2. Definition• Heart failure (HF) is a clinical syndrome that occurs in patients who, because of an inherited or acquired abnormality of cardiac structure and/or function, develop a constellation of clinical symptoms (dyspnea and fatigue) and signs (edema and rales) that lead to frequent hospitalizations, a poor quality of life, and a shortened life expectancy.
3. Epidemiology• more than 20 million people affected• The overall prevalence of HF in the adult population in developed countries is 2%• rising with age, and affects 6–10% of people over age 65• The overall prevalence of HF is thought to be increasing, in part because current therapies for cardiac disorders, such as myocardial infarction (MI), valvular heart disease, and arrhythmias, are allowing patients to survive longer.
4. TYPES (1) HF with a depressed EF (commonly referred to assystolic failure) or• (2) HF with a preserved EF (commonly referred to as diastolic failure).
5. Prognosis• the development of symptomatic HF still carries a poor prognosis.• Community-based studies indicate that 30–40% of patients die within 1 year of diagnosis and 60–70% die within 5 years• patients with symptoms at rest [New York Heart Association (NYHA) class IV] have a 30–70% annual mortality rate, whereas patients with symptoms with moderate activity (NYHA class II) have an annual mortality rate of 5–10%.
6. Basic Mechanisms of Heart FailureSystolic Dysfunction• LV remodeling• (1) myocyte hypertrophy,• (2) alterations in the contractile properties of the myocyte,• (3) progressive loss of myocytes through necrosis, apoptosis, and autophagic cell death• (4) adrenergic desensitization• (5) abnormal myocardial energetics and metabolism• (6) reorganization of the extracellular matrix with dissolution of the organized structural collagen weave surrounding myocytes and subsequent replacement by an interstitial collagen matrix that does not provide structural support to the myocytes.
7. Diastolic Dysfunction• Myocardial relaxation is (ATP)-dependent process that is regulated by uptake of cytoplasmic calcium into the SR by SERCA2A -• reductions in ATP concentration, as occurs in ischemia, may interfere with these processes and lead to slowed myocardial relaxation. Alternatively, if LV filling is delayed because LV compliance is reduced LV filling pressures will similarly remain elevated at end diastole .• In addition to impaired myocardial relaxation, increased myocardial stiffness secondary to cardiac hypertrophy and increased myocardial collagen content may contribute to diastolic failure.• Importantly, diastolic dysfunction can occur alone or in combination with systolic dysfunction in patients with HF.
8. Left Ventricular Remodeling• the changes in LV mass, volume, and shape and the composition of the heart . increase in LV end-diastolic volume, LV wall thinning occurs as the left ventricle begins to dilate. The increase in wall thinning, along with the increase in afterload created by LV dilation, leads to a functional afterload mismatch• Moreover, the high end-diastolic wall stress might be expected to lead to• (1) hypoperfusion of the subendocardium• (2) increased oxidative stress• (3) sustained expression of stretch-activated genes , hypertrophic signaling pathways.• Increasing LV dilation also results in tethering of the papillary muscles with resulting functional mitral regurgitation
9. central sleep apnoea
10. Diagnosis• Routine Laboratory Testing ; complete blood count, a panel of electrolytes, blood urea nitrogen, serum creatinine, hepatic enzymes, and a urinalysis.• Electrocardiogram (ECG)• Chest X-Ray• Biomarkers• Assessment of Lv Function
12. natriuretic peptide• Both B-type natriuretic peptide (BNP) and N-terminal pro- BNP, are relatively sensitive markers for the presence of HF with depressed EF; they also are elevated in HF patients with a preserved EF, albeit to a lesser degree.• However, it is important to recognize that natriuretic peptide levels increase with age and renal impairment, are more elevated in women, and can be elevated in right HF from any cause.• Levels can be falsely low in obese patients and may normalize in some patients after appropriate treatment.• Other biomarkers, such as troponin T and I, C-reactive protein, TNF receptors, and uric acid, may be elevated in HF and provide important prognostic information.
13. Assessment of Lv Function
14. Echocardiography• Transthoracic echocardiography can be performed without risk to the patient, does not involve radiation exposure, and can be performed at the bedside if necessary. It is particularly well suited for evaluating the structure and function of both the myocardium and heart valves and providing information about intracardiac pressures and flows. Echocardiography may be limited in some patients because available imaging planes and image quality depend on acoustic windows, which may be suboptimal as a result of obesity, emphysema, or other causes
15. Diagnosis and Management of AcuteHeart Failure SyndromesAHFS can be defined as the new onset or recurrence ofgradually or rapidly developing symptoms and signs of HFrequiring urgent or emergent therapy and resulting inhospitalization.• (1) stabilize the hemodynamic derangements that provoked the symptoms• (2) identify and treat the reversible factors that precipitated decompensation, and• (3) reestablish an effective outpatient medical regimen that will prevent disease progression and relapse.
16. Vasodilators• By stimulating guanylyl cyclase within smooth-muscle cells, nitroglycerin, nitroprusside, and nesiritide exert dilating effects on arterial resistance and venous capacitance vessels, results in a lowering of LV filling pressure, a reduction in mr, and improved forward co without increasing hr or causing arrhythmias
17. Inotropic Agents• direct hemodynamic benefits by stimulating cardiac contractility as well as by producing peripheral vasodilation. Collectively, these hemodynamic effects result in an improvement in cardiac output and a fall in LV filling pressures• short-term use provides hemodynamic benefits in cardiogenic shock ,but these agents are more prone to cause tachyarrhythmias and ischemic events .• If patients require sustained use of intravenous inotropes, strong consideration should be given to the use of an ICD to safeguard against the proarrhythmic effects of these agents.
18. Dobutamine and Milrinone• Dobutamine, exerts its effects by stimulating beta 1 and beta 2 receptors, with little effect on alpha1 receptors. Dobutamine is given as a continuous infusion at an initial infusion rate of 1–2 mic g/kg per min. Higher doses (>5 micr g/kg per min) are frequently necessary for severe hypoperfusion; however, there is little added benefit to increasing the dose above 10 micro g/kg per min.• Milrinone is a phosphodiesterase III inhibitor that leads to increases cAMP . Milrinone may act synergistically with - adrenergic agonists to achieve a greater increase in cardiac output , If the patient has a low bp, omit the bolus dose. Because milrinone is a more effective vasodilator than dobutamine, it produces a greater reduction in LV filling pressures, with a greater risk of hypotension.
19. Levosimendan• Levosimendan is a calcium sensitizer and ATP-dependent potassium channel opener that has positive inotropic and vasodilatory effect.• an improvement in patient self-assessment, a decrease in levels of BNP, and a shorter hospital stay were noted in patients admitted with HF and reduced ejection fraction• According to the ESC guidelines, levosimendan should be considered for patients with low cardiac output states despite the use of other therapies. Levosimendan should be started with a bolus dose (3 to 12 mg/kg) during 10 minutes, unless SBP <100 mm Hg, followed by a continuous infusion (0.05 to 0.2 mg/kg/min for 24 hours
21. Vasopressin Antagonists• three types of receptors, V1a, V1b, and V2. Selective V1a antagonists block the vasoconstricting effects of AVP in peripheral vascular smooth muscle cells, whereas V2 selective receptor antagonists inhibit recruitment of aquaporin channels in collecting duct• Combined V1a/V2 antagonists lead to a decrease in systemic vascular resistance and prevent the dilutional hyponatremia that occurs in HF patients• All four AVP antagonists increase urine volume, decrease urine osmolarity, and have no effect on 24-hour sodium excretion
22. Vasopressin Antagonists
23. Management of chronic Heart FailurePatients with Reduced Ejection Fraction
24. TREATMENT• Activity-routine modest exercise has been shown to be beneficial in patients with NYHA class I–III HF.• Diet-Dietary restriction of sodium (2–3 g daily) is recommended in all patients with HF and preserved or depressed EF. Further restriction (<2 g daily) may be considered in moderate to severe HF. Fluid restriction is generally unnecessary unless the patient develops hyponatremia (<130 meq/L)• Caloric supplementation is recommended for patients with advanced HF and unintentional weight loss or muscle wasting (cardiac cachexia);
26. • Many of the clinical manifestations of moderate to severe HF result from excessive salt and water retention that leads to volume expansion and congestive symptoms.• Diuretics are the only pharmacologic agents that can adequately control fluid retention in advanced HF and they should be used to restore and maintain normal volume status in patients with congestive symptoms or signs of elevated filling pressures• Se-electrolyte and volume depletion as well as worsening azotemia
27. Diuretic Resistance and Management• resistant to diuretic drugs when moderate doses of a loop diuretic do not achieve the desired reduction of the extracellular fluid volume• braking phenomenon• the potential delay in their rate of absorption• postdiuretic NaCl retention• loss of renal responsiveness to endogenous natriuretic peptides as HF advances• diuretics increase solute delivery to distal segments of the nephron, causing epithelial cells to undergo hypertrophy and hyperplasia• treating the diuretic-resistant patient is to administer two classes of diuretic concurrently• metolazone because its half-life is longer and remain effective even when the gfr is low
28. Prevention of disease progression
29. ACE Inhibitors• used in symptomatic and asymptomatic patients with a reduced EF <40%• ACEIs interfere with the RAS by inhibiting the enzyme that is responsible for the conversion of angiotensin I to angiotensin II• the upregulation of bradykinin• ACEIs stabilize LV remodeling, improve patient symptoms, prevent hospitalization, and prolong life• Abrupt withdrawal avoided in the absence of life-threatening complications (e.g., angioedema, hyperkalemia).• Side eff;-decreases in blood pressure , mild azotemia , nonproductive cough (10% to 15% of patients) and angioedema (1% of patients). hyperkalemia• who cannot tolerate ACEIs because of cough or angioedema, ARBs are the next recommended
30. Angiotensin Receptor Blockers• symptomatic and asymptomatic patients with an EF less than 40% who are ACE-intolerant for reasons other than hyperkalemia or renal insufficiency• ARBs block the effects of angiotensin II on the angiotensin type 1 receptor, the receptor subtype responsible for almost all the adverse biologic effects relevant to angiotensin II on cardiac remodeling• hypotension, azotemia, and hyperkalemia
31. Beta-Adrenergic Receptor Blockers• interfere with the harmful effects of sustained activation of the nervous system by competitively antagonizing one or more adrenergic receptors• most of the deleterious effects mediated by the beta1 receptor• When given in concert with ACEIs, beta blockers reverse the process of LV remodeling, improve patient symptoms, prevent hospitalization, and prolong life• beta blocker therapy is well tolerated by the great majority of HF patients (>85%), including patients with comorbid conditions such as dm, copd, and pvd
32. Renin Inhibitors• Aliskiren is an orally active renin inhibitor that appears to suppress RAS to a similar degree as ACE-inhibitors• Aliskiren is a nonpeptide inhibitor that binds to the active site of renin, preventing the conversion of angiotensinogen to angiotensin I
33. Management of Patients WHO RemainSymptomatic• Digoxin is recommended for patients with symptomatic LV systolic dysfunction with atrial fibrillation, and• for patients who have signs or symptoms of HF while receiving standard therapy, including ACE inhibitors and beta blockers.• Therapy with digoxin is commonly initiated and maintained at a dose of 0.125–0.25 mg daily. For the great majority of patients• the dose should be 0.125 mg daily, and the serum digoxin level should be <1 ng/mL
34. Cardiac Glycosides• Digoxin exerts its effects by inhibiting the Na+,K+-ATPase pump. leads to an increase in intracellular calcium and hence increased cardiac contractility• However, the more likely mechanism of digoxin in HF patients is to sensitize Na+,K+-ATPase activity in vagal afferent nerves, that counterbalances the increased activation of the adrenergic system in advanced HF.• Digoxin also inhibits Na+,K+-ATPase activity in the kidney and may therefore blunt renal tubular resorption of sodium.•
35. Complications of Digoxin Use• (1) cardiac arrhythmias, including heart block (especially in older patients) and ectopic and reentrant cardiac rhythms;• (2) neurologic complaints such as visual disturbances, disorientation, and confusion; and• (3) gastrointestinal symptoms such as anorexia, nausea, and vomiting• Oral potassium administration is often useful for atrial, AV junctional, or ventricular ectopic rhythms, even when the serum potassium level is in the normal range, unless high-grade AV block is also present• Potentially life-threatening digoxin toxicity can be reversed by antidigoxin immunotherapy using purified Fab fragments
36. Anticoagulation and Antiplatelet Therapy• Patients with HF have an increased risk for arterial or venous thromboembolic events.• In clinical HF trials, the rate of stroke ranges from 1.3 to 2.4% per year• Treatment with warfarin [goal (INR) 2–3] is recommended for patients with HF and chronic or paroxysmal afor with a history of systemic or pulmonary emboli, including stroke or tia.• Patients with symptomatic or asymptomatic ischemic cardiomyopathy and documented recent large anterior MI or recent MI with documented LV thrombus should be treated with warfarin (goal INR 2–3) for the initial 3 months after the MI unless there are contraindications to its use
37. Management of HF with a PreservedEjection Fraction (>40–50%)• no proven therapy• initial treatment efforts should be focused, wherever possible, on the underlying disease process (e.g., myocardial ischemia, hypertension) .• Precipitating factors such as tachycardia and af should be treated . Dyspnea may be treated by reducing total blood volume (dietary sodium restriction and diuretics), decreasing central blood volume (nitrates), or blunting neurohormonal activation with ACE inhibitors, ARBs, and/or beta blockers.• Treatment with diuretics and nitrates should be initiated at low doses to avoid hypotension and fatigue
39. Emerging Therapies and Strategies in theTreatment of Heart Failure• Stem and Progenitor Cells• Gene Therapy
40. Gene Therapy
41. Myocardial Stem and Progenitor CellsRepair and Regeneration
42. Pharmacogenetics• pharmacogenetics attempts to define common gene polymorphisms, or sets of polymorphisms, that underlie variability in drug action.• Given the tremendous heterogeneity that exists in HF patients, it is likely that genetic variations play a significant role in determining drug metabolism, disposition, and functional activity in HF patients
43. Metabolic Modulation• The prototype partial inhibitors of fatty acid oxidation (pFOX), etomoxir, oxfenicine, and perhexiline, act by inhibiting carnitine palmitoyltransferase I (CPT I), the gatekeeper of fatty acid entry to the mitochondrion , These agents shift energy use from free fatty acids to glucose by decreasing oxidation of free fatty acids.
44. Ranolazine (Ranexa)• Ranolazine (Ranexa) is a novel anti-ischemic drug that prolongs the QT interval and is the first pFOX inhibitor approved by the Food and Drug Administration for the treatment of angina.• the antianginal effects of ranolazine may be related to decreased sodium entry into cells by inhibition of the rapid component of the delayed rectifier K+ current, IKr• Ranolazine also increases the activity of pyruvate decarboxylase, a key regulator of glucose metabolism, most likely because of loss of inhibition of the end products of the beta-oxidation (NADH, acetyl-CoA)
46. Implantable Cardioverter Defibrillators• ICD as primary prevention of all-cause mortality in well- treated NYHA Class II and III patients with LVEFs of less than or equal to 30 percent There is generally a weaker recommendation for such patients with EFs of 31 to 35 percent.• unless they have a poor chance of survival related to some comorbidity or a contraindication to the implantation or use of this device.• Implantable cardioverter defibrillators are also strongly recommended in patients with hemodynamically destabilizing vt, vf, and resuscitated cardiac arrest, for the secondary prevention of mortality.
47. Cardiac Resynchronization Therapy• Biventricular pacing is accomplished through simultaneous pacing of both the left and right ventricles, with standard right sided transvenous lead placement as in dual-chamber and defibrillator lead implantation• CRT for patients with LVEFs less than or equal to 35 percent, normal sinus rhythm, and NYHA functional Class III or ambulatory Class IV symptoms despite recommended optimal medical therapy, who have ventricular dyssynchrony, unless contraindicated.• Currently, guidelines define ventricular dyssynchrony as a QRS duration of at least 120 msec.
51. INDICATIONS• 1.Decompansated end stage chronic heart failure• 2.Acute refractory cardiogenic shock• Long term devices are preferred for chf• Short term devices for acute refractory cardiogenic shock• Other consideration includes need for biventricular support,cost.device related risks,patient characteristics
52. SUMMARY• The severity of clinical presentation of AHFS does not always correlate with long-term outcomes• LV dysfunction and its progression are the main cause of the high rehospitalization rates and of the mortality observed in HF• Hemodynamic improvement should result from amelioration of myocardial dysfunction rather than from myocardial stimulation that may result in myocardial injury• Viable but dysfunctional myocardium, which may potentially be salvageable, is presumably present in a number of patients with AHFS and may represent an important target for therapy.• Myocardial or kidney injury may occur during an episode of AHF and may contribute to the progression of HF.•