Atrial fibrillation and QT corrected. What is the best formula to use?

BACKGROUND: QT interval varies with the heart rate (HR), so a correction in QT calculation is needed (QTc). Atrial fibrillation (AF) is associated with elevated HR and beat-to-beat variation. AIM: To find best correlation between QTc in atrial fibrillation (AF) versus restored sinus rhytm (SR) after electrical cardioversion (ECV) (primary end point) and to determine which correction formula and method are the best to determine QTc in AF (secondary end point). METHODS: During a 3-month period, we considered patients who underwent 12-lead ECG recording and received an AF diagnosis with indication for ECV. Exclusion criteria were as follows: QRS duration >120 ms, therapy with QT-prolonging drugs, a rate control strategy and a nonelectrical cardioversion. The QT interval was corrected using Bazzett's, Framingham, Fridericia and Hodges formulas during the last ECG during AF and the first one immediately after ECV. QTc mean was calculated as mQTc (average of 10 QTc calculated beat per beat) and as QTcM (QTc calculated from the average of 10 raw QT and RR for each beat). RESULTS: Fifty consecutive patients were enrolled in the study. Bazett's formula showed a significant change in mean QTc value between the two rhythms (421.5 ± 33.9 vs. 446.1 ± 31.9; p < 0.001 for mQTc and 420.9 ± 34.1 vs. 441.8 ± 30.9; p = 0.003 for QTcM). On the contrary, in patients with SR, QTc assessed by the Framingham, Fridericia, and Hodges formulas was similar to that in AF. Furthermore, good correlations between mQTc and QTcM are present for each formula, even in AF or SR. CONCLUSIONS: During AF, Bazzett's formula, seems to be the most imprecise in QTc estimation.

Gliflozins: From Antidiabetic Drugs to Cornerstone in Heart Failure Therapy-A Boost to Their Utilization and Multidisciplinary Approach in the Management of Heart Failure.

Heart failure (HF) is a complex, multifactorial, progressive clinical condition affecting 64.3 million people worldwide, with a strong impact in terms of morbidity, mortality and public health costs. In the last 50 years, along with a better understanding of HF physiopathology and in agreement with the four main models of HF, many therapeutic options have been developed. Recently, the European Society of Cardiology (ESC) HF guidelines enthusiastically introduced inhibitors of the sodium-glucose cotransporter (SGLT2i) as first line therapy for HF with reduced ejection fraction (HFrEF) in order to reduce hospitalizations and mortality. Despite drugs developed as hypoglycemic agents, data from the EMPA-REG OUTCOME trial encouraged the evaluation of the possible cardiovascular effects, showing SGLT2i beneficial effects on loading conditions, neurohormonal axes, heart cells' biochemistry and vascular stiffness, determining an improvement of each HF model. We want to give a boost to their use by increasing the knowledge of SGLT2-I and understanding the probable mechanisms of this new class of drugs, highlighting strengths and weaknesses, and providing a brief comment on major trials that made Gliflozins a cornerstone in HF therapy. Finally, aspects that may hinder SGLT2-i widespread utilization among different types of specialists, despite the guidelines' indications, will be discussed.

Loss of Neuron Navigator 2 Impairs Brain and Cerebellar Development.

Cerebellar hypoplasia and dysplasia encompass a group of clinically and genetically heterogeneous disorders frequently associated with neurodevelopmental impairment. The Neuron Navigator 2 (NAV2) gene (MIM: 607,026) encodes a member of the Neuron Navigator protein family, widely expressed within the central nervous system (CNS), and particularly abundant in the developing cerebellum. Evidence across different species supports a pivotal function of NAV2 in cytoskeletal dynamics and neurite outgrowth. Specifically, deficiency of Nav2 in mice leads to cerebellar hypoplasia with abnormal foliation due to impaired axonal outgrowth. However, little is known about the involvement of the NAV2 gene in human disease phenotypes. In this study, we identified a female affected with neurodevelopmental impairment and a complex brain and cardiac malformations in which clinical exome sequencing led to the identification of NAV2 biallelic truncating variants. Through protein expression analysis and cell migration assay in patient-derived fibroblasts, we provide evidence linking NAV2 deficiency to cellular migration deficits. In model organisms, the overall CNS histopathology of the Nav2 hypomorphic mouse revealed developmental anomalies including cerebellar hypoplasia and dysplasia, corpus callosum hypo-dysgenesis, and agenesis of the olfactory bulbs. Lastly, we show that the NAV2 ortholog in Drosophila, sickie (sick) is widely expressed in the fly brain, and sick mutants are mostly lethal with surviving escapers showing neurobehavioral phenotypes. In summary, our results unveil a novel human neurodevelopmental disorder due to genetic loss of NAV2, highlighting a critical conserved role of the NAV2 gene in brain and cerebellar development across species.

Non-Invasive Imaging Assessment in Patients with Aortic Coarctation: A Contemporary Review.

Coarctation of the aorta (CoA) is a congenital abnormality characterized by a narrowing of the aortic lumen, which can lead to significant morbidity and mortality if left untreated. Even after repair and despite significant advances in therapeutic management, these patients have overall reduced long-term survival due to the consequences of chronic afterload increase. Cardiovascular imaging is key from the first diagnosis to serial follow-up. In recent years, novel imaging techniques have emerged, increasing accessibility to advanced imaging modalities and enabling early and non-invasive identification of complications after repair. The aim of this paper is to provide a comprehensive review of the role of different imaging techniques in the evaluation and management of patients with native or repaired CoA, highlighting their unique strengths and limitations.

Prognostic value of two-dimensional strain in early ischemic heart disease: A 5-year follow-up study.

INTRODUCTION: Two-dimensional strain echocardiography (2D-SE) is a reliable method for measuring deformation of the left ventricle. AIM OF THE STUDY: Aim of the study was to determine changes in 2D-SE parameters over time collected during dipyridamole stress echo-cardiography (dipy-stress) and prognosis of patients with non-diagnostic dipy-stress results. METHODS: In the first phase of the study, assessment of a prospective enrolled population with a non-diagnostic dipy-stress test result was conducted, checking through coronary CT angiography (CCTA) the presence of coronary artery disease (CAD). In the follow-up phase, an echocardiographic re-evaluation and outcome analysis during a mean follow-up of 78 months was carried out. RESULTS: In the first phase, Global Circumferential Strain (GCS) values were similar in the CCTA positive and CCTA negative groups at rest and after stress. For Global Longitudinal Strain (GLS), there was a significant reduction (p < .0001) in the CCTA positive group compared to the CCTA negative group. After 78 ± 9 months none of the enrolled patients experimented cardiac events. Values of GCS, both at rest and after stress, did not differ statistically comparing follow-up values with baseline ones. No statistically significant changes were seen in the same analysis for GLS rest and stress values, between baseline and follow-up in the two groups. CONCLUSIONS: Performing 2D-SE during dipy-stress can detect mild CAD that conventional stress-tests miss. Patients with mild coronary stenosis may have a favorable mid-term prognosis, but efforts should be made to investigate the decrease trend in GLS, at rest and after stress, reported in this patient group.

Fibrosis after Myocardial Infarction: An Overview on Cellular Processes, Molecular Pathways, Clinical Evaluation and Prognostic Value.

The ischemic injury caused by myocardial infarction activates a complex healing process wherein a powerful inflammatory response and a reparative phase follow and balance each other. An intricate network of mediators finely orchestrate a large variety of cellular subtypes throughout molecular signaling pathways that determine the intensity and duration of each phase. At the end of this process, the necrotic tissue is replaced with a fibrotic scar whose quality strictly depends on the delicate balance resulting from the interaction between multiple actors involved in fibrogenesis. An inflammatory or reparative dysregulation, both in term of excess and deficiency, may cause ventricular dysfunction and life-threatening arrhythmias that heavily affect clinical outcome. This review discusses cellular process and molecular signaling pathways that determine fibrosis and the imaging technique that can characterize the clinical impact of this process in-vivo.

Anesthetic Strategies in Oncological Surgery: Not Only a Simple Sleep, but Also Impact on Immunosuppression and Cancer Recurrence.

Tumor recurrences or metastases remain a major hurdle in improving overall cancer survival. In the perioperative period, the balance between the ability of the cancer to seed and grow at the metastatic site and the ability of the patient to fight against the tumor (i.e. the host antitumor immunity) may determine the development of clinically evident metastases and influence the patient outcome. Up to 80% of oncological patients receive anesthesia and/or analgesia for diagnostic, therapeutic or palliative interventions. Therefore, anesthesiologists are asked to administer drugs such as opiates and volatile or intravenous anesthetics, which may determine different effects on immunomodulation and cancer recurrence. For instance, some studies suggest that intravenous drugs, such as propofol, may inhibit the host immunity to a lower extent as compared to volatile anesthetics. Similarly, some studies suggest that analgesia assured by local anesthetics may provide a reduction of cancer recurrence rate; whilst on the opposite side, opioids may exert negative consequences in patients undergoing cancer surgery, by interacting with the immune system response via the modulation of the hypothalamic-pituitary-adrenal axis and autonomic nervous system, or directly through the opioid receptors on the surface of immune cells. In this review, we summarize the main findings on the effects induced by different drugs on immunomodulation and cancer recurrence.

Autophagy in advanced low- and high-grade tubular adenocarcinomas of the stomach: An ultrastructural investigation.

Autophagy represents a catabolic process in which cellular protein and organelles are engulfed into autophagosomes, digested in lysosomes and reutilized for the cellular metabolism. In neoplastic conditions, autophagy may act either as a tumour suppressor avoiding the accumulation of damaged proteins and organelles or as a mechanism of cell survival promoting the tumour growth. Although enhanced autophagy has been reported in hypoxic areas of solid tumors, there are only few ultrastructural reports concerning the relationships between autophagy and tumor grade. In the present study, we have performed an ultrastructural investigation aimed to document autophagy in a cohort of advanced gastric carcinomas of tubular type, correlating the observed findings with low and high tumor grade. Among 71 surgically resected cases of advanced gastric carcinomas, we have selected twelve low-grade and thirteen high-grade tubular adenocarcinomas. Autophagic vacuoles (AV) were only occasionally found in low-grade tubular carcinomas, while they constituted a frequent finding in high-grade ones (p < 0.01). Moreover, in high-grade tubular adenocarcinomas, our data revealed a morphologic association between autophagy and nuclear changes, such as multinucleation, micronucleation and nuclear buds, largely considered as ultrastructural aspects of mitotic instability. However, an increased autophagy was associated with organelle-poor cytoplasm or a senescent phenotype, characterized by lipofuscin granules and cytoplasmic vacuoles. In the light of our observations, it may be suggested that autophagy should be considered a phenomenon mainly related to the cellular differentiation and tumor progression.