Post-acute sequelae of SARS-CoV-2 (PASC), or long COVID syndrome, is emerging as a major health issue in patients with previous SARS-CoV-2 infection. Symptoms commonly experienced by patients include fatigue, palpitations, chest pain, dyspnea, reduced exercise tolerance, and “brain fog”. Additionally, symptoms of orthostatic intolerance and syncope suggest the involvement of the autonomic nervous system. Signs of cardiovascular autonomic dysfunction appear to be common in PASC and are similar to those observed in postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. In this review, we report on the epidemiology of PASC, discuss current evidence and possible mechanisms underpinning the dysregulation of the autonomic nervous system, and suggest nonpharmacological and pharmacological interventions to treat and relieve symptoms of PASC-associated dysautonomia.

The myocardium is among the most energy-consuming tissues in the body, burning from 6 to 30 kg of ATP per day within the mitochondria, the so-called powerhouse of the cardiomyocyte. Although mitochondrial genetic disorders account for a small portion of cardiomyopathies, mitochondrial dysfunction is commonly involved in a broad spectrum of heart diseases, and it has been implicated in the development of heart failure via maladaptive circuits producing and perpetuating mitochondrial stress and energy starvation. In this bench-to-bedside review, we aimed to (i) describe the key functions of the mitochondria within the myocardium, including their role in ischemia/reperfusion injury and intracellular calcium homeostasis; (ii) examine the contribution of mitochondrial dysfunction to multiple cardiac disease phenotypes and their transition to heart failure; and (iii) discuss the rationale and current evidence for targeting mitochondrial function for the treatment of heart failure, including via sodium-glucose cotransporter 2 inhibitors.

Mitral valve (MV) and tricuspid valve (TV) apparatus geometry are essential to define mechanisms and etiologies of regurgitation and to inform surgical or transcatheter interventions. Given the increasing use of cardiovascular magnetic resonance (CMR) for the evaluation of valvular heart disease, we aimed to establish CMR-derived age- and sex-specific reference values for mitral annular (MA) and tricuspid annular (TA) dimensions and tethering indices derived from truly healthy Caucasian adults. 5065 consecutive UK Biobank participants underwent CMR using cine balanced steady-state free precession imaging at 1.5 T. Participants with non-Caucasian ethnicity, prevalent cardiovascular disease and other conditions known to affect cardiac chamber size and function were excluded. Absolute and indexed reference ranges for MA and TA diameters and tethering indices were stratified by gender and age (45–54, 55–64, 65–74 years). Overall, 721 (14.2%) truly healthy participants aged 45–74 years (54% women) formed the reference cohort. Absolute MA and TA diameters, MV tenting length and MV tenting area, were significantly larger in men. Mean ± standard deviation (SD) end-diastolic and end-systolic MA diameters in the 3-chamber view (anteroposterior diameter) were 2.9 ± 0.4 cm (1.5 ± 0.2 cm/m2) and 3.3 ± 0.4 cm (1.7 ± 0.2 cm/m2) in men, and 2.6 ± 0.4 cm (1.6 ± 0.2 cm/m2) and 3.0 ± 0.4 cm (1.8 ± 0.2 cm/m2) in women, respectively. Mean ± SD end-diastolic and end-systolic TA diameters in the 4-chamber view were 3.2 ± 0.5 cm (1.6 ± 0.3 cm/m2) and 3.2 ± 0.5 cm (1.7 ± 0.3 cm/m2) in men, and 2.9 ± 0.4 cm (1.7 ± 0.2 cm/m2) and 2.8 ± 0.4 cm (1.7 ± 0.3 cm/m2) in women, respectively. With advancing age, end-diastolic TA diameter became larger and posterior MV leaflet angle smaller in both sexes. Reproducibility of measurements was good to excellent with an inter-rater intraclass correlation coefficient (ICC) between 0.92 and 0.98 and an intra-rater ICC between 0.90 and 0.97. We described age- and sex-specific reference ranges of MA and TA dimensions and tethering indices in the largest validated healthy Caucasian population. Reference ranges presented in this study may help to improve the distinction between normal and pathological states, prompting the identification of subjects that may benefit from advanced cardiac imaging for annular sizing and planning of valvular interventions.

Background: Case-reports/series and cohorts of Guillain–Barré syndrome (GBS) associated with COVID-19 vaccination have been reported. Methods: A systematic review and meta-analysis of cohort studies of GBS after COVID-19 vaccination was carried out. Incidence and incidence rate ratio for a number of vaccine doses and risk of GBS, also considering the specific vaccine technology, were calculated in a random-effects model. Results: Of 554 citations retrieved, 518 were discarded as irrelevant. We finally included 15 studies. The random effect model yielded, regardless of the vaccine technology, 1.25 (95%CI 0.21; 2.83) GBS cases per million of COVID-19 vaccine doses, 3.93 (2.54; 5.54) cases per million doses for adenovirus-vectored vaccines and 0.69 (0.38; 1.06) cases per million doses for mRNA vaccines. The GBS risk was 2.6 times increased with the first dose. Regardless of the vaccine technology, the GBS risk was not increased but disaggregating the data it was 2.37 (1.67; 3.36) times increased for adenovirus-vectored vaccines and 0.32 (0.23; 0.47) for mRNA vaccines. Mortality for GBS after vaccination was 0.10 per million doses and 4.6 per GBS cases. Conclusions: Adenovirus-vectored vaccines showed a 2.4 times increased risk of GBS that was about seven times higher compared with mRNA-based vaccines. The decreased GBS risk associated with mRNA vaccines was possibly due to an elicited reduction of infections, including SARS-CoV-2, associated with GBS during the vaccination period. How adenovirus-vectored COVID-19 vaccines may trigger GBS is unclear and further studies should investigate the relationship between vaccine technologies and GBS risk.

Background and purpose: The association between Guillain−Barré syndrome (GBS) and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is debated. This study reappraises, after three pandemic years, the epidemiological data and the features of GBS in SARS‐CoV‐2 patients.Methods: A systematic review and meta‐analysis of case reports/series and cohort studies published between 1 January 2020 and 19 April 2023 was performed.Results: In all, 209 case reports/series (304 patients) and 26 cohort studies were included. The risk of GBS in northern Italy during the first pandemic wave was 2.85 times increased (95% confidence interval [CI] 1.54; 5.25) whereas in some countries the risk during the first pandemic year was 0.17 times reduced (risk ratio 0.83, 95% CI 0.75; 0.93). The incidence of GBS in SARS‐CoV‐2 Italian hospitalized cohorts was 8.55 per 1000 (95% CI 5.33; 12.49) with an estimated incidence of 0.13 GBS per 1000 in the SARS‐CoV‐2 infected population. In European cohorts the pooled rate of GBS with SARS‐CoV‐2 infection was 61.3% of the total. GBS patients with SARS‐CoV‐2 infection showed more frequently, but not differently from non‐infected patients, the classical clinical presentation and the demyelinating subtype. Cranial nerves were more frequently involved in SARS‐CoV‐2 infected patients.Conclusions: An increased risk of GBS occurred in northern Italy during early COVID‐19 pandemic. The recognition of the ‘Italian factor’ reconciles contrasting results of the epidemiological studies. The slightly reduced GBS risk in other countries and the relatively high frequency of GBS associated with SARS‐CoV‐2 infection can be explained by the adopted health measures that decreased the circulation of other GBS infective antecedents.

Nonalcoholic fatty liver disease is increasingly recognized as a major global health problem. Intertwined with diabetes, metabolic syndrome, and obesity, nonalcoholic fatty liver disease embraces a spectrum of liver conditions spanning from steatosis to inflammation, fibrosis, and liver failure. Compared with the general population, the prevalence of cardiovascular disease is higher among nonalcoholic fatty liver disease patients, in whom comprehensive cardiovascular risk assessment is highly desirable. Preclinical effects of nonalcoholic fatty liver disease on the heart include both metabolic and structural changes eventually preceding overt myocardial dysfunction. Particularly, nonalcoholic fatty liver disease is associated with enhanced atherosclerosis, heart muscle disease, valvular heart disease, and arrhythmias, with endothelial dysfunction, inflammation, metabolic dysregulation, and oxidative stress playing in the background. In this topical review, we aimed to summarize current evidence on the epidemiology of nonalcoholic fatty liver disease, discuss the pathophysiological links between nonalcoholic fatty liver disease and cardiovascular disease, illustrate nonalcoholic fatty liver disease–related cardiovascular phenotypes, and finally provide a glimpse on the relationship between nonalcoholic fatty liver disease and cardiac steatosis, mitochondrial (dys)function, and cardiovascular autonomic dysfunction.