Abbreviated cardiac magnetic resonance imaging versus echocardiography for interval assessment of systolic function in Duchenne muscular dystrophy: patient satisfaction, clinical utility, and image quality.

PURPOSE: Poor acoustic windows make interval assessment of systolic function in patients with (Duchenne Muscular Dystrophy) DMD by echocardiography (echo) difficult. Cardiac magnetic resonance imaging (CMR) can be challenging in DMD patients due to study duration and patient discomfort. We developed an abbreviated CMR (aCMR) protocol and hypothesized that aCMR would compare favorably to echo in image quality and clinical utility without significant differences in exam duration, patient satisfaction, and functional measurements. METHODS: DMD patients were recruited prospectively to undergo echo and aCMR. Modalities were compared with a global quality assessment score (GQAS), clinical utility score (CUS), and patient satisfaction score (PSS). Results were compared using Wilcoxon signed-rank tests, Spearman correlations, intraclass correlations, and Bland-Altman analyses. RESULTS: Nineteen DMD patients were included. PSS scores and exam duration were equivalent between modalities, while CUS and GQAS scores favored aCMR. ACMR scored markedly higher than echo in RV visualization and assessment of atrial size. Older age was negatively correlated with echo GQAS and CUS scores, as well as aCMR PSS scores. Higher BMI was positively correlated with aCMR GQAS scores. Nighttime PPV requirement and non-ambulatory status were correlated with worse echo CUS scores. Poor image quality precluding quantification existed in five (26%) echo and zero (0%) aCMR studies. There was moderate correlation between aCMR and echo for global circumferential strain and left ventricular four chamber global longitudinal strain. CONCLUSION: The aCMR protocol resulted in improved clinical relevance and quality scores relative to echo, without significant detriment to patient satisfaction or exam duration.

Natural History of Hypertrophic Cardiomyopathy in Noonan Syndrome With Multiple Lentigines.

BACKGROUND: We aimed to examine clinical features and outcomes of consecutive molecularly characterized patients with Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy. METHODS: A retrospective, longitudinal multicenter cohort of consecutive children and adults with a genetic diagnosis of Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy between 2002 and 2019 was assembled. We defined a priori 3 different patterns of left ventricular remodeling during follow-up: (1) an increase in ≥15% of the maximal left ventricular wall thickness (MLVWT), both in mm and z-score (progression); (2) a reduction ≥15% of the MLVWT, both in mm and z-score (absolute regression); (3) a reduction ≥15% of the MLVWT z-score with a stable MLVWT in mm (relative regression). The primary study end point was a composite of cardiovascular death, heart transplantation, and appropriate implantable cardioverter defibrillator-shock. RESULTS: The cohort comprised 42 patients with Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy, with a median age at diagnosis of 3.5 (interquartile range, 0.2-12.3) years. Freedom from primary end point was 92.7% (95% CI, 84.7%-100%) 1 year after presentation and 80.9% (95% CI, 70.1%-90.7%) at 5 years. Patients with MLVWT z-score >13.7 showed reduced survival compared with those with <13.7. During a median follow-up of 3.7 years (interquartile range, 2.6-7.9), absolute regression was the most common type of left ventricular remodeling (n=9, 31%), followed by progression (n=6, 21%), and relative regression (n=6, 21%). CONCLUSIONS: These findings provide insights into the natural history of left ventricular hypertrophy, and can help inform clinicians regarding risk stratification and clinical outcomes in patients with Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy.

Factors associated with morbidity, mortality, and hemodynamic failure after biventricular conversion in borderline hypoplastic left hearts.

OBJECTIVE: A subset of patients with borderline hypoplastic left heart may be candidates for single to biventricular conversion, but long-term morbidity and mortality persist. Prior studies have shown conflicting results regarding the association of preoperative diastolic dysfunction and outcome, and patient selection remains challenging. METHODS: Patients with borderline hypoplastic left heart undergoing biventricular conversion from 2005 to 2017 were included. Cox regression identified preoperative factors associated with a composite outcome of time to mortality, heart transplant, takedown to single ventricle circulation, or hemodynamic failure (defined as left ventricular end-diastolic pressure >20 mm Hg, mean pulmonary artery pressure >35 mm Hg, or pulmonary vascular resistance >6 international Woods units). RESULTS: Among 43 patients, 20 (46%) met the outcome, with a median time to outcome of 5.2 years. On univariate analysis, endocardial fibroelastosis, lower left ventricular end-diastolic volume/body surface area (when <50 mL/m2), lower left ventricular stroke volume/body surface area (when <32 mL/m2), and lower left:right ventricular stroke volume ratio (when <0.7) were associated with outcome; higher preoperative left ventricular end-diastolic pressure was not. Multivariable analysis demonstrated that endocardial fibroelastosis (hazard ratio, 5.1, 95% confidence interval, 1.5-22.7, P = .033) and left ventricular stroke volume/body surface area 28 mL/m2 or less (hazard ratio, 4.3, 95% confidence interval, 1.5-12.3, P = .006) were independently associated with a higher hazard of the outcome. Approximately all patients (86%) with endocardial fibroelastosis and left ventricular stroke volume/body surface area 28 mL/m2 or less met the outcome compared with 10% of those without endocardial fibroelastosis and with higher stroke volume/body surface area. CONCLUSIONS: History of endocardial fibroelastosis and smaller left ventricular stroke volume/body surface area are independent factors associated with adverse outcomes among patients with borderline hypoplastic left heart undergoing biventricular conversion. Normal preoperative left ventricular end-diastolic pressure is insufficient to reassure against diastolic dysfunction after biventricular conversion.

Quality Improvement in a Pediatric Echocardiography Laboratory: A Collaborative Process.

Transthoracic echocardiography (TTE) is an essential tool for diagnosis and management of congenital heart disease. Pediatric echocardiography presents unique challenges including complex anatomy, variable patient cooperation and provider expertise. Diagnostic errors inevitably occur. We designed a collaborative and stepwise quality improvement (QI) process to address diagnostic errors within our laboratory. We retrospectively reviewed medical records to identify diagnostic TTE errors in 100 consecutive cardiac surgery patients ≤ 5 years old (July 2020-January 2021). We identified 18 diagnostic errors. Most errors had minor impact (14/18), and 13 were preventable or possibly preventable. We presented these results to our sonographers and faculty and requested input on preventing and managing diagnostic errors. Our root cause analysis based on their responses yielded 7 areas for improvement (imaging, reporting, systems, time, environment, people, QI processes). Our faculty and sonographers chose QI processes and imaging as initial areas for intervention. We defined our SMART goal as a 10% reduction in diagnostic errors. We implemented interventions focused on QI processes. On initial follow up in May 2022, we identified 7 errors in 70 patients (44% reduction in error rate). Utilizing a stepwise and team-based approach, we successfully developed QI initiatives in our echocardiography laboratory. This approach can serve as a model for a collaborative QI process in other institutions.

Late gestation predictors of a postnatal biventricular circulation after fetal aortic valvuloplasty.

OBJECTIVES: Fetal aortic valvuloplasty (FAV) for severe aortic stenosis (AS) has shown promise in averting progression to hypoplastic left heart syndrome. After FAV, predicting which fetuses will achieve a biventricular (BiV) circulation after birth remains challenging. Identifying predictors of postnatal circulation on late gestation echocardiography will improve parental counseling. METHODS: Liveborn patients who underwent FAV and had late gestation echocardiography available were included (2000-2017, n = 96). Multivariable logistic regression and classification and regression tree analysis were utilized to identify independent predictors of BiV circulation. RESULTS: Among 96 fetuses, 50 (52.1%) had BiV circulation at the time of neonatal discharge. In multivariable analysis, independent predictors of biventricular circulation included left ventricular (LV) long axis z-score (OR 3.2, 95% CI 1.8-5.7, p < 0.001), LV ejection fraction (OR 1.3, 95% CI 1.0-1.8, p = 0.023), anterograde aortic arch flow (OR 5.0, 95% CI 1.2-20.4, p = 0.024), and bidirectional or right-to-left foramen ovale flow (OR 4.6, 95% CI 1.4-15.8, p = 0.015). CONCLUSION: Several anatomic and physiologic parameters in late gestation were found to be independent predictors of BiV circulation after FAV. Identifying these predictors adds to our understanding of LV growth and hemodynamics after FAV and may improve parental counseling.

Toward Improving the Fetal Diagnosis of Coarctation of the Aorta.

Coarctation of the aorta (CoA) is the most common ductal-dependent lesion missed on neonatal exam screening. Prenatal diagnosis of CoA improves outcomes through early initiation of prostaglandin. Fetal echocardiographic parameters including 2D and Doppler findings have been studied as predictive measures for fetal diagnosis of CoA, but diagnosis rates remain variable. A comprehensive set of predictor variables was applied to fetuses suspected of CoA to analyze which parameters were associated with postnatal CoA. UCSF Fetal Cardiovascular Program databases were queried for fetuses suspected of CoA (2008-2014). Retrospective measurements of aorta/pulmonary artery ratio (AoPA), LV/RV ratio, ascending aorta Z-score (AscAo), isthmus Z-score, isthmus/duct ratio (I/D), posterior "shelf" of descending aorta, and diastolic flow persistence at the isthmus were recorded. ROC analysis identified the parameters most predictive of postnatal CoA. Among 97 fetuses with probable CoA, 62 had complete follow-up. Of these fetuses, 45 (72.5%) had postnatal confirmation of CoA and 17 did not have CoA. The parameters most predictive of postnatal CoA included AscAo, isthmus Z-score, and I/D, with respective AUC of 0.80, 0.89, and 0.90. Diastolic flow persistence was seen more often in fetuses with postnatal CoA, but did not reach statistical significance. Combining 2D and Doppler criteria (AoPA < 0.65 or diastolic flow persistence) improved sensitivity to 87%, but introduced several false positives. Isthmus imaging and AoPA ratio are useful predictors of CoA. Doppler information was most helpful when 2D imaging was equivocal; its addition resulted in high sensitivity in an enriched cohort referred for fetal echocardiography.

Safety and efficacy of drug-eluting stents compared with bare metal stents in ST-elevation myocardial infarction.

Drug-eluting stents (DES) reduce restenosis and the need for repeat revascularization, but patients with ST-segment elevation myocardial infarction (STEMI) were excluded from many of the trials that established the safety and efficacy of DES. Because of the unstable nature of lesions associated with STEMI, these patients are considered high risk, and often experience higher rates of adverse events. There is concern that DES may increase the risk of stent thrombosis, particularly late and very late stent thrombosis, in STEMI patients. Evidence also suggests that although DES reduce target vessel revascularization, this benefit may be lost after extended follow-up due to procedures necessitated by increased stent thrombosis. Several randomized trials, meta-analyses, and registry studies have been conducted to compare DES with bare metal stents in patients with STEMI, but many of the studies are not large scale and the length of follow-up has been limited in duration. This review summarizes the data comparing DES with bare metal stents in patients with STEMI.

Synthesis of spiro-1,2-dioxolanes and their activity against Plasmodium falciparum.

Artemisinin-derived compounds play an integral role in current malaria chemotherapy. Given the virtual certainty of emerging resistance, we have investigated spiro-1,2-dioxolanes as an alternative scaffold. The endoperoxide functionality was generated by the SnCl(4)-mediated annulation of a bis-silylperoxide and an alkene. The first set of eight analogs gave EC(50) values of 50-150 nM against Plasmodium falciparum 3D7 and Dd2 strains, except for the carboxylic acid analog. A second series, synthesized by coupling a spiro-1,2-dioxolane carboxylic acid to four separate amines, afforded the most potent compound (EC(50) approximately 5 nM).