Early Results of the Modified Right Atrial Lesion Set for the Cox-CryoMaze Procedure.

OBJECTIVE: The standard right atrial lesion (RAL) set, as originally outlined in the Cox-Maze III procedure, can be technically challenging when using a cryoprobe to create the lesions. We report our initial experience with an alternative set of RALs for the surgical treatment of atrial fibrillation (AF). METHODS: Between September 2011 and January 2015, a total of 112 patients underwent a CryoMaze procedure with biatrial lesions using argon-based cryoablation (cryoprobe temperature, -160°C). Although the standard left atrial lesion set was used, the RAL pattern was modified in this cohort of patients. The intracaval superior vena cava-inferior vena cava lesion was performed as in the pattern described for the standard Cox-Maze III procedure. In addition, a horizontal atriotomy incision (the "T" lesion) in the mid free wall of the right atrium was based roughly in the midintercaval line and extended medially as a linear cryolesion to the lateral tricuspid annulus at the so-called 2-o'clock position as in the Cox-Maze III lesion pattern. Ordinarily, a linear cryolesion would be placed from the tip of the right atrial appendage (RAA) to the anterior tricuspid annulus at the so-called 10-o'clock position to prevent macro re-entry around the base of the RA appendage. Our modification consisted of, instead, a linear cryolesion directed perpendicularly from the mid portion of the atriotomy (T lesion) to the tip of the RA appendage, which simply interrupted RAA re-entry at another point. RESULTS: The mean ± standard deviation age was 72.7 ± 10.6 years, 56.3% were males, and 63.1% had long-standing persistent AF. There were three operative deaths (2.6% with an observed over expected of 0.58), all in the concomitant procedures with associated cardiac disease. Overall follow-up was 91.3%. Freedom from AF at discharge, 1-, 3-, 6-, 12-, 24-month, and last follow-up [16.1 ± 11.3 months (range, 0.4-43 months)], was 100%, 76.3%, 84.2%, 98.3%, 89.5%, 89.2%, and 90.5%, respectively. Similarly, freedom from antiarrhythmic drugs was 74% and 81%, whereas freedom from anticoagulants was 72% and 78% at 12 and 24 months, respectively. CONCLUSIONS: These results suggest the modified RAL set to be an effective alternative to the traditional RALs of Cox-Maze III. By substituting this lateral RAA lesion for the more technically difficult medial lesion, the procedure becomes easier to perform and favorably impacts operative time while achieving comparable results in reducing AF burden.

Mesenchymal stem cells preserve neonatal right ventricular function in a porcine model of pressure overload.

Limited therapies exist for patients with congenital heart disease (CHD) who develop right ventricular (RV) dysfunction. Bone marrow-derived mesenchymal stem cells (MSCs) have not been evaluated in a preclinical model of pressure overload, which simulates the pathophysiology relevant to many forms of CHD. A neonatal swine model of RV pressure overload was utilized to test the hypothesis that MSCs preserve RV function and attenuate ventricular remodeling. Immunosuppressed Yorkshire swine underwent pulmonary artery banding to induce RV dysfunction. After 30 min, human MSCs (1 million cells, n = 5) or placebo (n = 5) were injected intramyocardially into the RV free wall. Serial transthoracic echocardiography monitored RV functional indices including 2D myocardial strain analysis. Four weeks postinjection, the MSC-treated myocardium had a smaller increase in RV end-diastolic area, end-systolic area, and tricuspid vena contracta width (P < 0.01), increased RV fractional area of change, and improved myocardial strain mechanics relative to placebo (P < 0.01). The MSC-treated myocardium demonstrated enhanced neovessel formation (P < 0.0001), superior recruitment of endogenous c-kit+ cardiac stem cells to the RV (P < 0.0001) and increased proliferation of cardiomyocytes (P = 0.0009) and endothelial cells (P < 0.0001). Hypertrophic changes in the RV were more pronounced in the placebo group, as evidenced by greater wall thickness by echocardiography (P = 0.008), increased cardiomyocyte cross-sectional area (P = 0.001), and increased expression of hypertrophy-related genes, including brain natriuretic peptide, ß-myosin heavy chain and myosin light chain. Additionally, MSC-treated myocardium demonstrated increased expression of the antihypertrophy secreted factor, growth differentiation factor 15 (GDF15), and its downstream effector, SMAD 2/3, in cultured neonatal rat cardiomyocytes and in the porcine RV myocardium. This is the first report of the use of MSCs as a therapeutic strategy to preserve RV function and attenuate remodeling in the setting of pressure overload. Mechanistically, transplanted MSCs possibly stimulated GDF15 and its downstream SMAD proteins to antagonize the hypertrophy response of pressure overload. These encouraging results have implications in congenital cardiac pressure overload lesions.

Separation of mediastinal shed blood during aortic valve surgery elicits a reduced inflammatory response.

AIMS: The detrimental effects of inflammation following cardiopulmonary bypass (CPB) could negatively affect the postoperative outcome in a specific subset of high-risk patients. We therefore investigated the impact of a CPB circuit (Admiral, Eurosets, Italy) that allows separation of intracavitary and mediastinal blood on the release of biochemical markers and clinical outcome when compared with a conventional circuit. METHODS: Thirty patients undergoing aortic valve surgery were prospectively enrolled and assigned to Admiral group (Group 1, G1, n = 15) or conventional CPB group (Group 2, G2, n = 15). The Admiral oxygenator allows for a separate collection of mediastinal blood processed through a cell-saver before retransfusion. Clinical data and biochemical parameters were measured preoperatively, during CPB and at different time-points postoperatively. RESULTS: Preoperative demographics, intraoperative data (as CPB and aortic cross-clamping time) and perioperative complications did not differ between groups. Inflammatory response was significantly decreased in G1, as assessed by means of D-dimer (G1 = 1332.3  ±  953.9 vs. G2 = 2791.9  ±  1740.7  ng/ml, P = 0.02), C-reactive protein (G1 = 169.1  ±â€Š 164.8 vs. G2 = 57.1  ±  39.3  mg/l, P = 0.04), interleukin-6 (G1 = 11.8  ± 12.5 vs. G2 = 26.5  ±â€Š 24.9  pg/ml, P = 0.02) and tumour necrosis factor-alpha (G1 = 29  ±â€Š 28.7 vs. G2 = 45.5  ±â€Š 23.6 pg/ml, P = 0.03). CONCLUSION: Although no considerable difference was detected in terms of perioperative outcomes, the Admiral oxygenator did result in a significant reduction of inflammatory markers during the early postoperative course.

Stem cell therapy for CHD: towards translation.

Stem cell therapy has the optimistic goal of regenerating the myocardium as defined by re-growth of lost or destroyed myocardium. As applied to patients with heart failure, many confuse or limit the regenerative definition to just improving myocardial function and/or decreasing myocardial scar formation, which may not be the most important clinical outcome to achieve in this promising field of molecular medicine. Many different stem cell-based therapies have been tested and have demonstrated a safe and feasible profile in adult patients with heart failure, but with varied efficacious end points reported. Although not achieved as of yet, the encompassing goal to regenerate the heart is still believed to be within reach using these cell-based therapies in adult patients with heart failure, as the first-generation therapies are now being tested in different phases of clinical trials. Similar efforts to foster the translation of stem cell therapy to children with heart failure have, however, been limited. In this review, we aim to summarise the findings from pre-clinical models and clinical experiences to date that have focussed on the evaluation of stem cell therapy in children with heart failure. Finally, we present methodological considerations pertinent to the design of a stem cell-based trial for children with heart failure, as they represent a population of patients with very different sets of issues when compared with adult patients. As has been taught by many learned clinicians, children are not small adults!

Pediatric End-Stage Failing Hearts Demonstrate Increased Cardiac Stem Cells.

BACKGROUND: We sought to determine the location, expression, and characterization of cardiac stem cells (CSCs) in children with end-stage heart failure (ESHF). We hypothesized ESHF myocardium would contain an increased number of CSCs relative to age-matched healthy myocardium, and ESHF-derived CSCs would have diminished functional capacity as evidenced by reduced telomere length. METHODS: Tissue samples were obtained from the explanted hearts of children undergoing heart transplantation with ESHF, defined as New York Heart Association class III or IV and ejection fraction less than 0.20, and from age-matched congenital heart disease patients with normal myocardium. The expression profile of cardiac-specific stem cell markers was determined using quantitative real time polymerase chain reaction and immunofluorescence. Cardiac stem cell growth reserve was assessed with telomere length. RESULTS: There were 15 ESHF and 15 age-matched congenital heart disease patients. End-stage heart failure myocardium demonstrated increased expression of c-kit(+) and islet-1(+) CSCs by 2.0- and 2.5-fold, respectively, compared with myocardium from congenital heart disease patients. There was no difference in expression of c-kit(+) CSCs with advancing age from infants to children in ESHF myocardium. The c-kit(+) CSCs isolated from ESHF patients demonstrated significantly reduced telomere length, suggesting a diminished functional capability in these cells (8.1 ± 0.6 kbp versus 6.3 ± 0.3 kbp; p = 0.015). CONCLUSIONS: End-stage heart failure myocardium demonstrated an age-independent increase in CSCs relative to healthy myocardium; however, these CSCs from ESHF patients may have diminished proliferative ability and reduced functionality as an autologous cell therapy candidate. Further investigation is necessary to determine the role of ESHF-derived CSCs within the myocardium.

Cardiosphere-derived cells from pediatric end-stage heart failure patients have enhanced functional activity due to the heat shock response regulating the secretome.

We have demonstrated that human neonatal cardiosphere-derived cells (CDCs) derived from the young are more regenerative due to their robust secretome. However, it is unclear how the decompensated pediatric heart impacts the functional activity of their CDCs. Our aim was to characterize the potency of pediatric CDCs derived from normal functioning myocardium of control heart disease (CHD) patients to those generated from age-matched end stage heart failure (ESHF) patients and to determine the mechanisms involved. ESHF-derived CDCs contained a higher number of c-kit(+) , Islet-1(+) , and Sca-1(+) cells. When transplanted into an infarcted rodent model, ESHF-derived CDCs significantly demonstrated higher restoration of ventricular function, prevented adverse remodeling, and enhanced angiogenesis when compared with CHD patients. The superior functional recovery of the ESHF-derived CDCs was mediated in part by increased SDF-1α and VEGF-A secretion resulting in augmented recruitment of endogenous stem cells and proliferation of cardiomyocytes. We determined the mechanism is due to the secretome directed by the heat shock response (HSR), which is supported by three lines of evidence. First, gain of function studies demonstrated that increased HSR induced the lower functioning CHD-derived CDCs to significantly restore myocardial function. Second, loss-of function studies targeting the HSR impaired the ability of the ESHF-derived CDCs to functionally recover the injured myocardium. Finally, the native ESHF myocardium had an increased number of c-kit(+) cardiac stem cells. These findings suggest that the HSR enhances the functional activity of ESHF-derived CDCs by increasing their secretome activity, notably SDF-1α and VEGF-A.

Successful Repair of Complete Atrio-ventricular Septal Defect at the Beginning of the Second Decade.

Complete atrio-ventricular septal defects (CAVSD) are present in about 3% of children born with congenital heart pathologies. They usually require early surgical correction, mostly in infancy, and surgery is considered to be the gold standard. It is unlikely that anyone would survive beyond the first years without severe morbidity. However, we report a case of a Pakistani girl who underwent successful surgical repair of CAVSD at the age of 11.

Predictors of mortality after short-term ventricular assist device placement.

BACKGROUND: Risk assessment prior to long-term ventricular assist device (VAD) placement has been shown to be crucial for successful outcomes and efficient resource utilization. Short-term VADs are often used as salvage therapy in acute heart failure when the clinical scenario precludes such thorough preoperative assessment. Our goal was to devise a risk stratification system that may be used shortly after stabilization of hemodynamics with a short-term VAD to predict the likelihood of survival. METHODS: A retrospective study was performed of all patients undergoing Abiomed (Abiomed Cardiovascular Inc., Danvers, MA) or CentriMag (Levitronix LLC, Waltham, MA) placement at our institution or transferred to our institution with the device in place. From January 2001 until August 2009, 93 patients were identified. Preoperative and early postoperative variables were analyzed for their correlation with in-hospital mortality. RESULTS: Multivariable logistic regression analysis identified factors that were associated with death. A three-point scoring system, utilizing a diagnosis of postcardiotomy shock or graft failure, female sex, and postoperative day 3 total bilirubin greater than 5.2 mg/dL was devised. A score of 2 or greater was associated with an 86% mortality rate, whereas a score of 0 was associated with a 13% mortality rate. CONCLUSIONS: A simple scoring system based on readily available data may predict mortality after short-term VAD placement. Such a scoring system may be of prognostic value for physicians and patient families early in the support period and may help guide decisions.