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.     

Reduced atrial tachyarrhythmia susceptibility after upgrade of conventional implanted pulse generator to cardiac resynchronization therapy in patients with heart failure.

OBJECTIVES: We sought to identify the impact of cardiac resynchronization therapy (CRT) on atrial tachyarrhythmia (AT) susceptibility in patients with left ventricular (LV) systolic dysfunction in whom worsening heart failure (HF) resulted in upgrade from conventional dual-chamber pulse generator to cardiac resynchronization therapy-defibrillator (CRT-D). BACKGROUND: Cardiac resynchronization therapy with a defibrillator improves survival rates and symptoms in patients with LV systolic dysfunction but little is known about its effects on AT incidence in the same patient population. METHODS: Twenty-eight consecutive HF patients who underwent device upgrade to CRT-D were included. Patients had > or =2 device interrogations in the 1 year before upgrade and > or =3 interrogations in the 18- to 24-month follow-up after upgrade. Echocardiographic parameters were assessed before and at 3 to 6 months after CRT-D. Additional observations included number of hospital stays, HF clinical status, and concomitant pharmacological therapy. By virtue of this study design, each patient served as his/her own control. Statistical analysis was performed by 2-tailed paired t test and with nonparametric tests where appropriate. RESULTS: Within 3 months after CRT, the number of HF patients with documented AT decreased significantly from the immediate pre-CRT value and tended to decline with time. At 1-year follow-up, 90% of patients were AT-free compared with 14% of patients 3 months before CRT (p < 0.001). Furthermore, the number of AT episodes/year and their maximum duration decreased after CRT (mean +/- SD; 181 +/- 50 vs. 50 +/- 20.2, p < 0.05, and 220.8 +/- 87 s vs. 28 +/- 21 s, p < 0.05, respectively). Finally, CRT was associated with improved LV ejection fraction (mean +/- SD; from 26 +/- 5.3% to 31 +/- 7%, p < 0.001) and reduced number of HF or arrhythmia hospital stays (p < 0.05). CONCLUSIONS: Our findings support the view that CRT might decrease AT susceptibility in HF patients with LV systolic dysfunction.     

Influence of diabetes on cardiac resynchronization therapy with or without defibrillator in patients with advanced heart failure

ObjectivesWe performed a post hoc analysis to determine the influence of cardiac resynchronization therapy with a defibrillator (CRT-D) or without a defibrillator (CRT-P) on outcomes among diabetic patients with advanced heart failure (HF).BackgroundIn patients with systolic HF, diabetes is an independent predictor of morbidity and mortality. No data are available on its impact on CRT-D or CRT-P in advanced HF.MethodsThe database of the Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure trial was examined to determine the influence of CRT (CRT-D and CRT-P) on outcomes among diabetic patients. All-cause mortality or hospitalization, all-cause mortality or cardiovascular hospitalization, all-cause mortality or HF hospitalization, and all-cause mortality were analyzed among diabetic patients (n = 622). A Cox proportional hazard model, adjusting for age, gender, New York Heart Association, ischemic status, body mass index, left ventricular ejection fraction, heart rate, QRS, left or right bundle branch block, blood pressure, comorbidities (renal failure, carotid artery disease, peripheral vascular disease, hypertension, coronary artery bypass grafting, and atrial fibrillation), medications, and device (with or without defibrillator), was used to estimate hazard ratios (HRs) and significance.ResultsThe overall outcome of diabetic patients was similar to that of nondiabetic patients in the optimal pharmacologic therapy arm. With CRT, diabetic patients experienced a substantial reduction in all-cause mortality or all-cause hospitalization (HR = 0.77, 95% confidence interval [CI] 62–0.97), all-cause mortality or cardiovascular hospitalization (HR = 0.67, 95% CI 0.53–0.85), all-cause mortality or HF hospitalization (HR = 0.52, 95% CI 0.40–0.69), and all-cause mortality (HR = 0.67, 95% CI 0.45–0.99) compared with optimal pharmacologic therapy. Procedure-related complications and length of stay were identical in diabetic and nondiabetic patients.ConclusionIn diabetic patients with advanced HF, there is a substantial benefit from device therapy with significant improvement in all end points.     

Cardiac resynchronization therapy improves heart rate profile and heart rate variability of patients with moderate to severe heart failure.

OBJECTIVES: This study sought to report long-term changes of cardiac autonomic control by continuous, device-based monitoring of the standard deviation of the averages of intrinsic intervals in the 288 five-min segments of a day (SDANN) and of heart rate (HR) profile in heart failure (HF) patients treated with cardiac resynchronization therapy (CRT). BACKGROUND: Data on long-term changes of time-domain parameters of heart rate variability (HRV) and of HR in highly symptomatic HF patients treated with CRT are lacking. METHODS: Stored data were retrieved for 113 HF patients (New York Heart Association functional class III to IV, left ventricular ejection fraction < or =35%, QRS >120 ms) receiving a CRT device capable of continuous assessment of HRV and HR profile. RESULTS: The CRT induced a reduction of minimum HR (from 63 +/- 9 beats/min to 58 +/- 7 beats/min, p < 0.001) and mean HR (from 76 +/- 10 beats/min to 72 +/- 8 beats/min, p < 0.01) and an increase of SDANN (from 69 +/- 23 ms to 93 +/- 27 ms, p < 0.001) at three-month follow-up, which were consistent with improvement of functional capacity and structural changes. Different kinetics were observed among these parameters. The SDANN reached the plateau before minimum HR, and mean HR was the slowest parameter to change. Suboptimal left ventricular lead position was associated with no significant functional and structural improvement as well as no change or even worsening of HRV. The two-year event-free survival rate was significantly lower (62% vs. 94%, p < 0.005) in patients without any SDANN change (Delta change < or =0%) compared with patients who showed an increase in SDANN (Delta change >0%) four weeks after CRT initiation. CONCLUSIONS: Cardiac resynchronization therapy is able to significantly modify the sympathetic-parasympathetic interaction to the heart, as defined by HR profile and HRV. Lack of HRV improvement four weeks after CRT identifies patients at higher risk for major cardiovascular events.     

Intraventricular dyssynchrony predicts mortality and morbidity after cardiac resynchronization therapy: a study using cardiovascular magnetic resonance tissue synchronization imaging.

OBJECTIVES: We aimed to assess a novel measure of left ventricular (LV) dyssynchrony, a cardiovascular magnetic resonance-tissue synchronization index (CMR-TSI), in patients with heart failure (HF). A further aim was to determine whether CMR-TSI predicts mortality and major cardiovascular events (MCE) after cardiac resynchronization therapy (CRT). BACKGROUND: Cardiac dyssynchrony is a predictor of mortality in patients with HF. The unparalleled spatial resolution of CMR may render CMR-TSI a predictor of clinical benefit after CRT. METHODS: In substudy A, CMR-TSI was assessed in 66 patients with HF (age 60.8 +/- 10.8 years, LV ejection fraction 23.9 +/- 12.1% [mean +/- SD]) and 20 age-matched control subjects. In substudy B, CMR-TSI was assessed in relation to clinical events in 77 patients with HF and with a QRS > or =120 ms undergoing CRT. RESULTS: In analysis A, CMR-TSI was higher in patients with HF and a QRS <120 ms (79.5 +/- 31.2 ms, p = 0.0003) and in those with a QRS > or =120 ms (105.9 +/- 55.8 ms, p < 0.0001) than in control subjects (21.2 +/- 8.1 ms). In analysis B, a CMR-TSI > or =110 ms emerged as an independent predictor of the composite end points of death or unplanned hospitalization for MCE (hazard ratio [HR] 2.45; 95% confidence interval [CI] 1.51 to 4.34, p = 0.0002) or death from any cause or unplanned hospitalization for HF (HR 2.15; 95% CI 1.23 to 4.14, p = 0.0060) as well as death from any cause (HR: 2.6; 95% CI 1.29 to 6.73, p = 0.0061) and cardiovascular death (HR 3.82; 95% CI 1.63 to 16.5, p = 0.0007) over a mean follow-up of 764 days. CONCLUSIONS: Myocardial dyssynchrony assessed by CMR-TSI is a powerful independent predictor of mortality and morbidity after CRT.     

Mode of death in advanced heart failure: the Comparison of Medical, Pacing, and Defibrillation Therapies in Heart Failure (COMPANION) trial.

OBJECTIVES: The aim of this study was to evaluate the mode of death in patients with advanced chronic heart failure (HF) and intraventricular conduction delay treated with optimal pharmacologic therapy (OPT) alone or OPT with biventricular pacing to provide cardiac resynchronization therapy (CRT) or CRT + an implantable defibrillator (CRT-D). BACKGROUND: Limited data are available on mode of death in advanced HF. No data have existed on mode of death in these patients who also have an intraventricular conduction delay and are treated with CRT or CRT-D. METHODS: Using prespecified definitions and source materials, seven cardiologists assessed mode of death among the 313 deaths that occurred in the Comparison of Medical, Pacing, and Defibrillation Therapies in Heart Failure (COMPANION) trial. RESULTS: A primary cardiac cause was present in 78% of deaths. Pump failure (44.4%) was the most common mode of death followed by sudden cardiac death (SCD) (26.5%). Compared with OPT, CRT-D significantly reduced the number of cardiac deaths (38%, p = 0.006), whereas CRT alone was associated with a non-significant 14.5% reduction (p = 0.33). Both CRT and CRT-D tended to reduce pump failure deaths (29%, p = 0.11 and 27%, p = 0.14, respectively). The CRT-D significantly reduced SCD (56%, p = 0.02), but CRT alone did not. CONCLUSIONS: Pump failure deaths are the predominant mode of death in patients with advanced HF and are modestly reduced by both CRT and CRT-D. Only CRT-D reduced SCD and thus produced a favorable effect on cardiac mortality.     

心脏再同步治疗术后患者死亡原因分析

目的探讨心力衰竭患者心脏再同步治疗（CRT）术后的死亡原因及相关影响因素。方法对110例行CRT的心力衰竭患者[其中7例植入带有心脏再同步治疗除颤器（CRT—D）]进行长期随访,观察患者术后的转归情况,以及死亡患者的死亡原因、生存时间和相关影响因素。结果110例患者中有92例患者完成随访研究,随访1～132（48±28）个月,共死亡30例,死亡率为32．6％,5年生存率为66．9％±5．8％。24例为心脏性死亡,占总体死亡的80％,其中包括11例为心力衰竭恶化导致的死亡,13例为心脏性猝死（SCD）,其余6例为非心脏性死亡。14例行CRT的持续性心房颤动（房颤）患者中有8例死亡;71例行CRT的窦性心律患者中死亡22例;前组的中位生存时间短于后组（50比87,P=0．013）;7例植人CRT—D的患者均无死亡;3组患者的死亡率差异有统计学意义（P=0．01）。合并慢性肾功能衰竭的CRT患者死亡率（66．7％）较无肾功能不良者（20．6％）高（相对危险度：3．24,95％CI1．88～5．59,P〈0．001）。结论CRT患者的主要死亡原因是心脏性死亡,其中包括心力衰竭恶化和SCD。CRT—D和CRT两组患者之间的死亡率差异有统计学意义,接受CRT的窦性心律患者较持续性房颤患者有显著的生存获益。合并慢性肾功能衰竭的CRT患者预后较差。对于合并持续性房颤的CRT患者同时给予房室结消融有可能进一步提高生存率。     

Impact of diabetes mellitus on long-term survival in patients with congestive heart failure.

AIMS: To test the hypothesis that diabetic status may be used as a prognostic indicator in heart failure (HF) patients. METHODS AND RESULTS: We studied 1246 consecutive patients with left ventricular dysfunction. All patients had a cardiopulmonary exercise test and an echocardiogram. Cardiac catheterisation was systematically performed to define HF aetiology. Twenty-two percent of the patients were diabetic (hypoglycaemic drugs or fasting blood glucose >126 mg/dL); in diabetic patients, HF aetiology was ischaemic in 58% vs. 40% in non-diabetic patients ( p < 0.0001). Clinical follow-up (median 1200 days) was obtained for 1241 patients. There was a statistically significant effect of diabetes mellitus on cardiac survival that differed according to HF aetiology (interaction p > 0.01). Diabetes mellitus was an independent predictor of cardiovascular mortality in ischaemic patients (HR=1.54 [1.13; 2.09]; P = 0.006) but not in non-ischaemic patients (HR=0.65 [0.39; 1.07];p = 0.09). When diabetic patients were defined as patients receiving hypoglycaemic drugs at baseline, diabetes mellitus remained an independent predictor of cardiovascular mortality in ischaemic patients (HR=1.43 [1.03; 1.98]; p = 0.03) while diabetes mellitus was associated with a statistically significant decrease in cardiovascular mortality in non-ischaemic patients (HR=0.46 [0.23; 0.88]; p = 0.02). CONCLUSION: The prognostic impact of diabetes mellitus in HF patients is markedly influenced by the underlying aetiology and is particularly deleterious in those with ischaemic cardiomyopathy.     

Prognostic significance of tricuspid annular motion and plasma NT-proBNP in patients with heart failure and moderate-to-severe functional mitral regurgitation

BACKGROUND: The role of the right ventricle has been relatively neglected proportionate to its importance. We sought to evaluate the impact of right ventricular (RV) and NT-proBNP on the outcome of patients with heart failure (HF) and functional mitral regurgitation (MR). METHODS AND PATIENTS: Outpatients with left ventricular (LV) systolic HF (ejection fraction [EF] < or =45%) and moderate-to-severe MR measured by a vena contracta width > or =0.5 cm were prospectively enrolled (n=142). Indexes of LV and RV function, including tricuspid annular plane systolic excursion (TAPSE), RV fractional area change and tissue Doppler RV acceleration at isovolumic contraction and NT-proBNP plasma levels were measured at the time of the index echocardiogram. RESULTS: Multivariate predictors of all-cause mortality included TAPSE<16 mm (hazards ratio [HR]: 2.64; p=0.009) and plasma NT-proBNP> or =3283 pg/ml (HR: 2.58; p=0.011). TAPSE<16 mm and plasma NT-proBNP> or =3283 pg/ml added incremental prognostic information to LV EF< or =25%, NYHA classes 3-4, coronary artery disease, elderly age and male sex. The 36-month Kaplan-Meier curve showed that survival was worst in the group with TAPSE<16 mm and NT-proBNP> or =3283 pg/ml (p<0.0001). CONCLUSION: This study demonstrates the significance of TAPSE and plasma NT-proBNP in predicting all-cause mortality in patients with systolic HF and moderate-to-severe functional MR.     

Intrathoracic impedance changes reflect reverse left ventricular remodeling in response to cardiac resynchronization therapy in chronic heart failure patients

Intrathoracic impedance monitoring has been reported to be useful for prediction of worsening chronic heart failure (CHF). However, it has not revealed the relation between changes in intrathoracic impedance and improvement of cardiac function in CHF patients with cardiac resynchronization therapy (CRT) implantation. Therefore, we investigated whether intrathoracic impedance change reflects reverse left ventricular (LV) remodeling in response to CRT in patients with CHF. The study subjects consisted of 29 CHF patients (23 males, mean age 64 ± 12 years) with CRT-defibrillator (CRT-D) implantation. The patients were divided into two groups based on whether the Opti-vol Fluid Index^? reached over 60 ohms (group A, n = 7) or not (group B, n = 22) within 6 months of observation after CRT-D implantation. Levels of plasma B-type natriuretic peptide (BNP) were measured, and LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were evaluated before and 6 months after CRT-D implantation. In group B, BNP (556 ± 88 pg/mL versus 330 ± 70 pg/mL, P < 0.05), LVEDV (177 ± 18 mL versus 149 ± 14 mL, P < 0.01), and LVESV (128 ± 14 mL versus 100 ± 12 mL, P < 0.01) were significantly decreased 6 months after CRT-D implantation. LVEF (28 ± 2% versus 35 ± 2%, P < 0.01) was significantly increased after CRT-D implantation. On the other hand, no significant changes were detected in any parameters in group A. These data showed intrathoracic impedance changes reflected reverse LV remodeling in response to CRT in patients with CHF. Therefore, the monitoring of changes in intrathoracic impedance is useful for predicting CRT responders in patients with CHF.     

Cardiac resynchronization therapy for the treatment of heart failure in patients with intraventricular conduction delay and malignant ventricular tachyarrhythmias

OBJECTIVES: This study was conducted to assess the safety and effectiveness of cardiac resynchronization therapy (CRT) when combined with an implantable cardioverter defibrillator (ICD). BACKGROUND: Long-term outcome of CRT was measured in patients with symptomatic heart failure (HF), intraventricular conduction delay, and malignant ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]) requiring therapy from an ICD. METHODS: Patients (n = 490) were implanted with a device capable of providing both CRT and ICD therapy and randomized to CRT (n = 245) or control (no CRT, n = 245) for up to six months. The primary end point was progression of HF, defined as all-cause mortality, hospitalization for HF, and VT/VF requiring device intervention. Secondary end points included peak oxygen consumption (VO(2)), 6-min walk (6 MW), New York Heart Association (NYHA) class, quality of life (QOL), and echocardiographic analysis. RESULTS: A 15% reduction in HF progression was observed, but this was statistically insignificant (p = 0.35). The CRT, however, significantly improved peak VO(2) (0.8 ml/kg/min vs. 0.0 ml/kg/min, p = 0.030) and 6 MW (35 m vs. 15 m, p = 0.043). Changes in NYHA class (p = 0.10) and QOL (p = 0.40) were not statistically significant. The CRT demonstrated significant reductions in ventricular dimensions (left ventricular internal diameter in diastole = -3.4 mm vs. -0.3 mm, p < 0.001 and left ventricular internal diameter in systole = -4.0 mm vs. -0.7 mm, p < 0.001) and improvement in left ventricular ejection fraction (5.1% vs. 2.8%, p = 0.020). A subgroup of patients with advanced HF (NYHA class III/IV) consistently demonstrated improvement across all functional status end points. CONCLUSIONS: The CRT improved functional status in patients indicated for an ICD who also have symptomatic HF and intraventricular conduction delay.     

Acute effects of cardiac resynchronization therapy on functional mitral regurgitation in advanced systolic heart failure

OBJECTIVES: We studied the acute effects of cardiac resynchronization therapy (CRT) on functional mitral regurgitation in heart failure (HF) patients with left bundle branch block (LBBB). BACKGROUND: Both an decrease [corrected] in left ventricular (LV) closing force and mitral valve tethering have been implicated as mechanisms for functional mitral regurgitation (FMR) in dilated hearts. We hypothesized that an increase in LV closing force achieved by CRT could act to reduce FMR. METHODS: Twenty-four HF patients with LBBB and FMR were studied after implantation of a biventricular CRT system. Acute changes in FMR severity between intrinsic conduction (OFF) and CRT were quantified according to the proximal isovelocity surface area method by measuring the effective regurgitant orifice area (EROA). Results were compared with the changes in estimated maximal rate of left ventricular systolic pressure rise (LV+dP/dt(max)) and transmitral pressure gradients (TMP), both measured by Doppler echocardiography. RESULTS: Cardiac resynchronization therapy was associated with a significant reduction in FMR severity. Effective regurgitant orifice area decreased from 25 +/- 19 mm(2) (OFF) to 13 +/- 8 mm(2) (CRT). The change in EROA was directly related to the increase in LV+dP/dt(max) (r = -0.83, p < 0.0001). Compared with OFF, TMP increased more rapidly during CRT, and a higher maximal TMP was observed (OFF 73 +/- 24 mm Hg vs. CRT 85 +/- 26 mm Hg, p < 0.01). CONCLUSIONS: Functional mitral regurgitation is reduced by CRT in patients with HF and LBBB. This effect is directly related to the increased closing force (LV+dP/dt(max)). The results support the hypothesis that an increase in TMP, mediated by a rise in LV+dP/dt(max) due to more coordinated LV contraction, may facilitate effective mitral valve closure.     

Influence of Left Ventricular Lead Location on Outcomes in the COMPANION Study

Introduction: There are no randomized controlled trial data that evaluate mortality and hospitalization rates in cardiac resynchronization therapy (CRT) recipients based on left ventricular (LV) lead location. We analyzed the event-driven outcomes of mortality and hospitalization as well as functional outcomes including Functional Class, Quality-of-Life, and 6-minute walk distance in 1,520 patients enrolled in the COMPANION study of CRT versus optimal medical therapy.
Methods and Results: Over a mean follow-up after implantation of 16.2 months, patients randomized to CRT, regardless of lead location, experienced benefit compared with optimized pharmacologic therapy (OPT), with respect to all-cause mortality or heart failure hospitalization. All but a posterior location showed benefit with respect to the all-cause mortality or all-cause hospitalization outcome. Mortality benefit in CRT-D patients was indifferent to LV lead position. All functional outcomes including 6-minute walk distance, Quality-of-Life (QOL) and Functional Class improved with CRT, regardless of LV lead location.
Conclusion: LV lead location was not a major determinant of multiple measures of response to CRT therapy in the COMPANION Trial. While acute data indicate that a left lateral LV lead location results in the most favorable hemodynamic response, these chronic data suggest that positioning an LV lead in an anterior rather than a lateral or posterior LV location has similar benefit.     

Benefits of coronary revascularisation in diabetic and non-diabetic patients with ischaemic cardiomyopathy: role of myocardial viability

BACKGROUND: Diabetes mellitus in patients with coronary artery disease is associated with poor outcome. In this study, the relation between myocardial viability, diabetes, coronary revascularisation and outcome was evaluated. METHODS: 129 patients (31 diabetic, 98 non-diabetic) with ischaemic cardiomyopathy underwent dobutamine stress echocardiography to assess myocardial viability. Patients with >or=4 viable segments were defined as viable and patients with <4 viable segments as nonviable. Left ventricular ejection fraction (LVEF) was assessed before and 9-12 months post-revascularisation. At the same time-points, LV volumes were measured to evaluate LV remodelling. Finally, cardiac events were noted during 5-year follow-up. RESULTS: The extent of viable myocardium was comparable between diabetic and non-diabetic patients. After revascularisation, LVEF increased >or=5% in 44% of diabetic and in 40% of non-diabetic patients. LVEF only improved in patients with viable myocardium. Ongoing LV remodelling occurred in 36% and 35% of diabetic and non-diabetic patients respectively, and was related to non-viability, whereas viability protected against ongoing LV remodelling, both in diabetic and non-diabetic patients. Viability was the only predictor of survival after revascularisation. CONCLUSIONS: Diabetic, viable patients with ischaemic LV dysfunction exhibit improvement in LVEF post-revascularisation with prevention of ongoing LV remodelling, similar to non-diabetic patients. Myocardial viability was also the only predictor of long-term outcome.     

The current role of cardiac resynchronization therapy in reducing mortality and hospitalization in heart failure patients: a meta-analysis from clinical trials

Many diagnostic and therapeutic advances have been reached for congestive heart failure (HF). However, despite clinical improvement and longer survival conferred by new pharmacological options, this syndrome is associated with high morbidity and mortality. Atrial-synchronized biventricular pacing (cardiac resynchronization therapy, CRT) has proven to be effective treatment in symptomatic patients with reduced left ventricular ejection fraction and electromechanical dyssynchrony. To date, many papers have been published on the role of CRT in improving quality of life, functional and neurohormonal parameters and reducing mortality and hospitalization. Eligible studies were randomized controlled trials of CRT for the treatment of chronic, symptomatic left ventricular dysfunction. Our search began dating back to 1994 and was updated to October 2006. Pooled data from the 6 selected studies showed that CRT reduced all-cause mortality by 28% (hazard ration [HR] = 0.72; 95% confidence interval [CI]: 0.60-0.86) and new hospitalizations for worsening HF by 37% (HR = 0.63; 95% CI: 0.44-0.91). This meta-analysis showed that patients with implantable cardiac defibrillators (ICDs) alone and ICD+CRT had a significant reduction of worsening HF hospitalization rate compared to no CRT-no ICD patients. Among patients with ICDs, CRT showed a slight effect on all-cause mortality reduction but no clear impact on worsening HF rehospitalization.     

Prognostic value of N-terminal pro-type-B natriuretic peptide and Doppler left ventricular diastolic variables in patients with chronic systolic heart failure stabilized by therapy

Prognostication of patients with chronic heart failure (HF) stabilized by therapy may be difficult. Therefore, the aim was to evaluate whether combined assessment of plasma N-terminal pro-B natriuretic peptide (NT-pro-BNP) and Doppler left ventricular (LV) diastolic variables was relevant to the prognosis of patients with stable HF. Outpatients with LV systolic HF (ejection fraction < or =45%), classified using clinical criteria as decompensated (n = 94) and stable HF (n = 219), underwent a complete Doppler echocardiographic study. NT-pro-BNP was measured together with mitral wave velocities, E wave deceleration time, and tissue Doppler early septal annular velocity. Median follow-up was 22 months. Freedom from all-cause mortality or HF hospitalization at 24 months was worst (44%) in patients with decompensated HF, intermediate (58%) in patients with stable HF with NT-pro-BNP higher than the median (>1,129 pg/ml), and best (92%) in patients with lower NT-pro-BNP (log-rank p <0.0001). In patients with stable HF, NT-pro-BNP >1,129 pg/ml (hazard ratio [HR] 2.84, p = 0.003), E wave deceleration time <150 ms (HR 2.31, p = 0.004), and tissue Doppler early septal annular velocity <8 cm/s (HR 2.18, p = 0.01) were predictors of the end point at multivariate analysis. The addition of Doppler LV diastolic variables and NT-pro-BNP significantly improved the chi-square test for outcome prediction (from 14.4 to 46.4). In conclusion, NT-pro-BNP and spectral and tissue Doppler variables of LV diastolic dysfunction added independent and incremental contributions to prognostic stratification of patients with stable HF.     

Cardiac resynchronization pacing without defibrillator capability: is this a viable option?

Improved cardiac resynchronization by pacemakers (CRT-P) andimplantable defibrillators (CRT-D) benefits cardiac function,reduces heart failure (HF) admissions, and diminishes mortalityin patients with severe left ventricular (LV) dysfunction. Interms of mortality benefit, current evidence suggests that CRT-Dmay be better than CRT-P alone when a broad range of HF patientsis considered. However, the differential benefit may be smallin certain patients. In individuals with severe and worseningHF due to systolic LV dysfunction, HF complications other thanventricular tachyarrhythmias contribute importantly to bothquality-of-life (QoL) and duration of survival; these patientsmay be served cost-effectively by CRT-P enhancing QoL. A clinicaltrial evaluating CRT-D vs. CRT-P in terms of QoL and survivalin such patients would assist physicians and payers to understandbetter the relative roles of CRT-P and CRT-D in the care ofthe sickest HF patients.     

Triple-Site Versus Standard Cardiac Resynchronization Therapy Study (TRUST CRT): Clinical Rationale, Design, and Implementation

Background: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with heart failure (HF), lowered LV ejection fraction, and wide QRS. However, many patients (≤40%) do not respond to this form of pacing. TRUST CRT is a prospective, single-center, randomized, single-blind, parallel, and controlled study that has been designed to treat patients with moderate to severe HF (NYHA III-IV), QRS ≥120 ms, sinus rhythm, LV dysfunction (EF ≤ 35%), and signs of mechanical dyssynchrony.
Objective: The primary objective will evaluate the 6-month's combined endpoint of alive status, freedom from hospitalization for HF or heart transplantation, relative ≥10% increase in LV ejection fraction, ≥10% in peak oxygen consumption, and ≥10% in 6-minute walking distance.
Methods: Patients with HF receiving optimal pharmacotherapy, with LV dysfunction, mechanical dyssynchrony, wide QRS and sinus rhythm will be randomized in a 1: 1 fashion to standard or triple-site CRT-D. Patients will be followed for 1 week, 1, 3, and 6 months during a blind phase, then every 6 months until study completion. One hundred patients will be enrolled by the study center.
Conclusions: TRUST CRT is a randomized, clinical trial in CRT candidates to evaluate the effectiveness of triple-site pacing versus standard resynchronization in patients with HF.     

Comparison of outcomes for patients with nonischemic cardiomyopathy taking intravenous inotropes versus those weaned from or never taking inotropes at cardiac resynchronization therapy

Mixed cohorts of patients with ischemic and nonischemic end-stage heart failure (HF) with a QRS duration of ≥120 ms and requiring intravenous inotropes do not appear to benefit from cardiac resynchronization therapy (CRT). However, CRT does provide greater benefit to patients with nonischemic cardiomyopathy and might, therefore, be able to reverse the HF syndrome in such patients who are inotrope dependent. To address this question, 226 patients with nonischemic cardiomyopathy who received a CRT-defibrillator and who had a left ventricular ejection fraction of ≤35% and QRS of ≥120 ms were followed up for the outcomes of death, transplantation, and ventricular assist device placement. Follow-up echocardiograms were performed in patients with ≥6 months of transplant- and ventricular assist device-free survival after CRT. The patients were divided into 3 groups: (1) never took inotropes (n = 180), (2) weaned from inotropes before CRT (n = 30), and (3) dependent on inotropes at CRT implantation (n = 16). At 47 ± 30 months of follow-up, the patients who had never taken inotropes had had the longest transplant- and ventricular assist device-free survival. The inotrope-dependent patients had the worst outcomes, and the patients weaned from inotropes experienced intermediate outcomes (p <0.0001). Reverse remodeling and left ventricular ejection fraction improvement followed a similar pattern. Among the patients weaned from and dependent on inotropes, a central venous pressure <10 mm Hg on right heart catheterization before CRT was predictive of greater left ventricular functional improvement, more profound reverse remodeling, and longer survival free of transplantation or ventricular assist device placement. In conclusion, inotrope therapy before CRT is an important marker of adverse outcomes after implantation in patients with nonischemic cardiomyopathy, with inotrope dependence denoting irreversible end-stage HF unresponsive to CRT.     

Electrical devices for left ventricular dysfunction and heart failure: do we need revised guidelines?

Three recent trials have demonstrated the benefit of cardiac resynchronization therapy (CRT) in the New York Heart Association (NYHA) class II patients with heart failure (HF) with ischemic or nonischemic cardiomyopathy as well as in NYHA class I (asymptomatic) patients mostly with ischemic cardiomyopathy. Earlier intervention with CRT in asymptomatic or minimally symptomatic patients improves survival and reduces HF hospitalizations. The reduction or the prevention of HF hospitalizations is of paramount importance because the HF episodes seem to alter the natural history of disease and are associated with deterioration of left ventricular (LV) function and a marked increase in mortality. The CRT benefit is greatest in patients with a QRS ≥ 150 ms. At this time, it would seem prudent to consider CRT-D (D = ICD) therapy for class I NYHA patients with a QRS ≥ 150 ms and an LV ejection fraction ≤ 30% regardless of etiology. Although the data for NYHA class I patients with nonischemic cardiomyopathy are scanty, the recommendation for class I patients is justified because CRT achieves a much greater degree of LV reverse remodeling in nonischemic compared to ischemic patients. With regard to lone ICDs, there is no evidence that they prevent sudden cardiac death more efficiently in symptomatic than in asymptomatic patients. Cardiomyopathy should be the primary target for device therapy regardless of symptoms for both CRT and lone ICD therapy. New guidelines are needed to address the role of CRT in hospitalized NYHA class IV HF patients or those who depend on inotropic therapy or an LV assist device because randomized CRT trials have not included these patients. CRT in these patients remains controversial. The mortality of such patients even with CRT is very high despite the occasional positive response. The role of CRT in patients waiting for cardiac transplantation also needs guidelines. With the expansion of CRT indications to minimally symptomatic or asymptomatic patients, the benefit of device therapy must be carefully weighed against the potential risk of lifelong device complications.