Pulmonary vascular mechanical consequences of ischemic heart failure and implications for right ventricular function

Area of Science:

• Cardiology
• Pulmonary Medicine
• Pathophysiology

Background:

• Left heart failure (LHF) is a primary driver of pulmonary hypertension (PH), significantly increasing patient morbidity and mortality.
• While pulmonary vascular resistance is a known prognostic factor in LHF, the detailed mechanical effects on the pulmonary vasculature and right ventricle (RV) remain poorly understood.

Purpose of the Study:

• To investigate the mechanical mechanisms underlying pulmonary vascular and RV dysfunction in a rodent model of LHF.
• To elucidate the pathophysiology of PH secondary to LHF with reduced ejection fraction.

Main Methods:

• LHF was induced in mice via left anterior descending artery ligation, creating myocardial infarction.
• Echocardiography and invasive hemodynamic measurements were used to assess cardiac function and pulmonary pressures.
• Ex vivo analyses evaluated pulmonary arterial elastance, perivascular fibrosis, and RV contractility.

Main Results:

• Post-myocardial infarction, mice developed sustained LHF with elevated left ventricular volumes and reduced ejection fraction.
• Pulmonary hypertension was confirmed by elevated RV systolic pressure, with increased pulmonary arterial elastance and vascular resistance.
• Perivascular fibrosis was observed, alongside significant RV contractile dysfunction, decreased RV end-systolic elastance, and impaired ventricular-vascular coupling.

Conclusions:

• In this LHF model, pulmonary fibrosis exacerbates RV afterload, while diminished RV contractility drives RV dysfunction.
• The findings highlight key pathological features of human PH secondary to LHF with reduced ejection fraction.
• This model provides a robust platform for testing novel therapeutic strategies targeting pulmonary vascular and RV dysfunction in LHF.