What causes elevated right heart pressures in patients with a history of cardiovascular disease or respiratory disease, such as chronic obstructive pulmonary disease (COPD) or left ventricular dysfunction?

Elevated Right Heart Pressures: Causes and Mechanisms

Elevated right heart pressures result from three primary mechanisms: increased pulmonary vascular resistance (most common in respiratory disease), elevated left-sided filling pressures transmitted backward through the pulmonary circulation, and high-output states that overwhelm the pulmonary vascular bed. 1

Primary Mechanisms by Disease Category

Pulmonary Vascular Disease (Precapillary Pulmonary Hypertension)

In patients with COPD and chronic respiratory disease, elevated right heart pressures develop through hypoxic pulmonary vasoconstriction, destruction of the pulmonary vascular bed from emphysematous changes, and extensive remodeling of all layers of the pulmonary arterial walls characterized by intimal thickening and proliferation of smooth muscle cells. 2, 3

• Hypoxic pulmonary vasoconstriction is a direct response to alveolar hypoxia that increases pulmonary vascular resistance 2
• Vascular remodeling decreases luminal cross-sectional area through intimal proliferation and deposition of elastic and collagen fibers 2
• Approximately 50% of patients with severe COPD develop pulmonary hypertension, though only 1-3% develop "out-of-proportion" severe pulmonary hypertension with significantly higher mortality 2
• These changes are minimally reversible with supplemental oxygen due to permanent structural remodeling 3

Left Heart Disease (Postcapillary Pulmonary Hypertension)

Left ventricular systolic or diastolic dysfunction, valvular disease, and elevated left atrial pressure are the most common causes of elevated pulmonary artery pressures in general cardiology populations, far exceeding true pulmonary vascular disease. 1

• About 22% of patients with mean pulmonary artery pressure 19-24 mm Hg and 78% with mean pulmonary artery pressure >25 mm Hg have elevated pulmonary capillary wedge pressures (>15 mm Hg) 1
• Left ventricular diastolic dysfunction increases with age and is independently associated with elevated pulmonary artery systolic pressure 1
• The transpulmonary gradient (mean pulmonary artery pressure minus wedge pressure) is NOT significantly elevated in patients whose pulmonary hypertension is due to left heart disease, distinguishing this from true pulmonary arterial hypertension 1

A critical subset of patients with left heart disease develops "out of proportion" pulmonary hypertension with pulmonary vascular resistance >3 Wood units and transpulmonary gradient >20 mm Hg, indicating superimposed pulmonary vascular disease. 1

High-Output States

Elevated pulmonary artery pressure occurs with high transpulmonary flow in exercise, anemia, pregnancy, sepsis, portopulmonary syndrome, and thyrotoxicosis, where the pulmonary vascular bed is anatomically normal and pulmonary hypertension resolves when cardiac output returns to normal. 1

Ventricular Interdependence and Right Ventricular Failure

As the right ventricle dilates from chronic pressure overload, it mechanically compresses the left ventricle through leftward shift of the interventricular septum, increasing left ventricular end-diastolic pressure, reducing left ventricular transmural filling pressure, and impairing left ventricular diastolic filling. 1, 2

• Ventricular interdependence is defined as forces directly transmitted from one ventricle to the other through the myocardium and pericardium 1, 2
• The right ventricle, anatomically designed to handle volume changes rather than pressure loads, has a thin wall compared to the left ventricle and cannot sustain chronic pressure overload without progressive dysfunction 1, 2
• When faced with increased pressure load, right ventricular stroke volume decreases significantly more than the left ventricle would under similar pressure increases 2

In COPD patients specifically, left ventricular diastolic dysfunction is present even with normal pulmonary artery pressure and worsens as right ventricular afterload increases. 4, 5

• The early filling velocity/late filling velocity (E/A) ratio is markedly decreased in COPD patients (0.79 vs 1.38 in controls), indicating left ventricular diastolic dysfunction 4
• Left ventricular isovolumic relaxation time is prolonged in COPD patients (125 ms vs 98 ms in controls) 5
• Both right and left ventricular dysfunction are present even in patients with mild airways obstruction, suggesting cardiac comorbidities commence early in COPD development 5

Progression of Right Ventricular Dysfunction

The progression follows a predictable sequence: initial compensatory phase with right ventricular hypertrophy → development of isovolumic phases of contraction and relaxation with increased right ventricular systolic pressure and higher end-diastolic volume → concomitant rise in pulmonary vascular resistance and right atrial pressure → declining cardiac output → reduction in pulmonary artery pressure despite persistently elevated pulmonary vascular resistance (an ominous clinical finding). 1, 2

Additional Contributing Factors in COPD

• Air trapping and dynamic hyperinflation increase right atrial pressure and further compromise cardiac function during exercise 2
• Right ventricular coronary perfusion is compromised by decreased perfusion pressure, elevated end-diastolic pressure, and potential subendocardial ischemia 2
• Chronic hypoxemia directly stimulates pulmonary vasoconstriction, increases ventilatory demand, and stimulates lactic acid production 2
• Erythrocytosis in chronic hypoxemic states increases effective pulmonary vascular resistance 2

Diagnostic Distinction: Passive vs. Precapillary Pulmonary Hypertension

Pulmonary vascular resistance distinguishes passive pulmonary hypertension (elevated mean pulmonary artery pressure, normal pulmonary vascular resistance) from pulmonary hypertension caused by pulmonary vascular disease (elevated mean pulmonary artery pressure, elevated pulmonary vascular resistance). 1

• Right heart catheterization with accurate assessment of pulmonary vascular resistance is required to confirm the diagnosis and define the hemodynamic profile, as echocardiographic estimates have limited precision 1
• Pulmonary arterial hypertension requires both mean pulmonary artery pressure >25 mm Hg AND pulmonary vascular resistance >3 Wood units after excluding lung disease, thromboembolic disease, left ventricular disease, or valve disease 1

Clinical Prevalence in Heart Failure

Progressive right heart failure increases in prevalence with more advanced left heart failure, occurring in approximately 48% of patients with heart failure with reduced ejection fraction, and is associated with 2.4-fold increased risk of mortality. 1

• Right ventricular dysfunction is more common in nonischemic dilated cardiomyopathy (65%) compared with ischemic cardiomyopathy (16%) 1
• Heart failure is extremely common in COPD patients independent of cor pulmonale, with prevalence ranging from 20-70% 2
• 40% of mechanically ventilated COPD patients with hypercapnic respiratory failure have evidence of left ventricular dysfunction 2