Daniela Demarie

Colchicine in Addition to Conventional Therapy for Acute Pericarditis Results of the COlchicine for acute PEricarditis (COPE) Trial

Background—Colchicine is effective and safe for the treatment and prevention of recurrent pericarditis and might ultimately serve as the initial mode of treatment, especially in idiopathic cases. The aim of this work was to verify the safety and efficacy of colchicine as an adjunct to conventional therapy for the treatment of the first episode of acute pericarditis. Methods and Results—A prospective, randomized, open-label design was used. A total of 120 patients (mean age 56.9±18.8 years, 54 males) with a first episode of acute pericarditis (idiopathic, viral, postpericardiotomy syndromes, and connective tissue diseases) were randomly assigned to conventional treatment with aspirin (group I) or conventional treatment plus colchicine 1.0 to 2.0 mg for the first day and then 0.5 to 1.0 mg/d for 3 months (group II). Corticosteroid therapy was restricted to patients with aspirin contraindications or intolerance. The primary end point was recurrence rate. During the 2873 patient-month follow-up, colchicine significantly reduced the recurrence rate (recurrence rates at 18 months were, respectively, 10.7% versus 32.3%; P=0.004; number needed to treat=5) and symptom persistence at 72 hours (respectively, 11.7% versus 36.7%; P=0.003). After multivariate analysis, corticosteroid use (OR 4.30, 95% CI 1.21 to 15.25; P=0.024) was an independent risk factor for recurrences. Colchicine was discontinued in 5 cases (8.3%) because of diarrhea. No serious adverse effects were observed. Conclusions—Colchicine plus conventional therapy led to a clinically important and statistically significant benefit over conventional treatment, decreasing the recurrence rate in patients with a first episode of acute pericarditis. Corticosteroid therapy given in the index attack can favor the occurrence of recurrences.

Indicators of Poor Prognosis of Acute Pericarditis

Background— The clinical search for indicators of poor prognosis of acute pericarditis may be useful for clinical triage of patients at high risk of specific causal conditions or complications. The aim of the present article is to assess the relationship between clinical features at presentation and specific causes or complications. Methods and Results— A total of 453 patients aged 17 to 90 years (mean age 52±18 years, 245 men) with acute pericarditis (post–myocardial infarction pericarditis was excluded) were prospectively evaluated from January 1996 to August 2004. A specific cause was found in 76 of 453 patients (16.8%): autoimmune in 33 patients (7.3%), neoplastic in 23 patients (5.1%), tuberculous in 17 patients (3.8%), and purulent in 3 patients (0.7%). In multivariable analysis, women (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.03 to 2.70; P=0.036) and patients with fever >38°C (HR 3.56, 95% CI 1.82 to 6.95; P<0.001), subacute course (HR 3.97, 95% CI 1.66 to 9.50; P=0.002), large effusion or tamponade (HR 2.15, 95% CI 1.09 to 4.23; P=0.026), and failure of aspirin or of nonsteroidal anti-inflammatory drugs (HR 2.50, 95% CI 1.28 to 4.91; P=0.008) were at increased risk of specific causal conditions. After a mean follow-up of 31 months, complications were detected in 95 patients (21.0%): recurrences in 83 patients (18.3%), tamponade in 14 patients (3.1%), and constriction in 7 patients (1.5%). In multivariable analysis, women (HR 1.65, 95% CI 1.08 to 2.52; P=0.020) and patients with large effusion or tamponade (HR 2.51, 95% CI 1.37 to 4.61; P=0.003) and failure of aspirin or of nonsteroidal anti-inflammatory drugs (HR 5.50, 95% CI 3.56 to 8.51; P<0.001) were at increased risk of complications. Conclusions— Specific clinical features (fever >38°C, subacute course, large effusion or tamponade, and aspirin or NSAID failure) may be useful to identify higher risk of specific causal conditions and complications.

A Randomized Trial of Colchicine for Acute Pericarditis

BACKGROUND Colchicine is effective for the treatment of recurrent pericarditis. However, conclusive data are lacking regarding the use of colchicine during a first attack of acute pericarditis and in the prevention of recurrent symptoms. METHODS In a multicenter, double-blind trial, eligible adults with acute pericarditis were randomly assigned to receive either colchicine (at a dose of 0.5 mg twice daily for 3 months for patients weighing >70 kg or 0.5 mg once daily for patients weighing ≤70 kg) or placebo in addition to conventional antiinflammatory therapy with aspirin or ibuprofen. The primary study outcome was incessant or recurrent pericarditis. RESULTS A total of 240 patients were enrolled, and 120 were randomly assigned to each of the two study groups. The primary outcome occurred in 20 patients (16.7%) in the colchicine group and 45 patients (37.5%) in the placebo group (relative risk reduction in the colchicine group, 0.56; 95% confidence interval, 0.30 to 0.72; number needed to treat, 4; P<0.001). Colchicine reduced the rate of symptom persistence at 72 hours (19.2% vs. 40.0%, P=0.001), the number of recurrences per patient (0.21 vs. 0.52, P=0.001), and the hospitalization rate (5.0% vs. 14.2%, P=0.02). Colchicine also improved the remission rate at 1 week (85.0% vs. 58.3%, P<0.001). Overall adverse effects and rates of study-drug discontinuation were similar in the two study groups. No serious adverse events were observed. CONCLUSIONS In patients with acute pericarditis, colchicine, when added to conventional antiinflammatory therapy, significantly reduced the rate of incessant or recurrent pericarditis. (Funded by former Azienda Sanitaria Locale 3 of Turin [now Azienda Sanitaria Locale 2] and Acarpia; ICAP ClinicalTrials.gov number, NCT00128453.).

Myopericarditis versus viral or idiopathic acute pericarditis

Objective: To investigate the relative incidence, clinical presentation and prognosis of myopericarditis among patients with idiopathic or viral acute pericarditis. Design: Prospective observational clinical cohort study. Setting: Two general hospitals from an urban area of 220 000 inhabitants. Patients: 274 consecutive cases of idiopathic or viral acute pericarditis between January 2001 and June 2005. Main outcome measures: Relative prevalence of myopericarditis. Clinical features at presentation including echocardiographic data (ejection fraction (EF), wall motion score index (WMSI)) and follow-up data at 12 months including complications, results of echocardiography, electrocardiography and treadmill testing. Results: Myopericarditis was recorded in 40/274 (14.6%) consecutive patients. At presentation, the following clinical features were independently associated with myopericarditis: arrhythmias (odds ratio (OR) = 17.6, 95% confidence interval (CI) 5.7 to 54.1; p<0.001), male gender (OR = 6.4, 95% CI 2.3 to 18.4; p = 0.01), age <40 years (OR = 6.1, 95% CI 2.2 to 16.9; p = 0.01), ST elevation (OR = 5.4, 95% CI 1.4 to 20.5; p = 0.013) and a recent febrile syndrome (OR = 2.8, 95% CI 1.1 to 7.7; p = 0.044). After 12 months’ follow-up an increase of EF (basal EF 49.6 (5.1)% vs 12-month EF 59.1 (4.6)%; p<0.001) and decrease of WMSI (basal WMSI 1.19 (0.27) vs 12-month WMSI 1.02 (0.09); p<0.001) were recorded in patients with myopericarditis, with a normalisation of echocardiography, electrocardiography and treadmill testing in 98% of cases. Use of heparin or other anticoagulants (OR = 1.1, 95% CI 0.3 to 3.5; p = 0.918) and myopericarditis (OR = 2.3, 95% CI 0.7 to 7.6; p = 0.187) was not associated with an increased risk of cardiac tamponade or recurrences. Conclusions: Myopericarditis is relatively common and shows a benign evolution also in spontaneous cases not related to vaccination.

Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial

BACKGROUND Colchicine is effective for the treatment of acute pericarditis and first recurrences. However, conclusive data are lacking for the efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis. METHODS We did this multicentre, double-blind trial at four general hospitals in northern Italy. Adult patients with multiple recurrences of pericarditis (≥two) were randomly assigned (1:1) to placebo or colchicine (0·5 mg twice daily for 6 months for patients weighing more than 70 kg or 0·5 mg once daily for patients weighing 70 kg or less) in addition to conventional anti-inflammatory treatment with aspirin, ibuprofen, or indometacin. Permuted block randomisation (size four) was done with a central computer-based automated sequence. Patients and all investigators were masked to treatment allocation. The primary outcome was recurrent pericarditis in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00235079. FINDINGS 240 patients were enrolled and 120 were assigned to each group. The proportion of patients who had recurrent pericarditis was 26 (21·6%) of 120 in the colchicine group and 51 (42·5%) of 120 in the placebo group (relative risk 0·49; 95% CI 0·24-0·65; p=0·0009; number needed to treat 5). Adverse effects and discontinuation of study drug occurred in much the same proportions in each group. The most common adverse events were gastrointestinal intolerance (nine patients in the colchicine group vs nine in the placebo group) and hepatotoxicity (three vs one). No serious adverse events were reported. INTERPRETATION Colchicine added to conventional anti-inflammatory treatment significantly reduced the rate of subsequent recurrences of pericarditis in patients with multiple recurrences. Taken together with results from other randomised controlled trials, these findings suggest that colchicine should be probably regarded as a first-line treatment for either acute or recurrent pericarditis in the absence of contraindications or specific indications. FUNDING Azienda Sanitaria 3 of Torino (now ASLTO2).

Pulmonary stenosis with intact ventricular septum: documentation of development of the lesion echocardiographically during fetal life

We describe a case of severe pulmonary stenosis with intact interventricular septum diagnosed during fetal life at 34 weeks gestational age. An echocardiographic examination had been performed on the same fetus at 20 weeks, when no cardiac anomalies were observed. It is concluded that this form of pulmonary stenosis might be a lesion either acquired during fetal life or becoming progressively more severe in the prenatal period.

Rationale and design of the COPPS trial: a randomised, placebo-controlled, multicentre study on the use of colchicine for the primary prevention of postpericardiotomy syndrome.

Rationale Colchicine seems to be well tolerated and effective in the treatment and prevention of pericarditis. A preliminary clinical trial has shown that colchicine may be considered not only for the treatment of postpericardiotomy syndrome (PPS), but also for its primary prevention. Study design The COPPS study is a multicentre, double-blind, randomised trial. On the third postoperative day, 360 patients, 180 in each treatment arm, will be randomised to receive placebo or colchicine (1.0 mg twice daily for the first day followed by a maintenance dose of 0.5 mg twice daily for 1 month in patients ≥70 kg, and halved doses for patients <70 kg or intolerant to the highest dose). The primary efficacy endpoint is the incidence of PPS at 12 months. Secondary endpoints are disease-related hospitalisation, cardiac tamponade, constrictive pericarditis, and relapses at 18 months. Additional analysis will include the time to PPS. Implications The COPPS trial will evaluate the use of colchicine for the primary prevention of PPS. This study will also provide important information on the frequency, clinical presentation, and prognosis of this syndrome in clinical practice.

Cardiovascular-associated disease in an addicted population: an observation study.

Background Illicit drugs such as cocaine, and methadone can induce acquired long QT syndrome. Objective The aim of this study was to evaluate the prevalence of cardiovascular disease and to assess the risk of torsades de pointes in substance abuse patients either with methadone or buprenorphine maintenance therapy, or without any specific therapy for opiate addiction. Methods From November 2008 to December 2009, 190 patients (153 men, mean age 38.2 years, 22–56 years) with a substance use disorder according to DSM IV TR criteria were included in the study. All patients underwent blood tests, serial electrocardiogram (ECG) and, when necessary, additional testing, including echocardiogram, exercise test and Holter monitoring. Age and sex-matched healthy controls were also evaluated and compared with the cases. Results One hundred and twenty-five patients (65.7%) had associated diseases. The prevalence of coronary artery disease and hypertension was, respectively, 2.1 and 5.2% in the addicted population. The percentage of abnormal ECGs was 34.2% in the addicted population and 4.7% in the nonaddicted population (P < 0.001). Twenty-five addicted patients had a QT interval prolongation (10 patients ≥480 ms). There were no sudden deaths or major cardiac events during the observation period. Conclusions Our results indicate that the QT interval prolongation is not a negative prognostic marker in the addicted population, even with associated diseases. ECG should be performed when other drugs potentially prolonging QT interval are associated. Substance abuse patients should be followed by multidisciplinary teams, and blood tests and ECGs should be performed regularly.

Conservative management of fetal bigeminy arrhythmia leading to persistent bradycardia

A case of persistent fetal bradycardia first detected at 32 weeks of gestational age is described. The diagnosis of atrial ectopic beats was made by means of M-mode echocardiography. Since the fetus was normally grown and showed no signs of distress, the vaginal route of delivery was allowed, also because continuous M-mode echocardiographic monitoring was possible during labour.

Acute endocarditis of the patch caused by Staphylococcus capitis in treated tetralogy of Fallot. An unusual location by an unusual bacterium

We present the case of a 46 year-old male, HCV infected, treated with corrective surgery for tetralogy of Fallot (TOF) immediately after percutaneous closure of the Blalock Taussig shunt. Four months later, the patient had infective endocarditis by Staphylococcus capitis localised on the right side of the patch, treated by oxacillin and gentamycin. The particularity of our report is the unusual location of the acute endocarditis and the bacterium involved: the pulmonary valve is much more likely to be involved in endocarditis in TOF patients and the patch endocarditis has rarely been reported. Moreover, Staphylococcus capitis has never been reported as a cause of acute endocarditis in corrected TOF patients. We believe that antibiotic therapy should be instituted as soon as possible even though an aggressive surgical treatment is mandatory to achieve complete recovery, mainly when clinical condition and inflammation markers do not improve.