Left Ventricular-Arterial Coupling as an Independent Predictor of Adverse Events in Young Patients with ST Elevation Myocardial Infarction-A 3D Echocardiographic Study.

Left ventricular-arterial coupling (VAC) is a key determinant of global cardiovascular performance, calculated as the ratio between arterial elastance (EA) and left ventricular end-systolic elastance (EES). Over the years, acute myocardial infarction (STEMI) has remained an important cause of morbidity and mortality worldwide. Although, until recently, it was considered a disease occurring mostly in older patients, its prevalence in the young population is continuously rising. In this study, we aimed to investigate the role of 3D VAC and its derived indices in predicting adverse outcomes in young patients with STEMI. We prospectively enrolled 84 young patients (18-51 years) with STEMI who underwent primary PCI and 28 healthy age and sex-matched controls. A 3D echocardiography was used for non-invasive measurements of end-systolic elastance (EES), arterial elastance (EA), and VAC (EA/EES). The occurrence of major adverse cardiac events (MACE) was assessed one year after the index STEMI. Out of 84 patients, 15.4% had adverse events at 12 months follow-up. Patients were divided into two groups according to the presence or absence of MACE. There were no significant differences in arterial elastance between the two groups. EA was higher in the MACE group but without statistical significance (2.65 vs. 2.33; p = 0.09). EES was significantly lower in the MACE group (1.25 ± 0.34 vs. 1.91 ± 0.56. p < 0.0001) and VAC was higher (2.2 ± 0.62 vs. 1.24 ± 0.29, p < 0.0001). ROC analysis showed that VAC has a better predictive value for MACE (AUC 0.927) compared with EA or EEA but also compared with a classical determinant of LV function (LVEF and LVGLS). A VAC value over 1.71 predicts unfavourable outcome with 83.3% sensitivity and 97.1% specificity. In both univariate and multivariate COX regression analysis, VAC remained an independent predictor for MACE and demonstrated incremental prognostic value over LVEF and LVGLS in the proposed statistical models. In conclusion, 3D VAC is an independent predictor of adverse events in young patients with STEMI at a 12 month follow-ups and could be used for a more accurate risk stratification in the acute phase.

Impact of rs1805127 and rs55742440 Variants on Atrial Remodeling in Hypertrophic Cardiomyopathy Patients with Atrial Fibrillation: A Romanian Cohort Study.

Atrial fibrillation (AFib) is characterized by a complex genetic component. We aimed to investigate the association between variations in genes related to cardiac ion handling and AFib in a cohort of Romanian patients with hypertrophic cardiomyopathy (HCM). Forty-five unrelated probands with HCM were genotyped by targeted next-generation sequencing (NGS) for 24 genes associated with cardiac ion homeostasis. Subsequently, the study cohort was divided into two groups based on the presence (AFib+) or absence (AFiB-) of AFib detected during ECG monitoring. We identified two polymorphisms (rs1805127 located in KCNE1 and rs55742440 located in SCN1B) linked to AFib susceptibility. In AFib+, rs1805127 was associated with increased indexed left atrial (LA) maximal volume (LAVmax) (58.42 ± 21 mL/m2 vs. 32.54 ± 6.47 mL/m2, p < 0.001) and impaired LA strain reservoir (LASr) (13.3 ± 7.5% vs. 24.4 ± 6.8%, p < 0.05) compared to those without respective variants. The rs55742440 allele was less frequent in patients with AFib+ (12 out of 25, 48%) compared to those without arrhythmia (15 out of 20, 75%, p = 0.05). Also, AFib+ rs55742440 carriers had significantly lower LAVmax compared to those who were genotype negative. Among patients with HCM and AFib+, the rs1805127 variant was accompanied by pronounced LA remodeling, whereas rs55742440's presence was related to a milder LA enlargement.

Increasing clinical impact and microbiological difficulties in diagnosing coagulase-negative staphylococci in infective endocarditis - a review starting from a series of cases.

Coagulase-negative staphylococci (CoNS) are an emergent aetiology of infective endocarditis (IE) on native valves in previously healthy individuals, its presence is associated with prosthetic valves or with other cardiac implants. The identification of CoNS in cultures was customarily seen as contamination, but more recent epidemiological studies have revealed an increasing number of causative and virulent new CoNS species. Starting from two clinical cases of community-acquired CoNS IE on native valves, the review debates the difficulties in identifying CoNS as the causal pathogens, comprising differentiation of contamination from infection in IE, alongside the challenges raised by antibiotic resistance. Even if the risk of CoNS IE is more increased in subjects with prosthetic materials or other foreign devices and immunodeficiencies, native valve infections with these staphylococci are increasing and should be considered important pathogens in IE. Despite the lack of sensitive and specific tools to correctly differentiate contamination from infection in CoNS endocarditis, a comprehensive evaluation with clinical and paraclinical data accurately succeeds in establishing the diagnosis. The genetic profile of CoNS predisposes to antibiotic multi-resistance, making the treatment of IE challenging; the rapid identification of antibiotic susceptibility is essential to prescribe the appropriate therapy and improve outcomes.

Inflammatory markers in acute myocardial infarction and the correlation with the severity of coronary heart disease.

INTRODUCTION: The inflammatory hypothesis of atherosclerosis is appealing in acute coronary syndromes, but the dynamics and precise role are not established. OBJECTIVES: The study investigates the levels of C reactive protein (CRP), interleukin 1ß (IL-1ß) and stromal-derived factor 1α (SDF-1α) at the time of acute myocardial infarction (AMI) and at 1 and 6 months afterwards, compared with a control group. RESULTS: In the acute phase of AMI, CRP and SDF-1α were significantly higher, while IL-1ß showed lower levels compared with controls. CRP positively correlated with coronary stenosis severity (rho = 0.3, p=.05) and negatively related with left ventricle ejection fraction (LVEF) at 1 month (rho= -0.43, p=.05). IL-1ß weakly correlated with the severity of coronary lesions (rho =0.29, p=.02) and strongly with LVEF (rho= -0.8, p=.05). SDF-1α, slightly correlated with LVEF at 1 month (rho = 0.22, p=.01) and with the severity of coronary atherosclerosis (rho= -0.41, p=.003). CONCLUSIONS: CRP, IL-1ß and SDF-1α have important dynamic in the first 6 months after AMI and CRP and SDF-1α levels correlated with the severity of coronary lesions and LVEF at 1 month after the acute ischaemic event.

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.

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.

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.

Modulating factors of progenitor stem cell kinetics in STEMI patients undergoing primary angioplasty - a pilot study.

AIMS: To investigate the circulating progenitor stem cells (cPCs) count evolution during seven days hospitalization period in ST segment elevation myocardial infarction (STEMI) patients, and to correlate their evolution with some clinical and angiographic parameters. MATERIALS AND METHODS: Twelve Caucasian patients with STEMI undergoing primary percutaneous coronary intervention (PCI) were enrolled. Blood samples were obtained in the emergency room and then daily, for seven days, we evaluated the number of cPCs (CD34+CD45+, CD133+CD34+CD45+, KDR+CD34+CD45+ and KDR+CD133+CD34+CD45+) by flow cytometry using fluorochrome-marked specific monoclonal antibodies. RESULTS: There is a statistically significant increase in cPCs counts in the following days after STEMI, with a different behavior depending on their phenotype. Mature cPCs (CD34+CD45dim, KDR+CD34+CD45dim) have two fairly similar peaks, first around the third day of evolution followed by a short decrease and a new raise in the seventh day, the more immature cPCs (CD133+CD34+CD45dim, KDR+CD133+CD34+CD45dim) have just one spike on the third day, and then almost disappear from the peripheral circulation. In a multivariate regression analysis, preprocedural TIMI (Thrombolysis In Myocardial Infarction) flow, postprocedural myocardial blush and LVEF (Left Ventricular Ejection Fraction) proved to be independent predictors for cPCs variation in the first week after STEMI. CONCLUSIONS: In our study, we demonstrated that all four main phenotypes of circulating progenitor stem cells boosted up in the next days after STEMI, with different patterns depending on cell type; preprocedural TIMI flow, postprocedural myocardial blush and LVEF proved to be independent predictors for cPCs mobilization in the first days after STEMI.

Sleep deprivation attenuates experimental stroke severity in rats.

Indirect epidemiological and experimental evidence suggest that the severity of injury during stroke is influenced by prior sleep history. The aim of our study was to test the effect of acute sleep deprivation on early outcome following experimental stroke. Young male Sprague-Dawley rats (n=20) were subjected to focal cerebral ischemia by reversible right middle cerebral artery occlusion (MCAO) for 90 min. In 10 rats, MCAO was performed just after 6-h of total sleep deprivation (TSD) by "gentle handling", whereas the other rats served as controls. Neurological function during the first week after stroke was monitored using a battery of behavioral tests investigating the asymmetry of sensorimotor deficit (tape removal test and cylinder test), bilateral sensorimotor coordination (rotor-rod and Inclined plane) and memory (T-maze and radial maze). Following MCAO, control rats had impaired behavioral performance in all tests. The largest impairment was noted in the tape test where the tape removal time from the left forelimb (contralateral to MCAO) was increased by approximately 10 fold (p<0.01). In contrast, rats subjected to TSD had complete recovery of sensorimotor performance consistent with a 2.5 fold smaller infarct volume and reduced morphological signs of neuronal injury at day 7 after MCAO. Our data suggest that brief TSD induces a neuroprotective response that limits the severity of a subsequent stroke, similar to rapid ischemic preconditioning.