3. Becoming and increasingly common as the US populations ages and survival rates after acute MI increase. 5. Furthermore, heart failure is a progressive condition: once symptoms appear, subsequent morbidity and mortality are high. 5- year survival rates are estimated to be 59% in men and 45% in women.
Basic pathopysiology makes treatment principles easier to understand The capacity of the heart to adapt to short-term changes in preload or afterload is remarkable, but sudden or sustained changes in the preload (acute mitral regurg, excessive Iv hydration) or afterload (aortic stenosis, severe uncontrolled hypertension) or demand (from severe anemia, or hyperthyroidism) may lead to progressive failure of myocardial function. Asymptomatic dysfunction progresses steadily to overt heart failure. The mechanism by which this occurs are neurohumoral adaptations which are “double-edged swords” great in the acute setting and harmful in the long term setting. Although they are useful because they maintain arterial perfusion pressure in the face of a reduction in cardiac output, they increase the hemodynamic burden and oxygen requirements of the failing ventricle. The signs and symptoms of heart failure (HF) are due in part to compensatory mechanisms utilized by the body in an attempt to adjust for a primary deficit in cardiac output. Neurohumoral adaptations , such as activation of the renin-angiotensin-aldosterone and sympathetic nervous systems by the low output state, can contribute to maintenance of perfusion of vital organs in several ways ….
Neurohumoral adaptations help by maintenance of perfusion of the vital organs by: Maintenance of systemic pressure by vasoconstriction, resulting in redistribution of blood flow to vital organs Restoration of cardiac output by increasing myocardial contractility and heart rate and by expansion of the extracellular fluid volume
FIRST, the response to a decrease in cardiac output…….is that the Decreased perfusion pressure sensed by carotid sinus and aortic arch receptors results in increased sympathetic and decreased parasympathetic tone, and 2. also enhance release of ADH and stimulation of thirst. Circulating catecholamines are elevated (like norepinephrine), and direct sympathetic outflow to the heart, peripheral vasculature, and muscles is increased. Short-term consequences include 1. increased contractility and heart rate to augment cardiac output, systemic vasoconstriction to increase preload and maintain blood pressure, and redistribution of blood flow away from the skin, muscles, and kidneys to vital organs The long-term cardiovascular effects of sympathetic activation, however, are deleterious.These include myocyte necrosis and apoptosis (cell suicide), and interstitial fibrosis causing further impairment in systolic and diastolic function; cardiac norepinephrine depletion and beta-receptor down-regulation, resulting in inotropic (contractility) and chronotropic (rate or timing) incompetence; calcium overload and proarrhythmia; With this response and the response to decreased cardiac output lead to the activation of the renin-angiotensin-aldosterone system.
When cardiac output declines the RAAS is activated. Increased concentrations of circulating angiotensin II and albdosterone are both increased, the former contributing to excess vasoconstriction and the latter to the retention of salt and water. The combination of decreased water excretion and increased water intake via thirst often leads to a fall in the plasma sodium concentration. The severity of these defects tends to parallel the severity of the heart failure. As a result, the degree of hyponatremia is an important predictor of survival.
However, if the neruohumoral response continues maladaptive changes occur. The elevation in diastolic pressures is transmitted to the atria and to the pulmonary and systemic venous circulations; the ensuing elevation in capillary pressures promotes the development of pulmonary congestion and peripheral edema 2. The increase in left ventricular afterload induced by the rise in peripheral resistance can both directly depress cardiac function and enhance the rate of deterioration of myocardial function (show figure 2)  3. Catecholamine-stimulated contractility and increased heart rate can worsen coronary ischemia 4. Catecholamines and angiotensin II may promote the loss of myocytes by apoptosis, the induction of maladaptive fetal isoforms of proteins involved in contraction, and hypertrophy (see below) 5. If chronic, neurohumoral activation may lead to decompensation due to excessive vasoconstriction and volume retention, electrolyte abnormalities, direct myocardial toxicity, and cardiac arrhythmias. The relative importance of these beneficial and detrimental effects is not fully defined. However, the slowing of disease progression and improvement in survival observed with angiotensin converting enzyme (ACE) inhibitors and beta blockers in patients with heart failure due to systolic dysfunction suggest that there is, over time, a net negative effect of the neurohumoral adaptations on ventricular function SUMMARY — In the short term, neurohumoral activation is beneficial in patients with HF since the elevations in cardiac contractility and vascular resistance and renal sodium retention tend to restore the cardiac output and tissue perfusion toward normal. However, the deleterious effects may predominate over the long-term, leading to pulmonary and peripheral edema, increased afterload, pathologic myocardial remodeling, and more rapid progression of myocardial dysfunction. The ability of ACE inhibitors and beta blockers to improve survival and slow the progression of the heart failure is compatible with this hypothesis.
Systolic and Diastolic Dysfunction Diastolic dysfunction caused by compromise myocardial relaxation in the presence of myocardial contractility and ejection fraction. One third to one half of patients with heart failure have normal ventricular contractile function, and are said to have diastolic heart failure. Abnormal diastolic function may be due to impaired early relaxation, increased stiffness of the ventricle, or both. Diastolic dysfunction results in impairment in ventricular filling. LV end-diastolic pressures are elevated, leading to pulmonary venous congestion. Diastolic dysfunction is most commonly associated with left ventricular hypertrophy (LVH) due to hypertension, and occurs frequently in elderly women. Increased resistance to filling results from the increased LV mass itself, and also from interstitial fibrosis and subendocardial ischemia. Diastolic dysfunction can occur in the absence of LVH due to ischemia, myocardial infiltration (e.g., amyloidosis), or pericardial constriction. Systolic Heart Failure Most commonly, heart failure reflects an abnormality of ventricular contractile function. End-systolic volume, end-diastolic volume, and end-diastolic pressure are increased, and stroke volume falls. Symptoms of reduced cardiac output (e.g., fatigue) develop. In addition, increased LV end-diastolic pressure is transmitted back to the pulmonary veins, resulting in transudation of fluid into the pulmonary interstitium and symptoms of pulmonary congestion. The most common cause of contractile dysfunction is loss of myocytes due to myocardial infarction. Other causes of systolic heart failure include dilated cardiomyopathy, myocarditis, and chronic alcohol use. The most common form of heart failure , that due to coronary artery disease, often reflects a combination of systolic and diastolic dysfunction. Systolic dysfunction is due to prior infarction and ischemia-induced decrease in contractility. Diastolic dysfunction is due to chronic replacement fibrosis and ischemia-induced decrease in distensibility.
High output Failure- occurs when the demand for blood exceeds the capacity of an otherwise normal heart to meet the demand Low cardiac output- fatigue and loss of lean muscle mass as their most prominent symptoms, may also have dsypnea, impaired renal function or altered mental status Although the symptoms, causes, prevalence and epidemiology of the six different types are somewhat different the is substantial overlap, and type may coexist. Therefore, this review present an approach to diagnosis that is appropriate regardless of the type or cause of heart failure.
Labs Basic chemistry, CBC, TSH BNP to support dx, assess decompensation, measure response to therapy Other labs as directed by hx (i.e iron studies)
Rigorous Criteria for identifying heart failure based on clinical history and physical findings were developed for the Framingham study. However, heart failure may not be recognized in up to 40% of patients due to the limited reliability of these findings.
A normal chest radiograph slightly decrease the probability of heart failure and helps identify pulmonary causes of dyspnea. A normal EKG makes heart failure less likely as well. If both ekg and chest x-ray are normal heart failure is unlikely and your differential should broaden. Chest x-ray should look for cardiomegaly, pulmonary vascular congestion. Early radiologic signs of pulmonary venous hypertension and interstitial edema include distension of the pulmonary veins extending upward from the hila, haziness of hilar shadow and thickening of the interlobular septae (Kelye’s B Lines) Therefore, patients with dyspnea and suggestive abnormalities on the ekg and cxr should undergo ECHO Hyponatremia (increased vasopressin levels) in addition to sodium restriction , diuretic therapy and expansion of extracellular volume. It is a negative prognostic indicator at the time of hospital admission, and predicts decreased long-term survival BNP Β NP is a 32-amino acid polypeptide secreted from the cardiac ventricles in response to ventricular volume expansion and pressure overload. The major source of BNP is the cardiac ventricles, and because of its minimal presence in storage granules, its release is directly proportional to ventricular dysfunction. It is a simple and rapid test that reliably predicts the prescience or absence
Slide ID: 7753 The American College of Cardiology/American Heart Association (ACC/AHA) writing committee decided to take a new approach to the classification of heart failure – one that emphasized the evolution and progression of the disease. Only Stages C and D qualify for the traditional clinical diagnosis of heart failure. This classification is intended to complement, but not replace, the New York Heart Association (NYHA) Functional Classification. ACC/AHA Heart Failure Stage Stage A: patients who are at high risk for developing heart failure but have no structural disorder of the heart. Stage B: patients with structural disorders of the heart who have never had symptoms of heart failure. Stage C: patients with past or current symptoms of heart failure associated with underlying structural heart disease. Stage D: patients with end-stage disease who require specialized treatment strategies such as mechanical circulatory support, continuous IV inotrope infusions, cardiac transplantation, or hospice care. NYHA Functional Classification Assigns patients to 1 of 4 functional classes depending on the degree of effort needed to elicit symptoms. Patients with very low LV ejection fractions may be asymptomatic, whereas patients with preserved LV systolic function may have many symptoms. The apparent discordance between severity of systolic dysfunction and the degree of functional impairment is not well understood. Class I: symptoms of heart failure only at levels that would limit normal individuals (asymptomatic). Class II: symptoms of heart failure on ordinary exertion. Class III: symptoms of heart failure on less-than-ordinary exertion. Class IV: symptoms of heart failure at rest. References Hunt SA et al. J Am Coll Cardiol . 2001;38:2101-2113. Farrell MH et al. JAMA . 2002;287:290-297.
Reduction in combined end points of death and hospitalization by heart failure (numbers needed to treat+11) over 4-5 years regarless of severity but favor more severe cases. Good tolerability with major side effects being cough, angioedema, altered taste, hyperkalemia, and dizziness Hypotension and lightheadedness are common side effects of ACE-I particularly in patients with marked activation of the RAS. Hold diuretic and then start ACE-I and titrate slowly Collaborative Group on ACE inhibitor Trials CONSENSUS Trial Study Group SOLVD Investigators
Consensus- COOPERATIVE NORTH SCANDINAVIAN ENALAPRIL SURVIVAL STUDY pt were already taking digoxin and diuretics. Subsequent SOLVD- STUDIES OF LEFT VENTRICULAR DYSFUNCTION- Proved consensus at a earlier stage of heart failure even asymptomatic
ARBs are comparable to ACE-I in reduction all-cause mortality and heart failure-related hospitalizations in patients with NYHA classes II and III heart failure.
Adding an ARB to ACE-inhibitor therapy provides further mortality benfit in slected patients. In this trial of patients with NYHA classes II to IV heart failure, candesartan added to existing ACE-I therapy reduced cardiovasular death (NNT, 28 over 3.5 years) and reduced heart-failure related hospital admission. A second study found no benefit
POTENTIAL CONCERNS REGARDING INITIATION OF β BLOCKERS BEFORE DISCHARGE The 1999 guidelines of the Heart Failure Society of America suggested that, to maximize safety, there should be a period of clinical stability while on standard therapy before instituting β blockers and that initiation in patients who have HF requires a careful baseline evaluation of clinical status. 26 Because it is based on early, large-scale trials in which patients who had chronic HF were treated with standard therapy consisting of ACE inhibitors, digoxin, and a diuretic for ≥2 months before starting β-blocker therapy, this recommendation led to many HF clinicians postponing β-blocker therapy for ≥2 to 4 weeks until stability had been achieved. This plays into the concern many practitioners have that beginning β blockade in patients who have HF will necessarily worsen HF during the titration period. In the Randomized Evaluation of Strategies for Left Ventricular Dysfunction, there was a significantly larger number of hospitalizations for worsening HF with controlled-release metoprolol than with placebo (p = 0.026). However, there was also a 54% lower risk of death with controlled-release metoprolol (p = 0.057) and a significant increase in LV ejection fraction (p = 0.001). 2 , 27 In the COPERNICUS study, there were significantly fewer patients who used carvedilol and then developed serious adverse events than those who used placebo (p <0.002). 10 This trial showed that the adverse event of utmost concern to clinicians regarding the initiation of β blockers, i.e., worsening HF, occurred less frequently with carvedilol than with placebo. 10 , 28 The COPERNICUS, in effect, indicated that the early initiation of life-saving therapies should be approached with a sense of urgency and provides a mandate for expediting the administration of β-blocker therapy in patients who have HF. After comparing initiation before and after discharge with respect to tolerability and safety in the IMPACT-HF study, it was found that there were no significant differences between groups in the occurrence of serious adverse events (bradycardia, hypotension, and worsening HF) or the occurrence of these events leading to the permanent withdrawal of the β blocker. Fewer patients developed worsening of HF before than after discharge (0.5% vs 1.7%), and there was a lower composite rate of death and rehospitalization. 25 These major trials clearly refute the common practices and perceptions regarding β-blocker therapy for HF that lead to unnecessary delays in treatment and deny patients established benefits of this therapy. Specifically, the results of these studies challenge the beliefs commonly held by many clinicians that initiation of β blockade is characterized by an unfavorable benefit/risk ratio, that survival curves do not diverge in favor of β blockers for many months, and that early initiation necessarily carries the risk of worsening HF or intolerance that leads to withdrawal of treatment. Rather, these studies clearly demonstrate the high degree of tolerability for β blockers and that there is a lower relative rate of discontinuation with β blockers than with placebo. Several β blockers, e.g., atenolol, timolol, and propranolol, have proven efficacy as secondary prevention after myocardial infarction but not as therapy for HF. Among those agents that have established efficacy in HF, e.g., carvedilol, bisoprolol, and metoprolol, there are pharmacologic differences that may alter the clinical responses to these agents in HF 24 and may have an affect on in-hospital initiation of therapy. The β-1–specific blockers may decrease cardiac output, increase vascular resistance, or decrease renal blood flow, all of which can contribute to worsening HF. 30 The β blockers with an α blockade, such as carvedilol, increase cardiac output and decrease vascular resistance. The vasodilatory activity due to α-1 blockade offsets myocardial depression due to β blockade, and the broad-based sympathetic antagonism may protect the patient against worsening HF in the early stages of initiation. 30 In the MERIT-HF trial of patients who had HF of New York Heart Association classes III and IV, a decrease in the mortality rate was observed with the use of metoprolol, a β-1–specific blocker; however, the metoprolol-treated group had a higher rate (8.1%) of withdrawal in the first 90 days than did the placebo-treated group (5.9%). 31 Data from COPERNICUS trial showed that the carvedilol-treated group had a lower rate of worsening HF (5.1%) than did the placebo group (6.4%) during the initiation phase. 25 In the IMPACT-HF study, only 0.5% of patients withdrew due to worsening HF if they had been initiated with carvedilol before discharge versus 1.7% of patients who had been initiated with a β blocker of the physician's choice after discharge. 25 Therefore, these considerations may make carvedilol a better agent for initiating β-blocker therapy in the hospital setting.
6 RCT’s that included more than 9,000 patients already taking ACE-I showed a significant reduction in total mortality and sudden dearth (NNT 24, and #% over 1-2 years) Carvedilol or Metoprolol European Trial 2003 In a recent trial , patient with NYHA classes II to IV heart failure who were treated with carvedilol had greater reductions in mortality (NNT, 18 over 5 years) and cardiovascular mortality (NNT, 16 over five years) than those treated with metoprolol but, hypotension was more common among the carvedilol group (14 versus 11 percent) Bisoprolol and metoprolol are b1-selective with no vasodilating properties Coreg- is alpha 1 beta 1 and beta 2 with vasoldilating properties
Add aldactone in moderate to severe heart failure, favorable effects on LV remodeling Randomized Aldactone RALES-survival benefit of spironolactone in patient with severe heart failure and favorable effexts on LV remodeling Most common risk is hyperkalemia and 10 % of men will experinece breast pain an gynecomastia Eplerenone-newer more selective aldosterone inhibitor has been shown to reduce all-cause mortality following myocardial infraction with Left ventricular dysfunction (NNT, 43 for 16 months) Has not yet been studied in patient with CHF who have not yet had a MI
Some studies report a decease in all cause morality of 28% and a more recent trial with enlaptirl showed no difference but over 30% dropped out due to side effects. Side effects are flushing, headaches, gi upset, less frequently can cause positive ANA titers and lupus-like syndrome
Vasodilator combination that improves endothelial function by increasing NO levels A-HeFT (Taylor AI et al. N Engl J Med 2004;351:2049-57): 1050 African American patients with primarily NYHA Class III sx Randomized to standard therapy vs. standard therapy plus hydralazine and isosorbide dinitrate Significant decrease in morbidity and mortality with additional treatment Most frequent adverse effects: HA, dizziness
Patients taking digoxin are less lekely to be hospitalized for worseing heart failrue (NNT, 27 to 115 over three years) and their heart failure symptoms may worsen if digoxin is withdrawn Positive inotrope with autonomic effects: increased parasympathetic tone DIG Trial (Garg R et al. N Engl J Med 1997;336:525-33.) : 6,800 pts w/ EF < 45% randomized to digoxin vs. placebo (Background tx: ACEI, diuretic) No difference in mortality between two groups 25% reduction in CV death or hospitalization for HF (p<0.001) 28% reduction in hospitalization for HF (p<0.001) Toxicity: renal dysfunction, elderly
Help symptoms regardless of NYHA classification
Aspirin may mitigate the beneficial effects of ACE-I
$530/dy Decreased 30 days survival Side effect of hypotension No benefit as an outpatient basis
Restriction of sodium-can aid in control of fluid and symptoms but no dec in morbidity or mortality Exercise-moderate exercise 2-3 hours per week improves quaility of life, decreased motality (nnt 4 for 14 months) A multidisciplinary, disease-management approach to heart failure includes intensive patient education about the condition and its treatment, dietary assessment and instruction, medication analysis, and follow-up by telephone and home visits. Usually it also includes aggressive management of comorbidities and risk factors, including control of blood glucose levels in patients with diabetes, treatment of hypertension to a target measurement of 140/90 mm Hg (130/80 mm Hg in patients with diabetes and those with chronic renal insufficiency), and lipid management to a target low-density lipoprotein level of less than 100 mg per dL (1 g per L) in high-risk patients and less than 70 mg per dL for very high-risk patients.38 This approach results in fewer hospitalizations (NNT, five for three months) and reduced cost of care.39 It also decreases the frequency of unplanned and repeat hospitalizations, and increases functional status and quality of life.40 WE do poorly at starting and keeping the correct dose of medicaion, these programs help!
SCD (sudden cardiac death)
Pt more mobile, less depressed and less symptomatic Use as a bridge to transplant as well REMATCH said can use it as therapy instead of just a bridge to transplant REMATCH (Rose EA et al. N Engl J Med 2001;345:1345-43) 129 patients with end-stage HF Randomized to standard therapy vs. standard therapy plus LVAD 48% decrease in mortality with LVAD
Congestive Heart Failure Madi Capoccia DO 5 Jun 2007 Dewitt Army Hospital
Objectives <ul><li>Definition and Epidemiology </li></ul><ul><li>Pathophysiology </li></ul><ul><li>Diagnosis and Classification </li></ul><ul><li>Treatment of Systolic Dysfunction </li></ul><ul><ul><li>Medical Therapy </li></ul></ul><ul><ul><li>Device Therapy </li></ul></ul>
What is CHF? <ul><li>Definition </li></ul><ul><li>Abnormality of cardiac function that leads to the inability of the heart to pump blood to meet the body’s basic metabolic demands or when it can do so only with an elevated filling pressure </li></ul>
Epidemiology <ul><li>Prevalence </li></ul><ul><ul><li>Affects nearly 5 million Americans currently, >500,000 new cases diagnosed each year </li></ul></ul><ul><li>Cost </li></ul><ul><ul><li>Annual direct cost in >10 billion dollars </li></ul></ul><ul><li>Incidence increased with age </li></ul><ul><ul><li>Effects 1-2% of patient from 50-59-years-old and 10% of patient over the age of 75 </li></ul></ul><ul><li>Frequency </li></ul><ul><ul><li>It is the most common inpatient diagnosis in the US for patients over 65 years of age </li></ul></ul><ul><ul><li>Visits to their family practitioner on average 2-3 times per year </li></ul></ul><ul><li>Gender </li></ul><ul><ul><li>Men> women in those between 40 and 75 years of age </li></ul></ul><ul><ul><li>The sexes are equal over 75 years of age </li></ul></ul>
Pathophysiology of Heart Failure <ul><li>Hemodynamic Model </li></ul><ul><li>Neurohumoral Adaptations </li></ul><ul><ul><li>“ double-edged swords” </li></ul></ul><ul><ul><li>Renin-Angiotensin-Aldosterone System </li></ul></ul><ul><ul><li>Sympathetic Nervous System </li></ul></ul><ul><ul><li>Antidiuretic Hormone </li></ul></ul><ul><ul><li>Atrial and B-type Natriuretic Peptides </li></ul></ul><ul><ul><li>Endothelin </li></ul></ul>
Help initially <ul><li>Vasoconstriction </li></ul><ul><ul><li>Redistributes blood to vital organs </li></ul></ul><ul><li>Restoration of Cardiac Output </li></ul><ul><ul><li>Increased myocardial contractility and heart rate </li></ul></ul><ul><ul><li>Expansion of the extracellular fluid volume </li></ul></ul>
Systolic vs. Diastolic <ul><li>Diastolic dysfunction </li></ul><ul><ul><li>EF normal or increased </li></ul></ul><ul><ul><li>Hypertension </li></ul></ul><ul><ul><li>Due to chronic replacement fibrosis & ischemia-induced decrease in distensibility </li></ul></ul><ul><li>Systolic dysfunction </li></ul><ul><ul><li>EF < 40% </li></ul></ul><ul><ul><li>Usually from coronary disease </li></ul></ul><ul><ul><li>Due to ischemia-induced decrease in contractility </li></ul></ul><ul><li>Most common is a combination of both </li></ul>
Classification of Heart Failure: ACC/AHA Stage vs NYHA Class
Principles of Treatment <ul><li>Systolic HF </li></ul><ul><li> Preload </li></ul><ul><li> Afterload </li></ul><ul><li> Ionotropy </li></ul><ul><li> Neurohumoral </li></ul><ul><li>activity </li></ul><ul><li>ACE-I, Beta-blockers, and aldosterone antagonist are the mainstay of treatment </li></ul>
Treatment of Systolic Heart Failure <ul><li>ACE Inhibitors- </li></ul><ul><ul><li>Works to inhibit the over stimulation of the RAS that leads to myocardial hypertrophy and fibrosis </li></ul></ul><ul><ul><li>Causes balanced vasodilation </li></ul></ul><ul><ul><li>Decrease the rate of morbidity & mortality in all pts with systolic heart failure </li></ul></ul><ul><ul><li>-If treating acute HF, can start after BP tolerates and pulmonary edema is relieved </li></ul></ul>
ACE-I <ul><li>SOLVD-Enalapril 20mg/day (41 mo) </li></ul><ul><li>2569 Patients with and EF <35% </li></ul><ul><ul><li>Earlier stages of HF even asymptomatic </li></ul></ul><ul><ul><li>NYHA Class II-III </li></ul></ul><ul><li>All cause mortality dec by 16% </li></ul><ul><li>Morality rate from HF dec by 16% </li></ul><ul><li>CONSENSUS-Enalapril 2.5-40mg (188 days) vs placebo </li></ul><ul><li>Pts were already taking digoxin and diuretics </li></ul><ul><li>253 Patient with NYHA Class IV </li></ul><ul><li>Dec mortality at: </li></ul><ul><ul><li>6 months -40% </li></ul></ul><ul><ul><li>1 Year – 27% </li></ul></ul>
Angiotensin-Receptor Blockers <ul><ul><li>Comparable to ACE inhibitors </li></ul></ul><ul><ul><li>Reduce all-cause mortality </li></ul></ul><ul><ul><li>Suitable alternative for patient with adverse events (angioedema, cough, hyperkalemia) occur with ace-i </li></ul></ul>
ACE + ARB <ul><li>CHARM-Added (Lancet 2003) </li></ul><ul><ul><li>2548 NYHA II-IV; LVEF < 40% </li></ul></ul><ul><ul><li>CV death, hospital admission </li></ul></ul><ul><ul><li>NNT=25 </li></ul></ul><ul><ul><li>Second study found no benefit </li></ul></ul><ul><li>But 23% discontinued due to side effects (increased cr, hypotension, hyperkalemia) </li></ul><ul><li>Currently Ace + Arb is not recommended </li></ul>
Beta-Blockers <ul><li>34% reduction in all mortality with use of beta-blockers </li></ul><ul><li>Decrease Cardiac Sympathetic Activity </li></ul><ul><li>Use in stable, chronic disease (start as early as discharge-IMPACT-HF) </li></ul><ul><li>Titrate slowly </li></ul><ul><li>Contraindications-bradycardia, heart block or hemodynamic instability </li></ul><ul><li>Mild asthma was not a contraindication </li></ul><ul><li>Work irrespective of the etiology of the heart failure </li></ul>
Beta- blocker therapy-which to pick? <ul><li>Three beta-blockers : </li></ul><ul><li>Bisoprolol (Zebeta) -Trial CIBIS-II </li></ul><ul><li>Metoprolol (Toprol XL) –Trial MERIT-HF (sustained release) </li></ul><ul><li> Carvedilol (Coreg) Trial-COPERNICUS </li></ul><ul><li>6 RCT’s with > 9,000 pts already taking ACE-I showed a significant reduction in total mortality and sudden death (NNT 24, and 35 over 1-2 years) regardless of severity </li></ul><ul><li>Carvedilol vs. Metoprolol (COMET 2003) </li></ul><ul><ul><li>3029 pts; carvedilol 25mg bid vs. metoprolol 50 mg bid </li></ul></ul><ul><ul><li>Patient with NYHA Classes II-IV </li></ul></ul><ul><ul><li>Carvedilol –greater reduction in mortality (NNT, 18 over 5 years) and cardiovascular mortality (NNT, 16 over 5 years) than metoprolol but hypotension was greater in carvedilol (14 vs 11 percent) </li></ul></ul>
Initial and Target Doses of beta-blockers for HF Medication Starting Dose Target Dosage Bisoprolol 1.25mg daily 10mg daily Carvedilol 3.125mg bid 25mg bid Metoprolol CR/XL 12.5-25mg daily 200mg daily
Aldosterone Antagonists <ul><li>Spironolactone (Aldactone; RALES 1999) </li></ul><ul><ul><li>Pts 1,663 Class III/IV, ACE, Loop,Dig, EF < 35% </li></ul></ul><ul><ul><li>Decreased all cause mortality of 30%, NNT=10 </li></ul></ul><ul><ul><li>Hyperkalemia, gynecomastia </li></ul></ul><ul><li>Eplerenone (Inspra; EPHESUS 2003 ) </li></ul><ul><ul><li>Pts 6,642 asym LV dysfunction, DM, or after MI </li></ul></ul><ul><ul><li>Dec CV mortality of 13%, NNT=43 </li></ul></ul><ul><ul><li>Newer more selective inhibitor; fewer side effects </li></ul></ul><ul><ul><li>More pts on beta-blockers </li></ul></ul>
Hydralazine (Apresoline) and isosorbide dinitrate (Sorbitrate) <ul><li>Hydralazine </li></ul><ul><li>Reduces systemic vascular resistance by preferentially dilating arterioles </li></ul><ul><li>Isosorbide Dinitrate </li></ul><ul><li>Preferential Venodilator-reduces ventricular filling pressure and treat pulmonary congestion </li></ul><ul><li>Reduces mortality – upto 28% </li></ul><ul><li>Poor tolerability->30% drop out of study </li></ul><ul><li> flushing, headaches, gi upset, less frequently can cause positive ANA titers and lupus-like syndrome </li></ul>
Hydralazine (Apresoline) and isosorbide dinitrate (Sorbitrate) <ul><li>African-American Heart Failure Trial (A-HeFT) </li></ul><ul><ul><li>advanced HF and a fixed dose of isosorbide dinitrate and hydralazine </li></ul></ul><ul><ul><li>Added to Standard B-blocker/Ace-I therapy </li></ul></ul><ul><ul><li>Some survival improvement </li></ul></ul>
Digoxin <ul><li>May relieve symptoms, does not reduce mortality </li></ul><ul><li>Pts taking digoxin are less likely to be hospitalized (25% reduction) </li></ul><ul><li>More admissions for suspected digoxin toxicity </li></ul>
Loop Diuretics <ul><li>Mainstay of symptomatic treatment </li></ul><ul><ul><li>Improve fluid retention </li></ul></ul><ul><ul><li>Increase exercise tolerance </li></ul></ul><ul><ul><li>No effects on morbidity or mortality </li></ul></ul>
Antiplatelet Therapy and Anticoagulation <ul><li>Increased risk of Thromboembolic events, 1.6-3.2% per year </li></ul><ul><li>Antiplatelet therapy (aspirin) in not useful in patient in sinus rhythm </li></ul><ul><li>Coumadin for patient with atrial fibrillation or a previous thromboembolic event </li></ul>
Nesiritide (Natrecor) <ul><li>Recombinant form of human BNP </li></ul><ul><li>Causes venous and arterial vasodilation </li></ul><ul><ul><li>has been shown to improve dyspnea and global assessments at 3 hours after initiation in pts with Acute HF. </li></ul></ul><ul><ul><li>Risks- deleterious effect on renal function and decreased 30 day survival </li></ul></ul>
ICD <ul><li>SCD-HeFT (sudden cardiac death) </li></ul><ul><li>2521 patients with depressed LV systolic function and Class II-III HF </li></ul><ul><li>Randomized to standard therapy vs. standard therapy plus ICD vs. standard therapy plus amiodarone </li></ul><ul><li>23% reduction in mortality with ICD </li></ul><ul><li>No difference in mortality with amiodarone </li></ul><ul><li>Results did not vary based on etiology of LV dysfunction </li></ul>
ICD <ul><li>Recommended in pts with EF<30% and mild to moderate symptoms of HF </li></ul><ul><li>Survival with good functional capacity is anticipated for > 1 year </li></ul>
CRT <ul><li>COMPANION Trial </li></ul><ul><li>1520 patients most with Class III-IV HF, QRS duration >120 ms </li></ul><ul><li>Randomized in 1:2:2 ratio to standard therapy vs standard therapy plus CRT vs standard therapy plus CRT with device that also defibrillated </li></ul><ul><li>34% reduction in death or any hospitalization with CRT </li></ul><ul><li>40% reduction when combined with ICD </li></ul>
Left Ventricular Assist Devices (LVAD) <ul><li>REMATCH Trial- </li></ul><ul><li>1 yr survival 52% (LVAD) vs 24% (rx) </li></ul><ul><li>2 yr survival 23% vs 8% </li></ul><ul><li>End-Stage (Class IV) </li></ul><ul><li>HF pts ineligible for transplant due to: </li></ul><ul><ul><li>>65yo </li></ul></ul><ul><ul><li>DM with EOD </li></ul></ul><ul><ul><li>CRI </li></ul></ul>
Diastolic Dysfunction <ul><li>Acute Management is the SAME </li></ul><ul><li>Chronic Management is CONTROVERSIAL </li></ul><ul><ul><li>Diuretics-dec fluid volume </li></ul></ul><ul><ul><li>CCB-promote left ventricular relaxation </li></ul></ul><ul><ul><li>ACE-I-promote regression of left ventricular hypertrophy </li></ul></ul><ul><ul><li>Beta-blockers/antiarrhytmic agents-control heart rate or maintain atrial contraction </li></ul></ul>
Recent Inservice Exam Questions <ul><li>1. Which one of the following is considered a contraindication to the use of beta-blockers for congestive heart failure? </li></ul><ul><ul><li>A) Mild Asthma </li></ul></ul><ul><ul><li>B) Symptomatic Heart Block </li></ul></ul><ul><ul><li>C) New York Heart Association (NYHA) Class III heart failure </li></ul></ul><ul><ul><li>D) NYHA Class I heart failure in a patient with a history of a previous myocardial infarction </li></ul></ul><ul><ul><li>E) An ejection fraction <30% </li></ul></ul>
<ul><li>1. Answer B </li></ul><ul><li>According to several randomized, controlled trial, mortality rates are improved in patient with heart failure who receive beta blockers in addition to diuretics, ACE inhibitors, and occasionally, digoxin. Contraindications to beta blocker use include hemodynamic instability, heart block, bradycardia, and severe asthma. Beta-blockers may be tried in patients with mild asthma or COPD as long as them are monitored for potential exacerbations. B-blocker use has been shown to be effective in patient with NYHA Class II or III heart failure. There is no absolute threshold ejection fraction . B-blockers have also been shown to decrease mortality in patients with a previous history of myocardial infarction, regardless of their NYHA classification </li></ul>
<ul><li>2. Which one of the following serologic tests would be the most helpful for detecting left ventricular dysfunction? </li></ul><ul><ul><li>A) B -type natriuetic peptide (BNP) </li></ul></ul><ul><ul><li>B) Troponin-T </li></ul></ul><ul><ul><li>C) C-reactive protein (CRP) </li></ul></ul><ul><ul><li>D) D dimer </li></ul></ul><ul><ul><li>E) Cardiac interleukin-2 </li></ul></ul>
<ul><li>2. Answer A. </li></ul><ul><li>Β NP is a 32-amino acid polypeptide secreted from the cardiac ventricles in response to ventricular volume expansion and pressure overload. The major source of BNP is the cardiac ventricles, and because of its minimal presence in storage granules, its release is directly proportional to ventricular dysfunction. It is a simple and rapid test that reliably predicts the prescence or absence of heart failure. </li></ul>
<ul><li>3. Which one of the following is a risk factor for perioperative arrhythmias? </li></ul><ul><ul><li>A) Supraventricular Tachycardia </li></ul></ul><ul><ul><li>B) Congestive Heart Failure </li></ul></ul><ul><ul><li>C) Age >60 </li></ul></ul><ul><ul><li>D) Premature Atrial Contractions </li></ul></ul><ul><ul><li>E) Past history of hyperthyroidism </li></ul></ul>
<ul><li>3. Answer B </li></ul><ul><li>Significant predictors of intraoperative and perioperative ventricular arrhythmias include preoperative ventricular (not supraventricular) ectopy, CHF, and tobacco use. Age and history of hyperthyroidism are not significant predictors of perioperative ventricular arrhythmias. </li></ul>
<ul><li>4. Which one of the following is preferred for chronic treatment of congestive heart failure due to left ventricular systolic dysfunction? </li></ul><ul><ul><li>A) Diuretics </li></ul></ul><ul><ul><li>B) Digoxin </li></ul></ul><ul><ul><li>C) Calcium Channel Blockers </li></ul></ul><ul><ul><li>D) ACE inhibitors </li></ul></ul><ul><ul><li>E) Hydralazine (Apresoline) plus isosorbide dinitrate (Isordil, Sorbitrate) </li></ul></ul>
<ul><li>4. Answer D </li></ul><ul><ul><li>ACE-I are the preferred drugs for CHF due to LV systolic dysfunction, because they are associated with the lowest mortality. The combination of hydralazine/isosorbide dinitrate is a reasonable alternative, and diuretics should be used cautiously. It is not known whether Digoxin affects mortality, although it can help with symptoms. </li></ul></ul>
<ul><li>5. A 72-year-old male with class III CHF due to systolic dysfunction asks if he can take ibuprofen for his “aches and pains.” </li></ul>
<ul><ul><li>A) NSAIDs are a good choice for pain relief, as they decrease systemic vascular resistance </li></ul></ul><ul><ul><li>B) NSAIDs are a good choice for pain relief, as they augment the effect of his diuretic </li></ul></ul><ul><ul><li>C) High-dose aspirin (325mg/day) is preferable to other NSAIDs for patients talking ACE-I </li></ul></ul><ul><ul><li>D) NSAIDs, including high-dose aspirin, should be avoided in CHF patient because they can cause fluid retention </li></ul></ul>
<ul><li>5. Answer D </li></ul><ul><ul><li>If possible, NSAIDs should be avoided in patients with heart failure. They cause sodium and water retention, as well as an increase in systemic vascular resistance which may lead to cardiac decompensation. NSAIDs may negate or decrease entirely the beneficial unloading effects of ACE inhibition. </li></ul></ul>
References <ul><li>REFERENCES : 1 Hunt S.A., Baker D.W., Chin M.H., Cinquegrani M.P., Feldman A.M., Francis G.S., Ganiats T.G., Goldstein S., Gregoratos G., Jessup M.L, ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure) . J Am Coll Cardiol (2001) 38 : pp 2101-2113 . </li></ul><ul><li>2 Packer M., Cohn J.N., Consensus recommendations for the management of chronic heart failure . Am J Cardiol (1999) 83 : pp 1A-38A . 3 Pitt B., Williams G., Remme W., Martinez F., Lopez-Sendon J., Zannad F., Neaton J., Roniker B., Hurley S., Burns D, The EPHESUS trial: eplerenone in patients with heart failure due to systolic dysfunction complicating acute myocardial infarction Eplerenone Post-AMI Heart Failure Efficacy and Survival Study . Cardiovasc Drugs Ther (2001) 15 : pp 79-87 . 4 Pitt B., Zannad F., Remme W.J., Cody R., Castaigne A., Perez A., Palensky J., Wittes J., The effect of spironolactone on morbidity and mortality in patients with severe heart failure Randomized Aldactone Evaluation Study Investigators . N Engl J Med (1999) 341 : pp 709-717 . </li></ul><ul><li>5 SOLVD Investigators Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure The SOLVD Investigators . N Engl J Med (1991) 325 : pp 293-302 . </li></ul>
<ul><li> CONSENSUS Trial Study Group Effects of enalapril on mortality in severe congestive heart failure Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group . N Engl J Med (1987) 316 : pp 1429-1435 . 7 Hjalmarson A., Goldstein S., Fagerberg B., Wedel H., Waagstein F., Kjekshus J., Wikstrand J., El Allaf D., Vitovec J., Aldershvile J, Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF) MERIT-HF Study Group . JAMA (2000) 283 : pp 1295-1302 . 8 CIBIS-II Investigators The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial . Lancet (1999) 353 : pp 9-13 . 9 Packer M., Bristow M.R., Cohn J.N., Colucci W.S., Fowler M.B., Gilbert E.M., Shusterman N.H., The effect of carvedilol on morbidity and mortality in patients with chronic heart failure U.S. Carvedilol Heart Failure Study Group . N Engl J Med (1996) 334 : pp 1349-1355 . 10 Packer M., Fowler M.B., Roecker E.B., Coats A.J., Katus H.A., Krum H., Mohacsi P., Rouleau J.L., Tendera M., Staiger C, Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Study . Circulation (2002) 106 : pp 2194-2199 . </li></ul>
<ul><li>11 Fonarow G., Gheorghiade, M., Abraham, W., Importance of In-Hospital Initiabtion of Evidence-Based Medical Therapies for Heart Failure-A Review. J Am Coll Cardiol (2004) 94 : pp 1155-1159 </li></ul><ul><li>12 Chavey WE 2 nd , The Importance of Beta Blocker in the Treatment of Heart Failure Am Fam Physician - (2000) 62(11): 2453-62 </li></ul>