Heart Failure Lecture PDF

Heart Failure Dr. Ghada Osama Intended Learning Outcomes Define Heart failure and the underlying etiologies of the disease. Describe the factors affecting cardiac output and pathophysiology of HF. Differentiate between systolic and diastolic heart failu...

Heart Failure Dr. Ghada Osama Intended Learning Outcomes Define Heart failure and the underlying etiologies of the disease. Describe the factors affecting cardiac output and pathophysiology of HF. Differentiate between systolic and diastolic heart failure. Identify signs and symptoms of heart failure. Characterize the different Pharmacological classes used for the management of HF regarding mechanism of action and side effects.  Chronic Heart Failure It is a complex clinical syndrome caused by any structural and functional cardiac disorder that: Impairs the ability of the ventricle to fill with or eject blood in order to meet the body’s metabolic demands. Congestion & Hypoperfusion Chronic Heart Failure term has replaced the term Congestive Heart Failure Acute Heart Failure: Acute decompensation of a patient with a history of chronic heart failure or new onset HF symptoms  Ejection Fraction Ejection fraction: The fraction (percentage) of blood ejected by the ventricle in each cardiac cycle relative to its end-diastolic volume. It is a representation of LV systolic performance. EF = Amount of blood pumped out of the ventricle in each beat Total amount of blood in ventricle at the end of diastolic filling time EF = (SV / EDV) x 100 Normal = LVEF 50% to 70% Mild dysfunction = LVEF 40% to 49% Moderate dysfunction = LVEF 30% to 39% Severe dysfunction = LVEF less than 30%  Etiology Ischemic Non-ischemic 70% secondary to HTN Thyroid diseases CAD Valvular Cardiotoxins disorders Viral illness  Pathophysiology of HF Factors controlling CO ↑ HR…….. ↑ CO Contractility: Influenced to a large Stroke Volume degree by adrenergic nerve activity and circulating catecholamines. ↑ Contractility …….. ↑ SV…….. ↑ CO Compensatory Mechanisms  Compensatory Mechanisms Activation SNS of RAAS stimulation Hypertrophy Natriuretic & Peptides Remodeling Activation of RAAS Sudden decrease in CO, decreases the renal perfusion and results in activation of RAAS which stimulates formation of angiotensin II and release of aldosterone. This results in increased peripheral resistance (↑afterload) and retention of sodium and water (↑ preload). ↑ Preload impairs contractile function in the failing heart CO  Sympathetic Nervous system stimulation Baroreceptors sense a decrease in BP and activate SNS: SNS stimulation of β1 receptors Increased HR and a greater force of contraction, in turn, ↑ CO. Increase myocardial oxygen demand, worsen underlying ischemia, contribute to proarrhythmia, and further impair both systolic and diastolic function RAAS & SNS vasoconstriction Arterial vasoconstriction leads to impaired forward ejection of blood from the heart due to an increase in afterload CO and continued stimulation of compensatory responses vicious cycle of neurohormonal activation  Cardiac Hypertrophy and Remodeling Ventricular Cardiac remodeling Hypertrophy Adaptive increase in ventricular Dilation and other slow muscle mass due to growth of structural changes that existing myocytes, occurs in occur in the stressed response to an increased myocardium. hemodynamic burden Stretching of the heart muscle Regulated by angiotensin II leads to a stronger contraction of and aldosterone. the heart  Cardiac Hypertrophy and Remodeling Ventricular Cardiac remodeling Hypertrophy Continued hypertrophy results in Myocytes in the failing heart weaker contractions, diminished die at an accelerated rate ability to eject blood, impairment of through apoptosis, leaving the diastolic filling, and alterations in remaining myocytes subject to ventricular geometry. even greater stress. Normal Heart Failing Heart  Counter regulatory Hormones (Natriuretic Peptides) ANP & BNP Release of ANP and BNP is stimulated by increased cardiac chamber wall stretch usually indicative of volume load Natriuresis Inhibition of renin and aldosterone release Vasodilation through cGMP pathway Reduction in myocardial fibrosis. Higher concentrations of NPs correlate with a more severe HF functional class and prognosis  Types of Heart Failure HFrEF (< 40%) HFpEF (> 50%) Coronary artery diseases are the HTN is responsible for 60-90% cases, most important cause. diabetes and to a lesser extent, CAD and atrial fibrillation. Clinical Picture  Goals of Therapy Modify or control risk factors Eliminate or minimize HF (e.g., HTN, obesity, DM, CAD) symptoms Reduce morbidity and mortality Block compensatory neurohormonal activation caused by reduced CO Slow progression of Prevent or minimize Na and worsening cardiac function water retention  Non-Pharmacological Therapy Sodium restriction Fluid restriction Smoking cessation Weight reduction in obese patients Supervised regular physical activity Control of HTN (goal BP < 130/80 mm Hg, DM, CAD and screen for and treat depression  Drug Classes for HF Neurohormonal Blocking agents Inotropic Agents ACEIs Aldosterone Vaso- and ARBs antagonists Venodilators β-blockers If Channel Blocker ARNI Diuretics 1- Neurohormonal Blocking agents Slowing Improving disease survival in progression chronic HF Improving symptoms 1-ACEIs & ARBs  1-ACEIs & ARBs Cornerstone of treatment Mechanisms for Help attenuating their for HF specially HFrEF decreased HF progression detrimental effects on and mortality cardiac muscle (remodeling, hypertrophy, fibrosis, Current or prior Hemodynamic cell death and improvement (decrease inflammatory changes). symptoms, unless preload and afterload + contraindicated leading to decreased cardiac workload) Dosing Recommendations low doses and titrated Improvements in clinical up to target doses over symptoms Reduce the angiotensin several weeks Exercise tolerance II–mediated increase in depending on LV size and function sympathetic discharge tolerability (adverse and aldosterone effects and blood and quality of life. pressure)  2- Aldosterone Antagonists Spironolactone Eplerenone ✓ Produce weak diuretic effects while sparing K+ concentrations. They oppose the Aldosterone detrimental Effects ✓ Inhibit cardiac extracellular matrix and collagen deposition, thereby diminishing cardiac fibrosis, hypertrophy and remodeling. ✓ Use of these agents has been shown to decrease mortality (improve survival) particularly in those with a LVEF of 35% or less. ✓ These agents should not be given when creatinine clearance is less than 30 mL/minute or serum creatinine is greater than 2.5 mg/dL in men or greater than 2 mg/dl in women.  3. β- Blockers Reduces ventricular mass Antiarrhythmic effects Slow or reverse catecholamine-induced ventricular remodeling Decrease myocyte death from catecholamine induced necrosis or apoptosis Consequently, β-blockers improve EF, reduce all-cause and HF related hospitalizations, and decrease all-cause mortality in patients with systolic HF  β- Blockers Three β-blockers have been shown to reduce mortality in systolic HF, including the selective β1-antagonists Bisoprolol and Metoprolol Succinate, and the non- selective β1and α1-antagonist Carvedilol. Add to existing ACE inhibitor therapy (at least at a low dose) when HF symptoms are stable and patients are euvolemic.  β- Blockers Should not be prescribed without diuretics in patients with current or recent history of fluid retention. Volume overload at the time of β-blocker initiation increases the risk for worsening symptoms The key to utilizing β-blockers in systolic HF (HFrEF) is: Initiation with low doses and slow titration (double) the dose every 2 weeks (or slower, if needed) target doses over weeks to months (Aim to achieve target dose in 8–12 weeks). Carvedilol Provides blockade at β1- β2& α1 vasodilatory effects & more complete antagonism of sympathetic stimulation In-vitro antioxidant activity reduce vascular and cardiac oxidative damage Increase LVEF, improved cardiac hemodynamics, and slowed remodeling more than metoprolol tartrate. Preferred in patients with uncontrolled HTN by providing additional antihypertensive efficacy (↓afterload)  3. Angiotensin Receptor–Neprilysin Inhibitor To maximize the effect of natriuretic peptides, stimulation of the RAAS must be offset without ARB, instead of an ACE inhibitor, is combined with a further increase in neprilysin inhibitor to reduce the incidence of bradykinin. angioedema.  ARNI: Sacubitril/valsartan Inhibition of neprilysin results in increased concentration of natriuretic peptides, leading to natriuresis, diuresis, vasodilation, and inhibition of fibrosis. Together, the combination decreases afterload, preload, and myocardial fibrosis. An ARNI improves survival and clinical signs and symptoms of HF, as compared to therapy with an ACE inhibitor. Therapeutic use ✓ An ARNI should replace an ACE inhibitor or ARB in patients with HFrEF who remain symptomatic on optimal doses of a β-blocker and an ACE inhibitor or ARB. Contraindications Side effects History of angioedema related Hypotension to previous ACE inhibitor or ARB hyperkalemia concomitant use of ACE inhibitors or Aliskiren Cough Pregnancy Dizziness hyperkalemia Renal failure Stop ACE inhibitor for 36 hours before starting Angioedema treatment with ARNI  4. Diuretics Diuretics are used for: Relief of acute symptoms of congestion (dyspnea on exertion, orthopnea, and peripheral edema) Maintenance of euvolemia in symptomatic patients. Note: diuretics have no long-term benefit on mortality rate in HF patients Diuretics decrease plasma volume and, subsequently, decrease venous return to the heart (↓ preload). This decreases cardiac workload and oxygen demand. Diuretics may also decrease afterload by reducing plasma volume, thereby decreasing blood pressure.  Loop Diuretics Furosemide Bumetinide Torsemide ✓ Loop diuretics are the most widely used diuretics in HF. ✓ They retain their diuretic ability in patients with poor renal function. ✓ In patients with evidence of mild to moderate volume overload, diuretics should be initiated at a low dose and titrated to achieve a weight loss of up to 0.5-1 kg of weight loss per day. ✓ Once a patient reaches a euvolemic state, diuretics may be cautiously tapered and then withdrawn in appropriate patients.  5. Inotropic Agents Digoxin β-Adrenergic Phosphodiesterase agonists Inhibitors Milrinone Dobutamine Dopamine Positive inotropic agents enhance cardiac contractility and, thus, increase CO.  Digoxin The cardiac glycosides are often called digitalis glycosides, because most of the drugs come from the digitalis (foxglove) plant. Digoxin is the only available therapeutic agent.  Digoxin 1- Direct Positive Inotropic effect Digoxin increases the force of cardiac contraction, causing cardiac output to more closely resemble that of the normal heart.  Digoxin 2- Increase vagal activity and reduce sympathetic activity (negative chronotropic effect) ✓ Low-dose digoxin inhibits sympathetic activation while enhancing vagal tone. ✓ It causes inhibition of the SA node (decrease HR) and slows conduction velocity through the AV node.  Digoxin Therapeutic Uses ✓ Digoxin is used for patients with HFrEF who remain symptomatic despite an optimal HF regimen consisting of an ACEI or ARB, β-blocker, and diuretic. ✓ It improves symptoms and exercise tolerance in addition to decreasing HF-related hospitalizations but doesn’t decrease HF progression or improve survival. ✓ Useful for atrial arrhythmias and atrial fibrillation management. ✓ Digoxin is not indicated in diastolic heart failure  Adverse Effects Determination of plasma digoxin concentration is mandatory as it has a narrow therapeutic index and toxicity is common due to inappropriate use Cardiovascular: atrial or ventricular arrhythmia, as well as AV block. Potassium may help in alleviating arrhythmias. GIT: Anorexia, nausea and vomiting. CNS: Headache, fatigue, and confusion Eye: Blurred vision, altered color perception, yellow haloes on dark objects may be initial indicators of toxicity (reducing the dose of the drug is required).  Factors predisposing Treatment of Digoxin to toxicity toxicity Electrolyte disturbances: Hypokalemia: due to thiazides or loop diuretics, Stopping the drug. hypomagnesemia and hypercalcemia. administration of digitalis Drug-Drug Interaction (drugs antibodies (digoxin immune fab) that inhibit its excretion or (Digibind). metabolism) Administration of potassium Renal impairment  Drug Interactions: Digoxin should be used with caution with other drugs that slow AV conduction: β-blockers, verapamil, diltiazem Diltiazem, quinidine, amiodarone, clarithromycin and verapamil reduce digoxin clearance by inhibiting P- glycoprotein mediated renal excretion, thereby contributing to digitalis toxicity. Antacids and cholestyramine can reduce the absorption of digoxin and decrease its therapeutic effects. Their administration should be separated by at least 2 hours. β-Adrenergic agonists Phosphodiesterase inhibitors  β-Adrenergic agonists Dobutamine Dopamine ✓ Improve cardiac performance: ✓ IV infusion ✓ Positive inotropic effects ✓ Short-term treatment of acute (increase in CO) HF in the hospital setting ✓ and vasodilation (decrease in ✓ Cardiogenic shock ventricular filling pressure). Adverse effects: ✓ Dobutamine is the most widely ✓ Tachycardia used in patients with heart ✓ Potential for producing failure. angina or arrhythmias in patients with CAD  Phosphodiestrase Inhibitors Milrinone ✓ IV bolus followed by ✓ Increase cardiac IV infusion contractility ✓ Only for acute HF ✓ Important ✓ Severe exacerbation vasodilating effect. of CHF Adverse effects: ✓ long-term use can cause thrombocytopenia and ventricular arrhythmias ✓ Associated with increased mortality in patients with severe HF.  6. Vaso- and Venodilators Reduction in afterload Reduction in preload (through arteriolar Or Both (through venodilation) dilation) Some of them can be used for long term management of CHF Or IV in acute HF Hydralazine: arterio-dilator Nitrates Hydralazine/Isosorbide Mainly venodilators dinitrate combination  Hydralazine & Isosorbide Dinitrate Combination therapy for those unable to tolerate an ACEIs or ARB or as add-on therapy in African Americans with HFrEF Hydralazine: is an arterial vasodilator (reduces afterload) & increases effect of nitrates through antioxidant mechanisms in addition to reduction in the development of nitrate tolerance. Isosorbide dinitrate: Stimulates nitric acid signaling in the endothelium leading to Venodilation (reduces preload) and reliefs pulmonary congestion. Long-term use can also reduce the damaging remodeling of the heart and improve survival.  8. If Channel Blocker Ivabradine The inhibition of “If channel,” results in: Selectively reducing heart rate without affecting the force of contraction, In patients with HFrEF, a slower HR AV conduction, or increases SV and improves symptoms of BP. HF.