INTRODUCTION: The ever-changing landscape of the US health care system is characterized by innovation and high-level care, yet it remains in a state of crisis. With the system seemingly locked in this dire state of rising costs, it becomes increasingly important to take costs into account when deciding between multiple treatments for a particular disease by undertaking cost-effectiveness analysis (CEA) studies. In the present study, a model for mitral regurgitation (MR)—a cardiac valvular disease for which multiple treatment options exist with varying degrees of effectiveness, making it a suitable candidate for CEA —was developed to determine the cost-effectiveness of the four main treatments of medical therapy (MT), mitral valve repair (MVR), mitral valve replacement with a mechanical valve (MVPm) and mitral valve replacement with a bioprosthetic valve (MVPb). The goal of the present undertaking was to determine the most cost-effective treatment option for a reference patient given patient-specific inputs to test the functionality of the developed model. METHODS: Input values for costs, probabilities of event’s occurrences and quality-adjusted life-year (QALY) estimates for each treatment option were first obtained from databases and relevant literature. These values were then standardized to account for source variability and input into a decision tree (DT) model created specifically for the present analysis that included branches for each of the four potential interventions, from each of which were three potential outcome arms representing the potential endpoints of each treatment: death, alive with complications and alive without complications. The costs, probabilities and QALY –values of each of the four complications of interest in the study—atrial fibrillation (AFib), stroke, congestive heart failure (CHF) and reoperation—were combined and averaged to create a unified endpoint for the alive with complications branches of the DT. Following the development of the model, the relevant cost, probability and utility values were used to run a simulation to test the functionality of the model using values associated with a fictional 65-year-old Medicare-covered patient with chronic MR to act as a representative of a sizable real-life population. The model results were then used to calculate the incremental cost-effectiveness ratio (ICER)—the standard comparison used in CEA—between treatment options to determine the most cost-effective among them. Following this simulation, one-way sensitivity analyses (SA) were conducted to determine the susceptibility of the result to variations in select input values. RESULTS: The probability-weighted costs of MT, MVR, MVPm and MVPb were found to be $40,387, $60,249, $76,293 and $74,320, respectively, with respective probability-weighted QALYs of 4.298, 4.740, 4.428 and 5.119. The calculation of ICERs from these values led to the conclusion that MVPb dominated all other treatments and had an ICER of $41,370/QALY gained over MT, which was treated as the baseline treatment option. The societal willingness-to-pay (WTP) threshold used in the present study ($62,000/QALY gained) was greater than the ICER, indicating that MVPb is a cost-effective solution to society. The results of the SA indicated that variations in mortality rate within the ranges in the relevant literature have significant effect on the cost-effectiveness of the interventions, with roughly a 4.74% increase in mortality for MVPb or a 5.09% decrease in the rate of MT leading MVPb to be considered cost-ineffective. CONCLUSIONS: The simulation study concluded that for the 65-year-old reference case, MVPb was the most cost-effective option and the additional cost to society was deemed less than society’s WTP for the additional health benefit. The successful simulation of the model indicates it may hold real-world potential and be applicable to numerous other situations with varying input values. Further research into more accurate input values for a larger number of variables need to be determined in order to increase the accuracy and maximize the applicability of the present model. In addition, the model will require further complication via the inclusion of an increasing number of variables to allow for a more accurate determination of cost-effectiveness in a wider range of health scenarios. Thus, the current model described here and a further evolved future model hold great potential for use all across health care in order to help contain rising costs plaguing the current health care system in the United States.

Approximately 2% of the population have mitral regurgitation (MR) and many may be not tolerant for mitral valve surgery. The objective of this thesis was to investigate the comparative safety, effectiveness, and cost-effectiveness of percutaneous mitral valve repair using MitraClip System for patients with severe MR. Articles in MEDLINE, Embase, CNKI, and the Cochrane Library published from 1997 to February 2017 were searched for evidence of safety and effectiveness. A systematic review was conducted to address the uncertainty in the safety and effectiveness of MitraClip system in patients with MR. A cost-effectiveness analysis and cost-utility analysis in U.S. settings was conducted to address the uncertainty in health economic evaluation for the MitraClip system. One randomized trial and seven observational studies were included in the systematic review. The pooled data show that 30-day, one-year and two-year survival are similar in MitraClip arm and surgery arm. Residual MR occurs more frequently after MitraClip therapy than surgery, especially in younger patients, functional MR patients, and patients whose LVEF<50%. The risk of 30-day major adverse event from lower odds ratio appeared to be lower in older patients and patients whose LVEF≥50%.For economic evaluation, the base case incremental costs per LY and per QALY were $ 28,217.18 and $27,344.38 US dollars, respectively. Results were most sensitive to alternative assumptions regarding time horizon and long-term survival. Therefore, low quality of evidence due to lack of conclusive RCT data suggested that MitraClip system may provide improvements in MR, patients’ quality of life and survival advantage. It is cost-effective as threshold of $50,000 U.S. dollars per QALY gained for high surgical risk patients. Future RCT designed to reduce confounding and lessen participant attrition, which have adequate sample size, consistent reporting of outcomes, and adequate length of follow-up period will better evaluate the clinical benefits of the MitraClip System. / Thesis / Master of Health Sciences (MSc) / Mitral regurgitation is an abnormal leakage of blood back into the left heart chambers. About 2% of the population who have chronic mitral regurgitation are elderly and are at high risk for surgery. For such patients, a treatment has been proposed that involves a catheter puncturing the skin of the groin and travelling all the way to the affected valve to deploy a device that clips and repairs the valve leaflets (a mitral valve clip). This thesis sought to compare the safety, effectiveness and cost-effectiveness of mitral valve clips with current standards of care in patients at high risk for surgery. To address this question, we searched, critically appraised, and collated existing research evidence. We found that this new treatment was not harmful and may provide a survival advantage. In addition, the approach may be cost-effective when compared to current stand of care in patients at high risk for surgery.

No description available.

Pacemaker implantation can be associated with several complications, including myocardial perforation with or without pericardial effusion, venous thrombosis, vegetations of the tricuspid valve (TV) or pacing lead, and tricuspid regurgitation (TR). The TR is thought to be derived from deformity or perforation of the TV by the pacing lead or secondary to atrioventricular discordance with asynchronous ventricular pacing. Severe TR can be deleterious to the patient because it raises the central venous pressure by increasing the right sided preload. Chronically, the increase in right sided blood volume can result in an increase in the right atrial pressure leading to a decrease in venous return and low cardiac output. Severe TR from leaflet adhesion to the pacemaker lead has not been reported before. With the aging of the population and the expanding use of pacemakers and implantable cardioverter defibrillators (ICD) in clinical practice, this complication may be seen more frequently. We present a patient diagnosed with severe TR, years after his pacemaker implantation. His TR was thought to be caused by adhesion of the tricuspid valve to his pacemaker lead.

Objectives A substantial number of patients with severe tricuspid regurgitation (TR) and congestive heart failure (CHF) are medically managed without undergoing corrective surgery. We sought to assess the characteristics and outcomes of CHF patients who underwent tricuspid valve surgery (TVS), compared with those who did not. Methods Retrospective observational study involving 2556 consecutive patients with severe TR from the Cleveland Clinic Echocardiographic Database. Cardiac transplant patients or those without CHF were excluded. Survival difference between patients who were medically managed versus those who underwent TVS was compared using Kaplan-Meier survival curves. Multivariate analysis was performed to identify variables associated with poor outcomes. Results Among a total of 534 patients with severe TR and CHF, only 55 (10.3%) patients underwent TVS. Among the non-surgical patients (n=479), 30% (n=143) had an identifiable indication for TVS. At 38 months, patients who underwent TVS had better survival than those who were medically managed (62% vs 35%; p<0.001). On multivariate analysis, advancing age (HR: 1.23; 95% CI 1.12 to 1.35 per 10-year increase in age), moderate (HR: 1.39; 95% CI 1.01 to 1.90) and severe (HR: 2; 95% CI 1.40 to 2.80) right ventricular dysfunction were associated with higher mortality. TVS was associated with lower mortality (HR: 0.44; 95% CI 0.27 to 0.71). Conclusion Although corrective TVS is associated with better outcomes in patients with severe TR and CHF, a substantial number of them continue to be medically managed. However, since the reasons for patients not being referred to surgery could not be ascertained, further randomised studies are needed to validate our findings before clinicians can consider surgical referral for these patients. / Revisión por pares

This study evaluates the impact of untreated preoperative severe mitral valve regurgitation (MR) on outcomes after left ventricular assist device (LVAD) implantation. Of the 234 patients who received LVAD therapy in the Heart Center Leipzig during a 6-year period, we selected those who had echocardiographic images of good quality and excluded those who underwent mitral valve replacement prior to or mitral valve repair during LVAD placement. The 128 patients selected were divided into 2 groups: Group A with severe MR (n = 65) and Group B with none to moderate MR (n = 63, 28 with moderate MR). We evaluated transthoracic echocardiography preoperatively [15 (7–28) days before LVAD implantation; median (interquartile range)] and postoperatively up to the last available follow-up [501 (283–848) days after LVAD]. We collected mortality, complications and clinical status indicators of the patient cohort. We observed a significant decrease in the severity of MR after LVAD implantation (severe MR 51% pre- vs 6% post-LVAD implantation, P < 0.001). There was no difference between groups in terms of right heart failure, rate of urgent heart transplantation, pump thrombosis or ventricular arrhythmias. There was no difference in 1-year survival and 3-year survival (87.7% vs 88.4% and 71.8% vs 66.6% for Groups A and B, respectively, P = 0.97). We concluded that preoperative severe MR resolves in the majority of patients early on after LVAD implantation and is not associated with worse clinical outcomes or intermediate-term survival.:Inhaltsverzeichnis Abkürzungsverzeichnis 3 1. Einführung 4 2. Formatierte Publikation 12 3. Zusammenfassung der Arbeit 19 4. Literaturverzeichnis 23 5. Anlagen 28 5.1. Statistical analysis of echocardiographic parameters in follow-up 28 5.2. Statistical Models Used 30 Darstellung des eignen wissenschaftlichen Beitrages 32 Erklärung über die eigenständige Abfassung der Arbeit 33 Lebenslauf 34 Publikationen 37 Danksagung 38

Since living conditions have improved and antibiotics have entered routine use, valvular heart disease (VHD) in the developed world is mostly degenerative in origin, rather than rheumatic. Our population is increasing with age, and therefore the burden of VHD is likely to increase. Despite this, the epidemiology & prognostication in VHD remain poorly understood. A better understanding of the prevalence of VHD in our population, and improved methods of predicting outcomes, are essential if we are to be better equipped to meet the challenges of this new “epidemic”. This thesis aims to improve our knowledge of the prevalence of VHD in the elderly, and the potential benefits of cardiac magnetic resonance (CMR) assessment of patients with clinically significant mitral regurgitation. The prevalence of undiagnosed valvular heart disease in those aged 65 and over is examined in Chapters 2 and 3. Chapter 2 outlines a population-based screening study for VHD in primary care in Oxfordshire, which the author played a central role in establishing. The results show that VHD is extremely common in this cohort, and is strongly associated with increasing age. In chapter 4, the level of anxiety provoked by screening for VHD is looked at; this demonstrates that only a small number of patients have significant anxiety levels, but it is more likely in those with a new diagnosis of VHD, and in women. From Chapter 5 onwards, the thesis focuses on the use of CMR in patients with significant mitral regurgitation (MR). In Chapter 5, the clinical value of quantitative assessment of MR using CMR is examined, showing that it was able to predict progression to symptoms or surgery in these patients. In conclusion, this thesis offers insights into the prevalence of VHD in the elderly population, and looks at the anxiety associated with looking for VHD in this group. The potential clinical benefits of CMR in patients with MR are examined, and quantification of MR with this modality would appear to be of prognostic utility.

Universiẗat, Diss., 2002--Jena.

Background: Accurate assessment of left ventricular (LV) systolic function in chronic severe primary mitral regurgitation (MR) is important as the aim is to consider surgical repair prior to the onset of irreversible LV dysfunction. However this can be difficult to judge as conventional measures of LV function (such as ejection fraction, EF) may remain normal despite impaired LV contractility due to the increased preload of the condition. Advanced echocardiographic techniques, including deformation imaging, appear promising as they are less load dependent. As the earliest symptoms in severe MR are usually exertional, this study aimed to assess markers of LV deformation on exercise in patients with normal resting EF in order to try and identify the earliest signs of LV decompensation.Methods: Transthoracic echocardiography was carried out at rest and on submaximal supine exercise in asymptomatic patients with moderate to severe chronic primary MR and matched controls. Conventional contractile reserve (CR) as measured by EF change on exercise was used to subdivide patients into those with preserved (CR+) and abnormal (CR-) LV function. Myocardial strain and twist were assessed using the speckle tracking technique.Results: MR patients failed to show the normal enhancement in systolic twist on exercise. The onset and peak of untwisting were delayed in MR at rest and normalised on exercise in CR+ but not in CR-. Abnormalities in twist on exercise worsened with increasing resting preload. Longitudinal strain tended to increase normally on exercise in CR+ but not in CR-. Systolic longitudinal strain rate correlated with twist at rest and on exercise, whereas diastolic strain rate correlated with the timing of untwisting on exercise.Conclusion: Abnormalities in myocardial deformation are seen at rest and on exercise in patients with severe MR, particularly in those with decompensated LV function. This may contribute to the development of functional impairment with progressive disease.

Hyperthyroidism may present with signs and symptoms related to dysfunction of a variety of organs. Cardiovascular pathology in hyperthyroidism is common. A few case reports describe isolated right heart failure, tricuspid regurgitation, and pulmonary hypertension as the prominent cardiovascular manifestations of hyperthyroidism. Although most textbooks do not mention hyperthyroidism as a cause of pulmonary hypertension and isolated right heart failure, the literature suggests that some hyperthyroid patients may develop reversible pulmonary hypertension and isolated right heart failure. We report a case of hyperthyroidism presenting with signs and symptoms of isolated right heart failure, tricuspid regurgitation, and pulmonary hypertension, which resolved with treatment of hyperthyroidism.