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.

Reduction in lead exposures with lead-free ammunition in an advanced urban assault course.

The training of soldiers for urban conflict involves marksmanship instruction on outdoor flat ranges and the teaching of close-quarter battle techniques in indoor facilities, referred to as shoot houses, where intense firing exercises can generate high air lead levels from small arms ammunition, flash bang grenades, and explosive devices. Levels of lead and copper in air were evaluated during five training activities of a 45-day training course using both stationary general area and breathing zone sampling over a 2-year period. Individual blood lead values were determined prior to and at course completion. Mean breathing zone lead concentrations for the five training activities ranged from 0.014 on the outdoor flat range to 0.064 mg/m3 inside shoot houses; with a change to lead-free ammunition the values were reduced to a range of 0.006-0.022 mg/m3. Isolated flash bang grenades generated very high general area lead concentrations (2.0 mg/m3), which in training were associated with the highest measured breathing zone concentration (0.16 mg/m3). For copper, mean breathing zone concentrations increased from 0.010 to 0.037 mg/m3 with the change to lead-free frangible ammunition on the outdoor range, but remained below the permissible exposure limit for copper fume. Inside shoot houses, mean breathing zone copper concentrations exceeded the permissible exposure limit with ball and lead-free frangible ammunition, ranging from 0.077-0.13 mg/m3. With the introduction of lead-free ammunition, when comparing the blood lead differences between start and finish of the course, there was a significant reduction in the mean blood lead difference from 13.3 µg/dL to 5.4 µg/dL. Options for mitigation of potentially high exposure areas using improved ventilation designs are discussed. These results advocate for improved designs for shoot house training facilities, stress the importance of removing lead from ammunition and explosive devices for training, and promote the continued need for implementation of controls to mitigate and manage metal exposures during training.

Randomized, Controlled Trial of an Advance Care Planning Video Decision Support Tool for Patients With Advanced Heart Failure.

BACKGROUND: Conversations about goals of care and cardiopulmonary resuscitation (CPR)/intubation for patients with advanced heart failure can be difficult. This study examined the impact of a video decision support tool and patient checklist on advance care planning for patients with heart failure. METHODS: This was a multisite, randomized, controlled trial of a video-assisted intervention and advance care planning checklist versus a verbal description in 246 patients ≥64 years of age with heart failure and an estimated likelihood of death of >50% within 2 years. Intervention participants received a verbal description for goals of care (life-prolonging care, limited care, and comfort care) and CPR/intubation plus a 6-minute video depicting the 3 levels of care, CPR/intubation, and an advance care planning checklist. Control subjects received only the verbal description. The primary analysis compared the proportion of patients preferring comfort care between study arms immediately after the intervention. Secondary outcomes were CPR/intubation preferences and knowledge (6-item test; range, 0-6) after intervention. RESULTS: In the intervention group, 27 (22%) chose life-prolonging care, 31 (25%) chose limited care, 63 (51%) selected comfort care, and 2 (2%) were uncertain. In the control group, 50 (41%) chose life-prolonging care, 27 (22%) selected limited care, 37 (30%) chose comfort care, and 8 (7%) were uncertain (P<0.001). Intervention participants (compared with control subjects) were more likely to forgo CPR (68% versus 35%; P<0.001) and intubation (77% versus 48%; P<0.001) and had higher mean knowledge scores (4.1 versus 3.0; P<0.001). CONCLUSIONS: Patients with heart failure who viewed a video were more informed, more likely to select a focus on comfort, and less likely to desire CPR/intubation compared with patients receiving verbal information only. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01589120.

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.

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.

Multidisciplinary care of patients receiving cardiac resynchronization therapy is associated with improved clinical outcomes.

AIMS: Although cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with heart failure, a significant minority of patients do not respond adequately to this therapy. The objective of this study was to examine the impact of a 'multidisciplinary care' (MC) approach on the clinical outcome in CRT patients. METHODS AND RESULTS: The clinical outcome in patients prospectively receiving MC (n = 254) was compared with a control group of patients who received conventional care (CC, n = 173). The MC group was followed prospectively in an integrated clinic setting by a team of subspecialists from the heart failure, electrophysiology, and echocardiography service at 1-, 3-, and 6-months post-implant. All patients had echocardiographic-guided optimization at their 1-month visit. The proportional hazards model (adjusting for all covariates) and Kaplan-Meier time to first event curves were compared between the two groups, over a 2-year follow-up. The long-term outcome was measured as a combined endpoint of heart failure hospitalization, cardiac transplantation, or all-cause mortality. The clinical characteristics between the MC and CC groups at baseline were comparable (age, 68 ± 13 vs. 69 ± 12; NYHA III, 90 vs. 82%; ischaemic cardiomyopathy 55 vs. 64%, P = NS, respectively). The event-free survival was significantly higher in the multidisciplinary vs. the CC group (P = 0.0015). A significant reduction in clinical events was noted in the MC group vs. the CC group (hazard ratio: 0.62, 95% CI: 0.46-0.83, P = 0.001). CONCLUSION: Integrated MC may improve 2-year event-free survival in patients receiving cardiac resynchronization therapy. Prospective randomized studies are needed to validate our findings.

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.

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.

The Impact of a Culinary Coaching Telemedicine Program on Home Cooking and Emotional Well-Being during the COVID-19 Pandemic.

The coronavirus pandemic enforced social restrictions with abrupt impacts on mental health and changes to health behaviors. From a randomized clinical trial, we assessed the impact of culinary education on home cooking practices, coping strategies and resiliency during the first wave of the COVID-19 pandemic (March/April 2020). Participants (n = 28) were aged 25-70 years with a BMI of 27.5-35 kg/m2. The intervention consisted of 12 weekly 30-min one-on-one telemedicine culinary coaching sessions. Coping strategies were assessed through the Brief Coping with Problems Experienced Inventory, and resiliency using the Brief Resilient Coping Scale. Home cooking practices were assessed through qualitative analysis. The average use of self-care as a coping strategy by the intervention group was 6.14 (1.66), compared to the control with 4.64 (1.69); p = 0.03. While more intervention participants had high (n = 5) and medium (n = 8) resiliency compared to controls (n = 4, n = 6, respectively), this difference was not significant (p = 0.33). Intervention participants reported using home cooking skills such as meal planning and time saving techniques during the pandemic. The key findings were that culinary coaching via telemedicine may be an effective intervention for teaching home cooking skills and promoting the use of self-care as a coping strategy during times of stress, including the COVID-19 pandemic.

Home Meal Preparation: A Powerful Medical Intervention.

One of the principles of culinary medicine is to help patients learn how to make nutritious eating simple and easy. In this column, you will learn tools for preparing and storing food; a key component to successful home cooking. While this article is intended to help clinicians learn about food preparation, it is also designed to be used as an educational tool for patients.

Culinary Medicine: Paving the Way to Health Through Our Forks.

Recent findings reveal that suboptimal diet is responsible for more deaths than any other risk factor nationally and globally. It is estimated that with improving eating behaviors, 1 in 5 deaths can be prevented, underscoring the urgent need for effective dietary interventions.

Prognosis, Communication, and Advance Care Planning in Heart Failure: A Module for Students, Residents, Fellows, and Practicing Clinicians.

INTRODUCTION: The increasing prevalence, high symptom burden, and medical advances that often prolong the advanced phase of heart failure mandate an organized and thoughtful approach to medical decision making. However, many clinicians have difficulty discussing prognosis and goals of care with patients. Barriers include disease- and therapy-specific prognostication challenges in heart failure and a lack of evidence-based primary palliative care education initiatives. METHODS: In response, we developed this 45-minute training module, which consists of a case-based small-group session and a communication guide. The curriculum highlights prognostication challenges in heart failure and introduces an illness trajectory-based framework to cue iterative goals of care conversations. RESULTS: We piloted this learning module with 46 internal medicine residents and interdisciplinary palliative care fellows in groups of three to 15 and obtained anonymous quantitative and qualitative postsession learner survey data to examine feasibility and acceptability. Trainees rated the session highly. One hundred percent of learners either strongly agreed or agreed the session was clinically useful. Learners unanimously found the teaching methods effective, and most felt they could easily apply these skills to their clinical work. In open-ended feedback, learners said the session gave them a better understanding of the heart failure illness trajectory, an improved framework for discussing goals of care with heart failure patients, and specific language to use when having these discussions. DISCUSSION: This module represents a new paradigm for teaching both prognostication and advance care planning in heart failure in which illness trajectory guides timing and content of goals of care conversations.

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.

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.

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.

Device-Based Approaches to Modulate the Autonomic Nervous System and Cardiac Electrophysiology.

Alterations in resting autonomic tone can be pathogenic in many cardiovascular disease states, such as heart failure and hypertension. Indeed, autonomic modulation by way of beta-blockade is a standard treatment of these conditions. There is a significant interest in developing non-pharmacological methods of autonomic modulation as well. For instance, clinical trials of vagal stimulation and spinal cord stimulation in the treatment of heart failure are currently underway, and renal denervation has been studied recently in the treatment of resistant hypertension. Notably, autonomic stimulation is also a potent modulator of cardiac electrophysiology. Manipulating the autonomic nervous system in studies designed to treat heart failure and hypertension have revealed that autonomic modulation may have a role in the treatment of common atrial and ventricular arrhythmias as well. Experimental data on vagal nerve and spinal cord stimulation suggest that each technique may reduce ventricular arrhythmias. Similarly, renal denervation may play a role in the treatment of atrial fibrillation, as well as in controlling refractory ventricular arrhythmias. In this review, we present the current experimental and clinical data on the effect of these therapeutic modalities on cardiac electrophysiology and their potential role in arrhythmia management.

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.

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.