Long-term outcome of patients with chronotropic incompetence after an acute myocardial infarction

Figures & data

Table I. Characteristics of the study population according to maximal chronotropic response index.

	CRI ≥ 39 n = 422	CRI < 39 n = 72	P value
Men, n	335 (79)	51 (71)	0.122
Age, years	60 ± 10	65 ± 9	<0.001
BMI, kg·m^−2	28 ± 4	28 ± 5	0.176
Smoking, n	142 (34)	24 (33)	1.000
Diabetes, n	65 (15)	28 (41)	<0.001
History of MI, n	67 (16)	22 (31)	0.005
Hypertension, n	188 (45)	40 (56)	0.096
NYHA class ≥ 2	102 (24)	31 (43)	0.001
LVEF, %	47 ± 8	46 ± 8	0.224
EC, METs	5.8 ± 1.5	4.1 ± 1.2	<0.001
EC, %	68 ± 16	55 ± 17	<0.001
HRpeak, bpm	128 ± 19	92 ± 12	<0.001
Features of MI:
Anterior MI, n	184 (44)	39 (54)	0.098
Q-wave MI, n	236 (56)	32 (44)	0.074
MI treatment:
PTCA or CABG, n	86 (20)	9 (13)	0.145
Thrombolysis, n	227 (54)	29 (40)	0.041
Medical treatment
Aspirin or warfarin, n	377 (89)	63 (88)	0.682
Beta-blockers, n	422 (100)	72 (100)	1.000
Statins, n	173 (41)	24 (33)	0.243
ACE inhibitors or AT II blockers, n	146 (35)	32 (44)	0.113
Ca-channel blockers, n	18 (4)	10 (14)	0.003
Diuretics, n	54 (13)	33 (46)	<0.001
Follow-up events:
Non-fatal MI, n	47 (11)	12 (17)	0.174
PTCA or CABG, n	136 (32)	27 (27)	0.416

Values are expressed as mean ± SD or number of subjects (%).

ACE = angiotensin-converting enzyme; AT II = angiotensin II; CABG = coronary artery bypass grafting; BMI = body mass index; CRI = maximal chronotropic response index; EC = exercise capacity; HR = heart rate; LVEF = left ventricular ejection fraction; MI = myocardial infarction; NYHA = New York Heart Association classification; PTCA = percutaneous transluminal coronary angioplasty; SCD = sudden cardiac death.

Figure 1. Left ventricular ejection fraction (LVEF) (A), maximal chronotropic response index (CRI) (B), and their combination (C) in prediction of cardiac death in Kaplan-Meier survival analysis.

Figure 2. Predicted and observed rates of cardiac mortality before (open circles) and after (solid circles) inclusion of chronotropic incompetence in the risk model for cardiac death in the patients divided into deciles according to predicted risk. Age, diabetes, New York Heart Association classification, history of myocardial infarction, left ventricular ejection fraction, and exercise capacity were included in the initial model. The calibration of the risk model is better when the data points fall closer to the 45° line.

Table II. Association of chronotropic incompetence to cardiac death and sudden cardiac death in subgroups divided according to other predictive variables.

				Cardiac death			SCD
		CRI ≥ 39 n = 422	CRI < 39n = 72	RR (95% CI)	P value	P value for interaction	RR (95% CI)	P value	P value for Interaction
Age, years
	≥66	144 (34)	38 (53)	9.1 (3.8–21.4)	<0.001	0.259	12.9 (2.5–66.9)	0.002	0.274
	<66	278 (66)	34 (47)	4.3 (1.5–12.3)	0.006		3.8 (1.0–14.5)	0.047
Diabetes
	Yes	65 (15)	28 (39)	3.3 (1.1–9.4)	0.029	0.108	2.4 (0.3–17.4)	0.372	0.275
	No	357 (85)	44 (61)	9.9 (4.5–21.4)	<0.001		9.0 (3.1–26.0)	<0.001
History of MI
	Yes	67 (16)	22 (31)	4.4 (1.6–12.0)	0.005	0.306	7.8 (0.7–86.4)	0.095	0.872
	No	355 (84)	50 (69)	8.3 (3.8–18.3)	<0.001		6.1 (2.2–17.3)	0.001
NYHA class
	≥2	102 (24)	31 (43)	6.2 (2.3–16.3)	<0.001	0.960	13.0 (1.3–125.9)	0.027	0.382
	<2	320 (76)	41 (57	7.3 (3.2–16.6)	<0.001		5.1 (1.7–15.4)	0.003
LVEF, %
	<45	132 (31)	26 (36)	6.7 (3.0–14.7)	<0.001	0.684	6.1 (1.8–20.1)	0.003	0.940
	≥45	290 (69)	46 (64)	8.8 (3.2–24.4)	<0.001		6.1 (1.4–27.2)	0.018
EC%, %
	<57	91 (22)	37 (49)	3.9 (1.7–9.0)	0.002	0.259	4.0 (1.1–15.1)	0.039	0.969
	≥57	331 (78)	35 (49)	9.3 (3.6–23.5)	<0.001		6.0 (1.5–24.0)	0.011

CI = confidence interval; CRI = maximal chronotropic response index; EC = exercise capacity; LVEF = left ventricular ejection fraction; MI = myocardial infarction; NYHA = New York Heart Association classification; RR = relative risk; SCD = sudden cardiac death.

Table III. Discrimination of the final risk model and the models where each risk marker has been removed one at a time using c-index with confidence intervals obtained from 250 bootstrap resamplings and binary R².

	Cardiac death, n = 40		SCD, n = 18
	c-index (95% CI)	Binary R^2	c-index (95% CI)	Binary R^2
Final model	0.817 (0.754–0.902)	0.273	0.774 (0.693–0.918)	0.154
Removed variable:
Age ≥ 66 years	0.814 (0.734–0.892)	0.261	0.770 (0.683–0.917)	0.154
Diabetes	0.810 (0.746–0.898)	0.268	0.766 (0.687–0.907)	0.152
History of MI	0.814 (0.746–0.899)	0.268	0.768 (0.676–0.913)	0.147
NYHA ≥ 2	0.816 (0.751–0.900)	0.271	0.763 (0.667–0.905)	0.136
LVEF < 45	0.791 (0.714–0.875)	0.221	0.731 (0.661–0.896)	0.107
EC% < 57%	0.798 (0.736–0.879)	0.248	0.776 (0.689–0.911)	0.138
CRI < 39	0.778 (0.704–0.873)	0.208	0.706 (0.625–0.866)	0.089

CI = confidence interval; CRI = maximal chronotropic response index; EC = exercise capacity; LVEF = left ventricular ejection fraction; MI = myocardial infarction; NYHA = New York Heart Association classification; SCD = sudden cardiac death.