T-wave inversion through inhomogeneous voltage diffusion within the FK3V cardiac model.

The heart beats are due to the synchronized contraction of cardiomyocytes triggered by a periodic sequence of electrical signals called action potentials, which originate in the sinoatrial node and spread through the heart's electrical system. A large body of work is devoted to modeling the propagation of the action potential and to reproducing reliably its shape and duration. Connection of computational modeling of cells to macroscopic phenomenological curves such as the electrocardiogram has been also intense, due to its clinical importance in analyzing cardiovascular diseases. In this work, we simulate the dynamics of action potential propagation using the three-variable Fenton-Karma model that can account for both normal and damaged cells through a the spatially inhomogeneous voltage diffusion coefficient. We monitor the action potential propagation in the cardiac tissue and calculate the pseudo-electrocardiogram that reproduces the R and T waves. The R-wave amplitude varies according to a double exponential law as a function of the (spatially homogeneous, for an isotropic tissue) diffusion coefficient. The addition of spatial inhomogeneity in the diffusion coefficient by means of a defected region representing damaged cardiac cells may result in T-wave inversion in the calculated pseudo-electrocardiogram. The transition from positive to negative polarity of the T-wave is analyzed as a function of the length and the depth of the defected region.

Visceral fat and cardiometabolic future in children and adolescents: a critical update.

Cardiovascular disease (CVD) is a process whose pathogenetic mechanisms start very early in life. Recently, the importance of visceral adipose tissue (VAT) has been highlighted in the development of CVD. VAT does not always depend on body mass index (BMI) and has been implicated in unfavorable metabolic activity and cardiovascular adverse events. Abnormally high deposition of VAT is associated with metabolic syndrome, obesity-associated phenotype, and cardiometabolic risk factors. Although the importance of visceral fat has not been studied broadly or extensively in long-term studies in children and adolescents, it appears that it does not have the same behavior as in adults, it is related to the appearance of cardiac risk factors. In adolescents, it plays a role in the pathogenesis of CVD that occur later in adulthood. Excess body weight and adiposity may lead to the development of early myocardial and pathological coronary changes in childhood. The purpose of this review is to summarize the risk factors, the clinical significance, and the prognostic role of visceral obesity in children and adolescents. In addition, extensive reference is made to the most commonly used techniques for the evaluation of VAT in clinical settings. IMPACT: Visceral obesity, plays an important role in cardiovascular health from very early in an individual's life. Visceral adipose tissue (VAT) distribution is not entirely related to body mass index (BMI) and provides additional prognostic information. There is a need to pay more attention to the assessment of VAT in young people, to develop methods that would go beyond the measurement of only BMI in clinical practice and to identify individuals with excess visceral adiposity and perhaps to monitor its changes.

Hybrid imaging of neuroendocrine tumors in the heart: Union is strength.

Cardiac neuroendocrine tumors (NETs) are particularly rare tumors that can lead to a very poor clinical outcome, partly because of metastases but mainly because of manifestations of the hormonal activity they exhibit. Prompt diagnosis is important in order to start the most effective treatment for their removal or management, with the fewest complications. They are often difficult to diagnose, especially in their early stages. One of the reasons for this is that the heart is an organ with a high rate of metabolism and is located in close proximity to other high-metabolism organs. In addition, the anatomic location and their small size render their diagnosis extremely challenging. In recent years, hybrid imaging methods have revolutionized the diagnostic approach to oncology patients and have established a place in the diagnosis of cardiac NETs, because they provide both anatomical and functional information at the same time. Positron emission tomography/computed tomography (PET/CT), PET/magnetic resonance imaging (PET/MRI) and single-photon emission computed tomography/CT (SPECT/CT) are widely used in clinical practice because of the very important metabolic information, the high sensitivity and specificity. However, prospective studies are needed to confirm the true clinical and prognostic value of various hybrid imaging diagnostic techniques in cardiac NETs.

Artificial intelligence-based opportunistic screening for the detection of arterial hypertension through ECG signals.

OBJECTIVES: Hypertension is a major risk factor for cardiovascular disease (CVD), which often escapes the diagnosis or should be confirmed by several office visits. The ECG is one of the most widely used diagnostic tools and could be of paramount importance in patients' initial evaluation. METHODS: We used machine learning techniques based on clinical parameters and features derived from the ECG, to detect hypertension in a population without CVD. We enrolled 1091 individuals who were classified as hypertensive or normotensive, and trained a Random Forest model, to detect the existence of hypertension. We then calculated the values for the Shapley additive explanations (SHAP), a sophisticated feature importance analysis, to interpret each feature's role in the Random Forest's results. RESULTS: Our Random Forest model was able to distinguish hypertensive from normotensive patients with accuracy 84.2%, specificity 78.0%, sensitivity 84.0% and area under the receiver-operating curve 0.89, using a decision threshold of 0.6. Age, BMI, BMI-adjusted Cornell criteria (BMI multiplied by RaVL+SV 3 ), R wave amplitude in aVL and BMI-modified Sokolow-Lyon voltage (BMI divided by SV 1 +RV 5 ), were the most important anthropometric and ECG-derived features in terms of the success of our model. CONCLUSION: Our machine learning algorithm is effective in the detection of hypertension in patients using ECG-derived and basic anthropometric criteria. Our findings open new horizon in the detection of many undiagnosed hypertensive individuals who have an increased CVD risk.

A case series of Brugada syndrome with a novel mutation in the ankyrin-B gene: an unusual unmasking in acute myocarditis.

BACKGROUND: Brugada syndrome (BrS) is a genetically heterogeneous channelopathy that may lead to sudden death. We report a novel mutation of the ankyrin-B gene that is probably related to the occurrence of BrS in two brothers. CASE SUMMARY: First, we present the case of a 27-year-old male who was admitted to the hospital with acute myocarditis. The patient showed left ventricular dysfunction and was given carvedilol. Six days later, while asymptomatic and afebrile, the patient exhibited an electrocardiogram (ECG) with repolarization 'saddleback' ST changes in V2. A procainamide provocative test was performed with a response for Type 1 Brugada ECG pattern. Genetic testing revealed a novel mutation, c.5418T>A (+/-) (p.His1806Gln), in the ankyrin-B gene encoding. His 34 years old brother had an ECG J point elevation in leads V1 and V2 of 1 mm not fulfilling diagnostic criteria for Brugada ECG pattern. He also experienced arrhythmia-related syncope. Flecainide provocation test changed ECG towards a Type 1 Brugada pattern. A subcutaneous implantable defibrillator (ICD) was implanted. Patient 1 remains asymptomatic while Patient 2 experienced an appropriate ICD shock during follow-up. DISCUSSION: In this case series, two brothers with BrS exhibited the same mutation of the ankyrin-B gene. Ankyrin-B is associated with the stability of plasma membrane proteins in the voltage-gated ion channels. Our finding provides a foundation for further investigation of this mutation in relation to BrS. Moreover, the timing of its presentation raises concerns as to whether myocarditis or beta-blockers are associated with the presentation of BrS ECG.

Long-term prognostic value of myocardin expression levels in non-ischemic dilated cardiomyopathy.

The mortality of patients with non-ischemic dilated cardiomyopathy (NIDCM) remains substantial. We evaluated gene expression levels of myocardin, an early cardiac gene, in the peripheral blood cells of NIDCM patients as a prognostic biomarker in their long-term outcome and mortality from congestive HF (CHF). We retrospectively analyzed 101 consecutives optimally treated NIDCM patients of Cretan origin who were enrolled from the HF clinic of our hospital from November 2005 to December 2008. Our patient data were either taken from their medical files or recorded during visits to the HF unit or hospitalizations. Follow-up was carried out by telephone interview and by accessing information from general practitioners and cardiologists in private practice. The median follow-up period was 8 years (mean follow-up 7 ± 3.4 years). The overall mortality during follow-up was 61.4%, while mortality due to congestive heart failure (CHF) was 49.5%. Higher CHF and all-cause mortality were observed in patients with myocardin levels < 14.26 (p < 0.001 for both CHF and all-cause mortality). A multivariate Cox regression analysis showed that myocardin level of expression had independent significant prognostic value for the risk of death from CHF (HR 14.5, 95% confidence interval (CI) 5.3-39) in those patients. Peripheral blood cells gene expression of myocardin, an early myocardial marker, may serve as prognostic biomarkers of the long-term outcome of patients with NIDCM. Our findings open new prospects in the risk stratification of these patients.

Detection of abnormal left ventricular geometry in patients without cardiovascular disease through machine learning: An ECG-based approach.

Cardiac remodeling is recognized as an important aspect of cardiovascular disease (CVD) progression. Machine learning (ML) techniques were applied to basic clinical parameters and electrocardiographic features, in order to detect abnormal left ventricular geometry (LVG) even before the onset of left ventricular hypertrophy (LVH), in a population without established CVD. The authors enrolled 528 patients with and without essential hypertension, but no other indications of CVD. All patients underwent a full echocardiographic evaluation and were classified into 3 groups; normal geometry (NG), concentric remodeling without LVH (CR), and LVH. Abnormal LVG was identified as increased relative wall thickness (RWT) and/or left ventricular mass index (LVMi). The authors trained supervised ML models to classify patients with abnormal LVG and calculated SHAP values to perform feature importance and interaction analysis. Hypertension, age, body mass index over the Sokolow-Lyon voltage, QRS-T angle, and QTc duration were some of the most important features. Our model was able to distinguish NG from CR+LVH combined, with 87% accuracy on an unseen test set, 75% specificity, 97% sensitivity, and area under the receiver operating curve (AUC/ROC) equal to 0.91. The authors also trained our model to classify NG and CR (NG + CR) against those with LVH, with 89% test set accuracy, 93% specificity, 67% sensitivity, and an AUC/ROC value of 0.89, for a 0.4 decision threshold. Our ML algorithm effectively detects abnormal LVG even at early stages. Innovative solutions are needed to improve risk stratification of patients without established CVD, and ML may enable progress in this direction.

Clinical characteristics and management of patients with diabetes mellitus and stable coronary artery disease in daily clinical practice. The SCAD-DM Registry.

BACKGROUND: Patients with diabetes mellitus (DM) and coronary artery disease (CAD) represent a high-risk population, where comorbidities are common and the progression of coronary heart disease is relatively rapid and extensive. The present survey, conducted nationwide in a Eurozone country, Greece, with a properly organized national health system, aimed to record specific data from a significant number of patients with diabetes and documented stable CAD (SCAD). METHODS AND RESULTS: We conducted our survey across the country, in private and public primary, secondary, and tertiary care centers. A total of 1900 patients aged 71 ± 10 years old who suffered from both DM and chronic coronary syndromes were registered. Of the patients registered, 574 (30.24%) were women. It was found that 506 (26.6%) of the 1900 surveyed patients showed typical angina symptoms, while another 560 (29.5%) patients had developed angina-equivalent symptoms according to their history. Additionally, 324 (17%) patients had atypical symptoms that could not easily be attributed to existing CAD and the remaining 510 (26.8%) of the 1900 patients did not exhibit any angina symptoms during their daily activities. Functional testing for myocardial ischemia was not performed in 833 patients (43.8%). Myocardial scintigraphy was the most commonly used noninvasive technique (644 patients, 34%), while 492 patients (25.9%) had an exercise test and 159 (8.4%) underwent stress echocardiography. CONCLUSION: Real-world data in this specific high-risk population of diabetic patients with SCAD offer the opportunity to identify and improve diagnostic and therapeutic practice in the healthcare system of a European Union country.

Short-term effects of angiotensin receptor-neprilysin inhibitors on diastolic strain and tissue doppler parameters in heart failure patients with reduced ejection fraction: A pilot trial.

OBJECTIVE: Although sacubitril/valsartan has recently shown its long-term benefits on morbidity and mortality in symptomatic patients with chronic heart failure with reduced ejection fraction (HFrEF), its short-term effects on diastolic function remain uncertain. We sought to assess 30-day effects of sacubitril/valsartan on left ventricular (LV) diastolic paremeters determined by speckle tracking and tissue Doppler imaging (STI and TDI respectively) as well as their association with functional capacity change evaluated by peak oxygen uptake (VO2max) in stable patients with symptomatic HFrEF. METHODS: A total of 35 patients (aged 61 ± 9 years) eligible for sacubitril/valsartan underwent a complete two-dimension (2D) echocardiographic study and a cardiopulmonary exercise test at baseline and 30 days after the initiation of therapy. RESULTS: Significant improvements in ratio of trans-mitral inflow early diastolic velocity E to mitral annulus early diastolic velocity E' (ΔΕ//Ε' = -35.9%, p = 0.001), peak early diastolic strain rate SRE (ΔSRE = +22.5%, p = 0.024) and ratio E/SRE (ΔE/SRE = -33.2%, p = 0.025) were observed after 1-month therapy. Compared with baseline, VO2max also increased significantly by 16.7 % (p = 0.001). Baseline E/SRE and ΔE/SRE were the strongest independent predictors of VO2max improvement (beta = -0.43, p = 0.004 and beta = 0.45, p = 0.021 respectively) in the multivariate analysis. CONCLUSION: Sacubitril/valsartan was associated with early improvement in LV diastolic function determined by TDI and 2D STI. Baseline E/SRE was stronger than standard echocardiographic parameters in predicting the early benefit of sacubitril/valsartan therapy.

Long-term outcome of hypertensive patients with heart failure with mid-range ejection fraction: The significance of blood pressure control.

Heart failure (HF) with mid-range ejection fraction (HFmrEF) is a newly suggested entity in HF. Since it has been inadequately addressed, there is an urgent need to determine the profile of HFmrEF patients and the optimal approach to their management. The present study aimed to assess the long-term clinical outcomes of hypertensive patients with HFmrEF and the impact of blood pressure (BP) on their mortality and cardiovascular outcome. We performed a retrospective observational study that included 121 hypertensive patients with HFmrEF and 149 hypertensives with heart failure and preserved ejection fraction (HFpEF). The median follow-up was 84 months (22-122). Our analysis did not reveal any statistically significant difference between the two groups in total mortality (P = 0.34) or cardiovascular mortality (P = 0.54). The total mean survival time was 102.9 months (100.5-110.1), while the mean survival time was 105.3 months (80.4-90.2) in HFpEF and 97.6 months (92.7-102.6) in HFmrEF. An office systolic BP > 139 mm Hg and diastolic BP > 89 mm Hg were significantly associated with both all-cause mortality (P = 0.02 and P = 0.013, respectively) and cardiovascular mortality (P = 0.02 for both). In HFpEF patients, no significant association was found between outcome and office BP. HFpEF and HFmrEF have similar long-term outcomes. Suboptimal BP levels are a significant risk factor for an adverse outcome in HFmrEF. Our results emphasize the importance of good BP control in order to achieve better outcomes in hypertensives with impaired EF and HF symptomatology.

Salt-induced effects on microvascular function: A critical factor in hypertension mediated organ damage.

Salt has been linked very closely to the occurrence and complications of arterial hypertension. A large percentage of patients with essential hypertension are salt-sensitive; that is, their blood pressure increases with increased salt intake and decreases with its reduction. For this reason, emphasis is placed on reducing salt intake to better regulate blood pressure. In day-to-day clinical practice this is viewed as mandatory for hypertensive patients who are judged to be salt-sensitive. Previous studies have highlighted the negative effect of high-salt diets on macrovascular function, which also affects blood pressure levels by increasing peripheral resistances. More recent studies provide a better overview of the pathophysiology of microvascular disorders and show that they are largely due to the overconsumption of salt. Microvascular lesions, which have a major impact on the functioning of vital organs, are often not well recognized in clinical practice and are not paid sufficient attention. In general, the damage caused by hypertension to the microvascular network is likely to be overlooked, while reversion of the damage is only rarely considered as a therapeutic target by the treating physician. The purpose of this review is to summarize the impact and the harmful consequences of increased salt consumption in the microvascular network, their significance and pathophysiology, and at the same time to place some emphasis on their treatment and reversion, mainly through diet.

Analysis of Echocardiographic Markers and Pulse Wave Velocities in a Patient Who Developed New Cardiac Symptoms after Implantation of an Aortic Endograft.

Increased arterial stiffness has been related to altered cardiovascular hemodynamics, left ventricular hypertrophy, and a higher risk for cardiac events. Pulse wave velocity (PWV) has been used as a surrogate marker for arterial stiffness. Treatment of abdominal aortic aneurysms (AAAs) involves insertion of a rigid graft or endograft inside the arterial system which has been shown to increase arterial stiffness, but the cardiac implications of these alterations are mostly unknown. We report a case of a patient with a previous AAA surgical repair (>10 years ago) who developed a para-anastomotic pseudoaneurysm which was excluded with implantation of an endoluminal graft. From a cardiac perspective, this patient was asymptomatic and had a normal baseline preoperative evaluation. He had an initially high PWV (17 m/sec). Postprocedurally, the patient developed cardiac symptoms, and he underwent coronary angiography which indicated significant coronary artery disease, and he subsequently underwent bypass grafting. One week after the endovascular repair, the patient presented with an increased PWV at 21 m/sec. Echocardiographic indices were mostly unaltered (ejection fraction, left ventricular mass index, and left atrium volume index) compared with the preoperative evaluation, except for the global longitudinal strain which deteriorated from -25 to -21%. This case provides insight into hemodynamic alterations after implantation of an endograft which may result in deterioration of asymptomatic heart disease.

Troponin-I levels as a potential prognostic biomarker of sacubitril/valsartan treatment response in heart failure with reduced ejection fraction: Who will benefit most?

BACKGROUND: Despite robust data on the benefits of sacubitril/valsartan (LCZ696) in patients with chronic heart failure with reduced ejection fraction (HFrEF), there is no evidence yet on prespecified predictive markers of its efficacy. Hypothesis The objective of this study was to identify potential prognostic factors of LCZ696 treatment response. METHODS: We included 48 symptomatic patients with chronic HFrEF (left ventricular ejection fraction ≤35%) and New York Heart Association (NYHA) class II/III: Group A (N = 23) received LCZ696 (105 ± 30 mg twice daily), whereas it was not prescribed in group B (N = 25) according to physician's judgment. Analysis of biochemical parameters, cardiopulmonary exercise testing, and echocardiographic evaluation was performed at baseline and 6 months later. RESULTS: The baseline serum troponin-I levels (TnI) and peak oxygen uptake (VO2 max) were positively associated with the increase in VO2 max (ΔVO2 max = +14.11%, P < 0.05 vs group B) after sacubitril/valsartan treatment (r = 0.68, P = 0.001 and r = 0.57, P = 0.004, respectively). Positive correlations were reported between ΔVO2 max and the improvements in the ratio of early diastolic filling to myocardial tissue velocity (ΔE/E') and the tricuspid annular peak systolic velocity (ΔSa) in group A (r = 0.58, P = 0.004 and r = 0.60, P = 0.002, respectively). In multiple regression analysis, ΔVO2 max was correlated significantly with TnI (beta = 0.35, P = 0.048), ΔE/E' (beta = 0.36, P = 0.031) and ΔSa (beta = 0.37, P = 0.035). CONCLUSIONS: TnI levels may be an independent predictive marker of sacubitril/valsartan efficacy in HFrEF.

The long non-coding RNAs MHRT, FENDRR and CARMEN, their expression levels in peripheral blood mononuclear cells in patients with essential hypertension and their relation to heart hypertrophy.

Long non-coding RNAs (lncRNAs) participate in the modulation of cardiac hypertrophy, and they represent potential therapeutic targets in cardiovascular disease. We investigated the expression profiles of selected lncRNAs in peripheral blood mononuclear cells of patients with essential hypertension in relation to left ventricular hypertrophy. We assessed the expression levels of the lncRNAs MHRT, FENDRR and CARMEN using real-time reverse transcription polymerase chain reaction. Hypertensive patients showed significantly higher MHRT, FENDRR and CARMEN expression levels compared with healthy controls. In addition, we observed significant negative correlations of MHRT (r = -0.323, P = 0.003) and FENDRR (r = -0.380, P = 0.001) and a positive correlation of CARMEN (r = 0.458, P < 0.001) expression levels with left ventricular mass index. Our data reveal that the lncRNAs MHRT, FENDRR and CARMEN show distinct expression profiles in hypertensive patients and they possibly represent candidate therapeutic targets in hypertensive heart disease.

MicroRNAs in Peripheral Mononuclear Cells as Potential Biomarkers in Hypertensive Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: MicroRNAs (miRs) regulate gene expression and play an important role in ventricular and vascular remodeling. However, there are limited data regarding their role in heart failure with preserved ejection fraction (HFpEF). The aim of this study was to assess gene expression of miR-1, miR-133a, miR-21, miR-208b, miR-499, and miR-26b in peripheral blood mononuclear cells (PBMCs) in hypertensive patients with HFpEF and to evaluate their association with their exercise capacity. METHODS: We included 56 hypertensive patients with HFpEF (age 67.29 ± 7.75 years). Forty-two hypertensive patients without HFpEF (age 66.83 ± 7.17 years) served as controls. All subjects underwent a cardiopulmonary exercise test (CPXT). PBMCs were isolated and levels of miRs were determined by quantitative real-time reverse transcription polymerase chain reaction. RESULTS: For hypertensive patients with HFpEF, higher expression levels in PBMCs were found only for miR-26b (7.6 ± 7.3 vs. 4.0 ± 3.6, P = 0.002), miR-208b (28.8 ± 35.3 vs. 7.5 ± 13.3, P < 0.001), and miR-499 (14.2 ± 22.4 versus 3.5 ± 2.9, P = 0.001). The strongest correlations with CPXT parameters were found for miR-208b levels, which had a positive correlation with maximal oxygen uptake (peakVO2) (r = 0.671, P < 0.001), exercise duration (r = 0.445, P = 0.001), and minute ventilation-carbon dioxide production relationship (VE/VCO2) (r = 0.437, P = 0.001) in the HFpEF group. CONCLUSIONS: miR-26b, miR-208b, and miR-499 show a distinct in profile in hypertensive patients with HFpEF that is related with functional capacity. Further studies are needed to assess the role of miRs as prognostic tools or as therapeutic targets in those patients.

Bradykinin receptors gene expression in white adipose tissue in nondiabetic patients with coronary artery disease.

OBJECTIVES: Adipose tissue plays a key role in cardiovascular physiology. Kinin receptors are important determinant of the effect of adiposity on endothelial function and cardiovascular function. We examined the gene expression levels of kinin receptors in the subcutaneous white adipose tissue (sWAT) of nondiabetic patients with and without coronary artery disease (CAD). PATIENTS AND METHODS: We evaluated 21 patients with CAD (13 men, age: 68±8 years) and 23 patients without CAD (15 men, age: 66±5 years) who underwent catheterization through the femoral route. sWAT biopsies were obtained from the site of vessel puncture before the procedure and analyzed for bradykinin receptor type 1 (BKR1) and 2 (BKR2) gene expression by real-time quantitative PCR. RESULTS: Although BKR2 expression levels did not differ significantly (413.12±532.41 in CAD patients vs. 378.33±534.45 in controls, P=NS), BKR1 expression in sWAT was significantly greater in patients with CAD (352.69±455.12 vs. 46.5±46.7, P<0.05). Notably, BKR1 gene expression levels showed a significant positive correlation with BMI (r=0.45, P<0.002) and total cholesterol levels (r=0.53, P<0.001), and a negative correlation with fasting blood glucose (r=-0.4, P=0.006). CONCLUSION: There is a divergence in BKR1 gene expression in sWAT between patients with and without CAD and is associated with metabolic parameters. More studies are needed to determine the pathophysiological role of BKRs in adipogenesis, fat expansion, and atheromatous disease.