What is the relationship between pulmonary hypertension (PH) and heart failure (HF)?

From the Guidelines

Pulmonary hypertension secondary to left heart disease (PH-LHD) should be managed primarily by optimizing heart failure therapy, with a focus on reducing morbidity, mortality, and improving quality of life. For patients with PH-LHD, the primary approach is optimizing heart failure therapy with medications like ACE inhibitors (e.g., lisinopril 10-40mg daily), ARBs (e.g., losartan 25-100mg daily), beta-blockers (e.g., carvedilol 3.125-25mg twice daily), and diuretics (e.g., furosemide 20-80mg daily) 1. SGLT2 inhibitors (e.g., empagliflozin 10mg daily) should be added for patients with reduced ejection fraction.

Key Considerations

• The true prevalence of PH-LHD in heart failure remains unknown, mostly because the definition of PH in epidemiological studies has been based on echocardiography, with a variety of cut-off values 1.
• PH develops in LHD in response to a passive backward transmission of filling pressures, mainly driven by LV diastolic function, enhanced by exercise-induced mitral regurgitation and a loss of LA compliance 1.
• The definitions of PH and the difference between pre- and post-capillary PH are based on pressure cut-off, which explains why TPG, i.e. the difference between PAPm and PAWP, has been used to distinguish ‘passive’ PH (TPG <12 mmHg) from ‘reactive’ PH (TPG ⩾12 mmHg) 1.

Management Approach

• Optimizing heart failure therapy is the primary approach for managing PH-LHD, with a focus on reducing symptoms, improving exercise tolerance, and preventing disease progression 1.
• For pulmonary arterial hypertension (PAH), specific therapies include phosphodiesterase-5 inhibitors (e.g., sildenafil 20mg three times daily), endothelin receptor antagonists (e.g., bosentan 62.5-125mg twice daily), and prostacyclin analogs (e.g., epoprostenol IV infusion) 1.
• Combination therapy is often necessary for optimal results, and oxygen therapy should be provided to maintain saturation above 90% 1.
• Regular echocardiographic monitoring is essential to assess right ventricular function and pulmonary pressures, and patients should restrict sodium intake to less than 2g daily, limit fluid intake if needed, engage in supervised exercise rehabilitation, and receive vaccinations against influenza and pneumococcal disease to prevent respiratory infections that could worsen pulmonary hypertension 1.

From the FDA Drug Label

Sildenafil is an inhibitor of cGMP specific phosphodiesterase type-5 (PDE-5) in the smooth muscle of the pulmonary vasculature, where PDE-5 is responsible for degradation of cGMP. Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation In patients with PAH, this can lead to vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation. After chronic dosing of 80 mg TID sildenafil to patients with PAH, lesser reductions than above in systolic and diastolic blood pressures were observed (a decrease in both of 2 mmHg)

Pulmonary Hypertension and Heart Failure: Sildenafil can lead to vasodilation of the pulmonary vascular bed, which may be beneficial in patients with pulmonary arterial hypertension (PAH). However, the effect on heart failure is not directly addressed in the provided text.

• The drug label does mention the decrease in blood pressure in patients with PAH, but it does not provide information on the effect of sildenafil on heart failure. 2

From the Research

Pulmonary Hypertension and Heart Failure

• Pulmonary hypertension (PH) is a common feature of heart failure, affecting approximately 60% to 80% of patients with heart failure 3.
• PH due to left heart disease (LHD), also known as group 2 PH, is the most common reason for increased pressures in the pulmonary circuit 4.
• The pathophysiology of PH in heart failure involves a multistage hemodynamic evolution, including an initial passive increase in pulmonary artery pressure, followed by pulmonary vasoconstriction, endothelial dysfunction, and remodeling of the small-resistance pulmonary arteries 4.

Classification and Diagnosis

• PH is classified into 5 clinical subgroups: pulmonary arterial hypertension (PAH), PH due to left-sided heart disease, PH due to chronic lung disease, chronic thromboembolic PH (CTEPH), and PH with an unclear and/or multifactorial mechanisms 5.
• Diagnosis of PH involves routine tests such as electrocardiography, chest radiography, and pulmonary function tests, as well as transthoracic echocardiography to estimate the probability of PH 5.
• Right-sided heart catheterization is essential for accurate diagnosis and classification of PH 5.

Treatment and Management

• Management of PH resulting from left-sided heart disease primarily involves treatment of the underlying condition 5.
• Targeted treatments such as phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators, endothelin receptor antagonists, prostacyclin analogues, and prostacyclin receptor agonists are licensed for patients with PAH 5, 6, 7.
• Surgical pulmonary endarterectomy is the treatment of choice for eligible patients with CTEPH 5.
• Randomized clinical trials with interventions targeting heart failure patients with elevated pulmonary artery pressure are justified 3.