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Contents Foreward: Comorbid Conditions in Heart Failure: An Unhappy Marriage ix Mandeep R. Mehra and Javed Butler Preface xi Faiez Zannad and Hector O. Ventura Erratum xiii Arterial Hypertension in Patients with Heart Failure 233 Javier Díez Hypertensive heart disease (HHD) has been considered the adaptive hypertro- phy of the left ventricle wall to increased blood pressure. Recent findings in hypertensive animals and patients now challenge this paradigm by showing that HHD also results from pathologic structural remodeling of the myocardium in response to hemodynamic and nonhemodynamic factors that are altered in arterial hypertension. The possibility that hypertensive patients predisposed to develop heart failure may be detected before the appearance of clinical manifes- tations provides a new way to prevent this major arterial complication. Sleep-Disordered Breathing in Patients with Heart Failure 243 Robert J. Mentz and Mona Fiuzat Sleep-disordered breathing (SDB) is prevalent in patients with heart failure, and is associated with increased morbidity and mortality. SDB is proinflammatory, with nocturnal oxygen desaturations and hypercapnia appearing to play a pivotal role in the development of oxidative stress and sympathetic activation. Preliminary data suggest that attention to the diagnosis and management of SDB in patients with heart failure may improve outcomes. Ongoing research into the roles of comorbidities such as SDB as a treatment target may lead to better clinical outcomes and improved quality of life for patients with heart failure. Cardiorenal Syndrome 251 Claudio Ronco and Luca Di Lullo Cardiorenal syndrome (CRS) includes a broad spectrum of diseases within which both the heart and kidneys are involved, acutely or chronically. An effec- tive classification of CRS in 2008 essentially divides CRS in two main groups, cardiorenal and renocardiac CRS, based on primum movens of disease (cardiac or renal); both cardiorenal and renocardiac CRS are then divided into acute and chronic, according to onset of disease. The fifth type of CRS integrates all cardiorenal involvement induced by systemic disease. This article addresses the pathophysiology, diagnosis, treatment, and outcomes of the 5 distinct types of CRS. Co-morbidities in Heart Failure

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Co-morbidities in Heart Failure

Contents

Foreward: Comorbid Conditions in Heart Failure: An Unhappy Marriage ix

Mandeep R. Mehra and Javed Butler

Preface xi

Faiez Zannad and Hector O. Ventura

Erratum xiii

Arterial Hypertension in Patients with Heart Failure 233

Javier Díez

Hypertensive heart disease (HHD) has been considered the adaptive hypertro-phy of the left ventricle wall to increased blood pressure. Recent findings inhypertensive animals and patients now challenge this paradigm by showingthat HHD also results from pathologic structural remodeling of the myocardiumin response to hemodynamic and nonhemodynamic factors that are altered inarterial hypertension. The possibility that hypertensive patients predisposed todevelop heart failure may be detected before the appearance of clinical manifes-tations provides a new way to prevent this major arterial complication.

Sleep-Disordered Breathing in Patients with Heart Failure 243

Robert J. Mentz and Mona Fiuzat

Sleep-disordered breathing (SDB) is prevalent in patients with heart failure, andis associated with increased morbidity and mortality. SDB is proinflammatory,with nocturnal oxygen desaturations and hypercapnia appearing to play apivotal role in the development of oxidative stress and sympathetic activation.Preliminary data suggest that attention to the diagnosis and management ofSDB in patients with heart failure may improve outcomes. Ongoing researchinto the roles of comorbidities such as SDB as a treatment target may lead tobetter clinical outcomes and improved quality of life for patients with heartfailure.

Cardiorenal Syndrome 251

Claudio Ronco and Luca Di Lullo

Cardiorenal syndrome (CRS) includes a broad spectrum of diseases withinwhich both the heart and kidneys are involved, acutely or chronically. An effec-tive classification of CRS in 2008 essentially divides CRS in two main groups,cardiorenal and renocardiac CRS, based on primum movens of disease (cardiacor renal); both cardiorenal and renocardiac CRS are then divided into acute andchronic, according to onset of disease. The fifth type of CRS integrates allcardiorenal involvement induced by systemic disease. This article addressesthe pathophysiology, diagnosis, treatment, and outcomes of the 5 distinct typesof CRS.

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Anemia and Iron Deficiency in Heart Failure 281

Natasha P. Arora and Jalal K. Ghali

Anemia is a common comorbidity in patients with heart failure (HF) and is asso-ciated with poor prognosis. Iron deficiency, with or without anemia, confersincreased risk of mortality and morbidity. Along with the altered iron metabolismin HF patients, inflammation creates challenges in the interpretation of laboratoryparameters used to diagnose anemia in HF. Since the RED-HF trial failed to dem-onstrate any benefit from the use of erythropoiesis-stimulating agents (ESAs) onmortality or morbidity in HF patients, ESAs are no longer considered a treatmentoption, although intravenous iron has potential as therapy for anemic and nonane-mic HF patients.

Heart Failure and Depression 295

Amy Newhouse and Wei Jiang

Depression frequently accompanies heart failure and has been linked with increasedmorbidity and mortality. Patients with heart failure who have depression have moresomatic symptoms, hospitalizations, increased financial burden, and poorer qualityof life. Furthermore, depression has been shown to be an independent predictor offuture cardiac events in patients with heart failure, regardless of disease severity,making it worthwhile to consider among other cardiac risk factors, such as diabetesand smoking. This article summarizes the trials assessing the treatment of depres-sion in heart failure and provides an algorithm for approaching these patients.

Atrial Fibrillation and Congestive Heart Failure 305

Sudarone Thihalolipavan and Daniel P. Morin

Heart failure (HF) and atrial fibrillation (AF) commonly coexist and adversely affectmortality when found together. AF begets HF and HF begets AF. Rhythm restorationwith antiarrhythmic drugs failed to show a mortality benefit but can be effective inimproving symptoms. Nonpharmacologic treatment of AF may be of value in theHF population.

Obesity Paradox, Cachexia, Frailty, and Heart Failure 319

Carl J. Lavie, Alban De Schutter, Martin A. Alpert, Mandeep R. Mehra, Richard V. Milani,and Hector O. Ventura

Overweight and obesity adversely affect cardiovascular (CV) risk factors and CVstructure and function, and lead to a marked increase in the risk of developing heartfailure (HF). Despite this, an obesity paradox exists, wherein those who are over-weight and obese with HF have a better prognosis than their leaner counterparts,and the underweight, frail, and cachectic have a particularly poor prognosis. In lightof this, the potential benefits of exercise training and efforts to improve cardiorespi-ratory fitness, as well as the potential for weight reduction, especially in severelyobese patients with HF, are discussed.

The Impact of Peripheral Arterial Disease on Patients with Congestive Heart Failure 327

Amit N. Keswani and Christopher J. White

Congestive heart failure (CHF) is a prevalent disease with many comorbidities and isassociated with high health care expenditures. Peripheral arterial disease (PAD) is

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a known comorbidity of CHF and is associated with worse morbidity and mortality.CHF and PAD share risk factors, pathophysiology, treatment strategies, andprognostic features. We review the impact of PAD on patients with CHF using sev-eral studies to support PAD’s influence on outcomes in CHF. Based on the evidenceand current guidelines, patients with heart failure who are smokers, and those whohave known coronary artery disease and/or diabetes should be screened for PAD.

Cardiovascular Comorbidity in Rheumatic Diseases: A Focus on Heart Failure 339

Kerry Wright, Cynthia S. Crowson, and Sherine E. Gabriel

Rheumatic diseases are associated with an increased risk of cardiovascular (CV)mortality attributed to a higher incidence of heart failure (HF) and ischemic heartdisease. Although traditional CV risk factors contribute to the increased incidenceseen in this population, by themselves they do not account for the increased risk;in fact, obesity and hyperlipidemia may play a paradoxic role. Immune-mediatedmechanisms and chronic inflammation likely play a role in the pathogenesis of CVdisease in patients with rheumatic diseases. The usual clinical features of ischemicheart disease and HF are less likely to be seen in this patient population.

The Role of Coronary Artery Disease in Heart Failure 353

Anuradha Lala and Akshay S. Desai

Enhanced survival following acute myocardial infarction and the declining pre-valence of hypertension and valvular heart disease as contributors to incidentheart failure (HF) have fueled the emergence of coronary artery disease (CAD) asthe primary risk factor for HF development. Despite the acknowledged role ofCAD in the development of HF, the role of coronary revascularization in reducingHF-associated morbidity and mortality remains controversial. The authors reviewkey features of the epidemiology and pathophysiology of CAD in patients with HFas well as the emerging data from recent clinical trials that inform the modernapproach to management.

Comorbidities and Polypharmacy 367

Thomas G. von Lueder and Dan Atar

Heart failure (HF) is predominantly a disease that affects the elderly population,a cohort in which comorbidities are common. The majority of comorbidities andthe degree of their severity have prognostic implications in HF. Polypharmacy inHF is common, has increased throughout the past 2 decades, and may posea risk for adverse drug interactions, accidental overdosing, or medication nonadher-ence. Polypharmacy, in particular in the elderly, is rarely assessed in traditional clin-ical trials, highlighting a need for entirely novel HF research strategies.

Index 373