DIASTOLIC DYSFUNCTION

DIASTOLIC DYSFUNCTION AGING OR DISEASE

Intro • CHF afflicts over 3 million Americans • 400,000 new cases &800,000 hospitalizations annually • CHF : primarily a disorder of the elderly • Among the elderly, it is the most frequent hospital discharge • consumes over 10 billion health care dollars

Intro • Nearly half o f HF patients have normal LV systolic function : diastolic dysfunction • Diastolic dysfunction is a major contributor to hospital admissions • CV conditions associated with diastolic dysfunction: particularly high prevalence in the elderly • associated with high morbidity

Intro • Major change in demographics in North America • mean age of population increasing significantly: fastest growth in 65 yrs and older • In the US, 40% of non-interest federal money spending goes to this population • population of the elderly will increase x4 by 2030

Intro • CV disease is the commonest cause of morbidity &mortality in this group, yet few studies • elderly were systematically excluded from the trials • Thus, CV specialists are least prepared to deal with an age group that includes most pts with CV disease, and that is growing

Age Related Changes

Aging & CV Finction • Increased systemic blood pressure & systemic vascular resistance : diastolic dysfunction • Increased LV stiffness • Change in diastolic LV filling pattern: reduced early diastolic filling & increased late atrial filling

Altered Diastolic Filling • Confounding influences: • 1. Wide variety of CV disorders are accompanied by altered diastolic filling; most are common in the elderly • 2. Doppler parameters could be altered by changes in HR, preload, afterload, & contractility (frequently seen with aging) • 3. Practically all CV meds alter Doppler diastolic filling

Aging or Disease • Data showing that altered diastolic filling pattern is, independent of confounding factors, likely a primary, biologic aging effect • E/A <1.1 in the elderly • E/A > 1.2 in the young • no overlap

Population Doppler Filling Data • Aging alone is one of the most potent factors ( perhaps the most potent factor), affecting the E/A ratio • Aging or Disease? • CHS data : examining diastolic filling in 5000 community-dwelling elderly • Figure 3

CHS Data • E/A average 1.0 in the elderly subgroup of subjects 65-100, with range of 0.65-1.50 • Also, substantial overlap between this healthy subgroup & subgroups with manifest CV disease, including HTN, HF, ischemic heart disease • Figure 4

Aging or Disease • Aside from normative reference ranges (Figure 3 & 4), three additional factors can aid in determining abnormal from normal: • 1. Filling patterns • 2. Early deceleration time • 3. Pulmonary vein flow

LV Diastolic Filling Pattern

Normal Pattern • Seen in healthy young & middle-aged persons • In sinus rhythm, there are 2 peaks in doppler diastolic filling profile • Peaks occur in response to the pressure gradient between the LA & LV: • 1. Early in diastole following mitral valve opening when LV pressure falls below LA pressure;

Normal Pattern • 2. Late in diastole when atrial contraction increases LA pressure above LV pressure • Predominant rapid filling early in diastole with modest additional filling during atrial contraction • Quantified by measuring the peak early diastolic flow velocity (E) & peak flow velocity during atrial contraction (A), E/A>1

Etdec • Time required for deceleration of the early diastolic flow (Etdec) & the rate of deceleration are additional elements that help characterize LV filling pattern • In normal young & middle-aged subjects, Etdec>190 msec • Etdec most helpful • Etdec increases slightly with age

Altered LV Filling PatternDelayed Relaxation • Reduced peak rate & amount of early filling • Relative importance of atrial filling is enhanced resulting in reversed E/A • Decreased peak rate of early filling owing to a decreased early diastolic LA to LV pressure gradient, caused by a slowed rate of LV relaxation • Etdec is either similar or slightly prolonged

Delayed Relaxation • Can be seen in pts with LVH, arterial HTN, CAD • Most are asymptomatic, & vigorous atrial contraction compensates for the reduced early filling caused by impaired LV relaxation • This pattern is normally seen in healthy older persons • NOT ABNORMAL

Pseudo-Normalization • Abnormal • E/A >1 as seen in young normals (only the young pattern can be normal!!!) • Pattern seen in patients with more severe impairment of diastolic function • results from an increase in LA pressure that compensates for the slowed rate of LV relaxation

Pseudo-normalization • Restores early diastolic LV pressure gradient to the baseline level seen in younger persons • shortened early deceleration time (Etdec) owing to increased LV stiffness • Animal studies have shown that there is a fixed relationship between Etdec & LV chamber stiffness(shortened Etdec)

Pseudo-Normalization • Relatively uncommon • “false-positive “ pattern seen with significant MR, which is more common in the elderly • In false -positive pseudo-normalization Etdec is normal

Restrictive pattern • Early filling is increased abnormally, even above that seen in young normals, exceeding the filling velocity seen during atrial contraction • E/A increased abnormally, often greater than two • increased early filling results from an increase in LA pressure that more than offsets delayed LV relaxation

Restrictive pattern • The deceleration rate of early flow is rapid because of increased LV stiffness • short Etdec • This pattern is seen in pts with severe diastolic dysfunction, pulmonary congestion, end-stage DCM • imparts substantially increased mortality • its prognostic power persists regardless of age

Pattern Summary • Each abnormal pattern results from a variable combination of delayed early relaxation, increased LA pressure, and increased LV chamber stiffness • a continuum from normal to severe diastolic dysfunction • Unifying themes: increasing LV chamber stiffness & decreasing Etdec

Diastolic Heart Failure • HF is the commonest hospital discharge diagnosis in the elderly • HF in the elderly is the major cause of death & disability in US: fatality up to 25%; 90-day hospital readmission up to 50% • DHF is a clinical syndrome manifested by HF symptoms & normal or even small LV cavity size with thickened walls & nl LV EF

DHF • First descibed by Luchi et al in 1982 • Luchi suggested this syndrome could account for 1/3 to 1/2 of cases of CHF • It has also been found that compared with those with reduced EF, those with a normal EF were much more likely to be women • Population-based databases (CHS) suggest that over 50% of the elderly with CHF have nl EF

DHF pathophysiology • Pts with this syndrome have an inability to increase stroke volume by Frank-Starling mechanism despite severely increased LV filling pressure, indicative of diastolic dysfunction • Severe exercise intolerance due to a reduction in exercise cardiac output and early lactate formation

DHF • Primary symptom, similar to systolic dysfunction, is exercise intolerance, manifested as exertional dyspnea & fatigue • increased prevalence of systemic hypertension in diastolic HF • Severe HTN is frequently present during the early phases of acute episodes of CHF in such pts

DHF • Systemic HTN increases afterload • LV diastolic relaxation is sensitive to increased afterload • Neurohormonal activation: atrial natriuretic peptide & barin natriuretic peptide have been found to be substantially elevated, similar to systolic dysfunction

DHF Summary • Hallmarks of the syndrome: older age, female preponderance, a history of hypertension, nl or small LV cavity size with significant hypertrophy, normal or supernormal contractility, increased LV filling pressure, and increased neurohormonal activation

DHF Summary • Therapeutic goals should include: mild reduction in LV filling pressure, controlling systemic arterial pressure, LVH regression, improving LV diastolic distensibility, and mitigating the effect of neuroendocrine activation.

DIASTOLIC DYSFUNCTION