Cracking the Code on Heart Failure’s Stiffest Challenge

Key Takeaway: The American College of Cardiology has released a new Expert Consensus Decision Pathway for Heart Failure with Preserved Ejection Fraction (HFpEF), which accounts for approximately half of all heart failure cases. This document provides clinicians with an updated, practical algorithm for the diagnosis, phenotyping, and treatment of HFpEF, incorporating rapid therapeutic advances in recent years, including SGLT2 inhibitors, mineralocorticoid receptor antagonists, and targeted comorbidity management.

A New Strategic Guide for Medicine’s Most Elusive Form of Heart Failure

The American College of Cardiology (ACC) has published a new roadmap for managing Heart Failure with Preserved Ejection Fraction (HFpEF), the most challenging and common form of heart failure. For decades, this condition had left cardiologists at a loss. Although the heart’s pumping function appeared normal on imaging, patients would become breathless climbing a single flight of stairs, their ankles would swell, and their quality of life steadily eroded. Studies of drugs that had radically improved outcomes in heart failure with reduced ejection fraction (HFrEF) repeatedly failed when applied to HFpEF. That era of therapeutic nihilism is now over. The ACC’s new Expert Consensus Decision Pathway arrives at a moment when clinicians, for the first time, have multiple evidence-based tools at their disposal and a pressing need for a framework on how to use them^[1].

The Significance of This Document

An Expert Consensus Decision Pathway (ECDP) published by the ACC is not a mere opinion piece. It is a formally structured document, prepared by the ACC Solution Set Oversight Committee, that synthesizes the best available evidence into practical, actionable algorithms. This specific pathway focuses on HFpEF, generally defined as heart failure in patients with a left ventricular ejection fraction of 50% or greater^[2]. The document addresses the entire continuum of clinical management: making the (still quite difficult) diagnosis, identifying the patient’s specific phenotype and comorbidity profile, initiating guideline-directed medical therapy (GDMT), and managing a cluster of conditions that co-occur with HFpEF, such as obesity, atrial fibrillation, hypertension, diabetes, and chronic kidney disease.

I would like to summarize this expert consensus under general headings. This guideline, also published as full text, provides highly valuable information:

Diagnostic Approach and Clinical Scoring Systems

Diagnosing HFpEF is clinically challenging because echocardiography alone does not provide a pathognomonic finding, and natriuretic peptide (BNP/NT-proBNP) levels can be within normal limits in a significant portion of cases. The guideline highlights three main scoring systems and their specific use cases to confirm the diagnosis and prevent misdiagnosis:

• H2FPEF Score (For Cardiology Practice): Developed using invasive exercise hemodynamics as a reference, this is the most accurate system for clinical application. It consists of six parameters: Heavy obesity (Body Mass Index – BMI > 30, 2 points), use of 2 or more antihypertensives (1 point), Atrial Fibrillation (3 points), Pulmonary Hypertension (PASP > 35 mmHg on Doppler echocardiography, 1 point), Age (>60 years, 1 point), and High Filling Pressures (E/e’ ratio > 9, 1 point). A total score of 6 or higher makes the diagnosis of HFpEF nearly certain. This scoring system is crucial and can be highly useful for diagnosis in clinical practice.

• HFA-PEFF Algorithm (European/Combined Approach): This is a more complex, four-step process (pre-test assessment, echocardiography/biomarker score, functional stress testing, and final etiology). Unlike the H2FPEF score, the HFA-PEFF algorithm directly includes Left Ventricular Hypertrophy (LVH / Left Ventricular Mass Index) in its morphological criteria for scoring. Its specificity is higher than that of the H2FPEF score. However, because its later stages requiring a diastolic stress test or invasive hemodynamic measurement are difficult to implement, it is recommended that for patients presenting with intermediate scores, guideline-directed medical therapy be initiated directly and the response monitored.

• HFpEF-ABA Score (For Primary Care and Screening): This is the newest mathematical score, which works with only 3 practical parameters (Age, Body Mass Index [BMI], Atrial Fibrillation [AF]) without requiring echocardiogram or laboratory data. It is designed for primary care physicians or electronic health record systems to identify patients with suspected HFpEF early and refer them to a specialized center.

• The Natriuretic Peptide “Trap”: The guideline specifically emphasizes that BNP and NT-proBNP levels can be normal or low in HFpEF patients who are obese, female, Black, or have insulin resistance, due to suppressed levels. Therefore, a “normal natriuretic peptide level” should never be used in isolation to rule out HFpEF. The clarification provided by the guideline on this common clinical finding is valuable.

• Exclusion of LVH and HFpEF Mimics: It is essential to rule out conditions that can mimic the clinical picture before making a diagnosis. When significant LVH is detected on echocardiography, it must be determined whether this is classic HFpEF due to hypertension or a mimic requiring specific treatment, such as Cardiac Amyloidosis or Hypertrophic Cardiomyopathy (HCM). Additionally, cardiac and non-cardiac conditions like Constrictive Pericarditis, Advanced Renal Failure, and High-Output Heart Failure must be systematically excluded.

Critical Details in Treatment and Medication Updates

The fundamental treatment classifications officially updated by the guideline are as follows:

• Priority of Non-Steroidal MRA (Finerenone): Based on data from the FINEARTS-HF trial, Finerenone significantly reduced cardiovascular death and recurrent heart failure hospitalizations in HFpEF patients with an LVEF of 40% and above, and it received formal FDA approval in July 2025. The guideline positions Finerenone as the first-line choice in the MRA class due to its favorable side-effect profile (lower risk of hyperkalemia) and renal-protective effects. Spironolactone is offered as an alternative in cases of cost or access limitations.
• Incretin-Based Therapies (GLP-1 RA / Tirzepatide) and “Sarcopenic Obesity” Warning: The STEP-HFpEF (Semaglutide) and SUMMIT (Tirzepatide) trials demonstrated significant weight loss, symptom improvement, and enhanced quality of life in HFpEF patients with a BMI of 30 or higher. However, the guideline issues a warning that these drugs, while promoting rapid fat loss, can also lead to critical muscle mass loss, potentially triggering “Sarcopenic Obesity,” particularly in the elderly population. Therefore, it is stated that these therapies must be administered in conjunction with resistance/exercise training and a high-protein diet.
• Defined Role for ARNI and ARB: Although the guideline accepts LVEF ≥ 50% as the general threshold for HFpEF, it notes that ARNI (Sacubitril/Valsartan) therapy has shown significant clinical benefit, particularly in HFpEF patients whose ejection fraction is in the lower-normal range (LVEF below 55–60%) and in women. When ARNI (Sacubitril/Valsartan) use is not possible or tolerated, the ARB Candesartan is an alternative option, with effects on reducing hospitalizations and controlling blood pressure. In contrast, ACE inhibitors (Perindopril, etc.) are not considered a suitable alternative in HFpEF treatment, as they have failed to show benefit in clinical trials. Beta-blockers are not recommended unless there is a specific indication, such as angina or rate control in atrial fibrillation, as they may lead to chronotropic incompetence and impair exercise capacity.

CKM Syndrome and Comorbidity Management

• Cardiovascular-Kidney-Metabolic (CKM) Framework: The guideline defines HFpEF not as an isolated organ failure but as the cardiac manifestation of CKM Syndrome, a condition where visceral obesity, insulin resistance, chronic kidney disease, and hypertension feed into one another. SGLT2 inhibitors, Finerenone, and GLP-1 receptor agonists are presented as foundational agents offering a “triple protective shield” (cardiac-renal-metabolic).
• “U-Shaped Risk” in Blood Pressure and the Optimal Target: According to pooled analyses of the I-PRESERVE, TOPCAT, PARAGON-HF, and DELIVER trials, both a systolic blood pressure of 140 mmHg and above, as well as a reduction below 120 mmHg, increase the risk of cardiovascular death and hospitalization in HFpEF patients. The guideline establishes the optimal systolic blood pressure target as the narrow range of 120–129 mmHg for these patients.

Current Status of Interventional and Device Therapies

• Implantable Pulmonary Artery Monitors (CardioMEMS / Cordella): In line with the CHAMPION, GUIDE-HF, and MONITOR-HF trials, for HFpEF patients who remain symptomatic (NYHA Class III) despite optimal medical therapy, have highly variable volume status, and experience frequent hospitalizations, remote home monitoring of pulmonary artery pressure reduces hospital admissions by 40% to 50%.
• Atrial Shunt Devices and Splanchnic Ablation: Based on the results of the RELIEVE-HF and REDUCE LAP-HF trials, interatrial shunt devices have not provided a routine benefit in the general HFpEF population and have even increased the risk of cardiovascular events in some patients. The guideline emphasizes that interventions such as shunts and splanchnic nerve ablation are not yet part of routine care.

Why Was HFpEF So Difficult to Treat, and What Has Changed?

To appreciate the importance of this consensus pathway, one must understand why HFpEF has been such a clinical enigma. In HFrEF, the heart muscle weakens and dilates; the pump is mechanically failing. Neurohormonal blockade with beta-blockers, ACE inhibitors, and aldosterone antagonists interrupts the vicious cycle of sympathetic activation and fluid retention, dramatically reducing mortality^[3].

HFpEF, however, is a fundamentally different disease. The heart contracts adequately, but its relaxation is impaired. The left ventricle becomes stiff, filling pressures rise, and fluid backs up into the lungs and peripheral tissues. The underlying pathophysiology stems not from a single failing pump but from a systemic syndrome characterized by microvascular inflammation, endothelial dysfunction, and myocardial fibrosis^[4]. Obesity, metabolic syndrome, and aging conspire to create a pro-inflammatory milieu that stiffens the heart at a cellular level: collagen accumulates between cardiomyocytes, and the giant intracellular protein titin becomes hypophosphorylated, losing its elastic compliance^[5].

This heterogeneity explains why no single drug class could be a panacea for every patient with HFpEF. It also explains why, when breakthroughs finally arrived, they came from unexpected directions. The EMPEROR-Preserved trial showed that empagliflozin, an SGLT2 inhibitor originally developed for diabetes, reduced the risk of cardiovascular death or hospitalization for heart failure in patients with HFpEF^[6]. The DELIVER trial confirmed these benefits with dapagliflozin across a broad range of ejection fractions^[7]. Suddenly, clinicians had a class of drugs with consistent benefits and the challenge of integrating them into practice.

Mineralocorticoid receptor antagonists like spironolactone showed promising, albeit not definitive, benefits in the TOPCAT trial, with post-hoc analyses revealing significant reductions in heart failure hospitalizations among patients enrolled in the Americas^[8]. ARNIs, which proved their power in the PARAGON-HF trial, demonstrated benefits particularly in women and in patients at the lower end of the preserved ejection fraction range^[9]. GLP-1 receptor agonists and targeted weight-loss strategies have added another layer of therapeutic possibility for the large subset of HFpEF patients with obesity.

What This Means for Patients Tomorrow

For the estimated three million Americans living with HFpEF, this consensus pathway translates into several tangible changes at the point of care:

• Faster, more reliable diagnosis. The guideline provides a structured approach to identifying HFpEF by incorporating validated scoring systems like the H2FPEF and HFA-PEFF algorithms, which use a combination of clinical, echocardiographic, and biomarker data to make the diagnosis without requiring invasive hemodynamic testing in every case^[10].
• Phenotype-specific treatment. Rather than treating all HFpEF patients the same, the guideline encourages clinicians to identify dominant phenotypes—obesity-related, atrial fibrillation-driven, hypertensive, female, elderly, and those with CKM syndrome—and to tailor therapy accordingly.
• SGLT2 inhibitors as foundational therapy. On the strength of the evidence from the EMPEROR-Preserved and DELIVER trials, these agents are now positioned as essential pharmacotherapy for HFpEF, regardless of diabetes status.
• Defined Role for ARNI and ARB. The inclusion of these medications in the treatment regimen is an important update.
• Aggressive comorbidity management. The guideline emphasizes that treating the conditions surrounding HFpEF—controlling blood pressure, managing atrial fibrillation, achieving weight loss, and optimizing volume status with diuretics—is not ancillary care but central to the treatment strategy.

Important Caveats

An expert consensus pathway, no matter how proficient, is not the final word. It reflects an expert interpretation of the evidence available at the time it was written. HFpEF remains a heterogeneous syndrome, and many patients will not fit neatly into the proposed algorithms. The landmark trials that shaped this guideline, while practice-changing, may have included selected populations that do not perfectly represent every patient encountered in a busy clinic. Furthermore, the long-term outcomes of using SGLT2 inhibitors in combination with MRAs, ARNIs, and GLP-1 receptor agonists are still under active investigation. Individualized clinical judgment for the patient in front of you remains indispensable.

Conclusion

HFpEF was once a diagnosis of exclusion and a therapeutic frustration. The ACC’s new Expert Consensus Decision Pathway marks a turning point: clinicians now have a structured, evidence-based framework to diagnose these patients, match them with therapies of proven benefit, and manage the web of comorbidities that fuels this syndrome. For the millions of patients who have struggled with unexplained shortness of breath and swelling despite a ‘good-looking’ heart on their echocardiogram, this document has the potential to represent something medicine couldn’t offer them even five years ago: a real plan of action.

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Scientific Sources

1. Kittleson MM, et al. Management of Heart Failure With Preserved Ejection Fraction: 2026 ACC Expert Consensus Decision Pathway: A Report of the American College of Cardiology Solution Set Oversight Committee. Journal of the American College of Cardiology. 2026. PubMed: https://pubmed.ncbi.nlm.nih.gov/42494134/
2. Borlaug BA. Evaluation and management of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2020. DOI: 10.1038/s41569-020-0363-2
3. McMurray JJ, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2012. DOI: 10.1093/eurheartj/ehab368
4. Paulus WJ, Tschöpe C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol. 2013. DOI: 10.1016/j.jacc.2013.02.092
5. Zile MR, et al. Myocardial stiffness in patients with heart failure and a preserved ejection fraction. Circulation. 2015. DOI: 10.1161/CIRCULATIONAHA.114.013215
6. Anker SD, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021. DOI: 10.1056/NEJMoa2107038
7. Solomon SD, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022. DOI: 10.1056/NEJMoa2206286
8. Pitt B, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014. DOI: 10.1056/NEJMoa1313731
9. Solomon SD, et al. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med. 2019. DOI: 10.1056/NEJMoa1908655
10. Reddy YNV, et al. A simple, evidence-based approach to help guide diagnosis of heart failure with preserved ejection fraction. Circulation. 2018. DOI: 10.1161/CIRCULATIONAHA.118.034646

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