Publications by authors named "Antonio Abbate"

524 Publications

Recurrent pericarditis: an update on diagnosis and management.

Panminerva Med 2021 Feb 23. Epub 2021 Feb 23.

Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA.

Acute pericarditis is a disease of the pericardium characterized by inflammation. Around 16-38% of patients develop recurrent events after the first episode. Recurrent pericarditis (RP) seems to be caused by a pathologic immune response. An inadequate treatment in terms of drug choice, dose, duration of therapy or tapering, has been shown to increase the risk of recurrences. Symptoms, physical signs and electrocardiographic signs are usually less severe during a recurrent event as compared to the first episode, thus favoring imaging as a tool to confirm the diagnosis of RP. Cardiac magnetic resonance is becoming the technique of choice because of its ability to detect active pericardial inflammation. Inflammatory biomarkers can be used to assess the risk of recurrences and to guide the tapering of treatments. First-line treatment is based on non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine. NSAIDs are useful for pain control, and colchicine has shown to reduce the risk of further recurrences. Glucocorticoids are often used as second-line drugs, but they are associated with a high rate of recurrent events. Interleukin-1 inhibitors, such as anakinra and rilonacept, significantly reduce the risk of recurrences in patients with RP while on treatment.
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http://dx.doi.org/10.23736/S0031-0808.21.04210-5DOI Listing
February 2021

Usefulness of the Duke Activity Status Index to Select an Optimal Cardiovascular Exercise Stress Test Protocol.

Am J Cardiol 2021 Feb 1. Epub 2021 Feb 1.

VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia.

Exercise testing represents the preferred stress modality for individuals undergoing evaluation of suspected myocardial ischemia. Patients with limited functional status may be unable to achieve an adequate exercise stress, thus influencing the diagnostic sensitivity of the results. The Duke Activity Status Index (DASI) is a clinically applicable tool to estimate exercise capacity. The purpose of the current study was to assess the utility of the DASI to identify patients unable to achieve an adequate exercise stress result. Patients referred for exercise stress testing were administered the DASI pre-exercise. Baseline characteristics and exercise variables were evaluated including DASI-metabolic equivalents (DASI-METs), peak METs, exercise time (ET), and %-predicted maximal heart rate (%PMHR). Criteria for determining adequate exercise stress was defined as ≥85%PMHR or ≥ 5-METs at peak exercise. In 608 cardiovascular stress tests performed during the study period; 314 were exercise stress. The median DASI-METs (8.4 [interquartile range; 6.7 to 9.9]) was associated with estimated peak exercise METs (R=0.50, p <0.001), ET (R=0.29, p <0.001), and %PMHR (R=0.19, p = 0.003). DASI-METs were different between those with < or ≥85%PMHR (7.9 [6.6-9.0] vs. 8.9 [7.1-9.9], P=0.025) and those with < or ≥5-METs (5.8 [4.6 to 6.6] versus 8.9 [7.3-9.9], p <0.001). Receiver operating characteristic curve analysis identified a DASI-MET threshold of ≤/>7.4 to optimally predict adequate exercise stress (sensitivity=93%, specificity=71%). In conclusion, the DASI correlates with peak METs, ET, and %PMHR among patients referred for exercise testing and can be used to identify patients with an increased likelihood of an inadequate stress test result.
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http://dx.doi.org/10.1016/j.amjcard.2021.01.030DOI Listing
February 2021

bacteraemia in a patient with heart failure: case report and literature review.

Eur Heart J Case Rep 2020 Dec 12;4(6):1-6. Epub 2020 Nov 12.

Division of Infectious Diseases, Department of Internal Medicine, VCU Health System, VMI Building, Suite 205, 1000 East Marshall Street, Richmond, VA 23298, USA.

Background: A 29-year-old male with recently diagnosed biventricular failure from myopericarditis and subsequent constrictive pericarditis on home milrinone presented to the Emergency Department with fevers/chills.

Case Summary: On arrival to the Emergency Department, he was found to have septic shock and required vasopressor therapy. grew on his admission blood cultures, and he was treated with ciprofloxacin and piperacillin/tazobactam. He quickly improved, allowing for a successful pericardiectomy, was weaned off inotropes and discharged from the hospital.

Discussion: is an environmental Gram-negative rod found in groundwater. It is rarely associated with human infection, but is associated with indwelling lines and has been documented in immunocompromised patients. Treatment typically involves line removal and a fluoroquinolone or piperacillin/tazobactam; the most optimal antimicrobial regimen and duration of treatment are unknown.
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http://dx.doi.org/10.1093/ehjcr/ytaa338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793199PMC
December 2020

Clinical features and outcomes between African American and Caucasian patients with Takotsubo Syndrome.

Minerva Cardioangiol 2021 Jan 11. Epub 2021 Jan 11.

Pauley Heart Center, Virginia Commonwealth University Hospital, Richmond, VA, USA.

Background: Takotsubo syndrome (TS) is an acute, reversible form of heart failure, often mimicking an acute coronary syndrome (ACS). Data regarding racial differences in TS are inconsistent. The aim is to assess clinical features associated with unfavorable in-hospital outcomes between African American (AA) and Caucasian (CAU) patients.

Methods: A retrospective electronic health record query identified 44 AA patients and 110 CAU patients with a diagnosis of TS. Our primary outcome was a composite of death, stroke, and cardiogenic shock during hospitalization. Variables associated with an increased risk of the primary composite outcomes were included in a logistic regression model.

Results: Compared to CAU patients, AA patients were a more comorbid population, and presented a higher prevalence of history of illicit drug use (27.3% vs 13.6% p=0.044). There were no significant differences regarding in-hospital complication rates between AA and CAU patients. In the logistic regression model, infection was associated with greater risk of developing the primary outcome in AA patients (OR=7.26 95% CI [1.22-43.17], p=0.029), whereas angina was a protective factor (OR=0.11 95% CI [0.02-0.65], p=0.015). In CAU patients, severely depressed ejection fraction and worse peak creatinine during hospitalization increased risk of developing the primary outcome (OR=5.88 95% CI [2.01-17.17], p<0.001 and OR=1.64 95% CI [1.15-2.58], p=0.031, respectively). Meanwhile, emotional stressors were protective (OR=0.16 95% CI [0.03-0.88], p=0.004).

Conclusions: Despite experiencing the same rate of in-hospital complications, the clinical profiles of AA patients are distinct from CAU patients admitted for TS, and clinical variables correlated with worse in-hospital outcomes also differ by race.
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http://dx.doi.org/10.23736/S0026-4725.20.05456-0DOI Listing
January 2021

Resting-State Directional Connectivity and Anxiety and Depression Symptoms in Adult Cannabis Users.

Biol Psychiatry Cogn Neurosci Neuroimaging 2020 Oct 7. Epub 2020 Oct 7.

Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Richmond, Virginia; Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia; Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia; Department of Neurology, Virginia Commonwealth University, Richmond, Virginia.

Background: Anxiety and depression symptoms are common among cannabis users and could be a risk factor for cannabis use (CU) disorder. Thus, it is critical to understand the neuronal circuits underlying the associations between CU and these symptoms. Alterations in resting-state functional connectivity within and/or between the default mode network and salience network have been reported in CU, anxiety, and depressive disorders and thus could be a mechanism underlying the associations between CU disorder and anxiety/depression symptoms.

Methods: Using resting-state functional magnetic resonance imaging, effective connectivities (ECs) among 9 major nodes from the default mode network and salience network were measured using dynamic causal modeling in 2 datasets: the Human Connectome Project (28 CU participants and 28 matched non-drug-using control participants) and a local CU study (21 CU participants and 21 matched non-drug-using control participants) in separate and parallel analyses.

Results: Relative to the control participants, right amygdala to left amygdala, anterior cingulate cortex to left amygdala, and medial prefrontal cortex to right insula ECs were greater, and left insula to left amygdala EC was smaller in the CU group. Each of these ECs showed a reliable linear relationship with at least one of the anxiety/depression measures. Most findings on the right amygdala to left amygdala EC were common to both datasets.

Conclusions: Right amygdala to left amygdala and anterior cingulate cortex to left amygdala ECs may be related to the close associations between CU and anxiety/depression symptoms. The findings on the medial prefrontal cortex to right insula and left insula to left amygdala ECs may reflect a compensatory mechanism.
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http://dx.doi.org/10.1016/j.bpsc.2020.09.015DOI Listing
October 2020

An update on the pathophysiology of acute and recurrent pericarditis.

Panminerva Med 2020 Dec 18. Epub 2020 Dec 18.

Virginia Commonwealth University, Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Richmond, VA, USA.

Pericarditis is an inflammatory disease of the pericardium. Progress has been done in recent years in the understanding of its pathophysiology. In particular, pre-clinical and clinical studies have contributed to increasing our knowledge on the role of interleukin (IL)-1 and NLRP3 (NACHT, leucine- rich repeat, and pyrin domain- containing protein 3) inflammasome. Based on current evidence, pericarditis should be considered as an inflammatory reaction to various stimuli, including chemical/physical, infectious, or ischemic ones, with a viral infection being a common etiology. Interaction of pathogens or irritants with toll-like receptor (TLRs) and stimulation of IL-1 receptor by IL-1α and IL-1β lead to an increased transcription of pro-inflammatory genes, including those needed for NLRP3 inflammasome assembly. This pathway is confirmed indirectly by the beneficial effect of colchicine (an indirect NLRP3 inflammasome inhibitor) and IL-1 blockers in patients with recurrent pericarditis. More recently, a direct evidence of the NLRP3 inflammasome within the inflamed pericardium has been provided as well. It may, however, occur that selfantigens on the surface of mesothelial cells or microbial peptides may stimulate autoreactive T cells along with B cells producing anti-heart antibodies, although less evidence is available on this. Some uncertainties still remain about the role of neutrophils, neutrophil extracellular traps (NETs), and pericardial interstitial cells in recurrent and constrictive pericarditis. Unraveling these aspects might have a direct impact on the development of novel targeted therapies, especially considering the increasing number of drugs targeting NETs.
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http://dx.doi.org/10.23736/S0031-0808.20.04205-6DOI Listing
December 2020

The Chronic Kidney Disease Phenotype of HFpEF: Unique Cardiac Characteristics.

Am J Cardiol 2021 03 24;142:143-145. Epub 2020 Dec 24.

Virginia Commonwealth University, Richmond, Virginia.

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http://dx.doi.org/10.1016/j.amjcard.2020.12.012DOI Listing
March 2021

SCUBE Diving: Biomarker Discovery for Pulmonary Hypertension From Bench to Bedside.

JACC Basic Transl Sci 2020 Nov 23;5(11):1093-1094. Epub 2020 Nov 23.

Department of Internal Medicine, Division of Cardiology, VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia, USA.

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http://dx.doi.org/10.1016/j.jacbts.2020.09.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691277PMC
November 2020

Exercise intolerance in kidney diseases: physiological contributors and therapeutic strategies.

Am J Physiol Renal Physiol 2021 02 7;320(2):F161-F173. Epub 2020 Dec 7.

Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia.

Exertional fatigue, defined as the overwhelming and debilitating sense of sustained exhaustion that impacts the ability to perform activities of daily living, is highly prevalent in chronic kidney disease (CKD) and end-stage renal disease (ESRD). Subjective reports of exertional fatigue are paralleled by objective measurements of exercise intolerance throughout the spectrum of the disease. The prevalence of exercise intolerance is clinically noteworthy, as it leads to increased frailty, worsened quality of life, and an increased risk of mortality. The physiological underpinnings of exercise intolerance are multifaceted and still not fully understood. This review aims to provide a comprehensive outline of the potential physiological contributors, both central and peripheral, to kidney disease-related exercise intolerance and highlight current and prospective interventions to target this symptom. In this review, the CKD-related metabolic derangements, cardiac and pulmonary dysfunction, altered physiological responses to oxygen consumption, vascular derangements, and sarcopenia are discussed in the context of exercise intolerance. Lifestyle interventions to improve exertional fatigue, such as aerobic and resistance exercise training, are discussed, and the lack of dietary interventions to improve exercise tolerance is highlighted. Current and prospective pharmaceutical and nutraceutical strategies to improve exertional fatigue are also broached. An extensive understanding of the pathophysiological mechanisms of exercise intolerance will allow for the development of more targeted therapeutic approached to improve exertional fatigue and health-related quality of life in CKD and ESRD.
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http://dx.doi.org/10.1152/ajprenal.00437.2020DOI Listing
February 2021

Phase 1B, Randomized, Double-Blinded, Dose Escalation, Single-Center, Repeat Dose Safety and Pharmacodynamics Study of the Oral NLRP3 Inhibitor Dapansutrile in Subjects With NYHA II-III Systolic Heart Failure.

J Cardiovasc Pharmacol 2020 Oct 24;77(1):49-60. Epub 2020 Oct 24.

Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Pauley Heart Center, Richmond, VA.

Abstract: The NLRP3 inflammasome has been implicated in the development and progression of heart failure. The aim of this study was to determine the safety of an oral inhibitor of the NLRP3 inflammasome, dapansutrile (OLT1177), in patients with heart failure and reduced ejection fraction (HFrEF). This was a phase 1B, randomized, double-blind, dose escalation, single-center, repeat dose safety and pharmacodynamics study of dapansutrile in stable patients with HFrEF (New York Heart Association Class II-III). Subjects were randomized to treatment with dapansutrile for up to 14 days at a ratio of 4:1 into 1 of 3 sequential ascending dose cohorts (500, 1000, or 2000 mg) each including 10 patients. Subjects underwent clinical assessment, biomarker determination, transthoracic echocardiogram, and maximal cardiopulmonary exercise testing at baseline, day 14, and day 28 to ascertain changes in clinical status. Placebo cases (N = 2 per cohort) were used as a decoy to reduce bias and not for statistical comparisons. Thirty participants (20 men) were treated for 13 (12-14) days. No serious adverse events during the study were recorded. All clinical or laboratory parameters at day 14 compared with baseline suggested clinical stability without significant within-group differences in the dapansutrile-pooled group or the 3 dapansutrile cohorts. Improvements in left ventricular EF [from 31.5% (27.5-39) to 36.5% (27.5-45), P = 0.039] and in exercise time [from 570 (399.5-627) to 616 (446.5-688) seconds, P = 0.039] were seen in the dapansutrile 2000 mg cohort. Treatment with dapansutrile for 14 days was safe and well tolerated in patients with stable HFrEF.
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http://dx.doi.org/10.1097/FJC.0000000000000931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774821PMC
October 2020

Efficacy and safety of rilonacept for recurrent pericarditis: results from a phase II clinical trial.

Heart 2020 Nov 23. Epub 2020 Nov 23.

Kiniksa Pharmaceuticals Corp, Lexington, Massachusetts, USA.

Objective: Recurrent pericarditis (RP) incurs significant morbidity. Rilonacept inhibits both interleukin-1 alpha (IL-1α) and IL-1β; these cytokines are thought to play a major role in RP. This phase II study evaluated rilonacept efficacy and safety in RP.

Methods: This multicentre, open-label study enrolled adult patients with idiopathic or postpericardiotomy RP, symptomatic (≥2 pericarditis recurrences) or corticosteroid (CS) dependent (≥2 recurrences prior).Patients received rilonacept 320 mg SC load/160 mg SC weekly maintenance in a 6-week base treatment period (TP) followed by an optional 18-week on-treatment extension period (EP) (option to wean background therapy).

Results: Outcomes: pericarditis pain (numeric rating scale (NRS)) and inflammation (C reactive protein (CRP)) for symptomatic patients; disease activity after CS taper for CS-dependent patients.

Secondary Outcomes: health-related quality of life (HRQOL), pericarditis manifestations and additional medications. 25 unique patients enrolled, while 23 completed the EP (seven colchicine failures and five CS failures). In symptomatic patients, NRS and CRP decreased; response was observed after first rilonacept dose. NRS decreased from 4.5 at baseline to 0.7, and CRP decreased from 4.62 mg/dL at baseline to 0.38 mg/dL at end of TP. Median time to CRP normalisation: 9 days. Pericarditis manifestations resolved. 13 patients on CS at baseline completed the EP; 11 (84.6%) discontinued CS, and 2 tapered; CRP and NRS remained low without recurrence. Mean HRQOL scores improved in symptomatic patients. One serious adverse event (SAE) resulted in discontinuation of rilonacept.

Conclusions: Rilonacept led to rapid and sustained improvement in pain, inflammation (CRP and pericarditis manifestations) and HRQOL. CSs were successfully tapered or discontinued; safety was consistent with known rilonacept safety profile.

Trial Registration Number: NCT03980522.
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http://dx.doi.org/10.1136/heartjnl-2020-317928DOI Listing
November 2020

Phase 3 Trial of Interleukin-1 Trap Rilonacept in Recurrent Pericarditis.

N Engl J Med 2021 01 16;384(1):31-41. Epub 2020 Nov 16.

From the Center for the Diagnosis and Treatment of Pericardial Diseases, Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland (A.L.K., P.C.); University Cardiology, Cardiovascular, and Thoracic Department, Azienda Ospedaliero-Universitaria (AOU) Città della Salute e della Scienza di Torino and University of Turin, Turin (M.I.), the Department of Biomedical and Clinical Science, University of Milan, Fatebenefratelli Hospital, Milan (A.B.), and the Division of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome (A.I.) - all in Italy; Pauley Heart Center, Virginia Commonwealth University, Richmond (A.A.); Kiniksa Pharmaceuticals, Lexington, MA (F.F., A.P., J.F.P.); the Cardiology Unit, University of Vermont Medical Center, Burlington (M.L.); the Cardiovascular Clinical Research Institute, Lady Davis Carmel Medical Center and the Technion-Israel Institute of Technology, Haifa, Israel (B.S.L.); the Minneapolis Heart Institute, Abbott Northwestern Hospital, Minneapolis (D.L.), and the Division of Cardiovascular Ultrasound, Department of Cardiovascular Medicine, Mayo Clinic, Rochester (S.A.L.) - both in Minnesota; the Monash Cardiovascular Research Centre, Victorian Heart Institute, Monash University, Clayton, VIC, Australia (S.J.N.); and Kiniksa Pharmaceuticals, Hamilton, Bermuda (A.W.).

Background: Interleukin-1 has been implicated as a mediator of recurrent pericarditis. The efficacy and safety of rilonacept, an interleukin-1α and interleukin-1β cytokine trap, were studied previously in a phase 2 trial involving patients with recurrent pericarditis.

Methods: We conducted a phase 3 multicenter, double-blind, event-driven, randomized-withdrawal trial of rilonacept in patients with acute symptoms of recurrent pericarditis (as assessed on a patient-reported scale) and systemic inflammation (as shown by an elevated C-reactive protein [CRP] level). Patients presenting with pericarditis recurrence while receiving standard therapy were enrolled in a 12-week run-in period, during which rilonacept was initiated and background medications were discontinued. Patients who had a clinical response (i.e., met prespecified response criteria) were randomly assigned in a 1:1 ratio to receive continued rilonacept monotherapy or placebo, administered subcutaneously once weekly. The primary efficacy end point, assessed with a Cox proportional-hazards model, was the time to the first pericarditis recurrence. Safety was also assessed.

Results: A total of 86 patients with pericarditis pain and an elevated CRP level were enrolled in the run-in period. During the run-in period, the median time to resolution or near-resolution of pain was 5 days, and the median time to normalization of the CRP level was 7 days. A total of 61 patients underwent randomization. During the randomized-withdrawal period, there were too few recurrence events in the rilonacept group to allow for the median time to the first adjudicated recurrence to be calculated; the median time to the first adjudicated recurrence in the placebo group was 8.6 weeks (95% confidence interval [CI], 4.0 to 11.7; hazard ratio in a Cox proportional-hazards model, 0.04; 95% CI, 0.01 to 0.18; P<0.001 by the log-rank test). During this period, 2 of 30 patients (7%) in the rilonacept group had a pericarditis recurrence, as compared with 23 of 31 patients (74%) in the placebo group. In the run-in period, 4 patients had adverse events leading to the discontinuation of rilonacept therapy. The most common adverse events with rilonacept were injection-site reactions and upper respiratory tract infections.

Conclusions: Among patients with recurrent pericarditis, rilonacept led to rapid resolution of recurrent pericarditis episodes and to a significantly lower risk of pericarditis recurrence than placebo. (Funded by Kiniksa Pharmaceuticals; RHAPSODY ClinicalTrials.gov number, NCT03737110.).
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http://dx.doi.org/10.1056/NEJMoa2027892DOI Listing
January 2021

Long term outcomes of percutaneous or surgical treatment in left main disease.

Minerva Cardioangiol 2020 Nov 4. Epub 2020 Nov 4.

VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA.

Background: Long term efficacy and safety of either surgical or percutaneous treatment left main coronary artery disease treatment is lacking.

Methods: We conducted a systematic review and meta-analysis of the most updated randomized clinical trials that compared the efficacy of coronary artery bypass surgery (CABG) or percutaneous coronary intervention (PCI) for the Left Main Coronary Artery (LMCA) disease.

Results: We identified 6 studies, providing data on 5812 patients. The mean follow-up was 6.7 years. PCI was associated with an increased risk of major vascular events (MACE) (IRR 1.24, 95% confidence interval (CI) [1.03-1.67], p<0.01), and coronary revascularization (IRR 1.69, 95% CI [1.42-2.03], p<0.01) compared to CABG. Furthermore, all-cause death, MI and stroke events were not statistically different between the two therapeutic revascularization methodologies (IRR 1.06, 95% CI [0.90-1.24], p=0.47, IRR 1.35, 95% CI [0.84-2.16], p=0.03 and IRR 0.66, 95% CI [0.43-1.01], p=0.05, respectively).

Conclusions: LMCA PCI has an overall same survival compared to CABG in the long term follow up. Nevertheless, MACE and revascularization events were more frequent in PCI compared to CABG.
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http://dx.doi.org/10.23736/S0026-4725.20.05370-0DOI Listing
November 2020

Inflammasome formation in the lungs of patients with fatal COVID-19.

Inflamm Res 2021 Jan 20;70(1):7-10. Epub 2020 Oct 20.

VCU Pauley Heart Center, Virginia Commonwealth University, 1220 E Broad St, Richmond, VA, 23298, USA.

Objective: The orf8b protein of the coronavirus SARS-CoV, analogous to SARS-CoV-2, triggers the NLRP3 inflammasome in macrophages in vitro. Deregulated inflammasome-mediated release of interleukin-1 family cytokines is important in hyper-inflammatory syndromes, like happens in SARS-CoV-2-mediated cytokine release syndrome. We propose that an intense inflammasome formation characterizes the lungs of patients with fatal COVID-19 disease due to pneumonia and acute respiratory distress syndrome (ARDS).

Methods: Samples from four patients with confirmed COVID-19 pneumonia who had been hospitalized at the Hospital of the University of Trieste (Italy) and died of ARDS and four lung samples from a historical repository from subjects who had died of cardiopulmonary arrest and had not been placed on mechanical ventilation and without evidence of pulmonary infection at postmortem examination were collected. Pathology samples had been fixed in formalin 10% at time of collection and subsequently embedded in paraffin. We conducted staining for ASC (Apoptosis-associated Speck-like protein containing a Caspase recruitment domain), NLRP3 (NACHT, LRR, and PYD domains-containing protein 3), and cleaved caspase-1.

Results: Intense expression of the inflammasome was detected, mainly in leukocytes, within the lungs of all patients with fatal COVID-19 in the areas of lung injury. The number of ASC inflammasome specks per high power fields was significantly higher in the lungs of patients with fatal COVID-19 as compared with the lungs of control subjects (52 ± 22 vs 6 ± 3, P = 0.0064).

Conclusions: These findings identify the presence of NLRP3 inflammasome aggregates in the lungs of fatal COVID-19 pneumonia thus providing the potential molecular link between viral infection and cytokine release syndrome.
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http://dx.doi.org/10.1007/s00011-020-01413-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572246PMC
January 2021

Left ventricular concentric remodeling and impaired cardiorespiratory fitness in patients with heart failure and preserved ejection fraction.

Minerva Cardioangiol 2020 Sep 30. Epub 2020 Sep 30.

VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA -

Background: Left ventricular (LV) concentric remodeling refers to a process by which increased LV relative wall thickness alters myocardial geometry, resulting in reduced LV end-diastolic volume (LVEDV) and stroke volume (SV). While the degree of concentric remodeling is a negative prognostic factor in heart failure with preserved ejection fraction (HFpEF), it is not known how it contributes to cardiorespiratory fitness (CRF).

Methods: We performed a retrospective analysis of patients with HFpEF who underwent treadmill single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) and cardiopulmonary exercise testing (CPX). From exercise SPECT-MPI, we recorded post-exercise LVEDVi, LVESVi, SVi, LVEF, the presence and extent of perfusion defects, and perfusion reversibility. Peak oxygen consumption (VO2), the oxygen uptake efficiency slope (OUES), oxygen (O2) pulse, ventilatory efficiency (VE/VCO2 slope), ventilatory anaerobic threshold, respiratory exchange ratio, exercise time, and maximum heart rate were obtained from CPX. Data are expressed as mean (±standard deviation). Univariate and multivariate linear regression was performed.

Results: We identified 23 subjects who had completed both an exercise SPECT-MPI and a CPX. Patients were more commonly women (83%), black (65%), middle-age (50 [±7.3] years), and obese (body mass index [BMI] 39.7 [±6.0] kg/m2). Greater LVEDVi and LVESVi correlated positively with peak VO2 (R=+0.648, p=0.001; R=+0.601, p=0.002), O2 pulse (R=+0.686, p<0.001; R=+0.625, p=0.001) and OUES (R=+0.882, p<0.001; R=+0.779, p<0.001). The LVEF correlated inversely with peak VO2 and OUES (R=-0.450, p=0.031; R=-0.485, p=0.035). Perfusion defect area, grade of severity, and presence of reversibility were not associated with CRF variables.

Conclusions: Post-exercise reduced LV volumes correlate with measures of impaired CRF in patients with HFpEF, thus supporting a pathophysiologic role of concentric remodeling in impaired CRF in HFpEF.
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http://dx.doi.org/10.23736/S0026-4725.20.05295-0DOI Listing
September 2020

Differences in heart rate among recent marijuana use groups.

Minerva Cardioangiol 2020 Sep 29. Epub 2020 Sep 29.

Division of Cardiology, Hunter Holmes McGuire VA Medical Center, Richmond, VA, USA.

Background: Marijuana use increases cardiac sympathetic activity within minutes of its use and this effect may begin to decrease as soon as one hour after marijuana use. However, the cardiovascular effects of marijuana use more than an hour after use is poorly characterized. The purpose of the current study is to compare heart rate, a marker of cardiac sympathetic activity, across recent marijuana use groups (never used=63; recent use [in the past 24 hours; subacute] = 13; in the past 7 days, but not in the past 24 hours = 17). Overall, the current sample included 93 African American/Black college students, with a mean age of 20.03 (SD = 2.21).

Methods: Participants completed a demographic form, a brief battery of psychological questionnaires, and had their heart rate assessed at baseline.

Results: Analysis of covariance showed that heart rate was statistically significantly lower in the recent use group (M = 62.38) compared with the non-users group (M = 73.92). This difference persisted before and after statistically adjusting for demographic covariates.

Conclusions: These results suggest that there may be a cardiovascular process that occurs when using marijuana that results in a compensatory, reduced heart rate.
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http://dx.doi.org/10.23736/S0026-4725.20.05239-1DOI Listing
September 2020

RHAPSODY: Rationale for and design of a pivotal Phase 3 trial to assess efficacy and safety of rilonacept, an interleukin-1α and interleukin-1β trap, in patients with recurrent pericarditis.

Am Heart J 2020 10 14;228:81-90. Epub 2020 Jul 14.

Kiniksa Pharmaceuticals Corp., Lexington, MA.

Recurrent pericarditis (RP) occurs in 15% to 30% of patients following a first episode, despite standard treatment with nonsteroidal anti-inflammatory drugs, colchicine, and corticosteroids; many patients become dependent on corticosteroids. Rilonacept (KPL-914), an interleukin-1α and β inhibitor, is in development for the treatment of RP. RHAPSODY, a double-blind, placebo-controlled, randomized-withdrawal (RW) pivotal Phase 3 trial (NCT03737110), enrolls patients 12 years or older presenting with at least a third pericarditis episode, pericarditis pain score ≥4 (11-point numeric rating scale [NRS]), and C-reactive protein ≥1 mg/dL at screening. After a subcutaneous loading dose (adults, 320 mg; children, 4.4 mg/kg), all patients receive blinded weekly subcutaneous rilonacept (adults, 160 mg; children, 2.2 mg/kg) during the run-in period. Patients must taper and discontinue concomitant pericarditis medications during the blinded run-in period and achieve clinical response (C-reactive protein ≤0.5 mg/dL and weekly average NRS ≤2.0 during the 7 days prior to and including the day of randomization) by end of the run-in (while on rilonacept monotherapy) to be randomized to either continued rilonacept or placebo in the RW period. Primary efficacy end point was time to adjudicated pericarditis recurrence during the RW period; secondary efficacy end points were proportion of patients maintaining clinical response, percentage of days with NRS ≤2, and percentage of patients with no-to-minimal pericarditis symptoms at week 16 of the RW period. Safety evaluations include adverse event monitoring, physical examinations, and laboratory tests. The RHAPSODY trial will evaluate the efficacy and safety of rilonacept in the treatment of RP to improve outcomes and patient health-related quality of life.
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http://dx.doi.org/10.1016/j.ahj.2020.07.004DOI Listing
October 2020

Canakinumab in a subgroup of patients with COVID-19.

Lancet Rheumatol 2020 Aug 4;2(8):e457-ee458. Epub 2020 Jun 4.

Clinic of Infectious Diseases, Department of Medicine and Science of Aging, G. d'Annunzio University of Chieti-Pescara, Chieti 66100, Italy.

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http://dx.doi.org/10.1016/S2665-9913(20)30167-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272172PMC
August 2020

Role for Anti-Cytokine Therapies in Severe Coronavirus Disease 2019.

Crit Care Explor 2020 Aug 10;2(8):e0178. Epub 2020 Aug 10.

Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA.

The causative agent for coronavirus disease 2019, severe acute respiratory syndrome coronavirus 2, appears exceptional in its virulence and immunopathology. In some patients, the resulting hyperinflammation resembles a cytokine release syndrome. Our knowledge of the immunopathogenesis of coronavirus disease 2019 is evolving and anti-cytokine therapies are under active investigation. This narrative review summarizes existing knowledge of the immune response to coronavirus infection and highlights the current and potential future roles of therapeutic strategies to combat the hyperinflammatory response of patients with coronavirus disease 2019.

Data Sources: Relevant and up-to-date literature, media reports, and author experiences were included from Medline, national newspapers, and public clinical trial databases.

Study Selection: The authors selected studies for inclusion by consensus.

Data Extraction: The authors reviewed each study and selected approrpriate data for inclusion through consensus.

Data Synthesis: Hyperinflammation, reminiscent of cytokine release syndromes such as macrophage activation syndrome and hemophagocytic lymphohistiocytosis, appears to drive outcomes among adults with severe coronavirus disease 2019. Cytokines, particularly interleukin-1 and interleukin-6, appear to contribute importantly to such systemic hyperinflammation. Ongoing clinical trials will determine the efficacy and safety of anti-cytokine therapies in coronavirus disease 2019. In the interim, anti-cytokine therapies may provide a treatment option for adults with severe coronavirus disease 2019 unresponsive to standard critical care management, including ventilation.

Conclusions: This review provides an overview of the current understanding of the immunopathogenesis of coronavirus disease 2019 in adults and proposes treatment considerations for anti-cytokine therapy use in adults with severe disease.
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http://dx.doi.org/10.1097/CCE.0000000000000178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419062PMC
August 2020

IL-18 and infections: Is there a role for targeted therapies?

J Cell Physiol 2021 03 13;236(3):1638-1657. Epub 2020 Aug 13.

Division of Cardiology, Department of Internal Medicine, Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia.

Interleukin (IL)-18 is a pro-inflammatory cytokine belonging to the IL-1 family, first identified for its interferon-γ-inducing properties. IL-18 regulates both T helper (Th) 1 and Th2 responses. It acts synergistically with IL-12 in the Th1 paradigm, whereas with IL-2 and without IL-12 it can induce Th2 cytokine production from cluster of differentation (CD)4 T cells, natural killer (NK cells, NKT cells, as well as from Th1 cells. IL-18 also plays a role in the hemophagocytic lymphohistiocytosis, a life-threatening condition characterized by a cytokine storm that can be secondary to infections. IL-18-mediated inflammation was largely studied in animal models of bacterial, viral, parasitic, and fungal infections. These studies highlight the contribution of either IL-18 overproduction by the host or overresponsiveness of the host to IL-18 causing an exaggerated inflammatory burden and leading to tissue injury. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19). The damage in the later phase of the disease appears to be driven by a cytokine storm, including interleukin IL-1 family members and secondary cytokines like IL-6. IL-18 may participate in this hyperinflammation, as it was previously found to be able to cause injury in the lung tissue of infected animals. IL-18 blockade has become an appealing therapeutic target and has been tested in some IL-18-mediated rheumatic diseases and infantile-onset macrophage activation syndrome. Given its role in regulating the immune response to infections, IL-18 blockade might represent a therapeutic option for COVID-19, although further studies are warranted to investigate more in detail the exact role of IL-18 in SARS-CoV-2 infection.
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http://dx.doi.org/10.1002/jcp.30008DOI Listing
March 2021

Potential markers of healing from near infrared spectroscopy imaging of venous leg ulcer. A randomized controlled clinical trial comparing conventional with hyperbaric oxygen treatment.

Wound Repair Regen 2020 11 24;28(6):856-866. Epub 2020 Aug 24.

Istituto di Fisiologia Clinica-CNR, Pisa, Italy.

The aim of this study is to ascertain whether the simultaneous measurement of hemoglobin O saturation (StO ) and dimension of venous leg ulcers (VLU) by near infrared spectroscopy (NIRS) imaging can predict the healing course with protocols employing a conventional treatment alone or in combination with hyperbaric oxygen therapy (HBOT). NIRS 2D images of wound region were obtained in 81 patients with hard-to-heal VLU that had been assigned, in a randomized controlled clinical trial, to the following protocols: 30 HBOT sessions, adjunctive to the conventional therapy, either twice daily over 3 weeks (group A) or once daily over 6 weeks (group B), and conventional therapy without HBOT (group C). Seventy-three patients completed the study with a total of 511 NIRS images being analyzed. At the end of treatment, wound area was significantly smaller in all three groups. However, at the 3-week mark the wound area reduction tended to be less evident in group A than in the other groups. This trend continued up to the 6-week end-point when a significantly greater area reduction was found with group B (65.5%) and group C (56.8%) compared to group A (29.7%) (P < .01). Furthermore, a higher incidence of complete healing was noted with group B (20%) than with group A (4.5%) and group C (3.8%). When using a final wound reduction in excess of 40% to distinguish healing from nonhealing ulcers, it was found that only the former present NIRS StO values abating over the study period both at center and edge of lesions. In conclusion, NIRS analysis of StO and wound area can predict the healing course of VLU. Adjunctive HBOT significantly facilitates VLU healing compared to the conventional treatment alone. This positive action, however, becomes manifest only with a longer and less intensive treatment schedule.
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http://dx.doi.org/10.1111/wrr.12853DOI Listing
November 2020

Low-dose subcutaneous tocilizumab to prevent disease progression in patients with moderate COVID-19 pneumonia and hyperinflammation.

Int J Infect Dis 2020 Nov 6;100:421-424. Epub 2020 Aug 6.

Infectious Diseases Unit, Pescara General Hospital, Pescara, Italy. Electronic address:

Aim: This study aimed to evaluate the safety and efficacy profile of low-dose tocilizumab (TCZ), to prevent disease progression, subcutaneously administered to patients with moderate COVID-19 pneumonia and hyperinflammation.

Methods: Clinical characteristics and outcomes were retrospectively analysed of patients - with laboratory-confirmed bilateral COVID-19 pneumonia, hyperinflammation (C-reactive protein (CRP) ≥20 mg/dL), no hypoxaemia (oxygen saturation >90%), and no contraindications to TCZ - who were treated with subcutaneous TCZ (324 mg) administered within 48 h from hospitalization on top of standard of care (SOC). They were compared with matched controls treated with SOC only before TCZ was available at the institution. Clinical data were available for all patients until death or until day 35 for those discharged from hospital.

Findings: Ten consecutive patients (six males, median age 55 years) treated with TCZ on top of SOC, and ten patients (six males, median age 56 years) treated with SOC only were included. TCZ was well-tolerated with no clinically relevant adverse events. TCZ was associated with a reduction in CRP at day 1 (-50%, IQR -28 to -80) and day 3 (-89%, IQR -79 to -96; p =  0.005 for within-group), whereas there was no significant change in CRP values in the SOC group (p <  0.001 for between-group comparisons at both time points). TCZ resulted in a parallel improvement in oxygenation, as assessed by the ratio of partial pressure of oxygen to fraction of inspired oxygen (P/F) ratio, which increased at day 1 (+11%, IQR +6 to +16; p =  0.005 for within-group and p =  0.006 for between-group comparisons), and day 3 (+23%, IQR +16 to +34; p =  0.005 for within-group and p = 0.003 for between-group comparisons). None of the TCZ-treated patients had disease progression, defined as requirement of oxygen therapy or mechanical ventilation, whereas progression occurred in five (50%) patients among the SOC group.

Conclusions: Low-dose subcutaneous TCZ may be a safe and promising therapeutic option administered on top of SOC to prevent disease progression in hospitalised patients with moderate COVID-19 and hyperinflammation.
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http://dx.doi.org/10.1016/j.ijid.2020.07.078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406468PMC
November 2020

Cardiopulmonary exercise testing - refining the clinical perspective by combining assessments.

Expert Rev Cardiovasc Ther 2020 Sep 20;18(9):563-576. Epub 2020 Aug 20.

VCU Pauley Heart Center, Virginia Commonwealth University , Richmond, VA, USA.

Introduction: Cardiorespiratory fitness (CRF) is now established as a vital sign. Cardiopulmonary exercise testing (CPX) is the gold-standard approach to assessing CRF.

Areas Covered: A body of literature spanning several decades clearly supports the clinical utility of CPX in those who are apparently health and at risk for chronic disease as well as numerous patient populations. While CPX, in and of itself, is a valid and reliable clinical assessment, combining findings with other available assessments may provide a more comprehensive perspective that enhances clinical decision making and outcomes. The current review will accomplish the following: (1) define key CPX measures based upon current evidence; and (2) describe the current evidence addressing the relationships between CPX and echocardiography, serum biomarkers, and cardiovascular magnetic resonance.

Expert Opinion: Cardiopulmonary exercise testing provides prognostic and diagnostic information in apparently healthy individuals, those at risk for one or more chronic conditions, as well as numerous patient populations. Moreover, if the goal of an intervention is to improve one or more systems integral to the physiologic response to exercise, CPX should be considered as a central assessment to gauge therapeutic efficacy. To further refine the information obtained from CPX, combining other assessments has demonstrated promise.
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http://dx.doi.org/10.1080/14779072.2020.1806057DOI Listing
September 2020

Response to: 'Rational use of tocilizumab in COVID-19' by Jain and Sharma.

Ann Rheum Dis 2020 Jul 31. Epub 2020 Jul 31.

Infectious Diseases Unit, Pescara General Hospital, Pescara, Italy

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http://dx.doi.org/10.1136/annrheumdis-2020-218626DOI Listing
July 2020

Targeting GM-CSF in COVID-19 Pneumonia: Rationale and Strategies.

Front Immunol 2020 3;11:1625. Epub 2020 Jul 3.

Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, United States.

COVID-19 is a clinical syndrome ranging from mild symptoms to severe pneumonia that often leads to respiratory failure, need for mechanical ventilation, and death. Most of the lung damage is driven by a surge in inflammatory cytokines [interleukin-6, interferon-γ, and granulocyte-monocyte stimulating factor (GM-CSF)]. Blunting this hyperinflammation with immunomodulation may lead to clinical improvement. GM-CSF is produced by many cells, including macrophages and T-cells. GM-CSF-derived signals are involved in differentiation of macrophages, including alveolar macrophages (AMs). In animal models of respiratory infections, the intranasal administration of GM-CSF increased the proliferation of AMs and improved outcomes. Increased levels of GM-CSF have been recently described in patients with COVID-19 compared to healthy controls. While GM-CSF might be beneficial in some circumstances as an appropriate response, in this case the inflammatory response is maladaptive by virtue of being later and disproportionate. The inhibition of GM-CSF signaling may be beneficial in improving the hyperinflammation-related lung damage in the most severe cases of COVID-19. This blockade can be achieved through antagonism of the GM-CSF receptor or the direct binding of circulating GM-CSF. Initial findings from patients with COVID-19 treated with a single intravenous dose of mavrilimumab, a monoclonal antibody binding GM-CSF receptor α, showed oxygenation improvement and shorter hospitalization. Prospective, randomized, placebo-controlled trials are ongoing. Anti-GM-CSF monoclonal antibodies, TJ003234 and gimsilumab, will be tested in clinical trials in patients with COVID-19, while lenzilumab received FDA approval for compassionate use. These trials will help inform whether blunting the inflammatory signaling provided by the GM-CSF axis in COVID-19 is beneficial.
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http://dx.doi.org/10.3389/fimmu.2020.01625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348297PMC
August 2020

Clinical Presentation and Outcomes of Acute Pericarditis in a Large Urban Hospital in the United States of America.

Chest 2020 Dec 24;158(6):2556-2567. Epub 2020 Jul 24.

Pauley Heart Center, Virginia Commonwealth University, Richmond, VA. Electronic address:

Background: Acute pericarditis is the most common presentation of pericardial diseases. Although generally benign, complications such as constrictive pericarditis, cardiac tamponade, and recurrence can occur.

Research Question: What are the clinical factors associated with adverse outcomes in acute pericarditis?

Study Design And Methods: We used an informatics-based search engine to search for International Classification of Diseases codes related to pericardial disease between January 1, 2009 and November 14, 2018 and then extracted clinical information, including only patients meeting the European Society of Cardiology criteria for acute pericarditis. We then evaluated the predictive value of clinical characteristics for adverse outcomes (cardiac tamponade, constrictive pericarditis, failure of therapy, recurrences, or death).

Results: We identified 240 patients with a first episode of pericarditis (51 [34-62] years, 56% males and 50% white). Pericarditis was determined to be idiopathic in 126 (53%) cases and related to cardiac injury in 79 (33%). During a median follow-up time of 179 (20-450) days, 82 (34%) patients experienced at least one adverse outcome. Subacute presentation was an independent predictor of adverse outcomes. Patients with postcardiac injury pericarditis had a lower incidence in the composite of failure of treatment and recurrence (13% vs 26%; P = .022) compared with patients with idiopathic pericarditis. Troponin I measurements were obtained in 167 patients (70%). Elevated troponin I levels were associated with lower incidence of recurrences (4% vs 17%; P = .024) and of the composite outcome (13% vs 36%; P = .004).

Interpretation: Acute pericarditis is associated with at least one adverse outcome in 34% of patients. Subacute presentation and idiopathic etiology are associated with higher incidence of adverse outcomes, whereas elevated troponin I levels identify a group with reduced risk of recurrences.
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http://dx.doi.org/10.1016/j.chest.2020.07.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768931PMC
December 2020

Impact of Different Doses of Omega-3 Fatty Acids on Cardiovascular Outcomes: a Pairwise and Network Meta-analysis.

Curr Atheroscler Rep 2020 07 16;22(9):45. Epub 2020 Jul 16.

VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA.

Purpose Of Review: Omega-3 fatty acid (O3FA) supplementation has shown conflicting evidence regarding its benefit in cardiovascular events. We performed a pairwise and network meta-analysis to elucidate the benefit of different doses of O3FA supplementation in cardiovascular prevention.

Recent Findings: Fourteen studies were identified providing data on 125,763 patients. A prespecified cut-off value of < 1 g per day was set for low-dose (LD) O3FA and > 1 g per day for high-dose (HD) O3FA. The efficacy outcomes of interest were total death, cardiac death, sudden cardiac death, myocardial infarction, stroke, coronary revascularization, unstable angina, and major vascular events. Safety outcomes of interest were bleeding, gastrointestinal disturbances, and atrial fibrillation events. HD treatment was associated with a lower risk of cardiac death (IRR 0.79, 95% CI [0.65-0.96], p = 0.03 versus control), myocardial infarction (0.71 [0.62-0.82], p < 0.0001 versus control and 0.79 [0.67-0.92], p = 0.003 versus LD), coronary revascularization (0.74 [0.66-0.83], p < 0.0001 versus control and 0.74 [0.66-0.84], p < 0.0001 versus LD), unstable angina (0.73 [0.62-0.86], p = 0.0001 versus control and 0.74 [0.62-0.89], p = 0.002 versus LD), and major vascular events (0.78 [0.71-0.85], p < 0.0001 versus control and 0.79 [0.72-0.88], p < 0.0001 versus LD). HD treatment was associated with increased risk for bleeding events (1.49 [1.2-1.84], p = 0.0002 versus control and 1.63 [1.16-2.3], p = 0.005 versus LD) and increased atrial fibrillation events compared to control (1.35 [1.1-1.66], p = 0.004). HD O3FA treatment was associated with lower cardiovascular events compared to LD and to control, but increased risk for bleeding and atrial fibrillation events.
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http://dx.doi.org/10.1007/s11883-020-00865-5DOI Listing
July 2020

Stenting techniques for coronary bifurcation lesions: Evidence from a network meta-analysis of randomized clinical trials.

Catheter Cardiovasc Interv 2021 Feb 14;97(3):E306-E318. Epub 2020 Jul 14.

Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.

Objectives: We conducted a systematic review and network meta-analysis of available randomized clinical trials (RCTs) to compare cardiovascular outcomes involving stenting techniques in coronary bifurcation lesions.

Background: Although provisional stenting of the main branch and balloon angioplasty of the side branch is considered the standard approach, the use of two stents is often pursued with a wide variety of bifurcation stenting techniques available.

Methods: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and Clinicaltrials.gov from inception to December 2018. We performed a frequentist network meta-analysis to estimate relative risks (RR) of death, major adverse cardiovascular events (MACE), target vessel revascularization (TVR), target lesion revascularization (TLR), and stent thrombosis (ST) among different two stent bifurcation techniques.

Results: We identified 14 studies, yielding data on 4,285 patients. Double Kissing (DK) Crush and Mini-crush were associated with significant reductions in MACE, TVR, and TLR when compared with the Provisional stenting (RR 0.31-0.55 [all p < .01] and RR 0.42-0.45 [all p < .02], respectively) and with the remaining bifurcation techniques (RR 0.44-0.55 [all p < .05] for DK Crush and RR 0.37-0.45 [all p < .05] for Mini-crush). In addition, Culotte and Crush were associated with an increased risk for ST compared to Provisional stenting (RR 3.25-4.27 [both p < .05]) and to DK crush (RR 3.02-3.99 [both p < .05]).

Conclusions: DK crush and mini-crush were found to be associated with fewer events and complications compared to the other techniques reviewed, including the Provisional approach. Further, Culotte and Crush were associated with an increased risk of stent thrombosis when compared to the Provisional approach.
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http://dx.doi.org/10.1002/ccd.29097DOI Listing
February 2021

Early changes in NT-proBNP levels predict new-onset heart failure in patients with STEMI.

Minerva Cardioangiol 2020 Jul 10. Epub 2020 Jul 10.

Division of Cardiology, Department of Internal Medicine, Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA -

Background: Previous studies suggested that N-terminal pro-Brain natriuretic peptide (NT- proBNP) level is a powerful independent predictor of death or heart failure (HF) when measured at admission in patients with chest pain or acute coronary syndrome. Little is known about the role of NT-proBNP level measured during a hospitalization for ST segment elevation myocardial infarction (STEMI) in predicting clinical outcomes. We evaluated the optimal NT-proBNP timing (admission, 72 hours, or delta [Δ] NT-proBNP [72 hours minus admission]) to predict 1-year new-onset HF in STEMI patients.

Methods: We measured NT-proBNP levels at admission and 72 hours in 72 patients with STEMI. HF events were adjudicated and defined as hospitalization for HF or need for new initiation of a loop diuretic at 1-year follow-up. Values are presented as medians and interquartile range or frequencies (%) as appropriate. Cox regression analysis was used to determine predictors of adverse events. A receiver-operative-curve was constructed to identify the discriminative value and optimal cut-off points for NT-proBNP.

Results: Patients (age 56 [49-64] years, males 59 [82%]) were followed for a median duration of 365 [180-365] days. HF events were recorded in 9 (12.5%) patients. NT-proBNP values at admission, 72 hours, and ΔNT-proBNP were 89 (26-268) pg/mL, 452 (223-1064) pg/mL, and 283 (68-686) pg/mL, respectively. NT-proBNP at 72 hours and ΔNT-proBNP, but not admission NT- proBNP predicted new-onset HF events at follow-up (p=0.03, p=0.002 and p=0.89, respectively). The optimal area under the curve of 0.771 (95%, CI [0.630-0.912], p= 0.009) and cut-off value of 830 pg/mL (sensitivity 79%; specificity 76%) were found for NT-proBNP at 72 hours. The Kaplan- Meier survival curves for NT-proBNP at 72 hours dichotomized above and below this cut-off value, confirmed NT-proBNP at 72 hours >830 pg/mL as predictive of HF events (log-rank statistic=8.688, p=0.003).

Conclusions: NT-proBNP level at 72 hours and ΔNT-proBNP (72 hours minus admission), but not at time of admission, predicted HF events in patients following STEMI.
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http://dx.doi.org/10.23736/S0026-4725.20.05303-7DOI Listing
July 2020