1Universitätsklinikum Frankfurt Med. Klinik III - Kardiologie, Angiologie Frankfurt am Main, Deutschland; 2Universitätsklinikum Frankfurt Klinik für Thorax-, Herz- und Thorakale Gefäßchirurgie Frankfurt am Main, Deutschland; 3Krankenhaus Göttlicher Heiland Wien, Österreich; 4Universität Szeged / Medizinische Klinik Ablg. Elektrophysiologie Szeged, Ungarn; 5Evangelisches Klinikum Bethel Innere Medizin, Kardiologie, Nephrologie und Diabetologie Bielefeld, Deutschland; 6Medical Center, Hungarian Defense Forces Department of Cardiology Budapest, Ungarn
Background
Cardiac resynchronization therapy (CRT) has become a cornerstone in heart failure (HF) therapy reducing morbidity and mortality. While the rate of CRT-Defibrillator (CRT-D) implantations is reported to be higher in men than women the evidence from randomized controlled trials on the effects of gender on CRT response is scarce.
Methods
Perioperative and outcome data were prospectively collected from 786 consecutive patients (165 female, 621 male) after CRT-D implantation in three medical European centers (Frankfurt a. M., Bielefeld, Budapest). The primary endpoint was all-cause mortality. Secondary endpoint was response to CRT as measured in improvement of left ventricular ejection fraction (LVEF), NYHA functional class, and QRS shortening 6 months after implantation.
Results
Female patients had significantly higher baseline LVEF values (27.0±7.2% vs. 25.2±7.2%, p=0.003), smaller LV end-diastolic diameters (61.3±9.3mm vs. 66.3±10.1mm, p<0.001) as well as significantly lower rates of ischemic cardiomyopathy (ICM; 38.8% vs 61.4%, p<0.001) and atrial fibrillation (AF; 28.5% vs. 39.0%, p=0.014). During the median follow-up period of 28.3 months (IQR: 13.7-54.0) the primary endpoint of all-cause death occurred in 266 patients (33.8%) and more often in males (n= 220, 36.1%) than in females (n=42, 25.5% p=0.01, figure 1).
With respect to secondary endpoints, echocardiographic response to CRT was significantly greater in female than in male patients (ΔLVEF 9.2±10.8 vs 6.0±9.2, p=0.002). Regarding the other parameter indicating response to CRT (change in NYHA functional class, QRS shortening and, percentage of biventricular stimulation), we found no significant difference between males and females.
Conclusion
This multicentric cohort results suggest that women with symptomatic heart failure have a lower long-term all-cause mortality following CRT implantation compared to men. CRT response as measured as improvement in LVEF is more frequent and more pronounced in women than men while NYHA response and QRS shortening remain equally distributed between men and women during follow-up.
Further investigations with larger patient cohort and a 50% female inclusion rate are urgently warranted to confirm these findings.
Table 1. Baseline Data
|
Gender (n) |
Male (621) |
Female (165) |
P |
|
Age, years |
68.3±30.9 |
67.4±11.6 |
0.722 |
|
LVEF baseline, % |
25.2 ± 7.2 |
27.0 ± 7.2 |
0.003 |
|
LVEDD baseline, mm |
66.3± 10.1 |
61.3± 9.3 |
<0.001 |
|
NYHA baseline, class |
2.7±0.64 |
2.7 ±0.6 |
0.518 |
|
Baseline QRS, ms |
159.7± 27.9 |
157.0± 25.8 |
0.246 |
|
ICM, n (%) |
381 (61.4) |
64 (38.8) |
<0.001 |
|
Amiodaron, n (%) |
145 (23.4) |
32 (19.4) |
0.296 |
|
Primary Prevention, n (%) |
486 (78.3) |
138 (83.6) |
0.189 |
|
AF, n (%) |
242 (39.0) |
47 (28.5) |
0.014 |
|
Upgrade Procedure, n (%) |
191 (30.8) |
49 (29.8) |
0.849 |
LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; NYHA, New York heart association; ICM, ischemic cardiomyopathy; AF, atrial fibrillation.
Figure 1. Primary Outcome: Mortality in CRT Patients depending on gender
Table 2. Six Months Follow-Up Data
|
Gender |
Male |
Female |
P |
|
LVEF 6 Mo, % |
30.6±10.0 |
35.6±11.1 |
<0.001 |
|
ΔLVEF, % |
6.0 ± 9.2 |
9.2±10.8 |
0.002 |
|
LVEDD, mm |
64.9± 10.5 |
57.8±11.5 |
<0.001 |
|
ΔLVEDD, mm |
-1.4±10.5 |
-1.9±14.9 |
0.769 |
|
NYHA, classification |
2.0±0.7 |
2.0±0.7 |
0.668 |
|
Improvement in NYHA Class, n (%) |
396 (68.8) |
100 (64.5) |
0.831 |
|
QRS, ms |
148.2 ± 26.8 |
144.4 ± 26.3 |
0.246 |
|
ΔQRS, ms |
-11.3± 34.4 |
-8.5 ± 28.3 |
0.490 |
|
Biventricular Stimulation, % |
91.3± 19.1 |
93.2± 19.1 |
0.381 |
|
ICD Shock, n (%) |
4 (0.6) |
1 (0.6) |
1.000 |