Thyrotoxicosis and dilated cardiomyopathy in developing countries.

BACKGROUND: Thyrotoxicosis is the state of thyroid hormone excess. But, in sub-Saharan Africa (SSA), specifically Northern Ethiopia, scientific evidence about thyrotoxicosis and its cardiac complications like dilated cardiomyopathy is limited. Therefore, this study aimed to explore the thyrotoxicosis presentation and management and identify factors associated with dilated cardiomyopathy in a tertiary hospital in Northern Ethiopia. METHODS: An institution-based cross-sectional study was conducted in Ayder Comprehensive Specialized Hospital from 2017 to 2018. Data from 200 thyrotoxicosis cases were collected using a structured questionnaire. After describing variables, logistic regression was conducted to identify independent predictors of dilated cardiomyopathy. Statistical significance was declared at p < 0.05. RESULTS: Mean age at presentation of thyrotoxicosis was 45 years and females accounted for 89 % of the cases. The most frequent etiology was multinodular toxic goiter (51.5 %). As well, the most common symptoms and signs were palpitation and goiter respectively. Thyroid storm occurred in 6 % of the cases. Out of 89 patients subjected to echocardiography, 35 (39.3 %) of them had dilated cardiomyopathy. And, the odds of dilated cardiomyopathy were higher in patients who had atrial fibrillation (AOR = 15.95, 95 % CI:5.89-38.16, p = 0.001) and tachycardia (AOR = 2.73, 95 % CI:1.04-7.15, p = 0.040). All patients took propylthiouracil and 13.0 % of them experienced its side effects. Concerning ß-blockers, propranolol was the most commonly (78.5 % of the cases) used drug followed by atenolol (15.0 %). Six patients underwent surgery. CONCLUSIONS: In developing countries like Ethiopia, patients with thyrotoxicosis have no access to methimazole which is the first-line anti-thyroid drug. Besides, they greatly suffer from dilated cardiomyopathy (due to late presentation) and side effects of propylthiouracil. Therefore, we recommend that patients should get adequate health information about thyrotoxicosis and anti-thyroid drugs including their side effects. Additionally, hospitals and other concerned bodies should also avail of TSH tests and methimazole at an affordable cost. Furthermore, community awareness about iodized salt and iodine-rich foods should be enhanced.

Cost-effectiveness of implantable ventricular assist devices in older children with stable, inotrope-dependent dilated cardiomyopathy.

BACKGROUND: In a stable, inotrope-dependent pediatric patient with dilated cardiomyopathy, we evaluated the cost-effectiveness of continuous-flow VAD implantation compared to a watchful waiting approach using chronic inotropic therapy. METHODS: We used a state-transition model to estimate the costs and outcomes of 14-year-old (INTERMACS profile 3) patients receiving either VAD or watchful waiting. We measured benefits in terms of lifetime QALYs gained. Model inputs were taken from the literature. We calculated the ICER, or the cost per additional QALY gained, of VADs and performed multiple sensitivity analyses to test how our assumptions influenced the results. RESULTS: Compared to watchful waiting, VADs produce 0.97 more QALYs for an additional $156 639, leading to an ICER of $162 123 per QALY gained from a healthcare perspective. VADs have 17% chance of being cost-effective given a cost-effectiveness threshold of $100 000 per QALY gained. Sensitivity analyses suggest that VADs can be cost-effective if the costs of implantation decrease or if hospitalization costs or mortality among watchful waiting patients is higher. CONCLUSIONS: As a bridge to transplant, VADs provide a health benefit to children who develop stable, inotrope-dependent heart failure, but immediate implantation is not yet a cost-effective strategy compared to watchful waiting based on commonly used cost-effectiveness thresholds. Early VAD support can be cost-effective in sicker patients and if device implantation is cheaper. In complex conditions such as pediatric heart failure, cost-effectiveness should be just one of many factors that inform clinical decision-making.

Generation of two iPSC lines (FAMRCi006-A and FAMRCi006-B) from patient with dilated cardiomyopathy and Emery-Dreifuss muscular dystrophy associated with genetic variant LMNAp.Arg527Pro.

Mutations in LMNA gene are known to cause a broad range of diseases called laminopathies. We have generated two induced pluripotent stem cell lines FAMRCi006-A and FAMRCi006-B from a patient carrying LMNA p. p.Arg527Pro mutation associated with Emery-Dreifuss muscular dystrophy and dilated cardiomyopathy. Patient-specific peripheral blood mononuclear cells were reprogrammed to iPSCs using Sendai virus reprogramming system. Characterization of iPSCs had revealed pluripotency marker expression, normal karyotype, ability to differentiate into three embryonic germ layers. The reported iPSC lines could be a useful tool for in vitro modeling of laminopathies associated with LMNA genetic variants.

Preliminary report on the cost effectiveness of ventricular assist devices.

The aim of the present study was to perform a cost-effectiveness analysis (CEA) of ventricular assist devices (VAD) implantation surgery in the Japanese medical reimbursement system. The study group consisted of thirty-seven patients who had undergone VAD implantation surgery for dilated cardiomyopathy (n = 25; 67.6 %) or hypertrophic cardiomyopathy (n = 4; 10.8 %), and others (n = 8; 21.6 %). Quality-adjusted life years (QALYs) were calculated using the utility score and years of life. Medical reimbursement bills were chosen as cost indices. The observation period was the 12-month period after surgery. Then, the incremental cost-effectiveness ratio was calculated according to the VAD type. In addition, the prognosis after 36 months was estimated on the basis of the results obtained using the Markov chain model. The mean preoperative INTERMACS profile score was 2.35 ± 0.77. Our results showed that the utility score, which indicates the effectiveness of VAD implantation surgery, improved by 0.279 ± 0.188 (ΔQALY, p < 0.05). The cost of VAD implantation surgery was 313,282 ± 25,275 (ΔUS$/year) on the basis of medical reimbursement bills associated with therapeutic interventions. The calculated result of CEA was 364,501 ± 190,599 (ΔUS$/QALY). The improvement in the utility score was greater for implantable versus extracorporeal VADs (0.233 ± 0.534 vs. 0.371 ± 0.238) and ICER was 303,104 (ΔUS$/ΔQALY). Furthermore, when we estimated CEA for 36 months, the expected baseline value was 102,712 (US$/QALY). Therefore, VAD implantation surgery was cost effective considering the disease specificities.

Epidemiology and cost of heart failure in children.

Heart failure in children is a complex disease process, which can occur secondary to a variety of aetiologies, including CHD, cardiomyopathy, or acquired conditions as well. Although the overall incidence of disease is low, the associated morbidity and mortality are high. Mortality may have decreased slightly over the last decade, and this is likely due to our ability to shepherd patients through longer periods of significant morbidity, with lasting effects. Costs of heart failure are significant - on the order of $1 billion annually as hospital charges for inpatient admissions alone. The value, or benefit to patient life and quality of life at this cost, is not well delineated. Further research is needed to optimise not only outcomes for these patients but also the high costs associated with them.

The cost-effectiveness of primary prophylactic implantable defibrillator therapy in patients with ischaemic or non-ischaemic heart disease: a European analysis.

AIMS: It remains unclear whether primary prophylactic implantable cardioverter-defibrillator (ICD) therapy is cost-effective compared with a 'no ICD strategy' in the European health care setting. We performed a cost-effectiveness analysis for a cohort of patients with a left ventricular ejection fraction <40% and ischaemic or non-ischaemic heart disease. METHODS AND RESULTS: A Markov decision analytic model was used to evaluate long-term survival, quality-adjusted life years (QALYs), and lifetime costs for a cohort of patients with a reduced left ventricular function without previous arrhythmias, managed with a prophylactic ICD. Input data on effectiveness were derived from a meta-analysis of primary prophylactic ICD-only therapy randomized trials, from a prospective cohort study of ICD patients, from a health care utilization survey, and from the literature. Input data on costs were derived from a micro-cost analysis. Data on quality-of-life were derived from the literature. Deterministic and probabilistic sensitivity analysis was performed to assess the uncertainty. Probabilistic sensitivity analysis demonstrated a mean lifetime cost of €50 685 ± €4604 and 6.26 ± 0.64 QALYs for patients in the 'no ICD strategy'. Patients in the 'ICD strategy' accumulated €86 759 ± €3343 and an effectiveness of 7.08 ± 0.71 QALYs yielding an incremental cost-effectiveness ratio of €43 993/QALY gained compared with the 'no ICD strategy'. The probability that ICD therapy is cost-effective was 65% at a willingness-to-pay threshold of €80 000/QALY. CONCLUSION: Our results suggest that primary prophylactic ICD therapy in patients with a left ventricular ejection fraction <40% and ischaemic or non-ischaemic heart disease is cost-effective in the European setting.

Cost-effectiveness of implantable cardioverter-defibrillators in children with dilated cardiomyopathy.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) improve survival and are cost-effective in adults with poor left ventricular function. Because of differences in heart failure etiology, sudden death rates, and ICD complication rates, these findings may not be applicable to children. METHODS AND RESULTS: We developed a Markov model to compare typical management of childhood dilated cardiomyopathy with symptomatic heart failure to prophylactic ICD implantation plus typical management. Model costs included costs of outpatient care, medications, complications, and transplantation. Time horizon was up to 20 years from model entry. Total costs were $433,000 (ICD strategy) and $355,000 (typical management). Although quality adjusted survival was greater in the ICD group (6.78 versus 6.43 quality adjusted life-years [QALY]), the incremental cost-utility ratio was $281,622/QALY saved with the ICD strategy. In sensitivity analyses, the ICD strategy cost less than the $100,000/QALY benchmark for cost-effectiveness only when the annual probability of sudden death exceeded 13% or when strong, sustained benefits in quality of life from the ICD were assumed. CONCLUSIONS: Prophylactic ICD use in children with dilated cardiomyopathy, poor ventricular function, and symptomatic heart failure does not appear to be cost-effective. This is likely due to lower sudden death rates in this population.

Role of implantable cardioverter defibrillators in non-ischaemic dilated cardiomyopathy.

Patients with non-ischaemic dilated cardiomyopathy (NICM) are at significant risk of sudden cardiac death. Multiple randomised trials have shown that implantable cardioverter defibrillators (ICDs) reduce mortality in high-risk patients with NICM. However, despite this, the National Institute for Health and Clinical Excellence specifically excluded patients with NICM from its updated guidance concerning ICD use. This lack of guidance poses clear problems for both clinicians managing patients with NICM and those who commission healthcare services. This review aims to help guide clinicians in this difficult, high-cost and high-risk area.

Economic evaluation and survival analysis of immunoglobulin adsorption in patients with idiopathic dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy (DCM) is a life-threatening heart disease and a major reason for heart transplantations. The medical efficacy of immunoadsorption (IA) for DCM patients has been demonstrated in initial clinical studies. This prospective matched-case control study examined 5-year survival rates, direct medical costs, and cost-effectiveness in Germany (n=34) from a health-care system perspective. In a cost-effectiveness analysis costs per life year gained were calculated. Patients treated with IA showed a greater survival rate: 5-year survival rate in the intervention group was 82% vs. 41% in controls. Log rank statistics after Kaplan-Meier analysis of cumulated survival probability were highly significant. Initial intervention costs for IA were found to be 28,400 euro per patient treated. Direct medical costs for a 5-year follow-up were 128,600 euro per patient treated with IA and 75,500 euro in controls. Considering only the actual survival time we calculated annual treatment costs of 24,900 euro in the IA group and 28,900 euro in controls. The cost-effectiveness ratio expressed in costs per life year gained was 34,400 euro. This is the first controlled study to perform 5-year survival analysis and economic evaluation of this new emerging technology for patients with DCM. Although high initial treatment costs for IA are incurred, the significantly better survival rates lead to reasonable costs per live year gained.

Amiodarone versus implantable cardioverter-defibrillator:randomized trial in patients with nonischemic dilated cardiomyopathy and asymptomatic nonsustained ventricular tachycardia--AMIOVIRT.

OBJECTIVES: The purpose of this multicenter randomized trial was to compare total mortality during therapy with amiodarone or an implantable cardioverter-defibrillator (ICD) in patients with nonischemic dilated cardiomyopathy (NIDCM) and nonsustained ventricular tachycardia (NSVT). BACKGROUND: Whether an ICD reduces mortality more than amiodarone in patients with NIDCM and NSVT is unknown. METHODS: One hundred three patients with NIDCM, left ventricular ejection fraction < or =0.35, and asymptomatic NSVT were randomized to receive either amiodarone or an ICD. The primary end point was total mortality. Secondary end points included arrhythmia-free survival, quality of life, and costs. RESULTS: The study was stopped when the prospective stopping rule for futility was reached. The percent of patients surviving at one year (90% vs. 96%) and three years (88% vs. 87%) in the amiodarone and ICD groups, respectively, were not statistically different (p = 0.8). Quality of life was also similar with each therapy (p = NS). There was a trend with amiodarone, as compared to the ICD, towards improved arrhythmia-free survival (p = 0.1) and lower costs during the first year of therapy ($8,879 US dollars vs. $22,039 US dollars, p = 0.1). CONCLUSIONS: Mortality and quality of life in patients with NIDCM and NSVT treated with amiodarone or an ICD are not statistically different. There is a trend towards a more beneficial cost profile and improved arrhythmia-free survival with amiodarone therapy.

[The 6 minute walking test: a cost-effective alternative to spiro-ergometry in patients with chronic heart failure?]. / Der 6-Minuten-Gehtest: Eine kostengünstige Alternative zur Spiroergometrie bei Patienten mit chronischer Herzinsuffizienz?

In contrast to the often debated NYHA classification, the determination of peak oxygen uptake (peak VO2) by cardiopulmonary exercise testing allows an objective assessment of the exercise capacity of patients with congestive heart failure (CHF). However, cardiopulmonary exercise testing is a time consuming and costly diagnostic tool, which requires sophisticated equipment and specially trained personel. Exercise capacity can also be determined by the 6 minute walk test. This test simply measures the distance covered by strong walking on a hallway level within 6 minutes. The 6 minute walk test is a submaximal exercise test, which is associated with much smaller increments in heart rate, blood pressure and plasma catecholamines than cardiopulmonary exercise testing. It is characterized by a very small intraindividual variance. Furthermore, it can be easily performed and, due to low logistic and personal requirements, it is very cost effective. The results of the 6 minute walk test--as well as of cardiopulmonary exercise testing--are influenced by extracardial exercise-limiting disorders, such as pulmonary diseases. Independent from the etiology of CHF, the results of the 6 minute walk test are closely related to peak VO2. In serial exercise testing the distance covered within 6 minutes allow to predict the individual peak VO2. Like peak VO2 the 6 minute walk test has been shown to be a predictor of morbidity and mortality in CHF, with its predictive value being independent from left ventricular ejection fraction and other potential prognostic parameters. In CHF patients a walking distance < 300 m is associated with a one-year-mortality of up to 50%, whereas the one-year-mortality in patients reaching a walking distance > 450 m amounts to only a few percent. In addition, the hospitalization rate of patients reaching a walking distance of < 300 m is several fold higher than in those with a walking distance > or = 450 m. Like cardiopulmonary exercise testing, the 6 minute walk test allows to control the efficiency of specific treatments and to monitor the natural course of the disease. The 6 minute walk test is, thus, a cost effective alternative to cardiopulmonary exercise testing in CHF patients. However, neither the 6 minute walk test alone nor the results of cardiopulmonary exercise testing alone are sufficient for selecting patients, e.g., for cardiac transplantation, as each individual case requires a synopsis of all relevant facts and parameters.

Other primary prevention trials-what is clinically and economically necessary?

There are a number of important primary prevention implantable cardioverter defibrillator (ICD) trials underway which will help define the role of the ICD in high risk patients. High risk is defined by low ejection fraction, although a number of electrical markers (e.g., the signal averaged ECG and invasive electrophysiologic test) are also under evaluation. The trials currently underway (including SCD-HEFT, MADIT II, and the CABG-PATCH substudy) are analyzing patients with either coronary or idiopathic cardiomyopathy who have an EF of 35% or under. Patients are randomized to either ICD therapy or no antiarrhythmic drug therapy. Maximal congestive heart failure therapy with ACE inhibitors and beta blockers is used in both arms of each trial. At the conclusion of these trials we should have a better understanding of which group of presumably high risk patients, if any, will benefit from the ICD. Another group of high risk patients that is being encountered more frequently: those who have a high risk diagnosis. These patients are present in such small numbers that a large randomized trial is impossible. As many of these patients are receiving ICDs, a national registry of firing rates will be helpful.

Metoprolol: a pharmacoeconomic and quality-of-life evaluation of its use in hypertension, post-myocardial infarction and dilated cardiomyopathy.

Metoprolol is a beta 1-selective adrenoceptor antagonist that is widely used in several indications. A recent investigation has also highlighted a potential role for metoprolol in selected patients with idiopathic dilated cardiomyopathy. Pharmacoeconomic and quality-of-life data for metoprolol are limited to the areas of hypertension, post-myocardial infarction and idiopathic dilated cardiomyopathy. In these settings, metoprolol has shown beneficial effects on morbidity and mortality, or closely-related end-points. Controlled release formulations offer the potential to maximise the confirmed antihypertensive benefits of metoprolol by maintaining clinically effective plasma drug concentrations within a narrow range over a 24-hour interval between doses. Recent data support the use of controlled release metoprolol at the low dose of 50 mg/day. Metoprolol is at least as effective as many other antihypertensive drugs, although compared with thiazide diuretics at relatively high doses in the MAPHY (Metoprolol Atherosclerosis Prevention in Hypertensives) trial, metoprolol was associated with a more favourable effect on mortality. Pharmacoeconomic analysis, also based on the MAPHY trial, indicates that metoprolol is more cost effective than high dose thiazide diuretics in middle-aged men with mild to moderate hypertension. However, the advantage for beta-blockade in this trial is not supported by results of other studies, and the applicability of these data to current medical practice using lower thiazide doses is therefore questionable. Quality of life in patients with mild to moderate hypertension did not deteriorate in most investigations with metoprolol. Furthermore, quality of life was similar for controlled release metoprolol and atenolol. With conventional/matrix-based sustained release metoprolol, quality of life was less satisfactory than with lisinopril but was only marginally different from that with diltiazem (at lower than usual therapeutic doses). Nevertheless, these newer agents have no proven beneficial effect on mortality, and further studies are also warranted with controlled release metoprolol 50 mg/day. When administered post-myocardial infarction, conventional metoprolol was associated with significant improvements in quality of life and was cost saving over a 3-year period. Significant improvements in quality of life were also evident for metoprolol-treated patients with idiopathic dilated cardiomyopathy. In summary, available data support the continued extensive usage of metoprolol as treatment for hypertension and as therapy post-myocardial infarction. Pharmacoeconomic data supporting an advantage for metoprolol over high dose thiazides in hypertension needs further assessment in settings reflecting usual general practice approaches to managing patients with hypertension, while differences in quality of life between metoprolol and other antihypertensive agents appear to be marginal.(ABSTRACT TRUNCATED AT 400 WORDS)