Comparison of myocardial deformation and velocity dyssynchrony for identification of responders to cardiac resynchronization therapy.

AIMS: It is unclear whether myocardial velocity or deformation indices of dyssynchrony are better at predicting response to cardiac resynchronization therapy (CRT). Therefore, two indices of left ventricular (LV) dyssynchrony based on myocardial velocity and deformation were compared to predict success of CRT. METHODS AND RESULTS: Sixty patients with dilated cardiomyopathy, New York Heart Association class III-IV, LV ejection fraction (EF) < or =35%, QRS >120 ms underwent CRT. The standard deviation of the averaged time-to-peak longitudinal negative strain (Tepsilon-SD) and positive systolic velocity (Tv-SD) of 12 LV segments were calculated before and after 6 months of CRT. Responders were defined at month 6 by > or =20% EF increase and/or > or =15% end-systolic volume (ESV) decrease with respect to baseline. On univariable analysis, baseline Tepsilon-SD and Tv-SD were both significantly associated with CRT response; however, the area under the receiver operating characteristic curve was better for Tepsilon-SD. On bivariable analysis, only Tepsilon-SD retained an independent prognostic value for CRT response. Results of the analysis did not change when the logistic models were adjusted for aetiology. CONCLUSION: Baseline dyssynchrony of longitudinal myocardial peak deformation (Tepsilon-SD) appears to be better than dyssynchrony of longitudinal myocardial peak systolic velocities (Tv-SD) for the identification of CRT responders.

Effectiveness of cardiac resynchronisation therapy in patients with echocardiographic evidence of mechanical dyssynchrony.

OBJECTIVE: Cardiac resynchronisation therapy has proven to be effective in refractory heart failure (HF) patients with QRS >120-130 ms. Therefore, the aim of our study was to verify the long-term effectiveness of cardiac resynchronisation therapy in HF patients with echocardiographic evidence of mechanical asynchrony regardless of QRS duration. METHODS: One hundred and six patients with New York Heart Association class II-IV HF and echocardiographic documentation of interventricular and intraventricular asynchrony underwent biventricular stimulation. A clinical and functional evaluation was performed at baseline, 1, 3, 6 months, and every 6 months thereafter. RESULTS: After a median follow-up of 16 months, a significant improvement was noted in ejection fraction, left ventricular diameters, mitral regurgitation jet area, interventricular and intraventricular echocardiographic indexes of asynchrony, and the 6-min walking distance (P < 0.001 for all). Death rates for all causes and for cardiac causes were 18.2 (95% confidence interval 12.8-25.9) and 13.5 (95% confidence interval 9.0-20.3) per 100 person-years, respectively. Patients in New York Heart Association class IV had an almost three-fold increase in risk of dying as compared to class II-III (hazard ratio 2.97, 95% confidence interval 1.30-6.79). CONCLUSIONS: Interventricular and intraventricular asynchrony at echocardiography may be useful in identifying HF patients suitable for cardiac resynchronisation therapy, with results comparable to those obtained with QRS duration selection criteria.

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.

Effects of cardiac resynchronization therapy on insulin-like growth factor-1 in patients with advanced heart failure.

BACKGROUND: Although a more favorable neurohormonal balance may contribute to improving symptoms following cardiac resynchronization therapy (CRT), no information is available regarding the effects of CRT on insulin-like growth factor-1 (IGF-1). This study assessed the effects of CRT on IGF-1 levels and their correlation with changes in quality of life and left ventricular (LV) function. METHODS AND RESULTS: Patients with cardiomyopathy in New York Heart Association class III or IV (n = 18; age 71 +/- 10 years), left ventricular ejection fraction (LVEF) < or = 40% and QRS > or = 130 ms or ventricular dyssynchrony were enrolled in the study and followed up for 6 months. After 3 months, there was an improvement in LVEF (from 29 +/- 7 to 33 +/- 10%, P = 0.0136) and quality of life (from 33 +/- 14 to 13 +/- 12, P = 0.0000) and an increase in IGF-1 levels (from 137 +/- 79 to 175 +/- 111 ng/ml, P = 0.01353). The change in quality of life correlated with changes in IGF-1 levels (P = 0.02) but not with LVEF changes. CONCLUSIONS: In patients with advanced heart failure, CRT leads to a significant increase in plasma IGF-1 levels within 3 months. This increase is correlated with the improvement in quality of life, whereas the increase in LVEF is not. This finding suggests that IGF-1 may play a role as a mediator in the early phase of symptomatic improvement after CRT.

Left intraventricular myocardial deformation dyssynchrony identifies responders to cardiac resynchronization therapy in patients with heart failure.

AIMS: We tested the hypothesis that dyssynchrony of left ventricular (LV) myocardial deformation evaluated by ultrasound can predict success of cardiac resynchronization therapy (CRT) in patients with heart failure (HF). METHODS AND RESULTS: Thirty-seven patients with dilated cardiomyopathy, New York Heart Association class III-IV, LV ejection fraction (EF) < or =35%, QRS > 120 ms were studied before, at pre-discharge, and after 3 and 6 months of CRT. The M-mode peak septal-to-posterior wall motion and thickening delay (SPWMD and SPWTD, ms) and the standard deviation of the averaged time-to-peak strain (TPS-SD, ms) of 12 middle and basal LV segments obtained from the three standard apical views were calculated. Responders were defined at month 6 by > or =20% EF increase and/or > or =15% end-systolic volume (ESV) decrease with respect to baseline. Baseline SPWTD (not SPWMD) and TPS-SD differentiated responders from non-responders with good accuracy and reproducibility. A value > or =194 ms for SPWTD and > or =60 ms for TPS-SD was significantly associated with responder identification. Baseline dyssynchrony parameters correlated significantly with EF (r = 0.53 for SPWTD and r = 0.86 for TPS-SD) and ESV variations (r = -0.42 for SPWTD and r = -0.73 for TPS-SD). CONCLUSION: Patients with chronic HF should undergo ultrasound evaluation to quantify dyssynchrony of LV myocardial deformation, which would help identifying CRT responders.

The ALPHA study (T-wave alternans in patients with heart failure): rationale, design and endpoints.

BACKGROUND: Sudden death and pump failure are the main causes of death in patients with heart failure. Patients with ischemic and non-ischemic cardiomyopathy are at similar risk of arrhythmic mortality; however, standard non-invasive and invasive tests are not routinely available for non-ischemic patients. T-wave alternans (TWA) has been proposed as a potential marker of susceptibility to ventricular tachycardia-fibrillation in several groups of patients. METHODS: The ALPHA study was designed to evaluate the independent predictive value of the measurement of microvolt TWA on the combined occurrence, after 18 months of follow-up, of cardiac death and life-threatening arrhythmias in a population of patients with non-ischemic dilated cardiomyopathy and NYHA class II and III. This is a multicenter prospective observational study. A total of 370 patients, with measurable TWA, will be enrolled during routine follow-up for heart failure treatment; a logbook will be used to collect basic information on the whole screened population. Patients will be enrolled during a 2-year period and will be followed up for 18 months. The primary endpoint of the study will be the combined incidence of cardiac death and life-threatening ventricular arrhythmias. The study will complete recruitment by mid 2004 and report in 2006.