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Biomedical subjects

Meroula Richardson

Publications and source records attributed to Meroula Richardson.

9 recordsLinked to original sources

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(R), 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 mm(2) (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.

Feasibility Studies↗

Early institution of mechanical support improves outcomes in primary cardiac allograft failure.

BACKGROUND: Primary graft failure (PGF) is the leading cause of early mortality after cardiac transplantation, accounting for 27.1% of deaths within 30 days. PGF is defined as severe dysfunction of the cardiac allograft without any obvious anatomic or immunological cause. The purpose of this study was to analyze our last 9 years of experience with cardiac transplantation to determine predictors of PGF and the influence on survival of our policy of early institution of mechanical circulatory support (MCS) in these patients. METHODS: Data on 214 consecutive cardiac transplants performed at The Alfred Hospital between January 1996 and August 2004 were reviewed. PGF was defined as right or left or biventricular failure manifesting as hypotension (systolic blood pressure <90 mm Hg), low cardiac output (cardiac index <2.0 liter/min/m2 and pulmonary capillary wedge pressure >20 mm Hg after coming off cardiopulmonary bypass despite inotropic support of up to 5 mug/min adrenaline and without any other obvious cause for the graft dysfunction. RESULTS: PGF developed in 51 patients (24%). Significant factors in the development of PGF were long ischemic time, which became significant over 4 hours (odds ratio, 1.43; p = 0.01) and increased donor age (odds ratio, 1.027; p = 0.045). Fifteen patients required mechanical support, and of these, 10 survived to leave hospital. CONCLUSIONS: PGF is the major cause of early mortality after cardiac transplantation. Significant risks for PGF are long allograft ischemic time and increased donor age. Once the patient has survived 30 days, however, the longer-term survival is not influenced by PGF. Our management strategy of early mechanical support has yielded good outcomes in this population with a high risk of early death.

Age Factors↗

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.

Acute Disease↗

Heterotopic heart transplantation: an expanding role in the twenty-first century?

BACKGROUND: Heterotopic heart transplantation was first performed in humans in 1974, the main advantage being the continuing function of the patient's native heart, in the event of life-threatening acute rejection. The effect of cyclosporine on acute rejection saw the heterotopic transplantation technique wane. Our unit revisited heterotopic transplantation in response to a growing number of waiting list patients with high pulmonary artery pressures. We also anticipated an increased cardiac allograft utilization, and improvement of our waiting list times. METHODS: We retrospectively analyzed 151 patients undergoing heart transplantation by our unit between August 1997 and September 2003. Twenty received allografts in the heterotopic position. This cohort was compared with the 131 contemporary orthotopic heart transplant recipients with respect to their outcomes. RESULTS: The indication for transplantation was ischemic cardiomyopathy in 14 (70%) of the heterotopic cohort and 47 (36%) of the orthotopic cohort (p = 0.004), and dilated cardiomyopathy in 3 (15%) and 48 (37%) in the heterotopic and orthotopic groups, respectively (p = 0.06). Heterotopic recipients were significantly older than orthotopic recipients, and they had higher pulmonary artery pressures. The heterotopic donors were also older and the ischemic times were longer. A subgroup analysis was made among those patients who had high pulmonary artery pressures as these groups were better matched. Major morbidity in the heterotopic heart transplantation group consisted of reversible allograft dysfunction in 4 patients, renal dysfunction requiring hemofiltration in 3 patients, profound myopathy in 4 patients, and cerebrovascular events in 2 patients. There were two early deaths in the heterotopic transplant group and eight in the orthotopic group (p = 0.87). Kaplan-Meier survival analysis of survival was performed. CONCLUSIONS: Heterotopic heart transplantation is a viable transplant option for selected high-risk heart transplant recipients in spite of somewhat poorer outcomes.

Acute Kidney Injury↗

Demonstrating time sequence and extent of sustained decrease in native heart ejection fraction after heterotopic transplantation.

BACKGROUND: In this study we investigate the time sequence and extent of the sustained decrease in native heart ejection fraction (EF) after heterotopic heart transplantation (HHTx) when using gated cardiac blood pool scanning (GCBPS) and transthoracic echocardiography (TTE) One case report of 2 patients used post-operative GCBPS and TTE and found a significant deterioration in native heart EF post-operatively over the course of several years. Comparison with pre-operative measurements using these techniques in a series of patients has not been performed previously. METHODS: Thirteen of 16 HHTx patients with adequate pre- and post-operative GCBPS follow-up were included in this study. All patients also underwent TTE post-operatively and the GCBPS results were correlated with the TTE findings. RESULTS: GCBPS demonstrated a marked (21.1 +/- 4.7% vs 10.5 +/- 3.7%, p < 0.0001) decrease in native EF post-HHTx. Spontaneous echo contrast in the native left ventricle and/or poor opening of the mitral/aortic valves was noted at Day 1 in 4 of 5 patients who had a TTE at this stage. No further decline was noted between the first and last post-operative GCBPS (10.8 +/- 3% vs 8.6 +/- 2.1%, p = NS). CONCLUSIONS: A dramatic decrease in native heart EF post-HHTx occurs as early as Day 1 post-transplant. Dissociation of ventricular contraction is the most likely cause. Studies have demonstrated that paced linkage (counterpulsation) between the ventricles results in improved hemodynamics. This may have clinical implications as to the timing of ejection of blood from a left ventricular assist device (LVAD) and for providing the best hemodynamics for the ventricle being assisted and for optimizing its chances of long-term recovery.

Echocardiography↗

Controlled trial of continuous positive airway pressure in obstructive sleep apnea and heart failure.

Obstructive sleep apnea (OSA) is highly prevalent among patients with congestive heart failure (CHF) and may contribute to progression of cardiac dysfunction via hypoxia, elevated sympathetic nervous system activity, and systemic hypertension. Our aim was to assess the long-term effect of OSA treatment with nocturnal continuous positive airway pressure (CPAP) on systolic heart function, sympathetic activity, blood pressure, and quality of life in patients with CHF. Fifty-five patients with CHF and OSA were randomized to 3 months of CPAP or control groups. End points were changes in left ventricular ejection fraction, overnight urinary norepinephrine excretion, blood pressure, and quality of life. Nineteen patients in the CPAP group and 21 control subjects completed the study. Compared with the control group, CPAP treatment was associated with significant improvements in left ventricular ejection fraction (delta 1.5 +/- 1.4% vs. 5.0 +/- 1.0%, respectively, p = 0.04), reductions in overnight urinary norepinephrine excretion (delta 1.6 +/- 3.7 vs. -9.9 +/- 3.6 nmol/mmol creatinine, p = 0.036), and improvements in quality of life. There were no significant changes in systemic blood pressure. In conclusion, treatment of OSA among patients with CHF leads to improvement in cardiac function, sympathetic activity, and quality of life.

Adolescent↗

Impact of sleep apnea on sympathetic nervous system activity in heart failure.

OBJECTIVES: To compare and establish the relevance of the relative degree of sympathetic nervous system activity (SNSA) in groups of patients with congestive heart failure (CHF) and obstructive sleep apnea (OSA), and in a control group. BACKGROUND: Elevated SNSA is a characteristic feature of CHF, as well as of OSA and nonhypercapnic central sleep apnea (CSA). OSA and CSA commonly occur with CHF; however, the relative contribution of apnea-related hypoxemia and sleep fragmentation to the SNSA of patients with CHF is not known. METHODS: This was a prospective, controlled, observational trial in which the overnight urinary norepinephrine (UNE) level, which is a measure of integrated overnight SNSA while asleep, was measured in 15 healthy male volunteers, 15 male OSA patients who did not have CHF, and 90 CHF patients (77 men). CHF patients also had right heart pressure measurements and then were grouped by the presence of sleep apnea. RESULTS: Compared with healthy individuals, the mean (+/- SD) UNE level was significantly elevated in the OSA group and was even further elevated in the CHF group (13.4 +/- 5.6 vs 19.7 +/- 12.3 vs 32.2 +/- 20.2 nmol/mmol creatinine, respectively; p < 0.001 [by analysis of variance]). Within the CHF group, the mean UNE levels were greatest in the CHF-CSA group compared with the CHF-OSA group and the CHF nonapnea group (43.9 +/- 24.1 vs 24.0 +/- 10.8 vs 22.4 +/- 8.9 nmol/mmol creatinine, respectively; p < 0.001). Using a multivariate regression model, the variance of the UNE level in the CHF group was predicted, in descending order, by pulmonary capillary wedge pressure (14% variance), rapid eye movement sleep (8%), and the mean sleep pulse oximetry level (7%). CONCLUSIONS: Overnight SNSA is significantly greater in CHF patients than in OSA patients. Moreover, the hemodynamic severity of CHF contributes to the elevation of SNSA in CHF patients to a greater degree than apnea-related hypoxemia.

Adult↗

Sirolimus allows renal recovery in lung and heart transplant recipients with chronic renal impairment.

BACKGROUND: Until recently, there has been no practical alternative to the use of calcineurin inhibitors (CIs) as primary immunosuppressants in lung transplantation (LTx) and heart transplantation (HTx). Sirolimus (SRL) is a novel powerful immunosuppressant without renal toxicity, a common post-transplant problem associated with CI therapy. METHODS: SRL was used in 20 LTx and 5 HTx recipients >90 days post-transplant, where serious renal impairment was limiting CI dosing. Patients started on 2 to 5 mg/day orally at a median of 1,185 days post-transplant. Dosage adjustments were made according to trough levels, toxicity and perceived efficacy. With SRL initiation, 48% ceased CI therapy and the remainder decreased their dose substantively. RESULTS: After 30 days, 4 of 5 dialyzed patients ceased dialysis and 15 of 20 patients with an elevated serum creatinine (Cr) (mean Cr 0.29 mmol/liter) improved their Cr. The direction of change in Cr at 30 days predicted longer term Cr. The starting Cr did not predict the 30-day or long-term value. There were two bouts of acute and one bout of chronic rejection. There were 35 infectious complications in 16 patients and 24 episodes of potential SRL-related toxicity in 17 patients. These events generally responded to dose reduction or temporary cessation and were level-related. Fifteen recipients presently remain on the drug. None of the 7 deaths could be directly related to toxicity. CONCLUSION: SRL is a useful alternative immunosuppressant, allowing significant CI withdrawal in transplant recipients with renal impairment. Whether the resulting improvement in Cr can be maintained in the long term probably depends on the balance between the extent of acute and chronic renal damage.

Adult↗