Left ventricular non-compaction in paediatrics: a novel semi-automated imaging technique bridging imaging findings and clinical outcomes.

AIMS: We set out to design a reliable, semi-automated, and quantitative imaging tool using cardiac magnetic resonance (CMR) imaging that captures LV trabeculations in relation to the morphologic endocardial and epicardial surface, or perimeter-derived ratios, and assess its diagnostic and prognostic utility. METHODS AND RESULTS: We queried our institutional database between January 2008 and December 2018. Non-compacted (NC)-to-compacted (C) (NC/C) myocardium ratios were calculated and our tool was used to calculate fractal dimension (FD), total mass ratio (TMR), and composite surface ratios (SRcomp). NC/C, FD, TMR, and SRcomp were assessed in relation to LVNC diagnosis and outcomes. Univariate hazard ratios with cut-offs were performed using clinically significant variables to find 'at-risk' patients and imaging parameters were compared in 'at-risk' patients missed by Petersen Index (PI). Ninety-six patients were included. The average time to complete the semi-automated measurements was 3.90 min (SEM: 0.06). TMR, SRcomp, and NC/C were negatively correlated with LV ejection fraction (LVEF) and positively correlated with indexed LV end-systolic volumes (iLVESVs), with TMR showing the strongest correlation with LVEF (-0.287; P = 0.005) and SRcomp with iLVESV (0.260; P = 0.011). We found 29 'at-risk' patients who were classified as non-LVNC by PI and hence, were missed. When compared with non-LVNC and 'low-risk' patients, only SRcomp differentiated between both groups (1.91 SEM 0.03 vs. 1.80 SEM 0.03; P = 0.019). CONCLUSION: This method of semi-automatic calculation of SRcomp captured changes in at-risk patients missed by standard methods, was strongly correlated with LVEF and LV systolic volumes and may better capture outcome events.

Dobutamine stress cardiac MRI is safe and feasible in pediatric patients with anomalous aortic origin of a coronary artery (AAOCA).

BACKGROUND: Risk stratification in anomalous aortic origin of a coronary artery (AAOCA) is challenged by the lack of a reliable method to detect myocardial ischemia. We prospectively studied the safety and feasibility of Dobutamine stress-cardiac magnetic resonance (DSCMR), a test with excellent performance in adults, in pediatric patients with AAOCA. METHODS: Consecutive DSCMR from 06/2014-12/2019 in patients≤20 years old with AAOCA were included. Hemodynamic response and major/minor events were recorded. Image quality and spatial/temporal resolution were evaluated. Rest and stress first-pass perfusion and wall motion abnormalities (WMA) were assessed. Inter-observer agreement was assessed using kappa coefficient. RESULTS: A total of 224 DSCMR were performed in 182 patients with AAOCA at a median age of 14 years (IQR 12, 16) and median weight of 58.0 kg (IQR 43.3, 73.0). Examinations were completed in 221/224 (98.9%), all studies were diagnostic. Heart rate and blood pressure increased significantly from baseline (p < 0.001). No patient had major events and 28 (12.5%) had minor events. Inducible hypoperfusion was noted in 31/221 (14%), associated with WMA in 13/31 (42%). Inter-observer agreement for inducible hypoperfusion was very good (Κ = 0.87). Asymptomatic patients with inducible hypoperfusion are considered high-risk and those with a negative test are of standard risk. CONCLUSIONS: DSCMR is feasible in pediatric patients with AAOCA to assess for inducible hypoperfusion and WMA. It can be performed safely with low incidence of major/minor events. Thus, DSCMR is potentially a valuable test for detection of myocardial ischemia and helpful in the management of this patient population.

Post-operative Assessment of the Arterial Switch Operation: A Comparison of Magnetic Resonance Imaging and Echocardiography.

After an arterial switch operation (ASO), serial imaging is necessary to monitor for maladaptive changes. We compared cardiac magnetic resonance imaging (CMR) to 2-D transthoracic echocardiography (TTE) in assessing post-operative ASO patients. We performed a retrospective review of patients at a single tertiary care center who underwent an ASO and subsequently had a CMR performed from 7/2010 to 7/2016. Those with single ventricle anatomy, congenitally corrected transposition of the great arteries, or previous atrial switch operation were excluded. TTE obtained within 6 months of the CMR was used for comparison. Parameters compared included ventricular size and systolic function, semilunar valve regurgitation, neo-aortic root dimension, and the presence of branch pulmonary artery (PA) stenosis (on CMR by the Nakata index or right/left flow differential; on TTE by peak velocity > 2 m/s or PA diameter Z score < - 2). Forty-seven patients with 90 CMR and 86 TTE studies met inclusion criteria. CMR and TTE assessment of right ventricular (RV) and left ventricular function did not statistically differ. RV dilation was overdetected by TTE (p = 0.046). Right pulmonary artery and left pulmonary artery (LPA) visualization by TTE was worse than CMR (p < 0.01). There was no statistically significant difference between CMR and TTE assessment of branch PA stenosis; however, there was poor agreement between the use of Z score and velocity when determining branch PA stenosis by TTE (κ < 0). Assessment of neo-pulmonary regurgitation (PR) and neo-aortic regurgitation (AR) was significantly different between CMR and TTE (p < 0.05). Assessment for delayed enhancement was performed in 18% of CMR studies (n = 16), with perfusion defects appreciated in three patients. Substantial differences between CMR and TTE exist when examining the post-operative ASO patient. CMR was superior for evaluation of the branch PAs, which commonly require re-intervention. TTE failed to recognize altered ventricular function in several cases. Differences between TTE and CMR could alter management is some cases. Incorporation of CMR into the routine surveillance of patients who received an ASO is warranted.

Correction of Doppler Gradients for Pressure Recovery Improves Agreement with Subsequent Catheterization Gradients in Congenital Aortic Stenosis.

BACKGROUND: In congenital aortic stenosis (AS), suboptimal agreement between Doppler-derived gradients and catheterization gradients may lead to inappropriate referrals for catheterization. To address this problem, the authors investigated whether adjusting Doppler gradients for pressure recovery (PR) improved their agreement with subsequent catheterization gradients. METHODS: One hundred encounters in which patients with congenital AS underwent echocardiography and subsequent catheterization were retrospectively identified. Peak instantaneous and mean transaortic Doppler gradients were recorded from an apical view. PR (mm Hg) was calculated as 4VCW(2) × (2 × EOA/AOA) × (1 - EOA/AOA), where VCW is continuous-wave peak velocity, EOA is effective orifice area (stroke volume/velocity-time integral), and AOA is aortic cross-sectional area (π × radius(2)). The PR-corrected peak Doppler gradient was calculated as peak Doppler gradient - PR. Doppler gradients were tested for correlation and agreement with the peak-to-peak systolic gradient at catheterization (cath gradient). RESULTS: The median age was 12.9 years (range, 0.7-24.6 years). Median AS gradients were as follows: cath, 39 mm Hg (range, 0-103 mm Hg); peak Doppler, 48 mm Hg (range, 10-94 mm Hg); mean Doppler, 25 mm Hg (range, 4-58 mm Hg); and PR-corrected peak Doppler, 35 mm Hg (range, 5-78 mm Hg). Correlation coefficients between the various Doppler and cath gradients were not significantly different. The mean difference between Doppler and cath gradients was smallest for the PR-corrected peak Doppler gradient (-4.1 ± 14.1 mm Hg), followed by the uncorrected peak Doppler gradient (9.7 ± 15.9 mm Hg) and the mean Doppler gradient (-14.6 ± 15.6 mm Hg) (P < .001). Receiver operating characteristic curve analysis for a cath gradient ≥ 35 mm Hg revealed a significantly larger area under the curve for the PR-corrected peak Doppler gradient (0.85) compared with the uncorrected peak Doppler gradient (0.80) (P = .004) and the mean Doppler gradient (0.78) (P = .001). A PR-corrected peak Doppler gradient ≥ 27 mm Hg was associated with a cath gradient ≥ 35 mm Hg with 90% sensitivity and 61% specificity. CONCLUSIONS: In congenital AS, correcting the peak Doppler gradient for PR significantly improved agreement with the subsequently measured cath gradient. This approach may improve decisions regarding referral for catheterization.

Cardiac medical conditions have become the leading cause of death in children with heart disease.

OBJECTIVE: Mortality among children with congenital and acquired heart disease has decreased significantly over the past decades. We sought to determine whether the underlying problems leading to death in these patients had changed over the past decade. METHODS: We reviewed medical records for 100 deaths of cardiac patients in 2004-2005 and 100 deaths in 1995-1996. Demographic, clinical, and procedural data as well as circumstances of death were collected. A consensus committee reviewed each case and sought to identify the condition leading to death. These conditions were classified as predominantly surgical or medical. RESULTS: General patient characteristics (age, gender, cardiac history, comorbidities, proportion of surgical patients) did not change significantly between the two time periods. However, in 1995-1996, 64% of deceased surgical patients had died within 30 days of surgery. This rate was nearly halved to only 38% by 2004-2005 (P= .003). Furthermore, the conditions leading to death changed significantly: 51% of patient deaths in 1995-1996 resulted from a surgical problem, 29% from a medical condition. This ratio was reversed in 2004-2005: Only 31% of patient deaths were due to a surgical problem, while 50% of deaths resulted from a medical condition (P= .005). The most common medical conditions resulting in death were pulmonary vein stenosis, pulmonary arterial hypertension, and primary myocardial failure. CONCLUSIONS: The proportion of deaths within 30 days of cardiac surgery decreased significantly over the past decade. While surgical causes accounted for the majority of these deaths in 1995-1996, most patient deaths in 2004-2005 resulted from cardiac medical causes.

Vaccination with tumor cells pulsed with foreign peptide induces immunity to the tumor itself.

EMT-6 mammary carcinoma and B16 melanoma (B16M) cells are lethal and barely immunogenic in syngeneic BALB/c and C57BL/6 mice, respectively. We show that mice vaccinated with tumor cells pulsed with a MHC class I-restricted peptide develop a T cell response, not only to the peptide, but also to the unpulsed tumor. These mice display protective immunity against the unpulsed tumor, and their T cells adoptively transfer tumor-specific protection to immunodeficient SCID mice. Our data have implications for cancer vaccine strategies. Grafting a single well-defined foreign peptide on tumor cells might suffice to trigger anti-tumor immunity.

Increased per cell IFN-gamma productivity indicates recent in vivo activation of T cells.

Immunization with vaccinia virus causes long-term immunity. Efforts have been made to characterize the T cells responsible for this protection. Recently, T cell subsets were described that not only co-express multiple cytokines, but also show increased per cell cytokine productivity. These highly productive cells are often considered to be the most protective. We used ELISPOT assays to measure per cell IFN-gamma productivity of vaccinia-specific T cells in childhood immunized adults immediately before and at different time points after vaccinia re-vaccination. Apart from an increase in frequency, we found a marked increase of IFN-gamma productivity following vaccinia re-vaccination. However, these changes were short-lived as both parameters quickly returned to baseline values within 22days after re-vaccination. Therefore, increased per cell IFN-gamma productivity seems to be a sign of recent in vivo T cell activation rather than a stable marker of a distinct T cell subset responsible for long-term immune protection.

Lack of disease specificity limits the usefulness of in vitro costimulation in HIV- and HCV-infected patients.

Measurements of antigen-specific T cell responses in chronic diseases are limited by low frequencies of antigen-specific cells in the peripheral blood. Therefore, attempts have been made to add costimulatory molecules such as anti-CD28 or IL-7/IL-15 to ELISPOT assays to increase sensitivity. While this approach has been successful under certain circumstances, results are often inconsistent. To date, there are no comprehensive studies directly comparing the in vitro effects of multiple costimulatory molecules in different disease settings. Therefore, in the present study we tested the effects of IL-7/IL-15, IFN-alpha, anti-ICOS, and anti-CD28 on antigen-specific T cell responses in patients infected with HCV or HIV versus healthy individuals. Our data show that none of the aforementioned molecules could significantly increase ELISPOT sensitivity, neither in HCV nor in HIV. Moreover, all of them caused false-positive responses to HCV and HIV antigens in healthy individuals. Our results question the broad use of in vitro costimulation.