Chronic and End-Stage Heart Failure

, Marc J. Semigran2 and Marc J. Semigran3



(1)
Harvard Medical School Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

(2)
Harvard Medical School, Boston, USA

(3)
Heart Failure and Cardiac Transplant Program, Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

 



Introduction

Definition of HF

Causes of Chronic HF

Pathophysiology of Chronic HF (Fig. )

Evaluation of Chronic HF

Prognosis of Chronic HF

Management of Chronic HF

Advanced HF

References


Abstract

Chronic heart failure (HF) is a common manifestation of cardiovascular (CV) disease, affecting more than six million adults in the United States. Despite overall improvements in cardiovascular health, the incidence of HF has remained stable due to the aging of the population as well as improved survival following myocardial infarction (MI). Among patients over the age of 65, the incidence of HF is approximately 1 % annually. Major advances have occurred in the understanding of HF pathophysiology and treatment, leading to significant declines in HF-related mortality. However, it remains a cause of significant morbidity and mortality, resulting in more than one million hospitalizations and 50,000 deaths annually.


Abbreviations


ACE

Angiotensin-converting enzyme

ACEI

Angiotensin-converting enzyme inhibitor

AF

Atrial fibrillation

AHA

American Heart Association

ARB

Angiotensin-receptor blocker

BB

Beta-blocker

BMI

Body mass index

BNP

B-type natriuretic peptide

BTT

Bridge to transplantation

CAD

Coronary artery disease

cAMP

Cyclic adenosine monophosphate

CO

Cardiac output

CPET

Cardiopulmonary exercise test

Cr

Creatinine

CV

Cardiovascular

DT

Destination Therapy

HCM

Hypertrophic cardiomyopathy

HDZ

Hydralazine

HF

Heart failure

HFpEF

Heart failure with preserved ejection fraction

HFrEF

Heart failure with reduced ejection fraction

HTN

Hypertension

IABP

Intra-aortic balloon pump

ICD

Implantable cardiac defibrillator

ISDN

Isosorbide dinitrate

JVP

Jugular venous pressure

K

Potassium

LV

Left ventricular

LVAD

Left ventricular assist device

LVEF

Left ventricular ejection fraction

LVH

Left ventricular hypertrophy

MCS

Mechanical circulatory support

MI

Myocardial infarction

NIDCM

Nonischemic dilated cardiomyopathy

NYHA

New York Heart Association

PH

Pulmonary hypertension

PVR

Pulmonary vascular resistance

RHC

Right heart catheterization

RRR

Relative risk reduction

RV

Right ventricular

RVEF

Right ventricular ejection fraction

SCD

Sudden cardiac death

TPG

Transpulmonary gradient

TTE

Transthoracic echocardiogram

VO2

Peak oxygen consumption

WU

Woods Units



Introduction


Chronic heart failure (HF) is a common manifestation of cardiovascular (CV) disease, affecting more than six million adults in the United States [1]. Despite overall improvements in cardiovascular health, the incidence of HF has remained stable due to the aging of the population as well as improved survival following myocardial infarction (MI). Among patients over the age of 65, the incidence of HF is approximately 1 % annually [1]. Major advances have occurred in the understanding of HF pathophysiology and treatment, leading to significant declines in HF-related mortality [2]. However, it remains a cause of significant morbidity and mortality, resulting in more than one million hospitalizations and 50,000 deaths annually [1].

For more, see Chaps.​ 14 and 17.


Definition of HF






  • Inability of heart to pump enough blood to meet metabolic needs of tissues


  • Can be caused by inability of ventricle to fill, inability to pump or systemic process causing excess metabolic demand


  • Symptoms: poor exercise tolerance (fatigue or dyspnea)


  • Signs: evidence of fluid retention or poor perfusion


  • American Heart Association (AHA) Classification – based on disease progression and therapeutic strategy [3]



    • Stage A – patients at high risk for development of HF without evidence of structural heart disease or symptoms of HF


    • Stage B – patients with structural heart disease but without symptoms or signs of HF


    • Stage C – patients with structural heart disease and current or prior symptoms of HF


    • Stage D – patients with refractory HF requiring advanced therapies


  • New York Heart Association (NYHA) classification – based on symptoms



    • Class I – No limitation of ordinary physical activity


    • Class II – mild symptoms with ordinary physical activity


    • Class III – marked limitation of physical activity


    • Class IV – symptoms of HF at rest or with minimal physical activity


Causes of Chronic HF






  • Ischemic cardiomyopathy – coronary artery disease (CAD) most common cause of left ventricular (LV) systolic dysfunction in developed countries



    • MI → regional scar and loss of contractility → adverse remodeling of remaining segments → LV dilatation and dysfunction


    • If hibernating myocardium present, revascularization may improve LV function


  • Nonischemic dilated cardiomyopathy (NIDCM)



    • Idiopathic – up to 50 % of NIDCM [4]


    • Toxins – HF potentially reversible with removal of offending agent



      • Alcohol – direct toxic effect on cardiomyocytes


      • Cocaine – unclear pathophysiology, may include coronary vasospasm, direct myocardial toxicity


      • Medications (Anthracyclines, Trastuzumab, Cyclophosphamide)


    • Hypertension (HTN)



      • Initially causes concentric LV hypertrophy (LVH) but can eventually progress to dilated cardiomyopathy


    • Viral myocarditis



      • Myocardial injury caused by virus or autoimmune response to viral remnants


      • Initial infection may present acutely or may be silent


    • Other infectious causes



      • HIV – associated with high viral titers


      • Chagas Disease – prevalent in Central and South America


      • Lyme Disease – typically associated with conduction disturbances


    • Genetic



      • Familial dilated cardiomyopathy


      • LV non-compaction


      • Arrhythmogenic right ventricular cardiomyopathy


    • Tachycardia-induced cardiomyopathy



      • Can be due to atrial arrhythmias, ventricular arrhythmias (VAs) or premature ventricular contractions


      • Resolves with control of heart rate or elimination of arrhythmia


    • Peripartum Cardiomyopathy



      • Occurs in last month of pregnancy or within 5 months of delivery


      • LV function usually improves but high rate of recurrent LV dysfunction with subsequent pregnancies


    • Hypothyroidism


    • Obstructive sleep apnea


    • Uremia


  • HF with preserved Ejection Fraction (HFpEF)



    • LV ejection fraction (LVEF)  >50 % in approximately half of all HF patients [5]


    • Compared to patients with LV systolic dysfunction, HFpEF patients are more likely to be older, female, hypertensive, and have atrial fibrillation (AF) [6]


    • Similar survival to HF with reduced ejection fraction (HFrEF) – median survival of 2.1 years from diagnosis [5, 6]


    • Presence of diastolic dysfunction (by echo or invasive hemodynamics) required for diagnosis but pathophysiology complex


    • No treatments proven to prolong survival or decrease HF hospitalizations in HFpEF patients


  • Valvular heart disease



    • Any valvular lesion can cause HF symptoms in presence or absence of LV systolic dysfunction


  • Hypertrophic cardiomyopathy (HCM)



    • Inherited disorder associated with mutation of sarcomere genes


    • Present in 1/500 people with varying degrees of expression [7]


    • Results in marked ventricular hypertrophy, often asymmetric with predominant interventricular septal thickening



      • May also have mid-ventricular and apical hypertrophy variants


    • HF symptoms result from dynamic outflow tract obstruction, mitral regurgitation, diastolic dysfunction


    • First-line therapy are beta-blockers or calcium-channel blockers to reduce contractility and obstruction


    • Refractory symptoms may respond to surgical septal myectomy or alcohol septal ablation


  • Restrictive cardiomyopathy



    • Idiopathic restrictive cardiomyopathy


    • Infiltrative diseases



      • Sarcoidosis – usually presents with arrhythmias or sudden death


      • Amyloidosis – senile, familial, or associated with abnormal light chain production (AL amyloidosis)



        • Initially normal LV systolic function, with subsequent deterioration of LVEF


    • Storage diseases



      • Fabry’s Disease



        • X-linked genetic disorder


        • Deficiency of α-galactosidase A → lysosomal storage disease


        • Characterized by marked LVH – may be confused for HCM


        • Can be treated with enzyme replacement


      • Hemochromatosis



        • Inherited genetic order or secondary to large volume of blood transfusions


        • Characterized by myocardial deposition of iron


    • Endomyocardial fibrosis



      • Diffuse fibrosis of ventricular endocardium of unclear etiology


      • Most common worldwide cause of restrictive cardiomyopathy


      • Mostly found in Africa, Asia and South America


    • Radiation Therapy



      • Damages blood vessels → inflammation → myocardial fibrosis → decreased ventricular compliance


  • Right ventricular (RV) failure



    • Almost always associated with pulmonary hypertension (PH)


    • Final consequence of many congenital heart lesions, particularly in context of Eisenmenger syndrome (irreversible PH)


  • Constrictive Pericarditis



    • May be caused by:



      • Prior cardiac surgery


      • Radiation


      • Infections (Tuberculosis, bacterial, parasitic)


    • Resolves with surgical pericardiectomy


Pathophysiology of Chronic HF (Fig. 15-1)




A306999_1_En_15_Fig1_HTML.gif


Figure 15-1
A schematic representation of the pathophysiology of chronic heart failure due to impaired LV systolic function. The initiating event is an injury that leads to myocardial dysfunction. The body compensates for decreased cardiac output by activating multiple neurohormonal systems. In the acute phase, these mechanisms act to maintain adequate perfusion of systemic organs, but may also result in congestion and HF symptoms. Over time, these compensatory systems have adverse effects on the LV, stimulating further neurohormonal activation, worsening HF symptoms and ultimately leading to HF mortality. Counter-regulatory systems, including the natriuretic peptides, are upregulated to prevent the adverse effects of neurohormonal activation. Abbreviations: RAAS renin-angiotensin-aldosterone system, SNS sympathetic nervous system, ADH anti-diuretic hormone, BNP B-type natriuretic peptide, ANP atrial natriuretic peptide, NO nitric oxide, cGMP cyclic guanosine monophosphate, HF heart failure





  • Acute injury to myocardium causes decreased cardiac output (CO) and end-organ perfusion


  • Neurohormonal activation



    • Upregulation of renin–angiotensin–aldosterone system



      • Increased angiotensin II → systemic and renal arterial vasoconstriction


      • Increased aldosterone → renal sodium retention


    • Sympathetic nervous system activation



      • Release of catecholamines (e.g. norepinephrine)


      • Results in enhanced myocardial contractility and systemic vasoconstriction


      • Decreases distal water delivery in kidney due to reduction in glomerular filtration rate (GFR) → decreased excretion of water


    • Release of anti–diuretic hormone



      • Enhances reabsorption of water by renal collecting tubules


    • Ventricular remodeling



      • Type of remodeling depends on type of stress placed on ventricle


      • Pressure overload (e.g. aortic stenosis)



        • Concentric remodeling → LVH


        • Reduced wall stress via LaPlace’s Law (stress inversely proportional to wall thickness)


      • Volume overload (e.g. mitral regurgitation)



        • Eccentric remodeling → ventricular dilatation


        • Increased preload maintains cardiac output via Frank-Starling mechanism


      • Myocardial injury (e.g. MI)



        • Stretching of scarred tissue → mixed pressure and volume load on non-infarcted tissue


        • Ventricular dilatation → maintenance of cardiac output


      • Acute compensatory responses become deleterious over time



        • Progressive ventricular dilatation → increased wall stress (LaPlace: stress proportional to chamber radius)


        • Ongoing ventricular remodeling causes progressive HF


Evaluation of Chronic HF






  • Comprehensive history with focus on potential etiologies of cardiomyopathy



    • Detailed alcohol, drug, toxin exposure


    • Atherosclerotic risk factors, history of MI


    • Systemic systems indicative of extracardiac disease


    • Family history of HF, CAD or sudden cardiac death


  • Symptom assessment



    • Dyspnea most common symptom


    • NYHA Classification


    • Congestion (orthopnea, paroxysmal nocturnal dyspnea)


    • Low CO (fatigue, impaired cognition)


  • Physical Examination



    • Signs of congestion



      • Rales and/or pleural effusions on pulmonary exam – can be absent in long-standing HF despite elevated left-sided pressures


      • Elevated jugular venous pressure (JVP)


      • Positive hepatojugular reflex – sustained rise in JVP with compression of right upper quadrant of abdomen


      • Ascites


      • Lower extremity edema


    • Signs of low CO



      • Hypotension


      • Sinus tachycardia


      • Narrow pulse pressure


      • Cool extremities


      • Diminished pulses


    • Other findings



      • Displaced and enlarged point of maximal impulse


      • Third heart sound (S3)


      • RV heave


      • Prominent pulmonic component of second heart sound (P2)


      • Murmurs of functional mitral and tricuspid regurgitation


  • Diagnostic testing



    • Laboratory analyses



      • Basic metabolic panel, complete blood count, liver function tests, thyroid-stimulating hormone, urinalysis, hemoglobin A1C or fasting glucose


      • HIV test, iron studies (to screen for hemochromatosis) and sleep study should be considered in most patients


      • Further testing in selected patients depending on risk factors for specific etiologies of HF


    • ECG – arrhythmias, conduction disturbances, voltage (high or low), ectopy


    • Chest X-ray – cardiac chamber enlargement, pleural effusions, interstitial or pulmonary edema


    • Transthoracic echocardiogram (TTE)



      • LV and RV systolic function


      • Presence of scar or wall motion abnormalities – suggestive of CAD


      • Diastolic function of LV


      • Quantification of chamber dilation and ventricular hypertrophy


      • Identification of valvular abnormalities


      • Presence of pericardial effusion


    • Assessment for obstructive CAD with coronary angiography or noninvasive imaging in patients with CAD risk factors


    • Cardiopulmonary exercise testing (CPET) – measurement of peak oxygen uptake (VO2) provides assessment of relative contributions of cardiac disease and pulmonary disease to dyspnea as well as prognostic information


    • Endomyocardial biopsy not helpful in most cases unless specific diagnosis suspected that would alter management


    • Signal-averaged electrocardiogram not recommended in routine assessment


Prognosis of Chronic HF






  • Factors associated with worse prognosis in chronic HF include:



    • LVEF – 39 % increase in mortality for each 10 % drop in LVEF [8]


    • RV ejection fraction (RVEF) <35 % [9]


    • PH [10]


    • QRS length >120 ms [11]


    • VO2 <14 ml/kg/min [12]


    • Chronic kidney disease – patients with severe renal dysfunction have 2× risk of death at 1 year compared to patients with normal renal function [13]


    • B-type Natriuretic Peptide (BNP)/amino-terminal (NT)-proBNP – one of strongest independent predictors of prognosis [14]


    • Troponin levels [15]


  • Risk scores have been developed for patient stratification



    • Seattle Heart Failure Model



      • Incorporates clinical variables, medications and devices


      • Highly accurate prediction of survival out to 3 years in general HF population [16]


    • Heart Failure Survival Score [17]



      • Incorporates CAD, heart rate, LVEF, blood pressure, intraventricular conduction delay, serum sodium, peak VO2


      • Used to risk stratify NYHA Class III–IV patients being considered for transplantation


Management of Chronic HF




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Jul 13, 2016 | Posted by in CARDIOLOGY | Comments Off on Chronic and End-Stage Heart Failure

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