Efficacy and safety of dabigatran in a "real-life" population at high thromboembolic and hemorrhagic risk: data from MonaldiCare registry.

OBJECTIVE: Dabigatran is a novel target specific oral anticoagulant for stroke prevention in non valvular atrial fibrillation. Little is still known about its real-world effectiveness and safety in the italian population. Aim of our study was to evaluate the efficacy and safety of dabigatran in a large single-center cohort of "real-life" italian population with non-valvular AF and to compare the results with those obtained from the RE-LY trial and the Medicare study. PATIENTS AND METHODS: We studied a prospective cohort of 2108 patients (1119 male; mean age 69.4 ± 9.4 years) who started the oral anticoagulant treatment with dabigatran 110 mg twice-daily (DAB 110; N = 1075; 51%) or 150 mg twice-daily (DAB 150; N = 1033; 49%). Follow-up data were obtained trough outpatients visits each 3-6 months for assessing the clinical status, adherence to treatment, occurrence of side effects and major cardiovascular complications. RESULTS: In DAB 150 group the mean age was 64.9 ± 8.8 years, 56.8% of patients was male. CHA2DS2Vasc Score was ≥ 3 in 94.3% and HAS-BLED was ≥ 3 in 59.7%. In DAB 110 group (N = 1075) the mean age was 73.9 ± 7.5 years; 49.5% of patients was male. CHA2DS2Vasc Score was ≥ 3 in 73.4% and HAS-BLED was ≥ 3 in 87.4% of DAB 110 patients. One patient taking Dabigatran 110 mg bid had ischemic stroke without significantly neurological sequelae. In both groups, no patient experienced hemorrhagic stroke during the follow-up period. 147 patients (6.9%) of MonaldiCare population reported adverse effects from treatment with dabigatran, of whom 121 patients (5.7%) discontinued therapy. We reported one case of subarachnoid hemorrhage (0.05%) in a patient with high thrombo-embolic and high hemorrhagic risk score who was taking dabigatran 150 mg bid and one case (0.05%) of bladder bleeding in a patient who was taking dabigatran 110 mg bid. No major gastrointestinal bleeding was observed in the MonaldiCare population. CONCLUSIONS: MonaldiCare registry showed a safety profile of both dosages of dabigatran regarding major of fatal bleeding in a "real life" single center italian population at high thromboembolic and hemorrhagic risk. The majority of MonaldiCare patients tolerated dabigatran treatment without significant side effects. The efficacy of dabigatran was demonstrated by very low prevalence of ictus/TIA, also when patients underwent electrical AF cardioversion independently of the transesophageal examination.

The effect of aortic coarctation surgical repair on QTc and JTc dispersion in severe aortic coarctation newborns: a short-term follow-up study.

Sudden death is a possible occurrence for newborns younger than 1 year with severe aortic coarctation (CoA) before surgical correction. In our previous study, we showed a significant increase of QTc-D and JTc-D in newborns with isolated severe aortic coarctation, electrocardiographic parameters that clinical and experimental studies have suggested could reflect the physiological variability of regional and ventricular repolarization and could provide a substrate for life-threatening ventricular arrhythmias. The aim of the current study was to evaluate the effect of surgical repair of CoA on QTc-d, JTc-d in severe aortic coarctation newborns with no associated congenital cardiac malformations. The study included 30 newborns (18M; 70+/-12 h old) affected by severe congenital aortic coarctation, without associated cardiac malformations. All newborns underwent to classic extended end-to-end repair. Echocardiographic and electrocardiographic measurements were performed in each patient 24 h before and 24 h after the interventional procedure and at the end of the follow-up period, 1 month after the surgical correction. All patients at baseline, 24 h and one month after CoA surgical repair did not significantly differ in terms of heart rate, weight, height, and echocardiographic parameters. There were no statistically significant differences in QTc-D (111.7+/-47.4 vs 111.9+/-63.8 ms vs 108.5+/-55.4 ms; P=0.4) and JTc-D (98.1+/-41.3 vs 111.4+/-47.5 vs 105.1+/-33.4 ms; P=0.3) before, 24 h and 1 month after CoA surgical correction. In conclusions, our study did not show a statistically significant decrease in QTc-D and JTc-D, suggesting the hypothesis that the acute left ventricular afterload reduction, related to successful CoA surgical correction, may not reduce the ventricular electrical instability in the short-term follow-up.

Masked hypertension in young patients after successful aortic coarctation repair: impact on left ventricular geometry and function.

Life expectancy is still reduced in aortic coarctation (AoC) patients despite a successful repair because of late arterial hypertension and atherosclerosis. Masked hypertension (MH) consists of an elevated daytime or awake ambulatory blood pressure (BP) in the presence of a normal BP on conventional measurement at the office. To assess the prevalence of MH among AoC normotensive young patients successfully treated and to evaluate the impact of MH on left ventricular (LV) geometry and function.We studied 76 AoC patients (mean age 14.5±5.7 years, male 64%). According to 24 h ambulatory BP monitoring (ABPM) our sample was divided in real normotensive patients (Group RN, n=40) and MH patients (Group MH, n=36). There was an increased pressure gradient in the aortic arch (15 mm Hg±4 vs 13 mm Hg±4.7, P<0.05), increased LV mass (51 g m(-2.7)±13 vs 46 g m(-2.7)±12, P<0.05), in MH AoC patients. Regional longitudinal deformation properties of the basal septal segment (-15%±2.4 vs -20%±5, P<0.01) and LV twist values (14°±1.6 vs 12°±1.9, P<0.0001) were reduced in the MH group. There is a high prevalence of MH in young patients with repaired AoC, which is associated with abnormal LV structure and function. Clinicians should consider 24 h ABPM measurements in apparently normotensive patients followed up for AoC repair.

Long term effects of bosentan treatment in adult patients with pulmonary arterial hypertension related to congenital heart disease (Eisenmenger physiology): safety, tolerability, clinical, and haemodynamic effect.

BACKGROUND: Oral bosentan is an established treatment for pulmonary arterial hypertension (PAH). OBJECTIVE: To evaluate safety, tolerability, and clinical and haemodynamic effects of bosentan in patients with PAH related to congenital heart disease (CHD). PATIENTS: 22 patients with CHD related PAH (8 men, 14 women, mean (SD) age 38 (10) years) were treated with oral bosentan (62.5 mg x 2/day for the first 4 weeks and then 125 mg x 2/day). MAIN OUTCOME MEASURES: Clinical status, liver enzymes, World Health Organisation (WHO) functional class, resting oxygen saturations and 6-min walk test (6MWT) were assessed at baseline and at 1, 3, 6, and 12 months. Haemodynamic evaluation with cardiac catheterisation was performed at baseline and at 12 month follow-up. RESULTS: 12 patients had ventricular septal defect, 5 atrioventricular canal, 4 single ventricle, and 1 atrial septal defect. All patients tolerated bosentan well. No major side effects were seen. After a year of treatment, an improvement was seen in WHO functional class (2.5 (0.7) v 3.1 (0.7); p<0.05), oxygen saturation at rest (87 (6%) v 81 (9); p<0.001), heart rate at rest (81 (10) v 87 (14) bpm; p<0.05), distance travelled in the 6MWT (394 (73) v 320 (108) m; p<0.001), oxygen saturation at the end of the 6MWT (71 (14) v 63 (17%); p<0.05), Borg index (5.3 (1.8) v 6.5 (1.3); p<0.001), pulmonary vascular resistances index (14 (9) v 22 (12) WU m(2); p<0.001), systemic vascular resistances index (23 (11) v 27 (10) WU.m(2); p<0.01), pulmonary vascular resistances index/systemic vascular resistances index (0.6 (0.5) v 0.9 (0.6); p<0.05); pulmonary (4.0 (1.3) v 2.8 (0.9) l/min/m2; p<0.001) and systemic cardiac output (4.2 (1.4) v 3.4 (1.1) l/min/m2; p<0.05). CONCLUSIONS: Bosentan was safe and well tolerated in adults with CHD related PAH during 12 months of treatment. Clinical status, exercise tolerance, and pulmonary haemodynamics improved considerably.

Prognostic value of intra-left ventricular electromechanical asynchrony in patients with mild hypertrophic cardiomyopathy compared with power athletes.

OBJECTIVES: We sought to assess the indexes of myocardial activation delay, using Doppler myocardial imaging (DMI), as potential diagnostic tools and predictors of cardiac events in patients with hypertrophic cardiomyopathy (HCM) compared with power athletes. BACKGROUND: the distribution and magnitude of left ventricular (LV) hypertrophy are not uniform in patients with HCM, which results in heterogeneity of regional LV systolic function. METHODS: The study population comprised 70 young patients with HCM (mean (SD) age 29.4 (5.9) years) with mild septal hypertrophy (15-19 mm) and 85 age and sex matched athletes with septal thickness >12 mm, followed up for 44.4 (10.8) months. Using pulsed DMI, myocardial peak velocities, systolic time intervals, and myocardial intraventricular and interventricular systolic delays were measured in six different basal myocardial segments. RESULTS: DMI analysis showed in HCM lower myocardial both systolic and early diastolic peak velocities of all the segments. Patients with HCM also showed significant interventricular and intraventricular delay (p<0.0001), whereas athletes showed homogeneous systolic activation of the ventricular walls. During the follow up, seven sudden deaths occurred in the HCM group, while no cardiovascular event was observed in the group of athletes. In patients with HCM, intraventricular delay on DMI was the most powerful independent predictor of sudden cardiac death (p<0.0001). An intraventricular delay >45 ms identified with high sensitivity and specificity patients with HCM at higher risk of ventricular tachycardia and cardiac events (test accuracy 90.6%). CONCLUSIONS: DMI may be a valid supporting tool for the differential diagnosis between HCM and "athlete's heart". In patients with HCM, DMI indexes of intraventricular delay may provide additional information for selecting subgroups of patients with HCM at increased risk of ventricular arrhythmias and sudden cardiac death at follow up. Accordingly, such patients may benefit from early intensive treatment and survey. MINIABSTRACT: Doppler myocardial imaging may represent a valid supporting tool for the differential diagnosis between mild hypertrophic cardiomyopathy (HCM) and "athlete's heart". In patients with HCM, DMI indexes of intraventricular delay may provide additional information for selecting subgroups of patients with HCM at increased risk of ventricular arrhythmias and sudden cardiac death at follow up.

Right ventricular myocardial dysfunction in adult patients late after repair of tetralogy of fallot.

AIM OF THE STUDY: To detect in adult patients late after repair of Tetralogy of Fallot (TOF) possible correlation between myocardial parameters assessed at rest by Tissue Doppler (TD) and cardiac performance during physical effort. METHODS: Doppler echo, treadmill test and pulsed TD of both mitral and tricuspid annulus were performed in 25 healthy subjects and in 40 adult patients who had undergone surgery for TOF at a mean age of 1.4+/-0.5 years. Exclusion criteria were echocardiographic evidence of residual pulmonary, either stenosis or regurgitation. By use of TD, the following parameters were assessed: systolic peak velocities (Sm), pre-contraction time, contraction time, early (E(m)) and late (A(m)) diastolic velocities, E(m)/A(m) ratio, relaxation time. By treadmill test, we measured: maximal heart rate (HR), systolic blood pressure (SBP), rate-pressure product, maximal workload, time duration of the exercise. RESULTS: the two groups were comparable for left ventricular measurements and for all transmitral and transtricuspid Doppler indexes, while tricuspid ring diameter was increased in TOF. TD analysis showed in TOF lower S(m), E(m) and E(m)/A(m) ratio and prolonged PCT(m) and Rt(m) at tricuspid annulus level, despite comparable TD mitral annulus indexes. By treadmill test, TOF showed reduced time of exercise, number of METS reached and rate-pressure product. Multiple linear regression models evidenced in TOF independent positive association between tricuspid Em velocity and time of exercise (p<0.0001), achieved METS at peak effort (p<0.001) and rate-pressure product (p<0.001). An E(m) peak velocity of tricuspid annulus lower than 0.13 m/s showed 90% sensitivity and 93% specificity in identifying TOF patients unable to perform maximal exercise test. CONCLUSIONS: despite normal Doppler parameters, adult patients late after correction of TOF showed impaired right ventricular myocardial function. In these patients pulsed TD may be taken into account as a valuable supporting tool to predict the effort response and possibly to assess long-term follow-up of cardiac functional reserve.

Right ventricular myocardial activation delay in adult patients with right bundle branch block late after repair of Tetralogy of Fallot.

Electromechanical interaction, with prolonged QRS duration due to right ventricular (RV) overload, has been described as a predictor of unfavorable outcome in patients late after correction of Tetralogy of Fallot (TOF). Aim of our study was to evaluate myocardial function and activation delay of both left and right ventricles in TOF patients. Doppler echo, treadmill test and pulsed Tissue Doppler (TD) were performed in 25 healthy subjects and in 30 adult patients who had undergone surgery for TOF, all with right bundle branch block on ECG. Exclusion criteria were evidence of residual pulmonary either stenosis or regurgitation. By use of TD, the level of both LV mitral and RV tricuspid annulus were measured: systolic (Sm), early- and late-diastolic (Em and Am) regional peak velocities. The indexes of myocardial systolic activation were calculated: precontraction time (PCTm) and interventricular activation delay (InterV-del) (difference of PCTm between RV and LV segments). The two groups were comparable for LV diameters and for Doppler indexes, while QRS duration was prolonged and RV end-diastolic diameter was increased in TOF. By TD analysis, only at the level of tricuspid annulus TOF patients had lower Sm and Em, and increased RV PCTm ( p<0.001 ) and InterV-del ( p<0.0001 ), even after adjustment for heart rate (HR) and QRS duration. By treadmill test, TOF showed reduced cardiac functional reserve. In seven patients non-sustained ventricular tachycardia was documented during physical effort. By multivariate analysis, RV Em ( p<0.001 ), and InterV-del ( p<0.01 ) were independently associated to maximal workload at peak effort. The same InterV-del was an independent determinant of risk of ventricular arrhythmias during effort ( p<0.01 ). A cut-off point of Em peak velocity of tricuspid annulus <0.13 m/s at rest showed a sensitivity of 91% and a specificity of 88% in identifying TOF patients with submaximal exercise test. A cut-off point of InterV-del >55 ms showed 87% sensitivity and 88% specificity to detect increased risk of ventricular arrhythmias during effort. In TOF patients, TD analysis at rest may be taken into account as a non-invasive and easy-repeatable tool to predict cardiac performance during physical effort, and to select subgroups of patients at increased risk of ventricular arrhythmias.

Risk factors for pacemaker implantation following aortic valve replacement: a single centre experience.

OBJECTIVE: To identify perioperative clinical predictors of permanent pacemaker implantation following aortic valve replacement. DESIGN AND PATIENTS: Prospective cohort study on 276 patients submitted for aortic valve replacement: 267 patients (mean (SD) age, 57.5 (14) years) with no conduction disturbances, and nine patients (67.7 (5) years) with severe conduction disturbances requiring permanent pacing; 65 perioperative variables (38 preoperative, eight intraoperative, and 19 postoperative) were considered. RESULTS: Nine patients (3.2%) had irreversible second or third degree atrioventricular (AV) block requiring permanent pacing. Risk factors for permanent pacing identified by univariate analysis were: preoperative: additional valvar disease, aortic regurgitation, myocardial infarction, pulmonary hypertension, anaemia, use of digitalis; intraoperative: cardiac arrest; postoperative: cardiac arrest, conduction disturbances, electrolytic imbalance, angiotensin converting enzyme inhibitor use. Multivariate logistic regression analysis identified preoperative aortic regurgitation (p < 0.005; odds ratio (OR) 6.6, 95% confidence interval (CI) 1.6 to 12.2), myocardial infarction (p < 0.0005; OR 15.2, 95% CI 6.3 to 19.9), pulmonary hypertension (p < 0.005; OR 12.5, 95% CI 3.2 to 18.3), and postoperative electrolyte imbalance (p < 0.01; OR 4.5, 95% CI 1.3 to 6.4). CONCLUSIONS: Irreversible AV block requiring permanent pacemaker implantation is an uncommon condition following aortic valve replacement. Previous aortic regurgitation, myocardial infarction, pulmonary hypertension, and postoperative electrolyte imbalance should be considered in order to identify patients at increased risk for advanced AV block.

Usefulness of Doppler tissue imaging for the assessment of right and left ventricular myocardial function in patients with dual-chamber pacing.

The aim of the study was to evaluate by Doppler tissue imaging (DTI) the combined effects of atrio-ventricular (AV) delay and heart rate (HR) changes on global and segmental right (RV) and left (LV) ventricular diastolic function in 15 patients with dual-chamber pacemakers paced in the DDD mode. RV and LV inflow velocities and regional systolic and diastolic pulsed-wave (PW) DTI parameters were analyzed at four different pacing modes: (1) HR 70 beats/min, AV delay 125 ms; (2) HR 70 beats/min, AV delay 188 ms; (3) HR 89 beats/min, AV delay 125 ms; (4) HR 89 beats/min, AV delay 188 ms. For each pacing mode selected, RV diastolic filling velocities always prevailed over LV ones. As for RV and LV adaptation to the four different stimulation protocols, a higher paced rate and a prolonged AV delay caused across both the AV valves a decrease of E wave and of E/A ratios. The intersegmental comparison of PW-DTI parameters outlined that RV free wall exhibited significantly higher peak systolic (Sm) and early-diastolic (Em) wall velocities, and longer systolic ejection time. Considering separately RV and LV segmental physiology at the four programmed pacing modes, an increase in HR determined a progressive shortening of systolic ejection times in all the segments analyzed. Moreover, in each region the Em/Am ratio decreased with higher HR and longer AV delay. Conversely, Em encountered a progressive reduction in RV free wall, while remaining quite unchanged in all the LV regions. Both ventricles shared a similar pattern of global and regional adaptation to programmed HR and AV delay modifications, consisting in a progressive greater contribution of late diastole to ventricular filling at higher HR and more prolonged AV delay. However, at a regional level the right ventricle exhibited higher systolic and diastolic wall velocities than all left ventricular regions.

Risk predictors of paroxysmal atrial fibrillation following aortic valve replacement.

BACKGROUND: Atrial fibrillation (AF) is the most frequently encountered arrhythmic complication associated with cardiac surgery. The aim of this paper was to identify the clinical predictors of AF occurrence following aortic valve replacement. METHODS: Three hundred and two patients were included in this study and divided into two groups according to the absence (SR group, 243 patients, mean age 55.6 +/- 15 years) or the evidence (AF group, 59 patients, mean age 63.8 +/- 11 years) of post-aortic valve replacement AF. Sixty-five perioperative variables (37 preoperative, 8 intraoperative and 20 postoperative) were considered. RESULTS: Post-aortic valve replacement paroxysmal AF occurred in 59 out of 302 patients (19%). At univariate analysis, post-aortic valve replacement AF was associated with advanced age, left atrial enlargement, preoperative episodes of paroxysmal AF, the use of a warm blood cardioplegic solution and normothermia, administration of inotropic agents, prolonged assisted ventilation but also with postoperative acidosis, electrolyte imbalance and atrioventricular and intraventricular conduction disorders. Stepwise forward multivariate logistic regression analysis identified age (p = 0.002, odds ratio--OR 1.04), left atrial enlargement (p = 0.004, OR 2.6), a prior history of paroxysmal AF (p = 0.0003, OR 10.9), and postoperative electrolyte imbalance (p = 0.01, OR 2.3) as independent correlates of AF, whereas the use of hypothermia appeared to be a protective factor (p = 0.0004, OR 0.26). CONCLUSIONS: According to our findings, post-aortic valve replacement AF seems to be associated with well-defined anatomical and electrical substrates generated by advanced age, increased left atrial dimensions, and a possible electrical remodeling consequent to prior repetitive episodes of paroxysmal AF. On these grounds, external factors such as postoperative electrolyte imbalance might enhance atrial ectopic activity and trigger postoperative sustained tachyarrhythmias, while the use of hypothermia might allow for better protection of the atrial myocardium against intraoperative ischemia.

Left ventricular remodeling and mechanics after successful repair of aortic coarctation.

Forty normotensive patients (mean age 12.3 +/- 6.5 years) followed up after a successful repair of aortic coarctation (mean age at coarctectomy 5.1 +/- 4.8 yrs) were studied by echo-Doppler to (1) evaluate left ventricular (LV) remodeling and endocardial and midwall mechanics, and (2) identify factors that might predispose to persistent abnormalities. Sex- and age-specific cutoff levels for LV mass/height2.7 and relative wall thickness were defined to assess LV geometry. To adjust for age-and growth-related changes in ventricular mechanics, all echocardiographic variables were expressed as a Z-score relative to the normal distribution. In addition, the smallest diameter of the aorta was assessed by magnetic resonance imaging and calculated as percent narrowing compared with the diameter of the aorta at the diaphragmatic level. In the study group, 24 of 40 patients (60%) had normal LV geometry. Among the 16 patients (40%) with abnormal LV geometry, 5 (12.5%) had a pattern of concentric remodeling and 11 (27.5%) an eccentric hypertrophy. LV hypertrophy was marked (LV mass index >51 g/m2.7) in 5 of these patients. No patient had a pattern of concentric hypertrophy. LV contractility was increased (Z-score >95th percentile) in 28 patients (70%) as assessed using the endocardial stress-velocity index. In contrast, LV contractility assessed using midwall stress-velocity index remained elevated (Z-score >95th percentile) in 15 patients (37.5%). The stepwise multiple logistic regression analysis was not able to detect any significant independent predictor of abnormal LV remodeling, including sex, age at surgical repair, length of postoperative follow-up, heart rate, body mass index, systolic and diastolic blood pressure, and smallest diameter of the aorta, as well as indexes of LV geometry (shape, mass, volume, mass/ volume ratio) and function (preload, afterload, pump function, and myocardial contractility). Thus, normotensive patients after surgical repair of aortic coarctation may be in an LV hyperdynamic cardiovascular state (more frequent in those who have undergone late repair) and have multiple patterns of LV geometry.

Atrial and ventricular electromechanical function in 1-ventricle hearts: influence of atrial flutter and Fontan procedure.

OBJECTIVE: Echocardiography was used to study electromechanical atrial and ventricular function in adult patients with a 1-ventricle heart who were in sinus rhythm to better understand the recurrence of atrial flutter in these conditions. Patients who had recent atrial flutter, with and without the Fontan procedure, were compared with those who had no arrhythmia. METHODS: This was a prospective study that used M-mode and 2-dimensional Doppler echocardiography and electrocardiography. Conventional measurements were used to evaluate ventricular long-axis function. Basic data were drawn from case notes. The setting was a designated quaternary service for grown-up congenital heart patients (GUCH) in a tertiary referral center for cardiology and cardiac surgery. From January 1997 to February 1998, 26 consecutive adult patients (aged >16 years) with a heart with one functioning ventricle and a history of atrial flutter were studied: group 1, with non-Fontan palliative surgery or no surgery (10 patients), and group 2, with Fontan-type repair (16 patients). Also studied were 20 patients with a 1-ventricle heart but no history of atrial flutter. These 20 patients were divided into 2 groups: control 1, which comprised 14 patients with previous shunts or no surgery, and control 2, which consisted of 6 patients with Fontan repair. RESULTS: P-wave duration on the electrocardiogram was similar in the 4 patient groups, but the amplitude was reduced in group 2 and control 2 (patients with Fontan surgery) (P <.016). Bifid P wave was seen in 5 (50%) of 10 patients in group 1 and in 6 (43%) of 14 patients in control 1, but it was not seen in patients with Fontan (P <.01). Ventricular systolic and diastolic dimensions and fractional shortening were not different between patients and controls. Right atrial transverse dimensions were greater in group 2 patients compared with those in controls. Significant atrioventricular valve regurgitation was seen in 9 of 10 group 1 patients but in none of the others. Right-sided total long-axis excursion and atrial A-wave amplitude were depressed in group 2 patients compared with the values in the others. The onset of right atrial shortening was delayed by 50 ms in group 2 compared with control 2, whereas the left atrial shortening was delayed by 30 ms in group 1 compared with control 1. This particular disturbance remained 6 months after cardioversion. CONCLUSION: In 1-ventricle hearts, significant atrioventricular valve regurgitation is commonly associated with atrial flutter in patients who did not undergo the Fontan procedure, and with electromechanical disturbances in those who did. Recognition of disturbances in ventricular long-axis function may thus assist in the identification of patients with a 1-ventricle heart who are prone to atrial flutter.

New insights in the pathophysiology of mitral and aortic regurgitation in pediatric age: role of angiotensin-converting enzyme inhibitor therapy.

This review has been focused on the new insights in the pathophysiology of mitral and aortic regurgitation and on the role of ACE-inhibitor therapy in children with chronic volume overload due to left-sided valvular lesions. Recent clinical studies show that these drugs have favorable effects when administered orally in chronic mitral and aortic regurgitation. Interestingly, the beneficial effects of ACE-inhibition regard the basic anatomic, hemodynamic and adaptive pathologic conditions related to volume overload, namely, the regurgitant orifice area and volume and ventricular remodeling. The heart is a plastic structure, constantly being altered in size, shape and composition in response to chronic volume overload. Thus, modulation of cardiac plasticity by ACE-inhibition raises the possibility of using new therapeutic strategies specifically designed to prevent and/or antagonize the mechanical disadvantages secondary to volume overload-induced cardiac remodeling. The beneficial effects of ACE-inhibition have also been observed in growing children with asymptomatic valvular regurgitation; thus, it appears that the unloading therapy has the potential of influencing the natural history of both mitral and aortic regurgitation and possibly delays surgical valve repair or replacement. These data justify early inhibition of the renin-angiotensin system in children with left ventricular volume overload due to mitral and aortic regurgitation.

Left ventricular outflow tract obstruction in the transposition of great arteries defined by transthoracic three-dimensional echocardiography.

We assessed the feasibility of transthoracic three-dimensional reconstruction of the pulmonary valve and subpulmonary left ventricular outflow tract in two patients with transposition of great arteries, ventricular septal defect, and obstruction to the left ventricular outflow tract. Three-dimensional reconstruction of the pulmonary valve could be displayed as "en face" through a three-dimensional generated "pulmotomy view," allowing an overview of the pulmonary aspect of the valve from a surgeon's perspective. In similar fashion, reconstruction of the subpulmonary outflow tract could be displayed along its longitudinal axis as seen through a left ventriculotomy. Unique views could be obtained equivalent to surgical or autopsy dissections, allowing more complete understanding of the morphology and severity of left-sided obstructive lesions.

QRS width in right bundle branch block. Accuracy and reproducibility of manual measurement.

BACKGROUND: The QRS prolongation and its relation to malignant ventricular arrhythmias are topics of interest. Controversies exist about the methodology of measuring the QRS. The aim of this study was to assess the accuracy and reproducibility of manual measurement of the QRS in standard electrocardiograms in patients with right bundle branch block and compare results with computer reading. METHODS AND RESULTS: Five experienced cardiologists at different levels of training were required to measure QRS duration in 30 electrocardiograms with different degrees of right bundle branch block collected from 24 randomly selected patients who had had radical repairs of tetralogy of Fallot. In each set of electrocardiograms there were six records which had been duplicated. The observers were neither told the purpose of the study nor how the electrocardiograms had been obtained, nor informed that some of the electrocardiograms were duplicates. Photocopies were identified by number, covering the patient's name and computerised measurement. Significant differences were found in the measurement of QRS in the same ECG calculated twice by the same observer (with an absolute variation up to 50 ms), within different observers (P=0.037) and measured manually or by computer (P=0.019). The width of the QRS did not influence the measurements as the biggest intra-observer variation (50 ms) was observed for relatively wide complex (median value between the two measurements 155 ms) and the biggest inter-observer (60 ms) for narrow complex (median value between the five measurements 110 ms). The QRS morphology appeared to influence the measurements, as the intra- and inter-observer variations were more consistent in the presence of obvious notching, slurrings and terminal slow vectors. CONCLUSIONS: Measurement of QRS is difficult, can be operator dependent and influenced by the presence of conduction abnormalities which reduce its accuracy and reproducibility.