Assessment of left ventricular dyssynchrony by three-dimensional echocardiography: Prognostic value in patients undergoing cardiac resynchronization therapy.

BACKGROUND: Systolic dyssynchrony index (SDI) using three-dimensional echocardiography (3DE) was shown to be a reliable measure of left ventricular (LV) dyssynchrony. However, the prognostic value of SDI on long-term outcomes after cardiac resynchronization therapy (CRT) remains unknown. METHODS AND RESULTS: A total of 414 patients (mean age 67 ± 10 years, 60% ischemic etiology) with 3DE evaluation before CRT implantation were included. SDI was evaluated as continuous value and in quartiles. The study endpoint was combined all-cause mortality, heart transplantation, and LV assist device implantation. At baseline, median SDI was 8.0% (IQR 5.6-11.3%). During a median follow-up of 45 months (IQR 25-59 months), the endpoint was observed in 94 (23%) patients. SDI was independently associated with the endpoint together with ischemic etiology, diabetes, and renal function (HR 0.914, P = 0.003) after adjustment for age, atrial fibrillation, hemoglobin level, NYHA functional class, and posterolateral LV lead position. Patients from the 1st, 2nd, and 3rd SDI quartiles showed similar survival and superior as compared to the 4th quartile with the lowest SDI values (≤5.5%; χ²: 30.4, log-rank P < 0.001). From receiver operating characteristic curve analysis, the optimal SDI cut-off value associated with the endpoint was >6.8% (area under the curve 0.634). Finally, a subgroup analysis (293 patients) demonstrated that a more pronounced reduction in SDI immediately after CRT (resynchronization) was independently associated with superior survival (HR 0.461, P = 0.011) after adjustment for prognostic relevant parameters. CONCLUSION: SDI is independently associated with long-term prognosis after CRT and might therefore be important to optimize risk-stratification in these patients.

Cardiac resynchronization therapy in adults with congenital heart disease.

Aims: In adults with congenital heart disease (CHD) heart failure is one of the leading causes of morbidity and mortality but experience with and reported outcome of cardiac resynchronization therapy (CRT) is limited. We investigated the efficacy of CRT in adults with CHD. Methods and results: This was a retrospective study including 48 adults with CHD who received CRT since 2003 in four tertiary referral centres. Responders were defined as patients who showed improvement in NYHA functional class and/or systemic ventricular ejection fraction by at least one category. Ventricular function was assessed by echocardiography and graded on a four point ordinal scale. Median age at CRT was 47 years (range 18-74 years) and 77% was male. Cardiac diagnosis included tetralogy of Fallot in 29%, (congenitally corrected) transposition of great arteries in 23%, septal defects in 25%, left sided lesions in 21%, and Marfan syndrome in 2% of the patients. The median follow-up duration after CRT was 2.6 years (range 0.1-8.8). Overall, 37 out of 48 patients (77%) responded to CRT either by improvement of NYHA functional class and/or systemic ventricular function. There were 11 non-responders to CRT. Of these, three patients died and four underwent heart transplantation. Conclusion: In this cohort of older CHD patients, CRT was accomplished with a success rate comparable to those with acquired heart disease despite the complex anatomy and technical challenges frequently encountered in this population. Further studies are needed to establish appropriate guidelines for patient selection and long term outcome.

Effect of induced LV dyssynchrony by right ventricular apical pacing on all-cause mortality and heart failure hospitalization rates at long-term follow-up.

BACKGROUND: Right ventricular apical (RVA) pacing may induce left ventricular (LV) dyssynchrony. The long-term prognostic implications of induction of LV dyssynchrony were retrospectively evaluated in a cohort of patients who underwent RVA pacing. METHODS: A total of 169 patients (62 ± 13 years, 69% male) with high RVA pacing burden were included. Echocardiographic evaluation of LV volumes, ejection fraction, and dyssynchrony were performed before and after device implantation. LV dyssynchrony was assessed by 2-dimensional radial strain speckle tracking echocardiography. Based on the median LV dyssynchrony value after RVA pacing, the patient population was dichotomized (induced and noninduced LV dyssynchrony groups) and was followed up for the occurrence of all-cause mortality and heart failure (HF) hospitalization. RESULTS: Baseline mean LV ejection fraction was 51 ± 11%. Median LV dyssynchrony value was 40 ms (12-85 ms) before RVA pacing and increased to 91 ms (81-138 ms) after a median of 13 months (3-26 months) after RVA pacing. Median follow-up duration was 70 months (interquartile range 42-96 months). Patients with induced LV dyssynchrony, defined as LV dyssynchrony value superior to the median at follow-up (≥91 ms), showed higher mortality rates (5% and 27% vs. 1% and 3% at 3 and 5 years follow-up; log-rank P = 0.003) and HF hospitalization rates (18% and 24% vs. 3% and 4% at 3 and 5 years follow-up; log-rank P < 0.001) than patients with LV dyssynchrony <91 ms after RVA pacing. A multivariate model was developed to identify independent associates of a combined endpoint of all-cause mortality or HF hospitalization. Induction of LV dyssynchrony was independently associated with increased risk of combined endpoint (HR [95% CI]: 3.369 [1.732-6.553], P < 0.001). CONCLUSION: Induction of LV dyssynchrony by RVA pacing is associated with worse long-term mortality and increased HF hospitalization rates.

Prognostic implications of left ventricular regional function heterogeneity assessed with two-dimensional speckle tracking in patients with ST-segment elevation myocardial infarction and depressed left ventricular ejection fraction.

The aim of the current study was to evaluate the prognostic implications of myocardial tissue heterogeneity assessed with two-dimensional speckle-tracking echocardiography in patients three months after first ST-segment elevation myocardial infarction (STEMI) with left ventricular ejection fraction (LVEF) ≤35 %. For this purpose, a total of 79 patients with first STEMI and LVEF ≤35 % at three months postinfarction were evaluated. Based on left ventricular (LV) speckle-tracking longitudinal strain echocardiography, the infarct core, border zone, and remote zone at baseline and three months' follow-up were defined. Patients were followed for the occurrence of the composite end point of appropriate implantable cardioverter-defibrillator (ICD) therapy and/or cardiac mortality. During a median follow-up of 46 months, 13 patients (17 %) reached the composite end point. At baseline, patients with and without events showed comparable values of LV longitudinal strain at the infarct, border, and remote zones. However, at three months' follow-up, patients with events showed significantly more impaired longitudinal strain at the border zone (-6.8 ± 3.1 % vs. -10.5 ± 4.9 %, P = 0.002), whereas LVEF was comparable (28 ± 6 % vs. 31 ± 4 %, P = 0.09). The median three-month LV longitudinal strain at the border zone was -9.4 %. Multivariate Cox regression analysis demonstrated that three-month longitudinal strain >-9.4 % at the border zone was independently associated with the composite end point (hazard ratio 3.94, 95 % confidence interval 1.05-14.70; P = 0.04). In conclusion, regional longitudinal strain at the border zone three months post-STEMI is associated with appropriate ICD therapy and cardiac mortality.

Effect of atrioventricular and ventriculoventricular delay optimization on clinical and echocardiographic outcomes of patients treated with cardiac resynchronization therapy: a meta-analysis.

BACKGROUND: Optimization of atrioventricular (AV) and ventriculoventricular (VV) delays of cardiac resynchronization therapy (CRT) devices maximizes left ventricular filling and stroke volume. However, the incremental value of these optimizations over empiric device programming remains unclear. The objective of this analysis was to perform a systematic review and meta-analysis of the effects of AV and VV delay optimization on clinical and echocardiographic end points of patients with heart failure treated with CRT. METHODS: A standardized search strategy was performed and identified 12 trials comparing AV and/or VV delay optimization and conventional CRT device programming and their effects on various clinical and echocardiographic outcomes. Pooled odds ratios were analyzed using random-effect meta-analysis with Mantel-Haenszel method. RESULTS: Combined data from a total of 4,356 patients with heart failure treated with CRT showed no differences in clinical or echocardiographic outcomes between patients who underwent AV and/or VV delay optimization and patients who underwent empiric device programming (Mantel-Haenszel odds ratio 0.86 [95% CI 0.68-1.09], P value for overall effect = .21 by intention-to-treat analysis). CONCLUSION: The current literature suggests that routine AV and/or VV delay optimization has a neutral effect on clinical and echocardiographic outcomes based on pooled data from randomized and nonrandomized studies. Standardization of patient selection and optimization timing and method may help to further define the role of CRT device optimization.

Clinical, echocardiographic, and neurohormonal response to cardiac resynchronization therapy: are they interchangeable?

BACKGROUND: The relationship between changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) and echocardiographic or clinical definitions of response to cardiac resynchronization therapy (CRT) has not been evaluated. The aims of the present evaluation were to assess: (1) the relationship between changes in NT-proBNP after 6 months of CRT and clinical and echocardiographic responses; (2) the association between NT-proBNP changes and long-term outcome. METHODS: In 170 patients treated with CRT (age 61 ± 11 years, 75% male), clinical and echocardiographic parameters and circulating NT-proBNP levels were assessed at baseline and 6 months after CRT. At 6 months follow-up, improvement in New York Heart Association class ≥ 1 point, decrease in left ventricular end-systolic volume ≥ 15%, and decrease in NT-proBNP ≥ 15% defined clinical, echocardiographic, and neurohormonal CRT response, respectively. All-cause mortality data were collected and related to neurohormonal response. RESULTS: Neurohormonal, echocardiographic, and clinical response rates were 54%, 58%, and 66%, respectively. The majority of patients (71%) showing echocardiographic response had NT-proBNP reduction ≥ 15%. In contrast, only 58% of patients who showed clinical response also had NT-proBNP reduction ≥ 15%. During a median follow-up of 32 months, 40 patients died. Patients with neurohormonal response demonstrated a superior long-term outcome compared to patients without neurohormonal response (log-rank P = 0.02). CONCLUSIONS: NT-proBNP reduction ≥ 15% showed better agreement with echocardiographic response compared to clinical response. Neurohormonal response was associated with superior long-term outcome compared to insufficient reduction in NT-proBNP levels.

Predictors of long-term benefit of cardiac resynchronization therapy in patients with right bundle branch block.

AIMS: The aims of this study were: (i) to characterize consecutive cardiac resynchronization therapy (CRT) recipients with right bundle branch block (RBBB) in comparison with left bundle branch block (LBBB) and (ii) to identify independent predictors of long-term outcome among CRT recipients with RBBB. The presence of RBBB has been associated with poorer prognosis after CRT compared with LBBB; however, little is known about the differences in cardiac mechanics between RBBB and LBBB patients. Furthermore, predictors of favourable outcome after CRT in patients with RBBB have not been identified. METHODS AND RESULTS: Five hundred and sixty-one consecutive CRT recipients (89 with RBBB and 472 with LBBB) underwent echocardiography before and 6 months after CRT to determine left ventricular (LV) size and function, and interventricular and LV dyssynchrony (as measured by tissue Doppler imaging). Long-term follow-up to identify a composite endpoint of all-cause mortality or heart failure hospitalization was available. Right bundle branch block patients exhibited a higher prevalence of male gender, ischaemic heart disease, atrial fibrillation, and lower exercise capacity when compared with LBBB patients, despite smaller LV volumes. In addition, the extent of both interventricular and LV dyssynchrony was less in RBBB patients. Six months after CRT, RBBB patients also showed limited LV reverse remodelling. At long-term follow-up, LV dyssynchrony and mitral regurgitation were identified as independent predictors of all-cause mortality or heart failure hospitalization among RBBB patients. CONCLUSION: Left ventricular dyssynchrony may be an important determinant of outcome following CRT in patients with RBBB and may help in the selection of CRT candidates.

Relation of Myocardial Contrast-Enhanced T1 Mapping by Cardiac Magnetic Resonance to Left Ventricular Reverse Remodeling After Cardiac Resynchronization Therapy in Patients With Nonischemic Cardiomyopathy.

Myocardial scar is known to be associated with limited left ventricular (LV) reverse remodeling after cardiac resynchronization therapy (CRT). However, the impact of diffuse myocardial interstitial fibrosis, as assessed with myocardial T1 mapping cardiac magnetic resonance (CMR), has not been studied in patients with CRT. Therefore, we aimed at evaluating the association between diffuse myocardial interstitial fibrosis, in nonischemic cardiomyopathy patients, and LV reverse remodeling after CRT. A total of 40 patients (61 ± 11 years) with nonischemic cardiomyopathy who underwent CMR before CRT implantation were included. Myocardial T1 mapping was performed using an inversion-recovery Look-Locker sequence after gadolinium injection. Myocardial contrast-enhanced T1 time values were assessed from segments without delayed contrast enhancement and normalized for heart rate. At 6-month follow-up, LV reverse remodeling was assessed by the reduction in LV end-systolic volume. Before CRT implantation, mean myocardial contrast-enhanced T1 time was 351 ± 46 ms. At 6-month follow-up, LV end-systolic volume decreased by 24 ± 21%. Myocardial contrast-enhanced T1 time showed a significant correlation with LV reverse remodeling (r = 0.5, p = 0.001) together with hemoglobin level, renal function, LV dyssynchrony, and presence of delayed contrast enhancement. Multivariate regression analysis identified myocardial contrast-enhanced T1 time (ß -0.160, p = 0.022), LV dyssynchrony (ß -0.267, p = 0.002), and renal function (ß -0.334, p = 0.021) as independent associates of LV reverse remodeling. In conclusion, in nonischemic cardiomyopathy, diffuse interstitial myocardial fibrosis quantified with T1 mapping CMR is independently associated with LV reverse remodeling after CRT and might, therefore, be used to optimize patient selection.

Usefulness of the CRT-SCORE for Shared Decision Making in Cardiac Resynchronization Therapy in Patients With a Left Ventricular Ejection Fraction of ≤35.

Individualized estimation of prognosis after cardiac resynchronization therapy (CRT) remains challenging. Our aim was to develop a multiparametric prognostic risk score (CRT-SCORE) that could be used for patient-specific clinical shared decision making about CRT implantation. The CRT-SCORE was derived from an ongoing CRT registry, including 1,053 consecutive patients (age 67 ± 10 years, 76% male). Using preimplantation variables, 100 multiple imputed datasets were generated for model calibration. Based on multivariate Cox regression models, cross-validated linear prognostic scores were calculated, as well as survival fractions at 1 and 5 years. Specifically, the CRT-SCORE was calculated using atrioventricular junction ablation, age, gender, etiology, New York Heart Association class, diabetes, hemoglobin level, renal function, left bundle branch block, QRS duration, atrial fibrillation, left ventricular systolic and diastolic functions, and mitral regurgitation, and showed a good discriminative ability (areas under the curve 0.773 at 1 year and 0.748 at 5 years). During the long-term follow-up (median 60 months, interquartile range 31 to 85), all-cause mortality was observed in 494 (47%) patients. Based on the distribution of the CRT-SCORE, lower- and higher-risk patient groups were identified. Estimated mean survival rates of 98% at 1 year and 92% at 5 years were observed in the lowest 5% risk group (L5 CRT-SCORE: -4.42 to -1.60), whereas the highest 5% risk group (H5 CRT-SCORE: 1.44 to 2.89) showed poor survival rates: 78% at 1 year and 22% at 5 years. In conclusion, the CRT-SCORE allows accurate prediction of 1- and 5-year survival rates after CRT using readily available and CRT-specific clinical, electrocardiographic, and echocardiographic parameters. The model may assist clinicians in counseling patients and in decision making.

Long-Term Echocardiographic Outcome in Super-Responders to Cardiac Resynchronization Therapy and the Association With Mortality and Defibrillator Therapy.

Super-response to cardiac resynchronization therapy (CRT) is associated with significant left ventricular (LV) reverse remodeling and improved clinical outcome. The study aimed to: (1) evaluate whether LV reverse remodeling remains sustained during long-term follow-up in super-responders and (2) analyze the association between the course of LV reverse remodeling and ventricular arrhythmias. Of all, primary prevention super-responders to CRT were selected. Super-response was defined as LV end-systolic volume reduction of ≥30% 6 months after device implantation. Cox regression analysis was performed to investigate the association of LV ejection fraction (LVEF) as time-dependent variable with implantable-cardioverter defibrillator (ICD) therapy and mortality. A total of 171 super-responders to CRT-defibrillator were included (mean age 67 ± 9 years; 66% men; 37% ischemic heart disease). Here of 129 patients received at least 1 echocardiographic evaluation after a median follow-up of 62 months (25th to 75th percentile, 38 to 87). LV end-diastolic volume, LV end-systolic volume, and LVEF after 6-month follow-up were comparable with those after 62-month follow-up (p = 0.90, p = 0.37, and p = 0.55, respectively). Changes in LVEF during follow-up in super-responders were independently associated with appropriate ICD therapy (hazard ratio 0.94, 95% CI 0.90 to 0.98; p = 0.005) and all-cause mortality (hazard ratio 0.95, 95% CI 0.91 to 1.00; p = 0.04). A 5% increase in LVEF was associated with a 1.37 times lower risk of appropriate ICD therapy and a 1.30 times lower risk of mortality. In conclusion, LV reverse remodeling in super-responders to CRT remains sustained during long-term follow-up. Changes in LVEF during follow-up were associated with mortality and ICD therapy.

Cardiac Resynchronization Therapy in CKD Stage 4 Patients.

BACKGROUND AND OBJECTIVES: Cardiac resynchronization therapy (CRT) is a well established heart failure treatment that has shown to improve renal function. However, landmark CRT trials excluded patients with severe renal dysfunction. Therefore, this study evaluated the effect of CRT on renal function and long-term prognosis in patients with stage 4 CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study evaluated 73 consecutive CRT patients (71±10 years) with stage 4 CKD who underwent echocardiographic and renal function evaluation at baseline and 6-month follow-up between 2000 and 2012. As a control group, 18 patients with stage 4 CKD who received an implantable cardioverter defibrillator (ICD) were selected. CRT recipients with ≥15% reduction in left ventricular end-systolic volume at 6-month follow-up were classified as CRT responders. During long-term follow-up (median, 33 months), appropriate defibrillator therapy, heart failure hospitalizations, and all-cause mortality (combined end point) were recorded. RESULTS: At 6-month follow-up, a significant reduction in left ventricular end-systolic volume was observed in CRT patients compared with patients with ICD (from 159±78 to 145±78 ml in CRT patients and from 126±54 to 119±49 ml in ICD patients; P=0.05), and CRT response was observed in 22 patients (30%). Compared with ICD patients, eGFR improved among CRT patients (from 25±4 to 30±9 ml/min per 1.73 m(2); interaction time and group, P=0.04) and was more pronounced among CRT responders (25±3 to 34±9 ml/min per 1.73 m(2); P<0.001). The combined end point was observed in 17 ICD and 62 CRT patients. CRT patients showed superior survival compared with ICD patients (log-rank P=0.03). More importantly, CRT response was independently associated with improved survival free from the combined end point (hazard ratio, 0.51; 95% confidence interval, 0.27 to 0.98; P=0.04) after adjustment for clinical and echocardiographic parameters. CONCLUSIONS: Response to CRT occurs in approximately 30% of patients with stage 4 CKD, which is less than in the average CRT population. CRT was associated with better clinical outcome, and particularly, CRT response was associated with improvement in eGFR and better long-term prognosis.

The relationship between time from myocardial infarction, left ventricular dyssynchrony, and the risk for ventricular arrhythmia: speckle-tracking echocardiographic analysis.

BACKGROUND: Differences in arrhythmogenic substrate may explain the variable efficacy of implantable cardioverter-defibrillators (ICDs) in primary sudden cardiac death prevention over time after myocardial infarction (MI). Speckle-tracking echocardiography allows the assessment left ventricular (LV) dyssynchrony, which may reflect the electromechanical heterogeneity of myocardial tissue. The aim of the present study was to evaluate the relationship among LV dyssynchrony, age of MI, and their association with the risk for ventricular tachycardia (VT) after MI. METHODS: A total of 206 patients (median age, 67 years; 87% men) with prior MIs (median MI age, 6.2 years; interquartile range, 0.66-15 years) who underwent programmed electrical stimulation, speckle-tracking echocardiography, and ICD implantation were retrospectively evaluated. LV dyssynchrony was defined as the standard deviation of time to peak longitudinal systolic strain values using speckle-tracking strain echocardiography. LV scar burden was evaluated by the percentage of segments exhibiting scar (defined as an absolute longitudinal strain of magnitude < 4.5%). Patients were followed up for the occurrence of first monomorphic VT requiring ICD therapy (antitachycardia pacing or shock) for a median of 24 months. RESULTS: In total, 75 individuals experienced the primary end point of monomorphic VT. LV dyssynchrony was independently associated with the occurrence of VT at follow-up (hazard ratio per 10-msec increase, 1.12; 95% confidence interval, 1.07-1.18; P < .001), together with nonrevascularization of the infarct-related artery and VT inducibility. Patients with older (>180 months) MIs had a higher likelihood of VT inducibility (88% vs 63%, P = .003) and greater scar burden (14.7 ± 15.8% vs 10.7 ± 11.4%, P = .03) compared with patients with recent (<8 months) MIs. CONCLUSIONS: LV dyssynchrony is independently associated with the occurrence of VT after MI.

Left ventricular reverse remodeling, device-related adverse events, and long-term outcome after cardiac resynchronization therapy in the elderly.

BACKGROUND: Limited data are available on efficacy, safety, and long-term prognosis after cardiac resynchronization therapy (CRT) in elderly patients. We aimed at evaluating the effect of CRT, device-related adverse events, and long-term outcome after CRT among elderly patients. METHODS AND RESULTS: A total of 798 CRT recipients (208 elderly: age, ≥75 years; 590 nonelderly: age, <75 years) underwent clinical and echocardiographic evaluation at baseline and 6-month follow-up. Elderly patients had similar improvements in clinical symptoms, left ventricular function, and left ventricular reverse remodeling as their counterparts. Similar rates of device-related in-hospital (within 24 hours; P=0.552), early (within 30 days; P=0.984), and long-term adverse events (entire follow-up; hazard ratio, 0.90; P=0.620) were observed between groups. During long-term follow-up (median, 38.6 months; interquartile range, 22.5-61.8 months), all-cause mortality rate was significantly higher among the elderly patients. However, the differences in cumulative event rates started after 4 years of follow-up (P=0.013), and the cause of death was mainly noncardiac (29% in the elderly versus 19% in nonelderly; P<0.001). Diabetes mellitus (hazard ratio, 2.322; P=0.019), impaired renal function (hazard ratio, 0.975; P=0.006), and reduced 6-minute walk distance (hazard ratio, 0.996; P<0.019) were independently associated with all-cause mortality in elderly patients. CONCLUSIONS: CRT efficacy and device-related adverse events in elderly patients were comparable with that of nonelderly patients. However, after 4 years of follow-up, elderly patients showed worse survival and the cause of death was mainly noncardiac. Diabetes mellitus, impaired renal function, and reduced 6-minute walk distance were independently associated with all-cause mortality of elderly patients.

Impact of right ventricular dyssynchrony on left ventricular performance in patients with pulmonary hypertension.

Pulmonary hypertension has been associated with right ventricular (RV) dyssynchrony which may induce left ventricular (LV) dysfunction and dyssynchrony through ventricular interdependence. The present study evaluated the influence of RV dyssynchrony on LV performance in patients with pulmonary hypertension. One hundred and seven patients with pulmonary hypertension (age 63 ± 14 years, systolic pulmonary arterial pressure 60 ± 19 mmHg) and LV ejection fraction (EF) >35% were evaluated. Ventricular dyssynchrony was assessed with speckle tracking echocardiography and defined as the standard deviation of the time to peak longitudinal strain of six segments of the RV (RV-SD) and the LV (LV-SD) in the apical 4-chamber view. Mean RV-SD and LV-SD assessed with longitudinal strain speckle tracking echocardiography were 51 ± 28 and 47 ± 21 ms, respectively. The patient population was divided according to the median RV-SD value of 49 ms. Patients with RV-SD ≥49 ms had significantly worse NYHA functional class (2.7 ± 0.7 vs. 2.3 ± 0.7, p = 0.004), RV function (tricuspid annular plane systolic excursion: 16 ± 4 vs. 19 ± 4 mm, p < 0.001), LVEF (50 ± 10 vs. 55 ± 8%, p = 0.001), and larger LV-SD (57 ± 18 vs. 36 ± 18 ms, p < 0.001). RV-SD significantly correlated with LV-SD (r = 0.55, p < 0.001) and LVEF (r = -0.23, p = 0.02). Multiple linear regression analysis showed an independent association between RV-SD and LV-SD (ß = 0.35, 95%CI 0.21-0.49, p < 0.001). RV dyssynchrony is significantly associated with LV dyssynchrony and reduced LVEF in patients with pulmonary hypertension.

Super-responders to cardiac resynchronization therapy remain at risk for ventricular arrhythmias and benefit from defibrillator treatment.

AIMS: Mortality and ventricular arrhythmias are reduced in patients responding to cardiac resynchronization therapy (CRT). This response is accompanied by improvement in LVEF, and some patients even outgrow original eligibility criteria for implantable cardioverter-defibrillator (ICD) implantation. It is however unclear if these patients still benefit from ICD treatment. The current study aimed to evaluate if the incidence of ICD therapy is related to the extent of CRT response. METHODS AND RESULTS: All patients who underwent primary prevention CRT-defibrillator implantation were included. They were divided into subgroups according to the reduction in LV end-systolic volume (LVESV) 6 months after implantation. Pre-defined subgroups were: negative responders (increased LVESV), non-responders (decreased LVESV 0-14%), responders (decreased LVESV 15-29%), and super-responders (decreased LVESV ≥30%). During a median follow-up of 57 months (25th-75th percentile 39-84), 512 patients were studied [101 (20%) negative responders, 101 (20%) non-responders, 149 (29%) responders, and 161 (31%) super-responders]. In the first year of follow-up super-responders received significantly less appropriate ICD therapy (3% vs. 12%; P < 0.001). The 5-year cumulative incidence of appropriate ICD therapy was 31% [95% confidence interval (CI) 19-43] in negative responders, 39% (95% CI 25-53) in non-responders, 34% (95% CI 25-43) in responders, and 27% (95% CI 18-35) in super-responders, respectively (p = 0.13). CONCLUSIONS: The extent of CRT response was associated with a parallel reduction of appropriate device therapy during the first year of follow-up. Thereafter, no association was observed. Furthermore, 23% of super-responders were treated for potentially life-threatening arrhythmias and benefit from ICD treatment.

Significant lead-induced tricuspid regurgitation is associated with poor prognosis at long-term follow-up.

BACKGROUND: Although the presence of an RV lead is a potential cause of tricuspid regurgitation (TR), the clinical impact of significant lead-induced TR is unknown. OBJECTIVE: To evaluate the effect of significant lead-induced TR on cardiac performance and long-term outcome after cardioverter-defibrillator (ICD) or pacemaker implantation. METHODS: A retrospective cohort of 239 ICD (n=191) or pacemaker (n=48) recipients (age 60±14 years, 77% male) from a tertiary care university hospital, with an echocardiographic evaluation before and within 1-1.5 years after device implantation were included. Significant lead-induced TR was defined as TR worsening, reaching a grade ≥2 at follow-up echocardiography. During long-term follow-up (median 58, IQR 35-76 months), all-cause mortality and heart failure related events were recorded. RESULTS: Before device implantation, most patients had TR grade 1 or 2 (64.0%) or no TR (33.9%), but after lead placement, significant TR was seen in 91 patients (38%). Changes in cardiac volumes and function at follow-up were similar between patients with and without significant lead-induced TR, except for larger RV diastolic area (17±6mm(2) vs 16±5mm(2), p=0.009), larger right atrial diameter (39±10 mm vs 36±8 mm, p<0.001) and higher pulmonary arterial pressures (41±15 mm Hg vs 33±10 mm Hg, p<0.001) in patients with significant lead-induced TR. Patients with significant lead-induced TR had worse long-term survival (HR=1.687, p=0.040) and/or more heart failure related events (HR=1.641, p=0.019). At multivariate analysis, significant lead-induced TR was independently associated with all-cause mortality (HR=1.749, p=0.047) together with age, LVEF and percentage RV pacing. CONCLUSIONS: Significant lead-induced TR is associated with poor long-term prognosis.

Effect of cardiac resynchronization therapy on the sequence of mechanical activation assessed by two-dimensional radial strain imaging.

Cardiac resynchronization therapy (CRT) induces left ventricular (LV) reverse remodeling by synchronizing LV mechanical activation. We evaluated changes in segmental LV activation after CRT and related them to CRT response. A total of 292 patients with heart failure (65 ± 10 years, 77% men) treated with CRT underwent baseline echocardiographic assessment of LV volumes and ejection fraction. Time-to-peak radial strain was measured for 6 midventricular LV segments with speckle-tracking strain imaging. Moreover, the time difference between the peak radial strain of the anteroseptal and the posterior segments was calculated to obtain LV dyssynchrony. After 6 months, LV volumes, segmental LV mechanical activation timings, and LV dyssynchrony were reassessed. Response to CRT was defined as ≥15% decrease in LV end-systolic volume at 6-month follow-up. Responders (n = 177) showed LV resynchronization 6 months after CRT (LV dyssynchrony from 200 ± 127 to 85 ± 86 ms; p <0.001) by earlier activation of the posterior segment (from 438 ± 141 to 394 ± 132 ms; p = 0.001) and delayed activation of the anteroseptal segment (from 295 ± 155 to 407 ± 138 ms; p <0.001). In contrast, nonresponders (n = 115) experienced an increase in LV dyssynchrony 6 months after CRT (from 106 ± 86 to 155 ± 112 ms; p = 0.001) with an earlier activation of posterior wall (from 391 ± 139 to 355 ± 136 ms; p = 0.039) that did not match the delayed anteroseptal activation (from 360 ± 148 to 415 ± 122 ms; p = 0.001). In conclusion, responders to CRT showed LV resynchronization through balanced lateral and anteroseptal activations. In nonresponders, LV dyssynchrony remains, by posterior wall preactivation and noncompensatory delayed septal wall activation.

Influence of diabetes on left ventricular systolic and diastolic function and on long-term outcome after cardiac resynchronization therapy.

OBJECTIVE: The influence of diabetes on cardiac resynchronization therapy (CRT) remains unclear. The aims of the current study were to 1) assess the changes in left ventricular (LV) systolic and diastolic function and 2) evaluate long-term prognosis in CRT recipients with diabetes. RESEARCH DESIGN AND METHODS: A total of 710 CRT recipients (171 with diabetes) were included from an ongoing registry. Echocardiographic evaluation, including LV systolic and diastolic function assessment, was performed at baseline and 6-month follow-up. Response to CRT was defined as a reduction of ≥15% in LV end-systolic volume (LVESV) at the 6-month follow-up. During long-term follow-up (median = 38 months), all-cause mortality (primary end point) and cardiac death or heart failure hospitalization (secondary end point) were recorded. RESULTS: At the 6-month follow-up, significant LV reverse remodeling was observed both in diabetic and non-diabetic patients. However, the response to CRT occurred more frequently in non-diabetic patients than in diabetic patients (57 vs. 45%, P < 0.05). Furthermore, a significant improvement in LV diastolic function was observed both in diabetic and non-diabetic patients, but was more pronounced in non-diabetic patients. The determinants of the response to CRT among diabetic patients were LV dyssynchrony, ischemic cardiomyopathy, and insulin use. Both primary and secondary end points were more frequent in diabetic patients (P < 0.001). Particularly, diabetes was independently associated with all-cause mortality together with ischemic cardiomyopathy, renal function, LVESV, LV dyssynchrony, and LV diastolic dysfunction. CONCLUSIONS: Heart failure patients with diabetes exhibit significant improvements in LV systolic and diastolic function after CRT, although they are less pronounced than in non-diabetic patients. Diabetes was independently associated with all-cause mortality.

Right ventricular function and survival following cardiac resynchronisation therapy.

OBJECTIVES: Right ventricular (RV) function is an important prognostic marker in heart failure. However, its impact on all-cause mortality following cardiac resynchronisation therapy (CRT) independent of confounding factors has not been evaluated. Furthermore, evidence concerning the effect of CRT on RV function is limited. The study's aims were to: (1) assess the prognostic importance of RV function among CRT recipients, and (2) characterise RV functional change following CRT and its determinants. DESIGN: Retrospective observational study. SETTING: Single tertiary centre. PATIENTS: A total of 848 CRT recipients (median age 65 years, 78% male, 60% ischaemic) underwent echocardiography before and 6 months after CRT. RV function was evaluated using tricuspid annular plane systolic excursion (TAPSE), with a ≤14 mm threshold indicating severe RV impairment. The primary endpoint was long-term all-cause mortality. RESULTS: Significant baseline RV dysfunction was observed in 286 (34%) individuals. After a median 44 months, 288 deaths occurred. RV impairment was associated with a greater incidence of all-cause mortality (log-rank p<0.001). Independent predictors of this endpoint were functional class, ischaemic aetiology, diabetes, atrial fibrillation, renal dysfunction, bigger left ventricular (LV) end-systolic volume, less LV dyssynchrony and reduced TAPSE. Importantly, TAPSE added prognostic value to these recognised prognostic parameters (likelihood-ratio test p<0.001). Furthermore, improvement in RV function after CRT was independent of the improvement in LV systolic function but significantly associated with the improvement in LV diastolic function. Importantly, a favourable RV functional response to CRT was associated with superior survival. CONCLUSIONS: RV function is an independent predictor of long-term outcome following CRT.

Gender-specific differences in clinical outcome of primary prevention implantable cardioverter defibrillator recipients.

OBJECTIVE: To assess differences in clinical outcome of implantable cardioverter-defibrillator (ICD) treatment in men and women. DESIGN: Prospective cohort study. SETTING: University Medical Center. PATIENTS: 1946 primary prevention ICD recipients (1528 (79%) men and 418 (21%) women). Patients with congenital heart disease were excluded for this analysis. MAIN OUTCOME MEASURES: All-cause mortality, ICD therapy (antitachycardia pacing and shock) and ICD shock. RESULTS: During a median follow-up of 3.3 years (25th-75th percentile 1.4-5.4), 387 (25%) men and 76 (18%) women died. The estimated 5-year cumulative incidence for all-cause mortality was 20% (95% CI 18% to 23%) for men and 14% (95% CI 9% to 19%) for women (log rank p<0.01). After adjustment for potential confounding covariates all-cause mortality was lower in women (HR 0.65; 95% CI 0.49 to 0.84; p<0.01). The 5-year cumulative incidence for appropriate therapy in men was 24% (95% CI 21% to 28%) as compared with 20% (95% CI 14% to 26%) in women (log rank p=0.07). After adjustment, a non-significant trend remained (HR 0.82; 95% CI 0.64 to 1.06; p=0.13). CONCLUSIONS: In clinical practice, 21% of primary prevention ICD recipients are women. Women have lower mortality and tend to experience less appropriate ICD therapy as compared with their male peers.