Effects of statin therapy on arrhythmic events and survival in patients with nonischemic dilated cardiomyopathy.

OBJECTIVES: We sought to evaluate whether statins were associated with a survival benefit and significant attenuation in life-threatening arrhythmias in patients with nonischemic dilated cardiomyopathy. BACKGROUND: Statins are associated with a reduction in appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with coronary artery disease and improved clinical status in nonischemic dilated cardiomyopathy. METHODS: The effect of statin use on time to death or resuscitated cardiac arrest and time to arrhythmic sudden death was evaluated in 458 patients enrolled in the DEFINITE (DEFIbrillators in Non-Ischemic cardiomyopathy Treatment Evaluation) study. The effect of statin use on time to first appropriate shock was analyzed only in the 229 patients who were randomized to ICD therapy. RESULTS: The unadjusted hazard ratio (HR) for death among patients on versus those not on statin therapy was 0.22 (95% confidence interval [CI] 0.09 to 0.55; p = 0.001). When controlled for statin effects, ICD therapy was associated with improved survival (HR 0.61; 95% CI 0.38 to 0.99; p = 0.04). There was one arrhythmic sudden death in the 110 patients receiving statin therapy (0.9%) versus 18 of 348 patients not receiving statins (5.2%; p = 0.04). The unadjusted HR for arrhythmic sudden death among patients on versus those not on statin therapy was 0.16 (95% CI 0.022 to 1.21; p = 0.08). The HR for appropriate shocks among patients on versus those not on statin therapy was 0.78 (95% CI 0.34 to 1.82) after adjustment for baseline differences in the two groups. CONCLUSIONS: Statin use in the DEFINITE study was associated with a 78% reduction in mortality. This reduction was caused, in part, by a reduction in arrhythmic sudden death. These findings should be confirmed in a prospective, randomized clinical trial.     

Echocardiographic predictors of morbidity and mortality in patients with advanced heart failure: the Beta-blocker Evaluation of Survival Trial (BEST)

OBJECTIVES: The aim of this study was to determine echocardiographic predictors of outcome in patients with advanced heart failure (HF) due to severe left ventricular (LV) systolic dysfunction in the Beta-blocker Evaluation of Survival Trial (BEST). BACKGROUND: Previous studies indicate that echocardiographic measurements of LV size and function, mitral deceleration time, and mitral regurgitation (MR) predict adverse outcomes in HF. However, complete quantitative echocardiograms evaluating all of these parameters have not been reported in a prospective randomized clinical trial in the era of modern HF therapy. METHODS: Complete echocardiograms were performed in 336 patients at 26 sites and analyzed by a core laboratory. A Cox proportional-hazards regression model was used to determine which echocardiographic variables predicted the primary end point of death or the secondary end point of death, HF hospitalization, or transplant. Significant variables were then entered into a multivariable model adjusted for clinical and demographic covariates. RESULTS: On multivariable analysis adjusted for clinical covariates, only LV end-diastolic volume index predicted death (events = 75), with a cut point of 120 ml/m(2). Three echocardiographic variables predicted the combined end point of death (events = 75), HF hospitalization (events = 97), and transplant (events = 9): LV end-diastolic volume index, mitral deceleration time, and the vena contracta width of MR. Optimal cut points for these variables were 120 ml/m(2), 150 ms, and 0.4 cm, respectively. CONCLUSIONS: Echocardiographic predictors of outcome in advanced HF include LV end-diastolic volume index, mitral deceleration time, and vena contracta width. These variables indicate that LV remodeling, increased LV stiffness, and MR are independent predictors of outcome in patients with advanced HF.     

Evidence of myocardial edema in patients with nonischemic dilated cardiomyopathy

Background:

Nonischemic dilated cardiomyopathy (DCM) is associated with high mortality and morbidity. Cardiovascular magnetic resonance allows for the noninvasive assessment of function, morphology, and myocardial edema. Activation of inflammatory pathways may play an important role in the etiology of chronic DCM and may also be involved in the disease progression.

Hypothesis:

The purpose of our study was to assess the incidence of myocardial edema as a marker for myocardial inflammation in patients with nonischemic DCM.

Methods:

We examined 31 consecutive patients ( mean age, 57 ± 12 years) with idiopathic DCM. Results were compared with 39 controls matched for gender and age (mean age, 53 ± 13 years). Parameters of left ventricular function and volumes, and electrocardiogram‐triggered, T2‐weighted, fast spin echo triple inversion recovery sequences were applied in all patients and controls. Variables between patients and controls were compared using t tests for quantitative and χ 2. tests for categorical variables.

Results:

Ejection fraction (EF) was 40.3 ± 7.8% in patients and 62.6 ± 5.0% in controls (P < 0.0001). In T2‐weighted images, patients with DCM had a significantly higher normalized global signal intensity ratio compared to controls (2.2 ± 0.6 and 1.8 ± 0.3, respectively, P = 0.0006), consistent with global myocardial edema. There was a significant but moderate negative correlation between signal intensity ratio in T2‐weighted images and EF (?0.39, P < 0.001).

Conclusions:

Evidence shows that myocardial edema is associated with idiopathic nonischemic DCM. Further studies are needed to assess the clinical and prognostic impact of these findings. Clin. Cardiol. 2012 DOI: 10.1002/clc.21979 The authors have no funding, financial relationships, or conflicts of interest to disclose.

     

Mitral valve surgery in patients with ischemic and nonischemic dilated cardiomyopathy

Congestive heart failure (CHF) is a chronic, progressive disease and its central element is the remodeling of the cardiac chamber associated with ventricular dilatation. Secondary mitral regurgitation is a complication of end-stage cardiomyopathy and is associated with a poor prognosis. It is due to progressive mitral annular dilatation and alteration in the geometry of the left ventricle. A vicious cycle of continuing volume overload, ventricular dilatation, progression of annular dilatation, increased left ventricular wall tension and worsening mitral regurgitation and CHF occurs. The mainstays of medical therapy are diuretics and afterload reduction, which are associated with poor long-term survival in these patients. Historically, the surgical approach to patients with mitral regurgitation was mitral valve replacement, but these patients were not considered operative candidates because of their high morbidity and mortality. Heart transplantation is now considered standard treatment for select patients with end-stage heart disease; however, it is applicable only to a small number of patients. Mitral valve replacement in these patients is associated with adverse consequences on left ventricular systolic function resulting from interruption of the annulus-papillary muscle continuity. Preserving the mitral valve apparatus and left ventricle in mitral valve repair enhances and maintains left ventricular function and geometry with an associated decrease in wall stress. Using these operative techniques to alter the shape of the left ventricle, in combination with optimal medical management for heart failure, improves survival and may avoid or postpone transplantation.     

Beta-blocker therapy induces ventricular resynchronization in dilated cardiomyopathy with narrow QRS complex.

OBJECTIVES: We sought to evaluate the effects of beta-blocker therapy on regional and global myocardial mechanics in addition to ventricular synchrony in patients with heart failure and normal QRS by using tissue Doppler and strain echocardiography. BACKGROUND: It is unknown whether beta-blocker therapy can influence mechanical synchrony. METHODS: Conventional and strain echocardiography were performed in 15 healthy age-matched volunteers and in 25 patients with idiopathic dilated cardiomyopathy (IDC). Of these, 15 IDC patients on standard heart failure therapy were studied prior to and at 1 and 6 months after initiation of carvedilol therapy and compared to the controls. RESULTS: There was significant mechanical dyssynchrony in IDC compared with control patients. Patients placed on carvedilol demonstrated a significant decrease in the inferoseptal to lateral wall delay in peak strain (normalized to the R-R interval) between baseline and 1 month and between baseline and 6 months. Similarly, global time to peak segmental strain (455 +/- 51 ms vs. 423 +/- 59 ms, respectively, p = 0.02, and 455 +/- 51 ms vs. 415 +/- 50 ms, respectively, p = 0.01) and the coefficient of variation of the time to peak segmental strain decreased (17 +/- 4% vs. 15 +/- 5%, respectively, p = 0.02, and 17 +/- 4% vs. 14 +/- 5%, respectively, p = 0.03), from baseline to 1 month and between baseline and 6 months, respectively. Global strain significantly increased from baseline to 1 month (-8.2 +/- 1.8 to -10.4 +/- 3.9, respectively, p = 0.01) and between baseline and 6 months (-8.2 +/- 1.8% to -12.0 +/- 3.2%, respectively, p = 0.008). Improvements in left ventricular ejection fraction and reverse remodeling were coincident with reductions in mechanical dyssynchrony. CONCLUSIONS: The use of carvedilol improves contractile function and dyssynchrony in heart failure patients with normal QRS.     

Myocardial oxidative metabolic supply-demand relationships in patients with nonischemic dilated cardiomyopathy.

BACKGROUND: Nonischemic dilated cardiomyopathy (NIDCM) is associated with left ventricular remodeling, hypertrophy, and mitochondrial metabolic abnormalities in vitro. We evaluated the hypothesis that energy supply, as judged by the rate of myocardial oxidative metabolism, is inadequate to meet oxygen demand in patients with NIDCM compared with normal subjects. METHODS AND RESULTS: We used positron emission tomography to determine the myocardial carbon 11 acetate decay rate (kmono) as an index of energy supply, and we compared kmono with the rate-pressure product (RPP) as an index of metabolic demand in 7 patients with NIDCM and 7 normal subjects. The mean kmono value (SEM) was 0.060 +/- 0.006 min(-1) in NIDCM patients versus 0.054 +/- 0.002 in normal subjects (P = not significant). The RPP was 9949 +/- 931 beats/min.mm Hg in NIDCM patients and 6521 +/- 476 in normal subjects (P = .007). The relationship of kmono to this index of demand (kmono/RPP) was 6.2 x 10(-6) in NIDCM patients but was 8.5 x 10(-6) in normal subjects (P = .003). Thus RPP, as an index of myocardial oxygen demand, was poorly matched by the rate of oxidative metabolism in those patients with NIDCM. The kmono was closely related to RPP in normal subjects (r = 0.83, P = .02) but not in NIDCM patients. Furthermore, there was no significant relationship between kmono and wall stress as another index of oxygen demand. CONCLUSIONS: These results are consistent with a mitochondrial metabolic abnormality in heart failure. This metabolic mismatch detected by positron emission tomography may contribute to the pathophysiology of congestive heart failure and left ventricular remodeling.     

心脏再同步化治疗晚期扩张型心肌病13例的效果

目的: 观察心脏再同步化治疗（CRT）晚期充血性心力衰竭的临床疗效。方法: 晚期扩张型心肌病患者13例接受CRT,NYHA心功能分级为Ⅲ～Ⅳ级,左室射血分数（LVEF）为（27.4±9.7）%,左室舒张末期内径（LVEDD）为(72.8±9.6)mm,QRS时限为( 137.8＋30.4)ms。术后观察QRS时限的变化,随访左室电极起博阈值、心功能分级、LVEF及LVEDD。结果: 术后QRS时限减少为（123.8±17.1）ms。所有患者随访3～38月,左室电极慢性阈值为（1.1±0.6）V/0.4 ms。与术前相比,NYHA心功能分级从(3.4±0.5)降低为(1.5±0.9); LVEF从(27.4±9.7)%上升至(43.5±18.5)%(P<0.05);LVEDD从(72.8±9.6)mm缩小为(65.5±11.6)mm（P<0.05）。结论: CRT可改善心功能,提高LVEF,并可逆转左心室重构。     

Prognostic value of an abnormal signal-averaged electrocardiogram in patients with nonischemic dilated cardiomyopathy

The usefulness of an abnormal signal-averaged ECG (SAECG) for the risk stratification of patients with dilated cardiomyopathy was studied prospectively in 76 patients. Multiple analysis showed that an abnormal SAECG predicted cardiac mortality (p = 0.0046), sudden cardiac death, and the need for resuscitation (p = 0.003); however, it did not predict death from heart failure and heart transplantation.     

左室收缩不同步在非缺血性扩张型心肌病患者中预后价值

目的:运用组织多普勒超声心动图研究左室收缩不同步在非缺血性扩张型心肌病患者中的预后价值。方法:入选72例非缺血性扩张型心肌病患者,均行心电图、超声心动图(包括组织多普勒超声心动图)及冠状动脉造影等检查;根据心室内延迟时间(IVD)将入选患者分为2组:IVD≤65 ms组(20例)和IVD>65 ms组(52例),主要终点定义为随访期内的全因死亡。结果:与IVD≤65 ms组比较,IVD>65 ms组患者有较长的IVD[(129±68)ms∶(58±9)ms;P<0.05],较高的左束支传导阻滞发生率(31%∶10%;P=0.05),较高的病死率(56%∶5%;P<0.01)。IVD≤65 ms组、IVD>65 ms组分别有1例、12例患者发生猝死;因进展性心力衰竭死亡的17例患者均发生在IVD>65 ms组。Kaplan-Meier生存分析显示IVD>65 ms组患者有较低的生存率(P<0.05),多因素分析显示IVD是惟一具有显著差异的死亡预测因子(P<0.01)。结论:高IVD是非缺血性扩张型心肌病患者死亡的独立预测因素。     

Increased inflammatory response in patients with dilated cardiomyopathy is associated with dyslipidemia: Effects of statin therapy

Dilated cardiomyopathy (DCM) is associated with increased inflammatory response reflected among other markers in high-sensitivity C-reactive protein (hsCRP) and soluble interleukin-2 receptor (sIL-2R) levels. We examined prospectively 60 consecutive patients with DCM. Of them, 30 were dyslipidemic (group I) and 30 normolipidemic (group II). Group I patients were randomized to either simvastatin therapy (20 mg/day, group Ia, n = 15) or hypolipidemic diet therapy (group Ib, n = 15). Patients were re-evaluated 6 months later. High-sensitivity C-reactive protein and sIL-2R levels were significantly higher in group I compared with group II patients (19.5 ± 3.4 vs 3.03 ± 3.5 mg/L, P = .01, 1137 ± 441 vs 599 ± 235 pg/mL, P = .001, respectively). There was a significant correlation between sIL-2R and hsCRP levels in dyslipidemic patients but not in normolipidemic patients. Significant reduction of hsCRP and sIL-2R levels was observed only in group Ia patients. Patients with DCM having dyslipidemia have increased inflammatory response, which is reduced after 6 months of statin therapy.     

High risk of ventricular arrhythmias in patients with nonischemic dilated cardiomyopathy presenting with syncope

It is not entirely clear whether the presentation of syncope in patients with nonischemic dilated cardiomyopathy (NIDC) is an ominous prognostic indicator, because randomized controlled implantable cardioverter-defibrillator (ICD) trials generally exclude such patients. This study compared 108 consecutive patients with NIDC presenting with syncope with 71 consecutive patients with NIDC who presented with sustained ventricular arrhythmias, with regard to freedom from any ventricular arrhythmias or life-threatening arrhythmias and all-cause mortality. There was no significant difference between the groups in the 3 outcomes during the follow-up of 43.5 +/- 32.1 months. Male gender and ICD therapy predicted increased risk for any ventricular arrhythmias. A reduced left ventricular ejection fraction and increased age were predictive of increased mortality. In conclusion, patients with NIDC presenting with syncope are a high-risk group, with event rates similar to patients with NIDC presenting with sustained arrhythmias, and should be considered for ICD therapy.     

左心室收缩不同步在非缺血性扩张型心肌病患者的预后价值

目的:运用组织多普勒超声心动图研究左心室收缩不同步在非缺血性扩张型心肌病患者中的预后价值。方法: 入选62例非缺血性扩张型心肌病患者,所有患者均行心电图、超声心动图（包括组织多普勒超声心动图）及冠状动脉造影,入选患者根据心室内延迟时间（IVD）分为2组:IVD≤65 ms组(n=10）和IVD>65 ms组(n=52）,主要终点定义为随访期内的全因死亡。结果: IVD>65 ms组患者有较长的心室内延迟时间［(129±68) ms vs.(58±9) ms;P<0.05］,较高的左束支传导阻滞发生率(31% vs. 10%;P=0.05),更长的QRS间期［(145±29) ms vs.(129±23) ms,P<0.05］较高的病死率(56% vs. 10%;P<0.01). IVD≤65 ms组中1例患者发生心源性猝死;而IVD>65 ms组中有12例发生,且其他原因引起的死亡也发生在组IVD>65 ms组。Kaplan-Meier生存分析显示IVD>65 ms组患者有较低的生存率(P<0.05),多因素分析显示IVD是唯一具有显著差异的死亡预测因子(P<0.01)。结论: 高IVD是非缺血性扩张型心肌病患者死亡的独立预测因素。