Severe chronic kidney disease is associated with poor survival after initial CRT-defibrillator tachyarrhythmia therapy.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) recipients who receive appropriate device therapies have limited survival, and survival benefit in chronic kidney disease (CKD) has been questioned. We examined the association between CKD and survival after cardiac resynchronization therapy (CRT)-defibrillator tachyarrhythmia therapies. METHODS: We compared overall survival after appropriate shocks or anti-tachycardia pacing in 439 CRT-defibrillator recipients with left ventricular ejection fraction (LVEF) ≤35%, non-right bundle-branch block QRS pattern, and QRS duration >130 ms according to glomerular filtration rate (GFR) at implant, including 31 patients with GFR ≤30, 164 patients with GFR 31-60, and 244 patients with GFR >60. At least one shock occurred in 302 patients (24 with GFR ≤30, 102 with GFR 31-60, and 176 with GFR >60). Serial echocardiograms were also compared. RESULTS: Patients were followed 64 months (interquartile range [IQR]: 29-94) after implant, including 32 months (IQR: 12-61) after first therapy. Time to first therapy or shock was similar across GFR groups. However, survival after first therapy declined directly with declining GFR (P < .001), with median postshock survival of 90 days for GFR ≤30 (95% confidence of interval [CI]: 0-233), 612 days (95% CI: 365-859) for GFR 31-60, and 1672 days (95% CI: 1396-1948) for GFR >60. Declining GFR category, ischemic heart disease, diabetes, and increasing age were independently associated with increased postshock mortality. Echocardiographic response was similar across GFR groups and was not associated with post-therapy survival. CONCLUSIONS: Survival after appropriate tachyarrhythmia therapies, particularly shocks, is attenuated in patients with GFR ≤30. This raises concern over potential lack of survival benefit conferred by CRT-defibrillators versus CRT-pacemakers in this population.

Amiodarone is associated with adverse outcomes in patients with sustained ventricular arrhythmias upgraded to cardiac resynchronization therapy-defibrillators.

INTRODUCTION: Amiodarone reduces recurrent ventricular tachyarrhythmias (VTA) but may worsen cardiovascular outcomes in heart failure (HF) patients. Cardiac resynchronization therapy (CRT) may also be antiarrhythmic. When patients with prior sustained VTA are upgraded to CRT defibrillators (CRT-D) from conventional implantable cardioverter-defibrillators (ICDs), should concomitant amiodarone be continued or is CRT's antiarrhythmic potential sufficient? METHODS AND RESULTS: We identified 67 patients from a prospective CRT registry with spontaneous sustained VTA, New York Heart Association (NYHA) II-IV HF, and left bundle-branch block (LBBB) who were upgraded to CRT defibrillators from conventional ICDs. We compared changes in QRS duration and left ventricular ejection fraction (LVEF) pre- and post-CRT, time to death, transplant or ventricular assist device (VAD), and time to recurrent VTA therapies between 37 patients continuing amiodarone therapy and 30 amiodarone-naïve patients. Amiodarone-treated patients had worse renal function and a higher prevalence of prior VTA storm compared with amiodarone-naïve patients. After CRT, amiodarone-treated patients demonstrated less QRS narrowing (8 vs 20 ms; P = 0.021) and less LVEF improvement (-2.7 vs +5.2%; P = 0.006). Over 29 months, 31 (47%) patients died and 13 (20%) received transplant or VAD. Risk of death, transplant, or VAD was greater in amiodarone-treated than -naïve patients (corrected hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.12-4.11; P = 0.022). Appropriate CRT-D therapies occurred in 37 (55%) patients; amiodarone use was not associated time to first therapy (HR, 1.13; 95% CI, 0.59-2.16; P = 0.72). CONCLUSION: In patients with sustained VTA and LBBB upgraded from conventional ICDs to CRT defibrillators, concomitant amiodarone use is associated with less QRS narrowing, less LVEF improvement, greater risk of death, transplant, or VAD, and similar risk of recurrent VTA.

Oral Anticoagulation for Atrial Fibrillation Thromboembolism Prophylaxis in the Chronic Kidney Disease Population: the State of the Art in 2019.

Atrial fibrillation (AF) is the most common cardiac rhythm disturbance and is associated with increased risk of thromboembolism. Oral anticoagulants are effective at reducing rates of thromboembolism in patients with AF in the general population. Patients with AF and concurrent chronic kidney disease (CKD) have higher risk of thromboembolism and bleeding compared with patients with normal renal function. Among moderate CKD and end-stage renal disease (ESRD) patients on chronic dialysis, the use of oral anticoagulants is controversial. Use of warfarin, while beneficial in non-CKD patients, raises a number of concerns such as increased bleeding risk, labile anticoagulant effect, and calciphylaxis, especially in the ESRD population. The newer direct oral anticoagulant (DOAC) agents have demonstrated comparable efficacy and improved safety profiles compared with coumadin but are not as well studied in the CKD population. This review highlights the efficacy and safety of coumadin and the DOACs for thromboembolism prophylaxis in non-valvular AF patients with CKD.

Sex-specific clinical outcomes after cardiac resynchronization therapy in left bundle branch block-associated idiopathic nonischemic cardiomyopathy: A NEOLITH II substudy.

BACKGROUND: Sex differences in clinical outcomes for left bundle branch block (LBBB)-associated idiopathic nonischemic cardiomyopathy (NICM) after cardiac resynchronization therapy (CRT) are not well described. METHODS: A retrospective cohort study at an academic medical center included subjects with LBBB-associated idiopathic NICM who received CRT. Cox regression analyses estimated the hazard ratios (HRs) between sex and clinical outcomes. RESULTS: In 123 total subjects (mean age 62 years, mean initial left ventricular ejection fraction 22.8%, 76% New York Heart Association class III, and 98% CRT-defibrillators), 55 (45%) were men and 68 (55%) were women. The median follow-up time after CRT was 72.4 months. Similar risk for adverse clinical events (heart failure hospitalization, appropriate implantable cardioverter-defibrillator shock, appropriate antitachycardia pacing therapy, ventricular assist device implantation, heart transplantation, and death) was observed between men and women (HR, 1.20; 95% confidence interval [CI] 0.57-2.51; p = 0.63). This persisted in multivariable analyses. Men and women had similar risk for all-cause mortality in univariable analysis, but men had higher risk in the final multivariable model that adjusted for age at diagnosis, QRS duration, and left ventricular end-diastolic dimension index (HR, 4.55; 95% CI, 1.26-16.39; p = 0.02). The estimated 5-year mortality was 9.5% for men and 6.9% for women. CONCLUSIONS: In LBBB-associated idiopathic NICM, men have higher risk for all-cause mortality after CRT when compared to women.

Myocardial recovery after cardiac resynchronization therapy in left bundle branch block-associated idiopathic nonischemic cardiomyopathy: A NEOLITH II substudy.

BACKGROUND: Baseline predictors of myocardial recovery after cardiac resynchronization therapy (CRT) in left bundle branch block (LBBB)-associated idiopathic nonischemic cardiomyopathy (NICM) are unknown. METHODS: A retrospective study included subjects with idiopathic NICM, left ventricular ejection fraction (LVEF) ≤35%, and LBBB. Myocardial recovery was defined as post-CRT LVEF ≥50%. Logistic regression analyses described associations between baseline characteristics and myocardial recovery. Cox regression analyses estimated the hazard ratio (HR) between myocardial recovery status and adverse clinical events. RESULTS: In 105 subjects (mean age 61 years, 44% male, mean initial LVEF 22.6% ± 6.6%, 81% New York Heart Association class III, and 98% CRT-defibrillators), myocardial recovery after CRT was observed in 56 (54%) subjects. Hypertension, heart rate, and serum blood urea nitrogen (BUN) had negative associations with myocardial recovery in univariable analyses. These associations persisted in multivariable analysis: hypertension (odds ratio (OR), 0.40; 95% confidence interval (CI), 0.17-0.95; p = 0.04), heart rate (OR per 10 bpm, 0.69; 95% CI, 0.48-0.997; p = 0.048), and serum BUN (OR per 1 mg/dl, 0.94; 95% CI, 0.88-0.99; p = 0.04). Subjects with post-CRT LVEF ≥50%, when compared to <50%, had lower risk for adverse clinical events (heart failure hospitalization, appropriate implantable cardioverter-defibrillator shock, appropriate anti-tachycardia pacing therapy, ventricular assist device implantation, heart transplantation, and death) over a median follow-up of 75.9 months (HR, 0.38; 95% CI, 0.16-0.88; p = 0.02). CONCLUSION: In LBBB-associated idiopathic NICM, myocardial recovery after CRT was associated with absence of hypertension, lower heart rate, and lower serum BUN. Those with myocardial recovery had fewer adverse clinical events.

New-onset left bundle branch block-associated idiopathic nonischemic cardiomyopathy and time from diagnosis to cardiac resynchronization therapy: The NEOLITH II study.

BACKGROUND: The optimal timing for cardiac resynchronization therapy (CRT) after diagnosis of new-onset left bundle branch block (LBBB)-associated idiopathic nonischemic cardiomyopathy (NICM) and treatment with guideline-directed medical therapy (GDMT) is unknown. The purpose of this study was to describe relationships between time from diagnosis to CRT and outcomes in new-onset LBBB-associated idiopathic NICM with left ventricular ejection fraction (LVEF) ≤35%. METHODS: A retrospective cohort study examined associations between time from diagnosis to CRT (≤9 months vs >9 months) and clinical and echocardiographic outcomes. RESULTS: In 123 subjects with LBBB-associated idiopathic NICM, time from diagnosis to CRT was ≤9 months in 60 (49%) subjects and 9 months in 63 (51%) subjects. Clinical outcomes were similar for those implanted ≤9 months versus >9 months for adverse clinical events (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.41-1.78; P = 0.67) and all-cause mortality (HR, 0.57; 95% CI, 0.19-1.70; P = 0.31). Multivariable analyses demonstrated similar results. In 105 subjects with post-CRT echocardiograms, LVEF improvement to >35% was more likely in those implanted ≤9 months when compared to >9 months (odds ratio [OR], 3.53; 95% CI, 1.32-9.46; P = 0.01). This association persisted in the final multivariable model adjusted for age at diagnosis, sex, QRS duration, post-GDMT LVEF, and time from CRT to post-CRT echocardiogram (OR, 5.10; 95% CI, 1.71-15.22; P = 0.004). CONCLUSION: In LBBB-associated idiopathic NICM, earlier CRT implantation was associated with more favorable cardiac remodeling. Delaying CRT may miss a critical period to halt and reverse progressive myocardial damage.

Oral anticoagulation and left atrial thrombi resolution in nonrheumatic atrial fibrillation or flutter: A systematic review and meta-analysis.

BACKGROUND: Oral anticoagulation (OAC) is prescribed for left atrial thrombi (LAT) in nonrheumatic atrial fibrillation (AF) and/or atrial flutter (AFL). The study objective was to review the existing evidence regarding LAT resolution in nonrheumatic AF and/or AFL with OAC agents. METHODS: Data sources included PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) between January 1, 1991 and February 10, 2017. English-language studies that assessed LAT resolution with OAC agents in subjects with nonrheumatic AF and/or AFL, by serial transesophageal echocardiography, and with follow-up times ≥ 3 weeks and < 1 year, were selected. Study quality was assessed using recommendations adapted from the Agency for Healthcare Research and Quality. Pooled LAT resolution rates were evaluated for vitamin K antagonist (VKA) studies and low risk of bias warfarin studies. RESULTS: The pooled LAT resolution rate of 619 subjects from 16 VKA studies was 63.7% (95% confidence interval [CI], 53.3%-72.9%). The pooled LAT resolution rate of 94 subjects from four studies that specified warfarin use, exclusion of prior long-term therapeutic OAC, and target international normalized ratio (INR) ≥ 2.0 and/or average achieved INR ≥ 2.0 was 79.3% (95% CI, 69.8%-86.4%). Two studies in direct-acting oral anticoagulants (DOACs) reported LAT resolution rates of 89.5% (17 of 19) for dabigatran and 41.5% (22 of 53) for rivaroxaban. CONCLUSIONS: Warfarin is the most studied initial OAC agent for treating LAT in nonrheumatic AF and/or AFL with a resolution rate of nearly 80%. Further studies in DOACs are warranted.

Left ventricular dimensions predict risk of appropriate shocks but not mortality in cardiac resynchronization therapy-defibrillator recipients with left bundle-branch block and non-ischemic cardiomyopathy.

AIMS: Patients with non-ischaemic cardiomyopathy (NICM) and left bundle-branch block (LBBB) often benefit markedly from cardiac resynchronization therapy (CRT). Cardiac resynchronization therapy responders have a lower risk of appropriate device shocks from CRT-defibrillators (CRT-D) than do non-responders. Larger baseline left ventricular (LV) dimensions may be associated with less CRT response and thus greater risk of appropriate shocks. METHODS AND RESULTS: We analysed all (n = 249; 55% female) primary prevention CRT-D recipients at our institution with LBBB, NICM, and measured LV dimensions prior to device implant for the outcomes of (i) appropriate shocks, (ii) any appropriate tachyarrhythmia therapies, and (iii) risk of death, transplant, or left ventricular assist device (LVAD). During 59 months (interquartile range 21.5-91.5) follow-up, 19 (8%) patients received ≥1 appropriate shock, and 67 (27%) patients died, received a transplant, or required LVAD. Receiver-operating characteristic analysis of LV end-diastolic diameter (LVEDD) per meter height vs. appropriate shock(s) revealed an area under the curve of 0.75 (95% CI 0.65-0.85; P < 0.001). No patient with indexed LVEDD <3.36 cm/m (n = 76) received a shock. There was no statistically significant difference in risk of death, transplant, or LVAD (corrected HR 1.67, 95% CI 0.90-3.03; P = 0.103) in patients with indexed LVEDD above this cut-off compared to those with smaller dimension. Among 102 patients with paired quantitative echocardiograms, there was no difference in LVEF change between patients with indexed LVEDD <3.36 cm/m (n = 27; median 11%) and larger (n = 75; median 14%). CONCLUSION: Patients with LVEDD <3.36 cm/m height prior to CRT-D implant in the setting of NICM and LBBB have minimal risk of appropriate shocks but similar risk of death, transplant- and LVAD and similar extent of LV functional improvement as patients with larger LVEDD. CRT-pacemakers may be appropriate in such patients.

Predictors and implications of early left ventricular ejection fraction improvement in new-onset idiopathic nonischemic cardiomyopathy with narrow QRS complex: A NEOLITH substudy.

BACKGROUND: Predictors and implications of early left ventricular ejection fraction (LVEF) improvement with guideline-directed medical therapy (GDMT) in new-onset idiopathic nonischemic cardiomyopathy (NICM) with narrow QRS complex are not well described. The objectives were to describe predictors of LVEF improvement after 3 months on GDMT and adverse cardiac events based on post-GDMT LVEF status (≤35% vs. >35%). METHODS: A retrospective cohort study was performed in subjects with new-onset NICM, LVEF ≤35%, and narrow QRS complex. Associations for baseline variables with post-GDMT LVEF improvement and absolute change in LVEF (∆LVEFGDMT ) were assessed. Cox proportional hazards models assessed associations for post-GDMT LVEF status with adverse cardiac events. RESULTS: In 70 subjects, 31 (44%) had post-GDMT LVEF ≤35% after a median follow-up time of 97.5 days (interquartile range, 84-121 days). In final multivariable models, severely dilated left ventricular end-diastolic diameter (LVEDD), compared with normal LVEDD, strongly predicted post-GDMT LVEF ≤35% (odds ratio, 7.77; 95% confidence interval [CI], 1.39-43.49; p = .02) and ∆LVEFGDMT (ß = -15.709; standard error = 4.622; p = .001). Subjects with post-GDMT LVEF ≤35% were more likely to have adverse cardiac events over a median follow-up time of 970.5 days (unadjusted hazard ratio, 2.15; 95% CI, 0.93-4.96; p = .07). In the post-GDMT LVEF ≤35% group, 9 of 26 subjects (35%) had long-term LVEF > 35%. CONCLUSION: In new-onset NICM with narrow QRS complex, nondilated LVEDD predicted early LVEF improvement. Those with post-GDMT LVEF ≤35% had higher risk of adverse cardiac events, but a substantial proportion demonstrated continued long-term LVEF improvement.

Clinical outcomes in cardiac resynchronization therapy-defibrillator recipients 80 years of age and older.

AIMS: Very elderly patients have not been well-represented in the randomized trials that established the benefits of cardiac resynchronization therapy (CRT) in heart failure (HF) patients. We therefore compared clinical outcomes in CRT-defibrillator (CRT-D) recipients ≥80 and <80 years old. METHODS AND RESULTS: We compared mortality and time to first appropriate shock in 258 consecutive CRT-D patients ≥80 years old with New York Heart Association II-IV HF, left ventricular ejection fraction ≤35%, QRS duration ≥120 ms, and no prior sustained ventricular tachyarrhythmias to 1058 patients <80 years old implanted with CRT-D during the same timeframe. Comorbidities and medical therapy differed significantly between the groups. During 52 ± 36 months, 123 (48%) patients ≥80 and 474 (45%) patients <80 died; mortality was significantly higher among patients ≥80 [corrected hazard ratio (HR) 1.39, 95% confidence interval (CI) 1.12-1.72; P = 0.003]. Among 258 patients ≥80 with device follow-up, only 20 (8%) received an appropriate shock compared with 172 (17%) shocks in 1053 patients <80 years old. Time to first appropriate shock was significantly shorter in patients <80 (corrected HR 0.51, 95% CI 0.30-0.87, P = 0.013). Older patients experienced 14 inappropriate shocks, and while life-threatening device complications were rare, complications related to the high-power components of the CRT-D system were not infrequent (n = 11). CONCLUSION: Mortality among CRT-D recipients ≥80 years old is higher than in younger patients but is not excessive. The risk of appropriate device shocks in older patients is relatively low and significantly less than in younger patients. These observations suggest that CRT-pacemakers should be given due consideration in elderly HF patients.

Characteristics and Outcomes of Concurrently Diagnosed New Rapid Atrial Fibrillation or Flutter and New Reduced Ejection Fraction.

BACKGROUND: Characteristics and outcomes of concurrently diagnosed new rapid atrial fibrillation (AF) or atrial flutter (AFL) and new heart failure with reduced left ventricular ejection fraction (LVEF) are not well described. METHODS: A retrospective cohort study of subjects referred for expedited transesophageal echocardiography-guided rhythm-control strategies for concurrent new rapid AF/AFL and new LVEF ≤ 40% diagnosed during the same admission was analyzed. RESULTS: Twenty-five subjects (median age 57 years; 96% male; 96% Caucasian; median CHA2 DS2 -VASc = 2) presented with new AF (n = 18) or AFL (n = 7) with rapid ventricular rate (median 135 beats/min) and new reduced LVEF (median 27%; range, 10-37.5%). Seven (28%) subjects had left atrial appendage thrombi (LAAT) and five (20%) subjects had heavy or binge alcohol use. Baseline characteristics were similar between those with and without LAAT. Thirteen subjects with AF and without LAAT underwent direct-current cardioversion (DCCV) and 10 (77%) had AF recurrence within 90 days. Improvement of long-term LVEF to >40% was comparable for subjects with and without initial LAAT (83% vs 94%; P = 0.46). Three of four subjects who received primary prophylaxis implantable cardioverter-defibrillators improved their LVEF to >35% after sinus rhythm maintenance. The median long-term follow-up time was 3.0 years. CONCLUSIONS: Subjects with concurrently diagnosed new rapid AF/AFL and new reduced LVEF are characterized by a high prevalence of LAAT and significant alcohol use. AF subjects without initial LAAT who underwent DCCV had a high 90-day AF recurrence rate. The presence of LAAT did not have a prognosticative effect on eventual LVEF improvement, which was observed in almost all subjects.

The relationship of QRS morphology and mechanical dyssynchrony to long-term outcome following cardiac resynchronization therapy.

AIMS: Because benefits of cardiac resynchronization therapy (CRT) appear to be less favourable in non-left bundle branch block (LBBB) patients, this prospective longitudinal study tested the hypothesis that QRS morphology and echocardiographic mechanical dyssynchrony were associated with long-term outcome after CRT. METHODS AND RESULTS: Two-hundred and seventy-eight consecutive New York Heart Association class III and IV CRT patients with QRS ≥120 ms and ejection fraction ≤35% were studied. The pre-specified primary endpoint was death, heart transplant, or left ventricular assist device over 4 years. Dyssynchrony assessed before CRT included interventricular mechanical delay (IVMD) and speckle-tracking radial strain using pre-specified cut-offs for each. Of 254 with baseline quantitative echocardiographic data available, 128 had LBBB, 81 had intraventricular conduction delay (IVCD), and 45 had right bundle branch block (RBBB). Radial dyssynchrony was observed in 85% of the patients with LBBB, 59% with IVCD*, and 40% with RBBB* (*P < 0.01 vs. LBBB). Of 248 (98%) with follow-up, LBBB patients had a significantly more favourable long-term survival than non-LBBB patients. However, non-LBBB patients with dyssynchrony had a more favourable event-free survival than those without dyssynchrony: radial dyssynchrony hazard ratio 2.6, 95% confidence interval (CI) 1.47-4.53 (P = 0.0008) and IVMD hazard ratio 4.9, 95% CI 2.60-9.16 (P = 0.0007). Right bundle branch block patients who lacked dyssynchrony had the least favourable outcome. CONCLUSION: Non-LBBB patients with dyssynchrony had a more favourable long-term survival than non-LBBB patients who lacked dyssynchrony. Mechanical dyssynchrony and QRS morphology are associated with outcome following CRT.

Impact of scar burden by single-photon emission computed tomography myocardial perfusion imaging on patient outcomes following cardiac resynchronization therapy.

AIMS: Ischaemic heart disease negatively impacts response to cardiac resynchronization therapy (CRT), yet the impact of infarct scar burden on clinical outcomes and its interaction with mechanical dyssynchrony have not been well described. METHODS AND RESULTS: We studied 620 NYHA classes III-IV heart failure patients with ejection fraction (EF) ≤ 35% and QRS duration ≥120 ms referred for CRT. Included were 190 ischaemic cardiomyopathy (ICM) CRT recipients with scar burden quantified by rest-redistribution Tl(201) myocardial perfusion imaging using a 17-segment (0 = normal to 4 = absence of uptake) summed rest score (SRS). Non-ICM (NICM) CRT recipients (n = 380) and 50 patients referred for CRT with unsuccessful LV lead implant comprised the comparison groups. Echocardiographic dyssynchrony analysis was performed in a subgroup of 150 patients. Follow-up left ventricular EF (LVEF) and volumes were examined at 7 ± 3 months in 143 patients. The outcome of death, cardiac transplant, or mechanical circulatory support was assessed in all. Over 2.1 ± 1.6 years, ICM patients had significantly worse survival and less LVEF improvement than NICM patients (P < 0.01). Ischaemic cardiomyopathy patients with low scar burden (SRS < 27) had favourable survival and LVEF improvement, similar to NICM patients. A high scar burden (SRS ≥ 27) was associated with reduced survival and lack of LV functional improvement (P ≤ 0.01), similar to those with unsuccessful LV lead implant, whereas baseline dyssynchrony was not predictive of outcome in these patients. CONCLUSION: Extensive scar burden in ICM patients unfavourably affected clinical and LV functional outcomes after CRT, regardless of baseline dyssynchrony measures. Patients with ICM and lower scar burden had significantly better outcomes, similar to NICM patients.

Relationship of echocardiographic dyssynchrony to long-term survival after cardiac resynchronization therapy.

BACKGROUND: The ability of echocardiographic dyssynchrony to predict response to cardiac resynchronization therapy (CRT) has been unclear. METHODS AND RESULTS: A prospective, longitudinal study was designed with predefined dyssynchrony indexes and outcome variables to test the hypothesis that baseline dyssynchrony is associated with long-term survival after CRT. We studied 229 consecutive class III to IV heart failure patients with ejection fraction ≤35 and QRS duration ≥120 milliseconds for CRT. Dyssynchrony before CRT was defined as tissue Doppler velocity opposing-wall delay ≥65 milliseconds, 12-site SD (Yu Index) ≥32 milliseconds, speckle tracking radial strain anteroseptal-to-posterior wall delay ≥130 milliseconds, or pulsed Doppler interventricular mechanical delay ≥40 milliseconds. Outcome was defined as freedom from death, heart transplantation, or left ventricular assist device implantation. Of 210 patients (89) with dyssynchrony data available, there were 62 events: 47 deaths, 9 transplantations, and 6 left ventricular assist device implantations over 4 years. Event-free survival was associated with Yu Index (P=0.003), speckle tracking radial strain (P=0.003), and interventricular mechanical delay (P=0.019). When adjusted for confounding baseline variables of ischemic origin and QRS duration, Yu Index and radial strain dyssynchrony remained independently associated with outcome (P<0.05). Lack of radial dyssynchrony was particularly associated with unfavorable outcome in those with QRS duration of 120 to 150 milliseconds (P=0.002). CONCLUSIONS: The absence of echocardiographic dyssynchrony was associated with significantly less favorable event-free survival after CRT. Patients with narrower QRS duration who lacked dyssynchrony had the least favorable long-term outcome. These observations support the relationship of dyssynchrony and CRT response.

Response to cardiac resynchronization therapy in patients with heart failure and renal insufficiency.

BACKGROUND: Renal insufficiency (RI) adversely impacts prognosis in heart failure (HF) patients, partly because renal and cardiac dysfunction are intertwined, yet few cardiac resynchronization therapy (CRT) studies have examined patients with moderate-to-severe RI. METHODS: We analyzed 787 CRT-defibrillator (CRT-D) recipients with a glomerular filtration rate (GFR) measured prior to implant. Patients were grouped by GFR (in mL/min/1.73 m(2)): >or=60 (n = 376), 30-59 (n = 347), and <30 (n = 64). Overall survival, changes in left ventricular (LV) ejection fraction and LV end-systolic diameter, and GFR change at 3-6 months were compared among CRT-D groups and with a control cohort (n = 88), also stratified by GFR, in whom LV lead implant was unsuccessful and a standard defibrillator (SD) was placed. All patients met clinical criteria for CRT-D. RESULTS: Among CRT-D recipients, overall survival improved incrementally with higher baseline GFR (for each 10 mL/min/1.73 m(2) increase, corrected hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.13-1.30, P < 0.0001). Survival among SD and CRT-D patients within GFR < 30 and GFR >or= 60 groups was similar, whereas CRT-D recipients with GFR 30-59 had significantly better survival compared to SD counterparts (HR 2.23, 95% CI 1.34-3.70; P = 0.002). This survival benefit was associated with improved renal and cardiac function. CRT recipients with GFR >or= 60 derived significant echocardiographic benefit but experienced a GFR decline, whereas those with GFR < 30 had no echocardiographic benefit but did improve GFR. CONCLUSIONS: CRT may provide the largest survival benefit in HF patients with moderate RI, perhaps by improving GFR and LV function. Severe baseline RI predicts poor survival and limited echocardiographic improvement despite a modest GFR increase, such that CRT may not benefit those with GFR < 30 mL/min/1.73 m(2). CRT recipients with normal renal function derive echocardiographic benefit but no overall survival advantage.

Baseline scintigraphic abnormalities by myocardial perfusion imaging predict echocardiographic response to cardiac resynchronization therapy in nonischemic cardiomyopathy.

BACKGROUND: Significant myocardial scar in the posterolateral left ventricle (LV) has been associated with a diminished response to cardiac resynchronization therapy (CRT) in patients with coronary artery disease, but the effects of resting perfusion abnormalities in nonischemic cardiomyopathy (NICM) are yet to be described. HYPOTHESIS: We sought to characterize the effect of myocardial perfusion abnormalities upon echocardiographic outcomes of CRT in patients with NICM. METHODS: Twenty-one patients (mean age 64.4 +/- 13.3; 71.4% male; mean left ventricular ejection fraction [LVEF] 20.2 +/- 6.9%) with NICM who underwent CRT implantation and Thallium-201 single positron emission computed tomography (SPECT) myocardial perfusion imaging (MPI) were included. MPI studies were read quantitatively, assigning each of 17 myocardial segments a perfusion score (0-4) and cumulatively generating a summed perfusion score (SPS). The LV lead position was determined by chest radiography. Echocardiograms were performed both before and after (median 12 mo) CRT in 15 patients. RESULTS: Echocardiographic response, defined as > or = 15% relative increase in LVEF, was documented in 8 (53.3%) of 15 patients. All patients (5/5) with an SP < or =6 responded to CRT, whereas only 30.0% (3/10) with an SPS > or = 6 responded (odds ratio 3.33 [95% confidence interval {CI} 1.29-8.59]; p = 0.01). All nonresponders had inferior perfusion defects. Defect density adjacent to the LV lead tip had little demonstrable effect upon CRT efficacy. CONCLUSIONS: The presence of significant myocardial perfusion defects negatively influences echocardiographic response to CRT in NICM. These findings warrant prospective confirmation and histopathological correlation with explanted hearts.

Scar burden, not intraventricular conduction delay pattern, is associated with outcomes in ischemic cardiomyopathy patients receiving cardiac resynchronization therapy.

BACKGROUND: Patients with nonspecific intraventricular conduction delay (IVCD) benefit less from cardiac resynchronization therapy (CRT) than patients with left bundle branch block (LBBB). OBJECTIVE: The purpose of this study was to determine whether post-CRT outcome differences in patients with ischemic cardiomyopathy (ICM) relate to intrinsic QRS pattern and/or scar burden. METHODS: We analyzed 393 consecutive ICM patients with left ventricular ejection fraction (LVEF) ≤35%, QRS duration >120 ms, and LBBB or nonspecific IVCD who underwent single-photon emission computed tomography myocardial perfusion imaging and CRT-defibrillator implant. We compared scar burden; QRS duration; LVEF change; risk of death, transplant, or ventricular assist device; and risk of appropriate device shocks between LBBB and IVCD patients, using multivariable analyses to determine relative associations between QRS pattern vs scar burden and outcomes. RESULTS: Nonspecific IVCD is associated with greater scar burden and narrower baseline QRS duration than LBBB. IVCD patients demonstrated less QRS narrowing with CRT than LBBB patients, even when excluding IVCD patients with QRS duration <150 ms. LVEF improved less in patients with IVCD vs LBBB, but only scar burden not QRS morphology or duration was associated with LVEF increase ≥5%. During 39-month follow-up, IVCD was associated with shorter survival free from transplant/ventricular assist device and shorter time to first appropriate device shock. Scar burden but not QRS morphology was independently associated with these outcomes on multivariate analysis. CONCLUSION: IVCD is associated with greater scar burden than LBBB in ICM CRT-defibrillator recipients. Scar burden, not QRS pattern, is independently associated with adverse clinical outcomes.

Scar burden by myocardial perfusion imaging predicts echocardiographic response to cardiac resynchronization therapy in ischemic cardiomyopathy.

BACKGROUND: About 30% of patients with heart failure do not respond to cardiac resynchronization therapy (CRT). We hypothesized that scar burden can predict poor response to CRT in patients with ischemic cardiomyopathy (ICM). METHODS: Fifty patients (age, 68.5 +/- 9.2 years; 84% men; mean left ventricular ejection fraction (LVEF), 19.7% +/- 5.2%) with ICM who underwent CRT-defibrillator implantation and 201Tl single photon emission computed tomography myocardial perfusion imaging were included. Myocardial perfusion imaging studies were read quantitatively, generating a summed perfusion score (SPS). Left ventricular (LV) lead position was determined by chest radiography. Echocardiograms were performed before and after (median, 11.0 months) CRT. RESULTS: Echocardiographic response, defined as > or = 15% relative increase in LVEF, was documented in 28 (56%) patients. The mean SPS (18.8 +/- 11.3 vs 33.7 +/- 11.1; P = .000025) and the average scar density in the segments immediately adjacent to the LV lead (0.70 +/- 0.91 vs 1.64 +/- 0.82; P = .0004) were significantly lower in responders versus nonresponders. Global scar burden (r = -0.53; P = .00007), scar burden near the LV lead (r = -0.49; P = .0003), and the number of segments with a score of 4 (r = -0.53; P = .0007) inversely correlated with increase in LVEF after CRT. The hazard ratio for nonresponse increased with increasing tertiles of global SPS, scar density in the vicinity of the LV lead, and number of segments with transmural scar (ie, perfusion score = 4). CONCLUSIONS: Higher overall scar burden, a larger number of severely scarred segments, and greater scar density near the LV lead tip portend an unfavorable response to CRT in ICM patients. Prospective confirmation of these findings is warranted.

Burden of atrial fibrillation after cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) may diminish atrial fibrillation (AF) burden in patients with chronic heart failure (HF). Each of 27 patients without permanent AF in whom CRT implantation was unsuccessful was paired with 2 active CRT patients-1 responder and 1 nonresponder-based on age, gender, cause of HF, and history of paroxysmal AF. Device-documented high atrial rates and mode-switching episodes were tabulated during a median follow-up of 386 days. CRT responders had significantly improved left ventricular (LV) ejection fraction and New York Heart Association functional class compared with nonresponders and controls. Left atrial dimension change was similar among the groups (+0.03 +/- 0.92 cm controls; -0.18 +/- 0.80 cm responders; -0.11 +/- 1.01 cm nonresponders) despite a significant reduction in mitral regurgitation in responders compared with nonresponders. There was no significant difference in AF burden between controls and patients who underewent CRT when indexed over time. Median AF-free follow-up was significantly longer in patients who underwent CRT without a history of AF (log-rank p = 0.04), but no differences were seen in the overall cohorts. In conclusion, despite inducing LV reverse remodeling and clinical improvement, CRT does not appear to decrease AF burden in responders compared with nonresponders or matched controls in whom CRT implantation failed. CRT may, however, delay onset of new AF.

Gender Differences in Cardiac Resynchronization Therapy Device Choice and Outcome in Patients ≥75 Years of Age with Heart Failure.

Cardiac resynchronization therapy (CRT) is an established therapy for heart failure and can be delivered through a CRT pacemaker (CRT-P) or a CRT defibrillator (CRT-D). CRT-P devices are smaller and less expensive, have better battery longevity, and have been subject to fewer recalls and advisories but cannot deliver high-energy shocks to terminate potentially lethal ventricular arrhythmias. As published guidelines do not distinguish between CRT-P and CRT-D indications, we examined the practice of prescribing these devices in older women and men with heart failure. A total of 512 CRT recipients (age ≥75 years, 26% women, 21% CRT-P) were included in this analysis. Baseline characteristics were collected on all patients, and overall survival was compared by gender and type of CRT device implanted. Women were more likely to receive CRT-Ps than men (26% vs 19%). Men with CRT-Ps were significantly older than women with CRT-Ps and both men and women with CRT-Ds (p = 0.04). In addition, women had lower all-cause mortality compared with men (hazard ratio [HR] 0.75, confidence interval [CI] 0.58 to 0.99, p = 0.04), mainly among CRT-P recipients (HR 0.48, CI 0.26 to 0.8, p = 0.02), but this association was attenuated after adjusting for differences in patient characteristics (HR 0.56, CI 0.26 to 1.18, p = 0.13). In conclusion, women are more likely to receive CRT-Ps than men. Whether this difference is driven by patient preference or physician biases remains unclear. Women with CRT, particularly CRT-Ps, have a better overall survival than men. These differences, which may be driven by unbalanced baseline characteristics of patients or by differences in gender response to CRT, deserve further investigation.