Contemporary evaluation and treatment of tricuspid regurgitation.

Valvular heart disease is a global health burden with substantial mortality. The left-sided valvular diseases have been extensively described using the robust treatment strategies available. By contrast, the right-sided diseases, particularly the tricuspid valve (TV) and associated regurgitation, still have much to be delineated. Worsening tricuspid regurgitation (TR) is associated with increased mortality; the non-invasive management is suboptimal; and surgical approaches carry significant risk. With advances in multimodality imaging, 3D echocardiography, improved understanding of TV anatomy, and pathophysiological mechanisms of primary and secondary regurgitation, as well as favorable data with transcatheter therapies, the field of TV management is rapidly evolving. This review aims to highlight pathophysiological mechanisms of TR, describe echocardiographic approaches to diagnosis and TV interrogation, and outline the latest transcatheter developments.

Indispensable Role of Multimodality Imaging in Diagnosis and Management of Coronary Arteriovenous Fistulas.

We describe a patient with right coronary artery to coronary sinus fistula requiring surgical elimination. The decision process in managing fistulas depends on the size, site of origin, and symptoms caused by the fistula. We highlight the pivotal role of multimodality cardiovascular imaging in the diagnosis and management of coronary fistulas. (Level of Difficulty: Intermediate.).

Acute Perimyocarditis Unmasking Anomalous Coronary Artery: Is Treating the Inflammation Enough? Does Surgery Fix All?

We report the case of a patient with anomalous right coronary artery (RCA) unmasked by acute perimyocarditis who continued to have ischemic symptoms despite total resolution of perimyocarditis and required surgical intervention of the anomalous RCA. This case was further complicated by ventricular arrhythmia after surgical repair. Collaboration among different cardiac specialists was essential in this case. (Level of Difficulty: Advanced.).

Surgical repair of tetralogy of Fallot using autologous right atrial appendages: short- to mid-term results.

OBJECTIVES: The prevention of pulmonary insufficiency (PI) is a crucial part of the tetralogy of Fallot repair. Many techniques have been introduced to construct valves from different materials for the right ventricular outflow tract, including the most commonly constructed monocusp valves. We are introducing a new bicuspid valve made intraoperatively using the autologous right atrial appendage (RAA) to prevent PI in these patients. METHODS: The RAA valve was constructed and used in 21 patients with tetralogy of Fallot. The effective preservation of the native valve was impossible in all patients because of either a severe valve deformity or a small annulus. The RAA valve was created after ventricular septal defect closure and right ventricular outflow tract myectomy and was covered with a bovine transannular pericardial patch. The perioperative data were evaluated, and the echocardiography results were assessed immediately after operations and in follow-up with a median of 10.5 months. The data were retrospectively compared with 10 other patients with similar demographic data but with only transannular patches. RESULTS: The mean age of the patients was 13.3 months. No mortality or related morbidity occurred after repair using the RAA valve. The PI severity early after the operation was trivial or no PI in 18 patients, and mild PI was observed in 3 patients, which progressed to moderate PI in one of them in the mean 12-month follow-up period. Fifteen patients had mild or no pulmonary stenosis, while moderate pulmonary stenosis was observed in 6 others. Compared with the other 10 patients with only transannular patches, the RAA valve patients had prolonged operative and clamping times, but no difference in postoperative course and shorter hospital stays. The degree of PI was, of course, significantly less in the RAA valve patients, but pulmonary stenosis was the same. CONCLUSIONS: The RAA valve construction is a safe and effective technique to prevent PI after the tetralogy of Fallot repair, at least in terms of short- and mid-term results. A longer follow-up period is needed to confirm if this new valve can eliminate or significantly delay the need for pulmonary valve replacement in these patients.

Succinate dehydrogenase gene mutations in cardiac paragangliomas.

Pheochromocytomas and paragangliomas are chromaffin cell tumors arising from neuroendocrine cells. At least 1/3 of paragangliomas are related to germline mutations in 1 of 17 genes. Although these tumors can occur throughout the body, cardiac paragangliomas are very rare, accounting for <0.3% of mediastinal tumors. The purpose of this study was to determine the clinical characteristics of patients with cardiac paragangliomas, particularly focusing on their genetic backgrounds. A retrospective chart analysis of 15 patients with cardiac paragangliomas was performed to determine clinical presentation, genetic background, diagnostic workup, and outcomes. The average age at diagnosis was 41.9 years. Typical symptoms of paraganglioma (e.g., hypertension, sweating, palpitations, headache) were reported at initial presentation in 13 patients (86.7%); the remaining 2, as well as 4 symptomatic patients, initially presented with cardiac-specific symptoms (e.g., chest pain, dyspnea). Genetic testing was done in 13 patients (86.7%); 10 (76.9%) were positive for mutations in succinate dehydrogenase (SDHx) subunits B, C, or D. Thirteen patients (86.7%) underwent surgery to remove the paraganglioma with no intraoperative morbidity or mortality; 1 additional patient underwent surgical resection but experienced intraoperative complications after removal of the tumor due to co-morbidities and did not survive. SDHx mutations are known to be associated with mediastinal locations and malignant behavior of paragangliomas. In this report, the investigators extend the locations of predominantly SDHx-related paragangliomas to cardiac tumors. In conclusion, cardiac paragangliomas are frequently associated with underlying SDHx germline mutations, suggesting a need for genetic testing of all patients with this rare tumor.

Cardiac Transplantation in the New Era.

The prevalence of heart failure continues to rise due to the aging population and longer survival of people with conditions that lead to heart failure, eg, hypertension, diabetes, and coronary artery disease. Although medical therapy has had an important impact on survival of patients and improving quality of life, heart transplantation remains the definitive therapy for patients that eventually deteriorate. Since the first successful heart transplantation in 1967, significant improvements have been made regarding donor and recipient selection, surgical techniques, and postoperative care. However, the number of potential organ donors has not changed and the growing number of patients in need for transplantation has resulted an increase in waiting list time, and the need for mechanical support. To overcome this issue, the United Network for Organ Sharing implemented an allocation system to prioritize the sickest patients on the list to receive organs. Despite the careful selection of patients, pretransplant immunological screening, and multidrug immunosuppressive regimens, acute and chronic rejections occur and potentially limit graft and patient survival. Treatment for rejection largely depends on the type of rejection, the presence of hemodynamic compromise, and time after transplantation. The limiting factor for long-term graft survival is allograft vasculopathy, an immune-mediated process causing diffuse narrowing of the coronary arteries. Percutaneous coronary intervention and coronary artery bypass surgery are often not an option for this vasculopathy due to the lack of focal lesions, and retransplantation is the only option in appropriate patients.

Inhibiting CXCL12 blocks fibrocyte migration and differentiation and attenuates bronchiolitis obliterans in a murine heterotopic tracheal transplant model.

OBJECTIVES: Fibrocytes are integral in the development of fibroproliferative disease after lung transplantation. Undifferentiated fibrocytes (CD45+anti-collagen 1+CXCR4+) preferentially traffic by way of the CXCR4/CXCL12 axis and differentiate into smooth muscle actin-producing (CD45+CXCR4+α-smooth muscle actin+) cells. We postulated that an antibody directed against CXCL12 would attenuate fibrocyte migration and fibro-obliteration of heterotopic tracheal transplant allografts. METHODS: A total alloantigenic mismatch murine heterotopic tracheal transplant model of obliterative bronchiolitis was used. The mice were treated with either goat-anti-human CXCL12 F(ab')(2) or goat IgG F(ab')(2). Buffy coat, bone marrow, and trachea allografts were collected and analyzed using flow cytometry. Tracheal luminal obliteration was assessed using hematoxylin-eosin and Direct Red 80 collagen stain. RESULTS: Compared with the controls, the anti-CXCL12-treated mice showed a significant decrease in tracheal allograft fibrocyte populations at 7 and 21 days after transplantation. Bone marrow and buffy coat aspirates showed the same trend at 7 days. In the anti-CXCL12-treated mice, there was a 35% decrease in luminal obliteration at 21 days (65% vs 100% obliterated; interquartile range, 38% vs 10%; P = .010) and decreased luminal collagen deposition at 21 and 28 days after transplantation (P = .042 and P = .012, respectively). CONCLUSIONS: Understanding the role of fibrocytes in airway fibrosis after lung transplantation could lead to a paradigm shift in treatment strategy. Anti-CXCL12 antibody afforded protection against infiltrating fibrocytes and reduced the deterioration of the tracheal allografts. Thus, the CXCR4/CXCL12 axis is a novel target for the treatment of fibro-obliteration after lung transplantation, and the quantification of fibrocyte populations could provide clinicians with a biomarker of fibrosis, allowing individualized drug therapy.

The universal bed model for patient care improves outcome and lowers cost in cardiac surgery.

OBJECTIVE: With the escalating demands to increase the efficiency and decrease the cost, innovations in postoperative cardiac surgical patient care are needed. The universal bed model is an innovative care delivery system that allows patient care to be managed in one setting from postoperation to discharge. We hypothesized that the universal bed model in the context of cardiac surgery would improve outcomes and efficacy. METHODS: A total of 610 consecutive patients were admitted to the universal bed unit and prospectively entered into the Society of Thoracic Surgeons National Cardiac Database. Intensive care unit level of care was determined by acuity and staffing needs. Telemetry was employed from admission to discharge, and multidisciplinary rounds were conducted twice daily. Postoperative outcomes were recorded during hospital stay, and comparisons were made with the Society of Thoracic Surgeons National Cardiac Database using identical variables over the same period of time. RESULTS: Decreased ventilation time, intensive care unit and hospital stay, and reduction in the incidence of atrial fibrillation and infectious complications yielded a financial benefit in the universal bed group compared with the traditional model of admission. Stroke rate and in-hospital mortality were the same compared with regional and national centers. Compared with regional centers, there was an average cost savings between $6200 and $9500 per patient depending on the operation. Patient care satisfaction by independent survey was in the 99th percentile. CONCLUSIONS: The universal bed patient care model allows for expedient and efficacious care as measured by decreased length of intensive care unit and hospital stay, improved postoperative outcomes, patient satisfaction, and cost savings.

Adenosine A2A agonist improves lung function during ex vivo lung perfusion.

BACKGROUND: Ex vivo lung perfusion (EVLP) is a novel technique than can be used to assess and potentially repair marginal lungs that may otherwise be rejected for transplantation. Adenosine has been shown to protect against pulmonary ischemia-reperfusion (IR) injury through its A(2A) receptor. We hypothesized that combining EVLP with adenosine A(2A) receptor agonist treatment would enhance lung functional quality and increase donor lung use. METHODS: Eight bilateral pig lungs were harvested and flushed with cold Perfadex (Vitrolife, Englewood, CO). After 14 hours of storage at 4°C, EVLP was performed for 5 hours on 2 explanted lung groups: (1) control group lungs (n = 4) were perfused with Steen Solution (Vitrolife) and dimethyl sulfoxide and (2) treated group lungs (n = 4) received 10 µM CGS21680, a selective A(2A) receptor agonist, in a Steen solution-primed circuit. Lung histologic features, tissue cytokines, gas analysis, and pulmonary function were compared between groups. RESULTS: Treated lungs demonstrated significantly less edema as reflected by wet-dry weight ratio (6.6 versus 5.2; p < 0.03) and confirmed by histologic examination. In addition, treated lung demonstrated significantly lower levels of interferon-γ (IFN- γ) (45.1 versus 88.5; p < 0.05). Other measured tissue cytokine levels (interleukin [IL]-1ß, IL-6, and IL-8) were lower in the treatment group, but values failed to reach statistical significance. The oxygenation index was improved in the treated group (1.5 versus 2.3; p < 0.01) as was mean airway pressure (10.3 versus 13; p < 0.009). CONCLUSIONS: Combined use of adenosine A(2A) agonist and EVLP significantly attenuates the inflammatory response in acutely injured lungs after IR and enhances pulmonary function. This combination may improve donor lung quality and could increase the donor lung pool for transplantation.

Geographic distance between donor and recipient does not influence outcomes after lung transplantation.

BACKGROUND: The shortage in organ donation is a major limiting factor for patients with end-stage lung disease. Expanding the donor pool would be beneficial. We investigated the importance of geographic distance between the donor and recipient and hypothesized that it would not be a critical determinant of outcomes after lung transplantation. METHODS: We retrospectively reviewed the United Network for Organ Sharing lung transplant database from 2000 to 2005 to allow sufficient time for bronchiolitis obliterans syndrome (BOS) development. Allograft recipients were stratified by geographic distance from their donors (local, regional, and national) and had yearly follow-up. The primary end points were the development of BOS and 1-year and 3-year mortality. Posttransplant outcomes were compared using a multivariable Cox proportional hazard model. Kaplan-Meier curves were compared by log-rank test. RESULTS: Of 6,055 allograft recipients, donors were local in 59%, regional in 19.3%, and national in 21.7%. BOS-free survival did not differ by geographic distance. Geographic distance did not independently predict BOS (hazard ratio, 1.03; 95% confidence interval, 0.96 to 1.10). Similarly, Kaplan-Meier survival curves were not significantly worse for recipients with national donors. Geographic distance did not independently predict 3-year mortality (hazard ratio, 0.95; 95% confidence interval, 0.89 to 1.01). CONCLUSIONS: With appropriate donor selection, moderately long geographic distance (average ischemic time < 6 hours) between the donor and recipient is not associated with the development of BOS or increased death after lung transplantation. By placing less emphasis on distance, more donors could potentially be used to expand the donor pool.

Brucellosis relapse causing prosthetic valve endocarditis and aortic root infective pseudoaneurysm.

We report a previously treated case of brucellosis and aortic root replacement, which became complicated by prosthetic valve endocarditis and a massive aortic root pseudoaneurysm. Preoperative blood and intraoperative pseudoaneurysm wall cultures were positive for Brucella, and the patient was managed successfully with a combination of surgical and medical treatment. Brucella endocarditis is further discussed.

Off-pump surgery for giant right coronary artery aneurysms.

Coronary artery aneurysms larger than 5 cm are exceedingly rare, and a standard treatment for them is lacking. We report two cases of giant right coronary artery aneurysms successfully treated by off-pump resection of the aneurysm and bypass grafting. The controversy surrounding the proper management of such cases is discussed.

Circulating fibrocytes correlate with bronchiolitis obliterans syndrome development after lung transplantation: a novel clinical biomarker.

BACKGROUND: Development of bronchiolitis obliterans syndrome (BOS) after lung transplantation confers increased patient morbidity and mortality. Fibrocytes are circulating bone marrow-derived mesenchymal cell progenitors that influence tissue repair and fibrosis. Fibrocytes have been implicated in chronic pulmonary inflammatory processes. We investigated the correlation of circulating fibrocyte number with BOS development in lung transplant patients. METHODS: We prospectively quantified circulating fibrocyte levels among lung transplant patients. Patients were stratified according to the development of BOS as indicated by predicted forced expiratory volume in 1 second. Fibrocyte activity was analyzed by flow cytometry (cluster of differentiation 45+, collagen 1+) in a blinded manner related to clinical presentation. RESULTS: Thirty-nine patients (61.5% men) underwent double (33.3%), left (25.6%), or right (41.0%) lung transplantation. Average patient age was similar between BOS and non-BOS patients (58.3±3.9 vs 60.3±2.0 years, p=0.67). Chronic obstructive lung disease was the most common indication for lung transplantation (41.0%). Median forced expiratory volume in 1 second was lower among BOS patients compared with non-BOS patients (1.08 vs. 2.18 L/s, p=0.001). Importantly, circulating fibrocyte numbers were increased in BOS patients compared with non-BOS patients (8.91 vs 2.96×10(5) cells/mL, p=0.03) by flow cytometry and were incrementally increased with advancing BOS stage (p=0.02). CONCLUSIONS: Increased circulating fibrocyte levels correlate with the development of BOS after lung transplantation and positively correlate with advancing BOS stage. Quantification of circulating fibrocytes could serve as a novel biomarker and possible therapeutic target for BOS development in lung transplant patients.

Pretreatment strategy with adenosine A2A receptor agonist attenuates reperfusion injury in a preclinical porcine lung transplantation model.

OBJECTIVE: Adenosine A(2A) receptor activation after lung transplantation attenuates ischemia-reperfusion injury by reducing inflammation. However, the effect of adenosine A(2A) receptor activation in donor lungs before transplant remains ill defined. This study compares the efficacy of 3 different treatment strategies for adenosine A(2A) receptor agonist in a clinically relevant porcine lung transplantation model. METHODS: Mature porcine lungs underwent 6 hours of cold ischemia before allotransplantation and 4 hours of reperfusion. Five groups (n = 6/group) were evaluated on the basis of treatment with ATL-1223, a selective adenosine A(2A) receptor agonist: thoracotomy alone (sham), transplant alone (ischemia-reperfusion), donor pretreatment via ATL-1223 bolus (ATL-D), recipient treatment via ATL-1223 infusion (ATL-R), and a combination of both ATL-1223 treatments (ATL-D/R). Lung function and injury were compared. RESULTS: Blood oxygenation was significantly higher among ATL-D, ATL-R, and ATL-D/R groups versus ischemia-reperfusion (392.0 ± 52.5, 428.9 ± 25.5, and 509.4 ± 25.1 vs 77.2 ± 17.0 mm Hg, respectively, P < .001). ATL-1223-treated groups had lower pulmonary artery pressures (ATL-D = 30.5 ± 1.8, ATL-R = 30.2 ± 3.3, and ATL-D/R = 29.3 ± 4.5 vs IR = 45.2 ± 2.1 mm Hg, P < .001) and lower mean airway pressures versus ischemia-reperfusion (ATL-D = 9.1 ± 0.8, ATL-R = 9.1 ± 2.6, and ATL-D/R = 9.6 ± 1.3 vs IR = 21.1 mm Hg, P < .001). Likewise, ATL-1223-treated groups had significantly lower lung wet/dry weight, proinflammatory cytokine expression, and lung injury scores by histology compared with ischemia-reperfusion. All parameters of lung function and injury in ATL-1223-treated groups were similar to sham (all P > .05). CONCLUSIONS: Pretreatment of donor lungs with ATL-1223 was as efficacious as other treatment strategies in protecting against ischemia-reperfusion injury. If necessary, supplemental treatment of recipients with ATL-1223 may provide additional protection. These results support the development of pharmacologic A(2A)R agonists for use in human clinical trials for lung transplantation.