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BACKGROUND After 3 years of continuous-flow left ventricular assist device (CF-LVAD) support, nearly a third of patients develop at least moderate aortic insufficiency (AI). Percutaneous occluder devices, surgical aortic valve replacement (SAVR), and urgent heart transplantation are available treatment options. Transcatheter aortic valve replacement (TAVR) has not been widely used for treating symptomatic AI in patients on LVAD support. METHODS Retrospective chart review and data analysis from October 2010 through August 2017 was performed. A total of 286 patients with end-stage heart failure (ESHF) were implanted with a durable CF-LVAD. Nine patients subsequently developed significant symptomatic AI, which was treated with TAVR. RESULTS All 9 patients had 1 TAVR procedure with resolution of AI and were discharged home. Procedural complications include valve migration warranting a second valve for stabilization, retroperitoneal and groin hematoma, and pseudoaneurysm requiring thrombin injection. A significant improvement of the New York Heart Association classification was noted from the time of implant to 6 months. Two patients had unplanned heart failure‒related hospitalizations within 6 months. At 6 months, 89% of patients were alive on LVAD support. CONCLUSIONS TAVR is a successful treatment modality for LVAD patients who develop symptomatic AI.

In two interim analyses of this trial, patients with advanced heart failure who were treated with a fully magnetically levitated centrifugal-flow left ventricular assist device were less likely to have pump thrombosis or nondisabling stroke than were patients treated with a mechanical-bearing axial-flow left ventricular assist device.We randomly assigned patients with advanced heart failure to receive either the centrifugal-flow pump or the axial-flow pump irrespective of the intended goal of use (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke or reoperation to replace or remove a malfunctioning device. The principal secondary end point was pump replacement at 2 years.This final analysis included 1028 enrolled patients: 516 in the centrifugal-flow pump group and 512 in the axial-flow pump group. In the analysis of the primary end point, 397 patients (76.9%) in the centrifugal-flow pump group, as compared with 332 (64.8%) in the axial-flow pump group, remained alive and free of disabling stroke or reoperation to replace or remove a malfunctioning device at 2 years (relative risk, 0.84; 95% confidence interval [CI], 0.78 to 0.91; P0.001 for superiority). Pump replacement was less common in the centrifugal-flow pump group than in the axial-flow pump group (12 patients [2.3%] vs. 57 patients [11.3%]; relative risk, 0.21; 95% CI, 0.11 to 0.38; P0.001). The numbers of events per patient-year for stroke of any severity, major bleeding, and gastrointestinal hemorrhage were lower in the centrifugal-flow pump group than in the axial-flow pump group.Among patients with advanced heart failure, a fully magnetically levitated centrifugal-flow left ventricular assist device was associated with less frequent need for pump replacement than an axial-flow device and was superior with respect to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755.).

Since the VLSI chips were invented, as predicted by Moore’s law, the performance, the power, and the cost of the VLSI chips have been improved, which brought a significant benefit to the economy. However, some of the analog circuits do not get a full benefit from the scaling, due to the increased device variability with transistors in smaller dimension. Under such circumstance, the calibration and trimming techniques are essential to overcome the sensitivity to the process variation. This paper presents the trimming technique to correct the direct current (dc) offset error of the bandgap voltage reference circuit, which complies with the high-volume manufacturing (HVM) requirements. The proposed trimming method consists of the combination of two different sequences, the coarse and fine trimming. The accuracy of the dc offset trimming is evaluated by the newly invented method that complies with the HVM requirements. With a compact silicon area of only 700 $\mu \text{m}^{2}$ , the dc offset trimming circuit achieved an accuracy of ±5 mV ( $4\sigma$ ) as a result of the coarse and fine trimming operations.

The thermal efficiency of cascading crossflow heat exchangers (HEX), networked in a parallel fashion to a cold plate, is investigated experimentally and computationally. A microcontroller is connected to the manifold system that dynamically branches coolant flow to multiple heat exchangers based on package power and its consequential junction temperature rise (Tj rise ) feedback from the heat dissipating device. Branching the recirculating coolant flow dynamically to multiple heat exchangers on a single cold plate for a heater dissipating 1kW of power, yielded a temperature reduction of 16°C compared to recirculating the coolant to just one HEX. Efficiency (η) of HEXs are characterized and a new efficiency parameter (T eff ) is proposed for characterizing heat exchanger efficiencies as an alternate to conventional HEX efficiency methods. Experimental data for a 1kW scenario on one HEX yields a system efficiency (η) of 67% and for 4 HEXs at identical power, it results in a system efficiency of 92.7%, which is a remarkable 25.7% improvement in the overall thermal efficiency of the system. A new efficiency parameter (T eff ) for HEX is introduced in this research not just to characterize the efficiency of HEX but is also proposed as an efficient compact modeling tool that reduces mesh count in the model as well. This has been adequately explained in this paper. A plug and play, adaptive, coolant flow branching system that removes human intervention and dynamically optimizes thermal efficiency based on real-time changing power conditions and achieving a junction temperature target is implemented and presented in this research. When implemented in data centers, this is projected to optimize TCO (Total Cost of Ownership) at the rack level and for large scale deployment & adoption. This method consequentially improves the overall Power Usage Effectiveness (PUE) of a data center. There have been numerous ways proposed to characterize heat exchanger efficiency specific to the design and analysis of how it is built. The proposed method is novel to the design of cascading network of crossflow heat exchangers where efficiency is shown to be closer to 100% compared to other methods.

Background Advanced heart failure (HF) is characterized by high morbidity and mortality. Conventional therapy may not sufficiently reduce patient suffering and maximize quality of life. Objectives The authors investigated whether an interdisciplinary palliative care intervention in addition to evidence-based HF care improves certain outcomes. Methods The authors randomized 150 patients with advanced HF between August 15, 2012, and June 25, 2015, to usual care (UC) (n = 75) or UC plus a palliative care intervention (UC + PAL) (n = 75) at a single center. Primary endpoints were 2 quality-of-life measurements, the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary and the Functional Assessment of Chronic Illness Therapy–Palliative Care scale (FACIT–Pal), assessed at 6 months. Secondary endpoints included assessments of depression and anxiety (measured via the Hospital Anxiety and Depression Scale [HADS]), spiritual well-being (measured via the FACIT–Spiritual Well-Being scale [FACIT–Sp]), hospitalizations, and mortality. Results Patients randomized to UC + PAL versus UC alone had clinically significant incremental improvement in KCCQ and FACIT–Pal scores from randomization to 6 months (KCCQ difference = 9.49 points, 95% confidence interval [CI]: 0.94 to 18.05, p = 0.030; FACIT–Pal difference = 11.77 points, 95% CI: 0.84 to 22.71, p = 0.035). Depression improved in UC + PAL patients (HADS-depression difference = −1.94 points; p = 0.020) versus UC-alone patients, with similar findings for anxiety (HADS-anxiety difference = −1.83 points; p = 0.048). Spiritual well-being was improved in UC + PAL versus UC-alone patients (FACIT–Sp difference = 3.98 points; p = 0.027). Randomization to UC + PAL did not affect rehospitalization or mortality. Conclusions An interdisciplinary palliative care intervention in advanced HF patients showed consistently greater benefits in quality of life, anxiety, depression, and spiritual well-being compared with UC alone. (Palliative Care in Heart Failure [PAL-HF]; NCT01589601)

Fully Integrated Voltage Regulators (FIVRs) are switching voltage regulators integrated on to the same die as the CPU and Graphics cores, in 4th and 5th generation Intel® Core™ microprocessors. Practical limitations prevent the application of traditional voltage regulator characterization methods to FIVRs. To overcome these challenges, new methods and techniques had to be developed for the testing and characterization of FIVRs. Power Efficiency (η) is one of the key performance metrics of voltage regulators. In this paper we explain the methods used to measure the Power Efficiency of FIVRs. These methods are applicable to Integrated VRs in general and are not specific to FIVRs alone. Description of power loss components and extraction of the loss coefficients from curve fitting technique is also presented. Measured results show that the proposed methods are highly repeatable with worst-case run-to-run variation of 0.4%. The results also show that the worst-case error is

The heat transfer distributions and associated flow field characteristics of impinging jets have been studied extensively, but mostly for submerged jet conditions on the hot target wall in confined channels. A review of the literature reveals that fewer studies have been expended for non-submerged single phase jets in confined channels. In this research, a total of 64 distinct CFD RANS simulations of turbulently impinging jets issued from a single circular nozzle and accelerated under an orifice plate comprising twenty tapered micro-scaled nozzles in confined channels at different nozzle to wall separation (1 ≤z/d ≤ 16) distances are examined using Icepak and Fluent - commercial finite-volume solvers to extract intricate details of impinging flow fields on a hot silicon wall. An overall heat transfer coefficient to the order of 170,000 W/m2 °K has been observed on the surface of the silicon using this multiple micro-jet impingement setup. The dielectric fluid jet impinging on a wall is a high power density bare die silicon wall dissipating a non-uniform power of 95 Watts and the heat flux power density is very high in certain regions of the die. Flow field simulations predict recirculating toroidal patterns for each impinging micro-jet on the die, entraining near the outflow which is a behavior that is consistent and concurring with the characteristics of confined flow fields. Large Eddy Simulations are used to predict the flow-field turbulent characteristics of a single circular jet impinging directly on the silicon wall for four significant cases with varying (0.5 ≤; z/d ≤ 2) distances at a Reynolds of 20,000 issued from main nozzle reveal intricate features of flow field distributions including entrainment effects on the bare die hot silicon. Results of flow entrainment, surface temperatures, and heat transfer rates along with average Nusselt numbers at the impinging silicon wall are presented for all the CFD simulations cases collated.

Impingement cooling with different tested fluids has been widely accepted and used to dissipate high transient and steady state localized heat loads. There are a plethora of advantages of direct impingement cooling over traditional cooling methods but till date the most alluring advantage is that of the boundary layer thickness proximity to the stagnation region being very small and consequentially leads to very high heat transfer rates. A numerical parametric setup involving 60 differing CFD simulations for a direct on-die multiple jet impingement in confined channels in the absence of phase change has been modeled for removing high heat fluxes emanating from the surface of die. The varying parameters for impingement setup includes Reynolds number (8000 ≤ Re ≤ 20000) based on the main inlet nozzle diameter, the nozzle jet orifice plate to the die (z/d) standoff (up to sixteen nozzle jet diameters distance), nozzle type, number of nozzles and aspect ratio. It is found for the higher aspect ratio tapered nozzle, the junction temperature of the silicon decreases 10° C - 20° C depending on the Reynolds number regime of the flow. Surface Nusselt number, a dimensionless heat transfer ratio is investigated on the surface of the die along with heat transfer coefficient (h) and it is shown that h increases with aspect ratio increase in the tapered nozzle and/or Reynolds number increase, and decreases with the tapered jet-to-target standoff distance. The fluid flow pattern reveals interesting features including a boundary layer separation point. The variation of secondary re-circulation zone downstream of the stagnation point with a Reynolds number increase is being investigated in Ansys Icepak, the commercial CFD package. A k-∈ model was used to predict the turbulent flow and associated characteristics. The findings from this investigation can improve the jet impingement design factors and performance of direct on-die impingement for high power density packages. The main objective of the present research is to gain insights computationally into the design and analysis of tapered micro nozzled jet impingement cooling for high power density packages so that robust and efficient impingement systems can be built for prototyping.

In an early analysis of this trial, use of a magnetically levitated centrifugal continuous-flow circulatory pump was found to improve clinical outcomes, as compared with a mechanical-bearing axial continuous-flow pump, at 6 months in patients with advanced heart failure.In a randomized noninferiority and superiority trial, we compared the centrifugal-flow pump with the axial-flow pump in patients with advanced heart failure, irrespective of the intended goal of support (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke (with disabling stroke indicated by a modified Rankin score of3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove a malfunctioning device. The noninferiority margin for the risk difference (centrifugal-flow pump group minus axial-flow pump group) was -10 percentage points.Of 366 patients, 190 were assigned to the centrifugal-flow pump group and 176 to the axial-flow pump group. In the intention-to-treat population, the primary end point occurred in 151 patients (79.5%) in the centrifugal-flow pump group, as compared with 106 (60.2%) in the axial-flow pump group (absolute difference, 19.2 percentage points; 95% lower confidence boundary, 9.8 percentage points [P0.001 for noninferiority]; hazard ratio, 0.46; 95% confidence interval [CI], 0.31 to 0.69 [P0.001 for superiority]). Reoperation for pump malfunction was less frequent in the centrifugal-flow pump group than in the axial-flow pump group (3 patients [1.6%] vs. 30 patients [17.0%]; hazard ratio, 0.08; 95% CI, 0.03 to 0.27; P0.001). The rates of death and disabling stroke were similar in the two groups, but the overall rate of stroke was lower in the centrifugal-flow pump group than in the axial-flow pump group (10.1% vs. 19.2%; hazard ratio, 0.47; 95% CI, 0.27 to 0.84, P=0.02).In patients with advanced heart failure, a fully magnetically levitated centrifugal-flow pump was superior to a mechanical-bearing axial-flow pump with regard to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755 .).

Background Higher body mass index ( BMI ) is associated with lower circulating levels of N‐terminal‐pro‐b‐type natriuretic peptide ( NT ‐pro BNP ). The Interaction between BMI and NT ‐pro BNP with respect to clinical outcomes is not well characterized in patients with acute heart failure. Methods and Results A total of 686 patients from the biomarker substudy of the ASCEND ‐ HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated HF ) clinical trial with documented NT ‐pro BNP levels at baseline were included in the present analysis. Patients were classified by the World Health Organization obesity classification (nonobese: BMI 2 , Class I obesity: BMI 30–34.9 kg/m 2 , Class II obesity BMI 35–39.9 kg/m 2 , and Class III obesity BMI ≥40 kg/m 2 ). We assessed baseline characteristics and 30‐ and 180‐day outcomes by BMI class and explored the interaction between BMI and NT ‐pro BNP for these outcomes. Study participants had a median age of 67 years (55, 78) and 71% were female. NT ‐pro BNP levels were inversely correlated with BMI ( P NT ‐pro BNP levels were associated with higher 180‐day mortality (adjusted hazard ratio for each doubling of NT ‐pro BNP, 1.40; 95% confidence interval, 1.16, 1.71; P NT ‐pro BNP on 180‐day death was not modified by BMI class (interaction P =0.24). Conclusions The prognostic value of NT ‐pro BNP was not modified by BMI in this acute heart failure population. NT ‐pro BNP remains a useful prognostic indicator of long‐term mortality in acute heart failure even in the obese patient. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT00475852.

Although the prognosis of ambulatory heart failure (HF) has improved dramatically there have been few advances in the management of acute HF (AHF). Despite regional differences in patient characteristics, background therapy, and event rates, AHF clinical trial enrollment has transitioned from North America and Western Europe to Eastern Europe, South America, and Asia-Pacific where regulatory burden and cost of conducting research may be less prohibitive. It is unclear if the results of clinical trials conducted outside of North America are generalizable to US patient populations. This article uses AHF as a paradigm and identifies barriers and practical solutions to successfully conducting site-based research in North America.

Alternatives have emerged for patients ineligible for cardiac transplantation under standard criteria. The purpose of our study was to compare outcomes in patients ineligible for cardiac transplantation under standard criteria, treated either with extended criteria cardiac transplantation (ECCT) or a continuous flow destination therapy left ventricular assist device (CF DT-LVAD). From 2005 to 2012, patients treated with either ECCT or CF DT-LVAD at our institution were retrospectively analyzed. In the overall unmatched cohort, we examined mortality and other outcomes, including index hospitalization length of stay, renal function, stroke, and readmission rates. After propensity score (PS) matching, outcomes were compared between ECCT and CF DT-LVAD recipients. Overall, 62 patients underwent ECCT, and 146 patients were treated with CF DT-LVAD. The 2-year mortality estimate for ECCT recipients was 27.3% (95% confidence interval 15.5% to 39.1%) and for CF DT-LVAD recipients was 11.2% (95% confidence interval 4.8% to 17.6%). After PS matching of 39 patients from each treatment group, there was no significant difference in overall survival after 2 years (p = 0.346). In both unmatched and PS-matched analyses, CF DT-LVAD patients compared with ECCT had a significantly higher estimated glomerular filtration rate at 1 year but also had significantly higher hospital readmission rates. Stroke also more commonly occurred after CF DT-LVAD compared with ECCT (17 vs 5, unmatched; and 2 vs 1, PS matched). However, there was no significant difference between PS-matched groups in 2-year stroke-free survival (p = 0.371). In conclusion, ECCT and CF DT-LVAD in select patients are comparable therapies with respect to 2-year survival.

Importance Pragmatic clinical trial designs have proposed the use of medical claims data to ascertain clinical events; however, the accuracy of billed diagnoses in identifying potential events is unclear. Objectives To compare the 1-year cumulative incidences of events when events were identified by medical claims vs by physician adjudication and to assess the accuracy of bill-identified events using physician adjudication as the criterion standard. Design, Setting, and Participants This post hoc analysis of a clinical trial assessed the medical claims forms and records for all rehospitalizations at 233 US hospitals within 1 year of the index acute myocardial infarction (MI) of 12 365 patients enrolled in the Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) study between April 1, 2010, and October 31, 2012. Fourteen patients (0.1%) died during the index hospitalization and were excluded from analysis. Recurrent MI, stroke, and bleeding events were identified per theInternational Classification of Diseases, Ninth Revision, Clinical Modificationdiagnosis and procedural codes in medical bills. These events were independently adjudicated by study physicians through medical record reviews using the prespecified criteria of recurrent MI and stroke and the bleeding definition by the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) scale. Medical claims were reported on a Uniform Bill-04 claims form; claims were collected from all hospitals visited by patients enrolled in TRANSLATE-ACS. Agreement between medical claims–identified events and physician-adjudicated events over the 12 months after discharge was assessed with the κ statistic. Data were analyzed from January 30, 2015, to March 2, 2017. Main Outcomes and Measures Event rates within 1 year after MI. Results Among 12 365 patients with acute MI, 8890 (71.9%) were men and mean (SD) age was 60 (11.6) years. The cumulative 1-year incidence of events identified by medical claims was 4.3% for MI, 0.9% for stroke, and 5.0% for bleeding. Incidence rates based on physician adjudication were 4.7% for MI, 0.9% for stroke, and 5.4% for bleeding. Agreement between medical claims–identified and physician-adjudicated events was modest, with a κ of 0.76 (95% CI, 0.73 to 0.79) for MI and 0.55 (95% CI, 0.41 to 0.68) for stroke events. In contrast, agreement between medical claims–identified and physician-adjudicated bleeding events was poor, with a κ of 0.24 (95% CI, 0.19 to 0.30) for any hospitalized bleeding event and 0.15 (95% CI, 0.11 to 0.20) for moderate or severe bleeding on the GUSTO scale. Conclusions and Relevance Event rates at 1 year after MI were lower for MI, stroke, and bleeding when medical claims were used to identify events than when adjudicated by physicians. Medical claims diagnoses were only modestly accurate in identifying MI and stroke admissions but had limited accuracy for bleeding events. An alternative approach may be needed to ensure good safety surveillance in cardiovascular studies. Trial Registration clinicaltrials.gov Identifier:NCT01088503

Background: Pragmatic clinical trial designs have proposed the use of claims data to ascertain clinical events. However, little is known about the accuracy of medical claims diagnosis in identifying events. Methods: Administrative claims were obtained for all rehospitalizations occurring within 12 months of index acute myocardial infarction (MI) in those enrolled in the TRANSLATE-ACS study. Outcome events (recurrent myocardial infarction [MI], stroke, and hospitalized bleeding) were identified based on all diagnosis and procedure codes in these claims. These clinical events were also independently adjudicated by physicians based on medical record review. The cumulative 1-year incidences for each outcome were compared when identified by administrative claims vs. physician adjudication. Kappa statistics assessed the accuracy of claims-identified events using physician adjudication as the gold standard. Results: Among 12,351 MI patients, the cumulative 1-year incidence of events identified by administrative claims were 4.3% for MI, 0.9% for stroke, and 5.0% for bleeding. Incidence rates based on physician adjudication of medical records were 4.7% for MI, 0.9% for stroke, and 5.4% for bleeding. Agreement between claims-identified and physician-adjudicated events was modest for MI and stroke events: kappa=0.76 and 0.55, respectively. In contrast, agreement was poor between claims-identified and physician-adjudicated bleeding events: kappa=0.24 for any hospitalized bleeding event and 0.15 for GUSTO moderate-severe bleeding. Conclusion: Event rates at 1 year were lower for MI, stroke and bleeding when using administrative claims to identify events in comparison with physician adjudication. Administrative claims diagnoses are modestly accurate in identifying recurrent MI and stroke admissions but have limited accuracy in identifying bleeding events, which suggests that an alternative approach is needed to ensure good safety surveillance in cardiovascular studies.

Advanced heart failure (HF) is characterized by high morbidity and mortality. Conventional therapy may not sufficiently reduce patient suffering and maximize quality of life.The authors investigated whether an interdisciplinary palliative care intervention in addition to evidence-based HF care improves certain outcomes.The authors randomized 150 patients with advanced HF between August 15, 2012, and June 25, 2015, to usual care (UC) (n = 75) or UC plus a palliative care intervention (UC + PAL) (n = 75) at a single center. Primary endpoints were 2 quality-of-life measurements, the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary and the Functional Assessment of Chronic Illness Therapy-Palliative Care scale (FACIT-Pal), assessed at 6 months. Secondary endpoints included assessments of depression and anxiety (measured via the Hospital Anxiety and Depression Scale [HADS]), spiritual well-being (measured via the FACIT-Spiritual Well-Being scale [FACIT-Sp]), hospitalizations, and mortality.Patients randomized to UC + PAL versus UC alone had clinically significant incremental improvement in KCCQ and FACIT-Pal scores from randomization to 6 months (KCCQ difference = 9.49 points, 95% confidence interval [CI]: 0.94 to 18.05, p = 0.030; FACIT-Pal difference = 11.77 points, 95% CI: 0.84 to 22.71, p = 0.035). Depression improved in UC + PAL patients (HADS-depression difference = -1.94 points; p = 0.020) versus UC-alone patients, with similar findings for anxiety (HADS-anxiety difference = -1.83 points; p = 0.048). Spiritual well-being was improved in UC + PAL versus UC-alone patients (FACIT-Sp difference = 3.98 points; p = 0.027). Randomization to UC + PAL did not affect rehospitalization or mortality.An interdisciplinary palliative care intervention in advanced HF patients showed consistently greater benefits in quality of life, anxiety, depression, and spiritual well-being compared with UC alone. (Palliative Care in Heart Failure [PAL-HF]; NCT01589601).

CIED Removal in LVAD Infections Introduction Heart failure patients with left ventricular assist devices (LVADs) are at risk for infection. Cardiac implantable electronic devices (CIEDs) are commonly present in these patients. The course of infections in patients with an LVAD and a CIED is not well described. Methods and Results We identified 6 patients with a durable LVAD that underwent CIED removal because of an LVAD associated infection (LVADI). Patient and infection characteristics, management strategy, and clinical outcomes are described. All 6 patients were male, and the mean age was 59.6 years (range 43–72). Four of 6 patients had an ischemic cardiomyopathy, and 3 patients were diabetic. The median creatinine clearance for patients was 40.5 mg/dL (range 19–65). Five of 6 patients had a continuous flow LVAD placed as destination therapy. Four of 6 patients had a previous LVADI managed medically before the current infection leading to CIED removal. The indication for CIED removal was a bloodstream infection in 5 of 6 patients. Three of these patients had potential vegetations identified by echocardiography on device leads. The mean implanted age of the removed leads was 62 months (range 1–179), and 1 of the 6 patients experienced a procedural complication (hematoma) from CIED removal. Four of 6 patients that underwent CIED removal for an LVADI had recurrence of infection. Five of 6 patients died during the initial presentation or from repeat presentation for infection. Conclusion Despite CIED removal for an LVADI, recurrent infections are common and mortality remains high.

In patients with atrial fibrillation (AF), oral anticoagulation is used to prevent stroke and systemic embolism. In a common clinical scenario, AF patients frequently undergo invasive procedures requiring temporary interruption of oral anticoagulation, thereby potentially exposing such patients to increased risk of thromboembolism. Bridging anticoagulation has been used clinically to mitigate this perceived thromboembolic risk, though this practice may also increase risk of periprocedural bleeding. High-quality data has not previously existed to inform decision-making in this clinical situation of bridging anticoagulation. We discuss recent results from the BRIDGE trial and secondary analyses from recent phase 3 randomized clinical trials of direct-acting oral anticoagulant (DOAC) use in non-valvular AF, that inform periprocedural anticoagulation with bridging strategies in AF patients. Updated data from these current trials favor against a strategy of bridging anticoagulation for elective procedures in the majority of AF patients, low or moderate in thromboembolic risk. Bridging anticoagulation is associated with an increased risk of bleeding and no decreased risk of thromboembolism.

Intra-aortic balloon pumps (IABPs) provide primarily left ventricular support, yet few data detail the efficacy of this temporary mechanical circulatory support device in patients with concomitant right ventricular failure. We compared the efficacy of IABPs in cardiogenic shock patients with isolated left ventricular versus biventricular failure.IABP-treated cardiogenic shock patients were identified from our center between 2006 and 2012, with patients stratified by either isolated left ventricular failure or biventricular failure. We compared baseline characteristics and 72-hour and 30-day outcomes between groups. Outcomes of interest included escalation of mechanical circulatory support, a clinical definition of IABP failure, and death.Among 107 patients, 60 patients (56%) had isolated left ventricular failure compared with 47 patients (44%) having biventricular failure. Patients with isolated left ventricular failure were older and more likely to have coronary artery disease ( p0.05, both). Patients with biventricular failure more often required escalation of mechanical circulatory support at both 72 hours (21% vs. 2%, p0.001) and 30 days (36% vs. 30%). However, there was no significant difference between groups for failure of IABP therapy at 72 hours ( p=0.27) or at 30 days ( p=0.62) and death at 30 days ( p=0.98). In adjusted analysis, there was no significant difference between groups with regard to risk for a clinical definition of IABP failure at 30 days (odds ratio=0.85, 95% confidence interval (0.27, 2.69)).IABP-treated cardiogenic shock patients with biventricular failure more often required early escalation of mechanical circulatory support. However, there were no significant differences by type of ventricular failure with regard to 30-day outcomes.

Higher rates of obesity and heart failure have been observed in African Americans, but associations with mortality are not well-described. We examined intermediate and long-term clinical implications of obesity in African Americans and associations between obesity and all-cause mortality, heart failure, and heart failure hospitalization.We conducted a retrospective analysis of a community sample of 5292 African Americans participating in the Jackson Heart Study between September 2000 and January 2013. The main outcomes were associations between body mass index (BMI) and all-cause mortality at 9 years and heart failure hospitalization at 7 years using Cox proportional hazards models and interval development of heart failure (median 8 years' follow-up) using a modified Poisson model. At baseline, 1406 (27%) participants were obese and 1416 (27%) were morbidly obese. With increasing BMI, the cumulative incidence of mortality decreased (P= .007), whereas heart failure increased (P .001). Heart failure hospitalization was more common among morbidly obese participants (9.0%; 95% confidence interval [CI] 7.6-11.7) than among normal-weight patients (6.3%; 95% CI 4.7-8.4). After risk adjustment, BMI was not associated with mortality. Each 1-point increase in BMI was associated with a 5% increase in the risk of heart failure (hazard ratio 1.05; 95% CI 1.03-1.06; P .001) and the risk of heart failure hospitalization for BMI greater than 32 kg/m(2) (hazard ratio 1.05; 95% CI 1.03-1.07; P .001).Obesity and morbid obesity were common in a community sample of African Americans, and both were associated with increased heart failure and heart failure hospitalization.

Although the prognosis of ambulatory heart failure (HF) has improved dramatically there have been few advances in the management of acute HF (AHF). Despite regional differences in patient characteristics, background therapy, and event rates, AHF clinical trial enrollment has transitioned from North America and Western Europe to Eastern Europe, South America, and Asia-Pacific where regulatory burden and cost of conducting research may be less prohibitive. It is unclear if the results of clinical trials conducted outside of North America are generalizable to US patient populations. This article uses AHF as a paradigm and identifies barriers and practical solutions to successfully conducting site-based research in North America.

Background Cardiac allografts are routinely evaluated by left ventricular ejection fraction (LVEF) before and after transplantation. However, myocardial deformation analyses with LV global longitudinal strain (GLS) are more sensitive for detecting impaired LV myocardial systolic performance compared with LVEF. Methods We analyzed echocardiograms in 34 heart donor-recipient pairs transplanted at Duke University from 2000 to 2013. Assessments of allograft LV systolic function by LVEF and/or LV GLS were performed on echocardiograms obtained pre-explanation in donors and serially in corresponding recipients. Results Donors had a median LVEF of 55% (25th, 75th percentile, 54% to 60%). Median donor LV GLS was −14.6% (−13.7 to −17.3%); LV GLS was abnormal (ie, >−16%) in 68% of donors. Post-transplantation, LV GLS was further impaired at 6 weeks (median -11.8%; −11.0 to −13.4%) and 3 months (median −11.4%; −10.3 to −13.9%) before recovering to pretransplant levels in follow-up. Median LVEF remained ≥50% throughout follow-up. We found no association between donor LV GLS and post-transplant outcomes, including all-cause hospitalization and mortality. Conclusions GLS demonstrates allograft LV systolic dysfunction in donors and recipients not detected by LVEF. The clinical implications of subclinical allograft dysfunction detected by LV GLS require further study.

Background: Few studies have described the accuracy of patient-reported hospitalizations and characterized patients who either under- or over-report hospitalizations. Methods: At scheduled interviews 6 weeks, 6 and 12 months after discharge, acute MI patients in the TRANSLATE-ACS study were asked to report any rehospitalizations. Bills from hospitals in the patient’s geographic area and from 12-month queries at the discharging institution were obtained to confirm reported and screen for unreported hospitalizations. We assessed the accuracy of patient-reported hospitalizations with bill validation as the reference. We also examined the characteristics of patients who accurately, over-, or under-reported the number of hospitalizations. Results: Among 12,302 acute MI patients, 5,668 patients (46%) reported 8,716 rehospitalizations within the 1 year post-discharge. Only 59% of patient-reported hospitalizations were confirmed by medical bill data (Table). Among the total number of hospital bills collected, 34% were never reported by the patient. Among 5,688 patients confirmed to be rehospitalized, 41% accurately reported the number of hospitalizations, 37% over-reported by a range of 1-12 hospitalizations (median 1) and 22% under-reported by 1-19 hospitalizations (median 1). Compared with accurate reporters, under-reporters were more likely to be female (36% vs. 31%), non-white race (17% vs. 12%), unemployed (67% vs. 54%), non-high school graduate (19% vs. 12%) or to have lower functional status (median EQ5D VAS score 65 vs. 75, p Conclusions: In a large community-based study, the accuracy of patient-reported hospitalizations was low when compared with validation by medical bills, with patients both under- and over-reporting events.

The novel oral anticoagulants (NOACs) have rapidly emerged as an alternative therapy to warfarin. Several recent phase 3 randomized control trials have demonstrated the efficacy and safety of the NOACs in the treatment for patients with nonvalvular atrial fibrillation. As the NOACs are incorporated in clinical practice, questions have begun to arise concerning their optimal use in commonly encountered situations. In this review, we provide a summary of the available evidence from the phase 3 randomized control trials specifically with regard to 1 such scenario, the periprocedural management of NOACs, with a goal of providing guidance for practicing clinicians.

Purpose of review Fluid removal and relief of congestion are central to treatment of acute heart failure. Diuretics have been the decongestive mainstay but their known limitations have led to the exploration of alternative strategies. This review compares diuretics with ultrafiltration and examines the recent evidence evaluating their use. Recent findings Relevant recent studies are the Diuretic Optimization Strategies Evaluation trial (of diuretics) and the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (of ultrafiltration). The Diuretic Optimization Strategies Evaluation study evaluated strategies of loop diuretic use during acute heart failure (continuous infusion versus intermittent bolus and high dose versus low dose). After 72 h, there was no significant difference with either comparison for the coprimary end points. Patients treated with a high-dose strategy tended to have greater diuresis and more decongestion compared with low-dose therapy, at the cost of transient changes in renal function. The Cardiorenal Rescue Study in Acute Decompensated Heart Failure study showed that in acute heart failure patients with persistent congestion and worsening renal function, ultrafiltration, as compared with a medical therapy, was associated with similar weight loss but greater increase in serum creatinine and more adverse events. Summary Decongestion remains a major challenge in acute heart failure. Although recent studies provide useful data to guide practice, the relatively poor outcomes point to the continued need to identify better strategies for safe and effective decongestion.

Transient and persistent worsening renal function (WRF) may be associated with different risks during hospitalization for acute heart failure. We compared outcomes of patients hospitalized for acute heart failure with transient, persistent, or no WRF.We identified patients 65 years or older hospitalized with acute heart failure from a clinical registry linked to Medicare claims data. We defined WRF as an increase in serum creatinine of ≥ 0.3 mg/dL after admission. We further classified patients with WRF by the difference between admission and last recorded serum creatinine levels into transient WRF (0.3 mg/dL) or persistent WRF (≥ 0.3 mg/dL). We examined unadjusted rates and adjusted associations between 90-day outcomes and WRF status.Among 27,309 patients, 18,568 (68.0%) had no WRF, 3,205 (11.7%) had transient WRF, and 5,536 (20.3%) had persistent WRF. Patients with WRF had higher observed rates of 90-day postdischarge all-cause readmission and 90-day postadmission mortality (P.001). After multivariable adjustment, transient WRF (hazard ratio [HR] 1.19, 99% CI 1.05-1.35) and persistent WRF (HR 1.73, 99% CI 1.57-1.91) were associated with higher risks of 90-day postadmission mortality (P.001 for both). Compared with transient WRF, persistent WRF was associated with a higher risk of 90-day postadmission mortality (HR 1.46, 99% CI 1.28-1.66, P.001).Transient and persistent WRF during hospitalization for acute heart failure were associated with higher adjusted risks for 90-day all-cause postadmission mortality. Patients with persistent WRF had worse outcomes.

Heart failure patients with left ventricular assist devices (LVADs) are at risk for infection. Cardiac implantable electronic devices (CIEDs) are commonly present in these patients. The course of infections in patients with an LVAD and a CIED is not well described.We identified 6 patients with a durable LVAD that underwent CIED removal because of an LVAD associated infection (LVADI). Patient and infection characteristics, management strategy, and clinical outcomes are described. All 6 patients were male, and the mean age was 59.6 years (range 43-72). Four of 6 patients had an ischemic cardiomyopathy, and 3 patients were diabetic. The median creatinine clearance for patients was 40.5 mg/dL (range 19-65). Five of 6 patients had a continuous flow LVAD placed as destination therapy. Four of 6 patients had a previous LVADI managed medically before the current infection leading to CIED removal. The indication for CIED removal was a bloodstream infection in 5 of 6 patients. Three of these patients had potential vegetations identified by echocardiography on device leads. The mean implanted age of the removed leads was 62 months (range 1-179), and 1 of the 6 patients experienced a procedural complication (hematoma) from CIED removal. Four of 6 patients that underwent CIED removal for an LVADI had recurrence of infection. Five of 6 patients died during the initial presentation or from repeat presentation for infection.Despite CIED removal for an LVADI, recurrent infections are common and mortality remains high.

Background Aortic insufficiency (AI) in patients supported with continuous-flow left ventricular assist devices (CF-LVAD) results in regurgitant volume returning from the aorta to the left ventricle, increased LVAD pump volume and reduced systemic cardiac output. One common strategy to address AI during CF-LVAD support is central oversewing of the aortic valve, which allows some opening between the valve leaflets laterally. However, the long-term durability of this technique has not been extensively described. Methods All patients who underwent central oversewing of the aortic valve during CF-LVAD support between January 2006 and March 2013 were included in this analysis. Pre- and post-procedure intra-operative transesophageal echocardiograms (TEEs) were reviewed to determine the efficacy of the surgical technique, whereas all subsequent transthoracic echocardiograms (TTEs) were reviewed to assess durability. AI severity was graded using the vena contracta (VC) width and the ratio between the VC and left ventricular outflow tract (LVOT) diameter. Results Nineteen patients with central aortic valve oversewing were identified. Median follow-up was 560 days (range 46 to 954 days). All but 1 patient had their aortic insufficiency reduced to "none/trace" on post-operative TEE. There was no statistically significant increase in the VC width and VC/LVOT ratio between the first and last follow-up echocardiograms, and only 2 patients developed more than mild aortic insufficiency after central oversewing. Central oversewing of the aortic valve did not adversely affect outcomes after LVAD implantation. Conclusion Central oversewing of the aortic valve is an effective and durable means of addressing greater than mild AI in patients with CF-LVAD.

Primary adrenal insufficiency or Addison's disease is a rare disorder often difficult to diagnose on presentation by the nature of its associated nonspecific symptoms, such as nausea or weakness. Cardiovascular complications of the condition are usually limited to hypovolemic hypotension; however, we highlight here a rare, dramatic case of a fulminant adrenal crisis in a young man primarily marked by acute biventricular systolic failure and cardiogenic shock. The patient was successfully treated with corticosteroid replacement and bridged with temporary mechanical circulatory support to eventual complete the recovery of native myocardial function.

Many studies have shown that the systemic administration of cytokines or vaccination with cytokine-secreting tumors augments an antitumor immune response that can result in eradication of tumors. However, these approaches are hampered by the risk of systemic toxicity induced by soluble cytokines. In this study, we have evaluated the efficacy of 4TO7, a highly tumorigenic murine mammary tumor cell line, expressing glycosyl phosphatidylinositol (GPI)-anchored form of cytokine molecules alone or in combination with the costimulatory molecule B7-1 as a model for potential cell or membrane-based breast cancer vaccines. We observed that the GPI-anchored cytokines expressed on the surface of tumor cells greatly reduced the overall tumorigenicity of the 4TO7 tumor cells following direct live cell challenge as evidenced by transient tumor growth and complete regression within 30 days post challenge. Tumors co-expressing B7-1 and GPI-IL-12 grew the least and for the shortest duration, suggesting that this combination of immunostimulatory molecules is most potent. Protective immune responses were also observed following secondary tumor challenge. Further, the 4TO7-B7-1/GPI-IL-2 and 4TO7-B7-1/GPI-IL-12 transfectants were capable of inducing regression of a wild-type tumor growing at a distant site in a concomitant tumor challenge model, suggesting the tumor immunity elicited by the transfectants can act systemically and inhibit the tumor growth at a distant site. Additionally, when used as irradiated whole cell vaccines, 4TO7-B7-1/GPI-IL-12 led to a significant inhibition in tumor growth of day 7 established tumors. Lastly, we observed a significant decrease in the prevalence of myeloid-derived suppressor cells and regulatory T-cells in the tumor microenvironment on day 7 post challenge with 4TO7-B7-1/GPI-IL-12 cells, which provides mechanistic insight into antitumor efficacy of the tumor-cell membrane expressed IL-12. These studies have implications in designing membrane-based therapeutic vaccines with GPI-anchored cytokines for breast cancer.

(aged 67610 years, n514 HFpEF, n512 control) underwent right heart catheterization at rest, during supine exercise, and with acute saline loading in a prospective study. Exercise and saline each increased cardiac output (CO) and pressures in the right atrium (RAP), pulmonary artery (PAP), and pulmonary capillary wedge positions (PCWP). However, the magnitudes of change were much greater with exercise compared to saline for mean PAP (+1769 vs +865 mmHg; p!0.0001), PCWP (+1368 vs +964mmHg; p50.01) and CO (+5.162.7 vs +1.861.3 L/min; p! 0.0001). These differential responses were restricted to the HFpEF group, who experienced w2-fold greater increases in PCWP with exercise compared to saline (+1865 vs +1064; p50.0002, Figure), in contrast to controls where changes in PCWP were similar with the two stresses (+664 vs +764mmHg, p50.46, Figure). The slope of increase in PCWP relative to the volume of saline infused was similar in HFpEF and controls (+23610 vs +1768 mmHg/ml/m, p50.11) whereas the slope of increase in PCWP from baseline to 20-Watts exercise was 3-fold steeper in HFpEF compared to controls (+0.860.3 vs +0.362 mmHg/Watt; p!0.0001). Conclusions: Exercise elicits greater PCWP elevation compared to saline in HFpEF but not controls, suggesting that hemodynamic stresses beyond passive stiffness and increased venous return explain the development of exertional pulmonary venous hypertension in HFpEF. Saline loading is less sensitive than exercise to detect hemodynamic abnormalities diagnostic of HFpEF.