What is the most likely cause of pulmonary hypertension in a patient with a low ejection fraction (EF), atrial fibrillation (AF), and ischemic heart disease (IHD)?

Pulmonary Hypertension in a 69-Year-Old Male with EF 33%, AF, and IHD

The pulmonary hypertension in this patient is almost certainly Group 2 PH due to left heart disease, specifically caused by left ventricular systolic dysfunction (EF 33%) with likely superimposed diastolic dysfunction. 1, 2

Primary Mechanism: Left Ventricular Systolic Dysfunction

Up to 60% of patients with severe left ventricular systolic dysfunction develop pulmonary hypertension as a direct complication of their heart failure. 1 The mechanism is straightforward:

• The failing left ventricle with EF 33% cannot adequately eject blood, leading to elevated left ventricular end-diastolic pressure 2, 3
• This pressure transmits retrograde through the left atrium into the pulmonary venous circulation 4, 5
• Chronic elevation of pulmonary capillary wedge pressure (PCWP) above 15 mmHg defines Group 2 PH due to left heart disease 5, 6, 7

Contributing Factor: Ischemic Heart Disease

The patient's ischemic heart disease directly contributes through multiple mechanisms:

• Myocardial ischemia impairs both systolic and diastolic ventricular function acutely and chronically 1, 3
• Prior myocardial infarction creates regional wall motion abnormalities that worsen overall ventricular performance 3
• Ischemia-induced mitral regurgitation can develop, further elevating left atrial pressure 3

Atrial Fibrillation as an Aggravating Factor

Atrial fibrillation significantly worsens the hemodynamic profile in this patient: 2

• Loss of atrial contraction reduces ventricular filling, particularly problematic when diastolic dysfunction coexists 2
• Irregular ventricular response compromises cardiac output 2
• AF itself is a marker of elevated left atrial pressure and advanced left heart disease 2, 7

Age-Related Considerations

At 69 years old, this patient fits the contemporary epidemiologic profile:

• PAH is now more frequently diagnosed in elderly patients (mean age 50-65 years in current registries), but this demographic shift has led to unintentional inclusion of patients with PH due to heart failure with preserved ejection fraction rather than true PAH 1
• Older patients with metabolic risk factors are highly suggestive of LHD etiology rather than pulmonary arterial hypertension 5

Diagnostic Confirmation Required

Right heart catheterization with careful measurement of PCWP and left ventricular end-diastolic pressure is essential to confirm Group 2 PH: 1, 2

• PCWP >15 mmHg confirms post-capillary PH secondary to left heart disease 2, 5, 6
• The patient should be assessed on optimized volume status before invasive hemodynamic assessment 1
• Measure transpulmonary gradient and pulmonary vascular resistance to determine if isolated post-capillary (ipcPH) or combined post- and pre-capillary PH (cpcPH) is present 5, 6

Critical Differential Considerations

While Group 2 PH is overwhelmingly likely, exclude these alternative causes:

• Chronic thromboembolic pulmonary hypertension (CTEPH): The patient's AF increases thromboembolic risk, making CTEPH a mandatory consideration 1
• Lung disease (Group 3 PH): Screen for COPD, interstitial lung disease, or sleep-disordered breathing, though these typically cause milder PH 1
• Combined mechanisms: Some patients have both left heart disease AND another PH etiology 1, 6

Treatment Implications

Management must target the underlying left heart disease, NOT pulmonary arterial hypertension therapies: 1, 2

• Optimize guideline-directed medical therapy for heart failure with reduced ejection fraction (beta-blockers, ACE inhibitors/ARBs, mineralocorticoid receptor antagonists, SGLT2 inhibitors) 2
• Aggressive volume management with diuretics to reduce left ventricular filling pressures 1, 2
• Maintain sinus rhythm or control ventricular rate in AF 2
• Consider revascularization if viable ischemic myocardium exists 2

Critical Pitfall to Avoid

PAH-specific therapies (phosphodiesterase-5 inhibitors, endothelin receptor antagonists, prostacyclins) are contraindicated and potentially harmful in Group 2 PH. 1, 2 Randomized trials of riociguat, epoprostenol, and bosentan in PH-LHD were terminated early due to lack of efficacy or increased adverse events 1, 2

The only exception is enrollment in randomized controlled trials specifically designed for PH-LHD patients, particularly those with combined pre- and post-capillary PH (high diastolic pressure gradient or PVR) 1, 6