Sex-Specific Differences in Ventricular Remodeling and Response After Cardiac Resynchronization Therapy.

In this study, we investigated the baseline characteristics and "trajectories" of clinical response in men and women after cardiac resynchronization therapy (CRT) implantation. Although women enjoy improved echocardiographic response after CRT compared with men, the kinetics of this response and its relation to functional performance and outcomes are less clear. We identified 592 patients who underwent CRT implantation at our center between 2004 and 2017 and were serially followed in a multidisciplinary clinic. Longitudinal linear mixed effects regression for cardiac response was specified, including interaction terms between time after CRT and sex , and Cox regression models were used to assess differences in all-cause mortality by gender after CRT. Women in our cohort were younger than men, had less frequent ischemic etiology of heart failure (24% vs 60% in men), a shorter QRS (151 vs 161 ms) and more frequent left bundle branch block (77% vs 52%) at baseline. Women had a greater improvement in left ventricular ejection fraction that was evident starting at approximately 1-month after CRT. We did not observe effect modification by gender in New York Heart Association class or 6-minute walk distance after CRT. Although women had improved mortality after CRT, after adjustment for potential confounders, gender was not associated with mortality after CRT. In conclusion, women were more likely to have CRT implantation for left bundle branch block and exhibited improved echocardiographic but not functional response within the first year after CRT. Clinical outcomes after CRT were not associated with gender in adjusted analysis.

Virtual multidisciplinary care for heart failure patients with cardiac resynchronization therapy devices during the Coronavirus Disease 2019 pandemic.

BACKGROUND: Heart failure (HF) patients with CRT devices are a vulnerable patient population during the Coronavirus Disease 2019 (COVID-19) Pandemic. It is important to develop innovative virtual care models to deliver multidisciplinary care while minimizing the risk of SARS-CoV2 exposure. OBJECTIVE: We aim to provide a description of how HF patients with CRT devices were assessed and managed in our virtual multidisciplinary clinic during the COVID-19 Pandemic. Clinical outcomes between this group of patients seen in virtual clinic and a historical cohort followed by in-person multi-disciplinary clinic prior to the pandemic were compared. METHOD: This is a retrospective cohort study of HF patients with CRT implants who were seen in the virtual multidisciplinary clinic from March 18th, 2020 to May 27th, 2020 (Virtual Visit Group, N = 43). A historical cohort of HF patients with CRT devices seen in the ReACT clinic in person during the same calendar time period in 2019 was used as a control group (In-Person Visit Group, N = 39). Both groups were followed until July 1st of the same calendar year (2020 or 2019) for clinical events. The primary outcome measure was a combined outcome of all-cause mortality and HF- or device-related hospitalizations during follow-up. The secondary outcome measures included patient satisfaction, COVID-19 infection, and other cardiovascular events. RESULTS: In the Virtual-Visit Group, 21 patients (48.8%) had their initial ReACT clinic visit (first visit after CRT implant) as a virtual visit; 22 patients (51.2%) had prior in-person ReACT clinic visits before the first virtual visit. During the virtual visits, 12 patients had either potential cardiac symptoms or significant device interrogation findings that required clinical intervention. In post-virtual clinic patient satisfaction survey, all 22 patients surveyed (100%) reported being very satisfied or satisfied with the overall experience of the virtual clinic, and every patient (100%) said they would like to use telemedicine again. During a median follow-up period of 82 days (interquartile range [IQR] 61-96 days), one patient died from pneumonia of unclear etiology at an outside hospital, without documentation of COVID-19 positivity. No patient was hospitalized for HF- or arrhythmia-related complications. No patient was diagnosed with COVID-19. Compared with the In-Person Visit Group, there was no significant increase in mortality or major cardiovascular events in the Virtual-Visit Group (2.3% versus 5.1%, P = 0.60). CONCLUSIONS AND RELEVANCE: Virtual multidisciplinary care was feasible for HF patients with cardiac resynchronization therapy devices and achieved good patient satisfaction. Virtual care was not associated with short-term increase in adverse events for HF patients with CRT device during the COVID-19 Pandemic. This virtual care model could help promote the adoption of digital health methodology for high-risk patients with multiple cardiac comorbidities.

Left ventricle and mitral valve reverse remodeling in response to cardiac resynchronization therapy in nonischemic cardiomyopathy.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves left heart geometry and function in nonischemic cardiomyopathy (NICMP). We aimed to detail the effects of CRT on left ventricular (LV) and mitral valve (MV) remodeling using 2-dimensional transthoracic echocardiography. METHODS: Forty-five consecutive patients with NICMP who underwent CRT implantation between 2009 and 2012, and had pre-CRT and follow-up echocardiograms available, were included. Paired t test, linear and logistic regression, and Kaplan-Meier survival analyses were used for statistical assessment. RESULTS: The mean age and QRS duration were 60 years and 157 ms, respectively, and 13 (28.9%) were female. At a mean follow-up of 3 years, there were 22 (48.9%) "CRT responders" (≥15% reduction in LV end-systolic volume index [LVESVi]). Significant improvements were observed in LV ejection fraction (26.3% vs 34.3%) and LVESVi (87.7 vs 71.1 mL/m2 ), as well as mitral regurgitation vena contracta width, MV tenting height and area, and end-systolic interpapillary muscle distance. Five-year actuarial survival was 87.5%. Multivariate regression analyses revealed the pre-CRT LVESVi (ß = 0.52), and MV coaptation length (ß = -0.34) and septolateral annular diameter (ß = 0.25) as good correlates of follow-up LVESVi. Variables associated with CRT response were pre-CRT MV coaptation length (OR 1.75, 95% CI 1.0-3.1) and posterior leaflet tethering angle (OR 1.07, 95% CI 1.0-1.14), irrespective of baseline QRS morphology and duration (all P < .05). CONCLUSIONS: Cardiac resynchronization therapy improves LV and MV geometry and function in half of patients with NICMP, which is paralleled by decreased mitral regurgitation severity. The extent of pre-CRT LV remodeling and MV tethering are associated with CRT response.

Left ventricular wall thickness assessed by cardiac computed tomography and cardiac resynchronization therapy outcomes.

AIMS: Up to 30% of selected heart failure patients do not benefit clinically from cardiac resynchronization therapy (CRT). Left ventricular (LV) wall thickness (WT) analysed using computed tomography (CT) has rarely been evaluated in response to CRT and mitral regurgitation (MR) improvement. We examined the association of LVWT and the ability to reverse LV remodelling and MR improvement after CRT. METHODS AND RESULTS: Fifty-four patients scheduled for CRT underwent pre-procedural CT. Reduced LVWT was defined as WT <6 mm and quantified as a percentage of total LV area. Endpoints were 6-month clinical and echocardiographic response to CRT [New York Heart Association (NYHA) class, LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV)], MR improvement and 2-year major adverse cardiac events (MACE). Patients were divided into three groups according to the percentage of LVWT <6 mm area: ≤20%, 20-50%, and ≥50%. At 6 months, 75%, 71%, and 42% of the patients experienced NYHA improvement in the ≤20%, 20-50%, and ≥50% group, respectively. Additionally, ≤20% group presented higher LVEF, LVEDV, and LVESV positive response rate (86%, 59%, and 83%, respectively). Both 20-50% and ≥50% groups exhibited a lower LVEF, LVEDV, and LVESV positive response rate (52% and 42%; 47% and 45%; and 53% and 45%, respectively). Additionally, ≥25% of LVWT <6 mm inclusive of at least one papillary muscle insertion was the only predictor of lack of MR improvement. Lastly, ≥50% group experienced significantly lower 2-year MACE survival free probability. CONCLUSION: WT evaluated using CT could help to stratify the response to CRT and predict MR improvement and outcomes. CLINICAL TRIAL REGISTRATION: NCT01097733.

The effects of cardiac resynchronization therapy on left ventricular and mitral valve geometry and secondary mitral regurgitation in patients with left bundle branch block.

BACKGROUND: Secondary mitral regurgitation (MR) is common in patients with left bundle branch block (LBBB) undergoing cardiac resynchronization therapy (CRT). We aimed to define CRT effects on left ventricular (LV) and mitral valve (MV) geometry, and their correlation with MR severity. METHODS: Forty-one patients with LBBB and ≥mild secondary MR underwent CRT between 2009 and 2012, and had baseline and follow-up echocardiograms available. Repeated measure and linear regression analyses were performed to assess for changes in MV and LV geometry and MR severity, and associations with follow-up MR grade. RESULTS: The mean age and baseline QRS duration were 65.5 ± 14.9 years and 160 ± 24 ms. At a mean follow-up of 2.6 ± 1.8 years, there was an increase in LV ejection fraction and reductions in LV end-systolic volume index, MR grade, and end-systolic interpapillary muscle distance (P < .05 for all). Linear correlations were observed between follow-up MR grade and baseline MV tenting height (r = .44), left atrial volume index (r = .41), LV end-systolic volume index (r = .4), MV tenting area (r = .38), LV ejection fraction (r = -.34), and end-systolic interpapillary muscle distance (r = .34) (P < .05 for all). Multiple regression analysis revealed associations between follow-up MR grade and baseline MV tenting height (ß/mm = 0.42, P = .006) and left atrial volume index (ß/mL/m2  = 0.4, P = .008), independent of QRS duration (ß/ms=-0.07; P = 0.6) and nonischemic cardiomyopathy (ß = -0.34, P = .02). CONCLUSIONS: Cardiac resynchronization therapy in patients with LBBB and secondary MR results in LV and MV geometric reverse remodeling and decreases MR severity. Extent of baseline MV tethering is independently associated with persistent MR at follow-up.

A new simplified electrocardiographic score predicts clinical outcome in patients treated with CRT.

Aims: Cardiac Resynchronization Therapy (CRT) reduces morbidity and mortality for patients with heart failure and wide QRS complex, but up to 1/3 of patients are "non-responders" to the therapy. This study examines the ability of a simple standard electrocardiogram (ECG)-based scoring system to predict clinical outcome. Methods and results: Four hundred and ninety-one consecutive patients with CRT-implants (79% males, mean age 71 years, LVEF 24%, 59% with ischemic cardiomyopathy, 83% in NYHA class III) were included from a single large volume centre. All patients met standard indications for CRT, and were followed for 3 years after CRT implantation. Three ECG parameters were measured on the post-implant ECG, and compared to pre-implantation measurements: QRS duration, time to intrinsicoid deflection onset (ID) in V1 lead, amplitude change in V1 lead. Each positive ECG variable was given a numerical value of 1 to create the score (ranging 0-3). Clinical outcome was assessed as a composite of all-cause death, left ventricular assist device implantation, cardiac transplantation and HF hospitalization. Event-free survival was predicted by shortening of QRS duration ≥20 ms (HR 0.66 [95% CI 0.48-0.90] P = 0.009), ≥50% decreased summed R + S amplitude in V1 lead (HR 0.67 [0.49-0.90] P = 0.009) and ≤40 msec ID time in lead V1 during pacing (HR 0.63 [0.46-0.86] P = 0.004). The total score was an independent predictor for both event-free survival (HR 0.65 [0.54-0.77] P < 0.001) and for ≥10% left ventricular ejection fraction improvement (OR 1.7 [1.3-2.3] P < 0.001). Conclusions: Composite data from 12-lead ECG during CRT-treatment can be used in a simple score to predict long-term clinical outcome.

Effects of cardiac resynchronization therapy after inferior myocardial infarction on secondary mitral regurgitation and mitral valve geometry.

BACKGROUND: The effects of cardiac resynchronization therapy (CRT) on secondary mitral regurgitation (MR), and mitral valve (MV) and left ventricular (LV) geometry, in patients with prior inferior myocardial infarction is not clearly defined. We assessed these outcomes utilizing two-dimensional echocardiography, and analyzed echocardiographic geometric variables that may correlate with follow-up MR severity. METHODS: Between 2009 and 2012, 229 CRT were implanted. Twenty-two had prior inferior myocardial infarction, ≥mild MR at baseline, and serial echocardiography. A left bundle branch block was present in 12 (54.5%) patients. The pre-CRT and follow-up echocardiograms were analyzed for: (1) MR severity; (2) MV and LV geometry; and (3) LV remodeling. RESULTS: The median follow-up time was 2.2 years (interquartile range, 0.7-4). In 16 patients without an inferior myocardial scar, there was a reduction in MR jet area/left atrial area ratio (33.2% vs 25.8%; P = 0.06) and MR grade (2.3 vs 1.8; P = 0.05), and an increased LV ejection fraction (26.1% vs 30.9%; P = 0.04) and end-systolic posterior ventricular sulcus-anterolateral papillary muscle angle (133.9 vs 143.9 degrees; P = 0.01). In six patients with scar, there was no change in LV or MR parameters. Regression analysis revealed linear associations between baseline MV tenting height (r = 0.57; P = 0.006), LV end-diastolic diameter index (r = 0.5; P = 0.02), mitral septolateral annular diameter (r = 0.48; P = 0.03), and MV tenting area (r = 0.46; P = 0.03), with follow-up MR jet area/left atrial area ratio. CONCLUSIONS: In patients with prior inferior myocardial infarction and no scar, CRT is associated with decreased MR severity, and improved papillary muscle alignment and LV systolic function at follow-up.

Impact of cardiac resynchronization therapy on mitral valve apparatus geometry and clinical outcomes in patients with secondary mitral regurgitation.

BACKGROUND: Cardiac resynchronization therapy (CRT) may improve secondary mitral regurgitation (MR) in patients with cardiomyopathy. The effects on mitral valve (MV) and left ventricular (LV) geometry, however, have not been clearly defined. METHODS: Between 2009 and 2012, 229 CRT implants were performed at a single academic center. Seventy-one had ≥mild MR at baseline and serial echocardiography, without subsequent MV intervention. The pre-CRT and follow-up echocardiograms were retrospectively reviewed for (1) MV and LV geometry measurements; (2) MR grade; and (3) LV remodeling indices. RESULTS: The mean age was 67 ± 15 years, and the cardiomyopathy was ischemic in 37 (52%). At a mean follow-up of 4.0 ± 1.9 years, there were significant improvements in LV ejection fraction and size, MR grade, MV tenting area and anterior leaflet tethering angle, and end-systolic interpapillary muscle distance (IPMD), and reductions in moderate-to-severe or severe MR (27% vs 15%; P = .04) and New York Heart Association functional class III/IV symptoms (83% vs 41%; P < .001). Multivariable analysis revealed the pre-CRT MV tenting height (OR 1.25, 95% CI 1.01-1.56; P = .04) and end-systolic IPMD (OR 1.14, 95% CI 0.99-1.32; P = .08) as independently associated with moderate or greater MR at follow-up. Finally, at 5 years post-CRT implantation, the estimated survival and freedom from LV assist device or cardiac transplantation was 61%. CONCLUSIONS: CRT results in favorable effects on MV and LV geometry and decreases the prevalence of moderate-to-severe or severe MR and heart failure symptoms. The pre-CRT MV tenting height and IPMD are independently associated with persistent MR at follow-up.

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.

Renal Response in Patients with Chronic Kidney Disease Predicts Outcome Following Cardiac Resynchronization Therapy.

BACKGROUND: Chronic kidney disease (CKD) severity is associated with increased morbidity and mortality in congestive heart failure. There is a paucity of data regarding renal improvement after cardiac resynchronization therapy (CRT) and its potential impact on clinical outcomes, especially in patients with severe CKD. METHOD: This was a retrospective analysis of a prospectively collected cohort of 260 patients with CKD undergoing CRT at a single center. Renal function was compared before and after CRT. The primary end point was a composite of death, heart transplant, and left ventricular assist device (LVAD), assessed at 5 years. RESULTS: Patients with more severe CKD demonstrated increased risk of death, transplant, or LVAD following CRT (P = 0.015). Renal response (estimated glomerular filtration rate improvement ≥10 mL/min/1.73 m(2) ) was observed in 14% of all patients and 28% of patients with stage IV CKD. Independent predictors of renal response included left ventricular ejection fraction improvement (odds ratio [OR] 1.06, confidence interval [CI] 1.01-1.10), angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use (OR 4.31, CI 1.08-17.23), and advanced CKD stage (OR 2.19, CI 1.14-4.23). Renal response independently decreased hazard of the primary outcome (HR 0.24, CI 0.08-0.73, P = 0.01). Renal responders with stage IV CKD had 80% 5-year event-free survival, compared to 0% for nonrenal responders in stage IV (P = 0.03). CONCLUSION: Although severity of CKD is associated with poorer outcome after CRT, improvement in renal function can occur in patients across all CKD stages. Renal responders, including those with stage IV CKD, demonstrate favorable 5-year outcomes. Assessment of renal response may help better prognostic outcomes following CRT.

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.

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.

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.

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.

The anatomic and electrical location of the left ventricular lead predicts ventricular arrhythmia in cardiac resynchronization therapy.

BACKGROUND: Both anatomic and electrical locations of the left ventricular (LV) lead have been identified as important predictors of clinical outcomes in cardiac resynchronization therapy (CRT). The impact of LV lead location on incident device-treated ventricular arrhythmia (VA), however, is not well understood. OBJECTIVE: To assess the relationship between electrical and anatomic LV lead location and device treated VAs in CRT. METHODS: Sixty-nine patients undergoing CRT implantation for standard indications were evaluated. Anatomic LV lead location was assessed by means of coronary venography and chest radiography and categorized as apical or nonapical. Electrical LV lead location was assessed by LV electrical delay (LVLED) and was calculated as the time between the onset of the native QRS on the surface electrocardiogram and sensed signal on the LV lead during implantation and corrected for native QRS. Incident appropriate device-treated VA was assessed via device interrogation. RESULTS: Apical lead placement was an independent predictor of VAs (hazard ratio 5.29; 95% confidence interval 1.69-16.5; P = .004). Among patients with a nonapical lead, LVLED<50% native QRS was an independent predictor of VAs (hazard ratio 6.90; 95% confidence interval 1.53-31.1; P = .012). Those with a nonapical lead and LVLED ≥ 50% native QRS were at substantially lower risk for first incident and recurrent VAs when compared to all other patients. CONCLUSIONS: The apical lead position is associated with an increased risk of VAs in CRT patients. Among patients with a nonapical lead position, an LVLED of<50% of the native QRS is associated with an increased risk of VAs.