Relation of right ventricular peak systolic pressure to major adverse events in patients undergoing cardiac resynchronization therapy

The degree to which increased right-sided heart pressures influence outcome in cardiac resynchronization therapy (CRT) is unclear. High right ventricular (RV) pressures may contribute to septal malpositioning, thus hindering effective resynchronization. We hypothesized that patients with high RV systolic pressures before CRT implantation would have poorer outcome. We evaluated echocardiograms, electrocardiograms, and clinical records from 75 consecutive patients with CRT. RV systolic pressure was calculated from the peak tricuspid regurgitant, time-velocity profile. The primary end point was a composite of mortality, cardiac transplantation, or need for a left ventricular assist device. Events were evaluated by Kaplan-Meier curves and Cox proportional hazard ratios. Patients grouped by RV systolic pressure divided at the median of 35 mm Hg were similar except for more renal insufficiency and RV dysfunction when RV systolic pressure was >35 mm Hg. Univariate analysis identified RV systolic pressure >35 mm Hg (hazard ratio [HR] 3.32), diabetes (HR 2.45), renal insufficiency (HR 3.52), atrial fibrillation (HR 3.07), use of nonamiodarone antiarrhythmic medications (HR 2.86), atrial pacing (HR 2.57), and prolonged PR interval (HR 1.009) as associated with poorer outcome. Normal sinus rhythm at implantation (HR 0.34), baseline left bundle branch block (HR 0.44), and beta-blocker use (HR 0.47) were associated with improved outcome. In a multivariable model, high RV systolic pressure (HR 3.71, 95% confidence interval 1.31 to 10.4), renal insufficiency (HR 3.18, 95% confidence interval 1.29 to 7.86), and atrial fibrillation (HR 4.22, 95% confidence interval 1.54 to 11.6) remained significant. In conclusion, despite resynchronization, patients with high RV pressures have significantly decreased survival after adjusting for significant contributing influences.     

Relation of response to cardiac resynchronization therapy to left ventricular reverse remodeling

Cardiac resynchronization therapy (CRT) reverses left ventricular (LV) remodeling in patients with congestive heart failure. However, the mechanisms leading to the clinical response to CRT remain unclear. The aim of this study was to analyze whether patients who improve clinically have greater LV reverse remodeling than nonresponders after a 12-month follow-up period. The sample comprised 64 consecutive patients with heart failure, complete left bundle branch block, and LV ejection fractions (EFs) < or =35% who were treated with CRT. Doppler echocardiographic scans were taken just before and immediately after the implantation of the pacemakers and at 6- and 12-month follow-up examinations. LV diameters, volumes, and EFs were compared. Responders were defined as those patients who were alive without cardiac transplantation and with > or =10% improvement in the 6-minute walking test after 1 year of follow-up. There were no clinical differences at baseline between responders and nonresponders. At 6- and 12-month follow-up, LV dimensions decreased significantly in responders but did not change in nonresponders. Furthermore, LVEFs improved only in responders. In conclusion, patients who clinically respond to CRT have greater LV reverse remodeling than nonresponders after 6 and 12 months of follow-up. The effect of CRT on LV remodeling may explain, at least in part, the clinical benefit of this therapy.     

Cellular evidence of reverse cardiac remodeling induced by cardiac resynchronization therapy

Left ventricular assist devices (LVADs) induce reverse cardiac remodeling by reducing myocyte size and collagen deposition. On the other hand, cardiac resynchronization therapy (CRT) induces reverse cardiac remodeling by improving electromechanical synchronization. The clinical and structural changes produced by CRT in failing myocardium are known, but whether these changes are accompanied by reverse cellular remodeling is unknown. A total of 12 patients with chronic heart failure (CHF) who underwent CRT and 15 patients who had LVAD therapy as clinically indicated and 8 healthy controls were compared. Demographics, echocardiographic data, and histologic samples from myocardial biopsies were analyzed and compared among groups. The authors found significant increases in myocyte size, myocardial fibrosis, and inflammation in both CHF groups who underwent CRT or LVAD, compared with healthy controls. After CRT or LVAD therapy, a significant decrease in myocyte size and tumor necrosis factor α (TNF-α) expression compared with healthy controls (P < .05) was found. In the CRT group, 6 of 8 patients demonstrated reduction in myocyte size and interstitial fibrosis. In addition, there was a decrease in myocyte size by 13%, total collagen by 27% and TNF-α by 49% in the CRT group vs 28%, 45%, and 45% in the LVAD group. CRT produces cellular reverse remodeling in failing human hearts that are comparable with those produced by LVAD therapy.     

心脏再同步化治疗与心力衰竭患者的心脏电学逆重构

目的探讨心脏再同步化治疗(CRT)是否会纠正心力衰竭患者的电重构现象。方法回顾分析伴有完全性左束支传导阻滞的心力衰竭患者接受CRT后随访观察1年,分别在术中电极安置后和术后1年测试自身心律下右室-左室电极的激动时间差(△t),右室电极刺激到左室电极感知时间(RVp-LV)及左室电极刺激到右室电极感知时间(LVp-RV),比较CRT应答者与无应答者的自身QRS波时限、双室起搏下QRS波时限和△t、RVp-LV、LVp-RV。结果共入选51例,应答组(36例),无应答组(15例)。应答组术前和术后1年相比,△t和RVp-LV缩短(P0.05)。无应答组术前与术后1年比较,△t、RVp-LV延长(P0.05)。两组自身QRS波时限无差异,但术后1年无应答组起搏下QRS波时限延长。结论 CRT应答患者发生了电学逆重构。起搏QRS波时限改变与CRT疗效有关。     

Relation of left ventricular lead placement in cardiac resynchronization therapy to left ventricular reverse remodeling and to diastolic dyssynchrony

The effects of left ventricular (LV) lead placement for cardiac resynchronization therapy (CRT) on LV remodeling and dyssynchrony are not well defined. Sixty-one patients (age 60 +/- 11 years, 76% men) were evaluated by echocardiography before and 4 +/- 2 months after CRT and grouped by the LV lead placement (lateral, posterolateral, or anterolateral). Echocardiographic measurements included LV volumes and LV ejection fraction. Tissue Doppler imaging was used to assess for inter- and intraventricular systolic and diastolic dyssynchrony. Analysis of variance was used to determine the effect of the LV lead placement on echocardiographic variables after CRT. The LV lead was placed in a lateral cardiac vein in 33 patients (54%), posterolateral in 15 (25%), and anterior in 13 (21%). Lateral LV lead placement was associated with significantly smaller LV volumes compared with the posterolateral lead placement (p <0.01). Diastolic dyssynchrony improved significantly with lateral lead placement compared with the anterior lead location (p <0.05). Improvement in LV ejection fraction and inter- and intraventricular systolic dyssynchrony was similar among the 3 groups. In conclusion, in patients undergoing CRT, a lateral lead location resulted in greater reverse LV remodeling and improved diastolic dyssynchrony compared with other lead placement locations.     

Septal to posterior wall motion delay fails to predict reverse remodeling or clinical improvement in patients undergoing cardiac resynchronization therapy.

OBJECTIVES: The aim of this study was to test the hypothesis that a longer septal-to-posterior wall motion delay (SPWMD) would predict greater reverse remodeling and an improved clinical response in heart failure patients randomized to cardiac resynchronization therapy (CRT) in the CONTAK-CD trial. BACKGROUND: The SPWMD predicted clinical benefit with CRT in two previous studies from the same center. METHODS: In this retrospective analysis of the CONTAK-CD trial, SPWMD was measured from the baseline echocardiogram of 79 heart failure patients (ejection fraction 22 +/- 7%, QRS duration 159 +/- 27 ms, 72% ischemic, 84% male) randomized to CRT and compared with six-month changes in echocardiographic and clinical parameters. Patients with a left ventricular end-systolic volume index (LVESVI) reduction of at least 15% were considered responders. RESULTS: The feasibility and reproducibility of performing the SPWMD measurements were poor. Larger values for SPWMD did not correlate with six-month changes in left ventricular end-diastolic volume index (p = 0.26), LVESVI (p = 0.41), or left ventricular ejection fraction (p = 0.36). Responders did not have a significantly different SPWMD than non-responders (p = 0.26). The SPWMD did not correlate with measures of clinical improvement. At a threshold of SPWMD >130 ms, the test characteristics to predict reverse remodeling or a clinical response were inadequate. CONCLUSIONS: The previous findings that SPWMD predicts reverse remodeling or clinical improvement with CRT were not reproducible in patients randomized in the CONTAK-CD trial.     

Relation of hemoglobin A1c to rate of major adverse cardiac events in nondiabetic patients undergoing percutaneous coronary revascularization

Abnormalities in plasma glucose below the "diabetic range" of glycemia are associated with increased cardiovascular morbidity and mortality in patients without diabetes mellitus. The purpose of this study was to investigate the relation between ambient glycemic levels as measured by hemoglobin A1c and outcome after elective percutaneous coronary intervention (PCI). Baseline laboratory studies, including hemoglobin A1c, were drawn in 500 consecutive patients before elective PCI. Nondiabetic patients were defined as those without a history of diet or pharmacologically controlled diabetes mellitus and a hemoglobin A1c level <7.0%. Of the 500 patients studied, 291 (59%) were nondiabetic patients. Abnormal hemoglobin A1c levels (6% to 7%) were found in 30% of nondiabetic patients. Nondiabetic patients with an abnormal hemoglobin A1c level had a significantly higher rate of major adverse cardiac events (33% vs 22%, p = 0.04), target vessel revascularization (31% vs 19%, p = 0.02), and cardiovascular mortality (4.6% vs 0.5%, p = 0.03) compared with nondiabetic patients with hemoglobin A1c levels <6%. Multivariate analysis disclosed that a hemoglobin A1c level of 6% to 7% was a significant independent predictor of major adverse cardiac events, target vessel revascularization, and cardiovascular mortality 12 months after PCI in nondiabetic patients. These data demonstrate that an abnormal hemoglobin A1c level may have prognostic significance in nondiabetic patients who undergo PCI.     

New equation for prediction of reverse remodeling after cardiac resynchronization therapy

Objectives: To integrate data from two‐dimensional echocardiography (2D ECHO), three‐dimensional echocardiography (3D ECHO), and tissue Doppler imaging (TDI) for prediction of left ventricular (LV) reverse remodeling (LVRR) after cardiac resynchronization therapy (CRT). It was also compared the evaluation of cardiac dyssynchrony by TDI and 3D ECHO. Methods: Twenty‐four consecutive patients with heart failure, sinus rhythm, QRS ≥ 120 msec, functional class III or IV and LV ejection fraction (LVEF) ≤ 0.35 underwent CRT. 2D ECHO, 3D ECHO with systolic dyssynchrony index (SDI) analysis, and TDI were performed before, 3 and 6 months after CRT. Cardiac dyssynchrony analyses by TDI and SDI were compared with the Pearson's correlation test. Before CRT, a univariate analysis of baseline characteristics was performed for the construction of a logistic regression model to identify the best predictors of LVRR. Results: After 3 months of CRT, there was a moderate correlation between TDI and SDI (r = 0.52). At other time points, there was no strong correlation. Nine of twenty‐four (38%) patients presented with LVRR 6 months after CRT. After logistic regression analysis, SDI (SDI > 11%) was the only independent factor in the prediction of LVRR 6 months of CRT (sensitivity = 0.89 and specificity = 0.73). After construction of receiver operator characteristic (ROC) curves, an equation was established to predict LVRR: LVRR =?0.4LVDD (mm) + 0.5LVEF (%) + 1.1SDI (%), with responders presenting values >0 (sensitivity = 0.67 and specificity = 0.87). Conclusions: In this study, there was no strong correlation between TDI and SDI. An equation is proposed for the prediction of LVRR after CRT. Although larger trials are needed to validate these findings, this equation may be useful to candidates for CRT. (Echocardiography 2012;29:678‐687)     

Elevated red cell distribution width is associated with impaired reverse ventricular remodeling and increased mortality in patients undergoing cardiac resynchronization therapy

Elevated red cell distribution width (RDW) has been associated with poor long-term outcomes in patients with systolic dysfunction. The relationship between baseline RDW and reverse ventricular remodeling in advanced heart failure patients undergoing cardiac resynchronization therapy (CRT) has not been established. The authors reviewed the pre-implant and follow-up echocardiograms of 233 patients undergoing the new implantation of a CRT device at the Cleveland Clinic between December 2001 and November 2006. Patients were included in the final cohort if they had an RDW level within 7 days of CRT implantation, a left ventricular ejection fraction (LVEF) ≤40%, and New York Heart Association class II to IV symptoms. Patients with a reduction in left ventricular end-systolic volume ≥15% following CRT were considered "responders." Multivariate models were created to assess the relationship between baseline RDW elevation with progressive remodeling and all-cause mortality. Of 233 patients, 217 patients met inclusion criteria. Patients in the highest RDW quartile (>16.1) derived significantly less improvement in LVEF (3.5%±9.3% vs 10.1%±10.9%, P=.001) than patients in the lowest quartile (<13.6). In multivariate analysis, elevated RDW was inversely associated with response (odds ratio, 0.83; 95% confidence interval, 0.69-0.99; P=.047). The presence of elevated RDW is associated with less reverse left ventricular remodeling in patients with advanced heart failure undergoing CRT.     

Unusual adverse consequence of reverse ventricular remodelling following cardiac resynchronization therapy

Cardiac resynchronization therapy has been shown to produce reverse ventricular remodelling in patients with severe heart failure. We report an unusual case of T-wave oversensing, most likely as a consequence of reverse ventricular remodelling resulting in change of the implantable cardioverter-defibrillator lead redundancy.     

Relationship between left ventricular dyssynchrony and reverse remodeling after cardiac resynchronization therapy

Background:

Cardiac resynchronization therapy (CRT) is recommended for patients with advanced chronic heart failure. The presence of left ventricular (LV) dyssynchrony before CRT is an important predictor of response to the therapy. We aimed to investigate time course of LV dyssynchrony after CRT and the relationship between LV dyssynchrony improvement and reverse remodeling (RR).

Hypothesis:

The relationship between the improvement of LV dyssynchrony and RR may differ according to criteria used to determine RR.

Methods:

Thirty patients with advanced heart failure, wide QRS complex, and LVEF ≤35% were included. Echocardiography coupled with tissue Doppler imaging was performed at baseline, and repeated at 1 and 6 months in follow‐up. Patients were divided into RR and no‐remodeling groups according to 10% decrease in left ventricular end‐systolic volume (LVESV) and/or 25% increase in LVEF.

Results:

Left ventricular dyssynchrony improvement was significant at the first month in both the RR and no‐remodeling groups according to LVESV decrease. Left ventricular dyssynchrony improvement was continued in the RR group; however, it did not improve significantly in the no‐remodeling group. Left ventricular dyssynchrony improvement was significant at the first and sixth month in the RR and no‐remodeling groups according to LVEF increase.

Conclusions:

Our study suggests that LV dyssynchrony improvement plays an important role in the development of RR according to decrease in LVESV. Reverse remodeling according to the increase in LVEF was developed independently from LV dyssynchrony improvement. The improvement in LV dyssynchrony is a necessary but not sufficient explanation for improvement in LVEF and LVESV. © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.     

Cardiac resynchronization therapy in patients undergoing open-chest cardiac surgery

Purpose

Few data are available on the effects of cardiac resynchronization therapy (CRT) in candidates for cardiac surgery and affected by severe heart failure (HF). The aim of our analysis is to evaluate the percentage of patients who maintain indication for CRT after surgery and the efficacy of CRT in those patients subsequently implanted.

Methods

We enrolled 124 HF patients with indication both to heart surgery and to CRT. During surgery, an epicardial left ventricular lead was implanted, tunneled to a subclavear pocket, and capped. Afterward, patients were periodically reassessed to confirm indication for CRT.

Results

CRT indication was confirmed within 1 month from surgery in 54 patients (group A) and in 33 patients within 6 months (group B). In group A and B, 63% and 71% of patients were considered responders according to an arbitrary five-point increase of left ventricular ejection fraction (LVEF), respectively. The assessment of clinical response at 1 year, based on the definitions proposed by Packer, identified 63% and 80% of responders in group A and B, respectively.

Conclusions

Our data show that a remarkable percentage of patients maintain an indication for CRT after cardiac surgery (76%), while in the remaining 24% the lack of an indication is confirmed by a higher LVEF at last follow-up. In combination with surgery, CRT proved to be an effective therapy in those patients who were subsequently implanted. The suggested method is simple, without significant adjunctive risks, and allows easier CRT implantation with stable thresholds.     

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.