Meroula Richardson

Influence of Pulmonary Capillary Wedge Pressure on Central Apnea in Heart Failure

BACKGROUND Recent studies suggest that acute pulmonary congestion induces hyperventilation and that hyperventilation-related hypocapnia leads to ventilatory control instability and central sleep apnea. Whether chronic pulmonary congestion due to congestive heart failure (CHF) is associated with central apnea is unknown. We hypothesized that CHF patients with central apnea would have greater pulmonary capillary wedge pressure (PCWP) than patients without central apnea and that PCWP would correlate with central apnea severity. METHODS AND RESULTS Seventy-five stable CHF patients underwent right heart catheterization and, on the basis of overnight sleep studies, were divided into central apnea (n=33), obstructive apnea (n=20), or nonapnea groups (apnea-hypopnea index [AHI] <5 events per hour). Mean PCWP was significantly greater in the central than in the obstructive and nonapnea groups (mean+/-SEM [range]: 22. 8+/-1.2 [11 to 38] versus 12.3+/-1.2 [4 to 21] versus 11.5+/-1.5 [3 to 28] mm Hg, respectively; P<0.001). Within the central apnea group, PCWP correlated with the frequency and severity of central apnea (AHI: r=0.47, P=0.006) and degree of hypocapnia (PaCO2: r=-0.42, P=0. 017). Intensive medical therapy in 7 patients with initially high PCWP and central apneas reduced both PCWP (29.0+/-2.6 [20 to 38] to 22.0+/-1.8 [17 to 27] mm Hg; P<0.001) and central apnea frequency (AHI) (38.5+/-7.7 [7 to 62] to 18.5+/-5.3 [1 to 31] events per hour; P=0.005). CONCLUSIONS PCWP is elevated in CHF patients with central apneas compared with those with obstructive apnea or without apnea. Moreover, a highly significant relationship exists between PCWP, hypocapnia, and central apnea frequency and severity.

Sirolimus in De Novo Heart Transplant Recipients Reduces Acute Rejection and Prevents Coronary Artery Disease at 2 Years A Randomized Clinical Trial

Background—Sirolimus reduces acute rejection in renal transplant recipients and prevents vasculopathy in nonhuman primates and in-stent restenosis in humans. Its effects on rejection and transplant vasculopathy in human heart transplant recipients are unknown. Methods and Results—In a randomized, open-label study, sirolimus was compared with azathioprine in combination with cyclosporine and steroids administered from the time of cardiac transplantation. We report 6-month rejection rates (primary end point), 12-month safety and efficacy data, and 6- and 24-month graft vasculopathy data in 136 cardiac allograft recipients randomly assigned (2:1) to sirolimus (n=92) or azathioprine (n=44). At 6 months, the proportion of patients with grade 3a or greater acute rejection was 32.4% for sirolimus 3 mg/d (P=0.027), 32.8% for sirolimus 5 mg/d (P=0.013), and 56.8% for azathioprine. Patient survival at 12 months was comparable among groups. Intracoronary ultrasound at 6 weeks, 6 months, and 2 years demonstrated highly significant progression of transplant vasculopathy in azathioprine-treated patients. At 6 months, a highly significant absence of progression in intimal plus medial proliferation and significant protection against luminal encroachment was evident in sirolimus-treated patients, and these effects were sustained at 2 years. Conclusions—Sirolimus use from the time of transplantation approximately halved the number of patients experiencing acute rejection. The measurable development of transplant vasculopathy at 6 months and 2 years in patients receiving azathioprine was not observed in patients receiving sirolimus.

Improved outcomes from a comprehensive management system for heart failure.

Congestive heart failure (CHF) is associated with a high readmission rate after diagnosis. We assessed the ability of a comprehensive management program (CMP) for CHF to reduce readmissions with secondary endpoints of improving quality of life, exercise capacity and targeted drug doses.

Feasibility and short‐term efficacy of percutaneous mitral annular reduction for the therapy of functional mitral regurgitation in patients with heart failure

Background: While functional mitral regurgitation (MR) commonly accompanies heart failure and contributes to heart failure progression, mitral repair in the setting of HF is not routinely practiced because of the attendant significant morbidity and mortality. This limitation has fostered the development of percutaneous devices to reduce MR, and our group has recently reported the short‐ and long‐term effectiveness of a percutaneous mitral annuloplasty device placed in the coronary sinus (Percutaneous Mitral Annuloplasty Device (PMAD), Cardiac Dimensions®, Inc., Kirkland, WA) in reducing MR in experimental animal models of heart failure with associated MR. In this article, we report results of a “first‐in‐human” study of temporary placement of the PMAD device. The aim of this study was to demonstrate the feasibility and safety of temporary deployment of this device in patients with functional MR in association with heart failure. Methods: Five patients undergoing scheduled coronary angiography with heart failure and functional MR (mean age 52 ± 9 [SD] years) were recruited, and four had anatomy suitable for deployment of the device. Transthoracic echocardiography and coronary angiography were performed before and after temporary placement and tensioning of the PMAD via the right internal jugular vein. Results: Temporary deployment of the device resulted in a significant reduction in the septal‐lateral mitral annular dimension from 35.5 ± 4.7 to 32.2 ± 4.6 mm (P = 0.02), with evidence of a reduction in the MR color Doppler area from 98.3 ± 43.6 to 83.3 ± 35.1 mm2 (P = 0.09). There were no complications. Conclusions: This first‐in‐human study of a novel device for percutaneous treatment of functional MR has shown that temporary placement of this device in the coronary sinus/great cardiac vein of patients with heart failure and MR is feasible and safe. Evidence of temporary reduction in MR and a reduction in mitral annular area indicate promise for device effectiveness in chronic implantation.

Diagnostic performance of multisequential cardiac magnetic resonance imaging in acute cardiac allograft rejection

We evaluated cardiac magnetic resonance imaging (CMR) as a non‐invasive test for cardiac allograft rejection.

Bridge to recovery with a left ventricular assist device for fulminant acute myocarditis

Acute fulminant myocarditis frequently causes circulatory collapse that is resistant to conventional therapy. We describe a case in which a patient with histologically confirmed viral myocarditis was supported by a left ventricular assist device (LVAD) as a bridge to recovery. The LVAD was successfully weaned 3 weeks later.

Prolonged cardiac allograft ischemic time – no impact on long‐term survival but at what cost?

Abstract:  Introduction:  The aim of this paper was to review the outcomes of cardiac transplantation with regards to short‐ and long‐term survival, focusing particularly on patients who receive organs with long ischemic times and the resource utilization necessary to support such patients through their postoperative period.

Post–cardiac transplantation gout: incidence of therapeutic complications

OBJECTIVE To study the clinical impact of gout treatment following cardiac transplantation. METHODS We performed an audit of all cardiac transplant recipients of the Alfred Hospital before August 1998 who lived in Victoria. RESULTS We studied 225 patients (81% men), with a mean post-transplant follow-up of 50.8 months (SD 36). Forty-three (19%) had pre-transplant gout, 19 recurring post-transplantation. Twenty-three patients developed gout de novo. Of the 24 patients who received allopurinol, 6 developed pancytopenia and required hospitalization. Fourteen received a change in immunosuppression: in 5 patients following pancytopenia, and in 9 to enable safe use of allopurinol. Thirty-two patients received colchicine; 5 developed neuromyopathy. Impaired renal function, diuretic use, and hypertension were more common in this sub-group. Non-steroidal anti-inflammatory agents, used in 16 patients, caused serious complications in 1 patient (life-threatening peptic ulceration and hemorrhage, precipitating dialysis-dependent chronic renal failure). CONCLUSIONS Cardiac transplant recipients, when treated for gout, are at high risk of therapeutic complications. Thus, gout treatment significantly affects care, health, and immunosuppression of these patients.

Recovery From Anthracycline Cardiomyopathy After Long-term Support With a Continuous Flow Left Ventricular Assist Device

We report the clinical course of a 16-year-old girl in remission from non-Hodgkins lymphoma who presented in cardiogenic shock due to a severe anthracycline cardiomyopathy. The patient was initially stabilized using central extracorporeal membrane oxygenation support, followed by conversion to a left ventricular assist device. Unexpected evidence of cardiac recovery 9 months after implant enabled device weaning during a 3-month period, culminating in successful device explantation 1 year after implant. The patient survives 18 months after explant in New York Heart Association class I, on conventional heart failure medical management and metabolic therapy.

A Bioavailability Study of Cyclosporine: Comparison of Neoral Versus Cysporin in Stable Heart Transplant Recipients

BACKGROUND Cyclosporine in the form of a microemulsion (Neoral) has been the cornerstone of the majority of immunosuppression regimes in thoracic organ transplantation. Cysporin, an alternative form of cyclosporine, is now available. Although bioavailability has been studied in healthy volunteers and stable renal transplant recipients, there are no bioequivalence data currently available for the population of thoracic organ transplant recipients. This randomized, 2-arm, crossover, open-label study compares the pharmacokinetic profiles of two formulations of cyclosporine (Neoral and Cysporin) in stable heart transplant patients. METHODS The pharmacokinetics of Neoral and Cysporin were assessed on 2 study days in 16 stable heart transplant recipients already receiving Neoral, who were at least 15 months post-transplant and had not undergone dose adjustments of Neoral for the previous 3 months. Participants were randomized to receive one study drug for at least 2 weeks with crossover to the other arm for a further 2 weeks. Drug levels were measured from blood samples obtained on the study day at the end of each phase at baseline (pre-dose) and 1, 1.5, 2, 2.5, 3, 4, 6 and 8 hours post-dose. RESULTS The two formulations of cyclosporine were not found to be bioequivalent for C(max). There was less cyclosporine absorbed with Cysporin than with Neoral (ratio 1.31, 90% confidence intervals 1.20 to 1.42) and, although statistically bioequivalent for area under the curve (AUC), a reduction was observed with the new formulation (ratio 1.17, 90% confidence intervals 1.1 to 1.23). The best fit with AUC was observed at 6 hours post-dose for Neoral and 1.5 hours for Cysporin, not the 2 hours post-dose used clinically. CONCLUSIONS This study suggests that Cysporin may not be clinically bioequivalent to Neoral in heart transplant recipients. The clinical implications of this observation require further exploration in a larger patient cohort.