Episodes Archives - Cardionerds

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Episodes Archives - Cardionerds episodes

October 23, 2024397. Guidelines: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure – Question #36 with Dr. Shelley Zieroth
The following question refers to Sections 2.1
and 4.2 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.
The question is asked by CardioNerds Academy Intern Dr. Adriana Mares, answered first by CardioNerds FIT Trialist Dr. Christabel Nyange, and then by expert faculty Dr. Shelley Zieroth.
Dr. Zieroth is an advanced heart failure and transplant cardiologist, Head of the Medical Heart Failure Program, the Winnipeg Regional Health Authority Cardiac Sciences Program, and an Associate Professor in the Section of Cardiology at the University of Manitoba. Dr. Zieroth is a past president of the Canadian Heart Failure Society. She has been a PI Mentor for the CardioNerds Clinical Trials Program.
The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.
Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.
American Heart Association’s Scientific Sessions 2024
As heard in this episode, the American Heart Association’s Scientific Sessions 2024 is coming up November 16-18 in Chicago, Illinois at McCormick Place Convention Center. Come a day early for Pre-Sessions Symposia, Early Career content, QCOR programming and the International Symposium on November 15. It’s a special year you won’t want to miss for the premier event for advancements in cardiovascular science and medicine as AHA celebrates its 100th birthday. Registration is now open, secure your spot here!
When registering, use code NERDS and if you’re among the first 20 to sign up, you’ll receive a free 1-year AHA Professional Membership!
Question #36

A 50-year-old woman presents to establish care. Her medical history includes COPD, prediabetes, and hypertension. She is being treated with chlorthalidone, amlodipine, lisinopril, and a tiotropium inhaler. She denies chest pain, dyspnea on exertion, or lower extremity edema.

On physical exam, blood pressure is 154/88 mmHg, heart rate is 90 beats/min, and respiration rate is 22 breaths/min with an oxygen saturation of 94% breathing ambient room air. BMI is 36 kg/m2. Jugular venous pulsations are difficult to assess due to her body habitus. Breath sounds are distant, with occasional end-expiratory wheezing. Heart sounds are distant, and extra sounds or murmurs are not detected. Extremities are warm and without peripheral edema. B-type natriuretic peptide level is 28 pg/mL (28 ng/L).

A chest radiograph shows increased radiolucency of the lungs, flattened diaphragms, and a narrow heart shadow consistent with COPD. An electrocardiogram shows evidence of left ventricular hypertrophy. The echocardiogram showed normal LV and RV function with no significant valvular abnormalities.

In which stage of HF would this patient be classified?
A
Stage A: At Risk for HF
B
Stage B: Pre-HF
C
Stage C: Symptomatic HF
D
Stage D: Advanced HF

Answer #36

Explanation
The correct answer is A – Stage A or at risk for HF.

This asymptomatic patient with no evidence of structural heart disease or positive cardiac biomarkers for stretch or injury would be classified as Stage A or “at risk” for HF.

The ACC/AHA stages of HF emphasize the development and progression of disease with specific therapeutic interventions at each stage. Advanced stages and disease progression are associated with reduced survival. The stages were revised in this edition of guidelines to emphasize new terminologies of “at risk” for Stage A and “pre-HF” for Stage B.

At Stage A, emphasis is placed on the prevention of structural heart disease by aggressive risk factor modification. Healthy lifestyle habits, including regular physical activity, maintaining a normal weight, healthy dietary habits, and avoiding smoking, help reduce the future risk of HF.

For patients with established hypertension, coronary disease, or diabetes, optimal control of risk factors is crucial.

For hypertension, the SPRINT trial and subsequent meta-analysis of 35 BP-lowering trials have demonstrated a substantial reduction in incident HF and mortality with aggressive BP control.

For diabetes, SGLT2 inhibitors have demonstrated reductions in HF hospitalizations regardless of baseline HF status.

Screening patients “at risk” for HF for disease progression may be beneficial. The STOP-HF study randomized patients with risk factors but without established LV systolic dysfunction or symptomatic HF to screening with BNP testing or usual care. Screening with BNP followed by an echocardiogram and referral to a cardiovascular specialist for those with levels ≥50 pg/mL led to a reduction in the composite endpoint of incident asymptomatic LV dysfunction with or without newly diagnosed HF. Accordingly, BNP or NT–proBNP–based screening followed by team-based care, including a cardiovascular specialist, has a Class 2a (LOE B-R) recommendation in patients at risk of developing HF to prevent the development of LV dysfunction or new-onset HF.

Our patients should be counseled on healthy lifestyles, smoking cessation, and weight loss. Her anti-hypertensive regimen should be intensified for blood pressure optimization. Her ASCVD risk should be calculated, and counseling regarding statin use should be provided accordingly. If she develops overt diabetes, she should be started on an SGLT-2 inhibitor. Given her BNP level, she does not currently warrant further evaluation with an echocardiogram or referral to a specialist.
Main Takeaway
Patients with Stage A HF are those who are at risk for HF but are without symptoms, structural heart disease, or cardiac biomarkers of stretch or injury. At this stage, the emphasis should be on identifying and modifying risk factors.
Guideline Loc.
Sections 2.1 and 4.2

Decipher the Guidelines: 2022 Heart Failure Guidelines Page
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6 min
October 21, 2024396. Case Report: Unmasking Constrictive Pericarditis Using Multimodality Imaging – University of Nebraska
CardioNerds (Dr. Dan Ambinder and Dr. Rick Ferraro) join Dr. Mansi Oberoi and Dr. Mohan Gudiwada from the University of Nebraska Medical Center discuss a case of constrictive pericarditis. Expert commentary is provided by Dr. Adam Burdorf, who serves as the Program Director for the Cardiovascular Medicine Fellowship at the University of Nebraska Medical Center.
The case discussed involves a 76-year-old woman with a history of monoclonal gammopathy of undetermined significance, chronic obstructive pulmonary disease, type 2 diabetes mellitus, and squamous cell carcinoma was admitted to the hospital for worsening shortness of breath, swelling in lower extremities, hyponatremia, and urinary tract infection. CT chest to evaluate for pulmonary embolism showed incidental pericardial calcifications; the heart failure team was consulted for the management of her decompensated heart failure. Echo images were nondiagnostic. Subsequent invasive hemodynamic monitoring showed elevated right and left-sided filling pressures, diastolic equalization of LV and RV pressures, and positive RV square root sign with ventricular interdependence. Cardiac MRI showed septal flattening on deep inspiration and septal bounce, suggestive of interventricular dependence. After a heart team discussion and with shared-decision making the patient opted for medical management owing to her comorbidities and frailty.
Enjoy this 2024 JACC State-of-the-Art Review to learn more about pericardial diseases and best practices for pericardiectomy (Al-Kazac et al., JACC 2024)
We Were Thrilled to Join the American Heart Association’s Scientific Sessions 2025!
AHA Scientific Sessions 2025 took place November 7–10 in New Orleans, LA — one of the premier annual gatherings in cardiovascular science and education.
It was an incredible opportunity to connect with colleagues, hear cutting-edge research, and contribute to the ongoing conversations shaping the future of cardiovascular care.
We’re grateful to everyone who joined us in New Orleans and made this year’s meeting so impactful.
“To study the phenomena of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all.” – Sir William Osler. CardioNerds thank the patients and their loved ones whose stories teach us the Art of Medicine and support our Mission to Democratize Cardiovascular Medicine.
Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.
US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.
CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll
CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!
Case Media – Constrictive Pericarditis
Echo: Left Ventricular ejection fraction = 55-60%. Unclear septal motion in the setting of atrial fibrillation
MRI: Diastolic septal flattening with deep inspiration as well as a septal bounce suggestive of interventricular dependence and constrictive physiology
References
Garcia, M. Constrictive Pericarditis Versus Restrictive Cardiomyopathy. Journal of the American College of Cardiology, vol. 67, no. 17, 2016, pp. 2061–2076.
Pathophysiology and Diagnosis of Constrictive Pericarditis. American College of Cardiology, 2017.
Geske, J., Anavekar, N., Nishimura, R., et al. Differentiation of Constriction and Restriction: Complex Cardiovascular Hemodynamics. Journal of the American College of Cardiology, vol. 68, no. 21, 2016, pp. 2329–2347.
Constrictive Pericarditis. ScienceDirect.
Constrictive Pericarditis. Journal of the American College of Cardiology, vol. 83, no. 12, 2024, pp. 1500-1512.
38 min
October 10, 2024395. Beyond the Boards: Channelopathies with Dr. Michael Ackerman
Dr. Amit Goyal, along with episode chair Dr. Dinu Balanescu (Mayo Clinic, Rochester), and FIT leads Dr. Sonu Abraham (University of Kentucky) and Dr. Natasha Vedage (MGH), dive into the fascinating topic of channelopathies with Dr. Michael Ackerman, a genetic cardiologist and professor of medicine, pediatrics, and pharmacology at Mayo Clinic, Rochester, Minnesota. Using a case-based approach, they review the nuances of diagnosis and treatment of channelopathies, including Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia (CPVT), and long QT syndrome. Dr. Sonu Abraham drafted show notes. Audio engineering for this episode was expertly handled by CardioNerds intern, Christiana Dangas.
The CardioNerds Beyond the Boards Series was inspired by the Mayo Clinic Cardiovascular Board Review Course and designed in collaboration with the course directors Dr. Amy Pollak, Dr. Jeffrey Geske, and Dr. Michael Cullen.
We Were Thrilled to Join the American Heart Association’s Scientific Sessions 2025!
AHA Scientific Sessions 2025 took place November 7–10 in New Orleans, LA — one of the premier annual gatherings in cardiovascular science and education.
It was an incredible opportunity to connect with colleagues, hear cutting-edge research, and contribute to the ongoing conversations shaping the future of cardiovascular care.
We’re grateful to everyone who joined us in New Orleans and made this year’s meeting so impactful.
Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.
US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.
CardioNerds Beyond the Boards Series
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll
CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!
Pearls and Quotes – Channelopathies
One cannot equate the presence of type 1 Brugada ECG pattern to the diagnosis of Brugada syndrome. Clinical history, family history, and/or genetic testing results are required to make a definitive diagnosis.
The loss-of-function variants in the SCN5A gene, which encodes for the α-subunit of the NaV1.5 sodium channel, is the only Brugada susceptibility gene with sufficient evidence supporting pathogenicity.
Exertional syncope is an “alarm” symptom that demands a comprehensive evaluation with 4 diagnostic tests: ECG, echocardiography, exercise treadmill test, and Holter monitor. Think of catecholaminergic polymorphic ventricular tachycardia (CPVT) in a patient with exertional syncope and normal EKG!
ICD therapy is never prescribed as monotherapy in patients with CPVT. Medical therapy with a combination of nadolol plus flecainide is the current standard of care.
Long QT syndrome is one of the few clinical scenarios where genetic testing clearly guides management, particularly with respect to variability in beta-blocker responsiveness.
Notes – Channelopathies
1. What are the diagnostic criteria for Brugada syndrome (BrS)?
Three repolarization patterns are associated with Brugada syndrome in the right precordial leads (V1-V2):
Type 1: Prominent coved ST-segment elevation displaying J-point amplitude or ST-segment elevation ≥2 mm, followed by a negative T wave.
Type 2/3: Saddleback ST-segment configuration with variable levels of ST-segment elevation.
It is important to note that only a type 1 pattern is diagnostic for Brugada syndrome, whereas patients with type 2/3 patterns may benefit from further testing.
The Shanghai score acknowledges that relying solely on induced type 1 ECG changes has limitations. Therefore, one cannot equate the presence of a type 1 Brugada ECG pattern alone to the diagnosis of Brugada syndrome. The score suggests incorporating additional information—such as clinical history, family history, and/or genetic testing results—to achieve a definitive diagnosis.
2. What is the significance of genetic testing in Brugada syndrome?
There are 23 alleged Brugada syndrome susceptibility genes published with varying levels of evidence. However, only one gene mutation, the loss-of-function variants in the SCN5A gene encoding for the α-subunit of the NaV1.5 sodium channel, is considered to have sufficient evidence.
The overall yield of BrS genetic testing is 20%. The presence of PR prolongation (>200 ms) along with type I EKG pattern increases the yield to 40%. On the contrary, in the presence of a normal PR interval, the likelihood of SCN5A positivity drops to <10%.
3. How would you risk-stratify a patient with Brugada syndrome?
Serious arrhythmic events (SAE), including resuscitated cardiac arrest and sudden cardiac death, rarely represent the initial symptoms of Brugada syndrome. Thus, risk stratification is important.
Factors that increase risk include:
Resuscitated cardiac arrest or history of cardiogenic syncope and the presence of a spontaneous type 1 ECG.
Positive genetic test – certain SCN5A variants were independent predictors for SAE.
Inducibility during programmed ventricular stimulation (EP study) using a double stimulation protocol (annualized risk is 1.5% per year for a positive study and 0.5% per year for a negative study).
4. What are the treatment options for Brugada syndrome?
The only drug with therapeutic potential in BrS is quinidine. The antiarrhythmic effect is achieved by prolonging the effective refractory period via inhibition of Ito potassium channel.
BrS plus a history of cardiac arrest, sustained VT, or syncope judged to be caused by ventricular arrhythmia would warrant an ICD.
In those refractory to first-line therapies, RVOT epicardial ablation is now an additional therapeutic option.
5. What are the four diagnostic tests to be done in a patient who presents with an episode of exertional syncope?
Exertional syncope is a high-risk presentation that demands a comprehensive evaluation! This includes:
EKG
Echocardiogram
Exercise treadmill test
Holter monitor
Do not stop at an EKG and echo alone!
Think of catecholaminergic polymorphic ventricular tachycardia (CPVT) in a patient with exertional syncope and a normal EKG!
6. What are the features on the exercise treadmill test that increase the suspicion for CPVT?
Bidirectional VT is considered a hallmark of CPVT, with digoxin toxicity being the only real imitator. This finding is specific in the absence of digoxin but not sensitive.
During exercise testing in CPVT, as the patient’s heart rate rises with increasing workload, PVCs begin to appear, progressing to bigeminy, couplets, and, in some instances, bidirectional couplets. The ectopy typically vanishes within 30 seconds of the recovery phase. This pattern increases suspicion of CPVT and warrants a detailed family history and genetic testing.
7. What are the genetic underpinnings of CPVT?
Mutations in the ryanodine receptor (RyR2 gene) render calcium release channels leaky, leading to diastolic calcium overload. This ultimately triggers arrhythmias in CPVT.
8. What are therapeutic interventions for a patient with CPVT?
Medical therapy is the mainstay of treatment in CPVT. Drugs include non-selective beta-blockers like nadolol or propranolol. Standard of care currently includes a combination of nadolol plus flecainide. An ICD is indicated only in the case of an aborted cardiac arrest. ICD therapy is never prescribed as monotherapy in these patients.
9. How do we correctly measure the QTc?
The QT interval is measured from the beginning of the QRS complex to the end of the T wave. The end of the T wave is determined using the maximum slope intercept method, in which a tangent line is drawn through the maximum down slope of the T wave. The point at which this tangent line crosses the isoelectric line is the end of the T wave. The U wave is excluded.
Best measured in leads II or V5.
Quick eyeball test: if the QT interval is more than ½ the RR interval, the QTc will be >460 ms.
10. What are the three primary mutations implicated in Long QT syndrome?
LQT1 (30-40% of cases)
Mutation: loss of function in potassium channel gene KCNQ1
ECG: broad-based T wave
Trigger: activity, adrenaline, exercise
BB responsiveness: +++ (nadolol or propranolol)
LQT2 (second most common)
Mutation: loss of function in potassium channel gene KCNH2
ECG: notched T wave
Trigger: auditory (alarm clock), post-partum
BB responsiveness: ++
LQT3
Mutation: gain of function or leakiness of sodium channel SCN5A (note: BrS is due to loss of function in the same gene)
ECG: normal T wave after prolonged isoelectric ST segment
Trigger: none, but typically happens during rest
BB responsiveness: + (propranolol); may consider combination therapy with mexiletine or mexiletine monotherapy.
References – Channelopathies
Charles Antzelevitch, Gan-Xin Yan, Michael J. Ackerman, Arthur A.M. Wilde et al. J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge, EP Europace, Volume 19, Issue 4, April 2017, Pages 665–694
Krahn AD, Behr ER, Hamilton R, Probst V, Laksman Z, Han HC. Brugada Syndrome. JACC Clin Electrophysiol. 2022 Mar;8(3):386-405. PMID: 35331438.
Chockalingam, P, Crotti, L, Girardengo, G. et al. Not All Beta-Blockers Are Equal in the Management of Long QT Syndrome Types 1 and 2: Higher Recurrence of Events Under Metoprolol. JACC. 2012 Nov, 60 (20) 2092–2099
Priori SG, Wilde AA, Tracy C et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm. 2013 Dec;10(12):1932-63. PMID: 24011539.
Viskin S, Rosovski U, Zeltser D et al. Inaccurate electrocardiographic interpretation of long QT: the majority of physicians cannot recognize a long QT when they see one. Heart Rhythm. 2005 Jun;2(6):569-74. PMID: 15922261.
Horner JM, Ackerman MJ. Ventricular ectopy during treadmill exercise stress testing in the evaluation of long QT syndrome. Heart Rhythm. 2008 Dec;5(12):1690. PMID: 19084807; PMCID: PMC3281579.
1 hr 6 min
October 02, 2024 394. 3rd Annual Sanjay V. Desai Lecture: Artificial Intelligence in Medical Education with Dr. Kathryn Berlacher, Dr. Melissa McNeil, and Dr. Alfred Shoukry
The CardioNerds Academy is excited to present the 3rd Annual Sanjay V. Desai Lecture in Medical Education, featuring a deep dive into the evolving role of Artificial Intelligence in Medical Education. Join us as Dr. Kathryn Berlacher, Dr. Melissa McNeil, and Dr. Alfred Shoukry explore the transformative potential of AI in training future healthcare professionals and enhancing educational methodologies. Their insightful discussion sheds light on the integration of cutting-edge technologies to improve medical learning and patient care. The conversation is faciliated by Dr. Tommy Das, Program Director of the CardioNerds Academy, and CardioNerds Academy Chiefs: Dr. Callie Clark, Dr. Rachel Goodman, Dr. Ronaldo Correa Fabiano, and Dr. Claire Cambron, who bring their expertise and enthusiasm to this engaging discussion on the future of medical education. Special thanks to Pace Wetstein, CardioNerds academy intern, for his exceptional audio editing in this episode.
Dr. Kathryn Berlacher is a graduate of The Ohio State University College of Medicine and completed her internal medicine residency, chief residency, and cardiology fellowship at UPMC, where she has been on faculty since 2012. She earned a master’s degree in medical education from the University of Pittsburgh and has served as the Program Director of the Cardiovascular Fellowship Program since 2015. In 2021, she was appointed Associate Chief of Education for the UPMC Heart and Vascular Institute. Additionally, Dr. Berlacher is the director of the McGee Women’s Heart Program and chief of medicine at McGee Women’s Hospital. Nationally, she serves as the chair for the American College of Cardiology’s Annual Scientific Sessions for 2025 and 2026, regularly speaking on women’s cardiology, medical education, diversity, inclusion, and health equity.

Dr. Alfred Shoukry graduated from Northwestern University with dual degrees in Neurobiology and Biomedical Engineering. He completed medical school and internal medicine residency at UPMC, where he also earned a certificate in medical education. Dr. Shoukry serves as core faculty at the University of Pittsburgh School of Medicine and cares for patients at the VA in Pittsburgh. As the course director for Population Health, he teaches on topics such as patient safety, quality improvement, and bioinformatics. He is an expert on the impact of large language models in medical education, presenting locally and nationally on the subject.

Dr. Melissa McNeil received her undergraduate degree from Princeton University, her MD from the University of Pittsburgh, and a Master of Public Health from the same institution. She is a professor emeritus of medicine at the University of Pittsburgh and recently joined the faculty at Brown University as a professor of medicine. Dr. McNeil serves as an academic hospitalist and senior consultant to the Women’s Health Division at Brown. Her expertise lies in developing training programs to foster leaders in women’s health education and research. She has been recognized nationally for her contributions, including being named the Society of General Internal Medicine Distinguished Professor of Women’s Health in 2014 and receiving their Career Achievement in Medical Education award in 2016.
Dr. Sanjay V Desai serves as the Chief Academic Officer, The American Medical Association and is the former Program Director of the Osler Medical Residency at The Johns Hopkins Hospital.
Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.
US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll
CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!
We Were Thrilled to Join the American Heart Association’s Scientific Sessions 2025!
AHA Scientific Sessions 2025 took place November 7–10 in New Orleans, LA — one of the premier annual gatherings in cardiovascular science and education.
It was an incredible opportunity to connect with colleagues, hear cutting-edge research, and contribute to the ongoing conversations shaping the future of cardiovascular care.
We’re grateful to everyone who joined us in New Orleans and made this year’s meeting so impactful.
1 hr 2 min
October 01, 2024393. SGLT Inhibitors: Clinical Implementation of SGLT Inhibitors with Dr. Alison Bailey
CardioNerds Drs. Jason Feinman, Gurleen Kaur, and Rick Ferraro discuss the implementation of SGLT inhibitors in clinical practice with Dr. Alison Bailey. Notes were drafted by Dr. Jason Feinman.
In this episode, we discuss the implementation of SGLTi in clinical practice scenarios, including for individuals with heart failure regardless of ejection fraction, those with chronic kidney disease, and those with diabetes mellitus. The group also discusses important side effects to monitor for, as well as how to counsel patients when prescribing these medications.
This episode was produced in collaboration with the American Society of Preventive Cardiology (ASPC) with independent medical education grant support from Lexicon Pharmaceuticals.
We Were Thrilled to Join the American Heart Association’s Scientific Sessions 2025!
AHA Scientific Sessions 2025 took place November 7–10 in New Orleans, LA — one of the premier annual gatherings in cardiovascular science and education.
It was an incredible opportunity to connect with colleagues, hear cutting-edge research, and contribute to the ongoing conversations shaping the future of cardiovascular care.
We’re grateful to everyone who joined us in New Orleans and made this year’s meeting so impactful.
Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.
US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.
CardioNerds Prevention Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll
CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!
Pearls – Clinical Implementation of SGLT Inhibitors
For patients with heart failure with reduced ejection fraction, SGLT inhibitors reduce the composite outcome of cardiovascular death or heart failure hospitalization by 25%.
SGLT inhibitors can be safely started in patients with an eGFR as low as 20. There are ongoing trials investigating the safety of these medications in individuals with eGFR lower than 20 or those who are receiving dialysis.
An eGFR decrease of 3-5 ml/min on average is expected after starting an SGLTi, but this will stabilize over time and provides protective effects of renal dysfunction in the long run.
Early data that suggested an association between SGLTi and bacterial UTI development hasn’t panned out in the long run, but there is an association between SGLTi and the development of either genital mycotic infections or yeast infections. Perineal hygiene is important to prevent the development of either.
A patient-centered, shared decision-making approach should guide the choice of agents for individuals with type 2 diabetes mellitus. In certain patients, it may be reasonable to choose an SGLTi as the first-line agent.
Show notes – Clinical Implementation of SGLT Inhibitors
What is the data supporting the use of SGLTi in HFpEF?
The EMPEROR-Preserved and DELIVER trials investigated the impact of empagliflozin and dapagliflozin, respectively, on cardiovascular outcomes in patients with mildly reduced or preserved ejection fraction.
The SOLOIST-WHF trial investigated a combined SGLT1/2 inhibitor, sotagliflozin, in patients with recently worsening heart failure, irrespective of ejection.SGLTi have been demonstrated to reduce the risk of cardiovascular death or worsening heart failure, including heart failure hospitalization, in these individuals.
A meta-analysis of the EMPEROR-Preserved and DELIVER trials demonstrated a hazard ratio of 0.80 for cardiovascular death or first hospitalization for heart failure for empagliflozin or dapagliflozin over placebo in the setting of HFpEF.
What is the data supporting the use of SGLTi in HFrEF?
In addition to the SOLOIST-WHF trial that was previously discussed, the EMPEROR-HF and DAPA-HF investigated the impact of SGLTi medications in patients with HFrEF.
In patients with HFrEF, SGLTi medications have been demonstrated to reduce the risk of either cardiovascular death or heart failure hospitalization.
Dapagliflozin and empagliflozin had a pooled risk reduction of all-cause death of 13%, a pooled risk reduction of cardiovascular death of 14%, and a 26% reduction in the combination of CV death or first hospitalization for heart failure.
What is the expected impact of SGLTi on renal function?
Dapagliflozin, empagliflozin, sotagliflozin, ertugliflozin, and canagliflozin have all been studied for their impact on renal dysfunction in individuals both with and without diabetes.
In the CANVAS trial, canagliflozin was associated with an initial decrease in eGFR of 3.2ml/min compared to placebo but overall decreased change from baseline in eGFR compared to placebo at trial end.In a large meta-analysis, SGLTi medications reduced the progression of kidney disease by 37%.
The risk of acute kidney injury was reduced by 23%.
What are the recommendations for SGLTi in patients with type 2 diabetes mellitus?
ADA guidelines emphasize a patient-centered shared decision-making approach when choosing which pharmacologic agent to prescribe for an individual with diabetes mellitus.
Factors in choosing which agent include the risk of cardiovascular disease, the risk of renal disease, and whether there is an emphasis on weight reduction.
What side effects should be monitored for when starting an individual on an SGLTi medication?
Side effects with SGLTi medications are overall rare but include DKA, genital mycotic infections, necrotizing fasciitis, and volume status derangements.
In the CANVAS trial, SGLTi was associated with an increased risk of amputation, but this has not been shown to be consistent in other trials. Nevertheless, in a meta-analysis including CANVAS, SGLTi medications were associated with a 15% relative risk of amputation over placebo medications.The relative risk of DKA in the same meta-analysis was 2.12.
Careful assessment of an individual’s volume status and whether they are on any other diuretic medications when initiating an SGLTi medication may allow for upfront adjustment of these medications to reduce the risk of dehydration.
References – Clinical Implementation of SGLT Inhibitors
Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. 2022;387(12):1089-1098.
Anker SD, Butler J, Filippatos G, et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021;385(16):1451-1461.
Bhatt DL, Szarek M, Steg PG, et al. Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. N Engl J Med. 2021;384(2):117-128.
Vaduganathan M, Docherty KF, Claggett BL, et al. SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials. Lancet. 2022;400(10354):757-767.
Packer M, Anker SD, Butler J, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020;383(15):1413-1424.
McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008.
Zannad F, Ferreira JP, Pocock SJ, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet. 2020;396(10254):819-829.
Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017;377(7):644-657.
Nuffield Department of Population Health Renal Studies Group; SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists’ Consortium. Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet. 2022;400(10365):1788-1801.
American Diabetes Association Professional Practice Committee. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2024. Diabetes Care. 2024;47(Suppl 1):S158-S178.
20 min
September 23, 2024392. Case Report: Heart Failure Out of the Blue, A Case of Cobalt Cardiomyopathy – Georgetown University
CardioNerds (Amit Goyal) join Dr. Merna Hussien, Dr. Akhil Kallur, Dr. Abhinav Saxena, and Dr. Brody Deb from the MedStar Georgetown – Washington Hospital Center in DC for a stroll around Rock Creek Park as they discuss an unusual case of cobalt cardiomyopathy. Expert commentary is provided by Dr. Nana Afari Armah. Episode audio was edited by CardioNerds Intern Christiana Dangas.
The case is of a middle-aged woman with a past medical history of hypertension, hyperlipidemia, and bilateral hip replacements, who presented with subacute progressive exertional dyspnea, orthopnea, and constitutional symptoms and was found to have SCAI Stage C cardiogenic shock. Transthoracic echocardiogram showed severely reduced left ventricular ejection fraction (LVEF, 20-25%) and a moderate pericardial effusion. Cardiac catheterization revealed biventricular failure with elevated filling pressures. A cardiac MRI showed diffuse late gadolinium enhancement (LGE) in the left ventricle. Endomyocardial biopsy showed nonspecific chronic inflammation. However, the evidence of mitochondrial heavy metal toxicity and elevated cobalt levels made the diagnosis of cobalt cardiomyopathy. The patient underwent revision of hip joint implants to ceramic implants and started chelation therapy. However, due to persistent stage D heart failure despite normalization of cobalt levels, she underwent orthotropic heart transplantation.
“To study the phenomena of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all.” – Sir William Osler. CardioNerds thank the patients and their loved ones whose stories teach us the Art of Medicine and support our Mission to Democratize Cardiovascular Medicine.
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Case MEdia – Cobalt Cardiomyopathy
Pearls – Cobalt Cardiomyopathy
A good history goes a long way in diagnosing non-ischemic cardiomyopathy (NICM).
Common problems can have uncommon presentations requiring a high degree of suspicion for diagnosis.
Imaging features can overlap between causes of NICM. History helps in targeting further histological workup and uncovering the root cause.
Multidisciplinary effort is essential in making a rare diagnosis.
Taken from1 – Singh M, Krishnan M, Ghazzal A, Halushka M, Tozzi JE, Bunning RD, Rodrigo ME, Najjar SS, Molina EJ, Sheikh FH. From Hip to Heart: A Comprehensive Evaluation of an Infiltrative Cardiomyopathy. CJC Open. 2021 Nov 1;3(11):1392–5.
Notes – Cobalt Cardiomyopathy
How common is cobalt cardiomyopathy? When should it be suspected?
Cobalt cardiomyopathy is incredibly rare, with only a handful of reported cases. 2 It is also known as beer drinkers’ cardiomyopathy, as cobalt was added to beer for fortification in Quebec 3, where it was first reported. Cobalt cardiomyopathy is characterized by its rapidly progressive nature, the presence of low voltages on EKG, and diffuse infiltration. Patients also complained of a previous history of anorexia and weight loss and were found to have polycythemia and thyroid abnormalities on labs. This syndrome was very similar to wet beriberi except for the absence of a therapeutic response to thiamine.
Taken from – 2
Later, this was noted in patients with total metal hip arthroplasty 4–6, especially in patients with metal-on-metal hip arthroplasty, which led to corrosion and leakage of cobalt into the bloodstream. The syndrome in these patients was similar to those in beer drinkers from Quebec.
This figure, taken from 2, shows the reports of Cobalt cardiomyopathy after cobalt alloy prostheses. [HX1]
What is the pathophysiology of cobalt cardiomyopathy?
Cobalt has a variety of effects on the heart, both microscopically and biochemically.
Cobalt may have multiple calcium-mediated cardiac effects and may also interfere with the Krebs cycle and ATP generation by mitochondria. Histology may show modest changes with no inflammatory response on microscopy and ultrastructural changes, including vacuolar degeneration and swollen and distorted mitochondria with loss of cristae.
Remarkably, cardiac dysfunction does not correlate with serum cobalt levels. 2
How does cobalt cardiomyopathy present, and how do we diagnose it?
Diagnosis is made with a consistent exposure history and high index of suspicion. Patients present with anorexia and cachexia and complain of rapid onset and progression of symptoms of cardiomyopathy.
Labs may show polycythemia and thyroid dysfunction. Cobalt levels should be elevated, but the severity of the disease does not correlate well with levels.
Cardiac workup: EKG shows low voltage from infiltration and pericardial effusion. Echocardiogram shows systolic dysfunction and pericardial effusion. MRI shows diffuse infiltrative pathology. Native heart pathology is often diagnostic. 2
How is cobalt cardiomyopathy managed?
Medical management of heart failure, including guideline directed medical therapy (GDMT), inotropic support, and mechanical circulatory support, implantable device or transplant where appropriate.
Oral chelating agents should be used.
The mainstay of management is the removal of the prosthesis or source of exposure. 2
What is the prognosis of Cobalt Cardiomyopathy?
In the beer-drinker population, the prognosis was bad. Patients in that population had rapid clinical progression leading to cyanosis, marked elevation of cardiac and hepatic enzymes, lactic acidosis, and shock, and a high mortality rate (of 10%–40%), which was proportional to the daily intake of beer. 2
Some patients may recover function after removal of the cobalt source and normalization of the levels. However, some patients, like our patient, continue to have deterioration of function despite lower Cobalt levels requiring mechanical support and heart transplant.
Infographic made by the team (Made with BioRender – license included)
References – Cobalt Cardiomyopathy
1.     Singh M, Krishnan M, Ghazzal A, et al. From Hip to Heart: A Comprehensive Evaluation of an Infiltrative Cardiomyopathy. CJC Open. 2021;3(11):1392-1395. https://www.ncbi.nlm.nih.gov/pubmed/34901809
2.     Packer M. Cobalt Cardiomyopathy. Circ Heart Fail. 2016;9(12):e003604. https://www.ahajournals.org/doi/epub/10.1161/CIRCHEARTFAILURE.116.003604
3.     Mercier G, Patry G. Quebec beer-drinkers’ cardiomyopathy: clinical signs and symptoms. Can Med Assoc J. 1967;97(15):884-888. https://pubmed.ncbi.nlm.nih.gov/6051257/
4.     Oldenburg M, Wegner R, Baur X. Severe cobalt intoxication due to prosthesis wear in repeated total hip arthroplasty. J Arthroplasty. 2009;24(5):825.e15-20. https://www.ncbi.nlm.nih.gov/pubmed/18835128
5.     Tower SS. Arthroprosthetic cobaltism: neurological and cardiac manifestations in two patients with metal-on-metal arthroplasty: a case report. J Bone Joint Surg Am. 2010;92(17):2847-2851. https://www.ncbi.nlm.nih.gov/pubmed/21037026
6.     Casian M, Bica R, Ionescu V, Predescu V, Țincu R, Jurcuț R. Too young for an acquired cardiomyopathy? Cobalt metallosis as a cardiac amyloidosis mimicker. ESC Heart Fail. 2024;11(2):1236-1241. https://onlinelibrary.wiley.com/doi/10.1002/ehf2.14695
35 min
September 19, 2024 391. Guidelines: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure – Question #35 with Dr. Mark Drazner

The following question refers to Section 2.2 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.
The question is asked by University of Colorado internal medicine resident Dr. Hirsh Elhence, answered first by University of Chicago advanced heart failure cardiologist and Co-Chair for the CardioNerds Critical Care Cardiology Series Dr. Mark Belkin, and then by expert faculty Dr. Mark Drazner.
Dr. Drazner is an advanced heart failure and transplant cardiologist, Professor of Medicine, and Clinical Chief of Cardiology at UT Southwestern. He is the President of the Heart Failure Society of America.
The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.
Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Question #35
A 50-year-old woman with a history of congestive heart failure, hypertension, type 2 diabetes mellitus, and obstructive sleep apnea presents to the outpatient clinic to follow up on her heart failure management. One year prior, echocardiogram showed an ejection fraction of 30% with an elevated BNP, for which she was started on appropriate GDMT. Repeat echocardiogram today showed an EF of 50%. Which of the following best describes her heart failure status?
A
HFrEF (HF with reduced EF)
B
HFimpEF (HF with improved EF)
C
HFmrEF (HF with mildly reduced EF)
D
HFpEF (HF with preserved EF)
Answer #35
Explanation
The correct answer is B – HFimpEF, or heart failure with improved ejection fraction, best describes her current heart failure status.
Left ventricular ejection fraction is an important factor in classifying heart failure given differences in prognosis, response to treatment, and use in clinical trial enrollment criteria.
The classification of heart failure by EF (adopted from the Universal Definition of HF):
–        HFrEF (HF with reduced EF): LVEF ≤40%
–        HFimpEF (HF with improved EF): previous LVEF ≤40%, a ≥10% increase from baseline LVEF, and a second measurement of LVEF >40%.
–        HFmrEF (HF with mildly reduced EF): LVEF 41%–49%, and
evidence of spontaneous or provokable increased LV filling pressures (e.g., elevated natriuretic peptide, noninvasive and invasive hemodynamic measurement)
–        HFpEF (HF with preserved EF): LVEF ≥50%, and evidence of spontaneous or provokable increased LV filling pressures (e.g., elevated natriuretic peptide, noninvasive and invasive hemodynamic measurement)
Patients with HFmrEF are usually in a dynamic state of improving from HFrEF or deteriorating towards HFrEF. Therefore, patients with HFmrEF may benefit from follow-up evaluation of systolic function and etiology of sub-normal EF.
Improvements in EF are associated with better outcomes but do not indicate full myocardial recovery or normalization of LV function. Indeed, structural and functional abnormalities such as LV dilation and systolic or diastolic dysfunction often persist. Moreover, EF may remain dynamic with fluctuations in either direction depending on factors such as GDMT adherence and re-exposure to cardiotoxic agents. As such, the term heart failure with “improved EF” was deliberately chosen over “recovered EF” and “preserved EF”. Importantly, in patients with HFimpEF while on GDMT, the EF may decrease after withdrawal of GDMT.
Main Takeaway
Classification of Heart failure helps direct and track management.
Guideline Loc.
Section 2.2

Decipher the Guidelines: 2022 Heart Failure Guidelines Page
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7 min
September 18, 2024390. Cardio-Rheumatology: Deciphering Cardiovascular Risk in Patients with Rheumatologic Conditions with Dr. Brittany Weber and Dr. Michael Garshick
CardioNerds Cardio-Rheumatology Series Co-Chairs Dr. Rick Ferraro, Dr. Gurleen Kaur, and and Dr. Bree Hansen discuss how to decipher cardiovascular risk in patients with rheumatological conditions with cardio-rheumatology experts Dr. Brittany Weber and Dr. Michael Garshick.
In this episode, Drs. Weber and Garshick take us through the role of inflammation in patients with rheumatologic conditions and cardiovascular disease. They discuss the increased prevalence of traditional cardiac risk factors in this population and how these standard cardiac risk factors do not account for the full extent of cardiovascular risk. Dr. Bree Hansen drafted show notes. Audio editing by CardioNerds intern Christiana Dangas.
Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.
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This episode is supported by the 5th Annual Going Back to the Heart of Cardiology (A MedscapeLIVE Conference). Join co-chairs Dr. Robert Harrington and Dr. Fatima Rodriguez January 24-26, 2025 at the Fontainebleau Hotel in Miami Beach, Florida.
The agenda will explore the latest advancements in cardiology including cardiovascular prevention, atherosclerosis and thrombosis, cardiovascular dysfunction, arrhythmias, and valvular heart disease. Network, attend engaging presentations by renowned cardiologists, visit the exhibit and poster hall, participate in an exclusive immersive experience, and earn up to 13 CME/CE credits.
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Pearls – Cardio-Rheumatology – Deciphering Cardiovascular Risk in Patients with Rheumatological Conditions
Cardiovascular disease prevalence: cardiovascular disease is common in patients with autoimmune rheumatologic disease; therefore, we must take every opportunity to screen patients early.
Limitations of Traditional Scores: conventional risk calculators often underestimate cardiovascular risk for autoimmune disease patients, necessitating additional methods to assess risk accurately.
Integration of Disease-Specific Biomarkers: using biomarkers specific to autoimmune diseases, such as lupus, enhances risk assessment and helps in tailoring treatment strategies.
Value of Imaging and Risk Enhancers: incorporating imaging (like CAC scoring and carotid ultrasound) and evaluating additional risk factors (such as lipoprotein(a) and high-sensitivity CRP) provides a more comprehensive view of cardiovascular risk and guides more effective management.
Show notes – Cardio-Rheumatology – Deciphering Cardiovascular Risk in Patients with Rheumatological Conditions
Show notes (Drafted by Dr. Bree Hansen):
How does inflammation contribute to atherosclerosis, specifically in autoimmune rheumatologic diseases like psoriasis?
Lipids need to enter the intimal space of blood vessels, which can be facilitated by endothelial damage caused by chronic cytokine stimulation, such as TNF or IL-6. Once in the intima, lipids are recognized as foreign, leading to the recruitment of monocytes that transform into macrophages to clear these lipids. However, this process often exacerbates the problem, leading to persistent inflammation and atherosclerotic plaque formation.
Specifically, in psoriasis, the endothelial damage is particularly pronounced due to cytokines like TNF, IL-17, and interferons. The inflammasome pathway, which is highly active in psoriasis, also contributes to endothelial damage. Additionally, hyperactivated platelets in psoriasis can further damage the endothelium and contribute to atherosclerosis.
Overall, atherosclerosis results from a combination of traditional risk factors and systemic inflammation, leading to the development of cardiovascular disease.
Which traditional cardiovascular risk factors are increased in patients with rheumatologic conditions?
Patients with autoimmune diseases may be up to > three times more likely to develop cardiovascular disease, similar to the risk of type 2 diabetes; therefore, it is important to screen patients with autoimmune rheumatologic disorders for cardiovascular disease
Most common cardiovascular risk factors, such as smoking, diabetes, hypertension, and dyslipidemia, are also increased in patients with autoimmune rheumatologic disorders. Smoking, specifically, is highly prevalent in psoriasis and exhibits a dose-response relationship with psoriasis severity.
Hyperlipidemia is another common risk factor present in patients with autoimmune rheumatologic disease; however, a “lipid paradox” also exists. The “lipid paradox,” where lower LDL (low-density lipoprotein) levels are associated with higher inflammation, seems counterintuitive since lower LDL is often thought to indicate lower cardiovascular risk. This paradox is particularly well-documented in rheumatoid arthritis (RA) but may apply to various other conditions as well. In clinical practice, it’s important to assess lipid levels not only during periods of high inflammation but also when the patient is in a state of disease remission or stability. This is because lipid levels can fluctuate based on the level of inflammation and the medications a patient takes, such as biologics.
How can cardiovascular disease risk be estimated in patients with rheumatologic conditions beyond that of traditional risk factor calculators?
Traditional cardiovascular risk scores like the Framingham Risk Score and ACC/AHA Pool Cohort Equation often underestimate risk, particularly for patients with autoimmune diseases. Risk calculators in women with RA underestimated cardiovascular risk at least 2‐fold.
The Run-On Risk Score includes inflammatory markers like CRP but can still fall short in risk assessment. While some specialized calculators like The British SCORE2 system, which initially included rheumatoid arthritis (RA), and later QRISK3, which added lupus and steroid use, include these autoimmune conditions, no standard tool is universally applied for these diseases. Therefore, clinicians need to integrate multiple data sources to assess risk effectively
Recent research, such as a study from Dr. Weber’s group, has highlighted that incorporating lupus-specific biomarkers such as persistently positive double-stranded DNA, low complement levels, and lupus anticoagulant into risk calculators improves risk prediction for lupus patients.
Thus, beyond traditional risk factors, clinicians should assess disease duration, activity biomarkers, and the impact of treatments (including medications like hydroxychloroquine that have potential cardiotoxicity). Clinicians should also use other risk enhancers, like lipoprotein(a) and high-sensitivity CRP, and consider imaging techniques like coronary artery calcium (CAC) scoring to evaluate atherosclerotic burden. Elevated lipoprotein(a) levels and high CAC scores indicate higher risk, even if traditional risk scores suggest otherwise.
References – Deciphering Cardiovascular Risk in Patients with Rheumatological Conditions
Conrad N, Verbeke G, Molenberghs G, et al. Autoimmune diseases and cardiovascular risk: a population‐based study on 19 autoimmune diseases and 12 cardiovascular diseases in 22 million individuals in the UK. Lancet. 2022;400:733–743.
Crowson CS, Liao KP, Davis JM 3rd, et al. Rheumatoid arthritis and cardiovascular disease. Am Heart J. 2013;166(4):622-628.e1. doi:10.1016/j.ahj.2013.07.010
Garshick MS, Ward NL, Krueger JG, Berger JS. Cardiovascular Risk in Patients With Psoriasis: JACC Review Topic of the Week. J Am Coll Cardiol. 2021;77(13):1670-1680. doi:10.1016/j.jacc.2021.02.009
Weber, B, Paik, J, Aghayev, A. et al. Novel Imaging Approaches to Cardiac Manifestations of Systemic Inflammatory Diseases: JACC Scientific Statement. JACC. 2023 Nov, 82 (22) 2128–2151. https://doi.org/10.1016/j.jacc.2023.09.819
Mortensen M, Jensen J, Sand N, et al. Association of Autoimmune Diseases with Coronary Atherosclerosis Severity and Ischemic Events. JACC. 2024. Jun, 83 (25) 2643-2654. Doi: 10.1016/j.jacc.2024.04.030
Choi M, Guan H, Yoshida K, et al. Personalizing cardiovascular risk prediction for patients with systemic lupus erythematosus. Seminars in Arthritis and Rheumatism. 2024. Aug:67:152468. Doi: 10.1016/j.semarthrit.2024.152468.
49 min
September 06, 2024389. Case Report: When “Normal” Cholesterol is Not Normal: Exposing an Unusual Presentation of Familial Hypercholesterolemia – National Lipid Association
CardioNerds Dan Ambinder and Dr. Devesh Rai join cardiology fellows and National Lipid Association lipid scholars Dr. Jelani Grant from Johns Hopkins University and Dr. Alexander Razavi from Emory University. They discuss a case involving a patient with familial hypercholesterolemia. Dr. Archna Bajaj from University of Pennsylvania provides expert commentary. Drs. Jelani Grant and Alexander Razavi drafted notes. CardioNerds Intern Pacey Wetstein engineered episode audio.
This episode is part of a case reports series developed in collaboration with the National Lipid Association and their Lipid Scholarship Program, with mentorship from Dr. Daniel Soffer and Dr. Eugenia Gianos.
A classic finding in patients with familial hypercholesterolemia is the presence of markedly elevated levels of total and low-density lipoprotein cholesterol (LDL-C) with an LDL-C concentration of 190 mg/dL or greater. However, severe hypercholesterolemia is not inevitably present, and many patients who carry this diagnosis may have lower LDL-C levels. This case history describes a young woman whose mother and brother met clinical and genetic criteria for heterozygous familial hypercholesterolemia but who had only a mild elevation in LDL-C, falling to 130 mg/dL after dietary intervention. Despite this finding, genetic testing revealed the presence of the same genetic variants as were noted in her mother and brother. In addition, a second genetic variant predisposing them to cholesterol gallstone formation was identified in all three family members. If genetic testing had not been performed, the diagnosis may have been missed or delayed, resulting in an increased risk for vascular complications associated with familial hypercholesterolemia. This case supports the value of genetic testing of family members of those with familial hypercholesterolemia, even when LDL-C levels are not severely elevated.
“To study the phenomena of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all.” – Sir William Osler. CardioNerds thank the patients and their loved ones whose stories teach us the Art of Medicine and support our Mission to Democratize Cardiovascular Medicine.
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Pearls – Exposing an Unusual Presentation of Familial Hypercholesterolemia – National Lipid Association
Familial hypercholesterolemia (FH) is among the most common autosomal co-dominant genetic conditions (approximately 1:200 to 1:300 for HeFH, 1:160,000 to 1:300,000 for HoFH).
Genetic testing has a role for all first-degree relatives when a family history of FH is strongly suggestive, regardless of LDL-C level.
Heterogeneity in ASCVD risk among individuals with FH is derived from background polygenic risk, clinical risk factors (e.g., timing of lipid-lowering initiation and adjacent risk factors), as well as subclinical atherosclerosis burden.
In clinical or genetically confirmed FH, an LDL-C goal of 55 mg/dL is recommended.
Beyond statins, FDA-approved non-statin therapies for FH include ezetimibe, PCSK9 mAb, bempedoic acid, inclisiran, evolocumab (only HoFH), lomitapide (only HoFH), and LDL apheresis.
Notes – Exposing an Unusual Presentation of Familial Hypercholesterolemia – National Lipid Association
What are the diagnostic criteria for FH?
Dutch Lipid Clinic Network1
Variables: family history, clinical history, physical exam, LDL-C level, DNA (LDLR, APOB, PCSK9)
Simon-Broome1
Variables: total or LDL-C, physical exam, DNA (LDLR, APOB, PCSK9), family history
Emphasis on clinical history and physical exam reduces sensitivity
U.S. Make Early Diagnosis Prevent Early Death (MEDPED) 1
Only one of the three where no genetic testing is required, may work well in cascade screening
Variables: age, total cholesterol, family relative (and degree) with FH
Definite, probable, possible, unlikely
Emphasis on clinical history and physical exam reduces sensitivity
How does FH affect CAD risk?
There is about a 20-fold higher risk of premature CHD in FH without treatment2
For any CHD3
As high as 100-fold greater risk in young men with FH
Risk is lower in women versus men (approximate 10-year age difference in development)
Up to one-half of men and one-third of women with FH will suffer fatal or non-fatal coronary events before age 50 and 60 years old, respectively 4
Despite this high risk, it is important to note heterogeneity in FH that can be attributable to:
Polygenic risk
Timing of lipid-lowering therapy initiation
Adjacent risk factors
Subclinical atherosclerosis burden 5 6 7
What is the role of genetic testing in FH?
Clinical value of genetic testing:
Providing prognostic information
Promotes initiation and adherence of lipid-lowering therapies
Serves as a basis for more effective cascade screening
Heterogeneity in FH may be attributable to other genes that regulate LDL-C, but which are not tested as part of the FH gene panel. For example, there are polygenic risk scoring systems to gauge the relative impact on LDL-C; however, this is not routinely done, but potentially impactful
Provide guideline-based recommendations for treatment
Beyond statins, FDA-approved non-statin therapies for FH include: ezetimibe, PCSK9 mAb, bempedoic acid, inclisiran, evinacumab (only HoFH), lomitapide (only HoFH), and LDL apheresis8.
Based on the 2022 ACC Expert Consensus Decision Pathway for Non-Statin Therapy, an LDL-C goal of <55 mg/dL is recommended for individuals with a clinical or genetic diagnosis of FH 8
When should a patient be referred to a lipid specialist?
*Based on 2022 ACC ECDP 8
Any patient with ASCVD
Baseline LDL >190 mg/dL
Inadequate reduction of LDL-C (>50% and LDL-C <70 mg/dL or non-HDL-C <100 mg/dL)
Intolerance to at least two statin therapies, with an attempt to initiate FDA-approved lowest dose of statin and a trial of an alternative statin therapy regimen such as every other day dosing
References
Vallejo-Vaz AJ, Ray KK. Epidemiology of familial hypercholesterolaemia: Community and clinical. Atherosclerosis. 2018;277. doi:10.1016/j.atherosclerosis.2018.06.855
Link to article
Austin MA, Hutter CM, Zimmern RL, Humpries SE. Familial hypercholesterolemia and coronary heart disease: A HuGE association review. Am J Epidemiol. 2004;160(5). doi:10.1093/aje/kwh237
Link to article
Watts GF, Lewis B, Sullivan DR. Familial hypercholesterolemia: A missed opportunity in preventive medicine. Nat Clin Pract Cardiovasc Med. 2007;4(8). doi:10.1038/ncpcardio0941
Link to article
Marks D, Thorogood M, Neil HAW, Humphries SE. A review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia. Atherosclerosis. 2003;168(1). doi:10.1016/S0021-9150(02)00330-1
Link to article
Mszar R, Grandhi GR, Valero-Elizondo J, et al. Absence of Coronary Artery Calcification in Middle-Aged Familial Hypercholesterolemia Patients Without Atherosclerotic Cardiovascular Disease. JACC Cardiovasc Imaging. 2020;13(4). doi:10.1016/j.jcmg.2019.11.001
Link to article
Miname MH, Bittencourt MS, Moraes SR, et al. Coronary Artery Calcium and Cardiovascular Events in Patients With Familial Hypercholesterolemia Receiving Standard Lipid-Lowering Therapy. JACC Cardiovasc Imaging. 2019;12(9). doi:10.1016/j.jcmg.2018.09.019
Link to article
Sandesara PB, Mehta A, O’Neal WT, et al. Clinical significance of zero coronary artery calcium in individuals with LDL cholesterol ≥190 mg/dL: The Multi-Ethnic Study of Atherosclerosis. Atherosclerosis. Published online 2020. doi:10.1016/j.atherosclerosis.2019.09.014
Link to article
Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2022;80(14):1366-1418. doi:10.1016/j.jacc.2022.07.006
Link to article
24 min
August 20, 2024388. Ironing out the Data: Iron Deficiency in Heart Failure with Dr. Robert Mentz
CardioNerds Cofounder Dr. Amit Goyal, Chair of the CardioNerds Heart Failure Committee Dr. Jenna Skowronski, and Episode FIT Lead Dr. Shazli Khan discuss iron deficiency and its impact on heart failure with Dr. Robert Mentz, Chief of Heart Failure at Duke University and principal investigator of the HEART-FID trial. In this case-based discussion, they cover the diagnostic criteria of iron deficiency in heart failure, epidemiology, and strengths and limitations of different iron formulations. They also review clinical trials examining the impact of iron deficiency on quality of life, heart failure hospitalizations, and mortality. Importantly, they stress the relevance of iron metabolism in heart failure, irrespective of the presence of anemia. They also discuss the approach to addressing outpatient management of iron in heart failure and future directions of research needed in this domain.
Notes were drafted by Dr. Shazli Khan, and Dr. Daniel Ambinder engineered episode audio.
Click here for CME.
This episode was created in collaboration with the Cardiometabolic Health Congress and is supported by an educational grant from American Regent. Please follow the link in the show notes for free CME. All CardioNerds education is planned, produced, and reviewed by CardioNerds.
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Pearls – Iron Deficiency in Heart Failure
Think about iron deficiency in ALL patients with heart failure and send appropriate diagnostic labs, even if there is no evidence of anemia!
Iron deficiency in heart failure has a specific and distinguished definition, defined as a ferritin level of <100 ng/mL, or a ferritin level between 100-300 ng/mL with a transferrin saturation of <20%.
Data thus far suggests that treatment of iron deficiency in heart failure results in improved quality of life, as well as a probable reduction in heart failure hospitalizations, and that administration of intravenous iron has a favorable safety profile.
Not all formulations of iron are created equal – intravenous iron formulations have been shown to be effective in this population, but oral iron therapy has not.
Management of iron deficiency in the outpatient setting is an evolving area of research, but patients should typically receive surveillance labs and additional treatment with IV iron if indicated.
Show notes – Iron Deficiency in Heart Failure
How is iron deficiency in heart failure defined, and how prevalent is iron deficiency in this patient population?
Iron deficiency is common in patients with heart failure, with an estimated prevalence of 50-60%.
Iron deficiency in heart failure is associated with worse outcomes, including increased hospitalization and mortality and poorer functional status and quality of life.
Iron deficiency in heart failure is defined as a ferritin level of <100 ng/mL or a ferritin level of 100-300 ng/mL plus a transferrin saturation of <20%.
There is an evolving school of thought that suggests transferrin saturation alone may be the best indicator of iron deficiency in heart failure, but more data are needed.
Importantly, iron deficiency in heart failure can be seen in patients with both reduced and preserved ejection fraction. Which patients should be screened for iron deficiency?
There is a class I indication to send iron studies in all patients with heart failure as a part of the initial diagnostic work-up for the underlying etiology of the cardiomyopathy, as well as to assess for the presence of iron deficiency.
The presence of anemia is not required to check iron studies, as many patients with iron deficiency in heart failure may not have concomitant anemia.
That is, all patients with heart failure should be evaluated for iron deficiency, irrespective of the presence of anemia.
What are the hypothesized mechanisms of iron deficiency in heart failure, and how does iron deficiency impact patients with heart failure?
Mechanisms causing iron deficiency in heart failure are multifactorial, including reduced oral intake, reduced gut absorption, reduced iron availability due to sequestration, and increased loss due to higher rates of bleeding.
Nutritional variation is one proposed mechanism, as patients living with heart failure tend to take in less iron in their diet, and the iron consumed tends to be less easily absorbed.
Due to chronic inflammation, there are increased levels of iron sequestration in cells in patients with heart failure, rendering the available iron stores unable to be used.
Patients with chronic heart failure also tend to be on anti-platelet agents and/or anticoagulants (due to often-occurring comorbidities), which may potentially lead to bleeding complications, consequently causing iron deficiency.
Iron deficiency has been associated with decreased exercise tolerance and functional status, worse quality of life, and increased risk of heart failure hospitalizations.
What are the key takeaways of the clinical trials done in patients with heart failure and iron deficiency?
The FAIR-HF trial published in 2009 demonstrated that treatment with IV ferrous carboxymaltose (FCM) in patients with heart failure led to improved symptoms and quality of life with an acceptable safety profile. These benefits were verified in a follow-up study known as CONFIRM-HF, demonstrating improvement in 6MWT and functional capacity.
The AFFIRM-AHF trial investigated IV FCM in patients with iron deficiency and a left ventricular ejection fraction of <50%. It was a neutral trial with no significant improvement in their primary endpoint, a composite of hospitalization and death. The trial did demonstrate the safety of FCM and decreased hospitalizations. Of note, this trial was significantly impacted by the COVID pandemic, which may have affected the results.
The IRONMAN trial was similar in design to AFFIRM-AHF but used a different iron formulation (iron derisomaltose) and had similar findings.
The HEART-FID trial was a larger study including 3000 patients with HFrEF investigating treatment with IV ferric carboxymaltose every six months if the patients remained iron deficient. The primary endpoint was a hierarchical composite of death within 12 months after randomization, hospitalizations for heart failure within 12 months after randomization, or change from baseline to 6 months in the 6-minute walk distance. While it was considered a neutral trial with a p=0.019 with a prespecified significance level of 0.01, it demonstrated a trend to improved mortality and six-minute walk.
Which patients should we treat with iron, and with what formulation? What do the guidelines recommend?
Patients who have chronic heart failure on maximally tolerated guideline-directed medical therapy with iron deficiency are candidates for intravenous iron supplementation with the goal of improving quality of life and reducing heart failure hospitalizations.
Intravenous iron has been shown to be effective, but oral iron therapy has shown no benefit in trials.
Per the updated 2023 ESC guidelines, there is a class IA recommendation to provide intravenous iron supplementation in symptomatic patients with heart failure with reduced and mid-range ejection fraction with iron deficiency to both alleviate HF symptoms and improve quality of life.
There is a class IIA recommendation to provide supplementation to reduce heart failure hospitalizations.
Surveillance labs in the outpatient setting, combined with continued treatment for persistent iron deficiency, are likely beneficial in patients with heart failure.
References – Iron Deficiency in Heart Failure
Packer M, Anker SD, Butler J, et al. Identification of three mechanistic pathways for iron-deficient heart failure. Eur Heart J. 2024;45(26):2281-2293. doi:10.1093/eurheartj/ehae284. https://academic.oup.com/eurheartj/article/45/26/2281/7668668
Salah HM, Savarese G, Rosano GMC, et al. Intravenous iron infusion in patients with heart failure: a systematic review and study-level meta-analysis. ESC Heart Fail. 2023;10(2):1473-1480. doi:10.1002/ehf2.14310. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10053151/
Ponikowski P, Kirwan BA, Anker SD, et al. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial. Lancet. 2020;396(10266):1895-1904. doi:10.1016/S0140-6736(20)32339-4. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32339-4/abstract
Kalra PR, Cleland JGF, Petrie MC, et al; IRONMAN Study Group. Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial. Lancet. 2022;400(10369):2199-2209. doi:10.1016/S0140-6736(22)02083
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02083-9/fulltext
Mentz RJ, Garg J, Rockhold FW, et al; HEART-FID Investigators. Ferric Carboxymaltose in Heart Failure with Iron Deficiency. N Engl J Med. 2023;389(11):975-986. doi:10.1056/NEJMoa2304968. https://www.nejm.org/doi/full/10.1056/NEJMoa2304968
McDonagh TA, Metra M, Adamo M, et al; ESC Scientific Document Group. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2023;44(37):3627-3639. doi:10.1093/eurheartj/ehad195. Erratum in: Eur Heart J. 2024;45(1):53. doi:10.1093/eurheartj/ehad613. https://academic.oup.com/eurheartj/article/44/37/3627/7246292?login=false
Anker SD, Comin Colet J, Filippatos G, et al. Ferric Carboxymaltose in Patients with Heart Failure and Iron Deficiency. N Engl J Med. 2009;361(25):2436-2448. doi:10.1056/NEJMoa0908355. https://www.nejm.org/doi/full/10.1056/NEJMoa0908355
Ponikowski P, van Veldhuisen DJ, Comin-Colet J, et al. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J. 2015;36(11):657-668. doi:10.1093/eurheartj/ehu385. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359359/
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