The CREATE-ECLA Randomized Controlled TrialThe CREATE-ECLA Trial Group Investigators* See also pp 427 and 489.

Background Left ventricular noncompaction cardiomyopathy ( LVNC ) is a genetically and phenotypically heterogeneous disease. This study aims to investigate the genetic basis and genotype‐phenotype correlations in a cohort of Chinese patients with LVNC . Methods and Results A total of 72 cardiomyopathy‐associated genes were comprehensively screened in 83 adults and 17 children with LVNC by targeted sequencing. Pathogenicity of the detected variants was determined according to their prevalence and American College of Medical Genetics and Genomics recommendations. Baseline and follow‐up clinical data were collected. The primary end point was a composite of death and heart transplantation. Overall, 42 pathogenic variants were identified in 38 patients (38%), with TTN , MYH 7 , MYBPC 3 , and DSP being the most commonly involved genes. At baseline, genotype‐positive adults had higher rates of atrial fibrillation and family history, and lower left ventricular ejection fraction, compared with genotype‐negative adults. During a median follow‐up of 4.2 years, more primary end points occurred in genotype‐positive adults than in genotype‐negative adults (50.0% versus 23.5%; P =0.013). Multivariable analysis demonstrated that genotype‐positive status was associated with higher risks of death and heart transplantation, independent of age, sex, and cardiac function at baseline in patients with LVNC (adjusted hazards ratio, 2.49; 95% confidence interval, 1.15–5.37; P =0.020). Conclusions Our study revealed a distinct genetic spectrum in Chinese patients with LVNC , with variants in TTN , MYH 7 , MYBPC 3 , and DSP being the most common. The presence of pathogenic variants is an independent risk factor for adverse outcomes and may aid in risk stratification in adult patients. Larger studies are needed to confirm these findings.

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Background Intra‐ventricular blood flow dynamics is considered as an important component of left ventricular (LV) function assessment. The purpose of this study was to evaluate the LV diastolic function in chronic kidney disease (CKD) with different degrees of LV diastolic dysfunction (LVDD) by using flow energetic parameters. Methods In this study, a total of 96 cases were recruited, including 58 CKD patients and 38 healthy controls. CKD patients were divided into 2 groups according to LVDD severity, named as DD1 and DD2. Vector flow‐mapping (VFM) analysis was executed to calculate left ventricle average energy loss (EL) during early filling phase (E‐EL_ave), atrial filling phase (A‐EL_ave), diastole phase (D‐EL_ave), and ejection phase (S‐EL_ave). Moreover, the average vortex circulation during early filling phase (E‐cir_ave) and atrial filling phase (A‐cir_ave) was also assessed in the apical three‐chamber view. The rate of average EL during early filling and atrial filling was expressed as E/A‐EL. Result Compared to the control group, A‐EL_ave, S‐EL_ave, and A‐cir_ave in the DD1 group were higher (P < 0.05), and all parameters were obviously higher in the DD2 group (P < 0.05). In the control group and the DD2 subgroup, the E‐EL_ave value was significantly higher than A‐EL_ave value, which was opposite to the DD1 group. As diastolic dysfunction worsened, E‐EL_ave and D‐EL_ave risen gradually (P < 0.05), and A‐EL_ave and S‐EL_ave were slightly elevated with no significance. There were significant correlations between LV diastolic function and flow energetic parameters. Stepwise multiple regression analysis revealed that various LV function parameters could be regarded as independent predictors of average diastolic EL (all P < 0.01). Conclusions For CKD patient with LVDD and LVEF > 50%, effective LV filling and systolic ejection with optimized energy consumption have been impaired. As a new flow‐derived index, EL can quantitatively evaluate LV diastolic function in terms of blood fluid dynamics in CKD with various LVDD.

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Background Titin‐truncating variants (TTNtv) have been recognized as the most prevalent genetic cause of dilated cardiomyopathy. However, their effects on phenotypes of left ventricular non‐compaction cardiomyopathy (LVNC) remain largely unknown. Hypothesis The presence of TTNtv may have an effect on the phenotype of LVNC. Methods TTN was comprehensively screened by targeted sequencing in a cohort of 83 adult patients with LVNC. Baseline and follow‐up data of all participants were collected. The primary endpoint was a composite of death and heart transplantation. The secondary endpoint was heart failure (HF) events, a composite of HF‐related death, heart transplantation, and HF hospitalization. Results Overall, 13 TTNtv were identified in 13 patients, with 9 TTNtv located in the A‐band of titin. There was no significant difference in baseline characteristics between patients with and without TTNtv. During a median follow‐up of 4.4 years, no significant difference in death and heart transplantation between the two groups was observed. However, more HF events occurred in TTNtv carriers than in non‐carriers (P = 0.006). Multivariable analyses showed that TTNtv were associated with an increased risk of HF events independent of sex, age, and baseline cardiac function (hazard ratio: 3.25, 95% confidence interval: 1.50‐7.01, P = 0.003). Sensitivity analysis excluding non‐A‐band TTNtv yielded similar results, but with less strength. Conclusions The presence of TTNtv may be a genetic modifier of LVNC and confer a higher risk of HF events among adult patients. Studies of larger cohorts are needed to confirm our findings.

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Background Inflammation underlies both the pathogenesis and prognosis in patients with acute aortic dissection (AAD). This study aimed to assess the association of ICU admission of white blood cell count (WBCc) with post-discharge mortality in these patients. Methods Clinical data were extracted from the MIMIC-III V1.4 database. After adjusted to covariables, Cox regression analysis and Kaplan–Meier survival curve were performed to determine the relationship between WBCc on admission and post-discharge mortality (30-day, 90-day, 1-year and 5-year) in AAD patients. Subgroup analysis and receiver operating characteristic (ROC) curve analysis were used to test the performance of WBCc in predicting mortality in AAD patients. Results A total of 325 eligible patients were divided into 2 groups: normal-WBCc group (≤ 11 k/uL) and high-WBCc group (> 11 K/uL). In univariate Cox regression analysis, high WBCc was significant risk predictor of 30-day, 90-day, 1-year and 5-year mortality [hazard ratio (HR), 95% CI, P 2.58 1.36–4.91 0.004; 3.16 1.76–5.70 0.000; 2.74 1.57–4.79 0.000; 2.10 1.23–3.54 0.006]. After adjusting for age and other risks, high WBCc remained a significant predictor of 30-day, 90-day and 1-year mortality in AAD patients (HR, 95% CI, P 1.994 1.058–3.76 0.033; 2.118 1.175–3.819 0.013; 2.37 1.343–4.181 0.003). The area under ROC curve of WBCc for predicting 30-day, 90-day, 1-year and 5-year mortality were 0.69, 0.70, 0.66 and 0.61, respectively. The results from subgroups analysis showed that there was no interaction in most strata and patients who were younger than 69 years of age or had history of respiratory disease with an elevated WBCc had an excess risk of 30-day mortality (HR, 95% CI, P 3.18 1.41–7.14 0.005; 3.84 1.05–14.13 0.043). Conclusions Higher than normal WBCc on admission may predict post-discharge mortality in patients with AAD.