Cardiac resynchronization therapy in patients with a narrow QRS complex.

OBJECTIVES: The purpose of this study was to evaluate the effects of cardiac resynchronization therapy (CRT) in heart failure patients with narrow QRS complex (<120 ms) and evidence of left ventricular (LV) dyssynchrony on tissue Doppler imaging (TDI). BACKGROUND: Cardiac resynchronization therapy is beneficial in selected heart failure patients with wide QRS complex (> or =120 ms). Patients with narrow QRS complex are currently not eligible for CRT, and the potential effects of CRT are not well studied. METHODS: Thirty-three consecutive patients with narrow QRS complex and 33 consecutive patients with wide QRS complex (control group) were prospectively included. All patients needed to have LV dyssynchrony > or =65 ms on TDI, New York Heart Association (NYHA) functional class III/IV heart failure, and LV ejection fraction < or =35%. RESULTS: Baseline characteristics, particularly LV dyssynchrony, were comparable between patients with narrow and wide QRS complex (110 +/- 8 ms vs. 175 +/- 22 ms; p = NS). No significant relationship was observed between baseline QRS duration and LV dyssynchrony (r = 0.21; p = NS). The improvement in clinical symptoms and LV reverse remodeling was comparable between patients with narrow and wide QRS complex (mean NYHA functional class reduction 0.9 +/- 0.6 vs. 1.1 +/- 0.6 [p = NS] and mean LV end-systolic volume reduction 39 +/- 34 ml vs. 44 +/- 46 ml [p = NS]). CONCLUSIONS: Cardiac resynchronization therapy appears to be beneficial in patients with narrow QRS complex and severe LV dyssynchrony on TDI, with similar improvement in symptoms and comparable LV reverse remodeling to patients with wide QRS complex. The current results need confirmation in larger patient cohorts.     

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.     

Evaluation of left bundle branch block as a reversible cause of non-ischaemic dilated cardiomyopathy with severe heart failure. A new concept of left ventricular dyssynchrony-induced cardiomyopathy.

OBJECTIVES: We sought to determine if amelioration of left bundle branch block (LBBB)-induced contraction disturbances achieved by left ventricular (LV)-based pacing could result in sustained reversal of severe LV dysfunction in certain patients with chronic heart failure due to non-ischaemic cardiomyopathy. BACKGROUND: It has been shown that LBBB induces asynchronous contraction of LV. However, whether such a functional contraction disturbance, if present for an extended period of time, could account for a dilated cardiomyopathy remains unknown. METHODS: The study population comprised 29 patients with dilated cardiomyopathy, sinus rhythm, LBBB and severe heart failure (14 patients in New York Heart Association (NYHA) class III and 15 in class IV). Patients were followed prospectively after resynchronization therapy. LV function was considered to be normalized when ejection fraction (EF) was >50% at 1 year. RESULTS: Five among the 29 patients (17%: group 1) demonstrated both complete normalization of LV function following resynchronization therapy (EF: from 19+/-6 to 55+/-3%, P = 0.001) and clinical improvement (mean NYHA class: 3.4+/-0.5 to 1.8+/-0.4, P = 0.02; 6-min walk distance: 300+/-136 to 444+/-75 m, P = 0.12; peak VO2: 11.9+/-4 to 15.8+/-2 ml/min/kg, p = 0.03). Among the remaining 24 patients (83%: group 2) EF improved but did not normalize (from 21+/-8 to 23+/-11%, ns). Baseline clinical features could not predict which patients would exhibit the reversal of LV dysfunction. CONCLUSIONS: Normalization of LV function 1 year after resynchronization therapy in a small but important number of patients suggests that long-standing LBBB may be a newly identified reversible cause of cardiomyopathy.     

Cardiac Resynchronization Therapy in Asymptomatic or Mildly Symptomatic Heart Failure Patients

Heart failure is a constantly progressing disease involving patients with ischemic and nonischemic cardiac disease. Cardiac resynchronization therapy (CRT) has been used successfully in patients with severe heart failure symptoms, poor left ventricular (LV) function, and a prolonged QRS duration. Large trials in patients with New York Heart Association (NYHA) class III/IV heart failure have demonstrated that heart failure symptoms can be reduced and exercise capacity improved, overall mortality decreased, and ventricular function increased. How long these beneficial effects of CRT will last in patients with an already advanced stage of heart failure, particularly in NYHA IV, is still unknown. Therefore, it is more reasonable to initiate CRT in appropriate patients who have structural heart disease but have not yet developed severe heart failure symptoms. Slowing heart failure progression seems to be the most important target. Medical treatment alone has not demonstrated that this can be achieved in patients with poor ventricular function and prolonged QRS (>120 ms). The recently published results of MADIT-CRT, as well as the extended follow-up of the REVERSE substudy of the European patient cohort, have shown that prevention of heart failure progression can be well accomplished with CRT and implantable cardioverter–defibrillator (ICD) backup (CRT-D). Heart failure events and death occurred significantly less often in patients with CRT-D than in those with an ICD only. A clinically important reversal of ventricular remodeling with reduced ventricular volumes and increased LV ejection fraction was found in the CRT-D–treated patients. The benefit was seen in patients with ischemic and nonischemic cardiomyopathy and in those with NYHA class I or II heart failure; the most benefit was demonstrated in patients showing a “classic” left bundle branch block electrocardiogram pattern (about 70% of the enrolled patients) and in female patients. Results from both trials support the view that future efforts regarding heart failure treatment should concentrate more on prevention of heart failure progression in mildly symptomatic or even asymptomatic candidates for CRT-D. It is time to change the guidelines for heart failure treatment.     

Heart failure: what proportion of patients satisfy the electrocardiographic criteria for cardiac resynchronization therapy?

BACKGROUND: Cardiac resynchronization therapy has emerged as a new therapeutic modality for patients with congestive cardiac failure and associated intraventricular conduction delay. The purpose of this study was to find out what proportion of Indian patients with congestive heart failure may be candidates for cardiac resynchronization therapy based on electrocardiographic characteristics. METHODS AND RESULTS: One hundred twenty-one consecutive patients with congestive cardiac failure due to various etiologies whose left ventricular ejection fraction was less than 40% were included in the study. Standard 12-lead electrocardiogram was recorded in all the patients, and various parameters (rhythm, conduction, QRS axis, chamber enlargement, chamber hypertrophy, and the presence of Q waves) were analyzed. The study population comprised 82 male (67.8%) and 39 female (32.2%) patients with a mean age of 53 +/- 13 years. Thirty-nine patients (32.2%) had NYHA class I-II symptoms, and 82 (67.8%) had NYHA class III-IV symptoms. The mean QRS duration was 111 +/- 27 ms. Bundle branch block was seen in 43 patients (35.5%), of whom 30 (24.8%) had left bundle branch block, and 13 (10.7%) had right bundle branch block. Of the 30 patients who had left bundle branch block, 19 (15.7%) had a QRS duration of between 120 and 149 ms, and 11 (9%) had a QRS duration > or = 150 ms. In the latter group, 7 patients (5.8%) were in NYHA classes III and IV. As the clinical severity of heart failure increased, the mean QRS duration also increased, but this increment was not statistically significant. CONCLUSIONS: Based on our data, it can be estimated that of the patients with heart failure who attend a tertiary care center, 2 5% of patients present with left bundle branch block. If we use the criteria for NYHA class III and IV congestive cardiac failure with QRS duration of > or = 150 ms in patients with left bundle branch block, 6% of patients are likely to need cardiac resynchronization therapy.     

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.     

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.     

Postero-lateral scar tissue resulting in non-response to cardiac resynchronization therapy

In large cardiac resynchronization therapy (CRT) trials, approximately 20-30% of patients did not respond to CRT. Recent studies indicated that left ventricular (LV) dyssynchrony is needed for response to CRT. However, the presence of LV dyssynchrony may not be the only determinant of response, because some patients with LV dyssynchrony do not benefit from CRT. In the current case report, we present a patient with ischemic cardiomyopathy, NYHA class III heart failure symptoms, and substantial LV dyssynchrony on tissue Doppler imaging who underwent CRT implantation but did not respond. Following CRT, LV dyssynchrony was not reduced and the patient did not improve in clinical symptoms or LV function. The lack of LV resynchronization was explained by the presence of extensive scar tissue in the region of the tip of the LV pacing lead resulting in ineffective LV pacing. In patients with ischemic cardiomyopathy and history of previous infarction, assessment of scar tissue should be considered before CRT implantation.     

Effect of cardiac resynchronization therapy in patients with New York Heart Association functional class IV heart failure

Cardiac resynchronization therapy (CRT) is considered a class I indication in treatment of patients with New York Heart Association (NYHA) functional class III and IV heart failure. However, only small numbers of patients in large clinical trials have been in NYHA functional class IV. Therefore, little is known about the effects of CRT in this group. Therefore, we evaluated the effects of CRT in patients with NYHA functional class IV heart failure. Of all patients referred for CRT implantation, 61 patients with symptoms according to NYHA functional class IV were included. All patients were evaluated before implantation and at 6-month follow-up for clinical changes according to the clinical composite score and changes in left ventricular (LV) volumes and function. In addition, survival was evaluated during long-term follow-up. At 6-month follow-up, 9 patients (15%) had died and 2 patients (3%) were admitted for worsening heart failure. The remaining 39 patients (64%) showed improvement according to the clinical composite score. Decreases in LV end-systolic volume (from 167 ± 88 to 147 ± 93 ml, p = 0.009) and LV end-diastolic volume (from 211 ± 100 to 199 ± 113 ml, p = 0.135) were observed, as was a significant increase in LV ejection fraction (from 22 ± 8% to 28 ± 9%, p <0.001). During a mean follow-up of 30 ± 26 months, 36 patients (59%) died, 27 (75%) from worsening heart failure. Respective 1- and 2-year mortality rates were 25% and 38%. In conclusion, CRT decreases LV volumes and improves cardiac function in patients with NYHA functional class IV heart failure. Nevertheless, (heart failure) mortality remains high in these patients.     

Sustained sympathoinhibitory effects of cardiac resynchronization therapy in severe heart failure

Evidence is available that in heart failure, cardiac resynchronization therapy by biventricular pacing improves myocardial function and exercise capacity. Whether this is accompanied by a sustained inhibition of heart failure-dependent sympathoexcitation is uncertain. In 11 heart failure patients (mean+/-SEM age, 68.4+/-1.5 years) in New York Heart Association (NYHA) class III and IV under medical treatment with an intraventricular conduction delay (QRS duration > or =130 ms), with a markedly depressed left ventricular ejection fraction, and undergoing implantation of a biventricular pacemaker, we measured beat-to-beat blood pressure and muscle sympathetic nerve traffic. Measurements, which also included echocardiographic and clinical variables, were performed before and approximately 10 weeks after successful resynchronization therapy. Ten age- and NYHA class-matched heart failure patients who were under medical treatment for the same time period served as controls. Long-term resynchronization therapy improved cardiac function and caused a significant increase in systolic blood pressure coupled with an improvement in maximal oxygen consumption and exercise capacity. These effects were coupled with a significant and marked reduction in sympathetic nerve traffic when expressed both as burst frequency over time (44.1+/-3.6 vs 30.7+/-3.0 bs/min, -30.5%, P<0.02) and as burst frequency corrected for heart rate (68.3+/-5.9 vs 47.3+/-4.3 bs/100 beats, -32.1%, P<0.02). No significant change in the aforementioned parameters was seen in the control group. These data provide the first direct evidence that in severe heart failure, resynchronization therapy exerts a marked and sustained sympathoinhibition. Because in heart failure sympathetic overactivity adversely affects prognosis, this may have important clinical implications.     

Cardiac Resynchronization Therapy in Mild Heart Failure: A Review of the REVERSE and MADIT-CRT Trials

Cardiac resynchronization therapy has become part of the treatment strategy for advanced, symptomatic heart failure, but newly published trials show that more patients than previously realized may benefit from this therapy, including those with mild heart failure symptoms. The REVERSE and MADIT-CRT trials showed that cardiac resynchronization therapy reduces risk of hospitalization for heart failure and leads to beneficial reverse remodeling of the left ventricle in mild heart failure, especially in patients with prolonged QRS complexes. Ongoing studies aim to expand the indications for this therapy even further, including in patients with normal ejection fractions and a need for frequent ventricular pacing. The current body of evidence favors cardiac resynchronization therapy in patients with a depressed ejection fraction and prolonged QRS, even with minimal or no heart failure symptoms.     

Biventricular and novel pacing mechanisms in heart failure

Biventricular pacing, often referred to as cardiac resynchronization therapy (CRT), improves subjective and objective measures and promotes reverse ventricular remodeling in patients with chronic New York Heart Association (NYHA) class III or IV heart failure despite optimal medical therapy, QRS duration of more than 130 ms, and left ventricular ejection fraction of less than 35%. However, there are many nonresponders and other patients who do not meet criteria for CRT, limiting the efficacy of therapy. Recent investigations (eg, the REVERSE trial) have shown that patients with minimal symptoms (NYHA class I-II) can benefit from the mechanical and functional effects of CRT, specifically reverse remodeling. Ongoing investigations include the possibility of earlier intervention in the postinfarct period with CRT. Additionally, a novel pacing mechanism known as cardiac contractility modulation has also shown promise in improving remodeling of the failing heart. In this article, we review CRT’s effects on reverse remodeling in an expanding patient population and as a novel pacing mechanism, its cardiac contractility modulation, and its benefits in patients with heart failure.     

Moderate exercise training improves functional capacity, quality of life, and endothelium-dependent vasodilation in chronic heart failure patients with implantable cardioverter defibrillators and cardiac resynchronization therapy.

BACKGROUND: The objective of this study was to determine the effects of a moderate exercise training program on functional capacity, quality of life, and hospital readmission rate in chronic heart failure patients with implantable cardioverter defibrillators and cardiac resynchronization therapy. METHODS AND RESULTS: We studied 52 men (mean age 55+/-10 years, ejection fraction 31+/-7%) in chronic heart failure II (n=29) and III (n=23) NYHA functional class with ischemic cardiomyopathy who received implantable cardioverter defibrillators with or without cardiac resynchronization therapy. Patients were randomized into two groups. Group T (n=30 patients, 15 implantable cardioverter defibrillator, 15 implantable cardioverter defibrillator+cardiac resynchronization therapy) underwent a supervised exercise training program at 60% of peak VO2 three times a week for 8 weeks. Group C (n=22 patients, 12 implantable cardioverter defibrillator, 10 implantable cardioverter defibrillator+cardiac resynchronization therapy) avoided physical training. At 8 weeks, only trained patients had improvements in peak VO2 (P<0.01 versus C), endothelium-dependent dilatation of the brachial artery (P<0.001 versus C) and quality of life (P<0.001 versus C). Among trained patients, those with cardiac resynchronization therapy had greater improvements in peak VO2 and quality of life. During the follow-up (24+/-6 months), eight controls had sustained ventricular tachycardia requiring hospital readmission, while no trained patients had adverse events (log rank 8.56; P<0.001). The improvement in peak VO2 was correlated with the improvement in endothelium-dependent dilatation (r=0.65). CONCLUSION: Moderate exercise training is safe and has beneficial effects after implantable cardioverter defibrillator implantation, especially when cardiac resynchronization therapy is present. These effects are associated with improvement in quality of life and outcome.     

Cardiac resynchronization therapy in advanced heart failure the multicenter InSync clinical study

BACKGROUND: recent short-term observations have shown an improvement in cardiac function and heart failure symptoms from atrio-biventricular pacing. This study was designed to assess the safety and feasibility of an atrio-biventricular transvenous pacing system, and examine the long-term effects of cardiac resynchronization in patients with advanced heart failure and ventricular conduction abnormalities. METHODS AND RESULTS: between August, 1997 and November, 1998, 103 patients received a cardiac resynchronization system (CRS) consisting of a pulse generator interfaced with an atrio-biventricular lead system, including a lead designed for left ventricular (LV) pacing via cardiac veins. Baseline evaluation included 12-lead electrocardiogram, estimation of New York Heart Association (NYHA) functional class, assessment of quality of life (QOL), and distance covered during a 6-min walk (6-MW). Detailed echocardiographic data were also collected in a subset of 46 patients. Measurements were repeated in all surviving patients at 1, 3, 6 and 12 months after implantation of the CRS. A single, self-limiting procedure-related complication occurred. Over a follow-up of 12 months, 21 patients died. The 12-month actuarial survival was 78% (CI 70-87%). Nine surviving patients were withdrawn from the study during long-term follow-up for miscellaneous reasons. At each point of follow-up, a significant shortening of QRS duration was measured. In addition, significant improvements were observed in mean NYHA functional class, 6-MW and QOL score. In the 46 patients with complete echocardiographic data, LV ejection fraction increased from 21.7+/-6.4% at baseline to 26.1+/-9.0% at last follow-up (P = 0.006), LV end diastolic dimension decreased from 72.7+/-9.2 to 71.6+/-9.1 mm (P = 0.233), interventricular mechanical delay decreased from 27.5+/-32.1 to 20.3+/-25.5 ms (P = 0.243), mitral regurgitation apical four-chamber area decreased from 7.66+/-5.5 to 6.69+/-5.9 cm(2) (P = 0.197), and left ventricular filling time increased from 363+/-127 to 408+/-111 ms (P = 0.002). CONCLUSIONS: long-term cardiac resynchronization can be safely and reliably achieved by transvenous atrial synchronized right and left ventricular pacing. These changes were accompanied by clinically relevant improvements in functional status and QOL, as well as a measurable increase in LV performance. The outcome of randomised controlled trials is awaited.     

Valsartan benefits left ventricular structure and function in heart failure: Val-HeFT echocardiographic study

OBJECTIVES: The objective of the study was to evaluate the effect of an angiotensin receptor blocker on left ventricular (LV) structure and function when added to prescribed heart failure therapy. BACKGROUND: The clinical benefit derived from heart failure therapy is attributed to the regression of LV remodeling. METHODS: At 302 multinational sites, 5,010 patients in New York Heart Association (NYHA) classification II to IV heart failure taking angiotensin-converting enzyme inhibitor (ACEI) and/or beta-blocker (BB) were randomized into valsartan and placebo groups and followed for a mean of 22.4 months. Serial echocardiographic measurements of left ventricular internal diastolic diameter (LVIDd) and ejection fraction (EF) were recorded. Total study reproducibility calculated to 90% power at 5% significance defined detectable differences of 0.09 cm for LVIDd and 0.86% for EF. RESULTS: Baseline LVIDd and EF for valsartan and placebo groups were similar: 3.6 +/- 0.5 versus 3.7 +/- 0.5 (cm/m(2)) and 26.6 +/- 7.3 versus 26.9 +/- 7.0 (%). Mean group changes from baseline over time were compared. Significant decrease in LVIDd and increase in EF began by four months, reached plateau by one year, and persisted to two years in valsartan compared with placebo patients, irrespective of age, gender, race, etiology, NYHA classification, and co-treatment therapy. Changes at 18 months were -0.12 +/- 0.4 versus -0.05 +/- 0.4 (cm/m(2)), p < 0.00001 for LVIDd, and +4.5 +/- 8.9 versus +3.2 +/- 8.6 (%), p < 0.00001 for EF. The exception occurred in patients taking both ACEI and BB as co-treatment, in whom the decrease in LVIDd and increase in EF were no different between valsartan and placebo groups. CONCLUSIONS: The Val-HeFT echocardiographic substudy of 5,010 patients with moderate heart failure demonstrated that valsartan therapy taken with either ACEI or BB reversed LV remodeling.     

The BRIGHT study: bifocal right ventricular resynchronization therapy: a randomized study.

AIMS: The BRIGHT study evaluated bifocal right ventricular (RV) (apex and outflow tract) pacing in a single, blind, randomized crossover study in patients eligible for cardiac resynchronization therapy (CRT). Forty-two patients were enrolled with the following characteristics: chronic drug refractory heart failure New York Heart Association (NYHA) class III-IV; ejection fraction (EF)<35%; QRS width >or= 120 ms; and a left bundle branch block. The aim of the study was to assess an improvement in left ventricular (LV) EF, 6 min walk test, Minnesota quality-of-life score, and NYHA classification. Methods and result Patients were randomized to receive either bifocal pacing or the control mode, each for a period of 3 months. Parameters were measured prior to randomization and after 3 months of control or bifocal pacing. Eight patients failed to make the 7 month follow-up, three patients died (one prior to randomization at the first month), five patients dropped out, and three patients refused further participation. One patient had a persistent lead problem, which was subsequently replaced with an LV lead, and one patient suffered with persistent atrial fibrillation. Compared with baseline, bifocal pacing improved EF from 26 +/- 12% to 36 +/- 11% (P < 0.0008), NYHA classification decreased from 2.8 +/- 0.4 to 2.3 +/- 0.7 (P < 0.007). Furthermore, the 6 min walk test improved from 372 +/- 129 m to 453 +/- 122 m (P < 0.05), and the Minnesota Living with Heart Failure scores decreased from 33 +/- 20 to 24 +/- 21 (P < 0.006). In the control group, no significant changes in any parameters were observed. Eight patients did not tolerate reprogramming from DDD BRIGHT to control pacing, with symptoms disappearing in all patients after reprogramming to bifocal pacing. CONCLUSION: Bifocal RV pacing in patients with a classic indication for CRT shows improvement in all parameters.     

Pivotal trials of cardiac resynchronization therapy: evolution to therapy in mild heart failure

Cardiac resynchronization therapy (CRT) has traditionally been reserved for patients with left ventricular (LV) dysfunction in the setting of advanced heart failure. Early clinical trials clearly demonstrated reverse ventricular remodeling and clinical benefits following CRT in this population. More recently, with the publication of the REVERSE, MADIT-CRT, and RAFT trials, the benefits of CRT have been demonstrated in patients with LV dysfunction and mild heart failure calling into question the optimal timing for biventricular pacemaker implantation. With the expanded indications for CRT arising from these studies, significant questions remain specifically with regards to the economic impact on health care systems and to the added risk of future morbidity due to device infection and malfunction.     

心脏再同步治疗发展的新时期

无疑,心脏再同步治疗（CRT）已成为当下心力衰竭非药物治疗的一线选择。一系列大规模临床试验以及我们亲身的临床实践都证实了CRT在改善心力衰竭患者症状,降低住院率和死亡率的卓越疗效。经过十几年的发展,CRT应用进入了一个全新时期,其远期发展可能关注于两个方面。一是在遵从现有指南的基础上,如何进一步提高CRT反应率,二是扩展CRT植入适应证,使潜在人群获益。     

Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine/adenosine triphosphate ratio in patients with heart failure.

AIMS: The addition of trimetazidine to standard treatment has been shown to improve left ventricular (LV) function in patients with heart failure. The aim of this study is to non-invasively assess, by means of in vivo 31P-magnetic resonance spectroscopy (31P-MRS), the effects of trimetazidine on LV cardiac phosphocreatine and adenosine triphosphate (PCr/ATP) ratio in patients with heart failure. METHODS AND RESULTS: Twelve heart failure patients were randomized in a double-blind, cross-over study to placebo or trimetazidine (20 mg t.i.d.) for two periods of 90 days. At the end of each period, all patients underwent exercise testing, 2D echocardiography, and MRS. New York Heart Association (NYHA) class, ejection fraction (EF), maximal rate-pressure product, and metabolic equivalent system (METS) were evaluated. Relative concentrations of PCr and ATP were determined by cardiac 31P-MRS. On trimetazidine, NYHA class decreased from 3.04+/-0.26 to 2.45+/-0.52 (P = 0.005), whereas EF (34+/-10 vs. 39+/-10%, P = 0.03) and METS (from 7.44+/-1.84 to 8.78+/-2.72, P = 0.03) increased. The mean cardiac PCr/ATP ratio was 1.35+/-0.33 with placebo, but was increased by 33% to 1.80+/-0.50 (P = 0.03) with trimetazidine. CONCLUSION: Trimetazidine improves functional class and LV function in patients with heart failure. These effects are associated to the observed trimetazidine-induced increase in the PCr/ATP ratio, indicating preservation of the myocardial high-energy phosphate levels.     

Prevalence of left ventricular dyssynchrony in patients with heart failure assessed by a novelprogrammer-cardioGRAF

Objectives Left ventricular systolic dyssynchrony is the most important determinant of response to cardiac resynchronization therapy （CRT）, playing a vital role to predict improvement of systolic function or LV reverse remodeling. CardioGRAF is a novel programmer based on the ECG gated single photon emission computed tomography （G-SPECT） imaging to detect LV systolic and diastolic dyssynchrony simultaneously. This study was to investigate the prevalence of systolic and diastolic left ventricular （LV） dyssynchrony in patients with heart failure. Methods We retrospectively studied 69 patients with heart disease, including 31 patients who had symptoms of heart failure （NYHA class Ⅱ-Ⅲ）, and 38 patients who had no symptoms of heart failure. （NYHA class Ⅰ）. G- SPECT data were analyzed by cardiaGRAF, and measurements included the time to end systole （TES）, the time to peak ejection （TPE）, the time to peak filling （TPF）, TES＋TPF and maximal difference （MD） of each parameters were obtained, using the 95th percentile of the control group as a cutoffof 150 ms for MD-TES, 139 ms for MD-TPE, 345 ms for MD-TPF and 315 ms for MD-TES＋TPF. Results The prevalence of LV systolic dyssynchrony was significantly higher in heart failure patients with reduced LV ejection fraction （LVEF）〈45% （72% for MD-TES; 64% for MD-TPE） compared with heart failure patients with preserved LVEF=45% （14% for both MD-TES and MD-TPE; P=0.002, P=0.005, respectively）; The prevalence of MD-TES〈150 ms was higher in NYHA class Ⅲ patients （64%） compared with NYHA class Ilpatients （27%, P=0.049）. However, the prevalence of the LV diastolic dyssynchrony were high but not difference between NYHA class III（47% for both MD-TPF and MD-TES＋TPF） and class Ⅲ（63% for MD-TPF; 69% for MD-TES＋TPF; P=NS） patients as well as between patients with preserved LVEF （43% for both MD-TPF and MD-TES＋TPF） and patients with reduced LVEF（64% for MD-TPF; 72% for MD-TES＋TPF; P=NS）. Conclusions The prevalence of LV systolic dyssynchrony was high in heart failure patients with reduced LVEF. Diastolic dyssynchrony was common in patients with heart failure. CardioGRAF maybe a useful method to detect LV dyssynchrony （J Gerlatr Cardio12009; 6：151-156）.