Non-invasive electromechanical assessment during atrial fibrillation identifies underlying atrial myopathy alterations with early prognostic value.

Electromechanical characterization during atrial fibrillation (AF) remains a significant gap in the understanding of AF-related atrial myopathy. This study reports mechanistic insights into the electromechanical remodeling process associated with AF progression and further demonstrates its prognostic value in the clinic. In pigs, sequential electromechanical assessment during AF progression shows a progressive decrease in mechanical activity and early dissociation from its electrical counterpart. Atrial tissue samples from animals with AF reveal an abnormal increase in cardiomyocytes death and alterations in calcium handling proteins. High-throughput quantitative proteomics and immunoblotting analyses at different stages of AF progression identify downregulation of contractile proteins and progressive increase in atrial fibrosis. Moreover, advanced optical mapping techniques, applied to whole heart preparations during AF, demonstrate that AF-related remodeling decreases the frequency threshold for dissociation between transmembrane voltage signals and intracellular calcium transients compared to healthy controls. Single cell simulations of human atrial cardiomyocytes also confirm the experimental results. In patients, non-invasive assessment of the atrial electromechanical relationship further demonstrate that atrial electromechanical dissociation is an early prognostic indicator for acute and long-term rhythm control.

Effect of Primary Care Center Characteristics, Healthcare Worker Vaccination Status and Patient Economic Setting on Patient Influenza Vaccination Coverage Rates.

BACKGROUND: Reaching the public health organizations targets of influenza vaccination in at-risk patient groups remains a challenge worldwide. Recognizing the relationship between the healthcare system characteristics and the economic environment of the population with vaccination uptake can be of great importance to improve. METHODS: Several characteristics were correlated in this retrospective ecological study with data from 6.8 million citizens, 15,812 healthcare workers across 258 primary care health centers, and average income by area of the care center in Spain. RESULTS: No correlation between HCW vaccination status and patient vaccination was found. A weak negative significant correlation between the size of the population the care center covers and their vaccination status did exist (6 mo.-59 yr., r = 0.19, p = 0.002; 60-64 yr., r = 0.23, p < 0.001; ≥65 yr., r = 0.23, p ≥ 0.001). The primary care centers with fewer HCWs had better uptake in the at-risk groups in the age groups of 60-64 yr. (r = 0.20, p = 0.002) and ≥65 (r = 0.023, p ≥ 0.001). A negative correlation was found regarding workload in the 6 mo.-59 yr. age group (r = 0.18, p = 0.004), which showed the at-risk groups that lived in the most economically deprived areas were more likely to be vaccinated. CONCLUSIONS: This study reveals that the confounding variables that determine influenza vaccination in a population and in HCWs are complex. Future influenza campaigns should address these especially considering the possibility of combining influenza and SARS-CoV-2 vaccines each year.

Increasing Influenza Vaccination in Primary Healthcare Workers Using Solidary Incentives: Analysis of Efficacy and Costs.

INTRODUCTION: Influenza vaccination campaigns have difficulty in reaching the 75% uptake in healthcare workers (HCWs) that public health organizations target. This study runs a campaign across 42 primary care centers (PCCs) where for every HCW vaccinated against influenza, a polio vaccine is donated through UNICEF for children in developing nations. It also analyses the efficacy and cost of the campaign. METHOD: This observational prospective non-randomized cohort study was conducted across 262 PCCs and 15.812 HCWs. A total of 42 PCCs were delivered the full campaign, 114 were used as the control group, and 106 were excluded. The vaccine uptake in HCWs within each of those PCCs was registered. The cost analysis assumes that campaign costs remain stable year to year, and the only added cost would be the polio vaccines (0.59€). RESULTS: We found statistically significant differences between both groups. A total of 1423 (59.02%) HCWs got vaccinated in the intervention group and 3768 (55.76%) in the control group OR 1.14, CI 95% (1.04-1.26). In this scenario, each additional HCW vaccinated in the intervention group costs 10.67€. Assuming all 262 PCCs had joined the campaign and reached 59.02% uptake, the cost of running this incentive would have been 5506€. The potential cost of increasing uptake in HCWs by 1% across all PCC (n = 8816) would be 1683€, and across all healthcare providers, 8862€ (n = 83.226). CONCLUSIONS: This study reveals that influenza vaccination uptake can be innovative by including solidary incentives and be successful in increasing uptake in HCWs. The cost of running a campaign such as this one is low.

Lesion Index Titration Using Contact-Force Technology Enables Safe and Effective Radiofrequency Lesion Creation at the Root of the Aorta and Pulmonary Artery.

BACKGROUND: Ablation of some myocardial substrates requires catheter-based radiofrequency delivery at the root of a great artery. We studied the safety and efficacy parameters associated with catheter-based radiofrequency delivery at the root of the aorta and pulmonary artery. METHODS: Thirty-six pigs underwent in-vivo catheter-based ablation under continuous contact-force and lesion index (power, contact-force, and time) monitoring during 60-s radiofrequency delivery with an open-irrigated tip catheter. Twenty-eight animals were allocated to groups receiving 40 W (n=9), 50 W (n=10), or 60 W (n=9) radiofrequency energy, and acute (n=22) and chronic (n=6) arterial wall damage was quantified by multiphoton microscopy in ex vivo samples. Adjacent myocardial lesions were quantified in parallel samples. The remaining 8 pigs were used to validate safety and efficacy parameters. RESULTS: Acute collagen and elastin alterations were significantly associated with radiofrequency power, although chronic assessment revealed vascular wall recovery in lesions without steam pop. The main parameters associated with steam pops were median peak temperature >42°C and impedance falls >23 ohms. Unlike other parameters, lesion index values of 9.1 units (interquartile range, 8.7-9.8) were associated with the presence of adjacent myocardial lesions in both univariate ( P=0.03) and multivariate analyses ( P=0.049; odds ratio, 1.99; 95% CI, 1.02-3.98). In the validation group, lesion index values using 40 W over a range of contact-forces correlated with the size of radiofrequency lesions (R2=0.57; P=0.03), with no angiographic or histopathologic signs of coronary artery damage. CONCLUSIONS: Lesion index values obtained during 40 W radiofrequency applications reliably monitor safe and effective lesion creation at the root of the great arteries.

QRS duration reflects underlying changes in conduction velocity during increased intraventricular pressure and heart failure.

Pressure overload and heart failure electrophysiological remodeling (HF-ER) in pigs are associated with decreased conduction velocity (CV) and dispersion of repolarization, which lead to higher risk of ventricular arrhythmia. This work aimed to establish the correlation between QRS complex duration and underlying changes in CV during increased intraventricular pressure (IVP) and/or HF-ER ex-vivo, and to determine whether QRS duration could be sensitive to an acute increase in left ventricular (LV) afterload in-vivo. HF-ER was induced in 7 pigs by high-rate ventricular pacing. Seven weight-matched animals were used as controls. Isolated Langendorff-perfused hearts underwent programmed ventricular stimulation to study QRS complex duration and CV under low/high IVP, using volume-conducted ECG and epicardial optical mapping, respectively. Four additional pigs underwent open-chest surgery to increase LV afterload by partially clamping the ascending aorta, while measuring QRS complex duration during sinus rhythm (SR). In 13 hearts included for analysis, both HF-ER and increased IVP showed significantly slower epicardial CV (-40% and -15%, p < 0.001 and p = 0.004, respectively), which correlated with similar widening of the QRS complex (+41% and +17%, p = 0.005 and p < 0.001, respectively). HF-ER hearts shower larger prolongation of the QRS complex than controls upon increasing the IVP (+21% vs. +12%, respectively. HF-ER*IVP interaction: p = 0.004). QRS complex widened after increasing LV afterload in-vivo (n=3), with correlation between QRS duration and aortic diastolic pressures (R = 0.58, p < 0.001). In conclusion, high IVP and/or HF-ER significantly decrease CV, which correlates with QRS widening on the ECG during ventricular pacing. Increased myocardial wall stress also widens the QRS complex during SR in-vivo.

Increased intraventricular pressures are as harmful as the electrophysiological substrate of heart failure in favoring sustained reentry in the swine heart.

BACKGROUND: Heart failure (HF) electrophysiological remodeling (HF-ER) often includes the effect of chronically increased intraventricular pressures (IVPs) and promotes ventricular tachycardia/ventricular fibrillation (VT/VF). In addition, acutely increased IVPs have been associated with a higher rate of VT/VF episodes in chronic HF. OBJECTIVE: We hypothesized that increased IVPs and/or an ionic-imbalanced (acidified), catecholamine-rich (adrenergic) milieu (AA milieu) may contribute as much as HF-ER to the substrate for reentry in HF. We used a porcine model of tachycardiomyopathy and evaluated the individual/combined contributions of (1) increased IVPs, (2) HF-ER, and (3) an AA milieu. METHODS: HF-ER was induced in 7 pigs by rapid pacing. Seven pigs were used as controls. Hearts were isolated and Langendorff perfused. Programmed ventricular stimulation was conducted under low or increased IVP and normal/AA milieu (4 combinations). Epicardial optical mapping was used to quantify conduction velocity (CV), action potential duration (APD), and dispersion of repolarization (DoR). RESULTS: HF-ER decreased CV (-34%; P = .002) and increased APD (11%; P = .024) and DoR (21%; P = .007). Increased IVP amplified DoR (36%; P < .001) and decreased CV (-17%; P = .001) and APD (-8%; P < .001). The AA milieu consistently modified only APD (-9%; P < .001) and led to amplified inter-/intra-subject heterogeneity. Increased IVP similarly raised the odds of inducing sustained VT/VF as the presence of HF-ER (>6-fold). CONCLUSION: By magnifying DoR, decreasing CV, and shortening APD, increased IVP was as harmful as HF-ER in favoring the substrate for sustained reentry in this model. The AA milieu contributed to a much lesser extent. Thus, a stricter control of IVP might be postulated as a useful add-on antiarrhythmic strategy in HF.

Morphological and thermodynamic comparison of the lesions created by 4 open-irrigated catheters in 2 experimental models.

INTRODUCTION: New generation open-irrigated catheters aim to improve irrigation efficiency. This may change lesion patterns, challenging operators. Indeed, safety issues have recently arisen. We aimed to experimentally assess 4 open-irrigated catheters, comparing lesion size, safety, and heat transfer. METHODS: The thigh lesion model was employed in 6 anesthetized pigs to assess the morphology of perpendicular and tangential lesions (n = 140) created by the newer catheters ThermoCool® SF, CoolFlex™, and Blazer™ Open-Irrigated, and the standard ThermoCool®, at a constant power of 30 W (60 seconds). To evaluate the propensity for deep-tissue overheating, a set of 120 applications were performed at 50 W (180 seconds) comparing pop rates. Thermal assessment of the lesion generation process (20 W, 60 seconds, n = 32) was performed with an infrared camera on bovine ventricular tissue. RESULTS: At 30 W, the newer catheters showed lower temperature readings compared with the ThermoCool®. No major efficacy or safety differences were found at tangential applications; however, at perpendicular applications: (1) the SF at 17 mL/min better preserved the superficial layers and focused its maximum thermal effect deeper, but at recommended flow rates (8 mL/min) it generated the largest superficial lesions; (2) CoolFlex™ created smaller lesions than SF and readily induced steam pops at 50 W without temperature control; and (3) no major differences were found comparing Blazer™ Open-Irrigated and ThermoCool®. CONCLUSIONS: The lower temperature readings in the newer catheters make them more prone to deliver the maximum programmed power. Under experimental conditions, the SF catheter focuses its maximum effect deeper and the CoolFlex™ can be more prone to induce steam pops at high power settings.

KATP channel opening accelerates and stabilizes rotors in a swine heart model of ventricular fibrillation.

AIMS: The mechanisms underlying ventricular fibrillation (VF) are still disputed. Recent studies have highlighted the role of KATP-channels. We hypothesized that, under certain conditions, VF can be driven by stable and epicardially detectable rotors in large hearts. To test our hypothesis, we used a swine model of accelerated VF by opening KATP-channels with cromakalim. METHODS AND RESULTS: Optical mapping, spectral analysis, and phase singularity tracking were performed in eight perfused swine hearts during VF. Pseudo-bipolar electrograms were computed. KATP-channel opening almost doubled the maximum dominant frequency (14.3 ± 2.2 vs. 26.5 ± 2.8 Hz, P < 0.001) and increased the maximum regularity index (0.82 ± 0.05 vs. 0.94 ± 0.04, P < 0.001), the density of rotors (2.0 ± 1.4 vs. 16.0 ± 7.0 rotors/cm²×s, P < 0.001), and their maximum lifespans (medians: 368 vs. ≥3410 ms, P < 0.001). Persistent rotors (≥1 movie = 3410 ms) were found in all hearts after cromakalim (mostly coinciding with the fastest and highest organized areas), but they were not epicardially visible at baseline VF. A 'beat phenomenon' ruled by inter-domain frequency gradients was observed in all hearts after cromakalim. Acceleration of VF did not reveal any significant regional preponderance. Complex fractionated electrograms were not found in areas near persistent rotors. CONCLUSION: Upon KATP-channel opening, VF consisted of rapid and highly organized domains mainly due to stationary rotors, surrounded by poorly organized areas. A 'beat phenomenon' due to the quasi-periodic onset of drifting rotors was observed. These findings demonstrate the feasibility of a VF driven by stable rotors in hearts whose size is similar to the human heart. Our model also showed that complex fractionation does not seem to localize stationary rotors.