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left ventricular diastolic dysfunction; heart failure with preserved ejection fraction (HFpEF)

Etiology: 1) common causes a) hypertension, especially systolic hypertension (most common cause) [3] b) ischemic heart disease c) aortic stenosis 2) less common causes a) hypertrophic cardiomyopathy b) restrictive cardiomyopathy - primary restrictive cardiomyopathy - amyloidosis - hemochromatosis - sarcoidosis 3) risk factors* a) myocardial ischemia b) myocardial fibrosis c) left ventricular hypertrophy d) aging e) left ventricular pressure overload f) parent with LV diastolic dysfunction [9] g) anemia * implantable defibrillator is a negative risk factor [34] Epidemiology: 1) most common form of heart failure in the elderly [34] - 55% of patients with heart failure [15] 2) incidence increases with age a) 28% of patients > 45 years b) 15% of middle-aged adults c) 40% of elderly patients d) 51% of elderly patients, mean age 72 years [22] 3) slightly more common in obese patients - 57% in obese elderly, mean age 72 years [22] 4) less common in blacks than whites [34] 5) 31-47% of patients hospitalized with heart failure [8] 6) more common in women than men (4:1) [7] Pathology: 1) inability of the left ventricle to fill normally during diastole 2) decreased compliance of the ventricle walls 3) LV ejection fraction is generally normal 4) elevated pressures required for ventricular filling 5) elevated pulmonary capillary pressure with pulmonary congestion may occur (diastolic heart failure) 6) reduced left ventricular filling volume leads to lowered stroke volumes & symptoms of poor cardiac output 7) shift in filling pattern to later in diastole, with increased dependence on atrial kick 8) compensatory left atrial enlargement predisposes to atrial fibrillation 9) pulmonary edema 10) left heart failure leads to right heart failure - peripheral edema 11) poor nitric oxide availability suggested to play a role [50] Clinical manifestations: 1) hypertension is present in 60% of patients with left ventricular diastolic dysfunction 2) exertional dyspnea & progressive exercise intolerance [63] 3) signs of right-sided heart failure - peripheral edema, rales 4) acute diastolic dysfunction may result in pulmonary edema - pulmonary edema more likely than peripheral edema with 1st episode of heart failure [64] 5) orthostatic hypotension may result from reduced stroke volume with increase in heart rate 6) wheezing may occur 7) poor exercise capacity 8) S4 heart sound 9) bradycardia common [37] Laboratory: - serum B-type natriuretic peptide (serum BNP) may be elevated [7] - useful for establishing cardiac vs non-cardiac causes of dyspnea - caution: serum BNP increases with age - caution: serum BNP may be normal, particularly in obese or patients with dyspnea on exertion only [40] - urine proteins associated with decreased risk of hospitalization for heart failure & for death include: - angiopoietin-like protein 2 (ANGPTL2) RR=0.57 - alpha amylase 2A (AMY2A) RR=0.55 - deoxyribonuclease-1 (DNASE1) RR=0.57 [71] - higher urinary levels of proteins involved the following processes portend a lower risk of death or hopsitalization for heart failure: - fibrosis (collagen VI alpha-1, collagen XV alpha-1 - metabolism (pancreatic alpha-amylase 2A/B, mannosidase alpha class 1A member 1 - inflammation (heat shock protein family D member 1, inducible T cell costimulatory ligand) [71] Special laboratory: 1) electrocardiogram a) left ventricular hypertrophy b) left atrial enlargement c) low voltage may be seen with cardiac amyloidosis 2) echocardiogram (diagnostic procedure of choice) a) LV ejection fraction > 40-50% [24]; > 50% [3] - LV ejection fraction > 60% common with 1st episode of heart failure b) decreased LV end-diastolic volume c) non-dilated, normally contracting myocardium d) left ventricular hypertrophy e) reveals presence & severity of outflow obstruction f) reversal of normal left ventricular diastolic trans- mitral inflow pattern (E/A < 1.0)* g) left atrial enlargement h) elevated filling pressures i) normal physiologic dependence on late, active filling with increasing age 3) H2FPEF risk score for patients presenting with dyspnea 4) exclusion of coronary artery disease (CAD) a) exercise stress testing b) stress echocardiography c) myocardial perfusion imaging 5) right heart catheterization if indeterminate noninvasive testing or evidence of pulmonary hypertension [40] * Early to Atrial ratio - increased dependence of LV filling on atrial contraction Complications: 1) congestive heart failure (with normal systolic function) a) increased risk of mortality 3.5 fold [5,15] b) despite increase in mortality, death from heart failure is rare 2) syncope in association with tachycardia - especially with paroxysmal atrial fibrillation 1] loss of atrial kick -> reduced left ventricular filling 2] diminished stroke volume & cardiac output 3) pulmonary hypertension - pulmonary venous hypertension, pulmonary edema - pulmonary hypertension associated with 24% 1 year mortality & 48% 5 year mortality [48] 4) independent predictor of mortality [6,8] - sudden cardiac death accounts for ~25-30% of deaths in clinical trials [43] 5) hospitalized patients with LV diastolic dysfunction discharged with systolic BP < 120 mm Hg at significantly higher risk of 30-day, 1-year, & long-term all-cause mortality [47] 6) comorbidities interacting adversely with HFpEF - atrial fibrillation, hypertension, coronary artery disease, diabetes mellitus, chronic kidney disease, obstructive sleep apnea, obesity [66] Differential diagnosis: - pericardial disease a) constrictive pericarditis b) pericardial effusion - transthyretin cardiac amyloidosis - restrictive cardiomyopathy - right heart failure, peripheral congestion - infiltrative heart disease on echocardiogram - restrictive filling pattern - biatrial enlargement [68] Management: 1) goals of therapy a) reduce the state of cardiopulmonary congestion - reduce volume overload b) maintain atrial contraction c) decrease heart rate d) prevent/treat myocardial ischemia e) control hypertension, target systolic BP < 130 mm Hg [3] - no difference in hospital readmission or mortality in patients with systolic BP > 130 mm Hg vs < 130 mm Hg [57] - systolic BP <120 mm Hg associated with poor outcomes [57] f) attenuate neurohormonal activation - renin-angiotensin-aldosterone axis - sympathetic tone g) prevent pulmonary fibrosis h) improve ventricular relaxation 2) pharmacologic agents a) SGLT-2 inhibitor (flozin) indicated [3,66] - empagliflozin, dapagliflozin [62] - lower risk for hospitalization for heart failure [3,72] - flozins may improve maximal exercise capacity & quality of life in patients with heart failure HFrEF or HFpEF [70] b) semaglutide improves symptoms of obesity-related heart failure [69] c) little evidence of improved outcomes other than flozins or GLP-1 agonists [24,40] d) diuretics for volume overload - increase current diuretic (preferably loop diuretic) for volume overload - loop diuretics reduce HF hospitalization - intravenous diuretic for patient not responding to escalating oral diuretic [68] - spironolactone (antifibrotic?) - not associated with clinical improvement [26,31,41] - improves diastolic function & quality of life [24,59] - reduces hospitalization in patients with increased serum BNP [24,59] - may have mortality benefit for women [51] - not all loop diuretics may be equal [41] - longer-acting chlorthalidone may be more effective than HCTZ [24] - may reduce LVH (8% [7]) e) beta blockers - theoretically beneficial for symptomatic disease - decrease myocardial oxygen demand - diminish heart rate with increase of LV filling - may promote regression of LVH (6%) [7]) - NO evidence to support a favorable influence on natural course of disease [41] - marginal reduction in early mortality (18% vs 20%) - only metoprolol succinate, carvedilol & bisoprolol reduce mortality [3] - reduction in mortality & hospitalization, but not statistically significant [20] - do NOT enhance myocardial relaxation - bradycardia complicates titration of beta-blocker [37] f) renin-angiotensin system antagonists - reduce HF hospitalization [71 - angiotensin converting enzyme (ACE) inhibitors - may reduce LVH (10% [7,14] - equivocal benefit on mortality & hospitalization for heart failure [32] - mortality benefit only in patients with chronic renal failure (GFR < 45 L/min/1.73 m2) (RR = 0.81) [33] - angiotensin receptor antagonist (ARB) - may reduce LVH (13% [7]) - irbesartan fails to improve outcomes (death, hospitalization for cardiovascular events) [17,21] - may improve all-cause mortality [25], no effect on mortality [72] - ACE inhibitors & ARBS have not improved prognosis in clinical trials [41] - useful to control hypertension in patients on diuretic - sacubitril/valsartan (ARNI) may be better than ACE inhibitor [52] - reduces cardiovascular & renal events in patients with mild HFrEF or HFpEF [67] g) calcium channel blockers - verapamil & diltiazem improve indices of LV diastolic dysfunction - may reduce LVH (11% [7]) - reserve for patients intolerant of beta-blockers [3] h) nitrates - treatment of ischemia - reduced preload i) nebulized inorganic sodium nitrite* TID of no benefit j) digoxin of no benefit [13] k) lowering blood pressure improves LV diastolic dysfunction regardless of drug type [16] l) sildenafil of no benefit [27] m) beta-blockers, ACE inhibitors, ARBs, or calcium-channel blockers may be effective in lowering blood pressure [36] n) any drug class that improves LV diastolic dysfunction reduces hospitalization (14% vs 16% with placebo), number needed to treat = 64 [46] o) no individual medication class yields significant improvements [46] p) benefit of any agent unproven [24] q) limitations of one-size-fits all approach may give rise to personalized medicine approach [44] 3) other measures a) salt restriction - adding any salt to cooking lowers risk for cardiovascular events & hospitalization for heart failure [61] - unclear whether participants in study were taking spironolactone b) renal dialysis - metoprolol (dialyzable) but not carvedilol (poorly dialyzable) reduces mortality during the first 6 months of renal dialysis when LVEF > 40% (RR=0.68) [58] c) plasmapheresis d) cardioversion for atrial fibrillation e) sequential AV pacing f) measures for ischemia - coronary artery bypass surgery - angioplasty g) radiofrequecy ablation of accessory conduction tract h) endurance exercise is effective in improving peak oxygen consumption [56] - exercise & calorie restriction in obese patients to achieve weight reduction improves exercise capacity [38] - high-intensity interval exercise no better than continous moderate intensity exercise in patients with HFpEF [56] i) extra virgin olive oil improves cardiopulmonary exercise testing [54] j) anticoagulation fails to provide a substantial benefit - reduces risk of stroke at cost of increased bleeding [53] 4) investigational - GDF11 reverses LV diastolic dysfunction in mice [28] * rationale is that poor nitric oxide availability may play role in LV diastolic dysfunction [50]

Related

aortic valvular stenosis (AS) echocardiography hypertension (HTN, high blood pressure, HBP) hypertensive heart disease hypertrophic cardiomyopathy (HCM), including idiopathic hypertrophic subaortic stenosis (IHSS) left ventricular hypertrophy (LVH) restrictive cardiomyopathy transthyretin cardiac amyloidosis; amyloid transthyretin cardiomyopathy (ATTR-CM)

General

diastolic dysfunction left ventricular failure diastolic heart failure

References

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