomic features that confer a higher risk of SCD:
    • Slit-like orifice of the coronary ostium
    • Acute angle of origin
    • Intramural segment: identification of an intramural segment is physiologically important (as discussed above), but also guides treatment. These patients can be potentially treated by coronary unroofing, unlikepatients with intraarterial course and no intramural segment
  • Some general considerations for CCTA evaluation:
    • Low heart rate is needed to optimize image quality. We commonly accomplish this by giving beta blocker and/or ivabridine.
    • Consider strategies to minimize radiation exposure as able (e.g., in ACAOS we can use prospective gating in which we choose only to image in a certain prespecified phase of the cardiac cycle rather than the whole cardiac cycle as done in retrospective gating)
  • To avoid radiation exposure and iodinated contrast administration with CCTA, cardiac MRI can be considered
    • Additionally, you can obtain concomitant assessment of ventricular size, function, shunt, perfusion, and viability
    • This comes at the expense of decreased spatial resolution, long examination time necessitating significant patient cooperation, and artifact and incompatibility (sometimes prohibitive) from pacemaker or other metallic implants

1. What is the role of left heart catheterization in the evaluation of MB and ACAOS?

• MB – myocardial bridging
  • Coronary angiography is useful for identifying MB, but is less sensitive than CCTA. Altogether, MB identified by coronary angiography may be more severe than those identified by CCTA, as the mechanical compression must be severe enough to be noticed angiographically. However, a majority of even these bridges have a benign natural history. Therefore, additional risk stratification may be obtained invasively to understand the functional significance of a MB. This can be obtained by combining invasive coronary angiography with tools such as instantaneous wave-free ratio (iFR) and intravascular ultrasound (IVUS).      
  • Fractional flow reserve (FFR) is the gold-standard for invasive assessment of intermediate fixed coronary stenoses and correlates with outcomes. iFR has been shown to be non-inferior to FFR.
  • However, FFR has not been validated in the assessment of dynamic compression, as with myocardial bridging. In dynamic compression, iFR offers some notable advantages over FFR:
    • In FFR we are checking the average of the blood pressure and flow over the whole cardiac cycle — systole and diastole. Because of systolic compression in MB, there is a spurious increase in the intracoronary systolic pressure that may yield a falsely normal FFR value — this is known as systolic pressure overshooting
    • In iFR, on the other hand, we are measuring intracoronary pressure during the diastolic “wave free” period — the period in the cardiac cycle when microvascular resistance is stable and minimized allowing the highest blood flow. This gives a more accurate assessment of functionally significant dynamic stenosis
    • iFR is considered positive if it is < 0.89. The grey zone in iFR studies is >0.86 and <0.93, so ideally, we want < 0.86 for a more definitive true positive.
    • Pre- and post-invasive intervention with dobutamine stress iFR testing in addition to relief of symptoms can help guide when to recommend to patients to return to exercise after an invasive intervention on the MB. IVUS imaging shows a highly specific “Half Moon” sign associated with MB—it is unclear why this happens. We can utilize assistance of provocative testing (dobutamine, acetylcholine, rapid A-pacing) to further assess the change in the vessel structure under stress
  • The Myocardial Bridge Study, led by Dr. Joanna Ghobrial, is an ongoing prospective study looking to correlate functional testing of MB (invasive and non-invasive) and long-term clinical outcomes.
• ACAOS – anomalous origination of coronary artery from the opposite sinus
  • Similar to in MB, iFR and IVUS are emerging tools utilized to help risk stratify patients with ACAOS
  • IVUS with concurrent dobutamine stress testing can allow for dynamic assessment of anomalous coronary arteries both at rest and under stress. The effects of physiologicor pharmacological stress on the morphology of the intramural segment of an interarterial coronary can provide additionaldata to guide which patients may warrant surgery – particularly patients with anomalous take-off of the right coronary artery from the left coronary sinus (in which surgical intervention is more controversial).

Wael Jaber, MD, is a staff cardiologist in the Section of Cardiovascular Imaging, Robert and Suzanne Tomsich Department of Cardiovascular Medicine, at the Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at Cleveland Clinic. Dr. Jaber specializes in cardiac imaging (both nuclear cardiology and echocardiography) and valvular heart disease. Dr. Jaber attended college at the American University in Beirut, graduating with a Bachelor of Science in biology. He then went on at the American University to receive his medical degree while making the Dean’s honor list. He completed his residency in internal medicine at the St. Luke’s-Roosevelt Hospital Center at Columbia University College of Physicians and Surgeons, where he also completed fellowships in cardiovascular medicine and nuclear cardiology. Dr. Jaber is currently is the Medical Director of the Nuclear Lab and of the Cardiovascular Imaging Core Laboratory in C5Research. He is fluent in English, French and Arabic. He is the author of Nuclear Cardiology review: A Self-Assessment Tool and cofounder of Cardiac Imaging Agora.

Dr. Aldo L Schenone is one of the current Chief Non-Invasive Cardiovascular Imaging Fellows at the Brigham and Women’s Hospital. He completed medical school at the University of Carabobo in Valencia, Venezuela, and then completed both his Internal Medicine residency and Cardiology fellowship at the Cleveland Clinic where he also served as a Chief Internal Medicine Resident.

Dr. Erika Hutt @erikahuttce is a cardiology fellow at the Cleveland Clinic. Erika was born and raised in Costa Rica, where she received her MD degree at Universidad de Costa Rica. She then decided to pursue further medical training in the United States, with the goal of becoming a cardiologist. She completed her residency training at Cleveland Clinic and went on to fellowship at the same institution. Her passions include infiltrative heart disease, atrial fibrillation, valvular heart disease and echocardiography among many. She is looking forward to a career in advanced cardiovascular imaging.

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17.       Lin S, Tremmel JA, Yamada R, et al. A novel stress echocardiography pattern for myocardial bridge with invasive structural and hemodynamic correlation. J Am Heart Assoc. Apr 2013;2(2):e000097.

18.       Monroy-Gonzalez AG, Alexanderson-Rosas E, Prakken NHJ, et al. Myocardial bridging of the left anterior descending coronary artery is associated with reduced myocardial perfusion reserve: a. Int J Cardiovasc Imaging. Feb 2019;35(2):375-382.

19.       Sen S, Asrress KN, Nijjer S, Petraco R, Malik IS, Foale RA, Mikhail GW, Foin N, Broyd C, Hadjiloizou N, Sethi A, Al-Bustami M, Hackett D, Khan MA, Khawaja MZ, Baker CS, Bellamy M, Parker KH, Hughes AD, Francis DP, Mayet J, Di Mario C, Escaned J, Redwood S, Davies JE. Diagnostic classification of the instantaneous wave-free ratio is equivalent to fractional flow reserve and is not improved with adenosine administration. Results of CLARIFY (Classification Accuracy of Pressure-Only Ratios Against Indices Using Flow Study).J Am Coll Cardiol. 2013; 61:1409–1420

20.       Stout KK, Daniels CJ, Aboulhosn JA, et al.2018 ACC/AHA Guideline for the managementof adults with congenital heart disease: AReport of the American College of Cardiology/American Heart Association Task Force onClinical Practice Guidelines. Circulation 2019;139:e698–800

21.       Tarantini G, Barioli A, Nai Fovino L, et al. Unmasking Myocardial Bridge-Related Ischemia by Intracoronary Functional Evaluation. Circ Cardiovasc Interv. 06 2018;11(6):e006247.

22.       Tarantini G, Migliore F, Cademartiri F, Fraccaro C, Iliceto S. Left Anterior Descending Artery Myocardial Bridging: A Clinical Approach. J Am Coll Cardiol. Dec 2016;68(25):2887-2899.

23.       Uusitalo V, Saraste A, Knuuti J. Multimodality Imaging in the Assessment of the Physiological Significance of Myocardial Bridging. Curr Cardiol Rep. Jan 2016;18(1):2.

• Wael Jaber, MD

CardioNerds (Amit Goyal & Daniel Ambinder) join University of Maryland cardiology fellows (Manu Mysore, Adam Zviman, and Scott Butler) for some cardiology and an Orioles game in Baltimore! They discuss a rare cause of postpartum angina and cardiac arrest due to coronary vasculitis. Program director Dr. Mukta Srivastava provides the E-CPR expert segment and a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Rick Ferraro with mentorship from University of Maryland cardiology fellow Karan Desai.

This case has been published in JACC Case Reports!

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A woman in her early 30s with a past medical history of Hashimoto’s thyroiditis and one prior miscarriage at <8 weeks presented with chest pain about 6 weeks postpartum from the birth of her third child. In the ED, she continued to report intermittent sharp chest discomfort and found to have a diastolic decrescendo murmur at the left upper sternal border and labs demonstrating a troponin-I of 0.07 ng/dL. Join the UMD Cardionerds for the incredible course and story of this young patient as we go through the differentia and approach to postpartum chest pain and ultimately arrive in a very rare diagnosis!   For a detailed course, enjoy the JACC case report.

Visit the JACC Case Reports to review the case media!

1. How Do We Evaluate Chest Pain in Younger Patients 

• Start with the same things as everyone else!  Think broadly about the big three concerning etiologies of chest pain: Cardiac, Gastric, and Pulmonary (The excellent Clinical Problems Solvers 4+2+2 construct here is always a great resource. Find them at: https://clinicalproblemsolving.com/dx-schema-chest-pain/).   
• Of course it is important to think about non-life threatening etiologies as well – esophageal spasm, gastric ulcer, rib fracture, skin lesion, among many others – given that high-risk chest pain is less likely in younger adults.  
• While less common, acute coronary syndrome is not uncommon in young patients, as 23% of patients with MI present at age <55 years.  

2. What About Chest Pain in Women?  

• As has been discussed on the Cardionerds podcast (Listen to episodes with Dr. Nanette Wenger, Dr Martha Gulati, and Dr. Leslie Cho), women generally present with acute coronary syndrome at a later age, with a higher burden of risk factors than men, and with greater symptom burden but are less likely to be treated with guideline-directed medical therapies, undergo cardiac catheterization and receive timely reperfusion. In one study of young patients with acute MI, women – 19% of cases overall – were less likely to undergo revascularization or receive guideline-directed therapy 
• The construct of classifying chest pain as “typical” and “atypical” likely leads to misdiagnosis or delayed diagnosis of acute myocardial infarction in women. Rather, it is important to recognize that while symptoms may not be “typical” for angina, coronary disease can manifest in many different ways.  
• While many women will presents with chest pain suggestive of angina, women are more likely than men to present with dyspnea, indigestion, weakness, nausea/vomiting and/or fatigue. Note, shoulder pain and arm pain are twice as predictive of an acute myocardial infarction diagnosis in women compared with men.  
• Furthermore, while obstructive epicardial disease remains the primary cause of acute MI in young women, it is also important to keep other causes of chest pain such as MINOCA, SCAD (see the UCLA episode), peripartum cardiomyopathy (see the Penn and MCW episodes), or coronary vasculitis on the differential. While these etiologies are rare, they are disproportionately represented in young women.  

3. How do we think about categorizing vasculitis? 

• Vasculitis is a broad term encompassing many forms of vessel wall (including arteries, veins or capillaries) inflammation.  This can be secondary to autoimmunity, infection, drug reaction, and malignancy to name a few underlying causes.  
• Generally vasculitis is divided by large vessel (e.g., Takayasu, Giant Cell), medium vessel (e.g., Polyarteritis Nodosa), and small vessel etiologies (e.g., Granulomatosis with Polyangitis, Eosinophilic Granulomatosis with Polyangiitis, Microscopic Polyangitis, Immune-mediated Vasculitis, amongst others). This characterization follows the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitis.  
• Other important categories includes variable vessel vasculitis (e.g., Behcet’s Disease, Cogan’s Syndrome) and vasculitis associated with systemic disease (e.g., Lupus vasculitis, Rheumatoid vasculitis, Sarcoid vasculitis).  

4. What Does Vasculitis Look Like in the Heart? 

• While inflammation can occur throughout the heart – e.g., pericarditis or myocarditis – vasculitis in the heart refers specifically to inflammation of the coronary arteries. This is a relatively rare process, with <10% of vasculitis patients exhibiting cardiac involvement.  
• Patients with coronary vasculitis rarely present with isolated coronary involvement and typically have systemic manifestations, such as constitutional symptoms in addition to cardiac symptoms (e.g., angina, heart failure, arrhythmia). Examination may reveal asymmetric pulses or BP readings between limbs and arterial bruits, with imaging revealing multi-organ infarcts without a clear embolic origin. Amongst the vasculitides, Takayasu Arteritis (TA) is one of the more frequent etiologies of coronary arteritis.  
• In Takayasu Arteritis (TA), the affected arteries are typically the aorta and its major branches. In contrast to giant cell arteritis (GCA), TA is quite rare and tends to have onset <40 years age; however, for both diagnoses coronary involvement is rare. TA patients will typically have constitutional symptoms and may have diminished/absent arterial pulses often accompanied by bruits. Weakness of the arterial walls may lead to aneurysms and specifically aortic root aneurysm may result in aortic valve insufficiency. When involving the coronaries, there are three main type of TA lesions: stenosis or occlusion of the ostia/proximal segments (Type 1); diffuse or focal coronary vasculitis involving all the epicardial branches or focal areas (Type 2); coronary aneurysms (Type 3). 

5. What Are the Complications of Coronary Vasculitis?  

• The consequences of coronary vasculitis are variable and much of the data we have comes from case reports. As in the case presented, severe coronary ischemia and its complications, including arrhythmia and cardiac arrest, are a major concern. However, cardiac arrest is rarely the first presentation of coronary vasculitis, especially if it is detected early. The manifestations of coronary vasculitis are also going to be dependent on the specific etiology of the arteritis.  
• Amongst the medium vessel vasculitis and specifically polyarteritis nodosa, 15-20% of patients will have cardiac involvement, with major complications including heart failure, myocardial infarction, or arrhythmia.  
• Amongst the small vessel vasculitis, eosinophilic granulomatosis with polyangiitis is the most common culprit for cardiac involvement, primarily secondary to eosinophilic toxicity. Cardiac involvement is a major cause of mortality and poor prognostic sign in EGPA. 

The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus.

We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director.

References

1. Kostner, M. J., & Warrington, K. J. (2019, March 13). Vasculitis of the Coronary Arteries. ACC.org. 
2. Ward, E. V., Nazari, J., & Edelman, R. R. (2012). Coronary artery vasculitis as a presentation of cardiac sarcoidosis. Circulation, 125(6), e344-e346. 
3. Awad, H. H., McManus, D. D., Anderson Jr, F. A., Gore, J. M., & Goldberg, R. J. (2013). Young patients hospitalized with an acute coronary syndrome. Coronary Artery Disease, 24(1), 54-60. 
4. Bugiardini, R., Cenko, E. (2020). Sex differences in myocardial infarction deaths. Lancet, 396:72–73 
5. DeFilippis, E.M., Collins, B.L., Singh A., et. al Women who experience a myocardial infarction at a young age have worse outcomes compared with men: the Mass General Brigham YOUNG-MI registry, European Heart Journal, ehaa662 
6. Miloslavsky, E., & Unizony, S. (2014). The heart in vasculitis. Rheumatic Disease Clinics, 40(1), 11-26. 
7. Mehta LS, Beckie TM, DeVon HA et al; American Heart Association Cardiovascular Disease in Women and Special Populations Committee of the Council on Clinical Cardiology, Council on Epidemiology and Prevention, Council on Cardiovascular and Stroke Nursing, and Council on Quality of Care and Outcomes Research. (2016) Acute Myocardial Infarction in Women: A Scientific Statement From the American Heart Association. Circulation. Mar 1;133(9):916-47. doi: 10.1161/CIR.0000000000000351.  

• Bibin Varghese, MD
• Rick Ferraro, MD
• Tommy Das, MD
• Eunice Dugan, MD
• Evelyn Song, MD
• Colin Blumenthal, MD
• Karan Desai, MD
• Amit Goyal, MD
• Daniel Ambinder, MD

CardioNerd Amit Goyal is joined by Dr. Erika Hutt (Cleveland Clinic general cardiology fellow), Dr. Aldo Schenone (Brigham and Women’s advanced cardiovascular imaging fellow), and Dr. Wael Jaber (Cleveland Clinic cardiovascular imaging staff and co-founder of Cardiac Imaging Agora) to discuss nuclear and complimentary multimodality cardiovascular imaging for the evaluation of myocardial viability. Show notes & #Tweetorial were created by Dr. Hussain Khalid (University of Florida general cardiology fellow and CardioNerds Academy fellow in House Thomas). To learn more about multimodality cardiovascular imaging, check out Cardiac Imaging Agora! 

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In response to ischemia the myocardium can dynamically change along a spectrum from myocardial stunning to myocardial hibernation to myocardial necrosis. The goals of viability testing are to identify patients who may benefit from revascularization as hibernating or stunned myocardium are potentially reversible causes of LV dysfunction. There are numerous imaging modalities available for the evaluation of myocardial viability. The broad range of ways in which myocardial viability is assessed speaks to the complexity of the disease spectrum and the difficulty in creating a unifying definition of viability to assess in clinical trials.  

Five Take Home Pearls

1. In response to an acute episode of ischemia with subsequent reperfusion, the myocardium can be exposed to a large flux of oxygen free radicals or calcium overload that affects the cellular membrane and contractile apparatus. This phenotypically results in decreased contractility of the affected region of myocardium that can persist for weeks, labeled myocardial stunning 

2. Repeated episodes of myocardial stunning or chronic low myocardial blood flow can lead to cellular changes such as resorption of the contractile apparatus in order to decrease oxygen demand and allow the myocardial cells to survive. Phenotypically, this might appear as regions of hypokinesis or akinesis at rest with a fixed perfusion defect on myocardial perfusion imaging. This is typically considered hibernating myocardium.  

3. The goal of myocardial viability testing is to be able to differentiate between stunned, hibernating and necrosed myocardium. In patients with known epicardial coronary disease, this differentiation allows us to identify who may benefit from revascularization with improved LV systolic function and overall survival.  

4. There are several imaging modalities that can be used in the assessment of myocardial viability. The most sensitive modalities are FDG-PET and CMR. The addition of Dobutamine or first pass perfusion with Gadolinium additionally increases the specificity of CMR. These modalities are more expensive and not as widely available.  

5. The dynamic nature of the myocardial hibernation and the lack of a unifying definition/phenotypic expression of myocardial hibernation and viability have made it difficult for clinical trials to show that re-establishing myocardial blood flow to hibernating myocardium is beneficial. As Dr. Jaber stated in the episode in his spin on the classic opening phrase from Leo Tolstoy’s masterpiece, Anna Karenina, “All normal hearts are normal in the same way, and all abnormal hearts are abnormal in different ways.” 

6. The PARR-2 trial was one of the few randomized, controlled trials of patients with LV systolic dysfunction and coronary artery disease who were randomized to either FDG-PET guided management or standard care with respect to whether to pursue revascularization. Overall, there was not a significant reduction in the primary composite endpoint between the FDG-PET arm and the standard care arm. However, not all patients received the revascularization strategy recommended by imaging. In patients whom the PDG-PET recommendation for revascularization was followed, there was a significant benefit compared to the standard care group.  

Quotable: 

“All normal hearts are normal in the same way, All abnormal hearts are abnormal in different ways”—0:54 

Detailed Show Notes

1. What is myocardial hibernation and myocardial stunning? How do these concepts fit into the discussion of myocardial viability?  
   • A common scenario encountered in clinical practice is the patient who has depressed LV systolic function and known obstructive epicardial coronary disease. For these patients, we may wonder if the myocardium supplied by the epicardial coronary arteries with obstructive lesions is living (viable) or dead(scarred), and whether there would be a benefit to revascularization. If the LV systolic function is decreased with hypokinesis or akinesis and perfusion deficits, then the myocardium is either dead (scarred), stunned, or hibernating! This is a spectrum. 
   • Stunned myocardium and hibernating myocardium were originally described in the late 1970s and popularized in the 1980s — stunned myocardium by Dr. Braunwald and Dr. Kloner and hibernating myocardium by Dr. Diamond and Dr. Rahimtoola. When first described, myocardial stunning was thought of as a “hit” (episode of severe ischemia), “run” (relief of ischemia before irreversible injury) and “stun” (a relatively long period of post-ischemia LV dysfunction). 
   • What are stunned myocardium and hibernating myocardium? When a region of myocardium becomes ischemic and that ischemia is severe and prolonged, myocardial necrosis occurs, there is no return of contractile function, and the myocardium is replaced by scar tissue. If, however, there is reperfusion and relief of the ischemia before necrosis occurs, the myocardium can become “stunned”. 
   • Myocardial stunning is a transient period of post-ischemic dysfunction that can persist for days to weeks prior to recovery of myocardial function. There are a variety of hypotheses as to why this occurs. Some of the leading hypotheses are: 
     • In response to ischemia, there can be a flux of oxygen free radicals that disrupt cellular membranes and the contractile apparatus of the cell. 
     • Calcium overload that affects myofilament responsiveness to calcium or leads to sarcoplasmic reticulum dysfunction. Phenotypically, this may manifest as hypokinesis or akinesis of the corresponding area of myocardium.    
   • If there are repetitive episodes of myocardial stunning or if there is chronic low myocardial blood flow to a region of the myocardium, this can lead to myocardial hibernation.  
     • Essentially, the myocardium undergoes metabolic adaptations and downregulation of function (e.g. resorption of the intracellular contractile apparatus) that allows the myocardium to survive by reducing myocardial oxygen demand. Phenotypically, this results in contractile abnormalities at rest that may manifest as hypokinesis or akinesis of the corresponding area of myocardium. This dysfunction may persist weeks to months even after revascularization as the contractile apparatus replenishes.  
     • As referenced in the episode, Dr. Rahimtoola popularized the concept of hibernating myocardium in a published report in the 1980s of a patient who had chronic angina, single vessel obstructive epicardial coronary disease in the LAD, depressed LV systolic function, and an anteroapical myocardial wall motion abnormality (WMA). After administration of nitroglycerin, the patients LV systolic function and WMA improved suggesting that this area of the myocardium was viable. The patient underwent coronary bypass surgery and their LV systolic function and wall motion eventually normalized—confirming that this area of myocardium was viable all along. 
     • As described by Dr. Kloner in a recent review, an analogy to hibernating myocardium is a broken arm that is casted. As the muscles are not being used, we can expect some atrophy and similarly with hibernating myocardium, the cardiac muscle is not contracting and some level of atrophy is not unexpected. As with a broken arm that is casted will need some time to recover near full function, revascularization will not lead to immediate normalization of cardiac function.  

1. What are our goals when it comes to viability testing? In which patients should we pursue viability testing (evaluation for myocardial stunning or myocardial hibernation)?   
   • The primary goals of viability testing are: 
     • To avoid attempting to revascularize dead myocardium as this  would unnecessarily expose them to the risks of an invasive procedure.  
     • To identify patients who may have an improvement in LV systolic function with revascularization. 
     • To potentially improve survival. 
   • There are certain patient populations in whom we should not pursue viability testing as the information provided by testing would not change our management: 
     • Patients who have normal coronary arteries or nonobstructive disease. 
     • Patients with obstructive epicardial coronary disease that is not amenable to revascularization. 
     • Patients with normal LV systolic function. 

• There are different modalities we can use to assess for myocardial viability. How can we conceptualize the different modalities and what are the advantages/disadvantages of each one? 
  • We can broadly differentiate the modalities used to assess for myocardial viability into those that are looking for “signs of life” (e.g., evidence of inducible contractility, cell membrane integrity, metabolic activity) and those that are looking for “signs of death” (e.g., myocardial wall thinning, presence of scar).  
  • How to look for signs of life: 
    • Dobutamine Stress Echocardiography 
      • With DSE, we are trying to prove that areas of the myocardium that are hypokinetic or akinetic have some reserve and contractile function. We start with low dose dobutamine, and as we increase the dose, the wall may start to contract better if it is viable. As we get to higher doses, the wall may become hypokinetic again due to ischemia and perfusion-contractile mismatch (e.g., the oxygen demand overwhelms the chronically hypoperfused area which has adapted to chronic ischemia by downregulating the intracellular contractile apparatus). 
      • This test has high specificity; however, sensitivity is ~70%. The positive predictive value of DSE is likely highest when there is a biphasic response: improvement at low dose dobutamine but worsening function at high dose. It is a good tool when you want to avoid radiation exposure or when you don’t have access to more advanced techniques. 
    • Nuclear Imaging 
      • Fluorodeoxyglucose (FDG)-positron emission tomography (PET) 
        • FDG uptake by cells is an indirect marker of viability as it establishes the cells in this region are metabolically active. Myocardial segments with a fixed perfusion defect are dead (scarred), hibernating but viable, or an admixture of scarred and hibernating myocardium. Those areas which “light up” on FDG-PET are metabolically active (sign of life) and thus likely viable. 
        • FDG-PET sensitivity for assessment of myocardial viability is up to 92% but specificity is relatively low compared to other studies (<70%). 
        • In the setting of an acute myocardial infarction (MI), FDG-PET may overestimate viability as infarcting segments are inflamed such that FDG uptake does not necessarily imply viable myocardium. 
      • Thallium-Single-photon emission computerized tomography (SPECT) 
        • Thallium is a potassium analog and uses a sodium-potassium ATPase (Na+/K+ ATPase) transport protein embedded in the plasma membrane to enter the cell. It has a long half-life of around 3 days. 
        • This is an indirect marker of viability as it establishes that myocardial cells have intact cellular membranes. This often requires a two day protocol in which you obtain baseline images and then reimage the patient 24 hours later. The myocardium that “lights up” is presumably viable. The 24-hour waiting period allows further slower uptake by cells and areas that we can classify as hibernating myocardium. Alternatively, we can reinject thallium on the second day and assess whether we have more myocardial uptake than on the first day—this helps improve the specificity of the study. Sensitivity of this method to detect hibernation is modest (around ~87%); however, specificity is very high. 
        • Most centers have abandoned this method because the patient has to present on two consecutive days for the procedure, they are exposed to significantly higher radiation, and the sensitivity is low. The American Society of Nuclear Cardiology has discouraged the use of thallium to minimize radiation exposure. 
      • Technetium (99mTc) Sestamibi SPECT 
        • 99mTc Sestamibi uptake in the myocardium is an indirect marker of viability as it taken up by cells with intact plasma membranes and mitochondrial membranes.  
        • 99mTc Sestamibi is given at rest. Nitroglycerin is then given to vasodilate the vessels that were not vasodilated at rest. This may enhance myocardial blood flow in the segments that were not taking up 99mTc Sestamibi prior to nitroglycerin. We then look for areas of myocardium that “light up” and represent likely hibernating myocardium 
        • Very few centers utilize this approach for viability testing. 

1. So we talked about ways to “look for signs of life.” How do we look for “signs of death” on viability imaging?  
   • Resting Echocardiography 
     • The presence of end-diastolic wall thickness less than or equal to 6 mm with a hypo-contractile segment is highly specific for nonviable myocardium and would not likely benefit from revascularization. If this is seen, you likely do not need to order follow up PET or other modality for further assessment of viability. 
   • Cardiac Magnetic Resonance Imaging (CMR): 
     • Whereas with PET, you are looking for areas to “light up” that are viable, with CMR, you are looking at late gadolinium enhancement (LGE)—areas of the myocardium that “light up” due to presence of scar. Because we know that scar in ischemic heart disease progresses from subendocardium to epicardium, we can quantify not only the extent (how many segments involved) of scar, but also the “transumurality” of the scar (the percentage of the wall thickness that is scar). We can quantify this in quartiles. For any segment that has >50% LGE, the chances of that segment recovering after revascularization are very low (<10%). If LGE is <25% of the wall thickness, the chances of wall recovery after revascularization are good (>60%). If LGE is 25-50%, this is the grey zone. For these patient’s we must consider individual patient factors such as age and comorbidities and complexity of the intervention when deciding whether to attempt revascularization. Remember—always consider risk vs benefit and incorporate informed shared decision-making! 
     • CMR additionally provides information on wall segment contractility and function, and big-picture information such as overall LV wall thickness and LV volumes. With this additional big picture information we can get a better understanding of the overall health of the ventricle and weigh this against the extent of hibernating myocardium when we are making a decision about revascularization.  
     • You can also use Dobutamine stress with CMR. If you are unsure/on the edge for deciding whether to revascularize a patient with 25-50% LGE on CMR, you can give dobutamine and see if that portion of the LV has augmented contractility (sign of life). This can give you more confidence that myocardial segment will recover. 
     • Finally, you can also do stress testing with CMR by using first pass perfusion with the injection of Gadolinium. You can knock everything out in one test—assessment for ischemia and viability!  
     • CMR has sensitivities similar to PET in regard to identifying viable myocardium and with the addition of dobutamine stress, you can have increased specificity. 
     • In contrast to PET, in the setting of an acute MI, CMR can underestimate viability because LGE can appear in areas of inflammation rather than scar. 
     • Enjoy Ep #33 – CMR with Dr. Kown for more! 

1. What are some challenges in viability testing to assess for hibernating myocardium prior to revascularization? Is there any data to support this approach? 
   • As we discussed above, myocardial stunning, hibernation, and necrosis with scarring represent a spectrum of disease processes in response to ischemia. This spectrum is dynamic. Additionally, as we saw above, there is a plethora of phenotypic expressions and definitions of hibernation and viability that we assess by our different imaging modalities in looking for signs of life versus death (e.g., mismatch between perfusion and metabolic activity, contractile reserve, wall thickness, evidence of an intact cellular membrane, degree of scar, etc.).  
   • The dynamic nature of the disease process and the lack of a unifying definition/phenotypic expression of myocardial hibernation and viability have made it difficult for clinical trials to show that re-establishing myocardial blood flow to hibernating myocardium is beneficial.  
   • As Dr. Jaber stated in the episode in his spin on the classic opening phrase from Leo Tolstoy’s masterpiece, Anna Karenina, “All normal hearts are normal in the same way, and all abnormal hearts are abnormal in different ways.”  With that being said, there are some notable studies that have assessed the benefit of myocardial viability testing prior to revascularization: 
     • In a 2002 meta-analysis by Allman et. al, myocardial viability testing and the impact of revascularization on prognosis in patients with coronary artery disease and left ventricular dysfunction was reviewed.  
       • This analysis consisted of >3000 patients w/CAD and LV systolic dysfunction. Viability testing was assessed using thallium perfusion SPECT, FDG metabolic imaging, or dobutamine echocardiography. In patients showing areas of viability, revascularization was associated with an annual mortality rate of 3.2% over 25 months compared to 16% in the medical treatment alone (no revascularization) groups p<0.0001—a 79.6% annual reduction in mortality. 
     • The PARR-2 trial was a randomized, controlled trial of 430 patients with LV systolic dysfunction and suspected coronary artery disease who were randomized to either FDG-PET guided management or standard care in regards to whether to pursue revascularization. The primary outcome was composite endpoint of cardiac death, MI, or recurrent hospital stay for cardiac cause, within 1 year. Overall, there was not a significant reduction in the primary composite endpoint between the FDG-PET arm and the standard care arm.  
       • However, for patients in the FDG-PET arm in whom the FDG-PET recommendation for revascularization was followed, there was a significant benefit compared to the standard care group.  
       • A substudy of the PARR-2 trial showed that in the FDG-PET group, the imaging study recommendation regarding whether to proceed with revascularization was not followed 25% of the time for a variety of reasons—persistent or resolved symptoms, renal failure, and anatomy not amenable to revascularization, for instance. In a post-hoc analysis of the 182 patients randomized to the FDG-PET arm of PARR-2 with LVEF <35% and CAD being considered for revascularization, a larger amount of hibernating myocardium was associated with improved outcomes following revascularization. 
     • The STITCH (Surgical Treatment for Ischemic Heart Failure) trial was a randomized controlled trial that enrolled 1212 patients with severe CAD and LVEF <35% to CABG + medical therapy vs. medical therapy alone. 610 of these patients had viability testing (SPECT and/or dobutamine stress echo). The primary endpoint was death from any cause.  
       • Overall, there was no survival benefit at 5 years of CABG + medical therapy compared to medical therapy alone and an 8% benefit at 10 years of the revascularization group.  
       • In a substudy analysis, viability testing did not identify patients who would have a survival benefit from CABG. 
       • Of note, patients were not randomized for assessment of hibernation (viability testing) in this trial. And importantly, FDG-PET and MRI were not used in the assessment of viability.  
     • The recently published International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial was not a trial designed to assess the value of assessing myocardial hibernation/viability and had very few FDG-PET or MRI assessments  

A patient w/ICM (LVEF 15%) p/w angina & DOE. SPECT shows a fixed defect & LHC shows LCx CTO.

…To revasc or not to revasc…

1st we need to know if the myocardium is dead or alive?! Check out this #Tweetorial on 🫀 viability to see how! pic.twitter.com/Y45F6vQnQL

Wael Jaber, MD, is a staff cardiologist in the Section of Cardiovascular Imaging, Robert and Suzanne Tomsich Department of Cardiovascular Medicine, at the Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at Cleveland Clinic. Dr. Jaber specializes in cardiac imaging (both nuclear cardiology and echocardiography) and valvular heart disease. Dr. Jaber attended college at the American University in Beirut, graduating with a Bachelor of Science in biology. He then went on at the American University to receive his medical degree while making the Dean’s honor list. He completed his residency in internal medicine at the St. Luke’s-Roosevelt Hospital Center at Columbia University College of Physicians and Surgeons, where he also completed fellowships in cardiovascular medicine and nuclear cardiology. Dr. Jaber is currently is the Medical Director of the Nuclear Lab and of the Cardiovascular Imaging Core Laboratory in C5Research. He is fluent in English, French and Arabic. He is the author of Nuclear Cardiology review: A Self-Assessment Tool and cofounder of Cardiac Imaging Agora.

Dr. Aldo L Schenone is one of the current Chief Non-Invasive Cardiovascular Imaging Fellows at the Brigham and Women’s Hospital. He completed medical school at the University of Carabobo in Valencia, Venezuela, and then completed both his Internal Medicine residency and Cardiology fellowship at the Cleveland Clinic where he also served as a Chief Internal Medicine Resident.

Dr. Erika Hutt @erikahuttce is a cardiology fellow at the Cleveland Clinic. Erika was born and raised in Costa Rica, where she received her MD degree at Universidad de Costa Rica. She then decided to pursue further medical training in the United States, with the goal of becoming a cardiologist. She completed her residency training at Cleveland Clinic and went on to fellowship at the same institution. Her passions include infiltrative heart disease, atrial fibrillation, valvular heart disease and echocardiography among many. She is looking forward to a career in advanced cardiovascular imaging.

1. Allman KC. 18F-FDG PET and myocardial viability assessment: trials and tribulations. J Nucl Med. Apr 2010;51(4):505-506. 

2. Allman KC, Shaw LJ, Hachamovitch R, Udelson JE. Myocardial viability testing and impact of revascularization on prognosis in patients with coronary artery disease and left ventricular dysfunction: a meta-analysis. J Am Coll Cardiol. Apr 2002;39(7):1151-1158. 

3. Beanlands RS, Nichol G, Huszti E, et al. F-18-fluorodeoxyglucose positron emission tomography imaging-assisted management of patients with severe left ventricular dysfunction and suspected coronary disease: a randomized, controlled trial (PARR-2). J Am Coll Cardiol. Nov 2007;50(20):2002-2012. 

4. Bonow RO, Maurer G, Lee KL, et al. Myocardial viability and survival in ischemic left ventricular dysfunction. N Engl J Med. Apr 2011;364(17):1617-1625. 

5. Cwajg JM, Cwajg E, Nagueh SF, et al. End-diastolic wall thickness as a predictor of recovery of function in myocardial hibernation: relation to rest-redistribution T1-201 tomography and dobutamine stress echocardiography. J Am Coll Cardiol. Apr 2000;35(5):1152-1161. 

6. D’Egidio G, Nichol G, Williams KA, et al. Increasing benefit from revascularization is associated with increasing amounts of myocardial hibernation: a substudy of the PARR-2 trial. JACC Cardiovasc Imaging. Sep 2009;2(9):1060-1068. 

7. Dilsizian V, Smeltzer WR, Freedman NM, Dextras R, Bonow RO. Thallium reinjection after stress-redistribution imaging. Does 24-hour delayed imaging after reinjection enhance detection of viable myocardium? Circulation. Apr 1991;83(4):1247-1255. 

8. Gerber BL, Raman SV, Nayak K, et al. Myocardial first-pass perfusion cardiovascular magnetic resonance: history, theory, and current state of the art. J Cardiovasc Magn Reson. Apr 2008;10:18. 

9. Gunning MG, Kaprielian RR, Pepper J, et al. The histology of viable and hibernating myocardium in relation to imaging characteristics. J Am Coll Cardiol. Feb 2002;39(3):428-435. 

10. Kloner RA. Stunned and Hibernating Myocardium: Where Are We Nearly 4 Decades Later? J Am Heart Assoc. 02 2020;9(3):e015502. 

11. Medrano R, Lowry RW, Young JB, et al. Assessment of myocardial viability with 99mTc sestamibi in patients undergoing cardiac transplantation. A scintigraphic/pathological study. Circulation. Sep 1996;94(5):1010-1017. 

12. Rahimtoola S. Coronary bypass surgery for chronic angina–1981. A perspective. Circulation. 1982;65(2):225-241. 

13. Velazquez EJ, Lee KL, Deja MA, et al. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med. Apr 2011;364(17):1607-1616. 

• Wael Jaber, MD

CardioNerd Amit Goyal is joined by Dr. Erika Hutt (Cleveland Clinic general cardiology fellow), Dr. Aldo Schenone (Brigham and Women’s advanced cardiovascular imaging fellow), and Dr. Wael Jaber (Cleveland Clinic cardiovascular imaging staff and co-founder of Cardiac Imaging Agora) to discuss nuclear and complimentary multimodality cardiovascular imaging for the evaluation of coronary microvascular disease.  To learn more about multimodality cardiovascular imaging, check out Cardiac Imaging Agora! 

Collect free CME/MOC credit just for enjoying to the episode! 

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Wael Jaber, MD, is a staff cardiologist in the Section of Cardiovascular Imaging, Robert and Suzanne Tomsich Department of Cardiovascular Medicine, at the Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at Cleveland Clinic. Dr. Jaber specializes in cardiac imaging (both nuclear cardiology and echocardiography) and valvular heart disease. Dr. Jaber attended college at the American University in Beirut, graduating with a Bachelor of Science in biology. He then went on at the American University to receive his medical degree while making the Dean’s honor list. He completed his residency in internal medicine at the St. Luke’s-Roosevelt Hospital Center at Columbia University College of Physicians and Surgeons, where he also completed fellowships in cardiovascular medicine and nuclear cardiology. Dr. Jaber is currently is the Medical Director of the Nuclear Lab and of the Cardiovascular Imaging Core Laboratory in C5Research. He is fluent in English, French and Arabic. He is the author of Nuclear Cardiology review: A Self-Assessment Tool and cofounder of Cardiac Imaging Agora.

Dr. Aldo L Schenone is one of the current Chief Non-Invasive Cardiovascular Imaging Fellows at the Brigham and Women’s Hospital. He completed medical school at the University of Carabobo in Valencia, Venezuela, and then completed both his Internal Medicine residency and Cardiology fellowship at the Cleveland Clinic where he also served as a Chief Internal Medicine Resident.

Dr. Erika Hutt @erikahuttce is a cardiology fellow at the Cleveland Clinic. Erika was born and raised in Costa Rica, where she received her MD degree at Universidad de Costa Rica. She then decided to pursue further medical training in the United States, with the goal of becoming a cardiologist. She completed her residency training at Cleveland Clinic and went on to fellowship at the same institution. Her passions include infiltrative heart disease, atrial fibrillation, valvular heart disease and echocardiography among many. She is looking forward to a career in advanced cardiovascular imaging.

1. Kaski, J.-C., Crea, F., Gersh, B. J., & Camici, P. G. (2018). Reappraisal of Ischemic Heart Disease. Circulation. https://doi.org/10.1161/circulationaha.118.031373
   
2. Jaber, W., & Gimelli, A. (n.d.). Cardiac Imaging Agora. https://www.cardiacimagingagora.com/list/
   
3. Taqueti, V. R., & Di Carli, M. F. (2018). Coronary Microvascular Disease Pathogenic Mechanisms and Therapeutic Options: JACC State-of-the-Art Review. In Journal of the American College of Cardiology. https://doi.org/10.1016/j.jacc.2018.09.042

• Wael Jaber, MD

CardioNerds (Amit Goyal & Carine Hamo) discuss the past, present, and future of Women’s Heart Health & Women in Cardiology with Dr. Nanette Wenger, Professor of Medicine in the Division of Cardiology at the Emory University School of Medicine. Dr. Wenger is a true leader in the field of women’s heart health and a strong proponent for women in cardiology and medicine. Her passion, dedication, and advocacy have inspired countless trainees to carry this torch and continue to build on her truly impactful work. Special introduction by Dr. Martha Gulati. This is a special encore in recognition of the Go Red campaign and celebration of women’s health.

Collect free CME/MOC credit for enjoying this episode! 

The Cardionerds CV prevention series  includes in-depth deep dives on so many prevention topics including the ABCs of prevention, approach to obesity, hypertension, diabetes mellitus and anti-diabetes agents, personalized risk and genetic risk assessments, hyperlipidemia, women’s cardiovascular prevention, coronary calcium scoring and so much more!

CardioNerds Prevention Page
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This episode initially ran as part of the CardioNerds Prevention Series which we produced in collaboration with the American Society for Preventive Cardiology! The ASPC is an incredible resource for learning, networking, and promoting the ideals of cardiovascular prevention!

1. Wenger NK (2005) Women in cardiology: The US experience. Heart.

2. Douglas PS, Rzeszut AK, Noel Bairey Merz C, Duvernoy CS, Lewis SJ, Walsh MN, Gillam L (2018) Career preferences and perceptions of cardiology among us internal medicine trainees factors influencing cardiology career choice. JAMA Cardiol.

3. Wenger NK, Speroff L, Packard B (1993) Cardiovascular Health and Disease in Women. N Engl J Med.

4. Burgess S, Shaw E, Zaman S (2019) Women in Cardiology. Circulation.

Dr. Nanette Wenger is Professor of Medicine in the Division of Cardiology at the Emory University School of Medicine. Dr. Wenger received her medical degree from Harvard Medical School in 1954 as one of their first female graduates followed by training at Mount Sinai Hospital where she was the first female to be chief resident in the cardiology department. She is among the first physicians to focus on heart disease in women with an expertise in cardiac rehabilitation and geriatric medicine.

Dr. Wenger has received numerous awards including the Distinguished Achievement Award from the Scientific Councils of the American Heart Association and its Women in Cardiology Mentoring Award, the James D. Bruce Memorial Award of the American College of Physicians for distinguished contributions in preventive medicine, the Gold Heart Award, the highest award of the American Heart Association, a Lifetime Achievement Award in 2009 and the Inaugural Bernadine Healy Leadership in Women’s CV Disease Distinguished Award, American College of Cardiology. She chaired the U.S. National Heart, Lung, and Blood Institute Conference on Cardiovascular Health and Disease in Women, is a Past President of the Society of Geriatric Cardiology and is past Chair, Board of Directors of the Society for Women’s Health Research. Dr. Wenger serves on the editorial boards of numerous professional journals and is a sought-after lecturer for issues related to heart disease in women, heart disease in the elderly, cardiac rehabilitation, coronary prevention, and contemporary cardiac care. She is listed in Best Doctors in America.

• Carine Hamo, MD
• Amit Goyal, MD

CardioNerd Amit Goyal is joined by Dr. Erika Hutt (Cleveland Clinic general cardiology fellow), Dr. Aldo Schenone (Brigham and Women’s advanced cardiovascular imaging fellow), and Dr. Wael Jaber (Cleveland Clinic cardiovascular imaging staff and co-founder of Cardiac Imaging Agora) to discuss nuclear and complimentary multimodality cardiovascular imaging for the evaluation of coronary ischemia. Show notes were created by Dr. Hussain Khalid (University of Florida general cardiology fellow and CardioNerds Academy fellow in House Thomas). To learn more about multimodality cardiovascular imaging, check out Cardiac Imaging Agora! 

Collect free CME/MOC credit for enjoying this episode! 

CardioNerds Multimodality Cardiovascular Imaging Page
CardioNerds Episode Page
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Five Take Home Pearls

1. We can broadly differentiate non-invasive testing into two different categories—functional and anatomical. Functional tests allow us to delineate the functional consequence of coronary disease rather than directly characterizing the burden of disease. Anatomical tests such as coronary CTA, on the other hand, allow us to directly visualize obstructive epicardial disease.

2. In general PET imaging provides higher quality images than SPECT imaging for a variety of reasons, including a higher “keV” of energy in PET radiotracers

3. If using a SPECT camera, we should use cameras that have attenuation correction. Without attenuation correction, the specificity of a SPECT camera drops to 50-60%.

4. In evaluating ischemic heart disease, cardiac nuclear imaging can provide a wide range of information including myocardial perfusion (rest and stress), ejection fraction assessment (rest and stress), absolute myocardial blood flow with quantitative flow reserve in all coronary territories (PET), assessment of myocardial viability (PET), and calcium score with CT attenuation correction.

5. To select the best non-invasive test, we should consider a variety of factors such as pretest probability of obstructive epicardial disease, patient-specific factors (e.g., ability to exercise) and whether a functional or an anatomical test will provide the best answer for our clinical question.

Detailed Show Notes

1. What are the basic non-invasive testing categories for evaluation of coronary artery disease?  
   • We have a variety of different non-invasive testing modalities that can be broadly separated into functional tests and anatomical tests.  
     • The basic principle underlying functional stress testing is to induce ischemia or coronary vasodilation (discussed below), followed by a functional assessment by different techniques (e.g., EKG, echocardiography, radionuclide imaging) to detect flow-limiting obstructive coronary artery disease. These tests delineate the functional consequence of the coronary disease, rather than directly characterizing the burden of disease itself.  
     • Functional tests can also allow us to assess the nature of a patient’s symptoms. For example, by having a patient exercise on a treadmill we can evaluate whether we can reproduce a patient’s chest pain syndrome. 
     • Anatomical tests allow us to visualize the presence of obstructive epicardial disease. For example, obtaining a Coronary Computed Tomography Angiography (CCTA) for a patient with chest pain would allow you to directly visualize possible obstructive epicardial disease.  

1. How do we induce ischemia for functional stress testing?  
   • To induce ischemia (and/or coronary vasodilation), we have many different stressors that can be broadly separated into exercise stressors and pharmacologic stressors. 
     • Treadmill exercise via standardized protocols is the most common method for inducing ischemia and has the advantage of assessing functional capacity, which has prognostic information. Supine bicycle is another common exercise modality that is utilized. 
     • There are also several pharmacologic stressors that vary in their mechanisms of action. Dobutamine is a synthetic catecholamine that stimulates myocardial beta-1 and beta-2 receptors to increase heart rate, contractility, and consequently myocardial oxygen demand with a small decrease in systemic vascular resistance.   
     • Adenosine and adenosine derivatives (e.g. regadenoson) induce coronary vasodilation and take advantage of differences in coronary flow reserve. With obstructive coronary lesions, the vessels distal to the obstruction are already dilated at baseline and have little flow reserve. Adenosine (and its derivatives) induce vasodilation and increase flow in normal coronary beds, but much less so in areas supplied by an obstructive lesion. Consequently, we can see disparate radiotracer uptake that correlates with different coronary territories.  
   • Once we’ve induced ischemia, we can assess it via electrocardiogram (EKG) alone or in conjunction with an imaging modality such as echocardiography, MRI, or nuclear imaging — such as Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET).   

1. What is the difference between SPECT and PET imaging quality? What are the advantages of using PET imaging? 
   • SPECT and PET imaging both use gamma cameras that detect gamma rays produced by the injected radionuclide tracer. SPECT utilizes a single-crystal camera to acquire multiple 2D images to be reconstructed into a 3D image, while PET imaging utilizes a multi-crystal camera which can detect more counts (e.g., quantification of radioactivity).  
   • SPECT studies usually use Technetium-based tracers which have nuclei that emit 140 keV of energy. PET studies usually use Rubidium or Ammonia which have nuclei that emit around 510 keV of energy. Either of these studies can also use Thallium which have nuclei that emit 68 keV of energy. In general, the higher the “keV”, the better the image quality. So, using thallium may result in poorer quality images and is not recommended as a first-line agent.  
     • Rubidium has a half-life of 76 seconds and Ammonia has a half-life of 10 minutes—so it is possible to do an exercise stress test if using Ammonia but not with using Rubidium! 
     • Because the radiotracers used for PET imaging have higher “keV” than those used in SPECT imaging, PET image quality is generally better with a higher resolution. 
   • If using a SPECT camera, you should use a camera that has attenuation correction. Attenuation artifact can occur when you have tissue such as breast or diaphragm that overlies the myocardium and decreases the intensity/strength of signal prior to reaching the myocardium. This can result in the false appearance of a myocardial perfusion defect in that region. Without attenuation correction, the specificity of a SPECT camera drops to 50-60%.  
   • In addition to improved spatial resolution and higher quality images resulting from using radiotracers with higher “keV”, PET cameras also do not require physical collimation. This allows for even further increase in spatial resolution and image quality.  
     • A collimator is a piece of lead with holes that absorb and stop most photons except for those that arrive almost perpendicular to the detector face. This allows the camera to accurately localize the radiotracer in the patient’s body over the organ of interest. Overall, PET has better sensitivity, specificity, and better accuracy to diagnose 50% and 70% lesions than SPECT!  
     • However, maintaining PET scanners comes at increased cost compared to SPECT. 

1. What diagnostic information can cardiac nuclear imaging provide us? What are some unique uses of nuclear imaging? 
   • In the evaluation of coronary disease, some diagnostic information provided by SPECT and PET imaging include: 
     • Assessment of myocardial perfusion and blood flow at both rest and stress 
     • Ejection fraction assessment at both rest and stress 
     • Quantitative flow reserve in all coronary territories (PET) 
     • Assessment of myocardial viability (PET) 
     • Prognostication 
     • Calcium Score with CT Attenuation Correction 
       • If using CT for attenuation correction, you should also use it for calcium score. A high coronary calcium score can change management—there is also data that shows that just showing patients the plaque on CT imaging can improve outcomes!  
   • There are many uses of nuclear imaging, and novel uses are continuously being described. In addition to its use in noninvasive stress testing and ischemic heart disease, we can also use it to assess etiology of cardiomyopathies:  
     • In patients with suspected cardiac sarcoidosis, fluorodeoxgylocse(FDG)-PET imaging with Rubidium can be utilized to detect sarcoid and prognosticate. Enjoy the upcoming discussion about sarcoidosis imaging as well as the CNCR from the University of Chicago!  
       • Nuclear scintigraphy with 99m-Technetium pyrophosphate can be used to assess for cardiac amyloidosis. Stay tuned for more on this as part of the amyloidosis imaging discussion.  
     • FDG PET and whole-body-white blood cell scan can be used to help evaluate for prosthetic valve endocarditis or LVAD-associated infections, which we will also discuss later in this imaging series! 
     • FDG-PET can help evaluate and differentiate aortopathies in patients presenting with chest pain 
   • Many novel uses of nuclear stress testing are being described for patients admitted to the cardiac intensive care unit (CICU).  
     • CT imaging and MRI require significant patient cooperation. MRI additionally is sometimes limited by patient compatibility issues. A full PET study can be done in 20-25 minutes, however, independent of renal and hepatic function.  
     • In patients admitted to the CICU with an intra-aortic balloon pump (IABP), exercise can be simulated by reducing the IABP support ratio from 1:1 to 1:3. A PET stress test can then be conducted using this “exercise” to evaluate for myocardial ischemia. 

1. How do you select the best non-invasive test? 
   • A variety of factors play a role in this decision. To begin, you can start with the picking whether a functional test or an anatomical test is best to answer your clinical question. 
     • Are you trying to identify the nature of a patient’s symptoms for a possible underlying cardiac etiology? Perhaps a functional test is best.  
     • Are you trying to rule out obstructive epicardial disease? Perhaps an anatomical test is best.  
     • In many instances functional and anatomical tests provide complimentary information. And if the patient has had multiple prior non-invasive testing of the same modality with equivocal answers to the clinical question, it may be more helpful to switch to a different modality. 
   • Many imaging and individual patient factors affect the selection for the best non-invasive test. For instance: 
     • Patient factors/comorbidities such as kidney disease, liver disease, devices, metallic implants, ability to exercise, baseline abnormal ECG or TTE, and patient cooperation issues affect the selection for the best non-invasive test. 
     • Cost-effectiveness of the study and radiation exposure should be a consideration. 
     • If the patient has a low pretest probability of obstructive CAD, perhaps testing is not needed, or you could consider an anatomical test such as a Coronary CTA 
     • If the patient has a low-intermediate pretest probability of obstructive CAD, one could consider obtaining CCTA anatomical testing in addition to an exercise tolerance test (ETT) with or without imaging as this has been shown to provide higher diagnostic ability and affects management. Rather than have premature closure when obstructive epicardial disease is ruled out, we can assess for nonobstructive plaque that warrants initiation of aggressive lifestyle and risk factor modifications. 
     • If the patient has a significant cardiovascular disease history (e.g. multiple prior stents or bypass surgery) but lower suspicion of symptomatic coronary ischemia, perhaps functional testing such as stress MRI, nuclear stress test, or stress echocardiogram is preferred. 
     • If the patient has a high pretest probability of obstructive epicardial disease, perhaps it is best to skip a non-invasive test and proceed straight to an invasive test. 
     • Do note that patients with angina who do not have obstructive epicardial stenoses on anatomical testing may have coronary microvascular disease which is still important to diagnose given important therapeutic and prognostic implications. More on this in the next episode!  
   • Below is a depiction of the how effective the different non-invasive modalities are to rule in or rule out significant coronary artery disease in stable CAD patients. It is based on follow-up invasive coronary angiography or FFR assessment, stratified by pretest probability. Notably, stress ECG requires a relatively lower pretest probability to rule out obstructive CAD and relatively higher pretest probability to rule in CAD. CCTA does not perform as well as functional imaging techniques in ability to rule-in and rule out FFR-significant CAD when comparing it to its ability to rule in and rule out significant CAD by invasive coronary angiography. 

Wael Jaber, MD, is a staff cardiologist in the Section of Cardiovascular Imaging, Robert and Suzanne Tomsich Department of Cardiovascular Medicine, at the Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at Cleveland Clinic. Dr. Jaber specializes in cardiac imaging (both nuclear cardiology and echocardiography) and valvular heart disease. Dr. Jaber attended college at the American University in Beirut, graduating with a Bachelor of Science in biology. He then went on at the American University to receive his medical degree while making the Dean’s honor list. He completed his residency in internal medicine at the St. Luke’s-Roosevelt Hospital Center at Columbia University College of Physicians and Surgeons, where he also completed fellowships in cardiovascular medicine and nuclear cardiology. Dr. Jaber is currently is the Medical Director of the Nuclear Lab and of the Cardiovascular Imaging Core Laboratory in C5Research. He is fluent in English, French and Arabic. He is the author of Nuclear Cardiology review: A Self-Assessment Tool and cofounder of Cardiac Imaging Agora.

Dr. Aldo L Schenone is one of the current Chief Non-Invasive Cardiovascular Imaging Fellows at the Brigham and Women’s Hospital. He completed medical school at the University of Carabobo in Valencia, Venezuela, and then completed both his Internal Medicine residency and Cardiology fellowship at the Cleveland Clinic where he also served as a Chief Internal Medicine Resident.

Dr. Erika Hutt @erikahuttce is a cardiology fellow at the Cleveland Clinic. Erika was born and raised in Costa Rica, where she received her MD degree at Universidad de Costa Rica. She then decided to pursue further medical training in the United States, with the goal of becoming a cardiologist. She completed her residency training at Cleveland Clinic and went on to fellowship at the same institution. Her passions include infiltrative heart disease, atrial fibrillation, valvular heart disease and echocardiography among many. She is looking forward to a career in advanced cardiovascular imaging.

1. Pitman AG, Kalff V, Van Every B, Risa B, Barnden LR, Kelly MJ. Contributions of subdiaphragmatic activity, attenuation, and diaphragmatic motion to inferior wall artifact in attenuation-corrected Tc-99m myocardial perfusion SPECT. J Nucl Cardiol. 2005;12:401–9. 

1. Heller GV, Bateman TM, Johnson LL, Cullom SJ, Case JA, Galt JR, et al. Clinical value of attenuation correction in stress-only Tc-99m sestamibi SPECT imaging. J Nucl Cardiol. 2004;11:273–81. 

1. Maddahi J, Packard RR. Cardiac PET perfusion tracers: current status and future directions. Semin Nucl Med. 2014;44(5):333-343. doi:10.1053/j.semnuclmed.2014.06.011 

1. van Dalen JA, Visser EP, Vogel WV, Corstens FH, Oyen WJ. Impact of Ge-68/Ga-68-based versus CT-based attenuation correction on PET. Med Phys. 2007 Mar;34(3):889-97. doi: 10.1118/1.2437283. 

1. Parker MW, Iskandar A, Limone B, Perugini A, Kim H, Jones C, Calamari B, Coleman CI, Heller GV. Diagnostic accuracy of cardiac positron emission tomography versus single photon emission computed tomography for coronary artery disease: a bivariate meta-analysis. Circ Cardiovasc Imaging. 2012 Nov;5(6):700-7. doi: 10.1161/CIRCIMAGING.112.978270. Epub 2012 Oct 10.  

1. Mettler FA, Guiberteau MJ. Essentials of nuclear medicine imaging. 6th ed. Philadelphia, PA: Elsevier/Saunders; 2012. 

1. SCOT-HEART Investigators, Newby DE, Adamson PD, Berry C, Boon NA, Dweck MR, Flather M, Forbes J, Hunter A, Lewis S, MacLean S, Mills NL, Norrie J, Roditi G, Shah ASV, Timmis AD, van Beek EJR, Williams MC. Coronary CT Angiography and 5-Year Risk of Myocardial Infarction. N Engl J Med. 2018 Sep 6;379(10):924-933. doi: 10.1056/NEJMoa1805971. Epub 2018 Aug 25. 

1. Juhani Knuuti, Haitham Ballo, Luis Eduardo Juarez-Orozco, Antti Saraste, Philippe Kolh, Anne Wilhelmina Saskia Rutjes, Peter Jüni, Stephan Windecker, Jeroen J Bax, William Wijns, The performance of non-invasive tests to rule-in and rule-out significant coronary artery stenosis in patients with stable angina: a meta-analysis focused on post-test disease probability, European Heart Journal, Volume 39, Issue 35, 14 September 2018, Pages 3322–3330, https://doi.org/10.1093/eurheartj/ehy267 

1. Jaber W, Gimelli A. Cardiac Imaging Agora. https://www.cardiacimagingagora.com/list 

• Wael Jaber, MD

CardioNerds (Carine Hamo, Amit Goyal and Daniel Ambinder) discuss personalized risk assessment for cardiovascular prevention with Dr. Amit Khera, the immediate past president for the American Society for Preventive Cardiology and Director of the Preventive Cardiology and Professor of Medicine at the University of Texas, Southwestern Medical School in Dallas, Texas. They dive into an illuminating discussion about traditional and next generation personalization of risk assessment which covers the need for personalization, traditional risk stratification, applying risk enhancing factors for decision making, biomarkers, familial hypercholesterolemia, and the use of -Omics. This episode is the 13th and final part of our in-depth prevention series produced in collaboration with the American Society for Preventive Cardiology!

Stay tuned for a bonus segment at the end of the episodeas we talk to Dr. Ankur Kalra, interventionist at the Cleveland Clinic, Podcast host of Parallax by Ankur Kalra, and founder of the non-profit startup, makeadent.org for a discussion about the CHAI (Cardiovascular Health in Asian Indians) Collaborative, an initiative that aims to identify genetic markers of heightened atherosclerosis in South Asians.

CardioNerds Cardiovascular Prevention Page
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Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Coming soon!

The Cardionerds CV prevention series  includes in-depth deep dives on so many prevention topics including the ABCs of prevention, approach to obesity, hypertension, diabetes mellitus and anti-diabetes agents, personalized risk and genetic risk assessments, hyperlipidemia, women’s cardiovascular prevention, coronary calcium scoring and so much more!

We are truly honored to be producing the Cardionerds CVD Prevention Series in collaboration with the American Society for Preventive Cardiology! The ASPC is an incredible resource for learning, networking, and promoting the ideals of cardiovascular prevention! This series is kicked off by a message from Dr. Amit Khera, President of the American Society for Preventive Cardiology and President of the SouthWest Affiliate of the American Heart Association.

Amit Khera, MD, MSc, FACC, FAHA, FASPC

Dr. Amit Khera is Professor of Medicine at the University of Texas, Southwestern Medical School in Dallas, Texas where he serves as Director of the Preventive Cardiology, and holder of the Dallas Heart Ball Chair in Hypertension and Heart Disease.  He is also currently President of the American Society for Preventive Cardiology and President of the SouthWest Affiliate of the American Heart Association. His clinical and research interests include the primary and secondary prevention of coronary artery disease, focusing on risk assessment and risk factor modification in those with premature and familial disease.

Dr. Khera received his undergraduate degree in American History from the University of Pennsylvania, with magna cum laude honors. He obtained his medical degree from Baylor College of Medicine where he served as class president and was inducted into the Alpha Omega Alpha honor medical society. He completed an Internal Medicine Residency at Brigham and Women’s Hospital, Harvard Medical School, followed by a Cardiology Fellowship at the University of Texas, Southwestern Medical Center. He also completed his Masters degree in Epidemiology at the Harvard School of Public Health.

He has published over 150 publications in the field of preventive cardiology and has served on numerous local and national committee and leadership roles for the American Heart Association, American College of Cardiology, and American Society for Preventive Cardiology.  He is currently Digital Strategies Editor and an Associate Editor for the journal Circulation.  Dr. Khera has been named Best Doctor in Dallas and Texas SuperDoctor every year since 2014 and was previously the Program Director for the Cardiology Fellowship at UT Southwestern from 2011-2019. 

Coming soon!

• Amit Khera, M.D.
• Carine Hamo, MD
• Amit Goyal, MD
• Daniel Ambinder, MD