Enrico Cecchi

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.

Clinical Characteristics and Outcome of Infective Endocarditis Involving Implantable Cardiac Devices

CONTEXT Infection of implantable cardiac devices is an emerging disease with significant morbidity, mortality, and health care costs. OBJECTIVES To describe the clinical characteristics and outcome of cardiac device infective endocarditis (CDIE) with attention to its health care association and to evaluate the association between device removal during index hospitalization and outcome. DESIGN, SETTING, AND PATIENTS Prospective cohort study using data from the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), conducted June 2000 through August 2006 in 61 centers in 28 countries. Patients were hospitalized adults with definite endocarditis as defined by modified Duke endocarditis criteria. MAIN OUTCOME MEASURES In-hospital and 1-year mortality. RESULTS CDIE was diagnosed in 177 (6.4% [95% CI, 5.5%-7.4%]) of a total cohort of 2760 patients with definite infective endocarditis. The clinical profile of CDIE included advanced patient age (median, 71.2 years [interquartile range, 59.8-77.6]); causation by staphylococci (62 [35.0% {95% CI, 28.0%-42.5%}] Staphylococcus aureus and 56 [31.6% {95% CI, 24.9%-39.0%}] coagulase-negative staphylococci); and a high prevalence of health care-associated infection (81 [45.8% {95% CI, 38.3%-53.4%}]). There was coexisting valve involvement in 66 (37.3% [95% CI, 30.2%-44.9%]) patients, predominantly tricuspid valve infection (43/177 [24.3%]), with associated higher mortality. In-hospital and 1-year mortality rates were 14.7% (26/177 [95% CI, 9.8%-20.8%]) and 23.2% (41/177 [95% CI, 17.2%-30.1%]), respectively. Proportional hazards regression analysis showed a survival benefit at 1 year for device removal during the initial hospitalization (28/141 patients [19.9%] who underwent device removal during the index hospitalization had died at 1 year, vs 13/34 [38.2%] who did not undergo device removal; hazard ratio, 0.42 [95% CI, 0.22-0.82]). CONCLUSIONS Among patients with CDIE, the rate of concomitant valve infection is high, as is mortality, particularly if there is valve involvement. Early device removal is associated with improved survival at 1 year.

Corticosteroids for Recurrent Pericarditis High Versus Low Doses: A Nonrandomized Observation

Background— Corticosteroid use is widespread in recurrent pericarditis, even if rarely indicated, and high doses (eg, prednisone 1.0 to 1.5 mg · kg−1 · d−1) are generally recommended, although only weak evidence supports their use with possible severe side effects. The aim of this work was to compare side effects, recurrences and other complications, and hospitalizations of a low- versus high-dose regimen of prednisone for recurrent pericarditis. Methods and Results— A retrospective review of all cases of recurrent pericarditis treated with corticosteroids according to different regimens from January 1996 to June 2004 was performed in 2 Italian referral centers. One hundred patients with recurrent pericarditis (mean age, 50.1±15.8 years; 57 females) were included in the study; 49 patients (mean age, 47.5±16.0; 25 females) were treated with low doses of prednisone (0.2 to 0.5 mg · kg−1 · d−1), and 51 patients (mean age, 52.6±15.3; 32 females) were treated with prednisone 1.0 mg · kg−1 · d−1. Baseline demographic and clinical characteristics were well balanced across the groups. Each initial dose was maintained for 4 weeks and then slowly tapered. After adjustment for potential confounders (age, female gender, nonidiopathic origin), only high doses of prednisone were associated with severe side effects, recurrences, and hospitalizations (hazard ratio, 3.61; 95% confidence interval, 1.96 to 6.63; P<0.001). Conclusions— Use of higher doses of prednisone (1.0 mg · kg−1 · d−1) for recurrent pericarditis is associated with more side effects, recurrences, and hospitalizations. Lower doses of prednisone should be considered when corticosteroids are needed to treat pericarditis.

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.

In-Hospital and 1-Year Mortality in Patients Undergoing Early Surgery for Prosthetic Valve Endocarditis

IMPORTANCE There are limited prospective, controlled data evaluating survival in patients receiving early surgery vs medical therapy for prosthetic valve endocarditis (PVE). OBJECTIVE To determine the in-hospital and 1-year mortality in patients with PVE who undergo valve replacement during index hospitalization compared with patients who receive medical therapy alone, after controlling for survival and treatment selection bias. DESIGN, SETTING, AND PARTICIPANTS Participants were enrolled between June 2000 and December 2006 in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), a prospective, multinational, observational cohort of patients with infective endocarditis. Patients hospitalized with definite right- or left-sided PVE were included in the analysis. We evaluated the effect of treatment assignment on mortality, after adjusting for biases using a Cox proportional hazards model that included inverse probability of treatment weighting and surgery as a time-dependent covariate. The cohort was stratified by probability (propensity) for surgery, and outcomes were compared between the treatment groups within each stratum. INTERVENTIONS Valve replacement during index hospitalization (early surgery) vs medical therapy. MAIN OUTCOMES AND MEASURES In-hospital and 1-year mortality. RESULTS Of the 1025 patients with PVE, 490 patients (47.8%) underwent early surgery and 535 individuals (52.2%) received medical therapy alone. Compared with medical therapy, early surgery was associated with lower in-hospital mortality in the unadjusted analysis and after controlling for treatment selection bias (in-hospital mortality: hazard ratio [HR], 0.44 [95% CI, 0.38-0.52] and lower 1-year mortality: HR, 0.57 [95% CI, 0.49-0.67]). The lower mortality associated with surgery did not persist after adjustment for survivor bias (in-hospital mortality: HR, 0.90 [95% CI, 0.76-1.07] and 1-year mortality: HR, 1.04 [95% CI, 0.89-1.23]). Subgroup analysis indicated a lower in-hospital mortality with early surgery in the highest surgical propensity quintile (21.2% vs 37.5%; P = .03). At 1-year follow-up, the reduced mortality with surgery was observed in the fourth (24.8% vs 42.9%; P = .007) and fifth (27.9% vs 50.0%; P = .007) quintiles of surgical propensity. CONCLUSIONS AND RELEVANCE Prosthetic valve endocarditis remains associated with a high 1-year mortality rate. After adjustment for differences in clinical characteristics and survival bias, early valve replacement was not associated with lower mortality compared with medical therapy in the overall cohort. Further studies are needed to define the effect and timing of surgery in patients with PVE who have indications for surgery.

Aetiological diagnosis in acute and recurrent pericarditis: when and how.

The cause of acute and recurrent pericarditis is often a major concern for the clinicians in clinical practice. Several possible causes of pericarditis can be listed, as the pericardium may be involved in a large number of systemic disorders or may be diseased, as an isolated process. The reported diagnostic yield of extensive laboratory evaluation and pericardiocentesis is low in the absence of cardiac tamponade or suspected neoplastic, tuberculous, and purulent pericarditis. Patients with pericarditis can be safely managed on an outpatient basis without a thorough diagnostic evaluation unless a specific cause is suspected or the patient has high-risk features, or both. A targeted aetiological search should be directed to the most common cause on the basis of the clinical background, epidemiological issues or specific presentations. In developed countries the clinicians should rule out neoplastic, tuberculous, and purulent pericarditis, as well as pericarditis related to a systemic disease.

Infective endocarditis in intravenous drug users from Italy: the increasing importance in HIV-infected patients.

Background:Intravenous drug users (IDUs) are at increased risk of infective endocarditis (IE).Patients and Methods:Episodes of IE in IDUs were retrospectively analyzed in this multicenter study. Cases were collected between 1986 and 1999. Only definite diagnosis according to the Duke criteria were analyzed.Results:Two hundred and sixty-three cases, including 100 cases in HIV-positive patients, were observed in IDUs. Any right-sided involvement was detected in 167 out of 263 cases (63.5%) and any left-sided involvement in 115 out of 263 cases (43.7%). The tricuspid valve (TV) alone was affected in 135 cases (51.3%), the mitral valve alone in 32 patients (12.1%), the aortic valve alone in 41 cases (15.6%) and the pulmonic valve alone in 3 cases. Staphylococcus aureus was isolated in 156 cases (59.3%) and Streptococcus spp. in 33 cases (12.5%). No major differences were observed between HIV-negative and HIV-positive patients. Any TV valve involvement was significantly associated with female rather than male gender (p = 0.02). There was a significant association between S. aureus etiology and TV involvement (p < 0.0001). The mortality rate was 16%. On multivariate analysis, only left-side IE (p = 0.0006; OR 5.2; 95% CI 2.0–13.5) and age greater than 35 years (p = 0.0068; OR 3.6; 95% CI 1.4–9.0) were independently associated with mortality.Conclusions:Infective endocarditis in IDUs is significantly associated with right-side localization (63.5% for any rightsided heart involvement vs 43.7% for any left-sided heart involvement; OR 2.24; 95% CI 1.55–3.23; p < 0.001). S. aureus is the microorganism most frequently isolated and is significantly associated with TV involvement. Any left-side involvement and age greater than 35 years are independently associated with mortality. HIV infection does not appear to have a significant effect on mortality.

Revisiting the effect of referral bias on the clinical spectrum of infective endocarditis in adults

Referral bias occurs because of the clustering of patients at tertiary care centers. This may result in the distortion of observed clinical manifestations of rare diseases. This analysis evaluates the effect of referral bias on the epidemiology of infective endocarditis (IE) in the International Collaboration on Endocarditis—Prospective Cohort Study (ICE-PCS). This is a prospective multicenter cohort study comparing transferred and non-transferred patients with IE. Factors independently associated with transfer status were evaluated using multivariable logistic regression. A total of 2,760 patients were included in the analysis, of which 1,164 (42.2%) were transferred from other medical centers. Transferred patients more often underwent surgery for IE (odds ratio [OR] = 2.5; 95% confidence interval [CI] 1.9–3.2). They were also more likely to have complications such as stroke (OR = 1.5; 95% CI 1.3–1.9), heart failure (OR = 1.4; 95% CI 1.1–1.6), and new valvular regurgitation (OR = 1.3; 95% CI 1.1–1.6). The in-hospital mortality rates were similar in both groups. Patients with IE who require surgery and suffer complications are referred to tertiary hospitals more frequently than patients with an uncomplicated course. Hospital transfer has no obvious effect on the in-hospital mortality. Referral bias should be taken into consideration when describing the clinical spectrum of IE.

Investigation on Colchicine for Acute Pericarditis: a multicenter randomized placebo-controlled trial evaluating the clinical benefits of colchicine as adjunct to conventional therapy in the treatment and prevention of pericarditis; study design amd rationale.

Background Colchicine is safe and effective in the treatment and prevention of recurrent pericarditis after failure of conventional treatment. The recent guidelines of the European Society of Cardiology suggest that colchicine might be useful even in the treatment of the first episode. However, the use of the drug is not based on any strong evidence obtained from clinical trials, and no randomized placebo-controlled trial is available to guide the management of acute pericarditis. Study design The Investigation on Colchicine for Acute Pericarditis (ICAP) trial will enrol 240 patients in a prospective, randomized, double-blind, multicenter investigation of colchicine compared to placebo in patients with acute pericarditis. The primary efficacy end point is the recurrence rate at 18 months. The secondary end points are symptom persistence at 72 h, remission rate at 1 week, number of recurrences, time to first recurrence, disease-related hospitalization, cardiac tamponade, and constrictive pericarditis. Implications The ICAP trial will be the first randomized placebo-controlled trial in this area. This trial will provide important evidence regarding the possible benefit of the early use of colchicine in the treatment of acute pericarditis and the primary prevention of recurrences, the most troublesome and commonest complication of pericarditis.

CORP (COlchicine for Recurrent Pericarditis) and CORP-2 trials--two randomized placebo-controlled trials evaluating the clinical benefits of colchicine as adjunct to conventional therapy in the treatment and prevention of recurrent pericarditis: study design and rationale.

Background Colchicine appears to be safe and effective in the treatment and prevention of recurrent pericarditis after failure of conventional therapies in case reports and non-randomized observational studies without control groups. On this basis, colchicine has been proposed as a therapeutic choice in the 2004 guidelines of the European Society of Cardiology. However, the exact number of responders is unknown, and no randomized placebo-controlled trial is available to guide the management of recurrent pericarditis. Moreover, some authors recommend the use of the drug at the first recurrence, whereas others propose to consider the drug only after failure of conventional therapies for the second or subsequent recurrence. Study Design The CORP trial will enrol 120 patients in a prospective, randomized, double-blind, multicentre investigation of colchicine compared with placebo in patients with a first episode of recurrent pericarditis. In the CORP-2 trial, 240 patients will be enrolled in a prospective, randomized, double-blind, multicentre investigation of colchicine compared with placebo in patients with two or more recurrences. In both trials, the primary efficacy end-point is the recurrence rate at 18 months, the secondary end-points are symptom persistence at 72 h, remission rate at 1 week, number of recurrences, time to recurrence, disease-related hospitalization, cardiac tamponade and constrictive pericarditis. Implications The CORP and CORP-2 trials will be the first randomized placebo-controlled trials in this area. These trials will provide important evidence regarding the possible benefit of the early use of colchicine for the treatment and prevention of recurrent pericarditis.