Episodes Archives - Cardionerds

The following question refers to Sections 3.3-3.4 of the 2021 ESC CV Prevention Guidelines. The question is asked by student Dr. Adriana Mares, answered first by early career preventive cardiologist Dr. Dipika Gopal, and then by expert faculty Dr. Allison Bailey.

Dr. Bailey is a cardiologist at Centennial Heart. She is the editor-in-chief of the American College of Cardiology’s Extended Learning (ACCEL) editorial board and was a member of the writing group for the 2018 American Lipid Guidelines. 

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.

Ms. Soya M. Alone is a 70-year-old woman of Bangladeshi ethnicity with a history of anxiety and depression. She currently lives at home by herself, does not have many friends and family that live nearby, and has had a tough year emotionally after the passing of her husband. She spends most of her time in bed with low daily physical activity and has experienced more weakness and exhaustion over the past year along with loss of muscle mass. Which of the following are potential risk modifiers in this patient when considering her risk for CVD?

A. Bangladeshi ethnicity
B. Psychosocial factors
C. Frailty
D. History of anxiety and depression
E. All of the above

The correct answer is E – All of the above.

Traditional 10-year CVD risk scores do not perform adequately in all ethnicities. Therefore, multiplication of calculated risk by relative risk for specific ethnic subgroups should be considered (Class IIa, LOE B). Individuals from South Asia have higher CVD rates. The ESC guidelines recommend using a correction factor by multiplying the predicted risk by 1.3 for Indians and Bangladeshis, and 1.7 for Pakistanis. These correction factors are derived from data from QRISK3. In the UK, the QRISK calculator algorithm has been derived and validated in 2.3 million people to estimate CVD risk in different ethnic groups and unlike other calculators, it counts South Asian origins as an additional risk factor. The reasons for such differences remain inadequately studied, as do the risks associated with other ethnic backgrounds. Barriers to developing accurate risk prediction tools include the wide heterogeneity amongst the population.

The 2019 ACC/AHA guidelines also list high-risk race/ethnicities such as South Asian ancestry as a risk-enhancing factor. However, there is no separate pooled cohort equation for different ethnicities, and consideration should be given that the pooled cohort equations will underestimate ASCVD risk in South Asians.

Psychosocial stress including loneliness and critical life events are associated, in a dose-response pattern, with the development and progression of ASCVD, with relative risks between 1.2 and 2.0. Conversely, indicators of mental health, such as optimism and a strong sense of purpose, are associated with lower risk. While there is not a specific way proposed by the guidelines for psychosocial factors to improve risk classification, it is important to screen patients with ASCVD for psychological stress, and clinicians should attend to somatic and emotional causes of symptoms as well. The ESC guidelines give a Class IIa (LOE B) recommendation for assessment of stress symptoms and psychosocial stressors.

This patient should also be formally screened for frailty, which is not the same as aging but includes factors such as slowness, weakness, low physical activity, exhaustion and shrinking, and makes her more vulnerable to the effect of stressors and is a risk factor for both high CV and non-CV morbidity and mortality. However, the ability of frailty measures to improve CVD risk prediction has not been formally assessed, so the guidelines do not recommend integrating it into formal CVD risk assessment. Frailty may however, influence treatment as it can help build an individualized care plan.

Mental disorders such as anxiety and depression are associated with the development of CVD as well. Detrimental effects may be potentially caused by unhealthy lifestyle, increased exposure to socioeconomic stressors, and cardiometabolic side-effects of medications. The ESC guidelines give a Class 1 (LOE C) recommendation that mental disorders with either significant functional impairment or decreased use of healthcare systems be considered as influencing total CVD risk.

Main Takeaway

Psychosocial stress and frailty are associated with risk of ASCVD and should be assessed in patients when considering CVD risk. In addition, current risk scores may under-or over-estimate CVD risk in different ethnic minority groups.

Guideline Location

Section 3.3.1, 3.3.2, 3.3.4, 3.4.10, page 3258 – 3259, 3265 – 3266

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The following question refers to Section 3.2 of the 2021 ESC CV Prevention Guidelines. The question is asked by student Dr. Hirsh Elhence, answered first by Mayo Clinic Fellow Dr. Teodora Donisan, 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.

You are seeing a 45-year-old woman with a past medical history of hypertension, overweight status, hyperlipidemia, and active tobacco use disorder. Her BMI is 27 kg/m2, BP is 150/75, HbA1C is 5.8%, total cholesterol is 234 mg/dL, HDL is 59 mg/dL, and LDL is 155 mg/dL. She is from Romania, a country with very high CVD risk. Which of the following statements is CORRECT?

A. LDL-C needs to be decreased by at least 50%, as small absolute LDL-C reductions would not provide clinical benefit

B. Hypertension is not an important CVD risk factor in our patient, as she is young.

C. Prediabetes is not a significant CV risk factor for our patient, as she is not yet diabetic.

D. Smoking confers a higher CVD risk for women than for men.

E. Her weight does not increase her CVD risk, as she is overweight rather than obese

The correct answer is D – Smoking confers a higher CVD risk for women than for men.

Prolonged smoking increases the CVD risk more in women than in men. Our patient is 45 years old. CVD risk in smokers < 50 years-old is 5x higher than in non-smokers. Of note, smoking is responsible for 50% of all avoidable deaths in smokers and a lifetime smoker will lose 10 years of life, on average. Secondhand smoke and smokeless tobacco can also increase the CVD risk.

Option A is incorrect. The SCORE2 risk chart for populations at very high CVD risk places her at a 14% (very high) 10-year risk for myocardial infarction, stroke, or cardiovascular death. She would derive benefit even from incremental reductions in LDL-C values. The absolute benefit of lowering LDL-C depends on both the absolute risk of ASCVD and the absolute reduction in LDL-C, so even a small absolute reduction in LDL-C may be beneficial in high- or very-high-risk patients. Furthermore, the reduction in CVD risk is proportional to the decrease in LDL-C, irrespective of the medications used to achieve such change. This remains true even when lowering LDL-C values to < 55 mg/dl.

Option B is incorrect. Hypertension is a major cause of CVD regardless of age, and the risk of death from either CAD or stroke increases linearly from BP levels as low as 90 mmHg systolic and 75 mmHg diastolic upwards. Particularly relevant for our patient, lifetime BP evolution differs in women compared to men, potentially resulting in an increased CVD risk at lower BP thresholds.

Option C is incorrect. Type 1 DM, type 2 DM, and prediabetes are all independent risk factors for ASCVD. Of note, it would be important to address this risk factor with our patient, as women who develop type 2 diabetes have a particularly high risk for stroke.

Option E is incorrect. All-cause mortality is lowest at a BMI on 20-25 kg/m2 in apparently healthy patients. Even overweight patients are at increased CVD risk. There is a linear relationship between BMI and mortality in non-smokers and a J-shaped relationship in ever-smokers. In patients with heart failure, a lower mortality risk has been observed with higher BMI – the “obesity paradox.” It would be important to evaluate the waist circumference in our patient, as both BMI and waist circumference are associated with ASCVD risk.

Main Takeaway

The main ASCVD risk factors are hyperlipidemia (elevated apolipoprotein-B-containing lipoproteins, of which LDL-C is most abundant), hypertension, cigarette smoking, diabetes, and adiposity. Identifying patients who will benefit most from ASCVD risk factor treatment is central to ASCVD prevention efforts. In general, the higher the absolute CVD risk, the higher the absolute benefit of risk factor treatment, and thus the lower the number needed to treat to prevent one CVD event during a period of time.

Guideline Location

Section 3.2.1., pages 3236, 3242, 3243.

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CardioNerds (Dr. Kelly Arps, Dr. Colin Blumenthal, Dr. Dan Ambinder, and Dr. Teodora Donisan) discuss the screening, detection, and diagnosis of atrial fibrillation (AF) with Dr. Ben Freedman. AF is frequently undiagnosed and its first manifestation can be a debilitating stroke. European and American guidelines differ slightly with regards to guidelines for AF screening in asymptomatic individuals. There are multiple methods available to screen for AF; the setting and the clinical scenario can help guide the choice. Consumer-led screening has its own challenges, as it can detect AF in a younger population where we should prioritize aggressive management of risk factors and comorbidities. There is uncertainty regarding the minimum AF burden that increases thromboembolic risk, however a high CHAD2S2-VASc score remains the strongest predictor of stroke risk independent of AF burden. Perioperative AF associated with non-cardiac surgery has increased risk of future stroke and adverse cardiac outcomes and should likely be treated as a new diagnosis of chronic AF.   

This CardioNerds Atrial Fibrillation series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Kelly Arps and Dr. Colin Blumenthal.

This series is supported by an educational grant from the Bristol Myers Squibb and Pfizer Alliance. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds.

We have collaborated with VCU Health to provide CME. Claim free CME here!

Disclosures: Dr. Ben Freedman disclosed that he has received grant or research support from Pfizer.

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1. “Stroke is a poor early sign of AF.”  
   1. AF remains frequently undiagnosed and there remains uncertainty about the optimal target population and screening methodology.  
2. “We have to tailor AF screening to the purpose we’re using it for”  
   1. If in a primary care setting, check the pulse. If the goal is to exclude high-risk AF –  handheld ECG for heart rhythm snapshots are appropriate. If the goal is to identify or exclude AF with a high level of certainty, continuous monitors are necessary for greater sensitivity. 
3. Consumer-led screening is performed by (mostly young) individuals using commercial monitors and smart watches, facilitating earlier recognition of paroxysmal AF in this population. In these cases, we should prioritize aggressive management of risk factors and comorbidities to reduce the risk of progression to persistent AF. 
4. There is no specific cutoff for AF duration which has been identified to predict elevated stroke risk; AF is likely both a risk factor and a risk marker for stroke, suggesting an underlying atrial myopathy. 
5. Non-cardiac surgeries and procedures can be considered “AF stress tests.” If AF occurs in these settings, it is usually more clinically significant and has a higher risk of stroke and death than AF associated with cardiac surgeries. 

Notes drafted by Dr. Teodora Donisan and reviewed by Dr. Kelly Arps

1. Why is it important to screen for AF and who should be screened? 

AF is frequently undiagnosed and its first manifestation can be a debilitating stroke or death. Let’s go over a few numbers: 

• 15% of people with AF are currently undiagnosed and 75% of those individuals would be eligible for anticoagulation.1   
• 10-38% of individuals with ischemic strokes are found to have AF as a plausible cause, and the true proportion may be even higher, given difficulties in detecting intermittent AF.2 

Current guideline recommendations:  

• European guidelines: opportunistic screening for AF is recommended for individuals ≥65 years old.3 

• American guidelines: AF screening is recommended in patients with cryptogenic strokes and those with device-recorded atrial high-rate episodes.4 

Opportunistic screening for AF can be done by checking the pulse or noticing the irregular heart rate on blood pressure monitors. When AF is found by opportunistic screening at a single time point, it is usually persistent AF. Continuous ambulatory heart rhythm monitoring can identify shorter episodes of paroxysmal AF, perhaps earlier in the AF disease course.  

In patients with unexplained stroke we have different ways to search for occult AF: 

• In the hospital: all patients should have 72h of ECG monitoring. There is evidence that nurse-led ECG surveillance detects more paroxysmal AF earlier and more frequently than 24-hour Holter recordings.5  
• After discharge: if clinical suspicion for occult AF is high (e.g., cerebral imaging concerning for cardioembolic source, evidence of left atrial enlargement, elevated BNP), consider more prolonged monitoring via cutaneous patches, multiple Holter recordings, or implantable cardiac monitors. 

2. What tools are currently available to screen for AF? 

There are multiple tools available for AF screening: pulse palpation, oscillometry, and ambulatory heart rhythm ECG monitoring with external or subcutaneous devices. Handheld ECG devices are very convenient options, as they can diagnose AF in 30 seconds directly, whereas other methods such as oscillometry would ultimately require ECG confirmation. 

• If in the office for a quick screen: check the pulse; 
• If you’re looking for high-burden AF: handheld one-time ECG; 
• If you’re looking to identify or rule out AF with a high degree of certainty: continuous monitoring with transcutaneous patch or implantable monitor. 

3. How should commercial monitor/smart watch data be incorporated into clinical practice? 

We need to be aware of the population who have access to and more often use these modern technologies; use is unequally distributed around the world and across the age span.6 These devices are most often used by people who are 35-40 years old, not the typical population for whom AF screening may be more impactful. If we do identify AF in these younger individuals, starting anticoagulation may not be indicated. It is important, however, to emphasize more aggressive management of risk factors and comorbidities (e.g., weight loss, diet, exercise, alcohol reduction, hypertension control, screening for and treating prediabetes and diabetes, screening for obstructive sleep apnea, and assessing thyroid function) to reduce the risk of AF progression. 

4. How much atrial fibrillation is clinically relevant? 

There is uncertainty regarding the minimum AF burden that increases the thromboembolic risk above an individual’s baseline risk, with studies exploring durations of ≥ 5 minutes to ≥ 24 hours.7,8 Several studies show that there isn’t a clear temporal relationship between device-detected high-rate episodes and strokes either, with only a small number of patients experiencing arrhythmia in the month before a stroke.9 

• The CHA2DS2-VASc score is very important when discussing thromboembolic risk: if it is low, then the risk of stroke is low; if it is high, risk of stroke is higher, even if there is a low burden of AF. 
• AF is likely both a risk factor and a risk marker for stroke, suggesting an underlying atrial myopathy. This would explain why a specific cutoff point for AF duration is not necessarily relevant to predict stroke risk. 

5. How should clinicians approach peri-operative AF? 

Perioperative AF is associated with increased perioperative morbidity, higher stroke rates, more readmissions, and lower survival.10 The significance of AF is different depending on the type of surgery: 

• With AF after cardiac surgery (which involves opening the pericardium and direct irritation of the atria), the incidence of perioperative AF is greater (20-30%). Roughly 25% of patients with AF after CABG experience asymptomatic recurrent AF episodes during the first month after the procedure.11 Many individuals with AF after cardiac surgery do not go on to have chronic AF. 
• With AF after general surgery, the chance of chronic AF and future risk of adverse events are significantly elevated, as AF should not be a direct result of the procedure itself and instead likely represents a previously undiagnosed atrial myopathy. Consider noncardiac procedures as an “AF stress test”.   

Give this information, we should strongly consider anticoagulation after identifying AF associated with non-cardiac surgeries or procedures, when indicated by the CHA2DS2-VASc score. We should start anticoagulation in individuals with AF associated with cardiac surgeries only if there are other risk factors or clini

Opportunistic screening for AF can be done by checking the pulse or noticing the irregular heart rate on blood pressure monitors. When AF is found by opportunistic screening at a single time point, it is usually persistent AF. Continuous ambulatory heart rhythm monitoring can identify shorter episodes of paroxysmal AF, perhaps earlier in the AF disease course.  

In patients with unexplained stroke we have different ways to search for occult AF: 

• In the hospital: all patients should have 72h of ECG monitoring. There is evidence that nurse-led ECG surveillance detects more paroxysmal AF earlier and more frequently than 24-hour Holter recordings.5  
• After discharge: if clinical suspicion for occult AF is high (e.g., cerebral imaging concerning for cardioembolic source, evidence of left atrial enlargement, elevated BNP), consider more prolonged monitoring via cutaneous patches, multiple Holter recordings, or implantable cardiac monitors.  

1. Turakhia MP, Shafrin J, Bognar K, et al. Estimated prevalence of undiagnosed atrial fibrillation in the United States. PLoS One. 2018;13(4):e0195088. 

2. Friberg L, Rosenqvist M, Lindgren A, Terént A, Norrving B, Asplund K. High prevalence of atrial fibrillation among patients with ischemic stroke. Stroke. 2014;45(9):2599-2605. 

3. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021;42(5):373-498. 

4. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2019;74(1):104-132. 

5. Yan B, Tu H, Lam C, et al. Nurse Led Smartphone Electrographic Monitoring for Atrial Fibrillation after Ischemic Stroke: SPOT-AF. J Stroke. 2020;22(3):387-395. 

6. Turakhia MP, Desai M, Hedlin H, et al. Rationale and design of a large-scale, app-based study to identify cardiac arrhythmias using a smartwatch: The Apple Heart Study. Am Heart J. 2019;207:66-75. 

7. Glotzer TV, Hellkamp AS, Zimmerman J, et al. Atrial high rate episodes detected by pacemaker diagnostics predict death and stroke: report of the Atrial Diagnostics Ancillary Study of the MOde Selection Trial (MOST). Circulation. 2003;107(12):1614-1619. 

8. Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med. 2012;366(2):120-129. 

9. Freedman B, Camm J, Calkins H, et al. Screening for Atrial Fibrillation: A Report of the AF-SCREEN International Collaboration. Circulation. 2017;135(19):1851-1867. 

10. Bianco V, Kilic A, Yousef S, et al. The long-term impact of postoperative atrial fibrillation after cardiac surgery. J Thorac Cardiovasc Surg. 2022. 

11. Ha ACT, Verma S, Mazer CD, et al. Effect of Continuous Electrocardiogram Monitoring on Detection of Undiagnosed Atrial Fibrillation After Hospitalization for Cardiac Surgery: A Randomized Clinical Trial. JAMA Netw Open. 2021;4(8):e2121867. 

Dr. Ben Freedman serves as Director of External Affairs at the Heart Research Institute and Leader of its Heart Rhythm and Stroke Prevention Group, Honorary Professor of Cardiology at The University of Sydney, Charles Perkins Centre. He formed the AF-SCREEN International Collaboration in 2015, which now has over 190 members from 38 countries, including some of the most prolific names in AF research. In 2011 he was awarded the Order of Australia Medal for service to medicine as a clinician, educator, and researcher.

Teodora Donisan @TDonisan is an internal medicine resident at Beaumont Hospital and rising cardiology fellow at Mayo Clinic. She completed medical school at the Carol Davila University of Medicine and Pharmacy, in her home country of Romania. After medical school, she worked as cardiology resident in Bucharest for 2 years, followed by a research rotation in interventional cardio-oncology at The University of Texas MD Anderson Cancer Center. Teo is passionate about medical education and loves the rush of the cardiac intensive care unit. She dreams of photographing wildlife in all National Parks in the United States.

CardioNerds Tommy Das (Program Director of the CardioNerds Academy and cardiology fellow at Cleveland Clinic), Rick Ferraro (cardiology fellow at the Johns Hopkins Hospital), and Dr. Xiaoming Jia (Cardiology Fellow at Baylor College Medicine) take a closer look at the mechanism of icosapent ethyl in triglyceride lowering and ASCVD risk reduction with Dr. Michael Shapiro, the Fred M. Parrish professor of cardiology at Wake Forest University and Director of the Center for Preventative Cardiology at Wake Forest Baptist Health. Audio editing by CardioNerds Academy Intern, student doctor Akiva Rosenzveig.

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. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are two major Omega-3 fatty acids found in fish oil. While both have been shown to lower triglycerides, only purified EPA formulations have been shown to reduce ASCVD risk.
2. Mechanisms of triglyceride (TG) lowering by icosapent ethyl are multiple and include reduction of hepatic VLDL production, stimulation of lipoprotein lipase activity, increased chylomicron clearance, reduced lipogenesis, increased beta oxidation, and reduced delivery of fatty acids to the liver.
3. There was only modest reduction of triglycerides in REDUCE-IT and JELIS despite association with significant reduction in cardiovascular outcome events, suggesting likely mechanisms outside of triglyceride lowering that may contribute to ASCVD reduction.
4. While there was an increased signal for peripheral edema and atrial fibrillation associated with icosapent ethyl in prior trials, overall side effect rates were very low.
5. Icosapent ethyl is considered to be cost-effective based on cost-effective analysis.

• EPA and DHA have differing biological properties that may explain differences in ASCVD risk reduction observed in cardiovascular outcome trials 1.
• The REDUCE-IT trial, which enrolled secondary prevention and high-risk primary prevention patients with elevated triglycerides who were on statin therapy, showed significant reduction of major adverse cardiovascular events in the icosapent ethyl group compared with a mineral oil placebo2. 
• Only modest reductions of TG were seen in the REDUCE-IT and JELIS trials despite association with significant reduction in events 2,3.  Potential mechanisms contributing favorable effects of EPA on ASCVD risk reduction include inhibition of cholesterol crystal formation, stabilization of membrane structures, reversal of endothelial dysfunction, inhibition of lipoprotein and membrane lipid oxidation 4.
• Pleotropic effects of EPA include influence on platelet aggregation, lower thromboxane activity, increased prostaglandin level, and effects on blood pressure, insulin resistance and inflammation.
• Triglycerides are a surrogate for triglycerides-rich lipoproteins, which are likely causally associated with ASCVD 5.
• There is increased signal for bleeding, lower extremity edema, and atrial fibrillation with icosapent ethyl but overall side effect rates are very low 2.
• In order to ensure higher rates of medication access and adherence, clinicians must be cognizant of the cost to the patient. In practice, it is important to have a structured approach to improve insurance approval rate for medications that require prior authorizations
• With icosapent ethyl, cost effectiveness analyses have shown the medication is cost-effect for ASCVD risk reduction in secondary prevention patients and high-risk diabetic patients6.
• While moderate hypertriglyceridemia (150-499mg/dL) is likely a marker for increased residual risk for ASCVD, those with severe hypertriglyceridemia (>=500mg/dL) are also at risk for acute pancreatitis. Remember that these are fasting levels and post-prandial levels are likely much higher (i.e., in the thousands).
• In most scenarios, hypertriglyceridemia is driven by a combination of environmental and genetic factors. Environmental factors to consider when treating these patients include diet, alcohol intake, metabolic syndrome, diabetes, hypothyroidism, nephrotic syndrome, CKD, medications (ie. anti-rejection medications, steroids, thiazides).
• Hypertriglyceridemia is very amenable to lifestyle modification – diet, weight loss, exercise, diabetes control, etc.
• Equations for estimating LDL-C are generally not accurate when TG is severely elevated. In these circumstances we can instead use direct LDL-C, non-HDL-C, or apoB.
• We are entering an exciting era of preventative cardiology with many new therapeutics in the pipeline.

1. Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol. 2011;58(20):2047-2067.
2. Bhatt DL, Steg PG, Miller M, et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019;380(1):11-22.
3. Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369(9567):1090-1098.
4. Jia X, Koh S, Al Rifai M, Blumenthal RS, Virani SS. Spotlight on Icosapent Ethyl for Cardiovascular Risk Reduction: Evidence to Date. Vasc Health Risk Manag. 2020;16:1-10.
5. Wall R, Ross RP, Fitzgerald GF, Stanton C. Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr Rev. 2010;68(5):280-289.
6. Weintraub WS, Bhatt DL, Zhang Z, et al. Cost-effectiveness of Icosapent Ethyl for High-risk Patients With Hypertriglyceridemia Despite Statin Treatment. JAMA Netw Open. 2022;5(2):e2148172.

Dr. Michael Shapiro the Fred M. Parrish professor of cardiology at Wake Forest University and leader in the field of cardiovascular prevention. He is the Director of the Center for Preventative Cardiology at Wake Forest Baptist Health and has published widely in the field of atherosclerosis imaging and cardiovascular health.

Dr. Xiaoming Jia is a cardiology fellow at Baylor College of Medicine

CardioNerd (Amit Goyal),  ACHD series co-chair Dr. Agnes Koczo (UPMC), and episode FIT lead, Dr. Logan Eberly (Emory University, incoming ACHD fellow at Boston Adult Congenital Heart) join Dr. Peter Ermis (Program Director of the Adult Congenital Heart Disease Program at Texas Children’s Heart Center), and Dr. Scott Cohen (Associate Professor and Director of the Adult Congenital Heart Disease Program at the Medical College of Wisconsin) for a discussion about transitions of care in congenital heart disease.  Audio editing by Dr. Gurleen Kaur (Director of the CardioNerds Internship and CardioNerds Academy Fellow).

Congenital heart disease (CHD) is the most common clinically significant congenital defect, occurring in approximately 1 in 100 live births. With modern advances in pediatric cardiology and cardiac surgery, over 90% of children born in the developed world with CHD will now survive into adulthood, and there are currently more adults than children living with CHD in the United States1.

As these children become adults, they will need to transition their care from pediatric to adult-centered care. Unfortunately, during this transition period, there is often delayed or inappropriate care, improper timing of the transfer of care, and undue emotional and financial stress on the patients, their families, and the healthcare system. At its worst, patients are lost to appropriate follow-up. In this episode, we review the current climate in transitions of care for CHD patients from child-centered to adult-centered care, discuss the difficulties that can occur during the transitions process. We further discuss how to mitigate them, and highlight the key elements to the successful transitions of care.

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

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1. There is a clear distinction between the TRANSFER of care and TRANSITION of care. Transfer is merely moving from a pediatric to adult provider. Transition involves the continuing education of the patient with regards to their congenital heart disease, the importance of longitudinal follow up, and leading patients toward more autonomous medical care. Transition begins in the pediatric cardiology clinic prior to the transfer of care and is an ongoing process that continues well after the physical transfer of care.

• A critical aspect of the transition and transfer of care is cultivating trust—that is, the new adult congenital heart disease (ACHD) provider must earn the trust of the patient and family. A failure to do so will inevitably prevent an optimal transition of care.

• During transition, parents are transitioning along with their children. With transition to adult care, there is also a goal to transition responsibility for medical care from the parent to the child. Setting goals and expectations can help both the parents and the child effectively make this transition.

• Loss to follow up is one of the most concerning complications of poor transition. Interestingly, there does not appear to be a strong association between complexity of congenital heart disease and the likelihood of loss to follow up. ACHD providers should not assume that patients with complex ACHD are less likely to be lost to follow up. For example, approximately 25-30% of Fontan patients have lapses or gaps in care. Effective transition of care is essential for all severity levels of ACHD. It is recommended in the 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease2, as well as in the 2011 AHA Scientific Statement on Best Practices in Managing Transition to Adulthood for Adolescents With Congenital Heart Disease3.

1. What is the current climate in transitions of care for patients from child-centered to adult-centered care, and what are some of the difficulties on the side of the provider as well as the patient during this process?

• Transition is a complex process, and there is no “one size fits all” approach to the effective transition of ACHD patients.
• Many patients live far away from an ACHD centers of excellence.
• There are also currently not enough ACHD cardiologists to care for ACHD patients.
• Due to these challenges, there can be anxiety with regards to transferring care to an ACHD provider from the perspective of both the patient and the pediatric cardiologist.
• This time in a young person’s life is not just a time of transition of medical care; there are many simultaneous immense life transitions as well. There may be a loss of focus on the importance of ongoing follow up in medical care.

2. What topics should be addressed at the first ACHD visit?

• The ACHD program and its relationship to both the pediatric and adult hospital should be thoroughly explained, and the patient needs to be informed where both inpatient and outpatient care take place.
• ACHD providers should ask open-ended questions to determine the patient’s understanding of their congenital heart disease and then provide education as needed.
• The first ACHD visit should focus on laying out a detailed, long-term plan of care for the patient. Patients should be advised what specifically will be monitored going forward (such as valve function, cardiac chamber size, arrhythmias, etc.), as well as what future diagnostic testing (echo, MRI/CT, stress testing, etc.) is to be expected. For female patients, contraception and the safety of pregnancy should be addressed starting in the first visit.
• One of the primary goals of the first ACHD visit is also to build trust. To this end, an ACHD provider should try to avoid any major changes to medical therapy at the first visit unless deemed absolutely necessary.

3. What are advantages and disadvantages of different models of transitions of care?

• There is no “one size fits all” model to transition, but there certainly are some guiding principles.
• Formal transition programs are important. They can help normalize transition and eliminate the sentiment that the patient is being “kicked out” of pediatric cardiology clinic. Additionally, formal transitions programs can reduce unexpected cardiac hospitalizations for ACHD patients2. This decreases the unnecessary utilization of hospital resources.
• An ACHD program that remains within a children’s hospital has the benefit that the patients are already familiar with the site, and they may also be less likely to be lost to follow up. However, there is the drawback that non-cardiology providers in a children’s hospital are often unfamiliar with the management of adult medical problems, which necessitates forming relationships with adult providers at partner institutions, and this can be challenging.
• Ultimately, ACHD patients can be cared for effectively at either a children’s hospital-based or adult hospital-based program. The model that is most effective for a particular institution is dependent upon the resources available and the investment of a supportive multi-disciplinary team.

4. What is the role of the parents in the transition process?

• Parents play a vital role in the transition process. They are often quite informed of their child’s history, so the new ACHD provider needs to carefully review the patient’s history prior to the first visit. Having thorough knowledge of a patient’s medical history will help build trust with patients and their families.
• ACHD providers should involve the parents in the transition process and should set goals and expectations. They should ask the parents to empower their child with regards to their medical care (such as encouraging them to manage their own medications, schedule their own medical appointments, etc.)
• ACHD providers need to have patience when working with parents during the transition process. Providers need to acknowledge that the parents have been the primary manager of their child’s medical care for many years, and it is often difficult to give up this role and to allow their child to be autonomous.
• It’s important to remember that parents are also transitioning. They transition from being the primary manager of their child’s health to being co-managers, before ultimately relinquishing the responsibility to their child.

5. What are some negative sequelae of a poor transition of care?

• The worst possible outcome is loss to follow up. This can result in potentially preventable medical complications.
• Inadequate or poor transition can lead to parental and/or patient distrust of the ACHD provider, which in turn increases the risk of being lost to follow up.
• Suboptimal transition increases the risk that the patient will engage in high-risk behaviors that can be harmful to their health.
• Patients who are not transitioned properly tend to utilize more hospital resources.

6. How should female ACHD patients be counseled on women’s health issues?

• In general, cardiologists are not well trained in addressing issues such as sexual health and contraception.
• However, discussions of topics such as family planning and the safety of pregnancy is important to begin during pediatric care. The longer the providers wait to address these issues, the higher the risk of unplanned pregnancy in a high-risk patient.
• Discussion of topics such as sex and contraception needs to be a routine part of every ACHD patient visit. A significant way to overcome the discomfort that both providers and patients have when talking about these issues is to make the discussion routine and therefore normal.
• There are several risk stratifications tools available (CARPREG II, modified WHO, see tables below) to help ACHD providers assess the cardiovascular risk of pregnancy for ACHD patients.
• Fortunately, overall mortality during pregnancy for ACHD patients is low, and most adult women with congenital heart disease can complete a pregnancy safely. However, close monitoring (particularly for heart failure and arrhythmias) is important.

7. What are the key elements in the successful transition of care?

• The transition process should be formal in its organization and deliberate.
• Communication is crucial, both between pediatric and adult providers, as well as between providers, patients, and their families.
• The transition and transfer of care needs to be specifically to an ACHD provider. Many ACHD patients end up under the care of general adult cardiologists, who often do not have the experience or expertise to effectively manage them. There is robust evidence that ACHD patients who do not follow at an ACHD Center of Excellence have worse outcomes. As mentioned prior, location in proximity to a Center of Excellence can be a barrier for patients when trying to complete a successful transition.

1. Moons, P., Bovijn, L., Budts, W., Belmans, A., & Gewillig, M. (2010). Temporal Trends in Survival to Adulthood Among Patients Born With Congenital Heart Disease From 1970 to 1992 in Belgium. Circulation,122(22), 2264-2272. doi:10.1161/circulationaha.110.946343.

2. Stout KK, Daniels CJ, Aboulhosn JA, Bozkurt B, Broberg CS, Colman JM, Crumb SR, Dearani JA, Fuller S, Gurvitz M, Khairy P, Landzberg MJ, Saidi A, Valente AM, Van Hare GF. 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Apr 2;139(14):e698-e800. doi: 10.1161/CIR.0000000000000603. Erratum in: Circulation. 2019 Apr 2;139(14):e833-e834. PMID: 30586767.

3. Sable C, Foster E, Uzark K, Bjornsen K, Canobbio MM, Connolly HM, Graham TP, Gurvitz MZ, Kovacs A, Meadows AK, Reid GJ, Reiss JG, Rosenbaum KN, Sagerman PJ, Saidi A, Schonberg R, Shah S, Tong E, Williams RG; American Heart Association Congenital Heart Defects Committee of the Council on Cardiovascular Disease in the Young, Council on Cardiovascular Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease. Best practices in managing transition to adulthood for adolescents with congenital heart disease: the transition process and medical and psychosocial issues: a scientific statement from the American Heart Association. Circulation. 2011 Apr 5;123(13):1454-85. doi: 10.1161/CIR.0b013e3182107c56. Epub 2011 Feb 28. PMID: 21357825. https://pubmed.ncbi.nlm.nih.gov/21357825/

4. Bushee, Chana & Ginde, Salil & Earing, Michael & Buelow, Matthew & Reinhardt, Emily & Cohen, Scott. (2021). Changes in care patterns associated with a transition program in adolescents with congenital heart disease: A single center study. Progress in Pediatric Cardiology. 101343. 10.1016/j.ppedcard.2021.101343.

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. Peter Ermis is the Medical Director for the Adult Congenital Heart Program at Texas Children’s Hospital and Assistant Professor at Baylor College of Medicine in Houston, TX. He earned his medical degree at the University of Texas Health Science Center in San Antonio in 2005 and later completed a combined Medicine/Pediatrics residency at Baylor College of Medicine in 2009. He then completed a combined Adult Cardiovascular Disease and Pediatric Cardiology Fellowship at Texas Children’s Hospital and the Texas Heart Institute in 2014. In addition to his role as medical director, Dr. Ermis is also the Program Director for the Adult Congenital Heart Disease Fellowship and the Head of Adult Medicine at Texas Children’s Hospital. Dr. Ermis’ interests include optimizing care for adult survivors of chronic childhood diseases, including adult congenital heart disease patients. He has been instrumental in the creation and opening of an outpatient and inpatient unit designed completely for ACHD patients at Texas Children’s Hospital which opened in 2020.

Dr. Scott Cohen is an Associate Professor and Director of the Adult Congenital Heart Disease Program at the Medical College of Wisconsin. He completed residency in med/peds as well as adult cardiology fellowship at the Warren Alpert Medical School of Brown University. He also completed a fellowship in both preventative medicine and ACHD at the VA in Rhode Island and then the Children’s Hospital of Wisconsin, respectively.

Dr. Logan Eberly was born in New Orleans but raised in Louisville, Kentucky. He attended Duke for his combined med/peds residency, and is now a general cardiology fellow at Emory and will be joining the BACH or Boston Adult Congenital Heart (BACH) and Pulmonary Hypertension Program to continue his training. He is passionate about cardiovascular imaging, cardio-obstetrics pulmonary hypertension, medical education and global health.

CardioNerds (Amit Goyal and Daniel Ambinder), join  Dr. Gurleen Kaur (Director of CardioNerds Internship and medicine resident at Brigham and Women’s Hospital),  Dr. Victoria Thomas (Cardionerds Ambassador, Vanderbilt University Medical Center) Dr. Katie Berlacher (Cardiology program director, University of Pittsburgh Medical Center), and Dr. Julie Damp (Vanderbilt University Medical Center Cardiovascular disease fellowship program director) to discuss becoming & thriving as a fellowship program director and more in this installment of the Narratives in Cardiology Series. Special message by Tennessee ACC State Chapter Governor, Dr. John L Jefferies. Audio editing by CardioNerds Academy Intern, student doctor Akiva Rosenzveig.

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.

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1/ Episode 212, @PaChapterACC & @CardioNerds Narratives in Cardiology episode featured a discussion w/ @Drvic_thomas, @KBerlacher, & @BoydDamp

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Drafted by Dr. Victoria Thomas.

1. What does it mean to be a big “E” when people say they are a clinician Educator?

• It can mean teaching students directly at bedside.  However, it is also a sacrifice of daily mentoring and listening to students’ challenges and difficulties.
• Being a clinician educator is just as much of a calling as is serving in medicine.
• Clinician Educators focus on medicine but also the science and best practices of teaching the art of doctoring.

2. What is physician burnout? Why is this important for to CardioNerds?

• Physician burnout is a syndrome of chronic workplace stress that leads to emotional exhaustion and a sense of dissatisfaction and disconnection personally and professionally. 
• 30-45% of cardiologists have reported physician burnout.

3. What factors affect physician burnout?

• Emotional and physical exhaustion often lead to physician burnout. First year of training as an intern or fellow and first year of serving as an attending are particularly high-risk periods. This is largely due to learning a new system and responsibilities mixed with a sense of decreased accomplishment.
• The sense of decreased accomplishment can lead to physicians suffering from impostor syndrome.
• Grit can be defined as a perseverance for long-term goals.  The level of grit was not associated with burnout among first-year Internal Medicine residents.

4. What are some of the solutions to prevent or address physician burnout?

• Physicians need to feel a sense of belonging and should be supported and celebrated when they have accomplished something by their colleagues and administrators. Fellows and attendings want to feel listened to and supported.
• Destigmatizing this idea of “perfection in medicine”. Physician should share with each other their accomplishments but also their mistakes to create a community of personal and professional connection and acceptance.
• Practicing mini acts of gratitude such as exercise or therapy can help with burnout.
• Delegation of work tasks and taking breaks have been shown to improve mental well-being.

5. What support do program directors have to help prevent burnout for themselves?

• Many local graduate medical education (GME) offices will have some resources for program directors depending on the size and funding. 
• The Accreditation Council for Graduate medical Education (ACGME) had developed an on-line series to help new program directors understand their new roles. 
• It is also recommended to network and create community of program directors to work with and bounce ideas from.

6. What are some of the differences found among cardiology program directors regarding support from leadership?

• 45% of men versus 29% of women program directors felt adequate support from leadership.  56% of late-career versus 35% mid-career and early-career program directors felt adequate support from leadership.
• There is no evidence to support this, however, but contributing factors may include the documented history of gender bias, wage inequality, and program size. 

1. Cullen, M. W., Damp, J. B., Soukoulis, V., Keating, F. K., Abudayyeh, I., Auseon, A., … & Weissman, G. (2021). Burnout and well-being among cardiology fellowship program directors. Journal of the American College of Cardiology, 78(17), 1717-1726.
2. Mehta, L. S., Lewis, S. J., Duvernoy, C. S., Rzeszut, A. K., Walsh, M. N., Harrington, R. A., … & American College of Cardiology Women in Cardiology Leadership Council. (2019). Burnout and career satisfaction among US cardiologists. Journal of the American College of Cardiology, 73(25), 3345-3348.Peckham C. Physician burnout: it just keeps getting worse. Medscape; 2015.
3. Klein, A. J., Grau, T., Spagnoletti, C. L., Rothenberger, S. D., & Berlacher, K. (2021). Grit Does Not Predict Burnout among First-Year Internal Medicine Residents. Southern Medical Journal, 114(5), 272-276.
4. Edwards, S. T., Helfrich, C. D., Grembowski, D., Hulen, E., Clinton, W. L., Wood, G. B., … & Stewart, G. (2018). Task delegation and burnout trade-offs among primary care providers and nurses in Veterans Affairs Patient Aligned Care Teams (VA PACTs). The Journal of the American Board of Family Medicine, 31(1), 83-93.
5. Shanafelt, T. D., & Noseworthy, J. H. (2017, January). Executive leadership and physician well-being: nine organizational strategies to promote engagement and reduce burnout. In Mayo Clinic Proceedings (Vol. 92, No. 1, pp. 129-146). Elsevier.

CardioNerds (Amit and Dan) join Dr. Omid Amidi (CardioNerds Academy Graduate) and Dr. Marwah Shahid from the UCLA Cardiology Fellowship program along with Dr. Evelyn Song (CardioNerds Academy House Faculty and Heart Failure Hospitalist at UCSF) to discuss a complex case focused on management of severe coronary artery disease in a patient with Glanzmann thrombasthenia. Dr. Rushi Parikh (Interventional cardiologist, UCLA) provides the ECPR for this episode. Audio editing by CardioNerds Academy Intern, student doctor Akiva Rosenzveig.

Glanzmann Thrombasthenia is a bleeding disorder due to impairment of platelet aggregation secondary to a mutation in the GPIIB/IIIA receptor. This case is focused on work up of stable coronary artery disease followed by a discussion on duration of dual antiplatelet therapy post percutaneous coronary intervention in a patient with Glanzmann thrombasthenia.  

Check out this published case in JACC: Case Reports

Jump to: Case media – Case teaching – References

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See the published case in JACC: Case Reports

1. Patients with Glanzmann thrombocytopenia (GT) may have a higher risk of bleeding, depending on their disease phenotype.

2. It is unclear whether the mechanism of GT protects patient against stent thrombosis in the setting of PCI. Additionally, there is little data on the use of antiplatelet agents in patients with GT.

3. Short-term DAPT may be a reasonably safe option for patients with GT undergoing PCI.

4. We report a successful case of percutaneous coronary intervention in a patient with GT with no complications at a 1 year follow up.

1. What is Glanzmann thrombasthenia?

GT is an inherited platelet disorder that is characterized by spontaneous bleeding with phenotypic variability ranging from minimal bruising to potentially fatal hemorrhaging.  GT is caused by autosomal recessive inheritance of quantitative or qualitative deficiencies of functional αIIbβ3 integrin coded by ITGA2B or ITGB3 genes for αIIb and β3, respectively. As a result, platelets may be stimulated, but the platelet glycoprotein IIb/IIIa receptor is unable to bind fibrinogen to cross-link platelets, rending them potentially ineffective. In platelet aggregation studies, there is lack of response to collagen, epinephrine, arachidonic acid, and ADP stimulation. Thus, platelet aggregation is impaired. 

2. What is known about PCI and antiplatelet therapy in the setting of Glanzmann thrombasthenia?

To the best of our knowledge, this is the first case report of percutaneous coronary intervention in the setting of GT. It is unclear if the mechanism of GT alone provides sufficient antiplatelet activity and whether antiplatelet therapy leads to significantly increased bleeding risk. The use of antiplatelet therapy is not well studied in the GT population. What we do know is that the mechanism of GT prevents platelet aggregation—the final step in platelet-related thrombosis—while oral antiplatelet therapy affects platelet activation, thus, in our patient we felt that short term DAPT was reasonable. It is important to note that in the event of an active bleed requiring platelet transfusion, donor platelets possess functional glycoprotein IIb/IIIa receptors and thus exponentially increase the risk of stent thrombosis. Therefore, unlike our case, if a patient is not maintained on chronic oral antiplatelet therapy, initiation of oral or intravenous antiplatelet therapy should be considered to prevent stent thrombosis at the time of platelet transfusion.

Like any other patient with a high bleeding risk, it is important to have clear indications to conduct a coronary angiogram in patients with GT. Shared decision making is vital in regard to the benefits and risk of an angiogram in relation to the patient’s presentation, symptoms and history. The same is true in regard to coronary revascularization in these patients. Besides functional stress testing, coronary CTA is a viable option to evaluate coronary anatomy to identify high risk anatomy in these patients.

1. Truong Katie P., Zhang Jessica J., Shahid Marwah, et al. Management of high-grade coronary artery disease and concomitant glanzmann thrombasthenia. JACC: Case Reports. 2021;3(14):1625-1629.
2. Lawton Jennifer S., Tamis-Holland Jacqueline E., et al. 2021 acc/aha/scai guideline for coronary artery revascularization. Journal of the American College of Cardiology. 2022;79(2):e21-e129.
3. Gulati Martha, Levy Phillip D., et al. 2021 aha/acc/ase/chest/saem/scct/scmr guideline for the evaluation and diagnosis of chest pain. Journal of the American College of Cardiology. 2021;78(22):e187-e285.

CardioNerds (Amit Goyal and Daniel Ambinder), Dr. Ahmed Ghoneem (CardioNerds Academy Chief of House Taussig and medicine resident at Lahey Hospital), and Dr. Gurleen Kaur (Director of CardioNerds Internship and medicine resident at Brigham and Women’s Hospital) discuss family history of premature ASCVD with Dr. Ann Marie Navar, Preventive Cardiologist and Associate Professor in the Departments of Internal Medicine and Population and Data Sciences at UT Southwestern Medical Center. They discuss the art of soliciting a nuanced family history, refining cardiovascular risk using risk models and novel markers, counseling patients with elevated risk, and more. Show notes were drafted by Dr. Ahmed Ghoneem and reviewed by Dr. Gurleen Kaur. Audio editing was performed by CardioNerds Intern, student Dr. Adriana Mares.

For related teaching, check out this Tweetorial about CAC by Dr. Gurleen Kaur, the Family History of Premature ASCVD Infographic by Dr. Ahmed Ghoneem, and the CardioNerds Cardiovascular Prevention Series.

CardioNerds Cardiovascular Prevention Page
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Patient summary: Mr. B is a 51-year-old gentleman who is referred to CardioNerds Prevention Clinic by his PCP. He does not have a significant past medical history. He is a former smoker but quit 2 years ago. His BP in clinic today is 138/84; he is not on any antihypertensives. His most recent lipid profile 2 weeks prior showed a total cholesterol level of 250 mg/dL, a TG level of 230 mg/dL, an LDL cholesterol of 174 mg/dL, and an HDL cholesterol of 30 mg/dL. He tells us that his father had a “heart attack” at the age of 52, and he would like to further understand his own risk. We calculate his ASCVD risk score, and it is 9.8%.

1. What constitutes a positive family history (FHx) of premature ASCVD? What is an approach to the art of soliciting the FHx from our patients?

• Definition of family history of premature ASCVD: the history of an atherosclerotic event (e.g., myocardial infarction or stroke) in a male first degree relative before the age of 55 or a female first degree relative before the age of 65.

• Dr. Navar’s approach to soliciting a family history:
  • Lead with a general question such as “what do you know about any medical conditions that run in your family?”.
  • Then ask more specific questions about the parents and siblings, such as “Is your mother still alive? How long did she live? Has she ever had a heart attack or stroke?”
  • If the answer is yes, ask about how old they were at the time of the event.
  • A challenging aspect of the FHx can be eliciting the difference between atherosclerotic events and sudden cardiac death. While atherosclerotic diseases are a much more common cause of unexplained sudden death, it’s important that we don’t miss the opportunity to identify inherited cardiomyopathies, channelopathies, inherited aortopathies or other heritable SCD syndromes.

2. Is the “dose” of family history important (for example: the number of affected relatives, the closeness of those relationships, the age of onset)?

• While conducting studies to test this may be difficult, the few studies that have looked at the number of affected relatives have found a dose-response type relationship, where increasing number of relatives affected increases the risk of heart disease.1,2

3. How does a family history affect cardiovascular risk stratification?

FHx of premature ASCVD does not improve the predictive ability of the Pooled Cohort Equations (PCE) at a population level. Therefore, it does not factor into the ASCVD risk calculation utilizing the PCE.

However, it enhances the patient’s risk at an individual level. The ACC/AHA guidelines recognize FHx of premature ASCVD as a risk-enhancing factor [together with CKD, chronic inflammatory conditions such as psoriasis, primary hypercholesterolemia, high-risk ethnicity such as South Asian ancestry, metabolic syndrome, history of premature menopause (before age 40 y) and history of pregnancy-associated conditions that increase later ASCVD risk, such as preeclampsia].3

Dr. Navar’s advice is to think of the PCE as a starting point during risk assessment, followed by searching for the other risk-enhancing factors, to come up with a more tailored risk assessment for that individual patient.

4. After we explained to our patient the enhanced risk, he tells us that he feels like his fate is sealed and that nothing he can do would improve his outcomes because it’s in his genes. We have data though, that shows that healthy lifestyles reduce the risk of coronary artery disease and individuals at high genetic risk of CAD.4

How would you handle this challenging conversation and counsel our patient?

• We should always think about how risk conversations can affect our patients emotionally. Many patients come to CV prevention clinic because they want to know what they can do about their risk. A “scared straight” approach can be de-motivating for these patients.
• “It’s never too late to start cardiovascular prevention. And there are never patients that are too high risk that we can’t do anything to lower their risk of heart disease” can be a reassuring beginning to the conversation.
• Reinforce any work that the patient has already done to lower their risk of heart disease such as quitting smoking. This shows the patients that they have already started making a difference.
• This can then be followed by discussing the available tools to lower this patient’s risk: diet modification, exercise, weight management, control of diabetes, control of blood pressure, statins, etc.

5. In addition to lifestyle management, would you recommend a statin for Mr. B, who has an intermediate CVD risk and risk enhancing factors such as positive family history?

• Dr. Navar’s short answer is YES. Even though the patient is at intermediate risk, his actual risk is higher given his family history. “The cornerstone of long-term risk prevention for this patient is going to be a statin”.
• Dr. Navar usually approaches this conversation using a simple yet effective analogy: “imagine that you’re out shopping, and there’s a vitamin that will lower your risk of heart disease over your lifetime by 30 to 50%, depending on your cholesterol level and how much your cholesterol is lowered. It’s very safe. It has minimal side effects and it’s all of $3 a month. But unlike vitamins, we actually have randomized control trial data that show that they make a difference. Would you take it?”.
• It’s important to identify the LDL goal for each patient before prescribing a statin.

6. Our patient is still uncertain about starting a statin mainly because he’s asymptomatic and doesn’t feel that his family history is a strong enough reason for him to have to take a daily medication for the rest of his life. The ACC/AHA guidelines highlight the importance of shared decision making with our patients. They also recommend measuring the coronary artery calcium or CAC score in intermediate risk patients to help facilitate a more informed risk discussion. Would a CAC score be of benefit in our patient’s case?

• The initial step in this decision-making process is to identify what are the patient’s thoughts on taking statins, i.e where they are on the “Statin Spectrum” as Dr. Navar eloquently described. It is important to discuss the current evidence for the benefit of statins, and that the relative risk reduction we see per degree of LDL lowering is actually highest in the youngest and lowest risk groups.
• Some patients are engaged and interested in taking statins from the beginning. It may not be beneficial to measure CAC scores in these patients.
• Other patients, like our patient, remain uncertain about statins. These patients are great candidates for CAC score, which acts as a “tie-breaker” in this situation. Being aware of the presence of CAC in their arteries can be a strong motivator for these patients to start statin therapy.
• In non-smoking patients with CAC=0, it would be reasonable to hold statin therapy and repeat a CAC score in five years (assuming no major change in other risk factors such as diabetes, return to smoking, etc.).5
• It is important to recognize the caveats of CAC scores:
  • The ACC/AHA guidelines identify some patients whom clinicians should not de-risk despite a CAC=0, such as active smokers.
  • CAC is less prevalent in young people, and less prevalent in women compared to men, raising the possibility of false reassurance.
  • CAC testing involves a small, but not insignificant, amount of radiation exposure.
  • It is often not covered by insurance.

7. There’ve been a lot of interest in novel lipid biomarkers such as lipoprotein(a) and Apolipoprotein B, and how elevated blood levels of these markers may be associated with ASCVD risk and are recognized as risk enhancing factors. How do you incorporate testing for Lp(a) and ApoB into your practice?

• Lipoprotein (a)
  • It is a type of cholesterol particle that looks like an LDL particle, but it has an additional protein on it on the surface. It doesn’t correlate with LDL levels or any of the traditional risk factors for ASCVD, and Lp(a) levels are very consistent throughout lifetime. Moreover, it is genetically determined, and elevated Lp(a) levels usually run in families.
  • The guidelines recommend measuring Lp(a) in patients with family history of premature ASCVD.3
  • There are no commercially available treatments at this time that lower Lp(a), however a number of novel therapies are currently in clinical trials.
  • Despite that fact, several preventive cardiologists (such as Dr. Navar) may measure Lp(a) to identify patients at increased risk, and subsequently target lower LDL levels in these patients (LDL<70, and in patients with multiple risk factors or established CVD, LDL<55).

• Apolipoprotein B
  • It reflects the total number of atherogenic lipoprotein particles, in contrast to LDL-C which measures the volume of LDL (but not the number of LDL particles).6
  • ApoB and LDL-C are not always concordant. A discordant phenotype exists, in which patients have a low LDL-C but a high ApoB; this confers an increased ASCVD risk.
  • Measuring ApoB is easy, cheap and is not affected by triglycerides so can be measured in a non-fasting state.
  • Check out this Tweetorial about ApoB by Dr. Christian Faaborg-Andersen.

8. Our patient decided to proceed with a coronary CT to calculate his CAC and he’ll consider taking a statin based on the results. However, he asks one final question. He has a 20-year-old son and a 25-year-old daughter. Should they be screened for ASCVD?

• Remember, it’s never too early to start thinking about cardiovascular prevention.
• It is important for this patient’s children to understand that they have a family history of ASCVD, that they could be at an increased risk, and that they should start adopting a healthy lifestyle early on.
• Screening can help identify individuals who may be eligible for early intervention, such as those with Familial Hypercholesterolemia (FH). Early identification and management of people with FH can vastly improve their outcomes.

1.   Silberberg JS, Wlodarczyk J, Fryer J, Robertson R, Hensley MJ. Risk associated with various definitions of family history of coronary heart disease. The Newcastle Family History Study II. Am J Epidemiol. 1998;147(12):1133-1139. https://pubmed.ncbi.nlm.nih.gov/9645791/

2.   Scheuner MT, Whitworth WC, McGruder H, Yoon PW, Khoury MJ. Expanding the definition of a positive family history for early-onset coronary heart disease. Genet Med. 2006;8(8):491-501. https://pubmed.ncbi.nlm.nih.gov/16912580/

3.   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;140(11):e596-e646. https://www.ahajournals.org/doi/10.1161/CIR.0000000000000678

4.   Khera AV, Emdin CA, Drake I, et al. Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease. New England Journal of Medicine. 2016;375(24):2349-2358. https://www.nejm.org/doi/full/10.1056/nejmoa1605086

5.   Dzaye O, Dardari ZA, Cainzos-Achirica M, et al. Warranty Period of a Calcium Score of Zero: Comprehensive Analysis From MESA. JACC Cardiovascular imaging. 2021;14(5):990-1002. https://pubmed.ncbi.nlm.nih.gov/33129734/

6. Sniderman AD, Thanassoulis G, Glavinovic T, et al. Apolipoprotein B Particles and Cardiovascular Disease A Narrative Review. JAMA Cardiology. 2019; 4(12):1287-1295. https://pubmed.ncbi.nlm.nih.gov/31642874/

It’s another session of CardioNerds Rounds! In these rounds, Co-Chairs, Dr. Karan Desai and Dr. Natalie Stokes and Dr. Tiffany Dong (FIT at Cleveland Clinic) joins Dr. Randall Starling (Professor of Medicine and Director of Heart Transplant and Mechanical Circulatory Support at Cleveland Clinic) to discuss the nuances of guideline directed medical therapy (GDMT) through real cases. As a past president of the Heart Failure Society of America (HFSA) and author on several guidelines, Dr. Starling gives us man pearls on GDMT. Come round with us today by listening to the episodes 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

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Case #1 Synopsis:

A man in his 60s with known genetic MYPBC3 cardiomyopathy and heart failure with a reduced ejection fraction of 30% presents with worsening dyspnea on exertion over the past 6 months. His past medical history also included atrial fibrillation with prior ablation and sick sinus syndrome with pacemaker implantation. Medications are listed below. He underwent an elective right heart catheterization prior to defibrillator upgrade for primary prevention. At the time of right heart catheterization, his blood pressure was 153/99 with a heart rate of 60. His RHC demonstrated a RA pressure of 15mmHg, RV 52/16, PA 59/32 (mean 41), and PCWP 28 with Fick CO/CI of 2.8 L/min and index of 1.2 L/min/m2. His SVR  was 1900 dynes/s/cm-5. He was admitted to the cardiac ICU and started on nitroprusside that was transitioned to a regimen of Sacubitril-Valsartan and Eplerenone. His final RHC numbers were RA 7, PA 46/18/29, PCWP 16 and Fick CO/CI 6.1/2.6. His discharge medications are shown below.

Takeaways from Case #1

1. Unless there are contraindications (cardiogenic shock or AV block), continue a patient’s home beta blocker to maintain the neurohormonal blockade benefits. A low cardiac index should be interpreted in the full context of the patient, including their symptoms, other markers of perfusion (e.g., urine output, mentation, serum lactate), and mean arterial pressure before holding or stopping beta blockade. Carvedilol, metoprolol succinate and bisoprolol are all evidence-based options for beta blockers in heart failure with reduced ejection fraction.
2. If there is concern of lowering blood pressure too much with Sacubitril/Valsartan, one method is to trial low dose of valsartan first and then transition to Sac/Val. Note, in the PARADIGM-HF trial, the initial exclusion criteria for starting Sac/Val included no symptomatic hypotension and SBP ≥ 100. At subsequent up-titration visits, the blood pressure criteria was decreased to SBP ≥ 95.
3. In multiple studies, protocol-driven titration of GDMT has shown to improve clinical outcomes, yet titration remains poor. The following image from Greene et al. in JACC shows that in contemporary US outpatient practices that GDMT titration is poor with few patients reaching target dosing.

Case #2 Synopsis:

A 43 year-old male with a past medical history of familial dilated cardiomyopathy requiring HVAD placement two years prior now comes in with low flow alarms. He is feeling well otherwise with chronic dyspnea on exertion. A CT chest and abdomen with contrast for showed outflow graft occlusion. Given a TTE showed LV recovery that correlated with invasive hemodynamics, his LVAD was decommissioned. He was tried on a low dose Sacubitril/Valsartan but was unable to tolerate it due to hypotension. He was discharged on carvedilol 3.125mg BID and lisinopril 5mg daily. Over the next 10 months in clinic, his GDMT was titrated to carvedilol 25mg BID, spironolactone 25mg daily and Sacubitril/Valsartan 49-51mg BID.

 Takeaways Case #2

1. In patients with ventricular assist devices, the differential for low flow alarms includes hypovolemia, arrhythmias, RV failure, cardiac tamponade and inflow cannula obstruction. A careful history, exam (with particular attention to the JVD), and bedside echocardiogram can help differentiate the cause.
2. EF recovery occurs in about 5% of patients in large LVAD registries. Favorable prognostic factors for EF recovery include female sex and nonischemic cardiomyopathy of short duration.
3. In the TRED-HF trial, patients were randomly assigned to phased withdrawal or continuation of GDMT over 6 months. The primary endpoint was relapse defined as a reduction in LVEF of more than 10% and to less than 50%, an increase in LVEDV by more than 10% and to higher than the normal range, a two-fold rise in NT-pro-BNP and to more than 400 ng/L or clinical evidence of heart failure. While a small trial (51 patients were enrolled), over the first 6 months, 44% of patients assigned to treatment withdrawal met the primary endpoint of relapse compared with none assigned to continue treatment (estimated of event rate 45.7% [95% CI 28.5-67.2]; p=0.0001).
4. We still do not have great predictors of relapse, and thus for most patients with HFrecEF, GDMT should continue indefinitely.

1. Halliday BP, Wassall R, Lota AS, et al. Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial. Lancet. 2019 Jan 5;393(10166):61-73. doi: 10.1016/S0140-6736(18)32484-X. Epub 2018 Nov 11. PMID: 30429050; PMCID: PMC6319251.
2. Greene SJ, Fonarow GC, DeVore AD, et al. Titration of Medical Therapy for Heart Failure With Reduced Ejection Fraction. J Am Coll Cardiol. 2019 May 21;73(19):2365-2383. doi: 10.1016/j.jacc.2019.02.015. Epub 2019 Mar 4. PMID: 30844480; PMCID: PMC7197490.
3. McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. doi: 10.1056/NEJMoa1409077. Epub 2014 Aug 30. PMID: 25176015.

Atrial fibrillation may reach pandemic proportions in the next 2-3 decades. Factors that drive this phenomenon have been studied in predominantly White populations, leading to a significant underrepresentation of certain racial/ethnic groups in atrial fibrillation epidemiological studies. Most atrial fibrillation epidemiology studies suggest that the non-Hispanic Black population has a lower incidence/prevalence of atrial fibrillation, despite a higher risk factor burden (“Afib paradox”). At the same time, non-Hispanic Blacks have worse outcomes compared to the White population and underrepresented populations and women are less likely than White men to receive optimal guideline-based therapies for atrial fibrillation.

In this episode, CardioNerds Dr. Kelly Arps (Co-Chair Atrial Fibrillation series, Cardiology fellow at Duke University), Dr. Colin Blumenthal (Co-Chair Atrial Fibrillation series, CardioNerds Academy House Faculty Leader for House Jones, Cardiology fellow at the University of Pennsylvania), and Dr. Dinu-Valentin Balanescu (CardioNerds Academy Faculty for House Jones, rising internal medicine chief resident at Beaumont Hospital), discuss with Dr. Larry Jackson (cardiac electrophysiologist and Vice Chief of Diversity, Equity, and Inclusion in the Division of Cardiology at Duke University) about atrial fibrillation epidemiology and health equity, challenges and possible solutions to improving diversity in clinical trials, and race/ethnicity/sex/gender differences in the detection, management, and outcomes of atrial fibrillation. Audio editing by CardioNerds Academy Intern, student doctor Akiva Rosenzveig.

This CardioNerds Atrial Fibrillation series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Kelly Arps and Dr. Colin Blumenthal.

This series is supported by an educational grant from the Bristol Myers Squibb and Pfizer Alliance. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds.

We have collaborated with VCU Health to provide CME. Claim free CME here!

Disclosure: Larry R. Jackson II, MD, MHs, has the following relevant financial relationships:
Advisor or consultant for: Biosense Webster Inc.
Speaker or a member of a speakers bureau for: Biotronik Inc.; Medtronic Inc.

Pearls • Notes • References • Guest Profiles • Production Team

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1. Atrial fibrillation confers an enormous public health burden. It is estimated that it will reach pandemic proportions over the next 30 years, with potentially 100-180 million people worldwide suffering from this condition.
2. Large epidemiological atrial fibrillation registries have very small populations of underrepresented groups. More diverse enrollment in clinical trials is essential and may be obtained by increasing diversity among research staff, principal investigators, and steering committees, and use of mobile/telehealth technologies to remove bias related to differences in presentation. The CardioNerds Clinical Trials Network specifically aims pair equitable trial enrollment with trainee personal and professional development.
3. Most atrial fibrillation epidemiology studies suggest that the non-Hispanic Black population has lower incidence/prevalence of atrial fibrillation, despite higher risk factor burden. This “paradox” is likely due to a multifactorial process, with clinical differences, socioeconomic factors, and genetic factors contributing.
4. Underrepresented populations are less likely than White patients to receive optimal guideline-based management of atrial fibrillation. Though there is a higher incidence of intracranial bleeding on vitamin K antagonists in this population, they are less likely to receive optimal anticoagulation for stroke prevention with direct oral anticoagulants. Also, despite overall worse outcomes, they are less likely to be prescribed rhythm control strategies or offered catheter-based ablation despite known data with improved outcomes with early rhythm control.
5. Gender-based differences in atrial fibrillation epidemiology, management, and outcomes also exist. Compared to men, women have a lower incidence/prevalence of atrial fibrillation but are more likely to be symptomatic. They are also more likely to receive rate instead of rhythm control strategies and suboptimal stroke reduction therapies Overall, women have worse outcomes than men. 

“I want to differentiate [equitable care] from equal care. I think this idea of equity means that we have to take into account the myriad of differences that we see between people of different races, ethnicities, genders, sexes, regions, whether they’re citizens or not, whether they’re disabled or not […] and make sure that we’re thinking about those in terms of prescriptions and discussion and communication, and offering our patients therapy, […] it’s not [enough] to offer different people the same therapy because they may have different barriers that may prevent them from uptaking that therapy or utilizing that.”

Drafted by Dr. Dinu-Valentin Balanescu and reviewed by Dr. Colin Blumenthal.

1. What factors contribute to the atrial fibrillation epidemic and where do we expect to be over the next 20-30 years?

• The current global prevalence of atrial fibrillation is unclear. It is estimated that over the next 30 years, the prevalence of atrial fibrillation may reach pandemic proportions, with potentially 100-180 million people worldwide suffering from this condition.1
• Factors that drive this increase:
  • Classic: heart failure, coronary artery disease, hypertension, diabetes, tobacco use, obesity.
  • Novel risk factors: obstructive sleep apnea, metabolic syndrome, left ventricular hypertrophy, left atrial enlargement.
  • Novel markers (inflammatory, biochemical): B-type natriuretic peptide, CRP.
• Many of the above factors have been determined by studying predominantly White populations.

2. There is conflicting data regarding the incidence of atrial fibrillation across race and ethnicity, with most studies suggesting a higher incidence in the non-Hispanic White population compared to non-Hispanic Black or Hispanic individuals, while some suggest a similar prevalence. How is this discrepancy explained?

• The discrepancy may stem from various rates of clinical detection, rather than incidence or prevalence, of atrial fibrillation between different race/ethnicity groups (“ascertainment bias”).
• Conflicting data persists even when detection is adjusted for. A cohort of the MESA study showed that the prevalence among race and ethnicity was similar when the diagnosis was made using Holter monitor data.2 Data from the ASSERT trial suggest that when using implantable loop recorders, the incidence of atrial fibrillation among the non-Hispanic Black population was lower than a European White population.3
• There is a substantial need for further study on the epidemiology of atrial fibrillation across race/ethnicity.

3. Non-Hispanic Black populations have a higher risk factor burden for atrial fibrillation than White patients, but as described above most studies demonstrate a lower incidence – how is this “paradox” explained?

• The “atrial fibrillation paradox” is a double paradox, as Dr. Jackson explains: despite a higher risk factor burden, non-Hispanic Blacks have a lower incidence/prevalence of atrial fibrillation. At the same time, non-Hispanic blacks have worse outcomes compared to the white population.4
• This is likely due to a multifactorial process, with clinical differences, socioeconomic factors, and genetic factors contributing.5 Specifically:
  • Ascertainment bias. Certain racial/ethnic groups may have access issues preventing them from seeking medical attention for rhythm assessment and/or may be less likely to be prescribed rhythm monitors for objective assessment. Additionally, it has been shown that the non-Hispanic Black population has more paroxysmal symptoms, which could lead to difficulties in diagnosis.
  • Survival bias. Non-Hispanic Whites have a longer life expectancy compared to underrepresented racial/ethnic groups, which may lead to a greater risk of developing atrial fibrillation over time.
  • Genetic/epigenetic differences. Stronger European ancestry within non-Hispanic Blacks is associated with a higher risk of atrial fibrillation. Genome-wide association studies suggest that non-Hispanic Blacks may have protective genes compared to whites.

4. What are barriers to the diagnosis of atrial fibrillation in understudied populations and how can inclusion in research studies be improved?

• Large epidemiological registries have traditionally included very small proportions of underrepresented groups. A more diverse enrollment in clinical trials is essential.
• Clinical trial participation of marginalized populations may be achieved by:
  • Using mobile/telehealth technologies to recruit and follow patients.
  • Increasing diversity and heterogeneity among research staff, principal investigators, steering committees, which has been shown to improve study diversity.
• From a clinical standpoint, barriers may be removed by:
  • Educating patients on atrial fibrillation, its complications, its treatments, and its outcomes.
  • Involving family and other social communities as part of decision-making support.

• The CardioNerds Clinical Trials Network specifically aims pair equitable trial enrollment with trainee personal and professional development

5. How are race and ethnicity associated with the workup for atrial fibrillation and the use of specialized diagnostic equipment?

• Clinicians should have a high index of suspicion for atrial fibrillation while understanding the racial/ethnic/gender differences in presentation and management.
• Patients from various racial/ethnic/gender groups may present with different symptoms of atrial fibrillation. For example, non-Hispanic Blacks are more likely to be more symptomatic, but also more paroxysmal. They are also more likely to have a have lower quality of life.6
• If clinical index of suspicion is high, ambulatory monitoring should be pursued.

6. What are the differences in management between White and black patients when it comes to rate versus rhythm control, anticoagulation, and procedures?

• With regards to anticoagulation:
  • Black patients are less likely than white patients to be prescribed anticoagulation or, if prescribed, are significantly less likely to be prescribed a direct oral anticoagulant (DOAC).7
  • Underrepresented populations have a higher risk of intracranial hemorrhage while on a vitamin K antagonists (VKA) compared to whites. DOACs overall have a lower risk of intracranial hemorrhage and should preferentially be prescribed over VKAs.8
  • Pivotal trials comparing DOACs to VKAs have had a very low enrollment of Hispanic and non-Hispanic black populations, so it is possible the benefit is even greater in this population.
• With regards to rhythm control strategies:
  • Black patients are less likely to receive rhythm control therapies (whether cardioversion, medical, or invasive) and more likely to receive rate control therapy.8
  • Black patients have a better response to catheter ablation of atrial fibrillation compared to white patients. This treatment may be preferred in underrepresented populations to improve outcomes compared to medical therapy alone.9

7. What are gender-based differences in AF epidemiology and management and are there underlying differences in the electrical conduction system between men and women that affect management decisions?

• Compared to men, women:
  • Have a lower incidence and prevalence of atrial fibrillation.
  • Are more likely to be symptomatic.
  • Are more likely to receive rate control strategies as opposed to rhythm control strategies.
  • Are less likely to receive stroke reduction therapies (e.g., anticoagulation or left atrial appendage closure).
  • Have worse outcomes: higher risk of stroke, QTc prolongation and torsades de pointes, heart failure, and mortality.10,11
• These differences may be due to:
  • Autonomic differences (especially in the 2nd-5th decades of life).
  • Differences in the effects of sex hormones. Estrogen can affect the differential expression of ion channel subunits, ion channel function, inhibits the hERG K channel. Certain sex hormones may also impact action potential duration and alter calcium metabolism.

8. Are the differences in the diagnosis, work-up, and treatment of atrial fibrillation among racial/ethnic/gender groups associated with differences in outcomes?

• Underrepresented groups have worse outcomes compared to the White population: higher risk of stroke, heart failure, and mortality.12
• Differences in the management of atrial fibrillation among racial/ethnic/gender groups contribute to these worse outcomes, e.g., lower rates of stroke prevention therapies and rhythm control strategies (patients in sinus rhythm had a 50% reduction in mortality in the AFFIRM trial).9
• The field needs to progress in a way that teaches clinicians to understand barriers in optimal care faced by certain racial/ethnic/gender groups.

9. Dr. Larry Jackson – what makes your heart flutter about electrophysiology and studying health inequity?

• The chance to provide equitable care.
• Equitable care is different from equal care. Equity implies acknowledging the differences between people of different races, ethnicity, genders, regions. These factors should be taken into account when offering therapies to our patients.
• It is not practical to offer different patients the same therapy, as they may have different barriers preventing them from utilizing that therapy.
• Optimal communication and assessment of patient goals with a focus on race/ethnicity/gender leads to better more personalized care.

1. Martinez C, Katholing A, Wallenhorst C, Granziera S, Cohen AT, Freedman SB. Increasing incidence of non-valvular atrial fibrillation in the UK from 2001 to 2013. Heart. Nov 2015;101(21):1748-54. doi:10.1136/heartjnl-2015-307808

2. Rodriguez CJ, Soliman EZ, Alonso A, et al. Atrial fibrillation incidence and risk factors in relation to race-ethnicity and the population attributable fraction of atrial fibrillation risk factors: the Multi-Ethnic Study of Atherosclerosis. Ann Epidemiol. Feb 2015;25(2):71-6, 76.e1. doi:10.1016/j.annepidem.2014.11.024

3. Lau CP, Gbadebo TD, Connolly SJ, et al. Ethnic differences in atrial fibrillation identified using implanted cardiac devices. J Cardiovasc Electrophysiol. Apr 2013;24(4):381-7. doi:10.1111/jce.12066

4. Mendys P, Jackson LR, 2nd, Solimon EZ, Howard G, Ferdinand K. The atrial fibrillation paradox -connecting hypertension to atrial disease and stroke. Am J Prev Cardiol. Dec 2021;8:100284. doi:10.1016/j.ajpc.2021.100284

5. Essien UR, Kornej J, Johnson AE, Schulson LB, Benjamin EJ, Magnani JW. Social determinants of atrial fibrillation. Nat Rev Cardiol. Nov 2021;18(11):763-773. doi:10.1038/s41569-021-00561-0

6. Norby FL, Benjamin EJ, Alonso A, Chugh SS. Racial and Ethnic Considerations in Patients With Atrial Fibrillation: JACC Focus Seminar 5/9. J Am Coll Cardiol. Dec 21 2021;78(25):2563-2572. doi:10.1016/j.jacc.2021.04.110

7. Ugowe FE, Jackson LR, 2nd, Thomas KL. Racial and ethnic differences in the prevalence, management, and outcomes in patients with atrial fibrillation: A systematic review. Heart Rhythm. Sep 2018;15(9):1337-1345. doi:10.1016/j.hrthm.2018.05.019

8. Golwala H, Jackson LR, 2nd, Simon DN, et al. Racial/ethnic differences in atrial fibrillation symptoms, treatment patterns, and outcomes: Insights from Outcomes Registry for Better Informed Treatment for Atrial Fibrillation Registry. Am Heart J. Apr 2016;174:29-36. doi:10.1016/j.ahj.2015.10.028

9. Meschia JF, Merrill P, Soliman EZ, et al. Racial disparities in awareness and treatment of atrial fibrillation: the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Stroke. Apr 2010;41(4):581-7. doi:10.1161/strokeaha.109.573907

10.     Schnabel RB, Pecen L, Ojeda FM, et al. Gender differences in clinical presentation and 1-year outcomes in atrial fibrillation. Heart. Jul 2017;103(13):1024-1030. doi:10.1136/heartjnl-2016-310406

11.     Westerman S, Wenger N. Gender Differences in Atrial Fibrillation: A Review of Epidemiology, Management, and Outcomes. Curr Cardiol Rev. 2019;15(2):136-144. doi:10.2174/1573403×15666181205110624

12.     Magnani JW, Norby FL, Agarwal SK, et al. Racial Differences in Atrial Fibrillation-Related Cardiovascular Disease and Mortality: The Atherosclerosis Risk in Communities (ARIC) Study. JAMA Cardiol. Jul 1 2016;1(4):433-41. doi:10.1001/jamacardio.2016.1025

Dr. Larry Jackson is a cardiac electrophysiologist and assistant professor of medicine in the Division of Cardiology at Duke University Medical Center. Dr. Jackson is also an expert researcher, focusing on analyzing racial and ethnic disparities and the impact of social determinants of health on arrhythmia care.

Dr. Dinu Balanescu. Dinu is an internal medicine resident and upcoming chief resident at Beaumont Hospital in Royal Oak, Michigan. He also serves as House Faculty for House Jones in the CardioNerds Academy.