Gender Differences in Outcome of ICD Recipients
Gender Differences in Outcome of ICD Recipients
A total of 2192 patients underwent ICD implantation for primary prevention of SCD since 1996 of whom 77 (3.5%) were lost to follow-up and 169 (8%) patients with congenital or monogenetic heart disease were excluded. The remaining 1946 patients were included in the current analyses, comprising of 1528 (79%) men and 418 (21%) women. Clinical characteristics are summarised in Table 1. Median age at implantation was 65 years (25th–75th percentile 57–72 years); majority of patients (66%) had ischaemic heart disease with a depressed LVEF (mean 29% ±12). Patients were followed for a median 3.3 years (25th–75th percentile 1.4–5.4 years).
Grouping by gender at implantation showed similar age and systolic function. Women had less ischaemic heart disease (71% vs 48%; p<0.001), and statin usage was lower (68% vs 55%; p<0.001). Women had more symptomatic heart failure (median NYHA class 2±1 vs 3±1; p<0.001), subsequently, usage of diuretics was higher (67% vs 73%; p=0.02), and they more often had a CRT-D (56% vs 66%; p<0.001). Furthermore, women had poorer renal function (creatinine clearance 81±37 vs 72±34; p<0.001) and lower body mass index (26.7 vs 26.1 kg/m; p=0.02). Patient characteristics by gender are summarised in Table 1.
During follow-up, 463 (24%) patients died, 387 (25%) men and 76 (18%) women. The annual mortality rate was 6.8% in men and 5.3% in women. Five-year cumulative all-cause mortality was 20% (95% CI 18% to 23%) in men and 14% (95% CI 9% to 19%) in women (figure 1A). Mortality risk was significantly lower in women, also after adjustment for age, aetiology of heart failure, device type, LVEF, NYHA functional class, history of atrial fibrillation/flutter, creatinine clearance and use of β-blockers (adjusted HR 0.65; 95% CI 0.49 to 0.84; p<0.01; Table 2).
(Enlarge Image)
Figure 1.
Gender differences in outcome of primary prevention implantable cardioverter-defibrillator (ICD) treatment. (A) Mortality by gender. (B) Appropriate ICD therapy (antitachycardia pacing/shock) by gender. (C) Appropriate ICD shock by gender. (D) Inappropriate ICD shock by gender.
In total, 494 (25%) patients (401 (26%) men, 93 (22%) women) received appropriate device therapy. The 5-year cumulative event rate of appropriate therapy was 24% (95% CI 21% to 28%) in men, compared with 20% (95% CI 14% to 26%) in women (figure 1B). A trend was observed that appropriate device therapy was lower in women (HR 0.81; 95% CI 0.65 to 1.02; p=0.07).
Additionally, at least one device shock was observed in 267 (14%) ICD recipients, consisting of 220 (14%) men and 47 (11%) women. Five-year cumulative event rates were, respectively, 13% (95% CI 10% to 16%) and 10% (95% CI 5% to 15%) in men and women (figure 1C). Women tended to experience less appropriate shocks (HR 0.78; 95% CI 0.57 to 1.07; p=0.12).
Furthermore, after adjustment (age, aetiology of heart failure, device type, LVEF, NYHA functional class, history of atrial fibrillation/flutter, creatinine clearance and use of β-blockers), a non-significant trend remained in both device therapy (HR 0.82; 95% CI 0.64 to 1.06; p=0.13; Table 2) and device shock (HR 0.79; 95% CI 0.56 to 1.13; p=0.19; Table 2).
Inappropriate shocks were experienced by 195 (10%) patients, 158 (10%) men and 37 (9%) women. Cumulative event rates of inappropriate shock at 5 years were 9% (95% CI 7% to 11%) in men and 8% (95% CI 3% to 12%) in women (figure 1D). There was no difference between genders in the rate of inappropriate shock (HR 0.87; 95% CI 0.61 to 1.25; p=0.46; Table 2).
During follow-up, 814 (42%) patients either received appropriate ICD therapy and/or died. This was the case in 667 (44%) men and 147 (35%) women. The combined endpoint was significantly different between genders (HR 0.78; 95% CI 0.65 to 0.92; p=0.005). After adjustment for covariates (for age, aetiology of heart failure, device type, LVEF, NYHA functional class, history of atrial fibrillation/flutter, creatinine clearance and use of β-blockers) the difference remained (HR 0.74; 95% CI 0.61 to 0.90; p=0.003).
Of 657 patients with non-ischaemic heart disease, 267 (41%) experienced appropriate ICD therapy or died. Significantly more male patients (189 (43%)) reached the combined endpoint than female patients (78 (36%); HR 0.76; 95% CI 0.58 to 0.98; p=0.03; figure 2A). In ischaemic heart disease patients (n=1274), although a trend towards a lower combined endpoint was observed in female compared with male patients, this difference was not significant. Respectively, 477 (44%) male vs 69 (34%) female patients reached the combined endpoint (HR 0.80; 95% CI 0.62 to 1.03: p=0.08).
(Enlarge Image)
Figure 2.
Gender differences in either implantable cardioverter-defibrillator (ICD) therapy and/or mortality by aetiology of heart failure and device type. (A) Mortality and ICD therapy in patients with ischaemic heart disease and patients with non-ischaemic heart disease. (B) Mortality and ICD therapy in ICD and cardiac resynchronisation therapy patients.
As illustrated in figure 2B, a subanalysis stratified for device type yielded the following results: of the 823 ICD recipients 316 (38%) reached the combined endpoint, here of were 263 (39%) men and 53 (37%) women, this was similar between the genders (HR 0.93; 95% CI 0.69 to 1.3; p=0.63). On the contrary, of the 1121 CRT-D recipients 498 (44%) reached the combined endpoint (404 (48%) men vs 94 (34%) women), which was significantly different between genders (HR 0.67; 95% CI 0.54 to 0.84; p=0.001).
Of all deceased ICD recipients, 216 (47%) suffered a cardiac death; 179 (46%) men and 37 (49%) women (Table 3). An arrhythmic death was observed in 17 (4%) cases, 15 (4%) men and 2 (3%) women. Heart failure was the cause of death in 169 (37%) of all diseased, 141 (37%) men and 28 (37%) women. Twenty-two (5%) suffered a sudden death which could not be qualified further, and in 77 patients (17%) the mode of death remained unknown.
Results
Patients
A total of 2192 patients underwent ICD implantation for primary prevention of SCD since 1996 of whom 77 (3.5%) were lost to follow-up and 169 (8%) patients with congenital or monogenetic heart disease were excluded. The remaining 1946 patients were included in the current analyses, comprising of 1528 (79%) men and 418 (21%) women. Clinical characteristics are summarised in Table 1. Median age at implantation was 65 years (25th–75th percentile 57–72 years); majority of patients (66%) had ischaemic heart disease with a depressed LVEF (mean 29% ±12). Patients were followed for a median 3.3 years (25th–75th percentile 1.4–5.4 years).
Grouping by gender at implantation showed similar age and systolic function. Women had less ischaemic heart disease (71% vs 48%; p<0.001), and statin usage was lower (68% vs 55%; p<0.001). Women had more symptomatic heart failure (median NYHA class 2±1 vs 3±1; p<0.001), subsequently, usage of diuretics was higher (67% vs 73%; p=0.02), and they more often had a CRT-D (56% vs 66%; p<0.001). Furthermore, women had poorer renal function (creatinine clearance 81±37 vs 72±34; p<0.001) and lower body mass index (26.7 vs 26.1 kg/m; p=0.02). Patient characteristics by gender are summarised in Table 1.
Mortality
During follow-up, 463 (24%) patients died, 387 (25%) men and 76 (18%) women. The annual mortality rate was 6.8% in men and 5.3% in women. Five-year cumulative all-cause mortality was 20% (95% CI 18% to 23%) in men and 14% (95% CI 9% to 19%) in women (figure 1A). Mortality risk was significantly lower in women, also after adjustment for age, aetiology of heart failure, device type, LVEF, NYHA functional class, history of atrial fibrillation/flutter, creatinine clearance and use of β-blockers (adjusted HR 0.65; 95% CI 0.49 to 0.84; p<0.01; Table 2).
(Enlarge Image)
Figure 1.
Gender differences in outcome of primary prevention implantable cardioverter-defibrillator (ICD) treatment. (A) Mortality by gender. (B) Appropriate ICD therapy (antitachycardia pacing/shock) by gender. (C) Appropriate ICD shock by gender. (D) Inappropriate ICD shock by gender.
Appropriate Device Therapy
In total, 494 (25%) patients (401 (26%) men, 93 (22%) women) received appropriate device therapy. The 5-year cumulative event rate of appropriate therapy was 24% (95% CI 21% to 28%) in men, compared with 20% (95% CI 14% to 26%) in women (figure 1B). A trend was observed that appropriate device therapy was lower in women (HR 0.81; 95% CI 0.65 to 1.02; p=0.07).
Additionally, at least one device shock was observed in 267 (14%) ICD recipients, consisting of 220 (14%) men and 47 (11%) women. Five-year cumulative event rates were, respectively, 13% (95% CI 10% to 16%) and 10% (95% CI 5% to 15%) in men and women (figure 1C). Women tended to experience less appropriate shocks (HR 0.78; 95% CI 0.57 to 1.07; p=0.12).
Furthermore, after adjustment (age, aetiology of heart failure, device type, LVEF, NYHA functional class, history of atrial fibrillation/flutter, creatinine clearance and use of β-blockers), a non-significant trend remained in both device therapy (HR 0.82; 95% CI 0.64 to 1.06; p=0.13; Table 2) and device shock (HR 0.79; 95% CI 0.56 to 1.13; p=0.19; Table 2).
Inappropriate Device Shocks
Inappropriate shocks were experienced by 195 (10%) patients, 158 (10%) men and 37 (9%) women. Cumulative event rates of inappropriate shock at 5 years were 9% (95% CI 7% to 11%) in men and 8% (95% CI 3% to 12%) in women (figure 1D). There was no difference between genders in the rate of inappropriate shock (HR 0.87; 95% CI 0.61 to 1.25; p=0.46; Table 2).
Combined: Mortality and Appropriate Device Therapy
During follow-up, 814 (42%) patients either received appropriate ICD therapy and/or died. This was the case in 667 (44%) men and 147 (35%) women. The combined endpoint was significantly different between genders (HR 0.78; 95% CI 0.65 to 0.92; p=0.005). After adjustment for covariates (for age, aetiology of heart failure, device type, LVEF, NYHA functional class, history of atrial fibrillation/flutter, creatinine clearance and use of β-blockers) the difference remained (HR 0.74; 95% CI 0.61 to 0.90; p=0.003).
Of 657 patients with non-ischaemic heart disease, 267 (41%) experienced appropriate ICD therapy or died. Significantly more male patients (189 (43%)) reached the combined endpoint than female patients (78 (36%); HR 0.76; 95% CI 0.58 to 0.98; p=0.03; figure 2A). In ischaemic heart disease patients (n=1274), although a trend towards a lower combined endpoint was observed in female compared with male patients, this difference was not significant. Respectively, 477 (44%) male vs 69 (34%) female patients reached the combined endpoint (HR 0.80; 95% CI 0.62 to 1.03: p=0.08).
(Enlarge Image)
Figure 2.
Gender differences in either implantable cardioverter-defibrillator (ICD) therapy and/or mortality by aetiology of heart failure and device type. (A) Mortality and ICD therapy in patients with ischaemic heart disease and patients with non-ischaemic heart disease. (B) Mortality and ICD therapy in ICD and cardiac resynchronisation therapy patients.
As illustrated in figure 2B, a subanalysis stratified for device type yielded the following results: of the 823 ICD recipients 316 (38%) reached the combined endpoint, here of were 263 (39%) men and 53 (37%) women, this was similar between the genders (HR 0.93; 95% CI 0.69 to 1.3; p=0.63). On the contrary, of the 1121 CRT-D recipients 498 (44%) reached the combined endpoint (404 (48%) men vs 94 (34%) women), which was significantly different between genders (HR 0.67; 95% CI 0.54 to 0.84; p=0.001).
Mode of Death
Of all deceased ICD recipients, 216 (47%) suffered a cardiac death; 179 (46%) men and 37 (49%) women (Table 3). An arrhythmic death was observed in 17 (4%) cases, 15 (4%) men and 2 (3%) women. Heart failure was the cause of death in 169 (37%) of all diseased, 141 (37%) men and 28 (37%) women. Twenty-two (5%) suffered a sudden death which could not be qualified further, and in 77 patients (17%) the mode of death remained unknown.
