A Multi-Mode System for Myocardial Functional and Physiological Assessment during Ex Situ Heart Perfusion.

Ex situ heart perfusion (ESHP) has proven to be an important and valuable step toward better preservation of donor hearts for heart transplantation. Currently, few ESHP systems allow for a convenient functional and physiological evaluation of the heart. We sought to establish a simple system that provides functional and physiological assessment of the heart during ESHP. The ESHP circuit consists of an oxygenator, a heart-lung machine, a heater-cooler unit, an anesthesia gas blender, and a collection funnel. Female Yorkshire pig hearts (n = 10) had del Nido cardioplegia (4°C) administered, excised, and attached to the perfusion system. Hearts were perfused retrogradely into the aortic root for 2 hours before converting the system to an isovolumic mode or a working mode for further 2 hours. Blood samples were analyzed to measure metabolic parameters. During the isovolumic mode (n = 5), a balloon inserted in the left ventricular (LV) cavity was inflated so that an end-diastolic pressure of 6-8 mmHg was reached. During the working mode (n = 5), perfusion in the aortic root was redirected into left atrium (LA) using a compliance chamber which maintained an LA pressure of 6-8 mmHg. Another compliance chamber was used to provide an afterload of 40-50 mmHg. Hemodynamic and metabolic conditions remained stable and consistent for a period of 4 hours of ESHP in both isovolumic mode (LV developed pressure: 101.0 ± 3.5 vs. 99.7 ± 6.8 mmHg, p = .979, at 2 and 4 hours, respectively) and working mode (LV developed pressure: 91.0 ± 2.6 vs. 90.7 ± 2.5 mmHg, p = .942, at 2 and 4 hours, respectively). The present study proposed a novel ESHP system that enables comprehensive functional and metabolic assessment of large mammalian hearts. This system allowed for stable myocardial function for up to 4 hours of perfusion, which would offer great potential for the development of translational therapeutic protocols to improve dysfunctional donated hearts.

Predictors of Postoperative Rehabilitation Therapy Following Congenital Heart Surgery.

BACKGROUND: Patients with congenital heart disease are at risk of motor, cognitive, speech, and feeding difficulties after cardiac surgery. Rehabilitation therapy could improve functional outcomes in this population if applied in the acute postcardiac surgical in-hospital stay. However, information on the types of acute postcardiac surgery therapy needs in children is scarce. Our goal was to describe rehabilitation therapy following congenital heart surgery and pre/intraoperative factors associated with need for therapy. METHODS AND RESULTS: This is a retrospective cohort study of patients <18 years undergoing heart surgery at our center from January 1, 2013 to January 31, 2015. Demographic, and pre-, intra-, and postoperative clinical and rehabilitation therapy (physical, occupational, speech, feeding therapy, and neurodevelopment intervention) data were collected. Need for rehabilitation therapy in the acute postoperative period, particularly following palliative repair, was the outcome variable in a multivariable logistic regression model to identify independent pre- and intraoperative factors associated with therapy. A total of 586 out of 1415 (41%) subjects received rehabilitation therapy postsurgery. Certain subgroups had increased rehabilitation therapy use such as neonates (80%). On multivariable analysis, palliative repair, prematurity, genetic syndrome, presurgical hospital stay of more than 1 day, and prolonged cardiopulmonary bypass time were independently associated with rehabilitation therapy. CONCLUSIONS: Nearly half of patients who underwent post-congenital heart surgery received rehabilitation therapy. Frequency of use and types of therapy vary according to patient characteristics; however, certain pre- and intraoperative factors are associated with need for rehabilitation therapy, and may aid decision-making for appropriate resource allocation.

Outcomes differ in patients who undergo immediate intraoperative revision versus patients with delayed postoperative revision of residual lesions in congenital heart operations.

OBJECTIVES: In a previous study of infants less than 6 month old, we found that delayed revision of residual lesions resulted in worse patient outcomes compared with intraoperative revision. We explored a larger cohort to determine if this finding persisted. METHODS: A prospective cohort followed from index surgery to discharge from January 2011 to September 2013 were divided into 4 groups: (1) intraoperative revisions (IO) of residual lesions, (2) delayed postoperative revision (PO) of residual lesions during the same hospital stay, (3) both intraoperative and delayed (BOTH) revision of residual lesions, (4) no intraoperative or postoperative revision (NO). Linear and logistic regression analyses were used to compare outcomes of postoperative hospital length of stay, postoperative adverse events (AE), hospital costs, and mortality, after adjusting for age, prematurity, presence of extracardiac anomalies, and RACHS-1 (Risk Adjustment for Congenital Heart Surgery-1) risk category known to affect outcomes. RESULTS: Of the 2427 patients discharged after a congenital cardiac operation, 1886 were eligible for this study after exclusion of adults, procedures performed off cardiopulmonary bypass, and transplants and assist devices. On multivariable modeling adjusting for other significant patient factors, the NO group fared better than the other 3 groups. The IO group had significantly lower postoperative length of stay, AE rate, and hospital costs compared with the PO and BOTH groups, but showed no significant differences in mortality. CONCLUSIONS: Intraoperative correction of residual lesions results in shorter length of stay, and lower postoperative AE and costs compared with delayed postoperative revision of residual lesions.

A new paradigm for obtaining marketing approval for pediatric-sized prosthetic heart valves.

OBJECTIVE: Congenital heart valve disease is one of the most common abnormalities in children. There are limited technological solutions available for treating children with congenital heart valve diseases. The aim of this study is to provide the details of the consensus reached in terms of pediatric definitions, design approach, in vitro testing, and clinical trials, which may be used as guidance for developing prosthetic heart valves for the pediatric indication. METHODS: In stark contrast to the various designs of adult-sized replacement valves available in the market, there are no Food and Drug Administration (FDA)-approved prosthetic heart valves available for use in the pediatric population. There is a pressing need for FDA-approved pediatric valve devices in the United States. The pediatric patient population has been typically excluded from replacement heart valve trials for several reasons. In January 2010, heart valve manufacturers and pediatric clinicians collaborated with academicians and FDA staff in a workshop to suggest ways to successfully evaluate pediatric prosthetic valves and conduct pediatric clinical trials to provide acceptable heart valve replacement options for this patient population. RESULTS: Recommendations, derived from ISO 5840:2005 and the 2010 FDA Draft Replacement Heart Valve Guidance, are provided for hydrodynamic, durability, and fatigue testing. CONCLUSIONS: The article specifically addresses in vitro and premarket and postmarket approval clinical studies that should be considered by a heart valve manufacturer for obtaining regulatory approval of pediatric sizes of prosthetic heart valve designs that are already approved for adult clinical use.

Technical performance scores in congenital cardiac operations: a quality assessment initiative.

BACKGROUND: Technical performance in congenital cardiac operations and its association with clinical outcomes was previously examined in infants and neonates. The purpose of this study was the development and implementation of a system for measuring technical performance in the majority of congenital cardiac operations to be used as a surgeon's self-assessment tool. METHODS: Using the methodologic framework piloted at our institution, measures of technical performance were created for more than 90% of all congenital cardiac operations. Each operation was divided into multiple subprocedures to be assessed separately. Criteria for technical scores were created using a consensus panel of senior clinicians and were based primarily on the predischarge echocardiographic findings and need for early postoperative reinterventions. This system of procedure modules was then piloted by prospectively assigning technical scores to all patients undergoing operations. RESULTS: Thirty modules were created covering more than 90% of the cardiac operations performed. One hundred eighty-five patients were enlisted. One hundred one (54.6%) cases were scored as class 1 (highest), 46 (24.9%) cases as class 2, 22 (11.9%) cases as class 3 (lowest); 16 cases (8.6%) could not be scored. The results were further analyzed by RACHS (Risk Adjustment for Congenital Heart Surgery) categories and outcomes. Valve-procedure-specific criteria were calibrated to reflect specific echocardiographic measurements. CONCLUSIONS: The development and implementation of a broad technical performance self-assessment system for congenital cardiac operations is possible. Based on this scoring system, the impact of a less than optimal (2 or 3) technical score depends on case risk category, with higher mortality in the higher risk group, and increased resource use for lower risk procedures.

Multi-Physics MRI-Based Two-Layer Fluid-Structure Interaction Anisotropic Models of Human Right and Left Ventricles with Different Patch Materials: Cardiac Function Assessment and Mechanical Stress Analysis.

Multi-physics right and left ventricle (RV/LV) fluid-structure interaction (FSI) models were introduced to perform mechanical stress analysis and evaluate the effect of patch materials on RV function. The FSI models included three different patch materials (Dacron scaffold, treated pericardium, and contracting myocardium), two-layer construction, fiber orientation, and active anisotropic material properties. The models were constructed based on cardiac magnetic resonance (CMR) images acquired from a patient with severe RV dilatation and solved by ADINA. Our results indicate that the patch model with contracting myocardium leads to decreased stress level in the patch area, improved RV function and patch area contractility.

Image-Based Patient-Specific Ventricle Models with Fluid-Structure Interaction for Cardiac Function Assessment and Surgical Design Optimization.

Recent advances in medical imaging technology and computational modeling techniques are making it possible that patient-specific computational ventricle models be constructed and used to test surgical hypotheses and replace empirical and often risky clinical experimentation to examine the efficiency and suitability of various reconstructive procedures in diseased hearts. In this paper, we provide a brief review on recent development in ventricle modeling and its potential application in surgical planning and management of tetralogy of Fallot (ToF) patients. Aspects of data acquisition, model selection and construction, tissue material properties, ventricle layer structure and tissue fiber orientations, pressure condition, model validation and virtual surgery procedures (changing patient-specific ventricle data and perform computer simulation) were reviewed. Results from a case study using patient-specific cardiac magnetic resonance (CMR) imaging and right/left ventricle and patch (RV/LV/Patch) combination model with fluid-structure interactions (FSI) were reported. The models were used to evaluate and optimize human pulmonary valve replacement/insertion (PVR) surgical procedure and patch design and test a surgical hypothesis that PVR with small patch and aggressive scar tissue trimming in PVR surgery may lead to improved recovery of RV function and reduced stress/strain conditions in the patch area.

National Institutes of Health funding for cardiothoracic surgical research.

OBJECTIVE: Our objective was determine the status of National Institutes of Health (NIH) funding for cardiothoracic surgery research. SUMMARY BACKGROUND DATA: (1) Funding from the NIH is critical if new procedures and devices are to be developed. (2) The success rate for NIH applications coming from cardiothoracic surgery faculty is thought to be inferior. (3) Per capita numbers of surgical NIH application and awards and application success rate have recently been found to be below the average for the NIH. METHODS: Application and award data for full-time academic cardiothoracic surgeons were obtained by matching records in the NIH IMPAC II database with membership rosters of The Society of Thoracic Surgeons and The American Association for Thoracic Surgery. Manpower data were obtained from 1999, 2003, and 2005 reports of the STS/AATS Workforce committee. Society membership was used as a surrogate for investigator experience. RESULTS: The number of NIH applications has increased steeply in the past 7 years; however, the number of awards has remained constant. This pattern was observed for surgery and cardiothoracic surgery as well. Until 2003, the cardiothoracic surgery application success rate was actually higher than that of surgery and the NIH as a whole (between 25% and 40%). Since then, however, the cardiothoracic surgery application success rate has declined steeply and is now only 14%. NIH applications and awards per 100 cardiothoracic surgeons, although similar to those of surgery, are very much less than the NIH as a whole. CONCLUSION: Per capita NIH funding of cardiothoracic surgeons is very much less than that of the NIH as a whole. The primary cause is the low per capita number of applications submitted by cardiothoracic surgeons. Junior cardiothoracic faculty should be encouraged to apply for career development awards. However, since the ability to shift cost from clinical to academic faculty is declining, affirmative action from the NIH may be necessary.

Cardiac magnetic resonance versus routine cardiac catheterization before bidirectional glenn anastomosis in infants with functional single ventricle: a prospective randomized trial.

BACKGROUND: Routine preoperative catheterization is standard practice in patients with single-ventricle physiology before bidirectional Glenn anastomosis. Because catheterization is invasive and exposes patients to ionizing radiation, cardiac magnetic resonance (CMR) may be a safe and effective alternative. METHODS AND RESULTS: We conducted a prospective, randomized, single-center clinical trial comparing catheterization with CMR in patients considered for bidirectional Glenn operation from February 2003 to June 2006. End points were frequency of adverse events of the preoperative evaluation and a composite score of clinically successful surgery. Of 92 eligible patients, 82 were enrolled on the basis of screening echocardiogram, fulfillment of inclusion criteria, and informed consent. Patients were randomized to catheterization (n=41) or CMR (n=41). There were no baseline differences between groups. Four treatment crossovers occurred, 3 to catheterization and 1 to CMR. Catheter interventions were performed in 17 patients (41%). Catheterization resulted in more minor adverse events (78% versus 5%; P<0.001), longer preoperative hospital stays (median, 2 versus 1 day; P<0.001), and higher hospital charges ($34 477 versus $14 921; P<0.001). There was 1 major adverse event in the CMR group (P=1.0). The operative course and frequency of postoperative complications were similar between the 2 groups. The proportion of patients who had a successful bidirectional Glenn operation was similar (71% versus 83%; P=0.3). At the 3-month follow-up, there were no differences in clinical status, oxygen saturation, or frequency of reinterventions. CONCLUSIONS: CMR is a safe, effective, and less costly alternative to routine catheterization in the evaluation of selected patients before bidirectional Glenn operation. Further studies are necessary to determine whether there are long-term benefits from transcatheter interventions in these patients.

Cytosolic calcium in the ischemic rabbit heart: assessment by pH- and temperature-adjusted rhod-2 spectrofluorometry.

OBJECTIVES: Cytosolic calcium ([Ca(2+)](i)) mediates ischemia-reperfusion (I/R) injury, but magnitude and time course of I/R-induced [Ca(2+)](i) overload remain unclear. Fluorescent indicators are commonly used to measure [Ca(2+)](i), and have a dissociation constant (K(d)) that depends on pH and temperature. We hypothesized that changes of K(d) during I/R lead to misleading interpretations of [Ca(2+)](i) recordings. METHODS: (1) In isolated rabbit hearts (n=4 each), intracellular pH was measured during I/R at 37 degrees C, 20 degrees C, and 4 degrees C with and without cardioplegic arrest by (31)P-NMR-spectroscopy. (2) K(d) for rhod-2 and calcium was determined at varying pH and temperature in in vitro experiments. (3) Isolated rabbit hearts were subjected to I/R, and [Ca(2+)](i) was recorded by surface rhod-2 spectrofluorometry. Finally, [Ca(2+)](i) was computed using either the conventional K(d), or the pH- and temperature-adjusted K(d). RESULTS: K(d)(Ca(2+)Rhod-2) remained stable between pH 7.1 and 6.8, but increased exponentially with lower pH and/or temperature. Calculations using a static K(d) indicated that [Ca(2+)](i) rose only mildly during warm ischemia and did not rise during cardioplegic arrest, while a large Ca(2+) influx appeared to occur during early reperfusion. When the pH and temperature-adjusted K(d) was used for calculation, [Ca(2+)](i) rose significantly during ischemia (431+/-37% during 20 min 37 degrees C ischemia, and 78+/-19% during 20 min cardioplegic arrest at 20 degrees C). During early reperfusion, [Ca(2+)](i) decreased rapidly, without significant further [Ca(2+)](i) elevation. CONCLUSIONS: In contrast to previous reports, [Ca(2+)](i) accumulation occurs during unprotected ischemia as well as hypothermic ischemia with cardioplegic arrest, without further net Ca(2+) influx on reperfusion. This finding has important implications for timing of protective strategies during myocardial ischemia.