Pulmonary Hypertension Associated With Left Heart Disease: Characteristics, Emerging Concepts, and Treatment Strategies
Section snippets
Methodology
A search was performed in MEDLINE and PubMed for original articles published between 1950 and 2011 that focused on left-sided PH and heart failure (HF). The search term used included “secondary pulmonary hypertension,” “pulmonary hypertension,” “heart failure,” “post capillary pulmonary hypertension,” “pulmonary remodeling,” and “valvular heart disease.” The search was limited to articles in English and French. For this review, we chose selected articles that reflect recent development in the
Definition and classification of PH in LHD
The classification of PH has gone through a series of changes since the first classification was proposed in 1973 at an international conference on primary PH endorsed by the World Health Organization (WHO).3, 4 Pulmonary hypertension is classified into 5 groups according to the pathophysiology and hemodynamic characteristics of PH (Table 1). Pulmonary hypertension associated with LHD represents group II PH in the Dana Point classification (2008).3, 4 Decades ago, mitral valve disease was the
Pathogenesis of PH in LHD
The pathogenesis of PH in LHD is complex (Fig 3). In all cases, there is a passive component associated with increased left atrial pressure. In some patients, a superimposed active component caused by pulmonary arterial vasoconstriction and vascular remodeling may lead to a further increase in PAP.38, 39, 40, 41, 42
In patients with left HF, both diastolic dysfunction and mitral regurgitation may lead to an increase in left atrial pressure.41 While diastolic dysfunction is observed in patients
Epidemiology of PH in LHD
Pulmonary hypertension in LHD has been reported in specific patient populations with variable frequency, depending on the stage of the disease, the referral population, and the definition used.1, 2, 3, 4 Also, in echocardiographic-based studies, the reported prevalence of PH is limited to patients in whom RV systolic pressure (RVSP) can be estimated. Because patients with trace tricuspid regurgitation often have lower PAP, echocardiographic-based studies may overestimate the prevalence of PH.
In
Clinical significance
When present, PH is usually associated with a poor prognosis in patients with LHD. (Table 2, Table 3, Table 4).9, 10, 11, 12, 13, 14, 15, 17, 24, 39, 40, 71 Pulmonary hypertension is regarded as a good marker of prognosis as it incorporates information on diastolic function, mitral regurgitation and pulmonary vascular disease.
In most outcome studies in left HF, PH emerged as an independent prognostic factor. In the few studies that included RV function and diastolic parameters as covariates, PH
Diagnostic approach to PH
The first step in the workup of patients suspected of PH is a comprehensive clinical and physical examination.4 Patients with PH often presents with symptoms of dyspnea, decreased exercise tolerance, or signs of congestive right or left HF. Infrequently, patients may present with hemoptysis or palpitations. The initial steps of the workup include basic metabolic panel, a chest x-ray, and an echocardiogram and occasionally cardiopulmonary exercise testing (Fig 5). The echocardiogram allows
Managing PH associated with LHD
Although PH is a strong prognostic factor in patients with LHD, it remains to be established whether PH should be a target of therapy. Several studies have in fact shown that PH usually regresses after optimization of HF or corrective valvular heart surgery.5, 8, 74, 77, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101 This explains why optimizing HF regimens and corrective valve surgery represent the cornerstone of the treatment of PH with LHD. Targeting pulmonary vascular remodeling could,
Conclusion
Heart failure is the most common cause of PH. Important determinants of PH in HF include LV diastolic dysfunction and mitral regurgitation. Imbalance in the NO pathways and ET also contribute to the pathophysiology of left-sided PH. When present, PH is associated with worse prognosis in patients with LHD. Priority in the management of left-sided disease is treating the primary cause with either medical or surgical management. Sildenafil is currently being evaluated as a potential new therapy
Statement of Conflict of Interest
All authors declare that there are no conflicts of interest.
Acknowledgments
This project was funded by educational support from the Vera Moulton Wall Center for Pulmonary Vascular Disease at Stanford Hospital.
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Statement of Conflicts of Interest: see page 164.