Publications by authors named "Massimo Imazio"

266 Publications

Pericardial Diseases in COVID19: a Contemporary Review.

Curr Cardiol Rep 2021 06 3;23(7):90. Epub 2021 Jun 3.

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, OH, USA.

Purpose Of Review: Coronavirus disease 2019 (COVID19) involves the heart, including pericardium. This article reviews the possible pathophysiological mechanisms in pericardial involvement in COVID19 and pericardial manifestations of COVID19. It also summarizes the patients with pericarditis secondary to COVID19 and outlines the contemporary treatment strategies in this patient population.

Recent Findings: A high degree of suspicion is required to identify the pericardial involvement in COVID19 patients. It is proposed that an underlying hyperinflammatory reaction in COVID19 leads to pericardial inflammation. Acute pericarditis with or without myocardial involvement is diagnosed on clinical presentation, serum inflammatory markers, electrocardiogram, and echocardiogram. Multimodality imaging may also have an additional diagnostic value. Patients are usually managed medically, but some patients develop a life-threatening pericardial tamponade necessitating pericardial drainage. Pericardial involvement is an important clinical manifestation of COVID19 requiring a proper workup. Timely diagnosis and a specific management plan based on the presentation and concomitant organ involvement usually lead to a complete recovery.
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http://dx.doi.org/10.1007/s11886-021-01519-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173318PMC
June 2021

A risk score for pericarditis recurrence.

Eur J Clin Invest 2021 May 29:e13602. Epub 2021 May 29.

First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Background: Currently, we remain uncertain about which patients are at increased risk for recurrent pericarditis. We developed a risk score for pericarditis recurrence in patients with acute pericarditis.

Materials And Methods: We prospectively recruited 262 patients with a first episode of acute pericarditis. Baseline patients' demographics, clinical, imaging and laboratory data were collected. Patients were followed up for a median of 51 months (interquartile range 21-71) for recurrence. Variables with <10% missingness were entered into multivariable logistic regression models with stepwise elimination to explore independent predictors of recurrence. The final model performance was assessed by the c-index whereas model's calibration and optimism-corrected c-index were evaluated after 10-fold cross-validation.

Results: We identified six independent predictors for pericarditis recurrence, that is age, effusion size, platelet count (negative predictors) and reduced inferior vena cava collapse, in-hospital use of corticosteroids and heart rate (positive predictors). The final model had good performance for recurrence, c-index 0.783 (95% CI 0.725-0.842), while the optimism-corrected c-index after cross-validation was 0.752. Based on these variables, we developed a risk score point system for recurrence (0-22 points) with equally good performance (c-index 0.740, 95% CI 0.677-0.803). Patients with a low score (0-7 points) had 21.3% risk for recurrence, while those with high score (≥12 points) had a 69.8% risk for recurrence. The score was predictive of recurrence among most patient subgroups.

Conclusions: A simple risk score point system based on 6 variables can be used to predict the individualized risk for pericarditis recurrence among patients with a first episode of acute pericarditis.
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http://dx.doi.org/10.1111/eci.13602DOI Listing
May 2021

Colchicine and the heart.

Eur Heart J 2021 May 7. Epub 2021 May 7.

GenesisCare, 3/140 Mounts Bay Rd, Perth, Western Australia, Australia.

Colchicine is a unique, sophisticated anti-inflammatory agent that has been used for decades for the prevention of acute inflammatory flares in gout and familial Mediterranean fever. In recent years, clinical trials have demonstrated its potential in a range of cardiovascular (CV) conditions. Colchicine is avidly taken up by leucocytes, and its ability to bind to tubulin and interfere with microtubular function affects the expression of cytokines and interleukins, and the ability of neutrophils to marginate, ingress, aggregate, express superoxide, release neutrophil extracellular traps, and interact with platelets. In patients with acute and recurrent pericarditis, clinical trials in >1600 patients have consistently shown that colchicine halves the risk of recurrence [relative risk (RR) 0.50, 95% confidence interval (CI) 0.42-0.60]. In patients with acute and chronic coronary syndromes, multicentre randomized controlled trials in >11 000 patients followed for up to 5 years demonstrated that colchicine may reduce the risk of CV death, myocardial infarction, ischaemic stroke and ischaemia-driven revascularization by >30% (RR 0.63, 95% CI 0.49-0.81). The use of colchicine at doses of 0.5-1.0 mg daily in CV trials has proved safe. Early gastrointestinal intolerance limits its use in ∼10% of patients; however, ∼90% of patients tolerate it well over the long term. Despite isolated case reports, clinically relevant drug interactions with moderate to strong CYP3A4 inhibitors/competitors or P-glycoprotein inhibitors/competitors are rare if this dosage of colchicine is used in the absence of advanced renal or liver disease. The aim of this review is to summarize the contemporary data supporting the efficacy and safety of colchicine in patients with CV disease.
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http://dx.doi.org/10.1093/eurheartj/ehab221DOI Listing
May 2021

[ANMCO Position paper: Current evidence on intra-aortic balloon pump in advanced acute heart failure].

G Ital Cardiol (Rome) 2021 May;22(5):404-423

U.O.C. Cardiologia, Ospedale Garibaldi-Nesima, Azienda di Rilievo Nazionale e Alta Specializzazione "Garibaldi", Catania - Fondazione per il Tuo cuore - Heart Care Foundation, Firenze.

The treatment of patients with advanced acute heart failure is still challenging. Intra-aortic balloon pump (IABP) has widely been used in the management of patients with cardiogenic shock. However, according to international guidelines, its routinary use in patients with cardiogenic shock is not recommended. This recommendation is derived from the results of the IABP-SHOCK II trial, which demonstrated that IABP does not reduce all-cause mortality in patients with acute myocardial infarction and cardiogenic shock. The present position paper, released by the Italian Association of Hospital Cardiologists (ANMCO), reviews the available data derived from clinical studies. It also provides practical recommendations for the optimal use of IABP in the treatment of cardiogenic shock and advanced acute heart failure. Data deriving from a national survey in Italian hospitals about IABP use are also provided.
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http://dx.doi.org/10.1714/3592.35751DOI Listing
May 2021

Pericarditis in patients with coronavirus disease 2019: a systematic review.

J Cardiovasc Med (Hagerstown) 2021 Apr 28. Epub 2021 Apr 28.

Vicerrectorado de Investigación, Universidad San Ignacio de Loyola Asociación para el Desarrollo de la Investigación Estudiantil en Ciencias de la Salud (ADIECS) Programa de Atención Domiciliaria (PADOMI), EsSalud Deparment of Emergency, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru Cardiology, Cardiothoracic Department, University Hospital "Santa Maria della Misericordia", ASUFC, Udine, Italy.

Aims: We performed a systematic review to summarize the clinical features, diagnostic methods, treatment, and outcomes of coronavirus disease 2019 (COVID-19) patients with pericarditis.

Methods: We searched electronic databases from inception to 17 December 2020. Studies that reported clinical data on patients with COVID-19 and pericarditis were included. Descriptive statistics were used for categorical and continuous variables [mean ± standard deviation or median (interquartile range)]. As an exploratory analysis, differences between patients with acute pericarditis and myopericarditis were compared.

Results: A total of 33 studies (32 case reports and 1 case series) involving 34 patients were included. The mean age was 51.6 ± 19.5 years and 62% of patients were men. Sixty-two percentage of patients were diagnosed with myopericarditis. The most frequent electrocardiographic pattern (56%) was diffuse ST-elevation and PR depression. Pericardial effusion and cardiac tamponade were reported in 76 and 35% of cases, respectively. The median values of C-reactive protein [77 mg/dl (12-177)] and white blood cells [12 335 cells/μl (5625-16 500)] were above the normal range. Thirty-eight percent and 53% of patients were treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine, respectively. These drugs were more frequently used in patients with acute pericarditis compared with myopericarditis. The in-hospital mortality was 6% without a significant difference between both groups.

Conclusion: Our review shows that COVID-19 patients with pericarditis had similar clinical features to other viral cardiotropic infections. However, NSAIDs and colchicine were used in half or less of the cases. Overall, the short-term prognosis was good across groups.
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http://dx.doi.org/10.2459/JCM.0000000000001202DOI Listing
April 2021

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

N Engl J Med 2021 04;384(15):1475-1476

Kiniksa Pharmaceuticals, Lexington, MA.

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http://dx.doi.org/10.1056/NEJMc2101978DOI Listing
April 2021

Diagnosis and treatment of cardiac amyloidosis. A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases.

Eur J Heart Fail 2021 Apr 7. Epub 2021 Apr 7.

2nd Department of Medicine, Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University, General University Hospital, Prague, Czech Republic.

Cardiac amyloidosis is a serious and progressive infiltrative disease that is caused by the deposition of amyloid fibrils at the cardiac level. It can be due to rare genetic variants in the hereditary forms or as a consequence of acquired conditions. Thanks to advances in imaging techniques and the possibility of achieving a non-invasive diagnosis, we now know that cardiac amyloidosis is a more frequent disease than traditionally considered. In this position paper the Working Group on Myocardial and Pericardial Disease proposes an invasive and non-invasive definition of cardiac amyloidosis, addresses clinical scenarios and situations to suspect the condition and proposes a diagnostic algorithm to aid diagnosis. Furthermore, we also review how to monitor and treat cardiac amyloidosis, in an attempt to bridge the gap between the latest advances in the field and clinical practice.
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http://dx.doi.org/10.1002/ejhf.2140DOI Listing
April 2021

Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases.

Eur Heart J 2021 04;42(16):1554-1568

2nd Department of Medicine, Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University, General University Hospital, Prague, Czech Republic.

Cardiac amyloidosis is a serious and progressive infiltrative disease that is caused by the deposition of amyloid fibrils at the cardiac level. It can be due to rare genetic variants in the hereditary forms or as a consequence of acquired conditions. Thanks to advances in imaging techniques and the possibility of achieving a non-invasive diagnosis, we now know that cardiac amyloidosis is a more frequent disease than traditionally considered. In this position paper the Working Group on Myocardial and Pericardial Disease proposes an invasive and non-invasive definition of cardiac amyloidosis, addresses clinical scenarios and situations to suspect the condition and proposes a diagnostic algorithm to aid diagnosis. Furthermore, we also review how to monitor and treat cardiac amyloidosis, in an attempt to bridge the gap between the latest advances in the field and clinical practice.
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http://dx.doi.org/10.1093/eurheartj/ehab072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060056PMC
April 2021

Efficacy and safety of colchicine for the prevention of major cardiovascular and cerebrovascular events in patients with coronary artery disease: a systematic review and meta-analysis on 12 869 patients.

Eur J Prev Cardiol 2021 Mar 29. Epub 2021 Mar 29.

Department of Cardiovascular and Thoracic, University Cardiology, A.O.U. Città della Salute e della Scienza di Torino, Corso Bramante 88, 10126 Turin, Italy.

Aims: The key role of inflammation in the pathogenesis of coronary artery disease (CAD) is an urgent call for innovative treatments. Several trials have proposed colchicine as a therapeutic option for secondary prevention in CAD patients but its utilization is hampered by fears about drug-related adverse events (DAEs) and conflicting evidences. The aim of this meta-analysis was to consolidate evidence on the efficacy and safety of colchicine for secondary prevention in patients with CAD.

Methods And Results: A systematic search in electronic bibliographic databases of Medline, Scopus, Embase, and the Cochrane Library was performed to identify randomized controlled trials (RCTs) assessing the cardiovascular effects of colchicine in CAD patients, compared with placebo. Outcomes of interest were the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) and DAEs. Estimates were pooled using inverse-variance random-effects model. A total of 11 RCTs, including 12 869 patients, were identified as eligible. A total of 6501 patients received colchicine, while 6368 received placebo. After a median follow-up of 6 months (interquartile range, 1-16), patients receiving colchicine had a lower risk of MACCE [6% vs. 8.8%, relative risk (RR) = 0.67, 95% confidence interval (CI) 0.56-0.80, I2 = 19%], myocardial infarction (3.3% vs. 4.3%, RR = 0.76, 95% CI 0.61-0.96, I2 = 17%), coronary revascularization (2.9% vs. 4.2%, RR = 0.61, 95% CI 0.42-0.89, I2 = 40%), stroke (0.4% vs. 0.9%, RR = 0.48, 95% CI 0.30-0.77, I2 = 0%), hospitalization for cardiovascular cause (0.9% vs. 2.9%, RR = 0.32, 95% CI 0.12-0.87, I2 = 0%). Colchicine was associated with an increased risk of gastrointestinal DAEs (11% vs. 9.2%, RR = 1.67, 95% CI 1.20-2.34, I2 = 76%), myalgia (18% vs. 16%, RR = 1.16, 95% CI 1.02-1.32, I2 = 0%) and DAEs-related discontinuation (4.1% vs. 3%, RR = 1.54, 95% CI 1.02-2.32, I2 = 65%). However, gastrointestinal DAEs and discontinuation may be prevented with a lower daily dose. Colchicine did not increase the risk of cardiovascular death (0.7% vs. 1%, RR = 0.73, 95% CI 0.45-1.21, I2 = 14%), all-cause death (2% vs. 1.9%, RR = 1.01, 95% CI 0.71-1.43, I2 = 16%), or other DAEs.

Conclusions: The use of colchicine in patients with CAD is safe and efficacious for MACCE prevention.
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http://dx.doi.org/10.1093/eurjpc/zwab045DOI Listing
March 2021

Anti-interleukin 1 agents for the treatment of recurrent pericarditis: a systematic review and meta-analysis.

Heart 2021 Mar 18. Epub 2021 Mar 18.

Department of Biomedical and Clinical Sciences, Fatebenefratelli Hospital, University of Milan, Milano, Italy.

Aims: Corticosteroid-dependent and colchicine-resistant recurrent pericarditis (RP) is a challenging management problem, in which conventional anti-inflammatory therapy (nonsteroidal anti-inflammatory drugs, colchicine, corticosteroids) is unable to control the disease. Recent data suggest a potential role for anti-interleukin-1 (IL-1) agents for this condition. This study was designed to assess the safety and efficacy of anti-IL-1 agents in this setting.

Methods: We performed a systematic review and meta-analysis of randomised controlled trials and observational studies assessing pericarditis recurrences and drug-related adverse events in patients receiving anti-IL-1 drugs for pericarditis.

Results: The meta-analysis assessed 7 studies including 397 pooled patients with RP. The median age was 42 years, 60% were women and the aetiology was idiopathic in 87%. After a median follow-up of 14 months (IQR,12-39), patients receiving anti-IL-1 agents (anakinra or rilonacept) had a significantly reduction in pericarditis recurrences (incidence rate ratio 0.06, 95% CI 0.03 to 0.14), compared with placebo and/or standard medical therapy. Anti-IL-1 agents were associated with increased risk of adverse events compared with placebo (risk ratio (RR) 5.38, 95% CI 2.08 to 13.92): injection-site reactions occurred in 15/41 (36.6%) vs none (RR 14.98, 95% CI 2.09 to 107.09), infections occurred in 13/51 (25.5%) vs 3/41 (7.3%; RR 3.65, 95% CI 1.23 to 10.85). Anti-IL-1 agents were not associated with increased risk of severe adverse events.

Conclusions: In patients with RP, anti-IL-1 agents (anakinra and rilonacept) are efficacious for prevention of recurrences, without severe adverse events.
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http://dx.doi.org/10.1136/heartjnl-2020-318869DOI Listing
March 2021

Colchicine efficacy and safety for the treatment of cardiovascular diseases.

Intern Emerg Med 2021 Mar 11. Epub 2021 Mar 11.

Departement of Medical Sciences, A.O.U. Città della Salute e della Scienza di Torino, University Cardiology, Corso Bramante 88, 10126, Turin, Italy.

The emerging role of colchicine in the treatment of cardiovascular diseases is a strong demand for a comprehensive understanding of its efficacy and safety. This meta-analysis and systematic review aimed to study the efficacy in the reduction of adverse cardiovascular outcomes (CO), and the risk of colchicine-related adverse events (CRAEs). Fourteen thousand and nine eighty three patients from 22 randomized controlled trials (RCTs) were included, 9 in patients with coronary artery disease-CAD, 9 in patients with pericarditis, 4 in patients with atrial fibrillation-AF or heart failure. Colchicine was efficacious in the reduction of adverse CO across different settings: pericardial diseases (reduced risk of recurrent pericarditis, 17.6% vs. 35%, RR 0.50, 95% CI 0.41-0.61), CAD (reduced risk of cardiac death, myocardial infarction, stroke,coronary revascularization or hospitalization, 6.1% vs. 8.5%, RR 0.73, 95% CI 0.64-0.83), AF (reduced risk of arrhythmia recurrence, 14.2% vs. 22.7%, RR 0.62, 95% CI 0.44-0.88). Colchicine was associated with increased risk of gastrointestinal CRAEs (11.2% vs. 8.8%, RR 1.87, 95% CI 1.41-2.47) and drug discontinuation (5.4% vs. 3.7%, RR 1.58, 95% CI 1.25-1.99). In both cases, the risk was proportional to the daily dose or duration of treatment, possibly due to early drug discontinuation or tolerance. Other CRAEs (muscle-related, liver,hematologic,cutaneous, infections) were not increased by colchicine, as long as all-cause death (2.2% vs. 1.9%, RR 1.11, 95% CI 0.79-1.54) or non-cardiovascular death (1.5% vs. 1%, RR 1.43, 95% CI 0.93-2.19). Colchicine is efficacious and safe for the treatment of cardiovascular diseases. The risk of gastrointestinal CRAEs and drug discontinuation is not significant if colchicine is used at lower doses (0.5 mg daily) or for longer periods of time (> 6 months).
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http://dx.doi.org/10.1007/s11739-021-02654-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947153PMC
March 2021

Non-high-density lipoprotein cholesterol versus low-density lipoprotein cholesterol in clinical practice: ANMCO position paper.

J Cardiovasc Med (Hagerstown) 2021 Mar 1. Epub 2021 Mar 1.

Clinical and Rehabilitative Cardiology Unit, San Filippo Neri Hospital ASL Roma 1, Rome Department of Translational and Precision Medicine, Sapienza University of Roma, Rome U.O.C. Cardiologia-UTIC, San Paolo Hospital, Bari Cardilogy-Intensive Care Unit, Ospedali di Città di Castello e Gubbio - Gualdo Tadino, Azienda USL Umbria 1, Perugia Cardiology Department, Le Scotte University Hospital, Siena Cardiology Unit, Bellaria Hospital, AUSL of Bologna, Bologna Cardiology Unit, Ospedale Santa Maria della Misericordia, Rovigo Cardilogy-Intensive Care Unit, Santa Maria degli Ungheresi Hospital, Polistena, Reggio Calabria Department of Cardiovascular and Thoracic Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome Cardiology Unit 2, ASST Grande Ospedale Metropolitano Niguarda Cà Granda, Milan Cardiology Unit, ASL 3, Ospedale Padre A. Micone, Genova Cardiology Division, Ospedale Garibaldi-Nesima, Azienda di Rilievo Nazionale e Alta Specializzazione 'Garibaldi' Catania, Catania Cardilogy Unit, Presidio Molinette, A.O.U. Città della Salute e della Scienza di Torino, Torino Cardiologia-UTIC-Emodinamica, Ospedale del Mare, Napoli Cardiovascular Center, University Hospital and Health Services of Trieste, Trieste Presidente Fondazione per il Tuo cuore, Heart Care Foundation, Florence Division of Cardiology, Augusto Murri Hospital, Fermo, Italy.

Bloodstream cholesterol is a central contributor to atherosclerotic cardiovascular diseases. For several decades, low-density lipoprotein cholesterol (LDL-C) has been the main biomarker for the prediction of cardiovascular events and therapeutic target of lipid-lowering treatments. More recently, several findings have supported the greater reliability of non-high-density lipoprotein cholesterol (non-HDL-C) as a predictive factor and possible therapeutic target in refining antiatherogenic treatments, especially among patients with lower LDL-C and higher triglyceride values. This article discusses the limits of current standard methods for assessing LDL-C levels and emphasizes the persistent residual cardiovascular risk in patients treated with lipid-lowering agents on the basis of recommended LDL-C targets. It highlights that patients with controlled LDL-C and non-targeted non-HDL-C have a higher cardiovascular risk. The article focuses on the role of non-HDL-C as a better predictor of atherosclerotic disease as compared with LDL-C and as a therapeutic target. Finally, this article includes an executive summary aimed at refining preventive approaches in atherosclerotic cardiovascular disease.
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http://dx.doi.org/10.2459/JCM.0000000000001175DOI Listing
March 2021

Commentary on "Use of Anakinra to Prevent Mechanical Ventilation in Severe COVID-19: A Case Series.": COVID-19 disease in patients with recurrent pericarditis during treatment with anakinra.

Arthritis Rheumatol 2021 Mar 1. Epub 2021 Mar 1.

Department of Biomedical and Clinical Science "Sacco", Università di Milano, Fatebenefratelli Hospital, Milan, Italy.

We read with interest the paper from Navarro-Millan about the use of anakinra in severe COVID-19 patients (1). On the other hand, there is the issue of patients treated with anakinra for their underlying condition and who develop COVID-19 (2).
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http://dx.doi.org/10.1002/art.41702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014857PMC
March 2021

Recurrent pericarditis: an update on diagnosis and management.

Intern Emerg Med 2021 Apr 28;16(3):551-558. Epub 2021 Feb 28.

University of Milano Statale, Milano, Italy.

Recurrent pericarditis is a true challenge for clinicians, especially when the patient becomes unresponsive or not tolerant to conventional treatments. An accurate diagnosis of recurrent pericarditis, possibly supported by advanced imaging tools, is critical to provide timely and appropriate treatment of symptoms and prevention of further episodes. The incessant research on the inflammatory pathways underlying cardiovascular diseases, led recently to the assessment of anti interleukin-1 agents in the setting of recurrent pericarditis. This review will focus on the diagnostic assessment of recurrent pericarditis, along with the most modern therapeutic advances in this field. Bibliographic databases were searched (MEDLINE/PubMed, BioMed Central, the Cochrane Collaboration Database of Randomized Trials, Scopus, ClinicalTrials.gov, EMBASE, Google Scholar) using the terms "recurrent pericarditis" AND "diagnosis" OR "treatment" OR "IL-1" OR "inflammation".
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http://dx.doi.org/10.1007/s11739-021-02639-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914388PMC
April 2021

Cardiac tamponade: an educational review.

Eur Heart J Acute Cardiovasc Care 2020 Jul 6. Epub 2020 Jul 6.

Cardiac tamponade is a pericardial syndrome characterised by an impairment of the diastolic filling of the ventricles causing reduction of cardiac output, usually producing signs and symptoms of cardiac arrest, if untreated. The main causes of cardiac tamponade include percutaneous cardiac interventions, malignacies, infectious/inflammatory causes, mechanical complications of myocardial infarction and aortic dissection. The diagnosis of cardiac tamponade is a clinical diagnosis based on a suggestive history and clinical presentation with worsening dyspnoea, distended jugular veins, muffled heart sounds and pulsus paradoxus, and should be confirmed by echocardiography. Cardiac tamponade is a life-threatening syndrome that requires urgent treatment by pericardiocentesis. Pericardiocentesis is an interventional technique to drain pericardial fluid by a percutaneous route. The standard technique for pericardiocentesis is guided by echocardiography or fluoroscopy under local anaesthesia. Pericardiocentesis should be performed by experienced operators and carries a variable risk of complications, mainly cardiac chamber puncture, arrhythmias (ventricular arrhythmias suggest puncture of the ventricle), coronary artery puncture or haemothorax, pneumothorax, pneumopericardium and hepatic injury. The prognosis of cardiac tamponade is essentially related to aetiology. Cardiac tamponade in patients with cancer and metastatic involvement of the pericardium has a bad short-term prognosis because it is a sign of advanced cancer, on the contrary, patients with cardiac tamponade and a final diagnosis of idiopathic pericarditis generally have a good long-term prognosis.
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http://dx.doi.org/10.1177/2048872620939341DOI Listing
July 2020

Usefulness of Beta-Blockers to Control Symptoms in Patients With Pericarditis.

Am J Cardiol 2021 05 1;146:115-119. Epub 2021 Feb 1.

University Cardiology, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy.

Exercise restriction is a nonpharmacological treatment of pericarditis that could reduce symptoms by slowing heart rate (HR). Beta-blockers allow pharmacological control of HR. Aim of this paper is to explore the possible efficacy of beta-blockers to improve control of symptoms in patients with pericarditis. We analyzed consecutive cases with pericarditis referred to our center. Beta-blockers were prescribed on top of standard anti-inflammatory therapy in symptomatic patients (chest pain and palpitations) with rest HR>75 beats/min. The primary end point was the persistence of pericardial pain at 3 weeks. The secondary end point was the occurrence of recurrent pericarditis at 18 months. Propensity score matching was used to generate 2 cohorts of 101 patients with and without beta-blockers with balanced baseline features. A clinical and echocardiographic follow-up was performed at 3 weeks, 1, 3, 6 months and then every 12 months. A total of 347 patients (mean age 53 years, 58% females, 48% with a recurrence, 81% with idiopathic/viral etiology) were included. Among them, 128 patients (36.9%) were treated with beta-blockers. Peak C-reactive protein values were correlated with heart rate on first observation (r=0.48, p<0.001). Using propensity-score matched cohorts, patients treated with beta-blockers had a lower frequency of symptoms persistence at 3 weeks (respectively 4% vs. 14%; p = 0.024) and a trend towards a reduction of recurrences at 18 months (p = 0.069). In conclusion the use of beta-blockers on top of standard anti-inflammatory therapies was associated with improved symptom control.
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http://dx.doi.org/10.1016/j.amjcard.2021.01.032DOI Listing
May 2021

Colchicine and coronary artery disease: a virtuous adoption.

Eur Heart J 2021 Jan 26. Epub 2021 Jan 26.

Division of Cardiology, Department of Medical Sciences, University of Turin, Città della Salute e della Scienza hospital, Corso Bramante 88/90, 10126, Turin, Italy.

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http://dx.doi.org/10.1093/eurheartj/ehab008DOI Listing
January 2021

Incessant Pericarditis as a Risk Factor for Complicated Pericarditis and Hospital Admission.

Circulation 2021 Jan 25;143(4):401-402. Epub 2021 Jan 25.

University Cardiology (M.I., A.A., C.S., C.G., G.M.D.F.), Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Turin, Italy.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.051156DOI Listing
January 2021

Interleukin 1α: a comprehensive review on the role of IL-1α in the pathogenesis and treatment of autoimmune and inflammatory diseases.

Autoimmun Rev 2021 Mar 20;20(3):102763. Epub 2021 Jan 20.

Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA. Electronic address:

The interleukin (IL)-1 family member IL-1α is a ubiquitous and pivotal pro-inflammatory cytokine. The IL-1α precursor is constitutively present in nearly all cell types in health, but is released upon necrotic cell death as a bioactive mediator. IL-1α is also expressed by infiltrating myeloid cells within injured tissues. The cytokine binds the IL-1 receptor 1 (IL-1R1), as does IL-1β, and induces the same pro-inflammatory effects. Being a bioactive precursor released upon tissue damage and necrotic cell death, IL-1α is central to the pathogenesis of numerous conditions characterized by organ or tissue inflammation. These include conditions affecting the lung and respiratory tract, dermatoses and inflammatory skin disorders, systemic sclerosis, myocarditis, pericarditis, myocardial infarction, coronary artery disease, inflammatory thrombosis, as well as complex multifactorial conditions such as COVID-19, vasculitis and Kawasaki disease, Behcet's syndrome, Sjogren Syndrome, and cancer. This review illustrates the clinical relevance of IL-1α to the pathogenesis of inflammatory diseases, as well as the rationale for the targeted inhibition of this cytokine for treatment of these conditions. Three biologics are available to reduce the activities of IL-1α; the monoclonal antibody bermekimab, the IL-1 soluble receptor rilonacept, and the IL-1 receptor antagonist anakinra. These advances in mechanistic understanding and therapeutic management make it incumbent on physicians to be aware of IL-1α and of the opportunity for therapeutic inhibition of this cytokine in a broad spectrum of diseases.
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http://dx.doi.org/10.1016/j.autrev.2021.102763DOI Listing
March 2021

Pericardial Involvement in Cancer.

Am J Cardiol 2021 04 15;145:151-159. Epub 2021 Jan 15.

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, Ohio. Electronic address:

Despite the monumental advances in the diagnoses and therapeutics of malignancy, several cancer patients have presented with pericardial involvement, including acute pericarditis, constrictive pericarditis, and pericardial effusion. Multiple factors can contribute to acute pericarditis, including direct metastasis to the heart, pericardial hemorrhage, infections due to immunosuppression, and cancer therapies that include chemotherapy, immunotherapy, and radiation. Pericardial effusion, either due to cancer invasion or cancer treatment, is one of the most common incidental findings in cancer patients, which significantly worsens morbidity and mortality. If left untreated, pericardial effusion is known to cause complications such as pericardial tamponade. Constrictive pericarditis can be due to radiation exposure, chemotherapy, or is a sequela of a previous episode of acute pericarditis. In conclusion, early detection, prompt treatment, and understanding of pericardial diseases are necessary to help improve the quality of life of cancer patients, and we aim to summarize the knowledge of pericardial involvement in patients with cancer.
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http://dx.doi.org/10.1016/j.amjcard.2020.12.092DOI Listing
April 2021

Adverse events of colchicine for cardiovascular diseases: a comprehensive meta-analysis of 14 188 patients from 21 randomized controlled trials.

J Cardiovasc Med (Hagerstown) 2021 Jan 4;Publish Ahead of Print. Epub 2021 Jan 4.

Department of Medical Sciences, University of Torino, University Cardiology, AOU Città della Salute e della Scienza di Torino, Turin, Italy Alessandro Andreis and Massimo Imazio contributed equally to this article.

Aims: Colchicine has an emerging role in the cardiovascular field, although, concerns for side effects, especially gastrointestinal, limit its prescription. We aimed at evaluating reported side effects of colchicine for cardiovascular indications.

Methods: We performed a meta-analysis of published randomized controlled trials on colchicine for the treatment of cardiovascular diseases. Random-effects meta-analysis was used to assess the risk of adverse events and drug withdrawal. Publication bias was assessed using the Egger test, and meta-regression was performed to assess sources of heterogeneity.

Results: Among 14 188 patients, 7136 patients received colchicine while the other 7052 received placebo. The occurrence of any adverse event with colchicine was reported in 15.3 vs. 13.9% patients [relative risk (RR) 1.26, 95% confidence interval (CI) 0.96-1.64, P = 0.09]. Gastrointestinal events were reported in 16.1 vs. 12.2% (RR 2.16, 95% CI 1.50-3.12, P < 0.001), while diarrhea was reported in 12.5 vs. 8.1% (RR 2.77, 95% CI 1.55-4.94, P < 0.001). The risk of gastrointestinal events increased with daily dose and shorter treatment duration. Myalgias were observed in 21 vs. 18% patients (RR 1.16, 95% CI 1.02-1.32, P = 0.03). Other adverse events such as myotoxicity, hepatic adverse events, hematologic adverse events, cutaneous adverse events, infection or death were not increased by colchicine treatment. Colchicine discontinuation was reported in 4.8 vs. 3.4% patients (RR 1.54, 95% CI 1.20-1.99, P < 0.001).

Conclusion: Colchicine is associated with increased risk of gastrointestinal events and myalgias, but not of other adverse events. The risk of gastrointestinal events may be avoided with lower dose (0.5 mg/daily) and is inversely related to treatment duration, possibly due to early drug discontinuation or drug tolerance.
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http://dx.doi.org/10.2459/JCM.0000000000001157DOI Listing
January 2021

Anti-IL-1 agents: a paradigm shift in medical therapy for recurrent pericarditis?

Authors:
Massimo Imazio

Heart 2020 Dec 24. Epub 2020 Dec 24.

University Cardiology, Cardiovascular and Thoracic Department, AOU Città della Salute e della Scienza di Torino, Torino, Italy

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http://dx.doi.org/10.1136/heartjnl-2020-318549DOI Listing
December 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

Gastroprotection in patients on antiplatelet and/or anticoagulant therapy: a position paper of National Association of Hospital Cardiologists (ANMCO) and the Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO).

Eur J Intern Med 2021 Mar 2;85:1-13. Epub 2020 Dec 2.

Gastroenterology and Digestive Endoscopy, Academic Hospital Cattinara, Trieste, Italy.

Aspirin and P2Y receptor antagonists are widely used across the spectrum of cardiovascular and cerebrovascular diseases. Gastrointestinal complications, including ulcer and bleeding, are relatively common during antiplatelet treatment and, therefore, concomitant proton pump inhibitor (PPI) treatment is often prescribed. However, potential increased risk of cardiovascular events has been suggested for PPIs, and, in recent years, it has been discussed whether these drugs may reduce the cardiovascular protection by aspirin and, even more so, clopidogrel. Indeed, pharmacodynamic and pharmacokinetic studies suggested an interaction through hepatic CYP2C19 between PPIs and clopidogrel, which could translate into clinical inefficacy, leading to higher rates of cardiovascular events. The FDA and the EMA sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. In addition, whether the use of PPIs may affect the clinical efficacy of the new P2Y receptor antagonists, ticagrelor and prasugrel, remains less known. According to current guidelines, PPIs in combination with antiplatelet treatment are recommended in patients with risk factors for gastrointestinal bleeding, including advanced age, concurrent use of anticoagulants, steroids or non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. Like vitamin K antagonists (VKAs), DOACs can determine gastrointestinal bleeding. Results from both randomized clinical trials and observational studies suggest that high-dose dabigatran (150 mg bid), rivaroxaban and high-dose edoxaban (60 mg daily) are associated with a higher risk of GI bleeding as compared with apixaban and warfarin. In patients taking oral anticoagulant with GI risk factor, PPI could be recommended, even if usefulness of PPIs in these patients deserves further data. Helicobacter pylori should always be searched, and treated, in patients with history of peptic ulcer disease (with or without complication). Given the large number of patients treated with antithrombotic drugs and PPIs, even a minor reduction of platelet inhibition or anticoagulant effect potentially carries a considerable clinical impact. The present joint statement by ANMCO and AIGO summarizes the current knowledge regarding the widespread use of platelet inhibitors, anticoagulants, and PPIs in combination. Moreover, it outlines evidence supporting or opposing drug interactions between these drugs and discusses consequent clinical implications.
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http://dx.doi.org/10.1016/j.ejim.2020.11.014DOI Listing
March 2021

Recurrence of Pericardial Effusion After Pericardiocentesis: Does Catheter-Induced Acute Pericardial Inflammation Play a Role?

Am J Med Sci 2021 05 12;361(5):676-678. Epub 2020 Oct 12.

1st Cardiology Clinic, National and Kapodistrian University of Athens, School of Medicine, Hippokration General Hospital, Athens, Greece.

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http://dx.doi.org/10.1016/j.amjms.2020.10.012DOI Listing
May 2021

[ANMCO/SIC Consensus document on the management of myocarditis].

G Ital Cardiol (Rome) 2020 Dec;21(12):969-989

S.C. Cardiologia, Dipartimento Cardiotoracovascolare, Azienda Sanitaria Universitaria Giuliano Isontina-ASUGI, Università di Trieste.

Myocarditis is an inflammatory heart disease that can occur acutely, as in acute myocarditis, or persistently, as in chronic myocarditis or chronic inflammatory cardiomyopathy. Different agents can induce myocarditis, with viruses being the most common triggers. Generally, acute myocarditis affects relatively young people and men more than women. Myocarditis has a broad spectrum of clinical presentations and evolution trajectories, although most cases resolve spontaneously. Patients with reduced left ventricular ejection fraction, heart failure symptoms, advanced atrioventricular block, sustained ventricular arrhythmias or cardiogenic shock (the latter known as fulminant myocarditis) are at increased risk for death and heart transplantation. The presentation of chronic inflammatory cardiomyopathy may be more subtle, with progressive symptoms of heart failure or appearance of rhythm disturbance, not rarely preceded by an infective episode. Autoimmune disorder or systemic inflammatory conditions can be another significant predisposing substrate of myocarditis, especially in women. Emerging causes of myocarditis are drug-related like the new anticancer therapies, the immune checkpoint inhibitors. In this Italian Association of Hospital Cardiologists (ANMCO) and Italian Society of Cardiology (SIC) expert consensus document on myocarditis, we propose diagnostic strategies for identifying possible causes of the disease and factors associated with increased risk. Finally, we propose potential treatments and when referring patients to tertiary centers, especially for high-risk patients. Even if endomyocardial biopsy is the invasive diagnostic tool for making definitive diagnosis and differentiation of histological subtypes (i.e., lymphocytic vs eosinophilic vs giant cell myocarditis), it is not always readily available in all centers. Thus, we propose when this exam is mandatory or when it can be postponed or substituted by cardiac magnetic resonance imaging. This document reflects the Italian perspective on managing patients with myocarditis and their follow-up, considering also current US and European scientific position statements.
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http://dx.doi.org/10.1714/3472.34551DOI Listing
December 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

What is the normal composition of pericardial fluid?

Heart 2020 Nov 11. Epub 2020 Nov 11.

Department of Biomedical and Clinical Sciences, University of Milano and ASST Fatebenefratelli-Sacco, Milano, Italy.

Objective: Biochemical and cytological pericardial fluid (PF) analysis is essentially based on the knowledge of pleural fluid composition. The aim of the present study is to identify reference intervals (RIs) for PF according to state-of-art methodological standards.

Methods: We prospectively collected and analysed the PF and venous blood of consecutive subjects undergoing elective open-heart surgery from July 2017 to October 2018. Exclusion criteria for study enrolment were evidence of pericardial diseases at preoperatory workup or at intraoperatory assessment, or any other condition that could affect PF analysis.

Results: The final study sample included 120 patients (median age 69 years, 83 men, 69.1%). The main findings were (1) High levels of proteins, albumin and lactate dehydrogenase (LDH), but not of glucose and cholesterol (2) High cellularity, mainly represented by mesothelial cells. RIs for pericardial biochemistry were: protein content 1.7-4.6 g/dL PF/serum protein ratio 0.29-0.83, albumin 1.19-3.06 g/dL, pericardium-to-serum albumin gradient 0.18-2.37 g/dL, LDH 141-2613 U/L, PF/serum LDH ratio 0.40-2.99, glucose 80-134 mg/dL, total cholesterol 12-69 mg/dL, PF/serum cholesterol ratio 0.07-0.51. RIs for pericardial cells by optic microscopy were: 278-5608 × 10 nucleated cells/L, 40-3790 × 10 mesothelial cells/L, 35-2210 × 10 leucocytes/L, 19-1634 × 10 lymphocytes/L.

Conclusions: PF is rich in nucleated cells, protein, albumin, LDH, at levels consistent with inflammatory exudates in other biological fluids. Physicians should stop to interpret PF as exudate or transudate according to tools not validated for this setting.
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http://dx.doi.org/10.1136/heartjnl-2020-317966DOI Listing
November 2020

Pericardiocentesis With Extended Drainage and Colchicine: New Indication for Malignant Pericardial Effusions?

Authors:
Massimo Imazio

J Am Coll Cardiol 2020 09;76(13):1562-1563

University Cardiology, AOU Città della Salute e della Scienza di Torino, Torino, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.jacc.2020.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505569PMC
September 2020