Innate Immune Activation and Mitochondrial ROS Invoke Persistent Cardiac Conduction System Dysfunction after COVID-19.

Background: Cardiac risk rises during acute SARS-CoV-2 infection and in long COVID syndrome in humans, but the mechanisms behind COVID-19-linked arrhythmias are unknown. This study explores the acute and long term effects of SARS-CoV-2 on the cardiac conduction system (CCS) in a hamster model of COVID-19. Methods: Radiotelemetry in conscious animals was used to non-invasively record electrocardiograms and subpleural pressures after intranasal SARS-CoV-2 infection. Cardiac cytokines, interferon-stimulated gene expression, and macrophage infiltration of the CCS, were assessed at 4 days and 4 weeks post-infection. A double-stranded RNA mimetic, polyinosinic:polycytidylic acid (PIC), was used in vivo and in vitro to activate viral pattern recognition receptors in the absence of SARS-CoV-2 infection. Results: COVID-19 induced pronounced tachypnea and severe cardiac conduction system (CCS) dysfunction, spanning from bradycardia to persistent atrioventricular block, although no viral protein expression was detected in the heart. Arrhythmias developed rapidly, partially reversed, and then redeveloped after the pulmonary infection was resolved, indicating persistent CCS injury. Increased cardiac cytokines, interferon-stimulated gene expression, and macrophage remodeling in the CCS accompanied the electrophysiological abnormalities. Interestingly, the arrhythmia phenotype was reproduced by cardiac injection of PIC in the absence of virus, indicating that innate immune activation was sufficient to drive the response. PIC also strongly induced cytokine secretion and robust interferon signaling in hearts, human iPSC-derived cardiomyocytes (hiPSC-CMs), and engineered heart tissues, accompanied by alterations in electrical and Ca 2+ handling properties. Importantly, the pulmonary and cardiac effects of COVID-19 were blunted by in vivo inhibition of JAK/STAT signaling or by a mitochondrially-targeted antioxidant. Conclusions: The findings indicate that long term dysfunction and immune cell remodeling of the CCS is induced by COVID-19, arising indirectly from oxidative stress and excessive activation of cardiac innate immune responses during infection, with implications for long COVID Syndrome.

Global Access to Cardiac Surgery Centers: Distribution, Disparities, and Targets.

BACKGROUND: Global data on cardiac surgery centers are outdated and survey-based. In 1995, there were 0.7 centers per million population, ranging from one per 120,000 in North America to one per 33 million in sub-Saharan Africa. This study analyzes the contemporary distribution of cardiac surgery centers and proposes targets relative to countries' cardiovascular disease (CVD) burdens. METHODS: Medical databases, gray literature, and governmental reports were used to identify the most recent post-2010 data that describe the number of centers performing cardiac surgery in each nation. The 2019 Institute for Health Metrics and Evaluation Global Burden of Disease Results Tool provided national CVD burdens. One-third of the CVD burden was assumed to be surgical. Center targets were proposed as the average or half of the average of centers per million surgical CVD patients in high-income countries. RESULTS: 5,111 cardiac surgery centers were identified across 230 nations and territories with available data, equaling 0.73 centers per million population. The median (interquartile range) number of centers ranged from 0 (0-0.06) per million in low-income countries to 0.75 (0-1.44) in high-income countries. Targets were 612.2 (optimistic) or 306.1 (conservative) centers per million surgical CVD incidence. In 2019, low-income, lower-middle-income, and upper-middle-income countries possessed 34.8, 149.0, and 271.9 centers per million surgical CVD incidence. CONCLUSION: Little progress has been made to increase cardiac surgery centers per population despite growing CVD burdens. Today's global cardiac surgical capacity remains insufficient, disproportionately affecting the world's poorest regions.

Septic Arthritis of Neonates: Descriptive Study of a Neonatal Intensive Care Unit Nosocomial Outbreak.

Purpose  This is a retrospective descriptive study of a nosocomial outbreak of septic arthritis in a neonatal intensive care unit with a Pseudomonas species as the predominant organism. There have been no previous reports of the same. The risk factors for this disease were analysed. The different diagnostic modalities that we used are described and the short-term outcomes are reported after antibiotic therapy and surgery. Methods  Fourteen patients and 16 joints were included in the study over a three-month period. The risk factors were analysed from the records and included prematurity, birth weight, sex and joint predilection. The causative organisms were also analysed from microbiological profiling. The outcomes after surgery and adjunctive antibiotic therapy were analysed in terms of clinical and laboratory parameters. Results  Pseudomonas aeruginosa was found to be the predominant organism in this series. The hip joint was predominantly involved and the majority of the patients were found to be premature. All the neonates affected were found to have low birth weight. Conclusion  Prematurity and low birth weight were found to have an association with risk for septic arthritis. In our setting of a nosocomial outbreak, a Pseudomonas species was more common than other organisms. A treatment regimen of arthrotomy surgery and adjunctive antibiotic therapy was found to be effective in all our patients.

FFR- Versus Angiography-Guided Revascularization for Nonculprit Stenosis in STEMI and Multivessel Disease: A Network Meta-Analysis.

OBJECTIVES: The aim of this study was to examine the efficacy and safety of fractional flow reserve (FFR)-guided versus angiography-guided approaches for nonculprit stenosis among patients with acute ST-segment elevation myocardial infarction (STEMI) and multivessel disease. BACKGROUND: The optimal strategy to guide revascularization of nonculprit stenosis among patients with STEMI and multivessel disease remains uncertain. METHODS: Electronic databases were searched for randomized trials evaluating the outcomes of culprit-only revascularization, angiography-guided complete revascularization (CR), or FFR-guided CR. A pairwise meta-analysis comparing CR versus culprit-only revascularization and a network meta-analysis comparing the different revascularization techniques were conducted. The primary outcome was major adverse cardiac events (MACE). RESULTS: The analysis included 11 trials with 8,195 patients. CR (ie, angiography-guided or FFR-guided CR) was associated with a lower incidence of MACE (odds ratio [OR]: 0.46; 95% CI: 0.35 to 0.59), cardiovascular mortality (OR: 0.63; 95% CI: 0.41 to 0.98), recurrent myocardial infarction (OR: 0.67; 95% CI: 0.48 to 0.95), and repeat ischemia-driven revascularization (OR: 0.26; 95% CI: 0.19 to 0.35). Network meta-analysis demonstrated that the incidence of MACE was lower with both angiography-guided CR (OR: 0.43; 95% CI: 0.31 to 0.58) and FFR-guided CR (OR: 0.52; 95% CI: 0.35 to 0.78) compared with a culprit-only approach, while there was no difference in risk for MACE between angiography-guided and FFR-guided CR (OR: 0.81; 95% CI: 0.51 to 1.29). CONCLUSIONS: Among patients with STEMI and multivessel disease, CR, with angiographic or FFR guidance for nonculprit stenosis, was associated with lower incidence of adverse events compared with culprit-only revascularization. FFR-guided CR was not superior to angiography-guided CR in reducing the incidence of adverse events. Future studies investigating other tools to risk-stratify nonculprit stenoses are encouraged.

Comparison of Rotational with Orbital Atherectomy During Percutaneous Coronary Intervention for Coronary Artery Calcification: A Systematic Review and Meta-Analysis.

BACKGROUND: Percutaneous coronary intervention (PCI) outcomes for patients with significant calcification have been consistently inferior compared to patients without significant calcification. Procedural success and long-term outcomes after PCI have been worse in patients with severe coronary calcium. OBJECTIVE: A Bayesian meta-analysis of outcomes comparing rotational atherectomy (RA) with orbital atherectomy (OA) was performed. METHODS: PubMed, Embase, and Cochrane Library databases were searched through 30th November 2018 and identified 4 observational studies. RESULTS: The primary end-point, Major Adverse Cardiac Event (MACE) composing of death, MI and stroke at 1 year was more likely with RA (OR = 1.61; 95% CI: 1.11-2.33; p = 0.01) as compared to OA. The driver of the difference in MACE between the two groups was a statistically significant difference in mortality favoring OA (OR = 4.65; 95% CI: 1.36-15.87; p = 0.01). Peri-procedural MI, the other component of the primary end-point was 1.3 times more likely in the RA arm (OR = 1.35; 95% CI 0.95-1.92; p-0.09) and was not statistically different between the groups. The odds of a vascular complication were not different in the two groups (OR = 1.26; 95% CI: 0.73-2.17; p = 0.41). In an adjusted Bayesian analysis, mortality (OR = 3.69; 95% CI: 0.30-38.51), MACE (OR = 1.68; 95% CI: 0.55-5.49), MI (OR = 1.42; 95% CI: 0.50-4.29) and dissections/perforations (OR = 0.38; 95% CI: 0.10-1.38) were not different in RA and OA groups. CONCLUSION: Our study is the first published Bayesian meta-analysis comparing MACE and peri-procedural outcomes in RA compared to OA. These findings lay the foundation for a randomized comparison between the two competing technologies.

Operator Experience and Outcomes after Transcatheter Left Atrial Appendage Occlusion with the Watchman Device.

BACKGROUND: Transcatheter left atrial appendage occlusion (LAAO) has become a suitable alternative to anticoagulation in patients with atrial fibrillation (AF). However, volume-outcome relationships at the individual operator level have not been studied. METHODS: Study population included 425 consecutive patients with AF undergoing LAAO from August 2015 to November 2018 by seven operators at BUMC-Phoenix. Operator volume was divided in tertiles by those with <40 cases/year (2 operators), 41-80 cases/year (3 operators) and >80 cases/year (2 operators). Patient data including comorbidities, labs, medications, procedural characteristics and outcomes were collected. The primary composite outcome was major adverse cardiac events (MACE) including mortality, stroke, bleeding and vascular complications. RESULTS: Mean age was 75 ±â€¯8 years and 251 (59%) were males. Mean CHA2DS2-VASc score was 4.5 ±â€¯1.3 points and mean HASBLED score was 3.9 ±â€¯1.0 points. MACE outcome was similar in the three operator groups in both unadjusted (p = 0.83) and adjusted (OR = 0.59: 95% Confidence Interval [CI]: 0.15-2.29, p = 0.45) analysis. The occurrence MACE was also similar between Interventional Cardiologist (IC) and Electrophysiologist (EP) operators in an unadjusted (p = 0.24) and adjusted (OR = 0.60: 95% CI: 0.21-1.68, p = 0.33) analysis. The secondary outcome of technical success did not differ among the three tertiles (p = 0.37) and among IC & EP operators respectively (p = 0.24) as well. CONCLUSION: Operator experience does not affect MACE and technical success even after adjusting for comorbidities. These results suggest a lower learning curve for LAAO with high technical success achievable even by low volume operators.

Superior safety of direct oral anticoagulants compared to Warfarin in patients with atrial fibrillation and underlying cancer: a national veterans affairs database study.

BACKGROUND: Studies evaluating safety of warfarin and direct oral anticoagulants (DOACs) for prevention of stroke in patients with atrial fibrillation (AF) are lacking. METHODS & RESULTS: All patients (n = 196,521) receiving care at veteran's affairs with active cancer and AF from 2010-2015 were included. One-year mortality was significantly higher in unadjusted analysis with warfarin (44.9%) compared to dabigatran (25%, P < 0.001), rivaroxaban (24.4%, P < 0.001) and apixaban (30%, P < 0.001) and after adjusting for age, sex and type of cancer mortality (OR = 2.66, 95% CI: 2.52-2.82, P < 0.001). Risk of ischemic stroke (13.5% vs. 11.1%, 12.0%, 14.0%) was similar, however risk of hemorrhagic stroke was significantly higher among patients receiving warfarin (1.2%) compared to patients receiving dabigatran (0.5%), rivaroxaban (0.7%) and apixaban (0.8%) respectively, P = 0.04. CONCLUSIONS: We demonstrated the superior safety profile of DOACs compared to warfarin among patients with underlying cancer and AF. Warfarin was associated with higher mortality, similar ischemic stroke risk but higher risk of hemorrhagic stroke.

Prognostic value of frontal QRS-T angle in predicting survival after primary percutaneous coronary revascularization/coronary artery bypass grafting for ST-elevation myocardial infarction.

BACKGROUND: Frontal QRS-T angle (FQRST) has previously been correlated with mortality in patients with stable coronary artery disease, but its role as survival predictor after ST-elevation myocardial infarction (STEMI) remains unknown. METHODS: We evaluated 267 consecutive patients with STEMI undergoing reperfusion or coronary artery bypass grafting. Data assessed included demographics, clinical presentation, electrocardiograms, medical therapy, and one-year mortality. RESULTS: Of 267 patients, 187 (70%) were males and most (49.4%) patients were Caucasian. All-cause mortality was significantly higher among patients with the highest (101-180°) FQRST [28% vs. 15%, p = 0.02]. Patients with FQRST 1-50° had higher survival (85.6%) compared with FQRST = 51-100° (72.3%) and FQRST = 101-180° (67.9%), [log rank, p = 0.01]. Adjusting for significant variables identified during univariate analysis, FQRST (OR = 2.04 [95% CI: 1.31-13.50]) remained an independent predictor of one-year mortality. FQRST-based risk score (1-50° = 0 points, 51-100° = 2 points, 101-180° = 5 points) had excellent discriminatory ability for one-year mortality when combined with Mayo Clinic Risk Score (C statistic = 0.875 [95%CI: 0.813-0.937]. A high (>4 points) FQRST risk score was associated with greater mortality (32% vs. 19%, p = 0.02) and longer length of stay (6 vs. 2 days, p < 0.001). CONCLUSION: FQRST represents a novel independent predictor of one-year mortality in patients with STEMI undergoing reperfusion. A high FQRST-based risk score was associated with greater mortality and longer length of stay and, after combining with Mayo Clinic Risk Score, improved discriminatory ability for one-year mortality.