MultiPole pacing in non-responders to cardiac resynchronization therapy: Results from the QP ExCELs/MPP sub-study.

BACKGROUND: Multisite LV stimulation therapy allows for stimulation of two different left ventricular pacing vectors within a single LV lead and may improve responsiveness to cardiac resynchronization therapy (CRT). This study prospectively evaluated the safety and efficacy of the MultiPole Pacing (MPP) feature in CRT non-responder patients. METHODS AND RESULTS: CRT non-responders with a standard CRT-D indication were eligible for enrollment into the MPP Sub-Study. Patient status, NYHA classification, Patient Global Assessment (PGA), and adverse events were collected at follow-up. A clinical composite score (CCS) was determined at the 6 month follow-up visit. The primary objective was defined as the proportion of patients with an improved CCS. Safety was evaluated as freedom from MPP system related adverse events requiring additional invasive intervention to resolve. A total of 53 patients were enrolled across 26 U.S. centers. The cumulative follow-up duration was 24.1 years. CCS was improved in 35.6% of patients (p < .0001 when compared to a performance goal of 3%) after 6 months of MPP therapy. When incorporating patient feedback into a modified CCS, 60.0% of patients showed an improvement. Three patients (5.7%) experienced hospitalization for heart failure, and three patient deaths occurred over the follow-up period. No MPP system-related events were reported for an AE-free rate of 100% (95% CI 93.28% to 100.0%). CONCLUSIONS: The results of this small, non-randomized study suggest that the MPP feature is safe, and may be effective at converting a percentage of CRT non-responders to responders. Larger, randomized studies are needed to confirm this result.

Microvolt T-Wave Alternans Is Modulated by Acute Low-Level Tragus Stimulation in Patients With Ischemic Cardiomyopathy and Heart Failure.

Aims: Microvolt T-wave alternans (TWA), an oscillation in T-wave morphology of the electrocardiogram (ECG), has been associated with increased susceptibility to ventricular tachy-arrhythmias, while vagus nerve stimulation has shown promising anti-arrhythmic effects in in vivo and ex vivo animal studies. We aimed to examine the effect of non-invasive, acute low-level tragus stimulation (LLTS) on TWA in patients with ischemic cardiomyopathy and heart failure. Methods: 26 patients with ischemic cardiomyopathy (left ventricular ejection fraction <35%) and chronic stable heart failure, previously implanted with an automatic implantable cardioverter defibrillator (ICD) device with an atrial lead (dual chamber ICD or cardiac resynchronization therapy defibrillator), were enrolled in the study. Each patient sequentially received, (1) Sham LLTS (electrode on tragus, but no stimulation delivered) for 5 min; (2) Active LLTS at two different frequencies (5 and 20 Hz, 15 min each); and (3) Active LLTS, during concomitant atrial pacing at 100 bpm at two different frequencies (5 and 20 Hz, 15 min each). LLTS was delivered through a transcutaneous electrical nerve stimulation device (pulse width 200 µs, frequency 5/20 Hz, amplitude 1 mA lower than the discomfort threshold). TWA burden was assessed using continuous ECG monitoring during sham and active LLTS in sinus rhythm, as well as during atrial pacing. Results: Right atrial pacing at 100 bpm led to significantly heightened TWA burden compared to sinus rhythm, with or without LLTS. Acute LLTS at both 5 and 20 Hz, during sinus rhythm led to a significant rise in TWA burden in the precordial leads (p < 0.05). Conclusion: Acute LLTS results in a heart-rate dependent increase in TWA burden.

Low-Level Tragus Stimulation Modulates Atrial Alternans and Fibrillation Burden in Patients With Paroxysmal Atrial Fibrillation.

Background Low-level tragus stimulation (LLTS) has been shown to significantly reduce atrial fibrillation (AF) burden in patients with paroxysmal AF. P-wave alternans (PWA) is believed to be generated by the same substrate responsible for AF. Hence, PWA may serve as a marker in guiding LLTS therapy. We investigated the utility of PWA in guiding LLTS therapy in patients with AF. Methods and Results Twenty-eight patients with AF were randomized to either active LLTS or sham (earlobe stimulation). LLTS was delivered through a transcutaneous electrical nerve stimulation device (pulse width 200 µs, frequency 20 Hz, amplitude 10-50 mA), for 1 hour daily over a 6-month period. AF burden over 2-week periods was assessed by noninvasive continuous ECG monitoring at baseline, 3 months, and 6 months. A 5-minute control ECG for PWA analysis was recorded during all 3 follow-up visits. Following the control ECG, an additional 5-minute ECG was recorded during active LLTS in all patients. At baseline, acute LLTS led to a significant rise in PWA burden. However, active patients receiving chronic LLTS demonstrated a significant reduction in both PWA and AF burden after 6 months (P<0.05). Active patients who demonstrated an increase in PWA burden with acute LLTS showed a significant drop in AF burden after 6 months of chronic LLTS. Conclusions Chronic, intermittent LLTS resulted in lower PWA and AF burden than did sham control stimulation. Our results support the use of PWA as a potential marker for guiding LLTS treatment of paroxysmal AF.

Anemia and its association with clinical outcome in heart failure patients undergoing cardiac resynchronization therapy.

PURPOSE: Although a substantial proportion of patients with heart failure (HF) have anemia, there is a paucity of data evaluating the impact of anemia on clinical outcome in CRT patients. Our goal was to examine the ability of baseline hemoglobin (Hb) level and change in Hb level over time to predict clinical 2-year outcome and echocardiographic response to CRT. METHODS: Three hundred consecutive CRT patients (median 72 years [interquartile range (IQR) 16 years], 19% female) with baseline and follow-up hematological profiles available were examined. Baseline anemia was defined as Hb <12 g/dL in women and <13 g/dL in men, and patients were grouped into equal quartiles based on change in Hb. Two-year clinical outcome was determined using a composite endpoint that included HF hospitalization, left ventricular assist device (LVAD) placement, heart transplantation, and all-cause mortality. Echocardiographic reverse remodeling was examined at 6-month follow-up. RESULTS: One hundred fifty-one anemic patients were compared to 149 non-anemic patients. Changes in left ventricular dimensions and ejection fraction were similar for both groups. Univariate predictors of 2-year clinical outcome included baseline creatinine level, diuretic usage, and anemia; in multivariable regression, baseline anemia was an independent predictor for outcome (hazard ratio [HR] 1.79, 95% confidence interval [CI] [1.22-2.63], p = 0.003). The quartile with the most negative change in Hb concentration over time (≤-1.00 g/dL) had poorer event-free 2-year survival (HR 1.84, CI [1.13-3.00], p = 0.014). CONCLUSIONS: Baseline anemia and early postimplantation decline in Hb levels are associated with a worse 2-year prognosis in CRT patients, even though the magnitude of left ventricular reverse remodeling is similar compared to non-anemic patients.

Prognostic implication of baseline PR interval in cardiac resynchronization therapy recipients.

BACKGROUND: Prolongation of the baseline ECG PR interval is frequently encountered among cardiac resynchronization therapy (CRT) recipients. There are conflicting data regarding the association of a prolonged PR interval with long-term clinical outcome in this patient group. OBJECTIVE: The purpose of this study was to compare clinical outcomes and response to CRT in patients with normal (<200 ms) vs prolonged (≥200 ms) baseline PR interval. METHODS: In this study, 283 patients (normal PR interval: n = 158; prolonged PR interval: n = 125) with documented baseline intrinsic PR interval were followed for 3 years after CRT implantation. The study population consisted of 24.7% women (mean age 66 ± 13 years, left ventricular ejection fraction 24% ± 7%). RESULTS: A Cox proportional hazard model identified baseline PR interval as a predictor of the composite end-point (all-cause mortality, heart failure hospitalization, left ventricular assist device implantation, and heart transplantation) in univariate analysis (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.02-2.17, P = .04) but not in multivariate analysis. It also predicted heart failure hospitalization in univariate (HR 1.6, 95% CI 1.1-2.4, P = .02) and multivariate analysis (HR 1.6, 95% CI 1.0-2.3, P = .03). A prolonged PR interval was associated with lower probability of reverse remodeling defined as ≥10% improvement in ejection fraction (64% vs 77%, P = .057), especially in patients with non-left bundle branch block ECG morphology (41% vs 68%, P = .03). CONCLUSION: Among patients with CRT, a prolonged baseline PR interval is an independent predictor of worse prognosis and lower probability of reverse remodeling, especially for patients with non-left bundle branch block morphology on ECG.

Patient engagement with a mobile web-based telemonitoring system for heart failure self-management: a pilot study.

BACKGROUND: Intensive remote monitoring programs for congestive heart failure have been successful in reducing costly readmissions, but may not be appropriate for all patients. There is an opportunity to leverage the increasing accessibility of mobile technologies and consumer-facing digital devices to empower patients in monitoring their own health outside of the hospital setting. The iGetBetter system, a secure Web- and telephone-based heart failure remote monitoring program, which leverages mobile technology and portable digital devices, offers a creative solution at lower cost. OBJECTIVE: The objective of this pilot study was to evaluate the feasibility of using the iGetBetter system for disease self-management in patients with heart failure. METHODS: This was a single-arm prospective study in which 21 ambulatory, adult heart failure patients used the intervention for heart failure self-management over a 90-day study period. Patients were instructed to take their weight, blood pressure, and heart rate measurements each morning using a WS-30 bluetooth weight scale, a self-inflating blood pressure cuff (Withings LLC, Issy les Moulineaux, France), and an iPad Mini tablet computer (Apple Inc, Cupertino, CA, USA) equipped with cellular Internet connectivity to view their measurements on the Internet. Outcomes assessed included usability and satisfaction, engagement with the intervention, hospital resource utilization, and heart failure-related quality of life. Descriptive statistics were used to summarize data, and matched controls identified from the electronic medical record were used as comparison for evaluating hospitalizations. RESULTS: There were 20 participants (mean age 53 years) that completed the study. Almost all participants (19/20, 95%) reported feeling more connected to their health care team and more confident in performing care plan activities, and 18/20 (90%) felt better prepared to start discussions about their health with their doctor. Although heart failure-related quality of life improved from baseline, it was not statistically significant (P=.55). Over half of the participants had greater than 80% (72/90 days) weekly and overall engagement with the program, and 15% (3/20) used the interactive voice response telephone system exclusively for managing their care plan. Hospital utilization did not differ in the intervention group compared to the control group (planned hospitalizations P=.23, and unplanned hospitalizations P=.99). Intervention participants recorded shorter average length of hospital stay, but no significant differences were observed between intervention and control groups (P=.30). CONCLUSIONS: This pilot study demonstrated the feasibility of a low-intensive remote monitoring program leveraging commonly used mobile and portable consumer devices in augmenting care for a fairly young population of ambulatory patients with heart failure. Further prospective studies with a larger sample size and within more diverse patient populations is necessary to determine the effect of mobile-based remote monitoring programs such as the iGetBetter system on clinical outcomes in heart failure.

Association of hypothyroidism with adverse events in patients with heart failure receiving cardiac resynchronization therapy.

Hypothyroidism is associated with an adverse prognosis in cardiac patients in general and in particular in patients with heart failure (HF). The aim of this study was to evaluate the impact of hypothyroidism on patients with HF receiving cardiac resynchronization therapy (CRT). Additionally, the impact of level of control of hypothyroidism on risk of adverse events after CRT implantation was also evaluated. We included consecutive patients in whom a CRT device was implanted from April 2004 to April 2010 at our institution with sufficient follow-up data available for analysis; 511 patients were included (age 68.5±12.4 years, women 20.4%); 84 patients with a clinical history of hypothyroidism, on treatment with thyroid hormone repletion or serum thyroid-stimulating hormone level≥5.00 µU/ml, were included in the hypothyroid group. The patients were followed for up to 3 years after implant for a composite end point of hospitalization for HF, left ventricular assist device placement, or heart transplant and cardiac death; 215 composite end point events were noted in this period. In a multivariate model, hypothyroidism (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.027 to 2.085, p=0.035), female gender (HR 0.64, 95% CI 0.428 to 0.963, p=0.032), and creatinine (HR 1.26, 95% CI 1.145 to 1.382, p<0.001) were significantly associated with occurrence of the composite end point; 53.6% of patients with hypothyroidism at baseline developed the composite end point compared with 39.8% of those with euthyroidism (p=0.02). In conclusion, hypothyroidism is associated with a worse prognosis after CRT implantation.

Progressive ventricular dysfunction among nonresponders to cardiac resynchronization therapy: baseline predictors and associated clinical outcomes.

BACKGROUND: Cardiac resynchronization therapy (CRT) nonresponders have poor outcomes. The significance of progressive ventricular dysfunction among nonresponders remains unclear. OBJECTIVE: We sought to define predictors of and clinical outcomes associated with progressive ventricular dysfunction despite CRT. METHODS: We conducted an analysis of 328 patients undergoing CRT with defibrillator for standard indications. On the basis of 6-month echocardiograms, we classified patients as responders (those with a ≥5% increase in ejection fraction) and progressors (those with a ≥5% decrease in ejection fraction), and all others were defined as nonprogressors. Coprimary end points were 3-year (1) heart failure, left ventricular assist device (LVAD), transplantation, or death and (2) ventricular tachycardia (VT) or ventricular fibrillation (VF). RESULTS: Multivariable predictors of progressive ventricular dysfunction were aldosterone antagonist use (hazard ratio [HR] 0.23; P = .008), prior valve surgery (HR 3.3; P = .005), and QRS duration (HR 0.98; P = .02). More favorable changes in ventricular function were associated with lower incidences of heart failure, LVAD, transplantation, or death (70% vs 54% vs 33%; P < .0001) and VT or VF (66% vs 38% vs 28%; P = .001) for progressors, nonprogressors, and responders, respectively. After multivariable adjustment, progressors remained at increased risk of heart failure, LVAD, transplantation, or death (HR 2.14; P = .0029) and VT or VF (HR 2.03; P = .046) as compared with nonprogressors. Responders were at decreased risk of heart failure, LVAD, transplantation, or death (HR 0.44; P < .0001) and VT or VF (0.51; P = .015) as compared with nonprogressors. CONCLUSION: Patients with progressive deterioration in ventricular function despite CRT represent a high-risk group of nonresponders at increased risk of worsened clinical outcomes.

Does prior valve surgery change outcome in patients treated with cardiac resynchronization therapy?

AIMS: Cardiac valve surgery (CVS) has been implicated as a potential barrier to optimal response after cardiac resynchronization therapy (CRT) though prospective data regarding outcome remains limited. We sought to determine CRT response in patients with a prior history of CVS. METHODS AND RESULTS: We performed a retrospective analysis of a prospectively acquired cohort of CRT patients with history of CVS. Echocardiographic response was evaluated at baseline and 6 months. The coprimary endpoints were time to first heart failure (HF) hospitalization and a composite of all-cause mortality, transplantation and left ventricular assist device (LVAD) assessed over a 3-year follow-up period. The study group consisted of 569 patients undergoing CRT. Of these, 86 patients had a history of CVS (46.5% aortic, 37.2% mitral, 16.3% combined, and tricuspid), and were compared to 483 patients with no history of CVS. Baseline clinical and echocardiographic characteristics were not significantly different between the groups except for a higher incidence of atrial fibrillation (AF; 74.4% vs. 55.3%; P = 0.001), coronary artery bypass surgery (CABG; 58.1% vs. 38.7%; P = 0.001), and longer QRS duration (167.6 ± 29.3 milliseconds vs. 159.4 ± 27.5 milliseconds; P = 0.01) in those with prior CVS. Survival with respect to HF hospitalization and composite outcome was comparable in both groups. Echocardiographic response (improvement in left ventricular ejection fraction of ≥10%) was similar. No difference in clinical or echocardiographic outcome was found by type of valve surgery performed. CONCLUSION: Despite a higher incidence of AF, CABG, and longer QRS duration, history of CVS is not associated with worse clinical or echocardiographic outcome after CRT.

Pre-capillary pulmonary hypertension and right ventricular dilation predict clinical outcome in cardiac resynchronization therapy.

OBJECTIVES: This study examined the prognostic significance of pre- and post-capillary components of pulmonary hypertension (PH) in patients receiving cardiac resynchronization therapy (CRT). BACKGROUND: PH is common in patients with left ventricular systolic dysfunction (LVSD) receiving CRT. The impact of PH subtype on clinical outcome in CRT is unknown. METHODS: The study population consisted of 101 patients (average age 66 ± 13 years, left ventricular ejection fraction 0.23 ± 0.07, and New York Heart Association functional class 3.2 ± 0.4) who underwent right heart catheterization in the 6 months before CRT. PH was defined as a mean pulmonary artery pressure ≥25 mm Hg; a significant pre-capillary contribution to elevated mean pulmonary artery pressure was defined as a transpulmonary gradient (TPG) ≥12 mm Hg. Clinical endpoints were assessed at 2 years and included all-cause mortality and a composite of death, left ventricular assist device, or cardiac transplantation. RESULTS: Patients with TPG ≥12 mm Hg were more likely to experience all-cause mortality (hazard ratio [HR]: 3.2; 95% confidence interval [CI]: 1.3 to 7.4; p = 0.009) and the composite outcome (HR: 3.0; 95% CI: 1.4 to 6.3; p = 0.004) compared with patients with TPG <12 mm Hg. After multivariate adjustment for hemodynamic, clinical, and echocardiographic variables, only TPG ≥12 mm Hg and baseline right ventricular (RV) dilation (RV end-diastolic dimension >42 mm) were associated with the composite clinical outcome (p = 0.05 and p = 0.04, respectively). CONCLUSIONS: High TPG PH and RV dilation are independent predictors of adverse outcomes in patients with LVSD who are receiving CRT. RV pulmonary vascular dysfunction may be a therapeutic target in select patients receiving CRT.

Usefulness of hyponatremia as a predictor for adverse events in patients with heart failure receiving cardiac resynchronization therapy.

Hyponatremia portends a poor prognosis in patients with heart failure (HF). The aim of this study was to evaluate prognostic implication of hyponatremia on adverse events in patients with HF receiving cardiac resynchronization therapy (CRT). Additionally, the impact of improvement of hyponatremia after CRT device implantation was also evaluated. In this retrospective analysis, we included patients in whom a CRT device was implanted between April 2004 and April 2010 at our institution and had a baseline sodium level obtained within 72 hours of implantation. The patients were followed up for 3 years after implantation for subsequent primary composite end points, that is, hospitalization for HF, left ventricular assist device or heart transplant, and all-cause death. Sodium levels were followed up at 3 to 6 months after device implantation. Hyponatremia was defined as a serum sodium level of <135 mmol/L. A total of 402 patients were included (age 68.7 ± 12.3 years, women 20.9%). One hundred seventy-nine adverse events were noted in this period. In a Cox proportional hazards univariate model, hyponatremia (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.113 to 2.131, p = 0.009), creatinine (HR 1.267, 95% CI 1.156 to 1.389, p <0.001), and diuretics (HR 2.652, 95% CI 1.401 to 5.019, p = 0.003) were associated with occurrence of the composite end point. A total of 57.9% of patients with hyponatremia at baseline had the composite end point compared with 40.7% of those with normal sodium concentration (p = 0.004). Kaplan-Meier curve showed that hyponatremic patients fared worse. Also, patients in whom hyponatremia resolved after CRT device implantation had lower incidence of the composite end point compared with patients who had normal pre-CRT sodium levels but developed hyponatremia later. In conclusion, baseline hyponatremia is associated with poor prognosis in patients with HF. CRT can resolve hyponatremia in some patients after device implantation. Patients with postimplantation hyponatremia (either newly developed or persistent from baseline) have a poor clinical outcome. Post-CRT improvement of hyponatremia is associated with improved clinical outcomes.

Device-measured physical activity versus six-minute walk test as a predictor of reverse remodeling and outcome after cardiac resynchronization therapy for heart failure.

Implanted devices can provide objective assessment of physical activity over prolonged periods. The purpose of this study was to investigate the prognostic value of device-measured physical activity data compared with a six-minute walk test (6MWT) in predicting clinical response to cardiac resynchronization therapy (CRT). This was a single-center study in which patients who underwent CRT for standard indications were evaluated. Daily physical activity and 6MWT were evaluated postimplant at 1, 3, and 6 months. The primary end point was a composite of heart failure hospitalization, transplant, left ventricular (LV) assist device, and all-cause death at 3 years. Echocardiographic response, defined as a ≥10% improvement in LV ejection fraction (LVEF), at 6 months was the secondary end point. About 164 patients were included: average age was 67.3 ± 12.9 years, 77% were men, baseline LVEF was 25% ± 7%. Kaplan-Meier curves showed superior freedom from the composite end point in the highest tertile of both 6MWT and physical activity compared with the lowest tertile (41 vs 23 cases, respectively, p <0.001) for 6MWT and for activity (22 vs 7 cases, respectively, p = 0.001). In an adjusted multivariate model, independent predictors of improved clinical outcome included 1-month physical activity (hazard ratio 0.546, 95% confidence interval [CI] 0.361 to 0.824, p = 0.004) and 6MWT (hazard ratio 0.581, 95% CI 0.425 to 0.795, p = 0.001). An additional hour of higher activity at 1 month translated to a 1.38 times (95% CI 1.075 to 1.753, p = 0.011) higher likelihood of improved echocardiographic response. In conclusion, device-based measures of physical activity may be useful in predicting echocardiographic reverse remodeling and long-term clinical outcome in patients receiving CRT.

Soluble concentrations of the interleukin receptor family member ST2 and ß-blocker therapy in chronic heart failure.

BACKGROUND: Concentrations of soluble (s)ST2 predict prognosis in heart failure. We recently found changing doses of ß-blocker (BB) may affect sST2 concentrations. It remains unclear whether sST2 concentrations identify benefit of BB therapy, however. METHODS AND RESULTS: A total of 151 subjects with heart failure attributable to left ventricular systolic dysfunction were examined in this post hoc analysis; >96% were taking BB at enrollment. Medication regimen and sST2 values were obtained during 10 months. Cardiovascular events were examined as a function of baseline sST2 status (low ≤35 versus high >35 ng/mL) and final achieved BB dose (high ≥50 versus low <50 mg daily equivalent dose of metoprolol succinate). Patients with low sST2 titrated to high-dose BB had the lowest cardiovascular event rate at 0.53 events (P=0.001), and lowest cumulative hazard (P=0.003). Those with low sST2/low-dose BB, or high sST2/high-dose BB had intermediate outcomes (0.92 and 1.19 events). Patients with high sST2 treated with low-dose BB had the highest cardiovascular event rate (2.08 events) and the highest cumulative hazard. Compared with low sST2/high-dose BB, those with high sST2 treated with low-dose BB had an odds ratio of 6.77 (P<0.001) for a cardiovascular event. Patients with low sST2/low-dose BB or high sST2/high-dose BB had intermediate odds ratios for cardiovascular events (P=0.18 and 0.02). Similar results were found for heart failure hospitalization and cardiovascular death. CONCLUSIONS: Although BB therapy exerted dose-related benefits across all study participants, sST2 measurement identifies patients with chronic heart failure who may particularly benefit from higher BB doses. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00351390.

Usefulness and consequences of cardiac resynchronization therapy in dialysis-dependent patients with heart failure.

Cardiac resynchronization therapy (CRT) is often deferred in dialysis-dependent patients with heart failure (HF) because of a perceived lack of benefit and potentially higher risks, although the outcomes associated with CRT in dialysis have not been reported. We therefore studied our center's experience with CRT in dialysis-dependent patients. We constructed a descriptive assessment of these patients (n = 15) and performed a case-control analysis matching for age, gender, bundle branch morphology, diabetes mellitus, cardiomyopathy origin, and ß-blocker and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use. Baseline and 6-month echocardiograms were assessed for evidence of reverse remodeling. No periprocedural or long-term complications were observed among dialysis patients. Heterogenous improvement in ejection fraction (+3.1 ± 9.2%) was noted and 2 patients derived absolute improvements of 8% and 22%, respectively. Dialysis patients demonstrated the following 3-year event rates: HF hospitalization, 31%; all-cause hospitalization, 100%; mortality, 73%; and HF hospitalization or death, 82%. In the case-control analysis, controls demonstrated superior reverse remodeling (+9.2 ± 9.5% increase in ejection fraction), decreased mortality (73% vs 44%, p = 0.038), and all-cause hospitalizations (76% vs 100%, p = 0.047), with no difference in HF hospitalizations (p = 0.39), compared with dialysis patients. In conclusion, at our center, the dialysis-dependent patients with HF who underwent CRT implantation did so safely and no serious complications were observed. Certain dialysis patients demonstrated compelling improvement after device implantation. Compared with matched controls, dialysis patients were at increased risk for adverse events and worsened echocardiographic outcomes.

QRS morphology, left ventricular lead location, and clinical outcome in patients receiving cardiac resynchronization therapy.

AIMS: Several studies have reported a poor outcome with cardiac resynchronization therapy (CRT) in non-left bundle branch block (LBBB) patients. Although the left ventricular (LV) lead location is an important determinant of the clinical outcome, there is scant information regarding its role in non-LBBB patients. This study sought to examine the impact of electrical and anatomical location of the LV lead in relation to baseline QRS morphology on the CRT outcome. METHODS AND RESULTS: A left ventricular lead electrical delay (LVLED) was measured intra-procedurally as an interval between QRS onset on the surface electrocardiogram (ECG) to the peak of sensed electrogram on LV lead and corrected for QRS width. The impact of the LVLED on time to first heart failure hospitalization (HFH), and composite outcome of all-cause mortality, HFH, LVAD implantation, and cardiac transplantation at 3 years was assessed. Among 144 patients (age 67 ± 12 years, QRS duration 156 ± 28 ms, non-LBBB 43%), HFH was higher in non-LBBB compared with LBBB (43.5 vs. 24%, P = 0.015). Within LBBB, patients with the long LVLED (≥50%) had 17% HFH vs. 53% in the short LVLED (<50%), P = 0.002. Likewise in non-LBBB, patients with the long LVLED compared with the short LVLED had a lower HFH (36 vs. 61%, P = 0.026). In adjusted Cox proportional hazards model, the long LVLED in LBBB and non-LBBB was associated with an improved outcome. Specifically, in non-LBBB, LVLED ≥50% was associated with improved event-free survival with respect to time to first HFH (HR: 0.34; P = 0.011) and composite outcome (HR: 0.41; P = 0.019). CONCLUSION: Cardiac resynchronization therapy delivered from an LV pacing site characterized by the long LVLED was associated with the favourable outcome in LBBB and non-LBBB patients.

Characterization and prediction of natriuretic peptide "nonresponse" during heart failure management: results from the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) and the NT-proBNP-Assisted Treatment to Lessen Serial Cardiac Readmissions and Death (BATTLESCARRED) study.

Many proven heart failure (HF) therapies decrease N-terminal pro B-type natriuretic peptide (NT-proBNP) values over time, yet some patients have an NT-proBNP >1000 pg/mL following treatment, which is associated with poor outcomes. A total of 151 patients with left ventricular systolic dysfunction were treated with aggressive HF therapy in the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) study. Clinical characteristics and NT-proBNP were measured at each visit during 10 months. In this post hoc analysis, biomarker nonresponse was defined as an NT-proBNP >1000 pg/mL and its relationship with echocardiographic and clinical characteristics and outcomes were explored. A risk model predictive of nonresponse was derived and externally validated. A rising NT-proBNP over time was associated with increased cardiovascular event rates while a decreasing NT-proBNP was associated with better clinical outcomes (58.2% vs 27.6%, P=.001). A higher percentage of time in biomarker response was associated with lower event rates (P<.001). Importantly, responders showed improved left ventricular remodeling parameters (all P<.001), while nonresponders did not. A risk model for predicting nonresponse had a C statistic of 0.82 (P<.001) and predicted outcomes well. Using data from the NT-proBNP-Assisted Treatment to Lessen Serial Cardiac Readmissions and Death (BATTLESCARRED) cohort, the risk score was validated for its ability to predict nonresponse (C statistic 0.73, P<.001). Serial changes in NT-proBNP inform risk for adverse outcome and are associated with prognostically meaningful metrics. Prediction of future NT-proBNP nonresponse to HF therapy is possible.

Right ventricular lead adjustment in cardiac resynchronization therapy and acute hemodynamic response: a pilot study.

PURPOSE: Optimal left ventricular (LV) lead position has emerged as an important determinant of response after cardiac resynchronization therapy (CRT). Comparatively, strategy for right ventricular (RV) lead optimization remains uncertain. METHODS: Three variations of RV lead position (apex, mid-septal, and high septal) were tested in seven consecutive patients. At each location, intra-procedural measurement of LV lead electrical delay (LVLED) was obtained during intrinsic rhythm and RV pacing (RV-LVLED). Simultaneous cardiac output assessment was performed using the LiDCO™ (lithium chloride indicator dilution) system. Final RV lead location was selected based on best-measured cardiac output. Clinical and echocardiographic outcomes were assessed at baseline and 6 months. RESULTS: Adjustment of RV lead position after securing a LV lead site led to an incremental change of 30 ± 18 % (range, 7-52 %) in the cardiac index (CI). There was substantial variation in acute hemodynamic response (∆CI, 14 ± 13 %; range, 3-41 %) seen with pacing from each patient's worst to best RV lead position; no single RV lead position emerged as optimal across all patients. Paced RV-LVLED was not correlated with percent change in CI (r = 0.18; p = NS). LV ejection fraction (LVEF) increased significantly (28 ± 4 to 40 ± 8 %, p = 0.006) at 6 months. LVLED measured during intrinsic rhythm, but not during RV pacing, correlated with percent change in LVEF (r = 0.88, p = 0.02). CONCLUSIONS: RV lead position adjustment can be used to enhance acute hemodynamic response during CRT. Measurement of paced RV-LVLED, however, does not reliably predict change in cardiac output.

Characteristics of responders to cardiac resynchronization therapy: the impact of echocardiographic left ventricular volume.

BACKGROUND: One-third of patients who receive cardiac resynchronization therapy (CRT) are classified as nonresponders. Characteristics of responders to CRT have been studied in multiple clinical trials. HYPOTHESIS: Independent predictors of CRT response may be identified by studying a series of patients in routine clinical practice. METHOD: One hundred twenty-five patients were examined retrospectively from a multidisciplinary CRT clinic program. Echocardiographic CRT response was defined as a decrease in left ventricular (LV) end-systolic volume of ≥15% and/or absolute increase of 5% in LV ejection fraction at the 6-month visit. RESULTS: There were 81 responders and 44 nonresponders. By univariate analyses, female sex, nonischemic cardiomyopathy etiology, baseline QRS duration, the presence of left bundle branch block (LBBB), and left ventricular end-diastolic volume (LVEDV) index predicted CRT response. However, multivariate analysis demonstrated that only QRS duration, LBBB, and LVEDV index were independent predictors (QRS width, odds ratio [OR]: 1.027, 95% confidence interval [CI]: 1.004-1.050, P = 0.023; LBBB, OR: 3.568, 95% CI: 1.284-9.910, P = 0.015; LVEDV index, OR: 0.970, 95% CI: 0.953-0.987, P = 0.001). Although female sex and nonischemic etiology were associated with an improved CRT response on univariate analyses, after adjusting for LV volumes they were not independent predictors. CONCLUSIONS: QRS width, LBBB, and LVEDV index are independent predictors for echocardiographic CRT response. Previously reported differences in CRT response for sex and cardiomyopathy etiology are associated with differences in baseline LV volumes in our clinical practice.

Heart rescue: the role of mechanical circulatory support in the management of severe refractory cardiogenic shock.

PURPOSE OF REVIEW: Cardiogenic shock is present in 3.5% of patients presenting with acute decompensated heart failure. Despite advances in therapy, mortality remains high, approaching 70% in some settings. Recent management strategies have incorporated the use of mechanical circulatory support (MCS), which has been associated with better survival in nonrandomized trials. MCS is increasingly used in the acute setting and has become an important treatment modality for cardiogenic shock. RECENT FINDINGS: Small studies have demonstrated improved survival when MCS is instituted early in the management of cardiogenic shock. Numerous case reports support the benefit of MCS for various causes of cardiogenic shock, including acute myocardial infarction, cardiac allograft rejection, myocarditis and refractory arrhythmias. SUMMARY: This article will review novel strategies in the management of cardiogenic shock including percutaneous MCS (intra-aortic balloon pump, Impella, TandemHeart, venoarterial extracorporeal membrane oxygenation) and surgically implanted devices (CentriMag) that are used for short-term management. We will review the mechanisms involved in cardiogenic shock and discuss management and device selection strategies.