Diastolic Dysfunction: Hypertension to Hypertrophy to Heart Failure

Transcription

1 Diastolic Dysfunction: Hypertension to Hypertrophy to Heart Failure Dr. Shelley Zieroth FRCPC Assistant Professor, Cardiology, University of Manitoba Director of Cardiac Transplant and Heart Failure Clinics St Boniface General Hospital, Winnipeg, MB Head, Medical Heart Failure Program WRHA Cardiac Sciences Program

2 Objectives Definitions Diagnosis Epidemiology Treatment

3 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. Circulation 2002;105:

4 Causes of Heart Failure Courtesy Dr. Mancini

5 Determinants of Diastolic Function Myocardial relaxation Load Inactivation (Ca homeostasis, myofilaments, 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; Heerebeek et al., Circulation. 2006;113:

6 Determinants of Myocardial Inactivation Ca 2+ homeostasis Ca 2+ concentration Sarcolemmal and SR Ca 2+ transport Modifying proteins (phospholambin( phospholambin, calmodulin, calsequestrin) Myofilaments Tn-C C Ca 2+ binding TN-I phosphorylation Ca 2+ sensitivity α/ β -MHC ATPase ratio Energetics ADP/ATP ratio ADP and Pi concentration Leite-Moreira, Heart 2006;92; Heerebeek et al., Circulation. 2006;113:

7 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:

8 JACC 1997;30:8-18 Braunwald s Heart Disease 8 th Edition

9 Diastolic Dysfunction

10 Persson et al., JACC Vol. 49, No. 6, 2007:687 94

11 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

12 EPICA Study Population based study showing increased prevalence of Diastolic HF with age and with female gender Eur Journal Heart Failure 2002;4:

13 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:

14 Survival: What we thought Reproduced from: Zile MR. Treatment and prognosis of diastolic heart failure. 3/2/07

15 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

16 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

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

18 L. Mandinov et al. Cardiovascular Research 45 (2000)

19 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

20 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

21 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

22 Regression of LVH Reproduced from: Zile MR. Treatment and prognosis of diastolic heart failure. 3/2/07

23 The RAAS

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

25 ImCardia Device

26 ImCardia Reduces LVEDP

27 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.