Long term follow-up of heart rate variability in healthcare workers with mild COVID-19.

Introduction: Prior investigations into post-COVID dysautonomia often lacked control groups or compared affected individuals solely to healthy volunteers. In addition, no data on the follow-up of patients with SARS-CoV-2-related autonomic imbalance are available. Methods: In this study, we conducted a comprehensive clinical and functional follow-up on healthcare workers (HCWs) with former mild COVID-19 (group 1, n = 67), to delineate the trajectory of post-acute autonomic imbalance, we previously detected in a case-control study. Additionally, we assessed HCWs for which a test before SARS-CoV-2 infection was available (group 2, n = 29), who later contracted SARS-CoV-2, aiming to validate findings from our prior case-control investigation. We evaluated autonomic nervous system heart modulation by means of time and frequency domain heart rate variability analysis (HRV) in HCWs during health surveillance visits. Short-term electrocardiogram (ECG) recordings, were obtained at about 6, 13 months and both at 6 and 13 months from the negative SARS-CoV-2 naso-pharyngeal swab (NPS) for group 1 and at about 1-month from the negative NPS for group 2. HCWs who used drugs, had comorbidities that affected HRV, or were hospitalized with severe COVID-19 were excluded. Results: Group 1 was split into three subgroups clinically and functionally followed at, about 6 months (subgroup-A, n = 17), 13 months (subgroup-B, n = 37) and both at 6 and 13 months (subgroup-C, n = 13) from the negative SARS-CoV-2 NPS. In subgroup-A, at 6-month follow-up compared with baseline, the spectral components in the frequency domain HRV parameters, showed an increase in normalized high frequency power (nHF) (t = 2.99, p = 0.009), a decrease in the normalized low frequency power (nLF) (t = 2.98, p = 0.009) and in the LF/HF ratio (t = 3.13, p = 0.006). In subgroup B, the comparison of the spectral components in the frequency domain HRV parameters, at 13-month follow-up compared with baseline, showed an increase in nHF (t = 2.54, p = 0.02); a decrease in nLF (t = 2.62, p = 0.01) and in the LF/HF ratio (t = 4.00, p = 0.0003). In subgroup-C, at both 6 and 13-month follow-ups, the spectral components in the frequency domain HRV parameters were higher than baseline in nHF (t = 2.64, p = 0.02 and (t = 2.13, p = 0.05, respectively); lower in nLF (t = 2.64, p = 0.02 and (t = 2.13, p = 0.05, respectively), and in LF/HF (t = 1.92, p = 0.08 and (t = 2.43, p = 0.03, respectively). A significant proportion of HCWs reported persistent COVID-19 symptoms at both the 6 and 13-month follow-ups, seemingly unrelated to cardiac autonomic balance. In group 2 HCWs, at 1-month follow-up compared with baseline, the spectral components in the frequency domain HRV parameters, showed a decrease in nHF (t = 2.19, p = 0.04); an increase in nLF (t = 2.15, p = 0.04) and in LF/HF (t = 3.49, p = 0.002). Conclusion: These results are consistent with epidemiological data suggesting a higher risk of acute cardiovascular complications during the first 30 days after COVID-19. The SARS-CoV-2 associated autonomic imbalance in the post-acute phase after recovery of mild COVID-19 resolved 6 months after the first negative SARS-CoV-2 NPS. However, a significant proportion of HCWs reported long-term COVID-19 symptoms, which dot not seems to be related to cardiac autonomic balance. Future research should certainly further test whether autonomic imbalance has a role in the mechanisms of long-COVID syndrome.

Persistent Increase of Sympathetic Activity in Post-Acute COVID-19 of Paucisymptomatic Healthcare Workers.

Healthcare workers (HCWs) represent a population with a significant burden of paucisymptomatic COVID-19, as the general population. We evaluated autonomic nervous system activity by means of heart rate variability (HRV) in HCWs during health surveillance visits. Short-term electrocardiogram (ECG) recordings were obtained 30 days (IQR 5.25-55.75) after a negative naso-pharyngeal swab for SARS-CoV-2 in 44 cases and compared with ECGs of 44 controls with similar age and sex distribution. Time and frequency domain HRV were evaluated. HCWs who used drugs, had comorbidities that affected HRV, or were hospitalized with severe COVID-19 were excluded. Frequency domain HRV analysis showed a significantly higher low/high-frequency power ratio (LF/HF) in the case study compared with controls (t = 2.84, p = 0.006). In time domain HRV analysis, mean standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) were significantly lower for cases compared with controls (t = -2.64, p = 0.01 and t = -3.27, p = 0.002, respectively). In the post-acute phase of infection, SARS-CoV-2 produces an autonomic imbalance mirrored by a reduction in HRV. These results are consistent with epidemiological data that suggest a higher risk of acute cardiovascular complications in the first 30 days after COVID-19 infection.

Modulation of TRPV-1 by prostaglandin-E2 and bradykinin changes cough sensitivity and autonomic regulation of cardiac rhythm in healthy subjects.

A neurogenic pathway, involving airway TRPV-1, has been implicated in acute cardiovascular events occurring after peaks of air pollution. We tested whether inhaled prostaglandin-E2 (PGE2) and bradykinin (BK) regulate TRPV-1 activity in vivo by changing cough response to capsaicin (CPS) and affecting heart rate variability (HRV), while also taking into account the influence of TRPV-1 polymorphisms (SNPs). Moreover, we assessed the molecular mechanism of TRPV-1 modulation in vitro. Seventeen healthy volunteers inhaled 100 µg PGE2, 200 µg BK or diluent in a randomized double-blind fashion. Subsequently, the response to CPS was assessed by cough challenge and the sympathetic activity by HRV, expressed by low (nLF) and high (nHF) normalized frequency components, as well as nLF/nHF ratio. Intracellular [Ca2+] was measured in HeLa cells, transfected with wild-type TRPV-1, pre-treated with increasing doses of PGE2, BK or diesel exhaust particulate (DEP), after CPS stimulation. Six functional TRPV-1 SNPs were characterized in DNA from each subject. Inhalation of PGE2 and BK was associated with significant increases in cough response induced by 30 µM of CPS (cough number after PGE2 = 4.20 ± 0.42; p < 0.001, and after BK = 3.64 ± 0.37; p < 0.01), compared to diluent (2.77 ± 0.29) and in sympathetic activity (nLF/nHF ratio after PGE2 = 6.1; p < 0.01, and after BK = 4.2; p < 0.05), compared to diluent (2.5-3.3). No influence of SNPs was observed on autonomic regulation and cough sensitivity. Unlike PGE2 and BK, DEP directly activated TRPV-1. Inhalation of PGE2 and BK sensitizes TRPV-1 and is associated with autonomic dysregulation of cardiac rhythm in healthy subjects.

Daily Exposure to Air Pollution Particulate Matter Is Associated with Atrial Fibrillation in High-Risk Patients.

Several epidemiological studies found an association between acute exposure to fine particulate matter of less than 2.5 µm and 10 µm in aerodynamic diameter (PM2.5 and PM10) and cardiovascular diseases, ventricular fibrillation incidence and mortality. The effects of pollution on atrial fibrillation (AF) beyond the first several hours of exposure remain controversial. A total of 145 patients with implantable cardioverter-defibrillators (ICDs), cardiac resynchronization therapy defibrillators (ICD-CRT), or pacemakers were enrolled in this multicentric prospective study. Daily levels of PM2.5 and PM10 were collected from monitoring stations within 20 km of the patient's residence. A Firth Logistic Regression model was used to evaluate the association between AF and daily exposure to PM2.5 and PM10. Exposure levels to PM2.5 and PM10 were moderate, being above the World Health Organization (WHO) PM2.5 and PM10 thresholds of 25 µg/m3 and 50 µg/m3, respectively, on 26% and 18% of the follow-up days. An association was found between daily levels of PM2.5 and PM10 and AF (95% confidence intervals (CIs) of 1.34-2.40 and 1.44-4.28, respectively) for an increase of 50 µg/m3 above the WHO threshold. Daily exposure to moderate PM2.5 and PM10 levels is associated with AF in patients who are not prone to AF.

Dietary and Lifestyle Patterns are Associated with Heart Rate Variability.

Assessment of heart rate variability (HRV) and cardiac ectopic beats is a clinically relevant topic. The present exploratory observational study aimed to inspect the relationships of lifestyle, dietary patterns, and anthropometrics with HRV, premature ventricular complexes (PVCs), and supraventricular premature complexes (SVPCs). A cross-sectional study enrolling subjects undergoing Holter monitoring was performed. Sociodemographic and clinical characteristics, body composition (full-body bio-impedentiometry), dietary patterns (validated food frequency questionnaire and 24 h dietary recall), and quality of life were assessed. Generalized additive models were estimated to evaluate the relationships between outcomes of interest and variables collected. The study enrolled 121 consecutive patients undergoing 24 h Holter monitoring. Upon univariable analysis, HRV was found to have an inverse association with mass of body fat (MBF) (p-value 0.015), while doing physical activity was associated with a significantly higher HRV (p-value 0.036). Upon multivariable analysis, fruit consumption in the 24 h dietary recall was found to be directly associated with HRV (p-value 0.044). The present findings might be useful for improving the management of patients attending cardiac rhythm labs, and to tailor ad hoc prevention strategies (modification of lifestyle and eating habits) based on Holter parameters.

Association between air pollution and ventricular arrhythmias in high-risk patients (ARIA study): a multicentre longitudinal study.

BACKGROUND: Although the effects of air pollution on mortality have been clearly shown in many epidemiological and observational studies, the pro-arrhythmic effects remain unknown. We aimed to assess the short-term effects of air pollution on ventricular arrhythmias in a population of high-risk patients with implantable cardioverter-defibrillators (ICDs) or cardiac resynchronisation therapy defibrillators (ICD-CRT). METHODS: In this prospective multicentre study, we assessed 281 patients (median age 71 years) across nine centres in the Veneto region of Italy. Episodes of ventricular tachycardia and ventricular fibrillation that were recorded by the diagnostic device were considered in this analysis. Concentrations of particulate matter of less than 10 µm (PM10) and less than 2·5 µm (PM2·5) in aerodynamic diameter, carbon monoxide, nitrogen dioxide, sulphur dioxide, and ozone were obtained daily from monitoring stations, and the 24 h median value was considered. Each patient was associated with exposure data from the monitoring station that was closest to their residence. Patients were followed up for 1 year and then scheduled to have a closing visit, within 1 more year. This study is registered with ClinicalTrials.gov, number NCT01723761. FINDINGS: Participants were enrolled from April 1, 2011, to Sept 30, 2012, and follow-ups (completed on April 5, 2014) ranged from 637 to 1177 days (median 652 days). The incidence of episodes of ventricular tachycardia and ventricular fibrillation correlated significantly with PM2·5 (p<0·0001) but not PM10. An analysis of ventricular fibrillation episodes alone showed a significant increase in risk of higher PM2·5 (p=0·002) and PM10 values (p=0·0057). None of the gaseous pollutants were significantly linked to the occurrence of ventricular tachycardia or ventricular fibrillation. In a subgroup analysis of patients with or without a previous myocardial infarction, only the first showed a significant association between particulate matter and episodes of ventricular tachycardia or ventricular fibrillation. INTERPRETATION: Particulate matter has acute pro-arrhythmic effects in a population of high-risk patients, which increase on exposure to fine particles and in patients who have experienced a previous myocardial infarction. The time sequence of the arrhythmic events suggests there is an underlying neurally mediated mechanism. From a clinical point of view, the results of our study should encourage physicians to also consider environmental risk when addressing the prevention of arrhythmic events, particularly in patients with coronary heart disease, advising them to avoid exposure to high levels of fine particulate matter. FUNDING: There was no funding source for this study.

Is Internet use associated with anxiety in patients with and at risk for cardiomyopathy?

OBJECTIVE: The aim of the study was to determine the relation between online health information seeking behavior and anxiety level among a sample of patients with manifested cardiomyopathy or at risk for cardiomyopathy. METHODS: The research is a cross-sectional study conducted among 104 patients with cardiomyopathy diagnosis and patients at risk for cardiomyopathy. Patients completed 3 different questionnaires: Use of Internet Health Information questionnaire about the use of Internet, Short Form SF-12 items questionnaire on quality of life, and State-Trait Anxiety Inventory measuring general anxiety levels. RESULTS: Forty-eight patients had a diagnosis of primary or secondary cardiomyopathy, and 56 patients, with conditions predisposing to cardiomyopathy. Eighty-five percent of the considered population is surfing the Internet to obtain nonspecific information about health in general, and the 65% use it to look specifically for heart disease. For both groups of patients with cardiomyopathy and at risk for cardiomyopathy, online health information seeking behavior is associated with substantially lower state anxiety levels (P = .041). CONCLUSION: Web use, as a source of health information, has been shown to be associated with anxiety reduction in patients with or at risk for cardiomyopathy, suggesting that Internet technology can be a useful instrument due to its informational power and its potentially therapeutic value.

Networking and data sharing reduces hospitalization cost of heart failure: the experience of GISC study.

RATIONALE, AIMS AND OBJECTIVES: Heart failure (HF) is a concerning public health burden in Western society because, despite the improvement of medical treatments, it is still associated with adverse outcomes (high morbidity and mortality), resulting in one of the most expensive chronic disease in Western countries. Hospital admission particularly is the most expensive cost driver among the several resources involved in the management of HF. The aim of our study was to investigate the cost of hospitalization before and after the enrolment to a new strategy (GISC) in the management of patients with HF. METHODS: We enrolled a cohort of 90 patients. Patients were eligible to the study if they were hospitalized with a new diagnosis of HF or a diagnosis of decompensated HF. The enrolment to the study corresponded to the enrolment to the GISC intervention. We calculated the cost for every hospital admission at 6 and 12 months before and after the enrolment using the tariff paid for the diagnosis-related group. RESULTS: Comparing per-patient cumulative cost before and after the enrolment, we showed that patient's hospitalization was less expensive after the enrolment to the GISC intervention. The strategy resulted in an average cumulative estimated saving of €439322.00 (95% CI €413890.70; €464753.40) at 6 months and of €832276.80 (95% CI €786863.70; €877690.00) at 12 months after the enrolment. CONCLUSIONS: We found out that the intervention was a cost-saving strategy for follow-up of the patients suffering from HF at 6 and 12 months after the enrolment compared with hospitalizations' cost before the recruitment.

Cost-effectiveness of early detection of atrial fibrillation via remote control of implanted devices.

RATIONALE, AIMS AND OBJECTIVES: Atrial fibrillation (AF) is an independent risk factor for stroke, and its incidence is high in patients implanted with pacemakers (PMs) and implantable cardioverter defibrillators (ICDs). The aim of our study is to evaluate the potential benefit of remote control (RC) on the incidence of stroke related to AF in patients with new-onset AF implanted with PMs and ICDs and to evaluate the impact of RC on the consumption of medical resources. METHOD: The study consisted of two cohorts of patients: group AMB (patients attending ambulatory care clinics from August to October 2013) and group RC (patients followed remotely). All detected cases of new-onset AF were confirmed by the electrogram stored in the device's memory or by standard electrocardiogram recording. Monte Carlo simulations were performed in order to evaluate the potential risk reduction of stroke related to AF. The costs were estimated from the perspectives of the hospital, the patients and the National Health Service. RESULT: We enrolled 223 patients in group RC and 359 in group AMB. We detected 20 new-onset cases of AF, and the median time to AF detection was 2 days in the RC and 78 days in the ambulatory care clinic control. Management of patients was more efficient with RC, with an average savings in direct costs of €40.88 per year per patient. Through the use of Monte Carlo simulations, we showed that the early detection of new-onset AF may provide a relative risk reduction of 94.3% for stroke in PM-implanted patients older than 55 years. CONCLUSION: RC potentially provides a risk reduction for stroke because it allows an early detection of new-onset AF. Moreover, it is also a cost-saving means of follow-up.

Remote monitoring for implantable defibrillators: a nationwide survey in Italy.

BACKGROUND: Remote monitoring (RM) permits home interrogation of implantable cardioverter defibrillator (ICD) and provides an alternative option to frequent in-person visits. OBJECTIVE: The Italia-RM survey aimed to investigate the current practice of ICD follow-up in Italy and to evaluate the adoption and routine use of RM. METHODS: An ad hoc questionnaire on RM adoption and resource use during in-clinic and remote follow-up sessions was completed in 206 Italian implanting centers. RESULTS: The frequency of routine in-clinic ICD visits was 2 per year in 158/206 (76.7%) centers, 3 per year in 37/206 (18.0%) centers, and 4 per year in 10/206 (4.9%) centers. Follow-up examinations were performed by a cardiologist in 203/206 (98.5%) centers, and by more than one health care worker in 184/206 (89.3%) centers. There were 137/206 (66.5%) responding centers that had already adopted an RM system, the proportion of ICD patients remotely monitored being 15% for single- and dual-chamber ICD and 20% for cardiac resynchronization therapy ICD. Remote ICD interrogations were scheduled every 3 months, and were performed by a cardiologist in 124/137 (90.5%) centers. After the adoption of RM, the mean time between in-clinic visits increased from 5 (SD 1) to 8 (SD 3) months (P<.001). CONCLUSIONS: In current clinical practice, in-clinic ICD follow-up visits consume a large amount of health care resources. The results of this survey show that RM has only partially been adopted in Italy and, although many centers have begun to implement RM in their clinical practice, the majority of their patients continue to be routinely followed-up by means of in-clinic visits.