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Diastolic Dysfunction

Definitions
Diastole encompasses the time period during which the myocardium loses its ability to generate force and shorten and returns to an unstressed length and force. Diastolic Dysfunction occurs when these processes are prolonged, slowed or incomplete. Diastolic Dysfunction is an abnormality of diastolic function and does not characterize clinical status of an individual. It can occur regardless of whether the EF is normal or abnormal and whether the patient is symptomatic or asymptomatic.

Diastolic Function

As many as 30 to 50 percent of patients with symptomatic HF exhibit diastolic rather than systolic dysfunction. Diastolic dysfunction is more common in women and the elderly, and in the latter it may be the dominant form of HF. Additional risk factors for diastolic dysfunction include a history of hypertension and diabetes mellitus.

Causes of Heart Failure

VISUALPATTERNS

PREVALENCE

AGEDISTRIBUTION

SURVIVALPATTERNS

A dramatic 5-year excess mortality was observed in patients with preserved and reduced EF compared to the expected survival

THEDIAGNOSISOFHFPEFREQUIRESTHREE CONDITIONSTOBESATISFIED:
Presence of signs or symptoms of CHF Presence of normal or only mildly abnormal left ventricular systolic function (LVEF > 4550%) Evidence of diastolic dysfunction (abnormal left ventricular relaxation or diastolic stiffness) ESC Guidelines for the Diagnosis and Treatment
of Acute and Chronic Heart Failure Eur Heart J 2008;29:2388-2442

PLASMABNPLEVELS

Bursl F et al JAMA 2006

LEFT ATRIAL SIZE:


Sensitive indicator of Diastolic Function 1. < 28ml/m2; Normal 2. >40ml/m2; Severe LVDD

PHYSIOLOGYOFDIASTOLE

PATTERNSOFDIASTOLICDYSFUNCTION

CONCEPTUAL-PHYSIOLOGICAL APPROACHES CARDIAC PERFORMANCE & METHODS OF ASSESSMENT

De Keulenaer, G. W. et al. Circulation 2009;119:3044-3046

INDICESOFCARDIACPERFORMANCE

LVSYSTOLICDYSFUNCTION(MUSCULARPUMP) INHFNEF

Mean Regional myocardial (Mean SM) Sustained systolic velocity by TDI

Systolic mitral annular amplitude by long axis M mode (S lax)

Determinants of Diastolic Function


Myocardial relaxation Load Inactivation (Ca homeostasis, myofilamentsmyofilaments, energetics energetics) Non uniformity Passive properties of ventricular wall Myocardial stiffness (cytoskeleton, extracellular matrix) Wall thickness Chamber geometry Other determinants Structures surrounding the ventricle (pericardium, lungs, remaining cardiac chambers) Left atrium, pulmonary veins and mitral valve Heart rate
Leite-Moreira, Heart 2006;92;712-718 Heerebeeket al., Circulation. 2006;113:1966-1973

Determinants of Myocardial Inactivation


Ca2+ 2+ homeostasis - Ca2+ concentration Sarcolemmal and SR Ca Ca2+ 2+ transport Modifying proteins ( phospholambin phospholambin, calmodulin calmodulin, calsequestrin calsequestrin) Myofilaments Tn-C Ca Ca2+ 2+ binding TN-I phosphorylation Ca2+ sensitivity / -MHC ATPase ratio Energetics ADP/ATP ratio ADP and Pi concentratio
Leite-Moreira, Heart 2006;92;712-718 Heerebeeket al., Circulation. 2006;113:1966-1973

Left Ventricular Pressure-Volume Loops in Systolic and Diastolic Dysfunction A .In systolic dysfunction, LV contractility is depressed, and the end-systolic pressure-volume line is displaced downward and to the right. B. Normal C. In diastolic dysfunction, the diastolic pressure-volume line is displaced upward and to the left.
NEJM 2004;351:1097-1105

JACC 1997;30:8-18

Braunwalds Heart Disease 8th Edition

Diastolic Dysfunction

Persson et al., JACC Vol. 49, No. 6, 2007:68794

Epidemiology

A. A large study of patients (n=4596) hospitalized with HF at a single institution over a 15 year period demonstrated that the percentage of patients who have a normal EF has increased over time B. This was the result of an increased number of admissions for HF with a normal EF; the number of admissions for HF with reduced EF remained stable

N Engl J Med 2006; 355; 251

EPICA Study

Population based study showing increased prevalence of Diastolic HF with age and with female gender

Eur Journal Heart Failure 2002;4:531-539

Diastolic Dysfunction in the Community


In 2042 random sample of residents in Olmsted County aged 45 yrs or older Presence of CHF was 2.2% with 44% having an EF > 50% 20.8% had mild DD, 6.6% moderate DD, and 0.7% had severe DD

JAMA 2003;289:194-202

Survival: What we thought

Zile MR. Treatment and prognosis o f diast olic heart failure . www .utdol. Com 3/ 2/ 07

Diastolic Dysfunction Survival

The survival rate was higher among patients with preserved ejection fraction although, the difference was small

Redfield et al., N Engl J Med 2006; 355; 251

Survival for patients with heart failure with normal EF has not improved

Survival for patients with HF with reduced EF was shown to be improving over time

No such improvement was observed for patients with HF no EF.


Redfield et al., N Engl J Med 2006; 355; 251

Morbidity Myth

Smith et al. JACC 2003; Vol. 41,1510-8

L. Mandinovet al. Cardiovascular Research 45 (2000) 813 825

Treatment

In contrast to treatment of HF due to reduced LVEF, few clinical trials are available to guide the management of patients with HF and relatively preserved LVEF Trials done have been small or have produced inconclusive results

JAMA 2003;289:194-202

Comorbid Conditions
Age HTN- most commonly associated cardiac condition in pts with HF and normal EF Obesity Atrial fibrillation Female gender Diabetes Renal dysfunction Ischemic Heart Disease
JAMA 2003;289:194-202

Treatment
The management of patients with Diastolic Dysfunction is based on control of physiological factors that are known to exert important effects on ventricular relaxation: Blood pressure - Heart rate - Blood volume - Myocardial Ischemia
JAMA 2003;289:194-202

THERAPEUTIC CONCEPTUAL MODEL


Cardiac Physiology ? Ca-Blockers, ? ACE, ARB, Improve Diastolic Relaxation Slow HR > Improve Filling Ca-Blockers, B-Blockers Improve Myocardial oxygen Supply/demand balance Ca-Blockers, B-Blockers, Reduce Congestion
nitrates Diuretics

? ACE, ARB, Aldosterone, Diuretics, nitrates

? ACE, ARB, Aldosterone

Peripheral Physiology Lower BP decrease afterload Improve Conduit Vessel Function

Structure Regression of cardiac hypertrophy Reduce fibrosis

Regression of LVH

Zile MR. Treatment and prognosis o f diast olic heart failure . www .utdol. com

Regression of LVH

Zile MR. Treatment and prognosis o f diast olic heart failure . www .utdol. com

Does Aldosterone Count as Part of the RAAS ????

ImCardia Device

ImCardia Reduces LVEDP

Conclusions
Diastolic Dysfunction is responsible for about one- half of cases of CHF. Morbidity and mortality associated is high and similar to LV systolic dysfunction. Older age, hypertension and female sex are commonly associated. Non invasive imaging techniques can be used for diagnosis. Further studies are needed to determine optimal treatment strategies.