Episodes Archives - Cardionerds

Aloha! CardioNerds (Amit Goyal & Karan Desai)  join University of Hawaii cardiology fellows (Isaac Mizrahi, Nath Limpruttidham, Nishant Trivedi, and Shana Greif) for some shaved iced on the Big Island’s north shore! They discuss a fascinating case of a patient presenting with decompensated heart failure found to have a giant coronary aneurysm. Program director Dr. Dipanjan Banerjee provides the E-CPR as well as a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Tommy Das with mentorship from University of Maryland cardiology fellow Karan Desai.  

Jump to: Patient summary – Case media – Case teaching – References

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A man in his early 60s with history of hypertension, peripheral arterial disease, atrial fibrillation, and AAA s/p repair presented with subacute fatigue, palpitations, shortness of breath, and lower extremity edema. On exam he was warm and well perfused, though hypotensive, tachycardic with an irregular rhythm, and had an elevated JVP. ECG showed AF with RVR without evidence of acute MI, and troponin was negative. TTE revealed a reduced LVEF and WMA in the inferolateral walls with akinesis of the basal mid septum; additionally, two large extracardiac structures were noted, one with heterogenous echotexture in the AV groove, and a second with an echolucent interior adjacent to the RA.

The patient underwent coronary angiography, showing a dilated and calcified proximal LAD with high grade stenosis adjacent to the first septal perforator, a ectatic LCX that supplied left to right collaterals, and a giant RCA aneurysm with TIMI 0 flow distally. CCTA confirmed these findings, showing thrombosed aneurysms of the LAD, LCX, and RCA. Interventional cardiology and cardiac surgery both evaluated the patient’s case, and determined that he was not a candidate for intervention. He was ultimately diuresed to euvolemia with significant improvement in symptoms, and plans to follow-up as an outpatient for heart transplant evaluation.

• A
• B
• C
• D

A. CXR
B. ECG: atrial fibrillation with RVR, left axis deviation, poor r wave progression
C. Wide complex tachycardia
D. CT chest demonstrating giant aneurysm

1) This case featured a patient with a giant coronary aneurysm – how are coronary artery aneurysms defined and classified?  

• Coronary artery aneurysms (CAA) are defined as a focal dilation of a coronary segment at least 1.5x the adjacent normal segment. Contrast this with coronary artery ectasia, which refers to a diffuse, as opposed to focal, coronary dilation.  
• CAA morphology can be classified as either saccular (transverse > longitudinal diameter) or fusiform (transverse < longitudinal diameter). 
• Giant CAA’s are >20mm in diameter. 
• Aortocoronary saphenous vein graft aneurysms have distinct characteristics and natural history compared to native coronary aneurysms. These aneurysms tend to present late (e.g., > 10 years following CABG) and tend to be larger than native CAA. 
• IVUS can help differentiate between a true aneurysm with preserved integrity of all 3 vessel layers (intima, media, and adventitia) and a pseudoaneurysm with loss of wall integrity and damage to the adventitia. 

2) Now that we have the language to define and classify coronary artery aneurysms, what are some causes these lesions?  

• Atherosclerosis: lipid deposition, focal calcification, and fibrosis can weaken the vessel wall and predispose to subsequent coronary artery dilation. Up to 50% of CAAs are linked to arteriosclerosis.  
• Autoimmune/inflammatory processes: Lupus and systemic vasculitis, such as Kawasaki’s disease and Takayasu arteritis, can all lead to CAAs. Vasculitic CAAs usually affect more than one artery.  
• Connective Tissue Disease: Marfan’s syndrome and Ehlers-Danlos disease, for instance, are characterized by deficiencies in vessel wall integrity, leading to CAAs. 
• Dynamic Wall Stress: Episodic hypertension and vasoconstriction, such as that seen in frequent cocaine use, can lead to wall stress, endothelial damage, and coronary artery aneurysms.  
• Direct Vessel Wall Injury: Intracoronary interventions, such as angioplasty, stent delivery, and brachytherapy, can cause shear wall stress that leads to CAAs.  
• Infectious Causes: Direct vessel wall invasion or immune complex deposition can be seen in bacterial, mycobacterial, fungal, and syphilitic infections. Septic emboli from infectious endocarditis can also lead to mycotic coronary aneurysms.  
• Genetic susceptibility: Certain HLA class II genotypes are susceptible to CAAs. This may be the underlying pathology in certain idiopathic and congenital CAAs.  

3) How do coronary artery aneurysms clinically present? 

• Most CAAs are asymptomatic, and are found incidentally on coronary angiography or CCTA.  
• Concomitant obstructive arteriosclerosis can cause angina or plaque rupture, and thrombosis in the aneurysm lumen can lead to distal embolization and myocardial infarction.  
• Massive enlargement of CAAs and saphenous vein graft aneurysms can compress adjacent structures. 
• CAA rupture is rare, though can cause cardiac tamponade.  
• Stress-induced myocardial ischemia can also occur due to microvascular dysfunction  

4) How do we diagnosis and assess CAAs? 

• Most CAAs are evaluated via coronary angiography, though a complete angiographic evaluation can be complicated by delayed antegrade contrast filling, segmental back flow, and contrast stasis. In giant aneurysms, a forceful and prolonged contrast injection is needed to avoid misinterpreting slow aneurysmal filling as thrombosis.  
• IVUS can help differentiate between true aneurysms, pseudoaneurysms, and coronary segments with aneurysmal appearance due to plaque rupture or stenosis. Furthermore, IVUS can assist in sizing aneurysm and planning for potential PCI.  
• Coronary CTA noninvasively allows for a more accurate assessment of aneurysm size and degree of thrombus than angiography. CCTA is particularly useful in patients with giant CAA as it can provide an understanding of mechanical complications of these aneurysms.  

5) How are coronary artery aneurysms managed?  

• Notably, there is a lack of randomized and large-scale trial data to guide the treatment of CAAs; most recommendations are made on the basis of small case series and expert opinion.  
• Medical Management: Given the association between CAA and arteriosclerosis, risk factor modification should be emphasized. The role of antiplatelet and anticoagulant agents is an area of ongoing debate, though there may be benefit in patients with multivessel ectasia. Furthermore, the context in which the patient presents (e.g., incidental finding vs. acute coronary syndrome) will guide the antiplatelet and/or anticoagulant strategy.  
• Invasive (Percutaneous) Management: PCI of an aneurysmal vessel in the setting of acute MI is associated with lower rates of procedural success, and higher rates of distal embolization and no-reflow phenomenon. Additionally, these patients have higher rates of stent thrombosis and mortality. Given the higher thrombus burden in aneurysmal arteries, thrombectomy may be helpful in aiding PCI. Some case studies have additionally utilized intracoronary thrombolytics. Another strategy is a stent-assisted coil embolization technique in cases where covered stent placement is not possible due to tortuosity, calcification, or risk of side branch compromise. To date, there haven’t been covered stents specifically designed for CAAs, but stents have been used off-label. 
• Surgical Management: The most common operative strategy is to open the aneurysm, suture the afferent and efferent vessels, and finish with bypass grafting if possible. Other operative strategies include aneurysm ligation, resection, or marsupialization with interposition graft.

References

1. Thibodeau, J. T., & Drazner, M. H. (2018). The Role of the Clinical Examination in Patients With Heart Failure. JACC. Heart failure, 6(7), 543–551.  
2. Abou Sherif, S., Ozden Tok, O., Taşköylü, Ö., et al. (2017). Coronary Artery Aneurysms: A Review of the Epidemiology, Pathophysiology, Diagnosis, and Treatment. Frontiers in cardiovascular medicine, 4, 24. 
3. Kawsara, A., Núñez Gil, I. J., Alqahtani, F., et al. (2018). Management of Coronary Artery Aneurysms. JACC. Cardiovascular interventions, 11(13), 1211–1223.  
4. Newburger, J. W., Takahashi, M., & Burns, J. C. (2016). Kawasaki Disease. Journal of the American College of Cardiology, 67(14), 1738–1749.  
5. McCrindle, B. W., Rowley, A. H., Newburger, J. W., et al. (2017). Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation, 135(17), e927–e999.  

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.

• 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

CardioNerds (Amit Goyal & Daniel Ambinder) join Georgetown University/Washington Hospital Center cardiology fellows (Nitin Malik, AJ Grant, and Tsion Aberra) for some fresh Maryland blue crab cakes at the Georgetown waterfront in Washington, DC. They discuss a rare case of histoplasmosis pericarditis complicated by cardiac tamponade. Dr. Patrick Bering provides the E-CPR and program director Dr. Gaby Weissman provides a message for applicants. Johns Hopkins internal medicine resident Colin Blumenthal with mentorship from University of Maryland cardiology fellow Karan Desai.  

Jump to: Patient summary – Case media – Case teaching – References

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.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Subscribe to our newsletter- The Heartbeat
Support our educational mission by becoming a Patron!
Cardiology Programs Twitter Group created by Dr. Nosheen Reza

A woman in her early 30s with a history of Crohn’s disease on TNF-inhibitor therapy and chronic prednisone presented to the ED after two months of abdominal pain and fevers. She was found to have a perforated bowel and taken to emergent surgery and eventually found to have disseminated histoplasmosis. Post-surgery, her hypotension worsened. At this point, the Georgetown University Cardionerds were involved. Listen to the podcast now to learn about histoplasmosis, it’s cardiac involvement, and management of acute effusive pericarditis!

• A
• B
• C
• D
• E

A. Left: Admission chest x-ray (PA film), which was overall unremarkable. Right: Chest x-ray from hospital day 12 – which revealed pulmonary edema with bilateral perihilar haziness, increased prominence of pulmonary vascularity, and small-moderate bilateral pleural effusions. Note increased size of cardiac silhouette. At the corresponding time, pericardial effusion (without tamponade) had been diagnosed.
B. EKG: Sinus tachycardia and low-voltage QRS complexes.
C. CT abdomen/pelvis on hospital day 14. Free air noted within the abdomen (left). Moderate pericardial effusion also incidentally appreciated (right).
D. Pulse-Wave Doppler of mitral inflow. Flow variation is present, but variation is less than <30%.
E. (A) Small bowel resection showing focal mucosal ulceration, serositis, and formation of a granuloma. (B) Transmural inflammation seen on small bowel resection. (C) Pathology of ileocecectomy showing focal histoplasmosis characterized by intracytoplasmic yeast-like forms (black circles)

1. How does one diagnose acute pericarditis? What are the most common etiologies?
   1. Based on the 2015 ESC guidelines on pericardial disease, acute pericarditis is diagnosed when at least two of the following four criteria are present:
      1. Chest pain characteristic of pericarditis
         1. Acute onset, improves with leaning forward, pleuritic
      2. Pericardial rub
      3. EKG changes consistent with pericarditis
         1. PR depressions, ST segment elevation though depending on time course these can normalize or become T wave inversions
      4. New or worsening pericardial effusion
   2. Etiology can vary by geography. In most developed countries, viruses are thought to be the most common cause, though even when a viral cause is suspected, the majority of cases end up being idiopathic. Other etiologies include bacterial (TB is the most common cause of pericarditis in developing countries), autoimmune, hypothyroidism, malignancy, radiotherapy-induced, and immune checkpoint inhibitor-associated pericarditis.
2. How does one medically manage acute pericarditis? What are the possible treatment strategies? What about recurrent pericarditis?
   1. High dose NSAIDs are typically used as first line treatment in acute pericarditis, though kidney disease and GIB are common comorbidities that can complicate their use. In patient with risk factors for GIB (e.g. age >65, history of PUD) a PPI should be added for gastrointestinal protection. In patients with concomitant CAD, aspirin is often preferred. NSAIDs are often used for 1-2 weeks until symptoms resolve and/or CRP normalizes, after which they should be tapered off. Multiple RCTs, including the COPE and ICAP trials, support the addition of colchicine to NSAIDs to reduce symptoms and recurrence. Colchicine is typically given for 3 months after an acute episode.
   2. Corticosteroids can also be used as 2nd or 3rd line treatment for acute pericarditis, but they have been associated with longer course of disease and higher recurrence rates in meta-analyses. To reduce this risk, low dose steroids are preferred (i.e. prednisone 0.2-0.5 mg/kg/day) and they should be slowly tapered after symptoms resolve and CRP normalizes with close CRP monitoring to detect recurrence. Steroids can be beneficial as first line therapy in cases of autoimmune or immune checkpoint inhibitor-associated pericarditis.
   3. In patients with a lack of response to initial therapy with NSAIDs + colchicine, further workup might be required as these treatments are most effective in viral or idiopathic pericarditis. Treatment failure could indicate the presence of bacterial or malignant pericarditis, which often do not respond to the typical anti-inflammatories.
   4. In patients with recurrence of symptoms after resolution, multiple clinical trials, including the CORE and CORP trials, support the use of colchicine for recurrent pericarditis. Low dose steroids as described above are also often used in patients who had recurrence with first line therapy.
   5. Immunologic therapies like anakinra, an IL-1 antagonist, have shown benefit in RCTs even in patients who are resistant to colchicine and steroid dependent. In the recently published phase III RHAPSODY trial, rilonacept (an IL-1alpha and IL-1beta cytokine trap) led to resolution of recurrent pericarditis compared to placebo.
3. How should pericardial effusions be managed in the setting of acute pericarditis? When should you consider draining a pericardial effusion?
   1. When a pericardial effusion is detected, the first step should be determining the size and hemodynamic significance with physical exam and echocardiography. For more on the relevant physical exam and echo findings, please see the show notes for Episode 72 on effusive-constrictive pericarditis! Hemodynamically significant effusions require urgent consultation for drainage. In this situation, pericardial drainage catheters should be left in place until drainage ceases, which improves apposition of the pericardial layers and reduces recurrence.
   1. Pericardiocentesis for diagnostic purposes is not routinely recommended. Patients who are resistant to initial treatment, or in whom a bacterial or neoplastic cause is suspected, should undergo pericardiocentesis with diagnostic studies to identify the underlying etiology.
4. What is histoplasmosis? How does it usually present? What is the difference between histoplasmosis and disseminated histoplasmosis? How common in pericardial involvement?
   1. Histoplasma capsulatum is a dimorphic fungus and the most prevalent endemic mycosis in the US. Endemic to the Ohio and Mississippi River valleys, it is inhaled into the lungs as a mold where it will become a yeast in tissues at 37 degrees C. Once it the lungs it is consumed by macrophages leading to lymphatic and eventually hematogenous spread. Even with systemic spread, most cases are asymptomatic, but approximately 1 in 2000 cases can result in a severe infection. Most cases of severe infection occur in those with high-inoculum exposure, the elderly, or severely immunocompromised as T-cells and TNF play a vital role in host immune response.
   2. When symptoms do arise, they are usually mild, self limited, and resolve without treatment. The most common symptoms are fever, chills, myalgias, cough, pleuritic chest pain, and headache.
   3. Even among severe infections, isolated pulmonary manifestations are most common. When infection spreads to other organ systems outside of the lungs it is labeled disseminated histoplasmosis.
   4. Pericarditis associated with histoplasmosis is uncommon and occurs in around 5-10% of cases. It is most common in pulmonary histoplasmosis and is thought to be primarily an inflammatory response to the pulmonary disease rather than an invasion of the infection in to the pericardium.
5. How is disseminated histoplasmosis treated? How does this differ from pulmonary histoplasmosis?
   1. Histoplasmosis can affect a wide range of organ systems including skin, GI tract, brain, bone marrow, and lungs. Most patients with isolated pulmonary symptoms or even disseminated histoplasmosis have minimal symptoms and the infection is self-limited and doesn’t require treatment.
   2. Patients with mild to moderate symptoms, either acute pulmonary histoplasmosis that does not resolve or mild to moderate disseminated histoplasmosis, can be treated with azole therapy (e.g., itraconazole). Liposomal amphotericin B is required for patients with severe symptoms regardless of location. After improvement in clinical status, patients can be transitioned to azole therapy to complete 12 months of treatment, though some patients with chronic disease require 18-24 months of therapy.
   3. Pearl: The differential for hyperferritinemia (greater than 10,000) should include disseminated histoplasmosis.

1. Adler, Y., Charron, P., Imazio, M., Badano, L., Barón-Esquivias, G., Bogaert, J., Brucato, A., Gueret, P., Klingel, K., Lionis, C., Maisch, B., Mayosi, B., Pavie, A., Ristić, A. D., Sabaté Tenas, M., Seferovic, P., Swedberg, K., Tomkowski, W., ESC Scientific Document Group, … Nesukay, E. (2015). 2015 ESC Guidelines for the diagnosis and management of pericardial diseases. European Heart Journal, 36(42), 2921–2964. https://doi.org/10.1093/eurheartj/ehv318
2. Assi, M. A., Sandid, M. S., Baddour, L. M., Roberts, G. D., & Walker, R. C. (2007). Systemic Histoplasmosis: A 15-Year Retrospective Institutional Review of 111 Patients. Medicine, 86(3), 162–169. https://doi.org/10.1097/md.0b013e3180679130
3. Brucato, A., Imazio, M., Gattorno, M., Lazaros, G., Maestroni, S., Carraro, M., Finetti, M., Cumetti, D., Carobbio, A., Ruperto, N., Marcolongo, R., Lorini, M., Rimini, A., Valenti, A., Erre, G. L., Sormani, M. P., Belli, R., Gaita, F., & Martini, A. (2016). Effect of Anakinra on Recurrent Pericarditis Among Patients With Colchicine Resistance and Corticosteroid Dependence: The AIRTRIP Randomized Clinical Trial. JAMA, 316(18), 1906. https://doi.org/10.1001/jama.2016.15826
4. Chiabrando Juan Guido, Bonaventura Aldo, Vecchié Alessandra, Wohlford George F., Mauro Adolfo G., Jordan Jennifer H., Grizzard John D., Montecucco Fabrizio, Berrocal Daniel Horacio, Brucato Antonio, Imazio Massimo, & Abbate Antonio. (2020). Management of Acute and Recurrent Pericarditis. Journal of the American College of Cardiology, 75(1), 76–92. https://doi.org/10.1016/j.jacc.2019.11.021
5. Klein AL, Imazio M, Cremer P, Brucato A, Abbate A, Fang F, Insalaco A, LeWinter M, Lewis BS, Lin D, Luis SA, Nicholls SJ, Pano A, Wheeler A, Paolini JF; RHAPSODY Investigators. Phase 3 Trial of Interleukin-1 Trap Rilonacept in Recurrent Pericarditis. N Engl J Med. 2021 Jan 7;384(1):31-41. doi:10.1056/NEJMoa2027892.
6. Imazio, M., & Adler, Y. (2013). Management of pericardial effusion. European Heart Journal, 34(16), 1186–1197. https://doi.org/10.1093/eurheartj/ehs372
7. Imazio, M., Belli, R., Brucato, A., Cemin, R., Ferrua, S., Beqaraj, F., Demarie, D., Ferro, S., Forno, D., Maestroni, S., Cumetti, D., Varbella, F., Trinchero, R., Spodick, D. H., & Adler, Y. (2014). Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): A multicentre, double-blind, placebo-controlled, randomised trial. The Lancet, 383(9936), 2232–2237. https://doi.org/10.1016/S0140-6736(13)62709-9
8. Imazio, M., Bobbio, M., Cecchi, E., Demarie, D., Pomari, F., Moratti, M., Ghisio, A., Belli, R., & Trinchero, R. (2005). Colchicine as first-choice therapy for recurrent pericarditis: Results of the CORE (COlchicine for REcurrent pericarditis) trial. Archives of Internal Medicine, 165(17), 1987–1991. https://doi.org/10.1001/archinte.165.17.1987
9. Imazio, M., Brucato, A., Cemin, R., Ferrua, S., Belli, R., Maestroni, S., Trinchero, R., Spodick, D. H., Adler, Y., & CORP (COlchicine for Recurrent Pericarditis) Investigators. (2011). Colchicine for recurrent pericarditis (CORP): A randomized trial. Annals of Internal Medicine, 155(7), 409–414. https://doi.org/10.7326/0003-4819-155-7-201110040-00359
10. Imazio, M., Brucato, A., Cemin, R., Ferrua, S., Maggiolini, S., Beqaraj, F., Demarie, D., Forno, D., Ferro, S., Maestroni, S., Belli, R., Trinchero, R., Spodick, D. H., & Adler, Y. (2013). A Randomized Trial of Colchicine for Acute Pericarditis. New England Journal of Medicine, 369(16), 1522–1528. https://doi.org/10.1056/NEJMoa1208536
11. Imazio, M., Pivetta, E., Restrepo, S. P., Sormani, P., Pedrotti, P., Quarta, G., Brucato, A., Bubbico, E., Corso, M. D., Milazzo, A., Quattrocchi, G., Andriani, M., Bodoni, L. L., Davini, O., Sironi, S., Giannattasio, C., Giustetto, C., Bogaert, J., Adler, Y., … Ferrari, G. M. D. (2020). Usefulness of Cardiac Magnetic Resonance for Recurrent Pericarditis. American Journal of Cardiology, 125(1), 146–151. https://doi.org/10.1016/j.amjcard.2019.09.026
12. Imazio Massimo, Bobbio Marco, Cecchi Enrico, Demarie Daniela, Demichelis Brunella, Pomari Franco, Moratti Mauro, Gaschino Gianni, Giammaria Massimo, Ghisio Aldo, Belli Riccardo, & Trinchero Rita. (2005). Colchicine in Addition to Conventional Therapy for Acute Pericarditis. Circulation, 112(13), 2012–2016. https://doi.org/10.1161/CIRCULATIONAHA.105.542738
13. Kauffman, C. A. (2017). Treatment of the Midwestern Endemic Mycoses, Blastomycosis and Histoplasmosis. Current Fungal Infection Reports, 11(3), 67–74. https://doi.org/10.1007/s12281-017-0281-x
14. Lotrionte, M., Biondi-Zoccai, G., Imazio, M., Castagno, D., Moretti, C., Abbate, A., Agostoni, P., Brucato, A. L., Di Pasquale, P., Raatikka, M., Sangiorgi, G., Laudito, A., Sheiban, I., & Gaita, F. (2010). International collaborative systematic review of controlled clinical trials on pharmacologic treatments for acute pericarditis and its recurrences. American Heart Journal, 160(4), 662–670. https://doi.org/10.1016/j.ahj.2010.06.015
15. Vecchié, A., Chiabrando, J. G., Dell, M. S., Bonaventura, A., Mauro, A. G., Wohlford, G., Van Tassell, B. W., Berrocal, D. H., Montecucco, F., Beutler, A., Paolini, J. F., Gal, T. S., & Abbate, A. (2020). Clinical Presentation and Outcomes of Acute Pericarditis in a Large Urban Hospital in the United States of America. Chest, S0012369220320584. https://doi.org/10.1016/j.chest.2020.07.039
16. Wang, J. J., & Reimold, S. C. (2006). Chest Pain Resulting From Histoplasmosis Pericarditis: A Brief Report and Review of the Literature. Cardiology in Review, 14(5), 223–226. https://doi.org/10.1097/01.crd.0000204751.21288.20
17. Wheat, L. J. (2006). Histoplasmosis: A review for clinicians from non-endemic areas. Mycoses, 49(4), 274–282. https://doi.org/10.1111/j.1439-0507.2006.01253.x
18. Wheat, L. J., Freifeld, A. G., Kleiman, M. B., Baddley, J. W., McKinsey, D. S., Loyd, J. E., & Kauffman, C. A. (2007). Clinical Practice Guidelines for the Management of Patients with Histoplasmosis: 2007 Update by the Infectious Diseases Society of America. Clinical Infectious Diseases, 45(7), 807–825. https://doi.org/10.1086/521259

• 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

CardioNerds (Amit Goyal & Karan Desai) join Medical University of South Carolina cardiology (MUSC) fellows (Carson Keck, Samuel Powell, and Ishan Shah) at MUSC Children’s Hospital cafeteria overlooking the gorgeous Charleston Harbor. They reflect on an informative case of exertional intolerance due to tricuspid regurgitation. Dr. Ryan Tedford provides the E-CPR and program director Dr. Daniel Judge provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident, Eunice Dugan, with mentorship from University of Maryland cardiology fellow Karan Desai.

Jump to: Patient summary – Case media – Case teaching – References

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.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Subscribe to our newsletter- The Heartbeat
Support our educational mission by becoming a Patron!
Cardiology Programs Twitter Group created by Dr. Nosheen Reza

Coming soon!

• A
• B

A. Tricuspid valve CW Doppler
B. Hepatic vein flow

Coming soon!

References

Coming soon!

• 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

CardioNerds (Amit Goyal & Daniel Ambinder) join Brown University cardiology fellows (Greg Salber, Vrinda Trivedi, and Esseim Sharma) for a gorgeous coastal boat ride in Providence, RI. They discuss an educational case of hypertrophic cardiomyopathy with superimposed stress cardiomyopathy. Dr. Katharine French provides the E-CPR and program director Dr. Raymond Russell provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Evelyn Song with mentorship from University of Maryland cardiology fellow Karan Desai.  

Jump to: Patient summary – Case media – Case teaching – References

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.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Subscribe to our newsletter- The Heartbeat
Support our educational mission by becoming a Patron!
Cardiology Programs Twitter Group created by Dr. Nosheen Reza

A man in his mid-70s with history of hypertension and diabetes presented with chest pain and ST elevation in V1-V3. Two weeks prior to his presentation he was diagnosed with HoCM after several months of progressive dyspnea. TTE at that time showed HCM with resting left ventricular outflow gradient of 35 mmHg and 83 mmHg with valsava and systolic anterior motion (SAM) of the mitral valve. Join the Brown University Cardionerds as they take us through the differential of chest pain in HCM, approach to wall motion abnormalities, and the fascinating management questions that arise.

• A
• B
• C
• D
• E

A. ECG 2 weeks prior to current presentation
B. Current ECG
C. CXR
D. M mode though the mitral valve demonstrating systolic anterior motion of the mitral valve
E. LVOT CW Doppler tracings with a peak velocity ~ 5 m/s

• Hypertrophic Cardiomyopathy Infographic

1. What’s the differential for LVH and what findings are more suggestive of HCM?

• Causes for LVH can be either pathological or physiological. Pathological causes include infiltrative diseases like hypertrophic cardiomyopathy (HCM), Amyloidosis, or Fabry disease and inflammatory diseases like myocarditis.
• Physiological causes are due to remodeling from increased cardiac output or workload like in athletic heart or from a high afterload state such as in aortic stenosis and hypertension.
• In hypertension, AS, and athletic heart, LV hypertrophy is more commonly concentric and rarely exceeds 15mm. In HCM, LV hypertrophy is more commonly asymmetric (basal anteroseptum > posterior wall), often >15mm, and typically involves the basal ventricular septum.
• Differentiating pathologic versus physiologic causes of LVH can typically be done from a detailed history and exam (e.g., evidence of hypertrophy out of proportion to pressure overload, multisystem involvement). Cardiac MRI can be used to differentiate between HCM and other phenocopies. In HCM, LGE is usually seen at the insertion point of the LV and RV or the most hypertrophied myocardial regions whereas in amyloidosis, endomyocardial LGE is more characteristic.

1. What are some characteristic exam findings seen in HoCM?

• Systolic murmur at the left sternal border can be heard in patients with obstructive HCM (HoCM). The murmur is a result of LVOT obstruction due to systolic anterior motion (SAM) of the mitral valve and LV basal septal hypertrophy.
  • Maneuvers that decrease preload, such as Valsalva or going from a sitting to upright position, will enhance the obstruction and increase the intensity of murmur.
  • Maneuvers that increase the preload or afterload, such as squatting or handgrip, will decrease the intensity of murmur.
  • Additionally, mitral valve pathology – whether a primary valve process or secondary to SAM/ abnormalities in the chordae – can lead to murmurs of mitral insufficiency. These murmurs will typically be best heard at the apex. The murmur associated with SAM will be mid to late peaking as the anterior leaflet is pulled away from the posterior leaflet, unlike the holosystolic murmur associated with intrinsic MV pathology.
• Pulsus bisferiens describes an aortic waveform with two peaks per cardiac cycle that’s characteristic of dynamic LVOT. The onset of systole leads to the initial peak in aortic waveform. Then the narrowing of LVOT leads to a transient occlusion, causing a midsystolic dip in the aortic waveform. Lastly, towards the end of systolic, the ventricle overcomes the obstruction, leading to the second peak in the aortic waveform.

1. What are the 4 Ps in management of HCM?

• Prevent symptoms: medical therapies with negative inotropy and chronotropy such as BB and CCB should be used. In the recent phase III EXPLORER-HCM, a cardiac myosin inhibitor, mavacamten, was shown to impressively reduce HF symptoms and LVOT gradient in patients with HoCM. In patients refractory to medical treatment, surgeries like myectomy or alcohol septal ablation are also options.
• Prevent stroke: HCM patients are at higher risk for atrial tachyarrhythmias and thus embolic stroke. All patients with atrial tachyarrhythmias should be anticoagulated regardless of their CHADSVASc score.
• Prevent sudden cardiac death (SCD) in family: HCM is an autosomal dominant genetic cardiomyopathy so all first relatives should undergo genetic testing and serial TTEs.
• Prevent SCD: HCM patients should undergo risk stratification for implantable cardiac defibrillators as VT/VF and SCD are major causes of morbidity and mortality in these patients. Some risk factors for primary prevention ICD include syncope without a clear cause, LV wall thickness > 30 mm, family history of SCD in a 1st-degree relative, repetitive episodes of NSVT on Holter, and failure to increase SBP > 20 mmHg with exercise.

1. What’s the Brockenbrough-Braunwald-Morrow sign?

• The Brockenbrough-Braunwald-Morrow sign is a useful catheterization laboratory maneuver that describes the characteristic LV pressure tracing pattern that’s seen in dynamic LV outflow tract obstructive and can be used to differentiate obstructive HCM from other fixed valvular or subvalvular obstruction.
• Normally in patients without dynamic outflow obstruction, a compensatory pause after a PVC increases the filling time during diastole, leading to a higher stroke volume and arterial pulse pressure. Per the Frank-Starling mechanism, the expanded EDV also increases cardiac muscle stretch resulting in an increase in myocardial contractility, systolic aortic pressure, and thus an increase in pulse pressure.
• In patients with obstructive HCM, the augmented inotropic response after a PVC actually aggravates the obstruction. Thus, there is a rise in LV systolic pressure but also a rise in the LVOT gradient, resulting in a paradoxical decrease in systolic aortic pressure and pulse pressure. This is called the Brockenbrough-Braunwald-Morrow sign.

1. How do we diagnose and treat Takotsubo cardiomyopathy?

• Takotsubo cardiomyopathy leads to transient heart failure caused by severe physical or emotional stress. Most patients will recover their EF but mortality is similar to that of anterior MI. 90% of cases occur in post-menopausal women. 
• The Revised Mayo Clinic criteria, widely used to diagnose Takotsubo CM, include:
  • Transient dyskinesis of LV midsegments, with or without apical involvement
  • Regional wall motion abnormalities (WMA) extending beyond a single epicardial vascular distribution
  • Absence of obstructive coronary disease in the territory of WMA or angiographic evidence of acute plaque rupture.
  • New EKG abnormalities or modest elevation in the cardiac troponin level
  • Absence of pheochromocytoma and myocarditis
• Treatment is largely supportive and continues until the LV function recovers, usually within 21 days of onset. Anticoagulation should be started in patients with large areas of cardiac hypokinesis because major cerebral or vascular events are major complications.

References

1. Geske, J. B., Ommen, S. R., & Gersh, B. J. (2018). Hypertrophic Cardiomyopathy: Clinical Update. JACC. Heart failure, 6(5), 364–375.
2. Boyd, B., & Solh, T. (2020). Takotsubo cardiomyopathy: Review of broken heart syndrome. JAAPA : official journal of the American Academy of Physician Assistants, 33(3), 24–29.
3. Méndez, C., Soler, R., Rodríguez, E., Barriales, R., Ochoa, J. P., & Monserrat, L. (2018). Differential diagnosis of thickened myocardium: an illustrative MRI review. Insights into imaging, 9(5), 695–707.
4. Lasam G. (2018). Brockenbrough-Braunwald-Morrow Sign: An Evaluative Hemodynamic Maneuver for Left Ventricular Outflow Tract Obstruction. Cardiology research, 9(3), 180–182.
5. Cui, H., Nguyen, A., & Schaff, H. V. (2018). The Brockenbrough-Braunwald-Morrow sign. The Journal of thoracic and cardiovascular surgery, 156(4), 1614–1615.

• 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

In Episode #82, we met Jeremy Keck as a patient born with L-TGA and DILV treated with Fontan procedure. Now, in this very special episode, we meet Jeremy Keck beyond his heart disease through the eyes of his loving wife Ana Keck. His legacy underscores the importance of seeing our patients as people beyond their illness, in the context of their lives, values, and loved ones. We learn to appreciate the full life one can live with complex adult congenital heart disease but also of the work that remains to be done. This powerful discussion is led by Dr. Evelyn Song (internal medicine resident at Johns Hopkins Hospital), Dr. Pablo Sanchez (cardiology fellow at Stanford University), and Dr. Michael Landzberg (cardiovascular and palliative care faculty and former director of ACHD at Brigham and Women’s Hospital). ​

Jeremy’s gofundme page
Jeremy’s case discussion – episode 82
Jeremy’s obituary page

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Jeremy Keck was a giant within the construction industry and accomplished so much in his 37 years of life. However, his greatest point of pride was his family. He is survived by his wife Ana, two young daughters, Emilee and Kaylee, his parents, Jeff and Terri Keck, brother Kevinn (Deana) Keck, nephews Jeremy and Payne, and nieces Taylore and Payge. Jeremy also had a heart for philanthropy. He was an active supporter of the Heart Center at Phoenix Children’s Hospital.

In an interview with The Arizona Republic in 2015, Jeremy said he wouldn’t change his experience even if he had the chance. “I have a perspective on life that you can’t teach anybody,” he said. “You can’t even explain it to people. The small things that happen that might not go your way seem pretty minor.” Jeremy had such a positive impact on those around him, inspiring everyone to live life to the fullest. He will be deeply missed.

Visit Jeremy’s gofundme page for more information.

Music Acknowledgements
Eternal Hope by Kevin MacLeod is licensed under a Creative Commons Attribution 4.0 license. https://creativecommons.org/licenses/by/4.0/ Source: http://incompetech.com/music/royalty-free/index.html?isrc=USUAN1100238. Artist: http://incompetech.com/

CardioNerds (Amit Goyal & Daniel Ambinder) join Stanford cardiology fellows (Pablo Sanchez, Natalie Tapaskar, Jimmy Tooley) for tacos while enjoying the sunshine on the Stanford Oval! They recount the story of a man with adult congenital heart disease (ACHD): L-TGA (levo-transposed great arteries) with double inlet LV post-Fontan complicated by VF arrest. Dr. Christiane Haeffele provides the E-CPR and program director Dr. Joshua Knowles provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Evelyn Song with mentorship from University of Maryland cardiology fellow Karan Desai and Cleveland clinic cardiology fellow Josh Saef.

Jump to: Patient summary – Case media – Case teaching – References

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.

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A man in his mid-30s with past medical history notable for L-TGA (levo-transposed great arteries) with double inlet LV s/p Fontan palliation was playing golf when he suddenly collapsed.  EMS arrived after three minutes of bystander CPR. An AED indicated the patient had suffered a VF arrest. ROSC was achieved after 1 round of Epi and 1 shock delivered. He was intubated and started on targeted temperature management protocol. Home medications were  notable for digoxin 0.25mg daily, sotalol 120mg BID, and warfarin 5mg daily. Initial labs were notable for Na 127, K 5.4, Cr 1.0 (unknown baseline), INR 4.5, Lactate 4.6, Troponin-I 0.532, VBG 7.06/61, and random Digoxin level 2.7.  EKG showed AV sequential pacing at a rate of 70 bpm. QTc prolonged at 571ms. No ischemic ST changes. Device interrogation showed sustained VT for 5 minutes prior to external shock. No internal shock was delivered. He was initially stabilized and his acidosis and hyperkalemia were corrected. Course was complicated by hemoptysis due to alveolar hemorrhagic and he was given concentrated prothrombin complex to reverse his coagulopathy. He eventually stabilized, and a formal TTE was obtained which showed a hypoplastic RV, single dilated LV with an akinetic posterior wall and hypokinetic lateral wall, all similar to his prior TTE in 2019. No obstruction noted at the IVC/Fontan anastomotic site. Coronary angiogram performed after his kidney function improved also did not show any significant obstructions or coronary anomalies. After multidisciplinary discussion, his VF arrest was attributed to a combination of prior ventricular fibrosis/scar, suspected digoxin toxicity, sotalol, dehydration, and renal failure. He had a subcutaneous ICD lead placed and was ultimately discharged home. 

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• B

A. CXR
B. ECG

1. What’s Transposition of the Great Arteries (TGA)? 
   • TGA is defined by a nontraditional ventricle-arterial relationship so that the aorta arises from the morphological RV and the pulmonary artery (PA) arises from the morphological LV 
   • There are two types of TGA, L or levo and D or dextro. 
     • D (rightward)-TGA: Systemic venous return flows into RA -> RV -> delivered to systemic circulation via Aorta, bypassing the lungs. The pulmonary veins flow into the LA -> LV-> delivered to the pulmonary circulation via the PA. The result is two parallel systems that fail to deliver oxygenated blood to the systemic circulation. This is not compatible with life unless another defect such as ASD, VSD, or PDA is present (or created) to allow mixing of deoxygenated and oxygenated blood. Patients with D-TGA usually require arterial switch procedures within 1 month of life. A simplified way to understand this is to say that the great vessels are malpositioned, leaving patients with two parallel circulation. 
     • L (leftward)-TGA: Deoxygenated blood flows into RA -> morphologic LV in the traditional RV position -> PA -> Lungs->  LA -> morphologic RV in the traditional LV position -> aorta to deliver oxygenated blood to the body. A simplified way to understand this is to say that the ventricles are malpositioned, leaving patients with two circulations in series (normal) with the pumps in the wrong places. There’s no cyanosis at birth and patients may be completely asymptomatic for years. This is more rare than D-TGA and only occurs in ~7 per 100,000 births.  
       • The problem in L-TGA is that the morphologic RV, being the systemic ventricle, is not meant to withstand systemic afterload and can result in significant TR and ventricular dysfunction. Additionally, the majority of the cases (80%) are associated with an additional heart defect, such as VSD, pulmonary stenosis, RV hypoplasia, or DILV as in our case.   
         
2. What’s Double Inlet Left Ventricle (DILV)? 
   • In DILV, both atrio-ventricular valves (mitral and tricuspid) lead into the LV and a large VSD is present to connect the LV and RV. DILV is very rare (~5 in 100,000 births). It coexists with L-TGA in about 65% of the cases. 
   • DILV leads to mixing of oxygenated and deoxygenated blood in the LV, resulting in inadequately oxygenated blood entering the systemic circulation and also over-circulation to the pulmonary system (increased Qp:Qs), resulting in LV congestion and heart failure over time.   
     
3. What’s the Fontan procedure? 
   • The Fontan procedure is typically performed as a palliation procedure to direct flow of systemic venous return to the lungs without passing through a subpulmonic ventricle. It’s typically performed in patients with complex congenital heart disease with a single functioning ventricle such as tricuspid atresia, pulmonary atresia, hypoplastic left heart syndrome, and DILV. In these conditions, intracardiac mixing of oxygenated and deoxygenated blood leads to cyanosis and ventricular volume overload without surgical intervention. 
   • The early variation of the Fontan procedure connected the pulmonary arteries to the RA. However, this led to RA dilation and loss of contractility, resulting in decreased pulmonary blood flow and increased risk for thrombus formation and arrhythmias. More modern Fontan palliation procedures connect both vena cavae directly to pulmonary arteries (via an intra- or extra-cardiac conduit), bypassing the RA and RV completely. 
   • Elevated pulmonary pressure is an absolute contraindication for the Fontan procedure since there’s no ventricular contraction to pump blood through the lungs (it relies on passive flow). Therefore, the cavopulmonary Fontan circulation can’t be created at birth given the normal high pulmonary vascular resistance in newborns.  
   • The modern Fontan palliation sequence is performed in a staged fashion to allow the patient’s body to adapt to the different hemodynamic states and reduce overall surgical morbidity and mortality. 
     1. Stage 1: systemic-pulmonary shunt; performed during neonatal period 
     • An artificial shunt is placed between a major systemic central vessel, usually subclavian artery, and proximal pulmonary artery. The goal of this step is to provide dedicated pulmonary blood flow to allow adequate oxygen delivery to tissues and pulmonary arterial growth.  
     1. Stage 2: superior cavopulmonary connection (Glenn procedure); performed between 4-12 months 
     • Anastomosis is made between the SVC and proximal right PA. The previous systemic-pulmonary shunt is usually ligated. This allows priming of the pulmonary vasculature over time before completion of the Fontan circulation.  
     1. Stage 3: completion of the Fontan circulation; performed between ages 1-5. 
     • Different surgical techniques are used, but the common endpoint is  IVC anastomosis to the right PA. 
   • After the Fontan procedure, cardiac output is completely dependent on passive flow into the lungs. LV preload is central to Fontan physiology.  Dehydration, an increase in pulmonary vascular resistance and/or worsening LV stiffness (and hence LV filling) can lead to decreased cardiac output.   
     
4. What are some complications associated with the Fontan procedure? 
   • RA dilatation was very common with the classic Fontan where atriopulmonary instead of cavopulmonary Fontan circulation was created, the RA is exposed to elevated pressure, leading to RA dilatation, thrombus formation, and arrhythmias. 
   • Ventricular failure usually develops after the first decade following completetion of the Fontan palliation. Patients will typically develop the classic symptoms of heart failure due to either HFrEF or HFpEF. Potential contributors to CHF include atrial tachycardia, valvular regurgitation, and volume-loading shunts. 
   • Atrioventricular valve (AVV) regurgitation can develop insidiously after the Fontan procedure and is a significant risk factor for long-term mortality post Fontan. AVV regurgitation can lead to volume overload, ventricular dilation, reduced ventricular contractility, and increased postcapillary and central venous pressures, compromising the Fontan circulation. Medical management of patients with AVV regurgitation post Fontan include diuretic therapy and afterload reduction. 
   • Protein-losing enteropathy (PLE) is the abnormal loss of serum proteins into the intestinal lumen and occurs in 5-12% of patients after a Fontan palliation. Its pathophysiology is incompletely understood, but thought to be due to chronic venous congestion-induced lymphatic insufficiency. PLE may lead to edema/ascites, growth failure, coagulopathy, decreased bone density, and lymphopenia. 
   • Plastic Bronchitis (PB) occurs in <5% of patients with Fontan and is characterized by production of thick, tenacious casts within the airway lumen. Similar to PLE, it’s believed to be due to spillage of protein-rich lymph through lymphatic-to-bronchial communications. Medical management includes diuretics, ARBs, and pulmonary vasodilators. 
   • Fontan associated liver disease (FALD) is a common complication after Fontan due to increased venous pressure, lymphatic overflow, and hepatic congestion. FALD spans the spectrum from liver fibrosis to cardiac cirrhosis and hepatocellular carcinoma. All patients with Fontan circulation should be counseled on avoiding hepatotoxins and undergo regular hepatic screening.   
     
5. What are the common long-term complications of congenital heart disease (CHD)? 
   • With advances in cardiology and cardiac surgery, 85% of neonates with CHD survive into adult life. The four most common complications seen in ACHD include Heart failure, Endocarditis, Arrhythmias, and Pulmonary Hypertension, or H.E.A.P 
   • Heart failure is a major cause of morbidity and mortality in ACHD patients. The pathophysiology of HF in ACHD is multifactorial and includes chronic pressure/volume ventricular loading, persistent arrhythmias, longstanding cyanosis, myocardial fibrosis, or pulmonary vascular disease. Medical management typically includes diuretics and ARBs; however, guidelines for treatment of HF in ACHD patients are lacking because all the trials excluded ACHD patients. Ultimately heart transplantation should be considered in those with refractory HF. Given high prevalence of pulmonary hypertension and RV dysfunction, the use of VADs is limited in this population. 
   • Endocarditis is more prevalent in patients with ACHD compared to the general population. The increased risk of IE in this population is related to both the underlying congenital defect and previous surgical interventions with reconstructed anatomy. The most common site for IE is the LV outflow tract, regardless of previous surgery. IE should be suspected in all ACHD patients presenting with fever, night sweats, or new manifestation of HF. Patients with cyanotic heart disease, history of IE, prosthetic valve, or prosthetic material/devices should receive prophylactic antibiotics prior to any invasive dental procedures. 
   • Arrhythmias account for the majority of ED visits in ACHD patients. For patients older than 20 years, >50% will have atrial tachyarrhythmias. Other common arrhythmias include AV node disease, PVCs, and NSVTs. Sustained ventricular arrhythmias, typically due to prior ventriculostomy scars or ventricular fibrosis, is the most common cause of SCD in the ACHD population. Additionally, pacemaker implantation in ACHD patients requires thorough understanding of underlying anatomy. At times, epicardial pacing is needed (i.e. Fontan patients) due to inability to access cardiac chambers. Pulmonary hypertension (PH) is defined as mean PAP >/= 25 mmHg, similar as in the general population. About 5-10% of ACHD patients have PH and these patients are at a higher risk for hospitalization and death. The clinical classification of ACHD-related PH has four main clinical groups: Eisenmenger’s syndrome, PAH associated with systemic-to-pulmonary shunts, PAH with small defects, and PAH after corrective cardiac surgery.  

References

1. Warnes C. A. (2006). Transposition of the great arteries. Circulation, 114(24), 2699–2709.  
2. Ministeri, M., Alonso-Gonzalez, R., Swan, L., & Dimopoulos, K. (2016). Common long-term complications of adult congenital heart disease: avoid falling in a H.E.A.P. Expert review of cardiovascular therapy, 14(4), 445–462.  
3. Rychik, J., et.al. American Heart Association Council on Cardiovascular Disease in the Young and Council on Cardiovascular and Stroke Nursing (2019). Evaluation and Management of the Child and Adult With Fontan Circulation: A Scientific Statement From the American Heart Association. Circulation, CIR0000000000000696. Advance online publication.  
4. Fredenburg, T. B., Johnson, T. R., & Cohen, M. D. (2011). The Fontan procedure: anatomy, complications, and manifestations of failure. Radiographics : a review publication of the Radiological Society of North America, Inc, 31(2), 453–463. 

• 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

CardioNerds (Amit Goyal & Karan Desai) join Massachusetts General Hospital cardiology fellows (Daniel Pipilas, Rachel Frank and Kemar Brown) on a luxurious sailboat for iced coffees and Modern Pastry delicacies! They discuss a rare case of Anomalous Left Coronary Artery from the Pulmonary Artery (ALCAPA). Program director, Dr. Doreen DeFaria Yeh provides the E-CPR and a message for applicants.  Episode notes were developed by Johns Hopkins internal medicine resident Evelyn Song with mentorship from University of Maryland cardiology fellow Karan Desai. 

Jump to: Patient summary – Case media – Case teaching – References

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A women in her early 30s who’s a Jehovah’s witness presented with three days of intermittent chest pain. Past medical history included anxiety. Initial vitals and physical exam were unremarkable. Labs were notable for an elevated troponin T of 360 ng/L and a low TSH of 0.02 mIU/L with an elevated free T4 of 5.1 ng/dL. EKG demonstrated lateral and inferior ST depressions. TTE demonstrated a normal LVEF of 58% with a subtle anterolateral wall motion abnormality. Given her lack of conventional risk factors for CAD, resolution of her chest pain, and downtrending troponin, coronary CTA was obtained next which did not show any CAD but demonstrated an anomalous left main coronary artery (LMCA) arising from the main pulmonary artery with evidence of left to right shunting from the left main into the PA and extensive coronary and bronchial collateralization. The anterior wall hypokinesis was also seen on CT, consistent with ischemia due to myocardial steal phenomenon. Given the abnormal thyroid function tests, thyroid US was also obtained which showed patchy heterogeneity consistent with thyroiditis. Ultimately, the patient was diagnosed with ALCAPA and her chest pain was attributed to steal phenomenon due to hyperthyroidism and increased cardiac demand. She was treated with long-acting nitrates and beta-blocker with resolution of symptoms and was referred to cardiac surgery on discharge.  

After a multidisciplinary discussion involving the cardiac surgery team, patient underwent ligation of LMCA with SVG bypass to LAD. One month after operation, she developed palpitations and chest pain during exertion and was taken to the hospital. Labs showed an elevated hs-troponin T of 711 ng/L and she was treated for type 1 NSTEMI with aspirin, heparin drip, and statin. Repeat TTE demonstrated normal LVEF and lack of WMA. LHC showed occlusion of SVG graft and possible thrombus in LAD near the site of graft anastomosis. RCA was large and patent, providing adequate collaterals to the left coronary system. Ultimately, PCI was deferred and medical management was pursued because she had adequate collaterals from right coronary system. She was treated with DAPT, beta-blocker, and atorvastatin and has been doing well since.  

• A
• B
• C
• D
• E
• F

A. CXR
B. ECG
C. Follow up ECG
D-F. Cardiac CT

1. How are the coronary arteries formed during embryology and how are anomalous coronary arteries formed?  
   • During embryology, according to one theory, the coronary ostia and artery formation begins with ingrowth of a capillary plexus into the aortic sinuses. This complex process heavily depends on the proliferation and migration of cells that originate outside the heart at the sinus venosus and then differentiate into endothelial cells, vascular smooth muscle cells, and fibroblasts. Proper migration of these cells to aorta, creating the coronary ostia, depend heavily on expression of growth factors like FGF-2, PDGF, and VEGF.  
   • Anomalous origin of a coronary artery from the aorta or from the pulmonary artery have a common defect: the cells of the capillary plexus surrounding the aorta and pulmonary artery fail to reach and/or penetrate the normal sites of developing aorta. This can be caused by different mutations affecting the growth factor signaling pathways.  
    
2. What is ALCAPA? 
   • ALCAPA stands for anomalous left coronary artery (LCA) origin from the pulmonary artery. There’s also ARCAPA which is anomalous RCA origin from the pulmonary artery.  
   • It occurs at an incidence of 1 in 300,000 live births or 0.25 to 0.5% of all congenital heart disease. It is difficulty to diagnose during infancy as it presents similarly to other more common pediatric conditions such as infantile colic, food intolerance, GERD, and bronchiolitis. The usual symptoms include inconsolable crying, poor feeding, rapid breathing, or symptoms of significant distress.  
   • Infants may develop myocardial infarction and CHF and a majority of them will die within the first year of life without surgical repair. Infants with ALCAPA rarely manifests in teenagers and adults, unlike the patient in our case.  
    
3. What are the hemodynamic consequences seen in ALCAPA? 
   • In fetal life, pulmonary artery pressure is the same as systemic pressure which allows adequate myocardial perfusion from the pulmonary artery to LCA. 
   • After birth, pulmonary vascular resistance falls precipitously and subsequently pulmonary artery pressure drops lower than systemic pressure. Furthermore, the pulmonary artery carries oxygen-poor blood; therefore, LCA is now perfused with desaturated blood at low pressure, resulting in inadequate perfusion to the myocardium, especially during exertion such as feeding or crying. Collateral vessels from a normally arising coronary artery can provide perfusion to the anomalous coronary; however, this can lead to “coronary steal” phenomenon and L-to-R shunt. 
   • The steal phenomenon and shunt occur because as the pulmonary resistance decreases further, the LCA and the collateral flow tends to pass into the low-pressure pulmonary artery rather than into the high-resistance myocardial blood vessels, resulting in coronary steal phenomenon and myocardial ischemia.  
   • When there are adequate collaterals, symptoms can be absent or very minor, allowing patients with ALCAPA to grow into adulthood. Adults with ALCAPA can either be asymptomatic or have exertional chest pain or even sudden cardiac death.  
     
4. What are some factors that will enable patients with ALCAPA to survive to adulthood? 
   • Factors that ultimately result in adequate perfusion of myocardium by the LCA will all enable patients survive to adulthood. These factors include: 
     • Abundant collateral vessels between the RCA and LCA allowing retrograde LV perfusion from the RCA system. 
     • Right dominant system which allows a smaller myocardial area to be supplied by the LCA, leading to less extensive myocardial ischemia. 
     • Ostial stenosis of the LCA or a restrictive opening into the pulmonary artery limits the left-to-right shunt and minimizes coronary steal from the pulmonary artery. 
     • Development of systemic blood supply to the LCA can occur when collaterals develop from the bronchial artery, providing adequate oxygenated blood flow and perfusion to the myocardium. 
    
5. What are some treatment options for ALCAPA? 
   • If an adult patient presents with CHF, medical management consists of the standard GDMT of afterload reduction, diuretics, and inotropic agents if needed. Once the patient is stabilized, surgical correction should be pursued. 
   • Previously, a simple ligation of the LCA at its origin was performed to prevent the steal phenomenon and myocardial ischemia. Essentially, the heart is converted to a one-vessel coronary system, entirely dependent on collaterals from the RCA. However, the one-vessel coronary system approach is no longer favored due to its high rate of complications such as recanalization of the ALCAPA, a greater risk of atherosclerosis, severe MR, and a persistent risk of SCD due to silent ischemia.  
   • Current surgical procedures are directed toward establishing a two-coronary vessel system through 3 main methods: 
     • Coronary button transfer which is direct reimplantation of the anomalous LCA into the aorta or left subclavian artery, after the pulmonary artery is transected. This is the most commonly used method in newborns. If done in adults, coronary friability increases the risk of tearing, bleeding, and kinking of the LCA.  
     • Takeuchi procedure which is creation of an aortopulmonary window – the pulmonary artery is opened and a baffle is created between the aorta and LCA. This method is commonly used in infants when coronary button transfer is not feasible but is rarely needed. Complications include supravalvular pulmonary stenosis, aortic insufficiency, and baffle obstruction or leaks. 
     • Placement of a coronary artery bypass graft (CABG) combined with ligation of the origin of LCA can be done to restore adequate perfusion. This is the preferred method in adults and what was done in this case. Complications include graft stenosis and occlusion which is what happened in this case.  

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

• Tomanek, R., & Angelini, P. (2019). Embryology of coronary arteries and anatomy/pathophysiology of coronary anomalies. A comprehensive update. International journal of cardiology, 281, 28–34. 
• Lardhi A. A. (2010). Anomalous origin of left coronary artery from pulmonary artery: A rare cause of myocardial infarction in children. Journal of family & community medicine, 17(3), 113–116.  
• Peña, E., Nguyen, E. T., Merchant, N., & Dennie, C. (2009). ALCAPA syndrome: not just a pediatric disease. Radiographics : a review publication of the Radiological Society of North America, Inc, 29(2), 553–565. 

• 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

CardioNerds (Amit Goyal & Daniel Ambinder) join Brigham and Women’s Hospital cardiology fellows (Mounica Yanamandala, Simin Lee and Maria Pabon Porras) for some fun times at the Charles River Esplanade! They discuss a complicated case of prosthetic valve endocarditis with aortic regurgitation. Dr. Dale Adler provides the E-CPR and program director Dr. Donna Polk provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Bibin Varghese with mentorship from University of Maryland cardiology fellow Karan Desai.

Jump to: Patient summary – Case media – Case teaching – References

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.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Subscribe to our newsletter- The Heartbeat
Support our educational mission by becoming a Patron!
Cardiology Programs Twitter Group created by Dr. Nosheen Reza

A male in his mid-40s with history of HIV on ART (undetectable VL, CD4 320) and idiopathic thoracic ascending aortic aneurysm (TAAA) with AR s/p bioprosthetic valve replacement 10 years prior presented with acute onset lightheadedness and pre-syncope. He was diagnosed with an idiopathic TAAA at age 30 after he was noted to have an incidental murmur. Over the next few years, his aortic root increased to over 7 cm with severe AR, LV dilation, and reduced LVEF of 45%. He underwent bioprosthetic aortic valve replacement and root repair with a Medtronic freestyle porcine aortic root with subsequent recovery of his  LVEF to 50% and improved LV dilation. Thereafter, he was doing well until he reported a flu like illness 3 weeks prior to presentation with reported fever up to 101.3 F and associated myalgias. He denied any sick contacts or recent travel and was adherent to his HIV regiment. On the day of presentation, he was walking his dogs when he developed acute onset lightheadedness with presyncope. On presentation, he had a low grade fever, tachycardia, tachypnea, and hypoxia. On exam, cardiac exam was notable for loud blowing diastolic murmur, non-distended JVP, decreased breath sounds, warm extremities with bounding pulses and without edema. There were no stigmata of endocarditis. Labs revealed elevated cardiac and inflammatory biomarkers. Blood cultures were initially NGTD. CXR corroborated the exam with bilateral interstitial and airspace opacification with effusions. TTE showed LVEF 35% with global hypokinesis, dilated LV with LVEDD 7.5 cm, mild RV systolic dysfunction, severe AR with holo-diastolic flow reversal in the abdominal aorta, no prosthetic stenosis, and aortic root 31 mm. TEE showed a well-seated AVR with leaflet thickening and several echodensities. CT surgery deemed patient to be high risk for the OR. After a few days, patient required intubation for increased work of breathing and acute decompensation requiring vasoactive infusions. After multidisciplinary discussions, the patient ultimately underwent ViV TAVR with successful placement of a 29 mm Edwards Sapien 3 valve. That day, he was weaned off pressors, and subsequently extubated. Infectious workup remained negative thereby resulting in a final diagnosis of prosthetic aortic valve culture-negative endocarditis vs sterile prosthetic valve deterioration. He was discharged on intravenous empiric antibiotics and was doing well in clinic 2 months later.  

• A
• B
• C
• D
• E
• F

A. CXR: Bilateral airspace and interstitial opacification. Small bilateral effusions. No pneumothorax.
B. ECG
C. CW Doppler across the aortic valve
D. PW Doppler showing holodiastolic flow reversal in the descending thoracic aorta 
E. Pre-TAVR LV and aortic pressure tracings
F. Post-TAVR LV and aortic pressure tracings

Coming soon!

• Pathophysiology of Aortic Regurgitation
• Severe Aortic Regurgitation

1. The patient had an idiopathic ascending aortic aneurysm. How do you typically approach the etiology for a thoracic aortic aneurysm? 

• Let us first differentiate the terminology for the aorta. The ascending aorta includes the aortic root (which contains the sinuses of Valsalva), the aortic arch which includes the great vessels. The descending aorta begins beyond the left subclavian artery. The isthmus is the point where the aortic arch and the descending aorta join (also the site of the ductus arteriosus which turns into the ligamentum arteriosum). The abdominal aorta begins distal to the diaphragm. 
• Thoracic Aortic Aneurysms (TAA) include aneurysms that occur from the aortic root to the crus of the diaphragm. There are various etiologies for TAAs, but the most common cause is medial necrosis. This is a non-specific pathologic finding that may be found in a number of conditions. The underlying histologic findings include loss of elastic fibers and vascular smooth muscle in the media, with accumulation of a basophilic ground substance leading to a cystic appearance.  
• There are several ways to approach the etiology of TAAs. The causes may be classified into degenerative, genetic, infectious, inflammatory, and other causes. Genetic causes include but are not limited to Marfan’s Syndrome, Loeys-Dietz Syndrome, Ehlers-Danlos Type IV, Familial TAA, and Turner syndrome. Inflammatory conditions include giant cell arteritis, Takayasu arteritis, and HLA-B27 associated spondyloarthropathies. An important infectious cause includes syphilis as we have previously discussed on our CNCR Series: Ep #47 – Syphilitic Aortitis!  
• Generally, aortopathies occurring proximal to the ligamentum arteriosum are more likely to be genetic while those occurring distally are more likely to be degenerative (related to atherosclerotic risk factors). 
• Remember, in terms of management, TAAs tend to grow more rapidly as they become larger and depending on the etiology, there may be a lower cut-off for elective procedures as the guidelines suggest earlier intervention for specific conditions. For instance, patients with Loeys-Dietz (amongst other genetic syndromes), can be considered for elective TAA at aneurysms less than 50 mm given the high occurrence of dissection after 50 mm. The approach should be individualized to the patient’s underlying condition, body size and sex (as there may be smaller absolute aortic root size and diameter in women). 

2. The patient had well controlled HIV and developed a TAA. What are the known cardiovascular risks associated with HIV? 

• Cardiovascular disease, including myocardial, pericardial, and vascular (including coronary) disease, has become a major cause of morbidity and mortality in patients with HIV 
• Vascular disease likely has several causes including traditional risk factors (e.g., diabetes, hypertension) and chronic inflammation which leads to accelerated atherosclerosis. Recall from the CardioNerds Prevention Series that HIV is a key “risk-enhancing factor”! 
• HIV is an important cause of heart failure, including HIV-associated dilated cardiomyopathy. Some data has suggested that the HIV-1 virus may infect myocardial cells directly in a patchy distribution leading to progressive damage and fibrosis. Furthermore , underlying ischemia, co-infection with other pathogens (e.g., EBV, CMV, coxsackievirus B), cardiac autoimmunity, and drug toxicities can contribute to the development of HF. Patients with HIV are additionally at higher risk of developing HFpEF. The mechanism remains to be elucidated, though the extent of chronic inflammation, T-cell activation, and loss of adaptive immunity likely all play a role.  
• Pericardial disease and specifically pericarditis was the most common manifestation of HIV-associated cardiac disease prior to the advent of potent ART. 
• Other manifestations include pulmonary arterial hypertension (WHO Group 1), increased risk of venous thromboembolism, and possibly sudden cardiac death. Infective endocarditis rates are similar to patients without HIV, once corrected for other exposures (e.g., IV drug use).  

3. The patient developed a new loud decrescendo blowing diastolic murmur which was concerning for aortic regurgitation. What are the other physical exam findings associated with aortic regurgitation? 

• As we reviewed in previous episodes (Ep #47 – Syphilitic Aortitis), the physical exam of patients with chronic AR is full of classic findings and eponyms! The classic murmur of AR is a diastolic, blowing, decrescendo murmur heard in the LUSB. The severity of AR correlates with the duration of the murmur more than the intensity. The increased blood flow across the AV can lead to a systolic flow murmur in the RUSB, and the regurgitant blood flow can limit opening of the MV causing a diastolic murmur best heard at the apex called the Austin-Flint murmur. 
• Note, in chronic AR there is a rapid increase in systole BP and fall in diastole, leading to a widened pulse pressure and bounding pulses. Some physical exam findings (not an all-inclusive list!) associated with hyperdynamic pulse are included below. Note, some of these findings are not necessarily specific to chronic AR alone, but can also be seen in other states of hyperdynamic circulation.  
  • Water hammer pulse: a bounding pulse with rapid systolic rise followed by rapid diastolic collapse that can be best appreciated at the radial or brachial artery. It is accentuated by slightly lifting up the patient’s arm. 
  • Corrigan’s pulse: bounding carotid pulse with rapid rise and collapse 
  • Traube sign: “pistol shot” sounds heard over femoral arteries in both systole and diastole 
  • Duroziez sign: diastolic murmur heard over the femoral artery after compressing distally or a systolic murmur when compressed proximally  
  • Quincke’s pulse: capillary pulsations in the nail beds  
  • Muller’s sign:  pulsations of the uvula 
  • de Musset sign: head bobbing synchronous with heartbeat 
  • Becker’s sign: visible pulsations of the retinal arteries on ophthalmoscopic examination 
  • Hill sign: positive when the popliteal cuff systolic pressure exceeds the brachial cuff systolic pressure by > 60 mmHg 

1. The etiology of the acute onset aortic regurgitation was thought to be from infective endocarditis. Returning to basics, what are the criteria for infective endocarditis? 

• The Duke Criteria are the most sensitive and specific diagnostic criteria for diagnosing native valve infective endocarditis. However, for prosthetic valve endocarditis (PVE), the Duke criteria have decreased sensitivity and specificity. For possible endocarditis or “rejected” endocarditis based on Duke Criteria where there is a persistent suspicion of PVE, further advanced imaging should be considered including TEE, 18F-FDG PET/CT, and/or 4D cardiac CTA.  
• There are pathologic and clinical Duke Criteria. The clinical criteria are included below from the Chambers and Bayer NEJM article  
• A “definite” clinical diagnosis of infective endocarditis requires two major criteria, or one major and three minor or five minor criteria. “Possible” clinical diagnosis of IE includes one major criteria and one minor criteria or three minor criteria. A “rejected” clinical diagnosis of IE requires a clear alternative diagnosis for the patient’s clinical manifestations suggestive of IE or resolution of those symptoms with antibiotics for 4 days or less. The absence of pathologic evidence of IE on autopsy or surgery after 4 days or less of antibiotics can also reject the diagnosis of IE.  

5.       When is valvular intervention considered in prosthetic valve endocarditis? 

• Prosthetic valve endocarditis (PVE) commonly requires a combined medical-surgical approach.. Early surgery in PVE, per the 2015 AHA scientific statement, is recommended for patients with one or more of the following clinical circumstances: (1) signs or symptoms of heart failure as a result of valve dehiscence, severe prosthetic valve dysfunction, or intracardiac fistula; (2) IE complicated by complete heart block or an aortic/annular abscess; (3) PVE caused by a fungal organism or a highly resistant organism; (4) persistent bacteremia despite antibiotic therapy ~ 7 days.  
• These recommendations are based on limited observational evidence. In the largest study to date early surgery for conditions other than valve dysfunction and perivalvular abscess was not associated with improved hospital or one-year survival. Other indications to consider potential surgery after weighing the risk and benefits are (1) aortic or mitral PVE with persistent vegetations >10 mm after one or more embolic episode despite appropriate antibiotic therapy; (2) aortic or mitral PVE with isolated very large vegetations (>30 mm); and (3) patients with relapsing PVE.  

References

1. Feinstein, M. J. et al. Characteristics, Prevention, and Management of Cardiovascular Disease in People Living With HIV: A Scientific Statement From the American Heart Association. Circulation 140, e98–e124 (2019). 
2. Chambers, H. F. & Bayer, A. S. Native-Valve Infective Endocarditis. N. Engl. J. Med. 383, 567–576 (2020). 
3. UpToDate Article

• 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

CardioNerds (Amit Goyal & Daniel Ambinder) join University of Washington cardiology fellows (Shannon McConnaughey, Betty Ashinne and Andrew Perry – host of the AP Cardiology podcast) for some tacos and beer at the water and discuss a puzzling case of recurrent troponin elevation. Dr. Kelly Branch provides the E-CPR and program director, Dr. Rosario Freeman, provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Eunice Dugan with mentorship from University of Maryland cardiology fellow Karan Desai.   

Jump to: Patient summary – Case media – Case teaching – References

CardioNerds Case Reports Page
CardioNerds Episode Page
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Subscribe to our newsletter- The Heartbeat
Support our educational mission by becoming a Patron!
Cardiology Programs Twitter Group created by Dr. Nosheen Reza

A female is her late 50s with past medical history of alcohol use disorder and intravenous drug use complicated by hepatitis C presented with generalized weakness and was found to have lower extremity fractures. Cardiology was consulted for pre-operative management. When obtaining a cardiac history, she reported rare, intermittent, and non-anginal chest pain. She had no current chest pain or dyspnea. On chart review, she had multiple presentations over the past 3 years for various complaints – some were chest pain – during which she was found to have elevated troponin I values. Most of the elevations were in the 0.5 to 1 ng/mL range, but one time, her peak troponin was 32 ng/mL. At one of those presentations, she had a TTE that showed septal wall motion abnormalities. She underwent coronary angiography on two occasions, which both showed proximal and mid-LAD calcifications, but no significant stenosis and she was managed medically.  

At the current presentation, her vitals were within normal limits and her exam did not show any cardiopulmonary abnormalities. Labs were notable for troponin I of 10 ng/mL but CK-MB was normal. Interestingly, alkaline phosphatase was 3 times the upper limit of normal, and rheumatoid factor was 1156 IU/mL compared to 70 previously (normal range 0-20 IU/mL). EKG was without ischemic changes. TTE showed no wall motion abnormalities, normal LVEF, and no significant valvular disease. Cardiac catherization was deferred, and the patient was not interested in cardiac MRI. Due to an incongruent troponin elevation with the clinical presentation, there was concern for interference with the troponin assay due to the elevated rheumatoid factor and alkaline phosphatase levels. Upon further investigation, dilution of the troponin yielded results lower than factor of dilution or undetectable results. Mayo testing of the sample showed troponin-T of 0.024 ng/mL (normal < 0.01 ng/mL), and troponin I of 0.02 ng/mL (normal < 0.04 ng/mL). Although there were still some aspects of her previous presentations including rising troponin pattern and previous wall motion abnormalities that are unexplained at this time, her troponin elevation at this presentation was attributed to assay interference.  

• A
• B
• C

A. ECG from May
B. Coronary angiography form May
C. ECG August (same year)

Coming soon!

• What is the universal definition of myocardial infarction?  

·       As per the current 4th universal definition, myocardial infarction is defined as an elevation in cardiac troponin (cTn) above the 99th percentile in high sensitivity assays in the setting of acute myocardial ischemia. It is considered acute if there is a characteristic rise/fall pattern in cTn.  

·       A type 1 event is a spontaneous MI related to ischemia as a result of a primary coronary event (e.g., plaque erosion or rupture, dissection). The definition requires the above biomarker threshold with at least one of the following as evidence of ischemia: symptoms of MI, new ischemic EGG changes including development of pathological Q waves, new imaging evidence of loss of viable myocardium, or identification of thrombosis by intracoronary imaging.  Unstable angina (UA) occurs in patients with symptoms suggestive of acute myocardial infarction but without biomarker elevation. 

·       Criteria for type 2 MI includes the biomarker definition above with evidence of ischemia secondary to mismatched myocardial oxygen demand and supply. It also requires at least one of the following: symptoms of MI, new ischemic EGG changes including development of pathological Q waves, or new imaging evidence of loss of viable myocardium.  

·       Chronic myocardial injury is elevated cTn on sequential testing with less than 20% variation. It could represent conditions such as structural heart disease or chronic kidney injury.  

What are cardiac biomarkers and how are they utilized?  

·       Myocardial necrosis can be recognized when various proteins are released into the blood, including cardiac troponin I and T, myoglobin, LDH, CK, amongst others. Cardiac troponin I and T are cardiac specific isoforms of regulatory proteins that mediate actin-myosin interactions. cTnI has been shown to only be present in the heart. cTnT is found to a small extent in skeletal muscles as well as the heart.   

·       Troponin levels elevate in the blood within 2-3 hours of ischemia, peaking between 12-48 hours and normalizing over 4-10 days. In the late 1990s, it was found to have almost 100% sensitivity in detecting myocardial injury, which was much improved compared to previous cardiac biomarkers.  

·       Creatinine kinase (CK) is a cytosolic enzyme that is found in many tissues, but especially skeletal and cardiac muscle. It exists as 3 isoenzymes: MM, MB or BB. The fraction of MB is higher in the heart, and so it can be a marker for cardiac damage. Since CK-MB levels normalize over 36-48 hours after infarction, it has been thought to be useful in detecting very early re-infarction. However, cTn also increases rapidly, though from an abnormal baseline. 

·       Apart from diagnosing MI, troponin values can also be useful after MI. Peak troponin levels or values at 72-96 hours have been validated by imaging studies to correlate to infarct size (especially with STEMI) and can aid in prognosis with higher values having worse prognosis.   

How does the troponin assay work? 

• There are many assays to detect troponin. They are all different from each other because they use different antibodies. Almost all of them are enzyme-linked immunosorbent assays (ELISA) where there is an antibody that binds to a specific epitome on the protein of interest and a separate tag antibody that labels it. Most of the capture antibodies are monoclonal antibodies. Some use multiple antibodies to increase yield.   
• Conventional troponin assays were relatively insensitive reporting values in the ng/mL or mcg/mL range. However, high-sensitivity troponin (hs-cTnI) assays are more sensitive and precise assays, particularly in the low range, and thus reported in ng/L units. 
• While detection of troponin in the conventional assays is certainly abnormal, it is not the case with high-sensitivity assays. Since the assays is so sensitive, it can detect mild elevations in normal or healthy people. Therefore, the definition of abnormal with hs-cTn assays is above 99th percentile of the normal reference population which is specific to each assay.   

How do I approach an elevated troponin?  

• When confronted with an elevated troponin, a 3 tiered approach may be helpful: (1) Supply, (2) Demand and (3) Other. 
• It is important to first evaluate for a primary supply issue which may be secondary to an acute plaque rupture/erosion, coronary dissection or coronary vasospasm, amongst other etiologies.  
• States that can increase myocardial oxygen demand include hypertension, tachycardia, aortic stenosis, PE, or congestive heart failure. Notably, both conditions of supply and demand can have the characteristic rise/fall pattern of troponin. 
• Other conditions to consider if there is no supply or demand issue include myocarditis, infiltrative processes, stress cardiomyopathy or ESRD. The pattern of troponin rise may vary, but these conditions are likely to have sustained stable elevations. 

How to I approach a suspected falsely elevated troponin? 

• In cases where the clinical presentation is discordant from the troponin assay, false elevations should be considered. A first step is to repeat the test to rule out spurious outliers, which is less likely when repeated. If there is an increase of >20%, there is likely myocardial necrosis and the test should be followed with imaging and possible intervention. 
• If the elevation persists but is less than a 20% increase, then it is reasonable to see if your laboratory offers other assays for testing. If there is a mismatch in the second assay, then testing for interference in the first assay must be pursued. If there is no alternative assay, then investigation for chronic myocardial injury is warranted by ruling out structural heart disease or coronary heart disease. If there is no pathology, then it is reasonable to pursue analytical interferences.  
• The most common reason for false positive results is cross-reacting antibodies (most commonly heterophile antibodies) that interact with the assay. A common way to remove the interferent is to perform dilution studies. The concentration of the mixed sample will not decrease with serial dilutions until the interferent is gone at which point the concentration will decrease steeply.  

References

• Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol 2018;Aug 25 
• Jaffe, A., Morrow, D. (2020). Troponin testing: Analytical considerations. Saperia G. (Ed.), UpToDate.  Retrieved November 12, 2020, from https://www.uptodate.com/contents/troponin-testing-analytical-considerations?search=cardiac%20biomarkers&topicRef=86&source=see_link 
• Jaffe, A., Morrow, D. (2020). Biomarkers of myocardial injury other than troponin. Saperia G. (Ed.), UpToDate.  Retrieved November 12, 2020, from https://www.uptodate.com/contents/biomarkers-of-myocardial-injury-other-than-troponin?search=cardiac%20biomarkers&topicRef=115187&source=see_link 
• Jaffe, A., Morrow, D. (2020). Troponin testing: Clinical use. Saperia G. (Ed.), UpToDate.  Retrieved November 12, 2020, from https://www.uptodate.com/contents/troponin-testing-clinical-use?search=cardiac%20biomarkers&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2#H516924473 
• Mair, Johannes, Bertil Lindahl, Christian Müller, Evangelos Giannitsis, Kurt Huber, Martin Möckel, Mario Plebani, Kristian Thygesen, and Allan S Jaffe. “What to Do When You Question Cardiac Troponin Values.” European Heart Journal: Acute Cardiovascular Care 7, no. 6 (September 1, 2018): 577–86. https://doi.org/10.1177/2048872617708973. 
• “Troponin – StatPearls – NCBI Bookshelf.” Accessed November 12, 2020. 

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.

• 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

CardioNerds (Amit Goyal) join University of Mississippi Medical Center cardiology fellows (Catherine Lowe, Chris Latour and Adi Sabharwal) as they sit at the reservoir enjoying a great view of the water at the Pelican Cove Grill in Jackson, MS. They discuss and educational case of decompensated heart failure and shock in the setting of severe functional mitral regurgitation treated with MitraClip. Dr. Kellan Ashley provides the E-CPR and program director Dr. Trey Clark provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Richard Ferraro with mentorship from University of Maryland cardiology fellow Karan Desai.  

Jump to: Patient summary – Case media – Case teaching – References

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.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Subscribe to our newsletter- The Heartbeat
Support our educational mission by becoming a Patron!
Cardiology Programs Twitter Group created by Dr. Nosheen Reza

A man his mid 70s with a history of non-ischemic heart failure status post CRT-D placement, A-Fib, and chronic kidney disease presented with progressive shortness of breath with limited exertion. The patient was found to have severe secondary mitral regurgitation. Listen to the episode now to learn about treatment options for severe mitral regurgitation in heart failure and specifically the evaluation for MitraClip!

• A
• B
• C
• D
• E

A. Right atrial pressure
B. Right ventricular pressure
C. Pulmonary artery pressure
D. Wedge pressure
C. Pre and post MitraClip left atrial pressure

1. What is Comprehensive Disease Modifying Therapy in HFrEF?

Comprehensive disease modifying therapy for heart failure with reduced ejection fraction (HFrEF) has become both more robust and better understood by practitioners inside and outside the cardiology community.  Comprehensive therapy is generally considered to consist of beta-blockade, mineralocorticoid receptor antagonist (MRA), sodium-glucose cotransporter-2 inhibitors (SGLT2i) and angiotensin receptor neprilysin inhibitor (ARNI), with ARNI being the preferred agent over angiotensin converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB).  Despite a greater understanding of HFrEF therapy by the medical community, significant gaps remain with recent data showing few patients on concomitant beta blockade, MRA, SGLT2i and ACE/ARB/ARNI, and even fewer at target doses. Compared to ACE, BB, and MRA alone, comprehensive therapy with MRA, BB, SGLT2i and ARNI could add an additional 6 years for middle-aged patients.

2. What role does Mitral Valve Disease have in Heart Failure Exacerbations?

For patients that remain symptomatic or with repeated hospitalizations for decompensated heart failure despite comprehensive therapy, it is important to look for additional pathology contributing to heart failure exacerbations.  Mitral valve disease is one such etiology, particular secondary mitral valve regurgitation (MR) which can be seen in heart failure due to changes in left ventricular anatomy.  Severe MR is associated with worsening left ventricular function and heart failure. For some time, however, it was an open question if functional MR was secondary to heart failure or an independent cause of heart failure exacerbations. Recent major trials suggest severe MR may act independently to worsen or lead to more frequent heart failure exacerbations.

3. How Do we Assess Mitral Valve Function in Heart Failure?

MR is primarily quantified by echocardiography, which allows for close observation of regurgitant flow. Once a diagnosis of secondary MR has been established by evaluating mitral valve morphology and leaflet motion (e.g., Carpentier Classification), there are several parameters including objective quantification of MR hemodynamics that are utilized to assess MR severity. However, the AHA/ACC guidelines and the ESC guidelines have different thresholds for severe secondary MR. In the ACC/AHA guidelines, important quantitative measures include calculation of the effective regurgitant orifice area (EROA), regurgitant volume (RVol) and regurgitant fraction (RF). When the MR is holosystolic and accounting for several limitations of these measures, EROA ≥0.4cm2, regurgitant volume ≥60mL, regurgitant fraction ≥ 50% are highly specific for severe MR. Vena contracta, the narrowest diameter of the regurgitant jet, is a semi-quantitative measure of MR severity and ≥0.7 cm (with a single jet) is consistent with severe MR. Remember, MR is dynamic and is dependent on the loading conditions. Thus, it is critical to record the patient’s blood pressure, estimated LV systolic pressure in the setting of aortic stenosis, rhythm and heart rate when reporting echocardiographic measures.

4. What are the Therapeutic Options for Mitral Valve Disease?

Repair options generally include chordal-sparing mitral valve replacement (generally preferred in secondary MR rather than surgical mitral valve repair) and MitraClip. Mitral valve replacement is generally performed by surgeons, and with some exceptions is performed via open heart surgery. MitraClip placement consists of a small device that enters the left atrium via a trans-septal approach, and attaches to and approximates the mitral valve leaflets to reduce the burden of MR.

5. How Does the Data Substantiate these Options?

The EVEREST II trial was the first major trial to show similar clinical improvement and improved safety of MitraClip placement as compared to conventional mitral valve replacement surgery.  The MITRA-FR and COAPT trials subsequently looked specifically at GDMT versus GDMT with percutaneous mitral valve repair in the treatment of heart failure. While MITRA-FR did not exhibit improvement in hospitalization for heart failure or mortality, the COAPT trial did show exhibit improvement in these markers.  While the topic is of much discussion, differences in heart failure severity and achievement of GDMT was suspected to drive in part the different findings in these two trials. Furthermore, the concept of proportionate and disproportionate MR is thought to also lead to differences in the two trials. Patients with “disproportionate” MR – the severity of the MR is unexpected to the degree of LV dilation – were more well-represented in the COAPT trial. These patients seemingly are more likely to respond to interventions on the valve in addition to GDMT. COAPT was therefore the first trial to show improvement in mortality and outcomes in patients with moderate-to-severe MR secondary to LV dysfunction.

References

1. Greene, S. J., Butler, J., Albert, N. M., et. al (2018). Medical therapy for heart failure with reduced ejection fraction: the CHAMP-HF registry. Journal of the American College of Cardiology, 72(4), 351-366.
2. Feldman, T., Foster, E., Glower, D. D. et. al. (2011). Percutaneous repair or surgery for mitral regurgitation. New England Journal of Medicine, 364(15), 1395-1406.
3. Obadia, J. F., Messika-Zeitoun, D., Leurent, G. et. al (2018). Percutaneous repair or medical treatment for secondary mitral regurgitation. New England Journal of Medicine, 379(24), 2297-2306.
4. Stone, G. W., Lindenfeld, J., Abraham, W. T., et. Al (2018). Transcatheter mitral-valve repair in patients with heart failure. New England Journal of Medicine, 379(24), 2307-2318.

• 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