Background: The complex interactions that exist between the pacemaker current, If, and the parasympathetic nervous system could significantly influence the course of patients undergoing chronic therapy with the If blocker ivabradine. We thus aimed to assess the effects of chronic ivabradine therapy on autonomic modulation and on the cardiovascular response to in situ and in vitro parasympathetic stimulation. The right atrial expression of HCN genes, encoding proteins for If, was also evaluated.Methods: Sympathetic and parasympathetic heart rate variability parameters and right atrial HCN(1-4) RNA levels were analyzed in 6 Control and 10 ivabradine-treated male Wistar rats (IVA; 3 weeks, 10 mg/kg/day). The heart rate (HR) and systolic blood pressure (SBP) responses to in situ electrical stimulation of the vagus nerve (2–20 Hz) were assessed in 6 additional Control and 10 IVA rats. The spontaneous sinus node discharge rate (SNDR) response to in vitro cholinergic receptors stimulation using carbamylcholine (10−9–10−6 mol/L) was also assessed in these later rats.Results: Ivabradine significantly increased vagal modulation and shifted the sympatho-vagal balance toward vagal dominance. In Control, in situ vagus nerve stimulation induced progressive decrease in both the SBP (p = 0.0001) and the HR (p< 0.0001). Meanwhile, in IVA, vagal stimulation had no effect on the HR (p = 0.16) and induced a significantly lower drop in SBP (p< 0.05). IVA also displayed a significantly lower SNDR drop in response to carbamylcholine (p< 0.01) and significantly higher right atrial HCN4 expression (p = 0.02).Conclusion: Chronic ivabradine administration enhanced vagal modulation in healthy rats. In addition, ivabradine reduced the HR response to direct muscarinic receptors stimulation, canceled the cardioinhibitory response and blunted the hemodynamic response to in situ vagal stimulation. These data bring new insights into the mechanisms of ivabradine-related atrial proarrhythmia and suggest that long-term If blockade may protect against excessive bradycardia induced by acute vagal activation.

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Arrhythmic and hemodynamic complications related to ST-segment elevation myocardial infarction (STEMI) represent a major clinical challenge. Several scores have been developed to predict mortality in STEMI. However, those scores almost exclusively include factors related to the acute phase of STEMI, and no score has been evaluated to date for its ability to specifically predict arrhythmic and hemodynamic complications. We, thus, aimed to assess the ability of chronic risk factors burden, as expressed by the CHA2DS2-VASc score, to predict STEMI-related arrhythmic and hemodynamic complications. Data were collected from 839 consecutive STEMI patients treated by primary percutaneous coronary interventions (pPCI). CHA2DS2-VASc and GRACE scores were calculated for all patients, and their ability to predict STEMI-related arrhythmic (i.e., new-onset atrial fibrillation (AF), ventricular tachycardia/fibrillation) and hemodynamic (i.e., cardiogenic shock, asystole) complications was assessed in univariate and multiple regression analysis. Arrhythmic and hemodynamic complications occurred in 14.8% and 10.2% of patients, respectively. Although the GRACE score outweighed the CHA2DS2-VASc score in the ability to predict STEMI-related hemodynamic complications (p < 0.0001), both scores had a similar predictive value for STEMI-related new-onset AF (p = 0.20), and both remained independent predictors of new-onset AF and of hemodynamic complications in the multiple regression analyses. A CHA2DS2-VASc score > 2 points independently predicted new-onset AF (p < 0.01) and hemodynamic complications (p = 0.04). Alongside the GRACE score, the CHA2DS2-VASc score independently predicted new-onset AF and hemodynamic complications in STEMI patients treated by pPCI. These data suggest that a combination of acute and chronic risk factors could provide additional benefit in identifying patients at risk of STEMI-related complications, who could benefit from closer follow-up and more intensive prophylactic and therapeutic strategies.

Introduction Methicillin-resistant Staphylococcus aureus (MRSA) is a leading pathogen responsible for bacteremia and valvular endocarditis. In patients with Coronavirus Disease 2019 (COVID-19), MRSA co-infection represents a challenging scenario, with increased morbidity and mortality. Case presentation We present a case of possible valvular endocarditis in a patient with acute COVID-19 and MRSA bacteremia. A 75-year-old woman presented with severe symptomatic aortic stenosis and moderate mitral stenosis. During hospitalization, she developed COVID-19 pneumonia with acute respiratory failure, and temporal and frontal intraparenchymal cerebral hemorrhage. Blood cultures were positive for MRSA, and the patient was started on a specific antibiotics regimen. The patient subsequently developed multi-organ failure and was transferred to the intensive care unit. Repeated computed tomography of the brain was consistent with a new occipitotemporal cortical hypodensity. Transthoracic echocardiography (TTE) showed a small (4 x 4 mm) mass attached to the aortic valve, but with TTE features inconclusive for infective endocarditis. The patient was scheduled for transesophageal echocardiography, but she suffered cardiac arrest, with no response to resuscitation maneuvers. Conclusions This case reveals the diagnostic and therapeutic challenges raised by MRSA and COVID-19 coinfection in a patient with preexisting valvular heart disease.

Background Bisphenol A (BPA) is a synthetic compound found in plastic bottles, sports equipment, or water pipes. The continuous and inevitable human exposure to BPA has been related to increased cardiovascular risk. In experimental studies, acute exposure to high BPA doses was associated with ventricular arrhythmias. However, the effects of chronic exposure to usual BPA doses (i.e., relevant for usual human exposure) on cardiac arrhythmogenicity have not been properly assessed. Purpose We aimed to assess the effects of chronic exposure to high and usual BPA doses on cardiac arrhythmias, electrophysiology, and autonomic modulation in rats. Methods Adult female Wistar rats were randomized into 3 groups: Control, BPA, and BPA-HD (n=7 each). BPA and BPA-HD rats received 50 μg/kg/day and 25 mg/kg/day of BPA, respectively, for 9 weeks. Rats were implanted with radiotelemetry ECG devices and 24-h ECG recordings were performed prior to and after application of transesophageal atrial burst pacing (4,000 stimuli/min for 20 s; 15 cycles). Heart rate variability (HRV) parameters and atrial and ventricular arrhythmias (i.e., atrial premature beats [APB], atrial fibrillation [AF], ventricular premature beats [VPB], ventricular tachycardia/fibrillation [VT/VF]) were assessed based on the 24-h ECG recordings. The left atrium was then collected and atrial depolarization velocity and action potential duration to 90% (APD90) and 50% (APD50) of complete repolarization were measured. Results Mean heart rate (p=0.48), the number of VPB (p=0.90), AF inducibility (p=0.68), and atrial action potential parameters (all p&gt;0.05) were all similar between the 3 groups. None of the animals presented VT/VF. There was no significant difference in the number of atrial or ventricular arrhythmic events nor in the HRV parameters between BPA and Control (all p&gt;0.05). However, BPA-HD presented a significantly higher number of APB both prior to (p=0.02) and after (p=0.04) atrial pacing, and a significantly higher number of post-pacing spontaneous AF episodes (p&lt;0.01) compared to Control. The parasympathetic indexes SDNN, RMSSD, pNN5, and the NHF of the HRV spectrum were all significantly higher (all p&lt;0.05), whereas the LF/HF ratio, an index of sympathetic and parasympathetic interactions, was significantly lower (p=0.01) in the BPA-HD compared with the Control rats. Conclusions In rats, chronic exposure to BPA doses relevant for usual human exposure was not associated in any significant change in cardiac arrhythmogenicity, electrophysiology, or autonomic modulation. However, high-dose BPA exposure, such as that occurring in workers in the plastics industry, led to significant increase in atrial arrhythmogenicity, including AF, that did not seem to be related to atrial electrophysiology changes. Instead, given the strong atrial proarrhythmic effects of vagal hyperactivity, this effect could be linked to the significant increase in vagal modulation induced by high-dose BPA exposure. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by a grant of the Romanian Ministry of Education and Research, CNCS – UEFISCDI