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- James T. Willerson, MD⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. James T. Willerson, Texas Heart Institute, 6770 Bertner (MC3-116), Houston, Texas 77030
As the use of device therapy broadens, we continue to see new clinical trials and studies intended to identify the patients who will benefit most from an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy with defibrillator (CRT-D). Two papers in the current issue of the Journal (1,2) deal with device therapy for patients with heart failure. Each study was an effort to more specifically identify a patient's needs according to sex, risk of sudden death, and in consideration of ischemic or nonischemic cardiomyopathy.
Arshad et al. (1) discuss a clinical trial that addressed sex differences in the use of either CRT-D or ICD to reduce death or heart failure. The authors report that in the 1,820 patients enrolled in the MADIT-CRT trial (453 women and 1,367 men), women had a better result from cardiac resynchronization therapy combined with a defibrillator (CRT-D), showing a significant 69% reduction in death or heart failure and a 70% reduction in heart failure alone compared with men who had CRT-D. Echocardiographic variables of left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF) improved to a greater degree with CRT-D therapy than with ICD therapy in both the female and male groups. Female patients had consistently greater improvements with CRT-D therapy than did male patients, with the most significant differences evident for the group as a whole and in those women with QRS ≥150 ms or left bundle branch block (LBBB). Women had 82% and 78% reductions in mortality among those with QRS ≥150 ms or with LBBB, respectively. The authors suggest that the differences seen between men and women in response to CRT-D may be related to greater reverse remodeling in women, especially those with QRS ≥150 MS or LBBB.
The study by Arshad et al. (1) is interesting, and its most important results include the clear findings that women with nonischemic cardiomyopathy and those with either prolonged QRS duration (QRS ≥150 ms) or with LBBB benefit from CRT-D. However, as one analyzes data related to clinical comparisons between men and women in this study, several concerns emerge. First, there were twice as many women with nonischemic cardiomyopathy as men and 2 to 3 times more men with ischemic heart disease than women (Table 1). Table 2 suggests that in women with nonischemic cardiomyopathies and women with LBBB or QRS ≥150 ms, CRT-D was superior in reducing the incidence of death or heart failure or heart failure alone. In women with ischemic heart disease, CRT-D did not reduce the incidence of death or heart failure when compared with men (Table 2). Moreover, Table 3 shows that, while there are some significant differences between women and men, such as the comparisons in hemodynamic variables with regard to reverse remodeling, the absolute differences in LVESV, LVEDV, and LVEF are very small. They are slightly larger for women with LBBB or QRS durations ≥150 ms than for men, but they are still quite small. I believe one can conclude from the study that women and men with LVEF <30%, QRS duration ≥130 ms and class I or class II symptoms benefit from CRT-D, and that is especially so for women with nonischemic cardiomyopathies and LBBB or QRS durations ≥150 ms. The clinical imbalance between the frequency of nonischemic versus ischemic cardiomyopathies between the 2 groups diminish our confidence in the concept that women benefit more than men. It is also difficult for one to feel very confident that the small differences in hemodynamic variables between men's and women's responses to CRT-D provide a complete explanation of the benefits found in selected women.
The Iles et al. (2) study was designed to evaluate the use of late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMRI) in patients with advanced cardiomyopathy who also had myocardial fibrosis and were at risk of sudden death. The investigators showed that in 103 patients with advanced cardiomyopathies who met the criteria for an ICD for primary prevention of sudden cardiac death (SCD), CMRI with LGE to identify regional fibrosis helped to identify patients with a high likelihood of appropriate ICD discharges. With a median follow-up of 573 days, LGE identified regional fibrosis in 31 of 61 patients with nonischemic cardiomyopathy and in all 42 patients with ischemic cardiomyopathy. There was a 29% discharge rate in the nonischemic cardiomyopathy patients with LGE compared with a 42% discharge rate in the ischemic cardiomyopathy group. There were no ICD discharges in the nonischemic group without LGE, which was significantly lower than the rate observed in the ischemic cardiomyopathy group and in the nonischemic cardiomyopathy patients with LGE. The LVEFs were similar in patients with and without device therapy and in patients with and without LGE. The authors conclude that patients with advanced cardiomyopathies and myocardial fibrosis demonstrated by LGE have an increased likelihood of appropriate ICD therapy.
While the investigators' conclusion is appropriate, the number of patients studied in each category is relatively small, and this study needs to be repeated by others with a larger sample size. In future studies, it would be important to quantify the volume of fibrosis in patients with and without appropriate ICD discharges. Clearly, there were patients with fibrosis in both groups who did not suffer an ICD discharge. It would also be helpful to compare the degree of hypertrophy and frequency of nonsustained ventricular tachycardia with the predictive ability of fibrosis detection by LGE, and to determine whether there is additive predictive power in combining the 3 methods. Comparisons with estimates of the “gray zone” (3) as defined by MRI by the Johns Hopkins School of Medicine group should also be informative.
In conclusion, as invasive therapies to assure the generation of electric myocardial activity (pacemakers), prevent sudden cardiac death (automatic ICDs), and improve the synchrony of cardiac contraction (CRT) evolve and become more efficacious and expensive, the need to identify the patients who benefit the most versus patients likely to be exposed to invasive procedures without clear-cut benefits also grows. The 2 papers discussed here represent important steps in this direction.
Dr. Willerson has reported that he has no relationships to disclose.
↵⁎ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
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