Cardionerds: A Cardiology Podcast

CardioNerds (Drs. Dr. Natalie Marrero, Dr. Ritika Tuli, and Dr. Rafael Toro Manotas) discuss multimodality imaging for risk stratification, evaluation, and management of chronic coronary artery disease with Dr. Panithaya Chareonthaitawee. Audio editing by CardioNerds intern Iman Razeghian.

This episode was produced as part of the CardioNerds Academy curriculum by House Taussig under the guidance of House Chief, Dr. Natalie Marrero and Academy Program Director, Dr. Gurleen Kaur. A matching review article will be published in US Cardiology Review, the official journal of CardioNerds. This discussion was planned in collaboration with the Mayo Clinic Cardiovascular Board Review Course.

In this episode, we discuss the pathophysiology and risk stratification of chronic coronary artery disease (CAD), as well as the current landscape of non-invasive evaluation of this condition. CAD remains a leading cause of morbidity and mortality despite advances in pharmacological and non-pharmacological strategies for the prevention and treatment of atherosclerotic disease. The concept of chronic CAD has shifted from the traditional model of stable, obstructive, flow-limiting disease, toward the current understanding of a dynamic process that extends beyond obstructive epicardial lesions to include non-obstructive plaque, diffuse atherosclerosis, and microvascular disease. Similarly, the imaging modalities used to evaluate CAD have evolved, and clinicians now have an extensive menu of options, each with distinct advantages and limitations, that must be selected carefully to maximize diagnostic accuracy and optimize treatment guidance, while also considering resource availability, local expertise, and high-value care. By the end of the episode, listeners will understand the pathophysiology of chronic CAD, risk-stratify patients with suspected CAD, recognize the advantages and pitfalls of each non-invasive diagnostic modality, and select the most appropriate diagnostic tool for a given clinical scenario.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

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Pearls:

Chronic CAD is a complex process that extends beyond obstructive epicardial stenosis to include non-obstructive disease, dynamic plaque burden and ischemia, diffuse atherosclerosis, microvascular dysfunction, vasospasm, among others.

When evaluating patients with suspected CAD, the diagnostic process should be guided by a specific and appropriate clinical question before ordering any tests.

The current diagnostic tool arsenal is broadly divided into anatomic and functional imaging modalities. These are complementary, each with distinct properties and limitations, addressing different clinical questions and assessing different aspects of disease.

Local availability and expertise, along with patient-specific considerations and contraindications, determine the choice of diagnostic modality. No single test is best for every patient.

INOCA and coronary microvascular dysfunction represent a common and increasingly recognized entity that is diagnosable and treatable; initial evaluation includes non-invasive testing such as stress PET and stress CMR.

References

Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2021;144(22):e368-e454. doi:10.1161/CIR.0000000000001029 https://pubmed.ncbi.nlm.nih.gov/34709879/

Vrints C, Andreotti F, Koskinas KC, et al. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J. 2024;45(36):3415-3537. doi:10.1093/eurheartj/ehae177 https://pubmed.ncbi.nlm.nih.gov/39210710/

Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2023;148(9):e9-e119. doi:10.1161/CIR.0000000000001168 https://pubmed.ncbi.nlm.nih.gov/37471501/

Edvardsen T, Asch FM, Davidson B, et al. Non-Invasive Imaging in Coronary Syndromes: Recommendations of The European Association of Cardiovascular Imaging and the American Society of Echocardiography, in Collaboration with The American Society of Nuclear Cardiology, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance. J Am Soc Echocardiogr. 2022;35(4):329-354. doi:10.1016/j.echo.2021.12.012 https://pubmed.ncbi.nlm.nih.gov/35379446/

Douglas PS, Hoffmann U, Patel MR, et al. Outcomes of anatomical versus functional testing for coronary artery disease. N Engl J Med. 2015;372(14):1291-1300. doi:10.1056/NEJMoa1415516 https://pubmed.ncbi.nlm.nih.gov/39210710/

Sharma A, Coles A, Sekaran NK, et al. Stress Testing Versus CT Angiography in Patients With Diabetes and Suspected Coronary Artery Disease. J Am Coll Cardiol. 2019;73(8):893-902. doi:10.1016/j.jacc.2018.11.056 https://pubmed.ncbi.nlm.nih.gov/30819356/

SCOT-HEART Investigators, Newby DE, Adamson PD, et al. Coronary CT Angiography and 5-Year Risk of Myocardial Infarction. N Engl J Med. 2018;379(10):924-933. doi:10.1056/NEJMoa1805971 https://pubmed.ncbi.nlm.nih.gov/30145934/

Li Z, Xu T, Wang Z, et al. Prognostic Significance of Computed Tomography-Derived Fractional Flow Reserve for Long-Term Outcomes in Individuals With Coronary Artery Disease. J Am Heart Assoc. 2025;14(2):e037988. doi:10.1161/JAHA.124.037988 https://pubmed.ncbi.nlm.nih.gov/39791423/

Bateman TM, Al-Mallah MH, et al. Clinical indications for positron emission tomography myocardial perfusion imaging and myocardial blood flow quantification: An American Society of Nuclear Cardiology position statement. J Nucl Cardiol. 2026;57:102619. doi:10.1016/j.nuclcard.2025.102619 https://pubmed.ncbi.nlm.nih.gov/41482140/

Taqueti VR, Di Carli MF. Coronary Microvascular Disease Pathogenic Mechanisms and Therapeutic Options: JACC State-of-the-Art Review. J Am Coll Cardiol. 2018;72(21):2625-2641. doi:10.1016/j.jacc.2018.09.042 https://pubmed.ncbi.nlm.nih.gov/30466521/

Taqueti VR, Hachamovitch R, Murthy VL, et al. Global coronary flow reserve is associated with adverse cardiovascular events independently of luminal angiographic severity and modifies the effect of early revascularization. Circulation. 2015;131(1):19-27. doi:10.1161/CIRCULATIONAHA.114.011939 https://pubmed.ncbi.nlm.nih.gov/25400060/

Mehta PK, Huang J, Levit RD, Malas W, Waheed N, Bairey Merz CN. Ischemia and no obstructive coronary arteries (INOCA): A narrative review. Atherosclerosis. 2022;363:8-21. doi:10.1016/j.atherosclerosis.2022.11.009 https://pubmed.ncbi.nlm.nih.gov/36423427/

Kunadian V, Chieffo A, Camici PG, et al. An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology & Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group. EuroIntervention. 2021;16(13):1049-1069. doi:10.4244/EIJY20M07_01 https://pubmed.ncbi.nlm.nih.gov/32624456/

CardioNerds (Dr. Apoorva Gangavelli, Dr. Cory Sejo, and Dr. Joseph Kassab), discuss tricuspid regurgitation evaluation and management with Dr. Sunil Mankad.

This episode was produced as part of the CardioNerds Academy curriculum by House Einthoven under the guidance of House Chief, Dr. Apoorva Gangavelli and Academy Program Director, Dr. Gurleen Kaur. A matching review article will be published in US Cardiology Review, the official journal of CardioNerds. This discussion was planned in collaboration with the Mayo Clinic Cardiovascular Board Review Course. 

Audio editing by CardioNerds intern Emma Winakur.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

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Key Points:

Tricuspid regurgitation is common and associated with increased mortality at every stage, regardless of etiology. Outcomes are worse with worsening severity, so accurate grading is critical.

Etiology is critical to guide treatment decisions. Etiology includes primary vs secondary (atrial or ventricular) vs CIED-related TR. 3D echocardiography can be very helpful in determining TR etiology, especially in CIED-related TR.

Diuresis with the goal of euvolemia is step one. Additionally, underlying contributory conditions (eg. pulmonary HTN, HFrEF, atrial fibrillation) should be addressed, if appropriate, and then TR severity reassessed.

The choice between T-TEER and TTVR hinges on anatomy, RV function, pulmonary hypertension, and the ability to tolerate anticoagulation. T-TEER is generally first line in atrial functional TR with appropriate anatomy, in patients with poor RV function who cannot tolerate a sudden increase in RV afterload, or in patients who cannot tolerate the necessary anticoagulation with TTVR. TTVR is preferred with wide coaptation gaps and CIED-related TR.

This is a team sport. Multidisciplinary discussions utilizing imaging (TTE/TEE, CT), risk scores (TRI-SCORE or TRIO), patient preference, and prior institutional experience are essential for the effective treatment of severe TR.

Notes:

What is the clinical importance of tricuspid regurgitation?

TR is very common with approximately 4% of people over 75 having moderate or greater severity.

TR (even mild) is associated with increased mortality. Those outcomes worsen as the TR severity worsens, and this phenomenon is independent of the mechanism of regurgitation.

What is unique about the tricuspid valve compared to the other cardiac valves?

It is at an anterior location which allows it to be imaged well with transthoracic echocardiography

It is the largest valve and composed generally of 3 leaflets (but very often can have 4+ leaflets).

Importantly, the RV is compliant and changes size and shape readily based on loading conditions. The TV annulus similarly changes size and shape based on hemodynamic conditions such as preload.

What is a good framework for approaching the causes of tricuspid regurgitation?

Determine the presence and define the severity of TR.

Using TTE, we want to measure the right atrial size, the RV size, and any other concomitant valvular lesions. 

Use TTE (2D and 3D) to characterize leaflet anatomy and characteristics.

Subtypes of TR mechanisms (many times etiology is mixed).

Primary: primary leaflet abnormality, occurs in ~10% of cases. Look for prolapse, flail, endocarditis, etc.

Secondary/functional: leaflets normal but surrounding structures are abnormal.

Atrial: RA and tricuspid annular dilation but normal RV size/shape, and can be related to arrhythmias like atrial fibrillation.

Ventricular: RV dilated and/or dysfunctional with leaflet tethering. Can be related to pulmonary hypertension or primary RV disease.

Cardiac implantable electronic device (CIED): Related to device (usually pacemakers or ICD) interaction with TV leaflets.

Includes perforation, entanglement in subvalvular apparatus, impingement, etc.

3D TTE particularly helpful to evaluate

How do we grade TR severity?

It is very important to grade the severity of TR, and this is generally done with echocardiography.

There are both quantitative and qualitative methods which use Doppler and various equations to estimate TR severity.

Current recommendations have expanded TR severity beyond mild/moderate/severe to include “massive” and “torrential” categories.

The most important parameters measured/calculated are vena contracta width, regurgitant volume, regurgitant fraction, and effective regurgitant orifice area. Helpful qualitative metrics include hepatic venous flow reversal.

When should additional studies beyond transthoracic echocardiography, such as transesophageal echocardiography (TEE), cardiac computed tomography (CT), and cardiac magnetic resonance imaging (MRI) be pursued?

TEE is particularly helpful if TTE views are poor. Since TEE is used during transcatheter intervention, a pre-procedure TEE to define anatomy, determine procedure candidacy, and plan for the procedure is critical. 

CT is also helpful for procedure planning and has particular strengths in defining annulus size and geometry. A CT is required prior to transcatheter tricuspid valve replacement (TTVR).

MRI is helpful for measuring RV volumes and function, but is not generally used to assess TR severity. 

What is the approach to the treatment for severe tricuspid regurgitation?

The first step is to try to determine the etiology. For secondary TR, treating the underlying condition is indicated. For example, pulmonary vasodilators for pulmonary HTN or guideline therapy for heart failure with reduced ejection fraction.

Diuretics are the mainstay for treatment, with the goal to obtain euvolemia. This may require inpatient admission to optimize volume status and medication regimen.

Once reversible etiologies are addressed, if the patient is still symptomatic from TR, additional therapies can be considered.

What is the role of right heart catheterizations (RHC) in patients with severe TR?

RHC is very helpful for many reasons. We use it in TR to help determine volume status, cardiac output, and RV function. Additionally, identifying and characterizing pulmonary hypertension (with pulmonary artery pressures and calculating pulmonary vascular resistance) is an important factor when choosing future therapies. 

With severe tricuspid regurgitation, when should we refer for intervention (either with surgery or transcatheter repair or replacement)?

Once reversible etiologies are addressed and euvolemia has been achieved, if the patient is still symptomatic from TR despite aggressive medical optimization, additional therapies can be considered.

Once euvolemic, a repeat TTE should be ordered to reassess the severity of the TR.

Use calculators (for example, either the TRI-SCORE or TRIO score) to predict operative mortality for isolated TR surgery.

What are our transcatheter treatment options in severe tricuspid regurgitation, and how do we choose between them?

The primary approved transcatheter treatment options for severe TR include transcatheter tricuspid edge-to-edge repair (T-TEER) and transcatheter tricuspid valve replacement (TTVR), of which the Edwards EVOQUE valve is the only one currently approved by the FDA. There are other TTVR device under investigation.

These decisions should be made with a multi-disciplinary team including representation from cardiac imaging, interventional cardiology, and cardiothoracic surgery.

Factors that go into the decision between T-TEER and TTVR include anatomy (annulus width, coaptation gap, leaflet length), RV reserve, pulmonary hypertension presence, ability to tolerate anticoagulation, patient preference, and institutional experience. 

T-TEER is generally the first line with atrial functional and suitable anatomy. It is successful at reducing TR but does not generally eliminate it. 

TTVR with EVOQUE is preferred in certain anatomic considerations like a large coaptation gap or when there is CIED-related TR (as this was excluded in T-TEER trials).

Patients must be suitable for anticoagulation to receive TTVR as there is risk of leaflet thrombosis without it.

If moderate/severe pulmonary hypertension is present, or there is poor RV function, TTVR may be avoided as the sudden elimination of TR causes a sudden increase in RV afterload which may not be tolerated.

What is the role in advanced metrics for evaluating RV function?

Advanced metrics like RV/PA coupling are under investigation but have not made it into the guidelines. The clinical utility is not yet known. 

Assessing the RV function is important as stated above. Dr. Mankad prefers using 3D TTE to calculate an RVEF, or tracking RV longitudinal free wall strain.

If you do encounter CIED-related TR, how do you treat it?

Evaluate with TTE or TEE. 3D is very helpful to identify relative anatomy and leaflet-device interactions.

There is no clear consensus about treatment if CIED-related TR is the primary mechanism of severe TR. If recently implanted, repositioning may be a valid option, but requires discussions with multiple teams including electrophysiology, advanced cardiac imaging, CT surgery, and interventional cardiology.

References

O’Gara PT, Lindenfeld J, Hahn RT, et al. 10 Issues for the Clinician in Tricuspid Regurgitation Evaluation and Management: 2025 ACC Expert Consensus Decision Pathway. J Am Coll Cardiol. 2025;S0735-1097(25)07047-0.

O’Gara PT, Little SH, Badhwar V, et al. Operator and Institutional Recommendations and Requirements for Tricuspid Interventions: 2026 ACC/AHA/ASE/HRS/STS Expert Consensus Systems of Care Document. J Am Coll Cardiol. 2026;S0735-1097(26)05481-1.

Hahn RT. Tricuspid Regurgitation. N Engl J Med. 2023;388(20):1876-1891.

Davidson LJ, Tang GHL, Ho EC, et al. The Tricuspid Valve: A Review of Pathology, Imaging, and Current Treatment Options: A Scientific Statement From the American Heart Association. Circulation. 2024;149(22):e1223-e1238.

CardioNerds (Dr. Apoorva Gangavelli, Dr. Rebecca Garber, and Dr. Tina Reddy), discuss pre-pregnancy risk stratification and counseling with Dr. Katy Young across a range of risks. 

This episode was produced as part of the CardioNerds Academy curriculum by House Einthoven under the guidance of House Chief, Dr. Apoorva Gangavelli and Academy Program Director, Dr. Gurleen Kaur. A matching review article will be published in US Cardiology Review, the official journal of CardioNerds. This discussion was planned in collaboration with the Mayo Clinic Cardiovascular Board Review Course.

Audio editing by CardioNerds intern, Dr. Patrick Pekyi-Boateng.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

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Notes: 

Why is pregnancy considered a “physiologic stress test,” and why does risk extend beyond delivery?

Blood volume, heart rate, and cardiac output rise while systemic vascular resistance falls, peaking in the late second/early third trimester; underlying (even undiagnosed) heart disease can be unmasked or worsened.

Postpartum (“fourth trimester”) is a high-risk period, not a safe zone – fluid shifts, rising SVR, and bleeding risk can precipitate decompensation in patients with heart failure, pulmonary hypertension, valvular disease, or aortopathy.

Adverse pregnancy outcomes (hypertensive disorders, gestational diabetes, preterm birth, fetal growth restriction, peripartum cardiomyopathy) are markers of future cardiovascular risk and warrant long-term preventive follow-up.

What is the practical framework for approaching pre-pregnancy cardiovascular risk?

Four broad categories: (1) patients who may need cardiac screening before pregnancy, (2) patients needing risk-factor/medication optimization, (3) known cardiovascular disease where pregnancy is reasonable with structured risk stratification, and (4) high-risk disease where pregnancy may need to be delayed, modified by intervention, or discouraged.

Testing should be targeted, not blanket – reserved for symptoms, abnormal exam, concerning family history, or reduced functional capacity.

How is risk stratified in patients with known cardiovascular disease?

Use a combination of tools per 2025 ESC guidelines: mWHO 2.0 (broad maternal risk category), CARPREG II (additional predictors of maternal cardiac events), and ZAHARA (useful in congenital heart disease).

Key lesion-specific factors: aortic size/growth, valve severity, ventricular function, symptoms, blood pressure, and family history of dissection.

Translate risk into practical terms for patients rather than leading with a numerical score.

Which cardiovascular medications require review before conception?

ACE inhibitors, ARBs, and ARNIs should be transitioned off before pregnancy; statins, MRAs, and SGLT2 inhibitors also need review.

DOACs are contraindicated in pregnancy and lactation; mechanical valve anticoagulation requires individualized shared decision-making, as no strategy is risk-free for mother and fetus.

Medication changes are best made proactively, before conception, rather than reactively.

This is not an exhaustive list! The medication list needs to be reviewed carefully.

Which conditions carry high or prohibitive risk in pregnancy?

Pulmonary arterial hypertension, Eisenmenger syndrome, severe ventricular dysfunction, prior peripartum cardiomyopathy with residual LV dysfunction, severe left-sided obstructive valve disease (e.g., severe mitral stenosis), mechanical valves, significant aortopathy, cyanotic congenital heart disease, and Fontan physiology.

Common theme: limited cardiovascular reserve and high risk of decompensation, thrombosis, arrhythmia, heart failure, aortic dissection, or death. These patients need expert multidisciplinary evaluation before pregnancy.

Severe mitral stenosis is poorly tolerated because tachycardia shortens diastolic filling time and raises left atrial pressure, risking pulmonary edema and decompensation.

When should genetic testing or counseling be offered?

Consider when a diagnosis may be inherited or affect the patient, pregnancy, or family members: inherited cardiomyopathies, aortopathies, channelopathies, select congenital heart disease, and some pulmonary hypertension syndromes.

Recurrence risk of congenital heart disease in offspring is roughly 6-10% when the mother has CHD; fetal echocardiography should be offered.

How should contraception be approached in high-risk cardiac patients?

Frame contraception as part of the cardiac care and reproductive safety plan to prevent unplanned high-risk pregnancy.

Long-acting reversible contraception is often preferred; progestin-only methods are generally safer than estrogen-containing options with thrombosis risk, pulmonary hypertension, or mechanical valves.

What are key delivery-planning considerations for cardiac patients?

Vaginal delivery is preferred unless there is an obstetric indication for cesarean or a specific cardiac reason (e.g., unstable maternal status, therapeutic INR) to avoid labor.

Planning should address delivery location, anesthesia involvement, telemetry needs, fluid management, and postpartum monitoring, clearly communicated across the multidisciplinary team in advance.

How should clinicians counsel patients when pregnancy is discouraged but strongly desired?

Acknowledge the patient’s goals and the emotional weight of the conversation; separate the goal (family building) from the timeline (safety now vs. after optimization).

If pregnancy remains prohibitively risky, discuss alternatives for family building and ensure adequate patient support.

What are the key gaps and future directions in cardio-obstetric risk stratification?

Current risk tools (mWHO, CARPREG II, ZAHARA) provide common language but do not fully capture functional status, prior pregnancy history, or how risk evolves over time.

Future direction: individualized, dynamic risk prediction incorporating imaging, biomarkers, exercise capacity, and social drivers of health, with better long-term links between pregnancy complications and cardiovascular prevention.

References

1. European Society of Cardiology. 2025 ESC Guidelines for the management of cardiovascular disease and pregnancy.

2. Mehta LS, et al. Cardiovascular Considerations in Caring for Pregnant Patients: A Scientific Statement From the American Heart Association. Circulation. 2020;141:e884-e903. PMID: 32362133. doi:https://doi.org/10.1161/CIR.0000000000000772

3. ACOG Practice Bulletin No. 212. Pregnancy and Heart Disease. Obstet Gynecol. 2019;133(5):e320-e356. PMID: 31022123. doi:https://doi.org/10.1097/AOG.0000000000003243

CardioNerds Dr. Rohit Nathani, Dr. Atefeh Ghorbanzadeh, and Dr. Mariam Riad, discuss Obesity-related Heart Failure with Preserved Ejection Fraction (HFpEF) with Dr. John Ostrominski. 

This episode was produced as part of the CardioNerds Academy curriculum by House Jones under the guidance of House Chief, Dr. Mariam Riad and Academy Program Director, Dr. Gurleen Kaur. A matching review article will be published in US Cardiology Review, the official journal of CardioNerds.

This episode highlights the diverse clinical phenotypes and complex, multifaceted pathophysiology of HFpEF. We take a deep dive into the therapeutic advances that represent paradigm shift in metabolic modulation aimed at improving outcomes in patients with HFpEF and metabolic syndrome.

Audio editing by CardioNerds intern Pacey Wetstein.

Enjoy this Circulation Paths to Discovery article to learn more about the CardioNerds mission and journey.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscripts here.

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Pearls

HFpEF is a constellation of symptoms often with different underlying pathophenotypes; cardiometabolic type is rising in incidence.

Diagnosis is predominantly based on the clinical scenario along with supporting evidence from imaging modalities such as echocardiogram, cardiac MRI, and right heart catheterization.

Cardiometabolic HFpEF is a complex syndrome characterized by dysregulated lipid metabolism, systemic inflammation, and hemodynamic abnormalities, all of which contribute to exercise intolerance and frailty.

Lifestyle interventions, comorbidities management, and HFpEF therapeutics go hand in hand for comprehensive HFpEF care and offer opportunities for multispecialty collaboration to achieve optimal patient outcomes.

References

Ostrominski, J, Højbjerg Lassen, M, Butt, J. et al. Adiposity-Related Anthropometrics and Clinical Outcomes in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Participant-Level Pooled Analysis of Randomized Clinical Trials. JACC. 2025 Nov, 86 (20) 1760–1777.https://doi.org/10.1016/j.jacc.2025.08.012 

Packer, M. The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment. JACC. 2025 Oct, 86 (16) 1269–1373.https://doi.org/10.1016/j.jacc.2025.06.055

Ahmed, N., Dalmasso, C., Turner, M.B. et al. From fat to filter: the effect of adipose tissue-derived signals on kidney function. Nat Rev Nephrol 21, 417–434 (2025). https://doi.org/10.1038/s41581-025-00950-5

Alicic, R.Z., Neumiller, J.J. & Tuttle, K.R. GLP-1 receptor agonists and next-generation metabolic hormone therapies in chronic kidney disease. Nat Rev Nephrol 22, 265–282 (2026). https://doi.org/10.1038/s41581-025-01036-y

Ostrominski, J, Harrington, J, Claggett, B. et al. Anthropometric Measures, Cardiovascular Outcomes, and Treatment Effects of Finerenone in Cardiovascular-Kidney-Metabolic Disease: Pooled Participant-Level Analysis of 3 Global Trials. JACC. 2025 Nov, 86 (20) 1781–1801.https://doi.org/10.1016/j.jacc.2025.08.039

CardioNerds (Drs. Apoorva Gangavelli, Jenna Skowronski, and Hannah Every) discuss the continuum of prevention and heart failure with Drs. Anu Lala and Martha Gulati. Grounded in a clinical case of a 55-year-old woman with uncontrolled hypertension, type 2 diabetes, and obesity who is on the trajectory toward heart failure, this episode unpacks a paradigm-shifting framework from a joint HFSA/ASPC Scientific Statement. The discussion explores how prevention should not be siloed from heart failure management but rather integrated across a patient’s lifespan—from primary prevention in at-risk individuals, to secondary prevention in those with established heart failure, to tertiary prevention in patients with advanced therapies such as LVADs and heart transplantation. The experts highlight the importance of aggressive risk factor management, biomarker-guided screening, the AHA’s Life’s Essential 8, and the need for multidisciplinary collaboration and systems-level change to shift heart failure care from reactive to proactive. Audio editing for this episode was performed by CardioNerds Intern, Dr. Julia Marques Fernandes.

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.

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Pearls

Systemic inflammatory diseases are associated with an elevated CVD risk that has significant implications for early detection, risk Heart failure prevention is a continuum, not a checkpoint. Prevention applies at every stage—from at-risk (Stage A) through advanced/post-transplant care—and every clinical encounter is an opportunity to intervene. The AHA’s Life’s Essential 8 (diet, physical activity, nicotine exposure, sleep, BMI, blood lipids, blood glucose, blood pressure) forms the foundation at every stage.

Hypertension carries the highest population-attributable risk for heart failure of any modifiable risk factor. In the Framingham Heart Study, 91% of patients with newly diagnosed HF had pre-existing hypertension. The SPRINT trial demonstrated a 38% reduction in HF incidence with intensive blood pressure targets (<120 mm Hg systolic). Agent selection matters: ACE inhibitors, ARBs, and thiazide diuretics should be prioritized for HF prevention.

Overlapping risk factors should prompt parallel, not sequential, intervention. Pharmacotherapies such as SGLT2 inhibitors and GLP-1 receptor agonists target multiple pathways simultaneously (diabetes, obesity, CKD, HF risk), making them ideal for patients with cardiometabolic multimorbidity. The cardio-kidney-metabolic (CKM) syndrome framework reinforces this integrated approach.

Biomarker screening with BNP/NT-proBNP should be used proactively in high-risk populations, not just reactively in the emergency department. Even modestly elevated natriuretic peptide levels (e.g., BNP >30 ng/L or NT-proBNP >125 ng/L) identify individuals at heightened risk for progression to symptomatic HF. The ACC/AHA/HFSA guidelines give a Class IIa recommendation for natriuretic peptide screening in at-risk patients. Urine albumin-to-creatinine ratio (UACR) is an underutilized screening tool that provides additional insight into CKM risk.

The heart failure label does not close the prevention window—it accentuates it. Secondary prevention through GDMT optimization (quadruple therapy in HFrEF) and continued risk factor management remains critical. Tertiary prevention extends to post-LVAD and post-transplant patients, where hypertension, diabetes, obesity, and CKD management remain essential to long-term outcomes.

Show notes

For a comprehensive review, please review the full HFSA/ASPC Joint Scientific Statement: Lala A, Beavers C, Blumer V, et al. The Continuum of Prevention and Heart Failure in Cardiovascular Medicine. J Card Fail. 2026;32:75-105. doi:10.1016/j.cardfail.2025.06.013

1. What is the “continuum of prevention” framework, and how does it differ from traditional approaches to heart failure prevention?

Historically, prevention and heart failure management have been treated as separate disciplines—primary prevention handled by preventive cardiologists and treatment managed by heart failure specialists. This joint HFSA/ASPC Scientific Statement reframes prevention as a dynamic, continuous process that spans a patient’s entire lifespan, regardless of HF stage or ejection fraction.

The framework maps onto the ACC/AHA HF staging system:

Primary prevention targets Stage A (“at risk”) and Stage B (“pre-HF”) patients to reduce the burden of incident HF.

Secondary prevention targets Stage C (symptomatic) and Stage D (advanced) patients to reduce the impact of established HF through GDMT optimization and ongoing risk factor management.

Tertiary prevention encompasses risk factor management in patients with LVADs or heart transplants—populations where hypertension, diabetes, and obesity still drive outcomes.

The Central Figure of the statement illustrates that Life’s Essential 8 (blood pressure and lipid control, diabetes management, exercise, sleep, smoking cessation, weight management, and diet/nutrition counseling) forms the foundation at every stage, with pharmacologic and device-based therapies layered on top as disease progresses (Figure)

2. How do traditional risk factors drive heart failure, and what should clinicians prioritize?

Hypertension carries the greatest population-attributable risk for HF. In the Framingham Heart Study (N=5,143), HTN was associated with a 2- to 3-fold increased risk of HF, with a population-attributable risk of 39% in men and 59% in women. The SPRINT trial showed a 38% reduction in HF incidence and 25% reduction in the primary composite outcome with intensive BP targets (<120 mm Hg). Not all antihypertensives are equal for HF prevention: the ALLHAT trial showed that amlodipine carried a 38% higher risk and lisinopril a 19% higher risk of incident HF compared with chlorthalidone. The statement recommends prioritizing ACE inhibitors, ARBs, or thiazide diuretics as first-line agents when HF prevention is a goal.

Type 2 diabetes confers a 5-fold risk of HF in women and 2-fold in men. Each 5-year increment in diabetes duration is associated with a 17% increased risk of incident HF. SGLT2 inhibitors have a Class 1 recommendation for HF prevention in patients with T2DM and established CVD or high cardiovascular risk. Finerenone (nonsteroidal MRA) reduced new-onset HF by 32% in the FIGARO-DKD trial among patients with T2DM and CKD. GLP-1 receptor agonists reduce CV events in patients with T2DM and ASCVD and are recommended in current guidelines.

Obesity independently leads to myocardial dysfunction through the leptin-aldosterone-neprilysin framework, ectopic fat deposition, and neurohormonal dysregulation. The SELECT trial demonstrated that semaglutide reduced HF composite endpoint events (HR 0.84; 95% CI 0.74–0.97) in patients with obesity and established CVD without T2DM. Women with obesity are at highest risk for HFpEF, while men with obesity are at highest risk for HFrEF.

Chronic kidney disease with albuminuria is deliberately included as a traditional risk factor in this statement. Albuminuria confers a 2- to 3-fold increased risk of incident HF. UACR screening is recommended for patients with T2DM and those at risk for CKD.

3. How can risk stratification tools and biomarkers be used to identify patients on the trajectory toward heart failure?

Natriuretic peptides (BNP/NT-proBNP): The ACC/AHA/HFSA guidelines give a Class IIa recommendation for BNP or NT-proBNP screening in patients at risk for HF. Even modestly elevated levels (BNP >30 ng/L or NT-proBNP >125 ng/L) are associated with heightened risk for progression to symptomatic HF. In the ARIC study, incorporating NT-proBNP reclassified 20% of older adults without HF into Stage B. Factors that affect interpretation include age, sex, obesity (lower values), and CKD (higher values).

High-sensitivity cardiac troponin (hs-cTn): Concentrations above the 99th percentile are now included in the definition of Stage B HF. Troponin testing may complement natriuretic peptides, particularly when BNP/NT-proBNP values are ambiguous.

Risk scores: The PCP-HF equation predicts 10-year HF risk using traditional risk factors plus QRS duration. The AHA PREVENT score incorporates HF risk calculation and includes markers of kidney function (albuminuria, eGFR), though it may underestimate risk in men and Black adults. The CKM syndrome staging framework (Stages 0–4) provides a holistic approach to assessing systemic cardiovascular-kidney-metabolic risk.

4. What are the key nontraditional risk factors and cross-cutting themes in heart failure prevention?

Genetics: Pathogenic cardiomyopathy variants exist in ~1 in 200 individuals in the general population. The HFSA and ACMG recommend cascade testing to identify at-risk family members. Polygenic risk scores for dilated cardiomyopathy show a 3.8-fold risk for DCM in the top 10th percentile compared with the median.

Sex-specific considerations: Women have 2.8 times the odds of developing HFpEF, while men have similarly increased odds of HFrEF. A complete obstetric/gynecologic history is essential—preeclampsia is associated with a 4-fold increased risk of HF. Peripartum cardiomyopathy requires intentional screening in high-risk populations.

Cardiotoxic exposures: Clinicians should be aware of medications that cause direct myocardial toxicity (e.g., anthracyclines, trastuzumab, tyrosine kinase inhibitors). A team-based approach with pharmacists can help optimize medication selection and risk factor modification.

Social determinants of health: Environmental exposures (air pollution, arsenic, lead, cadmium), food insecurity, financial instability, and limited healthcare access contribute to HF risk and progression. Equity-focused, risk-based prevention strategies are needed.

Psychological health: Depression is common in HF and independently associated with worse outcomes. Screening with brief questionnaires (e.g., PHQ-2) is recommended. Meditation, spirituality, and holistic wellness approaches remain underutilized.

5. What systems-level and policy changes are needed to move the needle on heart failure prevention?

Multidisciplinary HF prevention clinics that bring together preventive cardiologists, HF specialists, endocrinologists, nephrologists, dietitians, pharmacists, exercise physiologists, and genetic counselors are advocated by the statement.

EHR-embedded risk stratification could proactively flag patients on a trajectory toward HF—analogous to sepsis alerts or fall risk flags—enabling earlier intervention, particularly for patients who may not reach a cardiologist.

Cardiac rehabilitation remains underutilized, particularly in HFrEF (Class 2b recommendation) and HFpEF (not yet covered by Medicare). The HF-ACTION trial showed quality-of-life benefits, and the REHAB-HF trial showed particular benefit in older patients with HFpEF.

Policy priorities include expanding insurance coverage for preventive screening and novel therapies (SGLT2i, GLP-1 RAs, nsMRAs), reducing clinical inertia through team-based care models with closer follow-up intervals, and ensuring equitable access to evidence-based therapies across diverse populations.

Digital health and AI hold promise for personalized risk prediction, remote monitoring (e.g., wearable devices, implantable PA pressure monitors), and virtual cardiac rehabilitation to overcome access barriers.

Figure 

Lala A, Beavers C, Blumer V, et al. The continuum of prevention and heart failure in cardiovascular medicine: a joint scientific statement from the Heart Failure Society of America and the American Society for Preventive Cardiology. J Card Fail. 2026;32(1):75-105. doi:10.1016/j.cardfail.2025.06.013)

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