Prognostic value of electrocardiographic measurements before and after cardiac resynchronization device implantation in patients with heart failure due to ischemic or nonischemic cardiomyopathy

Postimplant QRS narrowing may predict clinical response after cardiac resynchronization therapy (CRT), but identification of nonresponders remains difficult. We studied the predictive value of electrocardiographic characteristics for mortality or cardiac transplantation in patients after CRT. Patients who had electrocardiograms available for review from before and after CRT device implantation were identified from a clinical database. Bivariate and multivariate Cox regression analyses were performed for the end point of death or transplantation. Of 337 patients (age 65+/-12 years, 76% men, left ventricular ejection fraction 22+/-12%, pre-QRS 175+/-30 ms), 84 died and 7 underwent transplantation during a follow-up of 27+/-15 months. Variables predictive of death or transplantation included QRS increase after CRT (45% vs 32%, p=0.03), older age, higher New York Heart Association class, lower left ventricular ejection fraction, and higher tertile of postimplant QRS (p=0.04), but not preimplant rhythm, QRS duration, or QRS morphology. After adjusting for confounding variables, independent predictors of mortality were older age (hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.00 to 1.05, p=0.04), lack of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (HR 2.17, 95% CI 1.16 to 4.08, p<0.02), and longer postimplant QRS by tertile (HR 1.50, 95% CI 1.09 to 2.05, p=0.01). In conclusion, wider QRS after CRT device implantation is an independent predictor of mortality or transplantation. In patients with increased QRS durations despite CRT, closer follow-up or reassessment for alternative management strategies may be warranted.     

Impact of left ventricular filling properties on the benefit of exercise training in patients with advanced chronic heart failure secondary to ischemic or nonischemic cardiomyopathy

This study examined left ventricular (LV) filling properties and exercise hemodynamics noninvasively before and after an exercise training program in patients with chronic heart failure (HF). Although exercise training did not improve LV filling properties in patients with advanced HF, LV filling properties determined the hemodynamic benefit attainable from exercise in this patient group.     

The influence of diastolic and systolic function on exercise performance in heart failure due to dilated cardiomyopathy or ischemic heart disease

BACKGROUND: Peripheral adaptations and ventricular abnormalities influence physical performance in chronic heart failure. However, the role of the heart in determining exercise capacity has not been completely elucidated. AIMS: To define cardiac determinants of exercise capacity in patients with dilated cardiomyopathy. METHODS: In 101 patients with heart failure (NYHA class II-III) due to primary or ischemic dilated cardiomyopathy we measured peak exercise oxygen consumption (Pvo2), left ventricular ejection fraction (EF), left and right atrial and ventricular cavity dimensions, mitral and tricuspid flows. Patients were subdivided in class A (Pvo2 > 20 ml/min per kg; n = 44), class B (Pvo2 16-20 ml/min per kg; n = 42) and class C (Pvo2 < 16 ml/min per kg; n = 15). RESULTS: Left ventricular diastolic and systolic dimensions, left atrial diameter, right atrial and ventricular areas were greater in class C than in class B and A; EF was lower in class C than in the other two classes; mitral peak flow velocity at early diastole (PFVE) and the ratio between early and late peak flow velocity (PFVE/PFVA) were higher in class C; mitral and tricuspid deceleration time (DT) in class B and A significantly exceeded those in class C. Peak vo2 was correlated with left and right ventricular dimensions, left atrial diameter, EF, mitral PFVE and PFVE/PFVA, mitral and tricuspid DT. Left ventricular EF, DT of the mitral valve and left ventricular diastolic diameter were independent predictors of peak vo2 at multivariate analysis. CONCLUSIONS: In patients with dilated cardiomyopathy Pvo2 is related to left and right ventricular dimensions, left and right ventricular filling pattern and EF. Both systolic and diastolic dysfunction influence functional capacity.     

Baseline predictors of cardiac events after cardiac resynchronization therapy in patients with heart failure secondary to ischemic or nonischemic etiology

We evaluated the value of baseline parameters derived from tissue Doppler imaging (TDI) for event prediction in patients with heart failure (HF) secondary to ischemic and nonischemic cause who underwent cardiac resynchronization therapy (CRT). Seventy-four consecutive patients with HF (mean age 59 +/- 11 years) underwent CRT. Baseline clinical parameters included New York Heart Association class, 6-minute walking distance, HF cause, and diabetes. TDI-derived parameters included lateral and septal E/E' ratios defined as peak early left ventricular (LV) filling velocity (E wave) to TDI-derived peak early diastolic velocity of the mitral annulus (E' wave). During a median follow-up of 720 days, 21 patients (28%) had cardiac death or hospitalization for HF. These patients more often had an ischemic cause (p <0.05), diabetes (p <0.05), and restrictive filling (p <0.001), less often had LV dyssynchrony (p <0.05), and had higher septal and lateral E/E' ratios (p <0.001 for the 2 comparisons). In a multivariable model using a forward selection algorithm, only the lateral E/E' ratio remained an independent predictor of cardiac outcome. After 3 months of CRT, TDI-derived systolic mitral annular systolic and diastolic velocities improved significantly in nonischemic patients for the septal and lateral sides. In contrast, in ischemic patients no significant improvements were seen. Significant improvements were seen in septal and lateral E/E' ratios in ischemic and nonischemic patients. However, the improvement in lateral E/E' ratio was significantly less and absolute 3-months E/E' ratios were worse in ischemic patients. In conclusion, baseline lateral E/E' ratio is an independent predictor for cardiac events in patients with HF treated with CRT. The worse clinical outcome in ischemic patients may be due to failure of improvement in systolic and diastolic mitral annular velocities after CRT, resulting in a less pronounced improvement in LV filling pressures as demonstrated by this E/E' ratio.     

Prognostic usefulness of the six-minute walk in patients with advanced congestive heart failure secondary to ischemic or nonischemic cardiomyopathy.

Clinicians have relied on history and results from physical examinations to guide treatment of patients with advanced congestive heart failure, but these results may not reflect disease severity or hemodynamic status. We assessed how the distance walked in 6 minutes relates to clinical outcomes and symptoms of such patients. We compared the rates of death, hospitalization, and their composite at 1 year by the distance walked in 6 minutes at baseline and at 1 month, and by the change in distance between baseline and 1 month in 440 patients enrolled in a randomized trial. We also assessed the relations of baseline distance walked to symptom score and New York Heart Association class. The median distance increased from 218 m at baseline to 280 m at 1 month. Of 365 patients able to perform the baseline walk, 121 (33%) died and 217 (60%) were hospitalized compared with 46 (61%) and 34 (45%) of 75 patients unable to walk at baseline. Baseline distance significantly predicted mortality (hazard ratio 0.58/100-m increase, 95% confidence interval 0.50 to 0.68, p <0.001), even after adjustment. Baseline distance also significantly predicted hospitalization and the composite end point, as did the 1-month distance walked. The change in distance walked from baseline to 1 month did not predict any end point. Baseline distance correlated only moderately with symptom score (r = -0.385, p <0.001) and New York Heart Association class (r = -0.468, p <0.001). Distance walked during 6 minutes independently and strongly predicts mortality and hospitalization in patients with advanced congestive heart failure. This may be a simple, noninvasive, objective way to risk-stratify these patients and standardize their treatment.     

Sudden cardiac death in patients with nonischemic cardiomyopathy

Sudden cardiac death (SCD) is an important cause of mortality worldwide. Although SCD is most often associated with coronary heart disease, the risk of SCD in patients without ischemic heart disease is well-established. Nonischemic cardiomyopathies, including idiopathic dilated cardiomyopathy, hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy represent three unique disease entities that have been shown to be highly associated with SCD and ventricular arrhythmias. A variety of risk stratification tools have been investigated, although the optimal strategy remains unknown. Identification of the arrhythmogenic substrate and treatment of ventricular arrhythmias in these subgroups can be challenging. Herein, we aim to discuss the current understanding of the anatomic and electrophysiologic substrate underlying ventricular arrhythmias and highlight features that may be associated with a higher risk of SCD in these 3 conditions.     

Cardiac resynchronization therapy in patients with systolic left ventricular dysfunction and symptoms of mild heart failure secondary to ischemic or nonischemic cardiomyopathy

Cardiac resynchronization therapy (CRT) is beneficial in selected patients with moderate to severe heart failure (New York Heart Association [NYHA] classes III to IV). Patients with mildly symptomatic heart failure (NYHA class II) are currently not eligible for CRT and the potential beneficial effects in these patients have not been well studied. Fifty consecutive patients in NYHA class II heart failure and 50 consecutive patients in NYHA classes III to IV (control group) were prospectively included. All patients had left ventricular (LV) ejection fraction120 ms. The effects of CRT in NYHA class II patients were compared with the results obtained in both groups. The severity of baseline LV dyssynchrony (assessed with color-coded tissue Doppler imaging) was comparable between patients in NYHA class II versus those in NYHA classes III to IV (83+/-49 vs 96+/-51 ms, p=NS); resynchronization was achieved in all patients. NYHA class II patients showed a significant improvement in LV ejection fraction (from 25+/-7% to 33+/-10%, p<0.001) and reduction in LV end-systolic volume (from 168+/-55 to 132+/-51 ml, p<0.001) after CRT, similar to patients in NYHA classes III to IV. In addition, only 8% of NYHA class II patients had progression of heart failure symptoms. In conclusion, CRT had comparable effects in patients in NYHA class II and in NYHA classes III to IV heart failure in terms of LV resynchronization, improvement in LV ejection fraction, and LV reverse remodeling.     

Prognostic value of T-wave alternans in patients with heart failure due to nonischemic cardiomyopathy: results of the ALPHA Study.

OBJECTIVES: The aim of this study was to assess the prognostic value of T-wave alternans (TWA) in New York Heart Association (NYHA) functional class II/III patients with nonischemic cardiomyopathy and left ventricular ejection fraction (LVEF) < or =40%. BACKGROUND: There is a strong need to identify reliable risk stratifiers among heart failure candidates for implantable cardioverter-defibrillator (ICD) prophylaxis. T-wave alternans may identify low-risk subjects among post-myocardial infarction patients with depressed LVEF, but its predictive role in nonischemic cardiomyopathy is unclear. METHODS: Four hundred forty-six patients were enrolled and followed up for 18 to 24 months. The primary end point was the combination of cardiac death + life-threatening arrhythmias; secondary end points were total mortality and the combination of arrhythmic death + life-threatening arrhythmias. RESULTS: Patients with abnormal TWA (65%) compared with normal TWA (35%) tests were older (60 +/- 13 years vs. 57 +/- 12 years), were more frequently in NYHA functional class III (22% vs. 19%), and had a modestly lower LVEF (29 +/- 7% vs. 31 +/- 7%). Primary end point rates in patients with abnormal and normal TWA tests were 6.5% (95% confidence interval [CI] 4.5% to 9.4%) and 1.6% (95% CI 0.6% to 4.4%), respectively. Unadjusted and adjusted hazard ratios were 4.0 (95% CI 1.4% to 11.4%; p = 0.002) and 3.2 (95% CI 1.1% to 9.2%; p = 0.013), respectively. Hazard ratios for total mortality and for arrhythmic death + life-threatening arrhythmias were 4.6 (p = 0.002) and 5.5 (p = 0.004), respectively; 18-month negative predictive values for the 3 end points ranged between 97.3% and 98.6%. CONCLUSIONS: Among NYHA functional class II/III nonischemic cardiomyopathy patients, an abnormal TWA test is associated with a 4-fold higher risk of cardiac death and life-threatening arrhythmias. Patients with normal TWA tests have a very good prognosis and are likely to benefit little from ICD therapy.     

左西孟旦治疗老年缺血性心肌病所致急性失代偿性心力衰竭的疗效和安全性分析

目的探讨左西孟旦治疗老年缺血性心肌病所致急性失代偿性心力衰竭患者的疗效和安全性。方法选择老年缺血性心肌病所致急性失代偿性心力衰竭患者60例,根据治疗方法随机分为左西孟旦组30例和常规治疗组30例。2组患者治疗前和治疗后1周分别测定血压、心率、左心室射血分数、血浆N末端钠尿肽前体和肌酐水平,并进行疗效和安全性比较。结果左西孟旦组治疗后左心室射血分数明显高于常规治疗组,血浆N末端钠尿肽前体水平明显低于常规治疗组(36.5%vs 34.0%,1872.9ng/L vs 2499.6ng/L,P0.05)。左西孟旦组与常规治疗组治疗后血压、心率和肌酐水平比较,差异无统计学意义(P0.05)。结论老年缺血性心肌病导致的急性失代偿性心力衰竭患者使用左西孟旦后,左心室射血分数升高,N末端钠尿肽前体水平降低,而血压、心率和肾功能并无异常,证实了左西孟旦治疗老年缺血性心肌病导致的急性失代偿性心力衰竭患者安全有效。     

心脏再同步治疗缺血性与非缺血性心肌病的临床应用

目的报道142例心脏再同步治疗缺血性与非缺血性心肌病临床应用。方法 142例心肌病慢性心力衰竭患者心功能Ⅲ-Ⅳ级(NYHA分级),男性91例,女性51例,平均年龄59．8岁,左心室内径平均72．32mm,平均左心室射血分数(LVEF)为0．29。患者均伴有室内阻滞,平均QRS波时限为(146．7±21．4)ms。142例患者中,扩张性心肌病98例,缺血性心肌病44例。分别观察双心室起搏前后LVEF变化。结果双心室同步起搏后,患者心功能得到明确改善,142例患者平均LVEF从术前的0．29±0．08增加至0．36±0．07,LVEF值平均提高0．07(P<0．05)。左心室充盈时间延长,二尖瓣反流量减少。扩张性心肌病患者平均LVEF从术前的0．28提高到术后的0．37。缺血性心肌病患者平均LVEF从术前的0．30提高到术后的0．36。均有显著改善。结论无论扩张性心肌病患者还是缺血性心肌病患者心脏再同步治疗后心功能均有显著提高。     

Correlation of echo-Doppler optimization of atrioventricular delay in cardiac resynchronization therapy with invasive hemodynamics in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

This study investigated the optimal echocardiographic indexes to determine the most hemodynamically appropriate atrioventricular (AV) delay in cardiac resynchronization therapy (CRT) for heart failure. Doppler echocardiographic optimization of AV delay in CRT has not been correlated with invasive hemodynamic indexes. In 30 patients who underwent CRT, invasive left ventricular (LV) pressure measurements with a sensor-tipped pressure guidewire and Doppler echocardiographic examination were performed <24 hours after pacemaker implantation. Invasively, the optimal sensed AV delay was determined by LV dP/dt(max). The Doppler echocardiographic methods evaluated were the velocity-time integral (VTI) of the transmitral flow (EA VTI), diastolic filling time (EA duration), the VTI of the LV outflow tract or aorta (LV VTI), and Ritter's formula. Biventricular pacing with optimized interventricular and AV delay increased LV dP/dt(max) from 777 +/- 149 to 1,010 +/- 163 dynes/s (p<0.0001). The optimal AV delay with the EA VTI method was concordant with LV dP/dt(max) in 29 of 30 patients (r = 0.96), with EA duration in 20 of 30 patients (r= 0.83), with LV VTI in 13 patients (r = 0.54), and with Ritter's formula in none of the patients (r = 0.35). In conclusion, to obtain the optimal acute hemodynamic benefit of CRT, Doppler echocardiography is a reliable tool to optimize the AV delay compared with the invasive LV dP/dt(max). The measurement of the maximal VTI of mitral inflow is the most accurate method.     

Abnormal coronary hemodynamics and myocardial energetics in patients with chronic heart failure caused by ischemic heart disease and dilated cardiomyopathy

Coronary sinus blood flow, transmyocardial oxygen extraction, myocardial oxygen consumption, and transmyocardial lactate extraction were determined, along with systemic hemodynamics, in 34 patients with chronic stable angina without heart failure (group 1), in 66 patients with heart failure associated with coronary artery disease (group 2), and in 28 patients with heart failure caused by dilated cardiomyopathy without coronary artery disease (group 3). Compared with group 1 patients, in patients with heart failure in groups 2 and 3, resting coronary sinus blood flow was 30% and 24% higher, respectively (p less than 0.05), myocardial oxygen consumption was 25% higher (p less than 0.01), and coronary sinus oxygen content was 33% lower (p less than 0.01). The rate-pressure product was not different between the three groups. In eight patients with heart failure (five in group 2 and three in group 3), myocardial lactate production was observed without angina. Thus in patients with chronic heart failure resulting from either chronic coronary artery disease or dilated cardiomyopathy, resting coronary blood flow and myocardial oxygen consumption tend to increase probably because of an increase in myocardial oxygen requirements. Silent myocardial ischemia may also occur in both the presence and absence of coronary artery disease in patients with chronic heart failure. The abnormal coronary hemodynamics and myocardial metabolic function may play a role in causing progressive deterioration in cardiac function in dilated cardiomyopathy.     

Losartan improves heart rate variability and heart rate turbulence in heart failure due to ischemic cardiomyopathy

BackgroundHeart rate variability (HRV) and heart rate turbulence are known to be disturbed and associated with excess mortality in heart failure. The aim of this study was to investigate whether losartan, when added on top of β-blocker and angiotensin-converting enzyme inhibitor (ACEI) therapy, could improve these indices in patients with systolic heart failure.Methods and ResultsSeventy-seven patients (mean age 60.4 ± 8.0, 80.5% male) with ischemic cardiomyopathy (mean ejection fraction 34.5 ± 4.4%) and New York Heart Association Class II-III heart failure symptoms, already receiving a β-blocker and an ACEI, were randomly assigned to either open-label losartan (losartan group) or no additional drug (control group) in a 2:1 ratio and the patients were followed for 12 weeks. The HRV and heart rate turbulence indices were calculated from 24-hour Holter recordings both at the beginning and at the end of follow-up. The baseline clinical characteristics, HRV, and heart rate turbulence indices were similar in the 2 groups. At 12 weeks of follow-up, all HRV parameters except pNN50 increased (SDNN: 113.2 ± 34.2 versus 127.8 ± 24.1, P = .001; SDANN: 101.5 ± 31.7 versus 115.2 ± 22.0, P = .001; triangular index: 29.9 ± 11.1 versus 34.2 ± 7.9, P = .008; RMSSD: 29.1 ± 20.2 versus 34.3 ± 23.0, P = .009; NN50: 5015.3 ± 5554.9 versus 6446.7 ± 6101.1, P = .024; NN50: 5.65 ± 6.41 versus 7.24 ± 6.99, P = .089; SDNNi: 45.1 ± 13.3 versus 50.3 ± 14.5, P = .004), turbulence onset decreased (−0. 61 ± 1.70 versus −1.24 ± 1.31, P = .003) and turbulence slope increased (4.107 ± 3.881 versus 5.940 ± 4.281, P = .004) significantly in the losartan group as compared with controls.ConclusionsA 12-week-long losartan therapy significantly improved HRV and heart rate turbulence in patients with Class II-III heart failure and ischemic cardiomyopathy already on β-blockers and ACEI.     

Impairment of endothelium-dependent and endothelium-independent peripheral vasodilation in patients with chronic heart failure due to nonischemic heart disease

The authors have examined changes in forearm blood flow during local intra-arterial infusion of acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (a direct dilator of smooth muscle) in patients with heart failure due to nonischemic heart disease. Incremental step-up doses of acetylcholine and nitroprusside were infused locally into the brachial artery in 10 healthy controls (group 1), 13 patients with no history of decompensated congestive heart failure (group 2), and 13 patients who exhibited congestive heart failure before admission (group 3). Forearm blood flow was measured by venous occlusion plethysmography. Systemic blood pressure and heart rate were not affected significantly by either infusion in any of the three groups. Groups 1 and 2 showed similar changes in forearm blood flow after endothelium-dependent and endothelium-independent vasodilation, but these changes were attenuated significantly in group 3 (both p<0.05). Although there were no significant differences in clinical characteristics including hemodynamic parameters between groups 2 and 3, plasma noradrenaline concentration was elevated in group 3 (p<0.01). A significant negative correlation was found between plasma noradrenaline level and nitroprusside- or acetylcholine-induced change in forearm blood flow (nitroprusside: r=−0.36, p<0.05; acetylcholine: r=−0.42, p<0.05). These observations demonstrate that the attenuation of the response to vasodilatory stimuli in the peripheral vasculature may persist in the convalescent phase after decompensated heart failure and that the vascular dysfunction may be due not only to endothelial dysfunction but also to an endothelium-independent mechanism such as neurohormonal activation.     

Relation of "inotropic reserve" to functional capacity in heart failure secondary to ischemic or nonischemic cardiomyopathy

Exercise capacity in patients with dilated cardiomyopathy, measured by peak oxygen consumption (VO(2)) during exercise, has virtually no relation to resting left ventricular (LV) function. We hypothesized that exercise-induced inotropic reserve may explain some of the variation between peak VO(2) and resting LV function. Treadmill stress echocardiography was performed simultaneously with peak VO(2) measurements in 35 patients with dilated cardiomyopathy. Resting and immediate postexercise echocardiographic images were scored for change in segmental contractility using the American Society of Echocardiography 16-segment system. Segment scores were summed and divided by 16 to determine the wall motion index. Right ventricular (RV) function was quantified on a 4-point scale. Patients had a mean age of 52 +/- 12 years (8 women) and a mean ejection fraction of 30 +/- 10 (25 nonischemic patients). Average peak VO(2) was 17.0 +/- 6 ml/kg/min. Patients were divided into 2 groups by peak VO(2): a high VO(2) group, >17 ml/kg/min (17 patients) and a low VO(2) group, < or =17 ml/kg/min (18 patients). LV ejection fraction was similar between the high and low VO(2) groups (31 +/- 9% vs 28 +/- 11%, p = NS) as were etiology of heart failure, medications used, and LV volume. In the high VO(2) group, wall motion index improved from 2.28 +/- 0.20 to 2.12 +/- 0.31 during exercise (p = 0.009). There was no improvement in the low VO(2) group. Resting RV function was significantly better in the high VO(2) group (1.4 +/- 0.8 vs 0.6 +/- 0.6 p = 0.004). Therefore, in patients with dilated cardiomyopathy and similar resting LV function, the presence of demonstrable LV inotropic reserve and preserved RV function partially account for variation in exercise performance.