Testosterone-related shortening of QTc interval in women with polycystic ovary syndrome.

CONTEXT: The presence of several cardiovascular risk factors is observed in women with polycystic ovary syndrome (PCOS). On the other hand, the QTc interval duration, which is related to cardiac arrhythmia and sudden death, has not been investigated thoroughly in PCOS population. OBJECTIVE: To investigate QTc interval duration and its relation to testosterone in women with PCOS. DESIGN: Cross sectional case-control study. SETTING: Outpatient setting, tertiary university medical centre. PATIENTS: We enrolled 119 consecutive patients in whom PCOS was diagnosed based on oligomenorrhea, infertility (>2 yr), ineffective ovarian stimulation, and ultrasonographic criteria. The control group (controls) included 64 age-matched healthy women without clinical or laboratory evidence of PCOS. INTERVENTIONS: In all participants we measured QTc interval duration on a standard electrocardiogram and determined plasma levels of high sensitivity C-reactive protein (hsCRP), endothelin-1 (ET-1), insulin, and testosterone. MAIN OUTCOME MEASURE: Shorter QTc interval duration in PCOS patients. RESULTS: When compared to controls, PCOS patients displayed higher values of hsCRP (2.35+/-2.14 mg/l vs 1.18+/-1.24 mg/l; p=0.01), ET-1 (23.6+/-10.3 ng/l vs 12.9+/-20.7 ng/l; p=0.03), insulin (18.5+/-7.8 mIU/l vs 10.7+/-9.1 mIU/l; p=0.02), and testosterone (2.7+/-2.1 nmol/l vs 1.4+/-1.7 nmol/l; p=0.01). QTc interval in PCOS patients was significantly shorter than in controls (401+/-61 msec vs 467+/-61 msec; p=0.007), and inversely related to the plasma levels of testosterone (Spearman -0.45, p=0.005). CONCLUSIONS: QTc interval in PCOS patients is short, and inversely associated with increased levels of testosterone. QTc interval duration is not part of an adverse cardiac risk profile in PCOS.

Heart retransplantation.

Retransplants comprise only a small minority (3-4%) of heart transplants, however outcome following retransplantation is compromised. Risk factors for a poor outcome following retransplantation include retransplantation early (<6 months) after primary transplant, retransplantation for acute rejection or early allograft failure, and retransplantation in an earlier era. The incidence of rejection and infection is similar following primary transplant and retransplantation. The compromised outcomes and risk factors for a poor outcome are similar in adult and pediatric heart retransplantation. However, due to the short half-life of the transplanted heart, it is an expectation that patients transplanted in childhood may require retransplantation. Based on the data available and the opinion of the working group, indications for heart retransplantation are (i) chronic severe cardiac allograft vasculopathy with symptoms of ischemia or heart failure (should be considered) or asymptomatic moderate or severe left ventricular dysfunction (may be considered) or (ii) chronic graft dysfunction with symptoms of progressive heart failure in the absence of active rejection. Patients with graft failure due to acute rejection with hemodynamic compromise, especially <6 months post-transplant, are inappropriate candidates for retransplantation. In addition, guidelines established for primary transplant candidacy should be strictly followed.

Comparison of intravenous ganciclovir and cytomegalovirus hyperimmune globulin pre-emptive treatment in cytomegalovirus-positive heart transplant recipients.

BACKGROUND: We compared the use of intravenous ganciclovir and cytomegalovirus hyperimmune globulin (CMVIG) as a pre-emptive treatment for cytomegalovirus (CMV)-positive heart transplant recipients. METHODS: Of 59 CMV-seropositive adult heart transplant recipients enrolled in Group 1, 37 tested positive for pp65 antigen within 12 weeks post-transplantation. These patients were randomized to receive either intravenous ganciclovir (n = 23) or CMVIG (n = 14). Group 2 included 133 CMV-seropositive heart transplant recipients who were not tested for CMV antigenemia and who received no anti-CMV therapy. RESULTS: CMV disease developed in 0 of 59 patients from Group 1, and in 27 of 133 patients (20%) in Group 2 (p = 0.0001). The incidence of superinfections was lower in Group 1 (0.28 +/- 0.46) than in Group 2 (1.10 +/- 1.33) (p = 0.01). The 2 groups did not differ with regard to incidence of rejection (0.7 +/- 0.9 in Group 1 vs 1.0 +/- 1.2 in Group 2; p = NS), transplant coronary artery disease at 1 year (14% in Group 1 vs 16% in Group 2; p = NS) or post-transplant lymphoproliferative disease (0% in Group 1 vs 2% in Group 2; p = NS). Ganciclovir and CMVIG therapies were associated with similar rates of rejection (0.52 +/- 0.6 with ganciclovir vs 0.50 +/- 0.60 with CMVIG; p = NS), superinfection (0.30 +/- 0.48 with ganciclovir vs 0.25 +/- 0.46 with CMVIG; p = NS), and transplant coronary artery disease at 1 year (13% with ganciclovir vs 14% with CMVIG, p = NS). CONCLUSIONS: The pre-emptive anti-CMV approach is superior to prophylaxis in CMV-seropositive heart transplant recipients. Both ganciclovir and CMVIG are equally effective.

Long-term follow-up of arrhythmias in pediatric orthotopic heart transplant recipients: incidence and correlation with rejection.

BACKGROUND: Arrhythmias in adult orthotopic heart transplant (OHT) recipients are common and have been used as predictors of rejection. Because of the paucity of information in pediatric OHT recipients, the purpose of this study was to determine the incidence and correlation of arrhythmias with rejection or with coronary artery disease (CAD) in children. METHODS: We retrospectively reviewed the records, electrocardiograms (ECGs), and 24-hour ambulatory ECGs of patients who underwent OHT from January 1984 to December 1999. We excluded arrhythmias occurring in the first 2 weeks after OHT. RESULTS: Sixty-nine patients underwent OHT, received triple-immunosuppression therapy, were discharged home, and have been followed for a mean of 4.7 years (0.3-13 years). Each patient had an average of 10 ECGs and three 24-hour ECGs. Twenty-six patients had 33 arrhythmias: sinus bradycardia (n = 9), atrial tachycardia (n = 9), ventricular tachycardia (n = 3), and Wenckebach periodicity (n = 6). Sinus bradycardia was treated with theophylline in 8 patients, and 2 required pacemakers. Atrial tachycardias (atrial flutter in 4 patients and atrial ectopic tachycardia in 5) were treated with digoxin, propranolol, or procainamide. Ventricular tachycardia was treated with mexiletine, lidocaine, and amiodarone. There were 65 episodes of rejection, 20 of which were moderate/severe (> or =3B). Only Wenckebach was associated with the presence of either rejection or CAD (p < 0.05). CONCLUSIONS: We noted clinically significant arrhythmias in 38% of the pediatric OHT recipients. Sinus bradycardia, atrial tachyarrhythmias, and ventricular tachycardia occurred with the same frequency. Only new-onset Wenckebach periodicity was noted in the presence of either CAD or rejection. No arrhythmia was of negative predictive value for rejection or CAD. From this data, we suggest that new-onset Wenckebach prompt evaluation for rejection or CAD.

Sirolimus therapy in cardiac transplantation.

Rapamycin powerfully inhibits the progression of antigen-activated T cells through the cell cycle. In animal heart transplantation models, rapamycin therapy has been associated with profound immunosuppressive effects on host humoral and cellular responses. In consequence, further studies have been conducted to evaluate the efficiency of rapamycin in preventing acute heart allograft rejection, treating refractory acute heart allograft rejection, inducing transplantation tolerance, and preventing and treating transplant coronary artery disease. The results of these studies indicated that rapamycin can effectively prevent acute graft rejection and inhibit refractory acute graft rejection in heart transplant recipients by exerting potent immunosuppressive and antiproliferative effects without adversely affecting renal function. This supports the use of rapamycin therapy in heart transplant recipients, especially in those with renal dysfunction, for whom treatment with calcineurin inhibitors is contraindicated. Rapamycin may also halt and even reverse the progression of cardiac allograft vasculopathy, which warrants further clinical trials in humans. Finally, rapamycin may be able to induce transplantation tolerance, thus making it one of the most promising modalities for improving the long-term survival of heart transplant recipients.

When should we consider right ventricular support?

Ventricular assist systems have become an important tool in the surgical management of acute and chronic heart failure. While indications for left ventricular support ar e well established, criteria for right ventricular support are much less defined. This report summarizes current knowledge on the implantation of right ventricular support in clinical settings of isolated right heart failure, biventricular failure, postcardiotomy failure and post-LVAD right heart failure.

Multicenter clinical evaluation of the HeartMate vented electric left ventricular assist system in patients awaiting heart transplantation.

BACKGROUND: Despite advances in heart transplantation and mechanical circulatory support, mortality among transplant candidates remains high. Better ways are needed to ensure the survival of transplant candidates both inside and outside the hospital. METHODS: In a prospective, multicenter clinical trial conducted at 24 centers in the United States, 280 transplant candidates (232 men, 48 women; median age, 55 years; range, 11-72 years) unresponsive to inotropic drugs, intra-aortic balloon counterpulsation, or both, were treated with the HeartMate Vented Electric Left Ventricular Assist System (VE LVAS). A cohort of 48 patients (40 men, 8 women; median age, 50 years; range, 21-67 years) not supported with an LVAS served as a historical control group. Outcomes were measured in terms of laboratory data (hemodynamic, hematologic, and biochemical), adverse events, New York Heart Association functional class, and survival. RESULTS: The VE LVAS-treated and non-VE LVAS-treated (control) groups were similar in terms of age, sex, and distribution of patients by diagnosis (ischemic cardiomyopathy, idiopathic cardiomyopathy, and subacute myocardial infarction). VE LVAS support lasted an average of 112 days (range, < 1-691 days), with 54 patients supported for > 180 days. Mean VE LVAS flow (expressed as pump index) throughout support was 2.8 L x min(-1) x m(-2). Median total bilirubin values decreased from 1.2 mg/dL at baseline to 0.7 mg/dL (P =.0001); median creatinine values decreased from 1.5 mg/dL at baseline to 1.1 mg/dL (P =.0001). VE LVAS-related adverse events included bleeding in 31 patients (11%), infection in 113 (40%), neurologic dysfunction in 14 (5%), and thromboembolic events in 17 (6%). A total of 160 (58%) patients were enrolled in a hospital release program. Twenty-nine percent of the VE LVAS-treated patients (82/280) died before receiving a transplant, compared with 67% of controls (32/48) (P <.001). Conversely, 71% of the VE LVAS-treated patients (198/280) survived: 67% (188/280) ultimately received a heart transplant, and 4% (10/280) had the device removed electively. One-year post-transplant survival of VE LVAS-treated patients was significantly better than that of controls (84% [158/188] vs 63% [10/16]; log rank analysis P =.0197). CONCLUSION: The HeartMate VE LVAS provides adequate hemodynamic support, has an acceptably low incidence of adverse effects, and improves survival in heart transplant candidates both inside and outside the hospital. The studies of the HeartMate LVAS (both pneumatic and electric) for Food and Drug Administration approval are the only studies with a valid control group to show a survival benefit for cardiac transplantation.

Aortic valve implantation in the calf: a successful approach using Heartport cannulation and minimally invasive techniques.

BACKGROUND AND AIM OF THE STUDY: Aortic valve replacement (AVR) for mechanical prosthetic valvular testing has not been performed in calves because of anatomic difficulties, and sheep have traditionally been used in this situation. Hemodynamically, however, the calf constitutes an excellent model due to vigorous myocardial contractility, high stroke volumes and high cardiac output, and so has been used for preclinical evaluation of mechanical assist devices and mechanical valves in the mitral and tricuspid positions, which can be approached with relative surgical ease. Recently, a juvenile bovine model has been used to test a newly developed mechanical valve in the aortic position. METHODS: Ten calves (body weight 91+/-11 kg) underwent AVR with a 21-mm mechanical prosthesis via a small left intercostal thoracotomy with the aid of a Heartport cannulation device. A standard cardiopulmonary bypass (CPB) circuit was used. To circumvent the short bovine ascending aorta and to gain additional space to perform the aortotomy, two aortic cannulas were inserted for arterial-systemic perfusion. Nine calves each received a 21-mm experimental trileaflet aortic central flow valve prosthesis, and one calf received a 21-mm St. Jude Medical prosthesis. RESULTS: Mean CPB duration was 154.2+/-44.4 min, and mean ischemic time 80.1+/-15.9 min. Mean study duration was 42.6+/-53.7 days. Three calves were killed prematurely: two on days 2 and 7 due to complications arising from inadvertent entrapment of the right coronary artery ostium by a suture, and one on day 0 due to an accidental overdose of magnesium. Three calves, all of which had a first-version test valve, were killed electively due to valve malfunction secondary to early valvular thrombosis. Four animals (three with the final version valve and one with a standard valve as a control) survived until killed electively (range: 33-172 days). CONCLUSION: Results indicate that replacement of the native bovine aortic valve with a mechanical prosthesis can be performed safely in calves. Complication-free survival of up to six months can be achieved in the growing calf, provided that the test valve design satisfies minimum hemodynamic and coagulation criteria.

Guillain-Barré syndrome after solid organ transplantation.

BACKGROUND: Neurological complications occur frequently in solid organ transplant recipients. However, the peripheral nerves are usually spared significant toxicity. Guillain Barré syndrome (GBS) is the most common cause of acute neuropathy in adults. Despite numerous reports of GBS in recipients of bone marrow transplants, GBS has rarely been reported in recipients of solid organ transplants. Recent evidence supports the role of the immune system in initiating and perpetuating the ongoing neural damage in this entity. Infectious agents may initiate the immune attack, and the association of GBS with cytomegalovirus (CMV) infection has been studied extensively. METHODS: To alert clinicians to the occurrence of GBS in the latter setting, we report five new cases of GBS after solid organ transplant and summarize five other cases previously reported in the literature. RESULTS: The GBS cases (published and unpublished) have much in common: all the patients were men, most had evidence of active CMV infection at or before the onset of GBS, and all but one developed GBS within 1 year after transplantation (range 1-26 months). CONCLUSION: The association of GBS with cytomegalovirus (CMV) infection in the nontransplant population and evidence of CMV infection in almost all reported cases of GBS in solid organ transplant recipients suggest that CMV may have a role in triggering this illness.

Regression of fibrosis and hypertrophy in failing myocardium following mechanical circulatory support.

BACKGROUND: The cellular and structural changes that occur during long-term ventricular unloading leading to cardiac recovery are poorly understood. However, we have previously demonstrated that left ventricular assist device (LVAD) support leads to a significant decrease in intracardiac tumor necrosis factor-alpha (TNF-alpha), a protein capable of producing hypertrophy and fibrosis. METHODS: To further define the beneficial effects of long-term ventricular unloading on cardiac function, we determined the effect of mechanical circulatory support on fibrosis and hypertrophy in paired myocardial samples of 18 patients with end-stage cardiomyopathy obtained at the time of LVAD implantation and removal. RESULTS: We determined total collagen as well as collagen I and III by a semiquantitative analysis of positive immune-stained areas in pre- and post-LVAD myocardial samples. We found that total collagen content was reduced by 72% (p < 0.001), whereas collagen I content decreased by 66% (p < 0.001) and collagen III content was reduced by 62% (p < 0.001). Next, we determined myocyte size by direct analysis of cellular dimensions utilizing a computerized edge detection system in pre- and post-LVAD myocardial samples. We found that myocyte size decreased in all patients studied for an average reduction of 26% (33.1 +/- 1.32 to 24.4 +/- 1.64 microm, p < 0.001). CONCLUSION: These data demonstrate that long-term mechanical circulatory support significantly reduces collagen content and decreases myocyte size. We suggest that the reduction of fibrosis and hypertrophy observed may in part contribute to the recovery of cardiac function associated with long-term mechanical circulatory support.