Causes of Mildly Reduced EF (41%) with Normal Chamber Size in Uncontrolled Hypertension
In a woman with uncontrolled hypertension presenting with LVEF 41% and normal chamber dimensions, the most likely cause is hypertensive heart disease with concentric remodeling and subclinical myocardial dysfunction—a transitional state between compensated hypertrophy and overt heart failure. 1, 2
Primary Mechanism: Hypertensive Heart Disease
Chronic pressure overload from uncontrolled hypertension causes concentric left ventricular hypertrophy with preserved or reduced chamber size, where increased wall thickness initially maintains ejection fraction despite impaired myocardial contractility. 2, 3
Why EF Can Be Reduced Despite Normal Chamber Size
Wall thickness amplifies endocardial shortening through a "contractile gradient"—thickened walls can preserve EF even when midwall myocardial fiber shortening is significantly depressed. 3
When this compensatory mechanism begins to fail, EF drops into the mildly reduced range (41-49%) before chamber dilatation occurs, representing early decompensation of hypertensive heart disease. 1, 2
The mathematical relationship shows that ejection fraction depends on both myocardial strain AND wall thickness—reduced strain with increased wall thickness can yield mildly reduced EF with normal dimensions. 4
Clinical Classification
This patient has HFmrEF (Heart Failure with Mildly Reduced EF, defined as LVEF 41-49%), which requires symptoms/signs of heart failure plus the reduced EF measurement. 5, 1
If symptomatic (dyspnea, fatigue, edema), this definitively meets HFmrEF criteria and should be treated as heart failure. 5
If asymptomatic, this represents Stage B heart failure (structural heart disease without symptoms) requiring aggressive risk factor modification. 5
Differential Diagnosis Beyond Hypertension
Nondilated Cardiomyopathy
14% of patients with reduced EF (≤45%) have nondilated cardiomyopathy with normal chamber dimensions, often associated with hypertrophic remodeling and atrial fibrillation. 6
These patients frequently show improvement in EF over time (from 33% to 40% on average), particularly if atrial fibrillation is present and rate-controlled. 6
Subclinical Contractile Dysfunction in HFpEF Spectrum
Computational modeling demonstrates that reduced myocardial contractility combined with increased afterload can produce both preserved/mildly reduced EF and reduced global longitudinal strain—a pattern seen in hypertensive heart disease. 7
Many patients classified as "HFpEF" actually have subtle reductions in contractility masked by concentric geometry; an EF of 41% represents unmasking of this dysfunction. 7, 3
Atrial Fibrillation-Related Dysfunction
43% of patients with nondilated cardiomyopathy have atrial fibrillation, which can cause reversible reduction in EF through tachycardia-mediated cardiomyopathy or loss of atrial contribution to filling. 6
Screen for paroxysmal or persistent atrial fibrillation with ECG or ambulatory monitoring, as rate control can improve EF significantly. 6
Diagnostic Workup
Essential Echocardiographic Parameters
Measure relative wall thickness (RWT = 2 × posterior wall thickness / LV end-diastolic diameter)—RWT >0.42 confirms concentric remodeling typical of hypertensive heart disease. 8
Assess global longitudinal strain (GLS)—reduced GLS (<18%) with mildly reduced EF indicates intrinsic myocardial dysfunction beyond geometric effects. 5
Evaluate diastolic function with E/e' ratio—E/e' ≥15 confirms elevated filling pressures and supports diagnosis of hypertensive heart disease with diastolic dysfunction. 5, 8
Measure left atrial volume index (LAVI)—enlargement indicates chronic pressure overload and predicts adverse outcomes. 5
Rule Out Alternative Etiologies
Exclude coronary artery disease with stress testing or coronary angiography, as ischemic cardiomyopathy is the most common cause of reduced EF and can coexist with hypertension. 1
Screen for infiltrative cardiomyopathies (amyloidosis, sarcoidosis) if wall thickness is disproportionate or if "sparkling" myocardial texture is present on echo. 8
Check thyroid function, as both hyperthyroidism and hypothyroidism can cause reversible cardiomyopathy with normal chamber size. 5
Obtain cardiac MRI if diagnosis remains unclear—late gadolinium enhancement patterns distinguish ischemic, hypertrophic, and infiltrative etiologies. 5
Management Priorities
Blood Pressure Control is Paramount
Target BP <130/80 mmHg using guideline-directed medical therapy—chlorthalidone or indapamide (thiazide-like diuretics) have superior efficacy in preventing heart failure progression compared to hydrochlorothiazide. 2
ACE inhibitors or ARBs are first-line for hypertension with LV dysfunction, as they reduce afterload, promote reverse remodeling, and have mortality benefit in HFrEF. 1, 2
Beta-blockers reduce mortality in HFrEF and may improve diastolic filling by reducing heart rate, but should be added after ACE inhibitor/ARB initiation. 1, 8
Heart Failure Therapy
SGLT2 inhibitors (dapagliflozin or empagliflozin) reduce heart failure hospitalization across the EF spectrum and should be initiated regardless of diabetes status. 8
Mineralocorticoid receptor antagonists (spironolactone 25 mg daily) may provide benefit, particularly in women and those with lower EF in the mildly reduced range. 8
Loop diuretics (furosemide 20-40 mg daily) should be used if volume overload is present, titrated to euvolemia. 8
Serial Monitoring
Repeat echocardiography in 3-6 months to assess for improvement in EF with treatment—many patients with nondilated cardiomyopathy show significant recovery, especially if atrial fibrillation is controlled. 6
Monitor natriuretic peptides (BNP or NT-proBNP) to track disease activity and guide diuretic therapy. 8
Critical Clinical Pitfalls
Do not dismiss mildly reduced EF as "borderline normal"—LVEF 41% represents definite systolic dysfunction requiring treatment, particularly in the setting of uncontrolled hypertension. 1, 9
Avoid NSAIDs, which worsen heart failure and hypertension through sodium retention and increased afterload. 8
Do not attribute all symptoms to hypertension alone—systematically exclude pulmonary, renal, and other cardiac causes of dyspnea. 8
Recognize that "decapitated hypertension" (normalization of previously elevated BP) can occur as pump function declines—normal BP does not exclude hypertensive heart disease as the etiology. 2