Heart faikure with preserverd ejection fraction vs refduce
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"heart failure preserved ejection fraction" AND "heart failure reduced ejection fraction" AND comparison
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heart failure preserved vs reduced ejection fraction comparison diagram
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Heart Failure with Preserved EF (HFpEF) vs. Reduced EF (HFrEF)
Definition & EF Cutoffs
| Feature | HFrEF | HFpEF |
|---|---|---|
| LVEF | ≤40% | ≥50% |
| "Mildly reduced" (HFmrEF) | -- | 41-49% (intermediate phenotype) |
| Primary dysfunction | Systolic (pump failure) | Diastolic (filling failure) |
| LV size | Dilated | Normal or small |
| LV wall | Thin / eccentric hypertrophy | Thickened / concentric hypertrophy |
Pathophysiology
HFrEF
- Loss of contractile function - the ventricle cannot eject blood effectively
- Neurohormonal activation: RAAS activation, sympathetic hyperactivity, elevated norepinephrine, angiotensin II, aldosterone
- Progressive cardiac remodeling: LV dilation, eccentric hypertrophy, myocyte loss, interstitial fibrosis
- Cardiomyocyte slippage, sarcomere dysfunction
- Common causes: ischemic heart disease (most common), dilated cardiomyopathy, myocarditis, valvular disease, chronic tachyarrhythmia, toxins (alcohol, doxorubicin)
HFpEF
-
The ventricle contracts normally but cannot relax or fill adequately
-
LV stiffness from hypertrophy + interstitial fibrosis, abnormal calcium cycling (impaired active relaxation)
-
Key molecular change: reduced phosphorylation of titin (sarcomeric spring protein) - increases passive stiffness
-
Microvascular endothelial inflammation driven by comorbidities - impairs nitric oxide (NO) signaling - myocardial stiffening (the "systemic inflammation" paradigm)
-
Elevated filling pressures at rest or with exertion - pulmonary congestion and dyspnea
-
Atrial fibrillation is especially poorly tolerated: in a stiff ventricle, atrial "kick" contributes a disproportionately large fraction of filling - loss of it causes hemodynamic decompensation
-
Common causes: hypertension (60-80%), age, obesity/metabolic syndrome, diabetes, ischemic heart disease
-
Goldman-Cecil Medicine, p. 2298-2302
Demographics
| Feature | HFrEF | HFpEF |
|---|---|---|
| Sex | More common in men | More common in women |
| Age | Younger on average | Older (prevalence increases sharply with age) |
| Obesity/metabolic syndrome | Less defining | Major driver |
| Hypertension as cause | Frequent | Dominant (60-80%) |
Clinical Presentation
Both share the same symptoms - dyspnea, orthopnea, PND, lower-limb edema, fatigue - making clinical distinction by symptoms alone impossible.
Key distinguishing clues:
- HFpEF: often no S3 gallop, may have S4 (reflecting stiff ventricle), hypertensive history, preserved or small LV on echo
- HFrEF: S3 gallop common, displaced apex beat, cardiomegaly on CXR
- Both: elevated BNP/NT-proBNP (though BNP may be lower in HFpEF due to reduced wall stress; obesity blunts BNP further)
The resting hemodynamic profile in HFpEF is frequently normal - but tachycardia or exercise provokes exaggerated filling pressure rises, which explains why symptoms are predominantly exertional.
Diagnosis
Both require:
- Symptoms/signs of HF
- Structural/functional cardiac abnormality
- Elevated filling pressures (natriuretic peptides or invasive)
Echocardiography is key:
- Measures LVEF
- Assesses diastolic dysfunction grading (E/e' ratio, LA volume, TR velocity, tissue Doppler)
- HFpEF diagnosis is harder - scoring systems (H2FPEF score, HFA-PEFF score) help when echo is non-diagnostic
Prognosis
-
Mortality is significant in both, but HFpEF has somewhat better survival than HFrEF, though the gap has narrowed with modern HFrEF therapies
-
Hospitalization rates and symptom burden are similar between the two
-
HFpEF has a higher proportion of non-cardiovascular deaths (driven by multimorbidity)
-
Braunwald's Heart Disease, p. 1035; Goodman & Gilman, p. 669
Treatment
This is where the two conditions differ most dramatically.
HFrEF - Evidence-Based "Quadruple Therapy" (all reduce mortality)
| Drug Class | Examples | Benefit |
|---|---|---|
| ACE inhibitor / ARB / ARNI | Enalapril, losartan, sacubitril-valsartan | Mortality ↓; PARADIGM-HF: sacubitril-valsartan superior to enalapril |
| Beta-blocker | Carvedilol, metoprolol succinate, bisoprolol | Mortality ↓ |
| Mineralocorticoid receptor antagonist (MRA) | Spironolactone, eplerenone | Mortality ↓ |
| SGLT2 inhibitor | Dapagliflozin, empagliflozin | CV death + HF hospitalization ↓ |
| Diuretics | Furosemide | Symptom relief |
| Devices | ICD (if EF <35%), CRT (if LBBB + EF ≤35%) | Mortality ↓ |
HFpEF - Historically Symptom-Focused, Now Evolving
Previously, all HFrEF drugs failed to show mortality benefit when trialed in HFpEF:
- ACE inhibitors (PEP-CHF): attenuated benefit over time
- ARBs (CHARM-Preserved, I-PRESERVE): reduced HF hospitalizations but no mortality benefit
- Spironolactone (TOPCAT): no primary endpoint benefit; regional analysis suggested possible benefit in Americas subgroup
- Beta-blockers (SENIORS subgroup): no clear benefit
- Digoxin (DIG Ancillary): modest HF hospitalization reduction only
- Sildenafil (RELAX), nitrates (NEAT-HFpEF): no benefit
- Sacubitril-valsartan (PARAGON-HF): 13% reduction in primary endpoint but missed statistical significance (p=0.06); possible benefit in women and lower-EF HFpEF
Recent breakthroughs for HFpEF:
- SGLT2 inhibitors (EMPEROR-Preserved: empagliflozin; DELIVER: dapagliflozin) - reduced CV death + HF hospitalization in HFpEF - now endorsed as foundational therapy regardless of EF in updated US and European guidelines
- GLP-1 agonists (STEP-HFpEF trial: semaglutide in obese HFpEF) - improved functional capacity and QOL with ~12% weight loss vs. placebo
- Tirzepatide (SUMMIT trial) - ongoing data
Current HFpEF management pillars:
- SGLT2 inhibitor (dapagliflozin or empagliflozin) - now Class I
- Diuretics for congestion control
- Blood pressure control (target <130/80)
- Heart rate/rhythm control (especially AF)
- Weight loss and exercise training (only intervention proven to increase peak VO₂)
- Aggressive comorbidity management: hypertension, diabetes, obesity, OSA, anemia/iron deficiency
- Harrison's 22E, p. 2542-2575; Goodman & Gilman, p. 1908
Summary Table
| Domain | HFrEF (EF ≤40%) | HFpEF (EF ≥50%) |
|---|---|---|
| Primary problem | Systolic dysfunction | Diastolic dysfunction |
| LV geometry | Dilated, thin-walled | Non-dilated, hypertrophied |
| Neurohormonal activation | Prominent (RAAS, SNS) | Less prominent |
| Key comorbidities | IHD, cardiomyopathy | HTN, obesity, DM, age |
| Sex predominance | Male | Female |
| BNP | Markedly elevated | Elevated but often lower |
| Mortality-reducing drugs | ACEi/ARB/ARNI, BB, MRA, SGLT2i | SGLT2i (recently proven); others lack mortality evidence |
| ARNI (sacubitril-valsartan) | Class I (PARADIGM-HF) | Borderline benefit (PARAGON-HF) |
| ICD/CRT | Yes (EF <35%) | No indication |
| Exercise training | Class I recommendation | Improves VO₂ and QOL |
A note on HFmrEF (41-49%): This intermediate phenotype may overlap with both. Current evidence supports treating HFmrEF patients with the same RAAS/BB/SGLT2i therapy as HFrEF, particularly if EF is closer to the lower end of this range.
Recent evidence flag: A 2024 systematic review on HFpEF diagnosis (PMID 37861854) highlights ongoing challenges in HFpEF diagnosis given its heterogeneous phenotype. A 2025 systematic review (PMID 40857067) is further characterizing HFpEF phenotypes in device and surgical trials - suggesting increasing recognition of HFpEF subgroups that may respond differently to therapy.
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