Elsevier

Heart Failure Clinics

Volume 8, Issue 3, July 2012, Pages 447-459
Heart Failure Clinics

Pulmonary Hypertension Associated with Left-Sided Heart Disease

https://doi.org/10.1016/j.hfc.2012.04.009Get rights and content

Introduction

Pulmonary hypertension (PH) is characterized hemodynamically by significantly elevated pulmonary arterial pressure, which, if sustained, can result in clinical deterioration due to progressive right-sided heart failure and death. Elevated pulmonary arterial pressure that results from abnormalities localized to the precapillary pulmonary arterioles is referred to as pulmonary arterial hypertension (PAH). Abnormalities of the left side of the heart that raise left-sided filling pressure may cause pulmonary venous hypertension (PVH) resulting from passive congestion that resolves when pulmonary venous pressure is normalized. Long-standing PVH may induce abnormalities in pulmonary artery endothelial function and upregulation of neurohormones, cytokines, and other mediators leading to reactive vasoconstriction and, in certain instances, significant vascular remodeling such that pulmonary arterial pressure fails to decrease when pulmonary venous pressure is normalized. The classification scheme for PH was recently revised and provides a useful framework to identify the underlying disease process.1 In some cases, such as in sickle cell disease, PH may result from simultaneous primary abnormalities of both the pulmonary arteries and the left-sided heart disease.2

Section snippets

Left-sided heart failure as a cause of PH

PH may complicate heart failure from left ventricular systolic dysfunction (heart failure with reduced ejection fraction [HFrEF]), diastolic dysfunction (heart failure with preserved ejection fraction [HFpEF]), and valvular heart disease (World Health Organization [WHO] Group II). Recent estimates report a high prevalence of left-sided heart failure (LHF) in 1% to 2% of the population, most commonly occurring in patients older than 65 years.3 PH may occur in up to 60% of patients with severe

Significance of PH in left-sided heart failure

It is now well established that PH in patients with LHF is associated with increased mortality and morbidity, worse exercise tolerance, and adverse outcomes after heart transplantation. In an early study of 28 patients with ischemic or idiopathic dilated cardiomyopathy and an ejection fraction (EF) less than 20%, those with a tricuspid regurgitant jet velocity (TRV) greater than 2.5 m/s after 28 months of follow-up had a mortality rate of 57%, 40% higher than patients with a TRV of 2.5 m/s or

Pathophysiology

Although the nomenclature, hemodynamic definitions, and criteria are quite variable in the literature, patients with PH and LHF have postcapillary PH with elevated left-sided filling pressures. However, this group presents with differing hemodynamic profiles. In many patients with PH and LHF, elevation in pulmonary artery pressure (PAP) results from elevated left-sided filling pressure that is passively transmitted retrograde to the pulmonary arterial tree. The TPG and the PVR are within normal

Diagnostic approach

The prognosis and treatment of PH varies dramatically depending on the underlying etiology of the disease. Patients who have signs and symptoms suggestive of PH should undergo a screening echocardiography. If consistent with a diagnosis of PH, a systematic, comprehensive, and exhaustive search for the underlying etiology of PH should be undertaken as recommended in the recently updated ACC/AHA guidelines.1

Patients may present with clinical features suggestive of LHF, including orthopnea,

Treatment

Although multiple agents for PAH are now available, none are currently approved by the Food and Drug Administration (FDA) for the treatment of PH resulting from LHF. In this setting, the initial approach in all patients should be optimal and aggressive management of the underlying heart disease (see Fig. 2) based on current published guidelines.3 In many patients, PH is secondary to passive congestion, and correction of volume status, blood pressure, and valvular heart disease will lead to

Summary

PH associated with LHF is an increasingly recognized problem. It is clear that PH with LHF is associated with higher morbidity and mortality, worse exercise capacity, and adverse outcomes after heart transplantation. Hemodynamic derangements and activation of neurohormones, cytokines, and other mediators with endothelial dysfunction contribute to the development of mixed PH. In patients undergoing an evaluation for PH, a complete cardiac evaluation to exclude left-sided heart disease as a cause

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      Although both pulmonary arterial and venous remodeling may occur in pulmonary hypertension due to left heart disease in most instances, the majority of the pre-capillary component is functional in nature, as evidenced by the rapid reduction of pre-capillary parameters after left ventricular assist device implantation and LV unloading.34–36 This functional component may in part be mediated by elevated ET1 levels.37 This paradigm may be supported by our observation that increased ET1 levels are associated with smaller LV volumes and a higher LV ejection fraction.

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      In view of the growing prevalence, the vague syndrome in patients is associated with a worse diagnosis, leading to a higher mortality. And the treatment primarily focuses on vasodilators by reducing the blood pressure of pulmonary vessels, with limited clinical therapeutic effects [2]. It is reported that proliferation of endothelial or smooth muscle cell may be contributing to the progression of pulmonary hypertension.

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      The rationale to use PAH therapies in PH-LHD has been supported by acute or short-term studies using prostanoids, endothelin receptor antagonists, and PDE5 inhibitors. Most of these studies consistently reported improvements in hemodynamic status, exercise capacity, and symptoms (28). However, the methodology (small sample size, single-center, unclear or no randomization process) does not provide enough evidence to support the use of these drugs in clinical management of patients.

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    Disclosures: Research grants: Novartis; Speaker’s Bureau: Actelion, United Therapeutics; Consultant: Actelion, Gilead, United Therapeutics.

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