Heart Rate Recovery After 6 Min Walk -- A Powerful Prognostic
Heart Rate Recovery After 6 Min Walk -- A Powerful Prognostic
No patients were lost to follow-up during the mean follow-up period of 22.8 ± 22.1 months. There were 50 cardiac-related events (48 deaths and 2 urgent transplantations) during the tracking period, yielding an annual event rate of 9.3%. None of the subjects in the study experienced a non-cardiac-related death. The mortality rate of patients diagnosed with non-ischaemic vs ischaemic aetiology of HF was not significantly different between survivors and non-survivors (65%, 82/126 vs. 60%, 18/30; P = 0.81). The mortality rate of patients diagnosed with HFrEF (19.1%, 41 of 215) and HFpEF (17.1%, 7 of 41) was similar (P = 0.76).
Table 1 lists patient characteristics as well as 6MWT and CPX variables between subjects who were event free and those who suffered a major cardiac event. Based on the patient characteristics and CPX results presented in Table 1, the patient population represents a mixed group with advanced and intermediate levels of HF. There were significant differences for all variables, with the exception of height, weight, 6MWT distance ambulated, and peak RER. Subjects who suffered a major cardiac event were significantly older, had poorer cardiac performance, and had a higher resting HR and lower peak HR (yielding a lower HR reserve). Moreover, subjects suffering a major cardiac event had significantly higher Borg RPE scores, a lower peak VO2, and a greater VE/VCO2 slope. A greater percentage of subjects suffering an event also presented with EOV. Although not statistically significant (P = 0.75), a greater number of patients with ischaemic HF (n = 32) experienced a major cardiac event compared with patients with non-ischaemic HF (n = 18).
The characteristics of patients with HFrEF (n = 216) and HFpEF (n = 42) were relatively similar except for significant differences in the LVEF (32.8 ± 8.3% vs. 55.2 ± 4.3%, respectively; P < 0.001) and peak RER (1.05 ± 0.13 vs. 1.10 ± 0.13, respectively; P < 0.01). No significant differences in the provision of medical therapies to patients with HFrEF and HFpEF were observed.
Figure 1 presents the ROC curves comparing 6MWT HRR with 6MWT distance ambulated and the 6MWT HRR with CPX HRR. The area under the ROC curve for 6MWT HRR was 0.813 compared to 0.600 for the 6MWT distance. The area under the ROC curve for HRR after CPX was slightly greater (0.827) than that for HRR after the 6MWT (0.813). The sensitivity and specificity of 6MWT HRR were 0.94 and 0.55, respectively. The sensitivity and specificity of CPX HRR were 0.88 and 0.74, respectively. The positive and negative predictive values of 6MWT HRR were 0.33 and 0.97, respectively. The positive and negative predictive values of CPX HRR were 0.44 and 0.96, respectively. The accuracy of 6MWT HRR was 0.62 compared with 0.76 for CPX HRR.
(Enlarge Image)
Figure 1.
Receiver operating characteristic curve comparing (A) 6MWT HRR and 6MWT distance and (B) 6MWT HRR and CPX HRR. 6MWT, 6 min walk test; HRR, heart rate recovery; CPX, cardiopulmonary exercise testing.
Table 2 lists the univariate Cox regression analyses for key 6MWT and CPX variables. With the exception of 6MWT resting HR and dichotomized 6MWT (6MWT distance ≤/> 300 m), all other variables were prognostically significant. The dichotomized HRR during the 6MWT (HRR at 1 min ≤/> 12 beats) was the strongest significant univariate predictor of major cardiac events (χ 60.9, P < 0.001) and the 6MWT distance was the least significant predictor of major cardiac events (χ 6.80, P < 0.01). Kaplan–Meier analysis for the HRR threshold of ≤/> 12 beats after the 6MWT is illustrated in Figure 2A.
(Enlarge Image)
Figure 2.
Kaplan–Meier analysis for (A) 6MWT HRR and (B) CPX HRR. 6MWT, 6 min walk test; HRR, heart rate recovery; CPX, cardiopulmonary exercise testing. A = HRR > 12 beats; B = HRR < 12 beats.
Univariate Cox regression analysis results for key CPX variables are also listed in Table 2. With the exception of CPX resting HR, all other variables were prognostically significant. The dichotomized HRR during CPX (HRR at 1 min ≤/> 12 beats) was the strongest significant univariate predictor of major cardiac events (χ 66.6, P < 0.001). The Borg RPE at peak exercise was also a significant predictor of major cardiac events (χ 63.0, P < 0.001). Exercise oscillatory ventilation and the VE/VCO2 slope were also highly significant predictors of major cardiac events (χ 35.9 and 21.3, respectively; P < 0.001). Kaplan–Meier analysis for the HRR threshold of ≤/> 12 beats after CPX is illustrated in Figure 2B.
Table 3 lists the univariate and multivariate Cox regression analyses for key resting and exercise variables. Age and LVEF were significant univariate predictors of major cardiac events (χ 7.11 and 5.99, respectively; P < 0.001 and P < 0.05, respectively). Multivariate analysis of the 6MWT variables revealed that the dichotomous 6MWT HRR was the most robust prognostic marker (χ 61.07, P < 0.001), while LVEF added significant predictive value (residual χ 6.12, P < 0.05) and was retained in the regression, whereas HF aetiology and all other key 6MWT variables were not significant univariate or multivariate prognostic markers.
Multivariate analysis of the CPX variables revealed that the dichotomous CPX HRR was the most robust prognostic marker (χ 53.82, P < 0.001), while the VE/VCO2 slope added significant predictive value (residual χ 6.65, P < 0.05) and was retained in the regression. HF aetiology and all other key CPX variables were not significant multivariate predictors of major cardiac events.
Separate univariate and multivariate Cox regression analyses of major cardiac events in patients with HFrEF and HFpEF using 6MWT variables as well as CPX variables were performed and found many similar significant predictors of major cardiac events in patients with HFrEF and HFpEF (Table 4). Univariate Cox regression analyses of only patients with HFrEF found all previous 6MWT and CPX variables to be significant predictors of major cardiac events, but with lower χ values. The HFrEF univariate Cox regression analysis results identified the dichotomized 6MWT HRR and CPX HRR as the most powerful predictors (χ 56.25 and 59.59, respectively; P < 0.001). Univariate Cox regression analyses of only patients with HFpEF found all previous 6MWT and CPX variables to be significant predictors of major cardiac events, except for 6MWT distance and CPX non-dichotomized HRR. Furthermore, the χ values of all significant HFpEF 6MWT and CPX variables were lower than the χ values of the HFrEF 6MWT and CPX variables. The most robust HFpEF 6MWT and CPX predictors of major cardiac events were peak HR and the VE/VCO2 slope, respectively (χ 13.51, P < 0.001 and 10.52, P < 0.01, respectively). Age and LVEF were both significant univariate predictors of major cardiac events in patients with HFrEF, but only age was a significant univariate predictor of major cardiac events in patients with HFpEF (Table 4).
Multivariate Cox regression analysis of patients with HFrEF found identical multivariate predictors of major cardiac events for the 6MWT and CPX, with dichotomous HRR being the strongest predictor (χ 56.25 and 51.51, respectively; P < 0.001) and LVEF adding significant predictive value (residual χ 12.22 and 6.17, respectively; P < 0.05), which was retained in both the 6MWT and CPX regressions. Multivariate Cox regression analysis of patients with HFpEF using 6MWT distance and dichotomous 6MWT HRR as predictors found the dichotomous 6MWT HRR to be the only significant predictor of major cardiac events (χ 6.11, P < 0.05). Multivariate Cox regression analysis of patients with HFpEF using the CPX variables dichotomous CPX HRR and the VE/VCO2 slope as predictors found the VE/VCO2 slope to be the only significant predictor of major cardiac events (χ 10.52, P < 0.01).
Results
Follow-up on Survival
No patients were lost to follow-up during the mean follow-up period of 22.8 ± 22.1 months. There were 50 cardiac-related events (48 deaths and 2 urgent transplantations) during the tracking period, yielding an annual event rate of 9.3%. None of the subjects in the study experienced a non-cardiac-related death. The mortality rate of patients diagnosed with non-ischaemic vs ischaemic aetiology of HF was not significantly different between survivors and non-survivors (65%, 82/126 vs. 60%, 18/30; P = 0.81). The mortality rate of patients diagnosed with HFrEF (19.1%, 41 of 215) and HFpEF (17.1%, 7 of 41) was similar (P = 0.76).
Baseline Characteristics
Table 1 lists patient characteristics as well as 6MWT and CPX variables between subjects who were event free and those who suffered a major cardiac event. Based on the patient characteristics and CPX results presented in Table 1, the patient population represents a mixed group with advanced and intermediate levels of HF. There were significant differences for all variables, with the exception of height, weight, 6MWT distance ambulated, and peak RER. Subjects who suffered a major cardiac event were significantly older, had poorer cardiac performance, and had a higher resting HR and lower peak HR (yielding a lower HR reserve). Moreover, subjects suffering a major cardiac event had significantly higher Borg RPE scores, a lower peak VO2, and a greater VE/VCO2 slope. A greater percentage of subjects suffering an event also presented with EOV. Although not statistically significant (P = 0.75), a greater number of patients with ischaemic HF (n = 32) experienced a major cardiac event compared with patients with non-ischaemic HF (n = 18).
The characteristics of patients with HFrEF (n = 216) and HFpEF (n = 42) were relatively similar except for significant differences in the LVEF (32.8 ± 8.3% vs. 55.2 ± 4.3%, respectively; P < 0.001) and peak RER (1.05 ± 0.13 vs. 1.10 ± 0.13, respectively; P < 0.01). No significant differences in the provision of medical therapies to patients with HFrEF and HFpEF were observed.
Receiver Operating Characteristic Curves and Related Diagnostic Analyses
Figure 1 presents the ROC curves comparing 6MWT HRR with 6MWT distance ambulated and the 6MWT HRR with CPX HRR. The area under the ROC curve for 6MWT HRR was 0.813 compared to 0.600 for the 6MWT distance. The area under the ROC curve for HRR after CPX was slightly greater (0.827) than that for HRR after the 6MWT (0.813). The sensitivity and specificity of 6MWT HRR were 0.94 and 0.55, respectively. The sensitivity and specificity of CPX HRR were 0.88 and 0.74, respectively. The positive and negative predictive values of 6MWT HRR were 0.33 and 0.97, respectively. The positive and negative predictive values of CPX HRR were 0.44 and 0.96, respectively. The accuracy of 6MWT HRR was 0.62 compared with 0.76 for CPX HRR.
(Enlarge Image)
Figure 1.
Receiver operating characteristic curve comparing (A) 6MWT HRR and 6MWT distance and (B) 6MWT HRR and CPX HRR. 6MWT, 6 min walk test; HRR, heart rate recovery; CPX, cardiopulmonary exercise testing.
Univariate Cox Regression Analyses
Table 2 lists the univariate Cox regression analyses for key 6MWT and CPX variables. With the exception of 6MWT resting HR and dichotomized 6MWT (6MWT distance ≤/> 300 m), all other variables were prognostically significant. The dichotomized HRR during the 6MWT (HRR at 1 min ≤/> 12 beats) was the strongest significant univariate predictor of major cardiac events (χ 60.9, P < 0.001) and the 6MWT distance was the least significant predictor of major cardiac events (χ 6.80, P < 0.01). Kaplan–Meier analysis for the HRR threshold of ≤/> 12 beats after the 6MWT is illustrated in Figure 2A.
(Enlarge Image)
Figure 2.
Kaplan–Meier analysis for (A) 6MWT HRR and (B) CPX HRR. 6MWT, 6 min walk test; HRR, heart rate recovery; CPX, cardiopulmonary exercise testing. A = HRR > 12 beats; B = HRR < 12 beats.
Univariate Cox regression analysis results for key CPX variables are also listed in Table 2. With the exception of CPX resting HR, all other variables were prognostically significant. The dichotomized HRR during CPX (HRR at 1 min ≤/> 12 beats) was the strongest significant univariate predictor of major cardiac events (χ 66.6, P < 0.001). The Borg RPE at peak exercise was also a significant predictor of major cardiac events (χ 63.0, P < 0.001). Exercise oscillatory ventilation and the VE/VCO2 slope were also highly significant predictors of major cardiac events (χ 35.9 and 21.3, respectively; P < 0.001). Kaplan–Meier analysis for the HRR threshold of ≤/> 12 beats after CPX is illustrated in Figure 2B.
Multivariate Cox Regression Analysis
Table 3 lists the univariate and multivariate Cox regression analyses for key resting and exercise variables. Age and LVEF were significant univariate predictors of major cardiac events (χ 7.11 and 5.99, respectively; P < 0.001 and P < 0.05, respectively). Multivariate analysis of the 6MWT variables revealed that the dichotomous 6MWT HRR was the most robust prognostic marker (χ 61.07, P < 0.001), while LVEF added significant predictive value (residual χ 6.12, P < 0.05) and was retained in the regression, whereas HF aetiology and all other key 6MWT variables were not significant univariate or multivariate prognostic markers.
Multivariate analysis of the CPX variables revealed that the dichotomous CPX HRR was the most robust prognostic marker (χ 53.82, P < 0.001), while the VE/VCO2 slope added significant predictive value (residual χ 6.65, P < 0.05) and was retained in the regression. HF aetiology and all other key CPX variables were not significant multivariate predictors of major cardiac events.
Univariate and Multivariate Cox Regression Subanalyses of Major Cardiac Events by Heart Failure Type
Separate univariate and multivariate Cox regression analyses of major cardiac events in patients with HFrEF and HFpEF using 6MWT variables as well as CPX variables were performed and found many similar significant predictors of major cardiac events in patients with HFrEF and HFpEF (Table 4). Univariate Cox regression analyses of only patients with HFrEF found all previous 6MWT and CPX variables to be significant predictors of major cardiac events, but with lower χ values. The HFrEF univariate Cox regression analysis results identified the dichotomized 6MWT HRR and CPX HRR as the most powerful predictors (χ 56.25 and 59.59, respectively; P < 0.001). Univariate Cox regression analyses of only patients with HFpEF found all previous 6MWT and CPX variables to be significant predictors of major cardiac events, except for 6MWT distance and CPX non-dichotomized HRR. Furthermore, the χ values of all significant HFpEF 6MWT and CPX variables were lower than the χ values of the HFrEF 6MWT and CPX variables. The most robust HFpEF 6MWT and CPX predictors of major cardiac events were peak HR and the VE/VCO2 slope, respectively (χ 13.51, P < 0.001 and 10.52, P < 0.01, respectively). Age and LVEF were both significant univariate predictors of major cardiac events in patients with HFrEF, but only age was a significant univariate predictor of major cardiac events in patients with HFpEF (Table 4).
Multivariate Cox regression analysis of patients with HFrEF found identical multivariate predictors of major cardiac events for the 6MWT and CPX, with dichotomous HRR being the strongest predictor (χ 56.25 and 51.51, respectively; P < 0.001) and LVEF adding significant predictive value (residual χ 12.22 and 6.17, respectively; P < 0.05), which was retained in both the 6MWT and CPX regressions. Multivariate Cox regression analysis of patients with HFpEF using 6MWT distance and dichotomous 6MWT HRR as predictors found the dichotomous 6MWT HRR to be the only significant predictor of major cardiac events (χ 6.11, P < 0.05). Multivariate Cox regression analysis of patients with HFpEF using the CPX variables dichotomous CPX HRR and the VE/VCO2 slope as predictors found the VE/VCO2 slope to be the only significant predictor of major cardiac events (χ 10.52, P < 0.01).
