Left ventricular diastolic dysfunction (LVDD) is an important precursor to many different cardiovascular diseases. Diastolic abnormalities have been studied extensively in the past decade, and it has been confirmed that one of the mechanisms leading to heart failure is a chronic, low-grade inflammatory reaction. The triggers are classical cardiovascular risk factors, grouped under the name of metabolic syndrome (MetS), or other systemic diseases that have an inflammatory substrate such as chronic obstructive pulmonary disease. The triggers could induce myocardial apoptosis and reduce ventricular wall compliance through the release of cytokines by multiple pathways such as (1) immune reaction, (2) prolonged cell hypoxemia, or (3) excessive activation of neuroendocrine and autonomic nerve function disorder. The systemic proinflammatory state causes coronary microvascular endothelial inflammation which reduces nitric oxide bioavailability, cyclic guanosine monophosphate content, and protein kinase G (PKG) activity in adjacent cardiomyocytes favoring hypertrophy development and increases resting tension. So far, it has been found that inflammatory cytokines associated with the heart failure mechanism include TNF-α, IL-6, IL-8, IL-10, IL-1α, IL-1β, IL-2, TGF-β, and IFN-γ. Some of them could be used as diagnosis biomarkers. The present review aims at discussing the inflammatory mechanisms behind diastolic dysfunction and their triggering conditions, cytokines, and possible future inflammatory biomarkers useful for diagnosis.

Background Echocardiographic evaluation of left ventricular (LV) structural and functional alterations in hypertension has some limitations, potentially overcome by using biomarkers. ST2, a prognostic biomarker for heart failure and myocardial infarction patients, was less studied in hypertension. Aim To analyze the relationship between serum ST2 levels and diastolic dysfunction (DD) in hypertension. Method We enrolled 88 hypertensive outpatients (average age 65 years, 69.3% females) in a prospective study, stratified for presence of LV hypertrophy (LVH). For each patient clinical examination, lab workup (routine and serum ST2 levels) and echocardiography were performed. Results Hypertensive patients with LVH had higher age, pulse pressure, mean arterial pressure, and serum ST2, while having lower serum albumin than those without LVH. Serum ST2 levels correlate with parameters of LV remodeling and DD. We found that 5.3% of ST2 level variability was caused by a 1-unit variation of cardiovascular risk. We identified cut-off values for discriminating hypertension with LVH versus that without LVH and grade 2 DD versus normal diastolic performance. Conclusion ST2 could be used as diagnostic biomarker for cardiac remodeling and altered diastolic performance in hypertension, providing additional data to echocardiography. It could represent a milestone in early detection of cardiac performance alteration.

Both MetS components and biomarkers of inflammation (IF) are predictive factors for LVDD. The best predictive multimarker model for LVDD in MetS patients is composed of waist, triglycerides (TGL), SBP, DBP, fasting glucose, IL-6, hs-CRP, and NT-proBNP. IL-6 remains an independent predictive biomarker for LVDD in MetS patients, underlining the importance of IF in the evolution of MetS to subclinical cardiac damage.

Background and aimThe involvement of leptin in atherosclerosis is very complex, including inflammation, the oxidative stress and thrombosis. Leptin has atherogenic and also antiatherogenic actions. In obesity elevated leptin levels are not sufficient to prevent disturbances of energy balance, suggesting that obese people are leptin resistant. The aim of the study was to investigate the relationship between baseline plasma levels of leptin and the incidence of new ischemic events in patients with CHD.MethodsPlasma levels of leptin in fifty nine consecutive patients (29 men and 30 women) with CHD hospitalized in the County Emergency Clinical Hospital of Cluj-Napoca were measured using commercially available ELISA at admission. Patients with active infectious disease, neoplasia, acute coronary syndrome, stroke, hepatic or renal failure and severe heart failure were excluded The relationship between leptin levels and incident cardiovascular events (angina, nonfatal myocardial infarction or heart failure) over two years follow-up was studied using MEDCALC version 9.6.Results73.6% patients with CHD were overweight or suffered of obesity. There were no significant differences between women and men regarding the plasma levels of leptin, the body mass index (BMI), the number of rehospitalizations, rehospitalizations/patient, diabetes mellitus, hypertension or dyslipidemia. Only in women plasma levels of leptin are correlated with BMI. As compared with men with overweight and obesity (BMI≥25kg/m2), plasma levels of leptin were significantly higher in women with overweight and obesity (3905.97±463.91 pg/ml vs 1835.17±533.9 pg/ml) (p<0.002). Patient gender could not be demonstrated to influence prognosis. During the two years we recorded one or more readmissions in 26 patients (44%). The analysis of time till readmission using Kaplan-Meier curves, showed that leptin level (cut-off 2000 pg/ml, HR 0.38, 95% CI 0.17–0.83; p=0.01) and BMI (cut-off 28 kg/m2, HR 0.3164, 95% CI 0.145–0.0689; p<0.01) were significantly associated with prognosis.ConclusionPatients with plasma levels of leptin >2000 pg/ml and BMI >28kg/m2 had a better prognosis, suggesting a protective role of leptin in overweight/mild obesity.

Background: Apelin is a potent endogenous inotropic peptide with a major role in counteracting the aldosterone and angiotensin II and their negative effects on the cardiovascular system. The exact role of apelin in the pathophysiology of this disease is not well understood. We aimed to investigate the possible associations of apelin-13with clinical and paraclinical characteristics in HF patients as well as studying its dynamics during the course of the heart failure. Method: We performed a prospective observational cohort single-center study. We compared the baseline serum levels of apelin-13 and NT-proBNP level in 53 heart failure patients (acute heart failure, chronic compensated heart failure and chronic decompensated heart failure). We divided the patients according to the apelin-13 level: above and below the median, and we analyzed the relationship between serum apelin-13 and the clinical, echocardiographic, electrocardiographic and biological parameters. Twenty patients were followed-up (after an average time interval of 9 months), investigating the same parameters. Results: The median of apelin-13 was 495pg/mL . We found strong, negative correlation between the serum levels of apelin-13 and p<0.001). For the reassessed patients the median apelin level was significantly higher at follow-up (460 pg/mL, IQR 342-871 pg/mL) as compared with the baseline level (395 pg/mL, IQR 270-603 pg/mL), p=0.019, and maintained the negative correlation with p<0.001

Background A number of patients with neurally mediated syncope (NMS) have isolated QRS complexes of very low voltage (≤0.3 mV) in the frontal plane leads on the 12‐lead electrocardiogram (ECG). Hypothesis The aim of this study was to assess the importance of QRS voltage in predicting response to tilt‐table testing (TTT) in patients with suspected NMS. Methods We included 216 patients (age: 49 ± 20 years, 103 men) with suspected NMS who had either a positive or negative response to TTT (n = 91 TTT+, and n = 125 TTT−). The QRS voltage was measured in mV on 12‐lead ECGs performed within 3 days of the TTT. The lowest QRS voltage (QRSmin), as well as the voltage in each of the 12 leads was also determined. Results Very low voltage (QRSmin  ≤ 0.3 mV) in the frontal leads was significantly more prevalent in the TTT+ group than in the TTT− group (74 vs 22%, respectively; P  < .001). Patients in the TTT+ group had significantly lower QRSmin when compared to patients in the TTT− group. QRSmin predicted a positive tilt‐table test in a multivariate model that also included patient gender, height, history of presyncope, QRS duration, and left ventricular end‐diastolic diameter indexed to height. ROC analysis showed that QRSmin of ≥0.3 mV discriminated between TTT+ and TTT− patients with a sensitivity of 78% and specificity of 68%. Conclusion Isolated very low QRS voltage in the frontal leads predicts a positive response to TTT in patients with suspected NMS.

Anticoagulant treatment is extremely important and frequently encountered in the therapy of various cardiovascular diseases. Vitamin K antagonists (VKA) are in use for the prevention and treatment of arterial and venous thromboembolism, despite the introduction of new direct-acting oral anticoagulants (NOAC). The VKA still have the clear recommendation in patients with a mechanical prosthetic heart valve replacement or moderate to severe mitral stenosis of the rheumatic origin, in deep vein thrombosis associated with congenital thrombophilia, and in cases where NOAC are prohibited by social condition (financial reason) or by comorbidities (extreme weight, severe renal or liver disease). VKA dosing required to reach the targeted therapeutic range varies largely between patients (inter-individual variability). This inter-individual variability depends on multiple environmental factors such as age, mass, diet, etc. but it is also influenced by genetic determinism. About 30 genes implicated in the metabolism coumarins derivatives were identified, the most important being CYP2C9 and VKORC, each with several polymorphisms. Herein, we review the data regarding genetic alterations in general and specific populations, highlight the diagnosis options in particular cases presenting with genetic alteration causing higher sensitivity and/or resistance to VKA therapy and underline the utility of NOAC in solving such rare and difficult problems.

Heart failure is a significant healthcare problem, because of its impact at the individual and populational level, through multiple rehospitalizations and increased morbi-mortality. At the individual level, the multidimensional impact of this clinical condition and its treatment on patients' daily lives is reflected in the quality of life (QoL). QoL needs to be accurately measured, because it's related to high hospitalization and mortality rates and provides valuable information that cannot be directly obtained using clinical, biological or imaging measurements. For these reasons, QoL evaluation (global score, subscale scores, answers to various items, etc.) is a significant parameter for assessing the impact of and for structuring the cardiac rehabilitation programs (exercise training, nutritional counseling, psychosocial support and interventions, etc). In order to increase the long-term efficiency, these programs need also to include strategies to optimize and increase adherence to lifestyle changes and to medical therapy.