Search

Background Concerns regarding long-term durability of surgical repair for functional mitral regurgitation are based on short-term data, with few comparisons of ischemic (IMR) versus non-ischemic (NIFMR) etiology. Methods 788 consecutive patients receiving mitral repair for functional mitral regurgitation were evaluated from a prospectively maintained database. Patients with other surgical procedures were included. Propensity score matching was used to compare outcomes in IMR versus NIFMR. Results Unmatched IMR patients tended to be older men with greater comorbidities. 198 matched pairs of IMR versus NIFMR patients had similar demographics with relatively preserved ejection fraction 40±13% and end-systolic diameter 4.3±1.1cm. Concomitant coronary revascularization occurred in 70% of matched IMR patients. All patients received an annuloplasty ring, usually 24-26 mm. Heart failure class improved from 2.8 preop to 1.5 at 5 years (P =2+) mitral regurgitation (27±4% v 26±4%, P=0.4), severe regurgitation (10±3% v 8±2%, P=0.5), and mitral reoperation (3±1% v 3±1%, P=0.4) were not different between IMR v NIFMR. Recurrent moderate regurgitation was associated with heart failure readmission but not with mortality. Conclusions In propensity-matched patients, IMR versus NIFMR had worse survival but similar repair durability, with moderate regurgitation in 27% at 10 years and rare severe regurgitation or mitral reoperation. In selected patients with relatively preserved function, mitral repair for IMR or NIFMR can improve symptoms with durable mild regurgitation in most patients out to 10 years.

Long-term continuous-flow left ventricular assist device (CFLVAD) therapy is limited by complications. Compared with stroke and renal dysfunction, post-CFLVAD bowel ischemia is poorly characterized. Adult patients who underwent first-time durable CFLVAD implantation at our institution between 2008 and 2018 were identified and screened for bowel ischemia using Current Procedural Terminology codes for abdominal surgical exploration and International Classification of Disease codes for intestinal vascular insufficiency. Patients who developed biopsy-proven bowel ischemia (cases) were matched to controls (1:1, nearest neighbor, caliper = 0.29) based on preoperative characteristics. Incidences of postoperative right heart failure and renal replacement therapy were compared using McNemar's test. One year survival was estimated using the Kaplan-Meier method. Overall, 711 patients underwent CFLVAD implantation. Nineteen (2.7%) developed bowel ischemia (cases) median 17 days postimplantation (IQR 8-71). The majority of cases were male (78.9%), Black (63.2%), received HeartMate II (57.9%), treated as destination therapy (78.9%), and had a history of hypertension (89.5%), chronic kidney disease (84.2%), hyperlipidemia (84.2%), smoking (78.9%), and atrial fibrillation (57.9%). Post-LVAD, case patients were more likely to develop moderate-severe right heart failure (89.5% vs. 68.4%, p = 0.005), require renal replacement therapy (21.1% vs. 0%, p < 0.001), and less likely to survive to discharge (52.6% vs. 89.5%, p = 0.02) compared with controls. Case subjects demonstrated worse 1 year survival. While less common than stroke and renal dysfunction, post-CFLVAD bowel ischemia is associated with high 1 year mortality. Multi-institutional registries should consider reporting abdominal complications such as bowel ischemia as an adverse event to further investigate these trends and identify predictors of this complication to reduce patient mortality.

PURPOSE: Clinical models to identify patients at high risk of primary graft dysfunction (PGD) after heart transplantation (HT) are limited, and the underlying pathophysiology of this common post-transplant complication remains poorly understood. We sought to identify whether pre-transplant levels of circulating proteins reporting on immune activation and inflammation are associated with incident PGD. METHODS: The study population consisted of 219 adult heart transplant recipients identified between 2016 and 2020 at Duke University Medical Center, randomly divided into derivation (n = 131) and validation (n = 88) sets. PGD was defined using modified ISHLT criteria. Proteomic profiling was performed using Olink panels (n = 354 proteins) with serum samples collected immediately prior to transplantation. Association between normalized relative protein expression and PGD was tested using univariate and multivariable (recipient age, creatinine, mechanical circulatory support, and sex; donor age; ischemic time) models. Significant proteins identified in the derivation set (p < 0.05 in univariate models), were then tested in the validation set. Pathway enrichment analysis was used to test candidate biological processes. The predictive performance of proteins was compared to that of the RADIAL score. RESULTS: Nine proteins were associated with PGD in univariate models in the derivation set. Of these, only CLEC4C remained associated with PGD in the validation set after Bonferroni correction (OR [95% CI] = 3.04 [1.74,5.82], p = 2.8×10(−4)). Patterns of association were consistent for CLEC4C in analyses stratified by biventricular/left ventricular and isolated right ventricular PGD. Pathway analysis identified interferon-alpha response and C-type lectin signaling as significantly enriched biologic processes. The RADIAL score was a poor predictor of PGD (AUC = 0.55). CLEC4C alone (AUC = 0.66, p = 0.048) and in combination with the clinical covariates from the multivariable model (AUC = 0.69, p = 0.018) improved discrimination for the primary outcome. CONCLUSIONS: Pre-transplantation circulating levels of CLEC4C, a protein marker of plasmacytoid dendritic cells (pDCs), may identify HT recipients at risk for PGD. Further studies are needed to better understand the potential role pDCs and the innate immune response in PGD.

The durability of surgical repair for degenerative versus ischemic mitral regurgitation (MR) is thought to be markedly different. We, therefore, examined late outcomes and durability for mitral repair in a large cohort of patients receiving a single annuloplasty device.A total of 749 consecutive patients receiving mitral repair for degenerative mitral regurgitation (DMR) or ischemic mitral regurgitation (IMR) were evaluated from a prospective database. Patients with tricuspid or maze surgery were included. Papillary muscle rupture and mixed valve etiologies were excluded. Outcomes were compared for IMR versus DMR.Patients with DMR were younger and less urgent. Patients with IMR had mean end-systolic diameter 4.5 ± 1.1 cm. All patients received the same complete semirigid annuloplasty device with median ring size 32 mm for DMR and 24 mm for IMR. New York Heart Association failure class improved from 2.8 to 1.5 (p .001). Patients with DMR had lower operative mortality (1/384 [0.3%] vs. 26/365 [7%], p .0001) and shorter length of stay. A 15-year survival was better with DMR (63% ± 3% vs. 13% ± 2%, p .001). At 10 years, the incidence of recurrent ≥2+ MR (10% ± 2% vs. 16% ± 2%, p = .16) was not significantly different. Predictors of recurrent ≥2+ MR were female gender (odds ratio [OR]: 3.0 (1.9-4.8, p .0001), and prior operation (OR: 2.4 [1.3-4.5], p = .02) but not IMR (OR: 1.4 [0.9-2.3], p = .15).In this series, where patients with IMR had relatively preserved ventricular dimensions, the primary determinants of late recurrent MR were female gender and prior operation but not IMR versus DMR. Selected patients with IMR can obtain relatively durable mitral repair despite higher operative risk and lower survival compared to DMR.

Supplemental Digital Content is available in the text., The study aim was to examine the impact time in therapeutic range (TTR, International Normalized Ratio [INR] 2.0–3.0) has on survival and adverse events in patients receiving the HeartWare HVAD System in the ENDURANCE and ENDURANCE Supplemental Trials. Evaluable subjects (n = 495) had >1 INR value recorded 1–24 months postimplant and were categorized as: low TTR (10–39%), moderate TTR (40–69%), and high TTR (≥70%). Baseline characteristics, adverse events, and survival were analyzed. Low TTR patients experienced higher rates of major bleeding (1.69 vs. 0.54 events per patient year [EPPY]; p < 0.001), GI bleeding (1.22 vs. 0.38 EPPY; p < 0.001), stroke (0.47 vs. 0.17 EPPY; p < 0.001), thrombus requiring exchange (0.05 vs. 0.01 EPPY; p = 0.02), infection (1.44 vs. 0.69 EPPY; p < 0.001), and renal dysfunction (0.23 vs. 0.05 EPPY; p < 0.001) compared with high TTR. Moderate TTR had higher rates of major bleeding (0.75 vs. 0.54 EPPY; p < 0.001), thrombus requiring exchange (0.05 vs. 0.01 EPPY; p = 0.007), cardiac arrhythmia (0.32 vs. 0.24 EPPY; p = 0.04), and infection (0.90 vs. 0.69 EPPY; p = 0.001) compared with high TTR. Two year survival was greater among moderate and high versus low cohorts (Log-rank p = 0.001). The significant reduction in morbidity and mortality in destination therapy (DT) HVAD patients with well-controlled TTR (≥70%) emphasizes the importance of vigilant anticoagulation management.

Background Left ventricular assist devices (LVAD) are increasingly used for durable mechanical circulatory support in advanced heart failure. While LVAD therapy provides substantial improvement in mortality and quality of life, long-term therapy confers increased risk for device complications. We evaluated if cardiac computed tomography (CCT) improves the detection of cardiomechanical complications among patients with LVAD and suspected device malfunction. Methods In this study, we compared the diagnostic performance of CCT and transthoracic echocardiography (TTE) for the identification of cardiomechanical LVAD complications, including thrombus or neointimal hyperplasia, inflow cannula malposition with dynamic obstruction, fixed outflow obstruction, device infection, and severe aortic regurgitation. Complications were confirmed with surgical evaluation, pathologic assessment, or response to therapeutic intervention. Results Among 58 LVAD patients, who underwent CCT and TTE for suspected LVAD dysfunction, there were 49 confirmed cardiomechanical LVAD complications among 43 (74.1%) patients. The most common LVAD complication was thrombus or neointimal hyperplasia (65.3%), followed by dynamic obstruction (26.5%). Individually, CCT identified 29 of the 49 (59.2%) confirmed LVAD cardiomechanical complications, whereas TTE alone identified a complication in 11 cases (22.4%). However, diagnostic performance was greatest when the two modalities were used in combination, yielding a sensitivity of 67%, specificity of 93%, PPV of 97%, NPV of 47% and diagnostic accuracy of 73%. Conclusion The novel and complementary use of CCT with TTE for the evaluation of suspected device malfunction improves the accurate identification of cardiomechanical LVAD complication compared to either modality alone.

BACKGROUND: In the era of antiretroviral therapy, HIV-positive patients have reduced mortality from HIV infection and increased morbidity from end stage heart failure. The number of HIV-positive heart transplantation recipients remains scant. Long-term survival has not been rigorously studied. We compared survival outcomes of heart transplantation in HIV-positive recipients to HIV-negative recipients. METHODS: Clinical data from all adult heart transplantations were extracted from the UNOS Dataset. The impact of recipient HIV status was analyzed with Cox proportional hazards modeling, 1:3 propensity score matching and Kaplan-Meier survival analysis. RESULTS: Seventy-five HIV-positive recipients and 29,848 HIV-negative recipients were identified. Race distributions differed between the recipient groups, with Blacks comprising a larger proportion of the HIV-positive recipient group (46.7% versus 20.9%, p

OBJECTIVE: Conventional ultrafiltration (CUF) during cardiopulmonary bypass (CPB) serves to hemoconcentrate blood volume to avoid allogeneic blood transfusions. Previous studies have determined weight-indexed CUF volumes as a continuous variable are associated with postoperative AKI after cardiac surgery but optimal weight-indexed volumes that predict AKI have not been described. DESIGN: Retrospective cohort SETTING: Single-center university hospital PARTICIPANTS: 1,641 consecutive patients that underwent elective cardiac surgery between June 2013-December 2015. INTERVENTIONS: CUF volume was removed during CPB in all participants as part of our routine practice. We investigated the association of dichotomized weight indexed CUF volume removal with postoperative AKI development to provide pragmatic guidance for clinical practice at our institution. MEASUREMENTS AND MAIN RESULTS: Primary outcomes of postoperative AKI was defined by the KDIGO staging criteria and dichotomized, weight indexed CUF volumes (ml/kg) were defined by (i) extreme quartiles (Q3) and by (ii) Youden’s criterion that best predicted AKI development. Multivariable logistic regression models were developed to test the association of these dichotomized indices with AKI status. Postoperative AKI occurred in 827 patients (50.4%). Higher CUF volumes were associated with AKI development by quartiles (CUF >Q(3)=32.6 vs. CUF 32 mL/kg increased the risk for postoperative AKI development. Importantly, CUF volume removal of any amount did not mitigate allogeneic blood transfusion during elective cardiac surgery. Prospective studies are needed to validate these findings.

Whether to repair nonsevere tricuspid regurgitation (TR) during surgery for ischemic mitral valve regurgitation (IMR) remains uncertain.The goal of this study was to investigate the incidence, predictors, and clinical significance of TR progression and presence of ≥moderate TR after IMR surgery.Patients (n = 492) with untreated nonsevere TR within 2 prospectively randomized IMR trials were included. Key outcomes were TR progression (either progression by ≥2 grades, surgery for TR, or severe TR at 2 years) and presence of ≥moderate TR at 2 years.Patients' mean age was 66 ± 10 years (67% male), and TR distribution was 60% ≤trace, 31% mild, and 9% moderate. Among 2-year survivors, TR progression occurred in 20 (6%) of 325 patients. Baseline tricuspid annular diameter (TAD) was not predictive of TR progression. At 2 years, 37 (11%) of 323 patients had ≥moderate TR. Baseline TR grade, indexed TAD, and surgical ablation for atrial fibrillation were independent predictors of ≥moderate TR. However, TAD alone had poor discrimination (area under the curve, ≤0.65). Presence of ≥moderate TR at 2 years was higher in patients with MR recurrence (20% vs. 9%; p = 0.02) and a permanent pacemaker/defibrillator (19% vs. 9%; p = 0.01). Clinical event rates (composite of ≥1 New York Heart Association functional class increase, heart failure hospitalization, mitral valve surgery, and stroke) were higher in patients with TR progression (55% vs. 23%; p = 0.003) and ≥moderate TR at 2 years (38% vs. 22%; p = 0.04).After IMR surgery, progression of unrepaired nonsevere TR is uncommon. Baseline TAD is not predictive of TR progression and is poorly discriminative of ≥moderate TR at 2 years. TR progression and presence of ≥moderate TR are associated with clinical events. (Comparing the Effectiveness of a Mitral Valve Repair Procedure in Combination With Coronary Artery Bypass Grafting [CABG] Versus CABG Alone in People With Moderate Ischemic Mitral Regurgitation, NCT00806988; Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation, NCT00807040).

Many patients die while waiting for a heart transplant. Therefore, it is vital that all suitable organs are used for transplantation. We present a case of an allograft that was transplanted twice and outline considerations regarding tissue typing, the impact of repeated ischemic time, and ethical considerations with allograft retransplantation. (Level of Difficulty: Intermediate.), Central Illustration

This study sought to determine the indications, characteristics, and outcomes of cardiovascular implantable electronic device (CIED) surgery in patients with LVAD.Many patients with a left ventricular assist device (LVAD) will require implantable cardioverter-defibrillator generator change or device revision or are candidates for de novo implantable cardioverter-defibrillator implantation following LVAD implantation.We performed an observational retrospective study of all LVAD recipients who subsequently underwent CIED surgery at Duke University Hospital from 2009 to 2019.A total of 159 patients underwent CIED surgery following LVAD implantation, including generator change (n = 93), device revision (n = 38), and de novo implant (n = 28). The median (interquartile range) time from LVAD implantation to CIED surgery was 18.1 months (5.5 to 35.1 months). Pre-operative risk for infection was elevated in the overall cohort with a median (interquartile range) Prevention of Arrhythmia Device Infection Trial (PADIT) score of 7.0 (5.0 to 9.0). Pocket hematoma occurred in 21 patients (13.2%) following CIED surgery. Antimicrobial envelops were used in 43 patients (27%). Device infection due to CIED surgery occurred in 5 (3.1%) patients and occurred only in patients who developed post-operative pocket hematoma (p 0.001). Mortality at 1 year following CIED surgery was 20% (n = 32).CIED surgery following LVAD implantation is associated with an increased risk for pocket hematoma and CIED infection. Further studies are needed to determine the risk-benefit ratio of CIED surgery in patients with LVADs.

OptiVol (Medtronic PLC, Minneapolis, MN) is a diagnostic feature of some cardiac implantable electronic devices (CIEDs) based on changes in thoracic impedance (TI) over time. Changes in TI can predict heart failure (HF) hospitalizations and mortality in HF populations. However, the utility of this feature is unknown in patients with a left ventricular assist device (LVAD). To determine if OptiVol and TI correlate with clinical HF events in a population of LVAD patients, hospitalization outcomes were collected retrospectively from the electronic health records at a single academic medical center in 80 LVAD patients with an OptiVol-capable CIED. Demographics, medical history, and available clinical data were reviewed and reported. The primary outcomes of interest were TI and OptiVol trends before and after hospitalization, and association of trends before and after these events was evaluated. Most patients had a HeartMate II LVAD and most CIEDs were defibrillators, and 23 (29%) had at least one HF hospitalization during the study period. HF hospitalizations were preceded by signs of volume overload in Optivol (60%) and TI (78%) with recovery of these measures post hospitalization in 33% and 25% of patients, respectively. Monitoring of TI and OptiVol may be one effective component of HF management in LVAD patients as part of a comprehensive program.

Background Sensitized candidates with unacceptable antigens are a group that demands special attention in organ transplantation. Calculated panel reactive antigen (cPRA) is not used to modify allocation priorities in lung transplantation. The impact of cPRA on waiting list time and mortality is unknown. Methods We performed a retrospective review of candidates for lung transplantation listed from May 2005 to 2018. Data from the Organ Procurement and Transplantation Network/United Network for Organ Sharing STAR (Standard Analysis and Research) dataset was paired with additional unacceptable human leukocyte antigen (UA-HLA) data, which were used to calculate the listing cPRA. Candidates were stratified based on the lack of UA-HLAs or cPRA level for candidates with unacceptable antigens reported. Unadjusted competing risks and adjusted subdistribution hazard models were fit. Results A total of 29,085 candidates met inclusion criteria for analysis. Of these, 23,562 (81%) with no UA-HLAs, 3472 (11.9%) with a cPRA less than 50, and 2051 with a cPRA greater than or equal to 50 (7.1%). On adjusted analysis, a cPRA greater than or equal to 50 was independently associated with increased waitlist mortality at 1 year (hazard ratio, 1.71; 95% confidence interval, 1.55-1.88; P Conclusions Further evaluation of organ allocation with consideration of a candidate's cPRA may be warranted in order to optimize equity in access to transplants.

Background Short duration, antimicrobial prophylaxis that includes antistaphylococcal activity is recommended at the time of left ventricular assist device (LVAD) implantation to reduce infection-related complications. There continues to be wide variability in surgical infection prophylaxis (SIP) regimens among implantation centers. The aim of this study is to characterize current SIP regimens at different LVAD centers. Methods A survey study was conducted from 26 September 2017 to 25 October 2017. Surveys were distributed electronically to LVAD coordinators and infectious diseases specialists at 75 US medical centers identified as having an LVAD program. Data collection included information about antimicrobial selection, duration, Staphylococcus aureus screening, and decolonization procedures. Results We received 29 survey responses. The majority of surveys were completed by infectious diseases physicians (72.4% [21 out of 29]). Most responding centers reported LVAD programs established for greater than 10 years (20 out of 29 [69%]). Cardiac transplantation was performed in 28 out of 29 (96%) centers. Of centers reporting a defined SIP regimen for non-penicillin allergic patients (96% [28 out of 29]), 17.9% (5 out of 28) reported a four-drug regimen, 35.7% (10 out of 28) reported a three-drug regimen, and 46.4% (13 out of 28) reported a two-drug regimen, while no centers reported a single-drug regimen. Empiric fluconazole was common (50% [14 out of 28]) and 96.4% (27 out of 28) of regimens included vancomycin. Duration of antimicrobial prophylaxis (24 hours to 5 days), S. aureus screening, decolonization procedures, and alterations due to drug allergies varied across participating centers. Conclusions Our survey results indicate wide variation in SIP regimens among participating LVAD centers. These results highlight the need for studies evaluating the implications of SIP regimens, and whether clinical factors that prolong antimicrobial duration impact postoperative infection rates.

Background An early report of recipient heart transplantation outcomes under the new U.S. heart allocation system introduced in late 2018 found a lower post-transplant survival rate compared with that of the prior system. Objectives The aim of this study was to examine recipient survival under the new system by using an updated dataset. Methods The 2015 to 2019 United Network for Organ Sharing registry was queried for adult heart transplant recipients, stratified according to whether the subjects were listed and underwent transplant before or after October 18, 2018, when the new allocation system was implemented. The association between allocation system and recipient mortality was analyzed by using the Kaplan-Meier method and multivariable Cox proportional hazards regression. Results A total of 7,119 recipients met inclusion criteria: 6,004 (84%) and 1,115 (16%) listed and undergoing transplant in the old and new allocation systems, respectively. This registry update included 576 new-system recipients, more than double the amount previously analyzed. Recipients from the new system were more likely to be bridged to transplant with temporary mechanical circulatory support devices instead of durable left ventricular assist devices and had longer graft ischemic times. After adjustment, the new system was not associated with poorer survival on Kaplan-Meier survival analysis (log-rank test; p = 0.075) or multivariable Cox proportional hazards modeling (adjusted hazard ratio: 1.18; 95% confidence interval: 0.90 to 1.55). Conclusions The short-term survival of recipients listed and receiving a transplant under the old and new allocation systems seems to be comparable. The modification to the allocation system has resulted in several changes to the clinical profiles of patients undergoing transplants that must be closely monitored in the coming years.

Objectives The goal of this study was to assess the utility of transvenous lead extraction for cardiovascular implantable electronic device (CIED) infection in patients with a left ventricular assist device (LVAD). Background The utility of transvenous lead extraction for the management CIED infection in patients with a durable LVAD has not been well described. Methods Clinical and outcomes data were collected retrospectively among patients who underwent lead extraction for CIED infection after LVAD implantation at Duke University Hospital. Results Overall, 27 patients (n = 6 HVAD; n = 15 HeartMate II; n = 6 Heartmate III) underwent lead extraction for infection. Median (interquartile range) time from LVAD implantation to infection was 6.1 (2.5, 14.9) months. Indications included endocarditis (n = 16), bacteremia (n = 9), and pocket infection (n = 2). Common pathogens were Staphylococcus aureus (n = 10), coagulase-negative staphylococci (n = 7), and Enterococcus faecalis (n = 3). Sixty-eight leads were removed, with a median lead implant time of 5.7 (3.6, 9.2) years. Laser sheaths were used in all procedures, with a median laser time of 35.0 (17.5, 85.5) s. Mechanical cutting tools were required in 11 (40.7%) and femoral snaring in 4 (14.8%). Complete procedural success was achieved in 25 (93.6%) patients and clinical success in 27 (100%). No procedural failures or major adverse events occurred. Twenty-one patients (77.8%) were alive without persistent endovascular infection 1 year after lead extraction. Most were treated with oral suppressive antibiotics after extraction (n = 23 [82.5%]). Persistent infection after extraction occurred in 4 patients and was associated with 50% 1-year mortality. Conclusions Transvenous lead extraction for LVAD-associated CIED infection can be performed safely with low rates of persistent infection and 1-year mortality.

Acute kidney injury (AKI) and primary graft dysfunction (PGD) are serious complications after heart transplantation (HT). The relationship between AKI and PGD is poorly understood. We sought to examine the incidence of AKI and identify risk factors associated with AKI. We hypothesized that PGD is one of the risk factors independently associated with post-HT AKI. We gathered data for all adult patients who underwent HT between 2009 and 2014. AKI was defined by the KDIGO criteria. PGD was categorized using ISHLT criteria. We assessed univariable and multivariable logistic regression to identify risk factors independently associated with post-HT AKI. Out of 316 patients, postoperative AKI occurred in 273 (86%) patients: 188 (68%) stage I, 44 (16%) stage II, and 41 (15%) stage III. Stage II/III AKI was associated with increased risk of mortality at 1 year. There was significant association between severe PGD and stage II/III AKI (P = 0.001, OR 3.63, 95% CI: 1.69-7.94). Other clinical factors significantly associated with stage II/III AKI included longer donor brain death duration and lower recipient baseline creatinine. We found that stage II/III AKI is common and independently associated with severe PGD. Another potentially modifiable risk factor is donor brain death duration.

Introduction Lead dysfunction can lead to serious consequences including failure to treat ventricular tachycardia or fibrillation (VT/VF). The incidence and mechanisms of lead dysfunction following left ventricular assist device (LVAD) implantation are not well-described. We sought to determine the incidence, mechanisms, timing, and complications of right ventricular lead dysfunction requiring revision following LVAD implantation. Methods Retrospective observational chart review of all LVAD recipients with pre-existing implantable cardioverter-defibrillator (ICD) from 2009 to 2018 was performed including device interrogation reports, laboratory and imaging data, procedural reports, and clinical outcomes. Results Among 583 patients with an ICD in situ undergoing LVAD implant, the median (interquartile range) age was 62.5 (15.7) years, 21% were female, and the types of LVADs included HeartWare HVAD (26%), HeartMate II (52%), and HeartMate III (22%). Right ventricular lead revision was performed in 38 patients (6.5%) at a median (25th, 75th) of 16.4 (3.6, 29.2) months following LVAD. Mechanisms of lead dysfunction included macrodislodgement (n = 4), surgical lead injury (n = 4), recall (n = 3), insulation failure (n = 8) or conductor fracture (n = 7), and alterations in the lead-myocardial interface (n = 12). Undersensing requiring revision occurred in 22 (58%) cases. Clinical sequelae of undersensing included failure to detect VT/VF (n = 4) and pacing-induced torsade de pointes (n = 1). Oversensing occurred in 12 (32%) and sequelae included inappropriate antitachycardia pacing ([ATP], n = 8), inappropriate ICD shock (n = 6), and ATP-induced VT (n = 1). Conclusion The incidence of right ventricular lead dysfunction following LVAD implantation is significant and has important clinical sequelae. Physicians should remain vigilant for lead dysfunction after LVAD surgery and test lead function before discharge.

Left ventricular assist devices are (LVAD) used for circulatory support in patients with end-stage heart failure. Hemolysis/pump dysfunction is a well-known complication of this therapy with various etiologic causes. A small proportion of these complications are caused by outflow graft obstructions; this complication has received little attention in the scientific literature. Herein, we provide a comprehensive overview of the role of the LVAD outflow graft obstruction and its treatment options.

Background : Post-operative AF (POAF) is the most common complication following cardiac surgery, occurring in 30% to 60% of patients undergoing bypass and/or valve surgery. POAF is associated with longer intensive care unit/hospital stays, increased healthcare utilization, and increased morbidity and mortality. Injection of botulinum toxin type A into the epicardial fat pads resulted in reduction of AF in animal models, and in 2 clinical studies of cardiac surgery patients, without new safety observations. Methods : The objective of NOVA is to assess the use of AGN-151607 (botulinum toxin type A) for prevention of POAF in cardiac surgery patients. This randomized, multi-site, placebo-controlled trial will study one-time injections of AGN-151607 125 U (25 U / fat pad) and 250 U (50 U / fat pad) or placebo during cardiac surgery in ∼330 participants. Primary endpoint: % of patients with continuous AF ≥ 30 s. Secondary endpoints include several measures of AF frequency, duration, and burden. Additional endpoints include clinically important tachycardia during AF, time to AF termination, and healthcare utilization. Primary and secondary efficacy endpoints will be assessed using continuous ECG monitoring for 30 days following surgery. All patients will be followed for up to 1 year for safety. Conclusion : The NOVA Study will test the hypothesis that injections of AGN-151607 will reduce the incidence of POAF and associated resource utilization. If demonstrated to be safe and effective, the availability of a one-time therapy for the prevention of POAF would represent an important treatment option for patients undergoing cardiac surgery.

Stroke remains a significant complication of left ventricular assist device (LVAD) therapy. We performed a single-center retrospective study evaluating patients undergoing first-time HeartWare HVAD (Medtronic Inc) or HeartMate 3 (Abbott Inc) implantation from September 2009-February 2018.Exclusion criteria were age18 and preoperative ECMO. The primary endpoint was stroke-free survival. Stroke was defined as new neurological deficits persisting24 hours with corresponding radiographic evidence. Risk factors evaluated included demographics, medical comorbidities, heart failure etiology, LVAD indication, INTERMACS profile, and device type. Univariate predictors (P .15) and variables clinically suspected to raise stroke risk were entered in a multivariate hazard regression model, specified using backward selection of covariates and accounting for competing risks of transplant/LVAD exchange.A total of 163 HVAD and 84 HM3 patients were analyzed. Median follow up (until death, censoring for transplant/LVAD removal, or end of follow up) was 1.2 years in HVAD patients and 1.4 years in HM3 patients. Stroke occurred in 24 HVAD patients (15 ischemic, 9 hemorrhagic) and 6 HM3 patients (4 ischemic, 2 hemorrhagic). One-year stroke-free survival was 76.8% for HVAD and 84.3% for HM3. Thirty-day mortality following stroke was 41.7% for HVAD and 66.7% for HM3; 54.2% of HVAD strokes were disabling compared to 83.3% of HM3 strokes. Age, LVAD indication, and device type were associated (P .15) with stroke on univariate analysis. On multivariate analysis, the HVAD was associated with significantly higher stroke risk (hazard ratio, 2.57; 95% confidence interval, 1.02-6.44; P = .045).Different LVAD models appear to be associated with significantly different stroke risks.

We describe a case of inherited restrictive cardiomyopathy in a patient presenting with severe biatrial enlargement. We review the evaluation and management of restrictive cardiomyopathy with a focus on genetic etiologies. (Level of Difficulty: Intermediate.), Graphical abstract, We describe a case of inherited restrictive cardiomyopathy in a patient presenting with severe biatrial enlargement. We review the evaluation and…

The CARMAT-Total Artificial Heart (C-TAH) is designed to provide heart replacement therapy for patients with end-stage biventricular failure. This report details the reliability and efficacy of the autoregulation device control mechanism (auto-mode), designed to mimic normal physiologic responses to changing patient needs. Hemodynamic data from a continuous cohort of 10 patients implanted with the device, recorded over 1,842 support days in auto-mode, were analyzed with respect to daily changing physiologic needs. The C-TAH uses embedded pressure sensors to regulate the pump output. Right and left ventricular outputs are automatically balanced. The operator sets target values and the inbuilt algorithm adjusts the stroke volume and beat rate, and hence cardiac output, automatically. Auto-mode is set perioperatively after initial postcardiopulmonary bypass hemodynamic stabilization. All patients showed a range of average inflow pressures of between 5 and 20 mm Hg during their daily activities, resulting in cardiac output responses of between 4.3 and 7.3 L/min. Operator adjustments were cumulatively only required on 20 occasions. This report demonstrates that the C-TAH auto-mode effectively produces appropriate physiologic responses reflective of changing patients’ daily needs and represents one of the unique characteristics of this device in providing almost physiologic heart replacement therapy.

Clinically, both percutaneous and surgical approaches to deliver viral vectors to the heart either have resulted in therapeutically inadequate levels of transgene expression or have raised safety concerns associated with extra-cardiac delivery. Recent developments in the field of normothermic ex vivo cardiac perfusion storage have now created opportunities to overcome these limitations and safety concerns of cardiac gene therapy. This study examined the feasibility of ex vivo perfusion as an approach to deliver a viral vector to a donor heart during storage and the resulting bio distribution and expression levels of the transgene in the recipient post-transplant. The influence of components (proprietary solution, donor blood, and ex vivo circuitry tubing and oxygenators) of the Organ Care System (OC) (TransMedics, Inc., Andover MA) on viral vector transduction was examined using a cell-based luciferase assay. Our ex vivo perfusion strategy, optimized for efficient Adenoviral vector transduction, was utilized to deliver 5 × 1013 total viral particles of an Adenoviral firefly luciferase vector with a cytomegalovirus (CMV) promotor to porcine donor hearts prior to heterotopic implantation. We have evaluated the overall levels of expression, protein activity, as well as the bio distribution of the firefly luciferase protein in a series of three heart transplants at a five-day post-transplant endpoint. The perfusion solution and the ex vivo circuitry did not influence viral vector transduction, but the serum or plasma fractions of the donor blood significantly inhibited viral vector transduction. Thus, subsequent gene delivery experiments to the explanted porcine heart utilized an autologous blood recovery approach to remove undesired plasma or serum components of the donor blood prior to its placement into the circuit. Enzymatic assessment of luciferase activity in tissues (native heart, allograft, liver etc.) obtained post-transplant day five revealed wide-spread and robust luciferase activity in all regions of the allograft (right and left atria, right and left ventricles, coronary arteries) compared to the native recipient heart. Importantly, luciferase activity in recipient heart, liver, lung, spleen, or psoas muscle was within background levels. Similar to luciferase activity, the luciferase protein expression in the allograft appeared uniform and robust across all areas of the myocardium as well as in the coronary arteries. Importantly, despite high copy number of vector genomic DNA in transplanted heart tissue, there was no evidence of vector DNA in either the recipient’s native heart or liver. Overall we demonstrate a simple protocol to achieve substantial, global gene delivery and expression isolated to the cardiac allograft. This introduces a novel method of viral vector delivery that opens the opportunity for biological modification of the allograft prior to implantation that may improve post-transplant outcomes.

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.).

Intra-aortic balloon pump (IABP) is often used to support patients in decompensated heart failure. Placement of the IABP via the axillary artery facilitates long-term support with the device and may allow for the conversion of an acute heart failure (HF) patient into a chronic HF patient using a modified weaning protocol; allowing for medical symptom management and removal of mechanical support. We will discuss strategies for supporting these complicated patients.

Background Postoperative atrial fibrillation (POAF) frequently complicates cardiac surgery and is associated with worse outcomes. The cardiac autonomic nervous system is implicated in the pathogenesis of POAF. Objective The purpose of this study was to determine the efficacy and safety of selective cardiac autonomic modulation in preventing POAF. Methods In this randomized, double-blind, placebo-controlled trial, adults undergoing cardiac surgery were randomized 1:1 to intraoperative injection of 250 units onabotulinumtoxinA (botulinum toxin type A [BoNTA]) or placebo into epicardial fat pads. The study was powered to detect a 40% reduction in relative risk of POAF. Time to first episode of in-hospital POAF was the primary outcome, evaluated in patients receiving injection. Additionally, incidence of POAF, length of stay (LOS), and adverse events were examined. Results The trial assigned 145 patients to injection, 15 of whom were dropped before treatment, leaving 130 patients for analysis. Overall, 36.5% (23/63) of BoNTA-treated patients developed POAF compared with 47.8% (32/67) of placebo-treated patients. The time-to-event analysis revealed a hazard ratio of 0.69 (95% confidence interval 0.41–1.19; P = .18) for the BoNTA vs placebo arm. There were no significant differences in postoperative hospital LOS (median [interquartile range] 6.0 [3.4] vs 6.2 [3.7] days; P = .51) or adverse events prolonging LOS (27/63 [42.9%] vs 30/67 [44.8%]; P = .83) in patients receiving BoNTA vs placebo. Conclusion Epicardial injection of onabotulinumtoxinA was without discernible adverse effects, but we failed to detect a significant difference in risk of POAF. Future large-scale studies of epicardial onabotulinumtoxinA injection as a potential POAF prevention strategy should be designed to study smaller, but clinically meaningful, treatment effects.

Utilization of extracorporeal membrane oxygenation (ECMO) has increased dramatically over the last decade. Despite this trend, many medical centers have limited, if any, access to this technology or the resources necessary to manage these complex patients. In an effort to improve the current infrastructure of regional ECMO care, ECMO centers of excellence have an obligation to partner with facilities within their communities and regions to increase access to this potentially life-saving technology. While the need for this infrastructure is widely acknowledged in the ECMO community, few reports describe the actual mechanisms by which a successful interfacility transport program can operate. As such, the purpose of this document is to describe the elements of and methods for providing safe and efficient mobile ECMO services from the perspective of an experienced, high-volume tertiary ECMO center of excellence in the Southeastern United States.

Left ventricular assist devices (LVADs) improve quality of life (QoL) and functional capacity (FC) for patients with advanced heart failure. The association between adverse events (AEs) and changes in QoL and FC are unknown. Patients treated with the HeartWare ventricular assist device (HVAD) with paired 6-minute walk distance (6MWD, n = 263) and Kansas City Cardiomyopathy Questionnaires (KCCQ, n = 272) at baseline and 24 months in the ENDURANCE and ENDURANCE Supplemental Trial databases were included. Patients were stratified based upon occurrence of clinically significant AEs during the first 24 months of support and analyzed for the mean change in 6MWD and KCCQ. The impact of AE frequency on change in 6MWD and KCCQ from baseline to 24 months was evaluated. Of the AEs examined, only sepsis was associated with an improvement in 6MWD (109 m vs. 16 m, p = 0.002). Patients without improvement in 6MWD test from baseline to 24 months had significantly more AEs than those with FC improvement (p = 0.0002). Adverse events did not affect the KCCQ overall summary score. In this analysis, patients with fewer AEs had greater improvement in FC during the 24-month follow up. The frequency of AEs did not have a significant impact on QoL after LVAD implantation.

Stroke is a devastating complication of left ventricular assist device (LVAD) therapy. Understanding the characteristics, risk factors and outcomes of strokes associated with the centrifugal flow LVADs is important to devise better strategies for management and prevention. This is a retrospective cohort study at a single US academic medical center. The cohort includes patients who received a first time Heartmate 3 (HM3) or Heartware (HVAD) LVAD between September 2009 through February 2018 and had a stroke while the LVAD was in place. Descriptive statistics were used when appropriate. A logistic regression analysis was used to determine predictors of poor outcome. Out of a total of 247 patients, 12.1% (N = 30, 24 HVAD and 6 HM3) had a stroke (63% ischemic) and 3 of these patients had pump thrombosis. Events per patient year (EPPY) were similar for HVAD and HM3 patients (0.3 ± 0.1). INR was subtherapeutic in 47.4% of ischemic stroke patients and supratherapeutic in 18.2% of hemorrhagic stroke patients. Concurrent infections were more common in the setting of hemorrhagic stroke than ischemic stroke (45.4% vs 5.3%, p = 0.008). Strokes were severe in most cases, with initial NIH stroke scale (NIHSS) higher in HM3 patients compared to HVAD patients (mean 24.6 vs 16) and associated with high in-patient mortality (21.1% of ischemic stroke vs. 88.8% of hemorrhagic stroke). Predictors of death within 30 days and disability at 90 days included creatinine at stroke onset, concurrent infection, hemorrhaghic stroke, and initial stroke severity (NIHSS). A score derived from these variables predicted with 100% certainty mortality at 30 days and mRS ≥ 4 at 90 days. For patients with centrifugal flow LVADs, ischemic strokes were more common but hemorrhagic strokes were associated with higher in-patient mortality and more frequently seen in the setting of concurrent infections. Infections, sub or supratherapeutic INR range, and comorbid cardiovascular risk factors may all be contributing to the stroke burden. These findings may inform future strategies for stroke prevention in this population.

Introduction: There is a complex epidemiologic relationship between type two diabetes mellitus (DM) and heart failure (HF), and it is unclear whether the biochemical basis of HF differs in patients with and without DM. Hypothesis: Proteomic profiling of myocardial tissue from patients with and without DM will identify unique signatures of diabetic HF. Methods: Using the Olink aptamer-based platform, we performed proteomic profiling of 552 proteins on 37 myocardial tissue samples: 9 controls, 10 with HF, 7 with DM, and 11 with HF+DM. One-way ANOVA was first used to identify proteins that differed across the four groups. Associated proteins were then tested for differences between HF+DM and each other group independently; we retained proteins with the same direction of effect for each comparison. Each analysis was controlled for false discovery rate (q Results: We identified 12 proteins that differed significantly between HF+DM and all three other groups. Among these, six proteins were significant after FDR adjusted ANOVA and had the same direction of effect. These included 5’-NT (q=5.35E-07), a regulator of intracellular energy utilization, and carboxypeptidase A2, a metalloprotease that cleaves peptides during digestion (q=0.0003). Expression of myocardial leptin receptors (q=0.001), complement factor H related protein (q=0.003), and carbonic anhydrase (q=0.006) were also upregulated in diabetic HF, and have previously been linked to myocyte hypertrophy. Markers of endothelial dysfunction - ESM-1 (q=5.62E-06) and VEGFR-3 (q=0.024) - were also increased in HF+DM myocardium as compared to other groups (Figure 1). Conclusions: Proteomic profiling of HF, DM, and HF+DM myocardial tissue suggest alterations in intracellular energy substrate utilization as well as increased expression of tissue biomarkers previously associated with ventricular hypertrophy and myocardial remodeling.

Background Ventricular arrhythmias (VAs) and electrical storm (ES) are recognized complications following left ventricular assist device (LVAD) implantation; however, their association with long term-outcomes remains poorly understood. Objective The purpose of this study was to describe the clinical impact of ES in a population of patients undergoing LVAD implantation at a quaternary care center in the United States. Methods This was an observational retrospective study of patients undergoing LVAD implantation from 2009 to 2020 at Duke University Hospital. The incidence of ES (≥3 sustained VA episodes over a 24-hour period without an identifiable reversible cause) was determined from patient records. Risk factors for ES were identified using multivariable Cox proportional hazards modeling. Results Among 730 patients undergoing LVAD implant, 78 (10.7%) developed ES at a median of 269 (interquartile range [IQR] 7–766) days following surgery. Twenty-seven patients (34.6%) developed ES within 30 days, while 51 (65.4%) presented with ES at a median 639 (IQR 281–1017) days after implant. Following ES, 41% of patients died within 1 year. Patients who developed ES were more likely to have a history of VAs, ventricular tachycardia ablation, antiarrhythmic drug use, and perioperative mechanical circulatory support around the time of LVAD implant than patients without ES. Conclusion ES occurs in 1 in 10 patients after LVAD and is associated with higher mortality. Risk factors for ES include a history of VAs, VT ablation, antiarrhythmic drug use, and perioperative mechanical circulatory support. Optimal management of ES surrounding LVAD implant, including escalation of medical therapy, catheter ablation, or adjunctive sympatholytic therapies, remains uncertain.

Background: The NuPulseCV intravascular ventricular assist system (iVAS) provides extended duration ambulatory counterpulsation via a durable pump placed through the distal subclavian artery. Methods: We performed a prospective, single-arm, multicenter, US Food and Drug Administration-approved feasibility trial of iVAS therapy as a bridge to transplant or decision following the FIH (First-In-Human) trial. Results: Forty-seven patients were enrolled, and 45 patients (median 61 years old, 37 males, and 30 listed on United Network of Organ Sharing) received iVAS support for median 44 (25–87) days. There were no intraoperative complications. Success was defined as survival or transplant on iVAS therapy free from disabling stroke. Outcome success at 30 days (the primary end point of this study) and at 6 months was 89% and 80%, respectively. During 6 months of iVAS support, 2 patients died and 2 patients experienced disabling neurological dysfunction. Six-minute walk distance, 2-minute step test, and Kansas City Cardiomyopathy Questionnaire score improved during 4-week iVAS support. Conclusions: This feasibility trial demonstrated promising short-term outcomes of iVAS therapy with improved functional capacity and quality of life during the therapy. Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02645539.

Introduction: Stroke is a devastating complication of left ventricular assist device (LVAD) therapy and a leading cause of mortality in this group. The newer HeartMate (HVAD, 2012) and HeartMate 3 (HM3, 2017) devices use a continuous flow centrifugal pump with a magnetically levitated rotor that may cause less thrombosis and stroke. We aim to compare the rate and severity of strokes in the setting of the new generation LVADs. Methods: This was a single-center retrospective cohort study at a single US academic medical center. The cohort includes all subjects at Duke University Medical Center who received either an HM3 or HVAD LVAD between September 2009 through February 2018 and had a cerebrovascular accident while the LVAD was in place. Descriptive statistics were calculated to compare the clinical variables for individuals receiving either the HVAD or HM3 device. 95% confidence intervals were calculated when appropriate. Results: A total of 163 HVAD patients and 84 HM3 patients were included in the analysis. Strokes occurred more commonly among those with HVAD (14.7%, 9.7%-21.1%) compared to those with HM3 (6.0%, 2.0%-13.3%). About 62.1% of strokes were ischemic. Patients with HM3 were older and had a higher rate of cardiovascular risk factors. The initial mean NIHSS was higher in HM3 patients (24.6, 11.9-37.3) compared to those with HVADs (16, 10.9-21.1). Mortality within 30 days was higher in HM3 patients (60.0%, 14.7%-94.7%) compared to HVAD patients (45.8%, 25.6%-67.2%). Patients were more likely to be disabled (mRs> 3) at 3 months if they had an HM3 (80%, 28.4%-99.5%) compared to those who had an HVAD (54.2%, 32.8%-74.4%). Conclusion: Strokes occurred more commonly among those with HVAD compared to HM3, but the strokes in those with HM3 tended to be more severe at onset compared to HVAD with a higher 30 days mortality and more disability at 3 months. The difference in stroke frequency may suggest that the HM3 is less prone to thrombosis. The difference in mortality may have been secondary to patients with HM3 being older and with more cardiovascular risk factors or could be related to a reduction in minor strokes causing a shift to worse outcomes. Additional studies are needed to understand the predictors of stroke in the setting of the new generation LVADs.

Mechanically assisted circulation has become a mainstay in the treatment of acute and chronic advanced heart failure. Evolution of the blood pumps, a focused effort on improving management strategies, clinical trials, and large registries have all played pivotal roles in improving outcomes. The results with temporary circulatory support are dependent upon the underlying heart disease and the ability to correct the primary problem or transition to a more definitive therapy. The durable devices have been shown to reduce mortality, enhance quality of life, and improve submaximal exercise performance compared with standard treatments. Percutaneous devices have been introduced that can be rapidly deployed to partially or completely support the circulation in the setting of acute cardiogenic shock or in support of high-risk interventional procedures. Durable, implantable ventricular assist devices for chronic support are now miniaturized and provide blood flow in a continuous rather than pulsatile manner. Relative degrees of hemocompatibility are device specific, but all contemporary blood pumps require some form of anticoagulation and/or antiplatelet therapy. Many of the adverse events associated with these devices are directly related to the interaction of blood components with the pump surfaces.

BACKGROUND: Patients with end stage heart failure are increasingly being bridged to heart transplant (BTT) with mechanical circulatory support (MCS), however the association between a left ventricular assist device (LVAD) BTT strategy and post-transplant renal outcomes is unclear. The aim of this study was to analyze the association of LVAD BTT with the development of post-transplant renal failure using a large national registry. METHODS: We queried the 2009-2018 United Network for Organ Sharing (UNOS) registry for all adults undergoing first-time heart or heart-kidney transplantation and stratified patients by use of pre-transplant durable LVAD. The primary outcome of interest was post-transplant renal failure, which was evaluated with multivariable logistic regression. RESULTS: 18,307 patients met inclusion criteria including 7,887 (43%) and 10,420 (57%) that were and were not bridged to transplant with an LVAD, respectively. BTT patients had slightly better baseline renal function (eGFR 68.7 vs 65.8 mL/min, p

Background: The MOMENTUM 3 trial compares the centrifugal HeartMate 3 (HM3) with the axial HeartMate II (HMII) continuous-flow left ventricular assist system in patients with advanced heart failure, irrespective of the intended goal of therapy. The trial’s 2-year clinical outcome (n=366) demonstrated superiority of the HM3 for the primary end point (survival free of a disabling stroke or reoperation to replace or remove a malfunctioning pump). This analysis evaluates health resource use and cost implications of the observed differences between the 2 devices while patients were enrolled in the trial. Methods: We analyzed all hospitalizations and their associated costs occurring after discharge from the implant hospitalization until censoring (study withdrawal, heart transplantation, and pump exchange with a nonstudy device or death). Each adjudicated episode of hospital-based care was used to calculate costs (device-attributable and non–device-attributable event costs), estimated by using trial data and payer administrative claims databases. Cost savings stratified by subgroups (study outcome [transplant, death, or ongoing on device], intended goal of therapy, type of insurance, or sex) were also assessed. Results: In 366 randomly assigned patients, 361 comprised the as-treated group (189 in the HM3 group and 172 in the HMII group), of whom 337 (177 in the HM3 group and 160 in the HMII group) were successfully discharged following implantation. The HM3 arm experienced fewer total hospitalizations per patient-year (HM3: 2.1±0.2 versus HMII: 2.7±0.2; P =0.015) and 8.3 fewer hospital days per patient-year on average (HM3: 17.1 days versus HMII: 25.5 days; P =0.003). These differences were driven by patients hospitalized for suspected pump thrombosis (HM3: 0.6% versus HMII: 12.5%; P P =0.002). Controlled for time spent in the study (average cumulative cost per patient-year), postdischarge HM3 arm costs were 51% lower than with the HMII (HM3: $37 685±4251 versus HMII: $76 599±11 889, P Conclusions: In this 2-year outcome economic analysis of the MOMENTUM 3 trial, the HM3 demonstrated a reduction in rehospitalizations, hospital days spent during rehospitalizations, and a significant cost savings following discharge in comparison with the HMII left ventricular assist system, irrespective of the intended goal of therapy. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02224755.

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)

Purpose An increasing number of patients with end-stage heart failure are supported with left ventricular assist device (LVAD) implantation and must be maintained on a consistent anticoagulation regimen. Pre-emptive extraction of carious teeth in these patients is necessary to prevent seeding of the implanted device and endocarditis. Thus, the objective of this study was to evaluate bleeding complications after minor oral surgery, specifically teeth extractions, in this unique patient population requiring long-term anticoagulation. Materials and Methods This study was a retrospective single-center review. Adult patients supported on an implanted continuous-flow LVAD from January 1, 2007 to December 31, 2016 were included. Baseline characteristics were collected by retrospective chart review and the institutional LVAD registry. All extractions were performed in the operating room under local anesthesia with moderate sedation or general anesthesia with nasal intubation, and LVAD settings were monitored by a trained perfusionist. Preoperative and postoperative hematology laboratory values, such as hemoglobin and international normalized ratio (INR), were collected by chart review. Continuous variables were presented as mean ± standard deviation and compared using the Student t test. Categorical variables were presented as proportion and percentage and compared using the χ2 test or Fisher exact test as appropriate. Statistical significance was established at a P value less than .05. Results After screening 798 patients, 32 (4%) were found to have undergone dental extractions after LVAD implantation. The sample was composed of 32 patients with a mean age of 60.13 years and 81.25% were men. The average time from LVAD implantation to extraction was 445.19 ± 1,108.53 days. Average preoperative INR was 1.76 ± 0.47. Preoperative fresh frozen plasma was not administered to any patients. Twenty-eight patients (87.5%) were on Coumadin (warfarin) preoperatively. In 11 of these 28 patients (39.3%), Coumadin was held preoperatively. The average postoperative change in hemoglobin level was −0.79 ± 1.45. Only 1 patient (3%) required postoperative blood transfusion for a hemoglobin level of 7.6 that responded appropriately. There were no reoperations for bleeding. Conclusions Minor oral surgical procedures can be performed safely for patients being supported on LVAD therapy. With primary closure of the gingiva at the site of extraction, dental extractions can be performed without the full reversal of anticoagulation.

Objectives This study sought to determine the durability of tricuspid valve repair (TVr) performed concurrently with left ventricular assist device (LVAD) implantation and its association with the development of late right heart failure (RHF). Background Surgical management of tricuspid regurgitation (TR) at the time of LVAD implantation is performed in an attempt to reduce the occurrence of postoperative RHF. Limited data exist regarding the durability of TVr in patients with LVAD as well as its impact on development of late RHF. Methods A retrospective review was conducted of consecutive adult patients who underwent durable LVAD implantation and concurrent TVr at the authors’ institution between 2009 and 2017. Late RHF was defined as readmission for HF requiring inotropic or diuretic therapy. TVr failure was defined as moderate or severe TR at any follow-up echocardiographic examination after LVAD implantation. Results A total of 156 patients underwent LVAD and concurrent TVr during the study. Of the total, 59 patients (37.8%) had a failed TVr. The mean duration of echocardiographic follow-up was 23 ± 22 months. Of the 146 patients who were discharged after the index hospitalization, 53 patients (36.3%) developed late RHF. Multivariate Cox proportional hazard analysis demonstrated that TVr failure was an independent predictor of late RHF development (hazard ratio: 2.62; 95% confidence interval: 1.38 to 4.96; p = 0.003). Conclusions Failure of TVr in this cohort occurred at a significant rate. Failure of TVr is an independent risk factor for development of late RHF. Future studies should investigate strategies to reduce recurrence of significant TR.

Changes in heart transplantation (HT) donor and recipient demographics may influence the incidence of primary graft dysfunction (PGD). We conducted a retrospective study to evaluate PGD incidence, trends, and associated risk factors by analyzing consecutive adult patients who underwent HT between January 2009 and December 2014 at our institution. Patients were categorized as having PGD using the International Society for Heart & Lung Transplantation (ISHLT)–defined criteria. Variables, including clinical and demographic characteristics of donors and recipients, were selected to assess their independent association with PGD. A time-trend analysis was performed over the study period. Three-hundred seventeen patients met inclusion criteria. Left ventricular PGD, right ventricular PGD, or both, were observed in 99 patients (31%). Risk factors independently associated with PGD included ischemic time, recipient African American race, and recipient amiodarone treatment. Over the study period, there was no change in the PGD incidence; however, there was an increase in the recipient pretransplantation use of amiodarone. The rate of 30-day mortality was significantly elevated in those with PGD versus those without PGD (6.06% vs 0.92%, P = .01). Despite recent advancements, incidence of PGD remains high. Understanding associated risk factors may allow for implementation of targeted therapeutic interventions.