What is the best course of treatment for a 79-year-old female with concentric left ventricular (LV) hypertrophy, good systolic function, severe pulmonary hypertension, dilated right atrium and right ventricle, and symptoms of heart failure, including tricuspid annular plane systolic excursion (TAPSE) of 19?

Management of Severe Pulmonary Hypertension Secondary to Heart Failure with Preserved Ejection Fraction

This 79-year-old woman has pulmonary hypertension secondary to left heart disease (Group 2 PH-LHD), specifically from heart failure with preserved ejection fraction (HFpEF) due to concentric LV hypertrophy, and the primary treatment goal must be aggressive management of the underlying diastolic dysfunction rather than pulmonary arterial hypertension-specific therapies. 1, 2

Diagnostic Confirmation Required

Before initiating therapy, you must confirm this is truly PH-LHD rather than pulmonary arterial hypertension:

• Perform right heart catheterization with careful measurement of pulmonary capillary wedge pressure (PCWP) and left ventricular end-diastolic pressure (LVEDP) to establish that elevated left-sided filling pressures are the primary cause 1, 2
• PCWP >15 mmHg confirms post-capillary pulmonary hypertension secondary to left heart disease 2
• The clinical presentation strongly suggests PH-LHD: age >65 years, concentric LV hypertrophy, symptoms of heart failure, and dilated right heart chambers 1
• TAPSE of 19 mm indicates borderline RV systolic dysfunction (normal >17 mm), suggesting significant hemodynamic burden 3

Primary Treatment Strategy: Optimize Diastolic Dysfunction

1. Aggressive Volume Management (First Priority)

Initiate loop diuretics immediately to reduce left ventricular filling pressures and pulmonary venous congestion 1, 2:

• Start with furosemide 40-80 mg IV daily (or equivalent bumetanide/torsemide) 4
• Titrate to lowest effective dose that relieves congestion without causing hypotension or worsening renal function 1, 4
• Critical pitfall: Avoid excessive diuresis which may reduce preload excessively in this hypertrophied, stiff ventricle and worsen cardiac output 1, 4
• If inadequate response, consider adding thiazide diuretic (e.g., metolazone 2.5-5 mg daily) for sequential nephron blockade 1, 4
• Monitor daily weights, electrolytes (especially potassium), and renal function 4

2. Initiate SGLT2 Inhibitor (Disease-Modifying Therapy)

Start dapagliflozin 10 mg daily or empagliflozin 10 mg daily as first-line disease-modifying therapy 4:

• DELIVER trial showed dapagliflozin reduced worsening HF and cardiovascular death (HR 0.82,95% CI 0.73-0.92) 4
• EMPEROR-PRESERVED showed empagliflozin reduced HF hospitalization and CV death (HR 0.79,95% CI 0.69-0.90) 4
• Benefits occur independent of diabetes status 4
• Ensure eGFR >30 mL/min/1.73m² before initiation 4

3. Blood Pressure Control and Afterload Reduction

Optimize blood pressure control targeting <130/80 mmHg using ACE inhibitors or ARBs 1, 2:

• These agents prevent and potentially reverse LV hypertrophy, which is crucial in this patient 1, 2
• Start with ACE inhibitor (e.g., lisinopril 10-40 mg daily) or ARB if ACE inhibitor intolerant (e.g., losartan 50-100 mg daily) 1
• Regression of hypertrophy may take 18-24 months but improves diastolic properties 5, 6

4. Heart Rate Control and Diastolic Filling Optimization

Initiate beta-blocker therapy to optimize diastolic filling time and prevent tachyarrhythmias 1:

• Start with metoprolol succinate 25-50 mg daily or carvedilol 3.125-6.25 mg twice daily 1
• Beta-blockers improve diastolic filling by prolonging diastolic time and reducing myocardial oxygen demand 1
• Titrate slowly to avoid excessive bradycardia or hypotension 1

5. Consider Mineralocorticoid Receptor Antagonist

Add spironolactone 12.5-25 mg daily, particularly given the severe pulmonary hypertension 1, 4:

• TOPCAT trial showed spironolactone reduced HF hospitalizations (HR 0.83,95% CI 0.69-0.99) 4
• More effective in patients with LVEF in lower preserved range 4
• Monitor potassium closely (target <5.0 mEq/L) and renal function, especially when combined with ACE inhibitor/ARB 1, 4

Critical Medications to AVOID

Do NOT use pulmonary arterial hypertension-specific therapies (prostanoids, endothelin receptor antagonists, PDE-5 inhibitors) in this patient 1, 2:

• Riociguat showed no benefit in PH-LHD (201 patients, 16 weeks, no effect on primary endpoint) 1
• Bosentan in ENABLE trial showed increased early heart failure exacerbations due to fluid retention 1
• These agents are potentially harmful and contraindicated in Group 2 PH 2
• Exception: Only consider if patient fails maximal medical therapy and is being evaluated for advanced therapies (heart transplant, LVAD) 1

Avoid nondihydropyridine calcium channel blockers (diltiazem, verapamil) 1, 4:

• Negative inotropic effects increase risk of worsening heart failure 1, 4

Avoid nitrates 4:

• Associated with signal of harm in HFpEF 4

Management of Right Ventricular Failure

Given the dilated right heart chambers and borderline TAPSE:

• Maintain adequate preload but avoid volume overload 3, 7
• If hypotension develops, use vasopressors (norepinephrine) rather than aggressive fluid boluses 3
• Consider inhaled nitric oxide or inhaled epoprostenol if acute RV decompensation occurs 1
• Avoid intubation if possible as positive pressure ventilation worsens RV afterload 3

Identify and Treat Contributing Conditions

Screen for and aggressively manage common comorbidities that worsen PH-LHD 1:

• Sleep apnea syndrome (very common in this population) 1
• COPD 1
• Atrial fibrillation (maintain rate control, consider rhythm control if present) 1
• Metabolic syndrome features (obesity, diabetes) 1
• Coronary artery disease 1

Monitoring and Follow-up

• Reassess volume status, symptoms, and functional capacity every 2-4 weeks initially 4
• Repeat echocardiography in 3-6 months to assess response (LV mass regression, RV function, estimated PA pressures) 4
• Monitor electrolytes and renal function closely, especially with triple neurohormonal blockade 4
• Consider repeat right heart catheterization if clinical deterioration despite optimal medical therapy 1

Advanced Therapy Considerations

If patient remains severely symptomatic despite maximal medical therapy:

• Refer to advanced heart failure center for consideration of LVAD or heart transplantation 1
• LVAD implantation has been shown to lower pulmonary pressures through LV unloading 1
• Cardiac transplantation can be considered in eligible patients with advanced HFpEF refractory to therapy 4

Common Pitfalls to Avoid

• Do not treat this as primary pulmonary arterial hypertension - the concentric LV hypertrophy and age >65 clearly indicate Group 2 PH-LHD 1, 2
• Do not use PAH-specific therapies outside of clinical trials - no evidence supports their use and they may cause harm 1, 2
• Do not over-diurese - excessive volume depletion in severe concentric LV hypertrophy can cause rapid hemodynamic deterioration 1
• Do not overlook comorbidities - sleep apnea, COPD, and metabolic syndrome significantly impact outcomes 1