Episodes Archives - Cardionerds

This question refers to Sections 3.2 and 3.3 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern, student Dr. Hirsh Elhence, answered first by Ohio State University Cardiology Fellow Dr. Alli Bigeh, and then by expert faculty Dr. Eugene Yang.

Dr. Yang is professor of medicine of the University of Washington where he is medical director of the Eastside Specialty Center and the co-Director of the Cardiovascular Wellness and Prevention Program. Dr. Yang is former Governor of the ACC Washington Chapter and current chair of the ACC Prevention of CVD Section.

The CardioNerds Decipher The Guidelines Series for the 2021 ESC CV Prevention Guidelines represents a collaboration with the ACC Prevention of CVD Section, the National Lipid Association, and Preventive Cardiovascular Nurses Association.

A 48-year-old Pakistani woman with rheumatoid arthritis comes to your clinic asking how she can reduce her risk of ASCVD. Her mother died of an MI at age 45, her father is healthy at age 79. Her calculated 10-year risk based on SCORE2 is 3%. SBP is 120 mmHg, LDL is 120 mg/dL. What is the next best step? 

A. Order an echocardiogram 
B. Schedule a follow-up appointment in 1 year 
C. Discuss initiating a statin 
D. Repeat lipid panel in 3-5 years 

Answer: C. Discuss Initiating a statin 

The absolute benefit derived from risk factor modification depends on the absolute risk of CVD and the absolute improvements in each risk factor category. Risk factor treatment recommendations are based on categories of CVD risk (“low-to-moderate”, “high”, and “very high”). The cut-off risk levels for these categories are numerically different for various age groups to avoid undertreatment in the young and to avoid overtreatment in the elderly. As age is a major driver of CVD risk, but lifelong risk factor treatment benefit is higher in younger people, the risk thresholds for considering treatment are lower for younger people as per the ESC guidelines. Treatment decisions should be made with shared decision-making valuing patient preference.  

Option A is INCORRECT- there is a lack of convincing evidence that echocardiography improves CVD risk reclassification, and it is NOT recommended to improve CV risk prediction. (Class III, LOE B) 

Option B is INCORRECT- simply doing nothing is not appropriate for this patient with elevated CVD risk.  

Option C is CORRECT- This patient has a seemingly low 10-year CVD risk based on SCORE 2 of 3% and her SBP is controlled; however, given her age she is considered as having high CVD risk, therefore treatment should be considered. Stepwise approach involves targeting LDL <100 (class IIa) so initiating a statin would be appropriate. This patient also carries several risk enhancing modifiers including Pakistani ethnicity, family history of premature CVD, and inflammatory comorbidity. All patients should be counseled on smoking cessation, lifestyle modifications, and target SBP <160 mmHg. 

Option D is INCORRECT- repeating a lipid panel without risk factor modification will not change treatment recommendations for this patient with elevated CVD risk.  

Main Takeaway 

In summary, when a patient <50 years old without established ASCVD has an estimated 10-year risk 2.5 to <7.5% they are considered high CVD risk and risk factor treatment should be considered. Risk modifiers should also be taken into consideration. 

*Of note- ACC/AHA guidelines recommend the ASCVD risk calculator to estimate 10-year risk and do not restructure CVD risk groups according to age groups. High risk in the ACC/AHA guidelines is considered to be >20%. 

Guideline Location

• Table 5 and Figure 5, Page 3251
• 3.2.3.4, Page 3253
• 3.2.3, Figure 6 page 3252
• 3.3, Pages 3258-3259 

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CardioNerds (Amit Goyal and Daniel Ambinder) and guest host, Dr. Priya Kothapalli (UT Austin fellow and CardioNerds Ambassador), join SUNY Downstate cardiology fellows, Dr. Eric Kupferstein and Dr. Gautham Upadhya to discuss a case about a patient who had coronary artery bypass grafting that was complicated by a LIMA grafted to the great cardiac vein. Dr. Alan Feit (Professor of Medicine, SUNY Downstate) provides the E-CPR for this episode. Dr. Moritz Wyler von Ballmoos (Director, robotic cardiac and vascular surgery for Houston Methodist Cardiovascular Surgery Associates) provides a special perspective regarding coronary artery bypass grafting as it relates to this case. Episode introduction with CardioNerds Clinical Trialist Dr. Jana Lovell (Johns Hopkins).

Left Internal Mammary Artery (LIMA) to Left Anterior Descending (LAD) artery anastomosis is the cornerstone of Coronary Artery Bypass Graft (CABG) surgery. Anastomosis of the LIMA to the Great Cardiac Vein (GCV) is a known but rare complication of the surgery. Currently there are no clear guidelines in regard to further management. We report a case of a LIMA to GCV anastomosis managed with a drug eluting stent (DES) to the mid LAD after ruling out a significant left to right heart shunt.

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1. Listen to the patient’s story. The patient determines when the angina is no longer stable angina.
2. The placebo effect of our interventions should not be discounted.
3. LIMA to GCV anastomosis creates a left to right cardiac shunt. A Qp:Qs greater than 1.5 signifies a significant shunt.
4. Increasing the pressure in the coronary sinus may actually be beneficial to the patient.
5. LIMA-LAD is remains the most efficacious and long lasting graft but why not other arterial grafts?

Iatrogenic anastomosis of the LIMA to the GCV is a rare but noted complication of CABG surgery. Review of the literature has reported under 40 such cases of arteriovenous fistula formation in the coronary system. Detection of the anastomosis generally stems from recurrent angina which can be attributed to unresolved ischemia or coronary steal syndrome but also can be detected with new heart failure (namely right sided heart failure due to left to right shunting). Diagnosis is usually made with coronary angiography, but CT coronary angiography has also been reported. Due to the rarity of this complication, no clear guidelines are in place directing the management leaving it to the discretion of the various Heart Teams. Evaluating for signs of heart failure and/or ischemia, and measuring the Qp:Qs have been the most common signs directing management. Various options are available for closing the fistula and include coil or balloon embolization, vascular plugs, venous ligation or a covered stent. Redoing the surgery is also an option. Spontaneous closure of the fistula has also been reported. Lastly, if redo surgery is not performed then regardless of fistula closure, coronary intervention for the native diseased artery may be pursued to relieve symptoms.

1. Boden et al; COURAGE Trial Research Group. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007 Apr 12;356(15):1503-16. doi: 10.1056/NEJMoa070829. Epub 2007 Mar 26. PMID: 17387127.
2. Maron et al; ISCHEMIA Research Group. Initial Invasive or Conservative Strategy for Stable Coronary Disease. N Engl J Med. 2020 Apr 9;382(15):1395-1407. doi: 10.1056/NEJMoa1915922. Epub 2020 Mar 30. PMID: 32227755; PMCID: PMC7263833.
3. Klocke et al; ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging–executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). J Am Coll Cardiol. 2003 Oct 1;42(7):1318-33. doi: 10.1016/j.jacc.2003.08.011. PMID: 14522503.
4. Chow et al; Diagnostic accuracy and impact of computed tomographic coronary angiography on utilization of invasive coronary angiography. Circ Cardiovasc Imaging. 2009 Jan;2(1):16-23. doi: 10.1161/CIRCIMAGING.108.792572. PMID: 19808560.
5. Sheiban et al; Iatrogenic left internal mammary artery-coronary vein anastomosis treated with covered stent deployment via retrograde percutaneous coronary sinus approach. Catheter Cardiovasc Interv. 2006 Nov;68(5):704-7. doi: 10.1002/ccd.20842. PMID: 17039511.
6. Lumley et al; Inadvertent left internal mammary artery (LIMA): great cardiac vein anastomosis. BMJ Case Rep. 2013 Feb 15;2013:bcr2012007450. doi: 10.1136/bcr-2012-007450. PMID: 23417930; PMCID: PMC3618535.
7. Stout et al; AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019 Apr 2;73(12):e81-e192. doi: 10.1016/j.jacc.2018.08.1029. Epub 2018 Aug 16. Erratum in: J Am Coll Cardiol. 2019 May 14;73(18):2361-2362. PMID: 30121239.
8. Olshansky B. Placebo and nocebo in cardiovascular health: implications for healthcare, research, and the doctor-patient relationship. J Am Coll Cardiol. 2007 Jan 30;49(4):415-21. doi: 10.1016/j.jacc.2006.09.036. Epub 2007 Jan 16. PMID: 17258086.
9. Ido et al; Coronary sinus occlusion enhances coronary collateral flow and reduces subendocardial ischemia. Am J Physiol Heart Circ Physiol. 2001 Mar;280(3):H1361-7. doi: 10.1152/ajpheart.2001.280.3.H1361. PMID: 11179085.
10. Banai et al; Coronary sinus reducer stent for the treatment of chronic refractory angina pectoris: a prospective, open-label, multicenter, safety feasibility first-in-man study. J Am Coll Cardiol. 2007 May 1;49(17):1783-9. doi: 10.1016/j.jacc.2007.01.061. PMID: 17466229.
11. Gaudino et al; ATLANTIC (Arterial Grafting International Consortium) Alliance members. Arterial Grafts for Coronary Bypass: A Critical Review After the Publication of ART and RADIAL. Circulation. 2019 Oct 8;140(15):1273-1284. doi: 10.1161/CIRCULATIONAHA.119.041096. Epub 2019 Oct 7. PMID: 31934782.

CardioNerds (Daniel Ambinder), ACHD series co-chair,  Dr. Josh Saef (ACHD fellow at University of Pennsylvania), and ACHD FIT lead Dr. Charlie Jain (Mayo Clinic) join ACHD expert Dr. George Lui (Medical Director of The Adult Congenital Heart Program at Stanford and Program Director for the ACGME adult congenital heart disease fellowship at Stanford) to discuss Tetrology of Fallot. Audio editing by CardioNerds Academy Intern, Dr. Leticia Helms.

Tetralogy of Fallot (ToF) is the most common cyanotic heart disease and one of the most common congenital heart diseases that we see in adults overall. The anatomy includes a ventricular septal defect (VSD), an overriding aorta, and infundibular hypertrophy with subpulmonic +/- pulmonic valvular +/- supravalvular stenosis, which causes severe RV outflow obstruction and subsequent RV hypertrophy. Patients require surgery during childhood, which includes patching the VSD and relieving RV outflow obstruction. This results in pulmonic regurgitation (usually severe) and patients can live with this for decades. Adults with ToF commonly will require pulmonic valve replacement, potential relief of subvalvular or supravalvular stenoses, and tricuspid valve repair (for functional tricuspid regurgitation caused by RV dilation). These patients are at increased risk of atrial and ventricular arrhythmias and may warrant prophylactic ICDs.

The CardioNerds Adult Congenital Heart Disease (ACHD) series provides a comprehensive curriculum to dive deep into the labyrinthine world of congenital heart disease with the aim of empowering every CardioNerd to help improve the lives of people living with congenital heart disease. This series is multi-institutional collaborative project made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Josh Saef, Dr. Agnes Koczo, and Dr. Dan Clark.

The CardioNerds Adult Congenital Heart Disease Series is developed in collaboration with the Adult Congenital Heart Association, The CHiP Network, and Heart University. See more

Disclosures: None

Pearls • Notes • References • Guest Profiles • Production Team

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1. Tetralogy of Fallot is the most common cyanotic heart disease and the 4 anatomic features are: VSD, infundibular hypertrophy (with RVOT obstruction), overriding aorta, and RV hypertrophy. The most common lesion you will see in adults with repaired Tetralogy of Fallot is pulmonic regurgitation.
2. Pulmonic regurgitation (PR) can be easy to miss on exam as the murmur is brief and even shorter when the PR is severe. In patients with PR and aortic regurgitation, remember PR is clearest when laying supine, in comparison to aortic regurgitation which is loudest while leaning forward.
3. Patients with ToF may also have coronary anomalies (e.g. LAD off RCA), right-sided aortic arches, and also left-sided heart disease (LV diastolic or systolic dysfunction).
4. Patients with ToF are at risk for atrial and ventricular arrhythmias, and clinicians should consider prophylactic ICD for those with multiple risk factors for sudden death (e.g. QRS >180ms, scar on MRI).
5. In all patients with congenital heart disease, inspection is a key part of the physical exam (e.g. right thoracotomy could clue you into a prior BTT shunt) and in patients with prior BTT shunts and/or prior brachial cut-downs (look in the antecubital fossa for scars), radial arterial access is discouraged.

1. What is the embryologic origin of Tetrology of Fallot (i.e. anterocephalad deviation of spiral septum)?

With Tetralogy of Fallot, the most important considerations are in the embryology of the primitive outflow tract. 

• In normal anatomy, early in gestation, the outflow tract starts as a hollow tube termed the conotruncus. Neural crest tissue migrates into the tube and forms two major collections of endocardial cushion tissue. The collections develop opposite each other, rotating in a counterclockwise spiral through the entire conotruncus. These cushions then grow into balanced left and right ventricular outflow tracts and fuse with the interventricular septum inferiorly.
• In ToF, there is 1) anterocephalad deviation of the muscular outlet septum which causes a large interventricular communication (i.e. VSD) to form underneath the aortic valve, and 2) abnormal arrangement of the septoparietal trabeculations. These 2 abnormalities cause RV outflow obstruction and subsequent RV hypertrophy.1 There can be a wide spectrum of disease from isolated subpulmonic obstruction with a relatively small VSD to a large VSD with near pulmonary valve atresia.
• Most patients with Tetralogy do not have an identifiable genetic mutation. However, up to 15% may have some type of genetic syndrome, most commonly 22q11 microdeletion (Velocardiofacial, or DiGeorge syndrome).2 This is clinically relevant because 22q11 microdeletion is an autosomal dominant mutation thus impacts pre-conception counseling in patients considering pregnancy.

2. What are the key features of ToF anatomy (e.g. VSD, RVOT obstruction, overriding aorta, RVH)?

• The classic 4 abnormalities originally described by Dr. Fallot in 1888 are 1) RVOT obstruction (always subvalvular +/- valvular/supravalvular), 2) interventricular communication/VSD, 3) aortic override, 4) RV hypertrophy which occurs secondary to the obstruction.
• This is repaired by closure of the VSD, relief of obstructive RVOT muscle, and relief of any potential pulmonic valve or supravalvular stenosis. Commonly the pulmonic annulus is hypoplastic, and traditionally was treated with enlargement with a transannular patch. This causes severe pulmonic regurgitation.
• Associated anomalies include right aortic arch, atrial septal defect, and less commonly AV canal defects.
• Coronary anomalies are common and one of the most common is an anomalous LAD off of the RCA. This is particularly relevant as its course over the RVOT complicates the surgical approach.

3. What are the hemodynamic consequences of the above structural abnormalities (e.g. RVOT obstruction, VSD shunting)?

• Prior to any repair, the RVOT obstruction is dynamic and in ways comparable to hypertrophic cardiomyopathy, but with the twist that is the VSD. “Blue Tets,” or patients who had cyanosis, had significantly decreased pulmonary blood flow from severe RV outflow obstruction and would have worsened symptoms from hypoxemia and low flow by anything that worsened pulmonary blood flow. This would be worsened in situations which caused stress (faster HR, smaller ventricle, more obstruction), hyperventilation and /or hypoxemia (higher pulmonary vascular resistance), or exercise (faster HR and also SVR drops more than PVR). These so called “Tet Spells” could be improved by increasing venous return to the right heart and/or increasing systemic vascular resistance. These can both be achieved by squatting, thus children with unrepaired Tetralogy will do this almost instinctively and in babies with cyanosis during crying the parents will be instructed to bring the babies legs toward the chest.3
• “Pink Tets” on the other hand have relatively mild obstruction to RV outflow and therefore have a lot of VSD flow from LV to the pulmonary vascular tree. This can cause left heart volume overload and CHF early on in life. If this goes uncorrected for a long time, it can predispose to pulmonary vascular disease. “Pink Tets” over time may develop worsened RV outflow obstruction and subsequently become “Blue Tets.”

4. How would an adult with corrected ToF anatomy present (e.g., VT, RV failure, PV endocarditis)?

• As above, the most common lesion in adults with repaired Tetralogy is severe pulmonic regurgitation. While this may be tolerated for decades, pulmonic valve replacement is indicated when the patient has:4
  • ≥ moderate PR with symptoms (commonly fatigue, decreased exertional capacity)
  • Asymptomatic but has at least 2 of the following:
    • >mild RV or LV dysfunction
      • Severe RV enlargement (EDVi >160 or ESVI >80 or >2x LVEDV)
      • RVSP >2/3 LVSP
      • Reduction in objective exercise tolerance

• Transcatheter pulmonic valve replacements are being performed in many patients now, both with prior valve replacements (valve-in-valve) and also those with native outflow tracts. These interventions are likely changing the “natural” history of Tetralogy as now patients can avoid more trips to the operating room and the risks and debilitation that come along with it. That being said, patients with concomitant lesions (e.g., severe tricuspid regurgitation, small pulmonic annulus, multilevel RVOT obstruction) may still be best served by surgery.
• All patients with valve disease, particularly those with multiple prosthetic valve interventions are at increased risk of endocarditis. As many patients with ACHD have prostheses starting at a young age, they are at significantly increased risk of endocarditis over their lifetime. Dental hygiene should be discussed at every routine visit.
• Right bundle branch block is ubiquitous in Tetralogy given the septal anatomy and VSD patching.
• Patients with Tetralogy are at increased risk of both atrial and ventricular arrhythmias. Some patients may benefit from prophylactic ICD but we should always address underlying hemodynamic/structural lesions first. Risk factors for sudden death include:
  • QRS >180 ms
  • Multiple prior operations
  • Older age at repair
  • LV dysfunction (potentially even diastolic)4, 5

• ICDs are not benign! Inappropriate shocks are not uncommon and given the young age at which they are placed, patients are at increased risk for device infections over their lifetime.
• Aortic root dilation is seen in 30-50% of patients, though rarely (<5% patients) does this require intervention.4, 6

5. What makes your heart flutter about ACHD?

• Every patient is a history lesson! We learn a lot from our patients and every day are humbled by all they have gone through.
• There is a wide spectrum of presentation of each disease! Some patients with Tetralogy will have complicated surgical history such as the one presented here whereas others may go their whole life with only one or two surgeries! For example, Olympic and X-Games champion snowboarder Shaun White has Tetralogy of Fallot!
• It is an incredible interplay of anatomy and physiology. Every day we are challenged to apply what we know from acquired heart disease to our patient with unique anatomy and think about whether or not the fundamentals we usually rely on hold true here. For instance, patients with severe pulmonic regurgitation may have unimpressive murmurs because of the rapid equalization of PA and RV pressures. On echocardiography, the jet can be very rapid on color and CW Doppler and may even be called trivial by someone not familiar with looking at severe PR. We always have to be on our toes and think critically for our patients.
• ACHD incorporates all fields of cardiology – imaging, heart failure, electrophysiology, interventional, etc… and we have opportunities to be involved with all of these subspecialties – doing TEEs, hemodynamic catheterizations, caring for patients in the ICU. Furthermore, we work closely with surgeons and care closely for post-operative patients.

1.         Anderson RH, Spicer DE, Giroud JM, Mohun TJ. Tetralogy of Fallot: nosological, morphological, and morphogenetic considerations. Cardiol Young. Dec 2013;23(6):858-66. doi:10.1017/S1047951113001686

2.         Beauchesne LM, Warnes CA, Connolly HM, et al. Prevalence and clinical manifestations of 22q11.2 microdeletion in adults with selected conotruncal anomalies. J Am Coll Cardiol. Feb 15 2005;45(4):595-8. doi:10.1016/j.jacc.2004.10.056

3.         Kothari SS. Mechanism of cyanotic spells in tetralogy of Fallot–the missing link? Int J Cardiol. Oct 1992;37(1):1-5. doi:10.1016/0167-5273(92)90125-m

4.         Stout KK, Daniels CJ, Aboulhosn JA, et al. 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. Apr 2 2019;139(14):e698-e800. doi:10.1161/CIR.0000000000000603

5.         Khairy P, Aboulhosn J, Gurvitz MZ, et al. Arrhythmia burden in adults with surgically repaired tetralogy of Fallot: a multi-institutional study. Circulation. Aug 31 2010;122(9):868-75. doi:10.1161/CIRCULATIONAHA.109.928481

6.         Mongeon FP, Gurvitz MZ, Broberg CS, et al. Aortic root dilatation in adults with surgically repaired tetralogy of fallot: a multicenter cross-sectional study. Circulation. Jan 15 2013;127(2):172-9. doi:10.1161/CIRCULATIONAHA.112.129585

Adult Congenital Heart Association
Founded in 1998, the Adult Congenital Heart Association is an organization begun by and dedicated to supporting individuals and families living with congenital heart disease and advancing the care and treatment available to our community. Our mission is to empower the congenital heart disease community by advancing access to resources and specialized care that improve patient-centered outcomes. Visit their website (https://www.achaheart.org/) for information on their patient advocacy efforts, educational material, and membership for patients and providers

CHiP Network

The CHiP network is a non-profit organization aiming to connect congenital heart professionals around the world. Visit their website (thechipnetwork.org) and become a member to access free high-quality educational material, upcoming news and events, and the fantastic monthly Journal Watch, keeping you up to date with congenital scientific releases. Visit their website (https://thechipnetwork.org/) for more information.

Heart University
Heart University aims to be “the go-to online resource” for e-learning in CHD and paediatric-acquired heart disease. It is a carefully curated open access library of educational material for all providers of care to children and adults with CHD or children with acquired heart disease, whether a trainee or a practicing provider. The site provides free content to a global audience in two broad domains: 1. A comprehensive curriculum of training modules and associated testing for trainees. 2. A curated library of conference and grand rounds recordings for continuing medical education. Learn more at www.heartuniversity.org/

Dr. George Lui earned his medical degree from the Yale University School of Medicine in New Haven, Connecticut, and subsequently completed his combined medicine and pediatric residency training at Harvard University in Boston, Massachusetts. He completed his fellowship in adult cardiology and adult congenital heart disease at Columbia University Medical Center in New York, New York.

Dr. Lui is the Medical Director of The Adult Congenital Heart Program at Stanford, a Lucile Packard Children’s Hospital (LPCH) and Stanford Healthcare collaboration and Program Director for the ACGME accredited adult congenital heart disease fellowship at Stanford. Dr. Lui is also appointed Clinical Professor of Medicine and Pediatrics at Stanford University School of Medicine.

Dr. Lui is a board certified ACHD physician and has gained national recognition for both his clinical work and research. His research interests include management of adults with congenital heart disease, pregnancy and congenital heart disease, adolescent transition to adult care, and echocardiography.

Dr. Charlie Jain is currently in his Adult Congenital Heart Disease Fellowship at Mayo Clinic. He completed medical school at University of Illinois, Internal Medicine training at Massachusetts General Hospital, and general Cardiology at Mayo Clinic. He is interested in ACHD, non-invasive and invasive hemodynamic assessment, pulmonary hypertension, and cardio-obstetrics.

CardioNerds Rounds Co-Chairs, Dr. Karan Desai and Dr. Natalie Stokes and CardioNerds Academy Fellow, Dr. Najah Khan, join Dr. Martha Gulati – President-Elect of the American Society for Preventive Cardiology (ASPC) and prior Chief of Cardiology and Professor of Medicine at the University of Arizona – to discuss challenging cases in cardiac prevention. As an author on numerous papers regarding cardiac prevention and women’s health, Dr. Gulati provides many prevention pearls to help guide patient care. Come round with us today by listening to the episodes now and joining future sessions of #CardsRounds!

This episode is supported with unrestricted funding from Zoll LifeVest. A special thank you to Mitzy Applegate and Ivan Chevere for their production skills that help make CardioNerds Rounds such an amazing success. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds. Case details are altered to protect patient health information. CardioNerds Rounds is co-chaired by Dr. Karan Desai and Dr. Natalie Stokes. 

Speaker disclosures: None

Cases discussed and Show Notes • References • Production Team

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Case #1 Synopsis:

A 55-year-old South Asian woman presents to prevention clinic for an evaluation of an elevated LDL-C. Her prior history includes hyperlipidemia, hypertension, obesity, and pre-eclampsia. She was told she had “high cholesterol” a few years prior and would need medication. She started exercising regularly and cut out sweets from her diet. Before clinic, labs showed: Total Cholesterol (mg/dL) of 320, HDL 45, Triglycerides 175, and (directly measured) LCL-C 180. Her Lipoprotein(a) is 90 mg/dL (ULN being ~ 30 mg/dL). Her HbA1C is 5.2% and her 10-year ASCVD Risk (by the Pooled Cohorts Equation) is 5.4%. Her recent CAC score was 110. She prefers not to be on medication and seeks a second opinion.

Takeaways from Case #1

1. As Dr. Gulati notes, in the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease, South Asian ethnicity is considered a “risk enhancing factor.” The pooled cohort equations (PCE) may underestimate risk in South Asians. Furthermore, risk varies within different South Asian populations, with the risk for cardiovascular events seemingly higher in those individuals of Bangladeshi versus Pakistani or Indian origin. There are multiple hypotheses for why this may be the case including cultural aspects, such as diet, physical activity, and tobacco use. A better understanding of these factors could inform targeted preventive measures.
2. In the same 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease mentioned above, history of an adverse pregnancy outcome (APO) increases later ASCVD risk (e.g., preeclampsia) and is also included as a “risk-enhancing factor.” Studies have shown that preeclampsia is an independent risk factor for developing early onset coronary artery calcification.
3. Recent data has shown that the risk for developing preeclampsia is not the same across race and ethnicity, with Black women more likely to develop preeclampsia. Black women also had the highest rates of peripartum cardiomyopathy, heart failure, and acute renal failure. After adjustment for socioeconomic factors and co-morbidities, preeclampsia was associated with increased risk of CVD events in all women, the risk was highest among Asian and Pacific Islander women. Listen to Episode #174. Black Maternal Health with Dr. Rachel Bond to learn more about race-based disparities in cardio-obstetric care and outcomes.
4. Our patient thus has multiple risk-enhancing factors to help in shared decision making and personalize her decision for statin use. Another risk-enhancing factor for her is an elevated Lp(a), which is considered elevated when ≥ 50 mg/dL or ≥ 125 nmol/L.
5. One other aspect that Dr. Gulati briefly covered was how CAC score may inform Aspirin use for primary prevention. There continues to be debate over when to prescribe aspirin when there is demonstrable calcium on imaging. In the MESA study, for individuals with CAC ≥ 100, the NNT (for 5 years to prevent an ASCVD event) was a 140 and NNH was 518.

Case #2 Synopsis:

A 58-year-old woman presents to establish care at a general cardiology clinic for shortness of breath. Her history includes hypertension, cutaneous lupus, and ongoing tobacco use. A year ago, she started having nausea, more common with stress or on exertion. She saw her PCP who obtained an EKG and GI evaluation. Endoscopy was unrevealing and EKG showed non-specific ST-T changes inferiorly. She was treated for GERD and then 6 months prior she developed dyspnea on exertion while exercising on her stationary bike after 10 minutes; she previously could go 30 minutes. She suffered a left knee meniscal tear shortly thereafter. She sees a cardiologist and obtains a cardiac PET-Stress which showed a small area of reversible ischemia in the basal to mid inferior wall and borderline reduced coronary flow reserve. Her symptoms continued and she was referred for LHC which showed non-obstructive CAD. No intracoronary physiologic testing was done. She is started on aspirin but still having symptoms. She seeks your opinion on how to prevent cardiovascular events.

 Takeaways Case #2

1. In the VIRGO study, investigators interviewed 2009 women and 976 men aged 18 to 55 years hospitalized for acute myocardial infarction (AMI) at 103 United States hospitals. Approximately 29.5% of women and 22.1% of men sought medical care for similar chest pain symptoms before their hospitalization; however, 53% of women reported that their provider did not think these symptoms were heart-related in comparison with 37% of men (p < 0.001).
2. As Dr. Gulati noted, angiographically obstructive CAD is just the tip of the iceberg when it comes to ischemic heart disease. There are several important phenotypes including diffuse non-obstructive CAD and coronary microvascular dysfunction. Dr. Gulati shared the following image to demonstrate how ischemic heart disease is a unifying term for different syndromes.

Academy Fellow, Dr. Najah Khan, has created the following infographic that provides a distinction between INOCA (ischemia and no obstructive coronary artery disease) and MINOCA (myocardial infarction with non-obstructive coronary arteries).

Case #3 Synopsis:

A 50-year-old man presents to cardiology clinic after a STEMI. His history includes hypertension, diabetes, obesity, and prior tobacco use. Four months ago, the patient suffered an inferior STEMI complicated by VF arrest treated with PCI to the proximal RCA. There was significant residual CAD and tentative plan for staged CABG. The patient was discharged on Aspirin, Prasugrel, Metoprolol Succinate, Lisinopril, Metformin and Atorvastatin. However, he started having muscle aches and so he stopped his Atorvastatin. He sees his PCP and before clinic gets a Lipid Panel (mg/dL) with Total Ch at 230, TG 237, HDL at 36 and LDL-C at 140. The patient starts ezetimibe and then comes to see you a month later to discuss best secondary prevention measures.

Case #3 Takeaways:

1. There are multiple opportunities for secondary prevention following acute coronary syndrome, with many patients undertreated. This includes but not limited to LDL-lowering medications, smoking cessation, cardiac rehabilitation, blood pressure control, diabetes management, weight loss, and targeting non-LDL particles when appropriate.
2. Dr. Gulati points out that we need to make sure we categorize a patient’s risk appropriately, including patients at “very high risk” of ASCVD. This requires multiple ASCVD events (recent ACS, history of MI, history of ischemic stroke, symptomatic PAD) or an ASCVD event with multiple high-risk conditions (e.g., Age ≥ 65, heterozygous familial hypercholesterolemia, history of prior CABG or PCI outside of major ASCVD events, diabetes, hypertension, CKD, current tobacco use, persistently elevated LDL-C despite max statin therapy and ezetimibe, and/or history of congestive heart failure).
3. Patients at very high risk of ASCVD should be on a high intensity statin or maximally tolerated statin (Class I). If PCSK9 inhibitors are considered, it is Class I to add ezetimibe to maximal statin therapy before initiating PCSK9i. If a patient is deemed to be on the maximal LDL-C lowering therapy that s/he is able to tolerate but LDL-C remains ≥ 70 mg/dL or non-HDL-C ≥ 100 mg/dL, adding PCSK9i is reasonable (Class IIa).
4. A take home message from Dr. Gulati is that after more than a quarter century of treating LDL-C, generally the lower we can drive LDL-C levels the better for patient outcomes.

1. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Sep 10;140(11):e596-e646. doi: 10.1161/CIR.0000000000000678. Epub 2019 Mar 17. Erratum in: Circulation. 2019 Sep 10;140(11):e649-e650. Erratum in: Circulation. 2020 Jan 28;141(4):e60. Erratum in: Circulation. 2020 Apr 21;141(16):e774. PMID: 30879355; PMCID: PMC7734661.
2. Benschop L, Brouwers L, Zoet GA, et al. Early Onset of Coronary Artery Calcification in Women With Previous Preeclampsia. Circ Cardiovasc Imaging. 2020 Nov;13(11):e010340. doi: 10.1161/CIRCIMAGING.119.010340. Epub 2020 Nov 16. PMID: 33190533.
3. Cainzos-Achirica M, Miedema MD, McEvoy JW, et al. Coronary Artery Calcium for Personalized Allocation of Aspirin in Primary Prevention of Cardiovascular Disease in 2019: The MESA Study (Multi-Ethnic Study of Atherosclerosis). Circulation. 2020 May 12;141(19):1541-1553. doi: 10.1161/CIRCULATIONAHA.119.045010. Epub 2020 Apr 1. PMID: 32233663; PMCID: PMC7217722.
4. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019 Jun 25;73(24):3168-3209. doi: 10.1016/j.jacc.2018.11.002. Epub 2018 Nov 10. Erratum in: J Am Coll Cardiol. 2019 Jun 25;73(24):3234-3237. PMID: 30423391.
5. Lichtman JH, Leifheit EC, Safdar B, et al. Sex Differences in the Presentation and Perception of Symptoms Among Young Patients With Myocardial Infarction: Evidence from the VIRGO Study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients). Circulation. 2018 Feb 20;137(8):781-790. doi: 10.1161/CIRCULATIONAHA.117.031650. PMID: 29459463; PMCID: PMC5822747.
6. Minhas AS, Ogunwole SM, Vaught AJ, et al. Racial Disparities in Cardiovascular Complications With Pregnancy-Induced Hypertension in the United States. Hypertension. 2021 Aug;78(2):480-488. doi: 10.1161/HYPERTENSIONAHA.121.17104. Epub 2021 Jun 8. PMID: 34098730; PMCID: PMC8266726.
7. Volgman AS, Palaniappan LS, Aggarwal NT et al. Atherosclerotic Cardiovascular Disease in South Asians in the United States: Epidemiology, Risk Factors, and Treatments: A Scientific Statement From the American Heart Association. Circulation. 2018 Jul 3;138(1):e1-e34. doi: 10.1161/CIR.0000000000000580. Epub 2018 May 24. Erratum in: Circulation. 2018 Jul 31;138(5):e76. PMID: 29794080.

CardioNerds (Amit Goyal), Dr. Natalie Stokes (Cardiology Fellow at UPMC and Co-Chair of the Cardionerds Cardio-Ob series), and episode lead Dr. Priya Freaney (Northwestern University cardiology fellow) discuss “The Fourth Trimester” with Dr. Malamo Countouris and Dr. Alisse Hauspurg, from the University of Pittsburgh Departments of Cardiology and Obstetrics and Gynecology, respectively. We discuss the cardiovascular considerations after adverse pregnancy outcomes in the postpartum and long-term follow-up periods. The discussion is focused mainly on hypertensive disorders of pregnancy (HDP), guided by a series of clinical vignettes. We cover a wide range of topics from cardiovascular complications and management considerations in the immediate postpartum period after a HDP, postpartum outpatient follow-up, long term cardiovascular morbidity related to HDP and related preventive strategies, contraceptive considerations for the cardiologist, and interdisciplinary care management pearls for cardiologists working in a cardio-obstetrics team.

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1. Blood pressures >160/110 should be treated like a true emergency during pregnancy and the postpartum period, as the cerebrovascular circulation is more sensitive to hypertension, due to hormonal changes related to pregnancy.
2. Women with pre-eclampsia are at higher risk for peripartum cardiomyopathy. Have a low threshold to do a clinical heart failure evaluation (i.e., natriuretic peptides, echocardiogram), and administer diuretics as appropriate to improve volume status and blood pressure.
3. Women with HDP should have their blood pressures monitored closely after discharge, ideally with a home BP monitoring program, as they can have exacerbations of their HTN for up to 2 weeks postpartum.
4. The American Rescue Plan Act of 2021 included a landmark policy to extend postpartum Medicaid coverage up to a year postpartum (from 60 days).
5. Remember to take a reproductive history for every woman you see in cardiology clinic! This can be done in one minute. At a minimum, include obstetric history [number of pregnancies, outcome of each pregnancy, gestational age and weight at delivery, pregnancy complications (HDP, GDM, etc), and delivery method] and menopausal history (age at menarche, age at menopause).
6. The Pooled Cohort Equations may underestimate ASCVD risk for a woman who has had pregnancy complications or premature menopause – consider obtaining a CAC score to aid in risk-stratification in middle-aged women who may have underestimated risk.
7. Low dose aspirin during pregnancy in women who have risk factors for pre-eclampsia reduces the risk of development of HDP by 15-20%.

1. “Some of our traditional approaches to caring for women in the postpartum period just aren’t realistic…we need to think about how we can improve care from a policy standpoint to ensure women have access to care and think about how we deliver care.” – Dr. Alisse Hauspurg

1. “Silos are never good. Cardio-obstetrics is a space where you really want to have open communications, be truly collaborative – taking into consideration the expertise of multiple disciplines…because it’s really hard to do it alone.” – Dr. Malamo Countouris

For more on hypertensive disorders of pregnancy enjoy:

• Episode #128: Cardio-Obstetrics: Hypertensive Disorders of Pregnancy with Dr. Jennifer Lewey
• Episode #66: Case Report: Severe Pre-eclampsia & Cardio-Obstetrics – UPMC

1.     What are some of the immediate postpartum cardiovascular risks and complications following a hypertensive disorder of pregnancy (HDP) and how do you manage these?

• Persistent hypertension: there can be a spike in BP in the days following delivery, and clinicians should remember that preeclampsia may develop de novo intra- or early postpartum. BPs >160/110 are considered severe HTN and should be treated urgently with an aggressive rapid-acting anti-HTN regimen to prevent stroke. BPs should be monitored at least every 4 to 6 hours for at least 3 days postpartum.1 A return visit for BP monitoring should be arranged at 1 week following discharge; alternatively, a home BP monitoring program may be considered
• Pulmonary edema: Women with preeclampsia should be delivered if they develop pulmonary edema. This is more likely to occur in women who have more severe preeclampsia features. Clinical practice guidelines suggest limiting intrapartum fluid intake/replacement to 60-80mL/h to avoid risks of pulmonary edema, with a goal euvolemic fluid balance.1
• Peripartum cardiomyopathy: Preeclampsia, gestational hypertension, and chronic hypertension all strongly predispose women to peripartum cardiomyopathy (PPCM). PPCM is defined as cardiomyopathy with reduced EF, usually EF <45%, presenting toward the end of pregnancy or in the months following delivery in a woman without previously known structural heart disease.2 The two diseases are thought to share pathophysiologic mechanisms.3 If heart failure is suspected via clinical assessment in a woman with HDP in the intrapartum or immediate postpartum period, an echocardiogram should be performed immediately. Treatment of PPCM is similar to other forms of systolic heart failure – with control of volume status, implementation of neurohormonal blockade, and prevention of arrhythmic and thromboembolic complications.4
• Venous thromboembolism: Women with HDP are at higher risk for DVT/PE during pregnancy, postpartum period, and in the decades following pregnancy.5
• CVA: Severe uncontrolled HTN (>160/110) in the intra- and post-partum periods are associated with increased risk for stroke. BPs should be aggressively managed (see above) in the postpartum period to avoid this complication. 

2.     How should women who have had a HDP be followed in the postpartum period? What are the healthcare coverage considerations in the postpartum period?

• Blood pressures should be monitored closely in the postpartum period, especially in the 2 weeks following delivery – either via return in-person visits or a home BP monitoring program with remote visits
• Depending on the location of care, specialized postpartum cardio-obstetrics clinics may or may not exist. Regardless, women with HDP history should be counseled (whether by OB, cardiology, PCP, etc.) regarding their long-term risk for cardiovascular disease
• They should be counseled on the importance of optimizing their cardiovascular health (with maintenance of optimal weight and regular aerobic exercise).
• In addition to regular BP monitoring, these women should have periodic monitoring of their fasting lipids and blood sugars1
• Until recently, Medicaid coverage for pregnant women extended only 60 days postpartum, leaving many women uninsured just 2 months after delivery. In March 2021, the American Rescue Plan Act of 2021 was passed and calls for extension of Medicaid coverage from 60 days to 12-months postpartum.

3.     What are the long-term cardiovascular complications related to HDPs?

• A history of HDP increases a woman’s risk of a diverse range of long-term cardiovascular risk factors and cardiovascular diseases (including HTN, CAD, Stroke, HF, and CV Mortality) (see figure below)6

• Heart failure: A wide spectrum of changes in LV structure and function have been described in association with HDP. This includes increased LV wall thickness, adverse LV remodeling, and diastolic dysfunction (see below).7 Women with HDP also have been shown to have lower global longitudinal strain without overt systolic dysfunction8, PPCM (as described above) and later life cardiomyopathy.9

• ASCVD: Women with pre-eclampsia are more likely to have atherosclerotic cardiovascular disease (CAD, CVA) than women without pre-eclampsia, independent of other traditional risk factors.6
  • Despite significant independent association of HDP with long-term ASCVD, there was no incremental benefit in 10-year ASCVD risk prediction when added to the Pooled Cohort Equations (see below)10

4.     How do you take a reproductive history in cardiology clinic?

• An optimal well-woman preventive cardiovascular visit should include a thorough reproductive history to identify adverse pregnancy outcomes and menstrual risk factors, amongst other sex-specific cardiovascular disease risk factors11
  • Obstetric history: ask about pregnancies complicated by HDP (eclampsia, pre-eclampsia, gestational hypertension), low birth weight (<2500 grams), preterm delivery (<37 weeks gestation), or gestational diabetes
  • Menstrual history: ask about age at menarche and presence of premature menopause (defined by most as menopause <40years and others as menopause <45 years). If premature menopause present, ask about natural versus surgical menopause (removal of both ovaries)

5.     What methods of contraception are optimal for women with a history of cardiovascular risk factors or cardiovascular disease?

• It is important to discuss contraceptive options in women with history of HDP, cardiovascular RFs, and cardiovascular disease
• Often, in these women, long-acting reversible contraception (LARC) such as IUDs and implants are best. Permanent sterilization procedures can also be considered if a woman has completed desired childbearing.
• Dr. Hauspurg highly recommends the following app from the CDC for those interested in medical eligibility criteria for various contraceptive methods, sorted by specific medical conditions:
  • https://www.cdc.gov/reproductivehealth/contraception/mmwr/mec/summary.html
  • Screenshots below of app in iPhone App Store and example of output from app for woman with history of HDP:

1.         Brown MA, Magee LA, Kenny LC, et al. Hypertensive Disorders of Pregnancy: ISSHP Classification, Diagnosis, and Management Recommendations for International Practice. Hypertension. Jul 2018;72(1):24-43. doi:10.1161/HYPERTENSIONAHA.117.10803

2.         Sliwa K, Hilfiker-Kleiner D, Petrie MC, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of peripartum cardiomyopathy: a position statement from the Heart Failure Association of the European Society of Cardiology Working Group on peripartum cardiomyopathy. Eur J Heart Fail. Aug 2010;12(8):767-78. doi:10.1093/eurjhf/hfq120

3.         Bello N, Rendon ISH, Arany Z. The relationship between pre-eclampsia and peripartum cardiomyopathy: a systematic review and meta-analysis. J Am Coll Cardiol. Oct 29 2013;62(18):1715-1723. doi:10.1016/j.jacc.2013.08.717

4.         Arany Z, Elkayam U. Peripartum Cardiomyopathy. Circulation. Apr 5 2016;133(14):1397-409. doi:10.1161/CIRCULATIONAHA.115.020491

5.         Scheres LJJ, Lijfering WM, Groenewegen NFM, et al. Hypertensive Complications of Pregnancy and Risk of Venous Thromboembolism. Hypertension. Mar 2020;75(3):781-787. doi:10.1161/HYPERTENSIONAHA.119.14280

6.         Ying W, Catov JM, Ouyang P. Hypertensive Disorders of Pregnancy and Future Maternal Cardiovascular Risk. J Am Heart Assoc. Sep 4 2018;7(17):e009382. doi:10.1161/JAHA.118.009382

7.         Countouris ME, Villanueva FS, Berlacher KL, Cavalcante JL, Parks WT, Catov JM. Association of Hypertensive Disorders of Pregnancy With Left Ventricular Remodeling Later in Life. J Am Coll Cardiol. Mar 2 2021;77(8):1057-1068. doi:10.1016/j.jacc.2020.12.051

8.         Shahul S, Rhee J, Hacker MR, et al. Subclinical left ventricular dysfunction in preeclamptic women with preserved left ventricular ejection fraction: a 2D speckle-tracking imaging study. Circ Cardiovasc Imaging. Nov 2012;5(6):734-9. doi:10.1161/CIRCIMAGING.112.973818

9.         Behrens I, Basit S, Lykke JA, et al. Association Between Hypertensive Disorders of Pregnancy and Later Risk of Cardiomyopathy. JAMA. Mar 8 2016;315(10):1026-33. doi:10.1001/jama.2016.1869

10.       Stuart JJ, Tanz LJ, Cook NR, et al. Hypertensive Disorders of Pregnancy and 10-Year Cardiovascular Risk Prediction. J Am Coll Cardiol. Sep 11 2018;72(11):1252-1263. doi:10.1016/j.jacc.2018.05.077

11.       Brown HL, Warner JJ, Gianos E, et al. Promoting Risk Identification and Reduction of Cardiovascular Disease in Women Through Collaboration With Obstetricians and Gynecologists: A Presidential Advisory From the American Heart Association and the American College of Obstetricians and Gynecologists. Circulation. Jun 12 2018;137(24):e843-e852. doi:10.1161/CIR.0000000000000582

12.       Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. Sep 10 2019;140(11):e596-e646. doi:10.1161/CIR.0000000000000678

Dr. Malamo Countouris is a Clinical Instructor and T32 Postdoctoral Scholar at UPMC Heart and Vascular Institute. She is primarily based at Magee Women’s Heart Center and specializes in women’s heart disease and cardio-obstetrics. Her research is focused on pregnancy complications and links with later life CVD.

Dr. Alisse Hauspurg is an Assistant Professor in the Department of Obstetrics and gynecology where she practices in Maternal Fetal Medicine. She is currently a K12 Scholar in the Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) program funded by the NIH/Office of Research on Women’s Health. Her research interests focus on mechanisms leading to cardiovascular disease after preeclampsia and development of remote and innovative postpartum interventions to improve long-term maternal cardiovascular health.

Dr. Priya Freaney is interested in preventive cardiology for women. She grew up in Kentucky, attended Duke for college, Ohio State for medical school, University of Chicago for her residency, and is now a 3rd year cardiology fellow at Northwestern University. She is a recent past chief fellow for her program and an ACC/Merck fellowship awardee this year for her work surrounding APO-related CVD.

CardioNerds (Amit Goyal & Karan Desai)  join Dr. Matthew Delfiner (Cardiology fellow, Temple University Hospital) and Dr. Katie Vanchiere (Internal medicine resident, Temple University Hospital) in the beautiful Fairmount Park in Philadelphia. They discuss a case of a 53-year-old man with an LVAD who presents with progressive dyspnea since LVAD implant due to right-to-left shunting due to a PFO. Dr. Val Rakita (Assistant professor of medicine and advanced heart failure and transplant specialist at Temple University Hospital) provides the E-CPR for this episode. Episode introduction by CardioNerds Clinical Trialist Dr. Anthony Peters (Duke Heart Center). This case has been published by Circulation: Heart failure. See Invasive Hemodynamic Study Unmasks Intracardiac Shunt With Ventricular Assist Device.

Claim free CME just for enjoying this episode! 

Disclosures: None
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A 53-year-old man with an LVAD placed 3 months prior presents with progressive dyspnea since LVAD implant, though it has acutely worsened over the past 2 weeks. Two weeks ago, he had a hemodynamic and echocardiographic ramp study, where the LVAD speed was increased. By increasing the speed, his LV was more adequately decongested, and flow improved. In the Emergency Department, he was hypoxic on room air, and remained so with escalation ultimately with intubation. Even then he remained severely hypoxic requiring cannulation to veno-venous ECMO.

Chest imaging was normal, and LVAD parameters were normal without any alarms. An astute clinician noticed that when the patient became hypertensive, his oxygen saturation improved. A subsequent echocardiogram revealed a patent foramen ovale, with right to left shunting. The patient then went to the cath lab, where simultaneous right atrial and left atrial pressures and oxygen pressures were measured, along with trans-esophageal echocardiography, while adjusting LVAD speed. It became evident that right-to-left shunting occurred only when there was high LVAD speed and low peripheral blood pressure. Essentially, faster LVAD speeds (sucking blood from the LV) and low systemic blood pressure (reducing LV afterload) increased right to left shunting by decreasing the left atrial pressure relative to the right atrial pressure. The PFO was closed at that time, drastically improving oxygenation. He was decannulated and extubated the following day.

Invasive Hemodynamic Study Unmasks Intracardiac Shunt With Ventricular Assist Device | Circulation: Heart Failure (ahajournals.org)

1. PFOs are present in up to 25% of individuals, including those with LVADs.
2. LV unloading, and therefore LA decompression, depends on both LVAD speed and systemic vascular resistance.
3. Blood pressure dependent hypoxia may be suggestive of a right-to-left intracardiac shunt.
4. Hypoxia refractory to mechanical ventilation should raise suspicion for intracardiac shunt.
5. Patients with LVADs can suffer from the same diseases that anyone can.

1. What factors influence LVAD flow?

Factors that influence LVAD flow include pump speed, blood pressure, volume status, RV function, cardiac rhythm, and some other variables. The faster the pump is spinning, the more flow you should provide (to an extent). However, if your LV is underfilled, either from systemic hypovolemia or an RV not providing the needed LV preload, then you have no blood to flow! If you have high systemic vascular resistance, then you will have less forward flow, just as a native heart would.  We must always think about the interaction between a patient and the LVAD, not just the machine settings.

2. What can cause dyspnea and hypoxia in LVAD patients?

The same things that cause dyspnea in any other patient! But also… inadequate unloading of the LV due to the above factors in addition to possible suction events. Aortic regurgitation can cause an endless loop of flow from: LV > LVAD > aorta > AV > LV. Pump malfunction must always be considered, including inflow/outflow obstruction and pump thrombosis. Anemia may also contribute, as patients with LVAD are prone to both bleeding and hemolysis.

3. What are the ideal LVAD settings?

There are no standard settings for LVADs, especially because there are different manufacturers. But most importantly, every patient is different, and therefore the patient-LVAD interaction is different. Overall, the ideal LVAD speed would decongest the heart while preserving RV function, maintaining the interventricular septum midline, and having intermittent aortic valve opening.

4. Explain how PFOs can result in hypoxemia.

PFOs, or any septal defect, allow intra-cardiac flow from one side of the heart to the other. Flow will follow a pressure gradient. Usually, the left heart will have higher pressures than the right heart, but if the right heart pressure exceeds the left, then de-oxygenated venous blood can bypass the pulmonary circulation and enter the left heart and systemic circulation, causing hypoxemia.

5. List the methods that are used to diagnose and evaluate the severity of intra-cardiac shunts.

Doppler color flow and bubble study with TTE or TEE. Blood gas measurement across various chambers can be used as well.

For an in-depth review of LVADs, enjoy Ep #15. LVAD 101 with Dr. Steve Hsu​.

Uriel, Nir, et al. “Clinical hemodynamic evaluation of patients implanted with a fully magnetically levitated left ventricular assist device (HeartMate 3).” The Journal of Heart and Lung Transplantation 36.1 (2017): 28-35.

Adamson, R. M., et al. “Single center, 23 year experience with PFO management during HeartMate LVAD implants.” The Journal of Heart and Lung Transplantation 34.4 (2015): S219.

Bacich, Daniela, et al. “Patent foramen ovale-related complications in left ventricular assist device patients: A reappraisal for cardiovascular professionals.” Journal of Artificial Organs 23.2 (2020): 98-104.

Burkhoff, Daniel, et al. “Hemodynamics of mechanical circulatory support.” Journal of the American College of Cardiology 66.23 (2015): 2663-2674.

Jaski, Brian E., et al. “Assessment of recurrent heart failure associated with left ventricular assist device dysfunction.” The Journal of heart and lung transplantation 24.12 (2005): 2060-2067.

Stainback, Raymond F., et al. “Echocardiography in the management of patients with left ventricular assist devices: recommendations from the American Society of Echocardiography.” Journal of the American Society of Echocardiography 28.8 (2015): 853-909.

CardioNerds, Daniel Ambinder and CardioNerds Academy Program Director, Dr. Tommy Das (Cardiology fellow, Cleveland Clinic), Dr. Jacqueline Latina (Structural heart fellow, Johns Hopkins) discuss aortic stenosis and the story of TAVR from both the historical perspective and in terms of future directions with Dr. Jon Resar, Professor of Medicine and Director of the Adult Catheterization Laboratory and Interventional Cardiology at the Johns Hopkins Hospital. This episode is brought to you for Heart Valve Disease Awareness Day. Audio editing by CardioNerds Academy Intern, Shivani Reddy.

As many as 11 million Americans have heart valve disease (HVD)—a potentially disabling and deadly disease—yet 3 out of 4 Americans know little to nothing about heart valve disease. Learn more about valve disease.

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(TAVR/TAVI are using interchangeably)

1. In the 1990s, patients with severe aortic stenosis (AS) who were deemed to be at high surgical risk would weigh the risks of surgery and prolonged recovery. Balloon Aortic Valvuloplasty (BAV) was first performed by Dr. Alain Cribier in 1986. The technique was based on the foundation of pulmonary valvuloplasty performed initially in 1982 by Drs. Jean Kan and Bob White, and mitral valvuloplasty in 1984. BAV was initially touted as an efficacious cure for aortic stenosis, but unfortunately it had a high restenosis rate as well as high risks for stroke and vascular complications (no closure devices at that time) with an overall poor long-term prognosis. Balloon aortic valvuloplasty was primarily used for decompensated Class IV heart failure in non-surgical candidates.

2. Transcatheter aortic valve replacement (TAVR/TAVI) was developed and first performed in human in 2002.(1) This was performed by Dr. Alain Cribier in France in 2002, initially by trans-septal approach and then by retroaortic approach. Here is a representative diagram of the procedure.

3. The PARTNER trial was first published in a landmark NEJM article in extreme surgical risk patients comparing TAVR (with a balloon-expandable aortic valve implant) versus stndard “medical” therapy of aortic stenosis. TAVR markedly reduced the composite outcome of all-cause mortality and repeat hospitalization in these patients.(2)  PARTNER then compared TAVR to aortic valve surgery in high risk patients, and TAVR performed quite well, though there were more strokes and vascular complications in the TAVR group compared to surgery.(3)

4. CoreValve/Medtronic then published their results for their self-expanding valve, enrolling over 1400 participants.(4) The rate of death in the TAVR group was non-inferior to the SAVR group, and a subsequent test for superiority actually showed TAVR was superior to surgery in these high risk patients.

5. Both balloon expandable (PARTNER 3) and self-expanding valves (Evolut Low Risk) have since been studied in intermediate and low surgical risk patients.(5-8)  In low risk patients, the balloon expandable valve showed the rate of the composite of death, stroke, or rehospitalization at 1 year was significantly lower with TAVR than with surgery. In low risk patients, TAVR with a self-expanding supraannular bioprosthesis was noninferior to surgery with respect to the composite end point of death or disabling stroke at 24 months.

6. Coronary artery disease in TAVR patients: the decision for coronary revascularization prior to TAVR is complex and practice is evolving. Initially, most patients were being revascularized for obstructive coronary artery stenosis electively prior to TAVR. More recently, if the disease is not proximal (or a small area of myocardium at risk) and if angina is not a prominent symptom, we have moved towards deferring coronary revascularization.

1. Cribier A, Eltchaninoff H, Tron C et al. Early experience with percutaneous transcatheter implantation of heart valve prosthesis for the treatment of end-stage inoperable patients with calcific aortic stenosis. J Am Coll Cardiol 2004;43:698-703.

2. Leon MB, Smith CR, Mack M et al. Transcatheter Aortic-Valve Implantation for Aortic Stenosis in Patients Who Cannot Undergo Surgery. New England Journal of Medicine 2010;363:1597-1607.

3. Smith CR, Leon MB, Mack MJ et al. Transcatheter versus Surgical Aortic-Valve Replacement in High-Risk Patients. New England Journal of Medicine 2011;364:2187-2198.

4. Adams DH, Popma JJ, Reardon MJ et al. Transcatheter Aortic-Valve Replacement with a Self-Expanding Prosthesis. New England Journal of Medicine 2014;370:1790-1798.

5. Leon MB, Smith CR, Mack MJ et al. Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients. N Engl J Med 2016;374:1609-20.

6. Reardon MJ, Van Mieghem NM, Popma JJ et al. Surgical or Transcatheter Aortic-Valve Replacement in Intermediate-Risk Patients. N Engl J Med 2017;376:1321-1331.

7. Popma JJ, Deeb GM, Yakubov SJ et al. Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients. N Engl J Med 2019;380:1706-1715.

8. Mack MJ, Leon MB, Thourani VH et al. Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients. N Engl J Med 2019;380:1695-1705.

Dr. Jon Resar received his medical degree from the Medical College of Wisconsin and completed fellowships in cardiovascular medicine and interventional cardiology at The Johns Hopkins Hospital where he serves as the director of the adult cardiac catheterization and serves as Professor of Medicine. He has been a pioneer in percutaneous management of coronary artery disease and structural heart disease.

Dr. Jacqueline Latina is currently a Structural Heart Fellow at Johns Hopkins. She was born and raised in the suburbs of Boston, MA, but fortunately escaped without a Boston accent. She is a graduate of Princeton University with an A.B. in chemistry. She earned her M.D. at Tufts University School of Medicine. Her internship and internal medicine residency were completed at Mount Sinai Hospital in New York City, where she stayed on for an American Heart Association postdoctoral research fellowship. She completed an M.S. in clinical research methods at the Columbia Mailman School of Public Health during that time. She completed general and interventional cardiology fellowships at Johns Hopkins.

CardioNerds (Amit Goyal and Daniel Ambinder), Dr. Leticia Helms (Internal medicine resident at Columbia University), Dr. Silia DeFilippis (AHFT FIT at Columbia University), and Dr. Anu Lala (AHFT faculty and program director at Mount Sinai Hospital) to discuss diversity and inclusion in academic cardiology and more in this installment of the Narratives in Cardiology Series. The President of the New York ACC Chapter Dr. Hima Vidula discusses D&I initiatives at her chapter. Episode introduction and audio editing by CardioNerds Academy Intern, Shivani Reddy.

Although women compose 50% of medical students in the United States, cardiology remains a male dominated field. Gender disparity is even more prominent when we look at leadership positions. In this episode we discuss why and how cardiology (and advanced heart failure) can be such a rewarding field for women. The episode reflects on the significant contributions women have made to the field in the past and how they continue to move the field with respect to clinical care and research.

The PA-ACC & CardioNerds Narratives in Cardiology is a multimedia educational series jointly developed by the Pennsylvania Chapter ACC, the ACC Fellows in Training Section, and the CardioNerds Platform with the goal to promote diversity, equity, and inclusion in cardiology. In this series, we host inspiring faculty and fellows from various ACC chapters to discuss their areas of expertise and their individual narratives. Join us for these captivating conversations as we celebrate our differences and share our joy for practicing cardiovascular medicine. We thank our project mentors Dr. Katie Berlacher and Dr. Nosheen Reza.

Video Version • Notes • Production Team

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1/ In Episode 180 @PaChapterACC & @CardioNerds Narratives in Cardiology episode, @PrettiPimentaMD, @ersied727, @AmitGoyalMD, & @Dr_DanMD talk with @dranulala

Follow this #CardsNarratives🧵on the discussion about Raising Women Leaders in Academic Cardiology pic.twitter.com/meza3170Pa

1. “We all have multiple roles – and those roles don’t always have to be completely distinct and separate from one another. You know, our ability in one role, maybe it makes us better at another.”
2. “I felt like being there was like in medical Disneyland for research.” – Anu Lala
3. “Heart failure is unique in that it truly requires that cross disciplinary collaboration at the precipice of what is often life and death.” – Anu Lala
4. “It points to the importance of seeing people do things before you who look like you.” – Anu Lala
5. “All human beings want to feel heard. They want to feel seen and they want to feel like their voice matters.”  – Anu Lala
6. “consciously deliberately disruptive”
7. “I like the idea of calling it work-life harmony.”

1. How do women compare to men in cardiology in 2022?
   • Although nearly 50% of US medical graduates and more than 40% of internal medicine graduates are women, the field of cardiology remains male dominated.
   • Approximately 20% of general cardiology fellows are women, which is comparable to women in surgical subspecialties like neurosurgery (17%), thoracic surgery (21%), and orthopedic surgery (15%) (Reza 2021).
   • Additionally, women hold significantly fewer leadership positions and are less likely to be promoted to senior academic ranks.
   • Out of LBCT presented at ACC 2021, zero had a female first author and zero were presented by women (Kaur 2021).
2. What may make heart failure unique with respect to the recruitment of women?
   • Heart failure is the only subspecialty of cardiology that was founded by a woman. Dr. Sharon Hunt is often described as the founder of the subspecialty.
   • She posited a few reasons why heart failure may attract a higher proportion of women including presence of models and mentors for women, women have been included since the inception of the field, and one that requires collaboration (Hunt 2019).
   • The number of women in HF training programs ranges between 26 to 36% which is much higher than that of women in other subspecialties like EP and interventional cardiology (Reza 2021).
3. How can we increase diversity in clinical trial leadership?
   • Women only represent 1 in 10 authors of cardiovascular trials in high impact journals (Van Spall 2021).
   • Build diverse research team.
   • Hold stakeholders accountable including academic institutions, professional societies, industry sponsors, funding agencies, and scientific journals (Van Spall 2021).
   • Be deliberate about editorial authorship as well as equal representation of women on manuscripts.
4. How can we increase the diversity of participants in clinical trials?
   • We know that increasing the diversity of women investigators in clinical trials is associated with increased enrollment of women participants (Reza 2020).
   • Increased enrollment of diverse populations is key to increasing the generalizability of findings (Van Spall 2021).
   • Build partnerships with the community and community-level providers.
   • Meet social and cultural needs such as family and child care responsibilities; socioeconomic and financial barriers; as well as absenteeism from work (Reza 2022).
   • Provide sex-specific materials to encourage enrollment.
   • For a related discussion, enjoy Ep #135. Underrepresentation in Clinical Trials & Guidelines with Dr. Clyde Yancy.
5. How has the COVID-19 pandemic affected women in academic medicine?
   • Women often bear disproportionate demands of personal life including schooling and caregiving duties and affected by school closures (Reza 2021).
   • Data have suggested that female academic productivity has been affected as measured by decreased publication authorship which may translate into decreased research support (DeFilippis 2021).
   • The decreased submission of manuscripts has been particularly pronounced among junior cohorts of women in academics (Squazzoni 2021).

CardioNerds Tommy Das (Program Director of the CardioNerds Academy and cardiology fellow at Cleveland Clinic), Rick Ferraro (Director of CardioNerds Journal Club and cardiology fellow at the Johns Hopkins Hospital), and CardioNerds Healy Honor Roll Ambassador Dr. Justice Oranefo (UConn cardiology fellow) discuss omega-3 fatty acids acid with Dr. Ty Gluckman, preventive cardiologist and medical director of the Center for Cardiovascular Analytics, Research, and Data Science (CARDS) at the Providence St. Joseph Heart Institute in Portland, Oregon. Audio editing by CardioNerds Academy Intern, Christian Faaborg-Andersen.

In the recent years, purified omega 3 fatty acids and its esters have emerged as a potential new tool in our arsenal for management of hypertriglyceridemia and atherosclerotic coronary artery disease. In this episode we review the sources and basic structure of these compounds, as well as their metabolic effects as it pertains to cardiovascular disease. Using hypothetical patient cases, we also discuss scenarios in which these therapies can be useful.

This episode is part of the CardioNerds Lipids Series which is a comprehensive series lead by co-chairs Dr. Rick Ferraro and Dr. Tommy Das and is developed in collaboration with the American Society For Preventive Cardiology (ASPC).

Relevant disclosures: None

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1. Omega 3 (n-3) fatty acids are a class of polyunsaturated fatty acids [PUFA]. The most studied n-3 fatty acids include eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA] and alpha linoleic acid [ALA]. ALA is found in certain vegetable oils while EPA and DHA are abundant in fish sources.
2. Cardiovascular benefits of n-3 fatty acids include blood pressure reduction, enhanced diastolic function, triglyceride reduction, and immunomodulatory properties.
3. Inflammation plays a major role in the atherogenic process and plaque rupture. Inflammatory marker hs-CRP is a risk enhancing factor for predicting future ASCVD risk. Ongoing trials are investigating therapy that target the inflammatory process in treatment of atherosclerotic heart disease.
4. Prevention and management of ASCVD require aggressive lifestyle modifications and medical therapy addressing risk factors and underlying inflammatory conditions.
5. Purified forms of n-3 fatty acids are approved for the treatment of severe hypertriglyceridemia and as an adjunct therapy to statins for reduction of coronary events in high-risk individuals.

1. What are omega 3 (n-3) fatty acids? What are the natural sources of n-3 fatty acids?

• n-3 fatty acids are class of polyunsaturated fatty acids [PUFA]. PUFA are types of unsaturated fats that have more than one double bond in their backbone. PUFAs are important constituents of the phospholipids of all cell membranes.
• The most studied n-3 fatty acids include eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA] and alpha linoleic acid [ALA].
• ALA is found in certain vegetable oils including walnuts, flaxseeds, chia seeds. EPA and DHA are abundant in cold water fish oils such as salmon, mackerel, tuna sardines. Interestingly, farm raised fish usually have higher levels of EPA and DHA than wild caught fish; however, this depends on what the fish are fed. Another important class of PUFAs are omega 6 (n-6) fatty acids, found in vegetable oils (1,2). 

2. What are the metabolic effects of omega 3 fatty acids?

• Multiple early studies have demonstrated the anti-inflammatory properties of n-3 fatty acids.
• The typical Western diet with a high arachidonic acid (an n-6 fatty acid) content promotes atherogenesis leading to the high incidence of CAD in this population.
• Supplementation with diets rich in DHA and EPA has been associated with reduced arachidonic acid content as well as reduced markers of inflammation. The relative dietary ratios of n-6:n-3 fatty acids have major implications for cardiovascular health.
• Anti-inflammatory mechanism of n-3 fatty acids include cell membrane stabilization, anti-oxidant properties, reduced leukocyte chemotaxis. (1-3).
• Other studied cardiovascular benefits of n-3 fatty acids include triglyceride lowering properties (11, 12), blood pressure and heart rate reduction (13, 14), improved endothelial function and antithrombotic properties (15, 16).
• Importantly, EPA and DHA are distinct molecules (different hydrocarbon length and number of double bonds) with different biologic effects. EPA assumes an extended conformation in cellular membranes, allowing it to neutralize reactive oxygen species, facilitate membrane stabilization, and limit oxidation of LDL cholesterol more easily. In contrast, DHA has a longer carbon chain and has one additional double bond, resulting in less membrane stabilization. DHA also inhibits formation of Dihomo-γ-linolenic acid (DGLA), which is important for production of anti-inflammatory eicosanoids and thus can also increase levels of LDL cholesterol.

3. What role does inflammation play in coronary artery disease?

• The impact of inflammation in the pathogenesis of atherosclerosis and plaque rupture has been well studied. Inflammatory mediators such CRP, IL-6, and myeloperoxidase have been found to be associated with increased cardiovascular risk.
• The JUPITER trial demonstrated the benefit of statin therapy in patients with elevated hsCRP. Subsequent trials targeting inflammation in the management of CAD have shown promise. Examples include the LoDoCo which investigated colchicine therapy and the CANTOS trial with investigated the IL-1 beta inhibitor canakinumab.
• The pathogenic role of inflammation and potential therapeutic role of anti-inflammatory therapy remain key areas of interest and multiple pharmacologic agents are undergoing investigation. (6, 7, 8, 17, 18).
• Check out the #CardsJC on the LoDoCo 2 trial for more on Colchicine in the management of CAD. Table 1 below summarizes notable trials of anti-inflammatory therapies for ASCVD.

4. What is the role for n-3 fatty acids in management of coronary artery disease?

• While a diet rich in n-3 fatty acids is associated with a lower risk of cardiovascular events, supplementation with over-the-counter fish oil containing supplements have not demonstrated significant cardiovascular benefits.
• Purified forms of high dose n-3 fatty acid esters consisting of EPA and/or DHA have shown mixed results as therapies for ASCVD.
• In the JELIS trial, patients with hypercholesterolemia treated with high dose icosapent ethyl (an EPA ester) in addition to pravastatin 10mg/day or simvastatin 5mg/day experienced reduced incidence of cardiac events and reduced LDL with greater benefit seen in patients with impaired glucose metabolism.
• The REDUCE-IT trial showed similar results in patients with atherosclerotic disease and high risk patients with elevated fasting triglycerides.
• Interestingly, the STRENGTH trial, in which patients were treated with combination EPA+DHA, did not show a benefit in the treatment arm.
• Icosapent ethyl is currently indicated as an adjunct therapy in addition to maximally tolerated statin therapy in patients with triglyceride levels ≥150 mg/dL and either established cardiovascular disease or type 2 diabetes mellitus plus ≥2 risk factors for cardiovascular disease to reduce incidence of cardiac events. (19 – 21).
• Check out the #CardsJC on the STRENGTH trial for an overview of relevant trial data. Table 2 below summarizes notable trials of omega-3 fatty acids for ASCVD.

5. What is the role of n-3 fatty acids in management of hypertriglyceridemia?

• In the approach to hypertriglyceridemia, be sure to identify and treat secondary causes (alcoholism, hypothyroidism, uncontrolled diabetes, etc) before instituting pharmacotherapy. Enjoy the CardioNerds “Causes of Hypertriglyceridemia” infographic developed by Dr. Teodora Donisan.
• The 2021 ACC expert consensus decision pathway on the management of ASCVD in patients with hypertriglyceridemia provides guidelines and algorithmic strategies to management of hypertriglyceridemia in several patient populations (22).
• The triglyceride reducing properties of n-3 fatty acids have been demonstrated on several trials including the EVOLVE trial (11). One should note that while several therapies reduce triglycerides, the potential benefits from n-3 fatty acids likely extend beyond triglyceride reduction.

1. MOZAFFARIAN, D. & WU, J.H.Y., 2011. Omega-3 Fatty Acids and Cardiovascular Disease: Effects on Risk Factors, Molecular Pathways, and Clinical Events. Journal of the American College of Cardiology, 58(20), pp.2047–2067.
2. Calder, Philip C, 2010. Omega-3 fatty acids and inflammatory processes. Nutrients, 2(3), pp.355–374.
3. Raphael, William & Sordillo, Lorraine M, 2013. Dietary polyunsaturated fatty acids and inflammation: The role of phospholipid biosynthesis. International journal of molecular sciences, 14(10), pp.21167–21188.
4. Schwalfenberg, G., 2006. Omega-3 fatty acids: their beneficial role in cardiovascular health. Canadian family physician, 52(6), pp.734–740.
5. Hansson, Göran K, 2005. Mechanisms of disease: Inflammation, atherosclerosis, and coronary artery disease. The New England journal of medicine, 352(16), pp.1626–1695.
6. Ridker, Paul M et al., 2008. Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. The New England journal of medicine, 359(21), pp.2195–2207.
7. Ridker, Paul M et al., 2017. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. The New England journal of medicine, 377(12), pp.1119–1131.
8. Tardif, Jean-Claude et al., 2019. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. The New England journal of medicine, 381(26), pp.2497–2505.
9. Xin, Wei, Wei, Wei & Li, Xiaoying, 2012. Effects of fish oil supplementation on inflammatory markers in chronic heart failure: a meta-analysis of randomized controlled trials. BMC cardiovascular disorders, 12(1), p.77.
10. Li, Kelei et al., 2014. Effect of marine-derived n-3 polyunsaturated fatty acids on C-reactive protein, interleukin 6 and tumor necrosis factor α: A meta-analysis. PloS one, 9(2), p.e88103.
11. Skulas-Ray, Ann C et al., 2019. Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association. Circulation (New York, N.Y.), 140(12), pp.CIR0000000000000709–e691.
12. Bhatt, Deepak L et al., 2019. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. The New England journal of medicine, 380(1), pp.11–22.
13. Geleijnse, J.M. et al., 2002. Blood pressure response to fish oil supplementation : metaregression analysis of randomized trials. Journal of hypertension, 20(8), pp.1493–1499.
14. Mozaffarian, D. et al., 2005. Effect of fish oil on heart rate in humans. A meta-analysis of randomized controlled trials. Circulation (New York, N.Y.), 112(13), pp.1945–1952.
15. Dangardt, F. et al., 2010. Omega-3 fatty acid supplementation improves vascular function and reduces inflammation in obese adolescents. Atherosclerosis, 212(2), pp.580–585.
16. Goodfellow, J. et al., 2000. Dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia. Journal of the American College of Cardiology, 35(2), pp.265–270.
17. Nidorf, S.M. et al., 2020. Colchicine in Patients with Chronic Coronary Disease. The New England journal of medicine, 383(19), pp.1838–1847.
18. Nidorf, Stefan M., MD, MBBS et al., 2013. Low-Dose Colchicine for Secondary Prevention of Cardiovascular Disease. Journal of the American College of Cardiology, 61(4), pp.404–410.
19. Yokoyama, Mitsuhiro, Dr et al., 2007. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. The Lancet (British edition), 369(9567), pp.1090–1098.
20. Bhatt, D.L. et al., 2019. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. The New England journal of medicine, 380(1), pp.11–22.
21. Nicholls, S.J. et al., 2020. Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial. JAMA : the journal of the American Medical Association, 324(22), pp.2268–2280.
22. Virani, S.S. et al., 2021. 2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia. Journal of the American College of Cardiology, 78(9), pp.960–993.

Dr. Ty Gluckman is the medical director of the Center for Cardiovascular Analytics, Research, and Data Science (CARDS) at the Providence St. Joseph Heart Institute in Portland, Oregon and an adjunct faculty member of the Ciccarone Center for the Prevention of Heart Disease at the Johns Hopkins Hospital. He has previously served as National Clinical Quality Expert for the ACC Patient Navigator Program and currently serves as National Chair of the ACC Patient Navigator Program-Focus MI. Additionally, Dr. Gluckman is a leader not only in the field of cardiovascular prevention, but also care coordination, quality improvement, and even App development as the lead developer of the ACC/AHA ASCVD risk calculator app

Dr. Justice Oranefo is a cardiology fellow at University of Connecticut. Following his undergraduate degree in Biomedical Science in the United Kingdom, he completed medical school at St George’s University Grenada followed by Internal Medicine residency at University of Massachusetts. He is passionate about medical education and diversity in medicine.

CardioNerds (Amit Goyal and Daniel Ambinder) join Dr. Loie Farina (Northwestern University CardioNerds Ambassador), Dr. Josh Cheema, and Dr. Graham Peigh from Northwestern University for drinks along the shores of Lake Michigan at North Avenue Beach. They discuss a case of a 52-year-old woman with limited cutaneous systemic sclerosis who presents with progressive symptoms of heart failure and is found to have a severe, non-ischemic cardiomyopathy. The etiology of her cardiomyopathy is not clear until her untimely death. She is ultimately diagnosed with cardiac AL amyloidosis with isolated vascular involvement a real occam’s razor or hickam’s dictum conundrum. We discuss the work-up and management of her condition including a detailed discussion of the differential diagnosis, the underlying features of systemic sclerosis with cardiac involvement as well as cardiac amyloidosis, the role of a shock team in managing cardiogenic shock, and how to identify those with advanced or stage D heart failure. Advanced heart failure expert Dr. Yasmin Raza (Northwestern University) provides the ECPR segment. Episode introduction by CardioNerds Clinical Trialist Dr. Liane Arcinas. Audio editing by CardioNerds Academy Intern, Christian Faaborg-Andersen.

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This is a case of a 52-year-old woman with limited cutaneous systemic sclerosis who presented with progressive dyspnea on exertion and weight loss over the course of 1 year. Her initial work-up was notable for abnormal PFTs and finding of interstitial pneumonia on high-resolution CT, an ECG with frequent PVCs and normal voltage, a transthoracic echocardiogram with a mildly reduced ejection fraction of 40%, and a right/left heart catheterization with normal coronary arteries, filling pressures, and cardiac output. Scleroderma-related cardiac involvement is suspected. She is placed on GDMT, but her condition worsens over the next several months, and repeat echocardiogram shows severely reduced biventricular function, reduced LV global longitudinal strain (GLS) with apical preservation of strain, severely reduced mitral annular tissue Doppler velocities, and a normal left ventricular wall thickness. Scleroderma-related cardiac involvement remains highest on the differential, but because of some findings on the echo that are concerning for cardiac amyloidosis, an endomyocardial biopsy was obtained. It showed vascular amyloid deposition without interstitial involvement. The diagnosis of cardiac amyloid was discussed but deemed unlikely due to lack of interstitial involvement. However, a serologic work-up soon revealed a monoclonal serum lambda light chain and a follow-up bone marrow biopsy showed 20% plasma cells. She was discharged with very near-term follow-up in oncology clinic with a presumptive diagnosis of AL amyloidosis, but she unfortunately returned in shock and suffered a cardiac arrest. She initially survived and underwent emergent veno-arterial extracorporeal membrane oxygenation (VA ECMO) cannulation with subsequent left ventricular assist device placement (LVAD). However, she passed away due to post-operative hemorrhage. Autopsy was consistent with a final diagnosis of cardiac AL amyloidosis with isolated vascular involvement. 

1. Scleroderma causes repeated focal ischemia-reperfusion injuries which result in patchy myocardial fibrosis. Cardiac involvement in scleroderma is frequent but often not clinically evident; when symptomatic, it is associated with a poor prognosis. 

1. Myocardial dysfunction in cardiac AL amyloidosis can result from myocardial infiltration, vascular deposition causing microvascular dysfunction and ischemia, and direct cardiotoxicity from circulating light chains. 

1. While isolated vascular amyloid is very rare, it can occur and can be seen without key characteristics of interstitial amyloid deposition, namely left ventricular hypertrophy and low voltage on an ECG.  

1. Cardiogenic shock outcomes are improved by multi-disciplinary discussions, commonly referred to as a “shock team call.”  

1. Heart failure is a progressive, morbid, and potentially fatal condition. LVADs and heart transplantation improve life expectancy and decrease morbidity among patients with stage D heart failure. Identification of patients with advanced heart failure can be challenging – a helpful mnemonic is “I NEED HELP 

1. How does scleroderma affect the heart? 

• Scleroderma is a connective tissue disorder characterized by extracellular matrix deposition, with widespread fibrosis of the skin and visceral organs, microvascular injury, and evidence of immune system activation.  
• Cardiac involvement is common, although likely underestimated as it is often subclinical, and the estimated prevalence varies widely. Myocardial involvement is identified in up to 80% of patients in histological studies and clinical myocardial dysfunction is recognized in 15-25%. When clinically evident, cardiac involvement portends a poor prognosis, with up to a 70% mortality at 5 years. Approximately 25% of scleroderma-related deaths are due to cardiac causes. 
• Primary involvement is thought to be mediated by repeated focal ischemic-reperfusion injury, impaired microcirculation, inflammation, and eventual focal irreversible fibrosis leading to heart failure and arrhythmias. 
• Cardiac involvement can also occur secondary to lung or renal disease, pulmonary arterial hypertension, or other cardiovascular risk factors.  
• Cardiac manifestations: 
  • Myocardial failure: diastolic dysfunction is frequently reported but less commonly associated with diastolic heart failure. Systolic dysfunction can also occur, but severe systolic dysfunction is rare.  
  • Electrical failure: arrhythmias and conduction disorders 
  • Pericardial failure: pericarditis and pericardial effusion 
  • Coronary failure: coronary microvascular dysfunction 
  • Valvular failure: valvular involvement (uncommon)  

2. What is cardiac amyloidosis (CA) and what is the pathophysiology?  

• For an in-depth review of Cardiac Amyloidosis, enjoy the CardioNerds Cardiac Amyloid Series! 
• Amyloidosis is a process in which proteins misfold, aggregate, and form amyloid fibrils that deposit in various organs, thereby causing tissue injury and organ malfunction. The most common types of cardiac amyloidosis are AL (light chain) and TTR (transthyretin).  
• AL amyloidosis is a hematologic disorder of clonal plasma cells that overproduce light chains, which may deposit in any organ sparing the central nervous system, and commonly deposit in the heart and kidneys.  
• Delayed diagnoses are common, with an estimated one-third of patients visiting five or more physicians before receiving the diagnosis. Cardiac involvement with heart failure portends a particularly poor prognosis, with a median survival from onset of heart failure of less than six months without treatment. Stem cell transplantation has been shown to improve survival if performed prior to the diagnosis of advanced heart failure. Unfortunately, about 80% of patients are not candidates for aggressive therapy due to advanced stage of disease. 
• In CA, amyloid deposits infiltrate and expand the extracellular space which results in increased ventricular wall thickness and classically manifests as a restrictive cardiomyopathy with relatively preserved EF; however, a subset of patients may present with reduced LVEF and minimal or no ventricular wall thickening.  
• Patients with AL cardiac amyloidosis tend to have greater severity of heart failure than TTR despite less morphological involvement (in terms of LV wall thickness), felt due to the toxic effect of light chain amyloid fibrils on the tissue resulting in a toxic-infiltrative cardiomyopathy.  
• Additional mechanisms thought to play a major contributing role in cardiac AL amyloidosis: 
  • Circulating light chains cause direct cardiotoxicity through cardiomyocyte oxidant stress and abnormal vascular reactivity, impairing vasodilation  
  • Vascular amyloid deposition in the small intramural coronary vessels results in microvascular dysfunction and global myocardial ischemia. Vascular involvement is common in AL cardiac amyloidosis (much more common than in TTR cardiac amyloid). A pathology study demonstrated obstructive intramural coronary amyloidosis in 63 of 96 patients (66%) and 86% of these patients had microscopic evidence of myocardial ischemia. Isolated vascular involvement, however, is rare – 97% of patients in this study had interstitial involvement.  
  • Coronary microvascular dysfunction occurs via 3 major mechanisms:  
    • Structural – with amyloid deposition in the vessel wall causing wall thickening and luminal stenosis 
    • Extravascular – through extrinsic compression of the microvasculature from perivascular and interstitial amyloid deposits and decreased diastolic perfusion 
    • Functional – through autonomic and endothelial dysfunction 

3. What are common cardiac MRI (CMR) findings in scleroderma heart disease and cardiac amyloidosis? 

• First, a review of a few key concepts in CMR (also, enjoy Episode #33. Cardiac MRI with Dr. Deborah Kwon): 
  • Native T1 signals are increased by edema (e.g. acute infarction) and an increase in interstitial space (e.g. fibrosis, amyloidosis). T1 signals are decreased by lipid and iron overload.  
  • Gadolinium contrast agents are distributed throughout the extracellular space and shorten the T1 relaxation times of myocardium in proportion to local concentrations of gadolinium – areas of fibrosis/scar will exhibit shorter T1 relaxation times (due to higher gadolinium proportion). 
  • Extracellular volume fraction is calculated using myocardial and blood T1 before and after contrast is administered. It serves as a marker of myocardial tissue remodeling; ECV is increased in amyloid and excessive collagen deposition and serves as a robust marker of myocardial fibrosis. 
  • Late gadolinium enhancement (LGE) – depicts relative difference in the T1 recovery times between enhancing areas of fibrosis or scar (T1 shortened due to accumulation of extracellular gadolinium contrast agent) and normal nulled myocardium (longer T1 as gadolinium contrast agent is more rapidly washed out). 
  • T2 weighted imaging – sensitive to regional or global increases in myocardial water content (i.e. edema). 
• Scleroderma CMR findings:  
  • Perfusion defects – predominantly stress perfusion abnormalities, less common at rest 
  • Increased signal intensity on T2-weighted sequences 
  • Increase in ECV 
  • Delayed enhancement – mainly linear and typically mid-wall (spares the endocardium)  
  • Accurate assessment of RV function, which is particularly important given risk of PAH in these patients 
• Amyloid CMR findings: 
  • T1 signal abnormalities 
  • Increase in ECV 
  • Classically, causes global subendocardial LGE in a noncoronary distribution; however, LGE can also be diffuse and transmural or more localized and patchy 
  • Difficulty nulling the myocardium (the myocardium appears similar to the blood pool) 
    • Myocardial nulling” refers to an inversion recovery pulse sequence that is used to null the signal from a desired tissue to accentuate surrounding pathology.  
    • Normally, the blood pool nulls before the myocardium but in amyloid myocardium nulls simultaneously or before the blood pool 

4. How do we identify if someone has Stage D or advanced heart failure? 

• A topic of critical importance is identifying which patients have advanced or Stage D heart failure, those that are so sick that GDMT alone or interventions including cardiac resynchronization therapy, implantable pulmonary artery pressure monitor, or percutaneous mitral valve repair are unlikely to prolong life and prevent suffering. These patients benefit from timely evaluation for advanced heart failure therapies: left ventricular assist device (LVAD) or orthotopic heart transplant (OHT).  
• Heart failure is a progressive condition. A study in JACC HF in 2017 with Dr. Javed Butler as the senior author showed that in a cohort of outpatients with Stage C HF, 25% progressed to Stage D or died within a 3-year span. They estimated that 100,000 patients a year progress from Stage C to Stage D.  
• Unfortunately, it is not always clear who has made this transition until it is too late. This was reinforced by a study published in 2021 in the Journal of Cardiac Failure. This was a multi-center retrospective analysis of referral patterns for LVAD/transplant, and they showed that 40% of the 515 patients studied were deemed to be too sick to qualify for an advanced therapy, and 60% of the referrals coming from the inpatient setting, clearly too late in the disease course. 

• So how do we identify patients with advanced HF? In addition to the guideline document mentioned, there is a popular mnemonic that can help you remember red flags. 

The mnemonic is “I NEED HELP.” 

This identification schema is not perfect, and neither are our definitions for staging patients with heart failure. This is an area in need of active research.  

5. What is a “shock team” and what is its role in the management of cardiogenic shock?  

• In cardiogenic shock, diminished cardiac output leads to systemic hypoperfusion and resultant ischemia, inflammation, vasoconstriction, and salt/fluid retention with volume overload. The short-term mortality in CS is >40%. 
• A multidisciplinary shock team, composed of advanced heart failure, cardiac surgery, interventional cardiology, and critical care facilitates timely consultation and decision making. Observational studies suggest that a shock team approach may improve CS outcomes. A 2019 study published in JACC evaluated the impact of a standardized team-based approach in 204 consecutive patients with CS. 204 consecutive patients with CS were enrolled. They found that 30-day survival in 2017 and 2018 was 57.9% and 76.6%, respectively compared with a 30-day survival of 47% in 2016 (P<0.01).  
• For more on this, enjoy Episode #168. Cardiogenic Shock – Initial Assessment and The Shock Team Call with Dr. Anu Lala as part of the CardioNerds Cardiac Critical Care Series. 

1. Bissell LA, Anderson M, Burgess M, et al. Consensus best practice pathway of the UK Systemic Sclerosis Study group: management of cardiac disease in systemic sclerosis. Rheumatology (Oxford). 2017;56(6):912-921. https://pubmed.ncbi.nlm.nih.gov/28160468/ 

1. Bissell LA, Md Yusof MY, Buch MH. Primary myocardial disease in scleroderma-a comprehensive review of the literature to inform the UK Systemic Sclerosis Study Group cardiac working group. Rheumatology (Oxford). 2017;56(6):882-895. https://pubmed.ncbi.nlm.nih.gov/27940590/ 

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1. Alanna A. MorrisMD, MSc, FAHA, Chair, Prateeti Khazanie, MD, MPH, Vice Chair, Mark H. Drazner, MD, MSc, Vice Chair, Nancy M. Albert, PhD, Khadijah Breathett, MD, MS, FAHA, Lauren B. Cooper, MD, MHS, Howard J. Eisen, MD, Patrick O’Gara, MD, Stuart D. Russell, MD, on behalf of the American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Radiology and Intervention; and Council on Hypertension. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001016