Ulas Hoke

Impact of clinical and echocardiographic response to cardiac resynchronization therapy on long-term survival.

BACKGROUND Clinical or echocardiographic mid-term responses to cardiac resynchronization therapy (CRT) may have a different influence on a long-term prognosis of heart failure patients treated with CRT. The aim of the evaluation was to establish which definition of response to CRT, clinical or echocardiographic, best predicts long-term prognosis. METHODS AND RESULTS A total of 679 heart failure patients treated with CRT were included. All the patients underwent a complete history and physical examination and transthoracic echocardiogram prior to CRT implantation and at 6-month follow-up. The clinical and echocardiographic responses to CRT were defined based on clinical improvement (≥1 NYHA class) and LV reverse remodelling (reduction in LV end-systolic volume ≥15%) at 6-month follow-up, respectively. All the patients were prospectively followed up for the occurrence of death. The mean age was 65 ± 11 years and 79% of the patients were male. At 6-month follow-up, 510 (77%) patients showed clinical response to CRT and 412 (62%) patients showed echocardiographic response to CRT. During a mean follow-up of 37 ± 22 months, 140 (21%) patients died. Clinical and echocardiographic responses to CRT were both significantly related to all-cause mortality on univariable analysis. However, on multivariable Cox-regression analysis only echocardiographic response to CRT was independently associated with superior survival (hazard ratio: 0.38; 95% CI: 0.27-0.50; P < 0.001). CONCLUSION In a large population of heart failure patients treated with CRT, the reduction in LV end-systolic volume at the mid-term follow-up demonstrated to be a better predictor of long-term survival than improvement in the clinical status.

The mode of death in implantable cardioverter-defibrillator and cardiac resynchronization therapy with defibrillator patients: results from routine clinical practice.

BACKGROUND Although data on the mode of death of implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy with defibrillator (CRT-D) patients have been examined in randomized clinical trials, in routine clinical practice data are scarce. To provide reasonable expectations and prognosis for patients and physicians, this study assessed the mode of death in routine clinical practice. OBJECTIVE To assess the mode of death in ICD/CRT-D recipients in routine clinical practice. METHODS All patients who underwent an ICD or CRT-D implantation at the Leiden University Medical Center, the Netherlands, between 1996 and 2010 were included. Patients were divided into primary prevention ICD, secondary prevention ICD, and CRT-D patients. For patients who died during follow-up, the mode of death was retrieved from hospital and general practitioner records and categorized according to a predetermined classification: heart failure death, other cardiac death, sudden death, noncardiac death, and unknown death. RESULTS A total of 2859 patients were included in the analysis. During a median follow-up of 3.4 years (interquartile range 1.7-5.7 years), 107 (14%) primary prevention ICD, 253 (28%) secondary prevention ICD, and 302 (25%) CRT-D recipients died. The 8-year cumulative incidence of all-cause mortality was 39.9% (95% confidence interval 37.0%-42.9%). Heart failure death and noncardiac death were the most common modes of death for all groups. Sudden death accounted for approximately 7%-8% of all deaths. CONCLUSION For all patients, heart failure and noncardiac death are the most common modes of death. The proportion of patients who died suddenly was low and comparable for primary and secondary ICD and CRT-D patients.

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.

Changes in left ventricular function after mitral valve repair for severe organic mitral regurgitation.

BACKGROUND Limited data are available on the changes in left ventricular (LV) contractile function at long-term follow-up after mitral valve repair (MVr). Moreover, assessment of LV systolic function in patients undergoing MVr is troublesome with current methods, given that mitral regurgitation is characterized by increased preload and decreased afterload, potentially masking LV dysfunction. The aim of this study was to assess the value of LV global strain (longitudinal and circumferential) measured by speckle tracking analysis for detecting changes in contractile function after MVr. METHODS A total of 122 patients with organic mitral regurgitation who underwent successful MVr at an early stage (LV ejection fraction>60%, LV end-systolic diameter<40 mm) were included. Echocardiography was performed at baseline and at short-term (∼7 days) and long-term (1 to 3 years) follow-up after MVr. RESULTS At baseline, LV ejection fraction and LV global strain were higher in patients than in 40 normal control individuals. By contrast, LV forward stroke volume was higher in control individuals than in patients. At short-term follow-up, a significant decrease in LV ejection fraction and LV global strain was noted as a consequence of changes in loading conditions. At long-term follow-up, LV ejection fraction and LV global strain improved significantly. Correction of LV strain for LV size showed a subtle impairment of myocardial contractility at baseline, which significantly improved over time after MVr, together with the improvement in LV forward stroke volume. CONCLUSIONS Mitral valve repair for organic mitral regurgitation results in a significant increase in LV myocardial contractility as measured by LV global strain corrected by LV size.

The effect of cardiac resynchronization therapy on left ventricular diastolic function assessed with speckle-tracking echocardiography

Changes in left ventricular (LV) diastolic function after cardiac resynchronization therapy (CRT) in relation to LV reverse remodelling and heart failure aetiology have not been extensively characterized. The aims of the study were to evaluate changes in LV diastolic function with speckle‐tracking echocardiography in relation to: (i) cardiac resynchronization therapy response (LV remodelling) and (ii) heart failure aetiology.

Prediction of Response to Cardiac Resynchronization Therapy Combining Two Different Three-Dimensional Analyses of Left Ventricular Dyssynchrony

Triplane tissue synchronization imaging (TSI) and real-time 3-dimensional echocardiography (RT3DE) provide different characterizations of left ventricular (LV) mechanics and dyssynchrony. Triplane TSI assesses differences in time to peak systolic segmental myocardial tissue velocities, whereas RT3DE evaluates differences in time to minimum end-systolic regional volumes. Whether an approach using the 2 3D techniques predicts better significant reverse remodeling after cardiac resynchronization therapy (CRT) remains unknown. In 166 patients (mean age 66 ± 9 years, 78% men) treated with CRT, baseline LV dyssynchrony was assessed using RT3DE and triplane TSI. LV dyssynchrony was defined by a systolic dyssynchrony index ≥6.4% when assessed with RT3DE and SD of time to peak velocity of 12 segments (Ts-SD-12) ≥33 ms with triplane TSI. CRT response was defined by ≥15% decrease in LV end-systolic volume at 6-month follow-up. Mean LV dyssynchrony using Ts-SD-12 was 48 ± 26 ms and mean systolic dyssynchrony index was 8.51 ± 3.81%. Response to CRT was observed in 86.3% of patients showing LV dyssynchrony with the 2 methods. In contrast, 97% of patients who did not show significant LV dyssynchrony with any of the techniques were nonresponders (p <0.001). Importantly, systolic dyssynchrony index and LV dyssynchrony using Ts-SD-12 were independent predictors of response to CRT (p <0.001 for each technique). Assessment of LV dyssynchrony with the 2 techniques showed incremental value for prediction of significant LV reverse remodeling over its assessment with only 1 technique (chi-square 90.18, p <0.001). In conclusion, the combined use of 2 different 3D techniques to assess LV dyssynchrony permits accurate prediction of response to CRT.

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.

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.

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.