A principal components analysis of factors associated with successful implementation of an LVAD decision support tool.

BACKGROUND: A central goal among researchers and policy makers seeking to implement clinical interventions is to identify key facilitators and barriers that contribute to implementation success. Despite calls from a number of scholars, empirical insights into the complex structural and cultural predictors of why decision aids (DAs) become routinely embedded in health care settings remains limited and highly variable across implementation contexts. METHODS: We examined associations between "reach", a widely used indicator (from the RE-AIM model) of implementation success, and multi-level site characteristics of nine LVAD clinics engaged over 18 months in implementation and dissemination of a decision aid for left ventricular assist device (LVAD) treatment. Based on data collected from nurse coordinators, we explored factors at the level of the organization (e.g. patient volume), patient population (e.g. health literacy; average sickness level), clinician characteristics (e.g. attitudes towards decision aid; readiness for change) and process (how the aid was administered). We generated descriptive statistics for each site and calculated zero-order correlations (Pearson's r) between all multi-level site variables including cumulative reach at 12 months and 18 months for all sites. We used principal components analysis (PCA) to examine any latent factors governing relationships between and among all site characteristics, including reach. RESULTS: We observed strongest inclines in reach of our decision aid across the first year, with uptake fluctuating over the second year. Average reach across sites was 63% (s.d. = 19.56) at 12 months and 66% (s.d. = 19.39) at 18 months. Our PCA revealed that site characteristics positively associated with reach on two distinct dimensions, including a first dimension reflecting greater organizational infrastructure and standardization (characteristic of larger, more established clinics) and a second dimension reflecting positive attitudinal orientations, specifically, openness and capacity to give and receive decision support among coordinators and patients. CONCLUSIONS: Successful implementation plans should incorporate specific efforts to promote supportive and mutually informative interactions between clinical staff members and to institute systematic and standardized protocols to enhance the availability, convenience and salience of intervention tool in routine practice. Further research is needed to understand whether "core predictors" of success vary across different intervention types.

Jamestown Canyon virus encephalitis in a heart transplant patient.

Jamestown Canyon virus (JtCV) is an arbovirus and a member of the California serogroup. To our knowledge, all the cases of JtCV have been reported in immunocompetent patients since it was first detected in 1997. We report a case of JtCV encephalitis in a solid organ transplant patient. A 48-year-old woman from Wisconsin had multiple hospital admissions for symptoms of progressive confusion, visual hallucinations, and inability to perform self-care. Initial evaluation was significant for lymphocytes in cerebrospinal fluid (CSF), and multiple infectious and metabolic causes were excluded. Further investigation found JtCV IgM in serum, and CSF. The patient's clinical course was compatible with JtCV encephalitis, and she was treated with ribavirin in addition to reduction of her immunosuppressive medications. She showed gradual and significant improvement in her mental and functional status. JtCV can cause a variety of symptoms that range from a flu-like syndrome to encephalitis. There have been an increased number of reported cases in recent years which is attributed to increased physician awareness and the availability of laboratory testing. Optimal treatment is still not known.

Healthcare Resource Use and Cost Implications in the MOMENTUM 3 Long-Term Outcome Study.

BACKGROUND: The MOMENTUM 3 trial compares the centrifugal HeartMate 3 (HM3) with the axial HeartMate II (HMII) continuous-flow left ventricular assist system in patients with advanced heart failure, irrespective of the intended goal of therapy. The trial's 2-year clinical outcome (n=366) demonstrated superiority of the HM3 for the primary end point (survival free of a disabling stroke or reoperation to replace or remove a malfunctioning pump). This analysis evaluates health resource use and cost implications of the observed differences between the 2 devices while patients were enrolled in the trial. METHODS: We analyzed all hospitalizations and their associated costs occurring after discharge from the implant hospitalization until censoring (study withdrawal, heart transplantation, and pump exchange with a nonstudy device or death). Each adjudicated episode of hospital-based care was used to calculate costs (device-attributable and non-device-attributable event costs), estimated by using trial data and payer administrative claims databases. Cost savings stratified by subgroups (study outcome [transplant, death, or ongoing on device], intended goal of therapy, type of insurance, or sex) were also assessed. RESULTS: In 366 randomly assigned patients, 361 comprised the as-treated group (189 in the HM3 group and 172 in the HMII group), of whom 337 (177 in the HM3 group and 160 in the HMII group) were successfully discharged following implantation. The HM3 arm experienced fewer total hospitalizations per patient-year (HM3: 2.1±0.2 versus HMII: 2.7±0.2; P=0.015) and 8.3 fewer hospital days per patient-year on average (HM3: 17.1 days versus HMII: 25.5 days; P=0.003). These differences were driven by patients hospitalized for suspected pump thrombosis (HM3: 0.6% versus HMII: 12.5%; P<0.001) and stroke (HM3: 2.8% versus HMII: 11.3%; P=0.002). Controlled for time spent in the study (average cumulative cost per patient-year), postdischarge HM3 arm costs were 51% lower than with the HMII (HM3: $37 685±4251 versus HMII: $76 599±11 889, P<0.001) and similar in either bridge to transplant or destination therapy intent. CONCLUSIONS: In this 2-year outcome economic analysis of the MOMENTUM 3 trial, the HM3 demonstrated a reduction in rehospitalizations, hospital days spent during rehospitalizations, and a significant cost savings following discharge in comparison with the HMII left ventricular assist system, irrespective of the intended goal of therapy. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02224755.

Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies.

Background Peripartum cardiomyopathy shares some clinical features with idiopathic dilated cardiomyopathy, a disorder caused by mutations in more than 40 genes, including TTN, which encodes the sarcomere protein titin. Methods In 172 women with peripartum cardiomyopathy, we sequenced 43 genes with variants that have been associated with dilated cardiomyopathy. We compared the prevalence of different variant types (nonsense, frameshift, and splicing) in these women with the prevalence of such variants in persons with dilated cardiomyopathy and with population controls. Results We identified 26 distinct, rare truncating variants in eight genes among women with peripartum cardiomyopathy. The prevalence of truncating variants (26 in 172 [15%]) was significantly higher than that in a reference population of 60,706 persons (4.7%, P=1.3×10(-7)) but was similar to that in a cohort of patients with dilated cardiomyopathy (55 of 332 patients [17%], P=0.81). Two thirds of identified truncating variants were in TTN, as seen in 10% of the patients and in 1.4% of the reference population (P=2.7×10(-10)); almost all TTN variants were located in the titin A-band. Seven of the TTN truncating variants were previously reported in patients with idiopathic dilated cardiomyopathy. In a clinically well-characterized cohort of 83 women with peripartum cardiomyopathy, the presence of TTN truncating variants was significantly correlated with a lower ejection fraction at 1-year follow-up (P=0.005). Conclusions The distribution of truncating variants in a large series of women with peripartum cardiomyopathy was remarkably similar to that found in patients with idiopathic dilated cardiomyopathy. TTN truncating variants were the most prevalent genetic predisposition in each disorder.

The association between novel clinical factors and gastrointestinal bleeding among patients supported with continuous-flow left ventricular assist device therapy.

BACKGROUND: This study explores novel preimplantation risk factors associated with gastrointestinal bleeding (GIB) after continuous-flow left ventricular assist device (CF-LVAD) implantation. CF-LVAD therapy implantation for patients with advanced heart failure is associated with a 20% to 40% incidence of GIB. METHODS: This study includes patients receiving CF-LVAD at a quaternary medical center from 2006 to 2014 (n = 254). The primary endpoint was GIB within 12 months after implantation; the secondary outcome was 3-year all-cause mortality. The Student t test or the χ2 test compared continuous or categorical variables. Competing risks analysis calculated the cumulative incidence of GIB postimplantation. Cox proportional hazards model was used for univariate/multivariate models predicting GIB. RESULTS: Sixty-four patients had GIB, with incidence rates at 1, 3, and 12 months of 11.8%, 19.3%, and 25.2%, respectively. Endoscopy revealed no identified source of bleeding in 41%; 33% of lesions were localized in the upper gastrointestinal tract, with the bulk (39%) categorized as vascular. Patients with prior gastrointestinal abnormalities (n = 98) had a greater risk of GIB post-CF-LVAD (HR 1.85 [1.11-3.09]; P = 0.02) than those with normal gastrointestinal evaluation results (n = 45) and those without preimplantation gastrointestinal evaluation (n = 111). Baseline blood urea nitrogen, chronic obstructive pulmonary disease, and prior percutaneous coronary intervention were statistically associated with post-CF-LVAD GIB. The presence of GIB within 12 months of CF-LVAD implantation was associated with an increased risk of 3-year all-cause mortality (HR 2.57 [1.57-4.15]; P < 0.01). CONCLUSIONS: First-year GIB is associated with increased mortality post-CF-LVAD. We advocate a closer examination of several GIB risk factors when evaluating CF-LVAD candidates.

Xenoreactive antibodies and latent fibrin formation in VAD and cardiac transplant recipients can confound the detection and measurement of anti-AT1R antibodies.

Autoantibodies to the angiotensin II type 1 receptor (AT1R) are thought to be important in antibody-mediated rejection (AMR), especially in the absence of anti-HLA antibodies. We used a variety of methods to examine the specificity of a commercially available kit designed to quantitate anti-AT1R antibodies. We found that fibrin formation in serum samples from patients awaiting cardiac transplantation with ventricular assist devices (VADs) can produce falsely elevated anti-AT1R values. In addition, absorption studies with a variety of cell lines with or without expression of human AT1R, and those that express xenoantigens, suggest that many of the antibodies detected in the AT1R test system are heterophilic and have reactivity to xenoantigens. Furthermore, we provide data that show that reactivity to the sialic acid Neu5Gc is a common finding among samples that are highest in anti-AT1R levels. We conclude that a common laboratory method for quantitation of anti-AT1R antibodies is nonspecific and overestimates the frequency of true positives. A reevaluation of the role that anti-AT1R antibodies play in allograft function and patient outcomes is warranted.

A Multisite Randomized Controlled Trial of a Patient-Centered Ventricular Assist Device Decision Aid (VADDA Trial).

BACKGROUND: Studies indicate that decision making and informed consent among patients considering left ventricular assist device (LVAD) support for advanced heart failure could be improved. In the VADDA (Ventricular Assist Device Decision Aid) trial, we tested a patient-centered decision aid (DA) to enhance the quality of decision making about LVAD therapy. METHODS: After an extensive user-centered design process, we conducted a multisite randomized trial of the DA compared with standard education (SE) among inpatients considering LVAD treatment for advanced heart failure The main outcome was LVAD knowledge at 1 week and 1 month after administration of the DA versus the SE, according to a validated scale. Secondary measures included prespecified quality decision making measures recommended by the International Patient Decision Aid Standards collaboration. RESULTS: Of 105 eligible patients, 98 consented and were randomly assigned to the DA and SE arms. Patients receiving the VADDA exhibited significantly greater LVAD knowledge than the SE group at 1 week of follow-up (P = .01) but not at 1 month (P = .47). No differences were found between DA and SE patients in rates of acceptance versus decline of LVAD treatment (85% vs 78%; P = .74). Recipients in the DA arm reported greater satisfaction with life after implantation compared with nonrecipients (28 vs 23 out of 30; P = .008), although both arms reported high satisfaction. Patients rated the DA high in acceptability and usability. CONCLUSIONS: The VADDA enhances LVAD knowledge, particularly in the short term (1 week) during the peak period of decision making. The DA does not encourage decision direction and reflects patient, caregiver, and physician preferences for content and format. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02248974. The trial is registered with clinicaltrials.gov (NCT02248974).

Circulating T-Cell Subsets, Monocytes, and Natural Killer Cells in Peripartum Cardiomyopathy: Results From the Multicenter IPAC Study.

OBJECTIVE: The aim of this work was to evaluate the hypothesis that the distribution of circulating immune cell subsets, or their activation state, is significantly different between peripartum cardiomyopathy (PPCM) and healthy postpartum (HP) women. BACKGROUND: PPCM is a major cause of maternal morbidity and mortality, and an immune-mediated etiology has been hypothesized. Cellular immunity, altered in pregnancy and the peripartum period, has been proposed to play a role in PPCM pathogenesis. METHODS: The Investigation of Pregnancy-Associated Cardiomyopathy (IPAC) study enrolled 100 women presenting with a left ventricular ejection fraction of <0.45 within 2 months of delivery. Peripheral T-cell subsets, natural killer (NK) cells, and cellular activation markers were assessed by flow cytometry in PPCM women early (<6 wk), 2 months, and 6 months postpartum and compared with those of HP women and women with non-pregnancy-associated recent-onset cardiomyopathy (ROCM). RESULTS: Entry NK cell levels (CD3-CD56+CD16+; reported as % of CD3- cells) were significantly (P < .0003) reduced in PPCM (6.6 ± 4.9% of CD3- cells) compared to HP (11.9 ± 5%). Of T-cell subtypes, CD3+CD4-CD8-CD38+ cells differed significantly (P < .004) between PPCM (24.5 ± 12.5% of CD3+CD4-CD8- cells) and HP (12.5 ± 6.4%). PPCM patients demonstrated a rapid recovery of NK and CD3+CD4-CD8-CD38+ cell levels. However, black women had a delayed recovery of NK cells. A similar reduction of NK cells was observed in women with ROCM. CONCLUSIONS: Compared with HP control women, early postpartum PPCM women show significantly reduced NK cells, and higher CD3+CD4-CD8-CD38+ cells, which both normalize over time postpartum. The mechanistic role of NK cells and "double negative" (CD4-CD8-) T regulatory cells in PPCM requires further investigation.

Role of Echocardiography in the Evaluation of Left Ventricular Assist Devices: the Importance of Emerging Technologies.

The role of left ventricular assist devices (LVAD) in patients with end-stage heart failure is well known, both as a temporary treatment before transplantation and as destination therapy, in a scenario of a relative shortage of donors to satisfy the increasing requests for transplantation. The increased population of LVAD patients needs careful imaging assessment before, during, and after LVAD implantation; echocardiography is the best tool for their evaluation and is considered the diagnostic technique of choice for the assessment before, during, and after device implantation. Although the conventional echocardiographic assessment is quite effective in evaluating the main critical issues, the role of new technologies like three-dimensional echocardiography and myocardial deformation measurements is still not properly clarified. In this review, we aim to provide an overview of the main elements that should be considered in the assessment of these patients, underlining the role that could be played by new techniques to improve the diagnostic and prognostic effectiveness of echocardiography in this setting.

Mechanism of decreased sensitivity of dobutamine associated left ventricular wall motion analyses for appreciating inducible ischemia in older adults.

BACKGROUND: Dobutamine associated left ventricular (LV) wall motion analyses exhibit reduced sensitivity for detecting inducible ischemia in individuals with increased LV wall thickness. This study was performed to better understand the mechanism of this reduced sensitivity in the elderly who often manifest increased LV wall thickness and risk factors for coronary artery disease. METHODS: During dobutamine cardiovascular magnetic resonance (DCMR) stress testing, we assessed rate pressure product (RPP), aortic pulse wave velocity (PWV), LV myocardial oxygen demand (pressure volume area, PVA, mass, volumes, concentricity, and the presence of wall motion abnormalities (WMA) and first pass gadolinium enhanced perfusion defects (PDs) indicative of ischemia in 278 consecutively recruited individuals aged 69 ± 8 years with pre-existing or known risk factors for coronary artery disease. Each variable was assessed independently by personnel blinded to participant identifiers and analyses of other DCMR or hemodynamic variables. RESULTS: Participants were 80% white, 90% hypertensive, 43% diabetic and 55% men. With dobutamine, 60% of the participants who exhibited PDs had no inducible WMA. Among these participants, myocardial oxygen demand was lower than that observed in those who had both wall motion and perfusion abnormalities suggestive of ischemia (p = 0.03). Relative to those with PDs and inducible WMAs, myocardial oxygen demand remained different in these individuals with PDs without an inducible WMA after accounting for LV afterload and contractility (p = 0.02 and 0.03 respectively), but not after accounting for either LV stress related end diastolic volume index (LV preload) or resting concentricity (p = 0.31-0.71). CONCLUSIONS: During dobutamine stress testing, elderly patients experience increased LV concentricity and declines in LV preload and myocardial oxygen demand, all of which are associated with an absence of inducible LV WMAs indicative of myocardial ischemia. These findings provide insight as to why dobutamine associated wall motion analyses exhibit reduced sensitivity for identifying inducible ischemia in elderly. TRIAL REGISTRATION: This study was registered with Clinicaltrials.gov (NCT00542503).

Clinical significance of intermediate left ventricular trabeculations in cardiac magnetic resonance.

OBJECTIVE: Although the clinical importance of left ventricular noncompaction cardiomyopathy (LVNC) is known, few data exist that describe the prognosis associated with intermediate levels of LV trabeculations that do not meet criteria for LVNC. METHODS: Trabeculation/possible LVNC by CMR was retrospectively observed among 122 consecutive cases. We assessed the end-systolic noncompacted-to-compacted ratios (ESNCCR) along with deaths, embolic events, congestive heart failure (CHF) readmissions, ventricular arrhythmias, myocardial thickening (MT), and ejection fraction (EF). ESNCCRs were categorized as follows: <1, 1<1.5, 1.5<2, ≥2. General linear models were used to compare combined events (death, CHF readmission, embolism, ventricular arrhythmia) between categories of ESNCCR. There were 3 models used: model 1: unadjusted; model 2: adjusted for age, race, gender, body surface area, LV ejection fraction, and trabeculated segments; model 3: model 2+adjustment for myocardial thickening. RESULTS: In model 1, those with an ESNCCR<1 had a lower association with composite clinical events than those with a ratio between 1.5<2 and those≥2 (P<0.002 and P<0.001, respectively). In model 2, the lower association continued, (P=0.009 and P<0.001, respectively), but in model 3, those with a ratio from 1.5-2 only had a trend towards a higher association with composite clinical events than those with a ratio<1 (P=-0.09). Those with a ratio≥2 continued to have a higher association (P=-0.001). CONCLUSION: Patients with intermediate trabeculations not meeting criteria for LVNC had a higher association with composite clinical events, but it was mediated by decreased myocardial thickening in the associated compacted layer.

Mitral regurgitation in left ventricular noncompaction cardiomyopathy assessed by cardiac MRI.

BACKGROUND AND AIM OF THE STUDY: Previous case reports have described patients with left ventricular noncompaction cardiomyopathy (LVNC) with significant mitral regurgitation (MR). The study aim was to determine if LVNC is associated with MR, as assessed by cardiac magnetic resonance imaging (cMRI). METHODS: LVNC, assessed with cMRI, was observed retrospectively among 122 consecutive cases, 31 of whom had an end-systolic noncompacted-to-compacted ratio (ESNCCR) ≥ 2. In addition, 40 normal subjects undergoing cMRI and 40 with moderate to severe MR were included as controls. Using cine images, the ESNCCR and left ventricular (LV) and right ventricular (RV) stroke volumes were measured. The mitral regurgitant fraction (MRF) was calculated by dividing the difference between the RV and LV stroke volumes by the LV stroke volume. The total papillary muscle (TPM) area was measured from the mid short-axis view. Adjusting for age, race, gender and body surface area, an analysis of covariance was conducted to determine whether MRF and TPM were associated with ESNCCR ≥ 2. Adjusted means were presented with 95% confidence intervals. RESULTS: After adjustment, the MRF in patients with ESNCCR ≥ 2 was higher than in controls, but did not differ from that in patients with significant MR (21 ± 6.5% versus 2.7 ± 12% versus 29.2 ± 11%, p = 0.039 and p = 0.3, respectively). Further, patients with ESNCCR ≥ 2 had a lower TPM than normal controls or those with moderate to severe MR (1.89 ± 0.28 cm2 versus 3.6 ± 0.26 cm2 versus 3.7 ± 0.24 cm2; p < 0.001 and p < 0.001, respectively). CONCLUSION: LVNC is associated with increased MR, as assessed using cMRI. LVNC is also associated with abnormalities in the papillary muscle anatomy, which may predispose to MR.

Small, short-duration, dobutamine-induced perfusion defects are not associated with adverse prognosis in intermediate-risk individuals receiving cardiovascular magnetic resonance stress imaging.

OBJECTIVE: The objective of this study was to assess the frequency and prognostic utility of small, short-duration left ventricular myocardial perfusion defects during dobutamine cardiovascular magnetic resonance (DCMR) stress imaging. METHODS: We performed first-pass contrast-enhanced DCMR at peak stress in 331 consecutively recruited individuals (aged 68 ± 8 years, 50% men) at intermediate risk for a future cardiac event. Size, location, and persistence of low-signal intensity perfusion defects were recorded. Cardiac events were assessed by personnel blinded to imaging results for a median of 24 months after the DCMR. RESULTS: Among the 55 individuals (16.6%) who exhibited small (<25% myocardial thickness) and short-duration (<5 frames in persistence) perfusion defects, diabetes was more prevalent (P = 0.019) and no cardiac events were observed. Large, persistent perfusion defects were associated with coronary artery disease, prior myocardial infarction, and decreased left ventricular function (P < 0.001 for all) and increased 2-year risk for a cardiac event (hazard ratio, 10.3; P < 0.001; confidence interval, 3.3-33.0). CONCLUSIONS: In individuals with diabetes, hypertension, or coronary artery disease at intermediate risk for a future cardiac event, small, short-duration DCMR perfusion defects are not associated with increased 2-year risk for a subsequent cardiac event.

The practical role of echocardiography in selection, implantation, and management of patients requiring LVAD therapy.

Viable treatment options for advanced heart failure have not emerged as the number of people afflicted with this condition has grown. Although heart transplantation is the only curative strategy for patients with end-stage heart failure, the relative shortage of donors has led to a worldwide plateau of this option over the past 20 years. The result is an unacceptably high mortality rate among patients with advanced heart failure. Interest in developing alternative curative strategies based on chronic circulatory support, with the aim of prolonging and improving quality of life for these patients, has grown. Patients supported with left ventricular assist devices require structured longitudinal care from a team of providers. An integrated approach using basic echocardiography is critical to patient selection, implantation, and continued surveillance and success of patients with left ventricular assist devices.

Use of a Pulmonary Artery Pressure Sensor to Manage Patients With Left Ventricular Assist Devices.

BACKGROUND: Hemodynamic-guided management with a pulmonary artery pressure sensor (CardioMEMS) is effective in reducing heart failure hospitalization in patients with chronic heart failure. This study aims to determine the feasibility and clinical utility of the CardioMEMS heart failure system to manage patients supported with left ventricular assist devices (LVADs). METHODS: In this multicenter prospective study, we followed patients with HeartMate II (n=52) or HeartMate 3 (n=49) LVADs and with CardioMEMS PA Sensors and measured pulmonary artery pressure, 6-minute walk distance, quality of life (EQ-5D-5 L scores), and heart failure hospitalization rates through 6 months. Patients were stratified as responders (R) and nonresponders to reductions in pulmonary artery diastolic pressure (PAD). RESULTS: There were significant reductions in PAD from baseline to 6 months in R (21.5-16.5 mm Hg; P<0.001), compared with an increase in NR (18.0-20.3; P=0.002), and there was a significant increase in 6-minute walk distance among R (266 versus 322 meters; P=0.025) compared with no change in nonresponder. Patients who maintained PAD <20 compared with PAD ≥20 mm Hg for more than half the time throughout the study (averaging 15.6 versus 23.3 mm Hg) had a statistically significant lower rate of heart failure hospitalization (12.0% versus 38.9%; P=0.005). CONCLUSIONS: Patients with LVAD managed with CardioMEMS with a significant reduction in PAD at 6 months showed improvements in 6-minute walk distance. Maintaining PAD <20 mm Hg was associated with fewer heart failure hospitalizations. Hemodynamic-guided management of patients with LVAD with CardioMEMS is feasible and may result in functional and clinical benefits. Prospective evaluation of ambulatory hemodynamic management in patients with LVAD is warranted. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03247829.

Implantable cardiac defibrillators and sudden death in recent onset nonischemic cardiomyopathy: results from IMAC2.

BACKGROUND: Given the potential for recovery in recent onset nonischemic cardiomyopathy (ROCM), the timing and need for implantable cardioverter-defibrillator (ICDs) remains controversial. We examined the utilization of ICDs and the impact on survival for subjects with ROCM. METHODS AND RESULTS: An National Heart, Lung, and Blood Institute sponsored registry enrolled 373 subjects with ROCM, all with a left ventricular ejection fraction (LVEF) ≤0.40 and ≤6 months of symptoms. The mean age was 45 ± 14 years, 38% were female, 21% black, 75% New York Heart Association II/III, and the mean LVEF was 0.24 ± 0.08. Survival was comparable for subjects with an ICD within 1 month of entry (n = 43, 1/2/3 year % survival = 97/97/92) and those with no ICD at 1 month (n = 330, % survival = 98/97/95, P = .30) and between those with and without an ICD at 6 months (ICD, n = 73, 1/2/3 year % survival = 98/98/95; no ICD, n = 300, % survival = 98/96/95, P = .95). There were only 6 sudden cardiac deaths (SCD) noted (% survival free from SCD = 99/98/97) and these occurred in 1.9% of subjects without ICD and 0.9% of those with a device (P = .50). CONCLUSIONS: In a multicenter cohort of ROCM the risk of SCD was low at 1% per year. Early ICD placement did not impact survival and can be deferred while assessing potential for myocardial recovery.

Echocardiographic assessment of radial right ventricular function in heart transplant recipients.

AIMS: Right ventricular (RV) allograft dysfunction is present in half of all heart transplant (HT) recipients. Non-invasive assessment of RV function in the setting of rejection is not well described. We outline an echocardiographic technique, short-axis fractional area change (SAXFAC), to evaluate RV function in the HT population and correlate this with the grade of pathologic rejection. METHODS AND RESULTS: We retrospectively reviewed the electronic medical records of 110 people who received a HT between 1 January 2015 and 29 February 2020 and had no evidence of rejection. One hundred eighty-two transthoracic echocardiograms (TTEs) completed up to 1 year from the date of transplantation were analysed for the target acoustic window, the parasternal mid-ventricular short-axis view. Sixty-one TTEs from 23 healthy transplants were deemed appropriate for SAXFAC determination. Thirty-three organ recipients with at least grade 1R allograft rejection were also identified, and their TTEs screened for SAXFAC analysis. Two expert readers independently calculated SAXFAC as follows: RV end-diastolic area minus end-systolic area divided by end-diastolic area. Using commercially available software (Epsilon, Ann Arbor, Michigan), we quantified RV radial strain, longitudinal strain, and apical fractional area change (FAC). Twenty-eight transplant recipients with grade 0R or 1R rejection and nine patients with clinically significant rejection completed the study analysis. SAXFAC demonstrated significant variability in the entire population with an inverse relationship to severity of allograft rejection (P ≤ 0.01). Radial strain and FAC were also associated with clinically significant rejection (P ≤ 0.01). CONCLUSIONS: Short-axis fractional area change is a simple two-dimensional technique to assess RV function in HT recipients and showed no significant inter-observer variability. In our small, single-centre, retrospective case series, lower SAXFAC values were associated with clinically significant allograft rejection. The small sample size and infrequent occurrence of rejection make our observations hypothesis-generating only. We advocate dedicated RV SAXFAC imaging planes be included when assessing allograft function.

Impact of a pharmacist-inclusive post-discharge clinic on outcomes in heart failure patients with reduced ejection fraction: Rates of hospital readmission, emergency department visits, or death.

INTRODUCTION: Heart failure hospitalization is a hallmark of disease progression associated with increased morbidity and mortality. Benefits of multidisciplinary clinics have been established in the care of heart failure patients and can be particularly impactful post-hospital discharge. OBJECTIVE: This study aimed to investigate the impact of a clinical pharmacist-integrated model of care within a Heart Failure Bridge Clinic (HFBC) at a large tertiary care referral center. METHODS: In this single-center retrospective study, patients with left ventricular ejection fraction (LVEF) ≤40% discharged from Mission Hospital (Asheville, North Carolina) between August 2018 and July 2019 were screened. Patients in the HFBC arm had a clinic visit inclusive of a clinical pharmacist within 30 days of hospital discharge and were compared with a control group of patients with a usual care provider clinic visit. The HFBC provided clinical assessment, detailed heart failure education, and medication reconciliation and adjustment with an emphasis on optimization of Guideline Directed Medical Therapy (GDMT). Patients were followed for 90 days for the primary end point of hospitalization, emergency department (ED) visit, or death. RESULTS: A total of 1463 patients (HFBC, n = 307; control, n = 1156) comprised our final cohort. After accounting for baseline variables, 90-day cumulative probability of hospitalization, ED visit, or death favored HFBC patients (26% vs 32%, P = .0275). Comprehensive review of medications prior to and after HFBC appointment demonstrated significant alterations to therapies (30% GDMT addition, 27% GDMT titration, 7.2% discontinuation of medications associated with worsening heart failure, and 28% loop diuretic adjustment). CONCLUSION: Clinical pharmacist-integrated HFBC allows for focused medication review and optimization and is associated with a 19% relative risk reduction in hospitalization, ED visit, or death at 90 days.

Left ventricular assist systems and infection-related outcomes: A comprehensive analysis of the MOMENTUM 3 trial.

BACKGROUND: In a randomized controlled trial (MOMENTUM 3), the HeartMate 3 (HM3) fully magnetically levitated centrifugal-flow left ventricular assist device (LVAD) demonstrated superiority over the HeartMate II (HMII) axial-flow LVAD. These findings were driven by hemocompatibility-related outcomes, but infection-related outcomes were not altered by device choice. In this trial-level analysis, we analyzed the clinical patterns of infection-related outcomes over 2 years of support. METHODS: In MOMENTUM 3, 1,020 patients were implanted with either the HM3 (n = 515) or HMII (n = 505) pump. Clinical characteristics and morbidity- and mortality-related outcomes were evaluated to identify predictors associated with major infectious complications, using univariable and multivariable models. RESULTS: The cumulative number of infections at 2 years was 1,213 (634 HM3 and 579 HMII), and major infection occurred in 58% of patients with the HM3 and 56% of patients with the HMII (p = 0.57). Infections of a local nature unrelated to pump components were most common (n = 681/1,213; 56%), followed by driveline-associated infection (n = 329/1,213; 27%), sepsis (n = 194/1,213; 16%), and other events (n = 9/1,213; 0.7%). Bacterial pathogens were implicated in 806 of 1,213 events (66%); significant predictors of infection included sex (women vs men; hazard ratio [HR]: 1.38, p = 0.003), pre-implant use of intra-aortic balloon pump (HR: 1.33, p = 0.02), pre-implant history of cardiac surgery (HR: 1.28, p = 0.01), and body mass index ≥ 30 (HR: 1.40, p < 0.0001). Most deaths in those with infection occurred owing to non-infectious causes. CONCLUSION: Infection is the most common adverse effect in patients implanted with contemporary continuous-flow LVADs, with most such events unrelated to the pump or its peripheral components. Whether chronic mechanical circulatory devices confer an immunomodulatory effect pre-disposing to infection warrants closer scrutiny to understand and ameliorate this morbidity.

Benefits of Neurohormonal Therapy in Patients With Continuous-Flow Left Ventricular Assist Devices.

Left ventricular assist devices (LVADs) have dramatically improved short-term outcomes among patients with advanced heart failure. While neurohormonal blockade (NHB) is the cornerstone of treatment for patients with heart failure with reduced ejection fraction, its effect after LVAD placement has not been established. We reviewed medical records of 307 patients who underwent primary LVAD implantation from January 2006 to September 2015 at two institutions in the United States. Patients were followed for at least 2 years post-LVAD implantation or until explantation, heart transplantation, or death. Cox regression analysis stratifying on center was used to assess associations with mortality. Neurohormonal blockade use was treated as a time-dependent predictor. Stepwise selection indicated treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) (hazard ratio [HR] = 0.53 [0.30-0.95], p = 0.03), age at the time of implantation (HR = 1.28 [1.05-1.56] per decade, p = 0.02), length of stay postimplantation (HR = 1.16 [1.11-1.21] per week, p < 0.01) and INTERMACS profile of 1 or 2 (HR = 1.86 [1.17-2.97], p < 0.01) were independent predictors of mortality. In this large, retrospective study, treatment with ACEIs or ARBs was an independent factor associated with decreased mortality post-LVAD placement.