Michael V. Di Maria

RV stroke work in children with pulmonary arterial hypertension: estimation based on invasive haemodynamic assessment and correlation with outcomes

Background RV performance is an important determinant of outcomes in children with pulmonary arterial hypertension (PAH). RV stroke work (RVSW), the product of mean pulmonary artery pressure and stroke volume, integrates contractility, afterload and ventricular-vascular coupling. RVSW has not been evaluated in children with PAH. We tested the hypothesis that RVSW would be a predictor of outcomes in children with PAH. Methods Patients in the Childrens Hospital Colorado PAH database were evaluated retrospectively, and those with idiopathic PAH and those with minor or repaired congenital heart disease were included. Haemodynamic data were obtained by catheterisation and echocardiography, performed within 3 months. RVSW was calculated: mean pulmonary arterial pressure × stroke volume, and indexed to body surface area. Statistics included Kruskal–Wallis, Wilcoxon rank sum, and Spearman correlation. Results Fifty patients were included. Median age of the cohort was 9.5 (6.0, 15.7) years, with a median indexed pulmonary vascular resistance (PVRi) of 6.5 (3.7, 11.6) WU m2. RVSW had a significant association with PVRi (r=0.6, p<0.0001), tricuspid annular systolic plane excursion (r=0.55, p=0.0001), and RV fractional area change (r=−0.4, p=0.005). Grouped by WHO class, there was a significant difference in RVSW (p=0.04). Need for atrial septostomy and death were associated with higher RVSW (p=0.04 and p=0.03, respectively). Conclusions RVSW can be estimated in children with PAH, and is significantly associated with abnormal WHO class, the need for septostomy, as well as mortality. Indices accounting for RV performance as well as ventricular-vascular coupling may be useful in the prognosis and, hence, management of children with PAH.

Successful orthotopic heart transplant in an infant with an inflammatory myofibroblastic tumor of the left ventricle.

A female infant was diagnosed with an inflammatory myofibroblastic tumor involving the left ventricle, which compromised cardiac function. The tumor was endocardial in location and resection was not possible. In this study we report the first successful cardiac transplant and long-term follow-up for this indication.

Left Ventricular Rotational Mechanics in Tanzanian Children with Sickle Cell Disease

Background Sickle cell disease (SCD) is a common inherited hemoglobinopathy. Adults with SCD manifest both systolic and diastolic cardiac dysfunction, though the age of onset of dysfunction has not been defined. Left ventricular (LV) rotational mechanics have not been studied in children with SCD. The aim of this study was to investigate whether cardiac rotational mechanics differed between children with SCD and age-matched controls. Methods Basal and apical LV short-axis images were acquired prospectively in 213 patients with SCD (mean age, 14.1 ± 2.6 years) and 49 controls (mean age, 13.3 ± 2.8 years) from the Muhimbili Sickle Cohort in Dar es Salaam, Tanzania. The magnitude of basal and apical rotation, net twist angle, torsion, and untwist rate were obtained by two-dimensional speckle-tracking. The timing of events was normalized to aortic valve closure. Results Mean basal rotation was significantly lower in patients with SCD compared with controls (P = .012), although no difference was observed in apical rotation (P = .37). No statistically significant differences in torsion or net twist angle were detected. Rotation rate at the apex (P = .001) and base (P = .0004) were significantly slower in subjects with SCD compared with controls. Mean peak untwisting rate was also significantly slower in patients with SCD (P = .006). No associations were found between hemoglobin concentration and apical rotation, basal rotation, net twist, and torsion. Conclusion This study demonstrates alterations in LV rotational mechanics in children with SCD, including lower basal rotation, peak differential twist, and untwist rate. These abnormalities denote subclinical changes in LV systolic and diastolic performance in children with SCD. Future work may reveal an association between rotational metrics and long-term patient outcomes.

Impact of Aortic Stiffness on Ventricular Function in Patients with Fontan Circulation

Objective Elastic properties of the thoracic aorta are responsible for buffering systemic afterload, and may be particularly important in patients with Fontan circulation, in whom heart failure is a major source of attrition. The purpose of this study was to characterize regional stiffness in the ascending and descending aorta in patients with hypoplastic left heart syndrome and single left ventricle morphology after Fontan operation by cardiac magnetic resonance imaging, and to assess whether changes in aortic stiffness are associated with the ventricular function. Methods Phase‐contrast‐derived pulse‐wave velocity (PWV) and relative‐area change (RAC) were measured in the ascending and descending aorta of patients with hypoplastic left heart syndrome (n = 9), patients with single left ventricle circulation (n = 18), and normal controls (n = 8) by magnetic resonance imaging. Stiffness metrics were then correlated with the ventricular volumetric and functional indices. Results Patients with hypoplastic left heart syndrome had elevated ascending aortic PWV along with reduced RAC when compared with controls (both P values < .001). Patients with a single left ventricle presented no change in PWV but had reduced RAC in comparison to controls (P < .01). There were no differences in PWV and RAC between all considered groups in the descending aorta. PWV and RAC measured in the ascending aorta correlated with end‐systolic and end‐diastolic volume indices, ventricular ejection fraction, and ventricular‐vascular coupling ratio. Conclusions Aortic stiffness is most elevated in patients with hypoplastic left heart syndrome, yet patients with single left ventricle morphology show signs of abnormal stiffness as well in the form of reduced aortic strain. Stiffness indices measured in the ascending aorta were associated with overall ventricular function and measures of aortoventricular coupling in both patient populations.

Pulmonary Screening in Subjects after the Fontan Procedure

Objectives To review the pulmonary findings of the first 51 patients who presented to our interdisciplinary single‐ventricle clinic after undergoing the Fontan procedure. Study design We performed an Institutional Review Board–approved retrospective review of 51 patients evaluated following the Fontan procedure. Evaluation included history, physical examination, pulmonary function testing, and 6‐minute walk. Descriptive statistics were used to describe the population and testing data. Results Sixty‐one percent of the patients had a pulmonary concern raised during the visit. Three patients had plastic bronchitis. Abnormal lung function testing was present in 46% of patients. Two‐thirds (66%) of the patients had significant desaturation during the 6‐minute walk test. Patients who underwent a fenestrated Fontan procedure and those who underwent unfenestrated Fontan were compared in terms of saturation and 6‐minute walk test results. Sleep concerns were present in 45% of the patients. Conclusions Pulmonary morbidities are common in patients after Fontan surgery and include plastic bronchitis, abnormal lung function, desaturations with walking, and sleep concerns. Abnormal lung function and obstructive sleep apnea may stress the Fontan circuit and may have implications for cognitive and emotional functioning. A pulmonologist involved in the care of patients after Fontan surgery can assist in screening for comorbidities and recommend interventions.

Predictive value of presuperior cavopulmonary anastomosis cardiac catheterization at increased altitude

OBJECTIVE Infants with single ventricle physiology typically undergo cardiac catheterization prior to superior cavopulmonary anastomosis (SCPA) to assess operative suitability. Predictors of poor outcome at sea level include elevated pulmonary artery pressure (mPAP), indexed pulmonary vascular resistance (PVRi), age <3 months, significant atrioventricular valve regurgitation, among others. Increased altitude has vasoconstrictive effects on the pulmonary vasculature, which may affect pre-SCPA hemodynamics and outcomes. The goal of this study was to determine the predictive value of pre-SCPA catheterization data with regard to reaching Fontan palliation at altitude. DESIGN A retrospective review revealed 150 patients who underwent pre-SCPA catheterization over a 10-year period. Subjects were grouped by progression to Fontan vs aborted palliation, heart transplant or death. Statistics included t-tests, logistic regression and receiver operator characteristic (ROC) curve analysis. RESULTS Independent predictors of failure to achieve Fontan operation at increased altitude include decreased ventricular function, increased mPAP, increased PVRi, and prolonged hospitalization, after adjusting for ventricular morphology and sex. CONCLUSIONS Our data indicate that decreased ventricular function most strongly predicts failure to reach Fontan palliation. Additionally, mPAP and PVRi play an important role in determining outcomes at increased altitude. Prolonged hospitalization is likely a marker of increased medical complexity or more problematic physiology.

Acoustic radiation force impulse of the liver after Fontan operation: Correlation with cardiopulmonary exercise test

BACKGROUND The current management paradigm for children with single ventricle heart disease involves a series of palliative surgeries, culminating in the Fontan operation. This physiology results in a high central venous pressure, and in the setting of single ventricle heart disease, results in hepatic injury and fibrosis over time. Fontan-associated liver disease (FALD) is universally present in this cohort, and the current gold standard for diagnosis remains biopsy. Noninvasive assessments of liver fibrosis, such as ultrasound with elastography or acoustic radiation force impulse (ARFI), has been utilized in this cohort. The effect of poor cardiovascular efficiency, as measured by cardiopulmonary exercise test (CPET), on assessments of liver fibrosis remains poorly understood. METHODS Retrospective, cross-sectional study. Subjects were evaluated in a multidisciplinary clinic setting for patients who have undergone Fontan operation. CPETs, liver ultrasound with elastography (ARFI), and standard laboratory tests were performed as part of routine clinical care pathway. Statistical analysis included linear correlation. RESULTS There was a poor correlation between mean ARFI velocity and peak oxygen consumption (VO2max ) in this cohort (r = .20, P = NS). Similarly, there was poor correlation between ARFI and biomarkers of liver injury, time since Fontan operation and Fontan pressure. DISCUSSION ARFI had poor correlation with functional capacity after Fontan, as measured by VO2max obtained during CPET. While a single measurement of liver elastography was not associated with cardiopulmonary efficiency, longitudinal data may reveal an association.

Doppler-derived flow pattern in the descending aorta does not predict systemic to pulmonary arterial collateral flow in patients with single ventricle palliation: a cross-sectional study.

Background: Children with single ventricle heart disease are at risk for developing systemic to pulmonary arterial collateral vessels that adversely impact short-term outcomes, although the effect on long-term outcomes remains unclear. Collateral flow (CollF) can be quantified using cardiac magnetic resonance (CMR) flow quantification. The velocity–time integral (VTI), obtained from spectral Doppler tracings, has been used in “runoff” lesions like aortic regurgitation to quantify insufficiency. We hypothesized that the VTI ratio of the proximal descending aorta (DAo) after cavopulmonary anastomosis (CPA) would estimate CollF. Methods: A retrospective cross-sectional study was conducted. Patients who had a superior CPA or total CPA and underwent CMR between April 2008 and December 2012 were included. Those with greater than trivial semilunar valve insufficiency or aortic arch obstruction were excluded. In a subset (n = 88), spectral Doppler tracings of the DAo were analyzed to determine the VTI ratio. In another subset (n = 112), CMR was used to determine the ratio of retrograde to antegrade flow in the DAo. Results: There was no linear correlation between VTI ratio and CollF (r 2 = .006, P = .46). There was a weakly positive correlation with CollF (r 2 = .07, P = .007) and the CMR measured ratio of retrograde to antegrade flow. Holodiastolic flow reversal by echo did not predict higher CollF (P = .40), but those with holodiastolic flow reversal by CMR had significantly higher CollF (P = .04). Conclusions: The ratio of reverse to forward flow in the DAo as determined by Doppler echo does not accurately reflect CollF in children with single ventricle after CPA.

The Neonatal Transition of the Right Ventricle

The pulmonary circulation undergoes a dramatic transition at birth, which includes a marked fall in pulmonary vascular resistance (PVR) to accommodate an eight- to tenfold increase in pulmonary blood flow. Failure to achieve or sustain this normal drop in PVR leads to the syndrome of persistent pulmonary hypertension of the newborn (PPHN), which is characterized by profound hypoxemia due to extra-pulmonary shunt, poor cardiac output, and significant morbidity and mortality. The fetal myocardium must also adapt rapidly during the transition, and the right ventricle (RV) undergoes striking functional and structural changes after birth. The RV serves as the “systemic ventricle” in utero, as most of the RV output crosses the widely patent DA and provides 2/3 of combined ventricular output in the normal fetus. Increased systemic vascular resistance, the marked fall in PVR, and functional closure of the “fetal channels” account for the progressive decrease in RV wall thickness and increase in LV mass after birth. Unlike changes in the RV during the normal transition, RV hypertrophy persists in the setting of sustained elevations of PVR due to birth at altitude, PPHN, congenital heart disease, and other cardiopulmonary disorders. In addition to these striking physiologic changes, the neonatal transition of the RV is further characterized by remarkable cellular, molecular, and metabolic adaptations. The fetal heart grows and develops during normal intrauterine life at low oxygen tensions that would induce severe hypoxic stress during postnatal life, yet the fetus thrives and is well-prepared for the normal transition at birth. Insights into mechanisms underlying the normal metabolic and functional transition from fetal to neonatal life are not only important for better understanding of neonatal cardiopulmonary diseases, but will also provide insights into adaptive and maladaptive responses in the adult RV.