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Telemetry is done in a variety of settings with different levels of sophistication. The American College of Cardiology has made suggestions for telemetry monitoring but these are not in place in many smaller community hospitals that do telemetry monitoring. The objective of this study was to compare prospectively telemetry without a dedicated monitor watcher or full disclosure to results obtained on full disclosure. Patients included were admitted to a single community hospital with an indication for telemetry as judged by their primary physician. Telemetry results reported by the hospital staff were compared to over-read of full disclosure traces by an academic cardiology service and the patient was used as his own control. Significant rhythm disturbances including pauses of 2 seconds or greater and short runs of ventricular and supraventricular tachycardia were frequently missed when a dedicated monitor watcher and full disclosure were not in use. When a dedicated monitor watcher and full disclosure are not in use, telemetry results should be accepted with caution and attempts should be made to improve monitoring. [ABSTRACT FROM AUTHOR]

PURPOSE: Low socioeconomic status (SES) predicts coronary artery disease (CAD) onset, but its value among patients with CAD is uncertain. Geographic measures (e.g., residential neighborhood) may predict risk, but this requires further evaluation. METHODS: A cohort of 3410 patients with significant, angiographically-defined CAD (> or =1 lesion of > or =70% stenosis) joined a registry during the period between 1993 and 2000 and was followed for 6.7 years (median 3.7 years). A geographic SES measure-residential economic status (RES)-and insurance type were examined for association with mortality or myocardial infarction (MI). RESULTS: In Cox regression adjusting for 17 covariates, lower RES quartile was associated with increased death/MI (p-trend<0.001), death (p-trend=0.001), and MI (p-trend=0.07). First RES quartile (vs. fourth) predicted death/MI (hazard ratio [HR]=1.32, 95% confidence interval [CI]=1.07-1.62, p=0.01) and death (HR=1.46, CI=1.12-1.91, p=0.006), but not MI (HR=1.18, p=0.31). Compared with private insurance, self-pay (HR=1.88, p=0.053), charity care (HR=1.71, p<0.001), and Medicaid (HR=1.43, p=0.24), but not Medicare (HR=0.95, p=0.68), were associated with death/MI. CONCLUSIONS: Both geographic (RES) and economic (insurance) measures of SES independently predicted risk of death/MI in a large population with angiographically-defined CAD. This suggests that SES remains a significant predictor of health outcomes after CAD has developed, and that geographic measures of SES deserve further evaluation. [ABSTRACT FROM AUTHOR]

Background: Peripartum (PP) cardiomyopathy (CM) is a rare condition of unknown etiology that occurs in late pregnancy or early postpartum. Initial evidence suggests that genetic factors may influence PPCM. This study evaluated and replicated genome-wide association of single nucleotide polymorphisms with PPCM., Methods and Results: Genome-wide single nucleotide polymorphisms in women with verified PPCM diagnosis (n=41) were compared separately with local control subjects (n=49 postmenopausal age-discordant women with parity ≥1 and no heart failure) and iControls (n=654 women ages 30 to 84 years with unknown phenotypes). A replication study of independent population samples used new cases (PPCM2, n=30) compared with new age-discordant control subjects (local2, n=124) and with younger control subjects (n=89) and obstetric control subjects (n=90). A third case set of pregnancy-associated CM cases not meeting strict PPCM definitions (n=29) was also studied. In the genome-wide association study, 1 single nucleotide polymorphism (rs258415) met genome-wide significance for PPCM versus local control subjects (P=2.06×10(-8); odds ratio [OR], 5.96). This was verified versus iControls (P=7.92×10(-19); OR, 8.52). In the replication study for PPCM2 cases, rs258415 (ORs are per C allele) replicated at P=0.009 versus local2 control subjects (OR, 2.26). This replication was verified for PPCM2 versus younger control subjects (P=0.029; OR, 2.15) and versus obstetric control subjects (P=0.013; OR, 2.44). In pregnancy-associated cardiomyopathy cases, rs258415 had a similar effect versus local2 control subjects (P=0.06; OR, 1.79), younger control subjects (P=0.14; OR, 1.65), and obstetric control subjects (P=0.038; OR, 1.99)., Conclusions: Genome-wide association with PPCM was discovered and replicated for rs258415 at chromosome 12p11.22 near PTHLH. This study indicates a role of genetic factors in PPCM and provides a new locus for further pathophysiological and clinical investigation.

Aims: The complete blood count (CBC) and basic metabolic profile are common, low-cost blood tests, which have previously been used to create and validate the Intermountain Risk Score (IMRS) for mortality prediction. Mortality is the most definitive clinical endpoint, but medical care is more easily applied to modify morbidity and thereby prevent death. This study tested whether IMRS is associated with clinical morbidity endpoints., Methods and Results: Patients seen for coronary angiography (n = 3927) were evaluated using a design similar to a genome-wide association study. The Bonferroni correction for 102 tests required a P-value of ≤ 4.9 × 10⁻⁴ for significance. A second set of angiography patients (n = 10 413) was used to validate significant findings from the first patient sample. In the first patient sample, IMRS predicted heart failure (HF) (P(trend) = 1.6 × 10(-26)), coronary disease (P(trend) = 2.6 × 10(-11)), myocardial infarction (MI) (P(trend) = 3.1 × 10(-25)), atrial fibrillation (P(trend) = 2.5 × 10(-20)), and chronic obstructive pulmonary disease (P(trend) = 4.7 × 10⁻⁴). Even more, IMRS predicted HF readmission [hazard ratio (HR) = 2.29/category, P(trend) = 1.2 × 10⁻⁶), incident HF (HR = 1.88/category, P(trend) = 0.02), and incident MI (HR = 1.56/category, P(trend) = 4.7 × 10⁻⁴). These findings were verified in the second patient sample., Conclusion: Intermountain Risk Score, a predictor of mortality, was associated with morbidity endpoints that often lead to mortality. Further research is required to fully characterize its clinical utility, but its low-cost CBC and basic metabolic profile composition may make it ideal for initial risk estimation and prevention of morbidity and mortality. An IMRS web calculator is freely available at http://intermountainhealthcare.org/IMRS.

Objectives: This study investigates alterations in myocardial microvasculature, fibrosis, and hypertrophy before and after mechanical unloading of the failing human heart., Background: Recent studies demonstrated the pathophysiologic importance and significant mechanistic links among microvasculature, fibrosis, and hypertrophy during the cardiac remodeling process. The effect of left ventricular assist device (LVAD) unloading on cardiac endothelium and microvasculature is unknown, and its influence on fibrosis and hypertrophy regression to the point of atrophy is controversial., Methods: Hemodynamic data and left ventricular tissue were collected from patients with chronic heart failure at LVAD implant and explant (n = 15) and from normal donors (n = 8). New advances in digital microscopy provided a unique opportunity for comprehensive whole-field, endocardium-to-epicardium evaluation for microvascular density, fibrosis, cardiomyocyte size, and glycogen content. Ultrastructural assessment was done with electron microscopy., Results: Hemodynamic data revealed significant pressure unloading with LVAD. This was accompanied by a 33% increase in microvascular density (p = 0.001) and a 36% decrease in microvascular lumen area (p = 0.028). We also identified, in agreement with these findings, ultrastructural and immunohistochemical evidence of endothelial cell activation. In addition, LVAD unloading significantly increased interstitial and total collagen content without any associated structural, ultrastructural, or metabolic cardiomyocyte changes suggestive of hypertrophy regression to the point of atrophy and degeneration., Conclusions: The LVAD unloading resulted in increased microvascular density accompanied by increased fibrosis and no evidence of cardiomyocyte atrophy. These new insights into the effects of LVAD unloading on microvasculature and associated key remodeling features might guide future studies of unloading-induced reverse remodeling of the failing human heart., (Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation appears to be associated with increased mortality. However, the determination of which patients are at greater risk of developing postoperative RVF remains controversial and relatively unknown. We sought to determine the preoperative risk factors for the development of RVF after LVAD implantation. The data were obtained for 175 consecutive patients who had received an LVAD. RVF was defined by the need for inhaled nitric oxide for >/=48 hours or intravenous inotropes for >14 days and/or right ventricular assist device implantation. An RVF risk score was developed from the beta coefficients of the independent variables from a multivariate logistic regression model predicting RVF. Destination therapy (DT) was identified as the indication for LVAD implantation in 42% of our patients. RVF after LVAD occurred in 44% of patients (n = 77). The mortality rates for patients with RVF were significantly greater at 30, 180, and 365 days after implantation compared to patients with no RVF. By multivariate logistic regression analysis, 3 preoperative factors were significantly associated with RVF after LVAD implantation: (1) a preoperative need for intra-aortic balloon counterpulsation, (2) increased pulmonary vascular resistance, and (3) DT. The developed RVF risk score effectively stratified the risk of RV failure and death after LVAD implantation. In conclusion, given the progressively growing need for DT, the developed RVF risk score, derived from a population with a large percentage of DT patients, might lead to improved patient selection and help stratify patients who could potentially benefit from early right ventricular assist device implantation., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Midterm heart transplant outcomes of ABO-incompatible (ABO-I) organ use in infants are favorable. ABO-I transplantation has resulted in reduced waitlist mortality in some countries. This study assessed the effect of an ABO-I listing strategy on pre-transplant outcomes in the United States., Methods: The Organ Procurement and Transplantation Network (OPTN)/United Network of Organ Sharing (UNOS) database was used to identify infants aged younger than 1 year listed as status 1 for heart transplantation between January 1, 2001, and May 20, 2008. The cohort was divided into 2 groups: eligible for ABO-compatible (ABO-C) transplant and eligible for ABO-I transplant. Baseline characteristics, waitlist times, and outcomes were compared in univariate analysis. Competing risks analysis evaluated differences in time to transplant in the presence of other outcomes., Results: Of 1,029 infants listed for transplant, 277 (27%) were listed for an ABO-I transplant. Overall, 92% of transplant recipients received an ABO-C organ regardless of listing type. Among recipients eligible for ABO-I, only 27% received an ABO-I organ. The percentage that underwent transplant in each group did not differ. Although infants listed for an ABO-I organ had a shorter wait time for transplant, waitlist mortality was similar., Conclusions: Despite the intended merits of ABO-I heart transplantation, ABO-I listing and organ acceptance have not yielded lower waitlist mortality in the United States under the current UNOS allocation algorithm. Consideration should be given to altering the allocation system to one that gives less preference toward blood group compatibility in hopes of improving organ use and reducing waitlist mortality.

Background: Organ transplant candidates with serum antibodies directed against human leukocyte antigens (HLA) face longer waiting times and higher mortality while awaiting transplantation. This study examined the accuracy of virtual crossmatch, in which recipient HLA-specific antibodies, identified by solid-phase assays, are compared to the prospective donor HLA-type in heart transplantation., Methods: We examined the accuracy of virtual crossmatch in predicting immune compatibility of donors and recipients in heart transplantation and clinical outcomes in immunologically sensitized heart transplant recipients in whom virtual crossmatch was used in allograft allocation., Results: Based on analysis of 257 T-cell antihuman immunoglobulin complement-dependent cytotoxic (AHG-CDC) crossmatch tests, the positive predictive value of virtual crossmatch (the likelihood of an incompatible virtual crossmatch resulting in an incompatible T-cell CDC-AHG crossmatch) was 79%, and the negative predictive value of virtual crossmatch (the likelihood of a compatible virtual crossmatch resulting in a compatible T-cell CDC-AHG crossmatch) was 92%. When used in a cohort of 28 sensitized patients awaiting heart transplantation, 14 received allografts based on a compatible virtual crossmatch alone from donors in geographically distant locations. Compared with the other 14 sensitized patients who underwent transplant after a compatible prospective serologic crossmatch, the rejection rates and survival were similar., Conclusion: Our findings are evidence of the accuracy of virtual crossmatch and its utility in augmenting the opportunities for transplantation of sensitized patients.

Left ventricular assist device (LVAD) implantation before heart transplantation has been associated with formation of antibodies directed against human leukocyte antigens (HLA), often referred to as sensitization. This study investigated whether prior sensitization or LVAD type affected the degree of post-implantation sensitization. The records of consecutive HeartMate (HM) I and HM II LVAD patients were reviewed. Panel reactive antibody (PRA) was assessed before LVAD implantation and biweekly thereafter. Sensitization was defined as PRA > 10%, and high-degree sensitization was defined as PRA > 90%. An HM LVAD was implanted in 64 patients, and 11 received a HM II LVAD as a bridge to transplant. Ten HM I patients (16%) were sensitized before LVAD implantation (HM I-S), and 54 (84%) were not (HM I-Non-S). Nine HM I-S patients (90%) became highly sensitized (PRA > 90%) compared with 9 HM I-Non-S patients (16.7%; p < 0.001). The PRA remained elevated (> 90%) in 8 of the 9 (88.9%) highly sensitized HM I-S patients vs 5 of the 9 (55.6%) HM I-Non-S highly sensitized patients. The PRA levels in the rest of the HM I-S highly sensitized patients declined from 93% +/- 4% to 55% +/- 15% (p = 0.01). Among the 11 HM II patients, 1 (9%) was sensitized before LVAD implantation (PRA, 40%) and the PRA moderately increased to 80%. No other HM II patient became sensitized after implantation. Thus, 1 of 11 (9%) HM II patients became sensitized compared with 29 of 64 (45%) HM I patients (p = 0.04). Pre-sensitized patients are at higher risk for becoming and remaining highly HLA-allosensitized after LVAD implantation. The HeartMate II LVAD appears to cause less sensitization than HeartMate I.

Background: Little has been reported on the clinical significance of asymptomatic antibody-mediated rejection (AMR) alone or mixed rejection (MR), defined as concurrent cellular rejection (CR) and AMR in heart transplantation. In this study, we examined whether a differential impact on cardiovascular mortality (CVM) existed when comparing asymptomatic AMR, to stable MR or CR., Methods: The Utah Transplantation Affiliated Hospitals (UTAH) Cardiac Transplant Program pathology database of all heart transplant recipients between 1985 and 2004 was queried. Patients were classified as cellular, antibody-mediated, or mixed rejectors based on their predominant pattern of rejection type in the first three months post-transplant. Kaplan-Meier survival curves were fit to each of the three groups and analyses were adjusted for age at the time of transplant, gender, and underlying primary cardiac disease., Results: Eight hundred and sixty nine heart transplant recipients qualified for analysis. Over the study period, patients with asymptomatic AMR or stable MR patterns had significantly worse CVM when compared to patients with stable CR pattern (AMR, 21.2%; MR, 18.0%; CR, 12.6%; AMR vs. CR, p = 0.009; MR vs. CR, p = 0.001). In contrast, CVM was comparable in patients with asymptomatic AMR or stable MR patterns (p = 0.9)., Conclusions: Asymptomatic or subclinical AMR and MR are clinically relevant, should be recognized, and deserve consideration for therapeutic intervention in hopes of avoiding adverse outcomes.

Background: Some components of the complete blood count and basic metabolic profile are commonly used risk predictors. Many of their components are not commonly used, but they might contain independent risk information. This study tested the ability of a risk score combining all components to predict all-cause mortality., Methods: Patients with baseline complete blood count and basic metabolic profile measurements were randomly assigned (60%/40%) to independent training (N = 71,921) and test (N = 47,458) populations. A third population (N = 16,372) from the Third National Health and Nutrition Examination Survey and a fourth population of patients who underwent coronary angiography (N = 2558) were used as additional validation groups. Risk scores were computed in the training population for 30-day, 1-year, and 5-year mortality using age- and sex-adjusted weights from multivariable modeling of all complete blood count and basic metabolic profile components., Results: Area under the curve c-statistics were exceptional in the training population for death at 30 days (c = 0.90 for women, 0.87 for men), 1 year (c = 0.87, 0.83), and 5-years (c = 0.90, 0.85) and in the test population for death at 30 days (c = 0.88 for women, 0.85 for men), 1 year (c = 0.86, 0.82), and 5 years (c = 0.89, 0.83). In the test, the Third National Health and Nutrition Examination Survey, and the angiography populations, risk scores were highly associated with death (P <.001), and thresholds of risk significantly stratified all 3 populations., Conclusion: In large patient and general populations, risk scores combining complete blood count and basic metabolic profile components were highly predictive of death. Easily computed in a clinical laboratory at negligible incremental cost, these risk scores aggregate baseline risk information from both the popular and the underused components of ubiquitous laboratory tests.

Background: The basic metabolic profile (BMP) is a common blood test containing information about standard blood electrolytes and metabolites. Although individual variables are checked for cardiovascular health and risk, combining them into a total BMP-derived score, as to maximize BMP predictive ability, has not been previously attempted., Methods: Patients (N = 279,337) that received a BMP and had long-term follow-up for death were studied. Risk models were created in a training group (60% of study population, n = 167,635), validated in a test group (40% of study population, n = 111,702), and confirmed in the NHANES III (Third National Health and Nutrition Examination Survey) participants (N = 17,752). The BMP models were developed for 30-day, 1-year, and 5-year death using logistic regression with adjustment for age and sex. The BMP parameters were categorized as low, normal, or high based on the standard range of normal. Glucose was categorized as normal, intermediate, and high. Creatinine >or=2 mg/dL was further categorized as very high., Results: Average age was 53.2 +/- 20.1 years, and 44.3% were male. The areas under the curve for the training and test groups for 30-day, 1-year, and 5-year death were 0.887 and 0.882, 0.850 and 0.848, and 0.858 and 0.847, respectively. The predictive ability of these risk scores was further confirmed in the NHANES III population and independent of the Framingham Risk Score., Conclusion: In large, prospectively followed populations, a highly significant predictive ability for death was found for a BMP risk model. We propose a total BMP score as an optimization of this routine baseline test to provide an important new addition to risk prediction.

An increasing number of patients are living with ventricular assist devices (VADs). Many of these patients will require noncardiac surgery for conditions not directly related to their VADs. The aim of this study was to assess the risks and outcomes of noncardiac surgery in these patients. Perioperative and follow-up data from patients with VADs who underwent noncardiac surgery from 1993 to 2006 were analyzed. In that period, 184 VADs were implanted in 155 patients. Thirty-seven patients (24%) subsequently underwent 59 noncardiac surgeries. The mean duration of VAD support before surgery was 229 days. Bleeding was the most common postsurgical complication (10%), necessitating reexploration in 20% of abdominal surgeries. Thirty-day mortality was 12%. No deaths were caused by direct complications of surgery. Successful transplantation occurred in 72% of bridge to transplantation patients who required noncardiac surgery, compared with 71% of these patients who did not require noncardiac surgery (relative risk 1.0, p = 0.9). The average duration of VAD support after noncardiac surgery for destination therapy patients was 324 days, most of which time was spent at home. In conclusion, outcomes after noncardiac surgery in patients with VADs are favorable, and most patients continue to benefit from the intended purpose of mechanical circulatory support after recovering from noncardiac surgery.

Endomyocardial biopsy is the gold standard to diagnose cardiac allograft rejection, although a noninvasive modality such as brain natriuretic peptide (BNP) is attractive. The authors examined the correlation of BNP levels with rejection patterns and allograft function in cardiac allograft recipients followed up to 8 years. One hundred forty-four consecutive patients underwent endomyocardial biopsy, right heart catheterization, and blood sampling. BNP levels decreased during the first 6 months after transplant but then reached a plateau. Time-dependent correlations were made between BNP levels and allograft rejection, left ventricular ejection fraction, pulmonary capillary wedge pressure, right atrial pressure, and serum creatinine. BNP levels were not different between patients with any rejection pattern and no rejection prior to or after 6 months following transplant. BNP levels did not correlate with ejection fraction, pulmonary capillary wedge pressure, right atrial pressure, or creatinine in the first 6 months after transplant. Statistically significant correlations existed between BNP and these parameters after 6 months following transplant. In cardiac transplant recipients, BNP levels decrease in the first 6 months following transplant and then reach a plateau regardless of the presence, type, or severity of allograft rejection. BNP levels do predict allograft rejection but correlate with allograft function after 6 months following transplant.

Background: The current International Society for Heart and Lung Transplantation (ISHLT) diagnostic criteria for antibody-mediated rejection (AMR) designate AMR as either absent (AMR 0) or present (AMR 1), without grading its severity. Yet, the extent of histologic and immunofluorescence (IF) findings of AMR varies across endomyocardial biopsies (EMBs). In this study, we hypothesized that the severity of AMR, as assessed on EMBs, correlates with cardiovascular mortality in heart transplant recipients., Methods: All EMBs from 1985 to 2005 were evaluated. Biopsy specimens were uniformly studied by light microscopy and IF early post-transplant. A comprehensive vascular score (V1: no AMR, to V5: severe AMR) was prospectively assigned to each EMB, based on severity of both histologic and IF findings. Univariate Cox proportional hazards regressions were performed using indicators of vascular scores alone, combined, and cumulatively., Results: Nine hundred six patients were transplanted and included in the study. Mean age was 46.6 +/- 15.5 years and 82% were male. A total of 26,236 EMBs comprised the study data. As expected, histologic and immunopathologic findings of AMR varied in severity. An incremental risk of cardiovascular mortality was found with more severe AMR whether vascular scores were analyzed individually (p = 0.001), in combination (p = 0.01) or cumulatively (p = 0.006)., Conclusions: The severity of AMR on EMBs correlates with an incremental cardiovascular mortality risk after heart transplantation, suggesting that AMR should be viewed as a spectrum rather than just as present or absent. Supplementing the ISHLT AMR diagnostic guidelines with a consensus severity scale is warranted.

Mycophenolic acid (MPA) dose reduction is associated with increased risk of rejection and graft loss in renal transplantation. This analysis investigated the impact of MPA dose changes with enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) in de novo heart transplant recipients. In a 12-month, single-blind trial, 154 patients (EC-MPS, 78; MMF, 76) were randomized to either EC-MPS (1080 mg bid) or MMF (1500 mg bid) in combination with cyclosporine and steroids. The primary efficacy variable was the incidence of treatment failure, comprising a composite of biopsy-proven (BPAR) and treated acute rejection, graft loss or death. Significantly fewer patients receiving EC-MPS required > or =2 dose reductions than patients on MMF (26.9% vs. 42.1% of patients, p = 0.048). Accordingly, the average daily dose of EC-MPS as a percentage of the recommended dose was significantly higher than for MMF (88.4% vs. 79.0%, p = 0.016). Among patients requiring > or =1 dose reduction, the incidence of treated BPAR grade > or =3A was significantly lower with EC-MPS compared with MMF (23.4% vs. 44.0%, p = 0.032). These data suggest that EC-MPS-treated heart transplant patients are less likely to require multiple dose reductions than those on MMF which may be associated with a significantly lower risk of treated BPAR > or =3A.

Objective: To examine patterns of resource use and the cost of care for patients with advanced heart failure treated with medical management (MM) during the final 2 years of life., Methods and Results: The study population (n=47, mean age 70.4 years+/-7.06) included patients randomized to the MM arm of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial. Inpatient and outpatient use data were obtained from the clinical dataset and Centers for Medicare and Medicaid Services (beginning January 1, 1998). Cost and resource use were tracked from the date of death (t(d)) backward in 3-month intervals (eg, t(d-1), t(d-2)). In the primary analysis, costs were summed across intervals. The mean cost of MM in the final 2 years of life was $156,169, with 50.5% ($78,880.39) expended in the final 6 months. The mean quarterly cost increased (P < .01) 4.9-fold from t(d-8) ($8,816 +/- $14,270) to t(d-1) ($42,836 +/- $41,407). The number of inpatient days increased (P < .01) 6.6-fold from 3.8+/-4.7 days to 22.2+/-23.5 days during the same time intervals., Conclusion: This current economic analysis extends on previous findings by demonstrating that medical therapy in advanced and end-stage heart failure is associated with significant costs and resource consumption; these costs and resource consumption increase significantly as death approaches.

Coronary artery disease (CAD) is common and multifactorial. Members of the Church of Jesus Christ of Latter-day Saints (LDS, or Mormons) in Utah may have lower cardiac mortality than other Utahns and the US population. Although the LDS proscription of smoking likely contributes to lower cardiac risk, it is unknown whether other shared behaviors also contribute. This study evaluated potential CAD-associated effects of fasting. Patients (n(1) = 4,629) enrolled in the Intermountain Heart Collaborative Study registry (1994 to 2002) were evaluated for the association of religious preference with CAD diagnosis (> or = 70% coronary stenosis using angiography) or no CAD (normal coronaries, <10% stenosis). Consequently, another set of patients (n(2) = 448) were surveyed (2004 to 2006) for the association of behavioral factors with CAD, with routine fasting (i.e., abstinence from food and drink) as the primary variable. Secondary survey measures included proscription of alcohol, tea, and coffee; social support; and religious worship patterns. In population 1 (initial), 61% of LDS and 66% of all others had CAD (adjusted [including for smoking] odds ratio [OR] 0.81, p = 0.009). In population 2 (survey), fasting was associated with lower risk of CAD (64% vs 76% CAD; OR 0.55, 95% confidence interval 0.35 to 0.87, p = 0.010), and this remained after adjustment for traditional risk factors (OR 0.46, 95% confidence interval 0.27 to 0.81, p = 0.007). Fasting was also associated with lower diabetes prevalence (p = 0.048). In regression models entering other secondary behavioral measures, fasting remained significant with a similar effect size. In conclusion, not only proscription of tobacco, but also routine periodic fasting was associated with lower risk of CAD.

Objective: Destination therapy experience using long-term left ventricular assist devices was analyzed relative to the benchmark Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial to evaluate the potential for improving outcomes with this groundbreaking therapy for advanced heart failure., Methods: The largest single-center experience with destination therapy in the United States (Utah Artificial Heart Program, LDS Hospital, Salt Lake City, UT) was retrospectively analyzed. All destination therapy recipients (n = 23) presented with chronic, advanced heart failure, meeting indications for destination therapy adopted from the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial. All received HeartMate left ventricular assist devices (Thoratec Corp, Pleasanton, Calif), with 87% receiving an improved XVE model. Advanced practice guidelines were implemented using a multidisciplinary approach. Survivals (Kaplan-Meier, log-rank analyses) and adverse events (Poisson regression) were compared with those of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure left ventricular assist device group (n = 68)., Results: Survival in the destination therapy group was significantly increased (P = .007), with an overall reduction in mortality of 66%. The 2-year survival was 77% for destination therapy compared with 29% for the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure left ventricular assist device group (P < .0001). The 1-year survival was 77% for destination therapy compared with the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure left ventricular assist device rate of 52% (P = .036). Adverse events decreased by 38% (3.90 per patient-year in the destination therapy group compared with the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure left ventricular assist device rate of 6.32). Factors related to severity of illness met Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure-like criteria for both groups., Conclusions: This analysis provides evidence that long-term destination therapy can be improved well beyond the pioneering experience of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial. With continued evolution of devices, management, and patient selection, outcomes approaching those of heart transplantation may be possible.

Background: In 2002, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) established four heart failure (HF) core measures to standardize and improve health care quality in the United States. Although adherence to these HF care processes may be improving, their collective impact on survival is not yet settled., Methods: JCAHO HF measures were implemented within a 20-hospital health care system. Eligible patients had a principal discharge diagnosis of HF. Metrics representing compliance with these measures were derived and their relationship with 1-year survival was examined using an adjusted Cox proportional hazards regression., Results: A total of 2958 patients met study criteria. The average age was 73 years, 50% were male, and 9.9% were smokers. One-year survival benefits were seen in an item-by-item evaluation of HF measures for angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy (hazard ratio [HR] = 0.69), left ventricular function assessment (HR = 0.83), and patient education (HR = 0.79). When assessed collectively, improved survival was seen among patients eligible for two (HR = 0.53), three (HR = 0.36), or four HF measures (HR = 0.65). Further, we found a positive and incremental relationship between the degree of adherence and survival (P = .008)., Conclusion: Adherence to JCAHO HF core measures is associated with improved 1-year survival after HF hospitalization. This validates these simple and effective performance measures and justifies efforts to implement them in all eligible patients with HF.

Background: The International Society for Heart and Lung Transplantation (ISHLT) recently established a diagnostic scheme for antibody-mediated rejection (AMR). Currently, however, confirmatory immunohistochemistry studies are recommended only if AMR is clinically or histologically suspected. In this study, we examine whether a pattern of repetitive AMR occurred early enough after transplantation to warrant prospective immunohistochemistry screening in all recently transplanted recipients., Methods: We queried our pathology database of adult and pediatric endomyocardial biopsies (EMBs) from 1985 to 2005. All EMB specimens were prospectively studied by immunofluorescence in the early post-operative period. AMR was defined as the presence of complement and immunoglobulin deposits on frozen section. Only patients classified as antibody-mediated rejectors (>or=3 episodes of AMR) were included. Cumulative incidence and time from transplant to first and third AMR episodes were obtained., Results: Three hundred seventy-five of 870 heart transplant recipients had >or=3 episodes of AMR. Mean age of recipients was 45.6 years and 78% were male. A total of 19,569 EMBs comprised the study data. By 100 days post-transplant, 85% of patients had their first and 54% their third AMR. In addition, patients showed a clear trend of early clustering of AMR-positive biopsies. Results were similar regardless of whether or not muromonab-CD3 (Orthoclone OKT3) induction was used., Conclusions: We advocate early immunohistochemical surveillance testing for AMR to supplement the diagnostic algorithm established by the ISHLT, because a pattern of AMR becomes manifest soon after transplantation. This change will allow earlier detection of asymptomatic AMR and may prompt changes in immunosuppression strategies to avoid adverse outcomes.

Background: Outcomes of patients with a prior diagnosis of peri-partum cardiomyopathy (PPCM) undergoing heart transplantation are not well described but may be worse than for women who undergo transplantation for other etiologies., Methods: Between 1999 and 2005, 69 women aged younger than 40 underwent transplantation for PPCM in 29 institutions participating in the Cardiac Transplant Research Database. Patients with PPCM were compared with 90 female recipients of similar age with idiopathic dilated cardiomyopathy (IDC) and history of pregnancy (P+), 53 with no prior pregnancy (P-), and with 459 men of a similar age with IDC. Rejection, infection, cardiac allograft vasculopathy, and survival were compared., Results: Recipients with PPCM accounted for 1% of all transplants and 5% of transplants in women. Comparisons of the 4 patient groups were made. The risk of cumulative rejection was higher in the PPCM Group compared with the P- Group (p < 0.04) and the men (p < 0.0001). Cumulative risk of infection was lowest in the PPCM Group. Freedom from cardiac allograft vasculopathy was similar or higher in the PPCM Group compared with the other groups. Finally, the long-term survival of PPCM patients was comparable with the survival of men (p = 0.9), and there was a trend toward improved survival compared with the P+ Group (p = 0.07) and improved survival compared with the P- Group (p = 0.05)., Conclusions: Heart transplantation for PPCM remains relatively infrequent. Survival and freedom from cardiac allograft vasculopathy in patients who receive a transplant for PPCM are no worse than in women who require a transplant for other indications, regardless of parity.

Management of heart failure (HF) remains complex with low 5-year survival. The Seattle Heart Failure Model (SHFM) is a recently described risk score derived predominantly from clinical trial populations that may enable the prediction of survival in patients with HF. This study sought to validate the SHFM in an independent, nonclinical trial-based HF population. Patients (n = 4,077) from the hospital-based Intermountain Heart Collaborative Study registry with a diagnosis of HF were evaluated using prospectively collected data (mean +/- SD follow-up 4.4 +/- 3.1 years). The SHFM was used to calculate a risk score for each patient. Receiver-operating characteristic area under the curve provided SHFM predictive ability for a composite end point of survival free from death, transplantation, or left ventricular assist device implantation. Addition of creatinine, serum urea nitrogen, diabetes status, and B-type natriuretic peptide (BNP) to the SHFM was also evaluated. Patient age averaged 67 +/- 13 years and 61% were men. Area under the curves were 0.70 (95% confidence interval 0.66 to 0.70), 0.67 (95% confidence interval 0.66 to 0.69), 0.67 (95% confidence interval 0.065 to 0.68), and 0.66 (95% confidence interval 0.63 to 0.67) for 1-, 2-, 3-, and 5-year survivals, respectively. Area under the curves were slightly attenuated in patients >75 years of age (n = 1,339), implantable cardioverter-defibrillator recipients (n = 693), and patients with an ejection fraction >40% (n = 1,634). BNP added significantly to the model (area under the curve +0.06). BNP was found to add additional predictive ability at 1 year (area under the curve change +0.05) and nominally at 5 years (area under the curve change +0.02). In conclusion, the SHFM predicts survival in patients with HF in a hospital-based population, with areas under the curve similar to those from data on which models were initially fit.

Background: Heart failure (HF) patients may require cardiac assist device implantation prior to transplantation (Tx) because of either acute cardiogenic shock (ACS), with no prior history of HF, or for progression of pump failure in the setting of chronic HF., Aims: To investigate whether patients implanted with a cardiac assist device for ACS, have similar post-Tx outcomes as those who underwent cardiac assist device implantation because of progressive chronic HF., Methods and Results: We compared post-Tx outcomes of consecutive patients bridged due to ACS (Acute Group) with the outcomes of patients bridged due to deterioration of chronic HF (Chronic Group). Seventy-three patients had a cardiac assist device implanted and underwent subsequent cardiac Tx. Thirty-five patients (48%) had a cardiac assist device implanted due to ACS, most often caused by massive acute myocardial infarction, and 38 patients (52%) because of progressive chronic HF. Despite greater compromise at the time of implantation, the Acute Group recovered satisfactorily and underwent Tx with similar post-Tx survival rates as the Chronic Group patients [1-year survival: 88.6% vs 86.8%, p=0.80, actuarial survival (mean follow-up 4.2 years): 80.0% vs 81.6%, p=0.86)]. Furthermore, no significant differences were observed between the 2 groups in various post-Tx events., Conclusion: Patients with ACS who underwent emergency cardiac assist device implantation as bridge to Tx had similar post-Tx outcomes as their more chronically ill counterparts who underwent device implantation on a non-urgent basis.

Objective: Allosensitization of left ventricular assist device recipients has been associated with perioperative transfusion of cellular blood products. The relative sensitizing contribution of leukofiltered cellular blood products, however, remains unclear. We investigated the pattern of sensitization in left ventricular assist device recipients in relation to cellular blood product transfusions received., Methods: Seventy-one consecutive nonsensitized recipients of the HeartMate left ventricular assist device (Thoratec Corporation, Pleasanton, Calif) as a bridge to transplantation were reviewed. Panel-reactive HLA antibody levels at consecutive times after device implantation were correlated with perioperative cellular blood product transfusions., Results: Fifty-four patients received leukofiltered cellular blood products (transfused), whereas 17 patients received only fresh-frozen plasma (nontransfused). Among nontransfused patients, 58.8% (10/17) became sensitized during mechanical support, versus 35.2% of transfused patients (19/54, P = .15). There was a trend toward more sensitization during the 12 weeks after device placement in nontransfused patients. Kaplan-Meier analysis revealed significantly more sensitization in nontransfused patients than in transfused patients, despite equal rates of transplantation (P = .05). A dose-response analysis revealed significant trends toward less sensitization and lower peak panel-reactive antibody level with more cellular blood product transfusions (P = .04). Multivariate Cox regression revealed only increasing transfusions to be associated with a reduced risk of sensitization (hazard ratio 0.18, P = .01)., Conclusions: Sensitization becomes more prevalent with increasing length of support. Avoidance of perioperative leukocyte-filtered cellular blood product transfusions does not decrease the incidence or degree of HLA sensitization. Conversely, cellular blood product transfusions may be associated with lessened alloimmunization and may mitigate the sensitization seen in recipients of the HeartMate left ventricular assist device as a bridge to transplantation.

Background: Conflicting data exist regarding the impact of reversible pulmonary hypertension (PHTN) on post-transplant (Tx) outcomes. In this study we sought to determine the influence of reversible PHTN on outcomes after Tx., Methods: We retrospectively reviewed the records of adult patients who underwent heart Tx from 1993 to 2002. Patients were grouped depending on their measured pulmonary vascular resistance (PVR). Group 1 patients had a pre-Tx pulmonary vascular resistance (PVR) of < 3 Wood units (WU). Patients with reversible PHTN, defined as pre-Tx PVR > or = 3 WU and reversing to < 3 WU either with sub-lingual or intravenous vasodilatory agents, were divided into two groups based on their PVR before the reversibility test (PVR: Group 2, 3 to 4.5 WU; Group 3, > 4.5 WU)., Results: Records for 222 adult heart recipients were reviewed (Group 1, n = 171; Group 2, n = 35; Group 3, n = 16). Baseline clinical characteristics (age, gender, heart failure etiology, history of diabetes, ischemic time, donor age and gender) were similar in the three groups and the average follow-up was 58 months. One-month and 1-year mortality (Groups 1, 2 and 3: 2%, 0% and 13%; and 8%, 0% and 13%, respectively) did not differ significantly between groups. Actuarial mortality was assessed using Cox regression analysis, adjusted for age and gender, and no increased risk of death was demonstrated for patients with reversible PHTN (for Group 2: multivariate hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.17 to 1.32, p = 0.15; for Group 3: HR 0.98, CI 0.34 to 2.84, p = 0.97). No differences were observed between the three groups for various post-Tx events, such as hospital stay, ICU stay, extubation time, transfusions, acute allograft dysfunction, acute hepatic dysfunction, acute and chronic renal dysfunction, infections, neurologic complications, gastrointestinal complications and coronary allograft vasculopathy., Conclusions: Reversible pulmonary hypertension is associated with similarly good post-transplant survival outcomes and morbidity, regardless of severity.

Background: Determining which pretransplantation (TX) characteristics predict the development of chronic renal dysfunction (CRD) or death after heart TX would enable more accurate risk assessment at the time of candidate evaluation., Methods: A cohort of 278 patients underwent TX in three hospitals between 1993 and 2002. Predictive models for CRD (serum creatinine consistently above 2 mg/dL) and allograft loss (death or re-TX) were constructed using logistic and Cox regression, respectively., Results: Using logistic regression, CRD was more likely to develop in TX patients if they had a larger body surface area (odds ratio [OR] = 5.8 per m2, 95% confidence interval [CI] = 1.04 to 31.9, p = 0.04) or were inotrope dependent (OR = 1.8, 95% CI = 0.90 to 3.7, p = 0.09). Notably, the implementation of mechanical circulatory support as bridge to transplantation decreased the risk of CRD (OR = 0.30, 95% CI = 0.12 to 0.72, p = 0.007). Cox analysis demonstrated independent predictive ability of improved survival for males (hazard ratio [HR] = 0.42, 95% CI = 0.21 to 0.83, p = 0.01). Worse survival was observed with prior sternotomy (HR = 3.5, 95% CI = 2.0 to 6.0, p < 0.001), diabetes mellitus (HR = 1.9, 95% CI = 0.98 to 3.9, p = 0.06), and elevated serum creatinine (HR = 2.8 per mg/dL, 95% CI = 1.3 to 5.8, p = 0.007)., Conclusions: Certain pretransplant characteristics clearly predispose a patient to the development of CRD or increased mortality after heart transplantation. Interestingly, the risk of CRD after heart transplantation is greater for patients bridged to transplant with inotropes than with mechanical circulatory support. When hemodynamically indicated, timely implementation of pretransplant mechanical circulatory support should be considered.

Background: Increased homocysteine (HCY) is associated with increased risk of vascular disease. Whether HCY affects development of congestive heart failure (CHF) independent of coronary artery disease (CAD) is uncertain. We evaluated whether increased HCY predicts low ejection fraction or clinical CHF., Methods: Patients (n = 2,842) undergoing coronary angiography had HCY measured between 1994 and 1999 and were prospectively studied. Left ventricular dysfunction (LVD) was defined as ejection fraction < or =40%. Multivariable regressions assessed predictive strength of HCY for LVD or LVD/CHF., Results: The average age was 64 +/- 12 years; 69% were men, and 74% had CAD. LVD was present in 12% and the combination of either LVD or clinical CHF was present in 21.9%. Quartiles of HCY were: < or =10.5 (Q1), 10.5-13.2 (Q2), 13.3-17.0 (Q3) and > or =17.1 micromol/l (Q4). LVD and LVD/CHF were more prevalent in Q3 (15, 25%) and Q4 (15, 27%) than in Q1 HCY (8.4, 18%; p < 0.001 vs. Q4). After adjustment, Q3 and Q4 HCY independently predicted LVD (OR = 1.7, 95% CI 1.2-2.5, p = 0.004; OR = 1.8, 95% CI 1.3-2.6, p = 0.002) or LVD/CHF (OR = 1.4, 95% CI 1.04-1.8, p = 0.03; OR = 1.7, 95% CI 1.3-2.2, p < 0.001). Findings did not differ by disease etiology: for Q4 among non-CAD patients, OR = 1.7 for LVD and OR = 1.7 for LVD/CHF. Further, there was no interaction of results with gender., Conclusion: High HCY levels (Q3/4 > or =13.3 micromol/l) are associated with LVD and combined endpoint of LVD/clinical CHF. This relationship is independent of CHF etiology and gender. Further research is indicated to distinguish between a causal or noncausal mechanism for this association., (Copyright 2007 S. Karger AG, Basel.)

Background: Whereas C-reactive protein (CRP) is a nonspecific marker of coronary artery disease (CAD) and cardiovascular (CV) events, Lp-PLA2 may be a nonvariable inflammatory biomarker. We evaluated the independent association of lipoprotein-associated phospholipase A2 (Lp-PLA2) to angiographic CAD and CV events adjusting for standard factors, lipids, and CRP., Methods: Lipoprotein-associated phospholipase A2 (PLAC test, diaDexus, Inc, San Francisco, CA) and CRP were measured from samples donated by consecutive consenting patients (N = 1493) enrolled in the registry of the Intermountain Heart Collaborative Study. All patients underwent coronary angiography (1996-1998) for CAD determination and were followed for 6.7 +/- 0.5 years (range 5.7-7.9 years) for CV events (death [including all-cause, CAD, and non-CAD CV death], myocardial infarction, and cerebrovascular accident)., Results: Lipoprotein-associated phospholipase A2 weakly correlated with lipids (low-density lipoprotein: r = 0.22, P < .001; high-density lipoprotein: r = -0.13, P < .001), but not CRP (r = 0.03, P = .26). Increasing quartile (Q) of Lp-PLA2 predicted greater the presence of CAD (vs Q1) for Q2 (adjusted odds ratio [OR] 1.15, 95% CI 0.78-1.71, P = .48), for Q3 (OR 1.53, 95% CI 1.02-2.31, P = .042), and for Q4 (OR 2.44, 95% CI 1.58-3.79, P < .001), although CRP was also predictive (vs Q1, Q2: OR 1.47, P = .057; Q3: OR 1.93, P = .002; Q4: OR 3.43, P < .001). In Cox regression, Lp-PLA2 predicted CAD death (vs Q1; Q2: adjusted hazard ratio [HR] 1.27, 95% CI 0.58-2.78, P = .55; Q3: HR 2.18, 95% CI 1.04-4.57, P = .04; Q4: HR 1.73, 95% CI 0.84-3.61, P = .14)., Conclusion: Lipoprotein-associated phospholipase A2 was confirmed to predict the presence of CAD, even among patients undergoing coronary angiography. Uniquely, Lp-PLA2 predicted the risk of CAD death, but not all-cause death, myocardial infarction, or cerebrovascular accident.

Background: In our previously published work dealing with antibody-mediated (vascular) rejection (AMR), we defined patterns of rejection (AMR and cellular rejection [CR]) based on a review of biopsy diagnoses taken in the first 6 to 12 weeks post-transplant. We have shown the significance of these pattern designations in relation to patient and allograft outcome in five outcome analyses. The current retrospective analysis was done to determine whether our previous criteria for pattern designations provided the greatest degree of discrimination between AMR and CR., Methods: Six hundred sixty-five patients from the U.T.A.H. Cardiac Transplant Program were included in our study. Patients induced with OKT3 immunosuppression were excluded. We analyzed the relationship of a number of either AMR or CR episodes to cardiovascular mortality. We constructed Kaplan-Meier survival curves to assess the impact of incremental numbers of AMR or CR episodes on cardiovascular mortality., Results: Three or more episodes of AMR resulted in a statistically significant increase in cardiovascular mortality. By contrast, CR episodes did not increase the risk of cardiovascular mortality., Conclusions: Based on our findings, we believe that clinical trials should be designed to test treatments based on predominant rejection patterns and that end-points for trials should be defined by number of biopsies positive for either CR or AMR. This approach may lead to improved patient and allograft survival.

Although increased cholesterol levels predict mortality in patients with coronary artery disease, it is unclear whether hypercholesterolemia is associated with adverse survival in patients with heart failure. A cohort of subjects derived from the Intermountain Heart Collaborative Study Registry (1993 to 2003) who had ejection fractions < or = 40% or clinical diagnoses of heart failure and long-term follow-up for death were studied (n = 1,646). Total cholesterol (TC) was divided into quartiles: quartile 1, < 141.3 mg/dl; quartile 2, 141.3 to 167.9 mg/dl; quartile 3, 168.0 to 201.0 mg/dl; and quartile 4, > 201.0 mg/dl. Multivariate Cox regression models were used to evaluate the associations of cholesterol, statin therapy, and C-reactive protein to mortality. The mean age was 65.5 years; 65% of the subjects were men and 65% had coronary artery disease. Although 53% were using statins, statin use was not different across TC quartiles. Average time to death was 2.4 years (maximum 10). Mortality for quartile 4 versus quartile 1 was not different (hazard ratio [HR] 1.12, p = 0.52); mortality was reduced for quartile 3 versus quartile 1 (HR 0.66, p = 0.027) and tended to be reduced for quartile 2 versus quartile 1 (HR 0.77, p = 0.14). Subanalysis of patients not using statins (n = 737, death = 20.2%) found no association between TC and survival (for quartile 3 vs quartile 1, HR 0.97, p = 0.89), but for patients using statins (n = 848, death = 16.3%), the effect was even greater for quartile 3 versus quartile 1 (HR 0.40, p = 0.002) than in the overall population. Nonsurvivors had higher levels of C-reactive protein than survivors. In conclusion, elevated TC appears to be associated with improved survival. The effect was stronger in patients receiving statin therapy, but the cause of this differential effect is uncertain.

Background: The use of left ventricular assist devices is associated with human leukocyte antigen (HLA) allosensitization. We investigated whether prophylactic treatment with low-dose intravenous immunoglobulin (IVIG), analogous to the use of IgG anti-D (anti-Rh) in preventing Rh immunization, can abrogate HLA allosensitization after left ventricular assist device implantation., Methods: We retrospectively reviewed the data from 84 consecutive heart failure patients who underwent implantation of a left ventricular assist device as a bridge to transplantation. After implantation, panel reactive antibody (PRA) was measured biweekly to assess sensitization (defined by PRA > 10%). Patients who were sensitized before left ventricular assist device implantation were excluded from further analysis (n = 12). Patients who either did not require perioperatively transfusions of cellular blood products or received other immunomodifying regimens were also excluded from further analysis (n = 21). The rest of the patients were divided into two groups based on whether they received IVIG, 10 g daily for 3 days (IVIG group, n = 26; non-IVIG group, n = 25). The decision as to whether patients received IVIG was not randomized but was based on surgeon preference., Results: The sensitization rates (expressed as ratio of sensitized patients to total patients at risk) in the two groups were similar at consecutive time points (2, 4, 6, 8, 12, 20 weeks) after left ventricular assist device implantation. Also, mean PRA at the same time points did not differ between the two groups. Overall, 34.6% (9 of 26) of the IVIG group became sensitized during mechanical support, compared with 32% (8 of 25) of the non-IVIG group (p = 1.0). A PRA of 90% or greater (high-degree sensitization) occurred in 15.3% (4 of 26) of the IVIG group and 12.0% (3 of 25) of the non-IVIG group (p = 0.5)., Conclusions: The use of low-dose prophylactic IVIG after left ventricular assist device implantation affects neither the incidence nor the severity of HLA allosensitization.

Background: Enteric-coated mycophenolate sodium (EC-MPS, myfortic) is an advanced formulation that delays the release of mycophenolic acid (MPA). Its efficacy and safety has been proven in several clinical trials in renal transplantation., Methods: In a single-blind, multicenter trial, a total of 154 de novo heart transplant patients were randomized to either EC-MPS 1,080 mg twice daily or mycophenolate mofetil (MMF) 1,500 mg twice daily. Eligible patients included men or women aged 18 to 65 years, undergoing primary heart transplantation, who were treated with cyclosporine microemulsion and corticosteroids as basic immunosuppression. The primary study objective was to investigate the incidence of biopsy-proven and treated acute rejection, graft loss or death (defined as treatment failure) for EC-MPS vs MMF during the first 6 months of treatment in de novo heart transplant recipients. Secondary objectives included assessment of the overall safety and tolerability of EC-MPS vs MMF in the study population., Results: The primary efficacy variable, treatment failure at 6 months, was similar for both treatments: 52.6% for EC-MPS and 57.9% for MMF (2-sided 95% confidence interval [CI]: -21.0% to 10.4%). At 12 months, treatment failure was 57.7% for EC-MPS and 60.5% for MMF (2-sided 95% CI: -18.4 to 12.7), and death and graft loss rate was 5.1% vs 9.2% for EC-MPS and MMF at 12 months, respectively (2-sided 95% CI: -12.2 to 4.1). The overall safety profile was similar for both groups. Significantly more patients on MMF had two or more study medication dose reductions during the treatment period., Conclusions: These 6- and 12-month results show that EC-MPS is therapeutically similar to MMF in de novo heart transplant recipients and has a comparable safety profile.

Background: Mechanical circulatory support (MCS) before heart transplantation was previously associated with worse post-transplant outcomes than when MCS was not required. Given the changes in technology, expertise, patient selection, and timing of subsequent transplantation, we hypothesized that patients who require MCS before heart transplantation have similar outcomes after transplantation as those not requiring pre-transplant MCS., Methods: We retrospectively reviewed 278 patients who underwent cardiac transplantation from 1993 to 2002. MCS was required in 72 patients (HeartMate LVAS in 66, CardioWest Total Artificial Heart in 6) and was not required in 206 patients. The influence of pre-transplant MCS on post-transplant outcomes was assessed in the 2 groups., Results: Baseline clinical characteristics (age, gender, etiology of heart failure, history of diabetes mellitus, and donor age and gender) were similar in the 2 groups. One-month and 1-year survival after transplantation did not differ between the groups (MCS, 92% and 85%, respectively vs no MCS, 97% and 92%, respectively). Similar proportions of patients were free from rejection (International Society for Heart and Lung Transplantation score >or=3A) at 1 year of follow-up (MCS, 56% vs no MCS, 52%, p = 0.60). No difference was observed between MCS and no MCS patients in other post-transplant events such as hospital stay, intensive care unit stay, extubation time, acute allograft dysfunction, reoperation rates, acute renal dysfunction, acute hepatic dysfunction, infections, arrhythmias, thromboembolic complications, neurologic complications, gastrointestinal complications and the development of cardiac allograft vasculopathy. The incidence of chronic renal insufficiency was actually lower in the MCS Group (15.3% vs 37.9%, p = .001)., Conclusion: Post-transplant outcomes after pre-transplant use of MCS are similar to those when MCS is not required.

Background: Tricuspid valve insufficiency (TI) is common after orthotopic heart transplantation. However, tricuspid valve replacement or repair (TVR) is rare. The aim of this study is to evaluate our experience with TVR in cardiac transplant recipients., Methods: The Utah Transplantation Affiliated Hospitals (UTAH) Cardiac Transplant Program database was queried for TVR in all adult and pediatric heart transplant recipients. Pre-operative parameters and cardiac hemodynamics were compared with post-operative findings., Results: Since 1985, we identified in our database 17 patients who had 16 TVR, and 2 tricuspid valve repair procedures. Thirty-four heart transplant recipients from the same period were used as controls. The indication for TVR was symptomatic right heart failure (RHF) in 89% of cases, and there was no significant difference between the control group and the surgery group in the average number of biopsies. A flail leaflet was found in 16 cases (89%). One patient died post-operatively due to cardiogenic shock, and 1 patient died 8 months after TVR due to progressive RHF. Improvement in heart failure symptoms was seen in 12 cases. The central venous pressure (CVP) decreased from 17.8 +/- 4.1 mm Hg to 11.0 +/- 7.3 mm Hg (p = 0.013). There was no significant change in cardiac output or renal function. However, the furosemide dose decreased significantly from 47.69 +/- 56.44 mg/day to 26.54 +/- 46.43 mg/day (p = 0.009)., Conclusions: After orthotopic heart transplantation, TVR is a safe and effective procedure to alleviate RHF symptoms. Flail leaflets are the most common operative finding, suggesting that biopsy-induced trauma is the likely cause of severe TI in these patients.

Purpose: Heart failure (HF) patients often have comorbid conditions that confound management and adversely affect prognosis. The purpose of this study was to determine whether the obesity paradox is also present in hospitalized HF patients in an integrated healthcare system., Data Sources: A cohort of 2707 patients with a primary diagnosis of HF was identified within an integrated, 20-hospital healthcare system. Patients were identified by ICD-9 codes or a left ventricular ejection fraction < or =40% dating back to 1995. Body mass index (BMI) was calculated using the first measured height and weight when hospitalized with HF. Survival rates were calculated using Kaplan Meier estimation. Hazard ratios for 3-year mortality with 95% confidence intervals were assessed using Cox regression, controlling for age, gender, and severity of illness at time of diagnosis., Conclusions: Three-year survival rates paradoxically improved for patients with increasing BMI. Survival rates for the larger three BMI quartiles were significantly better than for the lowest quartile after adjusting for severity of illness, age, and gender., Implications for Practice: While obesity increases the risk of developing HF approximately twofold, reports involving stable outpatients suggest that obesity is associated with improved survival after the development of HF. This finding is paradoxical because obesity increases the risk and worsens the prognosis of other cardiovascular diseases.

Background: Diagnostic criteria for antibody-mediated rejection (AMR) of the cardiac allograft have recently been proposed as part of the International Society for Heart and Lung Transplantation (ISHLT) biopsy grading scheme. Histologic features of vascular adherence of macrophages (VASC) and endothelial activation or swelling in capillaries (ENDO) are proposed as criteria to prompt the immunohistochemical investigation of biopsies for AMR. The aim of this study was to determine whether VASC and ENDO are adequate to act as screening parameters to trigger further AMR investigation., Methods: We examined our database of biopsy findings where histologic vascular parameters as well as immunofluorescence (IF) to detect AMR were collected (n = 3,170). Histologic parameters were graded semi-quantitatively on a scale from 1 to 5, where 1 = absence and 5 = obvious and generalized presence of the finding., Results: Seven hundred sixty-eight of 3,170 biopsies had IF findings diagnostic of AMR in the absence of cellular rejection (ISHLT = 0). ENDO had a sensitivity of 63% and a specificity of 80%. VASC had a sensitivity of 30% and specificity of 99%. Combining the interpretation of the 2 tests did not result in a significant improvement of test sensitivity., Conclusions: Neither ENDO, VASC nor the combination of the tests indicated sufficiently high sensitivity to serve as a screening tool before further diagnostic investigation for AMR. Immunohistochemical testing remains necessary in the majority of cases to identify AMR.