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Background: Tricuspid regurgitation (TR) is common after heart transplantation. However, the incidence of severe TR and the incidence of symptoms after echocardiographic diagnosis of severe TR have not been documented. The purpose of this study is to determine the incidence of severe TR and its clinical significance in the heart transplant population. Methods We reviewed echocardiograms (echo) of all heart transplant patients coming for regular echocardiographic follow-up between 1990 and 1995. We reviewed the charts of all patients who had echo diagnosis of severe TR. Results A total of 336 patients had echo follow-up during this time period. The number of months post-heart transplant to last echo was 54 ± 50 (range, 1 to 265 months). Ninety patients had moderate TR and 23 patients had severe TR. Mean time from heart transplantation to diagnosis of severe TR was 43 ± 38 months (range, 1 to 132). Using Cutler-Ederer analysis, at 5 years, 92.2% of surviving patients were free from severe TR. At 10 years, 85.8% of surviving patients were free from severe TR. Of the 23 patients with severe TR, 17 had charts available for review. The mean number of prior endomyocardial biopsies was 28 ± 21 (range, 3 to 88). These patients were followed for 35 ± 18 months after diagnosis. During this period, they developed significant heart failure and peripheral edema. Six patients eventually underwent tricuspid valve replacement. Conclusions Moderate to severe TR commonly occurs following heart transplantation. Severe TR is associated with significant morbidity.

Background —This study examines the hypothesis that metabolic abnormalities of dysmetabolic syndrome are risk factors for transplant coronary artery disease (TxCAD). Methods and Results —Sixty-six patients without overt diabetes, 2 to 4 years after surgery, underwent intracoronary ultrasound (ICUS), measurement of plasma glucose and insulin after oral glucose (75 g), and fasting lipid and lipoproteins. TxCAD incidence by angiography or autopsy was prospectively determined during subsequent follow-up (8 years). Coronary artery intimal thickness (IT) and subsequent outcomes were compared in patients stratified as having “high” versus “low” plasma glucose (>8.9 mmol/L) and insulin (>760 pmol/L) 2 hours after glucose challenge; and “abnormal” versus “normal” fasting lipid and lipoprotein concentrations as defined by the National Cholesterol Education Program. Patients with high glucose or insulin concentrations had greater IT: 0.38±0.05 versus 0.22±0.02 mm, P ≤0.05, and 0.39±0.05 versus 0.20±0.02 mm, P ≤0.01, respectively. Freedom from TxCAD was 56±11% versus 81±6% ( P P P P 0.3 mm than with IT ≤0.3 mm. TxCAD incidence was higher in patients with high plasma TG and VLDL and low HDL. Conclusions —These data suggest that insulin resistance plays a role in TxCAD.

Behcet's disease is a rare autoimmune disease characterized by oral and genital ulcers, and by multisystem disease, including arthritis, neurologic complications and vasculitis. Large-vessel and coronary artery aneurysms are often an indication for surgery, but the return of aneurysms, thrombosis, and the tendency to exhibit an exaggerated inflammatory response at puncture sites (pathergy) complicate surgical recovery. As such, cardiac transplantation, which requires atrial and large-vessel anastomoses, has not been reported in patients with Behcet's disease. We report the first orthotopic heart transplant with >1-year survival in a patient with Behcet's disease despite major complications. The investigators remain pessimistic about cardiac transplantation in patients with Behcet's disease until advances in preventing recurrent vascular pathology ensue.

Transplant recipients have a higher incidence of cancer compared with the general population. This increased risk is related to the intensity and chronicity of immunosuppression that these patients receive. The common types and presentations of posttransplant tumors are reviewed and discussed. Regular surveillance is of paramount importance in detecting such tumors. Treatment invariably includes attempts to reduce immunosuppression.

Since the early 1980s, a 3-drug regimen that includes cyclosporine, azathioprine, and usually corticosteroids has been the mainstay of immunosuppression for patients undergoing cardiac transplantation. This regimen, however, has a variety of inherent toxicities and is not associated with any lesser incidence of graft coronary artery disease than the earlier regimen. For these reasons, there has been a widely perceived need for the introduction of improved immunosuppressive agents. Two such agents have thus far been introduced into clinical organ transplantation: mycophenolate mofetil and tacrolimus. Mycophenolate mofetil is used as a substitute for azathioprine and has been shown to result in significantly lower mortality rates and freedom from rejection in heart transplant recipients. Tacrolimus can be used as a substitute for cyclosporine but (at least in the short-term) seems to offer no important advantage in terms of survival or rejection. The combination of these 2 new agents seems to have no short-term disadvantage and longer-term follow-up is pending.

Background —Coronary remodeling plays a significant role in lumen loss in transplant allograft vasculopathy (TxCAD), but the determinants of remodeling are unknown. We assessed the relationship between remodeling and plaque topography, coronary compliance, and blood flow in TxCAD. Methods and Results —One artery in each of 27 transplant patients was investigated with simultaneous intravascular ultrasound and coronary flow measurements (basal and hyperemic by Doppler flow wire). At 4 to 8 different cross sections (mean 5.1±1.2), plaque topography (concentric or eccentric) was determined, and total vessel area, lumen area, and intimal/medial area (IMA) were measured. Mean remodeling ratio (vessel area/IMA) in eccentric lesions (E, n=28) was significantly larger than that in concentric lesions (C, n=70) (E 5.87±0.93 versus C 3.58±0.62; P P =NS) and distribution of imaged segments. Remodeling ratio was consistently larger in eccentric lesions in all 3 vessel segments when analyzed separately, and mean remodeling ratio for each artery was larger in vessels with predominantly eccentric lesions. Coronary compliance ([Δ lumen area/diastolic lumen area]/Δ mean arterial pressure×10 3 ) was also significantly greater in eccentric lesions versus concentric lesions (proximal 1.00±0.39 versus 0.22±0.04; mid 0.71±0.17 versus 0.21±0.10; distal 0.43±0.13 versus 0.01±0.08; all P P Conclusions —Vessel remodeling in transplant vasculopathy is significantly greater in eccentric lesions than in concentric lesions, possibly due to greater coronary compliance and resistive vessel function.

Parkinson's Disease (PD) is a chronic, progressive disorder of the central nervous system characterized by tremors, stiffness, slowness of movement, and impaired balance and coordination. It affects over one million people in the U.S. today, including such personalities as actor Michael J. Fox, former boxer Muhammad Ali, and evangelist Billy Graham. At present, the cause and the cure for PD remain elusive but active, promising research is being done in this field. This article discusses selected sites and resources available on the Web for PD.

Background —Coronary artery disease occurs in an accelerated fashion in the donor heart after heart transplantation (TxCAD), but the cause is poorly understood. The risk of developing TxCAD is increased by cytomegalovirus (CMV) infection and decreased by use of calcium blockers. Our group observed that prophylactic administration of ganciclovir early after heart transplantation inhibited CMV illness, and we now propose to determine whether this therapy also prevents TxCAD. Methods and Results —One hundred forty-nine consecutive patients (131 men and 18 women aged 48±13 years) were randomized to receive either ganciclovir or placebo during the initial 28 days after heart transplantation. Immunosuppression consisted of muromonab-CD3 (OKT-3) prophylaxis and maintenance with cyclosporine, prednisone, and azathioprine. Mean follow-up time was 4.7±1.3 years. In a post hoc analysis of this trial designed to assess efficacy of ganciclovir for prevention of CMV disease, we compared the actuarial incidence of TxCAD, defined by annual angiography as the presence of any stenosis. Because calcium blockers have been shown to prevent TxCAD, we analyzed the results by stratifying patients according to use of calcium blockers. TxCAD could not be evaluated in 28 patients because of early death or limited follow-up. Among the evaluable patients, actuarial incidence of TxCAD at follow-up (mean, 4.7 years) in ganciclovir-treated patients (n=62) compared with placebo (n=59) was 43±8% versus 60±10% ( P 40 years (relative risk, 2.7; CI, 1.3 to 5.5; P P =0.04). Stratification on the basis of calcium blocker use revealed differences in TxCAD incidence when ganciclovir and placebo were compared: no calcium blockers (n=53), 32±11% (n=28) for ganciclovir versus 62±16% (n=25) for placebo ( P P =NS). Conclusions —TxCAD incidence appears to be lower in patients treated with ganciclovir who are not treated with calcium blockers. Given the limitations imposed by post hoc analysis, a randomized clinical trial is required to address this issue.

Background: The experience with 30 years of cardiac transplantation at Stanford University Medical Center was reviewed. A total of 954 transplants were performed in 885 patients. Patients were divided into 3 groups based on immunosuppression received: group I, no cyclosporine (INN: ciclosporin) (n = 201) (January 1968–November 1980); group II, cyclosporine (n = 248) (December 1980–June 1987); and group III, cyclosporine + OKT3 (n = 436) (July 1987–March 1998). Results:The 1-, 5-, and 10-year actuarial survivals were 68%, 41%, and 24% (group I); 80%, 57%, and 37% (group II); and 85%, 68%, and 46% (group III) (I vs II, P < .01; I vs III, P < .005; and II vs III, P < .005). The 1-, 5-, and 10-year actuarial death rates from rejection were 8%, 12%, and 14% (group I); 5%, 7%, and 7% (group II); and 2%, 5%, and 5% (group III) (I vs II, P = not significant; I vs III, P < .005; and II vs III, P < .005). The 1-, 5-, and 10-year actuarial death rates from infection were 25%, 43%, and 50% (group I); 8%, 17%, and 29% (group II); and 6%, 11%, and 16% (group III) (I vs II, P < .005; I vs III, P < .005; and II vs III, P < .05). The 1-, 5-, and 10-year actuarial death rates from graft coronary artery disease were 0%, 5%, and 13% (group I); 0%, 12%, and 19% (group II); and 1%, 6%, and 9% (group III) (I vs II, P < .01; I vs III, P < .005; and II vs III, P = not significant). There have been 69 retransplants in 67 patients with 1-, 5-, and 10-year actuarial survivals of 49%, 27%, and 15%, respectively. Conclusions: The evolution of 3 decades of experience with cardiac transplantation has resulted in improved overall survival. The incidence of rejection and of death from infection and graft coronary artery disease have decreased over time, primarily as a result of improvements in immunosuppression and in the prevention and treatment of infection. Continued advances in perioperative management and the development of more specific, less toxic immunosuppressive agents could further refine this initial experience and improve the survival and quality of life of patients after cardiac transplantation. (J Thorac Cardiovasc Surg 1999;117:939-51)

Heart failure is increasing in frequency and is associated with substantial morbidity and mortality. The incidence of heart failure is highest among older adults [(1,2)][1]. Treatment of heart failure, a leading cause of hospitalization for people older than 65 years of age, costs more than $30

Spinal cord injury is a devastating event, with individuals facing a lifetime of specialized care and rehabilitation. Each year, approximately 10,000 individuals suffer such an injury; there are estimated to be 200,000 spinal-cord-injured individuals in the United States today. Superman actor Christopher Reeve's 1995 injury, along with interesting research being done in this area, has brought this health problem into the public eye in recent years. This article discusses a select list of spinal cord injury resources available on the Internet covering organizations, health care facilities, care and treatment, research, statistics, periodicals, and discussion forums.

Elderly (n = 1,539) aged 60 and older residing in rural counties of nine southeastern states who volunteered to participate in the study were interviewed. Information collected included socio-economic information, food intake by 24-hour recall for two non-consecutive days, and questions on diet knowledge, attitudes, and practice. Diet Knowledge Index (DKJ) was assessed from the average scores of individual knowledge of dietary fiber, cholesterol/fat, and food group servings. Number of servings of grains/cereals/ breads/pasta, milk/cheese, fruits, and vegetables was significantly higher for those with higher DKJ; intakes for many nutrients were greater, and quality of diets was superior for those with higher DKJ. Those with higher DKJ had higher education and income; and proportions of males, blacks and persons who lived alone decreased as DKJ increased. Nutrition education programs should target rural elders with low income and education and who live alone.

Right bundle branch block (RBBB) is the most common electrocardiographic abnormality in heart transplant recipients, but the cause remains unknown, data regarding the prognosis are conflicting, and all previous studies have been limited to100 patients. This was a study of patients who underwent heart transplantation at Stanford University Medical Center from 1981 to 1995 with known outcomes andor=2 available electrocardiograms (ECGs). Outcomes were assessed in those with and without conduction disturbances recorded from the ECGs closest to the time of transplantation and the most recent ECGs. Of the 322 heart transplant recipients studied, 141 (44%) died over a mean follow-up of 9 +/- 3.5 years, and 40 (13%) died of sudden cardiac death. In the first ECG obtained, a mean of 1.8 +/- 2.4 years after transplantation, 44 patients (14%) had incomplete RBBB and 26 (8%) had RBBB; in the second ECG, obtained a mean of 5.6 +/- 3.7 years after transplantation, 59 patients (18%) had incomplete RBBB and 63 (20%) had RBBB. Increasing time from transplantation was associated with a greater likelihood for RBBB on the first and second ECGs (p = 0.001 and p0.0001, respectively). QRS duration, incomplete RBBB, RBBB, or the development of RBBB was not associated with mortality or sudden cardiac death. In conclusion, although RBBB was the most common electrocardiographic abnormality in our study, the prevalence was lower than previously reported. The cause of RBBB appears to be largely related to events that occur well after transplantation, and the prognosis is benign.

This article summarizes the rationale for and major clinical points of the recently updated ACC/AHA guidelines for management of chronic heart failure in the adult.

The study aim was to determine the health-related quality of life (HRQL) in conjunction with clinical outcomes following aortic valve replacement (AVR) surgery. In these times of healthcare change, quality measures of the success of a procedure go beyond clinical outcomes, with patient reports of HRQL considered important.All patients who had undergone AVR surgery were followed prospectively through the authors' valve registry and the local Society of Thoracic Surgery (STS) database. The HRQL (Short-Form 12 and Minnesota Living with Heart Failure Questionnaire) was collected preoperatively, and at six and 12 months after surgery.Since 2005, a total of 459 patients have undergone isolated AVR surgery. The mean age, ejection fraction and STS risk score were 65.8 +/- 13.6 years, 57.7 +/- 11.0%, and 2.8 +/- 3.5 (range: 0.4-47.9), respectively. The median (IQR) length of hospital stay was 5 (3-7) days. Compared to the STS national norms, all clinical outcomes were excellent. A Kaplan-Meier analysis showed the two year cumulative survival as 92.0%. After 12 months the physical and mental HRQL had improved significantly, surpassing age and heart disease norms (p0.001 and p = 0.02, respectively). Multivariate analysis determined that a higher 12-month physical HRQL was predicted by a lower STS risk score (B = -1.3, p0.001) and a lower perioperative morbidity (B = -5.5, p = 0.02) after adjustment for baseline HRQL, age, and gender. In a subset of patients classified as 'symptomatic', as determined by higher MLHF scores, the HRQL scores were increased to age norms and surpassed the heart disease norms.Patients who undergo AVR can expect excellent clinical and HRQL outcomes, with greater benefits the earlier the surgery is carried out. The tracking of HRQL is valuable in understanding the success of a procedure from the patients' perspective.

Background & Aims Treatment for CH-C contains interferon with substantial associated side effects and health-related quality of life (HRQL) impairment. Currently, there is no published data assessing the impact of interferon-free regimens on HRQL. The aim is to report the HRQL of patients who participated in clinical trials of sofosbuvir (SOF) for CH-C. Methods CH-C patients were treated with sofosbuvir (SOF), pegylated interferon (PegIFN), ribavirin (RBV), or placebo in different combinations and duration (POSITRON, FISSION, FUSION, and NEUTRINO phase III trials). HRQL was assessed using SF-36 at baseline, during treatment, at the end of treatment, and at follow-up, and compared between treatment arms. Results HRQL scores decreased over the course of treatment for all treatment arms in all studies; however, patients returned to their baseline score by the end of follow-up. Compared to placebo, SOF and RBV was not associated with HRQL impairment (POSITRON). Compared to SOF and RBV, HRQL was significantly more impaired in the PegIFN and RBV arm (FISSION). For those treated with SOF and RBV, there was no difference in HRQL between 12weeks or 16weeks of treatment (FUSION). Multivariate analysis demonstrated that depression, fatigue, and insomnia were important predictors of patients' HRQL prior, during or after treatment. Additionally, anemia and receiving interferon were predictors of HRQL impairment during treatment. Achieving sustained virologic response after 12weeks of follow-up (SVR-12) with SOF and RBV was associated with improvement in HRQL scores from baseline. Conclusions Treatment-related HRQL impairment during SOF and RBV regimen is mild, and does not increase with longer treatment duration. Achieving SVR-12 with SOF and RBV is associated with an improvement in HRQL.

Background & Aims Hepatitis C (HCV) is a common cause of chronic liver disease worldwide. Current standard treatment for genotype-1 patients uses a triple combination of pegylated-interferon alpha (IFN), ribavirin (RBV) and a direct-acting antiviral agent (DAA) with 75–80% sustained virologic response (SVR) rates. The aim is to determine cost-effectiveness of staging-guided vs. treat all HCV genotype-1 patients with interferon-based vs. interferon-free regimens. Methods A decision analytic Markov model simulating patients until death compared four strategies for treating HCV genotype-1: Triple therapy (IFN, RBV, DAA) with staging-guidance or treat all, and oral IFN-free regimen with staging-guidance or treat all. Strategies with staging initiated treatment at fibrosis stages F2-F4, with staging repeated every 5years until age 70. The reference case was a treatment-naive 50-year-old. Analysis was repeated for 50% increase in cost of oral therapy. Effectiveness was measured in quality-adjusted life years (QALYs). Results Treatment of all patients with oral IFN-free regimen was the most cost-effective strategy, with an ICER of $15,709/QALY at baseline cost of oral therapy. The ICER remained below $50,000/QALY in sensitivity analyses for baseline and +50% cost of oral therapy scenarios. The treat all strategy was also the most effective strategy; associated with the lowest risk of developing advanced liver disease. Conclusions Treating all HCV patients with oral IFN-free regimen reduced the number of patients developing advanced liver disease and increased life expectancy. Additionally, IFN-free regimen without staging may be the most cost-effective approach for treating HCV genotype-1 patients. The efficacy and safety of these regimens must be confirmed using randomized clinical trials.

Objective One established predictor for failure of surgical ablation for atrial fibrillation is increased left atrial size. Surgeon perception is that surgical ablation in these patients is ineffective and should not be performed. The purpose of this study was to determine whether a larger left atrial size carries a prohibitive risk for failure and embolic events after surgical ablation. Methods In patients undergoing surgical ablation without left atrial reduction (N = 373), left atrial size was measured via transthoracic echocardiography within 6 months before surgery. Large (>5.5 cm; n = 83) and small (≤5.5 cm; n = 290) left atrial size groups were compared on outcomes. Results Patients in the large left atrium group were younger ( P = .02) and had lower operative risk (European System for Cardiac Operative Risk Evaluation, P = .01), but they were not different in type ( P = .51) or duration of atrial fibrillation ( P = .93). The large left atrium group was less likely to be in sinus rhythm at 1 year (86% vs 93%, P = .04), but there was no difference in sinus rhythm without antiarrhythmic drugs (77% vs 85%, P = .10). By 2 years, the large and small left atrium groups were similar in sinus rhythm (85% vs 90%, P = .35). Freedom from embolic stroke was similar ( P = .70) despite the majority of patients not taking anticoagulation at 1 year. Conclusions The large left atrium group had acceptable return to sinus rhythm and sinus rhythm without antiarrhythmic drugs. The embolic stroke rate was low despite the majority of patients not taking anticoagulation. If patients are managed appropriately post-ablation, left atrial size should not be a discouragement when evaluating surgical candidates with atrial fibrillation.

Objectives Observational studies identified increased age, left atrial (LA) size, type and duration of atrial fibrillation (AF) as independent predictors for failure of AF surgical ablation. Rhythm at discharge following the Cox maze (CM) procedure for AF was never considered a significant predictor of success. The purposes of this study were to: (i) Determine the association of sinus rhythm (SR) at discharge and maintenance of SR. (ii) Identify the variables associated with discharge rhythm. (iii) Identify the effects of discharge rhythm on health-related quality of life (HRQL) post-CM procedure. Methods A prospective study (n = 534) of CM III/IV patients. Rhythm captured during hospitalization, discharge, 3, 6, 12 and 24 months and verified by electrocardiogram and 24-h holter. Subsequent SR interventions were captured. Logistic regression identified predictors of discharge rhythm. HRQL (Short-Form 12; AF symptom frequency and Severity Checklist V3) obtained during follow-up. Results Eighty-eight percent were discharged in SR (n = 469). LA size (OR = 1.36, CI: 1.02-1.82, P = 0.035) and long-standing AF type (OR = 2.68, CI: 1.31-5.50, P = 0.007) were the only independent predictors of non-SR at discharge. Lower rates of SR at 2 years were found in patients discharged in non-SR (75 vs 91%, P = 0.01). Patients discharged in SR had fewer perioperative morbidities [prolonged ventilation >24 h (6 vs 14%, P = 0.03), renal failure requiring dialysis (0.9 vs 5%, 0.04) and pneumonia (2 vs 9%, P = 0.005)]. During follow-up (mean = 43 ± 27 months), patients discharged in SR had fewer cardioversions (15 vs 29%, P = 0.006), similar percutaneous catheter ablations (6 vs 5%, P = 1.00) and no difference in late embolic strokes (1.5 vs 1.1%, P = 0.54). Conclusions In this large prospective cohort study, rhythm at discharge was found to be clinically significant with predicting SR at 24 months. Surgeons should be aware that the prognosis of non-SR patients at discharge remains excellent with high rates of SR at 24 months if managed appropriately using rhythm rather than rate control strategies.

Background Accelerated coronary artery disease is a major cause of mortality in heart transplant recipients; however, it does not appear to play a major role in the clinical outcome of heart-lung transplant recipients. The purpose of this study was to determine whether the incidence and severity of transplant coronary artery disease as detected by intracoronary ultrasound in heart-lung transplant recipients are less than those encountered in heart transplant recipients. Methods and Results We studied the left anterior descending coronary artery with the use of intracoronary ultrasound imaging in 22 heart-lung transplant recipients at the time of their routine annual coronary angiogram. Twenty-two heart transplant recipients were case matched for number of years after transplant at ultrasound study, recipient age, donor age, and diagnosis of nonischemic cardiomyopathy. Mean intimal area, intimal index, Stanford class, and incidence of at least moderate disease (Stanford class ≥3) were measured and calculated in each group and then compared between the two groups. Mean intimal area (1.6±2.5 versus 3.8±2.8 mm 2 ), mean intimal index (0.07±0.10 versus 0.22±0.14), mean Stanford class (1.7±1.0 versus 2.7±1.2), and incidence of Stanford class ≥3 (14% versus 45%) were significantly lower in the heart-lung transplant recipient group. Conclusions The incidence and severity of transplant coronary artery disease are much less in patients receiving heart-lung transplants than in those receiving heart transplants alone.

Background The mechanisms underlying cardiac contractile dysfunction after transplantation remain poorly defined. Previous work has revealed that inducible nitric oxide synthase (iNOS) is expressed in the rat heterotopic cardiac allograft during rejection; resultant overproduction of nitric oxide (NO) might cause cardiac contractile dysfunction via the negative inotropic and cytotoxic actions of NO. In this investigation, we tested the hypothesis that induction of iNOS may occur and be associated with cardiac allograft contractile dysfunction in humans. Methods and Results We prospectively studied 16 patients in the first year after cardiac transplantation at the time of serial surveillance endomyocardial biopsy. Clinical data, the results of biopsy histology, and echocardiographic and Doppler evaluation of left ventricular systolic and diastolic function were recorded. Total RNA was extracted from biopsy specimens, and mRNA for β-actin, detected by reverse transcription–polymerase chain reaction (RT-PCR) using human specific primers, was used as a constitutive gene control; iNOS mRNA was similarly detected by RT-PCR using human specific primers. iNOS protein was detected in biopsy frozen sections by immunofluorescence. Myocardial cGMP was measured by radioimmunoassay, and serum nitrogen oxide levels (NO x =NO 2 +NO 3 ) were measured by chemiluminescence. iNOS mRNA was detected in allograft myocardium at some point in each patient and in 59 of 123 biopsies (48%) overall. In individual patients, iNOS mRNA expression was episodic and time dependent; the frequency of expression was highest during the first 180 days after transplant ( P =.0006). iNOS protein associated with iNOS mRNA was detected by immunofluorescence in cardiac myocytes. iNOS mRNA expression was not related to the ISHLT histological grade of rejection or to serum levels of NO x but was associated with increased levels of myocardial cGMP ( P =.01) and with both systolic ( P =.024) and diastolic ( P =.006) left ventricular contractile dysfunction measured by echocardiography and Doppler. Conclusions These data support a relation between iNOS mRNA expression and contractile dysfunction in the human cardiac allograft.

Cytomegalovirus (CMV) infection is associated with an increased incidence of other opportunistic infections in organ transplant recipients. Whether this is related to immunomodulating effects of CMV or independent of CMV but associated with a host risk factor common to both infections is unclear. The purpose of this study was to determine whether the reduction in CMV infections seen with prophylactic ganciclovir treatment after heart transplantation is associated with a reduced incidence of other opportunistic infections. Of 149 patients prospectively enrolled in a multicenter, randomized, double-blind, placebo-controlled trial of ganciclovir to prevent CMV disease, 74 patients enrolled at this center (33 control and 41 ganciclovir-treated) were retrospectively identified. All received prophylactic OKT-3 and standard 3 drug maintenance immunosuppressive therapy. Actuarial survival and rejection rates and incidence of opportunistic infections (bacterial, fungal, and protozoal) for the 2 treatment groups were determined and compared using Cox-Mantel analysis. CMV disease occurred 2.5 times more frequently in the control group. There were no significant differences in survival or rejection rates nor in bacterial or protozoal infection incidence between the 2 groups. Bacterial infections occurred in 54% of control and 39% of ganciclovir-treated patients (P=0.18). There were significantly fewer fungal infections in the ganciclovir-treated group (7% vs. 27%, P=0.0071). CMV and fungal infections were both significantly reduced in patients who received ganciclovir prophylaxis. This suggests that active CMV disease may be causally associated with the development of opportunistic fungal infections.

Objectives. This study sought to analyze the outcomes of revascularization procedures in the treatment of allograft coronary disease. Background. Allograft vasculopathy is the main factor limiting survival of heart transplant recipients. Because no medical therapy prevents allograft atherosclerosis, and retransplantation is associated with suboptimal allograft survival, palliative coronary revascularization has been attempted. Methods. Thirteen medical centers retrospectively analyzed their complete experience with percutaneous transluminal coronary angioplasty, directional coronary atherectomy and coronary bypass graft surgery in allograft coronary disease. Results. Sixty-six patients underwent coronary angioplasty. Angiographic success (≤ 50% residual stenosis) occurred in 153 (94%) of 162 lesions. Forty patients (61%) are alive without retransplantation at 19 ± 14 (mean ± SD) months after angioplasty. The consequences of failed revascularization were severe. Two patients sustained periprocedural myocardial infarction and died. Angiographic restenosis occurred in 42 (55%) of 76 lesions at 8 ± 5 months after angioplasty. Angiographic distal arteriopathy adversely affected allograft survival. Eleven patients underwent directional coronary atherectomy. Angiographic success occurred in 9 (82%) of 11 lesions. Two periprocedural deaths occurred. Nine patients are alive without transplantation at 7 ± 4 months after atherectomy. Bypass graft surgery was performed in 12 patients. Four patients died perioperatively. Seven patients are alive without retransplantation at 9 ± 7 months after operation. Conclusions. Coronary revascularization may be an effective palliative therapy in suitable cardiac transplant recipients. Angioplasty has an acceptable survival in patients without angiographic distal arteriopathy. Because few patients underwent atherectomy and coronary bypass surgery, assessment of these procedures is limited. Angiographic distal arteriopathy is associated with decreased allograft survival in patients requiring revascularization.

Supplemental Digital Content is available in the text, The interferon (IFN)-free regimens for chronic hepatitis C (CHC) have high efficacy and superior health-related quality of life (HRQOL) in European/North American patients. The impact of these regimens on HRQOL of the Japanese CHC patients is not known. The Short Form-36 was administered before, during, and after treatment to CHC patients with genotype 1 treated with ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV) for 12 weeks and genotype 2 treated with SOF + RBV for 12 weeks in clinical trials. The HRQOL data were analyzed with reference to treatment regimens and clinical factors. A total of 494 CHC patients were included (19% cirrhotic, 69% genotype 1, 52% treatment-naive; 153 received SOF + RBV, 170 received LDV/SOF + RBV, 171 received LDV/SOF). The sustained virologic response-12 rates for these regimens were 97%, 98%, and 100%, respectively. CHC patients treated with LDV/SOF, SOF + RBV, or LDV/SOF + RBV regimens had similar HRQOL scores at baseline. During treatment, more adverse events were experienced by those treated with RBV-containing regimens (46% vs 22%, P

Supplemental Digital Content is available in the text, Patients’ experience during treatment may affect treatment adherence. Our aim was to assess the impact of patient-reported outcomes (PROs) on adherence to different anti-hepatitis C virus (HCV) regimens. Clinical, demographic, and PRO data (short form-36 [SF-36], chronic liver disease questionnaire-hepatitis C version [CLDQ-HCV], functional assessment of chronic illness therapy-fatigue [FACIT-F], work productivity and activity impairment: specific health problem [WPAI:SHP]) from 13 multinational clinical trials of anti-HCV treatment were available. Treatment adherence was defined as >80% of prescribed doses taken. Included were 4825 HCV patients. Regimens were grouped into: interferon- and ribavirin (RBV)-containing (±sofosbuvir [SOF]), interferon-free RBV-containing (RBV + SOF ± ledipasvir [LDV]), and interferon-free RBV-free (LDV/SOF). The adherence to these regimens were 77.6%, 84.3%, and 96.2%, respectively (P 0.05) for the small number of patients who were nonadherent to LDV/SOF. In multivariate analysis, being treatment-naive, longer treatment duration, and receiving an interferon- or RBV-containing regimen were associated with a lower likelihood of adherence (all P

Over the last 2 decades, improved understanding of the pathophysiology of heart failure has led to significant progress in the treatment of this syndrome. Nevertheless, heart failure remains a clinical problem of truly epidemic proportions, affecting nearly 5 million people in the United States.1,2 Moreover, the lifetime risk of developing heart failure may be as high as 20%, with an annual incidence of new cases of well over a half million per year.1–3 Beyond this human crisis, heart failure also presents a tremendous economic challenge as a result of the enormous costs of caring for this patient population.4 Unfortunately, this clinical and economic burden predictably will continue to increase as further therapeutic advances are made in the treatment of ischemic heart disease, creating an older surviving population at risk for developing heart failure. Although there has been some improvement in heart failure survival over the years, overall mortality remains high at >30% despite the introduction of ACE inhibitor and β-blocker therapies,2,5 which have been proven in landmark trials to markedly improve survival.6,7 This lack of striking improvement in survival rates outside of clinical trials may be a result of the well-documented obstacles faced in effecting appropriate changes in physician behavior,8 which in turn lead to significant under-use of proven medications and therapies.9 It is also possible that the ever-increasing complexity and multitude of recommended treatments is simply daunting and difficult to understand, causing these therapies not to be used, especially by practitioners who lack the time or the expertise to pursue the kind of “micromanagement” required with complex regimens. Numerous studies have attempted to address this issue by comparing the management provided by generalists and by cardiologists. In a small retrospective study of 403 patients, Ansari et al10 found that cardiologist care …

Background We evaluated the potential effects of granulocyte colony-simulating factor (G- CSF) on the incidence of rejection and allograft vasculopathy in heart transplant recipients. Methods Of 247 patients undergoing heart transplantation from 2000 to 2007, 52 (21%) developed leukopenia (white blood cell [WBC]

Heart disease is the leading cause of death for women. Previous studies suggest that women undergoing coronary artery bypass (CABG) surgery present with a higher severity of disease and that this may be an indicator of delays in treatment preceding diagnosis thus presenting challenges for recovery. The aim of this study was to examine gender differences in CABG morbidity and reported health-related quality of life (HRQL) at baseline and six months post-surgery. It was hypothesized that female gender would be an independent predictor for lower HRQL at six months following CABG surgery.Four hundred and ninety-six (n=496) adult patients who underwent a first-time, isolated CABG procedure with baseline and 6-month follow-up were included. Stepwise multivariate regressions were conducted to evaluate the factors predictive of 6-month HRQL scores.Females had more preoperative co-morbidities and scored significantly lower on HRQL compared to males at both baseline (p values0.01) and six months (p values0.01) on all ten domains. Gender was a significant predictor of 6-month HRQL in regression models for 8 out of 10 HRQL domains including Physical Component Summary score (B=-2.54, p=0.02).Female patients were at higher risk as reflected by their perioperative risk factors and baseline HRQL. These findings may reflect a delayed referral for surgery. Results indicated that female gender predicts lower HRQL 6-months post-CABG surgery, which can have an impact on recovery and outcomes. Efforts should be made to identify and treat female patients earlier to improve post-surgical outcomes.

The Cox-Maze procedure (CM) for atrial fibrillation (AF) is associated with a high rate of sinus restoration. This study assessed the safety and efficacy of concomitant CM using an argon-based cryosurgical platform only.Data were collected prospectively for 250 consecutive patients undergoing concomitant cryosurgical CM. We examined baseline characteristics, perioperative and postoperative outcomes, health-related quality of life (Medical Outcomes Trust SF-12 Health Survey and AF Symptom Checklist) and Kaplan-Meier survival analysis.Mean age was 64.3 ± 12.1 years, AF duration was 35.7 ± 54.2 months, left atrial size was 5.2 cm (range, 3.1 to 11.0 cm; 16.8%6 cm), 86% had nonparoxysmal AF, with history of cardioversion in 32% and catheter ablation in 8%. Concomitant procedures were mitral valve operation in 69.6%, coronary artery bypass graft in 29.2%, aortic valve replacement in 22.0%, with 46% multiple concomitant procedures and 16% with a previous cardiac operation. Perioperative outcomes were 5 deaths (2%), 3 strokes (1%), 1 transient ischemic attack (1%), and 4 pacemakers for sinus node dysfunction (2%). There were no late thromboembolic events (mean follow-up, 28.2 ± 23.7 months), and 11% were taking warfarin for atrial arrhythmia at 1 year. Significant improvement in health-related quality of life (p0.001) was noted. At 24 months, 92.4% of patients were in sinus rhythm; with 82.8% in sinus rhythm off antiarrhythmic drugs. Two-year cumulative survival was 91%.The cryosurgical CM procedure can be performed safely and effectively as defined by the low number of postoperative morbidities, high return to sinus rhythm off antiarrhythmic drugs, and low rate of thromboembolic events, with most patients off anticoagulation by 2 years.

Background— Microvascular dysfunction is emerging as a strong predictor of outcome in heart transplant recipients. At this time, the determinants and consequences of early microvascular dysfunction are not well established. The objective of the study was to determine the risk factors and functional correlates associated with early microvascular dysfunction in heart transplant recipients. Methods and Results— Sixty-three heart transplant recipients who had coronary physiology assessment, right heart catheterization, and echocardiography performed at the time of their first annual evaluation were included in the study. Microvascular dysfunction was assessed using the recently described index of microcirculatory resistance. The presence of microvascular dysfunction, predefined by an index of microcirculatory resistance >20, was observed in 46% of patients at 1 year. A history of acute rejection and undersized donor hearts were associated with microvascular dysfunction at 1 year, with odds ratio of 4.0 (1.3–12.8) and 3.6 (1.2–11.1), respectively. Patients with microvascular dysfunction had lower cardiac index (3.1±0.7 versus 3.5±0.7 L/min per m 2 ; P =0.02) and mild graft dysfunction measured by echocardiography-derived left and right myocardial performance indices ([0.54±0.09 versus 0.43±0.09; P P Conclusions— A history of acute rejection during the first year and smaller donor hearts were identified as risk factors for early microvascular dysfunction. Microvascular dysfunction assessed using index of microcirculatory resistances at 1 year was also associated with worse graft function and possibly worse clinical outcomes.

Objective Several risk models exist to predict operative outcomes after cardiac surgery and are used in selecting patients for alternative procedures such as transcatheter valve implantation. We sought to evaluate the performance of the Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) model in accurately identifying patients at high risk for aortic valve replacement (AVR). Methods Three hundred and ninety four consecutive patients who underwent isolated AVR from January 1, 2001, to July 1, 2007, at a tertiary care center were analyzed using the STS database. Patients were stratified into tertiles according to operative surgical risk calculated by the four models [STS-PROM, European system for cardiac operative risk evaluation (EuroSCORE), Ambler, and Providence]. Vital status at 1 year was determined using the National Death Index and Social Security Death Index. Results There were 310 low-risk patients, 56 intermediate-risk patients, and 28 high-risk patients with respect to the STS-PROM. The predicted risk of death for the low-risk, intermediate-risk, and high-risk groups were 2.4% ± 1.1%, 6.9% ± 1.4%, 15.8% ± 7.6% (P < 0.001) with respect to the STS-PROM model. Actual operative mortality for each respective group was 1.94%, 5.36%, 14.29% (P < 0.001) and 1-year mortality was 3.23%, 12.50%, 21.43% (P < 0.001), respectively. Conclusions High-risk patients have significantly high mortality after AVR. The STS-PROM accurately predicts operative mortality and can be used to predict 1-year survival as well. This risk model may be preferentially used instead of the EuroSCORE.

We analyzed our experience with 496 patients who underwent primary cardiac transplantation since the introduction of cyclosporine immunosuppression (Dec. 16, 1980, to Jan. 7, 1993). There were 388 male and 108 female patients. Mean recipient age was 40 ± 16 years (range 0.1 to 70 years, median 44 years). Recipient diagnoses included coronary disease in 188, idiopathic cardiomyopathy in 196, viral cardiomyopathy in 35, and congenital heart disease in 28 patients. Donor age was 25 ± 10 years (range 1 to 53 years, median 24 years). Graft ischemic time was 148 ± 57 minutes (range 38 to 495 minutes, median 149 minutes). Operative mortality (hospital death) rate was 7.9% ± 1.3% (70% confidence intervals). Multivariate logistic regression analysis revealed that (higher) pulmonary vascular resistance and gender (female) were the only independent predictors of hospital death ( p p p

BARRY H. GREENBERG, MD, INDER S. ANAND, MD, PhD, JOHN C. BURNETT JR, MD, JOHN CHIN, MD, KATHLEEN A. DRACUP, RN, DNSc, ARTHUR M. FELDMAN, MD, PhD, THOMAS FORCE, MD, GARY S. FRANCIS, MD, STEVEN R. HOUSER, PhD, SHARON A. HUNT, MD, MARVIN A. KONSTAM, MD, JOANN LINDENFELD, MD, DOUGLAS L. MANN, MD, MANDEEP R. MEHRA, MD, SARA C. PAUL, RN, DNP, FNP, MARIANN R. PIANO, RN, PhD, HEATHER J. ROSS, MD, HANI N. SABBAH, PhD, RANDALL C. STARLING, MD, MPH, JAMES E. UDELSON, MD, CLYDE W. YANCY, MD, MSc, MICHAEL R. ZILE, MD, AND BARRY M. MASSIE, MD

Background: Heart valve surgery is indicated for a number of presenting conditions and is performed even in young patients. It is known that younger age can be protective for surgical outcomes, such as mortality, but less is know about how age impacts quality of life in patients undergoing valve surgery. Objective: To determine if age was associated with health related quality of life (HRQL) after valve surgery. Methods: Patients who underwent valve surgery (stand alone or concomitant) since late 2005 were included in these analyses (N=288). The age range for this sample was 21-87. Patients were divided into tertiles based on age: younger (age < 60 years; n=95), older (age ≥ 60 and < 72; n=93) and oldest (age ≥ 72; n=100). HRQL was measured using the Medical Outcomes Trust Short Form 12 (SF-12) prior to surgery, and at 6 and 12 months post-surgery. The SF-12 mental component summary (MCS) and physical component summary (PCS) scores were calculated to assess differences in HRQL over time based on age groups. Results: There was a significant main effect of time for MCS (F=5.6, p Conclusion: Improvement in HRQL was shown across all age groups in both MCS and PCS. Despite the fact that the younger patients had the highest physical HRQL, this group had the lowest mental HRQL regardless of time point. These results suggest that valve disease in the younger patients had a detrimental effect on their mental HRQL prior to and after surgery. Further study is needed to investigate the impact of valve disease and surgery on quality of life in younger patients, particularly on how to improve the psychological experience.

Background: Reports of successful cardiac surgical outcomes have focused on mortality and morbidity. However, health related quality of life (HRQL) is now being recognized as an important outcome measure. The objective of this study was to assess the impact of in-hospital postoperative complications on physical and mental HRQL in cardiac surgery patients from baseline to 6 and 12 months after surgery. Methods: Patients who underwent cardiac surgery since September 2005 were included (n=702). All patients completed the Short Form Health Survey (SF-12) prior to surgery, and at 6 and 12 months after surgery. Norm-based physical and mental components of HRQL were calculated, with higher scores indicating better HRQL. In-hospital postoperative complications were defined using the Society of Thoracic Surgeons guidelines. Results: Group 1 (n=533) had no in-hospital postoperative complications and Group 2 (n=169) experienced complications. The groups did not differ at baseline on physical or mental HRQL. There were significant main effects of time (F=32.9, p Conclusion: In-hospital postoperative complications significantly affect improvements in HRQL. Patients that did not experience postoperative complications had a significantly better and faster improvement in physical HRQL from baseline to 1 year. Despite these differences in physical HRQL, the two groups increased similarly on mental HRQL. Further study is needed to explore this finding with a larger sample and longer follow-up time points after surgery.