| BackgroundHeart failure (HF) is a complex clinical syndrome that resulted from impairment of diastolic or systolic function caused by any of cardiovascular diseases, and is the clinical outcome of the majority of cardiovascular diseases in end-stage. HF incidence increases with age, and is one of the leading causes of death currently. Although breakthrough has made in the field of drugs for the treatment of heart failure, the quality of life of HF patients is still in a low level and the absolute mortality rate for HF remains high.Cardiac resynchronization therapy (CRT) is now a well-established treatment for patients with chronic heart failure and wide QRS duration. CRT helps to restore atrio-ventricular, inter-ventricular and intra-ventricular synchrony, decrease mitral regurgitation and ventricular septal dyskinesis, increase left ventricular filling time, and even reduce the activation of neuro-endocrine system, thus induce reverse myocardial remodeling and improve the symptoms of heart failure. With the publication of MUSTIC, MIRACLE, COMPANION, CARE-HF, MADIT-CRT and RAFT trials, these results further confirm the role of CRT played in the treatment of patients with mild to moderate heart failure, not only can it improve heart failure symptoms, increase exercise tolerance, and enhance the quality of life, but also it can significantly decrease heart failure re-hospitalization and mortality.Despite these advances in the field of CRT for the treatment of heart failure, it is broadly assumed that approximately30%of CRT patients do fail to benefit from this therapy during the follow-up, called "non-responders", some researchers reported that CRT "non-responders" even up to45%. Nevertheless, identifying reliable factors for predicting CRT response still remains a major challenge in clinical practice. Nowadays, the association between QRS morphology or duration and the efficacy of CRT in patients with heart failure and identifying predictors for CRT response are still under research. In order to study the hot topics mentioned above, we performed retrospective analysis mainly about the two topics below:(1) impact of QRS morphology and duration on clinical outcomes after cardiac resynchronization therapy;(2) Predictors for cardiac resynchronization therapy response.Part1:Impact of QRS Morphology and Duration on clinical Outcomes after Cardiac Resynchronization TherapyObjective:To investigate the impact of QRS morphology and duration on clinical outcomes, with respect to symptom relief, left ventricular remodeling and prognosis of Cardiac Resynchronization Therapy (CRT) in patients with chronic heart failure.Methods:We retrospectively analyzed the data of chronic heart failure patients with wide QRS complex who underwent CRT-P/D implantation from January2006to December2013in the Second Affiliated Hospital of Zhejiang University School of Medicine. According to the baseline QRS morphology and QRS complex duration, patients were classified into four groups:left bundle branch block (LBBB) with QRS duration≥150ms, LBBB with QRS duration120-149ms, Non-LBBB with QRS duration≥150ms and Non-LBBB with QRS duration120-149ms. The primary endpoint of this study was heart failure re-hospitalization or all-cause death after CRT. We compared the differences of heart function (NYHA class and six-minute walking distance), left ventricular ejection fraction (LVEF), left ventricular end diastolic/systolic diameter (LVEDD/LVESD) and left atrium diameter(LAD) pre-and post CRT among different groups, further analyzed the incidence of primary study endpoint and discussed the potential factors predicting the primary endpoint after CRT.Results:197patients were included in the study, composed of132male(67.0%) and65female(33.0%) with a mean age (63.85±11.68) years.99patients (50.3%) had LBBB and a QRS duration≥150ms,25(12.7%) had LBBB and a QRS duration (120-149)ms,14(7.1%) had non-LBBB and a QRS duration≥150ms, and59(29.9%) had non-LBBB and a QRS duration (120-149)ms. After a median follow-up of3.1years after CRT, both patients with LBBB regardless of QRS duration and non-LBBB with QRS duration (120-149)ms had significant improvement in LVEF, LVEDD, LVESD, NYHA class and6MWD when compared with baseline (P≤0.001), but only patients with LBBB and QRS duration≥150ms showed significant improvements in LAD (P≤0.001). Patients with non-LBBB and QRS duration≥150ms also showed improvements in LVEDD(P=0.001) and LVESD (P=0.011), however, no obvious changes were observed in LAD (P=0.80)、LVEF (P=0.40)、NYHA class (P=0.26) and6MWD (P=0.26) in those patients. The magnitude of improvement in echocardiographic and heart function parameters between patients with LBBB and a QRS duration≥150ms and those with LBBB and a QRS duration (120-149) ms were similar (P>0.05), and both showed better benefit from CRT than those with non-LBBB morphology regardless of QRS duration (P<0.05). There were no significant difference between non-LBBB with QRS≥150ms and non-LBBB with QRS duration (120-149) ms in the magnitude of improvement in echocardiographic parameters (P>0.05), but patients with non-LBBB and QRS duration>150ms showed significantly greater magnitude improvement in NYHA class and6MWD compared with those had non-LBBB and a QRS duration (120-149) ms (P<0.05). Kaplan Meier analysis showed significant difference among four groups in the facet of primary endpoint (P<0.001)6.1%vs12.0%vs35.7%vs35.6%,. The primary endpoint occurred in6.1%of the LBBB and QRS duration≥150ms group,12.0%of the LBBB and QRS duration (120-149)ms group,35.7%of non-LBBB and QRS duration≥150ms group,35.6%of non-LBBB and QRS duration (120-149)ms group. However, further analysis showed that there was no significant difference in all-cause mortality among the four group (5.1%vs8.0%vs21.4%vs6.8%,P=0.18), whereas heart failure re-hospitalization rate was significantly lower in LBBB group than non-LBBB group regardless of QRS duration(6.1%vs12.0%vs35.7%vs35.6%,P<0.001). The specific groups were significant predictors for the primary endpoint after CRT in a univariate or multivariate Cox model (P<0.001). Interestingly, when QRS duration and QRS morphology were entered as separate candidate variables in a stepwise Cox model, QRS was no longer significant, but QRS morphology still had a predicting value for the primary endpoint after CRT(P<0.001).Conclusions:Patients with LBBB derived best benefit from CRT; and there was no significant difference between QRS duration≥150ms and QRS duration120-149ms, followed by those with non-LBBB and QRS duration120-150ms, and those with non-LBBB and QRS duration≥150ms benefit little from CRT. Compared to QRS duration, QRS morphology proved to be more valuable in predicting the prognosis of long-term outcomes after CRT. Part2:Predictors for Cardiac Resynchronization Therapy responseObjective:Although Cardiac Resynchronization Therapy (CRT) is a well-established treatment for a subset of patients with chronic heart failure, and it has been shown to mitigate heart failure symptoms, induce reverse remodeling, there are still a considerable proportion of eligible patients fail to benefit from this treatment. The aim of this study was to identify potential independent predictors of being responders to CRT.Methods:A single-center, retrospective analysis was conducted in patients with heart failure and wide QRS complex who successfully underwent CRT device implantation from January2006to December2012. Clinical characteristics, left ventricular lead position, electrocardiography and echocardiography were evaluated before and12months after CRT. Left ventricular lead position was defined by fluoroscopy in two views upon implantation, the left anterior oblique45°and the right anterior oblique30°views.The short-axis circumferential position was classified as anterior, lateral, posterior on LAO45°view. Using the right anterior oblique30°view, the longitudinal lead position was divided into three locations:apical, mid-ventricular, and basal. A presumed optimal left ventricular lead position (LV-Ps) was defined as lateral in the short-axis view combined with a longitudinal position of basal or mid-ventricular segments. Response to CRT was defined as an absolute increase of≥5%in left ventricular ejection fraction (LVEF) compared with baseline during12months follow-up after CRT implantation without heart failure re-hospitalization or any cause of death.Results:193patients with chronic heart failure who underwent successful implantation of a CRT-P/D were included in this study. There were132responders (68%) and61non-responders (32%). There were more left bundle branch block (LBBB) and sinus rhythm, longer QRS duration, less history of ventricular tachycardia (VT), milder tricuspid regurgitation, smaller left atrium size and more frequence of optimal left ventricular lead position (LV-Ps) among CRT responders. By univariate logistic analysis, presence of non-left bundle bunch block (non-LBBB) and QRS duration, chronic atrial fibrillation (AF), history of VT, degree of tricuspid regurgitation and LA dimension at baseline,△QRS duration, and LV-Ps were associated with predicting CRT response. However, on multivariate analysis, only LV-Ps, chronic atrial fibrillation and presence of non-LBBB remained independently predictive for CRT response, with an odds ratio of2.22(95%confidence interval [CI]:1.06-4.65, P=0.035),0.36(95%CI:0.15-0.86, P=0.022),0.16(95%CI:0.08-0.33, P<0.001), respectively. Kaplan-Meier analysis revealed that CRT responders had a significantly lower mortality or heart failure re-hospitalization compared with CRT non-responders (P<0.001); patients with non-optimal LV-Ps or non-LBBB morphology had a significantly higher mortality or heart failure re-hospitalization as compared with those with optimal LV-Ps or LBBB morphology (p<0.05), however, there was no significant difference between sinus rhythm and chronic atrial fibrillation (P=0.17).Conclusion:CRT candidates with LBBB QRS morphology are more likely to benefit from this device therapy. A presumed optimal LV-Ps is associated with a better response in patients treated with CRT. |
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