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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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Patients with Becker muscular dystrophy–related cardiomyopathy typically survive into their 30s, when they succumb to complications of cardiomyopathy or receive heart transplants. The cardiomyopathy is related to an abnormality in the protein dystrophin; no successful medical responses have been reported to date. We describe a patient with Becker muscular dystrophy–related cardiomyopathy in whom we noted improvement of cardiac status with carefully titrated medical therapy. Successful therapy suggests a trial of medical therapy may be beneficial when patients with Becker muscular dystrophy–related cardiomyopathy are evaluated for transplant. [Copyright &y& Elsevier]

The author discusses treatment for heart failure and reverse remodeling. Statistics relating to a study regarding the effectiveness of ventricular devices are provided. The author questions which medications utilized in the study were the most effective, and whether or not the patients in the study genuinely had end-stage heart failure. The effectiveness of medications such as inotropic agents and beta-blockers is discussed. The author suggests that the results of the study require corroboration, but do provide hope for patients with stage D heart failure.

A letter to the editor is presented in response to critical replies to the article "Building a bridge to heart transplantation," by D. G. Renlund.

Discusses heart transplantation and the use of mechanical circulatory support before transplantation, known as "bridging." Risk of death for patients with compromised health; Reasons for bridging before transplantation; Way that it can help patients who must wait for transplants; Need for physicians to embrace this technology because it increases the ability to help some patients.

The article discusses the stages of the progression of heart failure, its prevention and treatment. Prevention strategies are recommended for patients with risk factors for developing heart failure. Patients with Stage B heart failure are difficult to diagnose but treatment options are available. Stage C heart failure patients manifest a number of symptoms but may be improved through appropriate therapeutic approach. Heart failure patients with end-stage disease should be given palliative care.

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. [Copyright &y& Elsevier]

The article offers clinical information on heart failure. Heart failure is the leading cause of hospitalizations in the U.S. Its treatment includes medications and device therapies. The risk factors for and common symptoms of heart failure are highlighted. The preventive measures and treatment options for heart failure are also discussed.

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) (Ptrend = 1.6 × 10−26), coronary disease (Ptrend = 2.6 × 10−11), myocardial infarction (MI) (Ptrend = 3.1 × 10−25), atrial fibrillation (Ptrend = 2.5 × 10−20), and chronic obstructive pulmonary disease (Ptrend = 4.7 × 10−4). Even more, IMRS predicted HF readmission [hazard ratio (HR) = 2.29/category, Ptrend = 1.2 × 10−6), incident HF (HR = 1.88/category, Ptrend = 0.02), and incident MI (HR = 1.56/category, Ptrend = 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. [ABSTRACT FROM AUTHOR]

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 &y& Elsevier]

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 β 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 &y& Elsevier]

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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

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 ≥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 ≥1 dose reduction, the incidence of treated BPAR grade ≥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 ≥3A. [ABSTRACT FROM AUTHOR]

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 (≥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. [Copyright &y& Elsevier]

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 (≥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 ≥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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

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 ≥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. [Copyright &y& Elsevier]

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 ≤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: ≤10.5 (Q1), 10.5–13.2 (Q2), 13.3–17.0 (Q3) and ≥17.1 μmol/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 ≥13.3 μmol/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 [ABSTRACT FROM AUTHOR]

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 ≤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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

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 ≥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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

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 ≤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. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP) has been associated with atherosclerotic complications, and we hypothesized that CRP levels might also predict death in non-ischemic patients with left ventricular dysfunction. Two hundred and three patients with non-ischemic left ventricular dysfunction undergoing cardiac catheterization were included and were followed for 2.4 ± 1.4 years to determine the incidence of fatal events. Death occurred in 15% of patients with low CRP (1st and 2nd tertiles) and 30% of patients with high CRP (3rd tertile). After adjustment for 11 covariates, high CRP (p = 0.037, hazard ratio = 2.0) significantly and independently predicted mortality. Even in the absence of coronary artery disease, patients with left ventricular dysfunction are at increased risk of mortality based on their baseline CRP concentrations. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: We sought to determine the predictive ability of total white blood cell (WBC) count and its subtypes for risk of death or myocardial infarction (MI). Background: An elevated WBC count has been associated with cardiovascular risk, but which leukocyte subtypes carry this risk is uncertain. Methods: Consecutive patients without acute MI who were assessed angiographically for coronary artery disease (CAD) and were followed up long-term were studied. The predictive ability for death/MI of quartile (Q) 4 versus Q1 total WBC, neutrophil (N), lymphocyte (L), and monocyte (M) counts and N/L ratio were assessed using Cox regressions. Results: A total of 3,227 patients was studied. Mean age was 63 years; 63% of patients were male, and 65% had CAD. In multivariable modeling entering standard risk factors, presentation, and CAD severity, the total WBC (hazard ratio [HR] 1.4, p = 0.01) and M (HR 1.3, p &#60; 0.02) were weaker and N (HR 1.8, p &#60; 0.001), L (HR 0.51, p &#60; 0.001), and N/L ratio (HR 2.2, p &#60; 0.001) were independent predictors of death/MI. When WBC variables were entered together, N/L ratio and M were retained as independent predictors. Risk associations persisted in analyses restricted to CAD patients or including acute MI patients. Conclusions: Total WBC count is confirmed to be an independent predictor of death/MI in patients with or at high risk for CAD, but greater predictive ability is provided by high N (Q4 >6.6 × 103/μl) or low L counts. The greatest risk prediction is given by the N/L ratio, with Q4 versus Q1 (>4.71 versus &#60;1.96) increasing the hazard 2.2-fold. These findings have important implications for CAD risk assessment. [Copyright &y& Elsevier]

Beta-blocker therapy has been shown to benefit patients who have coronary artery disease and present with acute myocardial infarction (AMI) and/or congestive heart failure (HF). However, whether β-blocker therapy provides a similar benefit in patients who have coronary artery disease but not AMI or HF is unknown. A population of 4,304 patients who did not have HF but did have angiographically confirmed coronary artery disease (≥1 stenosis of ≥70%) without AMI at hospital presentation was evaluated. Baseline demographics, cardiac risk factors, clinical presentation, therapeutic procedures, and discharge medications were recorded. Patients were followed for a mean of 3.0 ± 1.9 years (range 1 month to 6.9 years) for outcomes of all-cause death or AMI. Patients'' average age was 65 ± 11 years and 77% were men. Overall, 10% died and 5% had a nonfatal AMI. Discharge β-blocker prescription was associated with an increased event-free AMI survival rate for all-cause death (no β blocker 88.3%, β blocker 94.5%, p &#60;0.001) and death/AMI (no β blocker 83.4%, β blocker 89.2%, p &#60;0.001) but not non-fatal AMI (no β blocker 93.6%, β blocker 94.1%, p = 0.60). After adjustment for 16 covariates, including statin prescription, angiotensin-converting enzyme inhibitor prescription, and type of baseline therapy, the effect of β blockers on the combination end point of death/AMI was eliminated. However, the effect of β blockers on death remained (hazard ratio 0.66, 95% confidence interval 0.47 to 0.93, p = 0.02). Thus, β blockers are clearly indicated for most patients who have HF or AMI, and our results suggest that patients who have coronary artery disease without these conditions have approximately the same protective benefit against death. No effect was observed on longitudinal incidence of AMI or the combination of death/nonfatal MI. [Copyright &y& Elsevier]

Background: Despite recent advances in the treatment and prevention of cardiovascular disease, a treatment gap for secondary prevention medications still exists. Objective: To develop and implement a program ensuring appropriate prescription of aspirin, statins, β-blockers, angiotensin-converting enzyme inhibitors, and warlarin at hospital discharge. Design: A nonrandomized before-after study comparing patients hospitalized before (1996-1998) and after (1999-2002) implementation of a discharge medication program (DMP). Patients were followed for up to 1 year. Setting: The 10 largest hospitals in the Utah-based Intermountam Health Care system. Patients: In the pre-DMP and DMP time periods, 26 000 and 31 465 patients, respectively, were admitted to cardiovascular services (n = 57465). Measurements: Prescription of indicated medications at hospital discharge; post discharge death or readmission. Results: By 1 year, the rate of prescription of each medication increased significantly to more than 90% (P< 0.001); this rate was sustained. At 1 year, unadjusted absolute event rates for readmission and death, respectively, were 210 per 1000 person-years and 96 per 1000 person-years before OMP implementation and 191 per 1000 person-years and 70 per 1000 person-years afterward. Relative risk for death and readmission at 30 days decreased after OMP implementation; hazard ratios (HRs) for death and readmission were 0.81 (95% CI, 0.73 to 0.89) and 0.92 (CI, 0.87 to 0.99) (P < 0.001 and P = 0.017, respectively). At I year, risk for death continued to decrease (hazard ratio, 0.79 [CI, 0.75 to 0.84]; P < 0.001) while risk for readmission stabilized (hazard ratio, 0.94 [CI, 0.90 to 0.98]; P= 0.002), probably because survivors had more opportunities to be readmitted. Limitations: The study design was observational and nonrandomized, and the authors could not control for potential confounders or determine the extent to which secular trends accounted for the observed improvements. Conclusions: A relatively simple quality improvement program aimed at enhancing the prescription of appropriate discharge medications among cardiovascular patients is feasible and can be sustained within an integrated multihospital system. Such a program may be associated with improvements in cardiovascular readmission rates and mortality. [ABSTRACT FROM AUTHOR]

: ObjectivesA protocol was designed to diagnose the common malfunctions of a left ventricular assist device (LVAD).: BackgroundMechanical circulatory support, primarily with an LVAD, is increasingly used for treatment of advanced heart failure (HF). Left ventricular assist device dysfunction is a recognized complication; but heretofore, a systematic method to accurately diagnose LVAD dysfunction has not been thoroughly described.: MethodsWe developed a catheter-based protocol designed to characterize a normally functioning LVAD and diagnose multiple types of dysfunction. A total of 15 studies of 10 patients supported with an LVAD were reviewed. All patients had been evaluated due to concerns regarding LVAD dysfunction.: ResultsOf 15 examinations performed, 11 documented severe LVAD inflow valve regurgitation. One of these cases proved to have coexistent severe mitral valve regurgitation. One case was diagnosed with distortion of the LVAD outflow graft. One case of suspected embolization from the pumping chamber excluded the outflow graft as the source of emboli. One study had aortic insufficiency.: ConclusionsAs LVAD use for treatment of end-stage HF becomes widespread and durations of support are extended, dysfunction will be increasingly prevalent. This catheter-based protocol provided a practical method to diagnose multiple causes of LVAD dysfunction. [Copyright &y& Elsevier]

: PurposeLow 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.: MethodsA cohort of 3410 patients with significant, angiographically-defined CAD (≥1 lesion of ≥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).: ResultsIn 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.: ConclusionsBoth 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. [Copyright &y& Elsevier]

A recent European case-control study suggested that statins increase the risk for polyneuropathy, a rare but serious neurologic condition. This risk was assessed in 272 patients with idiopathic polyneuropathy and 1,360 matched controls in the Intermountain Health Care electronic database. It was found that statin use before diagnosis was not significantly greater in patients than controls (odds ratio 1.30, 95% confidence interval 0.3 to 2.1, p = 0.27), nor were doses different between patients and controls. [Copyright &y& Elsevier]

A 24-year-old woman experienced severe tricuspid valve regurgitation 6 years after heart transplantation. Tricuspid valve replacement was performed using a cryopreserved mitral valve homograft. Severe tricuspid valve regurgitation recurred within 4 months, associated with an increase in the panel reactive antibody titers from zero to 72%. Tricuspid valve replacement was repeated with a porcine bioprosthesis with excellent recovery and function for >2 years. The mitral valve homograft displayed inflammatory features consistent with humoral immune-mediated destruction. [Copyright &y& Elsevier]