Partnership for sustainability in cardiac surgery to address critical rheumatic heart disease in sub-Saharan Africa: the experience from Rwanda.

IMPORTANCE: Rheumatic heart disease (RHD) in the developing world results in critical disability among children, adolescents, and young adults-marginalizing a key population at its peak age of productivity. Few regions in sub-Saharan Africa have independently created an effective strategy to detect and treat streptococcal infection and mitigate its progression to RHD. OBJECTIVE: We describe a unique collaboration, where the Rwanda Ministry of Health, the Rwanda Heart Foundation, and an expatriate humanitarian cardiac surgery program have together leveraged an innovative partnership as a means to expand Rwanda's current capacity to address screening and primary prevention, as well as provide life-saving cardiac surgery for patients with critical RHD. EVIDENCE REVIEW: Interviews with key personnel and review of administrative records were conducted to obtain qualitative and quantitative data on the recruitment of clinical personnel, procurement of equipment, and program finances. The number of surgical cases completed and the resultant clinical outcomes are reviewed. FINDINGS: From 2008 to 2013, six annual visits were completed. A total of 128 prosthetic valves have been implanted in 86 complex patients in New York Heart Association (NYHA) class III or IV heart failure, with excellent clinical outcomes (5 % 30-day mortality). Postoperative complications included a cerebrovascular accident (n = 1) and hemorrhage, requiring reoperation (n = 2). All procedures were performed with participation of local personnel. CONCLUSIONS AND RELEVANCE: This strategy provides a reliable and consistent model of sophisticated specialty care delivery; inclusive of patient-centered cardiac surgery, mentorship, didactics, skill transfer, and investment in a sustainable cardiac program to address critical RHD in sub-Saharan Africa.

Current strategies for myocardial gene delivery.

Existing methods of cardiac gene delivery can be classified by the site of injection, interventional approach and type of cardiac circulation at the time of transfer. General criteria to assess the efficacy of a given delivery method include: global versus regional myocardial transduction, technical complexity and the pathophysiological effects associated with its use, delivery-related collateral expression and the delivery-associated inflammatory and immune response. Direct gene delivery (intramyocardial, endocardial, epicardial) may be useful for therapeutic angiogenesis and for focal arrhythmia therapy but with gene expression which is primarily limited to regions in close proximity to the injection site. An often unappreciated limitation of these techniques is that they are frequently associated with substantial systemic vector delivery. Percutaneous infusion of vector into the coronary arteries is minimally invasive and allows for transgene delivery to the whole myocardium. Unfortunately, efficiency of intracoronary delivery is highly variable and the short residence time of vector within the coronary circulation and significant collateral organ expression limit its clinical potential. Surgical techniques, including the incorporation of cardiopulmonary bypass with isolated cardiac recirculation, represent novel delivery strategies that may potentially overcome these limitations; yet, these techniques are complex with inherent morbidity that must be thoroughly evaluated before safe translation into clinical practice. Characteristics of the optimal technique for gene delivery include low morbidity, increased myocardial transcapillary gradient, extended vector residence time in the coronary circulation and exclusion of residual vector from the systemic circulation after delivery to minimize extracardiac expression and to mitigate a cellular immune response. This article is part of a Special Section entitled "Special Section: Cardiovascular Gene Therapy".

Cardiac Surgery in Low- and Middle-Income Countries: A State-of-the-Art Review.

BACKGROUND: Six billion people in low- and middle-income countries (LMICs) lack timely or ready access to safe and affordable cardiac surgical care when needed, which remains a low priority on the global public health and global surgery agenda. Here, we report the results of a state-of-the-art review of cardiac surgical care in LMICs to highlight the important milestones and current progress as well as the challenges associated with the expansion of sustainable global cardiac surgery for those in need. METHODS: A literature review was performed searching the PubMed/MEDLINE and Google Scholar databases using a combination of cardiac surgery, global health, and LMIC keywords. The Institute for Health Metrics and Evaluation Global Burden of Disease Results Tool was used to assess the global burden of disease related to cardiovascular surgical diseases. RESULTS: High-income countries are estimated to have more than 100 times as many cardiac surgeons per million population compared with low-income countries. There are more than 4000 cardiac centers worldwide, but less than 1 center per 10 million population in LMICs. Approximately 1.5 million cardiac operations are performed globally, of which a disproportionally low number are in LMICs. Despite the high costs associated with cardiac operations, recent data suggest the favorable cost-effectiveness thereof in LMICs. Opportunities arise to sustainably integrate cardiac surgery in holistic health systems strengthening interventions. CONCLUSIONS: Skepticism underlying the need, feasibility, and cost-effectiveness of cardiac surgery in LMICs prevails, but recent advances, successful case studies, and existing data illustrate the potential of expanding cardiac care globally.

Global cardiovascular care: an overview of high-level political commitment.

BACKGROUND: Six billion people worldwide lack access to safe, timely, and affordable cardiac surgical and interventional care when needed. Cardiovascular diseases are the leading cause of mortality and morbidity around the world, and include a significant surgical backlog of rheumatic and congenital heart diseases. Here, we review the political commitment by the WHO, the UN, and the World Bank to build and strengthen healthcare services for cardiovascular diseases, with a particular focus on cardiac surgical and interventional cardiology services around the world. METHODS: A literature search was performed in the WHO, UN, and World Bank Governing Body databases to identify policy documents mentioning curative cardiovascular disease care. The Governing Body documentation, the Institutional Repository for Information Sharing database of the WHO, and the Official Document System of the UN were used. Documents only discussing prevention of cardiovascular diseases were excluded. RESULTS: Fifty-nine unique documents were identified, including 56 from the WHO, 3 from the World Bank, and none from the UN; 12 (20.4%) documents mentioned cardiac surgery, and 6 (10.2%) contained some actionable language to incorporate cardiac surgical services, but none was explicitly dedicated to cardiac surgical services. CONCLUSION: Although growing, high-level political commitment for curative cardiovascular health services remains minimal. Increased awareness is needed to develop comprehensive cardiovascular care that is necessary to mitigate the increasing burden of premature morbidity and mortality from cardiac disease, and to work towards the Sustainable Development Goals and Universal Health Coverage.

Ten-year clinical experience of humanitarian cardiothoracic surgery in Rwanda: Building a platform for ultimate sustainability in a resource-limited setting.

OBJECTIVE: Despite its near complete eradication in resource-rich countries, rheumatic heart disease remains the most common acquired cardiovascular disease in sub-Saharan Africa. With a ratio of physicians/population of 1 per 10,500, including only 4 cardiologists for a population of 11.4 million, Rwanda represents a resource-limited setting lacking the local capacity to detect and treat early cases of strep throat and perform lifesaving operations for advanced rheumatic heart disease. Humanitarian surgical outreach in this region can improve the delivery of cardiovascular care by providing sustainability through mentorship, medical expertise, training, and knowledge transfer, and ultimately the creation of a cardiac center. METHODS: We describe the experience of consecutive annual visits to Rwanda since 2008 and report the outcomes of a collaborative approach to enable sustainable cardiac surgery in the region. The Ferrans and Powers Quality of Life Index tool's Cardiac Version (http://www.uic.edu/orgs/qli/) was administered to assess the postoperative quality of life. RESULTS: Ten visits have been completed, performing 149 open procedures, including 200 valve implantations, New York Heart Association class III or IV, with 4.7% 30-day mortality. All procedures were performed with the participation of local Rwandan personnel, expatriate physicians, nurses, residents, and support staff. Early complications included cerebrovascular accident (n = 4), hemorrhage requiring reoperation (n = 6), and death (n = 7). Quality of life was assessed to further understand challenges encountered after cardiac surgery in this resource-limited setting. Four major domains were considered: health and functioning, social and economic, psychologic/spiritual, and family. The mean total quality of life index was 20.79 ± 4.07 on a scale from 0 to 30, for which higher scores indicated higher quality of life. Women had significantly lower "social and economic" subscores (16.81 ± 4.17) than men (18.64 ± 4.10) (P < .05). Patients who reported receiving their follow-up care in rural health centers also had significantly lower "social and economic" subscores (15.67 ± 3.81) when compared with those receiving follow-up care in urban health facilities (18.28 ± 4.16) (P < .005). Value afforded to family and psychologic factors remained high among all groups. Major postsurgical challenges faced included barriers to follow-up and systemic anticoagulation. CONCLUSIONS: This report represents the first account of a long-term humanitarian effort to develop sustainability in cardiac surgery in a resource-limited setting, Rwanda. With the use of volunteer teams to deliver care, transfer knowledge, and mentor local personnel, the results demonstrate superior outcomes and favorable indices of quality of life. The credibility gained over a decade of effort has created the opportunity for a partnership with Rwanda to establish a dedicated center of cardiac care to assist in mitigating the burden of cardiovascular disease throughout sub-Saharan Africa.

A Century of Surgical Innovation at a Boston Hospital.

BACKGROUND: Innovation has been a central focus of the Department of Surgery at the Brigham and Women's Hospital since its very inception. Here we review examples of innovations originating in this Department and analyze factors that have been critical to successful innovation. Finally, we discuss challenges to sustainability of innovation in this Department. METHODS: Narrative review of the literature, interviews, and personal observations. RESULTS: Examples of innovations reviewed here were each dependent on three critical elements: 1) multidisciplinary collaboration among surgical innovators and individuals outside of surgery who offered complementary skills and expertise, 2) a rich institutional environment that sustained a diverse complement of innovators working in close proximity, and 3) Department Chairmen who facilitated the work of innovators and promoted their contributions, rather than seeking personal prestige or financial gain. Contemporary challenges to sustainability of innovation include the prevailing emphasis on clinical efficiency and on cost containment. CONCLUSION: We have identified factors critical to successful innovation in a Department of Surgery. The relevance of these factors is unlikely to be diminished, even in the changing landscape of modern medicine.

Humanitarian Outreach in Cardiothoracic Surgery: From Setup to Sustainability.

Noncommunicable diseases account for 38 million deaths each year, and approximately 75% of these deaths occur in the developing world. The most common causes include cardiovascular diseases, cancer, respiratory diseases, and diabetes mellitus. Many adults with acquired cardiothoracic disease around the world have limited access to health care. In addition, congenital heart disease is present in approximately 1% of live births and is therefore the most common congenital abnormality. More than one million children in the world are born with congenital heart disease each year, and approximately 90% of these children receive suboptimal care or have no access to care. Furthermore, many children affected by noncongenital cardiac conditions also require prevention, diagnosis, and treatment. Medical and surgical volunteerism can help facilitate improvement in cardiothoracic health care in developing countries. As we move into the future, it is essential for physicians and surgeons to be actively involved in political, economic, and social aspects of society to serve health care interests of the underprivileged around the world. Consequently, in developing countries, a critical need exists to establish an increased number of reputable cardiothoracic programs and to enhance many of the programs that already exist. The optimal strategy is usually based on a long-term educational and technical model of support so that as case volumes increase, quality improves and mortality and morbidity decrease. Humanitarian outreach activities should focus on education and sustainability, and surgical tourism should be limited to those countries that will never have the capability to have free-standing cardiothoracic programs.

Training surgical residents for a career in academic global surgery: a novel training model.

Academic global surgery is a nascent field focused on improving surgical care in resource-poor settings through a broad-based scholarship agenda. Although there is increasing momentum to expand training opportunities in low-resource settings among academic surgical programs, most focus solely on establishing short-term elective rotations rather than fostering research or career development. Given the complex nature of surgical care delivery and programmatic capacity building in the resource-poor settings, many challenges remain before global surgery is accepted as an academic discipline and an established career path. Brigham and Women's Hospital has established a specialized global surgery track within the general surgery residency program to develop academic leaders in this growing area of need and opportunity. Here we describe our experience with the design and development of the program followed by practical applications and lessons learned from our early experiences.

Transjugular approach in valve-in-valve transcatheter mitral valve replacement: direct route to the valve.

With the recent emergence of transcatheter valve replacement, high-risk cases of structural valve deterioration after mitral bioprosthesis can be treated with valve-in-valve transcatheter mitral valve replacement (TMVR). The transapical approach has become the principal access for TMVR, but we report an alternative direct access for TMVR--transjugular transseptal route--in an 81-year-old woman with a degenerated mitral bioprosthesis.

MCARD-mediated gene transfer of GRK2 inhibitor in ovine model of acute myocardial infarction.

ß-Adrenergic receptor (ßAR) dysfunction in acute myocardial infarction (MI) is associated with elevated levels of the G-protein-coupled receptor kinase-2 (GRK2), which plays a key role in heart failure progression. Inhibition of GRK2 via expression of a peptide ßARKct transferred by molecular cardiac surgery with recirculating delivery (MCARD) may be a promising intervention. Five sheep underwent scAAV6-mediated MCARD delivery of ßARKct, and five received no treatment (control). After a 3-week period, the branch of the circumflex artery (OM1) was ligated. Quantitative PCR data showed intense ßARKct expression in the left ventricle (LV). Circumferential fractional shortening was 23.4 ± 7.1 % (baseline) vs. -2.9 ± 5.2 % (p < 0.05) in the control at 10 weeks. In the MCARD-ßARKct group, this parameter was close to baseline. The same trend was observed with LV wall thickening. Cardiac index fully recovered in the MCARD-ßARKct group. LV end-diastolic volume and LV end-diastolic pressure did not differ in both groups. MCARD-mediated ßARKct gene expression results in preservation of regional and global systolic function after acute MI without arresting progressive ventricular remodeling.

Cardiac surgery in Jehovah's Witness patients: ten-year experience.

BACKGROUND: Cardiac surgery in Jehovah's Witnesses poses unique challenges. We have developed a comprehensive multimodality program for these patients and have obtained excellent results. METHODS: Ninety-one Jehovah's Witness patients underwent cardiac surgery between 2000 and 2010. Preoperative, intraoperative, and postoperative considerations in the conduct of bloodless surgery in the Jehovah's Witness population are discussed. Mortality for isolated coronary artery bypass graft surgery and isolated aortic valve replacement was compared with predicted mortality from The Society of Thoracic Surgeons (STS) risk models. Perioperative outcomes were stratified by urgent and elective status of operations. RESULTS: Mean age was 65±12.4 years. Comorbid conditions included hypertension (84.6%), diabetes mellitus (48.4%), previous myocardial infarction (23.1%), chronic lung disease (38.5%), peripheral vascular disease (20.9%), and renal failure (11%). In-hospital mortality was 5.5% (n=5). Mortality for isolated coronary artery bypass graft surgery and isolated aortic valve replacement was 2.2% (observed to expected ratio=1.05, 95% confidence interval: 0 to 3.02) and 5.6% (observed to expected=1.46, 95% confidence interval: 0 to 3.76), respectively. Other complications included reoperation (all=8.8%, cardiac=2.2%), sepsis (2.2%), sternal wound infection (1.1%), transient ischemic attack (1.1%), renal failure requiring dialysis (1.1%), and prolonged ventilation (18.7%). Major complication rates were not significantly different between the elective group and the urgent group. CONCLUSIONS: Bloodless cardiac surgery in Jehovah's Witness patients can be performed with excellent outcomes in both elective and urgent situations. Mortality rates for isolated coronary artery bypass graft surgery and isolated aortic valve replacement are within the expected 95% confidence intervals of STS predicted mortality.

AAV6-ßARKct gene delivery mediated by molecular cardiac surgery with recirculating delivery (MCARD) in sheep results in robust gene expression and increased adrenergic reserve.

OBJECTIVE: Genetic modulation of heart function is a novel therapeutic strategy. We investigated the effect of molecular cardiac surgery with recirculating delivery (MCARD)-mediated carboxyl-terminus of the ß-adrenergic receptor kinase (ßARKct) gene transfer on cardiac mechanoenergetics and ß-adrenoreceptor (ßAR) signaling. METHODS: After baseline measurements, sheep underwent MCARD-mediated delivery of 10(14) genome copies of self-complimentary adeno-associated virus (scAAV6)-ßARKct. Four and 8 weeks after MCARD, mechanoenergetic studies using magnetic resonance imaging were performed. Tissues were analyzed with real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. ßAR density, cyclic adenosine monophosphate levels, and physiologic parameters were evaluated. RESULTS: There was a significant increase in dP/dt(max) at 4 weeks: 1384 ± 76 versus 1772 ± 182 mm Hg/s; and the increase persisted at 8 weeks in response to isoproterenol (P < .05). Similarly, the magnitude of dP/dt(min) increased at both 4 weeks and 8 weeks with isoproterenol stimulation (P < .05). At 8 weeks, potential energy was conserved, whereas in controls there was a decrease in potential energy (P < .05) in response to isoproterenol. RT-qPCR confirmed robustness of ßARKct expression throughout the left ventricle and undetectable expression in extracardiac tissues. Quantitative Western blot data confirmed higher expression of ßARKct in the left ventricle: 0.46 ± 0.05 versus 0.00 in lung and liver (P < .05). Survival was 100% and laboratory parameters of major organ function were within normal limits. CONCLUSIONS: MCARD-mediated ßARKct delivery is safe, results in robust cardiac-specific gene expression, enhances cardiac contractility and lusitropy, increases adrenergic reserve, and improves energy utilization efficiency in a preclinical large animal model.