Longitudinal Changes in Echocardiographic Parameters of Cardiac Function in Pediatric Cancer Survivors.

BACKGROUND: Childhood cancer survivors undergo serial echocardiograms to screen for cardiotoxicity. It is not clear whether small longitudinal changes in functional or structural parameters over time have clinical significance. OBJECTIVES: To assess the timing of changes in serial echocardiographic parameters in pediatric age childhood cancer survivors and to evaluate their associations with cardiomyopathy development. METHODS: We performed a multi-center retrospective case-control study of ≥1-year survivors following the end of cancer therapy. Cardiomyopathy cases (fractional shortening (FS) ≤28% or ejection fraction (EF) ≤50% on ≥2 occasions) were matched to controls (FS ≥30%, EF ≥55%, not on cardiac medications) by cumulative anthracycline and chest radiation dose, follow-up duration, and age at diagnosis. Digitally archived clinical surveillance echocardiograms were quantified in a central core lab, blinded to patient characteristics. Using mixed models with interaction terms between time and case status, we estimated the least square mean differences of 2D, M-mode, pulsed wave Doppler and tissue Doppler imaging derived parameters across time between cases and controls. RESULTS: We identified 50 matched case-control pairs from 5 centers. Analysis of 412 echocardiograms (cases, n=181; controls, n=231) determined that indices of LV systolic function (FS, biplane EF), diastolic function (mitral E/A ratio), and LV size (end diastolic dimension z-scores) were significantly different between cases and controls, even four years prior to the development of cardiomyopathy. CONCLUSIONS: Longitudinal changes in cardiac functional parameters can occur relatively early in pediatric age childhood cancer survivors and are associated with the development of cardiomyopathy.

Postnatal Outcome of Fetal Left Ventricular Hypertrabeculation/Noncompaction.

Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality of unknown etiology. Prenatal diagnosis of LVHT can be established by fetal echocardiography. A review of 106 published cases showed that 46 cases with prenatally diagnosed LVHT were alive 0.5-120 months after birth. Since the course of cases with prenatally LVHT after publication is unknown, we aimed to collect follow-up-information. Information regarding vital status, cardiac and extracardiac morbidity was gathered by contacting the authors of the 46 cases. Fourteen of the 28 authors answered and gave information about 18 cases (six females, seven males, five gender-unknown, age 18 months to 10 years, mean follow-up 60 months). No differences were found between the 18 cases with follow-up and the 28 cases without follow-up regarding age, gender, cardiac or extracardiac comorbidities, and interventions. Three of the 18 cases had died subsequently from heart failure, osteosarcoma, and enterocolitis, respectively. Mutations or chromosomal abnormalities were found in six of the seven examined patients, extracardiac abnormalities in nine patients. Three patients received a pacemaker because of complete AV block, and two patients underwent heart transplantation. Cardiac surgical or interventional procedures were carried out in four patients. None suffered from malignant arrhythmias or had a cardioverter-defibrillator implanted. Based on the limited information, there are indications that cases with fetal diagnosis of LVHT have a continuing morbidity and mortality, even if they receive appropriate care. Since fetal LVHT is frequently associated with genetic abnormalities, further research about survival and underlying genetic causes is needed.

Intraoperative transesophageal echocardiographic assessment of left ventricular Tei index in congenital heart disease.

BACKGROUND: Use of the Tei index has not been described to assess myocardial function before or after surgery in pediatric patients. This study was designed to evaluate the left ventricular (LV) function using the Tei index pre- and post-cardiopulmonary bypass in patients with lesion that result in a volume loaded right ventricle (RV). METHODS: Retrospective data on 55 patients who underwent repair of a cardiac defect were analyzed. Patients with volume overload RV (n = 15) were compared to patients without volume overload but with other cardiac defects (n = 40). We reviewed pre- and post-operative LV myocardial performance index (Tei index). Tei index was obtained from transesophageal Doppler echocardiogram. RESULTS: Patients with right heart volume overload, the mean preoperative Tei index was 0.6, with a postoperative mean decrease of 0.207 (P = 0.014). Patients without right heart volume overload, the mean preoperative Tei was 0.48 with no significant postoperative change (P = 0.82). CONCLUSION: Pre- and post-operative transesophageal echocardiogram assessment provides an easy and quick way of evaluating LV function intra-operatively using LV Tei index. Preoperative LV Tei index was greater in the RV volume overload defects indicating diminished LV global function. This normalized in the immediate postoperative period, implying an immediate improvement in LV function. In patients without right heart volume load, consist of other cardiac defects, demonstrated no changes in the pre- and post-operative LV Tei. This implies that LV function was similar after the surgery.

Evaluation of traditional and novel measures of cardiac function to detect anthracycline-induced cardiotoxicity in survivors of childhood cancer.

PURPOSE: Cardiovascular disease is the leading noncancer cause of death among survivors of childhood cancer. Ejection fraction (EF) and fractional shortening (FS) are common echocardiographic measures of cardiac function, but newer imaging modalities may provide additional information about preclinical disease. This study aimed to evaluate these modalities in detection of anthracycline-induced cardiac toxicity. METHODS: We compared mean radial displacement, EF, and FS among 17 adult survivors of childhood cancer exposed to ≥ 300 mg/m(2) of anthracyclines to 17 age- and sex-matched healthy controls. Survivors with a history of cardiac-directed radiation, diabetes, or heart disease were excluded. RESULTS: Survivors (35% male), mostly with history of treatment for a solid tumor, had a median age at diagnosis of 15 years (1-20) and 27 years (18-50) at evaluation. Median anthracycline exposure was 440 (range 300-645) mg/m(2). FS (35.5 vs. 39.6%, p < 0.01) and radial displacement (5.6 vs. 6.7 mm, p = 0.02) were significantly lower in survivors compared to controls, respectively. Although the mean EF was lower in survivors versus controls (55.4 vs. 59.7%), it was not statistically significant (p = 0.057). All echocardiographic measures were inversely associated with anthracycline dose, though radial displacement was no longer significantly correlated with anthracycline dose after controlling for survival time (p = 0.07), while EF remained correlated (p = 0.003). IMPLICATIONS FOR CANCER SURVIVORS: Radial displacement, EF, and FS are lower in childhood cancer survivors compared to controls. In this study, radial displacement added no new information beyond the traditional measures, but clinical utility remains undetermined and requires further longitudinal study.

Fetal complete common atrioventricular canal defect: spontaneous closure of the ventricular septal defect--in utero anatomic evolution and postnatal outcomes.

BACKGROUND: We describe in utero anatomic evolution and postnatal outcome of complete common atrioventricular canal defect (CCAVCD). METHODS: Retrospective data on 31 fetuses with CCAVCD were analyzed. We reviewed prenatal and postnatal echocardiograms, karyotype, and postnatal outcomes. RESULTS: A total of 20 fetuses had complete data, 18 with serial fetal echocardiograms and postnatal data and 2 terminations. At initial examination, isolated CCAVCD was seen in 12 (67%) fetuses while 6 (33%) were associated with heterotaxy syndrome. On follow-up, 4 fetuses (22%) had spontaneous closure of the inlet ventricular septal defect (VSD) component of the CCAVCD, seen both at 30 to 35 weeks of gestation and on postnatal echocardiograms. These 4 fetuses had previously demonstrated CCAVCD between 18 and 25 weeks of gestation. A total of 15 (83%) patients underwent operative correction, 10 with isolated complete atrioventricular septal defect and 5 with heterotaxy had surgical repair. Four infants in whom spontaneous intrauterine closure of the VSD component was observed had no VSD noted at surgery and underwent closure of primum atrial septal defect and repair of the left atrioventricular (AV) valve cleft. CONCLUSIONS: Our data demonstrate that CCAVCD diagnosed during fetal life is not a static anomaly. In our series, an inlet VSD less than 4 mm and Rastelli type A anatomy (AV valve attachment to septal crest) during second trimester may evolve during third trimester by formation of AV sulcus pouch and spontaneous closure of the VSD. To the best of our knowledge, this is the first study to report such anatomic evolution of CCAVCD in the fetus. This information is vital for appropriate counseling for expectant parents.

Pathology of the aortic arch in hypoplastic left heart syndrome: surgical implications.

Aortic arch reconstruction plays an important role in the success of the Norwood procedure (NP) for hypoplastic left heart syndrome (HLHS). This study investigated the cardiac specimens to determine the etiology of distal aortic arch obstruction after the NP for HLHS and to locate coarctation of the aorta in HLHS untreated by surgery. This study examined 17 cardiac specimens: 9 that had NP and 8 not treated by surgery. The findings after NP showed frequent failure to resect the coarctation segment completely and failure to extend the augmentation patch into the descending aorta. Five (62.5%) of the eight hearts not treated by surgery had significant periductal coarctation of the aorta. After NP for nine patients, three (33%) had residual coarctation of the aorta. To minimize the risk of recurrent or persistent aortic arch obstruction after NP and to improve the long- and short-term outcome, the ductal tissue and the coarctation segment encircling the aortic lumen should be resected. The distal wall incision should be extended at least 5 mm beyond the distal aspect of the ductal tissue. These steps could avoid major aortic arch obstruction, promote growth of the native aortic tissue, and avoid ventricular dysfunction.