Development of a novel hybrid strategy for transcatheter pulmonary valve placement in patients following transannular patch repair of tetralogy of fallot.

BACKGROUND: Transcatheter pulmonary valve replacement (tPVR) is an accepted therapy for treatment of dysfunctional right ventricular outflow tract (RVOT) conduits. At present, the majority of Fallot patients who undergo transannular patch (TAP) repair are not candidates for tPVR due to the large irregular nature of their RVOT. Herein, we describe a novel approach to assessing the RVOT in this group, which may then be used to design, test, and carry out hybrid RVOT modification and transcatheter valve implantation in this population. METHODS: A retrospective analysis of TAP patients who underwent 3D modeling of the RVOT which was then used to develop individualized hybrid procedures designed to modify the RVOT, thereby rendering patients suitable for transcatheter valve implantation. RESULTS: Eight consecutive patients underwent 3D RVOT modeling followed by hybrid implantation of a transcatheter valve via a perventricular approach. A landing zone stent was placed in all and four required additional intravascular geometric remodeling of the RVOT prior to valve implant. Transcatheter valves were successfully implanted in all. There were no instances of valve malposition, embolization, or death. There was one minor procedural complication. No patient had more than trivial pulmonary regurgitation at follow-up. CONCLUSIONS: Using a hybrid approach to remodel the RVOT in TAP patients supported by preprocedural 3D-model planning allows for successful tPVR implantation in this population. A larger cohort and longer follow-up will be needed to determine the ultimate utility of this approach.

Survival and right ventricular performance for matched children after stage-1 Norwood: Modified Blalock-Taussig shunt versus right-ventricle-to-pulmonary-artery conduit.

OBJECTIVE: Early survival advantages after Norwood with right-ventricle-(RV)-to-pulmonary-artery conduit (NW-RVPA) over Norwood-operation with a Blalock-Taussig shunt (NW-BT) are offset by concerns regarding delayed RV dysfunction. We compared trends in survival, RV dysfunction, and tricuspid valve regurgitation (TR) between NW-RVPA and NW-BT for propensity-matched neonates with critical left ventricular outflow tract obstruction (LVOTO). METHODS: In an inception cohort (2005-2014; 21 institutions), 454 neonates with critical LVOTO underwent Norwood stage 1. Propensity-score matching paired 169 NW-RVPA patients with 169 NW-BT patients. End-states were compared between NW-RVPA and NW-BT using competing-risks, multiphase, parametric, hazard analysis. Post-Norwood echocardiogram reports (n = 2993) were used to grade RV dysfunction and TR. Time-related prevalence of ≥moderate RV dysfunction and TR were characterized using nonlinear mixed-model regression, and compared between groups via multiphase, parametric models. RESULTS: Overall 6-year survival was better after NW-RVPA (70%) versus NW-BT (55%; P < .001). Additionally, transplant-free survival during this time was better after NW-RVPA (64%) versus NW-BT (53%; P = .004). Overall prevalence of ≥moderate RV dysfunction reached 11% within 3 months post-Norwood. During this time, RV dysfunction after NW-BT was 16% versus 6% after NW-RVPA (P = .02), and coincided temporally with an increased early hazard for death. For survivors, late RV dysfunction was <5% and was not different between groups (P = .36). Overall prevalence of ≥moderate TR reached 13% at 2 years post-Norwood and was increased after NW-BT (16%) versus NW-RVPA (11%; P = .003). Late TR was similar between groups. CONCLUSIONS: Among propensity-score-matched neonates with critical LVOTO, NW-RVPA offers superior 6-year survival with no greater prevalence of RV dysfunction or TR than conventional NW-BT operations.

Antibody-mediated rejection in a lung transplant recipient after acute stroke.

Antibody-mediated rejection (AMR) is becoming a more recognized problem in lung transplantation. We present a case of late onset AMR in a lung transplant recipient after an acute embolic stroke requiring thrombolytic therapy, who previously had a completely unremarkable course for over 3 years.

Predictors of retrograde aortic arch obstruction after hybrid palliation of hypoplastic left heart syndrome.

A potential complication after hybrid stage 1 palliation for hypoplastic left heart syndrome (HLHS) is retrograde aortic arch obstruction (RAAO). This can lead to increased morbidity and unplanned surgical or interventional procedures in the interstage period. This study aimed to identify potential predictors of RAAO by analyzing initial echocardiograms and angiograms before hybrid stage 1 palliation. For this study, 96 patients who underwent hybrid stage 1 palliation between July 2002 and July 2009 were reviewed, 68 of which had standard HLHS and met the inclusion criteria. The initial echocardiogram, hybrid stage 1 angiograms, and follow-up echocardiograms were reviewed. Anatomic and hemodynamic measurements were obtained by both modalities, and comparisons were made between those who developed RAAO and those who did not. Of the 68 patients, 20 (29%) had RAAO. The mean aortic root size was smaller for the patients who had RAAO (3.6 vs 4.4 mm; p = 0.036). The angiographic angle between the aortic isthmus and the patent ductus arteriosus (PDA) was significantly larger in the RAAO group (86° vs 63°; p = 0.008). The retrograde aortic arch velocities were higher in the RAAO group. Patients with RAAO have a smaller aortic root and higher retrograde velocities on initial echocardiogram. Patients with RAAO show a larger angle between the retrograde arch and PDA on angiogram. Because RAAO is an important potential complication after hybrid stage 1 palliation for HLHS, identification of predictors of RAAO may lead to improved care and outcome for patients with RAAO.

Right ventricular remodeling in restrictive ventricular septal defect.

Restrictive ventricular septal defect (rVSD) presents with little/no hemodynamic aberrations despite a patent septal defect. Clinically, these patients are observed with the hope that the defect will functionally close over time without the need for surgical repair and development of heart failure. Without evidence supporting a definitive therapeutic strategy, rVSD patients may have increased risk of a poor outcome. We tested the hypothesis that rVSD results in subclinical RV diastolic dysfunction and molecular remodeling. Five pigs underwent surgical rVSD creation. Echocardiography, hemodynamics, myocyte contractility experiments, and proteomics/Western blot were performed 6-weeks post-rVSD and in controls. *p<0.05. LV and RV hemodynamics in rVSD were comparable to controls. The tricuspid valve early/late diastolic inflow velocity ratio (TV E/A ratio) decreased from 1.6+/-0.05 in controls to 1.0+/-0.08* in rVSD, indicating RV diastolic dysfunction. rVSD RV myocytes showed abnormalities in contraction (departure velocity (Vd) -51%*, Vd time +55%*) and relaxation (return velocity (Vr) -50%*, Vr time +62%*). Mitochondrial proteins (fatty acid, TCA cycle) increased 2-fold*, indicating heightened RV work. Desmin protein upregulated 285%* in rVSD RV myocardium, suggesting cytoskeletal remodeling. rVSD causes RV diastolic dysfunction, myocyte functional impairment, and mitochondrial/cytoskeletal protein upregulation in our model. Desmin upregulation may hinder sarcomeric organization/relaxation, representing a key subclinical early marker for future RV dysfunction. TV E/A measurements are a non-invasive modality to assess rVSD patients for diastolic dysfunction. Translational research applications may lead to fundamental changes in the clinical management of rVSD by providing evidence for early repair of the defect.

Amplatzer septal occluder associated with late pulmonary venous obstruction requiring surgical removal with acquired aorta to left atrial fistula.

The Amplatzer septal occluder is currently the preferred device for the transcatheter closure of secundum atrial septal defects. Multiple studies have shown that device complications with the Amplatzer occluder are rare and often acute in presentation. The investigators describe the first reported case of late obstruction of the right pulmonary veins with an Amplatzer septal occluder and, in the same patient, an unusual intraoperative finding of a noncoronary aortic sinus to left atrium fistula after device removal.

Cytoskeletal remodeling of desmin is a more accurate measure of cardiac dysfunction than fibrosis or myocyte hypertrophy.

AIMS: Fibrosis and myocyte hypertrophy are classical remodeling parameters in heart failure (HF); however, an intriguing possibility is that myocytes undergo intracellular remodeling which decrease compliance, contributing to diastolic dysfunction. The most obvious candidates are cytoskeletal proteins. The cytoskeletal protein desmin reinforces the sarcomeres, enabling force generation. As a contributor to sarcomere performance, desmin may represent a better appraisal of dysfunction than fibrosis or myocyte hypertrophy. MAIN METHODS: HF was induced in sheep via coronary microembolization. Echocardiography was performed at baseline, 4-, and 12-months in HF. Desmin, fibrosis, and myocyte hypertrophy from infarcted LV posterior and noninfarcted LV anterior walls were measured using Western blot, immunohistochemistry, and digital image analysis. Multivariate regression analysis was performed, providing structure/function mechanisms. *p<0.05. KEY FINDINGS: EF decreased from 55% to 24%*. LV end-diastolic area (LVEDA) increased 123%* at month-12. Fibrosis increased only in posterior LV whereas myocyte hypertrophy increased in both LV posterior and LV anterior regions but only at month-12. Desmin content progressively increased 121% at month-4 and 182%* at month-12 in both LV posterior and anterior walls. Multivariate linear regression (beta coefficient standardization) demonstrated that desmin was a much better predictor of EF (beta=-0.38*) and LVEDA (beta=0.58*) than fibrosis or myocyte hypertrophy. SIGNIFICANCE: Desmin, fibrosis, and myocyte hypertrophy are temporally and spatially heterogeneous in HF. Desmin content more accurately correlated with remodeling than fibrosis or myocyte hypertrophy, suggesting that intra-myocyte responses, likely related to mechanical stretch, are better predictors of LV function and may represent novel targets for therapeutic intervention.

Effects of ischemic preconditioning and adenosine pretreatment on myocardial function and energetics in a clinically relevant model.

Preconditioning (PC) is a potential approach to myocardial protection. We hypothesize that brief ischemia or adenosine given prior to an extended period of warm ischemia may prevent myocardial stunning by altering myocardial metabolism. Using a global ischemia model, 19 dogs were subjected to no PC(control), two episodes of ischemia (2 min of global ischemia followed by 3 min of reperfusion) (IPC), or 30 min of pulmonary artery adenosine infusion (AP), to a maximum of 350 microg/kg/min, followed by 20 min of global warm ischemia on cardiopulmonary bypass. Left ventricular pressure-volume loops and myocardial oxygen consumption (MVO(2)) were measured at baseline and after 60 min of reperfusion, on right heart bypass. All data were compared between baseline and reperfusion. Load independent left ventricular function, defined as preload recruitable stroke work (PRSW), decreased in control and IPC groups (72+/-7%, 71+/-12%, respectively). AP blunted the decrease in PRSW (45+/-9%, p<.05 compared to control). Myocardial energetic conversion efficiency, defined as the slope of the MVO(2)-Stroke work relationship was not significantly changed for controls (2.17+/-0.47 to 1.84+/-0.68) and IPC (2.99+/-0.45 to 2.16+/-0.65), but was for AP (1.16+/-0.88 to 5.71+/-1.66, p<0.04). IPC did not prevent ventricular stunning or alter myocardial energetics. AP reduced ventricular stunning but resulted in worsened myocardial energy efficiency. The benefits to ventricular function of the adenosine pretreatment protocol used in this study were only possible at a cost of higher metabolic requirements.

Failure of right ventricular adaptation in children with tetralogy of Fallot.

BACKGROUND: The left ventricle (LV) adapts to chronic hypoxia by expressing protective angiogenic, metabolic, and antioxidant genes to improve O2 delivery and energy production, and to minimize reoxygenation injury. The ability of the right ventricle (RV) to adapt to hypoxia in children with tetralogy of Fallot (TOF) is unknown. METHODS AND RESULTS: Gene expression using real-time polymerase chain reaction was measured in RV myocardium obtained during surgical repair of TOF from 23 patients: 13 cyanotic and 10 acyanotic. Results were compared between the 2 groups and correlated with age at surgery, severity of cyanosis, and early postoperative course. The cyanotic patients were younger at surgery compared with acyanotic (5+/-3 versus 9+/-4 months; P=0.01), had higher hematocrit (43+/-4 versus 38+/-3 grams/dL; P=0.004), and lower O2 saturations (84+/-4% versus 98+/-2%; (P<0.001). Cyanotic patients had a significantly lower expression of vascular endothelial growth factor (VEGF), glycolytic enzymes, and glutathione peroxidase (GPX) (P<0.05), and a higher expression of collagen (P<0.01) compared with acyanotic patients. Gene expression correlated inversely with severity of cyanosis ie, preoperative hematocrit (P<0.01) and positively with preoperative saturation (P<0.05). The relationship between gene expression and cyanosis was independent of age at surgery. Ca2+ handling genes did not correlate with the severity of hypoxia. Lower angiogenic, glycolytic, and antioxidant gene expression correlated with increasing postoperative lactate (P<0.05). CONCLUSIONS: The RV fails to up regulate adaptive pathways in response to increasing hypoxia in children with TOF. The implications of an early maladaptive response of the RV on long-term RV function require further investigation.