Rheumatoid arthritis (RA) is a chronic immuno-mediated disease primarily affecting the joints, characterized by persistent high-grade systemic inflammation. Cardiovascular morbidity and mortality are significantly increased in RA, with >50% of premature deaths attributable to cardiovascular disease. In particular, RA patients were twice as likely to experience sudden cardiac death compared with non-RA subjects, pointing to an increased propensity to develop malignant ventricular arrhythmias. Indeed, ventricular repolarization (QT interval) abnormalities and cardiovascular autonomic nervous system dysfunction, representing two well-recognized risk factors for life-threatening ventricular arrhythmias in the general population, are commonly observed in RA. Moreover, large population-based studies seem to indicate that also the prevalence of atrial fibrillation is significantly higher in RA subjects than in the general population, thus suggesting that these patients are characterized by an abnormal diffuse myocardial electrical instability. Although the underlying mechanisms accounting for the pro-arrhythmogenic substrate in RA are probably intricate, the leading role seems to be played by chronic systemic inflammatory activation, able to promote arrhythmias both indirectly, by accelerating the development of ischaemic heart disease and congestive heart failure, and directly, by affecting cardiac electrophysiology. In this integrated mechanistic view, lowering the inflammatory burden through an increasingly tight control of disease activity may represent the most effective intervention to reduce arrhythmic risk in these patients. Intriguingly, these considerations could be more generally applicable to all the diseases characterized by chronic systemic inflammation, and could help elucidate the link between low-grade chronic inflammation and arrhythmic risk in the general population.

Systemic inflammation and arrhythmic risk: lessons from rheumatoid arthritis

Sudden cardiac death (SCD) represents about 25% of deaths in clinical cardiology. The identification of risk factors for SCD is the philosopher's stone of cardiology and the identification of non-invasive markers of risk of SCD remains one of the most important goals for the scientific community.The aim of this review is to analyze the state of the art around the heart rate variability (HRV) as a predictor factor for SCD.HRV is probably the most analyzed index in cardiovascular risk stratification technical literature, therefore an important number of models and methods have been developed.Nowadays, low HRV has been shown to be independently predictive of increased mortality in post- myocardial infarction patients, heart failure patients, in contrast with the data of the general population.Contrariwise, the relationship between HRV and SCD has received scarce attention in low-risk cohorts. Furthermore, in general population the attributable risk is modest and the cost/benefit ratio is not always convenient.The HRV evaluation could become an important tool for health status in risks population, even though the use of HRV alone for risk stratification of SCD is limited and further studies are needed.

Heart rate variability as predictive factor for sudden cardiac death.

The long QT syndrome (LQTS), classified as congenital or acquired, is a multi-factorial disorder of myocardial repolarization predisposing to life-threatening ventricular arrhythmias, particularly torsades de pointes. In the latest years, inflammation and immunity have been increasingly recognized as novel factors crucially involved in modulating ventricular repolarization. In the present paper, we critically review the available information on this topic, also analyzing putative mechanisms and potential interplays with the other etiologic factors, either acquired or inherited. Accumulating data indicate inflammatory activation as a potential cause of acquired LQTS. The putative underlying mechanisms are complex but essentially cytokine-mediated, including both direct actions on cardiomyocyte ion channels expression and function, and indirect effects resulting from an increased central nervous system sympathetic drive on the heart. Autoimmunity represents another recently arising cause of acquired LQTS. Indeed, increasing evidence demonstrates that autoantibodies may affect myocardial electric properties by directly cross-reacting with the cardiomyocyte and interfering with specific ion currents as a result of molecular mimicry mechanisms. Intriguingly, recent data suggest that inflammation and immunity may be also involved in modulating the clinical expression of congenital forms of LQTS, possibly triggering or enhancing electrical instability in patients who already are genetically predisposed to arrhythmias. In this view, targeting immuno-inflammatory pathways may in the future represent an attractive therapeutic approach in a number of LQTS patients, thus opening new exciting avenues in antiarrhythmic therapy.

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Long QT Syndrome: An Emerging Role for Inflammation and Immunity

Comprehensive study of cardiovascular morbidity in hospitalized inflammatory bowel disease patients

Background: In inflammatory bowel disease (IBD) number of thromboembolic events are increased due to hypercoagulupathy and platelet activation. Increases in mean platelet volume (MPV) can lead to platelet activation, this leads to thromboembolic events and can cause acute coronary syndromes. In IBD patients, QT-dispersion and P-wave dispersion are predictors of ventricular arrhythmias and atrial fibrilation; MPV is accepted as a risk factor for acute coronary syndromes, we aimed at evaluating the correlations of these with the duration of disease, its localization and activity.

Methods: The study group consisted of 69 IBD (Ulcerative colitis n: 54, Crohn's Disease n:15) patients and the control group included 38 healthy individuals. Disease activity was evaluated both endoscopically and clinically. Patients with existing cardiac conditions, those using QT prolonging medications and having systemic diseases, anemia and electrolyte imbalances were excluded from the study. QT-dispersion, P-wave dispersion and MPV values of both groups were compared with disease activity, its localization, duration of disease and the antibiotics used.

Results: The P-wave dispersion values of the study group were significantly higher than those of the control group. Duration of the disease was not associated with QT-dispersion, and MPV levels. QT-dispersion, P-wave dispersion, MPV and platelet count levels were similar between the active and in mild ulcerative colitis patients. QT-dispersion levels were similar between IBD patients and the control group. No difference was observed between P-wave dispersion, QT-dispersion and MPV values; with regards to disease duration, disease activity, and localization in the study group (p>0.05).

Conclusions: P-wave dispersion which is accepted as a risk factor for the development of atrial fibirilation was found to be high in our IBD patients. This demonstrates us that the risk of developing atrial fibrillation may be high in patients with IBD. No significant difference was found in the QT-dispersion, and in the MPV values when compared to the control group.

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Evaluation of QT and P Wave Dispersion and Mean Platelet Volume among Inflammatory Bowel Disease Patients

Cardiac involvement has been studied quite extensively in patients affected by inflammatory bowel disease but, as of now, there is no data regarding QT alterations which are well known to be linked to the risk of dangerous arrhythmias. In this study, QT parameters were digitally measured on standard 12-lead ECG in a population of 20 patients affected by inflammatory bowel disease (IBD), with no prior (recent or old) history of cardiac disease and no evidence of electrolyte imbalance. Eighteen healthy subjects formed the control group. The results obtained using non-parametric statistics (Wilcoxon–Mann–Whitney test) showed that heart rate corrected QT interval (QTc) and QTc dispersion (QTc d) values were both significantly higher in IBD patients than in the control group. QTc rank sum values in patients affected by inflammatory bowel disease were 469 versus 311 in healthy subjects (Z = 1.939, p = 0.0263). QTc d rank sum values were 460 in IBD patients versus 320 in controls (Z = 1.686 with p = 0.0459). Regardless of the cause of these QT alterations, it appears evident that accurate monitoring of QT parameters is required in these patients who often experience electrolyte disturbances and who may, in some cases, be undergoing treatment with potentially cardiotoxic drugs such as infliximab.

A study on QT interval in patients affected with inflammatory bowel disease without cardiac involvement.

Objective: Dopamine D1–D5 receptors subtypes were studied in human coronary vessels of healthy subjects to assess their localization and their expression.Methods: Samples of intraparenchymal and extraparenchymal branches of human coronary arteries and veins were harvested from four normal native hearts explanted from four young brain dead heart donors in case of orthoptic transplant, not carried out for technical reasons. In all the samples morphological, biochemical, immunochemical, and morphometrical studies were performed including quantitative analysis of images and evaluation of data.Results: Microanatomical section showed healthy coronary vessels, which expressed all dopamine receptors (from D1 to D5) with a different pattern of distribution between the different layers, in the intra and in the extraparenchymal branches.D1 and D5 (with a prevalence D1 over D5) were distributed in the adventitia and to a lesser extent in the outer media but they were absent in arterioles, capillaries and venules. End...

Dopamine receptor subtypes in the human coronary vessels of healthy subjects.

Introduction Diabetes mellitus (DM) can be complicated by an involvement of Neurovegetative System (NVS), conventionally and non-invasively diagnosed by the means of Ewing's test and Heart Rate Variability (HRV) analysis. It is well known that the NVS is physiologically responsible, via biological clocks, for the regulation of Circadian Rhythms (CR) characterizing the majority of biological functions. Therefore, this study is aimed at investigating the CR of Heart Rate (HR) and Blood Pressure (BP) in DM, postulating that the diagnosis of Silent Cardiac Dysautonomia (SCD) could be facilitated by detecting anomalous rhythmometric changes, including the worse one, i.e., the lose of a CR. Materials and methods The study has been performed on 30 clinically healthy subjects (CHS), 10 patients with DM1 and 30 patients with DM2, who underwent an ambulatory BP monitoring (ABPM) collecting data equidistantly every 30 minutes, under standardized conditions of lifestyle. The group specific monitored values of systolic (S), diastolic (D) BP, as well as HR have been analyzed via: 1. a conventional analysis of their intradiem variability; 2. a chronobiometric analysis (Cosinor method) of their CR. Results The conventional analysis disclosed that in CHS, DM1 and DM2, both the HR and BP show an intradiem variability that is significant (p less than 0.001). The chronobiological analysis showed that in CHS and DM2, both the HR and BP show a significant CR (p less than 0.001), viceversa in DM1 HR is characterized by a non significant CR (p=0.124), notwithstanding that the SBP and DBP maintain a significant CR (p less than 0.001). Conclusions The disappearance of HR CR in DM1 reveals the involvement of neurovegetative biological clock that selectively controls the HR CR, as it is demonstrated by the pathophysiological finding of an internal desynchronization between the HR and BP CR. The selective lose of HR CR in DM1 leads to conclude that the ABPM, along with its Cosinor analysis, might be a practical, repeatable, low cost, low risk technique for diagnosing the SCD, at least in DM1.

[Diagnosing silent cardiac dysautonomia via ambulatory blood pressure monitoring: early diagnosis shown by the lack of heart rate circadian rhythm in type 1 diabetes mellitus].

Objective Outcome data for patients ≥75 years with hypertrophic obstructive cardiomyopathy (HOCM) undergoing alcohol septal ablation (ASA) are lacking. Therefore, a retrospective single-centre analysis was conducted. Methods The data of all consecutive ASAs, that were performed at our institution between 1 September 1997 and 31 July 2021 in patients with HOCM with left ventricular outflow tract gradients (LVOTG) ≥50 mm Hg, were collected from patient reports. ASA was performed per institutional standards with 95% ethanol infused into a feasible septal branch. Differences regarding echocardiographic, procedural and clinical parameters at baseline and after 6 months between patients ≥75 years and <75 years were assessed. Results We found 208 ASAs in patients ≥75 years (85.1% female; age 78.0 years (IQR 76.0–80.0)) and 1430 ASAs in patients <75 years (42.0% female; age 56.0 years (IQR 46.0–65.0)). Patients ≥75 years had lower distances in 6 min walk test (baseline: 317.0 m (IQR 242.0–389.0) vs 438.0 m (IQR 353.3–504.0); p<0.0001). Exercise-induced LVOTG calculated at follow-up was lower in patients ≥75 years (29.5 mm Hg (IQR 18.0–54.0) vs 39.5 mm Hg (IQR 23.0–73.8); p=0.0007). There were more high-degree AV blocks after ASA in patients ≥75 years (25.5% vs 13.6%; p<0.0001). The in-hospital mortality did not differ between the groups (age ≥75 years: 1.0%; age <75 years: 0.6%; p=0.6580). Conclusion ASA had similar efficacy and intrahospital mortality in patients ≥75 years compared with younger patients. Higher rates of AV block with need for permanent pacemaker implantation were observed in patients ≥75 years of age.

Andi Tego

Papers

A study on QT interval in patients affected with inflammatory bowel disease without cardiac involvement.

Dopamine receptor subtypes in the human coronary vessels of healthy subjects.

[Diagnosing silent cardiac dysautonomia via ambulatory blood pressure monitoring: early diagnosis shown by the lack of heart rate circadian rhythm in type 1 diabetes mellitus].

Alcohol septal ablation in patients aged 75 years or older with hypertrophic obstructive cardiomyopathy