Images in cardiology: Cardiac sarcoidosis with delayed enhanced MRI.
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Biomedical subjects
Publications and source records attributed to S W Dubrey.
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BACKGROUND: Carvedilol therapy reduces mortality in patients with chronic heart failure. Multi-centre studies suggest a low first dose failure rate and high levels of tolerability to carvedilol. Little is known, however, concerning the eligibility and tolerance to treatment with carvedilol within a district general hospital setting. AIM: To evaluate the eligibility and tolerance of patients with heart failure to carvedilol within a district general hospital. DESIGN: Prospective clinical audit analysis. METHODS: We assessed 100 heart failure patients eligibility to commence carvedilol therapy. In those who satisfied clinical criteria, we evaluated first dose failure rate, target dose achievement, reasons for intolerance, heart rate and blood pressure reduction and resource requirements over a six-month period. RESULTS: Of 100 patients, 16% had contra-indications to commence carvedilol and 22% were receiving a beta-blocker as part of their existing heart failure therapy. Although 62% satisfied eligibility criteria, 1% refused therapy, thus 61% were initiated on carvedilol. The first dose failure rate was 11.5% and 6.6% of patients achieved 'target dose'. Mean heart rate and systolic blood pressure reductions were 15 (SE 1.2)bpm and 17 (SE 1.7) mmHg, respectively. Resource requirements included 155 hours of work-time for a trained heart failure specialist nurse and doctor. CONCLUSIONS: In the general setting, eligible patients appear to display a high first dose failure rate, poor tolerance to higher doses and achievement of a 'target dose' of carvedilol. Responses to adrenergic blockade were similar to previously published data, irrespective of the final tolerated dose, suggesting that the concept of achieving a 'target dose' may not be clinically useful. Guidelines and treatment protocols for heart failure should reflect not only what is considered gold standard, but also what is practical in general hospitals.
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OBJECTIVE: To determine the outcome of heart transplantation for end stage amyloid heart disease in patients treated at a single centre. DESIGN: Records of all patients with amyloid heart disease who underwent heart transplantation were examined to determine survival, graft involvement by amyloid, the course of systemic amyloid disease, and the cause of death. PATIENTS: 10 patients, mean (SD) age 54 (8) years, received transplants in the 13 year period 1984 to 1997. RESULTS: Two patients, both with AL amyloid (primary systemic amyloidosis), died perioperatively. Mean follow up in the remaining eight patients was 49.9 (39.5) months (range 3-116 months). Amyloid deposits in the grafts became evident histologically in five patients with AL amyloid at 5, 11, 12, 28, and 30 months after transplantation, and in one patient with familial amyloid at 60 months. Echocardiography showed no evidence of left ventricular systolic impairment at the time of recurrence. Seven patients died, at 3, 11, 26, 32, 49, 85, and 116 months after transplantation; four of these deaths were related to amyloidosis. Actuarial survival at one and two years was 60% and at five years, 30%. CONCLUSIONS: Heart transplantation for amyloid heart disease remains controversial because of the scarcity of hearts for transplantation, the systemic nature of amyloidosis, and the potential for amyloid deposition in the graft. Postoperative mortality was high (20%), reflecting extracardiac amyloid. Heart transplantation for end stage cardiac amyloidosis is feasible but, without treatment of the underlying process, it is a palliative procedure.
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Mycophenolate mofetil (MMF) is gaining momentum in its use as an immunosuppressant and in the field of heart transplantation because of its efficacy and ease of use without a reported need to monitor plasma levels. We describe a case in which standard dosage of MMF (initially 1.5 g twice daily) produced elevated trough levels of mycophenolic acid (MPA). Although organ rejection was eradicated by the use of MMF, the patient developed severe anemia, which required repeated blood transfusions while the patient was on therapy. This case illustrates the potential value of monitoring MPA concentrations.
A 49 year old man developed intractable heart failure three years after undergoing heart transplantation. Coronary angiography showed no evidence of graft vascular disease. An initial cardiac biopsy identified one episode of rejection which responded to augmented immunosuppressive treatment. The patient became inotrope dependent and has now survived at home for 22 months using an ambulatory delivery system for intravenous adrenaline (epinephrine), without significant complications. There has been a noticeable improvement in symptoms and left ventricular systolic performance, both clinically and as seen through echocardiographic and radiographic examination. This improvement was substantiated by the results of cardiac catheterisation, which showed a return to normal left ventricular filling pressure and cardiac output. The case is noteworthy because this treatment has allowed a patient who otherwise would have been hospital bound to return to the community. With the current shortage of organs, he would have been unlikely to receive a second transplant. The clinical features and outcome, and social, medicolegal, and financial issues are discussed.
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BACKGROUND: Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited disease associated with a mutant form of the protein transthyretin (TTR). It is characterized clinically by the systemic deposition of amyloid fibrils resulting in organ dysfunction and, ultimately, death. The majority of TTR is produced in the liver, and transplantation of the liver has been shown to ameliorate this source of mutant TTR, arresting the progression of this fatal disease. METHODS: Thirteen patients with FAP have undergone successful liver transplant surgery at our center since 1992. The impact of liver transplantation on amyloid-related polyneuropathy, cardiovascular, and gastrointestinal dysfunction is reported in this study. Three patients who died before cardiovascular and neurological follow-up are excluded from the analysis. RESULTS: Ten of 13 patients (77%) remain alive an average of 49 months (range, 17-64 months) after transplantation. Three patients suffered sudden death, with autopsy documentation of amyloid deposits involving the conduction system of the heart. Liver transplantation was performed more quickly, required less blood, and a shorter postoperative hospital stay in these patients, compared with patients with cirrhosis. Neurological and nutritional symptoms improved in the majority of affected patients. Those patients with echocardiographic evidence of ventricular wall and valve thickening before transplantation progressed postoperatively despite neurologic improvement. CONCLUSIONS: Liver transplantation offers the only cure for the genetic defect causing FAP and appears to result in subjective and objective improvement in neurological dysfunction. Patients with preexisting cardiovascular abnormalities progress despite transplantation; therefore, consideration for combined heart-liver transplantation may be warranted in this subset of patients.
We reviewed clinical presentation, investigations, therapy, prognosis and outcome of 232 patients with primary (AL) cardiac amyloidosis. There were 142 men and 90 women. Median age at presentation was 59 years (range 29-85). AL heart disease was unusual both in patients under the age of 40 (3.0%) and in non-Caucasians (6.5%). Fatigue and weakness were the commonest presenting symptoms. Hallmark features of periorbital ecchymoses and macroglossia were present in 12.5% and 27.2%, respectively. AL cardiac amyloidosis was unusual in isolation (3.9%), and most frequently patients had features of multiorgan dysfunction; heavy proteinuria and features of malabsorption predominating in this respect. Heart involvement represents the worst prognostic indicator, with a median survival from diagnosis of 1.08 years, falling to 0.75 years with the onset of heart failure. Current therapeutic procedures appear to prolong survival, with left ventricular wall thickness, mass and ejection fraction on echocardiography and late potentials on signal averaged electrocardiography of use in prognostic stratification. Cardiac involvement from AL amyloidosis is rapidly fatal. It should be suspected in all patients with heart failure who have wall thickening on echo, normal chamber sizes, low EKG voltages and evidence suggesting a multisystem disease.
Syncope is common in AL amyloid heart disease and in almost 1/3 of our patients who experienced syncope, it was precipitated by physiologic stress. Stress-precipitated syncope was associated with a poor prognosis in such patients, both in terms of their median survival of 2 months and was frequently a precursor of sudden cardiac death.
This study was designed to characterize the geometry and function of the right ventricle and its prognostic significance in patients with primary (AL) cardiac amyloidosis. AL amyloidosis is an infiltrative systemic disease that can result in thickening of heart structures and rapidly progressive congestive heart failure due to restrictive ventricular physiology and eventual systolic dysfunction. Thirty-seven patients with AL amyloid heart involvement and 20 normal control subjects were evaluated using 2-dimensional and Doppler echocardiography. Based on the ratio of left-to-right end-diastolic ventricular chamber areas, patients were classified into 2 groups: 25 patients with disproportionate right ventricular (RV) dilation (left ventricular to RV ratio < or = 2) and 12 with a ventricular area ratio > 2. Patients with a relatively dilated right ventricle (ratio < or = 2) had a shorter median survival (4 months) compared with patients with an area ratio > 2 (10 months, p <0.003). Of multiple clinical, echocardiographic, and Doppler features entered into a multifactorial model, a ventricular area ratio < or = 2 remained the only independent predictor of survival. Patients with AL amyloid heart disease represent a heterogeneous population with regard to both prognosis and the relative degree of right to left ventricular dilation. RV dilation in patients with amyloid heart disease appears to be associated with more severe involvement and is associated with a very poor prognosis with a median survival of only 4 months.
BACKGROUND: Familial amyloidosis (FAP) is characterized by the progression of neurologic and cardiac impairment ultimately leading to death within 7 to 15 years after the onset of the disease. Liver transplantation represents the only definitive therapy for this disease and has been performed since 1990. METHODS: To determine the effect of liver transplantation on disease progression, electrocardiography and Doppler echocardiography were performed and blindly analyzed on 11 patients with FAP who were followed 0.8 to 8.6 years before liver transplantation and 0.8 to 4.1 years after liver transplantation. RESULTS; After liver transplantation, five patients showed progression of left ventricular wall thickening with increased left ventricular mass, and three of these five showed a reduction in electrocardiographic voltage despite abolition of the mutant protein from the serum. Of the five patients showing progressive wall thickening, four had the transthyretin variant Glu 42 Gly and one patient had the Ala 36 Pro variant; none of the remaining six patients, all of whom possessed the Val 30 Met variant, showed echocardiographic changes. Although 9 of the 11 patients have shown symptomatic improvement in neurologic symptoms, 1 patient has developed heart failure and a second patient has suffered a sudden cardiac death. CONCLUSIONS: After liver transplantation, patients with FAP should have regular clinical evaluations including electrocardiographic and echocardiographic examinations to look for continued deterioration in heart structure or function.