Cardiac Remodeling and Ventricular Pacing: From Genes to Mechanics.

Cardiac remodeling and ventricular pacing represent intertwined phenomena with profound implications for cardiovascular health and therapeutic interventions. This review explores the intricate relationship between cardiac remodeling and ventricular pacing, spanning from the molecular underpinnings to biomechanical alterations. Beginning with an examination of genetic predispositions and cellular signaling pathways, we delve into the mechanisms driving myocardial structural changes and electrical remodeling in response to pacing stimuli. Insights into the dynamic interplay between pacing strategies and adaptive or maladaptive remodeling processes are synthesized, shedding light on the clinical implications for patients with various cardiovascular pathologies. By bridging the gap between basic science discoveries and clinical translation, this review aims to provide a comprehensive understanding of cardiac remodeling in the context of ventricular pacing, paving the way for future advancements in cardiovascular care.

Diagnostic performance of single-lead electrocardiograms for arterial hypertension diagnosis: a machine learning approach.

Awareness and early identification of hypertension is crucial in reducing the burden of cardiovascular disease (CVD). Artificial intelligence-based analysis of 12-lead electrocardiograms (ECGs) can already detect arrhythmias and hypertension. We performed an observational two-center study in order to develop a machine learning algorithm to proactively detect arterial hypertension from single-lead ECGs. This could serve as proof of concept with an eye towards todays wearables that record single-lead ECGs. In a prospective observational study, we enrolled 1254 consecutive subjects (539 male, aged 60.22 ± 12.46 years), with and without essential hypertension, and no indications of CVD. A 12-lead ECG of 10 seconds duration in resting position was performed on each subject using a digital electrocardiograph and lead I was isolated for analysis using a calibrated Random Forest (RF). Our RF model classified hypertensive from normotensive subjects on a hold-out test set, with 75% accuracy, ROC/AUC 0.831 (95%CI: 0.781-0.871), sensitivity 72%, and specificity 82% (sensitivity and specificity calculated using a threshold of 0.675). Increasing age, larger values of body mass index, the area under the T wave divided by the QRS complex area, and the area under QRS segment adjusted for BMI, were the four most important features that drove the classification decisions of our model. This study demonstrates the potential to opportunistically detect an undiagnosed hypertension, using a single-lead ECG. While studies with data from wearables are required to translate our findings to actual smartwatch settings, our results could pave the way to innovative technologies for hypertension awareness.

Cytokeratin 18 as a Novel Biomarker in Patients with Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a heart muscle disease associated with an increased risk for sudden cardiac death (SCD). Cytokeratin 18-based proteins, such as M30 and M65 antigens, are known cell-death biomarkers. M30 antigen is released from cells during apoptosis, and M65 antigen is released during cell death from any cause, such as apoptosis or necrosis. We aimed to study the expression of M30 and M65 antigens in peripheral blood obtained by 46 HCM patients and compare with 27 age- and sex-matched patients without HCM. We also investigated the CK18 expression in myocardium from postmortem HCM hearts. M30 and M65 antigens were significantly increased in the HCM vs. non-HCM group (Μ30: 338 ± 197 U/uL vs. 206 ± 166 U/uL, p = 0.003; M65: 428 ± 224 U/uL vs. 246 ± 214 U/uL, p = 0.001), and HCM patients with a higher expression of these markers (M30: 417 ± 208 vs. 271 ± 162 U/uL, p = 0.011; M65: 518 ± 242 vs. 351 ± 178 U/uL, p = 0.011) had a higher risk for SCD. In HCM, both apoptosis and necrosis are increased, but particularly necrosis (M30/M65 ratio: 0.75 ± 0.09 vs. 0.85 ± 0.02, p < 0.001). CK18 is expressed in the HCM myocardium (1.767 ± 0.412 vs. 0.537 ± 0.383, % of area, p = 0.0058). Therefore, M30 and M65 antigens may be novel biomarkers in HCM.

Increased Mortality in Elderly Patients Admitted with Hyponatremia: A Prospective Cohort Study.

Hyponatremia is the most common electrolyte disorder, commonly affecting older hospitalized individuals; however, the literature is not clear regarding its effect on mortality. The aim of this 2-year observational prospective cohort study was to evaluate the mortality and re-admission rates, the clinical and laboratory characteristics and the causes of hyponatremia in patients older than 65 years admitted with a corrected serum sodium of 130 mEq/L or less in an internal medicine ward of a tertiary Greek university hospital. During the observation period, 138 patients (mean age 80.5 years, 36.2% male) fulfilled the inclusion criteria and were prospectively followed for 1 year after admission. Symptoms of hyponatremia were present in 59.4% of patients. Hypovolemia was the main sole cause of hyponatremia, but in about one third of patients, hyponatremia was multifactorial. Only a low proportion of patients (12.3%) fulfilled the criteria of the syndrome of inappropriate antidiuresis (SIAD) at admission according to the current guidelines. The re-admission rates at 3- and 12-months following discharge was 34.2% and 51.8%, respectively. Mortality during hospitalization was 17.4% and was higher compared to non-hyponatremic admitted older patients, while the total mortality at 1 year after admission was 28.3%, indicating that hyponatremia at admission is a marker of significant mortality during and after hospitalization in elderly patients.

Peripheral Blood MicroRNAs as Potential Biomarkers of Myocardial Damage in Acute Viral Myocarditis.

BACKGROUND: microRNAs (miRs) have emerged as important modulators of cardiovascular development and disease. Our aim was to determine whether cardiac-related miRs such as miR-21-5p and miR-1-3p were differentially expressed in acute viral myocarditis and whether any of them was related with the extent of myocardial damage and left ventricular dysfunction. METHODS: We enrolled 40 patients with acute viral myocarditis. Blood samples were taken on admission and miRs expression levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. RESULTS: miR-21-5p, miR-1-3p were significantly elevated in acute myocarditis. miR-21-5p levels showed a strong correlation with global longitudinal strain (r = 0.71, p < 0.01), while miR-1-3p had significant correlations with troponin I (r = 0.79, p < 0.01). CONCLUSIONS: The expression of miR-21-5p and miR-1-3p in peripheral blood is increased in acute viral myocarditis, and this increase is correlated with myocardial damage and indicative of left ventricular systolic dysfunction in these patients.

Right ventricular dysfunction in arterial hypertension: still terra incognita?

The effects of systemic hypertension on left ventricular function have been well described, as has been the response of the resulting alterations to antihypertensive treatment. However, hypertension effects on the right ventricle (RV) have not been sufficiently investigated; only in recent years, with the development of new imaging modalities, has its importance become widely recognized. Indeed, evidence from clinical trials suggestive of RV functional and structural impairment early in the course of arterial hypertension continues to accumulate. Newer imaging techniques, especially speckle-tracking-derived myocardial deformation imaging, have provided new insights into the effect of systemic hypertension on this previously neglected cardiac chamber. Two- and three-dimensional echocardiography, along with cardiac magnetic resonance imaging, forms the cornerstone of RV structural and functional assessment. This article provides an overview of the effect of longstanding hypertension on RV structure and function, the respective underlying mechanisms, and the potential therapeutic implications. It summarizes the available options for RV structural and functional assessment, and evaluates the existing evidence with respect to RV alterations in hypertensive disease, aiming to assess the current limits of scientific knowledge about a heart chamber that has only recently become the focus of greater interest.

Cytomegalovirus Pneumonitis in a Patient with Homozygous ß-Thalassemia and Splenectomy.

Cytomegalovirus (CMV) rarely causes disease in immunocompetent individuals but may cause severe disease in immunocompromised patients. We report the case of a young woman who had undergone multiple transfusions and splenectomy for homozygous ß-thalassemia. She presented with prolonged fever and respiratory distress. Although broad-spectrum antibiotic therapy had initially been administered, the patient had clinically deteriorated. Serology and molecular blood testing established CMV infection and viremia. Computed tomography of the chest demonstrated pneumonitis and she was successfully treated with a 3-week administration of ganciclovir. In ß-thalassemia patients who undergo splenectomy necessitating multiple blood transfusions, CMV infection should be considered as a differential diagnosis.

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.

Intra-abdominal abscesses by Lactococcus lactis ssp cremoris in an immunocompetent adult with severe periodontitis and pernicious anemia.

We report the case of an immunocompetent man who presented with fever and abdominal pain and was found to have a hepatic abscess and a peri-renal abscess with a computerized tomography scan. The hepatic abscess was drained percutaneously and cultures revealed the presence of Lactococcus lactis that was sensitive to penicillin. The patient was successfully treated with ceftriaxone and metronidazole with resolution of the abscesses. Further work-up revealed atrophic gastritis, vitamin B12 deficiency, periodontitis and gingivitis, suggesting a possible site of entry for the development of the abscesses.

Increased platelet alpha2B-adrenergic receptor gene expression in well-controlled hypertensives: the effect of arterial stiffness.

Catecholamines play a major role in atherothrombotic mechanisms in essential hypertension. Alpha2B-adrenergic receptors (α2B-ARs) are implicated in the pathophysiology of platelet aggregation. In this study, we evaluated platelet α2B-AR gene expression levels in patients with well-controlled essential hypertension compared with normal individuals and investigated their association with increased arterial stiffness. Fifty-nine patients with well-controlled essential hypertension (34 men, mean age 65 ± 9 years) and 26 normotensives (19 men, mean age 64 ± 8 years) were included in the study. For each patient, carotid-femoral pulse wave velocity (PWV) and carotid-radial PWV were evaluated. In addition, blood samples were obtained and platelets were isolated. The α2B-AR gene expression levels in platelets were examined by real-time polymerase chain reaction for each participant. Well-controlled hypertensive patients showed significantly higher gene expression levels of α2B-Rs in platelets compared with normotensives (34.7 ± 29.5 vs 17.6 ± 12.5, respectively, P = .005). Interestingly, we found that carotid-femoral PWV and carotid-radial PWV were positively correlated with platelet α2B-R gene expression levels (r = 0.59, P < .001, and r = 0.39, P = .002, respectively).Platelet α2B-R gene expression levels are increased in patients with well-controlled essential hypertension compared with normotensives and are correlated with increased PWV in those patients. Our data indicate an association of arterial stiffness and platelet α2B-Rs gene expression and indicate the need for further research.