Hypertension and Arrhythmias: A Clinical Overview of the Pathophysiology-Driven Management of Cardiac Arrhythmias in Hypertensive Patients

Because of demographic aging, the prevalence of arterial hypertension (HTN) and cardiac arrhythmias, namely atrial fibrillation (AF), is progressively increasing. Not only are these clinical entities strongly connected, but, acting with a synergistic effect, their association may cause a worse clinical outcome in patients already at risk of ischemic and/or haemorrhagic stroke and, consequently, disability and death. Despite the well-known association between HTN and AF, several pathogenetic mechanisms underlying the higher risk of AF in hypertensive patients are still incompletely known. Although several trials reported the overall clinical benefit of renin-angiotensin-aldosterone inhibitors in reducing incident AF in HTN, the role of this class of drugs is greatly reduced when AF diagnosis is already established, thus hinting at the urgent need for primary prevention measures to reduce AF occurrence in these patients. Through a thorough review of the available literature in the field, we investigated the basic mechanisms through which HTN is believed to promote AF, summarising the evidence supporting a pathophysiology-driven approach to prevent this arrhythmia in hypertensive patients, including those suffering from primary aldosteronism, a non-negligible and under-recognised cause of secondary HTN. Finally, in the hazy scenario of AF screening in hypertensive patients, we reviewed which patients should be screened, by which modality, and who should be offered oral anticoagulation for stroke prevention

Load-dependent electrophysiological and structural cardiac remodelling studied in ultrathin myocardial slices.

Introduction: Myocardial slices are becoming an established system to study cardiac electrophysiology and pharmacological research and development. Unlike other preparations, cardiac slices are a multicellular preparation that has an intermediate, adequate complexity required for this research. Previous studies have successfully obtained slices from human biopsies and animal models, where the electrical and structural parameters could be maintained for several hours – a process which is comparable to other preparation types. Therefore, we aimed to use left ventricular myocardial slices obtained from rat models of mechanical unloading (HAHLT) and from two models of overload (TAC and SHR), to investigate electrophysiological and structural alterations in these models. Methods: Mechanical unloading was achieved by heterotopic abdominal heart and lung transplantation (HAHLT, 8 weeks) and overload was induced by thoracic aortic constriction (TAC, 10 and 20 weeks) in male Lewis rats. Spontaneous hypertensive rats (SHR) were also used as a second model of overload and were primarily induced by hypertension (3, 12 and 20 months). Brown Norway and Wistar Kyoto rats were used as the control groups for SHR. Myocardial slices from the left ventricle (LV) free wall were cut (300-350 µm thick) tangentially to the epicardial surface using a high-precision slow-advancing Vibratome and were point-stimulated using a multi-electrode array system (MEA), therefore, acquiring field potentials (FPs). Field potential duration (FPD) and conduction velocity (CV) were analysed locally and transmurally across the LV free wall. In addition, FPD heterogeneity within each slice was calculated. For the SHR group, the same slices used for the MEA recording were preserved and used subsequently to measure Cx43, Nav1.5 protein levels and fibrosis. Results: Slices obtained from normal rat hearts that are chronically unloaded were found to develop atrophy at a whole heart level. They showed an increase in FPD and its heterogeneity with preserved conduction properties when compared to controls. In TACs, an in vivo whole heart function assessment confirmed hypertrophy with no signs of cardiac dysfunction. Slices from TAC rats showed an increase in FPD at both 10 and 20 weeks after banding. FPD heterogeneity was increased at 10 weeks but normalised at 20 weeks. Changes in CV properties were observed in this group, showing a faster CV and longitudinal conduction velocity (CVL) at 10 weeks and no change at 20 weeks. Transverse conduction velocity (CVT) was unchanged in the TAC group. In SHRs, however, hypertrophy was confirmed and signs of dysfunction in the aged group (20 months) were observed due to the decrease in EF by 18%, especially when compared to the 12 months group. FPD and its heterogeneity was unchanged in SHR when compared to controls. Disease and age-related abnormalities in CV properties were observed in SHR and these were associated with changes in Cx43, Nav1.5 protein level and fibrosis. Conclusion: Myocardial slices are a suitable multicellular preparation to study electrophysiological remodelling obtained from different rat models of cardiovascular disease. In addition, it was possible to investigate the changes in CV and FPD transmurally in rats using this type of preparation method. Thus, this study supports the use of this multicellular preparation in understanding the mechanisms of cardiac disease and the testing of new treatments and therapeutic targets.Open Acces

Conduction abnormalities and ventricular arrhythmogenesis: The roles of sodium channels and gap junctions.

This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.ijcha.2015.10.003Ventricular arrhythmias arise from disruptions in the normal orderly sequence of electrical activation and recovery of the heart. They can be categorized into disorders affecting predominantly cellular depolarization or repolarization, or those involving action potential (AP) conduction. This article briefly discusses the factors causing conduction abnormalities in the form of unidirectional conduction block and reduced conduction velocity (CV). It then examines the roles that sodium channels and gap junctions play in AP conduction. Finally, it synthesizes experimental results to illustrate molecular mechanisms of how abnormalities in these proteins contribute to such conduction abnormalities and hence ventricular arrhythmogenesis, in acquired pathologies such as acute ischaemia and heart failure, as well as inherited arrhythmic syndromes.GT received a BBSRC Doctoral CASE Studentship at the Department of Biochemistry, University of Cambridge, in conjunction with Xention Discovery, for his Ph.D. studies. This manuscript is based, in part, on the doctoral thesis of GT. GT thanks Dr. Antony Workman of University of Glasgow, and Prof. Sarah Lummis, of University of Cambridge, for their helpful comments on an earlier draft of his thesis. We also thank two anonymous expert reviewers who have provided insightful comments and helpful suggestions which we have used to improve our original manuscript

Tracheal instillation of urban PM2.5 suspension promotes acute cardiac polarization changes in rats

The mechanisms by which PM2.5 increases cardiovascular mortality are not fully identified. Autonomic alterations are the current main hypotheses. Our objective was to determine if PM2.5 induces acute cardiac polarization alterations in healthy Wistar rats. PM2.5 samples were collected on polycarbonate filters. Solutions containing 10, 20, and 50 µg PM2.5 were administered by tracheal instillation. P wave duration decreased significantly at 20 µg (0.99 &#177; 0.06, 0.95 &#177; 0.06, and 0.96 &#177; 0.07; P < 0.001), and 50 µg (0.98 &#177; 0.06, 0.98 &#177; 0.07, and 0.96 &#177; 0.08; 60, 90 and 120 min, respectively) compared to blank filter solution (P < 0.001). PR interval duration decreased significantly at 20 µg (0.99 &#177; 0.06, 0.98 &#177; 0.07, and 0.97 &#177; 0.08) and 50 µg (0.99 &#177; 0.05, 0.97 &#177; 0.0, and 0.95 &#177; 0.05; 60, 90, and 120 min, respectively) compared to blank filter and 10 µg (P < 0.001). QRS interval duration decreased at 20 and 50 µg in relation to blank filter solution and 10 µg (P < 0.001). QT interval duration decreased significantly (P < 0.001) with time in animals receiving 20 µg (0.94 &#177; 0.12, 0.88 &#177; 0.14, and 0.88 &#177; 0.11) and 50 µg (1.00 &#177; 0.13; 0.97 &#177; 0.11 and 0.98 &#177; 0.16; 60, 90 and 120 min, respectively) compared to blank filter solution and 10 µg (P < 0.001). PM2.5 induced reduced cardiac conduction time, within a short period, indicating that depolarization occurs more rapidly across ventricular tissue.CNPqLIM-HCFMUS

Association between dietary acid load and the risk of cardiovascular disease: nationwide surveys (KNHANES 2008-2011)

BACKGROUND: Acid-base imbalance has been reported to increase incidence of hypertension and diabetes. However, the association between diet-induced acid load and cardiovascular disease (CVD) risk in the general population has not been fully investigated. METHODS: This was a population-based, retrospectively registered cross-sectional study using nationally representative samples of 11,601 subjects from the Korea National Health and Nutrition Examination Survey 2008-2011. Individual CVD risk was evaluated using atherosclerotic cardiovascular disease (ASCVD) risk equations according to 2013 ACC/AHA guideline assessment in subjects aged 40-79 without prior CVD. Acid-base status was assessed with both the potential renal acid load (PRAL) and the dietary acid load (DAL) scores derived from nutrient intake. RESULTS: Individuals in the highest PRAL tertile had a significant increase in 10 year ASCVD risks (9.6 vs. 8.5 %, P 10 %) group compared to those in the lowest PRAL tertile (odds ratio [OR] 1.23, 95 % confidence interval [CI] 1.22-1.35). The association between higher PRAL score and high CVD risk was stronger in the middle-aged group. Furthermore, a multiple logistic regression analysis also demonstrated this association (OR 1.20 95 % CI 1.01-1.43). Subgroup analysis stratified obesity or exercise status; individuals in unhealthy condition with lower PRAL scores had comparable ASCVD risk to people in the higher PRAL group that were in favorable physical condition. In addition, elevated PRAL scores were associated with high ASCVD risk independent of obesity, exercise, and insulin resistance, but not sarcopenia. Similar trends were observed with DAL scores. CONCLUSION: Diet-induced acid load was associated with increased risk of CVD, independent of obesity and insulin resistance.ope