Cardiac function evaluation in children with spinal muscular atrophy: A case-control study.

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by degeneration of lower motor neurons, resulting in progressive muscle weakness and atrophy. However, little is known regarding the cardiac function of children with SMA. METHODS: We recruited SMA patients younger than 18 years of age from January 1, 2022, to April 1, 2022, in the First Affiliated Hospital of Sun Yat-sen University. All patients underwent a comprehensive cardiac evaluation before treatment, including history taking, physical examination, blood tests of cardiac biomarkers, assessment of echocardiography and electrocardiogram. Age/gender-matched healthy volunteers were recruited as controls. RESULTS: A total of 36 SMA patients (26 with SMA type 2 and 10 with SMA type 3) and 40 controls were enrolled in the study. No patient was clinically diagnosed with heart failure. Blood tests showed elevated values of creatine kinase isoenzyme M and isoenzyme B (CK-MB) mass and high-sensitivity cardiac troponin T (hs-cTnT) in spinal muscular atrophy (SMA) patients. Regarding echocardiographic parameters, SMA children were detected with lower global left and right ventricular longitudinal strain, abnormal diastolic filling velocities of trans-mitral and trans-tricuspid flow. The results revealed no clinical heart dysfunction in SMA patients, but subclinical ventricular dysfunction was seen in SMA children including the diastolic function and myocardial performance. Some patients presented with elevated heart rate and abnormal echogenicity of aortic valve or wall. Among these SMA patients, seven patients (19.4%) had scoliosis. The Cobb's angles showed a significant negative correlation with LVEDd/BSA, but no correlation with other parameters, suggesting that mild scoliosis did not lead to significant cardiac dysfunction. CONCLUSIONS: Our findings warrant increased attention to the cardiac status and highlight the need to investigate cardiac interventions in SMA children.

Blinded, randomized trial of sonographer versus AI cardiac function assessment.

Artificial intelligence (AI) has been developed for echocardiography1-3, although it has not yet been tested with blinding and randomization. Here we designed a blinded, randomized non-inferiority clinical trial (ClinicalTrials.gov ID: NCT05140642; no outside funding) of AI versus sonographer initial assessment of left ventricular ejection fraction (LVEF) to evaluate the impact of AI in the interpretation workflow. The primary end point was the change in the LVEF between initial AI or sonographer assessment and final cardiologist assessment, evaluated by the proportion of studies with substantial change (more than 5% change). From 3,769 echocardiographic studies screened, 274 studies were excluded owing to poor image quality. The proportion of studies substantially changed was 16.8% in the AI group and 27.2% in the sonographer group (difference of -10.4%, 95% confidence interval: -13.2% to -7.7%, P < 0.001 for non-inferiority, P < 0.001 for superiority). The mean absolute difference between final cardiologist assessment and independent previous cardiologist assessment was 6.29% in the AI group and 7.23% in the sonographer group (difference of -0.96%, 95% confidence interval: -1.34% to -0.54%, P < 0.001 for superiority). The AI-guided workflow saved time for both sonographers and cardiologists, and cardiologists were not able to distinguish between the initial assessments by AI versus the sonographer (blinding index of 0.088). For patients undergoing echocardiographic quantification of cardiac function, initial assessment of LVEF by AI was non-inferior to assessment by sonographers.

The differential diagnostic value of selected cardiovascular biomarkers in Takotsubo syndrome.

INTRODUCTION: Takotsubo syndrome (TTS) is clinically indistinguishable from an acute coronary syndrome (ACS). In the absence of valid markers for differential diagnosis, coronary angiography has been indispensable. METHODS: In our study, we evaluated the serum levels of sST-2, GDF-15, suPAR and H-FABP in 92 patients with the suspicion of TTS (51 TTS and 41 ACS patients) and 40 gender matched controls (no coronary artery disease or signs of heart failure) at baseline. RESULTS: H-FABP was significantly higher in ACS patients compared to TTS patients. Even in in propensity score matching for left ventricular ejection fraction, sex and cardiovascular risk factors, differences in the plasma levels of H-FABP in the matched cohort of TTS vs ACS remained statistically significant. Whereas, sST-2 was significantly elevated in TTS patients. H-FABP was superior for prediction of an ACS with even higher accuracy than hs troponin in differential diagnosis (AUC 0.797, p ≤ 0.0001); the optimal cut off for discrimination towards a TTS was calculated as 2.93 ng/ml (sensitivity 70.0%, specificity 82.4%, PPV 75.7%, NPV 77.4%). sST-2 seemed most appropriate for identification of a TTS (AUC 0.653, p = 0.012). The optimal cut off for differential diagnosis was 11018.06 pg/ml (sensitivity 82.0%, specificity 51.2%, PPV 69.4%, NPV 71.9 %). CONCLUSION: H-FABP and sST-2 are the most promising markers with better accuracy than preexisting biomarkers in differential diagnosis in our study and therefore, could be crucial for the guidance of treatment in patients with high bleeding risk, advanced renal failure or multimorbidity.

Aumento do trabalho miocárdico desperdiçado como indicador de lesão coronariana significativa / Increased wasted myocardial work as an indicator of significant coronary lesion

Introdução: A avaliação dos índices de trabalho miocárdico global em condições basais pode ser útil para a estratificação clínica de pacientes com suspeita de obstrução coronariana. Objetivo: Correlacionar o valor do índice de trabalho miocárdico global e a presença de lesões obstrutivas coronarianas significativas. Método: Estudo transversal, com pacientes encaminhados para cinecoronarioangiografia eletiva. Foi realizado ecocardiograma com obtenção das medidas para cálculo do valor do trabalho miocárdico, sendo avaliada a presença de lesões obstrutivas coronarianas significativas à cinecoronarioangiografia. Resultados: A amostra foi composta de 30 pacientes, com a idade média de 64,2±12,8 anos, sendo a maioria do sexo masculino (63,3%), dos quais 68,4% apresentaram lesões obstrutivas coronarianas significativas. O índice de trabalho miocárdico global foi de 1.876mmHg%±253,8 no grupo com lesões obstrutivas coronarianas significativas e de 2.054,2mmHg%±417,3 naqueles sem lesões significativas (p=0,089). O trabalho miocárdio construtivo global nos pacientes sem lesões obstrutivas coronarianas significativas foi maior (2.329,3mmHg%±462,9) do que naqueles com lesões obstrutivas coronarianas significativas (2.109,5mmHg%±332,3; p=0,064). O trabalho miocárdio desperdiçado global foi maior nos pacientes com lesões obstrutivas coronarianas significativas (103,7mmHg%±47,1 versus 68,3mmHg%±33,8; p=0,038). O ponto de corte de 115mmHg% foi aquele com a melhor área sob a curva (0,625), com sensibilidade de 83,3%. Conclusão: O aumento do trabalho miocárdio desperdiçado global se correlacionou com a presença de lesões obstrutivas coronarianas significativas em nossa amostra.(AU)

Introduction: The assessment of global myocardial work indices under baseline conditions may be useful for the clinical stratification of patients with suspected coronary obstruction. Objective: To correlate the value of global myocardial work indices and the presence of significant obstructive coronary lesions. Method: Cross-sectional study, with patients referred for elective coronary angiography. An echocardiogram was performed to obtain measurements to calculate the value of myocardial work and evaluated the presence or presence of significant obstructive coronary lesions at coronary angiography. Results: The sample consisted of 30 patients, with a mean age of 64.2±12.8 years, the majority being male (63.3%), of which 68.4% had significant obstructive coronary lesions. The global myocardial work indices was 1,876mmHg%±253.8 in the group with significant obstructive coronary lesions and 2,054.2mmHg%±417.3 in those without significant lesions (p=0.089). Global constructive myocardial work in patients without significant obstructive coronary lesions was higher (2,329.3mmHg%±462.9) than in those with significant obstructive coronary lesions (2,109.5mmHg%±332.3; p=0.064). Global wasted myocardial work was higher in patients with significant obstructive coronary lesions (103.7mmHg%±47.1 versus 68.3mmHg%±33.8; p=0.038). The cutoff point of 115 mmHg% was the one with the best area under the curve (0.625), with a sensitivity of 83.3%. Conclusion: The increase in global wasted myocardial work correlated with the presence of significant obstructive coronary lesions in our sample. (AU)

Diagnostic and prognostic role of nitroglycerin-induced dilation in patients with suspected vasospastic angina, combined with ergonovine provocation test.

The diagnostic and prognostic role of nitroglycerin-induced dilation (NID) combined with ergonovine provocation test in patients with suspected VSA patients is not clear. A total of 438 consecutive patients who underwent the ergonovine provocation test for the diagnosis of vasospastic angina (VSA) were enrolled. Patients with VSA (n = 52) had a significantly greater coronary response to ergonovine (- 84.3 ± 10.5% vs. - 38.4 ± 17.9%, p < 0.001) and NID (26.3 ± 31.0% vs. 12.5 ± 19.0%, p < 0.001) than non-VSA patients. However, positive NID (more than 13.8% dilation, n = 170) showed a poor accuracy (AUC 0.64 [95% CI: 0.56-0.73], p = 0.001, sensitivity 60.4%, specificity 61.3%) for the diagnosis of VSA by ergonovine provocation test. Major adverse cardiovascular events (MACE) occurred more frequently in the VSA group than in the non-VSA group (9.6% vs. 2.2%, p = 0.006). In addition, the positive NID group showed a lower rate of MACE than the negative NID group (1.2% vs. 4.3%, p = 0.021). Interestingly, the group of VSA with negative NID had poor prognosis than any other combinations (Log-rank, p < 0.0001). Although NID had a limited role in the detection of VSA defined by ergonovine provocation test, NID combined with the ergonovine provocation test has an additive prognostic role in the clinical outcomes in patients with suspected VSA.

Extracellular vesicles fail to trigger the generation of new cardiomyocytes in chronically infarcted hearts.

Background: Extracellular vesicles (EV) mediate the therapeutic effects of stem cells but it is unclear whether this involves cardiac regeneration mediated by endogenous cardiomyocyte proliferation. Methods: Bi-transgenic MerCreMer/ZEG (n = 15/group) and Mosaic Analysis With Double Markers (MADM; n = 6/group) mouse models underwent permanent coronary artery ligation and received, 3 weeks later, 10 billion EV (from human iPS-derived cardiovascular progenitor cells [CPC]), or saline, injected percutaneously under echo guidance in the peri-infarcted myocardium. Endogenous cardiomyocyte proliferation was tracked by EdU labeling and biphoton microscopy. Other end points, including cardiac function (echocardiography and MRI), histology and transcriptomics were blindly assessed 4-6 weeks after injections. Results: There was no proliferation of cardiomyocytes in either transgenic mouse strains. Nevertheless, EV improved cardiac function in both models. In MerCreMer/ZEG mice, LVEF increased by 18.3 ± 0.2% between baseline and the end-study time point in EV-treated hearts which contrasted with a decrease by 2.3 ± 0.2% in the PBS group; MADM mice featured a similar pattern as intra-myocardial administration of EV improved LVEF by 13.3 ± 0.16% from baseline whereas it decreased by 14.4 ± 0.16% in the control PBS-injected group. This functional improvement was confirmed by MRI and associated with a reduction in infarct size, the decreased expression of several pro-fibrotic genes and an overexpression of the anti-fibrotic miRNA 133-a1 compared to controls. Experiments with an anti-miR133-a demonstrated that the cardio-reparative effects of EV were partly abrogated. Conclusions: EV-CPC do not trigger cardiomyocyte proliferation but still improve cardiac function by other mechanisms which may include the regulation of fibrosis.

Calcium dysregulation increases right ventricular outflow tract arrhythmogenesis in rabbit model of chronic kidney disease.

Chronic kidney disease (CKD) increases the risk of arrhythmia. The right ventricular outflow tract (RVOT) is a crucial site of ventricular tachycardia (VT) origination. We hypothesize that CKD increases RVOT arrhythmogenesis through its effects on calcium dysregulation. We analysed measurements obtained using conventional microelectrodes, patch clamp, confocal microscopy, western blotting, immunohistochemical examination and lipid peroxidation for both control and CKD (induced by 150 mg/kg neomycin and 500 mg/kg cefazolin daily) rabbit RVOT tissues or cardiomyocytes. The RVOT of CKD rabbits exhibited a short action potential duration, high incidence of tachypacing (20 Hz)-induced sustained VT, and long duration of isoproterenol and tachypacing-induced sustained and non-sustained VT. Tachypacing-induced sustained and non-sustained VT in isoproterenol-treated CKD RVOT tissues were attenuated by KB-R7943 and partially inhibited by KN93 and H89. The CKD RVOT myocytes had high levels of phosphorylated CaMKII and PKA, and an increased expression of tyrosine hydroxylase-positive neural density. The CKD RVOT myocytes exhibited large levels of Ito , IKr , NCX and L-type calcium currents, calcium leak and malondialdehyde but low sodium current, SERCA2a activity and SR calcium content. The RVOT in CKD with oxidative stress and autonomic neuron hyperactivity exhibited calcium handling abnormalities, which contributed to the induction of VT.

Galectin-3 for prediction of cardiac function compared to NT-proBNP in individuals with prediabetes and type 2 diabetes mellitus.

Use of galectin-3 for assessing cardiac function in prediabetes and type 2 diabetes mellitus (T2DM) needs to be established. Within the Gutenberg Health Study cohort (N = 15,010, 35-74 years) patient characteristics were investigated regarding galectin-3 levels. Prognostic value of galectin-3 compared to NT-proBNP concerning cardiac function and mortality was assessed in individuals with euglycaemia, prediabetes and T2DM in 5 years follow-up. Higher galectin-3 levels related to older age, female sex and higher prevalence for prediabetes, T2DM, cardiovascular risk factors and comorbidities. Galectin-3 cross-sectionally was related to impaired systolic (ß - 0.36, 95% CI - 0.63/- 0.09; P = 0.008) and diastolic function (ß 0.014, 95% CI 0.001/0.03; P = 0.031) in T2DM and reduced systolic function in prediabetes (ß - 0.34, 95% CI - 0.53/- 0.15; P = 0.00045). Galectin-3 prospectively related to systolic (ß - 0.656, 95% CI - 1.07/- 0.24; P = 0.0021) and diastolic dysfunction (ß 0.0179, 95% CI 0.0001/0.036; P = 0.049), cardiovascular (hazard ratio per standard deviation of galectin-3 (HRperSD) 1.60, 95% CI 1.39-1.85; P < 0.0001) and all-cause mortality (HRperSD 1.36, 95% CI 1.25-1.47; P < 0.0001) in T2DM. No relationship between galectin-3 and cardiac function was found in euglycaemia, whereas NT-proBNP consistently related to reduced cardiac function. Prospective value of NT-proBNP on cardiovascular and all-cause mortality was higher. NT-proBNP was superior to galectin-3 to assess reduced systolic and diastolic function.

Cardiopulmonary function findings of pediatric patients with patent ductus arteriosus.

ABSTRACT: Transcatheter occlusion and surgical ligation are the treatments of choice for most patent ductus arteriosus (PDA) in children. Fifty-five children who had PDA completed a pulmonary function test and a symptom-limited treadmill exercise test from 2016 to 2018 at 1 medical center in southern Taiwan. The study group was divided into surgical ligation and catheterization groups, which were compared to a healthy control group matched for age, sex, and body mass index. Data about the performance on the exercise test, including metabolic equivalent at anaerobic threshold and peak, were analyzed. No differences in the pulmonary function and ventilatory parameters were observed between the surgery, catheterization, and control groups. Heart rate at peak and at anaerobic threshold significantly differed in the investigated groups. The post hoc analysis showed that the surgery group had a lower heart rate at peak and threshold compared to the catheterization and control groups (P = .02, P < .001, respectively). No significant difference was found between the catheterization group and the control group. A larger and younger group of patients were recruited, allowing for newer data about the cardiopulmonary function to be obtained. The findings suggest that patients with PDA could undergo physical training after intervention. The imposition of restrictions to limit sports activities should be avoided.

A new approach to improve the hemodynamic assessment of cardiac function independent of respiratory influence.

Cardiovascular and respiratory systems are anatomically and functionally linked; inspiration produces negative intrathoracic pressures that act on the heart and alter cardiac function. Inspiratory pressures increase with heart failure and can exceed the magnitude of ventricular pressure during diastole. Accordingly, respiratory pressures may be a confounding factor to assessing cardiac function. While the interaction between respiration and the heart is well characterized, the extent to which systolic and diastolic indices are affected by inspiration is unknown. Our objective was to understand how inspiratory pressure affects the hemodynamic assessment of cardiac function. To do this, we developed custom software to assess and separate indices of systolic and diastolic function into inspiratory, early expiratory, and late expiratory phases of respiration. We then compared cardiac parameters during normal breathing and with various respiratory loads. Variations in inspiratory pressure had a small impact on systolic pressure and function. Conversely, diastolic pressure strongly correlated with negative inspiratory pressure. Cardiac pressures were less affected by respiration during expiration; late expiration was the most stable respiratory phase. In conclusion, inspiration is a large confounding influence on diastolic pressure, but minimally affects systolic pressure. Performing cardiac hemodynamic analysis by accounting for respiratory phase yields more accuracy and analytic confidence to the assessment of diastolic function.

Markers of Myocardial Damage Predict Mortality in Patients With Aortic Stenosis.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is increasingly used for risk stratification in aortic stenosis (AS). However, the relative prognostic power of CMR markers and their respective thresholds remains undefined. OBJECTIVES: Using machine learning, the study aimed to identify prognostically important CMR markers in AS and their thresholds of mortality. METHODS: Patients with severe AS undergoing AVR (n = 440, derivation; n = 359, validation cohort) were prospectively enrolled across 13 international sites (median 3.8 years' follow-up). CMR was performed shortly before surgical or transcatheter AVR. A random survival forest model was built using 29 variables (13 CMR) with post-AVR death as the outcome. RESULTS: There were 52 deaths in the derivation cohort and 51 deaths in the validation cohort. The 4 most predictive CMR markers were extracellular volume fraction, late gadolinium enhancement, indexed left ventricular end-diastolic volume (LVEDVi), and right ventricular ejection fraction. Across the whole cohort and in asymptomatic patients, risk-adjusted predicted mortality increased strongly once extracellular volume fraction exceeded 27%, while late gadolinium enhancement >2% showed persistent high risk. Increased mortality was also observed with both large (LVEDVi >80 mL/m2) and small (LVEDVi ≤55 mL/m2) ventricles, and with high (>80%) and low (≤50%) right ventricular ejection fraction. The predictability was improved when these 4 markers were added to clinical factors (3-year C-index: 0.778 vs 0.739). The prognostic thresholds and risk stratification by CMR variables were reproduced in the validation cohort. CONCLUSIONS: Machine learning identified myocardial fibrosis and biventricular remodeling markers as the top predictors of survival in AS and highlighted their nonlinear association with mortality. These markers may have potential in optimizing the decision of AVR.

Lung-to-finger circulation time can be measured stably with high reproducibility by simple breath holding method in cardiac patients.

Lung to finger circulation time (LFCT) has been used to estimate cardiac function. We developed a new LFCT measurement device using a laser sensor at fingertip. We measured LFCT by measuring time from re-breathing after 20 s of breath hold to the nadir of the difference of transmitted red light and infrared light, which corresponds to percutaneous oxygen saturation. Fifty patients with heart failure were enrolled. The intrasubject stability of the measurement was assessed by the intraclass correlation coefficient (ICC). The ICC calculated from 44 cases was 0.85 (95% confidence interval: 0.77-0.91), which means to have "Excellent reliability." By measuring twice, at least one clear LFCT value was obtained in 89.1% of patients and the overall measurability was 95.7%. We conducted all LFCT measurements safely. High ICCs were obtained even after dividing patients according to age, cardiac index (CI); 0.85 and 0.84 (≥ 75 or < 75 years group, respectively), 0.81 and 0.84 (N = 26, ≥ or < 2.2 L/min/M2). These results show that our new method to measure LFCT is highly stable and feasible for any type of heart failure patients.

A randomized controlled protocol on the effect of moxibustion on the cardiac function and quality of life in patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is the final result of various cardiovascular diseases, with high morbidity and high mortality, which seriously threaten people's health and quality of life. It has become a public health problem in the world. There is currently no specific treatment. Moxibustion, as a complementary and replacement therapy, has advantages in the treatment of chronic heart failure, but it lacks standard clinical studies to verify it. Therefore, the purpose of this randomized controlled trial is to evaluate the effect of moxibustion on the heart function and quality of life of patients with CHF. METHODS: This is a prospective randomized controlled trial to study the effect of moxibustion on the heart function and quality of life of patients with CHF. This is approved by the clinical research ethics committee of our hospital. Patients were randomly divided into observation group (moxibustion combined with Western medicine treatment group) or control group (conventional Western medicine treatment group). There is a follow-up for 3 months after 6 weeks of treatment. Observation indicators include total effective rate of cardiac function improvement, Minnesota Living with Heart Failure Questionnaire , left ventricular ejection fraction , N-terminal pro-brain natriuretic peptide , 6-minute walk test , adverse reactions, etc. Data were analyzed using the statistical software package SPSS version 18.0 (Chicago, IL). DISCUSSION: This study will evaluate the clinical efficacy of moxibustion in the treatment of CHF. The results of this study will provide a reliable reference for the clinical choice of moxibustion as an adjuvant treatment for chronic heart failure. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/29XE7.

Clinical predictors and prognostic role of high Killip class in patients with a first episode of anterior ST-segment elevation acute myocardial infarction.

AIMS: Killip classification is a simple and fast clinical tool for risk stratification of patients presenting with acute coronary syndrome (ACS). However, the clinical features and predictors of high Killip class at admission, and its prognostic impact in patients presenting with anterior ST elevation MI (STEMI) as first clinical cardiovascular event are still poorly known. The aim of this study was to identify the predictors of high Killip class and its impact on in-hospital and follow-up outcomes. METHODS: We prospectively enrolled patients with unheralded anterior STEMI because of proximal or mid left anterior descending (LAD) artery categorized according to Killip classification. Patients' characteristics, in-hospital complications and major adverse cardiovascular events (MACEs; composite of all-cause death, heart failure hospitalization and new-onset ACS) at follow-up were collected. RESULTS: We enrolled 147 patients [age 66.16±13.33, 113 male patients (76.9%)]. Killip class III--IV occurred in 22 (15%) patients. The median duration of follow-up was 12 [6--15.1] months. At multivariate analysis age [hazard ratio 1.137, 95% CI (1.068--1.209), P < 0.001], prehospital cardiac arrest [hazard ratio 12.145, 95% CI (1.710--86.254), P = 0.013] and proximal LAD lesion [hazard ratio 5.066, 95% CI (1.400--18.334), P = 0.013] were predictive of Killip class III--IV at admission. At multivariate analysis, Killip class III--IV was an independent predictor of in-hospital mortality [hazard ratio 7.790, 95% CI (1.024--59.276], P = 0.047 and of MACEs [hazard ratio 4.155 (1.558--11.082), P = 0.004) at follow-up. CONCLUSION: Killip classification performed at the time of admission is a simple and useful clinical marker of a high risk of early and late adverse cardiovascular events.

Extracellular vesicles derived from myocardial infarction plasma inhibit BMSCs apoptosis and enhance cardiac function via AKT signaling pathway.

This study aimed to investigate whether extracellular vesicles (EVs) secreted in myocardial infarction (MI) plasma could protect against apoptosis of bone marrow mesenchymal stem cells (BMSCs) following hypoxia or serum deprivation in vitro and improve cardiac function following MI in vivo. The plasma samples were taken from female rats 24 h after MI. EVs were obtained and co-cultured with BMSCs. We found that EVs could be taken up by BMSCs. Co-culturing with EVs attenuated hypoxia-induced apoptosis of BMSCs in EVs in a dose-dependent manner, which was reversed by the pharmacological inhibition of AKT signaling. Co-culturing with EVs improved transplantation efficiency and blunted MI-induced apoptosis of BMSCs in vivo. Furthermore, transplantation of BMSCs together with EVs can effectively promote the increase in capillary density both at the border and central zone of myocardium and ameliorate myocardial remodeling in MI rats. BMSCs and EVs transplantation treatment exhibited significant improvements in ejection fraction, fraction shortening, left ventricular end-diastolic dimensions, and left ventricular end-systolic dimensions, as evaluated by echocardiography four weeks after MI in rats. Finally, levels of differentiation- and apoptosis-related microRNAs expression in EVs that may mediate these effects were also identified by microarray and quantitative real-time PCR. In conclusion, the present results suggest a potential role of plasma-derived EVs in decreasing apoptosis of BMSCs by activating AKT signaling, promoting angiogenesis, ameliorating myocardial remodeling, and improving cardiac function in MI rats. EV application may be a novel option to ameliorate the therapeutic efficiency of BMSCs to improve cardiac function following MI.

Comparison of IQOS (heated tobacco) and cigarette smoking on cardiac functions by two-dimensional speckle tracking echocardiography.

AIMS: IQOS is a novel tobacco product claimed to be safer than conventional cigarette smoking due to the heat-not-burn system. This study aimed to evaluate the acute effects of IQOS smoking on myocardial systolic and diastolic functions and also compare the acute impacts of IQOS with cigarette smoking. METHODS: In this prospective study, twenty-seven healthy participants who were using IQOS were included. Transthoracic echocardiography was performed three times for each participant; before smoking any tobacco product (group1), after IQOS smoking (group 2), after cigarette smoking (group3). In addition to conventional echocardiographic measurements, left ventricle (LV) and right ventricle (RV) strain analyses were performed by speckle tracking echocardiography. RESULTS: In comparison with non-smoking status, LV global longitudinal strain (GLS) decreased after IQOS and cigarette smoking (-18.9 ± 2.4% in baseline vs. -17.9 ± 2.4% in IQOS vs. -17.9 ± 2.8% in cigarette smoking; p = 0.003, p = 0.001; respectively). LV global circumferential strain (GCS) reduced after IQOS and cigarette smoking (-19.8 ± 4.4% in baseline vs. -18.3 ± 3.9% in IQOS vs. -17.5 ± 3.9% in cigarette smoking; p = 0.005, p < 0.001; respectively). RV GLS was significantly lower in groups smoking IQOS and cigarette (-23.2 ± 4.6% in baseline vs. -21.4 ± 4.1% in IQOS vs. -19.4 ± 4.1% in cigarette smoking; p < 0.001, p = 0.001; respectively). CONCLUSION: IQOS (heat-not-burn) tobacco smoking impairs myocardial systolic and diastolic functions in the acute phase like conventional cigarette smoking. The use of IQOS is rising among young adults in recent years, so further studies should be designed to evaluate the chronic effects of IQOS on myocardial function.

Functional testing for variant prioritization in a family with long QT syndrome.

Next-generation sequencing platforms are being increasingly applied in clinical genetic settings for evaluation of families with suspected heritable disease. These platforms potentially improve the diagnostic yield beyond that of disease-specific targeted gene panels, but also increase the number of rare or novel genetic variants that may confound precise diagnostics. Here, we describe a functional testing approach used to interpret the results of whole exome sequencing (WES) in a family presenting with syncope and sudden death. One individual had a prolonged QT interval on electrocardiogram (ECG) and carried a diagnosis of long QT syndrome (LQTS), but a second individual did not meet criteria for LQTS. Filtering WES results for uncommon variants with arrhythmia association identified four for further analyses. In silico analyses indicated that two of these variants, KCNH2 p.(Cys555Arg) and KCNQ1 p.(Arg293Cys), were likely to be causal in this family's LQTS. We subsequently performed functional characterization of these variants in a heterologous expression system. The expression of KCNQ1-Arg293Cys did not show a deleterious phenotype but KCNH2-Cys555Arg demonstrated a loss-of-function phenotype that was partially dominant. Our stepwise approach identified a precise genetic etiology in this family, which resulted in the establishment of a LQTS diagnosis in the second individual as well as an additional asymptomatic family member, enabling personalized clinical management. Given its ability to aid in the diagnosis, the application of functional characterization should be considered as a value adjunct to in silico analyses of WES.

Decreased pulmonary artery distensibility as a marker for severity in acute pulmonary embolism patients undergoing ECG-gated CTPA.

To investigate the characteristics of pulmonary artery distensibility (PAD) in patients with acute pulmonary embolism (APE) and to assess whether a relationship exists between PAD and the disease severity. Clinical and radiological data of 30 APE patients who underwent retrospective electrocardiogram (ECG)-gated computed tomography pulmonary angiography (CTPA) with a definite diagnosis of APE were retrospectively reviewed in the present study, including 15 subjects in severe (SPE) group and 15 subjects in non-severe (NSPE) group. PAD and cardiac function parameters were compared between the two groups, their relationships were investigated, and receiver operating characteristic (ROC) curves were used to determine the sensitivity and specificity of the above parameters for the diagnosis of APE severity. The PAD decreased in the following order: NSPE group (6.065 ± 2.114) × 10-3 (%/mmHg), and SPE group (4.334 ± 1.777) × 10-3 (%/mmHg) (P < 0.05). All the cardiac function parameters except RA/LAdiameter showed statistically significant different values between the two groups (P < 0.05). As APE severity increased, the cardiac morphological measurements of RV/LVdiameter, RV/LVarea, RVEDV/LVEDV and RVESV/LVESV increased. There was a weak to moderate negative correlation between PAD and PAmax, PAmin, PA/AAmin, PA/AAmax, RV/LVdiameter, RV/LVarea (r = -0.393 to -0.625), that is, PAD was inversely correlated with cardiac function parameters. There was a moderate negative correlation between PAD and hemoptysis(r = -0.672). The area under the ROC curve (AUC) of PAD was 0.724, the critical value was 4.137 × 10-3  mm/Hg, and the sensitivity and specificity were 60.0% and 93.3%, respectively. PAmin showed the strongest discriminatory power to identify high-risk patients (AUC = 0.827), with the highest sensitivity of 100%, which was also achieved by RA/LAarea. The PAD obtained by retrospective ECG-gated CTPA could be an indicator to be used in the evaluation of the presence and severity of APE.

Relationship between extreme obesity and mortality in patients with reduced ejection fraction.

AIMS: Although obesity is associated with increased mortality, epidemiologic studies in heart failure have reported lower mortality in obese patients compared with matched nonobese patients (the 'obesity paradox'). However, the relationship between survival and extreme (morbid) obesity (BMI ≥ 40) is poorly understood. We evaluate survival in low ejection fraction patients across a range of BMI categories, including extreme obesity. METHODS: In a retrospective review, 12 181 consecutive patients receiving nuclear stress testing at a tertiary care center were stratified based on BMI and ejection fraction. Eight-year mortality data were collected using the social security death index. RESULTS: Normal ejection fraction patients (internal control, ejection fraction ≥50%) exhibited the J-shaped association between mortality and BMI that is observed in the general population. Among patients with reduced ejection fraction (<50%), survival improved as obesity increased (P < 0.0001). Those with extreme obesity had the lowest mortality (n = 1134, P < 0.05). CONCLUSION: In this cohort of reduced Ejection fraction patients, the obesity paradox was observed in all weight categories, with the highest survival of all observed in the extremely obese BMI category. This further supports hypotheses that an obesity-related physiologic phenomenon affects mortality in reduced ejection fraction patients.

Noninvasive Beat-To-Beat Stroke Volume Measurements to Determine Preload Responsiveness During Mini-Fluid Challenge in a Swine Model: A Preliminary Study.

ABSTRACT: Cardiac output (CO) is an important parameter in fluid management decisions for treating hemodynamically unstable patients in intensive care unit. The gold standard for CO measurements is the thermodilution method, which is an invasive procedure with intermittent results. Recently, electrical impedance tomography (EIT) has emerged as a new method for noninvasive measurements of stroke volume (SV). The objectives of this paper are to compare EIT with an invasive pulse contour analysis (PCA) method in measuring SV during mini-fluid challenge in animals and determine preload responsiveness with EIT. Five pigs were anesthetized and mechanically ventilated. After removing 25% to 30% of the total blood from each animal, multiple fluid injections were conducted. The EIT device successfully tracked changes in SV beat-to-beat during varying volume states, i.e., from hypovolemia and preload responsiveness to target volume and volume overload. From a total of 50 100-mL fluid injections on five pigs (10 injections per pig), the preload responsiveness value was as large as 32.3% in the preload responsiveness state while in the volume overload state it was as low as -4.9%. The bias of the measured SV data using EIT and PCA was 0 mL, and the limits of agreement were ±3.6 mL in the range of 17.6 mL to 51.0 mL. The results of the animal experiments suggested that EIT is capable of measuring beat-to-beat SV changes during mini-fluid challenge and determine preload responsiveness. Further animal and clinical studies will be needed to demonstrate the feasibility of the EIT method as a new tool for fluid management.