Status of the left ventricle after arterial switch operation for transposition of the great arteries Hemodynamic and echocardiographic evaluation

AbstractBackground : The potential for improved preservation of systemic ventricular function represents an important reason for the increasing popularity of the arterial switch operation. In support of this expectation, prior studies in patients early after arterial switch operation have found normal ventricular contractility and function. This study was conducted to extend those observations to up to 10 years of follow-up and to directly examine the effects of a coexisting ventricular septal defect or short-term preparatory banding of the pulmonary artery before the arterial switch operation. Methods : Patients operated on from 1983 through 1991 were included. Echocardiographic and catheterization data were collected as part of a prospective evaluation of outcome in all patients who undergo the arterial switch operation at Boston Children's Hospital, with inclusion of data from the most recent catheterization only. Echocardiograms performed at least 6 months after the operation were included, with assessment of both the most recent status as well as serial trends. Whenever possible, echocardiographic evaluation included data necessary to perform analysis of ventricular mechanics including indices of afterload, preload, and contractility. Comparison was made to normal values and between subgroups defined on the basis of an arterial switch operation with or without ventricular septal defect and those who had a rapid two-stage arterial switch operation. Results : Invasive measures of left and right ventricular filling pressures, cardiac index, and pulmonary vascular resistance did not differ among the three groups. Overall, echocardiographic left ventricular end-diastolic dimension, wall thickness, mass, afterload (end-systolic wall stress), function (fractional shortening and rate-corrected velocity of fiber shortening), contractility (stress-velocity and stress-shortening relations), and preload were normal, and none of these variables was different between the groups with and without a ventricular septal defect. Serial evaluation indicated a slight but significant trend toward ventricular dilatation, perhaps related to a relatively high incidence of at least mild aortic regurgitation (30%). In contrast, in the rapid two-stage group the echocardiographic indices of left ventricular function (fractional shortening and velocity of fiber shortening) and contractility (stress-velocity and stress-shortening relations) were found to be mildly but significantly reduced compared with normal subjects and with the other arterial switch operation groups. Over the duration of follow-up encompased by this study, no tendency toward progressive depression of function was seen. Conclusions : As the length of observation after the arterial switch operation continues to increase, left ventricular size, mass, functional status, and contractility continues to be normal, with no evidence of time-related deterioration of function. As previously reported, the rapid two-stage arterial switch operation does represent a higher risk for mild impairment of myocardial mechanics. (J T horac C ardiovasc S urg 1995;109:311-21

Double-inlet single left ventricle: Echocardiographic anatomy with emphasis on the morphology of the atrioventricular valves and ventricular septal defect

AbstractThe echocardiographic anatomy of double inlet single left ventricle was studied in 57 patients, aged 1 day to 27 years (mean 6 years); the variables examined included morphology, size and function of the atrioventricular AV) valves and ventricular septal defect and their relation to pulmonary stenosis, aortic stenosis and aortic arch obstruction. The visceroatrial situs was solitus and the heart was in the left side of the chest in all 57 patients. A d-loop ventricle was present in 21 patients and an l-loop ventricle in 36. The great arteries were normally related (Holmes heart) in 8 patients and transposed in 49.In all hearts, the right AV valve was anterior to the left AV valve. In 53 patients, the tricuspid valve (right valve in d-loop and left valve in l-loop) was closer to and had attachments on the septum. The tricuspid valve straddled the outflow chamber in eight patients. No significant difference was noted in the mean AV valve diameter when comparing mitral and tricuspid valves within the same group or between the groups with a d- or l-loop ventricle. The right AV valve diameter had a significant direct correlation with the aortic valve diameter and the size or (he ventricular septal defect regardless of ventricular loop. Both AV valves were functionally normal in 34 patients. Among patients with AV valve dysfunction, the tricuspid valve tended to be stenotic in patients with an l-loop ventricle and regurgitant in patients with a d-loop ventricle. Mitral valve dysfunction was uncommon.The ventricular septal defect (46 patients) was separated from the semilunar valves in 24 patients (muscular defect) and adjacent to the anterior semilunar valve as a result of hypoplasia or malalignment, or both, of the infundibular septum (subaortic defect) in 19 patients. Multiple defects were present in three patients. The difect was unrestrictive in 26 patients, restrictive in 23 and could not be evaluated in 8. Pulmonary artery banding had been performed in 8 of the 26 patients with an unrestrictive defect and in 10 of the 23 patients with a restrictive defect. Only 4 of 19 subaortic defects compared with 16 of 24 muscular defects were restrictive. The size of the defect was significantly correlated with the measured pressure gradient. Among patients with transposition, only 2 of 13 with pulmonary stenosis had a restrictive ventricular septal defect compared with 15 of 30 without pulmonary stenosis. In patients with transposition, the defect size was significantly smaller when coarctation was present

Valsartan for attenuating disease evolution in early sarcomeric hypertrophic cardiomyopathy: the design of the Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) trial

Background: Hypertrophic cardiomyopathy (HCM) is often caused by sarcomere gene mutations, resulting in left ventricular hypertrophy (LVH), myocardial fibrosis, and increased risk of sudden cardiac death and heart failure. Studies in mouse models of sarcomeric HCM demonstrated that early treatment with an angiotensin receptor blocker (ARB) reduced development of LVH and fibrosis. In contrast, prior human studies using ARBs for HCM have targeted heterogeneous adult cohorts with well-established disease. The VANISH trial is testing the safety and feasibility of disease-modifying therapy with an ARB in genotyped HCM patients with early disease. Methods: A randomized, placebo-controlled, double-blind clinical trial is being conducted in sarcomere mutation carriers, 8 to 45 years old, with HCM and no/minimal symptoms, or those with early phenotypic manifestations but no LVH. Participants are randomly assigned to receive valsartan 80 to 320 mg daily (depending on age and weight) or placebo. The primary endpoint is a composite of 9 z-scores in domains representing myocardial injury/hemodynamic stress, cardiac morphology, and function. Total z-scores reflecting change from baseline to final visits will be compared between treatment groups. Secondary endpoints will assess the impact of treatment on mutation carriers without LVH, and analyze the influence of age, sex, and genotype. Conclusions: The VANISH trial is testing a new strategy of disease modification for treating sarcomere mutation carriers with early HCM, and those at risk for its development. In addition, further insight into disease mechanisms, response to therapy, and phenotypic evolution will be gained

Individual pulmonary vein size and survival in infants with totally anomalous pulmonary venous connection

AbstractObjectives. We investigated whether mortality in totally anomalous pulmonary venous connection could be predicted from preoperative individual pulmonary vein size.Background. Some infants with this anomaly die with or without surgical repair because of stenosis of individual pulmonary veins.Methods. Individual pulmonary vein, vertical vein and pulmonary venous confluence diameters were retrospectively measured from preoperative echocardiograms in 32 infants with totally anomalous pulmonary venous connection presenting to Children's Hospital, Boston over a 1/2-year period. Data on body surface area, other cardiac anomalies, presence of initial pulmonary venous obstruction and early surgery and outcome were also recorded.Results. Of 32 patients, 6 (18.8%) died before hospital discharge, and 8 (25.0%) died subsequently. Six (75.0%) of the eight patients who died late had individual pulmonary vein stenosis at sites remote from the surgical anastomosis to the left atrium. The remaining 18 patients (56.3%) are alive at a mean follow-up period of 9.7 months. A Cox proportional hazard model revealed that small sum of individual pulmonary vein diameters (p = 0.0004), small confluence size (p = 0.02) and presence of heterotaxy syndrome (p = 0.008) were each significant univariate predictors of survival. Multivariate analysis showed that small pulmonary vein sum was a strong predictor of survival (p = 0.008), independent of the presence of heterotaxy syndrome. An analysis stratified by the presence of heterotaxy syndrome showed that the predictive effect of small pulmonary vein sum on survival was strongest in patients without heterotaxy syndrome.Conclusions. These data show that individual pulmonary vein size at diagnosis is a strong, independent predictor of survival in patients with totally anomalous pulmonary venous connection. In patients with this anomaly and small individual pulmonary veins, the anomaly may not be correctable by surgical creation of an anastomosis between the pulmonary venous confluence and the left atrium

Multipolar endocardial mapping of the right atrium during cardiac catheterization: description of a new technique

AbstractObjectives. Using a new mapping system that allows the simultaneous acquisition of date from 25 right atrial bipolar electrodes during cardiac catheterization, we mapped normal sinus rhythm and atrial reentrant tachycardia in 24 sheep (20 to 49 kg) and 7 pigs (25 to 35 kg).Background. Rapid, high resolution mapping during cardiac catheterization may shorten ablation procedures and permit ablation of otherwise refractory arrhythmias.Methods. A flexible, elliptic, basket-shaped recording catheter has five spokes, each with 10 electrodes arranged as 5 bipolar pairs. Catheter shape, electrode spacing and introduction technique were modified in response to the results of experiments in the first 23 animals. In the most recent eight animals, retraction of a string attached to the distal tip distended the basket, providing safe tissue contact. Filtered (30 to 250 Hz) bipolar recordings from all 25 electrode pairs, as well as a surface electrocardiogram, were recorded and digitized at 1,000 Hz using custom software. An activation map was digitally constructed and superimposed on anteroposterior and lateral fluoroscopic catheter images. Bipolar recordings were made in normal sinus rhythm (31 animals), with adequate signals recorded from >95% of electrode pairs. Rapid burst pacing and intentional right atrial air embolus (30 to 50 ml) induced sustained atrial reentrant tachycardia in five animais, which was also adequately recorded.Results. Catheter positioning and complete atrial mapping required <10 min after venous access in the most recent eight experiments. The catheter was left in position for up to 4 h. Postmortem evaluation revealed minor superficial abrasion of the venae cavae or right atrial endocardium in six animals and moderate abrasion in two. No other damage was observed.Conclusions. This new system may ultimately assist in mapping simple or complex atrial arrhythmias during cardiac eatheterization

Determination of a complex crystal structure in the absence of single crystals : analysis of powder X-ray diffraction data, guided by solid-state NMR and periodic DFT calculations, reveals a new 2′-deoxyguanosine structural motif

Derivatives of guanine exhibit diverse supramolecular chemistry, with a variety of distinct hydrogen-bonding motifs reported in the solid state, including ribbons and quartets, which resemble the G-quadruplex found in nucleic acids with sequences rich in guanine. Reflecting this diversity, the solid-state structural properties of 3′,5′-bis-O-decanoyl-2′-deoxyguanosine, reported in this paper, reveal a hydrogen-bonded guanine ribbon motif that has not been observed previously for 2′-deoxyguanosine derivatives. In this case, structure determination was carried out directly from powder XRD data, representing one of the most challenging organic molecular structures (a 90-atom molecule) that has been solved to date by this technique. While specific challenges were encountered in the structure determination process, a successful outcome was achieved by augmenting the powder XRD analysis with information derived from solid-state NMR data and with dispersion-corrected periodic DFT calculations for structure optimization. The synergy of experimental and computational methodologies demonstrated in the present work is likely to be an essential feature of strategies to further expand the application of powder XRD as a technique for structure determination of organic molecular materials of even greater complexity in the future

Differences in Presentation and Outcomes between Children with Familial Dilated Cardiomyopathy and Children with Idiopathic Dilated Cardiomyopathy: A Report from the Pediatric Cardiomyopathy Registry Study Group

Research comparing the survival of children with familial dilated cardiomyopathy (FDCM) to that of children with idiopathic dilated cardiomyopathy (IDCM) has produced conflicting results

Effect of L-type calcium channel blocker (amlodipine) on myocardial iron deposition in patients with thalassaemia with moderate-to-severe myocardial iron deposition: protocol for a randomised, controlled trial

Introduction: Sideroblastic cardiomyopathy secondary to repeated blood transfusions is a feared complication in thalassaemia. Control of myocardial iron is thus becoming the cornerstone of thalassaemia management. Recent evidence suggests a role for L-type Ca2+ channels in mediating iron uptake by the heart. Blocking the cellular iron uptake through these channels may add to the benefit of therapy to standard chelation in reducing myocardial iron. We aim to determine the efficacy of amlodipine (a calcium channel blocker) as an adjunct to standard aggressive chelation in retarding myocardial iron deposition in thalassaemics with or without cardiomyopathy.Outcomes: The primary outcome is to compare the efficacy of amlodipine+chelation (intervention) versus standard chelation (control) in retarding myocardial iron deposition. Secondary outcomes include the effect of amlodipine therapy on systolic and diastolic function, strain and strain rate and liver iron content.Methods and analysis: This is a single-centre, parallel-group, prospective randomised control trial. Twenty patients will be randomised in a 1:1 allocation ratio into the intervention and control arms. In addition to conventional echocardiography, MRI T2* values for assessment of cardiac and liver iron load will be obtained at baseline and at 6 and 12 months. Cardiac T2* will be reported as the geometric mean and per cent coefficient of variation, and an increase in cardiac T2* values from baseline will be used as an end point to compare the efficacy of therapy. A p Value of Study setting: Department of Pediatric and Child Health, Aga Khan University Hospital, Karachi, Pakistan.Ethics and dissemination: This study has been approved by the Ethics Review Committee and Clinical Trials Unit at The Aga Khan University with respect to scientific content and compliance with applicable research and human subjects regulations. Findings will be reported through scientific publications and research conferences and project summary papers for participants