Familial evaluation in catecholaminergic polymorphic ventricular tachycardia: disease penetrance and expression in cardiac ryanodine receptor mutation-carrying relatives.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome associated with mutations in the cardiac ryanodine receptor gene (Ryr2) in the majority of patients. Previous studies of CPVT patients mainly involved probands, so current insight into disease penetrance, expression, genotype-phenotype correlations, and arrhythmic event rates in relatives carrying the Ryr2 mutation is limited. METHODS AND RESULTS: One-hundred sixteen relatives carrying the Ryr2 mutation from 15 families who were identified by cascade screening of the Ryr2 mutation causing CPVT in the proband were clinically characterized, including 61 relatives from 1 family. Fifty-four of 108 antiarrhythmic drug-free relatives (50%) had a CPVT phenotype at the first cardiological examination, including 27 (25%) with nonsustained ventricular tachycardia. Relatives carrying a Ryr2 mutation in the C-terminal channel-forming domain showed an increased odds of nonsustained ventricular tachycardia (odds ratio, 4.1; 95% CI, 1.5-11.5; P=0.007, compared with N-terminal domain) compared with N-terminal domain. Sinus bradycardia was observed in 19% of relatives, whereas other supraventricular dysrhythmias were present in 16%. Ninety-eight (most actively treated) relatives (84%) were followed up for a median of 4.7 years (range, 0.3-19.0 years). During follow-up, 2 asymptomatic relatives experienced exercise-induced syncope. One relative was not being treated, whereas the other was noncompliant. None of the 116 relatives died of CPVT during a 6.7-year follow-up (range, 1.4-20.9 years). CONCLUSIONS: Relatives carrying an Ryr2 mutation show a marked phenotypic diversity. The vast majority do not have signs of supraventricular disease manifestations. Mutation location may be associated with severity of the phenotype. The arrhythmic event rate during follow-up was low.

Performance of classic electrocardiographic criteria for left ventricular hypertrophy in an African population.

ECG criteria for left ventricular hypertrophy (LVH) have been almost exclusively elaborated and calibrated in white populations. Because several interethnic differences in ECG characteristics have been found, the applicability of these criteria to African individuals remains to be demonstrated. We therefore investigated the performance of classic ECG criteria for LVH detection in an African population. Digitized 12-lead ECG tracings were obtained from 334 African individuals randomly selected from the general population of the Republic of Seychelles (Indian Ocean). Left ventricular mass was calculated with M-mode echocardiography and indexed to body height. LVH was defined by taking the 95th percentile of body height-indexed LVM values in a reference subgroup. In the entire study sample, 16 men and 15 women (prevalence 9.3%) were finally declared to have LVH, of whom 9 were of the reference subgroup. Sensitivity, specificity, accuracy, and positive and negative predictive values for LVH were calculated for 9 classic ECG criteria, and receiver operating characteristic curves were computed. We also generated a new composite time-voltage criterion with stepwise multiple linear regression: weighted time-voltage criterion=(0.2366R(aVL)+0.0551R(V5)+0.0785S(V3)+ 0.2993T(V1))xQRS duration. The Sokolow-Lyon criterion reached the highest sensitivity (61%) and the R(aVL) voltage criterion reached the highest specificity (97%) when evaluated at their traditional partition value. However, at a fixed specificity of 95%, the sensitivity of these 10 criteria ranged from 16% to 32%. Best accuracy was obtained with the R(aVL) voltage criterion and the new composite time-voltage criterion (89% for both). Positive and negative predictive values varied considerably depending on the concomitant presence of 3 clinical risk factors for LVH (hypertension, age >/=50 years, overweight). Median positive and negative predictive values of the 10 ECG criteria were 15% and 95%, respectively, for subjects with none or 1 of these risk factors compared with 63% and 76% for subjects with all of them. In conclusion, the performance of classic ECG criteria for LVH detection was largely disparate and appeared to be lower in this population of East African origin than in white subjects. A newly generated composite time-voltage criterion might provide improved performance. The predictive value of ECG criteria for LVH was considerably enhanced with the integration of information on concomitant clinical risk factors for LVH.

Bilinear models for spatio-temporal point distribution analysis: application to extrapolation of left ventricular, biventricular and whole heart cardiac dynamics

In this work we describe the usage of bilinear statistical models as a means of factoring the shape variability into two components attributed to inter-subject variation and to the intrinsic dynamics of the human heart. We show that it is feasible to reconstruct the shape of the heart at discrete points in the cardiac cycle. Provided we are given a small number of shape instances representing the same heart atdifferent points in the same cycle, we can use the bilinearmodel to establish this. Using a temporal and a spatial alignment step in the preprocessing of the shapes, around half of the reconstruction errors were on the order of the axial image resolution of 2 mm, and over 90% was within 3.5 mm. From this, weconclude that the dynamics were indeed separated from theinter-subject variability in our dataset.

Characterization of myocardial deformation in patients with different etiologies of left ventricular hypertrophy by using strain distribution from Magnetic Resonance Imaging

Introducción y objetivos. Se ha señalado que, en la miocardiopatía hipertrófica (MCH), la desorganización de las fibras regionales da lugar a segmentos en los que la deformación es nula o está gravemente reducida, y que estos segmentos tienen una distribución no uniforme en el ventrículo izquierdo (VI). Esto contrasta con lo observado en otros tipos de hipertrofia como en el corazón de atleta o la hipertrofia ventricular izquierda hipertensiva (HVI-HT), en los que puede haber una deformación cardiaca anormal, pero nunca tan reducida como para que se observe ausencia de deformación. Así pues, proponemos el empleo de la distribución de los valores de strain para estudiar la deformación en la MCH. Métodos. Con el empleo de resonancia magnética marcada (tagged), reconstruimos la deformación sistólica del VI de 12 sujetos de control, 10 atletas, 12 pacientes con MCH y 10 pacientes con HVI-HT. La deformación se cuantificó con un algoritmo de registro no rígido y determinando los valores de strain sistólico máximo radial y circunferencial en 16 segmentos del VI. Resultados. Los pacientes con MCH presentaron unos valores medios de strain significativamente inferiores a los de los demás grupos. Sin embargo, aunque la deformación observada en los individuos sanos y en los pacientes con HVI-HT se concentraba alrededor del valor medio, en la MCH coexistían segmentos con contracción normal y segmentos con una deformación nula o significativamente reducida, con lo que se producía una mayor heterogeneidad de los valores de strain. Se observaron también algunos segmentos sin deformación incluso en ausencia de fibrosis o hipertrofia. Conclusiones. La distribución de strain caracteriza los patrones específicos de deformación miocárdica en pacientes con diferentes etiologías de la HVI. Los pacientes con MCH presentaron un valor medio de strain significativamente inferior, así como una mayor heterogeneidad de strain (en comparación con los controles, los atletas y los pacientes con HVI-HT), y tenían regiones sin deformación.

Three-dimensional morphological analysis of intracranial aneurysms: a fully automated method for aneurysm sac isolation and quantification

Morphological descriptors are practical and essential biomarkers for diagnosis andtreatment selection for intracranial aneurysm management according to the current guidelinesin use. Nevertheless, relatively little work has been dedicated to improve the three-dimensionalquanti cation of aneurysmal morphology, automate the analysis, and hence reduce the inherentintra- and inter-observer variability of manual analysis. In this paper we propose a methodologyfor the automated isolation and morphological quanti cation of saccular intracranial aneurysmsbased on a 3D representation of the vascular anatomy.

Morphodynamic analysis of cerebral aneurysm pulsation from time-resolved rotational angiography

This paper presents a technique to estimate and model patient-specific pulsatility of cerebral aneurysms over onecardiac cycle, using 3D rotational X-ray angiography (3DRA) acquisitions. Aneurysm pulsation is modeled as a time varying-spline tensor field representing the deformation applied to a reference volume image, thus producing the instantaneousmorphology at each time point in the cardiac cycle. The estimated deformation is obtained by matching multiple simulated projections of the deforming volume to their corresponding original projections. A weighting scheme is introduced to account for the relevance of each original projection for the selected time point. The wide coverage of the projections, together with the weighting scheme, ensures motion consistency in all directions. The technique has been tested on digital and physical phantoms that are realistic and clinically relevant in terms of geometry, pulsation and imaging conditions. Results from digital phantomexperiments demonstrate that the proposed technique is able to recover subvoxel pulsation with an error lower than 10% of the maximum pulsation in most cases. The experiments with the physical phantom allowed demonstrating the feasibility of pulsation estimation as well as identifying different pulsation regions under clinical conditions.

Incidence and risk factors for Contegra graft infection following right ventricular outflow tract reconstruction: long-term results.

OBJECTIVES: The aim of this study was to evaluate the risk factors associated with Contegra graft (Medtronic Minneapolis, MN, USA) infection after reconstruction of the right ventricular outflow tract. METHODS: One hundred and six Contegra grafts were implanted between April 1999 and April 2010 for the Ross procedure (n = 46), isolated pulmonary valve replacement (n = 32), tetralogy of Fallot (n = 24), double-outlet right ventricle (n = 7), troncus arteriosus (n = 4), switch operation (n = 1) and redo of pulmonary valve replacement (n = 2). The median age of the patients was 13 years (range 0-54 years). A follow-up was completed in all cases with a median duration of 7.6 years (range 1.7-12.7 years). RESULTS: There were 3 cases of in-hospital mortality. The survival rate during 7 years was 95.7%. Despite the lifelong endocarditis prophylaxis, Contegra graft infection was diagnosed in 12 (11.3%) patients at a median time of 4.4 years (ranging from 0.4 to 8.7 years). Univariate analysis of preoperative, perioperative and postoperative variables was performed and the following risk factors for time to infection were identified: female gender with a hazard ratio (HR) of 0.19 (P = 0.042), systemic-to-pulmonary shunt (HR 6.46, P < 0.01), hypothermia (HR 0.79, P = 0.014), postoperative renal insufficiency (HR 11.97, P = 0.015) and implantation of permanent pacemaker during hospitalization (HR 5.29, P = 0.075). In 2 cases, conservative therapy was successful and, in 10 patients, replacement of the infected valve was performed. The Contegra graft was replaced by a homograft in 2 cases and by a new Contegra graft in 8 cases. Cox's proportional hazard model indicated that time to graft infection was significantly associated with tetralogy of Fallot (HR 0.06, P = 0.01), systemic-to-pulmonary shunt (HR 64.71, P < 0.01) and hypothermia (HR 0.77, P < 0.01). CONCLUSION: Contegra graft infection affected 11.3% of cases in our cohort, and thus may be considered as a frequent entity that can be predicted by both intraoperative and early postoperative factors. After the diagnosis of infection associated with the Contegra graft was confirmed, surgical treatment was the therapy of choice.

Extrasystoles ventriculaires idiopathiques de ta chambre de chasse: evaluation, pronostic et prise en charge [Idiopathic premature ventricular complexes originating from the ventricular outflow tract: evaluation, prognosis and management].

Idiopathic premature ventricular complexes originating from the ventricular outflow tract: evaluation, prognosis and management The prognosis of ventricular premature complexes (VPC) in the absence of heart disease is considered benign. VPC usually originate from the right or, less commonly, left ventricular outflow tract. QRS complexes therefore usually assume a left bundle branch block and inferior axis morphology. These VPC, particularly if very frequent (> 20,000 per day), may adversely affect left ventricular function and their suppression can restore normal function. Moreover, there is a clinical overlap with arrhythmogenic right ventricular dysplasia and this diagnosis should be considered when facing a left bundle branch block shaped VPC. However, the prognosis of outflow tract VPC is good for appropriately selected patients with normal left ventricular function, absence of syncope or ventricular tachycardia, and no evidence of cardiac disease.

Development of Implantable Flow-Through Left Ventricular Pressure Telemetric Transmitter for small Rodent Animals

Objective: Although 24-hour arterial blood pressure can be monitored in a free-moving animal using pressure telemetric transmitter mostly from Data Science International (DSI), accurate monitoring of 24-hour mouse left ventricular pressure (LVP) is not available because of its insufficient frequency response to a high frequency signal such as the maximum derivative of mouse LVP (LVdP/dtmax and LVdP/dtmin). The aim of the study was to develop a tiny implantable flow-through LVP telemetric transmitter for small rodent animals, which can be potentially adapted for human 24 hour BP and LVP accurate monitoring. Design and Method: The mouse LVP telemetric transmitter (Diameter: _12 mm, _0.4 g) was assembled by a pressure sensor, a passive RF telemetry chip, and to a 1.2F Polyurethane (PU) catheter tip. The device was developed in two configurations and compared with existing DSI system: (a) prototype-I: a new flow-through pressure sensor with wire link and (b) prototype-II: prototype-I plus a telemetry chip and its receiver. All the devices were applied in C57BL/6J mice. Data are mean_SEM. Results: A high frequency response (>100 Hz) PU heparin saline-filled catheter was inserted into mouse left ventricle via right carotid artery and implanted, LV systolic pressure (LVSP), LVdP/dtmax, and LVdP/dtmin were recorded on day2, 3, 4, 5, and 7 in conscious mice. The hemodynamic values were consistent and comparable (139_4 mmHg, 16634_319, - 12283_184 mmHg/s, n¼5) to one recorded by a validated Pebax03 catheter (138_2mmHg, 16045_443 and -12112_357 mmHg/s, n¼9). Similar LV hemodynamic values were obtained with Prototype-I. The same LVP waveforms were synchronically recorded by Notocord wire and Senimed wireless software through prototype-II in anesthetized mice. Conclusion: An implantable flow-through LVP transmitter (prototype-I) is generated for LVP accurate assessment in conscious mice. The prototype-II needs a further improvement on data transmission bandwidth and signal coupling distance to its receiver for accurate monitoring of LVP in a freemoving mouse.

Feasibility of transapical aortic valve replacement through a left ventricular apical diverticulum.

ABSTRACT: Transapical aortic valve replacement is an established technique performed in high-risk patients with symptomatic aortic valve stenosis and vascular disease contraindicating trans-vascular and trans-aortic procedures. The presence of a left ventricular apical diverticulum is a rare event and the treatment depends on dimensions and estimated risk of embolisation, rupture, or onset of ventricular arrhythmias. The diagnosis is based on standard cardiac imaging and symptoms are very rare. In this case report we illustrate our experience with a 81 years old female patient suffering from symptomatic aortic valve stenosis, respiratory disease, chronic renal failure and severe peripheral vascular disease (logistic euroscore: 42%), who successfully underwent a transapical 23 mm balloon-expandable stent-valve implantation through an apical diverticulum of the left ventricle. Intra-luminal thrombi were absent and during the same procedure were able to treat the valve disease and to successfully exclude the apical diverticulum without complications and through a mini thoracotomy. To the best of our knowledge, this is the first time that a transapical procedure is successfully performed through an apical diverticulum.

Computational fluid dynamics of the right ventricular outflow tract and of the pulmonary artery: a bench model of flow dynamics.

OBJECTIVES: The reconstruction of the right ventricular outflow tract (RVOT) with valved conduits remains a challenge. The reoperation rate at 5 years can be as high as 25% and depends on age, type of conduit, conduit diameter and principal heart malformation. The aim of this study is to provide a bench model with computer fluid dynamics to analyse the haemodynamics of the RVOT, pulmonary artery, its bifurcation, and left and right pulmonary arteries that in the future may serve as a tool for analysis and prediction of outcome following RVOT reconstruction. METHODS: Pressure, flow and diameter at the RVOT, pulmonary artery, bifurcation of the pulmonary artery, and left and right pulmonary arteries were measured in five normal pigs with a mean weight of 24.6 ± 0.89 kg. Data obtained were used for a 3D computer fluid-dynamics simulation of flow conditions, focusing on the pressure, flow and shear stress profile of the pulmonary trunk to the level of the left and right pulmonary arteries. RESULTS: Three inlet steady flow profiles were obtained at 0.2, 0.29 and 0.36 m/s that correspond to the flow rates of 1.5, 2.0 and 2.5 l/min flow at the RVOT. The flow velocity profile was constant at the RVOT down to the bifurcation and decreased at the left and right pulmonary arteries. In all three inlet velocity profiles, low sheer stress and low-velocity areas were detected along the left wall of the pulmonary artery, at the pulmonary artery bifurcation and at the ostia of both pulmonary arteries. CONCLUSIONS: This computed fluid real-time model provides us with a realistic picture of fluid dynamics in the pulmonary tract area. Deep shear stress areas correspond to a turbulent flow profile that is a predictive factor for the development of vessel wall arteriosclerosis. We believe that this bench model may be a useful tool for further evaluation of RVOT pathology following surgical reconstructions.

Acute effects of transmyocardial laser revascularization on left-ventricular function: an haemodynamic and echocardiographic study.

While the lesions produced by transmyocardial laser revascularisation (TMLR) induce scar formation, it is important to determine whether this procedure can be deleterious for the left-ventricular function, which is already impaired by the underlying ischaemic process in some patients. Ten channels were drilled in the left lateral wall of the hearts of ten pigs (mean weight, 61 +/- 8.2kg) with a Holmium:YAG laser. Haemodynamic measurements and echocardiographic assessment of left-ventricular function were performed before the TMLR procedure, 5 and 30 min after, and lastly after 5 min of pacing at a rate increased by 30% of the baseline value. Echocardiographic assessment was in the short axis at the level of the laser channels, and included left-ventricular ejection fraction and segmental wall motility of the lasered area (scale 0-3:0 = normal 1 = hypokinesia, 2 = akinesia, 3 = dyskinesia). Values at 5 and 30 min were compared with baseline values; the difference was considered significant if p < 0.05. Haemodynamical values were stable throughout all the procedures. The ejection fraction showed a slight but significant decrease 5 min after the creation of the channels (60.4 +/- 6.8% vs 54 +/- 7.6%, p=0.02) and recovered at 30min. The segmental motility score of the involved areas increased to 1 after 5 min in five animals, and came back to 0 at 30 min except in one animal. Even with pacing no segmental dysfunction occurred. The reversibility of the segmental hypokinesia induced by TMLR, as well as the absence of pace-induced dysfunction 30 min after the procedure strongly suggest the inocuity of TMLR in this experimental set-up.