Marfan Syndrome beyond Aortic Root-Phenotyping Using Cardiovascular Magnetic Resonance Imaging and Clinical Implications.

Marfan syndrome (MFS) is an inherited autosomal-dominant connective tissue disorder with multiorgan involvement including musculoskeletal, respiratory, cardiovascular, ocular, and skin manifestations. Life expectancy in patients with MFS is primarily determined by the degree of cardiovascular involvement. Aortic disease is the major cardiovascular manifestation of MFS. However, non-aortic cardiac diseases, such as impaired myocardial function and arrhythmia, have been increasingly acknowledged as additional causes of morbidity and mortality. We present two cases demonstrating the phenotypical variation in patients with MFS and how CMR (Cardiovascular Magnetic Resonance) could serve as a "one stop shop" to retrieveS all the necessary information regarding aortic/vascular pathology as well as any potential underlying arrhythmogenic substrate or cardiomyopathic process.

Cardiovascular magnetic resonance for the evaluation of patients with cardiovascular disease: An overview of current indications, limitations, and procedures.

Cardiovascular disease (CVD) is the most common cause of morbidity/mortality worldwide. Early diagnosis is the key to improve CVD prognosis, and cardiovascular imaging plays a crucial role in this direction. Echocardiography is the most commonly used imaging modality. However, the need for early diagnosis/treatment favors the development of modalities providing information about tissue characterization beyond echocardiography. In this context, the rapid evolution of cardiovascular magnetic resonance (CMR) led to the coexistence of cardiologists and radiologists in the CMR field. Our aim was to provide an overview of indications, sequences, and reporting of CMR findings in various CVDs. The indications/limitations of CMR as well as the pathophysiological significance of various sequences in adult/pediatric CVDs are presented and discussed in detail. The role of CMR indices in the evaluation of the most common clinical scenarios in cardiology and their impact on CVD diagnosis/prognosis were analyzed in detail. Additionally, the comparison of CMR versus other imaging modalities is also discussed. Finally, future research directions are presented. CMR can provide cardiac tissue characterization and biventricular/biatrial functional assessment in the same examination, allowing for early and accurate identification of important subclinical abnormalities, before clinically overt CVD takes place.

Cardiovascular Magnetic Resonance Imaging Patterns in Rare Cardiovascular Diseases.

Rare cardiovascular diseases (RCDs) have low incidence but major clinical impact. RCDs' classification includes Class I-systemic circulation, Class II-pulmonary circulation, Class III-cardiomyopathies, Class IV-congenital cardiovascular diseases (CVD), Class V-cardiac tumors and CVD in malignancy, Class VI-cardiac arrhythmogenic disorders, Class VII-CVD in pregnancy, Class VIII-unclassified rare CVD. Cardiovascular Magnetic Resonance (CMR) is useful in the diagnosis/management of RCDs, as it performs angiography, function, perfusion, and tissue characterization in the same examination. Edema expressed as a high signal in STIRT2 or increased T2 mapping is common in acute/active inflammatory states. Diffuse subendocardial fibrosis, expressed as diffuse late gadolinium enhancement (LGE), is characteristic of microvascular disease as in systemic sclerosis, small vessel vasculitis, cardiac amyloidosis, and metabolic disorders. Replacement fibrosis, expressed as LGE, in the inferolateral wall of the left ventricle (LV) is typical of neuromuscular disorders. Patchy LGE with concurrent edema is typical of myocarditis, irrespective of the cause. Cardiac hypertrophy is characteristic in hypertrophic cardiomyopathy (HCM), cardiac amyloidosis (CA) and Anderson-Fabry Disease (AFD), but LGE is located in the IVS, subendocardium and lateral wall in HCM, CA and AFD, respectively. Native T1 mapping is increased in HCM and CA and reduced in AFD. Magnetic resonance angiography provides information on aortopathies, such as Marfan, Turner syndrome and Takayasu vasculitis. LGE in the right ventricle is the typical finding of ARVC, but it may involve LV, leading to the diagnosis of arrhythmogenic cardiomyopathy. Tissue changes in RCDs may be detected only through parametric imaging indices.

Long-Term Impact of Hospitalization for Kawasaki Disease on Health-Related Quality of Life.

OBJECTIVE: To prospectively evaluate the long-term impact of Kawasaki disease (KD) hospitalization on health-related quality of life (HRQoL). METHODS: We merged the Outcomes Assessment Program and KD databases and queried for KD admissions between 1 month and 18 years of age. Patients with a diagnosis of community-acquired pneumonia were included as a comparison group. HRQoL was evaluated with the parent proxy Pediatric Quality of Life Inventory (PedsQL). Long-term follow-up PedsQL surveys were performed at least 1 year after initial diagnosis and hospitalization. Results for the entire cohort adjusted for significant differences were calculated. Propensity score-matched cohorts were constructed from the unmatched cohorts of patients with long-term survey responses. Subgroup analysis for the KD group was performed. RESULTS: Patients with KD (n = 61) versus pneumonia (n = 80) had a lower PedsQL total score on admission and experienced a significantly greater HRQoL decline from baseline to admission. At long-term follow-up, no difference occurred in HRQoL between patients with KD and pneumonia, and 89% of patients with KD reached their baseline PedsQL scores. KD diagnostic subtype, coronary artery dilatation, and need for longer follow-up were not associated with HRQoL outcomes at any time point. Intravenous immunoglobulin nonresponders demonstrated lower HRQoL at admission, which did not persist at follow-up. CONCLUSIONS: Children with KD experience acute and significant HRQoL impairment exceeding that of children with newly diagnosed pneumonia, but the scores return to baseline at long-term follow-up. The recoveries at short- and long-term intervals are similar to patients with pneumonia.

The Deconditioning Effect of the COVID-19 Pandemic on Unaffected Healthy Children.

The COVID-19 pandemic has had devastating direct consequences on the health of affected patients. It has also had a significant impact on the ability of unaffected children to be physically active. We evaluated the effect of deconditioning from social distancing and school shutdowns implemented during the COVID-19 pandemic on the cardiovascular fitness of healthy unaffected children. This is a single-center, retrospective case-control study performed in an urban tertiary referral center. A cohort of 10 healthy children that underwent cardiopulmonary exercise testing after COVID-19 hospital restrictions were lifted was compared to a matched cohort before COVID-19-related shutdowns on school and after-school activities. Comparisons of oxygen uptake (VO2) max and VO2 at anaerobic threshold between the pre- and post-COVID-19 cohorts were done. The VO2 max in the post-COVID cohort was significantly lower than in the pre-COVID cohort (39.1 vs. 44.7, p = 0.031). Only one out of ten patients had a higher VO2 max when compared to their matched pre-COVID control and was also the only patient with a documented history of participation in varsity-type athletics. The percentile of predicted VO2 was significantly lower in the post-COVID cohort (95% vs. 105%, p = 0.042). This study for the first time documented a significant measurable decline in physical fitness of healthy children as a result of the COVID-19 pandemic and its associated restrictions. Measures need to be identified that encourage and facilitate regular exercise in children in a way that are not solely dependent on school and organized after-school activities.

A Quality Initiative to Improve Appropriate Use of Initial Outpatient Echocardiography Among Pediatric Cardiologists.

INTRODUCTION: Appropriate use criteria (AUC) guide initial transthoracic echocardiogram (TTE) use in outpatient pediatrics. We sought to improve pediatric cardiologist TTE ordering appropriateness (mean AUC score) with a quality improvement initiative. METHODS: The outcome of interest was the prospective AUC score for all initial outpatient TTEs ordered between November 2016 and August 2017, categorized per the AUC: "appropriate" (score 7-9), "may be appropriate" (4-6), "rarely appropriate" (1-3). Interventions included a didactic review of 2014 AUC and participant documentation of AUC criteria for each TTE. Participants met quarterly to evaluate outcome, process, and balancing measures, intervention effectiveness, and to identify and mitigate barriers. RESULTS: Twenty-two pediatric cardiologists participated. TTE appropriateness level before (n = 216) and after (n = 557) intervention was high. There was no significant difference in mean baseline and post-intervention AUC score (7.42 ± 1.87 versus 7.16 ± 2.87, P = 0.1), nor in TTE sensitivity (27% versus 25%, P > 0.1) as a balancing measure. Among baseline studies, 81% were "appropriate," and 6% "rarely appropriate." Among post-intervention studies, 76% were "appropriate," and 11% "rarely appropriate." Barriers identified to implementing AUC include TTE indications not specified by current AUC, expectations of referring provider or parent to perform TTE, consistent provider application of AUC, and ability of AUC to capture comprehensive clinical judgment. CONCLUSIONS: Although the mean AUC appropriateness level was high, we were able to identify significant barriers to the implementation of AUC. Future efforts should focus on the reduction of "rarely appropriate" TTE ordering.

mDixon ECG-gated 3-dimensional cardiovascular magnetic resonance angiography in patients with congenital cardiovascular disease.

BACKGROUND: Cardiovascular magnetic resonance (CMR) angiography (CMRA) is an important non-invasive imaging tool for congenital heart disease (CHD) and aortopathy patients. The conventional 3D balanced steady-state free precession (bSSFP) sequence is often confounded by imaging artifacts. We sought to compare the respiratory navigated and electrocardiogram (ECG) gated modified Dixon (mDixon) CMRA sequence to conventional non-gated dynamic multi-phase contrast enhanced CMRA (CE-CMRA) and bSSFP across a variety of diagnoses. METHODS: We included 24 patients with CHD or aortopathy with CMR performed between September 2017 to December 2017. Each patient had undergone CE-CMRA, followed by a bSSFP and mDixon angiogram. Patients with CMR-incompatible implants or contraindications to contrast were excluded. The studies were rated according to image quality at a scale from 1 (poor) to 4 (excellent) based on diagnostic adequacy, artifact burden, vascular border delineation, myocardium-blood pool contrast, and visualization of pulmonary and systemic veins and coronaries. Contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR) and quantitative vascular measurements were compared between the two gated sequences. Bland-Altman plots were generated to compare paired measures. RESULTS: All scans were diagnostically adequate. Mean (SD) quality scores were 3.4 (0.7) for the mDixon, 3.2 (0.5) for the bSSFP and 3.4 (0.5) for the CE-CMRA. Qualitatively, the intracardiac anatomy and myocardium-blood pool definition were better in the bSSFP; however, mDixon images showed enhanced vessel wall sharpness with less blurring surrounding the anatomical borders distally. Coronary origins were identified in all cases. Pulmonary veins were visualized in 92% of mDixon sequences, 75% of bSSFP and 96% of CE-CMRA. Similarly, neck veins were identified in 92, 83 and 96% respectively. Artifacts prevented vascular measurement in 6/192 (3%) and 4/192 (2%) of total vascular measurements for the mDixon and bSSFP, respectively. However, the size of signal void and field distortion were significantly worse in the latter, particularly for flow and metal induced artifacts. CONCLUSION: In patients with congenital heart disease, ECG gated mDixon angiography yields high fidelity vascular images including better delineation of head and neck vasculature and pulmonary veins and fewer artifacts than the comparable bSSFP sequence. It should be considered as the preferred strategy for successful CHD imaging in patients with valve stenosis, vascular stents, or metallic implants.

Three-dimensional printing and virtual surgery for congenital heart procedural planning.

Complex unrepaired congenital heart disease requires extensive planning to determine the optimal procedural approach. Conventional noninvasive diagnostic imaging initially provides only two-dimensional (2D) representations of the complex, three-dimensional cardiovascular anatomy. With the expansion of 3D visualization techniques in imaging, a paradigm shift has occurred in complex congenital heart disease surgical planning using digital and 3D printed heart models. There has been early success in demonstrating the benefit of these models in interdisciplinary communication and education. The future goal of this work is to demonstrate a clinical outcome benefit using digital and 3D printed models to plan both surgical and catheterization-based interventional procedures. Ultimately, the hope is that advanced procedural planning with virtual surgery and 3D printing will enhance decision-making in complex congenital heart disease cases resulting in improved perioperative performance by reducing operative times, complications, and reoperations.

Kawasaki Disease Substantially Impacts Health-Related Quality of Life.

OBJECTIVE: To prospectively evaluate the acute impact of Kawasaki disease (KD) on health-related quality of life (HRQoL) and to assess deterioration in the HRQoL experienced by children with KD compared with other childhood diseases. STUDY DESIGN: We merged the Outcomes Assessment Program database obtained prospectively with the existing KD database and queried for KD admissions between 1 month and 13 years of age. HRQoL was evaluated with the parent-proxy Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core and Infant Scales. We compared the KD HRQoL results with those obtained from newly diagnosed patients with cancer and pneumonia, matched for age, sex and race. PedsQL total scores over time were assessed with ANCOVA models, adjusted for matching variables and PedsQL score prior to admission. RESULTS: We identified 89 patients with KD and compared 65 subjects with an equal number with pneumonia and with 67 subjects with newly diagnosed cancer. Patients with demonstrated lower PedsQL total score on admission and suffered a significantly greater HRQoL decline from baseline to admission than the other groups. KD diagnostic subtype (complete or incomplete) and coronary artery dilatation were not associated with HRQoL outcomes. However, non-intravenous immunoglobulin responders showed greater HRQoL decline than responders (P = .03). CONCLUSIONS: Children with KD suffer acute and significant HRQoL impairment exceeding that of children newly diagnosed with cancer. Lack of immediate treatment response may exert an additional HRQoL burden, whereas KD subtype and coronary artery dilatation do not.

Pediatric Appropriate Use Criteria for Outpatient Echocardiography: Practice Variations among Pediatric Cardiologists, Noncardiologist Subspecialists, and Primary Care Providers.

BACKGROUND: The first pediatric appropriate use criteria (AUC) address the use of initial transthoracic echocardiography in outpatients by all ordering providers. The aim of this study was to appraise the performance of the AUC across pediatric cardiologists, noncardiologist subspecialists, and primary care providers (PCPs). A further aim was to describe the variations in ordering patterns of different groups of practitioners, which could serve as the basis for targeted quality improvement activities. METHODS: Electronic health records for Seattle Children's Hospital and its four regional sites were retrospectively reviewed for initial transthoracic echocardiographic studies performed on patients aged ≤18 years. A sample of 1,000 consecutive studies and a sample of 1,514 studies in which studies ordered by noncardiologists were enriched were reviewed. The ordering provider type, study indication, and findings (normal, incidental, or abnormal) were classified. Indications mapped to three categories: appropriate (A), may be appropriate (M), and rarely appropriate (R). If multiple indications were documented, the highest level of appropriateness was used. RESULTS: In the consecutive sample, pediatric cardiologists ordered 81%, noncardiologist subspecialists 13%, and PCPs 5% of the total studies. In the enriched sample, only 4% were unclassifiable by the AUC. Abnormal findings were identified in 23% of A, 13% of M, and 9% of R studies (P = .03). Appropriateness varied among the three groups of providers (P < .001). For pediatric cardiologists, 67% of studies were indication category A, 13% M, and 14% R. Noncardiologist subspecialists ordered the highest percentage of A studies (88%) and the lowest percentage of R studies (1%). PCPs had the highest percentage of R indications (18%), and 23% could not be fully classified, because of insufficient order information. Yield of abnormal findings was highest for subspecialists (23%), intermediate for cardiologists (19%), and lowest for PCPs (15%; P = .03). CONCLUSIONS: The AUC performed well across all provider types, as measured by the low percentage of unclassifiable indications and the observed relationship between greater appropriateness and higher yield of abnormal findings. The three provider types differed in appropriateness rates and had distinct ordering patterns, which could form the basis for future targeted quality improvement efforts.

Inotropic agents improve the peripheral microcirculation of patients with end-stage chronic heart failure.

BACKGROUND: Skeletal muscle microcirculation impairment in patients with chronic heart failure (CHF) seems to correlate with disease severity. We evaluated the microcirculation by near-infrared spectroscopy (NIRS) occlusion technique before and after inotropic infusion. METHODS: We evaluated 25 patients with stable CHF, 30 patients with end-stage CHF (ESCHF) receiving treatment with intermittent infusion of inotropic agents, and 12 healthy subjects. Thenar muscle tissue oxygen saturation (StO(2)%) was measured noninvasively by NIRS before, during, and after 3-minute occlusion of the brachial artery (occlusion technique) in all subjects and in patients with ESCHF before and after 6 hours of inotropic infusion (dobutamine and/or levosimendan) or placebo (N = 5). RESULTS: Patients with ESCHF or CHF presented significantly lower StO(2)% than healthy subjects (74.5% +/- 7%, 78.6% +/- 6%, and 85% +/- 5%, respectively; P = .0001), lower oxygen consumption rate during occlusion (24.6% +/- 8%/min, 28.6% +/- 10%/min, and 38.1% +/- 11.1%/min, respectively; P = .001), and lower reperfusion rate (327% +/- 141%/min, 410% +/- 106%/min, and 480% +/- 133%/min, respectively; P = .002). After 6 hours of inotropic infusion, patients with ESCHF showed significantly increased StO(2)% (74.5% +/- 7% to 82% +/- 9%, P = .001), oxygen consumption rate (24.6% +/- 8%/min to 29.3% +/- 8%/min, P = .009), and reperfusion rate (327% +/- 141%/min to 467% +/- 151%/min, P = .001). No statistical difference was noted in the placebo group. CONCLUSION: Peripheral muscle microcirculation as assessed by NIRS is impaired in patients with CHF. This impairment is partially reversed by infusion of inotropic agents in patients with ESCHF.