Olga Toro-Salazar

Long-Term Follow-Up of Patients After Coarctation of the Aorta Repair

Late cardiovascular complications after operative repair of coarctation of the aorta include systemic hypertension, premature coronary artery disease, aortic valve abnormalities, aortic aneurysm, and recoarctation. We report the outcome in 274 subjects greater-than-or-equal50 years after coarctation repair. Operative repair of simple coarctation was performed on 274 patients at the University of Minnesota Hospital between 1948 and 1976. Twenty patients (7%) died in the immediate postoperative period. Of the 254 survivors, 2 were lost to follow-up, 45 (18%) died at a mean age of 34 years, and 207 (81%) were alive greater-than-or-equal50 years after the original operation. Coronary artery disease and perioperative deaths at the time of a second cardiac operation accounted for 17 of the 45 late deaths. Predictors of survival were age at operation and blood pressure at the first postoperative visit. Of the 207 long-term survivors, 92 (48%) participated in a clinical cardiovascular evaluation. Thirty-two of the 92 subjects had systemic hypertension that was predicted by age at operation, blood pressure at the first postoperative visit, and paradoxic hypertension at operative repair. New cardiovascular abnormalities detected at follow-up evaluation included evidence of a previous myocardial infarction, cardiomyopathy, atrial fibrillation, moderate to severe left ventricular outflow tract obstruction, moderate aortic valve regurgitation, recoarctation, and ascending aortic dilation. Thus, long-term survival is significantly affected by age at operation, with the lowest mortality rates observed in patients who underwent surgery between 1 and 5 years of age. More than 1/3 of the survivors developed significant late cardiovascular abnormalities.

Occult Cardiotoxicity in Childhood Cancer Survivors Exposed to Anthracycline Therapy

Background—More than 50% of >270 000 childhood cancer survivors in the United States have been treated with anthracyclines and are therefore at risk of developing cardiotoxicity. Cardiac magnetic resonance (CMR) has demonstrated utility to detect diffuse interstitial fibrosis and changes in regional myocardial function. We hypothesized that CMR would identify occult cardiotoxicity characterized by structural and functional myocardial abnormalities in a cohort of asymptomatic pediatric cancer survivors with normal global systolic function. Methods and Results—Forty-six long-term childhood cancer survivors with a cumulative anthracycline dose ≥200 mg/m2 and normal systolic function were studied 2.5 to 26.9 years after anthracycline exposure. Subjects underwent transthoracic echocardiography, CMR with routine cine acquisition, tissue characterization, and left ventricular strain analysis using a modified 16-segment model. Extracellular volume was measured in 27 subjects, all of whom were late gadolinium enhancement negative. End-systolic fiber stress was elevated in 45 of 46 subjects. Low average circumferential strain magnitude (&egr;cc) −14.9±1.4; P<0.001, longitudinal strain magnitude (&egr;ll) −13.5±1.9; P<0.001, and regional peak circumferential strain were seen in multiple myocardial segments, despite normal global systolic function by transthoracic echocardiography and CMR. The mean T1 values of the myocardium were significantly lower than that of control subjects at 20 minutes (458±69 versus 487±44 milliseconds; P=0.01). Higher mean extracellular volume was observed in female subjects (0.34 versus 0.22; P=0.01). Conclusions—Asymptomatic postchemotherapy pediatric patients have abnormal myocardial characteristics and strain parameters by CMR despite normal global cardiac function by standard transthoracic echocardiography and CMR measures.

HACEK endocarditis in infants and children: two cases and a literature review.

Wereport 2 cases of Haemophilus parainfluenzae endocarditis and review 34 cases of HACEK endocarditis from the literature. HACEK organisms are the most common cause of Gram-negative endocarditis in children. They have a propensity to form friable vegetations (especially H. parainfluenzae) that break off and cause symptomatic emboli. HACEK endocarditis (from a review of the 36 published cases) may involve previously normal hearts (33%), may be complicated by embolization (31%) and may require vegetectomy or other surgery (31%). Mortality with HACEK endocarditis was 14%. HACEK organisms may be resistant to penicillins but are susceptible to third generation cephalosporins.

Regional Implementation of a Pediatric Cardiology Chest Pain Guideline Using SCAMPs Methodology

BACKGROUND AND OBJECTIVES: Chest pain is a complaint for which children are frequently evaluated. Cardiac causes are rarely found despite expenditure of considerable time and resources. We describe validation throughout New England of a clinical guideline for cost-effective evaluation of pediatric patients first seen by a cardiologist for chest pain using a unique methodology termed the Standardized Clinical Assessment and Management Plans (SCAMPs). METHODS: A total of 1016 ambulatory patients, ages 7 to 21 years initially seen for chest pain at Boston Children’s Hospital (BCH) or the New England Congenital Cardiology Association (NECCA) practices, were evaluated by using a SCAMPs chest pain guideline. Findings were analyzed for diagnostic elements, patterns of care, and compliance with the guideline. Results from the NECCA practices were compared with those of Boston Children’s Hospital, a regional core academic center. RESULTS: Two patients had chest pain due to a cardiac etiology, 1 with pericarditis and 1 with an anomalous coronary artery origin. Testing performed outside of guideline recommendations demonstrated only incidental findings. Patients returning for persistent symptoms did not have cardiac disease. The pattern of care for the NECCA practices and BCH differed minimally. CONCLUSIONS: By using SCAMPs methodology, we have demonstrated that chest pain in children is rarely caused by heart disease and can be evaluated in the ambulatory setting efficiently and effectively using minimal resources. The methodology can be implemented regionally across a wide range of clinical practice settings and its approach can overcome a number of barriers that often limit clinical practice guideline implementation.

Cardiac magnetic resonance tissue tracking in right ventricle: Feasibility and normal values

PURPOSE To investigate right ventricular (RV) strain in patients without identified cardiac pathology using cardiac magnetic resonance tissue tracking (CMR TT). METHODS A total of 50 consecutive patients with no identified cardiac pathology were analyzed. RV longitudinal and circumferential strain was assessed by CMR TT. The age range was 4-81years with a median of 32years (interquartile range, 15 to 56years). RESULTS Analysis time per patient was <5min. The peak longitudinal strain (Ell) was -22.11±3.51%. The peak circumferential strains (Ecc) for global, basal, mid-cavity and apical segments were as follows: -11.69±2.25%, -11.00±2.45%, -11.17±3.36%, -12.90±3.34%. There were significant gender differences in peak Ecc at the base (P=0.04) and the mid-cavity (P=0.03) with greater deformation in females than in males. On Bland-Altman analysis, peak Ell (mean bias, 0.22±1.67; 95% CI -3.05 to 3.49) and mid-cavity Ecc (mean bias, 0.036±1.75; 95% CI, -3.39 to 3.47) had the best intra-observer agreement and inter-observer agreement, respectively. CONCLUSIONS RV longitudinal and circumferential strains can be quickly assessed with good intra-observer and inter-observer variability using TT.

Regional Implementation of a Pediatric Cardiology Syncope Algorithm Using Standardized Clinical Assessment and Management Plans (SCAMPS) Methodology

Background Pediatric syncope is common. Cardiac causes are rarely found. We describe and assess a pragmatic approach to these patients first seen by a pediatric cardiologist in the New England region, using Standardized Clinical Assessment and Management Plans (SCAMPs). Methods and Results Ambulatory patients aged 7 to 21 years initially seen for syncope at participating New England Congenital Cardiology Association practices over a 2.5‐year period were evaluated using a SCAMP. Findings were iteratively analyzed and the care pathway was revised. The vast majority (85%) of the 1254 patients had typical syncope. A minority had exercise‐related or more problematic symptoms. Guideline‐defined testing identified one patient with cardiac syncope. Syncope Severity Scores correlated well between physician and patient perceived symptoms. Orthostatic vital signs were of limited use. Largely incidental findings were seen in 10% of ECGs and 11% of echocardiograms. The 10% returning for follow‐up, by design, reported more significant symptoms, but did not have newly recognized cardiac disease. Iterative analysis helped refine the approach. Conclusions SCAMP methodology confirmed that the vast majority of children referred to the outpatient pediatric cardiology setting had typical low‐severity neurally mediated syncope that could be effectively evaluated in a single visit using minimal resources. A simple scoring system can help triage patients into treatment categories. Prespecified criteria permitted the effective diagnosis of the single patient with a clear cardiac etiology. Patients with higher syncope scores still have a very low risk of cardiac disease, but may warrant attention.

Defining late onset occult asymptomatic cardiotoxicity in childhood cancer survivors exposed to anthracycline therapy: a cardiac magnetic resonance imaging study

Background There are over 270,000 childhood cancer survivors in the US. Of these survivors, more than 50% have been treated with anthracyclines and are at risk of developing progressive cardiotoxicity. Novel cardiac magnetic resonance imaging (CMRI) techniques are now able to reliably detect diffuse myocardial fibrosis and changes in regional myocardial function. We hypothesized that these novel CMRI techniques will identify occult asymptomatic cardiotoxicity in a cohort of childhood cancer survivors with normal global systolic function. Methods Twenty seven long-term childhood cancer survivors between 11.8-28.8 years with a cumulative dose >240mg/ m2 (mean 363±89) and normal systolic function (SF>29%) were studied 2.4-24 years after exposure to anthracycline therapy. Patients underwent CMRI techniques to characterize changes in T1 relaxation time, left ventricular myocardial peak circumferential and longitudinal strain parameters and were analyzed using the 17-segment model. Extracellular volume (ECV) was measured in 13 subjects all of whom were late gadolinium enhancement (LGE) negative. We performed standard CMRI assessment and quantification of myocardial mass, end-systolic and end-diastolic volumes, ejection fraction, and end systolic fiber stress. Results Twenty seven of 60 planned subjects have been imaged. End systolic fiber stress was significantly increased with higher cumulative anthracycline dose (R2=0.18, p<0.03) and younger age at diagnosis (R2=0.20, p<0.02). Lower average circumferential strain magnitude (ecc) and regional changes in peak circumferential strain were seen in multiple segments despite n ormal values of global systolic function by echocardiography and CMRI (Figure1). T1 maps are depicted in Figure 1. The mean T1 values of the myocardium were not significantly different between patients and controls at 4 min (375±67ms vs.389±36, p<0.07) and 10 min (433±52 ms vs.435±36, p<0.39), but were significantly lower at 20 minutes (455±50ms vs. 487 ±44, p<0.003) (Figure 2). Low myocardial T1 at 20 minutes was significantly associated with increases in end systolic fiber stress (R2=0.7, p<0.002). Higher mean ECV was observed in patients with cumulative dose ≥400mg/m2 (0.27 vs. 0.21, p<0.05). Conclusions

Identification of a Novel microRNA Profile in Pediatric Cancer Patients treated with Anthracycline Chemotherapy

Anthracycline chemotherapy (AC) is associated with decline in left ventricular ejection fraction (LVEF), yet the mechanisms remain unclear. Although changes in microRNAs (miRs) have been identified in adult cardiovascular disease, miR profiles in pediatric patients with AC have not been well studied. The goal of this study was to examine miR profiles (unbiased array) in pediatric patients with AC compared with age-matched referent normal patients. We hypothesize that pediatric patients with AC will express a unique miR profile at the initiation and completion of therapy and will be related to LVEF. Serum was collected in pediatric patients (10-22 yr, n = 12) with newly diagnosed malignancy requiring AC within 24-48 h after the initiation of therapy (30-60 mg/m2) and ~1 yr after completing therapy. A custom microarray of 84 miRs associated with cardiovascular disease was used (quantitative RT-PCR) and indexed to referent normal profiles (13-17 yr, n = 17). LVEF was computed by cardiac MRI. LVEF fell from AC initiation at ~1 yr after AC completion (64.28 ± 1.78% vs. 57.53 ± 0.95%, respectively, P = 0.004). Of the 84 miRs profiled, significant shifts in 17 miRs occurred relative to referent normal ( P ≤ 0.05). Moreover, the functional domain of miRs associated with myocardial differentiation and development fell over threefold at the completion of AC ( P ≤ 0.05). Moreover, eight miRs were significantly downregulated after AC completion in those patients with the greatest decline in LVEF (≥10%, P < 0.05). This study demonstrates, for the first time, that changes in miR expression occur in pediatric patients with AC. These findings suggest that miRs are a potential strategy for the early identification of patients with AC susceptible to left ventricular dysfunction. NEW & NOTEWORTHY Although anthracycline chemotherapy (AC) is effective for a number of pediatric cancers, an all too often consequence of AC is the development of left ventricular failure. The present study identified that specific shifts in the pattern of microRNAs, which regulate myocardial growth, function, and viability, occurred during and after AC in pediatric patients, whereby the magnitude of this shift was associated with the degree of left ventricular failure.

A USUAL ARRHYTHMIA IN AN UNUSUAL HEART

Patients with congenital heart disease (CHD) may have variable locations of the AV node, either based on their anatomy or prior surgical interventions. Slow pathway locations may be unknown or located at unconventional sites, making catheter based interventions quite challenging. A 25-year-old man

Cardiac magnetic resonance characteristics of acute anthracycline-induced cardiotoxicity

Background Cardiac magnetic resonance imaging (CMR) is the gold standard for quantification of global and regional myocardial function and is able to detect subclinical myocardial dysfunction in the setting of a wide variety of myocardial disease processes, including anthracycline induced cardiomyopathy (AIC). Preliminary studies using T2-weighted sequences have demonstrated increase in signal intensity suggestive of myocardial edema during cancer therapy. We hypothesized that reductions in mid-wall peak circumferential (εcc) and longitudinal (ειι) strain magnitude and increase in T2 relaxation suggestive of myocardial edema would precede changes in EF in a cohort of pediatric patients newly diagnosed with cancer studied at baseline and after 24-48 hours at set intervals of anthracycline cumulative dose up to maximal therapy.