Advocate Christ Medical Center

BACKGROUND: Patients with advanced heart failure have improved survival rates and quality of life when treated with implanted pulsatile-flow left ventricular assist devices as compared with medical therapy. New continuous-flow devices are smaller and may be more durable than the pulsatile-flow devices. METHODS: In this randomized trial, we enrolled patients with advanced heart failure who were ineligible for transplantation, in a 2:1 ratio, to undergo implantation of a continuous-flow device (134 patients) or the currently approved pulsatile-flow device (66 patients). The primary composite end point was, at 2 years, survival free from disabling stroke and reoperation to repair or replace the device. Secondary end points included survival, frequency of adverse events, the quality of life, and functional capacity. RESULTS: Preoperative characteristics were similar in the two treatment groups, with a median age of 64 years (range, 26 to 81), a mean left ventricular ejection fraction of 17%, and nearly 80% of patients receiving intravenous inotropic agents. The primary composite end point was achieved in more patients with continuous-flow devices than with pulsatile-flow devices (62 of 134 [46%] vs. 7 of 66 [11%]; P<0.001; hazard ratio, 0.38; 95% confidence interval, 0.27 to 0.54; P<0.001), and patients with continuous-flow devices had superior actuarial survival rates at 2 years (58% vs. 24%, P=0.008). Adverse events and device replacements were less frequent in patients with the continuous-flow device. The quality of life and functional capacity improved significantly in both groups. CONCLUSIONS: Treatment with a continuous-flow left ventricular assist device in patients with advanced heart failure significantly improved the probability of survival free from stroke and device failure at 2 years as compared with a pulsatile device. Both devices significantly improved the quality of life and functional capacity. (ClinicalTrials.gov number, NCT00121485.)

BACKGROUND: 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. METHODS: 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. RESULTS: 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; P<0.001 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; P<0.001). 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. CONCLUSIONS: 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.).

BACKGROUND: Mechanical circulatory support with a left ventricular assist device (LVAD) is an established treatment for patients with advanced heart failure. We compared a newer LVAD design (a small intrapericardial centrifugal-flow device) against existing technology (a commercially available axial-flow device) in patients with advanced heart failure who were ineligible for heart transplantation. METHODS: We conducted a multicenter randomized trial involving 446 patients who were assigned, in a 2:1 ratio, to the study (centrifugal-flow) device or the control (axial-flow) device. Adults who met contemporary criteria for LVAD implantation for permanent use were eligible to participate in the trial. The primary end point was survival at 2 years free from disabling stroke or device removal for malfunction or failure. The trial was powered to show noninferiority with a margin of 15 percentage points. RESULTS: The intention-to treat-population included 297 participants assigned to the study device and 148 participants assigned to the control device. The primary end point was achieved in 164 patients in the study group and 85 patients in the control group. The analysis of the primary end point showed noninferiority of the study device relative to the control device (estimated success rates, 55.4% and 59.1%, respectively, calculated by the Weibull model; absolute difference, 3.7 percentage points; 95% upper confidence limit, 12.56 percentage points; P=0.01 for noninferiority). More patients in the control group than in the study group had device malfunction or device failure requiring replacement (16.2% vs. 8.8%), and more patients in the study group had strokes (29.7% vs. 12.1%). Quality of life and functional capacity improved to a similar degree in the two groups. CONCLUSIONS: In this trial involving patients with advanced heart failure who were ineligible for heart transplantation, a small, intrapericardial, centrifugal-flow LVAD was found to be noninferior to an axial-flow LVAD with respect to survival free from disabling stroke or device removal for malfunction or failure. (Funded by HeartWare; ENDURANCE ClinicalTrials.gov number, NCT01166347 .).

BACKGROUND: The landmark Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial first demonstrated that implantation of left ventricular assist devices (LVADs) as destination therapy (DT) can provide survival superior to any known medical treatment in patients with end-stage heart failure who are ineligible for transplantation. In the present study, we describe outcomes of DT in the post-REMATCH era in the United States. METHODS AND RESULTS: The present study included 280 patients who underwent HeartMate XVE LVAD implantation between November 2001 and December 2005. A preoperative risk score for in-hospital mortality after LVAD implantation was established in 222 patients with complete data. All patients were followed up until death or December 2006. The 1-year survival after LVAD implantation was 56%. The in-hospital mortality after LVAD surgery was 27%. The main causes of death included sepsis, right heart failure, and multiorgan failure. The most important determinants of in-hospital mortality were poor nutrition, hematological abnormalities, markers of end-organ or right ventricular dysfunction, and lack of inotropic support. Stratification of DT candidates into low (n=65), medium (n=111), high (n=28), and very high (n=18) risk on the basis of the risk score calculated from these predictors corresponded with 1-year survival rates of 81%, 62%, 28%, and 11%, respectively. CONCLUSIONS: Appropriate selection of candidates and timing of LVAD implantation are critical for improved outcomes of DT. Patients with advanced heart failure who are referred for DT before major complications of heart failure develop have the best chance of achieving an excellent 1-year survival with LVAD therapy.

BACKGROUND: 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. METHODS: 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 of >3; 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. RESULTS: 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 [P<0.001 for noninferiority]; hazard ratio, 0.46; 95% confidence interval [CI], 0.31 to 0.69 [P<0.001 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; P<0.001). 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). CONCLUSIONS: 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: The HeartWare left ventricular assist device (HVAD, HeartWare Inc, Framingham, MA) is the first implantable centrifugal continuous-flow pump approved for use as a bridge to transplantation. An infrequent but serious adverse event of LVAD support is thrombus ingestion or formation in the pump. In this study, we analyze the incidence of pump thrombus, evaluate the comparative effectiveness of various treatment strategies, and examine factors pre-disposing to the development of pump thrombus. METHODS: The analysis included 382 patients who underwent implantation of the HVAD as part of the HeartWare Bridge to Transplant (BTT) and subsequent Continued Access Protocol (CAP) trial. Descriptive statistics and group comparisons were generated to analyze baseline characteristics, incidence of pump thrombus, and treatment outcomes. A multivariate analysis was performed to assess significant risk factors for developing pump thrombus. RESULTS: There were 34 pump thrombus events observed in 31 patients (8.1% of the cohort) for a rate of 0.08 events per patient-year. The incidence of pump thrombus did not differ between BTT and CAP. Medical management of pump thrombus was attempted in 30 cases, and was successful in 15 (50%). A total of 16 patients underwent pump exchange, and 2 underwent urgent transplantation. Five patients with a pump thrombus died after medical therapy failed, 4 of whom also underwent a pump exchange. Survival at 1 year in patients with and without a pump thrombus was 69.4% and 85.5%, respectively (p = 0.21). A multivariable analysis revealed that significant risk factors for pump thrombus included a mean arterial pressure > 90 mm Hg, aspirin dose ≤ 81 mg, international normalized ratio ≤ 2, and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile level of ≥ 3 at implant. CONCLUSIONS: Pump thrombus is a clinically important adverse event in patients receiving an HVAD, occurring at a rate of 0.08 events per patient-year. Significant risk factors for pump thrombosis include elevated blood pressure and sub-optimal anti-coagulation and anti-platelet therapies. This suggests that pump thrombus event rates could be reduced through careful adherence to patient management guidelines.

BACKGROUND: SCIPIO is a first-in-human, phase 1, randomized, open-label trial of autologous c-kit(+) cardiac stem cells (CSCs) in patients with heart failure of ischemic etiology undergoing coronary artery bypass grafting (CABG). In the present study, we report the surgical aspects and interim cardiac magnetic resonance (CMR) results. METHODS AND RESULTS: A total of 33 patients (20 CSC-treated and 13 control subjects) met final eligibility criteria and were enrolled in SCIPIO. CSCs were isolated from the right atrial appendage harvested and processed during surgery. Harvesting did not affect cardiopulmonary bypass, cross-clamp, or surgical times. In CSC-treated patients, CMR showed a marked increase in both LVEF (from 27.5 ± 1.6% to 35.1 ± 2.4% [P=0.004, n=8] and 41.2 ± 4.5% [P=0.013, n=5] at 4 and 12 months after CSC infusion, respectively) and regional EF in the CSC-infused territory. Infarct size (late gadolinium enhancement) decreased after CSC infusion (by manual delineation: -6.9 ± 1.5 g [-22.7%] at 4 months [P=0.002, n=9] and -9.8 ± 3.5 g [-30.2%] at 12 months [P=0.039, n=6]). LV nonviable mass decreased even more (-11.9 ± 2.5 g [-49.7%] at 4 months [P=0.001] and -14.7 ± 3.9 g [-58.6%] at 12 months [P=0.013]), whereas LV viable mass increased (+11.6 ± 5.1 g at 4 months after CSC infusion [P=0.055] and +31.5 ± 11.0 g at 12 months [P=0.035]). CONCLUSIONS: Isolation of CSCs from cardiac tissue obtained in the operating room is feasible and does not alter practices during CABG surgery. CMR shows that CSC infusion produces a striking improvement in both global and regional LV function, a reduction in infarct size, and an increase in viable tissue that persist at least 1 year and are consistent with cardiac regeneration. CLINICAL TRIAL REGISTRATION: This study is registered with clinicaltrials.gov, trial number NCT00474461.

Background: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. Methods: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0–2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. Results: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients ( P <0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06–1.79; P =0.02). Likewise, excellent outcome (modified Rankin Score 0–1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13–1.92; P =0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P =0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier. Conclusions: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

IMPORTANCE: Hyperkalemia is a common electrolyte abnormality that may be difficult to manage because of a lack of effective therapies. Sodium zirconium cyclosilicate is a nonabsorbed cation exchanger that selectively binds potassium in the intestine. OBJECTIVE: To evaluate the efficacy and safety of zirconium cyclosilicate for 28 days in patients with hyperkalemia. DESIGN, SETTING, AND PARTICIPANTS: HARMONIZE was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial evaluating zirconium cyclosilicate in outpatients with hyperkalemia (serum potassium ≥5.1 mEq/L) recruited from 44 sites in the United States, Australia, and South Africa (March-August 2014). INTERVENTIONS: Patients (n = 258) received 10 g of zirconium cyclosilicate 3 times daily in the initial 48-hour open-label phase. Patients (n = 237) achieving normokalemia (3.5-5.0 mEq/L) were then randomized to receive zirconium cyclosilicate, 5 g (n = 45 patients), 10 g (n = 51), or 15 g (n = 56), or placebo (n = 85) daily for 28 days. MAIN OUTCOMES AND MEASURES: The primary end point was mean serum potassium level in each zirconium cyclosilicate group vs placebo during days 8-29 of the randomized phase. RESULTS: In the open-label phase, serum potassium levels declined from 5.6 mEq/L at baseline to 4.5 mEq/L at 48 hours. Median time to normalization was 2.2 hours, with 84% of patients (95% CI, 79%-88%) achieving normokalemia by 24 hours and 98% (95% CI, 96%-99%) by 48 hours. In the randomized phase, serum potassium was significantly lower during days 8-29 with all 3 zirconium cyclosilicate doses vs placebo (4.8 mEq/L [95% CI, 4.6-4.9], 4.5 mEq/L [95% CI, 4.4-4.6], and 4.4 mEq/L [95% CI, 4.3-4.5] for 5 g, 10 g, and 15 g; 5.1 mEq/L [95% CI, 5.0-5.2] for placebo; P < .001 for all comparisons). The proportion of patients with mean potassium <5.1 mEq/L during days 8-29 was significantly higher in all zirconium cyclosilicate groups vs placebo (36/45 [80%], 45/50 [90%], and 51/54 [94%] for the 5-g, 10-g, and 15-g groups, vs 38/82 [46%] with placebo; P < .001 for each dose vs placebo). Adverse events were comparable between zirconium cyclosilicate and placebo, although edema was more common in the 15-g group (edema incidence: 2/85 [2%], 1/45 [2%], 3/51 [6%], and 8/56 [14%] patients in the placebo, 5-g, 10-g, and 15-g groups). Hypokalemia developed in 5/51 (10%) and 6/56 patients (11%) in the 10-g and 15-g zirconium cyclosilicate groups, vs none in the 5-g or placebo groups. CONCLUSIONS AND RELEVANCE: Among outpatients with hyperkalemia, open-label sodium zirconium cyclosilicate reduced serum potassium to normal levels within 48 hours; compared with placebo, all 3 doses of zirconium cyclosilicate resulted in lower potassium levels and a higher proportion of patients with normal potassium levels for up to 28 days. Further studies are needed to evaluate the efficacy and safety of zirconium cyclosilicate beyond 4 weeks and to assess long-term clinical outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02088073.

BACKGROUND: Within the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework, we performed a systematic review and developed evidence-based recommendations to answer the following PICO (Population, Intervention, Comparator, Outcomes) question: should patients who present pulseless after critical injuries (with and without signs of life after penetrating thoracic, extrathoracic, or blunt injuries) undergo emergency department thoracotomy (EDT) (vs. resuscitation without EDT) to improve survival and neurologically intact survival? METHODS: All patients who underwent EDT were included while those involving either prehospital resuscitative thoracotomy or operating room thoracotomy were excluded. Quantitative synthesis via meta-analysis was not possible because no comparison or control group (i.e., survival or neurologically intact survival data for similar patients who did not undergo EDT) was available for the PICO questions of interest. RESULTS: The 72 included studies provided 10,238 patients who underwent EDT. Patients presenting pulseless after penetrating thoracic injury had the most favorable EDT outcomes both with (survival, 182 [21.3%] of 853; neurologically intact survival, 53 [11.7%] of 454) and without (survival, 76 [8.3%] of 920; neurologically intact survival, 25 [3.9%] of 641) signs of life. In patients presenting pulseless after penetrating extrathoracic injury, EDT outcomes were more favorable with signs of life (survival, 25 [15.6%] of 160; neurologically intact survival, 14 [16.5%] of 85) than without (survival, 4 [2.9%] of 139; neurologically intact survival, 3 [5.0%] of 60). Outcomes after EDT in pulseless blunt injury patients were limited with signs of life (survival, 21 [4.6%] of 454; neurologically intact survival, 7 [2.4%] of 298) and dismal without signs of life (survival, 7 [0.7%] of 995; neurologically intact survival, 1 [0.1%] of 825). CONCLUSION: We strongly recommend that patients who present pulseless with signs of life after penetrating thoracic injury undergo EDT. We conditionally recommend EDT for patients who present pulseless and have absent signs of life after penetrating thoracic injury, present or absent signs of life after penetrating extrathoracic injury, or present signs of life after blunt injury. Lastly, we conditionally recommend against EDT for pulseless patients without signs of life after blunt injury. LEVEL OF EVIDENCE: Systematic review/guideline, level III.

Among the most exciting developments in the field of heart failure in recent times has been the rediscovery of the natriuretic peptide system and its pleuripotent effects on cardiac structure and function. This is particularly true of its natriuretic and hemodynamic effects. There has been an explosion of the knowledge base seeking to understand the wide range of homeostatic, regulatory, and counter-regulatory functions in which the natriuretic peptide system participates. Additional interest has been stimulated by advances in technology such as point-of-care and core laboratory BNP assays and the use of the recombinant B-type natriuretic peptide nesiritide as a treatment option. Despite this recent interest, the available literature lacks a comprehensive expert review of the current science and roles of natriuretic peptides for diagnostic, prognostic, screening, treatment monitoring, and therapeutic purposes. More importantly, a summary updating and guiding the clinician on most of these advances was lacking. An expert Consensus Panel with basic, methodological, and clinical expertise was convened to summarize current knowledge in these areas and the findings and consensus statements are contained herein.

BACKGROUND: The HeartMate II (HMII) destination therapy (DT) trial demonstrated significant improvements in outcomes in continuous-flow left ventricular assist devices compared with patients implanted with the pulsatile-flow HeartMate XVE. The primary hypothesis of the current study is that trial patients enrolled after the initial data cohort would have better clinical outcomes. METHODS AND RESULTS: Two hundred eighty-one patients who underwent HMII for DT from May 2007 to March 2009 (Mid Trial [MT] group) were compared with the initial 133 HMII patients from March 2005 to May 2007 (Early Trial [ET] group). Patient entry criteria were the same during the 2 time periods. Survival, adverse events, and quality of life were compared between the 2 groups. Baseline characteristics were similar between the groups. Compared with the ET group, patients in the MT group had reduced adverse event rates for bleeding requiring transfusions (1.66 versus 1.13 events per patient-year, P<0.001), sepsis (0.38 versus 0.27, P=0.025), device-related infections (0.47 versus 0.27, P<0.001), and hemorrhagic stroke (0.07 versus 0.03, P=0.01). Other event rates were similar between groups including ischemic stroke (0.06 versus 0.05 events per patient-year, P=0.57). Survival at 1 year in the MT group was 73% versus 68% in the ET group (P=0.21). Additionally, there was a significant reduction in deaths caused by hemorrhagic stroke (P=0.01). Quality of life improvements were significant in both the groups (P<0.001). CONCLUSIONS: The benefit of DT therapy with the HMII is confirmed in subsequent trial patients, with improved adverse event rates and a strong trend for improvements in survival. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00121485.

Posterior circulation strokes represent approximately 20% of all ischemic strokes (1, 2). In contrast to the anterior circulation, several differences in presenting symptoms, clinical evaluation, diagnostic testing, and management strategy exist presenting a challenge to the treating physician. This review will discuss the anatomical, etiological, and clinical classification of PC strokes, identify diagnostic pitfalls, and overview current therapeutic regimens.

BACKGROUND: Ventricular assist devices (VADs) improve survival and quality of life in patients with advanced heart failure, but their use is frequently complicated by infection. There are limited data on the microbiology and epidemiology of these infections. METHODS AND RESULTS: One hundred fifty patients scheduled for VAD implantation were enrolled (2006-2008) at 11 US cardiac centers and followed prospectively until transplantation, explantation for recovery, death, or for 1 year. Eighty-six patients (57%) received HeartMate II devices. Data were collected on potential preoperative, intraoperative, and postoperative risk factors for infection. Clinical, laboratory, and microbiological data were collected for suspected infections and evaluated by an infectious diseases specialist. Thirty-three patients (22%) developed 34 VAD-related infections with an incidence rate of 0.10 per 100 person-days (95% confidence interval, 0.073-0.142). The median time to infection was 68 days. The driveline was the most commonly infected site (n=28); 18 (64%) were associated with invasive disease. Staphylococci were the most common pathogen (47%), but pseudomonas or other Gram-negative bacteria caused 32% of infections. A history of depression and elevated baseline serum creatinine were independent predictors of VAD infection (adjusted hazard ratio=2.8 [P=0.007] and 1.7 [P=0.023], respectively). The HeartMate II was not associated with a decreased risk of infection. VAD infection increased 1-year mortality (adjusted hazard ratio=5.6; P<0.0001). CONCLUSIONS: This prospective, multicenter study demonstrates that infection frequently complicates VAD placement and is a continuing problem despite the use of newer, smaller devices. Depression and renal dysfunction may increase the risk of VAD infection. VAD infection is a serious consequence because it adversely affects patient survival. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01471795.

Importance: Sleep-related impairment in physicians is an occupational hazard associated with long and sometimes unpredictable work hours and may contribute to burnout and self-reported clinically significant medical error. Objective: To assess the associations between sleep-related impairment and occupational wellness indicators in physicians practicing at academic-affiliated medical centers and the association of sleep-related impairment with self-reported clinically significant medical errors, before and after adjusting for burnout. Design, Setting, and Participants: This cross-sectional study used physician wellness survey data collected from 11 academic-affiliated medical centers between November 2016 and October 2018. Analysis was completed in January 2020. A total of 19 384 attending physicians and 7257 house staff physicians at participating institutions were invited to complete a wellness survey. The sample of responders was used for this study. Exposures: Sleep-related impairment. Main Outcomes and Measures: Association between sleep-related impairment and occupational wellness indicators (ie, work exhaustion, interpersonal disengagement, overall burnout, and professional fulfillment) was hypothesized before data collection. Assessment of the associations of sleep-related impairment and burnout with self-reported clinically significant medical errors (ie, error within the last year resulting in patient harm) was planned after data collection. Results: Of all physicians invited to participate in the survey, 7700 of 19 384 attending physicians (40%) and 3695 of 7257 house staff physicians (51%) completed sleep-related impairment items, including 5279 women (46%), 5187 men (46%), and 929 (8%) who self-identified as other gender or elected not to answer. Because of institutional variation in survey domain inclusion, self-reported medical error responses from 7538 physicians were available for analyses. Spearman correlations of sleep-related impairment with interpersonal disengagement (r = 0.51; P < .001), work exhaustion (r = 0.58; P < .001), and overall burnout (r = 0.59; P < .001) were large. Sleep-related impairment correlation with professional fulfillment (r = -0.40; P < .001) was moderate. In a multivariate model adjusted for gender, training status, medical specialty, and burnout level, compared with low sleep-related impairment levels, moderate, high, and very high levels were associated with increased odds of self-reported clinically significant medical error, by 53% (odds ratio, 1.53; 95% CI, 1.12-2.09), 96% (odds ratio, 1.96; 95% CI, 1.46-2.63), and 97% (odds ratio, 1.97; 95% CI, 1.45-2.69), respectively. Conclusions and Relevance: In this study, sleep-related impairment was associated with increased burnout, decreased professional fulfillment, and increased self-reported clinically significant medical error. Interventions to mitigate sleep-related impairment in physicians are warranted.

A consensus conference on frailty in kidney, liver, heart, and lung transplantation sponsored by the American Society of Transplantation (AST) and endorsed by the American Society of Nephrology (ASN), the American Society of Transplant Surgeons (ASTS), and the Canadian Society of Transplantation (CST) took place on February 11, 2018 in Phoenix, Arizona. Input from the transplant community through scheduled conference calls enabled wide discussion of current concepts in frailty, exploration of best practices for frailty risk assessment of transplant candidates and for management after transplant, and development of ideas for future research. A current understanding of frailty was compiled by each of the solid organ groups and is presented in this paper. Frailty is a common entity in patients with end-stage organ disease who are awaiting organ transplantation, and affects mortality on the waitlist and in the posttransplant period. The optimal methods by which frailty should be measured in each organ group are yet to be determined, but studies are underway. Interventions to reverse frailty vary among organ groups and appear promising. This conference achieved its intent to highlight the importance of frailty in organ transplantation and to plant the seeds for further discussion and research in this field.

Social Media usage has been shown to increase in situations of natural disaster and other crises. It is crucial for the scientific community to understand how social media works in order to enhance our capabilities and make a more resilient community. Through social media communication, the scientific community can collaborate around the globe in a faster way the most important findings of a disease, with a decreased knowledge transition time to other healthcare providers (HCPs). This is greatly important to coordinate research and knowledge during a time of uncertainty and protentional fake news. During the 2020 global pandemic, social media has become an ally but also a potential threat. High volumes of information compressed into a short period can result in overwhelmed HCPs trying to discern fact from noise. A major limitation of social media currently is the ability to quickly disseminate false information which can confuse and distract. Society relies on educated scientists and physicians to be leaders in delivering fact-based information to the public. For this reason, in times of crises it is important to be leaders in the conversation of social media to guide correct and helpful information and knowledge to the masses looking for answers.

OBJECTIVES: The aim of this study was to prospectively evaluate the impact of blood pressure management on stroke rates in patients receiving the HeartWare HVAD System. BACKGROUND: The ENDURANCE trial demonstrated noninferiority of the HeartWare HVAD System versus control (HeartMate II) in patients with advanced heart failure ineligible for heart transplantation. However, stroke was more common in HVAD subjects. Post hoc analyses demonstrated increased mean arterial blood pressure as a significant independent risk factor for stroke. METHODS: The ENDURANCE Supplemental Trial was a prospective, multicenter evaluation of 465 patients with advanced heart failure ineligible for transplantation, randomized 2:1 to HVAD (n = 308) or control (n = 157). The primary endpoint was the 12-month incidence of transient ischemic attack or stroke with residual deficit 24 weeks post-event. Secondary endpoints included the composite of freedom from death, disabling stroke, and need for device replacement or urgent transplantation, as well as comparisons of stroke or transient ischemic attack rates in HVAD cohorts in ENDURANCE Supplemental and ENDURANCE. RESULTS: The enhanced blood pressure protocol significantly reduced mean arterial blood pressure. The primary endpoint was not achieved (14.7% with HVAD vs. 12.1% with control, noninferiority [margin 6%] p = 0.14). However, the secondary composite endpoint demonstrated superiority of HVAD (76.1%) versus control (66.9%) (p = 0.04). The incidence of stroke in HVAD subjects was reduced 24.2% in ENDURANCE Supplemental compared with ENDURANCE (p = 0.10), and hemorrhagic cerebrovascular accident was reduced by 50.5% (p = 0.02). CONCLUSIONS: The ENDURANCE Supplemental Trial failed to demonstrate noninferiority of HVAD versus control regarding the pre-specified primary endpoint. However, the trial confirmed that BP management is associated with reduced stroke rates in HVAD subjects. HVAD subjects, relative to control subjects, more commonly achieved the composite endpoint (freedom from death, disabling stroke, and device replacement or urgent transplantation). (A Clinical Trial to Evaluate the HeartWare™ Ventricular Assist System [ENDURANCE SUPPLEMENTAL TRIAL] [DT2]; NCT01966458).

Kidney transplantation (KT) is the optimal therapy for end-stage kidney disease (ESKD), resulting in significant improvement in survival as well as quality of life when compared with maintenance dialysis. The burden of cardiovascular disease (CVD) in ESKD is reduced after KT; however, it still remains the leading cause of premature patient and allograft loss, as well as a source of significant morbidity and healthcare costs. All major phenotypes of CVD including coronary artery disease, heart failure, valvular heart disease, arrhythmias and pulmonary hypertension are represented in the KT recipient population. Pre-existing risk factors for CVD in the KT recipient are amplified by superimposed cardio-metabolic derangements after transplantation such as the metabolic effects of immunosuppressive regimens, obesity, posttransplant diabetes, hypertension, dyslipidemia and allograft dysfunction. This review summarizes the major risk factors for CVD in KT recipients and describes the individual phenotypes of overt CVD in this population. It highlights gaps in the existing literature to emphasize the need for future studies in those areas and optimize cardiovascular outcomes after KT. Finally, it outlines the need for a joint 'cardio-nephrology' clinical care model to ensure continuity, multidisciplinary collaboration and implementation of best clinical practices toward reducing CVD after KT.

OBJECTIVE: Comparison of health related quality of life (HRQOL) of patients with systemic lupus erythematosus (SLE) with other common chronic illnesses. METHODS: Responses from self-administered Medical Outcomes Study Short Form-36 (SF-36) questionnaires from 90 patients with SLE, recorded in the lupus database at the University of Chicago Hospital, were analyzed. Comparative norms and domain scores for patients with other chronic diseases [hypertension, congestive heart failure (CHF), adult onset diabetes mellitus, myocardial infarction, and depression] were used and are based on the general US population. T tests were used to make comparisons. RESULTS: Patients with SLE were younger than patients with most reference chronic conditions except for depression. Their Physical Component Scores and Mental Component Scores were 30 +/- 10.5 and 45.1 +/- 11, respectively. SLE patients fared significantly worse than age matched norms from the general US population for women (p = 0.0001) in all 8 domains. Their quality of life was significantly worse than for those with hypertension, diabetes, or myocardial infarction in all domains (p < 0.004). Patients with CHF were no worse than those with SLE in regard to physical function, role-physical, role-emotional, and vitality. CHF patients fared significantly better in mental health, bodily pain, social functioning, and general health, compared to patients with SLE. Patients with depression were significantly impaired in role-emotional and mental health domains (p = 0.0001) compared to SLE patients, but were no worse (role-physical, vitality, and social functioning) and even better (physical function, bodily pain, and general health) in some. General health of SLE patients was significantly lower than all comparative groups. CONCLUSION: HRQOL of patients with SLE seems to be significantly worse and affects all health domains at an earlier age in comparison to patients with some other common chronic diseases.