Nagib Dahdah

All-cause mortality and cardiovascular outcomes with prophylactic steroid therapy in Duchenne muscular dystrophy.

OBJECTIVES This study sought to determine the impact of steroid therapy on cardiomyopathy and mortality in patients with Duchenne muscular dystrophy (DMD). BACKGROUND DMD is a debilitating X-linked disease that afflicts as many as 1 in 3,500 boys. Although steroids slow musculoskeletal impairment, the effects on cardiac function and mortality remain unknown. METHODS We conducted a cohort study on patients with DMD treated with renin-angiotensin-aldosterone system antagonists with or without steroid therapy. RESULTS Eighty-six patients, 9.1 ± 3.5 years of age, were followed for 11.3 ± 4.1 years. Seven of 63 patients (11%) receiving steroid therapy died compared with 10 of 23 (43%) not receiving steroid therapy (p = 0.0010). Overall survival rates at 5, 10, and 15 years of follow-up were 100%, 98.0%, and 78.6%, respectively, for patients receiving steroid therapy versus 100%, 72.1%, and 27.9%, respectively, for patients not receiving steroid therapy (log-rank p = 0.0005). In multivariate propensity-adjusted analyses, steroid use was associated with a 76% lower mortality rate (hazard ratio: 0.24; 95% confidence interval: 0.07 to 0.91; p = 0.0351). The mortality reduction was driven by fewer heart failure-related deaths (0% vs. 22%, p = 0.0010). In multivariate analyses, steroids were associated with a 62% lower rate of new-onset cardiomyopathy (hazard ratio: 0.38; 95% confidence interval: 0.16 to 0.90; p = 0.0270). Annual rates of decline in left ventricular ejection fraction (-0.43% vs. -1.09%, p = 0.0101) and shortening fraction (-0.32% vs. -0.65%, p = 0.0025) were less steep in steroid-treated patients. Consistently, the increase in left ventricular end-diastolic dimension was of lesser magnitude (+0.47 vs. +0.92 mm per year, p = 0.0105). CONCLUSIONS In patients with DMD, steroid therapy is associated with a substantial reduction in all-cause mortality and new-onset and progressive cardiomyopathy.

New Equations and a Critical Appraisal of Coronary Artery Z Scores in Healthy Children

BACKGROUND The aim of this study was to find the best model to obtain valid and normally distributed Z scores for coronary artery (CA) diameters in a large, heterogeneous population of healthy children. METHODS Echocardiography was performed on 1,033 healthy children. Several regression models were tested with height, weight, body surface area, and aortic valve diameter. The computed Z scores were tested for normal distribution and stability. RESULTS CA diameter was best predicted using regression with the square root of body surface area. The weighted least squares method yielded normally distributed and very stable Z-score estimates for all CA segments. In prepubertal children, aortic valve diameter was also a valid predictor of CA diameter. CONCLUSIONS This study shows two valid methods to estimate Z scores for CA size in children of all ages. Such Z scores are important for risk stratification in patients with Kawasaki disease.

A Review and Critique of the Statistical Methods Used to Generate Reference Values in Pediatric Echocardiography

Several articles have proposed echocardiographic reference values in normal pediatric subjects, but adequate validation is often lacking and has not been reviewed. The aim of this study was to review published reference values in pediatric two-dimensional and M-mode echocardiography with a specific focus on the adequacy of the statistical and mathematical methods used to normalize echocardiographic measurements. All articles proposing reference values for transthoracic pediatric echocardiography were reviewed. The types of measurements, the methods of normalization, the regression models used, and the methods used to detect potential bias in proposed reference values were abstracted. The detection of residual associations, residual heteroscedasticity, and departures from the normal distribution theory predictions were specifically analyzed. Fifty-two studies met the inclusion criteria. Most authors (87%) used parametric normalization to account for body size, but their approaches were very heterogeneous. Linear regression and indexing were the most common models. Heteroscedasticity was often present but was mentioned in only 27% of studies. The absence of residual heteroscedasticity and residual associations between the normalized measurements and the independent variables were mentioned in only 9% and 22% of the studies, respectively. Only 14% of studies documented that the distribution of the residual values was appropriate for Z score calculation or that the proportion of subjects falling outside the reference range was appropriate. Statistical suitability of the proposed reference ranges was often incompletely documented. This review underlines the great need for better standardization in echocardiographic measurement normalization.

Etanercept as adjunctive treatment for acute kawasaki disease: Study design and rationale

BACKGROUND Kawasaki disease (KD) is a multisystem vasculitis affecting coronary arteries in children. Patients, refractory to standard treatment with intravenous immunoglobulin and aspirin, show higher rates of coronary artery dilation. Early tumor necrosis factor α receptor antagonism in KD may provide effective adjunctive therapy. STUDY DESIGN The EATAK trial is a multicenter, double-blind, randomized, and placebo-controlled trial intended to assess the efficacy of etanercept in reducing the intravenous immunoglobulin refractory rate during treatment of acute KD. Each arm will enroll 110 patients who will receive 3 doses of study drug over 2 weeks in conjunction with standard therapy. Coronary artery dilation parameters will serve as secondary end points. DISCUSSION The EATAK trial will test a new paradigm for treatment of acute KD involving tumor necrosis factor α antagonism by etanercept.

Value of amino-terminal pro B-natriuretic peptide in diagnosing Kawasaki disease

Background:  The aim of the present study was to investigate the diagnostic value of the N‐terminal B‐type natriuretic peptide (NT‐proBNP) in acute Kawasaki disease (KD) given that the clinical criteria and the current basic laboratory tests lack the necessary specificity for accurate diagnosis.

Coronary Wall Structural Changes in Patients With Kawasaki Disease: New Insights From Optical Coherence Tomography (OCT).

Background Coronary artery aneurysms (CAA) are serious complications of Kawasaki disease (KD). Optical coherence tomography (OCT) is a high-resolution intracoronary imaging modality that characterizes coronary artery wall structure. The purpose of this work was to describe CAA wall sequelae after KD. Methods and Results KD patients scheduled for routine coronary angiography underwent OCT imaging between March 2013 and August 2014. Subjects’ clinical courses, echocardiography, and coronary angiography examinations were reviewed retrospectively. OCT was performed in 18 patients aged 12.4±5.5 years, 9.0±5.1 years following onset of KD. Of those, 14 patients (77.7%) had a history of CAA (7 with giant CAA and 7 with regressed CAA at time of OCT). Intracoronary nitroglycerin was given to all patients (88.4±45.5 μg/m2). Mean radiation dose was 10.9±5.2 mGy/kg. One patient suffered from a transitory uneventful vasospasm at the site of a regressed CAA; otherwise no major procedural complications occurred. The most frequent abnormality observed on OCT was intimal hyperplasia (15 patients, 83.3%) seen at both aneurysmal sites and angiographically normal segments amounting to 390.8±166.0 μm for affected segments compared to 61.7±17 μm for unaffected segments (P<0.001). Disappearance of the media, and presence of fibrosis, calcifications, macrophage accumulation, neovascularization, and white thrombi were seen in 72.2%, 77.8%, 27.8%, 44.4%, and 33.3% of patients. Conclusions In this study, OCT proved safe and insightful in the setting of KD, with the potential to add diagnostic value in the assessment of coronary abnormalities in KD. The depicted coronary structural changes correspond to histological findings previously described in KD.

Treatment of Isolated Ventricular Septal Defects in Children: Amplatzer Versus Surgical Closure

BACKGROUND Isolated hemodynamically significant ventricular septal defects (VSD) were previously treated surgically. Since the introduction of percutaneous (PC) devices, the management of isolated VSD has evolved. In our center, Amplatzer devices have been implanted for selected isolated perimembranous VSD since 2002. METHODS The charts of all isolated PC perimembranous VSD closures and all surgical closures performed since 2002 were reviewed retrospectively. Clinical, electrocardiographic, and echocardiographic data were analyzed. The preclosure, immediate postclosure, and 1-month, 6-month, and 12-month postclosure results were assessed. RESULTS Thirty-seven patients underwent PC closure, and 34 had surgical treatment. Mean follow-up was 42.1 ± 26.0 months. The PC group was significantly older (p < 0.01) and larger in size (p < 0.001). Surgical patients had more severe congestive heart failure and a significantly lower VSD gradient (p < 0.004). At follow-up, there were no differences in the incidence of residual shunting between the two groups (p = 0.92). All valvular regurgitations improved over time, except for 3 aortic regurgitations (5.4%) in the PC group that got worse. Two permanent pacemakers were implanted for early complete heart block in the PC group, and one was implanted in the surgical group (p = 0.94). CONCLUSIONS The surgical results in our population were excellent. The selection of patients with perimembranous VSD remains a challenge to avoid post-PC intervention complications such as heart block and aortic insufficiency. For isolated VSD, PC closure, which avoids the morbidity of open heart surgery, should be considered as part of the therapeutic armamentarium.

Electrocardiographic Depolarization and Repolarization: Long-Term After Kawasaki Disease

AbstractTo assess myocardial electric potentials late after Kawasaki disease (KD) we measured signal-averaged electrocardiography (SAECG) and QT dispersion parameters. Thirteen patients with persistent coronary aneurysm (group I), 12 with late resolution of the aneurysm (>3 months) (group II), and 13 with early resolution (group III) were studied 7.9 ± 3.9, 6.7 ± 3.9, and 7.2 ± 3.6 years after the initial diagnosis (p = NS). In group I, myocardial infarction occurred in one patient during the acute illness, and coronary thrombosis in another; all except two patients had giant aneurysm (n = 8) and/or stenosis (n = 7). At 40-Hz high-pass filter SAECG, terminal 40-msec root mean square amplitude (RMS40) was significantly lower in group I versus II and III (64.1 ± 40.8 mV, 79.9 ± 47.2 mV, and 115 ± 65.4 mV, respectively; p <0.05). Global QT dispersion was significantly greater in group I versus III (52 ± 11 msec and 37 ± 11 msec, respectively; p <0.05), but not in comparison to group II (45 ± 13 msec). The same trend was present for rate-corrected QT dispersion, without reaching statistical significance (84.0 ± 34, 71.5 ± 31, and 61.8 ± 21 respectively). Both depolarization and repolarization parameters are altered in patients with persistent coronary artery aneurysms long-term after KD. This may represent risk factors for developing ventricular arrhythmia in a growing population.

Rejection of transplanted hearts in patients evaluated by the component analysis of multi-wavelength NAD(P)H fluorescence lifetime spectroscopy

Rejection of transplanted hearts remains one of the principal reasons for death of paediatric patients, but an appropriate diagnostic tool for the mild rejection in early stages is still missing. Tissue autofluorescence (AF) is one of the most versatile non-invasive tools for mapping the metabolic state in living tissues. Increasing interest in the imaging and diagnosis of living cells and tissues based on their intrinsic fluorescence rather than fluorescence labelling is closely connected to the latest developments in high-performance spectroscopy and microscopy techniques. In this contribution, we investigate individual components in spectrally- and time-resolved NAD(P)H fluorescence, revealed by linear unmixing, responsible for increased fluorescence in patients presenting mild rejection of transplanted hearts. Application of such approach has the potential to improve the diagnostics of the cardiac transplant rejection by helping currently used histological analysis.

Segmental myocardial contractility versus perfusion in Kawasaki disease with coronary arterial aneurysm

The impact of Kawasaki-related coronary injury on the myocardium was evaluated in 13 patients with persistent coronary aneurysm after a follow-up period of 7.92+/-3.97 years (range 1.8 to 14.3). Myocardial segmental perfusion and contractility integrity were assessed by resting and exercise echocardiography and technetium-99 (Tc-99m) sestamibi scan. Eight patients (61.5%) had giant aneurysms (> or = 8 mm) and 9 had multivessel involvement; the mean diameter of the largest aneurysm was 8.6+/-2.5 mm (range 5 to 14). During the acute phase, myocardial infarction occurred in 1 patient and coronary thrombosis in another. At the latest echocardiographic evaluation, the mean aneurysm diameter was 6.8+/-2.4 mm (range 4.5 to 12), there was persistent giant aneurysms in 5 of 8 patients, and 3 of 9 patients had multivessel involvement. Coronary angiography demonstrated stenosis in 7 of 10 patients, with multiple levels in 2. At sestamibi scan, all 13 patients had perfusion anomalies at rest, whereas only 7 had detectable hypokinesia on echocardiography. With exercise, perfusion returned to near normal in 3 patients, improved in 3, remained unchanged in 4, and worsened in 3 patients. Segmental contractility similarly deteriorated in the latter 3 patients but also in 2 patients whose perfusion scan had improved with exercise. Three patients, normal at rest, developed segmental hypokinesia during exercise. When present, the location of observed changes in contractility on stress echocardiography corresponded to that of perfusion defect. In conclusion, abnormal myocardial perfusion is present long term after complicated Kawasaki disease, the worst anomalies accompanying persistent giant aneurysms. Unfavorable perfusion response was coupled with abnormal contractility; however, enhanced perfusion with exercise correlated poorly with segmental contractility response.