Surgically implanted endovascular, microaxial left ventricular assist device: A single institution study.

Objective: The Impella 5.5 (Abiomed, Inc), a surgically implanted endovascular microaxial left ventricular assist device, is increasingly used worldwide and there have been more than 10,000 implants. The purpose of this study is to describe a large-volume, single-center experience with the use of the Impella 5.5. Methods: Data were obtained retrospectively from patients supported with the Impella 5.5 implanted at our institution from May 1, 2020, to December 31, 2022. Demographic, operative, and postoperative outcomes for each group are described. Results are reported in median (interquartile range) or n (%). The entire cohort was divided into 5 main groups based on the intention to treat at the time of the Impella 5.5 implantation: (1) patients who had a planned Impella 5.5 implanted at the time of high-risk cardiac surgery; (2) patients with cardiogenic shock; (3) patients bridged to a durable left ventricular assist device; (4) patients bridged to transplant; and (5) patients with postcardiotomy shock who received an unplanned Impella 5.5 implant. Results: A total of 126 patients were supported with the Impella 5.5. Overall survival to device explant was 76.2%, with 67.5% surviving to discharge. Midterm survival was assessed with a median follow-up time of 318 days and demonstrated an overall survival of 60.3% and a median of 650 days (549-752). Conclusions: Outcomes after using the Impella 5.5 are variable depending on the indication of use. Patient selection may be of utmost importance and requires further experience with this device to determine who will benefit from insertion.

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

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

Characterization of de novo malignancy after orthotopic heart transplantation: single-centre outcomes over 20 years.

OBJECTIVES: Malignancy is the leading cause of late mortality after orthotopic heart transplantation (OHT), and the burden of post-transplantation cancer is expected to rise in proportion to increased case volume following the 2018 heart allocation score change. In this report, we evaluated factors associated with de novo malignancy after OHT with a focus on skin and solid organ cancers. METHODS: Patients who underwent OHT at our institution between 1999 and 2018 were retrospectively reviewed (n = 488). Terminal outcomes of death and development of skin and/or solid organ malignancy were assessed as competing risks. Fine-Gray subdistribution hazards regression was used to evaluate the association between perioperative patient and donor characteristics and late-term malignancy outcomes. RESULTS: By 1, 5 and 10 years, an estimated 2%, 17% and 27% of patients developed skin malignancy, while 1%, 5% and 12% of patients developed solid organ malignancy. On multivariable Fine-Gray regression, age [1.05 (1.03-1.08); P < 0.001], government payer insurance [1.77 (1.20-2.59); P = 0.006], family history of malignancy [1.66 (1.15-2.38); P = 0.007] and metformin use [1.73 (1.15-2.59); P = 0.008] were associated with increased risk of melanoma and basal or squamous cell carcinoma. Age [1.08 (1.04-1.12); P < 0.001] and family history of malignancy [2.55 (1.43-4.56); P = 0.002] were associated with an increased risk of solid organ cancer, most commonly prostate and lung cancer. CONCLUSIONS: Vigilant cancer and immunosuppression surveillance is warranted in OHT recipients at late-term follow-up. The cumulative incidence of skin and solid organ malignancies increases temporally after transplantation, and key risk factors for the development of post-OHT malignancy warrant identification and routine monitoring.

Rare Variant Genetics and Dilated Cardiomyopathy Severity: The DCM Precision Medicine Study.

BACKGROUND: Dilated cardiomyopathy (DCM) can lead to advanced disease, defined herein as necessitating a durable left ventricular assist device or a heart transplant (LVAD/HT). DCM is known to have a genetic basis, but the association of rare variant genetics with advanced DCM has not been studied. METHODS: We analyzed clinical and genetic sequence data from patients enrolled between 2016 and 2021 in the US multisite DCM Precision Medicine Study, which was a geographically diverse, multiracial, multiethnic cohort. Clinical evaluation included standardized patient interview and medical record query forms. DCM severity was classified into 3 groups: patients with advanced disease with LVAD/HT; patients with an implantable cardioverter defibrillator (ICD) only; or patients with no ICD or LVAD/HT. Rare variants in 36 DCM genes were classified as pathogenic or likely pathogenic or variants of uncertain significance. Confounding factors we considered included demographic characteristics, lifestyle factors, access to care, DCM duration, and comorbidities. Crude and adjusted associations between DCM severity and rare variant genetic findings were assessed using multinomial models with generalized logit link. RESULTS: Patients' mean (SD) age was 51.9 (13.6) years; 42% were of African ancestry, 56% were of European ancestry, and 44% were female. Of 1198 patients, 347 had LVAD/HT, 511 had an ICD, and 340 had no LVAD/HT or ICD. The percentage of patients with pathogenic or likely pathogenic variants was 26.2%, 15.9%, and 15.0% for those with LVAD/HT, ICD only, or neither, respectively. After controlling for sociodemographic characteristics and comorbidities, patients with DCM with LVAD/HT were more likely than those without LVAD/HT or ICD to have DCM-related pathogenic or likely pathogenic rare variants (odds ratio, 2.3 [95% CI, 1.5-3.6]). The association did not differ by ancestry. Rare variant genetic findings were similar between patients with DCM with an ICD and those without LVAD/HT or ICD. CONCLUSIONS: Advanced DCM was associated with higher odds of rare variants in DCM genes adjudicated as pathogenic or likely pathogenic, compared with individuals with less severe DCM. This finding may help assess the risk of outcomes in management of patients with DCM and their at-risk family members. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03037632.

Clinical outcomes of a prospective randomized comparison of bioreactance monitoring versus pulse-contour analysis in a stroke-volume based goal-directed fluid resuscitation protocol in brain-dead organ donors.

Eighty percent of brain-dead (BD) organ donors develop hypotension and are frequently hypovolemic. Fluid resuscitation in a BD donor is controversial. We have previously published our 4-h goal-directed stroke volume (SV)-based fluid resuscitation protocol which significantly decreased time on vasopressors and increased transplanting four or more organs. The SV was measured by pulse-contour analysis (PCA) or an esophageal doppler monitor, both of which are invasive. Thoracic bioreactance (BR) is a non-invasive portable technology that measures SV but has not been studied in BD donors. We performed a randomized prospective comparative study of BR versus PCA technology in our fluid resuscitation protocol in BD donors. Eighty-four donors (53.1%) were randomized to BR and 74 donors to PCA (46.8%). The two groups were well matched based on 24 demographic, social, and initial laboratory factors, without any significant differences between them. There was no difference in the intravenous fluid infused over the 4-h study period [BR 2271 ± 823 vs. PCA 2230 ± 962 mL; p = .77]. There was no difference in the time to wean off vasopressors [BR 108.8 ± 61.8 vs. PCA 150.0 ± 68 min p = .07], nor in the number of donors off vasopressors at the end of the protocol [BR 16 (28.6%) vs. PCA 15 (29.4%); p = .92]. There was no difference in the total number of organs transplanted per donor [BR 3.25 ± 1.77 vs. PCA 3.22 ± 1.75; p = .90], nor in any individual organ transplanted. BR was equivalent to PCA in clinical outcomes and provides a simple, non-invasive, portable technology to monitor fluid resuscitation in organ donors.

Genetic Architecture of Dilated Cardiomyopathy in Individuals of African and European Ancestry.

Importance: Black patients with dilated cardiomyopathy (DCM) have increased familial risk and worse outcomes than White patients, but most DCM genetic data are from White patients. Objective: To compare the rare variant genetic architecture of DCM by genomic ancestry within a diverse population of patients with DCM. Design: Cross-sectional study enrolling patients with DCM who self-identified as non-Hispanic Black, Hispanic, or non-Hispanic White from June 7, 2016, to March 15, 2020, at 25 US advanced heart failure programs. Variants in 36 DCM genes were adjudicated as pathogenic, likely pathogenic, or of uncertain significance. Exposure: Presence of DCM. Main Outcomes and Measures: Variants in DCM genes classified as pathogenic/likely pathogenic/uncertain significance and clinically actionable (pathogenic/likely pathogenic). Results: A total of 505, 667, and 26 patients with DCM of predominantly African, European, or Native American genomic ancestry, respectively, were included. Compared with patients of European ancestry, a lower percentage of patients of African ancestry had clinically actionable variants (8.2% [95% CI, 5.2%-11.1%] vs 25.5% [95% CI, 21.3%-29.6%]), reflecting the lower odds of a clinically actionable variant for those with any pathogenic variant/likely pathogenic variant/variant of uncertain significance (odds ratio, 0.25 [95% CI, 0.17-0.37]). On average, patients of African ancestry had fewer clinically actionable variants in TTN (difference, -0.09 [95% CI, -0.14 to -0.05]) and other genes with predicted loss of function as a disease-causing mechanism (difference, -0.06 [95% CI, -0.11 to -0.02]). However, the number of pathogenic variants/likely pathogenic variants/variants of uncertain significance was more comparable between ancestry groups (difference, -0.07 [95% CI, -0.22 to 0.09]) due to a larger number of non-TTN non-predicted loss of function variants of uncertain significance, mostly missense, in patients of African ancestry (difference, 0.15 [95% CI, 0.00-0.30]). Published clinical case-based evidence supporting pathogenicity was less available for variants found only in patients of African ancestry (P < .001). Conclusion and Relevance: Patients of African ancestry with DCM were less likely to have clinically actionable variants in DCM genes than those of European ancestry due to differences in genetic architecture and a lack of representation of African ancestry in clinical data sets.

Screening for Dilated Cardiomyopathy in At-Risk First-Degree Relatives.

BACKGROUND: Cardiovascular screening is recommended for first-degree relatives (FDRs) of patients with dilated cardiomyopathy (DCM), but the yield of FDR screening is uncertain for DCM patients without known familial DCM, for non-White FDRs, or for DCM partial phenotypes of left ventricular enlargement (LVE) or left ventricular systolic dysfunction (LVSD). OBJECTIVES: This study examined the yield of clinical screening among reportedly unaffected FDRs of DCM patients. METHODS: Adult FDRs of DCM patients at 25 sites completed screening echocardiograms and ECGs. Mixed models accounting for site heterogeneity and intrafamilial correlation were used to compare screen-based percentages of DCM, LVSD, or LVE by FDR demographics, cardiovascular risk factors, and proband genetics results. RESULTS: A total of 1,365 FDRs were included, with a mean age of 44.8 ± 16.9 years, 27.5% non-Hispanic Black, 9.8% Hispanic, and 61.7% women. Among screened FDRs, 14.1% had new diagnoses of DCM (2.1%), LVSD (3.6%), or LVE (8.4%). The percentage of FDRs with new diagnoses was higher for those aged 45 to 64 years than 18 to 44 years. The age-adjusted percentage of any finding was higher among FDRs with hypertension and obesity but did not differ statistically by race and ethnicity (16.2% for Hispanic, 15.2% for non-Hispanic Black, and 13.1% for non-Hispanic White) or sex (14.6% for women and 12.8% for men). FDRs whose probands carried clinically reportable variants were more likely to be identified with DCM. CONCLUSIONS: Cardiovascular screening identified new DCM-related findings among 1 in 7 reportedly unaffected FDRs regardless of race and ethnicity, underscoring the value of clinical screening in all FDRs.

Effectiveness of the Family Heart Talk Communication Tool in Improving Family Member Screening for Dilated Cardiomyopathy: Results of a Randomized Trial.

BACKGROUND: Managing disease risk among first-degree relatives of probands diagnosed with a heritable disease is central to precision medicine. A critical component is often clinical screening, which is particularly important for conditions like dilated cardiomyopathy (DCM) that remain asymptomatic until severe disease develops. Nonetheless, probands are frequently ill-equipped to disseminate genetic risk information that motivates at-risk relatives to complete recommended clinical screening. An easily implemented remedy for this key issue has been elusive. METHODS: The DCM Precision Medicine Study developed Family Heart Talk, a booklet designed to help probands with DCM communicate genetic risk and the need for cardiovascular screening to their relatives. The effectiveness of the Family Heart Talk booklet in increasing cardiovascular clinical screening uptake among first-degree relatives was assessed in a multicenter, open-label, cluster-randomized, controlled trial. The primary outcome measured in eligible first-degree relatives was completion of screening initiated within 12 months after proband enrollment. Because probands randomized to the intervention received the booklet at the enrollment visit, eligible first-degree relatives were limited to those who were alive the day after proband enrollment and not enrolled on the same day as the proband. RESULTS: Between June 2016 and March 2020, 1241 probands were randomized (1:1) to receive Family Heart Talk (n=621) or not (n=620) within strata defined by site and self-identified race/ethnicity (non-Hispanic Black, non-Hispanic White, or Hispanic). Final analyses included 550 families (n=2230 eligible first-degree relatives) in the Family Heart Talk arm and 561 (n=2416) in the control arm. A higher percentage of eligible first-degree relatives completed screening in the Family Heart Talk arm (19.5% versus 16.0%), and the odds of screening completion among these first-degree relatives were higher in the Family Heart Talk arm after adjustment for proband randomization stratum, sex, and age quartile (odds ratio, 1.30 [1-sided 95% CI, 1.08-∞]). A prespecified subgroup analysis did not find evidence of heterogeneity in the adjusted intervention odds ratio across race/ethnicity strata (P=0.90). CONCLUSIONS: Family Heart Talk, a booklet that can be provided to patients with DCM by clinicians with minimal additional time investment, was effective in increasing cardiovascular clinical screening among first-degree relatives of these patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03037632.

Idiopathic Ventricular Fibrillation in a Previously Healthy Recreational Athlete.

There are several clinical challenges in the survivor of sudden cardiac arrest (SCA), including ensuring that a comprehensive diagnostic evaluation has been performed and providing counseling on return to activity. We report a case of a highly conditioned athlete who presented following aborted SCA during exercise with a diagnosis of idiopathic ventricular fibrillation arrest. (Level of Difficulty: Intermediate.).

The Novel Data Collection and Analytics Tools for Remote Patient Monitoring in Heart Failure (Nov-RPM-HF) Trial: Protocol for a Single-Center Prospective Trial.

BACKGROUND: Heart failure remains a leading cause of mortality and a major driver of health care utilization. Despite numerous medical advances in heart failure, associated hospitalizations continue to increase, owing largely to suboptimal outpatient management. Remote patient monitoring (RPM) aims to further address this current need in heart failure care by providing data to clinical teams to act pre-emptively to address clinical decompensation. However, to date, RPM approaches using noninvasive home-based patient sensors have failed to demonstrate clinical efficacy. OBJECTIVE: The Novel Data Collection and Analytics Tools for Remote Patient Monitoring in Heart Failure (Nov-RPM-HF) Trial aims to address current noninvasive RPM limitations. Nov-RPM-HF will evaluate a clinician co-designed RPM platform using emerging data collection and presentation tools for heart failure management. These tools include a ballistocardiograph to monitor nocturnal patient biometrics, clinical alerts for abnormal biometrics, and longitudinal data presentation for clinician review. METHODS: Nov-RPM-HF is a 100-patient single-center prospective trial, evaluating patients over 6 months. The outcomes will include patient adherence to data collection, patient/clinician-perceived utility of the RPM platform, medication changes including the titration of guideline-directed medical therapy to target doses, heart failure symptoms/performance status, and unplanned heart failure hospitalizations or emergency department visits. RESULTS: This prospective trial began enrollment in March 2020 and anticipates enrollment completion by June 2022, with trial completion by December 2022. CONCLUSIONS: This trial protocol aims to provide a systematic framework for the evaluation of heart failure RPM strategies, which are currently heavily used but seldom robustly studied. The trial results will help to inform the role of noninvasive RPM as a viable clinical management strategy in heart failure care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/32873.

Prevalence and Cumulative Risk of Familial Idiopathic Dilated Cardiomyopathy.

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Exposures: The presence of DCM in a proband. Main Outcomes and Measures: 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. Results: 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]). Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT03037632.

Competing Risks to Transplant in Bridging With Continuous-flow Left Ventricular Assist Devices.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

A pilot clinical trial of a self-management intervention in patients with a left ventricular assist device.

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.

Cardiac allograft rejection in the current era of continuous flow left ventricular assist devices.

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.

30 Years of Heart Transplant: Outcomes After Mechanical Circulatory Support From a Single Center.

BACKGROUND: Survival after bridge to transplantation with mechanical circulatory support (MCS) has yielded varying outcomes on the basis of device type and baseline characteristics. Continuous-flow left ventricular assist devices (CF-LVADs) have significantly improved waitlist mortality, but recent changes to the transplantation listing criteria have dramatically altered the use of MCS for bridge to transplantation. METHODS: Orthotopic heart transplantations from 1988 to 2019 at our institution (Washington University School of Medicine, Barnes-Jewish Hospital, St Louis, MO) were retrospectively reviewed and stratified by pretransplantation MCS status into CF-LVAD (n = 224), pulsatile LVAD (n = 49), temporary MCS (n = 71), and primary transplantation (n = 463) groups. Patients who underwent heart transplantation after the approval of CF-LVAD for bridge to transplantation and before the 2018 allocation policy changes underwent subgroup analysis to evaluate predictors of survival and complications in a contemporary cohort. RESULTS: Rates of primary transplantation declined from 88% to 14% over the course of the study. No significant difference in survival was detected in the cohort stratified by MCS status (P = .18). In the modern era, survival of patients treated with CF-LVADs and temporary MCS was noninferior to that seen with primary transplantation (P = .22). Notable predictors of long-term mortality included lower body mass index, peripheral vascular disease, previous coronary artery bypass graft, ABO nonidentical transplant, and increased donor age (all P ≤ .02). There were no differences in major postoperative complications. CONCLUSIONS: CF-LVAD has grown to account for the majority of transplantations at our center in the last decade, with no adverse effect on survival or postoperative complications. Temporary MCS increased after the 2018 listing criteria change, with acceptable early outcomes.

Variability in Blood Pressure Assessment in Patients Supported with the HeartMate 3TM.

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.

An early relook identifies high-risk trajectories in ambulatory advanced heart failure.

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.

The bleeding risk treatment paradox at the physician and hospital level: Implications for reducing bleeding in patients undergoing percutaneous coronary intervention.

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 (<2.0%), moderate (2.0%-6.4%), or high (≥6.5%) risk tertiles. BAS use was considered risk-concordant if: at least 1 BAS was used for moderate risk; 2 BAS were used for high risk and bivalirudin or vascular closure devices were not used for low risk. Absence of risk-concordant BAS use was defined as RTP. We analyzed inter-hospital and inter-physician variation in RTP, and the association of RTP with post-PCI bleeding. RESULTS: Amongst 28,005 patients undergoing PCI by 103 physicians at 7 hospitals, RTP was observed in 12,035 (43%) patients. RTP was independently associated with a higher likelihood of bleeding even after adjusting for predicted bleeding risk, mortality risk and potential sources of variation (OR 1.66, 95% CI 1.44-1.92, P < .001). A higher prevalence of RTP strongly and independently correlated with worse bleeding rates, both at the physician-level (Wilk's Lambda 0.9502, F-value 17.21, P < .0001) and the hospital-level (Wilk's Lambda 0.9899, F-value 35.68, P < .0001). All the results were similar in a subset of PCIs conducted since 2015 - a period more reflective of the contemporary practice. CONCLUSIONS: Bleeding RTP is a strong, independent predictor of bleeding. It exists at the level of physicians and hospitals: those with a higher rate of RTP had worse bleeding rates. These findings not only underscore the importance of recognizing bleeding risk upfront and using BAS in a risk-aligned manner, but also inform and motivate national efforts to reduce PCI-related bleeding.

Proinflammatory TH17 cytokine activation, disease severity and outcomes in peripartum cardiomyopathy.

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.

Acute kidney injury post-heart transplant: An analysis of peri-operative risk factors.

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 <170 min. Acute kidney injury was found to be associated with increased 30-day and 1-year mortality.