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Objectives: We aimed to identify the major determinants of cardiac troponin changes response to exercise among non-elite runners participating in the Beijing 2022 marathon, with a particular focus on the associations with the cardiac function assessed by tissue Doppler echocardiography and speckle tracking., Design: A prospective study., Methods: A total of 33 non-elite participants in the 2022 Beijing Marathon were included in the study. Echocardiographic assessment and blood sample collection were conducted before, immediately after, and two weeks after the marathon. Blood samples were analyzed using the same Abbot high-sensitivity cTnI STAT assay. Echocardiography included tissue Doppler and speckle tracking echocardiography., Results: Following the marathon, significant increases were observed in cardiac biomarkers, with hs-cTnI elevating from 3.1 [2.3-6.7] to 49.6 [32.5-76.9] ng/L (P < 0.0001). Over 72 % of participants had post-race hs-TnI levels surpassing the 99th percentile upper reference limit. There was a notable correlation between pre-marathon hs-cTnI levels (β coefficient, 0.56 [0.05, 1.07]; P = 0.042), weekly average training (β coefficient, -1.15 [-1.95, -0.35]; P = 0.009), and hs-cTnI rise post-marathon. Echocardiography revealed significant post-race cardiac function changes, including decreased E/A ratio (P < 0.0001), GWI (P < 0.0001), and GCW (P < 0.0001), with LVEF (β coefficients, 0.112 [0.01, 0.21]; P = 0.042) and RV GLS (β coefficients, 0.124 [0.01, 0.23]; P = 0.035) changes significantly associated with hs-TnI alterations. All echocardiographic and laboratory indicators reverted to baseline levels within two weeks., Conclusions: Baseline hs-cTnI levels and weekly average training influence exercise-induced hs-cTnI elevation in non-elite runners. Echocardiography revealed post-race changes in cardiac function, with LVEF and RV GLS significantly associated with hs-TnI alterations. These findings contribute to understanding the cardiac response to exercise and could guide training and recovery strategies., Competing Interests: Declaration of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fang Wang reports that financial support was provided by Ministry of Science and Technology of the People's Republic of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

LCZ696, an angiotensin receptor-neprilysin inhibitor, has shown promising clinical efficacy in patients with heart failure (HF) with reduced ejection fraction. However, its potential effects on heart failure with preserved ejection fraction (HFpEF) are still not fully understood. We evaluated the effect of LCZ696 on HFpEF in transverse aortic constriction mice and compared it with the effect of the angiotensin receptor blocker, valsartan. We found that LCZ696 improved cardiac diastolic function by reducing ventricular hypertrophy and fibrosis in mice with overload-induced diastolic dysfunction. In addition, there was superior inhibition of LCZ696 than stand-alone valsartan. As a potential underlying mechanism, we demonstrated that LCZ696 behaves as a potent suppressor of calcium-mediated calcineurin-nuclear factor of activated T cells (NFAT) signalling transduction pathways. Hence, we demonstrated the protective effects of LCZ696 in overload-induced HFpEF and provided a pharmaceutical therapeutic strategy for related diseases., (© 2022 John Wiley & Sons Australia, Ltd.)

Background: Ventricular interdependence may account for altered ventricular mechanics in congenital heart disease. The present study aimed to identify differences in load-dependent right ventricular (RV)-left ventricular (LV) interactions in porcine models of pulmonary stenosis (PS) and pulmonary insufficiency (PI) by invasive admittance-derived hemodynamics in conjunction with noninvasive cardiovascular magnetic resonance (CMR)., Methods: Seventeen pigs were used in the study (7 with PS, 7 with PI, and 3 controls). Progressive PS was created by tightening a Teflon tape around the pulmonary artery, and PI was created by excising 2 leaflets of the pulmonary valve. Admittance catheterization data were obtained for the RV and LV at 10 to 12 weeks after model creation, with the animal ventilated under temporary diaphragm paralysis. CMR was performed in all animals immediately prior to pressure-volume catheterization., Results: In the PS group, RV contractility was increased, manifested by increased end-systolic elastance (mean difference, 1.29 mm Hg/mL; 95% confidence interval [CI], 0.57-2.00 mm Hg/mL). However, in the PI group, no significant changes were observed in RV systolic function despite significant changes in RV diastolic function. In the PS group, LV end-systolic volume was significantly lower compared with controls (mean difference, 25.1 mL; 95% CI, -40.5 to -90.7 mL), whereas in the PI group, the LV showed diastolic dysfunction, demonstrated by an elevated isovolumic relaxation constant and ventricular stiffness (mean difference, 0.03 mL -1 ; 95% CI, -0.02 to 0.09 mL -1 )., Conclusions: The LV exhibits systolic dysfunction and noncompliance with PI. PS is associated with preserved LV systolic function and evidence of some LV diastolic dysfunction. Interventricular interactions influence LV filling and likely account for differential effects of RV pressure and volume overload on LV function., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Obesity and dyslipidemias are both signs of metabolic syndrome, usually associated with ventricular arrhythmias. Here, we tried to identify cardiac electrical alteration and biomarkers in nonobese rats with metabolic syndrome (MetS), and these findings might lead to more lethal arrhythmias than obese animals. The MetS model was developed in Wistar rats with high-sucrose diet (20%), and after twenty-eight weeks were obtained two subgroups: obese (OMetS) and nonobese (NOMetS). The electrocardiogram was used to measure the ventricular arrhythmias and changes in the heart rate variability. Also, we measured ventricular hypertrophy and its relationship with electrical activity alterations of both ventricles, using micro-electrode and voltage clamp techniques. Also, we observed alterations in the contraction force of ventricles where a transducer was used to record mechanical and electrical papillary muscle, simultaneously. Despite both subgroups presenting long QT syndrome (0.66 ± 0.05 and 0.66 ± 0.07 ms with respect to the control 0.55 ± 0.1 ms), the changes in the heart rate variability were present only in OMetS, while the NOMetS subgroup presented changes in QT interval variability (NOMetS SD = 1.8, SD2 = 2.8; SD1/SD2 = 0.75). Also, the NOMetS revealed tachycardia (10%; p < 0.05) with changes in action potential duration (63% in the right papillary and 50% in the left papillary) in the ventricular papillary which are correlated with certain alterations in the potassium currents and the force of contraction. The OMetS showed an increase in action potential duration and the force of contraction in both ventricles, which are explained as bradycardia. Our results revealed lethal arrhythmias in both MetS subgroups, irrespectively of the presence of obesity. Consequently, the NOMetS showed mechanical-electrical alterations regarding ventricle hypertrophy that should be at the NOMetS, leading to an increase of CV mortality., Competing Interests: The authors declare no competing interests., (Copyright © 2022 Julian Torres-Jacome et al.)

Many Fontan patients with and without systolic ventricular dysfunction are being treated with angiotensin-converting enzyme (ACE) inhibitors, despite its effectiveness remaining unclear. In the present study, we evaluated the short-term effect of enalapril on exercise capacity, vascular and ventricular function in pediatric Fontan patients with moderate-good systolic ventricular function. Fontan patients between 8 and 18 years with moderate-good systolic ventricular function and without previous ACE inhibitor treatment were included and were treated with enalapril for 3 months. During the first 2 weeks, the dosage was titrated according to systolic blood pressure (SBP). Exercise tests, ventricular function assessed by echocardiography, arterial stiffness measurements, and plasma levels of N-terminal pro-B-type natriuretic peptide assessed before and after a 3-month enalapril treatment period was compared. A total of 28 Fontan patients (median age 13.9 years, 6 to 15 years after Fontan operation) completed the study with a mean dosage of 0.3 ± 0.1 mg/kg/d. A total of 6 patients (21%) experienced a significant drop in SBP and 6 others (21%) experienced other adverse events. Enalapril treatment lowered the SBP (from 110 to 104 mmHg, p = 0.003) and levels of N-terminal pro-B-type natriuretic peptide (from 80 to 72 ng/L, p = 0.036). However, enalapril treatment did not improve exercise capacity, ventricular function, or arterial stiffness. In conclusion, short-term ACE inhibition has no beneficial effect in Fontan patients with moderate-good systolic ventricular function., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to prospectively examine cardiac structure and function in the kainic acid-induced post-status epilepticus (post-KA SE) model of chronic acquired temporal lobe epilepsy (TLE), specifically to examine for changes between the pre-epileptic, early epileptogenesis and the chronic epilepsy stages. We also aimed to examine whether any changes related to the seizure frequency in individual animals., Methods: Four hours of SE was induced in 9 male Wistar rats at 10 weeks of age, with 8 saline treated matched control rats. Echocardiography was performed prior to the induction of SE, two- and 10-weeks post-SE. Two weeks of continuous video-EEG and simultaneous ECG recordings were acquired for two weeks from 11 weeks post-KA SE. The video-EEG recordings were analyzed blindly to quantify the number and severity of spontaneous seizures, and the ECG recordings analyzed for measures of heart rate variability (HRV). PicroSirius red histology was performed to assess cardiac fibrosis, and intracellular Ca 2+ levels and cell contractility were measured by microfluorimetry., Results: All 9 post-KA SE rats were demonstrated to have spontaneous recurrent seizures on the two-week video-EEG recording acquired from 11 weeks SE (seizure frequency ranging from 0.3 to 10.6 seizures/day with the seizure durations from 11 to 62 s), and none of the 8 control rats. Left ventricular wall thickness was thinner, left ventricular internal dimension was shorter, and ejection fraction was significantly decreased in chronically epileptic rats, and was negatively correlated to seizure frequency in individual rats. Diastolic dysfunction was evident in chronically epileptic rats by a decrease in mitral valve deceleration time and an increase in E/E` ratio. Measures of HRV were reduced in the chronically epileptic rats, indicating abnormalities of cardiac autonomic function. Cardiac fibrosis was significantly increased in epileptic rats, positively correlated to seizure frequency, and negatively correlated to ejection fraction. The cardiac fibrosis was not a consequence of direct effect of KA toxicity, as it was not seen in the 6/10 rats from separate cohort that received similar doses of KA but did not go into SE. Cardiomyocyte length, width, volume, and rate of cell lengthening and shortening were significantly reduced in epileptic rats., Significance: The results from this study demonstrate that chronic epilepsy in the post-KA SE rat model of TLE is associated with a progressive deterioration in cardiac structure and function, with a restrictive cardiomyopathy associated with myocardial fibrosis. Positive correlations between seizure frequency and the severity of the cardiac changes were identified. These results provide new insights into the pathophysiology of cardiac disease in chronic epilepsy, and may have relevance for the heterogeneous mechanisms that place these people at risk of sudden unexplained death., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The clinical relevance of genetic variants in nonischemic dilated cardiomyopathy (DCM) is unsettled., Objectives: The study sought to assess the prognostic impact of disease-causing genetic variants in DCM., Methods: Baseline and longitudinal clinical data from 1,005 genotyped DCM probands were retrospectively collected at 20 centers. A total of 372 (37%) patients had pathogenic or likely pathogenic variants (genotype positive) and 633 (63%) were genotype negative. The primary endpoint was a composite of major adverse cardiovascular events. Secondary endpoints were end-stage heart failure (ESHF), malignant ventricular arrhythmia (MVA), and left ventricular reverse remodeling (LVRR)., Results: After a median follow-up of 4.04 years (interquartile range: 1.70-7.50 years), the primary endpoint had occurred in 118 (31.7%) patients in the genotype-positive group and in 125 (19.8%) patients in the genotype-negative group (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: 1.17-1.94; P = 0.001). ESHF occurred in 60 (16.1%) genotype-positive patients and in 55 (8.7%) genotype-negative patients (HR: 1.67; 95% CI: 1.16-2.41; P = 0.006). MVA occurred in 73 (19.6%) genotype-positive patients and in 77 (12.2%) genotype-negative patients (HR: 1.50; 95% CI: 1.09-2.07; P = 0.013). LVRR occurred in 39.6% in the genotype-positive group and in 46.2% in the genotype-negative group (P = 0.047). Among individuals with baseline left ventricular ejection fraction ≤35%, genotype-positive patients exhibited more major adverse cardiovascular events, ESHF, and MVA than their genotype-negative peers (all P < 0.02). LVRR and clinical outcomes varied depending on the underlying affected gene., Conclusions: In this study, DCM patients with pathogenic or likely pathogenic variants had worse prognosis than genotype-negative individuals. Clinical course differed depending on the underlying affected gene., Competing Interests: Funding Support and Author Disclosures This work was supported by grants from the following institutions: the Instituto de Salud Carlos III (AC16/0014, PI18/0004, PI20/0320) and the European Union (GENPROVIC project from ERA-CVD framework). The Hospital Universitario Puerta de Hierro and the Hospital Universitario Virgen de la Arrixaca are members of the European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (ERN GUARD-Heart). All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background The association of cardiac wall motion abnormalities (CWMAs) in patients with stroke who have major adverse cardiovascular events (MACE) remains unclear. The purpose of this study was to estimate the 50-month risk of MACE, including stroke recurrence, acute coronary events, and vascular death in patients with stroke who have CWMAs. Methods and Results We performed a retrospective analysis of prospectively collected acute stroke data (acute stroke and transient ischemic attack) over 50 months by electronic medical records. Data included demographic and clinical information, vascular imaging, and echocardiography data including CWMAs and MACE. Of a total of 2653 patients with acute stroke/transient ischemic attack, CWMA was observed in 355 (13.4%). In patients with CWMAs, the embolic stroke of undetermined source (50.7%) was the most frequent index stroke subtype and stroke recurrences ( P =0.001). In multivariate Cox regression after adjustment for demographics, traditional risk, and confounding factors, CWMA was independently associated with a higher risk of MACE (adjusted hazard ratio [HR], 1.74; 95% CI, 1.37-2.21 [ P =0.001]). Similarly, CWMA independently conferred an increased risk for ischemic stroke recurrence (adjusted HR, 1.50; 95% CI, 1.01-2.17 [ P =0.04]), risk of acute coronary events (aHR, 2.50; 95% CI, 1.83-3.40 [ P =0.001]) and vascular death (adjusted HR, 1.57; 95% CI, 1.04-2.40 [ P =0.03]), in comparison to the patients with stroke without CWMA. Conclusions In a multiethnic cohort of ischemic stroke with CWMA, CWMA was associated with 1.7-fold higher risks of MACE independent of established risk factors. Embolic stroke of undetermined source was the most common stroke association with CWMA. Patients with stroke should be screened for CWMA to identify those at higher risk of MACE.

Purpose: SARS-COV-2 infection can develop into a multi-organ disease. Although pathophysiological mechanisms of COVID-19-associated myocardial injury have been studied throughout the pandemic course in 2019, its morphological characterisation is still unclear. With this study, we aimed to characterise echocardiographic patterns of ventricular function in patients with COVID-19-associated myocardial injury., Methods: We prospectively assessed 32 patients hospitalised with COVID-19 and presence or absence of elevated high sensitive troponin T (hsTNT+ vs. hsTNT-) by comprehensive three-dimensional (3D) and strain echocardiography., Results: A minority (34.3%) of patients had normal ventricular function, whereas 65.7% had left and/or right ventricular dysfunction defined by impaired left and/or right ventricular ejection fraction and strain measurements. Concomitant biventricular dysfunction was common in hsTNT+ patients. We observed impaired left ventricular (LV) global longitudinal strain (GLS) in patients with myocardial injury (-13.9% vs. -17.7% for hsTNT+ vs. hsTNT-, p = 0.005) but preserved LV ejection fraction (52% vs. 59%, p = 0.074). Further, in these patients, right ventricular (RV) systolic function was impaired with lower RV ejection fraction (40% vs. 49%, p = 0.001) and reduced RV free wall strain (-18.5% vs. -28.3%, p = 0.003). Myocardial dysfunction partially recovered in hsTNT + patients after 52 days of follow-up. In particular, LV-GLS and RV-FWS significantly improved from baseline to follow-up (LV-GLS: -13.9% to -16.5%, p = 0.013; RV-FWS: -18.5% to -22.3%, p = 0.037)., Conclusion: In patients with COVID-19-associated myocardial injury, comprehensive 3D and strain echocardiography revealed LV dysfunction by GLS and RV dysfunction, which partially resolved at 2-month follow-up., Trial Registration: COVID-19 Registry of the LMU University Hospital Munich (CORKUM), WHO trial ID DRKS00021225.

Background: Computed Tomography (CT) Pulmonary Angiography is the most commonly used diagnostic study for acute pulmonary embolism (PE). Echocardiogram (ECHO) is also used for risk stratification in acute PE, however the diagnostic performance of CT versus ECHO for risk stratification remains unclear., Methods: CT and ECHO right ventricle (RV) and left ventricle (LV) diameters were measured in a retrospective cohort of patients with acute PE. RV:LV diameter ratios were calculated and correlation between CT and ECHO RV:LV ratio was assessed. Sensitivity and specificity for the composite adverse events endpoint of mortality, respiratory failure requiring intubation, cardiac arrest, or shock requiring vasopressors within 30 days of admission were assessed for CT or ECHO derived RV:LV ratio alone and in combination with biomarkers (troponin or B-type natriuretic peptide)., Results: A total of 74 subjects met the inclusion criteria and had a mean age of 62±18 years. The proportion of patients with RV:LV >1 was similar when comparing CT (37.8%) versus ECHO (33.8%) (P = 0.61). A statistically significant correlation was found between CT derived and ECHO derived RV:LV diameter ratio (r = 0.832, P < 0.001). The sensitivity and specificity to predict 30-day composite adverse events for CT versus ECHO derived RV:LV diameter ratio >1 together with positive biomarker status was similar with sensitivity and specificity of 87% and 41% versus 87% and 42%, respectively., Conclusions: In patients with acute PE, CT and ECHO RV:LV diameter ratio correlate well and identify similar proportion of PE patients at risk for early adverse events. These findings may streamline risk stratification of patients with acute PE., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Diastolic dysfunction is a common finding in patients receiving cancer therapy. This study evaluated the correlation of diastolic strain slope (Dss) with routine echocardiography diastolic parameters and its role in early detection of systolic dysfunction and cardiovascular (CV) mortality within this population., Methods: Data were collected from the Israel Cardio-Oncology Registry (ICOR), a prospective registry enrolling adult patient receiving cancer therapy. All patients performed at least three echocardiography exams (T1, T2, T3), including left ventricle Global Longitudinal Strain (LV GLS) and Dss. Systolic dysfunction was determined by either LV GLS relative reduction of ≥ 15% or LV ejection fraction reduction > 10% to < 53%. Dss was assessed as the early lengthening rate, measured by the diastolic slope (delta%/sec)., Results: Among 144 patients, 114 (79.2%) were female with a mean age of 57.31 ± 14.3 years. Dss was significantly correlated with e' average. Mid segment Dss change between T1 and T2 showed significant association to systolic dysfunction development (Odds Ratio (OR) = 1.04 [1.01,1.06]. p = 0.036). In multivariate prediction, Dss increase was a significant predictor for the development of systolic dysfunction (OR = 1.06 [1.03,1.1], P < 0.001).An 8% increase in Dss between T1 and T2 was associated with a trend in increased CV mortality (HR = 3.4 [0.77,15.4], p = 0.085)., Conclusions: This study is the first to use the novel measurement of Dss in patients treated with cancer therapies and to show significant correlation between routine diastolic dysfunction parameters and Dss. Changes in the mid segment were found to have significant independent early predictive value for systolic dysfunction development in univariate and multivariate analyses.

The aim of this study is assessment of importance of use of the modified myocardial performance index (Mod-MPI) for the evaluation of foetal cardiac function in foetuses of women with pregestational diabetes mellitus (PDM). In this study, data of 30 pregnant patients aged 18-45 years diagnosed with PDM and 30 pregnant women aged 18-45 years with normal pregnancy and their babies were evaluated. Foetal echocardiographic and doppler measurements, foetal biometric measurements, umbilical artery and ductus venosus pulsatility indexes were measured in both PDM and control groups. The Mod-MPI was significantly higher in foetuses of PDM women. Many influences especially cardiac and postpartum complications are observed in infants of PDM women. The Mod-MPI is a simple and useful method for assessing foetal ventricular function. Our study has shown that PDM is associated with foetal ventricular dysfunction.Impact statement What is already known on this subject? Although MPI is frequently used in routine clinical assessment of neonates, it is not used adequately in foetuses. Many influences especially cardiac and postpartum complications are observed in infants of PDM women. However, there are few studies focussed specifically on the assessment of foetal cardiac function in PDM. What do the results of this study add? MPI, which shows both diastolic and systolic functions is independent of ventricular anatomy and foetal heart rate, was found significantly higher in diabetic mother foetuses, can be said to be a valuable parameter in evaluating foetal cardiac functions globally. What are the implications of these findings for clinical practice and/or further research? Our study has shown that foetuses PDM are associated with foetal ventricular dysfunction. For this MPI measurement can be routinely performed at foetal cardiac measurements in foetuses of PDM mothers.

Trauma remains a leading global cause of mortality, particularly in the young population. In the United States, approximately 30,000 patients with blunt cardiac trauma were recorded annually. Cardiac damage is a predictor for poor outcome after multiple trauma, with a poor prognosis and prolonged in-hospitalization. Systemic elevation of cardiac troponins was correlated with survival, injury severity score, and catecholamine consumption of patients after multiple trauma. The clinical features of the so-called "commotio cordis" are dysrhythmias, including ventricular fibrillation and sudden cardiac arrest as well as wall motion disorders. In trauma patients with inappropriate hypotension and inadequate response to fluid resuscitation, cardiac injury should be considered. Therefore, a combination of echocardiography (ECG) measurements, echocardiography, and systemic appearance of cardiomyocyte damage markers such as troponin appears to be an appropriate diagnostic approach to detect cardiac dysfunction after trauma. However, the mechanisms of post-traumatic cardiac dysfunction are still actively being investigated. This review aims to discuss cardiac damage following trauma, focusing on mechanisms of post-traumatic cardiac dysfunction associated with inflammation and complement activation. Herein, a causal relationship of cardiac dysfunction to traumatic brain injury, blunt chest trauma, multiple trauma, burn injury, psychosocial stress, fracture, and hemorrhagic shock are illustrated and therapeutic options are discussed.

Second heart sound (S2) splitting results from nonsimultaneous closures between aortic (A2) and pulmonic valves (P2) and may be used to detect timing differences (dyssynchrony) in relaxation between right (RV) and left ventricle (LV). However, overlap of A2 and P2 and the change in heart sound morphologies have complicated detection of the S2 splitting interval. This study introduces a novel S-transform amplitude ridge tracking (START) algorithm for estimating S2 splitting interval and investigates the relationship between S2 splitting and interventricular relaxation dyssynchrony (IRD). First, the START algorithm was validated in a simulated model of heart sound. It showed small errors (<5 ms) in estimating splitting intervals from 10 to 70 ms, with A2/P2 amplitude ratios from 0.2 to 5, and signal-to-noise ratios from 10 to 30 dB. Subsequently, the START algorithm was evaluated in a porcine model employing a wide range of paced RV-LV delays. IRD was quantified by the time difference between invasively measured LV and RV pressure downslopes. Between LV pre-excitation to RV pre-excitation, mean S2 splitting interval decreased from 47 ms to 23 ms (p < .001), accompanied by a decrease in mean IRD from 8 ms to -18 ms (p < .001). S2 splitting interval was significantly correlated with IRD in each experiment (p < .001). In conclusion, the START algorithm can accurately assess S2 splitting and may serve as a useful tool to assess interventricular dyssynchrony., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder that initially affects the kidney progressing to multi-organ failure due to accumulation of cystine in all tissue compartments., Objective: The main objective of this study is the evaluation of cardiac function in cystinosis patients using non-conventional echocardiographic modalities like pulsed wave tissue Doppler imaging (PW-TDI) and 2D speckle tracking echocardiography (2D-STE)., Methods: This is a case control study conducted on fifteen patients with cystinosis and 15 normal controls. Echocardiography was done for all participants and PW-TDI was performed for measurement of S', E', A' velocities and myocardial performance index (MPI) at basal parts of septal, left ventricle (LV), and right ventricle (RV) free walls. 2D-STE was done for evaluation of global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) of LV. Mitral E and A velocities and tricuspid annular plane systolic excursion (TAPSE) were also measured., Results: The GLS, GRS, and S' velocity at basal septum and LV lateral wall were significantly lower in patients denoting LV systolic dysfunction (p = 0.005, p < 0.0001, p = 0.001, p = 0.006, respectively), while E/E' were significantly higher in patients group denoting LV diastolic dysfunction (p < 0.001). For RV function, TAPSE, S', and E' velocity were significantly lower in patients group (p 0.013, p < 0.01, p = 0.05, respectively) indicating RV systolic and diastolic dysfunction. The TDI-derived MPI for both LV and RV were significantly higher in patients group (p < 0.0001, p < 0.01, respectively) indicating both ventricular systolic and diastolic dysfunction. For prediction of cardiac dysfunction among patients, the receiver operating characteristic (ROC) curve showed that GRS ≤ 29% had sensitivity 93.3% and specificity 100%, GLS > - 20.1% had sensitivity 66.7% and specificity 93.3%, LV-E/E' >7.87 had sensitivity 73.3% and specificity 93.3%, and MPI-LV > 0.36 had sensitivity 100% and specificity 93.3% while MPI-RV > 0.29 had sensitivity 80% and specificity 93.3% and TAPSE ≤ 19 mm had sensitivity 80% and specificity 73.3%., Conclusions: Patients with cystinosis have significant both left and right ventricular dysfunction, which can be better evaluated using the non-conventional echocardiographic modalities like TDI and 2D-STE for early detection of subtle cardiac dysfunction.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to be a public health emergency and a pandemic of international concern. As of April 31st,  the reported cases of COVID-19 are three million in 186 countries. Reported case fatality has crossed 200 thousand among which more than fifty thousand has been in the USA. Most patients present with symptoms of fever, cough, and shortness of breath following exposure to other COVID-19 patients. Respiratory manifestations predominate in patients with mild, moderate, severe illness. Imaging of patients with COVID-19 consistently reports various pulmonary parenchymal involvement. In this article we wanted to reinforce and review the various reported imaging patterns of cardiac and mediastinal involvement in COVID-19 patients. Among patients with COVID 19 who underwent various imaging of chest various cardiac findings including pericardial effusion, myocarditis, cardiomegaly has been reported. Most of these findings have been consistently reported in patients with significant acute myocardial injury, and fulminant myocarditis. Acute biventricular dysfunction has also been reported with subsequent improvement of the same following clinical improvement. Details of cardiac MRI is rather limited. In a patient with clinical presentation of acute myocarditis, biventricular myocardial interstitial edema, diffuse biventricular hypokinesia, increased ventricular wall thickness, and severe LV dysfunction has been reported. Among patients with significant clinical improvement in LV structure and function has also been documented. With increasing number of clinical cases, future imaging studies will be instrumental in identifying the various cardiac manifestations, and their relation to clinical outcome.

Objective/background: This study aimed to clarify the relationship between migraine-like headache and ventriculo-arterial coupling after transcatheter closure of the atrial septal defect in children. We hypothesized that migraine headache after defect closure would be related to an abnormal hemodynamic response against an increased left ventricular filling., Design: A retrospective cohort study., Methods: We calculated the end-ventricular systolic elastance (Ees), effective arterial elastance (Ea), and ventricular energy efficiency approximated based on echocardiography before and after defect closure, and compared these parameters between the subjects with and without headache after defect closure., Results: A total of 167 subjects were studied. Age at the procedure, defect diameter, and pulmonary to systemic blood flow ratio were 11 (9-17) years, 12.8 (9.2-16.0) mm, and 1.8 (1.6-2.3), respectively. We identified 47 (28%) subjects with migraine headache after defect closure. Although there was no significant difference in the Ees, Ea, and ventricular energy efficiency before defect closure between the groups, the Ees (4.0 [3.4-4.9] vs 4.8 [3.7-6.1], P = .014) and ventricular energy efficiency (0.79 [0.76-0.82] vs 0.83 [0.79-0.85], P = .001) after defect closure in subjects with headache were significantly lower than those in subjects without headache. Migraine headache after defect closure was significantly associated with age (odds ratio: 0.97, 95% confidential interval: 0.94-1.00, P = .036) and a decrease in the ventricular energy efficiency after defect closure (odds ratio: 6.42, 95% confidential interval: 2.76-14.90, P < .001)., Conclusion: A loss of ventricular energy efficiency was common in pediatric subjects with migraine-like headache after transcatheter closure of the atrial septal defect, which suggested that the left ventricular function maladaptation was related to headache development after defect closure. We advocate that an impaired ventriculo-arterial coupling may be one of the mechanisms for developing attacks in not only this population but also in other patients with migraine., (© 2020 American Headache Society.)

Background: The American Society for Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) 2016 guidelines for assessment of diastolic dysfunction (DD) are based primarily on the effects of diastolic dysfunction on left ventricular filling hemodynamics. However, these measures do not provide quantifiable mechanistic information about diastolic function. The Parameterized Diastolic Filling (PDF) formalism is a validated theoretical framework that describes DD in terms of the physical properties of left ventricular filling., Aims: We hypothesized that PDF analysis can provide mechanistic insight into the mechanical properties governing higher grade DD., Methods: Patients referred for echocardiography showing reduced left ventricular ejection fraction (< 45%) were prospectively classified into DD grade according to 2016 ASE/EACVI guidelines. Serial E-waves acquired during free breathing using pulsed wave Doppler of transmitral blood flow were analyzed using the PDF formalism., Results: Higher DD grade (grade 2 or 3, n = 20 vs grade 1, n = 30) was associated with increased chamber stiffness (261 ± 71 vs 169 ± 61 g/s 2 , p < 0.001), increased filling energy (2.0 ± 0.9 vs 1.0 ± 0.5 mJ, p < 0.001) and greater peak forces resisting filling (median [interquartile range], 18 [15-24] vs 11 [8-14] mN, p < 0.001). DD grade was unrelated to chamber viscoelasticity (21 ± 4 vs 20 ± 6 g/s, p = 0.32). Stiffness was inversely correlated with ejection fraction (r = - 0.39, p = 0.005)., Conclusions: Higher grade DD was associated with changes in the mechanical properties that determine the physics of poorer left ventricular filling. These findings provide mechanistic insight into, and independent validation of the appropriateness of the 2016 guidelines for assessment of DD.

Clinical management of diabetic cardiomyopathy represents an unmet need owing to insufficient knowledge about the molecular mechanisms underlying the dysfunctional heart. The aim of this work is to better clarify the role of matrix metalloproteinase 2 (MMP-2) isoforms and of translocator protein (TSPO)/voltage-dependent anion-selective channel 1 (VDAC1) modulation in the development of hyperglycaemia-induced myocardial injury. Hyperglycaemia was induced in Sprague-Dawley rats through a streptozocin injection (35 mg/Kg, i.p.). After 60 days, cardiac function was analysed by echocardiography. Nicotinamide Adenine Dinucleotide Phosphate NADPH oxidase and TSPO expression was assessed by immunohistochemistry. MMP-2 activity was detected by zymography. Superoxide anion production was estimated by MitoSOX™ staining. Voltage-dependent anion-selective channel 1 (VDAC-1), B-cell lymphoma 2 (Bcl-2), and cytochrome C expression was assessed by Western blot. Hyperglycaemic rats displayed cardiac dysfunction; this response was characterized by an overexpression of NADPH oxidase, accompanied by an increase of superoxide anion production. Under hyperglycaemia, increased expression of TSPO and VDAC1 was detected. MMP-2 downregulated activity occurred under hyperglycemia and this profile of activation was accompanied by the translocation of intracellular N-terminal truncated isoform of MMP-2 (NT-MMP-2) from mitochondria-associated membrane (MAM) into mitochondria. In the onset of diabetic cardiomyopathy, mitochondrial impairment in cardiomyocytes is characterized by the dysregulation of the different MMP-2 isoforms. This can imply the generation of a "frail" myocardial tissue unable to adapt itself to stress.

This study aimed to evaluate the accuracy of the HOSPITAL Score (Haemoglobin level at discharge, Oncology at discharge, Sodium level at discharge, Procedure during hospitalization, Index admission, number of hospital admissions, Length of stay) LACE index (Length of stay, Acute/emergent admission, Charlson comorbidy index score, Emerency department visits in previous 6 months) and LACE+ index in predicting 30-day readmission in patients with diastolic dysfunction. Heart failure remains one of the most common hospital readmissions in adults, leading to significant morbidity and mortality. Different models have been used to predict 30-day hospital readmissions. All adult medical patients discharged from the SIU School of Medicine Hospitalist service from 12 June 2016 to 12 June 2018 with an International Classification of Disease, 10th Revision, Clinical Modification diagnosis of diastolic heart failure were studied retrospectively to evaluate the performance of the HOSPITAL Score, LACE index and LACE+ index readmission risk prediction tools in this patient population. Of the 730 patient discharges with a diagnosis of heart failure with preserved ejection fraction (HFpEF), 692 discharges met the inclusion criteria. Of these discharges, 189 (27%) were readmitted to the same hospital within 30 days. A receiver operating characteristic evaluation showed C-statistic values to be 0.595 (95% CI 0.549 to 0.641) for the HOSPITAL Score, 0.551 (95% CI 0.503 to 0.598) for the LACE index and 0.568 (95% CI 0.522 to 0.615) for the LACE+ index, indicating poor specificity in predicting 30-day readmission. The result of this study demonstrates that the HOSPITAL Score, LACE index and LACE+ index are not effective predictors of 30-day readmission for patients with HFpEF. Further analysis and development of new prediction models are needed to better estimate the 30-day readmission rates in this patient population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Electrical disparity can induce inefficient cardiac performance, representing an uncoordinated wall motion at an earlier activated ventricular wall: an early shortening followed by a systolic rebound stretch. Although regional contractility and distensibility modulate this pathological motion, the effect of a morphological factor has not been emphasized. Our strain analysis in 62 patients with single ventricle revealed that those with an activation delay in 60-70% of ventricular wall area suffered from cardiac dysfunction and mechanical discoordination along with prolonged QRS duration. A computational simulation with a two-compartment ventricular model also suggested that the ventricle with an activation delay in 70% of the total volume was most vulnerable to a large activation delay, accompanied by an uncoordinated motion at an earlier activated wall. Taken together, the ratio of the delayed ventricular wall has a significant impact on the pathophysiology due to an activation delay, potentially highlighting an indicator of cardiac dysfunction.

The prevalence of death from cardiovascular disease is significantly higher in elderly populations; the underlying factors that contribute to the age-associated decline in cardiac performance are poorly understood. Herein, we identify the involvement of sodium/glucose co-transporter gene (SGLT2) in disrupted cellular Ca 2+ -homeostasis, and mitochondrial dysfunction in age-associated cardiac dysfunction. In contrast to younger rats (6-month of age), older rats (24-month of age) exhibited severe cardiac ultrastructural defects, including deformed, fragmented mitochondria with high electron densities. Cardiomyocytes isolated from aged rats demonstrated increased reactive oxygen species (ROS), loss of mitochondrial membrane potential and altered mitochondrial dynamics, compared with younger controls. Moreover, mitochondrial defects were accompanied by mitochondrial and cytosolic Ca 2+ ([Ca 2+ ] i ) overload, indicative of disrupted cellular Ca 2+ -homeostasis. Interestingly, increased [Ca 2+ ] i coincided with decreased phosphorylation of phospholamban (PLB) and contractility. Aged-cardiomyocytes also displayed high Na + /Ca 2+ -exchanger (NCX) activity and blood glucose levels compared with young-controls. Interestingly, the protein level of SGLT2 was dramatically increased in the aged cardiomyocytes. Moreover, SGLT2 inhibition was sufficient to restore age-associated defects in [Ca 2+ ] i -homeostasis, PLB phosphorylation, NCX activity and mitochondrial Ca 2+ -loading. Hence, the present data suggest that deregulated SGLT2 during ageing disrupts mitochondrial function and cardiac contractility through a mechanism that impinges upon [Ca 2+ ] i -homeostasis. Our studies support the notion that interventions that modulate SGLT2-activity can provide benefits in maintaining [Ca 2+ ] i and cardiac function with advanced age., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Retrospective single institution observational study.The aim of the present study was to analyze the influence of early extensive posterior decompression on complications in patients with severe traumatic cervical spinal cord injury (tcSCI).Cervical SCI is associated with a high prevalence of hyponatremia and cardiopulmonary dysfunction. However, very few studies have focused on this exploration to reduce the incidence of SCI early complications.We reviewed the medical records of consecutive patients undergoing extensive posterior decompression within 24 h for severe tcSCI (American Spinal Injury Association Impairment Scale [AIS] A to C) admitted between January 2009 and January 2018. The data collected retrospectively included age, gender, mechanism, and level of SCI, AIS grade, fracture or dislocation, electrolyte, and cardiopulmonary complications.Of the 97 enrolled patients, the baseline AIS grade was AIS A in 14, AIS B in 31, and AIS C in 52. Improvement of at least two AIS grades was found in 26 (26.8%), and improvement of at least one grade was found in 80.4% of patients at discharge. Twenty-nine (29.9%) patients had mild hyponatremia, 8 (8.2%) had moderate hyponatremia, and 3 (3.1%) had severe hyponatremia during hospitalization. The incidences of hyponatremia, hypotension, and tracheotomy were 41.2%, 13.4%, and 6.2%, respectively. The mean forced vital capacity (FVC) on admission and at discharge was 1.34 ± 0.46 L and 2.21 ± 0.41 L (P < .0001), respectively. Five patients developed pneumonia.Our results suggest that early expansive posterior decompression significantly reduces the incidence of hyponatremia, hypotension, and tracheotomy by promoting recovery of spinal cord function after severe tcSCI.

Aims: Recently, the zebrafish has gained attention as an innovative experimental model to decipher molecular and cellular mechanisms involved in cardiovascular development and diseases. Nevertheless, the use of zebrafish models has been challenged because the transparency of these fish, which allows for accurate cardiac evaluation, disappears in adulthood. In this study, the epicardial outline method was performed to investigate the feasibility of echocardiography in assessing cardiac function in pathological adult zebrafish., Materials and Methods: We attempted to estimate heart failure in adult zebrafish treated with three distinct regulators of cardiac function: phenylhydrazine hydrochloride (PHZ), doxorubicin (DOX), and ethanol. B-mode and Doppler images were evaluated at frequencies of up to 50 MHz and 40 MHz, respectively. The correlation between alterations in cardiac function, haemoglobin concentration, and myocardial histopathology were assessed., Key Findings: Cardiac output (CO) in PHZ-treated zebrafish was significantly higher than that in control zebrafish (151 ± 67 vs. 84 ± 37 μl/min, P = 0.004), whereas ejection fraction (EF) was lower (36.3 ± 10.9 vs. 50.9 ± 8.7%, P < 0.001), indicating typical high output heart failure derived from anaemia. Additionally, ventricular dysfunction in DOX-treated zebrafish was characterised by low CO (57 ± 38 μl/min) and EF (28.8 ± 10.4%), accompanied by an enlarged ventricle in diastole and systole, representing low output heart failure. For ethanol-treated zebrafish, EF was markedly reduced (39.6 ± 7.2%) indicating a dilated heart, while CO remained unchanged (90 ± 40 μl/min)., Significance: The epicardial outline method is an effective way of using echocardiography to assess cardiac dysfunction in pathological adult zebrafish, unlocking a major bottleneck in this research field with limited cardiac functional assays., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Fragmented QRS (fQRS) is postulated to be associated with ventricular dyssynchrony and might be able to predict a nonresponse to cardiac resynchronization therapy (CRT) implantation. In this systematic review and meta-analysis, we aim to assess whether fQRS can be a marker of intraventricular dyssynchronies in patients with ischemic and nonischemic cardiomyopathy and whether it is an independent predictor of nonresponse in patients receiving CRT., Methods: We performed a comprehensive search on topics that assesses fQRS and its association with intraventricular dyssynchrony and nonresponse to CRT up until September 2019., Results: Fragmented QRS is associated with intraventricular dyssynchrony (OR 10.34 [3.39, 31.54], p < .001; I 2 : 80% with sensitivity 76.8%, specificity 77%, LR+ 3.3, and LR- 0.3). Subgroup analysis showed that fQRS is associated with intraventricular dyssynchrony in patients with narrow QRS complex (OR 20.92 [12.24, 35.73], p < .001; I 2 : 0%) and nonischemic cardiomyopathy (OR of 19.97 [12.12, 32.92], p < .001; I 2 : 0%). Fragmented QRS was also associated with a higher time-to-peak myocardial sustained systolic (Ts-SD) (OR 15.19 [12.58, 17.80], p < .001; I 2 : 0% and positive Yu index (OR 15.61 [9.07, 26.86], p < .001; I 2 : 0%). Fragmented QRS has a pooled adjusted OR of OR of 1.70 [1.35, 2.14], p < .001; I 2 : 62% for association with a nonresponse to CRT. QRS duration is found to be higher in nonresponders group mean difference -8.54 [-13.38, -3.70], p < .001; I 2 : 70%., Conclusion: Fragmented QRS is associated with intraventricular dyssynchrony and is independently associated with nonresponse to cardiac resynchronization therapy., (© 2020 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals, Inc.)

Aims: In cardiomyocytes, there is microRNA (miR) in the mitochondria that originates from the nuclear genome and matures in the cytoplasm before translocating into the mitochondria. Overexpression of one such miR, miR-181c, can lead to heart failure by stimulating reactive oxygen species (ROS) production and increasing mitochondrial calcium level ([Ca 2+ ] m ). Mitochondrial calcium uptake 1 protein (MICU1), a regulatory protein in the mitochondrial calcium uniporter complex, plays an important role in regulating [Ca 2+ ] m . Obesity results in miR-181c overexpression and a decrease in MICU1. We hypothesize that lowering miR-181c would protect against obesity-induced cardiac dysfunction., Methods and Results: We used an in vivo mouse model of high-fat diet (HFD) for 18 weeks and induced high lipid load in H9c2 cells with oleate-conjugated bovine serum albumin in vitro. We tested the cardioprotective role of lowering miR-181c by using miR-181c/d -/- mice (in vivo) and AntagomiR against miR-181c (in vitro). HFD significantly upregulated heart levels of miR-181c and led to cardiac hypertrophy in wild-type mice, but not in miR-181c/d -/- mice. HFD also increased ROS production and pyruvate dehydrogenase activity (a surrogate for [Ca 2+ ] m ), but the increases were alleviated in miR-181c/d -/- mice. Moreover, miR-181c/d -/- mice fed a HFD had higher levels of MICU1 than did wild-type mice fed a HFD, attenuating the rise in [Ca 2+ ] m . Overexpression of miR-181c in neonatal ventricular cardiomyocytes (NMVM) caused increased ROS production, which oxidized transcription factor Sp1 and led to a loss of Sp1, thereby slowing MICU1 transcription. Hence, miR-181c increases [Ca 2+ ] m through Sp1 oxidation and downregulation of MICU1, suggesting that the cardioprotective effect of miR-181c/d -/- results from inhibition of Sp1 oxidation., Conclusion: This study has identified a unique nuclear-mitochondrial communication mechanism in the heart orchestrated by miR-181c. Obesity-induced overexpression of miR-181c increases [Ca 2+ ] m via downregulation of MICU1 and leads to cardiac injury. A strategy to inhibit miR-181c in cardiomyocytes can preserve cardiac function during obesity by improving mitochondrial function. Altering miR-181c expression may provide a pharmacologic approach to improve cardiomyopathy in individuals with obesity/type 2 diabetes., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Coordinated functional balance of negative and positive transcription complexes maintain and accommodate gene expression in hearts during quiescent and hypertrophic conditions, respectively. Negative elongation factor (Nelf) complex has been implicated in RNA polymerase II (pol II) pausing, a widespread regulatory transcriptional phenomenon observed across the cardiac genome. Here, we examine the role of NelfA aka, Wolf-Hirschhorn syndrome candidate 2 (Whsc2), a critical component of the negative elongation complex in hearts undergoing pressure-overload induced hypertrophy. Alignment of high-resolution genome-wide occupancy data of NelfA, Pol II, TFIIB and H3k9ac from control and hypertrophied hearts reveal that NelfA associates with active gene promoters. High NelfA occupancy is seen at promoters of essential and cardiac-enriched genes, expressed under both quiescent and hypertrophic conditions. Conversely, de novo NelfA recruitment is observed at inducible gene promoters with pressure overload, accompanied by significant increase in expression of these genes with hypertrophy. Interestingly, change in promoter NelfA levels correlates with the transcript output in hypertrophied hearts compared to Sham, suggesting NelfA might be playing a critical role in the regulation of gene transcription during cardiac hypertrophy. In vivo knockdown of NelfA (siNelfA) in hearts subjected to pressure-overload results in early ventricular dilatation and dysfunction, associated with decrease in expression of inducible and cardiac-enriched genes in siNelfA hypertrophied compared to control hypertrophied hearts. In accordance, in vitro knockdown of NelfA in cardiomyocytes showed no change in promoter pol II, however significant decrease in in-gene and downstream pol II occupancy was observed. These data suggest an inhibited pol II progression in transcribing and inducible genes, which reflects as a decrease in transcript abundance of these genes. These results indicate that promoter NelfA occupancy is essential for pol II -dependent transcription. Therefore, we conclude that NelfA is required for active transcription and gene expression during cardiac hypertrophy., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest with the contents of this article., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Preclinical studies have suggested acute stiffening of the aorta following experimental thoracic endovascular aortic repair (TEVAR), resulting in acute elevated pulse pressure, hypertension and possibly heart failure. The aim of this study was to evaluate cardiac remodelling following TEVAR., Methods: From 2005 to 2018, 519 TEVAR procedures were performed at a single centre. Transthoracic echocardiography was performed pre- and post-TEVAR in 31 patients without previous replacement of the thoracic aorta. Patient characteristics, drug information, radiographic and follow-up data were evaluated. Aortic details were measured in multiplanar reconstruction., Results: Transthoracic echocardiography was performed 2 ± 2 years after TEVAR. At this time, patients received significantly more antihypertensive drugs compared to the pre-TEVAR intake (beta-blocker therapy: P = 0.037; calcium channel blocker: P = 0.022). Compared to pre-TEVAR, there was a significant reduction in the left ventricular ejection fraction (P = 0.008) and tricuspid annular plane systolic excursion (P = 0.013) post-TEVAR. A significant increase in the left ventricular mass was not detected in this study (P = 0.95). The mean distance of 163 ± 66 mm of the descending aorta was covered., Conclusions: This study suggests negative cardiac remodelling with a decrease in the left and right ventricular function following TEVAR despite an increase in oral antihypertensive medication. The impact of stiffer endovascular grafts compared with the native aortic wall should be considered by endovascular specialists and manufacturers., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Attention deficit hyperactivity disorder (ADHD) is a multifactorial neurodevelopmental disorder that manifests during childhood. Methylphenidate (MPH), which is a psychostimulant drug, has been often prescribed for the treatment of ADHD in patients. It may increase the risk of fatal arrhythmias by impairing ventricular repolarization. Indicators of ventricular repolarization in ECG are intervals of QT, corrected QT (QTc), QT dispersion (QTd), T-peak to T-end (Tp-e), and Tp-Te/QTc ratio. We aimed to determine ventricular repolarization findings before and after MPH drug therapy in children with ADHD. The study retrospectively examined the medical records of 33 children aged 6-15 years who received MPH for ADHD and who had a control ECG one month after medication. The ECG parameters, heart rate, intervals of QRS, QT, QTc, QTd, Tp-Te, and Tp-Te/QTc ratio, were compared for each patient before and after drug therapy. No significant change was observed in heart rate, QRS, QT, QTc, and QTd interval in ECGs of patients after treatment but pre and posttreatment mean Tp-Te interval was 73.4 ± 9.72 ms and 79.7 ± 10.48 ms, and mean Tp-Te/QTc ratio was 0.17 ± 0.024 and 0.18 ± 0.023, respectively (P = 0.015, P = 0.028). Tp-Te intervals and Tp-Te/QTc ratios remained within normal values after treatment with MPH, but values were higher than baseline.

There is increasing evidence that cardiac dysfunction is a key contributor to CDH pathophysiology. Dysfunction in both right and left ventricles is common in the early neonatal period, contributes to clinical disease severity, and is associated with adverse outcomes including death and ECMO use. Early and routine assessment of ventricular function and pulmonary artery pressure may guide individualized clinical decision-making, including use of pulmonary vasodilators, cardiotropes, ECMO, and timing of surgical repair. Minimizing cardiac dysfunction, whether by prenatal, postnatal or perinatal treatment strategies, may lead to improved outcome in CDH., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Vectorcardiogram (VCG) represents the trajectory of the tip of cardiac vectors in three dimensional space with varying time. It is a recurring, near-periodic pattern of cardiac dynamics that is constructed by drawing the instantaneous vectors from a zero reference point according to direction, magnitude and polarity in the space. Being a three dimensional entity, it is more informative and more sensitive than conventional ECG as an evaluation tool of the physiology of cardiac dynamics, because of its extra degree of freedom. Accordingly, it is possible to find out even a minute and early electrophysiological alteration in diseases. Each cardiac cycle primarily consists of three loops in VCG corresponding to P, QRS, and T wave activities. The morphological assessment of the QRS loop was carried out in three dimensional space in order to analyze the spatial vectors of the ventricles and their patho-physiological correlation in various cardiac diseases. Spatial Velocity (SV) is a virtual velocity that represents the rate of movement of the tip of the cardiac vector through space, coordinated by three orthogonal leads, and can be estimated by using simple mathematical formula. It is the rate of change in amplitude and the directionality of instantaneous vectors in seriatim in the three dimensional space to quantify their the temporo-spatial characteristic pattern. We propose to evaluate this novel VCG descriptor SV, in normal individuals and patients of ventricular dysfunction. The possible mechanisms consistent with the patho-physiological basis of ventricular dysfunction or heart failure with altered SV would enrich the current understanding of the disease. Heart failure is the final common pathway of multitude of cardiac pathologies. Despite etiological heterogeneity, there are common mechanisms involved in the complex electrophysiological alteration of the failing myocardium. The changes observed as a consequence of ventricular dysfunction involve ion channel remodeling, intercellular uncoupling, myocardial ischemia, alterations in calcium handling, remodeling of the extracellular matrix, the presence of scars, activation of the sympathetic & the renin-angiotensin-aldosterone system, dilatation as well as stretch of viscous etc. The source modulation of the depolarization wave and its propagation in the heart and body fluid volume conductor also influence the visual pattern of cardiac vectors. In addition, patients with heart failure receive pharmacological or non-pharmacological therapies that also influence the electrophysiological changes. We hypothesize that the spatial velocity of ventricular depolarization and repolarization vectors of the VCG loop alters with a characteristic pattern in the patients with ventricular dysfunction and can differentiate healthy individuals from patients with ventricular dysfunction and also differentiate various categories, gradations and severity stratifications of the patients with ventricular dysfunction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Congenital diaphragmatic hernia (CDH) is a neonatal pathology in which intrathoracic herniation of abdominal viscera via diaphragmatic defect results in aberrant pulmonary and cardiovascular development. Despite decades of study and many advances in the diagnosis and treatment of CDH, morbidity and mortality remain high, largely due to pulmonary hypertension (PH), along with pulmonary hypoplasia and cardiac dysfunction. In patients with CDH, hypoplastic pulmonary vasculature and alterations in multiple molecular pathways lead to pathophysiologic pulmonary vasculopathy and, for severe CDH, sustained, elevated pulmonary arterial pressures. This review addresses the multiple anatomic and physiologic changes that underlie CDH-associated PH (CDH-PH), along with the multimodal treatment strategies that exist currently and future therapies currently under investigation., (Copyright © 2019. Published by Elsevier Inc.)

Background: Preeclampsia and fetal growth restriction share some pathophysiologic features and are both associated with placental insufficiency. Fetal cardiac remodeling has been described extensively in fetal growth restriction, whereas little is known about preeclampsia with a normally grown fetus., Objective: To describe fetal cardiac structure and function in pregnancies complicated by preeclampsia and/or fetal growth restriction as compared with uncomplicated pregnancies., Study Design: This was a prospective, observational study including pregnancies complicated by normotensive fetal growth restriction (n=36), preeclampsia with a normally grown fetus (n=35), preeclampsia with fetal growth restriction (preeclampsia with a normally grown fetus-fetal growth restriction, n=42), and 111 uncomplicated pregnancies matched by gestational age at ultrasound. Fetal echocardiography was performed at diagnosis for cases and recruitment for uncomplicated pregnancies. Cord blood concentrations of B-type natriuretic peptide and troponin I were measured at delivery. Univariate and multiple regression analysis were conducted., Results: Pregnancies complicated by preeclampsia and/or fetal growth restriction showed similar patterns of fetal cardiac remodeling with larger hearts (cardiothoracic ratio, median [interquartile range]: uncomplicated pregnancies 0.27 [0.23-0.29], fetal growth restriction 0.31 [0.26-0.34], preeclampsia with a normally grown fetus 0.31 [0.29-0.33), and preeclampsia with fetal growth restriction 0.28 [0.26-0.33]; P<.001) and more spherical right ventricles (right ventricular sphericity index: uncomplicated pregnancies 1.42 [1.25-1.72], fetal growth restriction 1.29 [1.22-1.72], preeclampsia with a normally grown fetus 1.30 [1.33-1.51], and preeclampsia with fetal growth restriction 1.35 [1.27-1.46]; P=.04) and hypertrophic ventricles (relative wall thickness: uncomplicated pregnancies 0.55 [0.48-0.61], fetal growth restriction 0.67 [0.58-0.8], preeclampsia with a normally grown fetus 0.68 [0.61-0.76], and preeclampsia with fetal growth restriction 0.66 [0.58-0.77]; P<.001). Signs of myocardial dysfunction also were observed, with increased myocardial performance index (uncomplicated pregnancies 0.78 z scores [0.32-1.41], fetal growth restriction 1.48 [0.97-2.08], preeclampsia with a normally grown fetus 1.15 [0.75-2.17], and preeclampsia with fetal growth restriction 0.45 [0.54-1.94]; P<.001) and greater cord blood B-type natriuretic peptide (uncomplicated pregnancies 14.2 [8.4-30.9] pg/mL, fetal growth restriction 20.8 [13.1-33.5] pg/mL, preeclampsia with a normally grown fetus 31.8 [16.4-45.8] pg/mL and preeclampsia with fetal growth restriction 37.9 [15.7-105.4] pg/mL; P<.001) and troponin I as compared with uncomplicated pregnancies., Conclusion: Fetuses of preeclamptic mothers, independently of their growth patterns, presented cardiovascular remodeling and dysfunction in a similar fashion to what has been previously described for fetal growth restriction. Future research is warranted to better elucidate the mechanism(s) underlying fetal cardiac adaptation in these conditions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: This study was conducted in order to evaluate the accuracy of a compressed sensing (CS) real-time single-breath-hold cine sequence for the assessment of left and right ventricular functional parameters in daily practice., Methods: Cardiac magnetic resonance (CMR) cine images were acquired from 100 consecutive patients using both the reference segmented multi-breath-hold steady-state free precession (SSFP) acquisition and a prototype single-breath-hold real-time CS sequence, providing the same slice number, position, and thickness. For both sequences, the left (LV) and right ventricular (RV) ejection fractions (EF) and end-diastolic volumes (EDV) were assessed as well as LV mass (LVM). The visualization of wall-motion disorders (WMD) and signal void related to mitral or tricuspid regurgitation was also analyzed., Results: The CS sequence mean scan time was 23 ± 6 versus 510 ± 109 s for the multi-breath-hold SSFP sequence (p < 0.001). There was an excellent correlation between the two sequences regarding mean LVEF (r = 0.995), LVEDV (r = 0.997), LVM (r = 0.981), RVEF (r = 0.979), and RVEDV (r = 0.983). Moreover, inter- and intraobserver agreements were very strong with intraclass correlations of 0.96 and 0.99, respectively. On CS images, mitral or tricuspid regurgitation visualization was good (AUC = 0.85 and 0.81, respectively; ROC curve analysis) and wall-motion disorder visualization was excellent (AUC ≥ 0.97)., Conclusion: CS real-time single-breath-hold cine imaging reduces CMR scan duration by almost 20 times in daily practice while providing reliable measurements of both left and right ventricles. There was no clinically relevant information loss regarding valve regurgitation and wall-motion disorder depiction., Key Points: • Compressed sensing single-breath-hold real-time cine imaging is a reliable sequence in daily practice. • Fast CS real-time imaging reduces CMR scan time and improves patient workflow. • There is no clinically relevant information loss with CS regarding heart valve regurgitation or wall-motion disorders.

Cardiac dysfunction (CD) importantly contributes to mortality in trauma patients, who survive their initial injuries following successful hemostatic resuscitation. This poor outcome has been correlated with elevated biomarkers of myocardial injury, but the pathophysiology triggering this CD remains unknown. We investigated the pathophysiology of acute CD after trauma using a mouse model of trauma hemorrhage shock (THS)-induced CD with echocardiographic guidance of fluid resuscitation, to assess the THS impact on myocardial integrity and function. Mice were subjected to trauma (soft tissue and bone fracture) and different degrees of hemorrhage severity (pressure controlled ~MABP < 35 mmHg or <65 mmHg) for 1 h, to characterize the acute impact on cardiac function. In a second study, mice were subjected to trauma and hemorrhage (MABP < 35 mmHg) for 1 h, then underwent two echocardiographic-guided resuscitations to baseline stroke volume at 60 and 120 min, and were monitored up to 180 min to study the longer impact of THS following resuscitation. Naïve and sham animals were used as controls. At 60 min post-THS injury, animals showed a lower cardiac output (CO) and stroke volume (SV) and an early rise of heart fatty acid-binding protein (H-FABP = 167 ± 38 ng/ml; 90% increase from shams, 3.54 ± 3.06 ng/ml), when subjected to severe hemorrhage and injury. Despite resuscitation, these animals maintained lower CO (6 ml/min vs. 23 ml/min), lower SV (10 μl vs. 46 μl; both ~75% decreased), and higher H-FABP (levels (340 ± 115 ng/ml vs. 10.3 ± 0.2 ng/ml; all THS vs. shams, P < 0.001) at 180 min post-THS injury. Histopathological and flow-cytometry analysis of the heart confirmed an influx of circulatory leukocytes, compared to non-injured hearts. Myocardial injury was supported by an increase of troponin I and h-FABP and the widespread ultrastructural disorganization of the morphology of sarcomeres and mitochondria. DNA fragmentation and chromatin condensation driven by leakage of apoptosis-inducing factor (AIF) may suggest a mitochondria-driven progressive cell death. THS modeling in the mouse results in cardiomyocyte damage and reduced myocardial function, which mimics the cardiac dysfunction seen in trauma patients. This CD model may, therefore, provide further understanding to the mechanisms underlying CD and act as a tool for developing cardioprotective therapeutics to improve survival after injury., (Copyright © 2019 Wall, Naganathar, Praditsuktavorn, Bugg, McArthur, Thiemermann, Tremoleda and Brohi.)

Echocardiographic strain and strain-rate imaging is a promising tool for the evaluation of myocardial segmental function, for the early detection of myocardial dysfunction, and for the prediction of reverse remodeling. We aimed at studying the changes in left and right ventricular function in pulsatile left ventricular assist device pediatric patients by two-dimensional echocardiography and two-dimensional speckle-tracking echocardiography. Echocardiographic and clinical data of patients implanted with a pulsatile-flow left ventricular assist device from 2011 to 2018 were retrospectively reviewed before and after implantation at 1, 3, and 6 months. A total of 18 patients were enrolled. Median age and weight at implantation were 9 months (5-23 months) and 5.85 kg (4.85-8.75 kg), respectively; median left ventricular assist device support was 181 (114.5-289.5) days. 13 patients (73%) were transplanted and 5 patients (27%) died. At follow-up: left ventricular ejection fraction increase at 1 month (p = 0.001) and 3 months (p = 0.01), left ventricular global longitudinal strain improvement at 1 month (p = 0.0008) and 3 months (p = 0.02), and right ventricular free-wall longitudinal strain increase at 1 month (p = 0.01). At short term after left ventricular assist device implantation, both left ventricular and right ventricular mechanics improved. The temporary benefit seems to decrease over time. The worsening of left ventricular function has been followed by a worsening of right ventricular function probably due to the ventricular interdependence.

Background: Long-term cardiac remodeling after heart transplantation (HT) in children has been insufficiently characterized. The aim of our study was to evaluate ventricular size in HT patients using cardiovascular magnetic resonance (CMR) imaging, to find underlying factors related to potentially abnormal cardiac dimensions and to study its impact on functional class and ventricular function., Methods: Seventy-five pediatric HT recipients (age 14.0 ± 4.2 y) were assessed by using CMR 11.2 ± 5.4 years after HT. Right ventricular (RV) and left ventricular (LV) volumes and mass were derived from short-axis cine images and myocardial strain/strain rate was assessed using myocardial feature tracking technique. Results were compared with a healthy reference population (n = 79, age 13.7 ± 3.7 y)., Results: LV end-diastolic ventricular volumes were smaller (64 ± 12 versus 84 ± 12 mL/m; P < 0.001) while mass-to-volume ratio (0.86 ± 0.18 versus 0.65 ± 0.11; P < 0.001) and heart rate (92 ± 14 versus 78 ± 13 beats/min; P < 0.001) were higher in HT patients. LV-ejection fraction (EF) was preserved (66% ± 8% versus 64% ± 6%; P = 0.18) but RV-EF (58 ± 7 versus 62% ± 4%, P = 0.004), LV systolic longitudinal strain (-12 ± 6 versus -15% ± 5%; P = 0.05), diastolic strain rate (1.2 ± 0.6 versus 1.5 ± 0.6 1/s; P = 0.03), and intra and interventricular synchrony were lower in the HT group. Smaller LV dimensions were primarily related to longer follow-up time since HT (β = -0.38; P < 0.001) and were associated with worse functional class and impaired ventricular systolic and diastolic performance., Conclusions: Cardiac remodeling after pediatric HT is characterized by reduced biventricular size and increased mass-to-volume ratio. These adverse changes evolve gradually and are associated with impaired functional class and ventricular dysfunction suggesting chronic maladaptive processes affecting allograft health.

Objectives: Very low calorie diets (VLCDs) are effective at clearing hepatic steatosis and improving insulin sensitivity. Whilst long-term weight loss is beneficial to the cardiovascular system, the acute elevation in fatty acids during caloric restriction is potentially detrimental to cardiac metabolism and function. We sought to investigate any cardiovascular changes occurring over the course of a modern VLCD regime, alongside the expected peripheral metabolic improvements., Methods: 25 obese volunteers (BMI 36.8 ± 5.8 kg/m 2 ) underwent magnetic resonance imaging, echocardiography, metabolic profiling, and bio-impedance analysis before 1 and 8 weeks following a VLCD (800 kcal/day). Results were compared to 15 age- and sex-matched controls., Results: After 1 week of VLCD, despite only modest weight loss, significant drops occurred in liver fat and insulin resistance (HOMA-IR; by 14-50%, all p < 0.01). In contrast, myocardial triglyceride content (MTGC) increased (by 48%, p = 0.030), and was associated with deterioration in both systolic (LVEF by 4%, p = 0.041) and diastolic function (e/e' 8.6 ± 1.4 to 9.4 ± 1.7, p = 0.019). Aortic stiffness also increased by 35% (p = 0.015). At 8 weeks, liver steatosis and visceral fat were lower than baseline (by 20-55%, p < 0.001), and peripheral metabolic improvements continued. MTGC also fell to below baseline (1.5 ± 0.6 vs 2.1 ± 1%, p = 0.05) with improved myocardial function (e/e' 8.6 ± 1.4 to 7.5 ± 1.5, p = 0.003)., Conclusions: Whilst VLCDs result in dramatic improvements in insulin resistance, they are associated with transient but significant cardiovascular functional decline, which may have an impact on those with the coexisting cardiac disease. However, after 8 weeks, the diet was associated with normalisation of cardiac function, suggesting they may form a potential therapeutic intervention for diastolic dysfunction in obesity and diabetes.

AF-mediated cardiomyopathy (AMC) is an important reversible cause of heart failure that is likely underdiagnosed in today's clinical practice. AMC describes AF either as the sole cause for ventricular dysfunction or exacerbating ventricular dysfunction in patients with existing cardiomyopathy or heart failure. Studies suggest that irreversible ventricular and atrial remodeling can occur in AMC, making timely diagnosis and intervention critical to optimize clinical outcome. Clinical correlation between AF onset/burden and progression of cardiomyopathy/heart failure symptoms provides strong evidence for the diagnosis of AMC. Cardiac MRI, continuous cardiac monitoring, and biomarkers are important diagnostic tools. From the therapeutic standpoint, early data suggest that AF ablation may improve long-term outcomes in AMC patients compared with medical rate and rhythm control. Patients with more AF burden and less severe underlying structural heart disease are more likely to experience left ventricle function recovery with successful AF ablation. Despite recent advances, significant knowledge gaps exist in our understanding of the epidemiology, mechanisms, diagnosis, management strategies, and prognosis of AMC.

Background: Cardiac dysfunction and arrhythmia are common and onerous cardiovascular events in end-stage renal disease (ESRD) patients, especially those on dialysis. Fibroblast growth factor (FGF)-23 is a phosphate-regulating hormone whose levels dramatically increase as renal function declines. Beyond its role in phosphorus homeostasis, FGF-23 may elicit a direct effect on the heart. Whether FGF-23 modulates ventricular cardiac rhythm is unknown, prompting us to study its role on excitation-contraction (EC) coupling., Methods: We examined FGF-23 in vitro actions on EC coupling in adult rat native ventricular cardiomyocytes using patch clamp and confocal microscopy and in vivo actions on cardiac rhythm using electrocardiogram., Results: Compared with vehicle treatment, FGF-23 induced a significant decrease in rat cardiomyocyte contraction, L-type Ca2+ current, systolic Ca2+ transients and sarcoplasmic reticulum (SR) load and SR Ca2+-adenosine triphosphatase 2a pump activity. FGF-23 induced pro-arrhythmogenic activity in vitro and in vivo as automatic cardiomyocyte extracontractions and premature ventricular contractions. Diastolic spontaneous Ca2+ leak (sparks and waves) was significantly increased by FGF-23 via the calmodulin kinase type II (CaMKII)-dependent pathway related to hyperphosphorylation of ryanodine receptors at the CaMKII site Ser2814. Both contraction dysfunction and spontaneous pro-arrhythmic Ca2+ events induced by FGF-23 were blocked by soluble Klotho (sKlotho)., Conclusions: Our results show that FGF-23 reduces contractility and enhances arrhythmogenicity through intracellular Ca2+ mishandling. Blocking its actions on the heart by improving sKlotho bioavailability may enhance cardiac function and reduce arrhythmic events frequently observed in ESRD., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Heightened sympathetic nerve activity is associated with occurrence of ventricular arrhythmia (VA)., Objective: To investigate the association of skin sympathetic nerve activity (SKNA) and VA occurrence., Methods: We prospectively enrolled 65 patients with severe cardiomyopathy. Of these, 39 had recent sustained VA episodes (VA-1 group), 11 had intractable VA undergoing sedation with general anesthesia (VA-2 group), and 15 had no known history of VA (VA-Ctrl group). All patients had simultaneous SKNA and electrocardiogram recording. SKNA was assessed using an average value (aSKNA), a variable value (vSKNA), and the number of bursts of SKNA (bSKNA)., Results: The VA-1 group had higher aSKNA and vSKNA compared with the VA-Ctrl group (aSKNA: 1.41 ± 0.53 μV vs 0.98 ± 0.41 μV, P = .003; vSKNA: 0.52 ± 0.22 μV vs 0.30 ± 0.16 μV, P < .001) and the VA-2 group (aSKNA: 0.83 ± 0.22 μV, P < .001; vSKNA: 0.23 ± 0.11 μV; P < .001). Although the VA-2 group had more VA episodes than the VA-1 group (median, 5 vs 2; P = .01), their SKNA was the lowest among the 3 groups. Multivariate Cox regression analysis showed that a higher aSKNA at baseline was an independent predictor of lower VA recurrence rate during a 417 ± 279-day follow-up (hazard ratio, 0.325; 95% confidence interval [CI], 0.119-0.883; P = .03). A >15% reduction in aSKNA after therapy was associated with a lower subsequent VA event rate (hazard ratio, 0.222; 95% CI, 0.057-0.864; P = .03)., Conclusion: Patients with VA had increased SKNA as compared with control. Both SKNA and sustained VA could be suppressed by general anesthesia. The aSKNA at baseline was an independent predictor of VA recurrence., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of diabetes in pregnancy on fetal and neonatal cardiac geometry and function around the time of delivery., Methods: This was a prospective study of 75 pregnant women delivering at term, comprising 54 normal pregnancies and 21 with a diagnosis of pregestational or gestational diabetes mellitus. Fetal and neonatal conventional and spectral tissue Doppler and two-dimensional speckle-tracking echocardiography were performed a few days before and within hours after delivery. Fetal and neonatal cardiac geometry, global myocardial deformation and performance, diastolic and systolic function and left ventricular (LV) torsion were compared between normal pregnancies and those with diabetes, and perinatal changes within the diabetes group were assessed., Results: Compared with normal pregnancies, diabetic pregnancies demonstrated significant differences in fetal ventricular geometry, myocardial deformation and cardiac function (right ventricular (RV) sphericity index, 0.56 vs 0.65; LV torsion, 2.1 °/cm vs 5.6 °/cm; LV isovolumetric relaxation time, 101 ms vs 115 ms; and RV isovolumetric contraction time, 107 ms vs 119 ms; P < 0.001 for all). Compared with normal pregnancies, diabetic pregnancies demonstrated significant differences in neonatal cardiac parameters (mean RV sphericity index, 0.43 vs 0.55; mean LV torsion, 1.30 °/cm vs 2.78 °/cm; median LV myocardial performance index (MPI'), 0.39 vs 0.51; median RV-MPI', 0.34 vs 0.40; P < 0.01 for all). Paired comparison between fetal and neonatal cardiac indices in diabetic pregnancies demonstrated that delivery resulted in a significant improvement in some, but not all, cardiac indices (mean RV sphericity index, 0.65 vs 0.55; mean LV torsion, 5.60 °/cm vs 2.78 °/cm; median RV-MPI', 0.51 vs 0.40; P < 0.01 for all)., Conclusions: Compared with normal term fetuses and neonates, those of diabetic women exhibit cardiac indices indicative of myocardial impairment, reflecting a response to a relatively hyperglycemic intrauterine environment with alteration in fetal loading conditions (LV preload deprivation and increased RV afterload) and adaptation to subsequent acute changes in hemodynamic load at delivery. Elucidating mechanisms that contribute to the alterations in perinatal cardiac function in diabetic pregnancy could help in refining management and developing better therapeutic strategies to reduce the risk of adverse pregnancy outcomes. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

The optimal timing of stage-2-palliation (S2P) in single left ventricle is not clear. The aim of this study was to identify S2P related factors associated with outcomes after total cavopulmonary connection (TCPC), particularly relative to the dominant systemic ventricle. A total of 405 patients who underwent both S2P and TCPC at our institute between 1997 and 2017 was included. Patients were divided into two groups, dominant right ventricle (RV type, n = 235) and dominant left ventricle (LV type, n = 170). S2P related factors associated with mortality, postoperative ventricular function, and late exercise capacity following TCPC, were analyzed. The median age at S2P was 4 [3-7] and 6 [3-11] months in RV and LV type patients, respectively (p = 0.092). Survival after TCPC was similar in RV and LV type patients (p = 0.280). In those with RV type, risk factors for mortality following TCPC were older age (p < 0.001), heavier weight (p = 0.001), higher PAP (p < 0.001), higher TPG (p = 0.010), and lower SO2 (p = 0.008) at S2P. In those with LV type, no risk factor was identified. Risk factors for postoperative impaired ventricular function were older age and higher weight at S2P in both RV and LV type patients. Older age at S2P was also identified as a risk for inferior peak oxygen uptake (VO2) years after TCPC both in RV and LV type patients. Older age at S2P was associated with higher mortality after Fontan completion only in RV type patients. However, it was associated with postoperative ventricular dysfunction and lower exercise capacity after TCPC in both RV and LV type patients.

Background: Management of adults with repaired congenital heart disease (CHD) is still challenging. Heart failure secondary to residual anatomical sequels or arrhythmic events is not rare in this population. MRI has emerged as an accurate tool to quantify pulmonary transit time (PTT) of intravenous contrast agents and pulmonary blood volume (PBV)., Purpose: To determine the relationship between PTT, and conventional indexes of ventricular dysfunction and heart failure in a cohort of adults with CHD and to assess its association with adverse outcomes., Study Type: Retrospective., Subjects: 89 adult CHD patients (56 males, age 34 ± 11 years) and 14 age- and sex-matched healthy subjects., Field Strength/sequence: First-pass perfusion and standard sequences for ventricular volumes and function and flow analysis at 1.5T., Assessment: PTT was calculated as the time required for a bolus of contrast agent to pass from the right ventricle to the left atrium, expressed both in seconds (PTTS) and number of heartbeats (PTTB). The pulmonary blood volume index (PBVI) was measured by the product of PTTB and the pulmonary artery stroke volumes., Statistical Tests: Student's independent t-test analysis of variance (ANOVA) and Mann-Whitney nonparametric; Pearson's or Spearman's correlation; Kaplan-Meier method., Results: PTTS and PTTB were significantly higher in patients than in controls (7.6 ± 3 vs. 5.6 ± 1.2 sec, P = 0.01 and 8 ± 3 vs. 6 ± 1 bpm, P = 0.01, respectively). PTTS showed negative correlation with left ventricle ejection fraction (LVEF) and cardiac index (CI) (r = -0.3, P = 0.004, and r = -0.4, P < 0.001, respectively) as well as with left ventricle and atrial volumes. By Kaplan-Meier survival analysis, PTTB >8 bpm was associated with significant increased risk of adverse outcome at mid-term follow-up. Moreover, patients with both increased PTTB and PBV have higher amino-terminal portion of the prohormone brain natriuretic peptide (NT-proBNP) and lower LVEF., Data Conclusion: PTT is prolonged in adult CHD in comparison with healthy subjects, likely reflecting reduced CI and ventricular dysfunction., Level of Evidence: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:779-786., (© 2019 International Society for Magnetic Resonance in Medicine.)

Background: The authors previously observed that some high-performance athletes, irrespective of type of sport, can show echocardiographically determined low left ventricular ejection fractions (LVEF; <52%) together with normal heart rates and nondilated left ventricular (LV) cavities under resting conditions. The aim of this study was to determine if this phenomenon is associated with dyssynchronous motion of the interventricular septum relative to the lateral LV wall., Methods: Results of M-mode and two-dimensional echocardiography and pulsed-wave, pulsed-wave tissue, and color tissue Doppler were compared in 70 athletes (mean age, 20 ± 7 years; 77% men) with low LVEFs (<52%) participating in a wide variety of sports and a control group of 564 athletes (mean age, 22 ± 7 years; 61% men) with normal LVEFs (≥52%)., Results: No between-group differences were found in cardiac dimensions or QRS duration (indicating no electrical dyssynchrony in the low-LVEF group compared with the normal-LVEF group), but analysis of mechanical interventricular and intraventricular dyssynchrony showed that time intervals between QRS onset and the different systolic waves were all lengthened in the low-LVEF group (P < .05 for all). Values of interventricular mechanical delay were higher in the low-LVEF group (P = .012), though they did not reach pathologic limits. Peak aerobic performance was independent of LVEF. The results did not change materially when analyzing data separately by sex or sport., Conclusions: Some young highly trained athletes might show depressed LVEF (<52%) with a nondilated LV cavities in the early phase of cardiac adaptations, which seems to be linked to longer LV contraction times, with the right ventricle unaffected. These echocardiographic findings, although not highly prevalent, could be considered another characteristic of the cardiac adaptations to the demands of elite sports with no detriment in performance., (Copyright © 2019 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Adaptation to aortic valve stenosis leads to myocardial hypertrophy, which has been associated with inflammation, fibrosis and activation of the endocannabinoid system. Since the endocannabinoid system and the CB2 receptor provide cardioprotection and modulate immune response in experimental ischemia, we investigated the role of CB2 in a mouse model of cardiac pressure overload., Methods: Transverse aortic constriction was performed in CB2 receptor-deficient (Cnr2 -/- ) mice and their wild-type littermates (Cnr2 +/+ ). After echocardiography and Millar left heart catheter hemodynamic evaluation hearts were processed for histological, cellular and molecular analyses., Results: The endocannabinoid system showed significantly higher anandamide production and CB2 receptor expression in Cnr2 +/+ mice. Histology showed non-confluent, interstitial fibrosis with rare small areas of cardiomyocyte loss in Cnr2 +/+ mice. In contrast, extensive cardiomyocyte loss and confluent scar formation were found in Cnr2 -/- mice accompanied by significantly increased apoptosis and left ventricular dysfunction when compared with Cnr2 +/+ mice. The underlying cardiac maladaptation in Cnr2 -/- mice was associated with significantly reduced expression of myosin heavy chain isoform beta and less production of heme oxygenase-1. Cnr2 -/- hearts presented after 7 days with stronger proinflammatory response including significantly higher TNF-alpha expression and macrophage density, but lower density of CD4+ and B220+ cells. At the same time, we found increased apoptosis of macrophages and adaptive immune cells. Higher myofibroblast accumulation and imbalance in MMP/TIMP-regulation indicated adverse remodeling in Cnr2 -/- mice., Conclusions: Our study provides mechanistic evidence for the role of the endocannabinoid system in myocardial adaptation to pressure overload in mice. The underlying mechanisms include production of anandamide, adaptation of contractile elements and antioxidative enzymes, and selective modulation of immune cells action and apoptosis in order to prevent the loss of cardiomyocytes., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

His bundle pacing (HBP) has continued to evolve over the past decade and has started to become a global phenomenon. Evidence is mounting of its clinical benefits as compared to both right ventricular and left ventricular pacing. In this paper, we review recent data in support of His bundle pacing and some of the challenges facing us as we advocate its increasing role in clinical practice., (Copyright © 2018 Elsevier Inc. All rights reserved.)