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Post-heart transplantation bradycardic syncope and arrest could be due to preferential rejection of the conduction system. We present six heart transplant patients with this presentation, two of whom died. The autopsy of one of those patients demonstrated severe rejection of the conduction system, with only mild rejection throughout the rest of the myocardium. We postulate that aggressive therapy for rejection and pacemaker placement may result in improved survival in heart transplant recipients with this clinical presentation.

The syndrome of heart failure is characterized by symptoms that are relatively insensitive and nonspecific. Physical diagnosis may be unreliable even in the hands of experienced clinicians, despite the presence of significantly elevated filling pressures or a significantly depressed cardiac output. Instrumentation and devices such as the insertion of a pulmonary artery catheter and the implantable hemodynamic monitor have a major role in the diagnosis and management of cardiovascular disease. They provide a means of measuring intracardiac pressures for point-in-time measurements (cardiac catheterization), short term in an acute situation (insertion of a pulmonary arterial catheter), and, more recently, a long-term assessment increasing our understanding of the nuances of the hemodynamic derangements associated with heart failure and other conditions. With improved ability to accurately assess and monitor filling pressures, clinicians can more precisely adjust therapy with the goal of improving patient symptoms and possibly outcomes.

In this report we describe our experience with ibutilide, a relatively new Class III anti-arrhythmic agent, in 8 heart transplant patients with supraventricular tachycardia in various settings (3 patients with rejection, 2 after endomyocardial biopsy). Ibutilide treatment was successful in all patients, with the arrhythmia recurring early in 1 patient. There were no complications.

Background: Infection rates for ventricular assist devices (VADs) are improving but the presence of infections remains problematic. Intraperitoneal pump placement may decrease the rate of infection., Methods: This study is a single-institution, retrospective comparison of infections for an extraperitoneal vs an intraperitoneal position with a polytetrafluoroethylene (PTFE) sheet separating the VAD from visceral organs. Implants were performed by a single surgical team from January 1, 2002 to May 31, 2006 (n = 65) for bridge-to-transplant or destination therapy. Patients with paracorporeal pumps (17 patients) or implant times of <30 days (n = 7; 4 died, 3 ongoing, 0 with pocket infections) were excluded. Thirty-five pulsatile left VADs were analyzed, whereas 6 rotary VADs were excluded from analysis. Twenty-three pulsatile VADs were placed in an extraperitoneal pocket (pocket patients) in 18 patients (5 patients had more than one left VAD implant), whereas 12 patients had intraperitoneal (IP patients) VAD placement., Results: Infection with the implanted VAD occurred in 8 of 23 pocket implants (mean support 310 +/- 249 days) and 0 of 12 IP implants (mean support 220 +/- 131 days; pocket vs IP infections: p = 0.003). Staphylococcus and Enterococcus accounted for most of the infections. Four infections in the pocket group recurred during VAD support. Two infected pocket patients had dehiscence of the mid-line wound., Conclusions: Infections of implanted VADs are associated with serious morbidity (e.g., prolonged antibiotic therapy, recurrent device infections and wound dehiscence). Placing VADs in an intraperitoneal position with a PTFE barrier to protect the viscera may reduce the prevalence of these infections.

Background: Adherence to heart failure therapy is important in reducing morbidity and mortality over the course of the disease process. The aim of this study was to examine factors associated with non-adherence to warfarin in chronic heart failure patients., Methods: Eighty patients receiving warfarin therapy in 2002 were included. Adherence was defined as maintenance of international normalized ratio (INR) between 2 and 3.5 and keeping scheduled appointments for INR checks at least 75% of the time. Clinical variables examined included age, gender, race, insurance, left ventricular ejection fraction (LVEF), etiology, New York heart association (NYHA) class, comorbidities, smoking, and alcohol use., Results: Of 80 patients studied, 59 were male with mean age ( +/- standard deviation) 52 +/- 13 years, 24 had ischemic etiology with mean LVEF of 24% +/- 9%. Non-adherence was associated with tobacco use, odds ratio of 6.5 (p <0.01). Ischemic etiology was associated with adherence, odds ratio of 4.5 (p <0.01). Non-adherent patients were more likely to be insured with Medicare/Medicaid (p = 0.04) and have better NYHA class (p = 0.04). Adherence positively correlated with older age and lower LVEF, and negatively correlated with number of hospitalizations (p<0.01 for all). In a multiple regression model, patients with improvement in LVEF had decreased adherence over the year (p<0.01)., Conclusions: The profile of heart failure patients who demonstrated non-adherence to warfarin therapy included younger age, nonischemic etiology, better NYHA class, smoking, insurance with Medicare/Medicaid and improved LVEF over the study. Measures targeting these patients may result in improved adherence to other pharmacologic treatments of heart failure., (2007 Wiley Periodicals, Inc)

Context: Treatment disparities for socioeconomically disadvantaged populations have been widely reported, but few studies have sought explanations for these disparities., Objective: To compare the quality of care for patients insured by Medicare alone, Medicare plus Medicaid, or Medicare plus private insurance and investigate mediators for potential disparities., Design, Setting, and Participants: Retrospective, random chart review of 3122 African American or White Medicare patients >65 years of age hospitalized for unstable angina in 22 Alabama hospitals, 1993-1999., Main Outcome Measures: Echocardiogram within 20 minutes of presentation; evaluation by a cardiologist; appropriate anti-platelet therapy within 24 hours of admission and at discharge, heparin for high-risk patients, beta-blockers during hospitalization, and performance of appropriate coronary angiography., Results: 182 (5.8%) had Medicare only, 433 (13.9%) had Medicare plus Medicaid, and 2507 (80.3%) had Medicare plus private insurance. Medicaid patients were more frequently Black, female, >85 years old, had multiple co-morbidities, or were admitted to hospitals without cardiac catheterization facilities (P<.001). Fewer Medicaid patients were admitted to hospitals with cardiac catheterization capabilities. Even after adjustment for demographics and hospital characteristics, Medicaid patients were less likely to see a cardiologist (odds ratio [OR] .57, 95% confidence interval [CI] .44-.73), receive antiplatelet therapy within 24 hours of admission (OR .66, 95% CI .50-.87), or heparin (OR .71, 95% CI .53-.97). No differences were seen with regard to having an electrocardiogram within 20 minutes of admission. Beta-blockers were used least in the Medicare-only patients, with only 37.7% receiving them (P=.04). Suitable Medicaid patients received coronary angiography less often, even after adjustment for demographics, co-morbidity, and prior revascularization (OR .68, 95% CI .48-.97). However, when adjusted for hospital characteristics, this finding was no longer observed (OR .94, 95% CI .64-1.39)., Conclusions: Elderly Medicaid patients appear to receive poorer quality of care. This finding is partially, but not completely, explained by characteristics of the facilities where they are hospitalized.

The syndrome of heart failure is characterized by symptoms that are relatively insensitive and nonspecific. Physical diagnosis may be unreliable even in the hands of experienced clinicians despite the presence of significantly elevated filling pressures or a significantly depressed cardiac output. Over the past decade, the implantable hemodynamic monitor (IHM) has been developed as means of measuring intracardiac pressures over time and understanding the nuances of the hemodynamic derangements of this condition. With improved ability to accurately assess and monitor filling pressures, clinicians can more precisely adjust therapy with the goal of improving patient symptoms and possibly outcomes. Future directions include using the IHM to assist in management of other cardiovascular diseases, such as pulmonary arterial hypertension, and combining this technology with other implanted devices, such as defibrillators.

Background: Photopheresis therapy (photo) has been advocated as a therapy to improve outcome after recalcitrant or severe rejection, but objective evidence of a beneficial effect has been elusive. This study examined the hypothesis that photo provides protection against rejection, rejection with hemodynamic compromise (HC), and death from rejection after cardiac transplantation., Methods: Between 1990 and 2003, 36 adult patients (from 343 adult transplant recipients) received at least 3 months of photo (2-day treatment every 3 to 6 weeks for a target of 18 months) after HC rejection (n = 12), recurrent/recalcitrant rejection (n = 20), or as prophylaxis in the presence of anti-donor antibodies (n = 4). Survival and risk factors were examined by analysis using multivariate hazard function modulated renewal function., Results: Patients selected for photo were at greater risk for rejection (p < 0.0001) and HC rejection (p < 0.0001) than non-photo patients. After 3 months of photo therapy, rejection risk was decreased (p = 0.04). More importantly, the hazard for subsequent HC rejection or rejection death was significantly reduced toward the risk-adjusted level of lower-risk non-photo patients (p = 0.006)., Conclusions: This study provides objective evidence that photo reduces the risk of subsequent HC rejection and/or death from rejection when initiated for patients with high rejection risk. Photopheresis is recommended as an important therapeutic modality after rejection with hemodynamic compromise, although further studies are needed to define the precise mechanism of the effect and the potential for benefit in other patient sub-sets.

Management of mild to moderate aortic insufficiency in patients with a left ventricular assist device remains controversial. We report 3 patients with aortic insufficiency and pulsatile left ventricular assist devices treated with a central aortic valve coapting suture. Two of the repairs have been durable for more than 1 year and aspirin appears to be sufficient anticoagulation.

Background: The clinical significance of HLA-directed antibodies newly detected after transplantation (HT) is controversial., Methods: Seventy-one HT recipients consented to enroll. Mean follow-up time was 28 months (range 6-48). Panel reactive antibody (PRA) analysis was performed on posttransplant sera (2 weeks, 1, 2, 3, 6, and 12 months and annually thereafter) using Flow-PRA. A mean of 6.9+/-1.2 serum samples per patient were obtained. Severity of cellular rejection was measured using the ISHLT grading system. Coronary angiography and intravascular ultrasound (IVUS) studies were performed annually to evaluate severity of allograft vasculopathy., Results: Twenty-five recipients had newly detected HLA-directed antibodies during the first year postHT. HLA class I antibodies were detected in 18 patients (25.4%), and class II in 11 patients (15.5%). The majority of donor recipient pairs were HLA mismatched (4.6+/-1.2 of the six major HLA antigens). Only mismatches at HLA-A locus had significant association with de novo posttransplant antibody formation. Length of ischemia time was correlated with early and sustained presence of de novo HLA-directed antibodies postheart transplant. Importantly, an association between de novo HLA-directed antibodies and cellular rejection was notes (P=0.0002). De novo HLA class II directed antibodies are also associated with IVUS documented vasculopathy (P<0.002). Finally, death due to allograft failure is associated with the presence of de novo formed HLA class II directed antibodies (P=0.008)., Conclusions: Identifying the formation of de novo HLA-directed antibodies following heart transplantation may predict allograft outcome. This, in turn, may serve as a tool for individualization of immunosuppression protocols in heart transplant recipients.

Background: The relationship between post-heart transplant cachexia and obesity with subsequent morbidity and mortality has not yet been reported. Therefore, the purposes of this study were to: (1) describe change in body mass index (BMI) from before transplant through 5 years after transplant; (2) identify risk factors for increased BMI at 1 year post-transplant; and (3) determine whether post-transplant BMI is associated with post-transplant morbidity and mortality., Methods: Patients (n = 3,540) were from a non-random sample having received a heart transplant between January 1, 1996 and December 31, 2001 at 33 institutions of the Cardiac Transplant Research Database (CTRD). Patients were divided into groups using cut-offs for categories of BMI. Data were assessed according to frequencies, measures of central tendency, Pearson correlations, chi-square tests, multiple regression and stratified actuarial analyses with log-rank tests for comparisons. The level of statistical significance was set at p = 0.05., Results: The number of obese patients increased significantly from immediately before heart transplant to 5 years later (17% vs 38%) (p < 0.0001). Risk factors for increased BMI at 1 year after heart transplant (explaining 56% of variance) included increased BMI at transplant, younger age, black race, non-ischemic etiology of heart disease, Status I at time of transplant and non-use of mycophenolate mofetil. Patients who were underweight or obese at 1 year post-transplant were at greater risk for rejection over time than patients who were of normal weight or overweight (p = 0.009)., Conclusions: Both demographic and clinical factors are related to increased BMI at 1 year after heart transplantation. Post-transplant cachexia and obesity are risk factors for poor clinical outcomes after heart transplantation.

This article reviews infections that occur in patients with implanted mechanical circulatory support devices and presents recent data for signs of progress in controlling the incidence and impact of these infections. Two types of comparisons are used to examine this question. First, the outcomes of patients with HeartMate vented electric left ventricular assist devices (VADs) (Thoratec Corp, Pleasanton, CA) implanted during the REMATCH Trial are compared with the outcome of more recent patients who received this pump as destination therapy. Second, the outcome of patients who received a smaller left VAD (e.g., an axial flow VAD) or a fully implanted left VAD are reported and contrasted with results from the REMATCH era. Data are presented to support the hypothesis that improvements in patient selection, patient management, device durability, and device design have resulted in lower rates of infection and infection-related death for patients who require mechanical circulatory support.

Background: Ventricular assist devices (VADs) are commonly used to bridge patients to heart transplantation. Recipients of VADs may develop anti-human histocompatibility leukocyte antigen antibodies, as reflected by elevated panel-reactive antibodies (PRA). The purpose of this study was to evaluate the relationship between bridging with VAD before heart transplantation and development of cellular rejection, humoral rejection, and allograft vasculopathy after transplantation., Methods: Data on all patients who underwent cardiac transplantation between July 1994 and February 2001 at Rush Presbyterian St Luke's Medical Center were retrospectively reviewed. Data collected included sex, age, etiology of cardiomyopathy, percentage panel reactive antibodies (by cytotoxic method), type and duration of mechanical circulatory support, transfusion history, rejection history (both cellular and humoral) after cardiac transplantation, and development of allograft vasculopathy. Cellular rejection was treated when International Society of Heart and Lung and Transplantation Grade 2 or greater in the first 12 months after transplant and Grade 3 or greater after 12 months and treated with intensification of immunosuppression. Humoral rejection was defined clinically as allograft dysfunction by echocardiography without evidence of cellular rejection on endomyocardial biopsy or allograft vasculopathy. Allograft vasculopathy was defined by presence of any degree of luminal narrowing or pruning of distal vessels by coronary arteriography. Statistical analyses were performed by chi-square test, Fisher's exact test, and Wilcoxon rank sum test, as appropriate., Results: Ninety-eight patients underwent cardiac transplantation during the study period (87 men, mean age 49 years, 46 ischemic etiology). Of these, 48 were bridged with HeartMate VAD (20 patients received vented electric device, 28 received pneumatic device). Nineteen percent of VAD patients had a peak pretransplant PRA > or =10% vs 2% of patients without VAD (p = 0.014). PRA > or =10%, use of VAD, or duration of VAD support did not predict development of humoral rejection. Use of VAD did not predict development of cellular rejection or allograft vasculopathy. VAD use was not associated with sudden death after heart transplantation. In the entire group of 98 patients, neither humoral nor cellular rejection predicted development of allograft vasculopathy. Longer ischemic time correlated with increased cellular rejection and humoral rejection after transplantation (p = 0.01)., Conclusions: Some patients bridged to cardiac transplantation with VADs have increased PRA before heart transplantation, but this does not appear to translate into increased risk of either humoral or cellular rejection after transplantation or development of allograft vasculopathy as detected by coronary angiography.

An acquired form of sideroblastic anemia has been described in association with several drugs, especially anti-microbial agents. A case of sideroblastic anemia is presented in a patient with a left ventricular assist device drive-line infection who was receiving linezolid, an antibiotic used for serious infections with gram-positive organisms. This patient's anemia resolved after discontinuation of the drug; he subsequently underwent an uncomplicated orthotopic heart transplant with no recurrence of anemia. As linezolid has been shown to have hematologic side effects, blood count monitoring is recommended in patients receiving this drug for long-term therapy.

Background: Differences in mortality are thought to exist between African Americans and Caucasians with heart failure. These differences may be due to a variety of factors, including differences in disease process, socioeconomic status, and access to health care. Additionally, little data exist on racial differences between these two groups after cardiac transplantation. This study examines a single center, urban experience in treating African Americans and Caucasians with heart failure and after cardiac transplantation. We hypothesize that treatment in a specialized, comprehensive heart failure/cardiac transplantation program results in similar survival between African Americans and Caucasians., Methods: We retrospectively reviewed the Rush Heart Failure and Cardiac Transplant Database from July 1994 to August 2000. Variables analyzed in the cardiomyopathy patients included survival (until death, placement of left ventricular assist device or cardiac transplantation), number of hospitalizations per year, length of stay per year, and utilization of outpatient resources. Follow-up period was from initial visit to death, transplantation, or implantation of left ventricular assist device. In those who underwent cardiac transplantation, we examined rejection rates (cellular and humoral), rejection burden, hospitalization data, and 5-year survival. A subgroup bridged to cardiac transplantation with a left ventricular device was also analyzed., Results: Seven hundred thirty-four cardiomyopathy patients were identified: 203 were African Americans and 531 were Caucasians. The etiology of cardiomyopathy was more commonly ischemic in Caucasians as compared to non-ischemic in African Americans (P <.01). African Americans had more admissions to the hospital per year compared with Caucasians, 1.2 +/- 2.1 versus.5 +/- 1.1 (P <.01) with longer length of stay per year, 1.4 +/- 25.2 days versus 4.4 +/- 14.3 days (P <.01). Utilization of outpatient resources was significantly higher in African Americans compared with Caucasians with more use of continuous inotropes (13% versus 6%, P <.01), intermittent inotropes (11% versus 5%, P <.01), and home nursing after hospital discharge (52% versus 32% of hospital discharges, P <.01). Survival by Kaplan-Meier analysis was comparable between the two groups (mean survival 1,470 +/- 72 days in African Americans versus 1521 +/- 46 days in Caucasians, log rank test [P =.6]). During this time, 30 African Americans and 73 Caucasians underwent cardiac transplantation. Fifty-three were bridged to transplantation with a left ventricular assist device (20 African Americans, 33 Caucasians). There were no differences in 5-year survival by Kaplan-Meier analysis despite higher peak preoperative panel reactive antibody levels in African Americans versus Caucasians (12% +/- 30% compared with 5% +/- 15%, P =.04), more overall treated rejection episodes per year in the African Americans (P <.01), as well as more posttransplant hospitalizations (2.2 +/- 1.2 times per year as compared with 1.7 +/- 2.1 times per year, P =.04)., Conclusion: Delivery of care to heart failure patients in a comprehensive, specialized program results in similar survival regardless of race despite higher utilization of inpatient and outpatient resources. The finding that, after cardiac transplantation, African Americans do not have higher mortality rates, despite having higher rates of rejection overall and more hospitalizations, further supports the hypothesis that optimal care can improve outcomes despite unfavorable baseline clinical characteristics.

Because the transplanted heart is denervated, classic angina as a symptom of allograft coronary vasculopathy rarely is perceived. Any cardiac transplant patients who presents with decreased exercise capacity, shortness of breath, or syncope should be assessed thoroughly. Unfortunately, the initial presenting symptom of transplant vasculopathy may be acute myocardial infarction, heart failure, or even sudden death. Patients should be evaluated on an annual basis for the presence of transplant coronary vasculopathy in addition to when clinical suspicion warrants. Coronary angiography has been the main modality of invasive assessment, although it is insensitive. Recently, intracoronary ultrasound has been used in conjunction with angiography to detect the first evidence of transplant vasculopathy, manifested as thickening of the intimal layer of the vessel wall due to smooth muscle cell proliferation, which ultimately leads to luminal narrowing. Patients with evidence of vasculopathy should undergo functional evaluation with dobutamine echocardiography to document ischemic burden. Preventive measures include traditional coronary risk factor modification. Patients are started on statins early in the post-transplantation period and hypertension is treated aggressively using calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors. Because of their deleterious metabolic effects, steroids may be withdrawn under close surveillance for rejection. After transplant vasculopathy has developed, it is difficult to treat and options are limited. Patients with discrete luminal obstructions may undergo angioplasty, stenting, or coronary artery bypass. However, these procedures are palliative, and the only definitive therapy is retransplantation.

Management of anticoagulation in patients with heparin-induced thrombocytopenia (HIT) undergoing surgery requiring cardiopulmonary bypass (CPB), such as cardiac transplantation, represents a difficult clinical problem and no clear management strategy exists. The cases of 2 patients with HIT who underwent cardiac transplantation using differing anticoagulation strategies are presented with a discussion of potential advantages and pitfalls of each approach used.

Purpose: Limited options are available to improve the functional class of patients awaiting cardiac transplantation. We assessed the effect of carvedilol on New York Heart Association (NYHA) class, heart rate (HR), blood pressure (BP), jugular venous pressure (JVP), electrolytes and renal function in patients with markedly decreased left ventricular (LV) function referred for cardiac transplantation assessment., Methods: Sixty-one patients (age = 52 +/- 12 yr, EF = 23 +/- 7%, VO2 max = 16 +/- 5 mL/kg/min) referred to the cardiac transplant clinic were reviewed before and after the addition of carvedilol (starting dose 3.125 mg twice daily to target dose of 25 mg twice daily) to usual heart-failure therapy. Over a 1-yr period, at each visit prior to initiation, at baseline initiation visit and at each follow-up visit, NYHA class, BP, HR, JVP, electrolytes, and renal function were obtained. Statistical analysis was performed using random effects regression approach. A multiple logistic regression analysis was performed on 52/61 patients to determine possible associations between NYHA improvement and the following patient characteristics: sex, etiology of cardiomyopathy, initial NYHA class, and dose of carvedilol., Results: Three patients died (2 after stopping carvedilol) and 3 were transplanted. Median follow-up was 100 d. Sixteen patients reached the target dose after a mean of 137 d (2.75 visits). Estimated time-to-target dose is 8 months (5.6 visits). BP tended to increase (p = 0.07 for change in trend) with no change in JVP, electrolytes or renal function. HR decreased 6 +/- 3 b.p.m. (p = 0.03). Of 14 patients NYHA class I/II at baseline, none were class III/IV at last follow-up visit. Of 47 patients NYHA class III/IV at baseline, 25 were class I/II, and 22 were class III/IV at last follow-up (p < 0.001). Multiple logistic regression analysis did not demonstrate any factor predictive of subsequent NYHA class improvement., Conclusions: Despite less than target doses in most patients, a favorable effect of carvedilol on functional class in patients with severe congestive heart failure (CHF) referred for transplant was observed. Those with good functional status remained stable and those with poor functional status improved or remained stable. No baseline patient characteristic predicted improvement. The shortage of donor organ requires optimal use of medical regimens which may improve functional class while awaiting transplantation and which may delay the necessity for heart transplantation. Therefore, addition of carvedilol to usual medical therapy may be beneficial even in patients with severe LV dysfunction and poor NYHA classification.

Background: Pulmonary hypertension in patients with congestive heart failure (CHF) is a risk factor for increased mortality after orthotopic cardiac transplantation. Reversibility of elevated pulmonary vascular resistance (PVR) by pharmacologic agents predicts improved outcomes. Milrinone, a phosphodiesterase inhibitor with vasodilating and positive inotropic properties, has been shown to lower PVR in one previous study. However, no study has documented outcomes after cardiac transplantation in patients in whom reversibility of pulmonary hypertension was demonstrated after administration of milrinone., Methods: We retrospectively reviewed 19 patients with CHF and pulmonary hypertension defined as PVR > or = 3 Wood units, PVRI (pulmonary vascular resistance index) > or = 4 resistance units, or TPG (transpulmonary gradient = mean pulmonary artery pressure--mean capillary wedge pressure) > or = 12 mmHg being assessed for cardiac transplantation. A sub-group of 14 patients with severe pulmonary hypertension defined as PVR > or = 4, PVRI > or = 6 and TPG > or = 15 was also examined. Milrinone was administered as a bolus (50 ug/kg) and hemodynamic parameters were measured at 5, 10 and 15 minutes. Six patients received cardiac transplants., Results: Administration of milrinone significantly lowered PVR, PVRI, mean pulmonary artery pressure (PAM)(all p = 0.002) and pulmonary capillary wedge pressure (PCWP)(p = 0.006). Cardiac output (CO) increased significantly (p = 0.001). TPG did not change (p = 0.33). In patients with severe pulmonary hypertension, the magnitude of these changes was greater. In addition, TPG was significantly lowered (p = 0.02)., Conclusion: Milrinone lowered PVR by decreasing PAM and increasing CO significantly. In addition, PCWP was significantly lowered. These finding confirm both vasodilatory and inotropic effects of milrinone. Patients with severe pulmonary hypertension had more pronounced effects. There were no deaths in the group of patients proceeding to cardiac transplantation. Our study demonstrates the efficacy of milrinone in lowering PVR as well as suggesting safety in use in patients undergoing cardiac transplantation.