The Impact of Bicuspid Aortic Valve Leaflet Fusion Morphology on the Ascending Aorta and on Outcomes of Aortic Valve Replacement.

BACKGROUND: Patients with bicuspid aortic valves (BAVs) tend to develop dilation of the ascending aorta. The aim of this study was to analyze the impact of leaflet fusion pattern on aortic root diameter and outcomes in patients undergoing surgery for BAV vs tricuspid aortic valve (TAV) disease. METHODS: This is a retrospective review of 90 patients with aortic valve disease (mean [SD] age, 51.5 [8.2] years) who underwent aortic valve replacement for BAV (n = 60) and TAV (n = 30). Fusion of right-left (R/L) coronary cusps was identified in 45 patients, whereas the remaining 15 patients had right-noncoronary (R/N) cusp fusion. Aortic diameter was measured at 4 levels, and Z values were computed. RESULTS: There were no significant differences between the BAV and TAV groups for age, weight, aortic insufficiency grade, or size of implanted prostheses. However, a higher preoperative peak gradient at the aortic valve was significantly associated with R/L fusion (P = .02). Preoperative Z values of ascending aorta and sinotubular junction diameter were significantly higher in patients with R/N fusion than with the R/L (P < .001 and P = .04, respectively) and TAV (P < .001 and P < .05, respectively) subgroups. During the follow-up period (mean [SD], 2.7 [1.8] years), 3 patients underwent a redo procedure. At the last follow-up, the sizes of ascending aorta were similar among all 3 patient groups. CONCLUSION: This study suggests that preoperative dilation of the ascending aorta is more common in patients with R/N fusion than in patients with R/L and TAV but is not significantly different between all groups in the early follow-up period. R/L fusion was associated with an increased risk of preoperative presence of aortic stenosis.

Anomalous Aortic Origin of Right Coronary Artery: Outcomes of Surgical and Nonsurgical Treatment.

BACKGROUND: Anomalous aortic origin of right coronary artery (AAORCA) is a congenital heart lesion that may be associated with coronary ischemia and sudden death; however, the management of these patients remains controversial. The aim of this study was to analyze all patients with AAORCA managed at our center. METHODS: The medical records of patients with an isolated diagnosis of AAOCA were retrospectively reviewed, irrespective of symptoms, from 2007 to 2020. Follow-up was obtained by medical record review. AAORCA was diagnosed by echocardiogram and computed tomographic or magnetic resonance imaging studies in all patients. Treatment was based on anatomic, morphologic, and symptomatic features for patients older than 10 years with AAORCA. RESULTS: The review identified 86 patients with a median age of 16 years; of these, 26 (30%) were managed surgically and 60 (70%) are monitored nonsurgically. Surgical intervention included a "classic" unroofing in 10 (39%), neo-ostial creation in 7 (27%), modified unroofing with neo-ostial creation in 6 (23%), a "classic" unroofing with reimplantation in 2 (7%), and reimplantation only in 1 (4%). Surgical patients were significantly older (P = .01), described more chest pain symptoms (P = .004), had the presence of slitlike ostia (P = .03), and longer length of coronary artery narrowing (P = .0002). At follow-up (median, 3 years; range, 0-13 years), 100% of surgical patients underwent functional testing and had no evidence of ischemia. Postoperative evaluation included one or more of echocardiography, computed tomographic angiogram, magnetic resonance imaging, and exercise stress test. CONCLUSIONS: Our program uses a systematic approach for patients with AAORCA. With this paradigm, outcomes are excellent in the midterm, as validated with anatomic- and function-based testing.

Dilatable Pulmonary Artery Banding Palliation in Congenital Heart Disease.

BACKGROUND: Surgical pulmonary artery banding (PAB) has been limited in practice because of later requirement for surgical removal or adjustment. The aim of this study is to describe our experience creating a dilatable PAB via transcatheter balloon dilation (TCBD) in congenital heart disease (CHD) patients. METHODS: Retrospective chart review of adjustable PAB-outline anatomical variants palliated and patient outcomes. RESULTS: Sixteen patients underwent dilatable PAB-median age 52 days (range 4-215) and weight 3.12 kg (1.65-5.8). Seven (44%) of the patients were premature, 11 (69%) had ventricular septal defect(s) with pulmonary over-circulation, four (25%) atrioventricular septal defects, and four (25%) single ventricle physiology. Subsequent to the index procedure: five patients have undergone intracardiac complete repair, six patients remain well palliated with no additional intervention, and four single ventricles await their next palliation. One patient died from necrotizing enterocolitis (unrelated to PAB) and one patient required a pericardiocentesis postoperatively. Five patients underwent TCBD of the PAB without complication-Two had one TCBD, two had two TCBD, and another had three TCBD. The median change in saturation was 14% (complete range 6-22) and PAB diameter 1.7 mm (complete range 1.1-5.2). Median time from PAB to most recent outpatient follow-up was 868 days (interquartile range 190-1,079). CONCLUSIONS: Our institution has standardized a PAB technique that allows for transcatheter incremental increases in pulmonary blood flow over time. This methodology has proven safe and effective enough to supplant other institutional techniques of limiting pulmonary blood flow in most patients-allowing for interval growth or even serving as the definitive palliation.

Reconstruction of the Neopulmonary Root After Coronary Button Harvest for Arterial Switch Operation Using 2-ply Extracellular Matrix (Tyke): A Post-Implant Histology.

In children with Transposition of the Great Arteries (TGA), the pulmonary artery, and aorta are connected to the heart abnormally resulting in blue blood (deoxygenated) recirculating to the body and red blood (oxygenated) recirculating to the lungs. The arterial switch operation (ASO) is the standard of care for transposition of the great arteries (TGA), and given the low risk of early mortality and satisfactory long-term outcomes, focus is now on managing longer term complications such as neo-aortic root dilatation, and pulmonary artery stenosis. Since May 2016, we have used 2-ply extracellular matrix (ECM; Tyke) for reconstruction of the coronary button defects using a pantaloon patch. We present histology of implanted 2-ply ECM (Tyke) from a patient who went back to surgery for development of subaortic stenosis ~12 months after ASO.

The Destiny of Postoperative Residual Ventricular Septal Defects After Surgical Repair in Infants and Children.

PURPOSE: Residual ventricular septal defects (rVSDs) of small size are commonly seen on transesophageal echocardiography after surgical repair. This study aimed to determine the destiny of rVSD found on intraoperative echocardiogram. METHODS: Patients undergoing surgical repair of VSD as the primary procedure with available intraoperative and discharge echocardiograms between 2007 and 2017 were reviewed. Presence of an rVSD on intraoperative echo triggered review of discharge echo and of subsequent follow-up echocardiograms. RESULTS: One hundred four patients were analyzed. The mean age and weight for the entire cohort were 1.4 ± 2.9 years (median, 5.4 months; range, 29 days to 14 years) and 8.8 ± 9.9 kg (median, 5.1 kg; range, 2.7-58 kg), respectively. Sixty (57%) patients had rVSD at discharge, with mean size of residual VSD of 1.38 ± 0.92 mm (mode, 0.6; median, 2.2 mm; range, 0.5-3.9 mm). The mean follow-up time was 3.7 ± 3.1 years (range, 1 month to 9.3 years). Among those with rVSD at discharge, a residual shunt persisted in 73% at one-month follow-up. On follow-up at three years postdischarge, of the 60 patients with early rVSD, 6 had a persistent rVSD (10%) with a mean diameter of 3.0 ± 0.8 mm (range, 2.4-3.9 mm). CONCLUSIONS: Residual VSD after surgical repair is detected frequently on postoperative echocardiogram. The presence of rVSD was not associated with any preoperative, intraoperative, or postoperative factors. By three years of follow-up, only six patients continued to demonstrate rVSD with a mean diameter of 3 mm, suggesting that defects 3 mm or greater may be less likely to close spontaneously after three years.

Performance of SynerGraft Decellularized Pulmonary Allografts Compared With Standard Cryopreserved Allografts: Results From Multiinstitutional Data.

BACKGROUND: Structural deterioration of allografts over time is believed to be at least partly related to an immune response mounted against human leukocyte antigen specific to the transplanted tissue. SynerGraft (SG) processing (CryoLife, Kennesaw, GA) is a technology that decellularizes an allograft leaving only connective tissue, therefore, reducing immunogenicity and potentially increasing durability of the implant. METHODS: We performed a retrospective review of 163 SG patients and 124 standard allograft controls from 3 medical centers. Patient demographics were tabulated, and conduit stenosis and insufficiency were measured by echocardiography. RESULTS: There were 28 deaths (15 of 163 [9%] SG patients vs 13 of 124 [11%] standard patients; p = 0.72), but no deaths were attributed to structural failure of the conduit. The actuarial survival for SG vs standard cohorts was not different at 5 and 10 years. Among the 274 hospital survivors, 17% SG vs 42% standard had evidence for significant conduit dysfunction at the most recent follow-up or before conduit replacement. Freedom from conduit dysfunction was significantly worse at 10 years in the standard group (58%) than in the SG group (83%, p < 0.001). CONCLUSIONS: This study represents a multiinstitutional retrospective comparison of SG and standard cryopreserved allografts used in right ventricular outflow tract reconstruction in a broad range of patient ages. Our results demonstrate that at an intermediate-term to long-term follow-up, conduit dysfunction and pulmonary insufficiency and stenosis are higher among patients receiving standard allografts. We postulate that the improved durability of SG is related to decreased immunogenicity of the SG technology.

Feasibility and early effectiveness of a custom, hand-made systemic atrioventricular valve using porcine extracellular matrix (CorMatrix) in a 4-month-old infant.

A need persists for a prosthetic, systemic atrioventricular valve replacement in the pediatric population that can be customized to a wide range of annular sizes, has a low risk of thrombosis, possesses optimal hemodynamic performance, and has the potential to remodel and grow with the patient. We describe a technique for successful systemic atrioventricular valve replacement in a 4-month-old infant by use of a handmade, bileaflet systemic atrioventricular prosthesis constructed from porcine extracellular matrix.

Evidence for impaired vagus nerve activity in heart failure.

Parasympathetic control of the heart via the vagus nerve is the primary mechanism that regulates beat-to-beat control of heart rate. Additionally, the vagus nerve exerts significant effects at the AV node, as well as effects on both atrial and ventricular myocardium. Vagal control is abnormal in heart failure, occurring at early stages of left ventricular dysfunction, and this reduced vagal function is associated with worse outcomes in patients following myocardial infarction and with heart failure. While central control mechanisms are abnormal, one of the primary sites of attenuated vagal control is at the level of the parasympathetic ganglion. It remains to be seen whether or not preventing or treating abnormal vagal control of the heart improves prognosis.

Chronic vagus nerve stimulation improves autonomic control and attenuates systemic inflammation and heart failure progression in a canine high-rate pacing model.

BACKGROUND: Autonomic dysfunction, characterized by sympathetic activation and vagal withdrawal, contributes to the progression of heart failure (HF). Although the therapeutic benefits of sympathetic inhibition with beta-blockers in HF are clear, the role of increased vagal tone in this setting has been less studied. We have investigated the impact of enhancing vagal tone (achieved through chronic cervical vagus nerve stimulation, [VNS]) on HF development in a canine high-rate ventricular pacing model. METHODS AND RESULTS: Fifteen dogs were randomized into control (n=7) and VNS (n=8) groups. All dogs underwent 8 weeks of high-rate ventricular pacing (at 220 bpm for the first 4 weeks to develop HF and another 4 weeks at 180 bpm to maintain HF). Concomitant VNS, at an intensity reducing sinus rate approximately 20 bpm, was delivered together with the ventricular pacing in the VNS group. At 4 and 8 weeks of ventricular pacing, both left ventricular end-diastolic and -systolic volumes were lower and left ventricular ejection fraction was higher in the VNS group than in the control group. Heart rate variability and baroreflex sensitivity improved in the VNS dogs. Rises in plasma norepinephrine, angiotensin II, and C-reactive protein levels, ordinarily expected in this model, were markedly attenuated with VNS treatment. CONCLUSIONS: Chronic VNS improves cardiac autonomic control and significantly attenuates HF development in the canine high-rate ventricular pacing model. The therapeutic benefit of VNS is associated with pronounced anti-inflammatory effects. VNS is a novel and potentially useful therapy for treating HF.

Vagal denervation and atrial fibrillation inducibility: epicardial fat pad ablation does not have long-term effects.

BACKGROUND: Major epicardial fat pads contain cardiac ganglionated plexi of the autonomic, predominantly vagal nerves. Vagal denervation may improve the success rate of atrial fibrillation (AF) treatment. OBJECTIVES: The purpose of this study was to elucidate the long-term effects of fat pad ablation on the electrophysiologic characteristics of the atrium and AF inducibility. METHODS: Six mongrel dogs were studied. Cervical vagal stimulation was applied to determine effects on the sinus node, AV node, atrial effective refractory period (AERP), and AF inducibility. AERP and AF inducibility were evaluated at both the right atrial and left atrial appendages and at the right atrial and left atrial free walls. Radiofrequency energy was delivered epicardially to the entire areas of two major fat pads: right pulmonary vein fat pad and inferior vena cava-left atrium fat pad. Cervical vagal stimulation then was applied to confirm the acute effects of fat pad ablation. The same evaluation was repeated 4 weeks later. RESULTS: The effects of vagal stimulation on the sinus node, AV node, and AERP were significantly eliminated immediately after fat pad ablation. However, these denervation effects disappeared after 4 weeks. At baseline, AF inducibility was increased by vagal stimulation (right atrial appendage: 72% +/- 31% vs 4.8% +/- 12%; right atrial free wall: 75% +/- 31% vs 0.0% +/- 0.0%; left atrial appendage: 60% +/- 29% vs 0.0% +/- 0.0%; left atrial free wall: 65% +/- 42% vs 0.0% +/- 0.0%). Fat pad ablation significantly reduced this vagal stimulation effect (8.3% +/- 20%, 10% +/- 22%, 17% +/- 29%, and 25% +/- 29%, respectively). However, similar to baseline, AF inducibility was strongly augmented by vagal stimulation 4 weeks after fat pad ablation (96% +/- 10%, 100% +/- 0.0%, 100% +/- 0.0%, and 95% +/- 11%, respectively). CONCLUSION: Radiofrequency fat pad ablation may not achieve long-term suppression of AF induction in this canine model.

Chronic atrioventricular nodal vagal stimulation: first evidence for long-term ventricular rate control in canine atrial fibrillation model.

BACKGROUND: We have previously demonstrated that selective atrioventricular nodal (AVN) vagal stimulation (AVN-VS) can be used to control ventricular rate during atrial fibrillation (AF) in acute experiments. However, it is not known whether this approach could provide a long-term treatment in conscious animals. Thus, this study reports the first observations on the long-term efficacy and safety of this novel approach to control ventricular rate during AF in chronically instrumented dogs. METHODS AND RESULTS: In 18 dogs, custom-made bipolar patch electrodes were sutured to the epicardial AVN fat pad for delivery of selective AVN-VS by a subcutaneously implanted nerve stimulator (pulse width 100 micros or 1 ms, frequency 20 or 160 Hz, amplitude 6 to 10 V). Fast-rate right atrial pacing (600 bpm) was used to induce and maintain AF. ECG, blood pressure, and body temperature were monitored telemetrically. One week after the induction of AF, AVN-VS was delivered and maintained for at least 5 weeks. It was found that AVN-VS had a consistent effect on ventricular rate slowing (on average 45+/-13 bpm) over the entire period of observation. Echocardiography showed improvement of cardiac indices with ventricular rate slowing. AVN-VS was well tolerated by the animals, causing no signs of distress or discomfort. CONCLUSIONS: Beneficial long-term ventricular rate slowing during AF can be achieved by implantation of a nerve stimulator attached to the epicardial AVN fat pad. This novel concept is an attractive alternative to other methods of rate control and may be applicable in a selected group of patients.

Alpha7-nicotinic acetylcholine receptor subunit is not required for parasympathetic control of the heart in the mouse.

Nicotinic acetylcholine receptors (nAChR) are assembled from a pool of nine alpha-subunits and three beta-subunits into functional pentamers in peripheral autonomic neurons. The contribution of different subunits to native, physiologically important nAChR for synaptic transmission in autonomic ganglia is unclear. Here, we examined the importance of the alpha7-subunit for parasympathetic innervation of the heart. Normal (C57BL/6J), alpha7-deficient (Chrna7), and wild-type littermate mice were implanted with telemetry devices, and, under conscious, unsedated conditions, ECG recordings were obtained at baseline and after atropine, propranolol, and hexamethonium bromide administration. Spectral analysis of heart rate variability [power spectral analysis (PSA)] was performed for the evaluation of resting autonomic tone to the heart. At the completion of conscious studies, animals were anesthetized and underwent electrical stimulation of the vagus nerve (VS) while R-R intervals were recorded. Heart rate at baseline and after atropine, propranolol, or hexamethonium was similar in all three groups of animals. PSA curves were similar between normal, wild-type, and Chrna7 mice. VS showed no difference between control and Chrna7 mice throughout the range of stimulation (5-20 Hz). Mice deficient in the alpha7-nAChR subunit do not display differences in resting autonomic tone to the heart at baseline or under conditions of single and combined autonomic blockade. VS showed no difference in heart rate responses between normal and alpha7-deficient mice. These data support previous findings in vitro and highlight the important differences in function between nicotinic receptor subtypes because alpha3-deficient mice display major autonomic dysfunction. We conclude that the alpha7-subunit does not contribute critically to resting parasympathetic control of the heart.

Prevention of diminished parasympathetic control of the heart in experimental heart failure.

Decreased synaptic transmission in parasympathetic ganglia contributes to abnormal parasympathetic function in heart failure (HF). Because nicotinic ACh receptors (nAChR) mediate synaptic transmission at the ganglion and upregulate in response to chronic exposure to agonist in vitro, we tested the hypothesis that repeated exposures of ganglionic neurons to a nAChR agonist can prevent a loss of parasympathetic control in HF. Two sets of experiments were performed. In set 1, unpaced control dogs and dogs undergoing pacing-induced HF were treated with a repeated intravenous nicotinic agonist during the development of HF. Under conditions of sympathetic blockade, R-R responses to a bolus injection of 200 microg 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP; nicotinic agonist) were found to be increased five times over the untreated group after 6 wk. In experimental set 2, dogs treated with weekly DMPP injections and in HF were anesthetized and underwent electrical stimulation of the right vagus nerve, which showed sinus cycle length responses >10 times that of controls (P < 0.05). Complete ganglionic blockade with hexamethonium abolished all responses, confirming that synaptic transmission was mediated entirely by nAChRs in both controls and HF. Despite decreased ganglionic function leading to reduced parasympathetic control of the heart in HF, repeated exposure with a nicotinic agonist during the development of HF results in not only preserved but also supranormal effects of parasympathetic stimulation on the sinus node.

Mechanisms of altered vagal control in heart failure: influence of muscarinic receptors and acetylcholinesterase activity.

Parasympathetic control of the heart is attenuated in heart failure (HF). We investigated possible mechanisms and sites of altered vagal control in dogs with HF induced by rapid pacing. Muscarinic blockade reduced the R-R interval by 308 ms in controls but only by 32 ms in HF, indicating low levels of resting vagal tone. Vagomimetic doses of atropine sulfate prolonged the R-R interval by 109 ms in controls and increased standard deviation of the R-R interval by 66 ms but only by 46 and 16 ms, respectively, in HF. Bradycardia elicited by electrical stimulation of the vagus nerve was also attenuated in the HF group. Conversely, muscarinic receptor activation by bethanechol, and indirectly by neostigmine, elicited exaggerated R-R interval responses in HF. To investigate possible mechanisms, we measured muscarinic receptor density (Bmax) and acetylcholinesterase activity in different areas of the heart. In sinoatrial nodes, Bmax was increased (230 +/- 75% of control) and acetylcholinesterase decreased (80 +/- 6% of control) in HF. We conclude that muscarinic receptors are upregulated and acetylcholinesterase is reduced in the sinus node in HF. Therefore, reduced vagal control in HF is most likely due to changes of presynaptic function (ganglionic), because postsynaptic mechanisms augment vagal control in HF.