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The cardiac phenotype of hereditary transthyretin amyloidosis (hTTR) usually presents as a restrictive or hypertrophic cardiomyopathy, and, although rarely observed as dilated cardiomyopathy (DCM), TTR is routinely included in DCM genetic testing panels. However, the prevalence and phenotypes of TTR variants in patients with DCM have not been reported.Exome sequences of 729 probands with idiopathic DCM were analyzed for TTR and 35 DCM genes.Rare TTR variants were identified in 2 (0.5%; 95% CI = 0.1%-1.8%) of 404 non-Hispanic White DCM probands; neither of them had features of hTTR. In 1 proband, a TTR His110Asn variant and a variant of uncertain significance in DSP were identified, and in the other proband, a TTR Val50Met variant known to cause hTTR and a likely pathogenic variant in FLNC were identified. The TTR Val142Ile variant was identified in 8 (3.0%) non-Hispanic Black probands, comparable with African/African American Genome Aggregation Database controls (OR = 1.01; 95% CI = 0.46-1.99).Among the 729 DCM probands, 2 had rare TTR variants identified without the features of hTTR, and both had other plausible genetic causes of DCM. Moreover, the frequency of TTR Val142Ile was comparable to a control sample. These findings suggest that hTTR variants may have a limited role in patients with DCM without TTR-specific findings.

Introduction Patients with ambulatory advanced heart failure (HF) are increasingly considered for durable mechanical circulatory support (MCS) and heart transplantation and their effective triage requires careful assessment of the clinical trajectory. Methods REVIVAL, a prospective, observational study, enrolled 400 ambulatory advanced HF patients from 21 MCS/transplant centers in 2015-2016. Study design included a clinical re-assessment of Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile within 120 days after enrollment. The prognostic impact of a worsening INTERMACS Profile assigned by the treating physician was assessed at 1 year after the Early Relook. Results Early Relook was done in 325 of 400 patients (81%), of whom 24% had a worsened INTERMACS Profile, associated with longer HF history and worse baseline INTERMACS profile, but no difference in baseline LVEF (median 0.20), 6-minute walk, quality of life, or other baseline parameters. Early worsening predicted higher rate of the combined primary endpoint of death, urgent MCS, or urgent transplant by 1 year after Early Relook, (28% vs 15%), with hazard ratio 2.2 (95% CI 1.2- 3.8; p = .006) even after adjusting for baseline INTERMACS Profile and Seattle HF Model score. Deterioration to urgent MCS occurred in 14% vs 5% (p = .006) during the year after Early Relook. Conclusions Early Relook identifies worsening of INTERMACS Profile in a significant population of ambulatory advanced HF, who had worse outcomes over the subsequent year. Early reassessment of ambulatory advanced HF patients should be performed to better define the trajectory of illness and inform triage to advanced therapies.

BACKGROUND Bleeding is a common and costly complication of percutaneous coronary intervention (PCI). Bleeding avoidance strategies (BAS) are used paradoxically less in patients at high-risk of bleeding: "bleeding risk-treatment paradox" (RTP). We determined whether hospitals and physicians, who do not align BAS to PCI patients' bleeding risk (ie, exhibit a RTP) have higher bleeding rates. METHODS We examined 28,005 PCIs from the National Cardiovascular Data Registry CathPCI Registry for 7 hospitals comprising BJC HealthCare. BAS included transradial intervention, bivalirudin, and vascular closure devices. Patients' predicted bleeding risk was based on National Cardiovascular Data Registry CathPCI bleeding model and categorized as low (

Self-management is a health behavior known to predict treatment outcomes in patients with multiple co-morbidities and/or chronic conditions. However, the self-management process and outcomes in the left-ventricular assist device (LVAD) population are understudied. This pilot randomized control trial (RCT) evaluated the feasibility of a novel “smartphone app-directed and nurse-supported self-management intervention” in patients implanted with durable LVADs. Assessments included behavioral (self-efficacy and adherence), clinical (complications), and healthcare utilization (unplanned clinic, emergency room (ER) visits, and re-hospitalization) outcomes, completed at baseline (pre-hospital discharge) and months 1, 3, and 6 post-hospital discharge. Intervention patients (n = 14) had favorable patterns/trends of results across study outcomes than control patients (n = 16). Notably, intervention patients had much lower complications and healthcare utilization rates than controls. For example, intervention patients had 2 (14.3%) driveline infections in 6 months while control patients had 3 (19.0%). Additionally, at month 3, intervention patients had 0% ER visits versus 36% of control patients. At month 6, the mean cumulative number of re-hospitalizations for the control group was higher (0.9 ± 0.93) than intervention (0.3 ± 0.61) group. Despite the small sample size and limitations of feasibility/pilot studies, our outcomes data appeared to favor the novel intervention. Lessons learned from this study suggest the intervention should be implemented for 6 months post-hospital discharge. Further research is needed including large and rigorous multi-center RCTs to generate knowledge explaining the mechanism of the effect of self-management on LVAD treatment outcomes.

Targeted blood pressure (BP) control is a goal of left ventricular assist device medical management, but the interpretation of values obtained from noninvasive instruments is challenging. In the MOMENTUM 3 Continued Access Protocol, paired BP values in HeartMate 3 (HM3) patients were compared from arterial (A)-line and Doppler opening pressure (DOP) (319 readings in 261 patients) and A-line and automated cuff (281 readings in 247 patients). Pearson (R) correlations between A-line mean arterial (MAP) and systolic blood pressures (SBP) were compared with DOP and cuff measures according to the presence (>1 pulse in 5 seconds) or absence of a palpable radial pulse. There were only moderate correlations between A-line and noninvasive measurements of SBP (DOP R = 0.58; cuff R = 0.47) and MAP (DOP R = 0.48; cuff R = 0.37). DOP accuracy for MAP estimation, defined as the % of readings within ± 10 mmHg of A-line MAP, decreased from 80% to 33% for DOP ≤ 90 vs. >90 mmHg, and precision also diminished (mean absolute difference [MAD] increased from 6.3 ± 5.6 to 16.1 ± 11.4 mmHg). Across pulse pressures, cuff MAPs were within ±10 mmHg of A-line 62.9%-68.8% of measures and MADs were negligible. The presence of a palpable pulse reduced the accuracy and precision of the DOP-MAP estimation but did not impact cuff-MAP accuracy or precision. In summary, DOP may overestimate MAP in some patients on HM3 support. Simultaneous use of DOP and automated cuff and radial pulse may be needed to guide antihypertensive medication titration in outpatients on HM3 support.

Background: Coronary angiography to identify coronary artery disease has been foundational to distinguish the cause of dilated cardiomyopathy (DCM), including the assignment of idiopathic or ischemic cardiomyopathy. Late gadolinium enhancement (LGE) with cardiovascular magnetic resonance (CMR) has emerged as an approach to identify myocardial scar and identify etiology. Methods: The DCM Precision Medicine Study included patients with left ventricular dilation and dysfunction attributed to idiopathic DCM, after expert clinical review excluded ischemic or other cardiomyopathies. Ischemic cardiomyopathy was defined as coronary artery disease with >50% narrowing at angiography of ≥1 epicardial coronary artery. CMR was not required for study inclusion, but in a post hoc analysis of available CMR reports, patterns of LGE were classified as (1) no LGE, (2) ischemic-pattern LGE: subendocardial/transmural, (3) nonischemic LGE: midmyocardial/epicardial. Results: Of 1204 idiopathic DCM patients evaluated, 396 (32.9%) had a prior CMR study; of these, 327 (82.6% of 396) had LGE imaging (mean age 46 years; 53.2% male; 55.4% White); 178 of the 327 (54.4%) exhibited LGE, and 156 of the 178 had LGE consistent with idiopathic DCM. The remaining 22 had transmural or subendocardial LGE. Of these 22, coronary angiography was normal (13), showed luminal irregularities (3), a distant thrombus (1), coronary artery disease with Conclusions: Of 327 probands enrolled in the DCM Precision Medicine Study cohort who had LGE-CMR data available, an ischemic-pattern of LGE was identified in 22 (6.7%), all of whom had idiopathic DCM as adjudicated by expert clinical review. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03037632.

Background Ventricular assist devices provide improved outcomes for patients with advanced heart failure, but their benefit in the severely obese is not well documented. Methods Patients enrolled in the HeartWare ADVANCE trial (n=382) were divided into 2 body mass index (BMI) groups. Patients with severe obesity (>35 kg/m2) were compared with a control group with BMI ≤35 kg/m2. The association of BMI with survival was tested using Kaplan–Meier analysis and major adverse events were compared. Results At implantation, 48 (13%) of patients were severely obese. There was no difference in survival through 2 years of support between severely obese patients and the control group. Severely obese patients were at higher risk of driveline infection (P = .01) and acute renal dysfunction (P = .002). Both groups experienced similar improvements in quality of life. Functional capacity improved in both severely obese and control patients, although severely obese patients had smaller improvements than controls in their 6-minute walk scores. Conclusions Despite an increased risk of adverse events, severe obesity was not associated with reduced survival or quality of life. A better understanding of the risks and benefits of left ventricular assist device therapy in obese patients will help in the shared decision-making of the patient selection process.

Idiopathic dilated cardiomyopathy (DCM) aggregates in families, and early detection in at-risk family members can provide opportunity to initiate treatment prior to late-phase disease. Most studies have included only White patients, yet Black patients with DCM have higher risk of heart failure-related hospitalization and death.To estimate the prevalence of familial DCM among DCM probands and the age-specific cumulative risk of DCM in first-degree relatives across race and ethnicity groups.A family-based, cross-sectional study conducted by a multisite consortium of 25 US heart failure programs. Participants included patients with DCM (probands), defined as left ventricular systolic dysfunction and left ventricular enlargement after excluding usual clinical causes, and their first-degree relatives. Enrollment commenced June 7, 2016; proband and family member enrollment concluded March 15, 2020, and April 1, 2021, respectively.The presence of DCM in a proband.Familial DCM defined by DCM in at least 1 first-degree relative; expanded familial DCM defined by the presence of DCM or either left ventricular enlargement or left ventricular systolic dysfunction without known cause in at least 1 first-degree relative.The study enrolled 1220 probands (median age, 52.8 years [IQR, 42.4-61.8]; 43.8% female; 43.1% Black and 8.3% Hispanic) and screened 1693 first-degree relatives for DCM. A median of 28% (IQR, 0%-60%) of living first-degree relatives were screened per family. The crude prevalence of familial DCM among probands was 11.6% overall. The model-based estimate of the prevalence of familial DCM among probands at a typical US advanced heart failure program if all living first-degree relatives were screened was 29.7% (95% CI, 23.5% to 36.0%) overall. The estimated prevalence of familial DCM was higher in Black probands than in White probands (difference, 11.3% [95% CI, 1.9% to 20.8%]) but did not differ significantly between Hispanic probands and non-Hispanic probands (difference, -1.4% [95% CI, -15.9% to 13.1%]). The estimated prevalence of expanded familial DCM was 56.9% (95% CI, 50.8% to 63.0%) overall. Based on age-specific disease status at enrollment, estimated cumulative risks in first-degree relatives at a typical US advanced heart failure program reached 19% (95% CI, 13% to 24%) by age 80 years for DCM and 33% (95% CI, 27% to 40%) for expanded DCM inclusive of partial phenotypes. The DCM hazard was higher in first-degree relatives of non-Hispanic Black probands than non-Hispanic White probands (hazard ratio, 1.89 [95% CI, 1.26 to 2.83]).In a US cross-sectional study, there was substantial estimated prevalence of familial DCM among probands and modeled cumulative risk of DCM among their first-degree relatives.ClinicalTrials.gov Identifier: NCT03037632.

Introduction: Peripartum cardiomyopathy (PPCM) is a severe complication of pregnancy which is hallmarked by non-ischemic reduction in left ventricular ejection fraction (LVEF) to Methods: Thirty female patients 18-46 years of age underwent cardiac surgery for PPCM between 2012-2020. Primary heart transplant patients (n=2) were excluded. PPCM patients with a new MCS requirement (n=28) were classified by device type and escalations in device support. Results: Mean age was 29±7 years and 21 patients (75%) were African American. Median time from delivery to MCS requirement was 418 [91-1201] days. Nineteen (68%) patients required temporary MCS (tMCS): 12 (63%) on intraaortic balloon pump, 9 (47%) on veno-arterial extracorporeal membrane oxygenation, and 4 (21%) on Impella. Nine (32%) patients underwent left ventricular assist device (LVAD) implant after failure of medical therapy. LVEF and left ventricular end-diastolic diameter (LVEDD) at MCS insertion were 14±5mm and 68±11mm, respectively. LVEF progressed to 24%±16% post-insertion and 29%±17% one year (Figure 1). Of the 19 tMCS patients, 5 (26%) required escalations with additional modalities. Ten (53%) patients were bridged to durable LVAD. Complications included right ventricular failure (n=4), stroke (n=2), sepsis (n=1), dialysis (n=5), and cardiac arrest (n=3). Duration of support was 9±7 days for tMCS and 996±625 days for LVAD. Overall survival to discharge was 89% (n=25). Twelve patients underwent transplant (43%) and two (7%) recovered native heart function. Conclusions: Severe PPCM can be effectively managed with tMCS as a bridging strategy to either transplant or durable LVAD. Patients will often require multiple escalations in resource-intensive therapy, but outcomes are excellent with vigilant management.

Standardized donor‐derived cell‐free DNA (dd‐cfDNA) testing has been introduced into clinical use to monitor kidney transplant recipients for rejection. This report describes the performance of this dd‐cfDNA assay to detect allograft rejection in samples from heart transplant (HT) recipients undergoing surveillance monitoring across the United States. Venous blood was longitudinally sampled from 740 HT recipients from 26 centers and in a single‐center cohort of 33 patients at high risk for antibody‐mediated rejection (AMR). Plasma dd‐cfDNA was quantified by using targeted amplification and sequencing of a single nucleotide polymorphism panel. The dd‐cfDNA levels were correlated to paired events of biopsy‐based diagnosis of rejection. The median dd‐cfDNA was 0.07% in reference HT recipients (2164 samples) and 0.17% in samples classified as acute rejection (35 samples; P = .005). At a 0.2% threshold, dd‐cfDNA had a 44% sensitivity to detect rejection and a 97% negative predictive value. In the cohort at risk for AMR (11 samples), dd‐cfDNA levels were elevated 3‐fold in AMR compared with patients without AMR (99 samples, P = .004). The standardized dd‐cfDNA test identified acute rejection in samples from a broad population of HT recipients. The reported test performance characteristics will guide the next stage of clinical utility studies of the dd‐cfDNA assay., A large multicenter study in a broad heart transplant surveillance population demonstrates the ability of standardized donor‐ derived cell‐free DNA testing to identify both T cell–mediated and antibody‐mediated acute rejection with a high negative predictive value.

The number of Left Ventricular Assist Devices (LVADs) implanted each year is rising. Nevertheless, there are minimal data on device acceptance after LVAD implant, and on its relationship with patient-reported outcomes. We designed a cross-sectional study to address this knowledge gap and test the hypothesis that low device acceptance is associated with poorer quality of life, depression and anxiety. Self-report questionnaires were administered to assess quality of life (12-item Kansas City Cardiomyopathy Questionnaire quality of life subscale), level of anxiety (7-item Generalized Anxiety Disorder; GAD-7), level of depression (9-item Patient Health Questionnaire; PHQ-9) and device acceptance (Florida Patient Acceptance Survey; FPAS) to 101 consecutive patients presenting to LVAD clinic. Regression analysis showed a strong correlation between device acceptance and both psychological distress (p

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.).

Acute kidney injury is a common complication following heart transplantation, and the factors contributing to acute kidney injury are not well understood. We conducted a retrospective cohort study evaluating patients who underwent heart transplantation between 2009 and 2016 at a single institution. The primary endpoint was incidence of acute kidney injury as defined by Kidney Disease Improving Global Outcomes criteria. Secondary endpoints included 30‐day hospital readmission, 30‐day mortality, and 1‐year mortality. A total of 228 heart transplant patients were included in the study for analysis. In total, 145 (64%) developed acute kidney injury, where 43 (30%) were classified as stage I, 28 (19%) as stage II, and 74 (51%) as stage III. Risk factors found to be associated with the presence of acute kidney injury included increased use of vasopressors and inotropes post‐transplant. Protective factors included cardiopulmonary bypass time

Continuous-flow left ventricular assist device (CF-LVAD) support is a mainstay in the hemodynamic management of patients with end-stage heart failure refractory to optimal medical therapy. In this report we evaluated waitlist complications and competing outcomes for CF-LVAD patients compared with primary transplant candidates listed for orthotopic heart transplantation at a single center.All patients listed for orthotopic heart transplantation between 2006 and 2020 at our institution were retrospectively reviewed (CF-LVAD, 300; primary transplant, 244). Kaplan-Meier methodology with log-rank testing was used to evaluate survival outcomes. Terminal outcomes of death, delisting, and transplant were assessed as competing risks and compared between groups using Gray's test. Multivariable Fine-Gray regression was used to identify predictors of transplantation.One-year rates of transplant, delisting, and death were 48%, 8%, and 2%, respectively, for CF-LVAD patients and 45%, 15%, and 9%, respectively, for primary transplant (all P.001). Waitlist mortality at 5 years was 4% among CF-LVAD patients and 13% for primary transplants. All-cause mortality after listing was lower for CF-LVAD patients (P = .017). There was no difference in posttransplant survival between groups (P = .250). On multivariable Fine-Gray regression stroke (P = .017), respiratory failure (P = .032), right ventricular failure (P = .019), and driveline infection (P = .050) were associated with decreased probability of transplantation. Posttransplant survival was not significantly worse for CF-LVAD patients who experienced device-related complications (P = .901).Although device-related complications were significantly associated with decreased rates of transplant, CF-LVAD patients had excellent waitlist outcomes overall. In light of the 2018 allocation score change the risk of complications should be taken into account when deciding whether to offer CF-LVAD as a bridge to transplant.

Background Immune dysregulation is implicated in the development and clinical outcomes of peripartum cardiomyopathy (PPCM). Methods and results 98 women with PPCM were enrolled and followed for 1 year postpartum (PP). LVEF was assessed at entry, 6-, and 12-months PP by echocardiography. Serum levels of soluble interleukin (IL)-2 receptor (sIL2R), IL-2, IL-4, IL-17, IL-22, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were measured by ELISA at entry. Cytokine levels were compared between women with PPCM by NYHA class. Outcomes including myocardial recovery and event-free survival were compared by cytokine tertiles. For cytokines found to impact survival outcomes, parameters indicative of disease severity including baseline LVEF, medications, and use of inotropic and mechanical support were analyzed. Levels of proinflammatory cytokines including IL-17, IL-22, and sIL2R, were elevated in higher NYHA classes at baseline. Subjects with higher IL-22 levels were more likely to require inotropic or mechanical support. Higher levels of TNF-α and IL-22 were associated with poorer event-free survival. Higher TNF-α levels were associated with lower mean LVEF at entry and 12 months. In contrast, higher levels of immune-regulatory cytokines such as IL-4 and IL-2 were associated with higher LVEF during follow up. Conclusion Proinflammatory cytokines IL-22 and TNF-α were associated with adverse event-free survival. IL-17 and IL-22 were associated with more severe disease. In contrast, higher levels of IL-2 and IL-4 corresponded with higher subsequent LVEF. Increased production of TH17 type cytokines in PPCM correlated with worse disease and outcomes, while an increased immune-regulatory response seems to be protective.

Objective: Intra-aortic balloon pump (IABP) support has been used as a bridge to transplant (BTT) therapy for acutely deteriorating patients awaiting orthotopic heart transplantation (OHT). Given recent changes to the heart allocation algorithm which have expanded IABP use for BTT, the evaluation of device strategy, complications, and near-term survival is warranted. Methods: Patients bridged with IABP who underwent OHT between October 2018 and January 2020 at our institution were retrospectively reviewed (n=21). Chart review was conducted to assess IABP insertion site, timing of support, device-related complications, removal strategy, and thirty-day post-transplant mortality. Results: Patients were bridged with femoral (n=6), axillary (n=9), or femoral with axillary conversion (n=6) approaches for IABP insertion. Common complications included pump malposition (n=5), hematuria (n=4), pump exchange (n=9), and insertion site bleeding (n=2). Median duration of IABP support was 12 [7, 18] days and median time to removal after OHT was 1 [1, 2] day. IABP removal occurred at the bedside with direct pressure application for all femoral pumps (n=6). Among axillary pumps (n=15), 11 were removed at the bedside with direct pressure, 3 were removed in the operating room, and 1 was removed in the catheterization lab with device closure. There was no thirty-day mortality following OHT. Conclusion: Following the changes to the heart allocation algorithm, IABP has become the most common method of temporary mechanical circulatory support for patients awaiting OHT at our center with excellent early survival and acceptable complication rates. In addition to allowing patients to ambulate while on IABP, we find that axillary insertion did not result in excess bleeding complications and that bedside removal with direct pressure was a safe method for postoperative decannulation.

BACKGROUND: The clinical presentation of idiopathic dilated cardiomyopathy (IDCM) heart failure (HF) patients who will respond to medical therapy (responders) and those who will not (non-responders) is often similar. A machine learning (ML)-based clinical tool to identify responders would prevent unnecessary surgery, while targeting non-responders for early intervention. We used regional left ventricular (LV) contractile injury patterns in ML models to identify IDCM HF non-responders. METHODS: MRI-based multiparametric strain analysis was performed in 178 test subjects (140 normal subjects and 38 IDCM patients), calculating longitudinal, circumferential, and radial strain over 18 LV sub-regions for inclusion in ML analyses. Patients were identified as responders based upon symptomatic and contractile improvement on medical therapy. We tested the predictive accuracy of support vector machines (SVM), logistic regression (LR), random forest (RF), and deep neural networks (DNN). RESULTS: The DNN model outperformed other models, predicting response to medical therapy with an area under the receiver operating characteristic curve (AUC) of 0.94. The top features were longitudinal strain in 1) basal: anterior, posterolateral and 2) mid: posterior, anterolateral, and anteroseptal sub-regions. CONCLUSIONS: Regional contractile injury patterns predict response to medical therapy in IDCM HF patients, and have potential application in ML-based HF patient care.

Background: Patients with heart failure (HF) often have multiple chronic conditions that may impact health-related quality of life (HRQOL) despite HF therapy. We sought to determine the association between noncardiac comorbidities and HRQOL in ambulatory patients with advanced HF. Methods: Baseline data from 373 subjects in REVIVAL (Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life) were analyzed using multivariable general linear models to evaluate the relationship between comorbidities and HRQOL (EuroQol Visual Analogue Scale, EQ-5D-3L Index Score, and Kansas City Cardiomyopathy Questionnaire). The primary independent variables were a comorbidity index (sum of 14 noncardiac conditions), a residual comorbidity index (without depression), and depression alone. The median (25th to 75th percentile) number of comorbidities was 3 (2–4). Results: Increasing comorbidity burden was associated with a reduction in generic (EQ-5D Index, P =0.005) and HF-specific (Kansas City Cardiomyopathy Questionnaire, P =0.001) HRQOL. The residual comorbidity index was not associated with HRQOL when depression included in the model independently, while depression was associated with HRQOL across all measures. Participants with depression (versus without) scored on average 13 points (95% CI, 8–17) lower on the EuroQol Visual Analogue Scale, 0.15 points (95% CI, 0.12–0.18) lower on the EQ-5D Index, and 24.9 points (95% CI, 21.2–28.5) lower on the Kansas City Cardiomyopathy Questionnaire overall summary score. Conclusions: While noncardiac comorbidities were prevalent in ambulatory advanced HF patients, only depression was associated with decreased generic and HF-specific HRQOL. Other than depression, the presence of noncardiac comorbidities should not impact expected gains in HRQOL following ventricular assist device implantation, provided the conditions are not a contraindication to implant. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01369407.

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.

Objective Left ventricular assist device (LVAD) implantation has been shown to increase allosensitization before orthotopic heart transplantation, but the influence of LVAD support on posttransplant rejection is controversial. This study examines the postoperative incidence of acute cellular rejection (ACR) in patients bridged with continuous flow LVAD (CF-LVAD) relative to primary transplant (Primary Tx). Methods All patients who underwent orthotopic heart transplantation at our institution between July 2006 and March 2019 were retrospectively reviewed (n = 395). Patients were classified into Primary Tx (n = 145) and CF-LVAD (n = 207) groups. Propensity score matching on 13 covariates implemented a 0.1 caliper logistic model with nearest neighbor 1:1 matching. Development of moderate to severe (ie, 2R/3R) rejection was evaluated using a competing risks model. Potential predictors of 2R/3R ACR were evaluated using Fine-Gray regression on the marginal subdistribution hazard. Results Propensity score matching yielded 122 patients in each group (n = 244). At 12 and 24 months, the cumulative incidence of 2R/3R ACR was 17% and 23% for the CF-LVAD group and 26% and 31%, respectively, for the Primary Tx group (P = .170). CF-LVAD was not predictive of 2R/3R rejection on multivariable Fine-Gray regression (subdistribution hazard ratio, 0.73; 95% confidence interval, 0.40-1.33; P = .301). There was no difference in the 5-year incidence of antibody mediated rejection (10% [n = 12] vs 9% [n = 11]; P = .827). Conclusions After adjusting for covariates, CF-LVAD was not associated with an increased risk of moderate to severe ACR during the 24 months after cardiac transplantation. Further investigation is warranted with larger cohorts, but CF-LVAD may have minimal influence on posttransplant ACR.

Cerebrovascular events (CVE) are among the most common and serious complications after implantation of continuous-flow left ventricular assist devices (CF-LVAD). We studied the incidence, subtypes, anatomical distribution, and pre- and post-implantation risk factors of CVEs as well as the effect of CVEs on outcomes after CF-LVAD implantation at our institution. Retrospective analysis of clinical and neuroimaging data of 372 patients with CF-LVAD between May 2005 and December 2013 using standard statistical methods. CVEs occurred in 71 patients (19%), consisting of 35 ischemic (49%), 26 hemorrhagic (37%), and 10 ischemic+hemorrhagic (14%) events. History of coronary artery disease and female gender was associated with higher odds of ischemic CVE (OR 2.84 and 2.5, respectively), and diabetes mellitus was associated with higher odds of hemorrhagic CVE (OR 3.12). While we found a higher rate of ischemic CVEs in patients not taking any antithrombotic medications, no difference was found between patients with ischemic and hemorrhagic CVEs. Occurrence of CVEs was associated with increased mortality (HR 1.62). Heart transplantation was associated with improved survival (HR 0.02). In patients without heart transplantation, occurrence of CVE was associated with decreased survival. LVADs are associated with high rates of CVE, increased mortality, and lower rates of heart transplantation. Further investigations to identify the optimal primary and secondary stroke prevention measures in post-LVAD patients are warranted.

This study tested the applicability of the individual and family self-management theory (IFSMT) to self-management (SM) in patients with left ventricular assist devices (LVADs). From an existing data set, we extracted the following variables that correspond to IFSMT's conceptual dimensions: anxiety, depression, and cognition (context dimension); self-efficacy (SM process dimension); adherence and quality of life (QOL; outcome dimensions). Descriptive statistics and partial least squares path modeling procedures were used for data analyses. A total of 100 patients (mean age 52 ± 13.4 years) with continuous flow LVAD designs comprised the present study. Most patients were White (78%), married (69%), college-educated (72%), and on disability (53%). Their mean anxiety and depression scores were slightly above normal, while their cognitive function scores were slightly lower than normal. LVAD care self-efficacy, adherence, and QOL were within normal ranges. Factor loadings ranged from 0.50 to 1.0, and there were significant forward path relationships among the context, process, and outcome dimensions (β ranges from 0.02 to 0.60, all P values < 0.05). In conclusion, the IFSMT provides a good fit for SM in LVAD. Further research is needed to clarify how best to improve LVAD SM practice and treatment outcomes.

Treatment of advanced heart failure with implantable LVADs is increasing, driven by profound unmet patient need despite potential serious complications: bleeding, infection, and thrombus. The experimental objective was to develop a sensitive imaging approach to assess early thrombus accumulation in LVADs under operational high flow and high shear rates. Methods: A monomeric bifunctional ligand with a fibrin-specific peptide, a short spacer, and 99mTc chelating amino acid sequence (F1A) was developed and compared to its tetrameric PEG analogue (F4A). Results:99mTc attenuation by LVAD titanium (1 mm) was 23%. 99mTc-F1A affinity to fibrin was Kd ~10 µM, whereas, the bound 99mTc-F4A probe was not displaced by F1A (120,000:1). Human plasma interfered with 99mTc-F1A binding to fibrin clot (p

Background Patients supported with extracorporeal life support (ECLS) can experience severe complications from increased left ventricular (LV) afterload. The Impella (Abiomed, Danvers, MA) percutaneous ventricular assist device (PVAD) may offer an attractive option for unloading the LV in these patients. This study describes the efficacy and outcomes of PVAD use during ECLS compared with surgically placed LV vent. Methods In this retrospective study, we reviewed patients supported by ECLS with PVAD or surgical LV vent for cardiogenic shock between April 2010 and May 2016. Included were 23 patients with PVADs and 22 with surgical vents. Patients' baseline characteristics, hemodynamic data, and outcomes were collected immediately preceding combined support initiation, at 48 hours, intensive care unit discharge, and 30 days. Results After 48 hours, pulmonary artery diastolic pressure was significantly reduced in the PVAD (23.3 ± 8.4 vs 15.6 ± 4.2, p = 0.02) and surgical vent groups (20.1 ± 5.9 vs 15.6 ± 5.4, p = 0.01), and radiographic evidence of pulmonary edema was reduced or unchanged in 90% of PVAD patients and in 76% of surgical vent patients. The primary end points of survival to 30 days (43% vs 32%, p = 0.42) and intensive care unit discharge (35% vs 23%, p = 0.37) were not different between the two methods of support. The PVAD and surgical vent groups were also not significantly different in the rate of vascular complications or in the number decannulated from ECLS and transitioned to durable LV assist device. Conclusions PVAD use in ECLS patients is an effective means of LV unloading and preventing worsened pulmonary edema, with outcomes and complications that are comparable to surgical LV vent.

We analyzed humoral immune responses to nonhuman leukocyte antigen (HLA) after cardiac transplantation to identify antibodies associated with allograft rejection. Protein microarray identified 366 non-HLA antibodies (>1.5 fold, P1R) with an area under the curve of 0.87 (P&nbsp

Tick-borne infections represent a significant health risk each year in the United States. Immunocompromised patients are typically at risk of more severe disease manifestations than their immunocompetent counterparts. Here we report a case of a newly emerging phlebovirus, Heartland virus, in a heart transplant recipient.

Current guidelines recommend adenosine diphosphate receptor inhibitors (ADPRi) be discontinued 5-7 days prior to cardiac surgery due to increased bleeding events, rates of re-exploration, and transfusions. However, the risks of left ventricular assist device (LVAD) implantation in patients taking an ADPRi have not previously been studied. We retrospectively identified 134 eligible patients with ischemic cardiomyopathy that underwent LVAD implantation between July 2009 and August 2013. The cohorts received an ADPRi ≤5 days of surgery (n = 25) versus >5 days prior or not at all (n = 109). Subgroup analyses adjusted for differences in frequency of redo sternotomy between cohorts, excluded patients that received an ADPRi >1 year prior to surgery, and excluded patients with a redo sternotomy. The ADPRi and control groups did not have significant differences in the primary outcomes, intraoperative PRBC units transfused (3.0 vs. 4.0, p = 0.12) or chest tube output within 24 h of surgery (1.66 L vs. 1.80 L, p = 0.61). After adjusting for differences in frequency of redo sternotomy (ADPRi vs. control, 12 vs. 52%, p ≤ 0.001), no significant difference in PRBC units transfused (3.1 vs. 3.5, p = 0.59) or chest tube output (2.04 L vs. 2.04 L, p = 0.98) was seen. No significant difference in 30-day mortality (8.0 vs. 11.0%, p = 0.63), 90-day mortality (16.4 vs. 23.3%, p = 0.42), or length of stay (29.0 vs. 28.0, p = 0.61) was seen. In this single-center experience, use of an ADPRi ≤5 days prior to LVAD implantation was not associated with increased bleeding, length of stay, or mortality.

Purpose Acute kidney injury (AKI) is a common complication following heart transplant and has been found to be associated with increased morbidity and mortality. The goal of this study is to examine pre- and peri-operative risk factors for AKI post-heart transplant and to identify potentially modifiable risk factors. Methods We conducted a retrospective cohort study evaluating patients who underwent heart transplant between 2009 and 2016 at a single institution. Data were obtained from the Society of Thoracic Surgeons (STS) national database and retrospective chart review. Exclusion criteria were age Results A total of 189 heart transplant patients were included in the study for analysis. In total, 113 (60%) developed AKI, where 37 (33%) were classified as stage I, 23 (20%) as stage II, 53 (47%) as stage III, and 45 patients (24%) required dialysis. Risk factors found to be associated with the presence of AKI included elevated pre-op central venous pressure (CVP) (16 mmHg non-AKI group vs 19 mmHg AKI group, p = 0.020), increased use of vasopressors and inotropes post-transplant, number of blood products transfused (9 vs 11 units, p = 0.009), cardiopulmonary bypass time (163 vs 180 min, p = 0.002), and complications such as delayed sternal closure (19 (29%) vs 48 (45%), p = 0.030). Dialysis after discharge was needed for 7 (8%, p = 0.090) AKI patients. No significant association was found between presence of AKI and hospital readmission, 30-day mortality, and 1-year mortality. Conclusion Risk factors such as elevated pre-op CVP, high use of vasopressors and inotropes, number of blood products transfused, and delayed sternal closure were closely associated with the development of AKI. Delayed sternal closure and number of blood products transfused highlight the impact of bleeding, and the elevated pre-operative CVP is of particular interest due to its potentially modifiable nature.

Purpose There is a significant unmet patient need for heart transplantation, driven partly by low donor heart utilization. Donor left ventricular dysfunction (LVD) is the most common reason for non-allocation. A significant proportion of brain-dead donors will have transient LVD with subsequent recovery, and these donor hearts are considered an underutilized subset. However, their association with post-transplant outcomes, specifically primary graft dysfunction (PGD), remains unclear. This study investigates the relationship between donor clinical characteristics and post-transplant PGD. Methods Donor and post-transplant data was obtained for all donor hearts originating from a centralized diagnostic and recovery OPO that were transplanted at a single institution between 2010-2017. Transient LVD was defined as initial LV ejection fraction (LVEF) at OPO Results 152 heart transplant patients were identified with corresponding donor hearts originating from the OPO, of which 32 (21%) had post-transplant PGD. PGD was not associated with donor baseline characteristics, pressor requirements, or lab values (Table 1). PGD was associated with lower donor final LVEF (57.5% vs. 60%, p Conclusion This study indicates that patients receiving donor hearts with transient LV dysfunction have a two-fold increased risk of PGD. Given these findings, vigilance for PGD, careful consideration regarding donor-recipient matching, and early hemodynamic support should be considered in these patients.

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

Background Left ventricular (LV) dysfunction is the most common reason that potential donor hearts are not allocated. However, a significant proportion of brain-dead donors (BDDs) have transient LV dysfunction, and these allocated hearts have equivalent post-transplant outcomes. It is difficult to determine which potential donors with cardiac dysfunction on initial assessment are likely to recover. Stress-induced cardiomyopathy (SIC) patterns, specifically reverse takatsubo's- LV basal hypokinesis with apical hyperkinesis, are often observed in BDDs, however its association with donor LV recovery remains unclear. We retrospectively reviewed echocardiograms from our OPO's recovery center to determine if specific strain patterns predict functional recovery. Methods All BDDs managed at a single OPO recovery center between 1/1/2015-6/1/2018 with reduced initial LV ejection fraction (LVEF) ≤ 40% were included. Initial echocardiograms were adjudicated for image quality, with donors with poor quality or inability to obtain longitudinal strain (LS) excluded. All echocardiograms were interpreted by a single reader, with segmental and global longitudinal strain (SLS and GLS) analysis conducted in apical views. Composite LV apical and basal SLS obtained in each view were used to quantify apical-to-basal strain ratio. LV recovery was defined as an LVEF ≥ 50% on a subsequent echocardiogram during the evaluation process. Results 54 donors were included in this analysis, 29 (54%) had LV recovery and 25 (46%) donors did not have LV recovery. Donors with LV recovery had higher initial LVEF and greater overall LVEF improvement, with greater average overall LV and RV GLS (Table 1). The LV recovery group also had higher average LV apical and basal LS. However, LV, RV, apical, and basal LS were not independently associated with LV recovery when normalized for initial LVEF. Among all donors, the LV apical-to-basal LS ratio was 2.11 ± 1.7. There was no difference in apical-to-basal strain ratio between LV recovery and no recovery groups. Conclusion Reverse takatsubo's-type pattern with elevated apical-to-basal LS ratio was generally observed among all BDDs with LV dysfunction, however this ratio was not associated with LV recovery. Multiple echocardiographic measures were associated with recovery, including initial LVEF, LV GLS and SLS. However, strain does not appear to provide added predictive value for recovery when accounting for initial LVEF. Additional work, combining imaging and clinical data, is needed to better predict donor LV recovery and thus expand the cardiac donor pool.

Objectives The purpose of this study was to determine the risk factors for ischemic in hemorrhage cerebrovascular events in patients supported by the HeartWare ventricular assist device (HVAD). Background Patients supported with left ventricular assist devices are at risk for both ischemic and hemorrhagic cerebrovascular events. Methods Patients undergoing implantation with a HVAD as part of the bridge-to-transplant trial and subsequent continued access protocol were included. Neurological events (ischemic cerebrovascular accidents [ICVAs] and hemorrhagic cerebrovascular accidents [HCVAs]) were assessed, and the risk factors for these events were evaluated in a multivariable model. Results A total of 382 patients were included: 140 bridge-to-transplant patients from the ADVANCE (Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure) clinical trial and 242 patients from the continued access protocol. Patients had a mean age of 53.2 years; 71.2% were male, and 68.1% were white. Thirty-eight percent had ischemic heart disease, and the mean duration of support was 422.7 days. The overall prevalence of ICVA was 6.8% (26 of 382); for HCVA, it was 8.4% (32 of 382). Pump design modifications and a protocol-driven change in the antiplatelet therapy reduced the prevalence of ICVA from 6.3% (17 of 272) to 2.7% (3 of 110; p = 0.21) but had a negligible effect on the prevalence of HVCA (8.8% [24 of 272] vs. 6.4% [7 of 110]; p = 0.69). Multivariable predictors of ICVA were aspirin ≤81 mg and atrial fibrillation; predictors of HCVA were mean arterial pressure >90 mm Hg, aspirin ≤81 mg, and an international normalized ratio >3.0. Eight of the 30 participating sites had established improved blood pressure management (IBPM) protocols. Although the prevalence of ICVA for those with and without IBPM protocols was similar (5.3% [6 of 114] vs. 5.2% [14 of 268]; p = 0.99), those with IBPM protocols had a significantly lower prevalence of HCVA (1.8% [2 of 114] vs. 10.8% [29 of 268]; p = 0.0078). Conclusions Anticoagulation, antiplatelet therapy, and blood pressure management affected the prevalence of cerebrovascular events after implantation of the HVAD. Attention to these clinical parameters can have a substantial impact on the occurrence of serious neurological events. (Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure [ADVANCE]; NCT00751972)

Background Peripartum cardiomyopathy (PPCM) remains a major cause of maternal morbidity and mortality. Objectives This study sought to prospectively evaluate recovery of the left ventricular ejection fraction (LVEF) and clinical outcomes in the multicenter IPAC (Investigations of Pregnancy Associated Cardiomyopathy) study. Methods We enrolled and followed 100 women with PPCM through 1 year post-partum. The LVEF was assessed by echocardiography at baseline and at 2, 6, and 12 months post-partum. Survival free from major cardiovascular events (death, transplantation, or left ventricular [LV] assist device) was determined. Predictors of outcome, particularly race, parameters of LV dysfunction (LVEF), and remodeling (left ventricular end-diastolic diameter [LVEDD]) at presentation, were assessed by univariate and multivariate analyses. Results The cohort was 30% black, 65% white, 5% other; the mean patient age was 30 ± 6 years; and 88% were receiving beta-blockers and 81% angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The LVEF at study entry was 0.35 ± 0.10, 0.51 ± 0.11 at 6 months, and 0.53 ± 0.10 at 12 months. By 1 year, 13% had experienced major events or had persistent severe cardiomyopathy with an LVEF Conclusions In a prospective cohort with PPCM, most women recovered; however, 13% had major events or persistent severe cardiomyopathy. Black women had more LV dysfunction at presentation and at 6 and 12 months post-partum. Severe LV dysfunction and greater remodeling at study entry were associated with less recovery. (Investigations of Pregnancy Associated Cardiomyopathy [IPAC]; NCT01085955 )

The presentation, natural history, clinical outcomes, and response to therapy in patients with heart failure differ in some ways across populations. Women, older adults, and non-Caucasian racial or ethnic groups compose a substantial proportion of the overall heart failure population, but they have typically been underrepresented in clinical trials. As a result, uncertainty exists about the efficacy of some guideline-directed medical therapies and devices in specific populations, which may result in the under- or overtreatment of these patients. Even when guideline-based treatments are prescribed, socioeconomic, physical, or psychologic factors may affect non-Caucasian and older adult patient groups to a different extent and affect the application, effectiveness, and tolerability of these therapies. Individualized therapy based on tailored biology (genetics, proteomics, metabolomics), socioeconomic and cultural considerations, and individual goals and preferences may be the optimal approach for managing diverse patients. This comprehensive approach to personalized medicine is evolving, but in the interim, the scientific community should continue efforts focused on intensifying research in special populations, prescribing guideline-directed medical therapy unless contraindicated, and implementing evidence-based strategies including patient and family education and multidisciplinary team care in the management of patients.

Background Stromal cell-derived factor-1 (SDF-1) promotes tissue repair through mechanisms of cell survival, endogenous stem cell recruitment, and vasculogenesis. Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Heart Failure (STOP-HF) is a Phase II, double-blind, randomized, placebo-controlled trial to evaluate safety and efficacy of a single treatment of plasmid stromal cell-derived factor-1 (pSDF-1) delivered via endomyocardial injection to patients with ischaemic heart failure (IHF). Methods Ninety-three subjects with IHF on stable guideline-based medical therapy and left ventricular ejection fraction (LVEF) ≤40%, completed Minnesota Living with Heart Failure Questionnaire (MLWHFQ) and 6-min walk distance (6 MWD), were randomized 1 : 1 : 1 to receive a single treatment of either a 15 or 30 mg dose of pSDF-1 or placebo via endomyocardial injections. Safety and efficacy parameters were assessed at 4 and 12 months after injection. Left ventricular functional and structural measures were assessed by contrast echocardiography and quantified by a blinded independent core laboratory. Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Heart Failure was powered based on change in 6 MWD and MLWHFQ at 4 months. Results Subject profiles at baseline were (mean ± SD): age 65 ± 9 years, LVEF 28 ± 7%, left ventricular end-systolic volume (LVESV) 167 ± 66 mL, N-terminal pro brain natriuretic peptide (BNP) (NTproBNP) 1120 ± 1084 pg/mL, MLWHFQ 50 ± 20 points, and 6 MWD 289 ± 99 m. Patients were 11 ± 9 years post most recent myocardial infarction. Study injections were delivered without serious adverse events in all subjects. Sixty-two patients received drug with no unanticipated serious product-related adverse events. The primary endpoint was a composite of change in 6 MWD and MLWHFQ from baseline to 4 months follow-up. The primary endpoint was not met ( P = 0.89). For the patients treated with pSDF-1, there was a trend toward an improvement in LVEF at 12 months (placebo vs. 15 mg vs. 30 mg ΔLVEF: −2 vs. −0.5 vs. 1.5%, P = 0.20). A pre-specified analysis of the effects of pSDF-1 based on tertiles of LVEF at entry revealed improvements in EF and LVESV from lowest-to-highest LVEF. Patients in the first tertile of EF (

Objectives This study evaluated the Heartmate Risk Score (HMRS) and its potential benefits in clinical practice. Background The HMRS has been shown to correlate with mortality in the cohort of patients enrolled in the Heartmate II trials, but its validity in unselected, “real world” populations remains unclear. Methods This study identified a cohort of 269 consecutive patients who received a Heartmate II left ventricular assist device at our institution, the Barnes-Jewish Hospital in St. Louis, Missouri, between June 2005 and June 2013. Ninety-day and 2-year mortality rates, as well as frequency of several morbid events, were compared by retrospectively assigned HMRS category groups. The analysis was repeated within the subgroup of INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) class 1 patients. Results Receiver operating curve analysis showed that the HMRS correlated with 90-day mortality with an area under the curve of 0.70. Stratification in low, mid, and high HMRS groups identified patients with increasing hazard of 90-day mortality, increasing long-term mortality, increasing rate of gastrointestinal bleeding events, and increasing median number of days spent in the hospital in the first year post implant. Within INTERMACS class 1 patients, those in the highest HMRS group were found to have a relative risk of 90-day mortality 5.7 times higher than those in the lowest HMRS group (39.1% vs. 6.9%, p = 0.029). Conclusions HMRS is a valid clinical tool to stratify risk of morbidity and mortality after implant of Heartmate II devices in unselected patients and can be used to predict short-term mortality risk in INTERMACS class 1 patients.

Background Stroke is a significant complication in patients supported with continuous-flow left ventricular assist devices (CF-LVAD) and hypertension is a significant risk factor for stroke, but the association between blood pressure and stroke in LVAD patients is not well characterized. Methods We identified 275 consecutive patients who survived implant hospitalization between January 2005 and April 2013. Patients were grouped according to systolic blood pressure (SBP) as above a median and below a median of 100 mm Hg by their averaged systolic blood pressure during the 48 hours before discharge from implantation hospitalization. The groups were compared for the primary outcome of time to stroke. Results The above-median SBP group had mean SBP of 110 mm Hg and the below-median SBP group had mean SBP of 95 mm Hg. There were no significant between-group differences in body mass index, smoking, vascular disease, hypertension, atrial fibrillation, or prior stroke. During a mean follow-up of 16 months, stroke occurred in 16% of the above-median SBP group vs in 7% of the below-median SBP group (hazard ratio, 2.38; 95% confidence interval, 1.11–5.11), with a similar proportion of hemorrhagic and ischemic strokes in each group. In Cox proportional hazard models adjusting for age, diabetes, or prior stroke, the hazard ratio remained statistically significant. SBP as a continuous variable predictor of stroke had an area under the curve of 0.64 in a receiver operating characteristic curve analysis. Conclusions In this large, CF-LVAD cohort, elevated SBP was independently associated with a greater risk of subsequent stroke. These results identify management of hypertension as a potential modifiable risk factor for reducing the incidence of stroke in patients supported by CF-LVAD.

Summary Introduction Secondary pulmonary hypertension (PH) and right ventricular dysfunction are common and associated with poor prognosis in HF patients with left ventricular assist devices (LVADs). The role of pulmonary vasodilator therapy for these patients is currently unclear. Aims We sought to evaluate the safety and clinical course of patients treated with bosentan, an endothelin receptor antagonist, after the implementation of a LVAD. Results Between 10/2008 and 5/2011, 50 consecutive patients with mean PAP >25 mmHg were treated with bosentan after LVAD implantation for a mean duration of 15.7 (±12.4) months. Ten patients discontinued the drug for possible side effects, including three for LFT abnormalities. Comparison of baseline to 6-month follow-up data revealed laboratory evidence for decongestion with a decrease in bilirubin (2.3–0.6, P

The basis for increased mortality after heart transplantation in African Americans and other non-Caucasian racial groups is poorly defined. We hypothesized that increased risk of adverse events is driven by biologic factors. To test this hypothesis in the Invasive Monitoring Attenuation through Gene Expression (IMAGE) study, we determined whether the event rate of the primary outcome of acute rejection, graft dysfunction, death, or retransplantation varied by race as a function of calcineurin inhibitor (CNI) levels and gene expression profile (GEP) scores.We determined the event rate of the primary outcome, comparing racial groups, stratified by time after transplant. Logistic regression was used to compute the relative risk across racial groups, and linear modeling was used to measure the dependence of CNI levels and GEP score on race.In 580 patients monitored for a median of 19 months, the incidence of the primary end point was 18.3% in African Americans, 22.2% in other non-Caucasians, and 8.5% in Caucasians (p0.001). There were small but significant correlations of race and tacrolimus trough levels to the GEP score. Tacrolimus levels were similar among the races. Of patients receiving tacrolimus, other non-Caucasians had higher GEP scores than the other racial groups. African American recipients demonstrated a unique decrease in expression of the FLT3 gene in response to higher tacrolimus levels.African Americans and other non-Caucasian heart transplant recipients were 2.5-times to 3-times more likely than Caucasians to experience outcome events in the Invasive Monitoring Attenuation through Gene Expression study. The increased risk of adverse outcomes may be partly due to the biology of the alloimmune response, which is less effectively inhibited at similar tacrolimus levels in minority racial groups.

This study evaluated clinical outcomes associated with erythropoiesis stimulating agent (ESA) use in left ventricular assist devices (LVAD)-supported patients.Use of ESAs in patients with LVADs may minimize blood transfusions and decrease allosensitization. ESAs increase thrombotic events, which is concerning because LVADs are sensitive to pump thrombosis (PT).We retrospectively reviewed 221 patients at our center who received a HeartMate II (Thoratec Corp., Pleasanton, California) LVAD between January 1, 2009 and June 6, 2013. Patients were divided into those who received ESAs during index admission (n = 121) and those who did not (n = 100). Suspected PT was defined as evidence of thrombus in the LVAD or severe hemolysis (lactate dehydrogenase1,000 mg/dl or plasma-free hemoglobin40 mg/dl). Outcomes were compared between cohorts using inverse probability-weighted analyses.During a mean follow-up of 14.2 ± 11.9 months, suspected PT occurred in 37 patients (ESA 23%, no ESA 12%; p =0.03). The ESA cohort received ESAs 13.9 ± 60.9 days after LVAD implantation. At 180 days, event-free rates for suspected PT were ESA 78.6% versus no ESA 94.5% (p 0.001). ESA use had higher rates of suspected PT (hazard ratio [HR]: 2.35; 95% confidence interval [CI]: 1.38 to 4.00; p = 0.002). For every 100-unit increase in cumulative ESA dosage, the hazard of suspected PT increased by 10% (HR: 1.10; 95% CI: 1.04 to 1.16; p 0.001). After inverse probability weighting, ESA use was associated with a significantly higher rate of all-cause mortality (HR: 1.62; 95% CI: 1.12 to 2.33; p = 0.01).ESA use in LVAD patients is associated with higher rates of suspected PT.

Background After several neutral telehealth trials, the positive findings and subsequent Food and Drug Administration approval of an implantable pulmonary arterial pressure monitor (PAPM) led to renewed interest in remote patient monitoring (RPM). Here we seek to provide contemporary guidance on the appropriate use of RPM technology. Results Although early trials of external RPM devices suggested benefit, subsequent multicenter trials failed to demonstrate improved outcomes. Monitoring features of cardiac implantable electronic devices (CIEDs) also did not deliver improved HF outcomes, newer, multisensor algorithms may be better. Earlier technologies using direct pressure measurement via implanted devices failed to show benefit owing to complications or failure. Recently, 1 PAPM showed benefit in a randomized controlled trial. Although not showing cost reduction, cost-benefit analysis of that device suggests that it may meet acceptable standards. Additional research is warranted and is in progress. Consumer-owned electronic devices are becoming more pervasive and hold hope for future benefit in HF management. Practical aspects around RPM technology include targeting of risk populations, having mechanisms to ensure patient adherence to monitoring, and health care team structures that act on the data. Conclusions Based on available evidence, routine use of external RPM devices is not recommended. Implanted devices that monitor pulmonary arterial pressure and/or other parameters may be beneficial in selected patients or when used in structured programs, but the value of these devices in routine care requires further study. Future research is also warranted to better understand the cost-effectiveness of these devices.

Treatment of advanced heart failure with implantable LVADs is increasing, driven by profound unmet patient need despite potential serious complications: bleeding, infection, and thrombus. The experimental objective was to develop a sensitive imaging approach to assess early thrombus accumulation in LVADs under operational high flow and high shear rates. Methods: A monomeric bifunctional ligand with a fibrin-specific peptide, a short spacer, and 99mTc chelating amino acid sequence (F1A) was developed and compared to its tetrameric PEG analogue (F4A). Results: 99mTc attenuation by LVAD titanium (1 mm) was 23%. 99mTc-F1A affinity to fibrin was Kd ~10 µM, whereas, the bound 99mTc-F4A probe was not displaced by F1A (120,000:1). Human plasma interfered with 99mTc-F1A binding to fibrin clot (p

Although the incidence of driveline failure has been significantly reduced with the major modification to the driveline connection to the HeartMate II left ventricular assist device (LVAD), internal and external driveline damage continues to be a major reason for pump exchange or driveline repair. We report three cases of internal driveline damage under the costal margin and in the adjacent abdominal wall. All three cases developed occasional electrical disruptions 2–5 years after the original LVAD implant through the median sternotomy. Two patients underwent subcostal LVAD exchange and one had driveline externalization and repair. The driveline velour was well adhered to the costal margin and wire damage was found at the costal margin as well as the subsequent segment in the abdominal wall. Repeated ante-flex bending of the abdominal wall over years appeared to cause the chronic wear and tear of the vertically located driveline under the costal margin. This report will confirm a pitfall of the LVAD driveline location which can potentially cause driveline damage in the mid-to-long term.

Background: The HeartMate 3 (HM3) Left Ventricular Assist System (LVAS) (Abbott) is a centrifugal, fully magnetically levitated, continuous-flow blood pump engineered to enhance hemocompatibility and reduce shear stress on blood components. The MOMENTUM 3 trial (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) compares the HM3 LVAS with the HeartMate II (HMII) LVAS (Abbott) in advanced heart failure refractory to medical management, irrespective of therapeutic intention (bridge to transplant versus destination therapy). This investigation reported its primary outcome in the short-term cohort (n=294; 6-month follow-up), demonstrating superiority of the HM3 for the trial primary end point (survival free of a disabling stroke or reoperation to replace the pump for malfunction), driven by a reduced need for reoperations. The aim of this analysis was to evaluate the aggregate of hemocompatibility-related clinical adverse events (HRAEs) between the 2 LVAS. Methods: We conducted a secondary end point evaluation of HRAE (survival free of any nonsurgical bleeding, thromboembolic event, pump thrombosis, or neurological event) in the short-term cohort (as-treated cohort n=289) at 6 months. The net burden of HRAE was also assessed by using a previously described hemocompatibility score, which uses 4 escalating tiers of hierarchal severity to derive a total score for events encountered during the entire follow-up experience for each patient. Results: In 289 patients in the as-treated group (151 the HM3 and 138 the HMII), survival free of any HRAE was achieved in 69% of the HM3 group and in 55% of the HMII group (hazard ratio, 0.62; confidence interval, 0.42–0.91; P =0.012). Using the hemocompatibility score, the HM3 group demonstrated less pump thrombosis requiring reoperation (0 versus 36 points, P P =0.02), and fewer nondisabling strokes (6 versus 24 points, P =0.026) than the control HMII LVAS. The net hemocompatibility score in the HM3 in comparison with the HMII patients was 101 (0.67±1.50 points/patient) versus 137 (0.99±1.79 points/patient) (odds ratio, 0.64; confidence interval, 0.39–1.03; P =0.065). Conclusions: In this secondary analysis of the MOMENTUM 3 trial, the HM3 LVAS demonstrated greater freedom from HRAEs in comparison with the HMII LVAS at 6 months. Clinical Trial Registration: URL: http://clinicaltrials.gov . Unique identifier: NCT02224755.

Left ventricular assist device (LVAD)-supported patients are evaluated routinely with use of transthoracic echocardiography. Values of left ventricular unloading in this unique patient population are needed to evaluate LVAD function and assist in patient follow-up. We introduce a new M-mode measurement, the slope of the anterior mitral valve leaflet (SLAM), and compare its efficacy with that of other standard echocardiographically evaluated values for left ventricular loading, including E/e′ and pulmonary artery systolic pressures. Average SLAM values were determined retrospectively for cohorts of random, non-LVAD patients with moderately to severely impaired left ventricular ejection fraction (LVEF) ( The average SLAM in patients with an LVEF Evaluating ventricular unloading in LVAD patients remains challenging. Our novel M-mode value correlates with echocardiographic values of left ventricular filling in patients with moderate-to-severe systolic function and dynamically improves with the ventricular unloading of an LVAD.

The purpose of these studies was to determine the incidence and survival of patients with specific malignancies with respect to age and transplant year and to compare the data with the normal non-transplant population.Data from 6,211 primary cardiac transplants between July 31, 1993, and December 30, 2008, were collected by 35 institutions participating in the Cardiac Transplant Research Database. Data were compared with information collected by the Surveillance Epidemiology and End Results (SEER) Cancer Statistics Review 1975-2006.Multivariable analysis showed older age (relative risk [RR], 2.1; p0.0001) and earlier transplant year (RR, 1.8; p0.0001) were highly significant risk factors. Aggregate malignancy incidence in the modern era (2001 to 2008) did not differ significantly from the normal population, which appeared to be attributable to a lower rate of malignancies other than lung cancer, lymphoma, and melanoma (actual/expected ratio, 0.71). From 2001 to 2008, rates were significantly higher for lung cancer (actual/expected ratio, 1.86; p = 0.006) and lymphoma (actual/expected ratio, 4.3, p0.0001) than in the normal population. The highest risk for lymphoma was in younger adults who received transplants at ages 18 to 35 years (actual/expected ratio, 27). The highest risk for lung cancer was in patients who underwent transplantation at ages 55 to 65 years (actual/expected ratio, 28). Once diagnosed with malignancy, subsequent survival at 5 years was 21% for lung cancer and 32% for lymphoma.The risk of malignancy has markedly declined during a 15-year period such that the aggregate rate of malignancy approached that of the general population in the United States. However, the distribution of malignancies was not the same, with a greater prominence of lung cancer and lymphoproliferative disease.

Background Although atrial arrhythmias (AAs) are common in heart failure, the incidence of AAs subsequent to the placement of left ventricular assist devices (LVADs) has not been elucidated. Methods Patients receiving a HeartMate II LVAD in the bridge to transplant (n = 490) and destination therapy (n = 634) trials were included (n = 1125). AAs requiring treatment were recorded, regardless of symptoms. Using Cox models with and without a 60-day blanking period, risk factors for early and late AAs were determined. Results In total, there were 271 AAs in 231 patients (21%), most of which occurred within the first 60 days. Patients with and without AAs had similar survival (p = 0.16). Serum creatinine (hazard ratio [HR] = 1.49 per unit increase, 1.18 to 1.88; p