Arbolishvili GN, Mareev VY Institute of Clinical Cardiology, Moscow, Russia

Transcription

1 THE VALUE OF 24 H HEART RATE VARIABILITY IN PREDICTING THE MODE OF DEATH IN PATIENTS WITH HEART FAILURE AND SYSTOLIC DYSFUNCTION IN BETA-BLOCKING BLOCKING ERA Arbolishvili GN, Mareev VY Institute of Clinical Cardiology, Moscow, Russia ISHNE Heart Failure World-Wide Wide Internet Symposium,, 2006

2 Heart Rate Variability (HRV) LF 0,04-0,15 Hz HF 0,15-0,40 Hz SDNN Sympathetic/vagal modulation Parasympathetic modulation

3 Objectives: To assess the relationship between parameters of HRV and traditional clinical markers of unfavorable prognosis with total mortality and mode of death in pts with heart failure and LV dysfunction in beta-blocking blocking era.

4 Inclusion criteria Symptomatic heart failure (NYHA II-IV IV) Sinus rhythm Left ventricle systolic dysfunction (LVEF 40%) Stable clinical condition

5 Exclusion criteria non-sinus rhythm myocardial infarction (< < 3 months) diabetes mellitus SA and AV-block renal failure severe non-cardiac diseases (with poor prognosis)

6 Study design Prospective observational study

7 End points Primary endpoint all-cause mortality Secondary endpoints pump failure death (PFD) sudden death (SD)

8 Statistical analysis (stepwise regression analysis) Clinical variables HRV variables Univariable model p<0.1 Multivariable model p<0.05 Univariable model p<0.1 Multivariable model p<0.05 Final prognostic model based on forward stepwise Cox proportional hazard regression p<0.05 INDEPENDENT PREDICTORS

9 Baseline patients clinical characteristics Age, yrs Gender (m/f) Etiology (isch/nonisch) LVEF,, % NYHA VPCs (24h) NSVT (n) Characteristics NYHA II NYHA III NYHA IV Total (n=135) 52.4 ± /23 (82%/17%) 91/43 (68%/32%) 30.1 ± ± (42%) 55 (40%) 24 (18%) 219 (34-817)* 57 (35%( 35%) * Presented as median with 25th and 75th percentiles

10 Baseline treatment Diuretics Nitrates Treatment ACE Inhibitors Beta-blockers Digoxin Spironolactone Aspirin Amiodarone Warfarin % 90.3% 89.1% 79.4% 45.1% 68.6% 76.4% 11.1% 14.8% 5.6%

11 Heart Rate Variability in Heart Failure

12 HRV measures SDNN, ms SDANN, ms SD, ms RMSDD, ms pnn50,, % TP, ln ms 2 LF, ln ms 2 HF, ln ms 2 LF/HF VLF, ln ms 2 ULF, ln ms 2 Measures Value 107 ± ± ± ± ± ± 2,5 5.9 ± ± ± ± ± 1.6

13 Changes of Heart Rate and SDNN by NYHA * 69 * HR SDNN 20 0 NYHA II NYHA III NYHA IV *p value < 0.05

14 Changes of Frequency Domain HRV measures by NYHA ,1 5,4 4,8 NYHA II 2,2 9,1 5,2 4,6 NYHA III 2,3 8,3 * * 4,64,5 NYHA IV 1,6 * TP (ln) LF (ln) HF (ln) LF/HF *p value < 0.05

15 TOTAL MORTALITY

16 135 patients Follow-up ~2.4 years Non- cardiac 3 pts (5%) 63 patients died 36 pts (57%) PUMP FAILURE DEATH 3 pts (5%) Myocardial Infarction 21 pts (33%) SUDDEN DEATH

17 Univariable predictors of total mortality among clinical variables Variable RR p 95% CI (cut-off value) NYHA, III-IV IV NSVT LVEF 30 %

18 Univariable predictors of total mortality among HRV measures Variable (cut-off value) RR p 95% CI RR 746 ms SDNN < 90 ms SDANN < 70 ms TP ln < 9.05 ms LF ln < 5.1 ms VLF ln < 6.35 ms ULF ln < 8.1 ms

19 Multivariable predictors of total mortality Variable (cut-off value) NYHA, III-IV IV Clinical variables RR 2.0 p % CI Variable (cut-off value) SDNN 90 мс HRV measures RR 1.5 p % CI

20 Final prognostic multivariable model for total mortality (forward stepwise Cox proportional hazard regression) Variable RR p 95% CI (cut-off value) NYHA, III-IV IV SDNN 90 ms

21 Kaplan-Meier Survival by NYHA Cumulative Proportion Surviving (Kaplan-Meier) Complete Censored 1,0 Cumulative Survival Proportion Surviving 0,9 0,8 0,7 0,6 0,5 n=24 n=55 NYHA II NYHA IV NYHA III 0,4 0,3 Log-rank Total mortality Months Time p< Group 1 Group 2 Group 3

22 Kaplan-Meier Survival by SDNN Cumulative Proportion Surviving (Kaplan-Meier) Complete Censored 1,0 0,9 SDNN > 110 ms Cumulative Proportion Surviving Survival 0,8 0,7 0,6 0,5 0,4 SDNN ms SDNN < 90 ms n=49 n=42 n=37 0,3 0,2 Log rank Total mortality Months Time p<0.001 Group 1 Group 2 Group 3

23 PUMP FAILURE DEATH

24 Univariable predictors of pump failure death Variable (cut-off value) NYHA, III-IV IV NSVT LVEF 28 % Variable (cut-off value) RR 705 мс (85 ) SDNN 85 ms Clinical variables RR HRV measures RR p p % CI % CI

25 Multivariable predictors of pump failure death Variable (cut-off value) NYHA, III-IV IV Clinical variables RR 8.1 p % CI Variable (cut-off value) RR 705 ms (85 ) HRV measures RR 2.0 p % CI

26 Final prognostic multivariable model for pump failure death (forward stepwise Cox proportional hazard regression) Variable (cut-off value) NYHA, III-IV IV RR 8.0 p % CI RR 705 ms (85 )

27 Kaplan-Meier Survival by NYHA Cumulative Proportion Surviving (Kaplan-Meier) Complete Censored 1,0 NYHA II n=56 Cumulative Survival Proportion Surviving 0,9 0,8 0,7 0,6 n=42 NYHA IV NYHA III n=55 0,5 0,4 Log-rank Pump failure death Months Time p<0.05 Group 1 Group 2 Group 3

28 Kaplan-Meier Survival by mean RR Cumulative Proportion Surviving (Kaplan-Meier) Complete Censored 1,0 Cumulative Proportion Surviving Выживаемость Survival 0,9 0,8 0,7 0,6 0,5 n=89 n=40 RR > 705 ms (<85 bpm ) RR 705 ms ( 85 bpm) 0,4 Log-rank Pump failure death p= , Months Time Group 2, Group 1,

29 Kaplan-Meier Survival in 2 independent risk factor model n=43 NYHA II + RR mean > 705 ms (<85 bpm ) Survival n=33 NYHA III-IV + RR mean 705 ms ( 85 bpm ) Pump failure death Months

30 SUDDEN DEATH

31 Univariable predictors of sudden cardiac death Variable (cut-off value) NYHA, II LVEF 26 % Clinical variables RR p % CI Variable (cut-off value) LF< < 4.5, ln ms 2 LF/HF < 1.5 HRV measures RR p % CI

32 Multivariable predictors of sudden cardiac death Variable (cut-off value) NYHA, II Clinical variables RR 2.0 p % CI LVEF 26 % 1.1 0,

33 Multivariable predictors of sudden cardiac death HRV measures Variable (cut-off value) RR p 95% CI LF/HF <

34 Final prognostic multivariable model for sudden cardiac death (forward stepwise Cox proportional hazard regression) Variable (cut-off value) NYHA, II RR 3.5 p % CI LVEF 26 % 1.4 0, LF/HF <

35 1,05 Cumulative Proportion Surviving (Kaplan-Meier) Kaplan-Meier Complete Survival Censored by LF/HF 1.5 1,00 n=68 LF/HF > 1,5 Cumulative Proportion Surviving Survival 0,95 0,90 0,85 n=61 LF/HF 1.5 0,80 0,75 Log-rank Sudden death Months Time p=0.001 Group 1, Group 2,

36 Kaplan-Meier Cumulative Survival Proportion in Surviving 3 independent (Kaplan-Meier) risk factor model Complete Censored 1,0 Cumulative Proportion Surviving Survival 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0,0 LVEF<26%+LF/HF<1.5+NYHA II Log-rank LVEF>26% + LF/HF>1.5 + NYHA > II RR= = 9.5 (95% CI ) Months Time p=0,0001 Group 1 Group 2

37 Conclusions 1. The main HRV indices (both time- and frequency domain) are depressed in heart failure which relates to the severity of heart failure 2. III-IV IV NYHA and SDNN 90 ms are independent predictors of all-cause mortality. 3. III-IV IV NYHA and mean RR 705 ms (HR 85 ) are independent predictors of death from progressive pump failure. Their combination singles out pts at the most increased risk of pump failure death.

38 Conclusions (continued) 5. Patients in II NYHA, depressed LVEF 26%, and decreased LF/HF 1.5 are independent predictors of sudden death. Their combination singles out patients with heart failure at the most increased risk of sudden death. 6. HRV measures are advantageous over traditional markers of unfavorable prognosis (VPCs( VPCs,, NSVT) in identifying patients with heart failure at increased risk of sudden death.