Limited Supply Of Donor Hearts Research Articles

Engineered Tissue for Cardiac Regeneration: Current Status and Future Perspectives.

Heart failure (HF) is the leading cause of death worldwide. The most effective HF treatment is heart transplantation, the use of which is restricted by the limited supply of donor hearts. The human pluripotent stem cell (hPSC), including human embryonic stem cell (hESC) and the induced pluripotent stem cells (hiPSC), could be produced in an infinite manner and differentiated into cardiomyocytes (CMs) with high efficiency. The hPSC-CMs have, thus, offered a promising alternative for heart transplant. In this review, we introduce the tissue-engineering technologies for hPSC-CM, including the materials for cell culture and tissue formation, and the delivery means into the heart. The most recent progress in clinical application of hPSC-CMs is also introduced. In addition, the bottleneck limitations and future perspectives for clinical translation are further discussed.

PERCUTANEOUS TREATMENT OF LVAD KINK, A RARE CAUSE OF PUMP FAILURE!

Due to a limited supply of donor hearts, implantation of left ventricular assist device (LVAD) is getting widely accepted. LVAD implantation comes with multiple adverse effects including pump failure. Pump failure due to outflow graft obstruction is an uncommon complication and often requires open

Generation of bioartificial hearts using decellularized scaffolds and mixed cells

BackgroundPatients with end-stage heart failure must receive treatment to recover cardiac function, and the current primary therapy, heart transplantation, is plagued by the limited supply of donor hearts. Bioengineered artificial hearts generated by seeding of cells on decellularized scaffolds have been suggested as an alternative source for transplantation. This study aimed to develop a tissue-engineered heart with lower immunogenicity and functional similarity to a physiological heart that can be used for heart transplantation.Materials and methodsWe used sodium dodecyl sulfate (SDS) to decellularize cardiac tissue to obtain a decellularized scaffold. Mesenchymal stem cells (MSCs) were isolated from rat bone marrow and identified by flow cytometric labeling of their surface markers. At the same time, the multi-directional differentiation of MSCs was analyzed. The MSCs, endothelial cells, and cardiomyocytes were allowed to adhere to the decellularized scaffold during perfusion, and the function of tissue-engineered heart was analyzed by immunohistochemistry and electrocardiogram.ResultsMSCs, isolated from rats differentiated into cardiomyocytes, were seeded along with primary rat cardiomyocytes and endothelial cells onto decellularized rat heart scaffolds. We first confirmed the pluripotency of the MSCs, performed immunostaining against cardiac markers expressed by MSC-derived cardiomyocytes, and completed surface antigen profiling of MSC-derived endothelial cells. After cell seeding and culture, we analyzed the performance of the bioartificial heart by electrocardiography but found that the bioartificial heart exhibited abnormal electrical activity. The results indicated that the tissue-engineered heart lacked some cells necessary for the conduction of electrical current, causing deficient conduction function compared to the normal heart.ConclusionOur study suggests that MSCs derived from rats may be useful in the generation of a bioartificial heart, although technical challenges remain with regard to generating a fully functional bioartificial heart.

Identification of Novel Hemostatic Biomarkers of Adverse Clinical Events in Patients Implanted With a Continuous-Flow Left Ventricular Assist Device.

Heart failure affects over 5 million people in the United States. Its rising prevalence and the limited supply of donor hearts is increasing the use of mechanical cardiac support with the implantation of continuous-flow ventricular assist devices (CF-VAD). Patients with CF-VAD implants are at risk of complications, specifically adverse hemostatic events such as nonsurgical bleeding and thrombosis. Development of a pump thrombus requires clinical intervention and/or surgical replacement significantly increasing the risk of patient morbidity and mortality. Identification of biomarkers for these events could improve current risk assessment models, subsequent treatment, and quality of life prognoses for VAD-implanted patients. The standard means for identifying thrombus in VAD patients is currently limited to monitoring levels of lactate dehydrogenase (>2× upper limit of normal), which is incapable of predicting a future event, but describes the risk of a present thrombus. Surface-enhanced laser desorption ionization time-of-flight mass spectrometry is a technique used to identify biomarkers. In this study, 3 groups of unique peaks were identified in plasma from patients with left ventricular assist devices: 8.1-kDa, 11.7-kDa, and a 15.2-/16.1-kDa pair. Unique correlations were found for each peak, respectively, with microparticles (MPs) and MP procoagulant activity, C-reactive protein, and MP-tissue factor. Furthermore, the use of 8.1-kDa peaks may be able to differentiate thrombotic events from other hemostatic events.

HeartWare left ventricular assist device: Outcome in high risk INTERMACS I patients

Objectives: Because of the increasing number of heart failure patients and the limited supply of donor hearts, a remarkable increase in the number of ventricular assist device (VAD) implantation is observed worldwide. We present our experience with the HeartWare VAD (HeartWare, Framingham, MA) and its clinical outcome in critically sick INTERMACS I patients.

Cost of Ventricular Assist Devices

The societal cost of heart failure (HF) is matched by few other medical conditions. More than 670 000 new cases will be diagnosed this year.1 It commonly affects the aged and is associated with other chronic illnesses. Despite significant improvements in outcomes associated with contemporary medical and electric therapies, HF tends to be a progressive condition with a median survival of only 2 to 3 years after diagnosis.2 In addition, HF is the second most costly condition for Medicare.3 The total expenditure on this disease in the United States is estimated between $20 to $39 billion,1,4,5 which corresponds to 1.5% to 4% of total health care costs.6 Further, the majority of medical financial resources are consumed in the final 2 years of life, a cost estimated at nearly $155 000.7 Patients with advanced HF failing optimal treatments have limited therapeutic options. A small subset may qualify for cardiac transplantation, but stringent candidacy criteria and a limited supply of donor hearts limits its value to the larger HF population. In the past 5 years, improvements in left ventricular assist devices (LVAD) have made this a viable option to bridge a patient to transplant (BTT) or as permanent therapy (Destination Therapy, DT). The inability to define the size of the population that may ultimately be candidates for VAD therapy, particularly as DT, has led to widespread angst about the health care cost implications of this technology. The primary focus of this article is to critically review the available literature on the cost of VADs as well as alternative treatments for advanced HF. Patients with advanced HF have a 1-year survival of only 10% to 25%.8 Initial clinical trials of older pulsatile flow LVADs used as destination therapy demonstrated 1-year survival of …

Single center experience with HeartWare left ventricular assist device

Objectives: Because of the increasing number of heart failure patients and the limited supply of donor hearts, a remarkable increase in the number of ventricular assist device (VAD) implantation is observed world wide. Newer generation VADs have lower risk of fatal adverse events and are also smaller in size. We present our experience with the intrapericardial HeartWare VAD (HeartWare, Framingham, MA) and its clinical outcome.

Individual adapted platelet aggregation therapy in Heartware® patients – durable clopidogrel, acetylsalicylic acid or ticagrelor application

Objectives: Due to a limited supply of donor hearts, ventricular assist devices (VAD) are used as a bridge to transplantation and recovery. Like all artificial blood contacting devices, VAD therapy needs an exact adjustment to the anticoagulation regime, as bleedings and thrombosis are the most common adverse events. Generally, Heartware® patients receive coumarin and anti-platelet agents. The effectiveness of standard anti-platelet therapy (three times a week 75 mg clopidogrel) was analyzed in 49 Heartware® patients.

Defining and Refining Heart Failure Risk Stratification to Optimize Patient Selection for Cardiac Transplantation

VO2, BNP, GFR, RAP, CI, LVEDP, EF, Na, BUN, MR, LVEDD, PCWP, PVCs, VT, QRS, LBBB, COPD, DM, TpnI, alb, CAD, OSA, Hct, RDW, CRT, ICD, HRV—the complex alphabet soup of heart failure risk assessment used to inform clinical decision making, select patient cohorts for trials, and ensure that expensive and supply-limited treatments are utilized in the most effective and equitable manner. Despite the seeming complexity of this task, heart failure clinicians have become facile at integrating multiple distinct variables into a cohesive understanding of risk using baseline patient characteristics, measures of cardiac structure and function, biomarkers, and assessment of functional capacity. The prognostic significance of many risk-associated parameters, such as ejection fraction, ventricular size, and the pathogenesis of heart failure are firmly established. However, recognition of the importance of common comorbidities and the rapidly evolving field of novel biomarkers that represent perturbation of normal biological pathways or markers of early organ damage have reshaped and refined contemporary risk assessment. More recently, larger datasets have facilitated the derivation and validation of multivariable risk-prediction models, such as the Heart Failure Survival Score, the Seattle Heart Failure Model, and the ESCAPE Risk Score.1–3 Article see p 6 In this issue of Circulation: Heart Failure , Kato et al4 re-examine the pivotal role of cardiopulmonary exercise testing in heart failure risk assessment and extend the sentinel work by Mancini that validated VO2 as a potent predictor of short- and intermediate-term mortality.5 Mancini’s original observation that a peak VO2 <14 mL/kg per min was associated with excessive morality led to its …

Invited Commentary

Invited Commentary

Clinical Experience With HeartWare Left Ventricular Assist Device in Patients With End-Stage Heart Failure

The gold standard treatment for end-stage heart failure is cardiac transplantation. Because of the increasing number of heart failure patients and the limited supply of donor hearts, a ventricular assist device (VAD) is used as a bridge to transplantation, recovery, or decision. Newer generation VADs have lower risk of fatal adverse events and are also smaller in size. We present our experience with the intrapericardial HeartWare VAD (HeartWare, Framingham, MA) and its clinical outcome. The clinical outcome of HeartWare VAD implantations for end-stage heart failure patients performed at Harefield Hospital from March 2007 to June 2011 was studied. The study design was a retrospective review of the prospectively collected data. Thirty-four patients with a mean age of 51±10 years were included in this study. Twenty-nine patients were male (85%). The mean duration of mechanical support was 261±64 days. Five patients (15%) were successfully bridged to heart transplantation. The overall mortality was 24% (8 patients). There were 1 case of mechanical device failure (2%) and 3 cases of device failure due to thrombus formation (8%). Postoperative complications included 5 reoperations for bleeding (15%), 12 acute renal failures (36%), 7 respiratory failures (21%), 2 hepatic dysfunctions (6%), 3 neurologic dysfunctions (9%), 7 right-side heart failures (21%), and 5 driveline infections (15%). Although cardiac transplantation remains the gold standard for treatment of end-stage heart failure patients, the HeartWare VAD can be used as a safe alternative with a satisfactory clinical outcome.

Surgery, Mitral Regurgitation, and Heart Failure: The Valves Are All Repairable But the Patients Are Not

Despite advances in medical and surgical therapy, heart failure continues to be a formidable problem. More than 5 million individuals are affected by heart failure in the United States, and it is estimated that 550 000 new cases are diagnosed annually (www.americanheart.org). Advances have been made with medical therapy and cardiac resynchronization, but despite such measures, outcomes remain poor in individuals with advanced heart failure.1 Cardiac transplantation, the ultimate therapy for end-stage heart failure, is plagued by the limited supply of donor hearts and the need for lifelong immunosuppression. It remains, and will always be, a therapy that benefits, at best, only a few thousand individuals each year. Ventricular assist devices are improving but are still limited by problems such as infection and thromboembolism. Although several promising ventricular assist devices are in trial or recently approved, they are only available for those with the most advanced heart failure.2,3 For all intents and purposes the field of mechanical assistance remains, if not in its infancy, in its childhood. Many patients once thought to need transplant can benefit from conventional surgery like bypass and valve repair. Mahon et al4 from the Cleveland Clinic demonstrated equivalent intermediate survival for transplant and conventional surgery in a group of patients initially referred for transplant. We have learned from the ventricular reconstruction literature that many patients with advanced cardiomyopathy can have excellent long-term survival after conventional surgery.5–7 Surgeons who frequently deal with ischemic cardiomyopathy now no longer focus on left ventricular function, but rather the degree of hibernating myocardium that can be revascularized.8 Modern surgical heart failure specialists look for targets of opportunity which, when corrected, will help their patients’ compromised ventricles function more efficiently and potentially reverse remodel. Many heart failure patients can benefit from conventional surgical repairs but it …

Cost–effectiveness of left ventricular-assist devices in end-stage heart failure

With a limited supply of donor hearts, individuals with end-stage heart failure have been offered hope through the use of mechanical devices. Left ventricular-assist devices (LVADs) are a technology designed to work in parallel with the heart but have yet to see widespread use since uncertainty remains as to the cost–effectiveness of this evolving new technology. We have systematically reviewed evidence of cost–effectiveness for LVADs in the bridge-to-transplant and long-term chronic support indications. A total of 18 studies reporting costs were identified. Of these, only four studies reported results in cost–effectiveness terms; two in cost per life-year saved and two in cost per quality-adjusted life-year (QALY). The majority of the other studies were simple cost summations (cost per day or incremental cost) without consideration of efficacy. In the bridge-to-transplant indication, a Danish abstract reported a cost per life-year saved of DKK270k (US$48,000), a UK study reported a cost per QALY of GB£39,787 (US$78,000) and a Canadian study reported a cost per life-year saved of Can$91,332 (US$86,000). Regarding the long-term chronic support indication, the same Canadian study reported a cost per life-year saved of Can$59,842 (US$56,000), whereas a US study reported a cost per QALY of $36,255–60,057. Assuming a willingness to pay the threshold of GB£30,000 (US$59,000) per QALY, there is arguably stronger evidence to support the cost–effectiveness of LVAD technology for the long-term chronic support indication. However, the methodological quality of the majority of studies was poor, as was their generalizability, raising concerns over the reliability of these figures. With the limited and declining availability of donor hearts for transplantation, it appears that the future of this technology is in its use as long-term chronic support. Further analyses should be undertaken, particularly alongside randomized, controlled trials and utilizing second- and third-generation devices.

Anaesthesia for non-cardiac surgery in a patient with Beckerʼs muscular dystrophy supported with a left ventricular assist device

The Section and Board of Anaesthesiology of the European Union of Medical Specialists aims (EUMS/UEMS) at harmonization of training of anaesthesiologists and at improvement of patient care throughout Europe. Pain medicine is considered to be an area of expertise in anaesthesiology although exclusivity is not claimed. The Section and Board has approved both a core syllabus for pain medicine to be part of the specialist training in anaesthesiology and an additional qualification in pain medicine following the completion of a 5 yr basic specialty training in anaesthesiology. These proposals were prepared by the Working Party on Pain Medicine of the Section and Board. It considers a multidisciplinary approach to pain to contribute to quality in care and has taken the initiative to set up a Multidisciplinary Joint Committee on Pain Medicine within the EUMS/UEMS, for which these guidelines define the area of expertise of anaesthesiology.

The impact of cocaine on the donor heart: a case report

With a limited supply of donor hearts in the United States and a prevalent history of cocaine abuse among potential heart donors, the question of transplanting the hearts of cocaine users presents a dilemma to the surgeon. We report a patient who died of the acute right ventricular failure of a heart from a donor with a history of binge drinking and cocaine abuse and who had sustained traumatic brain death. The donor’s serum was positive for cocaine prior to transplantation, and autopsy findings were consistent with cocaine cardiomyopathy. This case illustrates the importance of accurate donor history and toxicologic screen prior to heart transplantation and suggests that hearts of cocaine users should not be transplanted, especially in a setting of traumatic brain death.

How old is too old for heart transplantation?

Heart transplantation is considered the treatment of choice for patients with advanced heart failure. Given the excellent results with transplantation, there has been growing pressure to liberalize eligibility criteria, especially with regard to age. Registry data and early reports have indicated that there may be increased posttransplantation mortality in older patients. A number of single-center reports have shown that survival of older patients may be similar to that of younger patients. The limited supply of donor hearts makes it imperative that careful consideration be given to transplantation results in older recipients and to the overall impact that expanding eligibility criteria for transplantation will have. The limited supply of donor hearts has also led to increased interest in the use of hearts from older donors. This review presents a current perspective on outcomes after heart transplantation in older recipients, use of older donor hearts, and the matching of donor and recipient risk.

HeartMate Left Ventricular Assist Device as Bridge to Heart Transplantation

Background. Because of the limited supply of donor hearts, prospective recipients continue to die while on the waiting list for heart transplantation. Use of long-term mechanical circulatory support devices as a bridge to transplantation may reduce this mortality. However, with the present state of technology, continued clinical evaluation of the various long-term, mechanical circulatory support devices available is mandatory. Methods. Sixteen patients were bridged with the HeartMate left ventricular assist device (LVAD) to heart transplantation for New York Heart Association functional class IV cardiac failure. Twelve pneumatic and six electric devices were used. The mean cardiac index and the mean pulmonary vascular resistance of the patient cohort were 1.7 1 · min −1 · m −2 and 3.1 Wood units, respectively. Results. The mean LVAD support time per transplanted patient was 237 days, with a cumulative LVAD support time of about 7.2 years. Bleeding was the main operative and postoperative complication. Two patients suffered from neurologic complications and there were two major incidents of device malfunction. Twelve patients (75%) now have received a transplant, 3 (19%) are awaiting a transplant, and in 1 patient (6%), the device was explanted after spontaneous left ventricular recovery. Eleven of the 12 patients who received a transplant are alive and doing well. The HeartMate LVAD gave adequate circulatory support over extended periods of time and reversed the vital organ dysfunction. Since the start of the LVAD program, only 1 patient has died on our heart transplantation waiting list, compared to nine deaths in the 2 preceding years. Conclusions. The HeartMate LVAD bridge to heart transplantation can be performed with low post-LVAD implantation and posttransplantation mortality and offers 1- and 2-year posttransplantation actuarial survival rates comparable to those for nonbridged heart transplant recipients.

The Development of Cardiac Transplantation

The history of cardiac transplantation provides an excellent prototype for the development of a therapeutic technique. The first observations on cardiac transplantation were made in animal models in the early 20th century. Surgical problems were solved through a series of technologic advances, and problems associated with immune-mediated rejection were discovered and successfully addressed. By the late 1960s, cardiac transplantation in humans had become feasible. Since the first successful transplantation of a heart in a human in 1967, the management of rejection and infection has steadily progressed, and the long-term outcome after cardiac transplantation has improved dramatically. The success of cardiac transplantation has led to an expansion of the potential recipient pool to include children and adults in the eighth decade of life. Unfortunately, the growth of cardiac transplantation has resulted in an inadequate supply of suitable donor hearts. The limited supply of donor hearts has provided the impetus for further research in xenotopic cardiac transplantation and for the development of implantable circulatory assist devices.