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.

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.

Cardiac sarcoid: a chameleon masquerading as hypertrophic cardiomyopathy and dilated cardiomyopathy in the same patient.

Sarcoidosis is a multisystem, granulomatous disease of unknown etiology often seen in young adults, with cardiac involvement in more than one-quarter of sarcoid patients. The clinical presentation of cardiac sarcoid depends upon the location and extent of myocardium involved. Although cardiac sarcoid may produce asymmetrical septal hypertrophy, it is most commonly considered in the differential diagnosis of dilated cardiomyopathy. The hypertrophic stage of cardiac sarcoid is rarely seen. We describe a case of cardiac sarcoid in a young patient wherein a distinctive appearance of the cardiac sarcoid spectrum from "hypertrophic" stage to thinned/scarred stage, masquerading as hypertrophic cardiomyopathy followed by dilated cardiomyopathy, is demonstrated.

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.

The first year post-heart transplantation: use of immunosuppressive drugs and early complications.

A large number of heart transplants are performed annually in different transplant centers in the United States. This is partly because of the improved survival of patients who undergo cardiac transplantation, thus making it a more viable option in the management of end-stage heart failure. The survival benefit after heart transplantation is a result of newer immunosuppressive drug regimens and a better understanding of their effects and interactions. Several studies, mostly involving a small number of patients, describe use and comparison of the many distinct immunosuppressive drugs available to date. Interestingly, many transplant centers perform in-house typical induction treatment regimens because of their own experience and intra-institutional preference. This review summarizes current practices of immunosuppressive drug therapy in the first year post-heart transplant based on the available clinical evidence and discusses future options of heart transplant immunosuppressive drug therapies.

Malignant cardiac phenotypic expression of Danon disease (LAMP2 cardiomyopathy).

INTRODUCTION: Danon disease is an X-linked lysosomal condition that causes a deficiency of lysosome-associated membrane protein 2 (LAMP2) gene. It is characterized clinically by a triad of skeletal myopathy, cardiomyopathy, and intellectual disability. METHODS: We examined clinical, echocardiographic, and genetic data on 5 patients with Danon disease, highlighting their clinical course and outcomes. RESULTS: All patients presented phenotypically with hypertrophic cardiomyopathy and later developed systolic dysfunction. The mean age at diagnosis was 19years (11-31years). All patients had diastolic dysfunction (mean e' of 5cm/s [3.5-6cm/s], mean E/e' of 17 [15-21]). Three patients required cardiac transplantation (ages 15, 27, and 42). Of the two deaths in this group, both were in women. CONCLUSION: We highlight the aggressive cardiac phenotype of Danon disease in our clinical experience with rapid progression to end-stage cardiomyopathy; this progression occurred in both men and women. A timely diagnosis and an early referral for cardiac transplantation is crucial for improved outcomes.

Monocyte chemoattractant protein 1-induced monocyte infiltration produces angiogenesis but not arteriogenesis in chronically infarcted myocardium.

BACKGROUND: Monocyte chemoattractant protein 1 (MCP-1) stimulates the invasion of monocytes into ischemic tissue with concomitant adhesion to endothelial cells. Monocyte stimulation has been shown to be involved in the induction of arteriogenesis, which is the development of functional arterioles resulting in improvement of perfusion. However, angiogenesis (newly developed capillaries contribute to improved tissue perfusion) in several models has not resulted in any improvement in blood flow. OBJECTIVE: The effects of MCP-1 on potential angiogenesis and arteriogenesis as well as changes in left ventricular function were tested in a chronic infarct model in rat hearts. METHODS: Anesthetized rats were subjected to open-chest ligation of the left coronary artery with subsequent myocardial infarction. After 6 weeks, animals were randomized to receive either MCP-1 (3 microL in 0.15 mL NaCl, group 1, n = 9) or saline (0.15 mL, group 2, n = 9), which was injected into the myocardium at the border zones of the infarcts. For assessment of left ventricular dimensions and global cardiac function, transthoracic two-dimensional echocardiography was performed at baseline, 6 weeks after myocardial infarction, and 4 weeks after MCP-1 or saline injection, by use of a 12-MHz pediatric transducer. For light microscopic analysis, myocardial tissue was stained with Elastica-van-Giesson and von Willebrand factor for blood vessels and endothelial cells, respectively. In a subset of animals, hearts were excised 24 hours after MCP-1 administration (n = 4) or saline administration (n = 4) for assessment of monocyte infiltration by immunohistologic staining of the CD31 antigen. RESULTS: Left ventricular dimensions and ejection fraction changed after coronary occlusion (from 60.4% +/- 2.85% to 24.8% +/- 5.01% ejection fraction in group 1, and from 58.4% +/-2.06% to 26.3% +/- 4.3% ejection fraction in group 2 at 6 weeks, P < .005) without any further change 4 weeks after treatment (ejection fraction in group 1, 26.3% +/- 2.7%, ejection fraction in group 2, 25.0% +/- 5.18%). The MCP-1 group resulted in 390.6 +/- 10.36 endothelial cells compared with 285.2 +/- 13.56 in group 2 (P < .005) at the injection site. Monocyte infiltration was observed at the MCP-1 injection site with an increase in capillary growth (angiogenesis). However, there was no difference in the number of arteriolar structures between animals treated with MCP-1 and saline animals (group 1, 19.0 +/- 1.52 vs group 2, 16.4 +/- 0.68, P > .05). CONCLUSION: A single intramyocardial injection of MCP-1 into the infarct border zone resulted in neo-angiogenesis and monocyte infiltration but not arteriogenesis in the rat heart. There was no functional change of chronically infarcted myocardium in the present model.

Practical value of identifying antibodies to cryptic HLA epitopes in cardiac transplantation.

BACKGROUND: Identification of antibodies to human leukocyte antigens (HLA) by single antigen bead arrays has led to the common practice of virtual crossmatching. However, inappropriate assignment of anti-HLA specificities can lead to false-positive virtual crossmatching, resulting in the decline of potentially crossmatch-negative organ offers. In this study we describe identification of antibodies to cryptic HLA present on denatured forms of HLA on single antigen bead array and provide a reassessment of calculated panel-reactive antibody (CPRA) based on elimination of false-positive reactions due to antibodies to cryptic HLA epitopes. METHODS: Sera from 96 patients with positive HLA antibodies detected on a standard single antigen bead platform were tested under denaturing conditions and with a new single antigen bead product (iBeads; One Lambda, Inc., Canoga Park, CA) to identify antibodies to cryptic HLA vs. native HLA. Flow cytometry crossmatching and complement-fixation assays were performed to assess clinical relevance. RESULTS: Antibodies to cryptic HLA were present in approximately 21% of patients on our waiting list for cardiac transplantation. These antibody responses were not associated with factors commonly thought to be associated with antibody responses to HLA such as age, gender, transfusions or presence of circulatory support. CONCLUSIONS: Antibodies to cryptic HLA can be reliably identified by iBeads technology, and usually do not fix complement nor produce positive flow cytometry crossmatches. Identification and removal of antibodies to cryptic HLA from the panel of unacceptable antigens may have dramatic and meaningful effects on CPRA and virtual crossmatch strategies.

Conivaptan: a selective vasopressin antagonist.

Complex neurohormonal interactions dictate the body's volume status in different disease states. Besides the known pathologic activation of the renin-angiotensin-aldosterone axis and the effect of the adrenergic system, arginine vasopressin (AVP) represents a key element that is responsible for volume homeostasis. Serum AVP levels have been shown to be chronically elevated in different pathologic conditions that exhibit an imbalance in volume status, particularly in congestive heart failure. Evidently, elevated levels of AVP play an important role in the pathogenesis and progression of these diseases. AVP has many other receptor-mediated deleterious effects on vascular smooth muscles and cardiomyocytes. These effects are an integral part of the neurohormonal milieu in patients with heart failure. This assumption has propelled agents that antagonize the effects of vasopressin receptors to the forefront of clinical research, especially in heart failure management. This paper reviews current knowledge on conivaptan, a novel dual V1a/V2 vasopressin receptor antagonist.