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Patients with diastolic heart failure likely represent the largest group of patients with a cardiovascular disorder of substantial public health impact.

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Presentation on theme: "Patients with diastolic heart failure likely represent the largest group of patients with a cardiovascular disorder of substantial public health impact."— Presentation transcript:

1 Patients with diastolic heart failure likely represent the largest group of patients with a cardiovascular disorder of substantial public health impact who have not been systematically studied. Am J Med, 2000 Diastolic Heart Failure: Miles to Go Before We Sleep Lynne W. Stevenson

2 Systolic HF Diastolic HF


4 NL EF 51% NL EF 51% Low EF 49% Low EF 49% Vasan et al J Am Coll Cardiol 1999 Kitzman et al Am J Cardiol 2001 NL EF 55% NL EF 55% Low EF 45% Low EF 45% 43% EF>50% 57% EF<50% Diastolic Heart Failure in the Community: Incident cases (11 to 78%!!!) Senni et al Circulation 1998

5 Prognosis of diastolic HF in Olmsted country, Minnesota, 1991 (LVEF 50%) SENNI et al., Circulation 1998; 98: 2282-2289. n = 59 (43%) Age = 78 12y NYHA III-IV = 69% Female = 69% HTN = 58% CAD = 31% Cardiomegaly = 64% 1 and 5 yrs mortality rate 24% and 52%

6 Ahmed A et al: Am Heart J 2002 Smith GL et al: JACC 2003 Diastolic and Systolic HF: Better Prognosis vs Worst Prognosis Varadarajan P et al: J Cardiac Fail, 2003 (n = 2.258)

7 Why so different results? Over and underdiagnosis Age of patients: it may be that the prognosis of DHF in elderly pts (>65 yo) is different Choice of diagnostic criteria/definition for CHF Type of population studied (hospitalized, out-pts, echo lab, population-based) Incident or recurrent CHF Timing of EF evaluation Racial differences Senni M & Redfield MM : JACC 2001

8 Heart Failure with Preserved Systolic Function or Diastolic Heart Failure Heart Failure with Preserved Systolic Function is a descriptive approach that makes no assumptions about our approach that makes no assumptions about our knowledge about the pathophysiology of this disorder knowledge about the pathophysiology of this disorder (Burkoff D, Maurer MS, Packer M. Circulation 2003) (Burkoff D, Maurer MS, Packer M. Circulation 2003) The predominant pathophysiological cause of heart failure in these patients is abnormal diastolic function. Therefore, is appropriate to use the term Diastolic Heart Failure to describe the abnormalities in these patients (Zile MR, Baicu CF, Gaash WH. NEJM 2004)


10 Metabolism of collagen and interstitial e perivascular fibrosis in hypertension Lopez B et al. Hypertension 2001 Perivascular fibrosis Decrease coronary reserve Schwartzkopff B. Circulation 1993 Kozakova M. Hypertension 2003

11 Progressivo Aumento del Rischio di Scompenso Cardiaco con laumento della Massa VS Gottdiener JS. JACC 2000;35:1628 1,0 1,1 1,5 1,9 2,8 0,0 0,5 1,0 1,5 2,0 2,5 3,0 Rischio Relativo di Scompenso Cardiaco Q1Q2Q3Q4Q5 Quintili di Massa Ventricolare Sinistra (ECG) 5888 soggetti Età > 65 anni 5888 soggetti Età > 65 anni The Cardiovascular Health Study

12 Patterns of Left Ventricular Hypertrophy (LVH) 1. Normal Pattern normal LV Mass normal RWT (<0.43) 2. Eccentric Hypertrophy increased LV Mass normal RWT (<0.43) 3. Concentric Hypertrophy increased LV Mass increased RWT (>0.43) 4. Concentric Remodeling normal LV Mass increased RWT (>0.43) 1. Normal2. Eccentric Hypertrophy 4. Concentric Remodeling Relative Wall Thickness (RWT) 0.43 LV Mass Index (LV MI) g/m 2 125 g/m 2 for M 110 g/m 2 for F Threshold: 3. Concentric Hypertrophy. Eventi CV + Eventi CV +++ Eventi CV ++

13 Cardiovascular events: LV mass and Midwall Fractional Shortening de Simone G et al. Circulation 1996;93:259-265 ? ?

14 J Card Fail 2002 ; 8(2): 101-7

15 Ventricular–vascular interaction in DHF (arterial elastance) Kawaguchi M et al. Circ 2003 Hypertensive pts symptomatic on effort Hypertensive pts symptomatic on effort Handgrip test Handgrip test

16 Circulation 2008; 117: 2051

17 Factors Responsible for Increased LV Diastolic Pressure Passive chamber stiffness Relaxation Diastolic pressure Asynchrony Ischemia Abnormal Ca ++ flux Cellular disarray Fibrosis Concentric hypertrophy Stiff titina Stiff titina

18 The Natural History of Diastolic Function and LV Filling 40 0 Normal Abnormal relaxation Pseudo- normalization Restriction (reversible) Restriction (irreversible) Mean LAP TAU NYHAI-IIII-IIIIII-IVIV GradeIIIIIIIV Mean LAP TAU NYHAI-IIII-IIIIII-IVIV GradeIIIIIIIV N-

19 Restrictive filling After therapy Abnormal relaxation

20 In absence of a comprehensive diastolic assessment Simple echocardiographic criteria - left atrial enlargement - normal LV dimension - left ventricular hypertrophy - wall motion abnormalities - elevated pulmonary pressures


22 Clinical differentiation of Diastolic vs. Systolic Dysfunction in patients with Heart Failure Systolic function Diastolic function SexMaleFemale Past historyMyocardial infarction Hypertension (CHD) HypertensionCKD, COPD, Obesity, OSAS DiabetesDiabetes, Anemia Chronic valvular insuffAortic stenosis Dilated CMPHCMP, Restrictive CMP ComorbiditiesNot frequentFrequent PresentationYounger than 65 years65 years or older Progressive SOBAcute pulmonary oedema Physical examinationDisplaced PMISustained PMI S3 gallopS4 gallop Radiographic findingsPulmonary congestionPulmonary congestion CardiomegalyNormal sized heart ElectrocardiogramQ wavesLVH, AF EchocardiogramDecreased LVEFNormal or increased LVEF Tresh DD et al. J Am Geriatr Soc 1995; 43:1035-1042.

23 Prevalence of CHD and Hypertension: Framingham Heart Study Subjects With Cardiac Failure 11 15 3037 40 19 37 0 20 40 60 80 100 MenWomen Frequency (%) CHD alone CHD + HTN HTN alone No HTN or CHD

24 Quality of Life in Older Patients with Systolic and Diastolic Heart Failure Jaarsma et al., Eur J Heart Fail 1999

25 CHF vs. Non CHF and CHF Systol.vs Non-Systol. In 452 Pts.with CHF: B-Type Natriuretic Peptide 0.0 0.51.0 0.5 1.0 0.0 0.5 1.0 AUC = 0.66;P<0.001 0.0 0.5 1.0 0.5 1.0 300 AUC = 0.90;P<0.001 1-SPEC.1-SPEC. 0.0 0.5 1.0 400 200 100 300 200 100 CHF vs. Non- CHF CHF Systol. vs. Non-Syst SENS.SENS. 1) BNP is accurate in distinguishing CHF and Non-CHF (BNP=100 pg/ml: Sens 90, Spec 73, Accur. 81) 2) BNP is not accurate in distinguishing Systol. Vs Non-Systol. CHF (BNP=100 pg/ml: Sens 95, Spec 14, Accur. 66) BNP pg/ml Maisel et al., JACC.2003

26 Clinical presentation –Acute pulmonary edema Response to treatment –Generally rapid Clinical course –Frequent relapses –Mild symptoms / Few LV abnormalities between the acute episodes Diastolic heart failure. Paroxysmal or chronic? Banerjee P, Clark AL, Nikitin N, Cleland JG. (Eur J Heart Fail. 2004 Jun;6(4):427-31) Diastolic Heart Failure is predominantly Acute Heart Failure

27 Do they need the same treatment? same treatment?

28 The Italian Network on Congestive Heart Failure (IN-CHF) Adjusted survival among outpatients with CHF, 1995 and 1999 Diastolic HF (FE>40%) P<0.02 TEMPORAL TRENDS IN SURVIVAL Systolic HF P<0.0001 Senni M, De Maria R, Gregori D et al.: J Card Fail 2005

29 Treatment of Diastolic Heart Failure There have been no large RCTs to establish the optimal evidence-based treatment Difficulties inherent in verifying the diagnosis Heterogeneity of the underlying causes Occurrence in elderly patients with multiple coexisting illnesses In the interim, the treatment remains empirical (aggressive treatment of underlying disease and precipitating factors) N Engl J Med 2001; 344: 56-59. Editorial. Diastolic HF – No Time to Relax.

30 Treatment of cardiac pathophysiological mechanisms Control congestion Diuretics Maintain atrial contractionCV for A Fib, AA drugs Prevent or reduce LVHAntihypertensive drugs Surgery (AVR for AS) Prevent/treat ischemia -blocker, Ca ++ entry blocker, Nitrates, revascularisation Reduce HR/increase -blocker, Ca ++ entry blocker, filling timeDigitalis (AF) Avoid LVOT obstructionAvoid arterial vasodilatators Reduce interstitial fibrosisAce-i/ARBs, antialdosterone Control associated illnessSpecific interventions Goal of therapyMethods of treatment

31 Meta-analysis of randomized, controlled trials of LV hypertrophy regression in essential hypertension -16 -14 -12 -10 -8 -6 -4 -2 0 0 Diuretics b-blockers Ca- antagonist Ca- antagonist ACE- inhibitors ACE- inhibitors ARBs -8% -6% -11% -10% -13% LV mass reduction (%) LV mass reduction (%) 80 randomized controlled trials; 4,113 patients Klingbeil AU et al. Am J Med. 2003;115:41-46.

32 Greater reduction in LVH during antihypertensive therapy is associated with a lower risk of HF Okin PM. Ann Intern Med. 2007;147:311-319.

33 Effects of antihypertensive treatment on the development of HF in hypertensive patients ACEI vs. placebo CA vs. placebo More vs. less ARB vs. control ACEI vs. D/BB CA vs. D/BB ACEI vs. CA 219/8233 104/3382 54/7494 302/5935 547/12498 732/23425 502/10357 269/8246 88/3274 72/13394 359/5919 809/18652 850/29734 609/10345 -5/-2 -8/-4 -4/-3 -2/-1 +2/0 +1/0 +1/+1 0.82 (0.69-0.98) 1.21 (0.93-1.58) 0.84 (0.59-1.18) 0.84 (0.72-0.97) 1.07 (0.96-1.19) 1.33 (1.21-1.47) 0.82 (0.73-0.92) Heart FailureEvents/participants 1 st Listed2 nd Listed Difference in BP (Mean, mmHg) Relative risk (95% CI) Relative Risk Favours 1 st listedFavours 2 nd listed 1. Table adapted from Blood Pressure Lowering Trialists Collaboration. Lancet. 2003;362:1527-1535. 2. Gottdiener JS et al. Ann Intern Med. 2002;137:631-639.

34 The Effects of Digoxin on Mortality and Morbidity in Patients with HF and LV Systolic Dysfunction (n=6800) or LVEF >45% (n=988) LVEF >45% LVEF <45% Death or WHF hospitalizations LVEF >45% LVEF <45% All-cause mortality Risk ratio (95% CI)

35 CHARM: CV death or hospitalisation for CHF candesartan better Hazard ratio placebo better Age 65 75 350/852421/884 LVEF 40333/1516366/1504 Gender Male813/2617917/2582 Female337/1186393/1214 NYHAII359/1730415/1686 III/IV791/2073895/2110 Overall1150/38031310/3796 Candesartan event/n Placebo event/n p=0.26 p=0.93 p=0.63 p=0.40 Test for interaction Limiti… Non TDI 14% con riconoscimento pattern pseudonormale 86% pattern pseudonormale riconosciuto con il BNP (?)

36 Hazard ratio and 95% CI Death or CV Hospitalisation by Subgroup Favours NebivololPlaceboNebivolol Favours Placebo 0.50 0.60 0.70 0.80 0.901.001.10 1.20 125 (33.6%)110 (28.9%) > 35 % LVEF 249 (36.3%)219 (32.1%) 35 % 125 (33.3%)101 (24.6%) Female Sex 250 (36.4%)231 (35.2%) Male 199 (37.1%)184 (34.8%) > 75 y Age 176 (33.5%)148 (27.5%) 70-75 y 375 (35.3%)332 (31.1%) Total

37 TDI non sistematicamente utilizzato 41% BMI>30 kg/m2 25% BNP <139-131 pg/ml PAS allingresso 137-136 mmHg 33% dei pz hanno sospeso il farmaco diuretici già in terapia nell82- 84% ++ pz già in inibitori RAAS prima dellarruolamento


39 Ma per validare una terapia per lo scompenso diastolico dobbiamo escludere (o trattare) … Malattia coronarica associata Diabete mellito Obesità/OSAS Distiroidismi Insufficienza renale BPCO Anemia ….

40 BOOKLETSCOMPENSO CARDIACO Coordinamento: Alberto Gianmarini Barsanti (CEFORMED); Valentino Moretti(FADOI); Andrea Di Lenarda(ANMCO) CEFORMED Battigelli D. Cuzzato A.L. Lucchini G. Ponga B. Potente D. Prelli L. Toffolo M. FADOI Bulfoni A. Bernardis V. Caliandro D. De Carli M. Donada C. Gerloni R. Iacono M.A. ANMCO Albanese M.C. Bonin M. Borgioni L. Chiozza R. Di Piazza R. Lo Giudice F. Pavan D. Zecchin M.

41 Booklet Scompenso Cardiaco Punti chiave Implementazione delle LG sullo SC nel mondo reale dellassistenza multidisciplinare al paziente con SC Condivisione del PDT tra i protagonisti dellassistenza al paziente con SC (MG, internisti, cardiologi) Apertura allutilizzo del BNP (per escludere) in MG Apertura ad una crescita culturale e professionale delle Medicine per la gestione del paziente con SC senza prospettive di intervento

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