In vivo fluid dynamics of the Ventura interatrial shunt device in patients with heart failure.

AIMS: Interatrial shunts are under evaluation as a treatment for heart failure (HF); however, their in vivo flow performance has not been quantitatively studied. We aimed to investigate the fluid dynamics properties of the 0.51 cm orifice diameter Ventura shunt and assess its lumen integrity with serial transesophageal echocardiography (TEE). METHODS AND RESULTS: Computational fluid dynamics (CFD) and bench flow tests were used to establish the flow-pressure relationship of the shunt. Open-label patients from the RELIEVE-HF trial underwent TEE at shunt implant and at 6 and 12 month follow-up. Shunt effective diameter (Deff) was derived from the vena contracta, and flow was determined by the continuity equation. CFD and bench studies independently validated that the shunt's discharge coefficient was 0.88 to 0.89. The device was successfully implanted in all 97 enrolled patients; mean age was 70 ± 11 years, 97% were NYHA class III, and 51% had LVEF ≤40%. Patency was confirmed in all instances, except for one stenotic shunt at 6 months. Deff remained unchanged from baseline at 12 months (0.47 ± 0.01 cm, P = 0.376), as did the trans-shunt mean pressure gradient (5.1 ± 3.9 mmHg, P = 0.316) and flow (1137 ± 463 mL/min, P = 0.384). TEE measured flow versus pressure closely correlated (R2 ≥ 0.98) with a fluid dynamics model. At 12 months, the pulmonary/systemic flow Qp/Qs ratio was 1.22 ± 0.12. CONCLUSIONS: When implanted in patients with advanced HF, this small interatrial shunt demonstrated predictable and durable patency and performance.

Association between right ventricular global longitudinal strain and mortality in intermediate-risk pulmonary embolism.

BACKGROUND: Right ventricular (RV) systolic dysfunction has been identified as a prognostic marker for adverse clinical events in patients presenting with acute pulmonary embolism (PE). However, challenges exist in identifying RV dysfunction using conventional echocardiography techniques. Strain echocardiography is an evolving imaging modality which measures myocardial deformation and can be used as an objective index of RV systolic function. This study evaluated RV Global Longitudinal Strain (RVGLS) in patients with intermediate risk PE as a parameter of RV dysfunction, and compared to traditional echocardiographic and CT parameters evaluating short-term mortality. METHODS: Retrospective single center cohort study of 251 patients with intermediate-risk PE between 2010 and 2018. The primary outcome was all-cause mortality at 30 days. Statistical analysis evaluated each parameter comparing survivors versus non-survivors at 30 days. Receiver operating characteristic (ROC) curves and Kaplan-Meier curves were used for comparison of the two cohorts. RESULTS: Altogether 251 patients were evaluated. Overall mortality rate was 12.4%. Utilizing an ROC curve, an absolute cutoff value of 17.7 for RVGLS demonstrated a sensitivity of 93% and specificity of 70% for observed 30-day mortality. Individuals with an RVGLS ≤17.7 had a 25 times higher mortality rate than those with RVGLS above 17.7 (HR 25.24, 95% CI = 6.0-106.4, p < .001). Area under the curve was (.855), RVGLS outperformed traditional echocardiographic parameters, CT findings, and cardiac biomarkers on univariable and multivariable analysis. CONCLUSIONS: Reduced RVGLS values on initial echocardiographic assessment of patients with intermediate-risk PE identified patients at higher risk for mortality at 30 days.

Interatrial shunt therapy in advanced heart failure: Outcomes from the open-label cohort of the RELIEVE-HF trial.

AIMS: Heart failure (HF) outcomes remain poor despite optimal guideline-directed medical therapy (GDMT). We assessed safety, effectiveness, and transthoracic echocardiographic (TTE) outcomes during the 12 months after Ventura shunt implantation in the RELIEVE-HF open-label roll-in cohort. METHODS AND RESULTS: Eligibility required symptomatic HF despite optimal GDMT with ≥1 HF hospitalization in the prior year or elevated natriuretic peptides. The safety endpoint was device-related major adverse cardiovascular or neurological events at 30 days, compared to a prespecified performance goal. Effectiveness evaluations included the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline, 1, 3, 6, and 12 months and TTE at baseline and 12 months. Overall, 97 patients were enrolled and implanted at 64 sites. Average age was 70 ± 11 years, 97% were in New York Heart Association class III, and half had left ventricular ejection fraction (LVEF) ≤40%. The safety endpoint was achieved (event rate 0%, p < 0.001). KCCQ overall summary score was improved by 12-16 points at all follow-up timepoints (all p < 0.004), with similar outcomes in patients with reduced and preserved LVEF. At 12 months, left ventricular end-systolic and end-diastolic volumes were reduced (p = 0.020 and p = 0.038, respectively), LVEF improved (p = 0.009), right ventricular end-systolic and end-diastolic areas were reduced (p = 0.001 and p = 0.030, respectively), and right ventricular fractional area change (p < 0.001) and tricuspid annular plane systolic excursion (p < 0.001) improved. CONCLUSION: Interatrial shunting with the Ventura device was safe and resulted in favourable clinical effects in patients with HF, regardless of LVEF. Improvements of left and right ventricular structure and function were consistent with reverse myocardial remodelling. These results would support the potential of this shunt device as a treatment for HF.

HeartWare Left Ventricular Assist Device Exercise Hemodynamics With Speed Adjustment Based on Left Ventricular Filling Pressures.

Functional capacity remains limited in heart failure patients with left ventricular assist devices (LVADs) due to fixed pump speed and inability to offload the left ventricle adequately. We hypothesized that manually adjusting LVAD speed during exercise based on pulmonary capillary wedge pressures would increase total cardiac output and maximal oxygen consumption. Two participants with a HeartWare LVAD underwent an invasive ramp study at rest followed by an invasive cardiopulmonary stress test exercising in two randomized phases: fixed speed and adjusted speed. In the latter phase, speed was adjusted every 1 minute during exercise at ±20 rpm/1 mm Hg change from baseline pulmonary capillary wedge pressure. There was no difference in maximal oxygen consumption between the two phases, with a modest increase in total cardiac output during speed adjustment. Filling pressures were initially controlled during speed adjustment until speed was capped at 4,000 rpm, at which point filling pressures increased. Blood pressure was variable. The pressure across the head of the pump (ΔP) was higher with speed adjustment. Contrary to our hypothesis, LVAD speed adjustment during exercise did not improve total cardiac output and functional capacity. This variable response may be attributed to the native cardiac reserve and baroreceptor response; however, additional studies are needed.

Association of activin A and postpartum blood pressure in peripartum cardiomyopathy.

BACKGROUND: Activin A has been implicated in the pathogenesis of patients with chronic hypertension and heart failure as well as patients with hypertensive disorders of pregnancy (HDP). Whether activin A correlates with blood pressure in patients with peripartum cardiomyopathy (PPCM) and HDP history has not previously been explored. METHODS AND RESULTS: 82 women with PPCM w/ and w/out HDP or hypertension history were selected for analysis from the Investigations in Pregnancy Associated Cardiomyopathy (IPAC) study. Serum biomarkers and blood pressure were assessed at the time of enrollment (median postpartum day 24). Levels of both sFlt-1 (SBP: r 0.47, p = 0.008; DBP: r 0.57, p < 0.001) and activin A (SBP: r 0.59, p < 0.001;DBP: r 0.68, p < 0.001) were noted to significantly correlate with blood pressure in patients with a history of HDP who went on to develop PPCM, but not in patients with chronic hypertension or no hypertensive history. The strongest correlation was between activin A levels and postpartum diastolic blood pressure for the subset with preeclampsia (DBP: r0.82, p < 0.001). This remained significant in multivariable linear regression analysis (DBP: ß = 0.011, p = 0.015). CONCLUSION: In patients with PPCM, activin A and sFlt-1 levels had direct correlations with both systolic (SBP) and diastolic blood pressures (DBP), but only in participants with history of HDP. This correlation was more evident for activin A and strongest with a history of preeclampsia. Our findings suggest that activin A may play an important role in blood pressure modulation in women with HDP who subsequently develop PPCM.

PRecision Event Monitoring for PatienTs with Heart Failure using HeartLogic (PREEMPT-HF) study design and enrolment.

AIMS: The HeartLogic multisensor index has been found to be a sensitive predictor of worsening heart failure (HF). However, there is limited data on this index's association and its constituent sensors with HF readmissions. METHODS AND RESULTS: The PREEMPT-HF study is a global, multicentre, prospective, observational, single-arm, post-market study. HF patients with an implantable defibrillator device or cardiac resynchronization therapy with defibrillator with HeartLogic capabilities were eligible if sensor data collection was turned on and the HeartLogic feature was not enabled. Thus, the HeartLogic Index/alert and heart sounds sensor trends were unavailable via the LATITUDE remote monitoring system to clinicians (blinded). Evaluation of subject medical records at 6 months and a final in-clinic visit at 12 months was required for collection of all-cause hospitalizations and HF outpatient visits. The purpose of this study is exploratory, no formal hypothesis tests are planned, and no adjustment for multiple testing will be performed. A total of 2183 patients were enrolled at 103 sites between June 2018 and June 2020. A significant proportion of the patients were implanted with implantable defibrillator devices (39%) versus cardiac resynchronization therapy with defibrillator (61%); were female (27%); over 65 (61%); New York Heart Association class I (13%), II (53%), and III (33%); ejection fraction < 25% (21%); ischaemic (50%); and with a history of renal dysfunction (23%). CONCLUSIONS: The PREEMPT study will provide clinical data and blinded sensor trends for the characterization of sensor changes with HF readmission, tachyarrhythmias, and event subgroups. These data may help to refine the clinical use of HeartLogic and to improve patient outcomes.

Serum Proteomic Analysis of Peripartum Cardiomyopathy Reveals Distinctive Dysregulation of Inflammatory and Cholesterol Metabolism Pathways.

BACKGROUND: The pathophysiology of peripartum cardiomyopathy (PPCM) and its distinctive biological features remain incompletely understood. High-throughput serum proteomic profiling, a powerful tool to gain insights into the pathophysiology of diseases at a systems biology level, has never been used to investigate PPCM relative to nonischemic cardiomyopathy. OBJECTIVES: The aim of this study was to characterize the pathophysiology of PPCM through serum proteomic analysis. METHODS: Aptamer-based proteomic analysis (SomaScan 7K) was performed on serum samples from women with PPCM (n = 67), women with nonischemic nonperipartum cardiomyopathy (NPCM) (n = 31), and age-matched healthy peripartum and nonperipartum women (n = 10 each). Serum samples were obtained from the IPAC (Investigation of Pregnancy-Associated Cardiomyopathy) and IMAC2 (Intervention in Myocarditis and Acute Cardiomyopathy) studies. RESULTS: Principal component analysis revealed unique clustering of each patient group (P for difference <0.001). Biological pathway analyses of differentially measured proteins in PPCM relative to NPCM, before and after normalization to pertinent healthy controls, highlighted specific dysregulation of inflammatory pathways in PPCM, including the upregulation of the cholesterol metabolism-related anti-inflammatory pathway liver-X receptor/retinoid-X receptor (LXR/RXR) (P < 0.01, Z-score 1.9-2.1). Cardiac recovery by 12 months in PPCM was associated with the downregulation of pro-inflammatory pathways and the upregulation of LXR/RXR, and an additional RXR-dependent pathway involved in the regulation of inflammation and metabolism, peroxisome proliferator-activated receptor α/RXRα signaling. CONCLUSIONS: Serum proteomic profiling of PPCM relative to NPCM and healthy controls indicated that PPCM is a distinct disease entity characterized by the unique dysregulation of inflammation-related pathways and cholesterol metabolism-related anti-inflammatory pathways. These findings provide insight into the pathophysiology of PPCM and point to novel potential therapeutic targets.

Remote Monitoring for Heart Failure Management at Home.

Early telemonitoring of weights and symptoms did not decrease heart failure hospitalizations but helped identify steps toward effective monitoring programs. A signal that is accurate and actionable with response kinetics for early re-assessment is required for the treatment of patients at high risk, while signal specifications differ for surveillance of low-risk patients. Tracking of congestion with cardiac filling pressures or lung water content has shown most impact to decrease hospitalizations, while multiparameter scores from implanted rhythm devices have identified patients at increased risk. Algorithms require better personalization of signal thresholds and interventions. The COVID-19 epidemic accelerated transition to remote care away from clinics, preparing for new digital health care platforms to accommodate multiple technologies and empower patients. Addressing inequities will require bridging the digital divide and the deep gap in access to HF care teams, who will not be replaced by technology but by care teams who can embrace it.

Transcatheter Left Ventricular Restoration in Patients With Heart Failure.

BACKGROUND: Left ventricular (LV) volume reshaping reduces myocardial wall stress and may induce reverse remodeling in patients with heart failure with reduced ejection fraction. The AccuCinch Transcatheter Left Ventricular Restoration system consists of a series of anchors connected by a cable implanted along the LV base that is cinched to the basal free wall radius. We evaluated the echocardiographic and clinical outcomes following transcatheter left ventricular restoration. METHODS AND RESULTS: We analyzed 51 heart failure patients with a left ventricular ejection fraction between 20% and 40%, with no more than 2+ mitral regurgitation treated with optimal medical therapy, who subsequently underwent transcatheter left ventricular restoration. Serial echocardiograms, Kansas City Cardiomyopathy Questionnaire scores, and 6-minute walk test distances were measured at baseline through 12 months. Primary analysis end point was change in end-diastolic volume at 12 months compared with baseline. Patients (n = 51) were predominantly male (86%) with a mean age of 56.3 ± 13.1 years. Fluoroscopy showed LV free wall radius decreased by a median of 9.2 mm amounting to a 29.6% decrease in the free wall arc length. At 12 months, the LV end-diastolic volume decreased by 33.6 ± 34.8 mL (P < .01), with comparable decreases in the LV end-systolic volume. These decreases were associated with significant improvements in the overall Kansas City Cardiomyopathy Questionnaire score (16.4 ± 18.7 points; P < .01) and 6-minute hall walk test distance (45.9 ± 83.9 m; P < .01). There were no periprocedural deaths; through the 1-year follow-up, 1 patient died (day 280) and 1 patient received a left ventricular assist device (day 13). CONCLUSIONS: In patients with heart failure with reduced ejection fraction without significant mitral regurgitation receiving optimal medical therapy, the AccuCinch System resulted in decreases of LV volume, as well as improved quality of life and exercise endurance. A randomized trial is ongoing (NCT04331769).

Design of the remede System Therapy (reST) study: A prospective non-randomized post-market study collecting clinical data on safety and effectiveness of the remede system for the treatment of central sleep apnea.

BACKGROUND: Central sleep apnea (CSA) is a disorder defined by lack of respiratory drive from the brain stem on breathing efforts. There is a lack of established therapies for CSA and most available therapies are limited by poor patient adherence, limited randomized controlled studies, and potentially adverse cardiovascular effects. The remede System (ZOLL Respicardia, Inc., Minnetonka, Minnesota) uses transvenous phrenic nerve stimulation to stimulate the diaphragm, thereby restoring a more normal breathing pattern throughout the sleep period. METHODS: The remede System Therapy (reST) Study is a prospective non-randomized multicenter international study evaluating long-term safety and effectiveness of the remede System in the post-market setting. Up to 500 adult patients with moderate to severe CSA will be enrolled and followed up to 5 years at approximately 50 sites in the United States and Europe. Safety objectives include evaluation of adverse events related to the implant procedure, device or delivered therapy, death, and hospitalizations. Effectiveness endpoints include assessment of changes in sleep-disordered breathing metrics from polysomnograms and home sleep tests, changes in daytime sleepiness using the Epworth Sleepiness Scale, and changes in QoL using the PROMIS-29 and Patient Global Assessment questionnaires. The subgroup of patients with heart failure will undergo additional assessments including echocardiography to assess cardiac reverse remodeling, 6-min walk distance, QoL assessment by Kansas City Cardiomyopathy Questionnaire and measurement of biomarkers. CONCLUSION: This will be the largest prospective study evaluating long-term safety and effectiveness of transvenous phrenic nerve stimulation for the treatment of moderate to severe CSA in adult patients.

The effect of cardiac resynchronization without a defibrillator on morbidity and mortality: an individual patient data meta-analysis of COMPANION and CARE-HF.

AIMS: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality for patients with heart failure, reduced left ventricular ejection fraction, QRS duration >130 ms and in sinus rhythm. The aim of this study was to identify patient characteristics that predict the effect, specifically, of CRT pacemakers (CRT-P) on all-cause mortality or the composite of hospitalization for heart failure or all-cause mortality. METHODS AND RESULTS: We conducted an individual patient data meta-analysis of the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) and Cardiac Resynchronization-Heart Failure (CARE-HF) trials. Only patients assigned to CRT-P or control (n = 1738) were included in order to avoid confounding from concomitant defibrillator therapy. The influence of baseline characteristics on treatment effects was investigated. Median age was 67 (59-73) years, most patients were men (70%), 68% had a QRS duration of 150-199 ms and 80% had left bundle branch block. Patients assigned to CRT-P had lower rates for all-cause mortality (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.56-0.81; p < 0.0001) and the composite outcome (HR 0.67, 95% CI 0.58-0.78; p < 0.0001). No pre-specified characteristic, including sex, aetiology of ventricular dysfunction, QRS duration (within the studied range) or morphology or PR interval significantly influenced the effect of CRT-P on all-cause mortality or the composite outcome. However, CRT-P had a greater effect on the composite outcome for patients with lower body surface area and those prescribed beta-blockers. CONCLUSIONS: Cardiac resynchronization therapy-pacemaker reduces morbidity and mortality in appropriately selected patients with heart failure. Benefits may be greater in smaller patients and in those receiving beta-blockers. Neither QRS duration nor morphology independently predicted the benefit of CRT-P. CLINICAL TRIAL REGISTRATION: COMPANION, NCT00180258; CARE-HF, NCT00170300.

Multiple cArdiac seNsors for mAnaGEment of Heart Failure (MANAGE-HF) - Phase I Evaluation of the Integration and Safety of the HeartLogic Multisensor Algorithm in Patients With Heart Failure.

BACKGROUND: Patients with heart failure (HF) and reduced ejection fraction suffer from a relapsing and remitting disease course, where early treatment changes may improve outcomes. We assessed the clinical integration and safety of the HeartLogic multisensor index and alerts in HF care. METHODS: The Multiple cArdiac seNsors for mAnaGEment of Heart Failure (MANAGE-HF) study enrolled 200 patients with HF and reduced ejection fraction (<35%), New York Heart Association functional class II-III symptoms, implanted with a cardiac resynchronization therapy-defibrillator or and implantable cardioverter defibrillator, who had either a hospitalization for HF within 12 months or unscheduled visit for HF exacerbation within 90 days or an elevated natriuretic peptide concentration (brain natriuretic peptide [BNP] of ≥150 pg/mL or N-terminal pro-BNP [NT-proBNP] of ≥600 pg/mL). This phase included the development of an alert management guide and evaluated changes in medical treatment, natriuretic peptide levels, and safety. RESULTS: The mean age of participants was 67 years, 68% were men, 81% were White, and 61% had a HF hospitalization in prior 12 months. During follow-up, there were 585 alert cases with an average of 1.76 alert cases per patient-year. HF medications were augmented during 74% of the alert cases. HF treatment augmentation within 2 weeks from an initial alert was associated with more rapid recovery of the HeartLogic Index. Five serious adverse events (0.015 per patient-year) occurred in relation to alert-prompted medication change. NTproBNP levels decreased from median of 1316 pg/mL at baseline to 743 pg/mL at 12 months (P < .001). CONCLUSIONS: HeartLogic alert management was safely implemented in HF care and may optimize HF management. This phase supports further evaluation in larger studies. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03237858).

Temporal Association of Atrial Fibrillation With Cardiac Implanted Electronic Device Detected Heart Failure Status.

OBJECTIVES: This study sought to investigate the temporal association between changes in physiologic heart failure (HF) sensors, atrial fibrillation (AF) progression, and clinical HF in patients with cardiac resynchronization therapy implantable defibrillators (CRT-D) designed to monitor AF and HF daily. BACKGROUND: AF is a common comorbidity in HF; however, it is unclear if HF triggers AF, or vice-versa. Current implantable cardiac devices have sensors capable of quantifying HF status, which permits a greater understanding of the impact of AF on HF status and may help guide treatment. METHODS: The MultiSENSE (Multisensor Chronic Evaluation in Ambulatory Heart Failure Patients) study collected multiple sensor data indicative of HF status in patients with CRT-D followed for up to 12 months. Patients were grouped according to their longest daily AF burden: 1) at least 24 hours of AF (HIGH AF); 2) between 6 minutes and 24 hours (MID AF); and 3) <6 minutes (NO AF). Sensor data were aligned to the first qualifying AF event or a randomly selected day for patients in the NO AF group. RESULTS: Among 869 patients with daily AF data available, 98 patients had HIGH AF, 141 patients MID AF, and 630 patients NO AF. At baseline, history of AF, N-terminal pro hormone B-type natriuretic peptide and device-measured S3 were associated with development of AF. HeartLogic index increased before AF onset (Δ HeartLogic = 9.83 ± 2.49; P < 0.001). Multivariable time-dependent Cox regression showed an increased risk for HF events following a 24-hour AF episode compared with no 24-hour AF (hazard ratio: 1.96; 95% confidence interval: 1.03-3.74). CONCLUSIONS: Device-measured HF indicators worsened before AF onset, whereas clinical HF deterioration only became apparent after AF occurred. Thus, the sensitivity of methods to ascertain AF and HF status appear to influence the direction of perceived causality. (Multisensor Chronic Evaluation in Ambulatory Heart Failure Patients [MultiSENSE]; NCT01128166).

Evaluation of Medicare Claims for the Development of Heart Failure Diagnostics.

BACKGROUND: Although claims data provide a large and efficient source of clinical events, validation is needed prior to use in heart failure (HF) diagnostic development. METHODS AND RESULTS: Data from the Multisensor Chronic Evaluations in Ambulatory Heart Failure Patients (MultiSENSE) study, used to create the HeartLogic HF diagnostic, were linked with fee-for-service (FFS) Medicare claims. Events were matched by patient ID and date, and agreement was calculated between claims primary HF diagnosis codes and study event adjudication. HF events (HFEs) were defined as inpatient visits, or outpatient visits with intravenous decongestive therapy. Diagnostic performance was measured as HFE-detection sensitivity and false-positive rate (FPR). Linkage of 791 MultiSENSE subjects returned 320 FFS patients with an average follow-up duration of 0.94 years. Although study and claims deaths matched exactly (n = 14), matching was imperfect between study hospitalizations and acute inpatient claims events. Of 239 total events, 165 study hospitalizations (69%) matched inpatient claims events, 28 hospitalizations matched outpatient claims events (12%), 14 hospitalizations were study-unique (6%), and 32 inpatient events were claims-unique (13%). Inpatient HF classification had substantial agreement with study adjudication (κ = 0.823). Diagnostic performance was not different between claims and study events (sensitivity = 75.6% vs 77.6% and FPR = 1.539 vs 1.528 alerts/patient-year). HeartLogic-detected events contributed to > 90% of the HFE costs used for evaluation. CONCLUSIONS: Acceptable event matching, good agreement of claims diagnostic codes with adjudication, and equivalent diagnostic performance support the validity of using claims for HF diagnostic development.

Letter to the editor to update the article "Remote monitoring for heart failure using implantable devices: a systematic review, meta-analysis, and meta-regression of randomized controlled trials".

Our recently published systematic review and meta-analysis of heart failure (HF) remote monitoring using implantable devices (Hajduczok et al. in HF Reviews 1-20, 1) has been updated to reflected new data from the GUIDE-HF trial (Lindenfeld et al. in Lancet 398(10304):991-1001, 2). Data from randomized controlled trials (RCTs) was assessed to determine the effectiveness of implantable remote monitoring on the improvement of outcomes in HF patients. With the inclusion of the data from 1000 patients followed for 12 months in GUIDE-HF, our conclusions remain unchanged: Compared to standard of care, remote monitoring using implantable devices did not reduce mortality, CV, or HF hospitalizations. However, right ventricular/pulmonary pressure monitoring may reduce HF hospitalizations.

Remote monitoring for heart failure using implantable devices: a systematic review, meta-analysis, and meta-regression of randomized controlled trials.

In heart failure (HF) patients, remote monitoring using implantable devices may be used to predict and reduce HF exacerbations and mortality. Data from randomized controlled trials (RCTs) was assessed to determine the effectiveness of implantable remote monitoring on the improvement of outcomes in HF patients. A systematic review and meta-analysis of RCTs testing remote monitoring versus standard of care for management of HF patients was performed. Primary endpoints were all-cause mortality and a composite of cardiovascular (CV) and HF hospitalizations. Rate ratios (RRs) and 95% confidence intervals (CI) were calculated. A secondary analysis tested for heterogeneity of treatment effect (HTE) comparing right ventricular/pulmonary pressure monitoring versus impedance-based monitoring on hospitalization. A regression analysis was performed using the mean follow-up time as the moderator on each primary endpoint. Eleven RCTs (n = 6196) were identified with a mean follow-up of 21.9 months. The mean age and reported ejection fraction were 64.1 years and 27.7%, respectively. Remote monitoring did not reduce mortality (RR 0.89 [95% CI 0.77, 1.03]) or the composite of CV and HF hospitalizations (RR 0.98 [0.81, 1.19]). Subgroup analysis found significant HTE for hospitalizations between those studies that used right ventricular/pulmonary pressure monitoring versus impedance-based monitoring (I2 = 87.1%, chi2 = 7.75, p = 0.005). Regression analysis found no relationship between the log rate ratio of remote monitoring's effect on mortality, CV hospitalization or HF hospitalization, and mean follow-up time. Compared to standard of care, remote monitoring using implantable devices did not reduce mortality, CV, or HF hospitalizations. However, right ventricular/pulmonary pressure monitoring may reduce HF hospitalizations, which will need to be explored in future studies.

Initial endoscopic intervention is not associated with reduced risk of recurrent gastrointestinal bleeding in left ventricular assist device patients.

BACKGROUND: Left ventricular assist devices (LVADs) are increasingly used for mechanical support of end-stage heart failure. Gastrointestinal bleeding (GIB) confers a significant morbidity in LVAD patients, with rates of up to 30% at 5 years. We assessed predictors of index and recurrent GIB (rGIB) in LVAD patients to risk stratify patients and evaluate if endoscopic approach and intervention at index GIB impacted rGIB. METHODS: A retrospective chart review of all LVAD patients at our institution from 01/01/2006 to 31/10/2016 was completed. Predictors for index and recurrent GIB were analyzed. Multivariate logistic regression analysis was created using only statistically significant dependent variables and adjusted for demographic variables. RESULTS: A total of 77/214 (36%) patients developed GIB, and 38/214 (17.8%) developed rGIB. Destination therapy (P=0.01), longer duration of LVAD (P=0.03), and low albumin (<3.5 g/dL) (P<0.001) were associated with increased risk of index GIB. Charlson Comorbidity Index, heart failure etiology, and Medicare were predictors of index GIB on univariate analysis, but this was not seen on multivariate analysis. Performing an endoscopy with/without intervention, non- angioectasia lesions, and location of bleeding were not statistically significant predictors of rGIB. Longer duration of hospitalization appeared to be protective for rGIB on univariate analysis. CONCLUSIONS: Index endoscopy and intervention is not associated with reduced risk of rGIB in LVAD patients. Several independent factors are associated with the risk of index GIB. Albumin is a potentially modifiable risk factor, and likely contributes to bleeding through poor nutrition. It is a surrogate marker for systemic illness, and may have pharmacologic implications.

The cost of non-response to cardiac resynchronization therapy: characterizing heart failure events following cardiac resynchronization therapy.

AIMS: The aim of this study is to quantify healthcare resource utilization among non-responders to cardiac resynchronization therapy (CRT-NR) by heart failure (HF) events and influence of comorbidities. METHODS AND RESULTS: The ADVANCE CRT registry (2013-2015) prospectively identified responders/CRT-NRs 6 months post-implant using the clinical composite score. Heart failure event rates and associated cost, both overall and separated for inpatient hospitalizations, office visits, emergency room visits, and observational stays, were quantified. Costs of events were imputed from payments for similar real-world encounters in subjects with CRT-D/P devices in the MarketScan™ commercial and Medicare Supplemental insurance claims databases. Effects of patient demographics and comorbidities on event rates and cost were evaluated. Of 879 US patients (age 69 ± 11 years, 29% female, ischaemic disease 52%), 310 (35%) were CRT-NR. Among CRT-NRs vs. responders, more patients developed HF (41% vs. 11%, P < 0.001), HF event rate was higher (67.0 ± 21.7 vs. 11.4 ± 3.7/100 pt-year, P < 0.001), and HF readmission within 30 days was more common [hazard ratio 7.06, 95% confidence interval (2.1-43.7)]. Inpatient hospitalization was the most common and most expensive event type in CRT-NR. Comorbid HF was increased by diabetes, hypertension, and pulmonary disorders. Over 2 years, compared to CRT responders, each CRT-NR resulted in excess cost of $6388 ($3859-$10 483) to Medicare (P = 0.015) or $10 197 ($6161-$17 394) to private insurances (P = 0.014). CONCLUSION: Healthcare expenditures associated with contemporary CRT non-response management are among the highest for any HF patient group. This illustrates an unmet need for interventions to improve HF outcomes and reduce costs among some CRT recipients.