Pulmonary Hypertension, An Issue of Heart Failure Clinics Book

Editorial: Treatment of Heart Failure in Pulmonary Arterial Hypertension-The Urgency of Getting This Right Ragavendra R. Baliga James B.Young xiii

Preface: Pulmonary Hypertension Srinivas Murali Raymond L. Benza xxi

Classification of Pulmonary Hypertension Dana McGlothlin 301

Pulmonary hypertension (PH) can develop in association with many different diseases and risk factors, and its presence is nearly always associated with reduced survival. The prognosis and management of PH is largely dependent upon its underlying etiology and severity of disease. The combination of clinical and hemodynamic classifications of PH provides a framework for the diagnostic evaluation of PH to establish a final clinical diagnosis that guides therapy. As our understanding of the different pathologic mechanisms that underlie the syndrome of PH evolves, so too will the classification and treatment of PH.

Genetics and Pharmacogenomics in Pulmonary Arterial Hypertension Benjamin P. Smith D. Hunter Best C. Gregory Elliott 319

Pulmonary arterial hypertension (PAH) is an uncommon disease in the general population, but a disease with significant morbidity and mortality. The prevalence of heritable PAH (HPAH) remains unknown. The reason for incomplete penetrance of HPAH is not well understood. A patient's clinical response to disease-specific therapy is complex, involving the severity of the patient's disease, other comorbidities, appropriateness of the prescribed therapy, and patient compliance. Warfarin is often used as an adjuvant therapy in patients with PAH.

Diagnostic Dilemmas in Pulmonary Hypertension Robert P. Frantz Michael D. McGoon 331

Dilemmas persist in the screening, assessment, and follow-up of patients with pulmonary hypertension, relating to issues of whom and how to screen, how to resolve ambiguities in the clinical classification of patients with multiple potential substrates of pulmonary vascular disease, how to interpret test results, how to integrate multiple clinical parameters into a global diagnosis, how to use ambiguous test results, how to determine disease severity and prognosis, and how to monitor patients on treatment. This article describes how to incorporate available information into the diagnostic process, and where lack of concrete data should impose caution in patient management.

Imaging in the Evaluation of Pulmonary Artery Hemodynamics and Right Ventricular Structure and Function Asghar A. Fakhri Rachel A. Hughes-Doichev Robert W.W. Biederman Srinivas Murali 353

Among the many approaches for evaluating patients with pulmonary hypertension (PH), imaging plays a crucial role. The primary role of imaging is to identify the severity of PH based on noninvasive hemodynamic assessment and to evaluate right ventricular morphology and function. The major modalities used in current clinical practice for these purposes are echocardiography and cardiac magnetic resonance (CMP.) imaging. This review discusses the merits, limitations, and clinical utility of several echocardiographic and CMR techniques used in the evaluation of PH. It also includes a brief discussion of the role of computed tomography and radionuclide imaging.

Prognostication in Pulmonary Arterial Hypertension Richa Agarwal Mardi Gomberg-Maitland 373

Despite the advances in diagnostic and treatment strategies, and contemporary survival estimates suggesting improved outcomes, the prognosis of patients with pulmonary arterial hypertension (PAH) remains poor. To date, there is no consensus on which prognostic variables or risk prediction strategies best predict survival, at baseline and at different time points in the disease course. Even less clear is whether current prognostic variables accurately reflect disease severity and can sufficiently guide therapeutic decisions. This article reviews the most common factors used for prognostication in PAH, emphasizing that proper strategies for identifying patients at greatest risk are paramount.

Pharmacotherapy for Pulmonary Arterial Hypertension Gautam V. Ramani Myung H. Park 385

Pulmonary arterial hypertension (PAH) is a disabling, progressive disease. The past decade has seen an explosion in the available therapies for the management of PAH. Choosing appropriate pharmacotherapy can be a daunting task for the practitioner, as no head-to-head comparisons between drugs have been published. This article aims to assist the practitioner in developing an evidence-based, rational pharmacologic treatment algorithm for the management of patients with PAH. Currently approved pharmacotherapy and the pivotal trials that led to approval for the respective agents are reviewed. Common dilemmas in the treatment of PAH for which strong evidence is lacking are discussed.

Right Ventricular Remodeling in Pulmonary Hypertension Veronica Franco 403

The right ventricle (RV) is in charge of pumping blood to the lungs for oxygenation. Pulmonary arterial hypertension (PAH) is characterized by high pulmonary vascular resistance and vascular remodeling, which results in a striking increase in RV after-load and subsequent failure. There is still unexploited potential for therapies that directly target the RV with the aim of supporting and protecting the right side of the heart, striving to prolong survival in patients with PAH.

Pulmonary Arterial Hypertension in Connective Tissue Diseases Stephen C. Mathai Paul M. Hassoun 413

Pulmonary arterial hypertension (PAH) may complicate diverse connective tissue diseases (CTDs). Approximately 10% of patients with systemic sclerosis develop PAH, the prevalence being much lower in other CTDs. However, PAH is an important contributor to morbidity and mortality in all forms of CTD. Despite similarities in presentation, hemodynamic perturbations, and pathogenesis, patients with CTD-associated PAH (CTD-PAH) usually have a poorer response to PAH-specific medications and poorer prognosis than patients with idiopathic PAH (IPAH). Select patients with CTD-PAH may be candidates for lung transplantation, but results are less favorable t than for IPAH because of comorbidities and complications specifically associated with CTD.

Congenital Heart Disease and Pulmonary Hypertension Vedant Gupta Adriano R. Tonelli Richard A. Krasuski 427

Many patients with congenital heart disease and systemic-to-pulmonary shunts develop pulmonary arterial hypertension (PAH), particularly if the cardiac defect is left unrepaired. A persistent increase in pulmonary blood flow may lead to obstructive adenopathy and increased pulmonary vascular resistance, a condition that can lead to reversal of shunt and cyanosis (Elsenmenger syndrome). Cardiac catheterization is crucial to confirm diagnosis and facilitate treatment. Bosentan is the only medication to date to be compared with placebo in a randomized controlled trial specifically targeting congenital heart disease-associated PAH. Lung transplantation with repair of the cardiac defect or combined heart-lung transplantation is reserved for recalcitrant cases.

Pulmonary Hypertension Associated with Left-Sided Heart Disease Christopher F. Barnett Teresa De Marco 447

Pulmonary hypertension (PH) is characterized hemodynamically by significantly elevated pulmonary artery pressure, which if sustained can result in clinical deterioration due to progressive right-sided heart failure and death. Establishing the etiology of PH in a patient before treatment is imperative. Effective evidence-based therapeutic agents for treating PH have been developed. However, appropriately powered, randomized trials in PH associated with left-sided heart failure are sparse, and those that have been performed have shown no benefit or harm. An improved understanding of the pathophysiology, definition, and development of new therapies for treating PH associated with left-sided heart failure is urgently needed.

Pulmonary Hypertension in Parenchymal Lung Disease Rosechelle M. Ruggiero Sonja Bartolome Fernando Torres 461

The pathophysiology of pulmonary hypertension (PH) in parenchymal lung diseases is partially related to hypoxic pulmonary vasoconstriction. PH treatment is controversial for these patients. This article focuses on group III PH, namely PH attributable to lung diseases and/or hypoxia. Group III includes chronic obstructive pulmonary disease and interstitial lung diseases, the most common parenchymal lung diseases associated with PH. It also includes sleep-disordered breathing and hypoventilation from any cause. Other parenchymal lung diseases associated with PH, namely sarcoidosis and systemic vasculitides (group V), are discussed. The data describing PH in specific parenchymal diseases are reviewed.

Chronic Thromboembolic Pulmonary Hypertension Robert J. Moraca Manreet Kanwar 475

Chronic thromboembolic pulmonary hypertension (CTEPH) is a potentially life-threatening condition characterized by obstruction of pulmonary arterial vasculature by acute or recurrent thromboemboli with subsequent organization, leading to progressive pulmonary hypertension and right heart failure. Until relatively recently, CTEPH was a diagnosis made primarily at autopsy, but advances made in diagnostic modalities and suraical pulmonary endarterectomv techniaues have made this disease treatable and even potentially curable. Although published guidelines are available, in the absence of randomized controlled trials regarding CTEPH there is a lack of standardization, and treatment options have to be individualized.

Exercise-Induced Pulmonary Hypertension Eduardo Bossone Robert Naeije 485

Exercise stress tests of the pulmonary circulation show promise for the detection of early or latent pulmonary vascular disease and may help us understand the clinical evolution and effects of treatments in patients with established disease. Exercise stresses the pulmonary circulation through increases in cardiac output and left atrial pressure. Recent studies have shown that exercise-induced increase in pulmonary artery pressure is associated with dyspnea-fatigue symptomatology, validating the notion of exercise-induced pulmonary hypertension. Exercise in established pulmonary hypertension has no diagnostic relevance, but may help in the understanding of changes in functional state and the effects of therapies.

Index 497