Based on the echocardiographic values (E/e' septal ≈32, E/e' average ≈23, global longitudinal strain –13% to –12%, TAPSE 14–20 mm, normal left‑atrial volume index, normal left‑ventricular size and mass, low mitral gradients, no significant regurgitation), what is the most likely diagnosis and the appropriate guideline‑directed therapy?

Heart Failure with Preserved Ejection Fraction (HFpEF)

Based on the markedly elevated E/e' ratios (septal ≈32, average ≈23), reduced global longitudinal strain (–13% to –12%), and borderline-reduced TAPSE (14–20 mm) despite normal left ventricular size, mass, and ejection fraction, this patient has HFpEF with elevated left ventricular filling pressures and biventricular dysfunction.

Diagnostic Rationale

Primary Evidence for Elevated Filling Pressures

• The E/e' septal ratio of 32.8 and average E/e' of 23.0 definitively indicate elevated left ventricular filling pressures, as values >14 (average) or >15 (septal) have high specificity for elevated filling pressures 1, 2
• The 2016 ASE/EACVI guidelines establish that average E/e' >14 is a primary criterion for elevated left atrial pressure 1
• Meta-analysis of HFpEF patients demonstrates that E/e' correlates with invasively measured filling pressures (pooled r=0.56) and predicts outcomes with a hazard ratio of 1.05 per unit increase 1

Systolic Dysfunction Despite Preserved Ejection Fraction

• Global longitudinal strain of –13% to –12% is markedly abnormal (normal range is –18% and lower, with abnormal defined as –16% or higher) 3
• In HFpEF patients, GLS is typically reduced below normal (mean –17.5%) and correlates independently with exercise capacity and diastolic parameters including E/e' (R=0.45) and left atrial volume index (R=0.48) 4
• GLS is superior to ejection fraction in identifying patients with impaired functional capacity and demonstrates the coupling between diastolic and longitudinal systolic dysfunction in HFpEF 4

Right Ventricular Involvement

• TAPSE values of 14–20 mm indicate borderline to reduced right ventricular function (normal ≥17 mm) 1
• Reduced TAPSE in the context of elevated left-sided filling pressures suggests secondary pulmonary hypertension affecting right ventricular function 5
• TAPSE is independently prognostic in heart failure and correlates with septal longitudinal motion 5

Supporting Diastolic Parameters

• The left atrial volume index progression (13.5→16.1→27.0 ml/m²) demonstrates chronic elevation of filling pressures, though the most recent value of 27.0 ml/m² remains below the abnormal threshold of >34 ml/m² 1
• Deceleration time of 177 ms (normal 150-220 ms) is at the lower end of normal, consistent with Grade I diastolic dysfunction but not yet restrictive physiology 1
• The combination of markedly elevated E/e' with Grade I diastolic dysfunction pattern indicates elevated filling pressures despite compensated mitral inflow pattern 1, 6

Guideline-Directed Medical Therapy for HFpEF

Core Pharmacologic Management

• SGLT2 inhibitors (empagliflozin or dapagliflozin) are first-line therapy, as they reduce heart failure hospitalizations and cardiovascular death in HFpEF patients regardless of diabetes status 1
• Diuretics for congestion management are essential given the markedly elevated E/e' ratios indicating elevated filling pressures; loop diuretics should be titrated to achieve euvolemia 1
• Mineralocorticoid receptor antagonists (spironolactone) should be considered, particularly given the evidence of elevated filling pressures 1

Blood Pressure and Comorbidity Management

• Aggressive blood pressure control targeting <130/80 mmHg using ACE inhibitors, ARBs, or ARNIs (sacubitril/valsartan) 1
• Treatment of atrial fibrillation if present, with rate control and anticoagulation as indicated 1
• Management of obesity, diabetes, and other metabolic comorbidities that contribute to HFpEF pathophysiology 1

Monitoring Strategy

• Serial echocardiography with GLS measurement every 6-12 months to track disease progression, as GLS provides superior assessment of subclinical dysfunction compared to ejection fraction alone 3, 4
• Reassessment of E/e' ratios and TAPSE to monitor filling pressures and right ventricular function 1
• Natriuretic peptide levels (BNP or NT-proBNP) for prognostic assessment and monitoring response to therapy 1

Critical Clinical Pitfalls

Limitations of E/e' in Isolation

• E/e' should never be interpreted in isolation; the modest correlation with invasive pressures (r=0.56) means it must be integrated with other parameters including tricuspid regurgitation velocity, left atrial volume index, and clinical assessment 1, 2
• E/e' has limited accuracy in mitral annular calcification, mitral valve disease, pericardial disease, regional wall motion abnormalities, and atrial fibrillation 1, 2

Underrecognition of Systolic Dysfunction

• Normal ejection fraction does not exclude significant systolic dysfunction; the reduced GLS demonstrates impaired longitudinal contractility despite preserved radial function 3, 4
• Failure to measure GLS leads to underestimation of myocardial dysfunction and may delay appropriate therapy 3

Right Ventricular Assessment

• Borderline TAPSE (14-20 mm) indicates early right ventricular dysfunction that warrants closer monitoring and consideration of pulmonary hypertension evaluation 5
• Progressive decline in TAPSE predicts worse outcomes and should trigger reassessment of left-sided filling pressures and pulmonary pressures 5