Editorial for Special Issue "Advance in Diagnostic and Management of Ischemic Heart Disease".

Ischemic heart disease is one of the leading causes of morbidity and mortality worldwide [...].

The Association between Apolipoprotein B, Cardiovascular Risk Factors and Subclinical Atherosclerosis-Findings from the SEPHAR National Registry on Hypertension in Romania.

The present study aimed to investigate the association between apolipoprotein B (Apo B) and classical features associated with clinical or subclinical atherosclerosis. A total of 811 adult patients from the general Romanian population, included in the national SEPHAR registry on hypertension, were divided into two groups based on Apo B value (low versus high Apo B with a cut-off established at 130 mg/dL) and subsequently into four subgroups according to the cut-offs recommended by the 2021 ESC Guidelines on Cardiovascular Disease Prevention. In all patients, lipid profile, uric acid, full blood count and presence of significant carotid plaques were assessed. Apo B levels were positively correlated with proatherogenic lipids (total cholesterol, triglycerides and LDL-cholesterol, p < 0.0001) and negatively correlated with HDL cholesterol (all p < 0.05). In comparison with patients with low Apo B levels, those with elevated Apo B levels more frequently presented significant carotid plaques (17% vs. 19% vs. 28% vs. 46%, p < 0.0001). Univariate regression analysis identified a strong association between the level of uric acid and increased value of Apo B in the four subgroups (uric acid 4.8 +/- 1.3 vs. 5 +/- 1.6 vs. 5.1 +/- 1.5 vs. 5.8 +/- 1.6, r = 0.2, p < 0.0001). The results of this nationwide registry on hypertension in Romania indicate that high Apo B may be considered as a risk factor for CVD, promoting atherosclerosis and associated with increased expression of classical markers of clinical or subclinical CVD.

Nine-Year Trends in Atrial Fibrillation Prevalence among Romanian Adult Hypertensives: A Post-Hoc Analysis of SEPHAR II-IV Surveys.

Objectives: There are limited epidemiological data regarding atrial fibrillation (AF) in hypertensive (HT) Romanian adults. We sought to evaluate AF prevalence trends in the SEPHAR surveys (Study for Evaluation of Prevalence of Hypertension and Cardiovascular Risk in an Adult Population in Romania) during a nine-year interval (2012−2016−2021). Methods: Three consecutive editions of a national epidemiological survey regarding HT included representative samples of subjects stratified by age, gender and area of residence (SEPHAR II-IV­in total, 5422 subjects, mean age 48.69 ± 16.65 years, 57.5% (n = 3116) females). A post-hoc analysis of AF prevalence and oral anticoagulation (OAC) rates was performed. AF definition was based on a documented medical history of AF and/or AF documentation by study electrocardiogram. Results: General AF prevalence was 5.5% (n = 297). AF prevalence in HT subjects was 8.9% (n = 209) and has risen since SEPHAR II­7.2% (n = 57) and SEPHAR III­8.1% (n = 72) to SEPHAR IV­11.8% (n = 80), respectively (p = 0.001). AF prevalence has increased in HT males (SEPHAR II­5.3% (n = 19), SEPHAR III­7.6% (n = 26) and SEPHAR IV­11.7% (n = 35) (p = 0.010)) and in HT from urban areas (SEPHAR II­7.8% (n = 37), SEPHAR III­7.8% (n = 40), SEPHAR IV­14.7% (n = 50), p < 0.001). In SEPHAR III-IV, only 19.3% (n = 23) of HT AF patients with OAC indication were anticoagulated. Conclusions: AF prevalence has increased by ~64% in hypertensive Romanian adults between 2012 and 2021. However, anticoagulation strategies may be suboptimal in patients with cardioembolic risk.

Lipoprofiling Assessed by NMR Spectroscopy in Patients with Acute Coronary Syndromes: Is There a Need for Fasting Prior to Sampling?

Most patients presenting in an emergency unit with acute coronary syndromes (ACS) (which include non-ST-elevation myocardial infarction (NSTEMI), ST-elevation MI (STEMI), and unstable angina) usually meet at least two cardiovascular risk factors, such as dyslipidemia, arterial hypertension, diabetes mellitus type 2, obesity, history of or current smoking, etc. Most ACS patients suffer from a type of dyslipidemia, and in addition to this there are ACS patients rushed into the emergency units for which the feeding status is unknown. Thus, we set out to evaluate the effect of fasting on 16 blood metabolite concentrations and 114 lipoprotein parameters on one control group and a group of statin-treated ACS patients hospitalized in a cardiovascular emergency unit, using Nuclear Magnetic Resonance (NMR) spectroscopy. The results indicated trends (in terms of number of cases, but not necessarily in terms of the magnitude of the effect) for as many as four metabolites and 48 lipoproteins. The effect was defined as a trend for results showing over 70% of the cases from either one or both groups that experienced parameter changes in the same direction (i.e., either increased or decreased). In terms of magnitude, the effect is rather low, leading to the overall conclusion that in cardiovascular (CV) emergency units, the blood samples analyzed in any feeding status would provide close results and very valuable information regarding prognosis and for fast decisions on patient's proper management.

IL-6, IL-1RA and Resistin as Predictors of Left Ventricular Remodelling and Major Adverse Cardiac Events in Patients with Acute ST Elevation Myocardial Infarction.

Despite continuous advances in diagnostic and therapeutic methods, acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. Considering the role of inflammation in AMI etiopathogenesis, we aimed to explore the role of a group of three inflammatory cytokines (IL-1RA, IL-6 and resistin) as an independent prognostic factor for LVR assessed by 3D echocardiography and MACE in patients with STEMI. We enrolled 41 patients with STEMI who underwent primary PCI. We assessed the occurrence of LVR (defined as an increase of over 20% in end-diastolic left ventricular volume at 6 months compared with baseline values) and MACE. Using the enzyme-linked immunosorbent assays (ELISA) method, we measured plasmatic levels of IL-6, IL-1RA and resistin (within 48 h after AMI and at 6 months). Out of 41 STEMI patients, 20.5% presented signs of LVR at follow up, and in 24.4%, MACE occurred. In univariate logistic regression analysis, baseline levels of IL-6 (OR = 1.042, p = 0.004), IL-1RA (OR = 1.004, p = 0.05) and resistin (OR = 1.7, p = 0.007) were all significantly associated with LVR. ROC analysis showed that the three cytokines as a group (AUC 0.946, p = 0.000) have a better predictive value for LVR than any individual cytokine. The group of cytokines also proved to have a better predictive value for MACE together than separately (AUC = 0.875, p = 0.000 for ROC regression model). IL-6, IL-1RA and resistin plasma levels at baseline have a good predictive value both as independent variables and also as a group for the development of adverse LVR and MACE at 6 months follow up after STEMI.

The Role of Left-Atrial Mechanics Assessed by Two-Dimensional Speckle-Tracking Echocardiography to Differentiate Hypertrophic Cardiomyopathy from Hypertensive Left-Ventricular Hypertrophy.

Hypertrophic cardiomyopathy (HCM) and arterial hypertension (HTN) are conditions with different pathophysiology, but both can result in left-ventricular hypertrophy (LVH). The role of left-atrial (LA) functional changes detected by two-dimensional speckle-tracking echocardiography (STE) in indicating LVH etiology is unknown. METHODS: We aimed to characterize LA mechanics using STE in LVH patients with HCM and HTN. LA 2D volumetric and STE parameters were analyzed in 86 LVH patients (43 HCM and 43 isolated HTN subjects) and 33 age- and sex-matched controls. RESULTS: The volumetric study showed that LA reservoir and conduit function were impaired in the HCM group compared to controls, while, in the HTN group, only LA conduit function was deteriorated. The HCM group had all three STE-derived LA functions impaired compared to controls. The HTN group, consistently with volumetric analysis, had solely LA conduit function reduced compared to controls. Ratios of LA booster-pump strain (S) and strain rate (SR) to interventricular septum (IVS) thickness were the most accurate parameters to discriminate between HCM and HTN. The subgroup harboring sarcomeric pathogenic (P)/likely pathogenic (LP) variants had reduced LA booster-pump S and SR compared with the genotype-negative subgroup. CONCLUSIONS: LA reservoir, conduit, and pump functions are decreased in HCM compared to HTN patients with similar LVH. We report the ratios between LA contraction S/SR and IVS thickness as novel parameters with high accuracy in discriminating LVH due to HCM. The presence of P/LP variants in sarcomeric or sarcomeric-associated genes could be associated with more severe LA dysfunction.

MicroRNAs in Acute ST Elevation Myocardial Infarction-A New Tool for Diagnosis and Prognosis: Therapeutic Implications.

Despite diagnostic and therapeutic advances, coronary artery disease and especially its extreme manifestation, ST elevation myocardial infarction (STEMI), remain the leading causes of morbidity and mortality worldwide. Early and prompt diagnosis is of great importance regarding the prognosis of STEMI patients. In recent years, microRNAs (miRNAs) have emerged as promising tools involved in many pathophysiological processes in various fields, including cardiovascular diseases. In acute coronary syndromes (ACS), circulating levels of miRNAs are significantly elevated, as an indicator of cardiac damage, making them a promising marker for early diagnosis of myocardial infarction. They also have prognostic value and great potential as therapeutic targets considering their key function in gene regulation. This review aims to summarize current information about miRNAs and their role as diagnostic, prognostic and therapeutic targets in STEMI patients.

The E/e' Ratio-Role in Risk Stratification of Acute Heart Failure with Preserved Ejection Fraction.

Background and Objectives: Heart failure with preserved ejection fraction (HFpEF) remains a worldwide management problem. Although there is a general effort for characterizing this population, few studies have assessed the predictive value of the echocardiographic E/e' ratio in patients with acute HFpEF. The aim of the study was to identify groups with different prognosis in patients hospitalized with a first acute episode of HFpEF. Materials and Methods: The primary endpoint of the study was heart failure readmissions (HFR) at 6 months, while the secondary outcome was six-month mortality. We consecutively enrolled 91 patients hospitalized for the first time with acute HFpEF. We examined the E/e' ratio as an independent predictor for HFR using univariate regression. Results: We identified and validated the E/e' ratio as an independent predictor for HFR. An E/e' ratio threshold value of 13.80 was calculated [(area under the receiver operating characteristic curve (AUROC) = 0.693, sensitivity = 78.60%, specificity = 55%, p < 0.004)] and validated as an inflection point for an increased number of HFR. Thus, we divided the study cohort into two groups: group 1 with an E/e' ratio < 13.80 (n = 39) and group 2 with an E/e' ratio > 13.80 (n = 49). Compared to group 1, group 2 had an increased number of HFR (p = 0.003) and a shorter time to first HFR (p = 0.002). However, this parameter did not influence all-cause mortality within six months (p = 0.84). Conclusions: The dimensionless E/e' ratio is a useful discriminator between patients with acute HFpEF. An E/e' value over 13.80 represents a simple, yet effective instrument for assessing the HFR risk. However, all-cause mortality at six months is not influenced by the E/e' ratio.

A Practical Risk Score for Prediction of Early Readmission after a First Episode of Acute Heart Failure with Preserved Ejection Fraction.

BACKGROUND: The first admission for acute heart failure with preserved ejection fraction (HFpEF) drastically influences the short-term prognosis. Baseline characteristics may predict repeat hospitalization or death in these patients. METHODS: A 103 patient-cohort, admitted for the first acute HFpEF episode, was monitored for six months. Baseline characteristics were recorded and their relation to the primary outcome of heart failure readmission (HFR) and secondary outcome of all-cause mortality was assessed. RESULTS: We identified six independent determinants for HFR: estimated glomerular filtration rate (eGFR) (p = 0.07), hemoglobin (p = 0.04), left ventricle end-diastolic diameter (LVEDD) (p = 0.07), E/e' ratio (p = 0.004), left ventricle outflow tract velocity-time integral (LVOT VTI) (p = 0.045), and diabetes mellitus (p = 0.06). Three of the variables were used to generate a risk score for HFR: LVEDD, E/e', LVOT VTI -DEI Score = - 28.763 + 4.558 × log (LVEDD (mm)) + 1.961 × log (E/e' ratio) + 1.759 × log (LVOT VTI (cm)). Our model predicts a relative amount of 20.50% of HFR during the first 6 months after the first acute hospitalization within the general population with HFpEF with a DEI Score over -0.747. CONCLUSIONS: We have identified three echocardiographic parameters (LVEDD, E/e', and LVOT VTI) that predict HFR following an initial acute HFpEF hospitalization. The prognostic DEI score demonstrated good accuracy.

Yield of Rare Variants Detected by Targeted Next-Generation Sequencing in a Cohort of Romanian Index Patients with Hypertrophic Cardiomyopathy.

BACKGROUND: The aim of this study was to explore the rare variants in a cohort of Romanian index cases with hypertrophic cardiomyopathy (HCM). METHODS: Forty-five unrelated probands with HCM were screened by targeted next generation sequencing (NGS) of 47 core and emerging genes connected with HCM. RESULTS: We identified 95 variants with allele frequency < 0.1% in population databases. MYBPC3 and TTN had the largest number of rare variants (17 variants each). A definite genetic etiology was found in 6 probands (13.3%), while inconclusive results due to either known or novel variants were established in 31 cases (68.9%). All disease-causing variants were detected in sarcomeric genes (MYBPC3 and MYH7 with two cases each, and one case in TNNI3 and TPM1 respectively). Multiple variants were detected in 27 subjects (60%), but no proband carried more than one causal variant. Of note, almost half of the rare variants were novel. CONCLUSIONS: Herein we reported for the first time the rare variants identified in core and putative genes associated with HCM in a cohort of Romanian unrelated adult patients. The clinical significance of most detected variants is yet to be established, additional studies based on segregation analysis being required for definite classification.

Left Atrial Strain for Predicting Atrial Fibrillation Onset in Hypertensive Patients.

INTRODUCTION: We aimed to find new predictive parameters for atrial fibrillation (AF) onset in hypertensive patients using two-dimensional (2D) conventional and speckle tracking echocardiography of the left atrium (LA). METHODS: One hundred and eight patients with essential hypertension (HTN) were prospectively enrolled, from which 67 patients had no other important comorbidities (HTN group), while 41 patients had a recent AF episode, but were in sinus rhythm at the moment of enrollment (HTN and AF group). LA diameters and maximal volume, LV mass, LV ejection fraction and diastolic function were assessed through 2D conventional echocardiography. Moreover, peak longitudinal and contractile strain of LA walls (PALS and PACS, respectively) were analyzed by speckle tracking technique. Patients were followed up for 1 year and recurrent 24-h rhythm monitoring was done, in order to identify atrial fibrillation. RESULTS: Age and time from diagnosis of HTN were higher in HTN and AF group than in HTN group (68.02 ± 19 years versus 57.2 ± 1.52 years, p = 0.001 and 62.2 ± 9.2 months versus 40.4 ± 6.4 months, p = 0.04). All LA diameters and LA maximal volume were significantly larger in HTN and AF group (for LA antero-posterior diameter p = 0.02, for all the rest p < 0.0001). LV ejection fraction was preserved in both groups, being significantly lower in HTN and AF patients (58.44 ± 0.79 versus 60.75 ± 0.57, p = 0.02). LV mass was higher in HTN and AF group and these patients had also a more severe diastolic dysfunction, (E/A ratio 1.8 ± 0.51 versus 0.9 ± 0.02, p = 0.04) and lower septal and lateral A' velocities (p < 0.0001 and p = 0.002). The peak LA longitudinal and contractile strain values were also significantly lower in HTN and AF group versus HTN group (for all p < 0.0001). Among the echocardiographic parameters, we identified PALS and PACS as predictors for AF, with a good discriminating capacity (AUC = 0.88 for PALS and AUC = 0.86 for PACS). CONCLUSIONS: Compared to patients with isolated hypertension, patients with hypertension and AF display several echocardiographic differences. Among them, LA strain parameters could be useful predictors of AF occurrence in hypertensive patients.

The Relationship Between Psychosocial Status and Hypertensive Condition.

PURPOSE OF REVIEW: The aim of the paper is to test the influence of social status and psychological well-being (independent variables) on hypertensive condition (dependent variable), when adjusting for traditional risk factors of cardiovascular disease (control variables). The analysis is based on data collected from SEPHAR III, a nationally representative epidemiologic study of the Romanian adult population. RECENT FINDINGS: Understanding the social roots of health issues is of considerable importance in developing effective strategies and policies. In this context, most studies explain the influence of social and psychological indicators on hypertension by considering the mediating effects of class-based lifestyle practices, i.e., the full range of economic, social, or symbolic resources available to particular social classes. However, the effect of traditional risk factors of cardiovascular disease in shaping the relationship between psychosocial status and hypertension has remained mostly unexplored. The influence of socioeconomic status and psychological well-being on hypertensive condition is assimilated by age as a variable with both biological and social foundations. Age appears not only as a risk factor for high blood pressure but also as an emergent component of psychosocial status. Furthermore, people without higher education are more likely to be known hypertensives with uncontrolled blood pressure values. Social and economic vulnerabilities (e.g., age, education) are interrelated with several health conditions, which support the necessity to develop and implement integrated public policies based on interventions coordinated across several domains. Moreover, social and psychological determinants that predispose to certain health risks should be considered in medical practice.

Factors associated with use of percutaneous coronary intervention among elderly patients presenting with ST segment elevation acute myocardial infarction (STEMI): Results from the ISACS-TC registry.

BACKGROUND: A substantial proportion of elderly with ST segment elevation myocardial infarction (STEMI) do not undergo percutaneous coronary intervention (PCI). We sought to investigate factors associated with the decision not to perform coronary angiography at admission in these patients. METHODS: We evaluated 1315 STEMI patients aged ≥75years old enrolled in the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS TC) registry between October 2010 and February 2015. They were compared with 6667 patients aged <75years old enrolled in the registry in the same time frame. RESULTS: Elderly patients were less likely to undertake invasive coronary evaluation compared with younger patients (62.1% vs. 78.9; p<0.001%). In the older group there were a lower proportion of patients presenting <12h after symptom onset (66.5% vs.76.9%, p<0.001), and a higher prevalence of comorbidities. Few elderly were treated with current recommended evidence based treatments (aspirin, clopidogrel, heparins, beta-blocker, statins, and ACE-inhibitors). Logistic analysis adjusted for age and sex showed that older age was associated with underuse of coronary angiography (OR 0.46, 95% CI: 0.41-0.53, p<0.001). Clinical factors that were associated with underuse of angiography in patients over 75 were: female sex (OR: 0.77), presence of comorbidities (OR: 0.91), anemia (OR: 0.44) and late hospital admission (OR: 0.89). CONCLUSIONS: In the ISACS-TC, more than one third of the elderly with STEMI did not undergo coronary angiography at admission. Sex, comorbidities, and late hospital admission were independent factors associated with the underuse of PCI in these patients.