Sex-related differences in the prognosis of patients with cardiac sarcoidosis treated with cardiac resynchronization therapy

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Long-term outcome in diabetic heart failure patients treated with cardiac resynchronization therapy

BACKGROUND: Diabetes mellitus is an independent risk factor for increased morbidity and mortality in heart failure (HF) patients. AIMS: To compare functional and structural improvement, as well as long-term outcome, between diabetic and non-diabetic HF patients treated with cardiac resynchronization therapy (CRT). METHODS: We compared response to CRT in 141 diabetic and 214 non-diabetic consecutive patients. Major events were; death from any cause, urgent heart transplantation and implantation of a left ventricular (LV) assist device. Frequencies of hospitalisation and defibrillator (CRT-D) discharges were also analyzed. RESULTS: CRT was able to significantly improve functional capacity, ventricular geometry and neurohumoral imbalance in both diabetic and non-diabetic patients over a median follow-up time of 34 months. Overall event-free survival was similar in diabetic and non-diabetic patients (HR 1.23, p=0.363), as was survival free from CRT-D interventions (HR 1.72; p=0.115) and hospitalisations (HR 1.12; p=0.500). On multivariable analysis, NYHA class IV (p=0.002), low LV ejection fraction (p=0.002), absence of beta-blocker therapy (p<0.001), impaired renal function (p=0.003), presence of an epicardial lead (p=0.025), but not diabetes (p=0.821) were associated with a poor outcome after CRT. CONCLUSIONS: Diabetic HF patients treated with CRT had a very favourable functional and survival outcome, which was comparable to non-diabetic patients.     

心脏再同步治疗不同反应者对心律失常的影响

目的 根据扩张型心肌病(DCM)患者对心脏再同步治疗(CRT)不同的反应性,对其心律失常的性质与数最进行临床观察.方法 随机选取近年来90例随访资料完整的心脏再同步治疗起博器(CRT-P)或心脏再同步治疗除颤器(CRT-D)纳入分析,根据其反应性分为超反应组、有反应组及无反应组.并在CRT术后第6个月及1年随访时,进行临床评估、动态心电图及超声心动图评价.结果 各组患者在基线状态除QRS时限、心力衰竭症状出现时间有明显差别外,其余参数在基线状态无明显区别.6个月及1年随访时超反应组的室性心律失常及房性心律失常均明显改善,无反应组则无明显变化.结论 CRT能改善患者室性及房性心律失常的发生,特别是对于超反应者效果更明显.     

心脏再同步化治疗慢性心衰的临床观察

目的观察心脏再同步化治疗(CRT)慢性心力衰竭(CHF)患者的临床疗效。方法选择2008年1月至2009年8月行CRT的患者32例,其中12例植入再同步心脏转复除颤器(CRT-D)。32例中30例为窦性心律,2例为房颤心律。随访21.5±6.2个月,观察患者NYHA心功能分级、QRS波时限、左室射血分数(LVEF)、左室舒张末内径(LVEDD)、6分钟步行距离(6MWD)、因心功不全住院时间等。结果 32例植入CRT(D)患者中,有24例临床症状明显改善,心功分级降低,LVEF和6MWD增加,QRS波时限、LVEDD减少,因心功不全住院时间明显减少约24.5%(p<0.05)。8例患者心功能没有明显改善,但因心功不全住院时间减少约8.3%(p<0.05)。4例患者记录到室性心律失常事件(12.5%),2例室速经抗心动过速起搏(ATP)有效转复,2例患者因室颤而放电,均成功转复,CRT-D均能有效识别和转复。结论 CRT可明显改善CHF患者的心功能,提高生活质量,缓解临床症状,植入CRT-D可有效预防心源性猝死(SCD)。     

Performance of the Seattle Heart Failure Model in implantable defibrillator patients treated with cardiac resynchronization therapy

The Seattle Heart Failure Model (SHFM) is a validated multivariate risk prediction model for mortality in patients with heart failure, using widely available clinical variables. The aim of this study was to assess the performance of the SHFM when applied to patients with heart failure who received cardiac resynchronization therapy devices with defibrillation. A total of 413 patients were identified from 2 prospective implantable cardioverter-defibrillator registries who received cardiac resynchronization therapy devices with defibrillation for the primary prevention of sudden death. Baseline laboratory and clinical data were entered in the SHFM to calculate predicted survival. The end point was all-cause mortality. During a median follow-up period of 2.8 years, 78 patients died and 9 underwent heart transplantation. Observed versus predicted 5-year mortality rates were 11.6% versus 11.4%, 21.5% versus 22.1%, and 41.4% versus 46.1% by ascending tertile of Seattle Heart Failure Score, respectively. No systematic or substantial errors of risk estimation were observed. Discrimination was excellent; the C-statistic ranged from 0.78 at 1-year follow-up to 0.70 at 5-year follow-up, and the Hosmer-Lemeshow chi-square statistic was 0.87 (p = 0.65). In conclusion, in patients with heart failure who received cardiac resynchronization therapy devices with defibrillation, the SHFM offers adequate discrimination of risk for all-cause mortality and estimation of mortality risk without substantial or systematic errors.     

Long-term survival of patients with heart failure and ventricular conduction delay treated with cardiac resynchronization therapy

This multicenter longitudinal observational trial was designed to analyze the long-term outcome of patients with heart failure (HF) treated with cardiac resynchronization therapy (CRT) alone or with implantable cardioverter-defibrillator (ICD) backup in a daily practice scenario. It is unknown whether the magnitude of survival benefits conferred by CRT in a daily practice scenario is comparable to what has been observed in randomized controlled trials and whether this benefit is sustained over the long term. The outcome of 1,303 consecutive patients with ischemic or nonischemic cardiomyopathy on optimal pharmacologic therapy treated from August 1, 1995 to August 1, 2004 at 4 European centers with CRT alone (44%) or with ICD backup for symptomatic HF and prolonged QRS duration was assessed. Cumulative event-free survival was evaluated for a combined end point, defined as death from any cause, urgent transplantation, or implantation of a left ventricular assist device. The cumulative incidence of competing events, HF, sudden cardiac death, and noncardiac death, was also assessed. Event-free survival was similar across the different centers. At 1 and 5 years, cumulative event-free survivals were 92% (95% confidence interval [CI] 91 to 94) and 56% (95% CI 48 to 64), respectively. The cumulative incidence of HF deaths was 25.1% (95% CI 19 to 31.7), whereas that of sudden death was 9.5% (95% CI 5.1 to 15.7). Using multivariate analysis, CRT with an ICD backup was associated with a nonsignificant decrease in mortality by 20% (hazard ratio 0.83, 95% CI 0.58 to 1.17, p = 0.284), with a highly significant protective effect against sudden cardiac death (hazard ratio 0.04, 95% CI 0.04 to 0.28, p <0.002). In conclusion, patients with advanced HF and a wide QRS complex routinely treated with CRT have a favorable long-term outcome that was reproducible at different centers. The leading cause of death in these patients remained HF, and this mode of death was competing with other causes in determining outcome. Total mortality was 20% lower with ICD backup (95% CI 42% lower to 17% higher) due to a protective effect against sudden cardiac death.     

心脏再同步化治疗心衰的手术操作和疗效回顾

目的:探讨和总结心脏再同步化治疗(CRT)器治疗心衰的疗效。方法:21例心功能Ⅲ～Ⅳ级的心力衰竭患者,符合左室射血分数(LVEF)35%、心电图QRS波宽度≥160ms、左室舒张末期内径60mm的CRT建议标准。评价手术时间、X线曝光时间和术前后的单次最远行走距离、6min步行距离、NYHA心功能分级。结果:经左侧(n=20)和右侧锁骨下静脉(n=1)CRT的手术时间分别为(143.3±30.8)min和235min,而X线曝光时间分别为(19.7±15.5)min和75min;CRT术后单次最远行走距离显著增加[(921.7±253.8)m:(675.8±172.1)m,P0.01],6min步行距离术后较术前显著增加[(409.8±43.6)m:(292.5±55.6)m,P0.01],而NYHA心功能IV级者所占的百分率术后比术前显著减少(23.8%:85.7%,P0.01)。结论:对左室射血分数35%、心电图QRS波宽度≥160ms、左室舒张末期内径60mm的心衰患者,行CRT可显著改善6min步行距离和NYHA心功能分级。     

Effects of cardiac resynchronization therapy on ventricular repolarization in patients with congestive heart failure

INTRODUCTION: Biventricular pacing has been shown to improve the clinical status of patients with congestive heart failure, but little is known about its influence on ventricular repolarization. The aim of our study was to evaluate the effect of biventricular pacing on ECG markers of ventricular repolarization in patients with congestive heart failure. METHODS AND RESULTS: Twenty-five patients with congestive heart failure, sinus rhythm (SR), and complete LBBB (6 females; age 61 +/- 8 years; NYHA class II-III; echocardiographic ejection fraction 21 +/- 5%; QRS > or = 130 ms) underwent permanent biventricular DDDR pacemaker implantation. A high-resolution 65-lead body-surface ECG recording was performed at baseline and during right-, left-, and biventricular pacing, and the total 65-lead root mean square curve of the QRST complex and the interlead QT dispersion were assessed. The QRS duration was increased during right (RV)- and left ventricular (LV) pacing (127 +/- 26% and 117 +/- 40%; P < 0.05), as compared to SR (100%) and biventricular pacing (93 +/- 16%; ns). The QTc interval was increased during RV and LV pacing (112 +/- 12% and 114 +/- 14%; P < 0.05) as compared to SR (100%) or biventricular pacing (99 +/- 12%). There was no effect on JT interval during all pacing modes. The T(peak-end) interval was increased during right (120 +/- 34%; P < 0.01) and LV pacing (113 +/- 29%; P < 0.05) but decreased during biventricular pacing (81 +/- 19%; P < 0.01). A similar effect was found for the T(peak-end) integral and the T(peak) amplitude. QT dispersion was increased during right ventricular (129 +/- 16 ms; P < 0.05) and decreased during biventricular pacing (90 +/- 12 ms; P < 0.01), as compared to SR (114 +/- 22 ms). CONCLUSIONS: Using a high-resolution surface ECG, biventricular pacing resulted in a significant reduction of ECG markers of ventricular dispersion of repolarization.     

超声指导下心脏再同步化治疗慢性心力衰竭12例

目的观察超声指导下心脏再同步化治疗(CRT)对慢性心力衰竭(简称心衰)患者心功能的影响。方法 12例扩张型心肌病慢性心衰患者行CRT治疗,其中2例永久性心房颤动患者同时行房室结消融术。于术后1周、3个月、6个月对AV和VV间期进行优化,观察术前及术后3个月、6个月的NYHA心功能分级、6min步行距离、QRS波时限、左室射血分数(LVEF)、左室舒张末内径(LVEDD)、二尖瓣返流量(MRA)及心脏同步化指标的变化。结果与术前比较,术后3个月、6个月心功能均得到改善,6min步行距离增加,LVEF增加,LVEDD缩小,MRA减少,心脏同步化指标得到改善。结论在超声指导下对AV、VV间期进行优化后心脏再同步化治疗可改善双心室的同步性和心脏功能。     

Myocardial gene expression in heart failure patients treated with cardiac resynchronization therapy responders versus nonresponders.

OBJECTIVES: We studied whether functional improvement after cardiac resynchronization therapy (CRT) is associated with reversal of the heart failure (HF) gene program. BACKGROUND: Cardiac resynchronization therapy improves exercise tolerance and survival in patients with advanced congestive HF and dyssynchrony. METHODS: Twenty-four patients referred for CRT underwent left ventricular (LV) endomyocardial biopsies immediately before CRT implantation (baseline). In addition, 17 of them underwent LV endomyocardial biopsy procurement 4 months later (follow-up). In 6 control patients with normal LV function, LV biopsies were obtained at the time of coronary artery bypass grafting. The LV messenger ribonucleic acid (mRNA) levels of contractile and calcium regulatory genes were measured by quantitative real time polymerase chain reaction and normalized for glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The HF patients showing an improvement in New York Heart Association (NYHA) functional class by >1 score and a relative increase in LV ejection fraction > or =25% at 4 months after CRT were considered as responders. RESULTS: The HF patients were characterized by lower LV mRNA levels of alpha-myosin heavy chain (alpha-MHC), beta-myosin heavy chain (beta-MHC), sarcoplasmic reticulum calcium ATPase 2alpha (SERCA), phospholamban (PLN), and higher brain natriuretic peptide (BNP) mRNA levels as compared with control subjects. Responders to CRT (n = 11) showed an increase in LVEF (p < 0.001), a decrease in left ventricular end-diastolic diameter (p = 0.003), and NYHA functional class (p = 0.002), and a reduction in N-terminal proBNP levels (p = 0.032) as compared with baseline. This was associated with an increase in mRNA levels of alpha-MHC (p = 0.035), SERCA (p = 0.032), a decrease in BNP mRNA levels (p = 0.002), and an increase in the ratio of alpha-/beta-MHC (p = 0.018) and SERCA/PLN (p = 0.012). No significant changes in molecular profile were observed in nonresponders. CONCLUSIONS: In HF patients with electromechanical cardiac dyssynchrony, functional improvement related to CRT is associated with favorable changes in established molecular markers of HF, including genes that regulate contractile function and pathologic hypertrophy.     

Reverse of left ventricular volumetric and structural remodeling in heart failure patients treated with cardiac resynchronization therapy

Patients with heart failure and mechanical dyssynchrony suffer a progressive increase in left ventricular (LV) mass and asymmetrical regional hypertrophy with eventual poor prognosis. The present study sought to investigate whether cardiac resynchronization therapy (CRT) could reverse these abnormalities. The study included 66 consecutive heart failure patients who received CRT. All patients underwent serial evaluation before, 3 months after, and 12 months after CRT. At 12 months after CRT, 50 patients (76%) were echocardiographic volumetric responders, defined as a >15% reduction in LV end-systolic volume. LV end-systolic volume was decreased from 214 +/- 97 ml to 179 +/- 88 ml at 3 months and was further decreased to 158 +/- 86 ml at 12 months after CRT (all p <0.01). LV ejection fraction was improved from 18% +/- 4% to 28% +/- 7% (p <0.001) at 3 months without further change at 12 months after CRT. LV mass was reduced from 242 +/- 52 g to 222 +/- 45 g at 3 months and was further reduced to 206 +/- 50 g at 12 months after CRT (all p <0.01). Improvement of LV geometry was seen as improvements of the end-diastolic (1.64 +/- 0.14 vs 1.77 +/- 0.17, p <0.001) and the end-systolic (1.63 +/- 0.14 vs 1.99 +/- 0.22, p <0.001) sphericity indexes, respectively, at 3 months, without further significant changes at 12 months after CRT. Volumetric responders had a reduction in LV mass from 240 +/- 50 to 210 +/- 38 at 3 months, and LV mass was further reduced to 186 +/- 37 g at 12 months after CRT (all p <0.01). In contrast, nonresponders had a progressive increase in LV mass from 248 +/- 59 g to 258 +/- 54 g at 3 months, and LV mass was further increased to 269 +/- 60 g at 12 months after CRT (all p <0.05). Likewise, only in volumetric responders, regression of the asymmetric hypertrophy of the lateral wall was noted. In conclusion, CRT results in not only volumetric improvement but also in true reverse LV structural remodeling, evidenced by progressive reduction in LV mass and restoration of regional wall symmetry.     

Effects of cardiac resynchronization therapy on disease progression in patients with congestive heart failure.

BACKGROUND: Cardiac resynchronization therapy (CRT) represents a new therapeutic modality of proven efficacy for selected patients with heart failure and ventricular asynchrony. The aim of this study was to assess the effects of CRT on clinical variables and cardiac remodeling in patients with moderate-to-severe congestive heart failure and inter/intraventricular conduction delays. METHODS: Thirty-seven patients (32 males, 5 females, mean age 73 +/- 7 years), in NYHA functional class III-IV, with left ventricular ejection fraction (LVEF) < or = 35%, QRS > or = 150 ms, and left ventricular end-diastolic diameter (LVEDD) > or = 55 mm, underwent CRT by biventricular pacing (InSync, InSync III, InSync ICD; Medtronic Inc.). Fourteen (37.8%) had a previous pacemaker, and 11 (29.7%) were in permanent atrial fibrillation. The QRS width, NYHA functional class, LVEDD, left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic volume (LVEDV), left ventricular endsystolic volume (LVESV), and LVEF were retrospectively evaluated in the period before CRT. For the purposes of the present study, the pre-CRT period was divided in two: T(-2) (from 6 to 3 years) and T(-1) (from 3 years to CRT). Moreover, these parameters were measured at the time of CRT (T0) and prospectively in the post-CRT follow-up (Tp). RESULTS: Before CRT, a progressive worsening of the parameters was observed. The QRS duration steadily increased from T(-2) to T(-1) and T0 (both p = 0.000). The NYHA functional class increased from T(-2) to T(-1) and T0 (both p = 0.000). LVEDD and LVESD also increased and were higher at T(-1) (p = 0.001 and p = 0.000, respectively) and at T0 (both p = 0.000) compared to T(-2). Similar results were observed for LVEDV and LVESV. Finally, LVEF was higher at T(-2) than T(-1) and T0 (both p = 0.000). After CRT, there was a reduction in the QRS duration and an improvement in the NYHA functional class compared to T0 (both p = 0.000). LVEDD and LVESD were also reduced (p = 0.005 and p = 0.016, respectively), LVEDV and LVESV decreased (both p = 0.000), and LVEF increased (p = 0.000) with respect to T0. A highly significant correlation was found between LVEDD and LVESD both in the pre- and post-CRT time intervals, with a non-significant difference between the two linear regression lines. Similar results were obtained for the correlations between LVEDV and LVESV. CONCLUSIONS: Congestive heart failure is associated with a progressive widening of the QRS complex and a worsening of the clinical status and results in anatomic remodeling with deterioration of the left ventricular function. CRT induces opposite changes in QRS duration, clinical status, and left ventricular remodelling.