Cost-effectiveness of homograft heart valve replacement surgery: an introductory study

The clinical effectiveness of heart valve replacement surgery has been well documented. Mechanical and homograft valves are used routinely for replacement of damaged heart valves. Homograft valves are produced in our country but we import the mechanical valves. To our knowledge the cost-effectiveness of homograft valve has not been assessed. The objective of the present study was to compare the cost-effectiveness of homograft valve replacement with mechanical valve replacement surgery. Our samples were selected from 200 patients that underwent homograft and mechanical heart valve replacement surgery in Imam-Khomeini hospital (2000–2005). In each group we enrolled 30 patients. Quality of life was measured using the SF-36 questionnaire and utility was measured in quality-adjusted life years (QALYs). For each group we calculated the price of heart valve and hospitalization charges. Finally the cost-effectiveness of each treatment modalities were summarized as costs per QALYs gained. Forty male and twenty female participated in the study. The mean score of quality of life was 66.06 (SD = 9.22) in homograft group and 57.85 (SD = 11.30) in mechanical group (P < 0.05). The mean QALYs gained in homograft group was 0.67 more than mechanical group. The incremental cost-effectiveness ratio (ICER) revealed a cost savings of 1,067 US$ for each QALY gained in homograft group. Despite limitation of this introductory study, we concluded that homograft valve replacement was more effective and less expensive than mechanical valve. These findings can encourage healthcare managers and policy makers to support the production of homograft valves and allocate more recourse for developing such activities.     

Iranian homograft heart valves: assessment of durability and late outcome

Durability and the rate of complications of homograft heart valves, adjusted for patient-related contributors and surgical techniques, rely mainly on the quality of allografts which in turn are mirrored in the donor characteristics and most importantly recovery and processing procedures. Aimed to assess the quality, a study was conducted to figure out the durability and late outcome following homograft replacement with valved conduits procured by the Iranian Tissue Bank. Retrospectively, the pre-implantation, perioperative and follow-up data of 400 non-consecutive recipients of cryopreserved heart valves (222 pulmonary and 178 aortic) from 2006 to 2015 were collected and analyzed in terms of variables reflecting late outcome including adverse events and durability. In the context of durability, the event of interest was defined as the need for homograft replacement and homograft-related death. The mean follow-up time (SD) of study entrants (male/female ratio, 1.4) was 49.8 (36.3) months. Median age at the time of implantation was 11 years. Total 10-years mortality was 21 % (84/400), including 66.7 % early (30-days mortality: 56/84) and 33.3 % late (28/84). Overall late complication rate was 2 %. Median survival time was 120 months (95 % CI 83.3–156.6). The pulmonary valves appeared to be more durable (P value <0.001) and survival probabilities in small sized grafts were lower (P value 0.008). One-, five-, and ten-year graft survival was 82, 76 and 73 %, respectively. The evidences suggest that the homografts function satisfactory with low rate of late complications; nevertheless, more emphasis should be given to make long-term durability comparable.     

The Changing Pattern of Aortic Valve Repair

The changes and improvements in the surgical treatment of aortic valve disease in 296 patients, who were operated on between 1953 and 1965, are illustrated and discussed in general terms. Several of the early techniques, such as transventricular dilation, insertion of a homograft aortic valve in the descending thoracic aorta, fabric replacement of one cusp or the entire valve, and ice-chip arrest of the heart, are now obsolete. Total replacement with a ball-valve prosthesis or an aortic valve homograft while the coronary arteries are perfused with blood is the currently popular technique. The results of a hemodynamic follow-up study two years after surgery are also included.     

Long-term follow-up studies after homograft replacement of the mitral valve

Follow-up studies on 132 patients who have received fresh aortic homograft replacement of the mitral valve since May 1967 indicate good long-term function of the valve. Clinically the majority of patients are greatly improved and are free from the risks of long-term anticoagulant therapy. Hemodynamic studies performed on 13 patients at 25 to 41 months postoperatively showed a significant decrease in left atrial and pulmonary artery pressures with a small increase in cardiac output. Late deterioration of the homograft produced severe insufficiency in four cases and organic stenosis in two cases. Reasons for isolated deterioration are suggested.     

Stem cell engineering for treatment of heart diseases: Potentials and challenges

Heart disorders are a major health concern worldwide responsible for millions of deaths every year. Among the many disorders of the heart, myocardial infarction, which can lead to the development of congestive heart failure, arrhythmias, or even death, has the most severe social and economic ramifications. Lack of sufficient available donor hearts for heart transplantation, the only currently viable treatment for heart failure other than medical management options (ACE inhibition, beta blockade, use of AICDs, etc.) that improve the survival of patients with heart failure emphasises the need for alternative therapies. One promising alternative replaces cardiac muscle damaged by myocardial infarction with new contractile cardiomyocytes and vessels obtained through stem cell-based regeneration.We report on the state of the art of recovery of cardiac functions by using stem cell engineering. Current research focuses on (a) inducing stem cells into becoming cardiac cells before or after injection into a host, (b) growing replacement heart tissue in vitro, and (c) stimulating the proliferation of the post-mitotic cardiomyocytes in situ. The most promising treatment option for patients is the engineering of new heart tissue that can be implanted into damaged areas. Engineering of cardiac tissue currently employs the use of co-culture of stem cells with scaffold microenvironments engineered to improve tissue survival and enhance differentiation. Growth of heart tissue in vitro using scaffolds, soluble collagen, and cell sheets has unique advantages. To compensate for the loss of ventricular mass and contractility of the injured cardiomyocytes, different stem cell populations have been extensively studied as potential sources of new cells to ameliorate the injured myocardium and eventually restore cardiac function. Unresolved issues including insufficient cell generation survival, growth, and differentiation have led to mixed results in preclinical and clinical studies. Addressing these limitations should ensure the successful production of replacement heart tissue to benefit cardiac patients.     

Urinary bladder matrix promotes site appropriate tissue formation following right ventricle outflow tract repair

The current prevalence and severity of heart defects requiring functional replacement of cardiac tissue pose a serious clinical challenge. Biologic scaffolds are an attractive tissue engineering approach to cardiac repair because they avoid sensitization associated with homograft materials and theoretically possess the potential for growth in similar patterns as surrounding native tissue. Both urinary bladder matrix (UBM) and cardiac ECM (C-ECM) have been previously investigated as scaffolds for cardiac repair with modest success, but have not been compared directly. In other tissue locations, bone marrow derived cells have been shown to play a role in the remodeling process, but this has not been investigated for UBM in the cardiac location, and has never been studied for C-ECM. The objectives of the present study were to compare the effectiveness of an organ-specific C-ECM patch with a commonly used ECM scaffold for myocardial tissue repair of the right ventricle outflow tract (RVOT), and to examine the role of bone marrow derived cells in the remodeling response. A chimeric rat model in which all bone marrow cells express green fluorescent protein (GFP) was generated and used to show the ability of ECM scaffolds derived from the heart and bladder to support cardiac function and cellular growth in the RVOT. The results from this study suggest that urinary bladder matrix may provide a more appropriate substrate for myocardial repair than cardiac derived matrices, as shown by differences in the remodeling responses following implantation, as well as the presence of site appropriate cells and the formation of immature, myocardial tissue.     

老年瓣膜病患者瓣膜置换术术后死亡原因分析

目的:分析老年瓣膜病在瓣膜置换术后的死亡原因,为降低术后死亡率提供科学依据。方法:回顾分析我院以瓣膜置换术治疗的329例老年瓣膜病变患者的资料,对比分析生存患者和死亡患者之间的差异,总结瓣膜置换术后患者死亡的危险因素。结果:心脏瓣膜置换术后死亡率8.51%,单因素分析发现年龄、心功能分级、置换瓣膜数、LAD、LVEF、LVEDD、CPB时间、主动脉阻断时间、置换瓣膜数目与术后死亡有关联(P0.05),Logistic回归分析发现高龄、心功能差、LVEED、CPB为死亡独立危险因素(P0.05)。结论:高龄、心功能差、LVEED过度增大、CPB过长均是瓣膜置换术后的老年瓣膜病患者死亡的独立危险因素,建议临床在诊治中加以警惕。     

What tissue bankers should know about the use of allograft heart valves

Heart valve allografts (usually referred to as ‘homografts’) have been used in cardiac surgery for over 45 years when they were amongst the first valves ever used. Today they remain an important part of valve replacement and reconstructive surgery, particularly in the field of congenital heart disease. There are currently seven tissue banks on the UK and Eire that procure, prepare and store these homografts for surgical implantation, currently providing around 700 grafts per year. This article reviews the history and applications of homografts and compares their performance and outcomes with current prosthetic alternatives. It also describes the processes of valve procurement and storage and describes their clinical applications, hopefully providing tissue bankers with the surgeon’s insight into what is required. Homograft degeneration and the natural history of these tissues is discussed, together with future expectations and developments in homograft valve technology.     

ARTERIAL HOMOGRAFTS—Long Term Observation of Results

In 29 consecutive cases of resection and aortic homograft replacement done between 1954 and 1958, the only surgical mortality occurred 14 days postoperatively and was due to a rupture of the implanted vessel.Seven patients have died (after a survival time averaging 21 months postoperatively) of causes not directly related to the aortic disease or to the operation.Twenty-one patients were still living some three to six and a half years after the implantation procedure—all of them active and showing no clinical evidence of aneurysmal dilatation.Infant thoracic aorta was used for homograft in the femoropopliteal area in three cases. Two of the patients were still living at the time of last report, four and five years after operation, with no evidence of obstruction or dilatation. This is perhaps indicative of the superiority of this material over plastic prosthesis for this purpose.     

Electrolyte disturbances and cardiac failure with hypomagnesaemia in anorexia nervosa.

A 32 year old woman with anorexia nervosa was admitted to hospital with severe hypocalcaemia and hypokalaemia that was refractory to replacement treatment but that responded immediately to an infusion of magnesium. She also had congestive cardiac failure that responded to magnesium replacement. The mild hypomagnesaemia found in this patient was responsible for the refractory hypocalcaemia. Minor deficiencies of magnesium may cause severe hypocalcaemia and hypokalaemia that are refractory to replacement treatment. Prompt replacement of magnesium may prevent prolonged tetany, cardiac arrhythmias, and heart failure.     

Mechanical circulatory support

Currently, almost five million Americans and 23 million people worldwide are living with congestive heart failure (CHF), with 2 million new cases diagnosed each year. The etiology is mostly ischemic, idiopathic, or viral, and more than $36 billion is spent each year on the care of congestive heart failure patients. Treatment of advanced CHF takes three forms: medical therapy, surgical therapy and cardiac replacement. Medical therapy, including inotropes and vasodilators, relieves symptoms by reducing cardiac work and increasing myocardial contractility. This has helped improve quality of life, but mortality remains unaffected. Surgical therapy, including revascularization, ventricular restoration and valve replacement/repair, relieves symptoms and improves function, but in most cases does not stop the underlying disease process from progressing. When conventional medical or surgical therapies are exhausted, cardiac assist or replacement, including ventricular assist device (VAD), heart transplant or a total artificial heart (TAH) may become the only therapeutic options. This article will not discuss the use of extracorporeal membrane oxygenation for cardiac support that is described in an additional article in this issue of Organogenesis.     

An Anthelmintic Drug,Pyrvinium Pamoate,Thwarts Fibrosis and Ameliorates Myocardial Contractile Dysfunction in a Mouse Model of Myocardial Infarction

Metabolic adaptation to limited supplies of oxygen and nutrients plays a pivotal role in health and disease. Heart attack results from insufficient delivery of oxygen and nutrients to the heart, where cardiomyocytes die and cardiac fibroblasts proliferate – the latter causing scar formation, which impedes regeneration and impairs contractility of the heart. We postulated that cardiac fibroblasts survive metabolic stress by adapting their intracellular metabolism to low oxygen and nutrients, and impeding this metabolic adaptation would thwart their survival and facilitate the repair of scarred heart. Herein, we show that an anthelmintic drug, Pyrvinium pamoate, which has been previously shown to compromise cancer cell survival under glucose starvation condition, also disables cardiac fibroblast survival specifically under glucose deficient condition. Furthermore, Pyrvinium pamoate reduces scar formation and improves cardiac contractility in a mouse model of myocardial infarction. As Pyrvinium pamoate is an FDA-approved drug, our results suggest a therapeutic use of this or other related drugs to repair scarred heart and possibly other organs.     

Cardiac differentiation of human pluripotent stem cells

Due to the extremely limited proliferative capacity of adult cardiomyocytes, human embryonic (pluripotent) stem cell derived cardiomyocytes (hESC-CMs) are currently almost the only reliable source of human heart cells which are suited to large-scale production. These cells have the potential for wide-scale application in drug discovery, heart disease research and cell-based heart repair. Embryonic atrial-, ventricular- and nodal-like cardiomyocytes can be obtained from differentiated human embryonic stem cells (hESCs). In recent years, several highly efficient cardiac differentiation protocols have been developed. Significant progress has also been made on understanding cardiac subtype specification, which is the key to reducing the heterogeneity of hESC-CMs, a major obstacle to the utilization of these cells in medical research and future cell-based replacement therapies. Herein we review recent progress in cardiac differentiation of hESCs and cardiac subtype specification, and discuss potential applications in drug screening and cell-based heart regeneration.     

Erythropoietin and retinoic acid,secreted from the epicardium,are required for cardiac myocyte proliferation

We have established a heart slice primary culture, which allows us to mechanically separate distinct cardiac cell populations and assay their relative mitogenic and trophic effects on cardiac myocyte proliferation and survival. Using this system, we have found that a signal(s) from the epicardium, but not the trabeculae and endocardium, is required in embryonic day 10 (E10) chick heart slices for continued cardiac myocyte proliferation and survival. An examination of potential epicardial growth or trophic factors has revealed that blockade of either retinoic acid (RA) or erythopoietin (epo) signaling from the epicardium inhibits cardiac myocyte proliferation and survival. The blockade of cardiac myocyte proliferation following administration of an RA antagonist can be rescued by exogenous epo. Conversely, the blockade of cardiac myocyte proliferation following administration of an anti-epo receptor antisera can be rescued by exogenous RA. Thus, our findings suggest that RA and epo signals work in parallel to support myocardial cell proliferation. In addition, we have found that these factors do not act directly on myocardial cells. Rather, they induce another soluble factor(s) in the epicardium that directly regulates proliferation of cardiac myocytes. We therefore postulate that the epicardium controls normal heart growth in ventricular segments of the embryonic chick heart by secreting a cardiac myocyte mitogen whose expression (or activity) is regulated by both RA and erythropoietin signaling.     

Cardiac toxicity of lung cancer radiotherapy

Radical radiotherapy of lung cancer with dose escalation has been associated with increased tumor control. However, these attempts to continually improve local control through dose escalation, have met mixed results culminating in the findings of the RTOG trial 0617, where the heart dose was associated with a worse overall survival, indicating a significant contribution to radiation-induced cardiac morbidity. It is, therefore, very likely that poorly understood cardiac toxicity may have offset any potential improvement in overall survival derived from dose escalation and may be an obstacle that limits disease control and survival of patients. The manifestations of cardiac toxicity are relatively common after high dose radiotherapy of advanced lung cancers and are independently associated with both heart dose and baseline cardiac risk. Toxicity following the treatment may occur earlier than previously thought and, therefore, heart doses should be minimized. In patients with lung cancer, who not only receive substantial heart dose, but are also older with more comorbidities, all cardiac events have the potential to be clinically significant and life-threatening.Sophisticated radiation treatment planning techniques, charged particle therapy, and modern imaging methods in radiotherapy planning, may lead to reduction of the heart dose, which could potentially improve the clinical outcomes in patients with lung cancer. Efforts should be made to minimize heart radiation exposure whenever possible even at doses lower than those generally recommended. Heart doses should be limited as much as possible.A heart dosimetry as a whole is important for patient outcomes, rather than emphasizing just one parameter.     

同期行冠状动脉旁路移植和心脏瓣膜置换术治疗冠心病合并心脏瓣膜病的临床研究

目的:总结同期行冠状动脉旁路移植(CABG)和心脏瓣膜置换术治疗冠心病合并心脏瓣膜病的临床经验。方法:回顾性分析我院收治的41例接受冠状动脉旁路移植同期行心脏瓣膜置换术的冠心病合并心脏瓣膜病患者的临床资料,对手术方法、主要并发症和术后处理方法进行分析总结。结果:41例患者中,行二次开胸4例(9.76%),应用IABP 2例(4.88%),发生低心排综合征6例(14.63%)、肾功能不全6例(14.63%)、肺功能不全7例(17.07%)、脑合并症1例(2.44%)、胸腔积液4例(9.77%),死亡6例(13.63%),其余患者康复出院。结论:CABG同期行心脏瓣膜置换术治疗冠心病合并心脏瓣膜病的近期疗效满意。术前改善心功能,成熟的手术技术,完全的心肌再血管化,良好的心肌保护,停机困难者尽早应用主动脉内球囊反搏(IABP)及加强术后处理是提高CABG同期行心脏瓣膜置换术疗效的重要措施。     

Growth and differentiation of human embryonic stem cells for cardiac cell replacement therapy

Due to the limited proliferation capacity of cardiac cells, cell replacement therapy has been proposed to restore cardiac function in patients suffering from ischemic heart disease and congestive heart failure. However, this approach is challenged by an insufficient supply of appropriate cells. Because of their apparent indefinite replicative capacity and their cardiac differentiation potential, human embryonic stem cells (hESCs) are potential candidates as sources of cells for cell replacement therapy. Significant progress has been made in improving culture conditions of undifferentiated hESCs, and using various methods, several laboratories have reported the generation of contracting cardiomyocytes from hESCs in vitro. Application of these cardiomyocytes to the clinic, however, still requires substantial experimentation to show that 1) they are functional in vitro; 2) they are efficacious in animal models of cardiac injury and disease; 3) they are safe and effective in human conditions, and 4) a sufficient amount of cardiomyocytes with expected characteristics can be generated in a reproducible manner. Here we review and discuss current findings on growth and differentiation of hESCs, and on characterization, enrichment and transplantation of hESC-derived cardiomyocytes.