Cardiovascular mechanisms of thyroid hormones and heart failure: Current knowledge and perspectives.

A multiple hormonal imbalance that accompanies heart failure (HF) may have a significant impact on the clinical course in such patients. The non-thyroidal illness syndrome (NTIS), also referred to as euthyroid sick syndrome or low triiodothyronine syndrome, can be found in about 30% of patients with HF. NTIS represents a systemic adaptation to chronic illness that is associated with increased cardiac and overall mortality in patients with HF. While conclusions on thyroid-stimulating hormone, free triiodothyronine, total and free thyroxine are currently unresolved, serum total triiodothyronine levels and the ratio of free triiodothyronine to free thyroxine seem to provide the best correlates to the echocardiographic, laboratory and clinical parameters of disease severity. HF patients with either hyper- or hypothyroidism should be treated according to the appropriate guidelines, but the therapeutic approach to NTIS, with or without HF, is still a matter of debate. Possible treatment options include better individual titration of levothyroxine therapy, combined triiodothyronine plus thyroxine therapy and natural measures to increase triiodothyronine. Future research should further examine the cellular and tissue mechanisms of NTIS as well as new therapeutic avenues in patients with HF.

Circulating thyroid hormones and clinical parameters of heart failure in men.

Heart failure (HF) is a multiple hormonal deficiency syndrome which includes alterations in the serum concentration of thyroid hormones (TH). This cross-sectional study enrolled 215 male patients hospitalised for acute HF. Data on cardiovascular risk factors, chronic medications, cardiac function assessed by echocardiography, and clinical parameters of HF were prospectively collected. The independent predictive association of TH with all investigated parameters of the HF severity were assessed. The patient's mean age was 74.4 years, 57.2% had arterial hypertension, 54.0% were consuming alcohol, and 42.3% were diabetics. Multivariate analysis revealed that total triiodothyronine (TT3) was an independent predictor of greater left ventricular ejection fraction (LVEF; ß = 0.223, p = 0.008), less progressed left ventricular diastolic dysfunction (LVDD; ß = - 0.271, p = 0.001) and lower N-terminal pro-brain natriuretic peptide (NT-proBNP; ß = - 0.365, p < 0.001). None of the TH other than TT3 was associated with LVDD or NT-proBNP, whereas free triiodothyronine (ß = - 0.197, p = 0.004), free thyroxine (ß = - 0.223, p = 0.001) and total thyroxine (ß = - 0.140, p = 0.041) were inversely associated with LVEF. The present study suggests that, among TH, serum TT3 level is most closely associated with echocardiographic, laboratory and clinical parameters of the severity of HF in men.

Systematic Review on S-ICD Lead Extraction.

BACKGROUND AND PURPOSE: Subcutaneous implantable cardioverter defibrillators (S-ICDs) have emerged in recent years as a valid alternative to traditional transvenous ICDs (TV-ICDs). Therefore, the number of S-ICD implantations is rising, leading to a consequent increase in S-ICD-related complications sometimes requiring complete device removal. Thus, the aim of this systematic review is to gather all the available literature on S-ICD lead extraction (SLE), with particular reference to the type of indication, techniques, complications and success rate. METHODS: Studies were identified by searching electronic databases (Medline via PubMed, Scopus and Web of Science) from inception to 21 November 2022. The search strategy adopted was developed using the following key words: subcutaneous, S-ICD, defibrillator, ICD, extraction, explantation. Studies were included if they met both of the following criteria: (1) inclusion of patients with S-ICD; (2) inclusion of patients who underwent SLE. RESULTS: Our literature search identified 238 references. Based on the abstract evaluation, 38 of these citations were considered potentially eligible for inclusion, and their full texts were analyzed. We excluded 8 of these studies because no SLE was performed. Eventually, 30 studies were included, with 207 patients who underwent SLE. Overall, the majority of SLEs were performed for non-infective causes (59.90%). Infection of the device (affecting either the lead or the pocket) was the cause of SLE in 38.65% of cases. Indication data were not available in 3/207 cases. The mean dwelling time was 14 months. SLEs were performed using manual traction or with the aid of a tool designed for transvenous lead extraction (TLE), including either a rotational or non-powered mechanical dilator sheath. CONCLUSIONS: SLE is performed mainly for non-infective causes. Techniques vary greatly across different studies. Dedicated tools for SLE might be developed in the future and standard approaches should be defined. In the meantime, authors are encouraged to share their experience and data to further refine the existing variegated approaches.

Long-Term Adverse Effects of Mild COVID-19 Disease on Arterial Stiffness, and Systemic and Central Hemodynamics: A Pre-Post Study.

COVID-19-associated vascular disease complications are primarily associated with endothelial dysfunction; however, the consequences of disease on vascular structure and function, particularly in the long term (>7 weeks post-infection), remain unexplored. Individual pre- and post-infection changes in arterial stiffness as well as central and systemic hemodynamic parameters were measured in patients diagnosed with mild COVID-19. As part of in-laboratory observational studies, baseline measurements were taken up to two years before, whereas the post-infection measurements were made 2-3 months after the onset of COVID-19. We used the same measurement protocol throughout the study as well as linear and mixed-effects regression models to analyze the data. Patients (N = 32) were predominantly healthy and young (mean age ± SD: 36.6 ± 12.6). We found that various parameters of arterial stiffness and central hemodynamics-cfPWV, AIx@HR75, and cDBP as well as DBP and MAP-responded to a mild COVID-19 disease. The magnitude of these responses was dependent on the time since the onset of COVID-19 as well as age (pregression_models ≤ 0.013). In fact, mixed-effects models predicted a clinically significant progression of vascular impairment within the period of 2-3 months following infection (change in cfPWV by +1.4 m/s, +15% in AIx@HR75, approximately +8 mmHg in DBP, cDBP, and MAP). The results point toward the existence of a widespread and long-lasting pathological process in the vasculature following mild COVID-19 disease, with heterogeneous individual responses, some of which may be triggered by an autoimmune response to COVID-19.

Acute myocardial infarction triggered by physical exertion: a systematic review and meta-analysis.

AIMS: While regular physical activity has clear benefits to cardiovascular health, physical exertion can trigger acute myocardial infarction (AMI). We aimed to estimate how many AMIs may be attributed to bouts of physical exertion and to explore possible modifiers of this association. METHODS AND RESULTS: MEDLINE, ISI Web of Science, and Scopus databases were searched for case-crossover studies reporting the relative risk (RR) of exertion-related AMI and exposure prevalence in the control periods. We used the random-effects model to pool the RR estimates and the mixed-effects model and random-effects meta-regression for subgroup analyses and estimated the population attributable fraction (PAF) at the population level and in different subgroups. The study met the Preferred Reporting Items for Systematic Reviews and Meta-Analyses requirements. Twelve studies including 19 891 AMI patients met the criteria for inclusion. There was a strong overall association between episodic physical exertion and AMI [RR = 3.46; 95% confidence interval (CI), 3.16-3.78]. The total PAF was 10.6% (95% CI, 9.44-11.83). For each additional year of age, the RR of exertion-related AMI increased by ∼3%, but the PAF decreased by 2%. For each additional time of habitual activity per week, the RR of exertion-related AMI decreased by ∼43%. The impact was greater among those engaged in physical exertion one to three times a week (≥20% of cases) and among those who did not take compared with those who took ß-blockers (P = 0.049). CONCLUSION: Every tenth AMI may be assigned to physical exertion. The impact was more pronounced among younger patients, those exposed to exertion one to three times a week, and those not taking ß-blockers.

Twelve case-crossover studies with 19 891 patients were included in our systematic review with meta-analysis to estimate how many acute myocardial infarctions may be attributed to bouts of physical exertion and to explore possible modifiers of this association.Approximately 10.6% of all acute myocardial infarctions may be attributed to physical exertion, but the impact was greater in younger individuals or those engaged in exertion one to three times/week. Among the latter, exertion triggers approximately every fifth infarction.Beta-blockers may provide a protection from the triggering effect of physical exertion.

Therapeutic vs. prophylactic anticoagulation in COVID-19 patients: a systematic review and meta-analysis of real-world studies.

INTRODUCTION: Coagulopathy, in the form of either venous or arterial thromboembolism, is one of the most severe sequelae of coronavirus disease (COVID-19) and has been associated with poorer outcomes. However, the role of therapeutic anticoagulation (tAC) or prophylactic anticoagulation (pAC) in COVID-19 patients has not been definitely established. Therefore, the aim of this systematic review and meta-analysis was to gather all the available real-world data in the field and to provide a reliable effect size of the effect on mortality of tAC compared to pAC in COVID-19 patients. EVIDENCE ACQUISITION: Real-world studies (RWS) were identified by searching electronic databases from inception to 31st October, 2021. Randomized controlled trials were excluded. Mortality and bleedings were considered as primary and secondary outcomes, respectively. EVIDENCE SYNTHESIS: 10 RWS and 5541 patients were included in the analysis. Overall, tAC was associated with lower mortality (HR=0.62, 95% CI: 0.54-0.71). There was asymmetry at the funnel plot suggesting publication bias, that was not confirmed at the Egger test (P=0.07). For the secondary endpoint, there was a non-statistically significant tendency for more bleedings in patients treated with tAC compared to pAC (RR=1.75, 95% CI: 0.81-3.81). CONCLUSIONS: Our meta-analysis, based on RWS and adjusted estimates of risk, suggests a survival benefit of tAC over pAC in COVID-19 patients in the real world.

Clinical predictors of hyponatremia in patients with heart failure according to severity of chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) has been associated with adverse clinical outcomes. Hyponatremia, a marker of illness severity and poor prognosis, is commonly exhibited in patients with CKD. METHODS: This cross-sectional study included patients hospitalized due to heart failure (HF). We used stepwise logistic regression to investigate the independent association of cardiovascular drugs, markers of HF severity, and baseline clinical characteristics with hyponatremia in three subgroups; normal renal function, mild-to-moderate CKD, and severe CKD. RESULTS: Of the 1232 patients, 38.6% were hyponatremic. Patients with severe CKD, compared to those with normal renal function and mild-to-moderate CKD, were more likely to be hyponatremic (47.1%, 34.4% and 36.6%, respectively; p ≤ 0.0001). Alcohol consumption, female sex, n-terminal pro-brain natriuretic peptide (NT-proBNP), hydrochlorothiazide (HCT), and mineralocorticoid receptor antagonist (MRA) use, or angiotensin II receptor I blocker (ARB) non-use were associated with hyponatremia in patients with normal renal function (p ≤ 0.03 in all cases). Current smoking, diabetes mellitus, NT-proBNP, loop diuretic dose, and MRA use were predictors in mild-to-moderate CKD (p ≤ 0.04 in all cases). ARB use, loop diuretic dose, and HCT use were predictors in severe CKD (p ≤ 0.03 in all cases). Non-use of dihydropyridine calcium channel blocker (CCB) was an independent predictor of hyponatremia in all CKD stages (p ≤ 0.04 in all cases). CONCLUSION: Apart from a firm favorable effect of CCBs, cardiovascular therapy should be carefully tailored to avoid hyponatremia in patients with cardiorenal syndrome.

Prevalence of asymptomatic atrial fibrillation among multimorbid elderly patients: diagnostic implications.

Advancing age of the global population is one of the main reasons for the uprising trend in atrial fibrillation (AF) prevalence worldwide leading to a proper "AF epidemic". Strictly related to the increasing prevalence of AF in the elderly is the relevant burden of cardiac end extra-cardiac comorbidities that these patients show. Patients with AF are frequently asymptomatic (i.e., asymptomatic or silent AF) and thus the arrhythmia is generally underdiagnosed. Detainment of proper treatment in elderly and comorbid patients may potentially result in significant morbidity and mortality. Therefore, in recent years, several screening strategies (systematic vs opportunistic screening) for asymptomatic AF have been developed and early diagnosis of AF is an important treatment goal that can improve prognosis. This review will focus on the prevalence of asymptomatic AF in the elderly, frequently associated comorbidities, screening strategies, and implications for a correct AF diagnosis.

Acute Myocardial Infarction and Daylight Saving Time Transitions: Is There a Risk?

Available evidence on the risk of acute myocardial infarction (AMI) in the days after the spring daylight saving time (DST) transition suggests either a modest increase or no risk increase. Partial sleep deprivation and enhanced circadian clock misalignment have been implicated as the underlying mechanisms for increased AMI risk, probably via enhanced thrombo-inflammatory processes and activation of the sympathetic nervous system. Most of the studies, as we suggest as a perspective here, have used potentially inappropriate control periods, including the two post-transitional weeks, because adjustment after the spring DST transition lasts at least four weeks for all chronotypes and probably even beyond this period for late chronotypes. The most plausible conclusions, at the moment, for the risk of AMI after the spring DST transition are: (1) the risk is increased, (2) a relatively modest risk increase could be currently underestimated or in some studies undetected, (3) late chronotypes and/or individuals with high levels of social jetlag (a proxy for circadian clock misalignment) could be more affected by the phenomenon, and (4) underlying pathophysiological mechanisms should be further explored. As a significant part of world's population continues to be affected by the biannual clock change, the question of increased AMI risk in the post-transitional period remains an intriguing public health issue.

Public health impact of daily life triggers of sudden cardiac death: A systematic review and comparative risk assessment.

BACKGROUND: Sudden cardiac death (SCD) may be triggered by daily circumstances and activities such as stressful psycho-emotional events, physical exertion or substance misuse. We calculated population attributable fractions (PAFs) to estimate the public health relevance of daily life triggers of SCD and to compare their population impacts. METHODS: We searched PubMed, Scopus and the Web of Science citation databases to retrieve studies of triggers of SCD and cardiac arrest that would enable a computation of PAFs. When more studies investigated the same trigger, a meta-analytical pooled risk random-effect estimate was used. RESULTS: Of the retrieved studies, eight provided data enabling computation of PAFs. The prevalence of exposure within population for SCD triggers in the control periods ranged from 1.06% for influenza infection to 8.73% for recent use of cannabis. Triggers ordered from the highest to the lowest risk increase were: physical exertion, recent cocaine use, episodic alcohol consumption, recent amphetamine use, episodic coffee consumption, psycho-emotional stress within the previous month, influenza infection, and recent cannabis use. The relative risk increase ranged from 1.10 to 4.98. By accounting for both the magnitude of the risk increase and the prevalence in the population, the present estimates of PAF assign 14.5% (95% confidence interval [CI] 4.9-28.5) of all SCDs to episodic alcohol consumption, 9.4% (95% CI 1.2-29.3) to physical exertion, 6.9% (95% CI 0.3-25.0) to cocaine, 6% (95% CI 1.2-14.6) to episodic coffee consumption, 3% (95% CI 0.4-6.8) to psycho-emotional stress in the previous month, 1.7% (95% CI -0.9 to 12.9) to amphetamines, 0.9% (95% CI -4.9 to 12.5) to cannabis, and 0.3% (95% CI 0.2-0.4) to influenza infections. CONCLUSIONS: In addition to episodic alcohol consumption, a trigger with the greatest public health importance for SCD, episodic physical exertion, cocaine use and coffee consumption also show a considerable population impact.