Renato S. Assad

New lead for in utero pacing for fetal congenital heart block

Complete heart block occurs in 4% to 15% of cases of fetal arrhythmia. Although it is usually well tolerated in the absence of complicating cardiac anomalies, as many as 25% of these fetuses have hydrops and die in utero. The pathophysiologic arguments for fetal ventricular pacing are compelling. We describe the case of a fetus presenting with complete heart block, hydrops, and associated structural heart defects, the mother of whom consented to attempts at in utero pacing. The purpose of this article is to describe a new lead for percutaneous implantation that minimizes surgical trauma to both the fetus and the mother.

Biventricular structural and functional responses to aortic constriction in a rabbit model of chronic right ventricular pressure overload

OBJECTIVES Chronic right ventricular (RV) pressure overload results in pathologic RV hypertrophy and diminished RV function. Although aortic constriction has been shown to improve systolic function in acute RV failure, its effect on RV responses to chronic pressure overload is unknown. METHODS Adjustable vascular banding devices were placed on the main pulmonary artery and descending aorta. In 5 animals (sham group), neither band was inflated. In 9 animals (PAB group), only the pulmonary arterial band was inflated, with adjustments on a weekly basis to generate systemic or suprasystemic RV pressure at 28 days. In 9 animals, both pulmonary arterial and aortic devices were inflated (PAB + AO group), the pulmonary arterial band as for the PAB group and the aortic band adjusted to increase proximal systolic blood pressure by approximately 20 mm Hg. Effects on the functional performance were assessed 5 weeks after surgery by conductance catheters, followed by histologic and molecular assessment. RESULTS Contractile performance was significantly improved in the PAB + AO group versus the PAB group for both ventricles. Relative to sham-operated animals, both banding groups showed significant differences in myocardial histologic and molecular responses. Relative to the PAB group, the PAB + AO group showed significantly decreased RV cardiomyocyte diameter, decreased RV collagen content, and reduced RV expression of endothelin receptor type B, matrix metalloproteinase 9, and transforming growth factor β genes. CONCLUSIONS Aortic constriction in an experimental model of chronic RV pressure overload not only resulted in improved biventricular systolic function but also improved myocardial remodeling. These data suggest that chronically increased left ventricular afterload leads to a more physiologically hypertrophic response in the pressure-overloaded RV.

Adverse Biventricular Remodeling in Isolated Right Ventricular Hypertension Is Mediated by Increased Transforming Growth Factor–β1 Signaling and Is Abrogated by Angiotensin Receptor Blockade

The pressure-loaded right ventricle (RV) adversely affects left ventricular (LV) function. We recently found that these ventricular-ventricular interactions lead to LV myocardial fibrosis through transforming growth factor-β1 (TGF-β1) signaling. We investigated the mechanisms mediating biventricular fibrosis in RV afterload and their potential modification by angiotensin receptor blockade. An adjustable pulmonary artery band (PAB) was placed in rabbits. In sham-operated control rabbits, the band was left uninflated (n = 6). In the RV afterload group, the PAB was sequentially inflated to generate systemic RV pressure at 28 days (n = 8). In a third group, the PAB was inflated to systemic levels, and the angiotensin receptor blocker losartan was added (n = 6). Five weeks after surgery, the animals were killed for assessments of biventricular hypertrophy, fibrosis, apoptosis, and the components of their signaling pathways. PAB animals developed biventricular hypertrophy, fibrosis, and apoptosis, versus sham rabbits, in which these conditions were decreased with losartan. RV and LV TGF-β1, connective tissue growth factor (CTGF) (CCN2), endothelin-1 (ET-1), endothelin receptor B, and matrix metalloproteinase 2/9 mRNA levels were increased in PAB animals versus sham animals, and decreased with losartan. Given the marked biventricular CTGF up-regulation in PAB and down-regulation with losartan, we investigated CTGF signaling. RV and LV Smad 2/3/4 protein levels and LV RhoA mRNA levels were increased with PAB and reduced with losartan. In conclusion, isolated RV afterload induces biventricular fibrosis and apoptosis, which are reduced by angiotensin receptor blockade. Adverse ventricular-ventricular interactions induced by isolated RV afterload appear to be mediated through TGF-β1-CTGF and ET-1 pathways.

Beneficial effects of vasopressors on right ventricular function in experimental acute right ventricular failure in a rabbit model.

BACKGROUND An acute increase in right ventricular (RV) afterload leads to RV dilation, reduced systolic function, and low cardiac output. It has previously been shown, experimentally, that an additional increase of left ventricular afterload by aortic constriction can reverse some of these changes. We studied the clinically more relevant effects of intravenous vasopressors on this phenomenon in an animal model. METHODS Acute RV failure was induced by pulmonary artery constriction in adult New Zealand white rabbits. We then assessed the effect of aortic constriction on the functional performance of the failing RV using conductance catheters. We compared the impact of aortic constriction on RV contractility with the effects of 0.05, 0.1, 0.5, and 1 mcg/kg × min(-1) norepinephrine and epinephrine. RESULTS Aortic constriction lead to increased RV end-systolic pressure-volume relation (RVESPVR 3.2 (±0.6) versus 5.2 (±0.7) mm Hg/mL (p = 0.0002). Cardiac output (131 (±23.7) versus 134.8 (±32.5) mL/min), and heart rate remained unchanged. Administration of norepinephrine and epinephrine lead to similar effects on RV contractility with the maximum increase in RVESPVR observed with 0.5 mcg/kg × min(-1) norepinephrine (RVESPVR 4.8 (±0.4) mm Hg/mL, p = 0.007). However, in contrast to aortic constriction, cardiac output also markedly increased during vasopressor therapy, the most significant effect seen with 1 mcg/kg × min(-1) epinephrine (214.8 (±46.8) mL/min, p = 0.04). CONCLUSIONS Aortic constriction improves RV contractility but not cardiac output in acute right heart failure. A comparable effect on RV functional performance with increased cardiac output was achieved by administration of systemic vasopressors. These data may have implications for management of clinical right heart failure.

New transcatheter techniques for creation or enlargement of atrial septal defects in infants with complex congenital heart disease

To describe a series of 8 consecutive infants (5 with transposition of the great arteries [TGA] and 3 with hypoplastic left heart syndrome [HLHS]) who underwent nonconventional septostomy techniques.

Fetal Heart Block: A New Experimental Model to Assess Fetal Pacing

Epicardial fetal pacing via thoracotomy has the potential of being a safer and more reliable procedure to treat congenital complete heart block (CHB) associated with fetal hydrops refractory to medical therapy. To assess the acute electrophysiological characteristics of two ventricular epicardial leads, a new experimental model of fetal heart block induced by cryosurgical ablation of the AV node without the need for fetal cardiac bypass was performed in 12 pregnant ewes at 110–115 days gestation. A modified screw‐in lead (1½ turns) was used in six fetal lambs and a stitch‐on lead in the other six lambs. CHB was achieved in 100% of the fetal lambs, with no ventricular escape rate noticed in any of the lambs. The acute stimulation thresholds were consistently low for both leads, with lower values for the screw‐in lead at pulse duration below 0.9 msec (P < 0.03). Current measured at voltage threshold with pulse width below 0.5 msec was lower for the screw‐in lead (P < 0.048). Stimulation resistance, measured during constant‐voltage pacing, was not statistically different between the two leads (441.8 ± 13.7 Ω for the screw‐in lead vs 480.2 ± 59.2 Ω for the stitch‐on lead). No significant differences (P > 0.20) were found in R wave amplitude between the two electrodes. Slew rates were significantly higher in the screw‐in group than in the stitch‐on group (1.40 ± 0.2 vs 0.62 ± 0.2 V/sec, P = 0.04). This model of CHB is a simple and reproducible method to assess fetal pacing. We find the screw‐in electrode to be a better option when fetal pacing is indicated.

Bandagem ajustável do tronco pulmonar: comparação de dois métodos de hipertrofia aguda do ventrículo subpulmonar

OBJECTIVE: This study compares ventricular hypertrophy induced by continuous versus intermittent systolic overload of the pulmonary ventricle (RV) of young goats. METHODS: Three groups of seven goats were used (control, continuous, and intermittent). Systolic overload was maintained for 96 hours in the continuous group, while the intermittent group suffered four 12-hour periods of systolic overload, alternating with 12-hour resting periods. Echocardiographic and hemodynamic evaluations were performed every day. The animals were then killed for myocardial water content and weight evaluation. RESULTS: Both study groups achieved significant increases in RV mass (p<0.05). However, significant increases of the septum mass were observed only in the Intermittent Group (p<0.05). A greater increase in the RV wall thickness was observed in the Intermittent Group (p<0.05). There was a significant difference in RV diastolic volume between the two groups (p= 0.01), with a greater RV dilation in the Continuous Group after 24 hours of continuous overload (p< 0.03). In both groups, the RV ejection fraction was maintained within the normal range throughout the protocol. A smaller RV perimeter was observed in the Intermittent Group after 96 hours of systolic overload (p<0.05). There was no significant difference in RV myocardial water content between the study groups and the Control Group. CONCLUSIONS: Adjustable pulmonary artery bandages permit rapid RV hypertrophy in both groups. Nevertheless, it is more efficient in the Intermittent Group. This study suggests that preparation of the pulmonary ventricle with intermittent systolic overload might provide better results for the 2-stage arterial switch operation.

Using the impact factor and H index to assess researchers and publications.

Described in 2005 by Jorge E. Hirsch as a tool to determine the relative quality of papers produced by theoretical physicists, the H index has become widely used in scientific circles as a way of measuring researchers’ productivity and impact. It was even incorporated into the Lattes Platform of the Brazilian Council of Scientific and Technological Development (CNPq)5. In this article, we discuss the impact factor as a means of assessing scientific journals and H index as a way of assessing researchers. Other bibliometric indexes will not be addressed in this paper, but it should be noted that only the impact factor and H index alone may not be sufficient to accomplish the task of evaluating journals, articles and authors.

Cryosurgical Ablation of Fetal Atrioventricular Node: New Model to Treat Fetal Malignant Tachyarrhythmias

BACKGROUND Sustained tachyarrhythmia resulting in fetal hydrops is often refractory to medical therapy. Fetal atrioventricular node ablation associated with epicardial fetal pacing has the potential to be an effective procedure for this morbid association. METHODS To assess the feasibility of therapeutic fetal heart block, we developed a technique of intrauterine cryosurgical ablation of fetal atrioventricular node without the need for cardiac bypass in 8 fetal lambs. Complete heart block was obtained by applying the cryoprobe over the coronary sinus. Fetal pacing was then performed to allow fetal survival. RESULTS Complete heart block was achieved in 100% of the fetal lambs. Postoperative evaluation revealed persistent atrioventricular block. The hearts were studied at different postoperative times. Morphologic evaluation of the area containing the cryosurgical lesion revealed varied extension of necrosis of the atrioventricular node and hemorrhage, with involvement of the His bundle and proximal right bundle branch. CONCLUSIONS This procedure is technically feasible and offers an alternative approach to the treatment of drug-resistant, life-threatening fetal supraventricular tachyarrhythmias associated with hydrops fetalis.

Reversible pulmonary trunk banding. VI: Glucose-6-phosphate dehydrogenase activity in rapid ventricular hypertrophy in young goats

OBJECTIVE Increased myocardial glucose-6-phosphate dehydrogenase (G6PD) activity occurs in heart failure. This study compared G6PD activity in 2 protocols of right ventricle (RV) systolic overload in young goats. METHODS Twenty-seven goats were separated into 3 groups: sham (no overload), continuous (continuous systolic overload), and intermittent (four 12-hour periods of systolic overload paired with a 12-hour resting period). During a 96-hour protocol, systolic overload was adjusted to achieve a 0.7 RV/aortic pressure ratio. Echocardiographic and hemodynamic evaluations were performed before and after systolic overload every day postoperatively. After the study period, the animals were humanely killed for morphologic and G6PD tissue activity assessment. RESULTS A 92.1% and 46.5% increase occurred in RV and septal mass, respectively, in the intermittent group compared with the sham group; continuous systolic overload resulted in a 37.2% increase in septal mass. A worsening RV myocardial performance index occurred in the continuous group at 72 hours and 96 hours, compared with the sham (P < .039) and intermittent groups at the end of the protocol (P < .001). Compared with the sham group, RV G6PD activity was elevated 130.1% in the continuous group (P = .012) and 39.8% in the intermittent group (P = .764). CONCLUSIONS Continuous systolic overload for ventricle retraining causes RV dysfunction and upregulation of myocardial G6PD activity, which can elevate levels of free radicals by NADPH oxidase, an important mechanism in the pathophysiology of heart failure. Intermittent systolic overload promotes a more efficient RV hypertrophy, with better preservation of myocardial performance and and less exposure to hypertrophic triggers.