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.).

Colchicine In Epistenocardiac Pericarditis.

Epistenocardiac pericarditis (EP) is a rare form of pericarditis which occurs in the early period after a myocardial infarction (MI) and is commonly regionalized to the area of infarction. The preferred treatment for EP is high-dose oral aspirin, given the compelling indication for aspirin use in the post-MI setting; however, high-dose aspirin use may be prohibitive in certain clinical situations such as with concomitant use of newer antiplatelet agents like ticagrelor. The treatment option with colchicine remains an alternative; however the efficacy of colchicine in EP is not well established. We herewith describe a case series of 11 patients with EP who were treated with colchicine.

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).

Colchicine for prevention of postpericardiotomy syndrome and postoperative atrial fibrillation: the COPPS-2 randomized clinical trial.

IMPORTANCE: Postpericardiotomy syndrome, postoperative atrial fibrillation (AF), and postoperative effusions may be responsible for increased morbidity and health care costs after cardiac surgery. Postoperative use of colchicine prevented these complications in a single trial. OBJECTIVE: To determine the efficacy and safety of perioperative use of oral colchicine in reducing postpericardiotomy syndrome, postoperative AF, and postoperative pericardial or pleural effusions. DESIGN, SETTING, AND PARTICIPANTS: Investigator-initiated, double-blind, placebo-controlled, randomized clinical trial among 360 consecutive candidates for cardiac surgery enrolled in 11 Italian centers between March 2012 and March 2014. At enrollment, mean age of the trial participants was 67.5 years (SD, 10.6 years), 69% were men, and 36% had planned valvular surgery. Main exclusion criteria were absence of sinus rhythm at enrollment, cardiac transplantation, and contraindications to colchicine. INTERVENTIONS: Patients were randomized to receive placebo (n=180) or colchicine (0.5 mg twice daily in patients ≥70 kg or 0.5 mg once daily in patients <70 kg; n=180) starting between 48 and 72 hours before surgery and continued for 1 month after surgery. MAIN OUTCOMES AND MEASURES: Occurrence of postpericardiotomy syndrome within 3 months; main secondary study end points were postoperative AF and pericardial or pleural effusion. RESULTS: The primary end point of postpericardiotomy syndrome occurred in 35 patients (19.4%) assigned to colchicine and in 53 (29.4%) assigned to placebo (absolute difference, 10.0%; 95% CI, 1.1%-18.7%; number needed to treat = 10). There were no significant differences between the colchicine and placebo groups for the secondary end points of postoperative AF (colchicine, 61 patients [33.9%]; placebo, 75 patients [41.7%]; absolute difference, 7.8%; 95% CI, -2.2% to 17.6%) or postoperative pericardial/pleural effusion (colchicine, 103 patients [57.2%]; placebo, 106 patients [58.9%]; absolute difference, 1.7%; 95% CI, -8.5% to 11.7%), although there was a reduction in postoperative AF in the prespecified on-treatment analysis (placebo, 61/148 patients [41.2%]; colchicine, 38/141 patients [27.0%]; absolute difference, 14.2%; 95% CI, 3.3%-24.7%). Adverse events occurred in 21 patients (11.7%) in the placebo group vs 36 (20.0%) in the colchicine group (absolute difference, 8.3%; 95% CI; 0.76%-15.9%; number needed to harm = 12), but discontinuation rates were similar. No serious adverse events were observed. CONCLUSIONS AND RELEVANCE: Among patients undergoing cardiac surgery, perioperative use of colchicine compared with placebo reduced the incidence of postpericardiotomy syndrome but not of postoperative AF or postoperative pericardial/pleural effusion. The increased risk of gastrointestinal adverse effects reduced the potential benefits of colchicine in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01552187.

The three integrated phases of left atrial macrophysiology and their interactions.

Our understanding of the left atrium is growing, although there are many aspects that are still poorly understood. The left atrium size as an imaging biomarker has been consistently shown to be a powerful predictor of outcomes and of different cardiovascular disorders, such as, but not limited to, atrial fibrillation, congestive heart failure, mitral regurgitation and stroke. Left atrial function has been conventionally divided into three integrated phases: reservoir, conduit and booster-pump. The highly dynamic left atrium and its response to the stretch and secretion of atrial neuropeptides leaves the left atrium far from being a simple transport chamber. The aim of this review is to provide an understanding of the left atrial physiology and its relation to disorders within the heart.

Interatrial block: a virtual pandemic requiring attention.

Interatrial block (IAB) denotes a conduction delay between the two atria (P-wave duration ≥110 ms). Depending on the severity of the block, IAB can be partial or advanced. Even though several studies have reported a high prevalence of IAB, it still remains a diagnosis many neglect without any follow-up. The crisis in IAB is undramatic until predictable complications appear. Nevertheless, the danger in IAB is real because of the major associations with multiple medical conditions, including atrial fibrillation, myocardial ischemia, left atrial enlargement, and systemic emboli. There are different treatment options for IAB to eliminate its consequences, including pacing and medical management with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Pacing has been shown to give promising results and could potentially prevent conditions related to cardiovascular disease such as hypertension or diabetes mellitus. Given the high prevalence of IAB, together with its potentially serious consequences, and yet being largely ignored, we stress attention to this potentially dangerous pandemic and raise consideration for further investigations.

Rationale and design of the COlchicine for Prevention of the Post-pericardiotomy Syndrome and Post-operative Atrial Fibrillation (COPPS-2 trial): a randomized, placebo-controlled, multicenter study on the use of colchicine for the primary prevention of the postpericardiotomy syndrome, postoperative effusions, and postoperative atrial fibrillation.

BACKGROUND: The efficacy and safety of colchicine for the primary prevention of the postpericardiotomy syndrome (PPS), postoperative effusions, and postoperative atrial fibrillation (POAF) remain uncertain. Although preliminary data from a single trial of colchicine given for 1 month postoperatively (COPPS trial) were promising, the results have not been confirmed in a large, multicenter trial. Moreover, in the COPPS trial, colchicine was given 3 days postoperatively. METHODS: The COPPS-2 study is a multicenter, double-blind, placebo-controlled randomized trial. Forty-eight to 72 hours before planned cardiac surgery, 360 patients, 180 in each treatment arm, will be randomized to receive placebo or colchicine without a loading dose (0.5 mg twice a day for 1 month in patients weighing ≥70 kg and 0.5 mg once for patients weighing <70 kg or intolerant to the highest dose). The primary efficacy end point is the incidence of PPS, postoperative effusions, and POAF at 3 months after surgery. Secondary end points are the incidence of cardiac tamponade or need for pericardiocentesis or thoracentesis, PPS recurrence, disease-related admissions, stroke, and overall mortality. CONCLUSIONS: The COPPS-2 trial will evaluate the use of colchicine for the primary prevention of PPS, postoperative effusions, and POAF, potentially providing stronger evidence to support the use of preoperative colchicine without a loading dose to prevent several postoperative complications. ClinicalTrials.gov Identifier: NCT01552187.

Electrocardiographic impacts of lung resection.

INTRODUCTION: Electrocardiographic (ECG) changes accompanying lung resection have not been well investigated previously in a large controlled series of human adults. Thus, our current investigation was undertaken for a better understanding of the ECG changes associated with lung resection. MATERIALS AND METHODS: Medical records of 117 patients who underwent lung resection (segmentectomy, lobectomy, or pneumonectomy) were reviewed. Their clinical course and ECGs were compared during early, intermediate and late postoperative course (<1 month, 1 month to 1 year and >1 year post-op respectively). RESULTS: Patients in the acute postoperative phase had higher heart rate, increased maximum P-duration and P-dispersion, increased incidence of atrial arrhythmias and frequent ST-T changes. P-vector and QRS-vector were significantly affected after the lung resections; the correlation being most consistent between the anatomical displacements and the QRS-vector in the majority of patients. The axial shifts also demonstrated a characteristic temporal relationship after left pneumonectomy (a leftward deviation in the acute, normal or slight rightward deviation in the intermediate and a rightward deviation in the late postoperative course). The precordial R/S transition is often affected due to the mediastinal shifts and the ECGs in patients after left lung resection may simulate acute anteroseptal myocardial infarction due to a delayed R/S transition. CONCLUSION: The understanding and recognition of the expected ECG findings after lung resection are imperative to avoid confusing these changes with other acute cardiopulmonary events which would prevent unnecessary further investigational work-up. These ECG changes are often dynamic and may bear a temporal relationship to the dynamic post-surgical changes in the thoracic anatomy.

Orthostatic hypertension: recognizing an underappreciated clinical condition.

Orthostatic hypertension refers to an increase in the blood pressure upon assuming an upright posture. This clinical condition has been understudied and is often underappreciated in clinical practice probably because of its unfamiliarity to many clinicians including subspecialists. We report a case of severely symptomatic orthostatic hypertension in a Caucasian female, which was likely secondary to an autonomic dysfunction caused by an underlying vascular adrenergic hypersensitivity and possibly also due to uncontrolled diabetes mellitus (causing baroreflex dysfunction associated with excessive sympathetic stimulation). The case work-up also illustrates a schematic diagnostic and management approach to this rarely encountered clinical entity.

Retrograde embolism from the descending thoracic aorta causing stroke: an underappreciated clinical condition.

The mechanism of retrograde aortic blood flow is a complex and underreported clinical phenomenon. Complex plaques of the aortic arch are considered high-risk sources of cerebral emboli.(1) Aortic plaques situated in the descending thoracic aorta are however often overlooked and in fact can be more frequent potential sources of cerebral embolism through the mechanism of retrograde aortic blood flow. We present the case of an elderly Caucasian female who experienced recurrent posterior circulation embolic strokes where the only possible underlying etiology was found to be an atheroma in the descending thoracic aorta, possibly showering retrograde emboli.

Colchicine reduces postoperative atrial fibrillation: results of the Colchicine for the Prevention of the Postpericardiotomy Syndrome (COPPS) atrial fibrillation substudy.

BACKGROUND: Inflammation and pericarditis may be contributing factors for postoperative atrial fibrillation (POAF), and both are potentially affected by antiinflammatory drugs and colchicine, which has been shown to be safe and efficacious for the prevention of pericarditis and the postpericardiotomy syndrome (PPS). The aim of the Colchicine for the Prevention of the Post-Pericardiotomy Syndrome (COPPS) POAF substudy was to test the efficacy and safety of colchicine for the prevention of POAF after cardiac surgery. METHODS AND RESULTS: The COPPS POAF substudy included 336 patients (mean age, 65.7±12.3 years; 69% male) of the COPPS trial, a multicenter, double-blind, randomized trial. Substudy patients were in sinus rhythm before starting the intervention (placebo/colchicine 1.0 mg twice daily starting on postoperative day 3 followed by a maintenance dose of 0.5 mg twice daily for 1 month in patients ≥70 kg, halved doses for patients <70 kg or intolerant to the highest dose). The substudy primary end point was the incidence of POAF on intervention at 1 month. Despite well-balanced baseline characteristics, patients on colchicine had a reduced incidence of POAF (12.0% versus 22.0%, respectively; P=0.021; relative risk reduction, 45%; number needed to treat, 11) with a shorter in-hospital stay (9.4±3.7 versus 10.3±4.3 days; P=0.040) and rehabilitation stay (12.1±6.1 versus 13.9±6.5 days; P=0.009). Side effects were similar in the study groups. CONCLUSION: Colchicine seems safe and efficacious in the reduction of POAF with the potentiality of halving the complication and reducing the hospital stay.

Ideal isoelectric reference segment in pericarditis: a suggested approach to a commonly prevailing clinical misconception.

Individual practice patterns of cardiologists and internists vary in interpreting electrocardiograms by measuring and defining significant ST deviation using different segments as isoelectric references. Even standard electrocardiography textbooks and recent literature studies provide variable opinions for using isoelectric references and measurement of ST-segment deflections. In our current manuscript, we aim to define a standard baseline/isoelectric segment using a short literature review and also to share our opinion for the use of a standard isoelectric reference for patients of pericarditis which is one of the commonest causes of nonischemic ST-segment elevation.

Pericardial involvement in diseases of the heart and other contiguous structures: part I: pericardial involvement in infarct pericarditis and pericardial involvement following myocardial infarction.

Active contiguous abnormalities can frequently involve the pericardium. Prominent among these are cardiac conditions which encroach on the pericardium, particularly transmural myocardial infarction (newly always with Q-waves). Complications of infarctions, notably myocardial pseudoaneurysm, have one wall which is pericardium. Furthermore, dissecting aneurysm of the aorta and the intramural aortic hemorrhage may rupture into the pericardium with tamponade, or, if limited, mimic acute pericarditis. Diseases of the lungs and pleura, including the diaphragmatic pleura, also result in pulmonary embolism which can produce several syndromes. Many mediastinal diseases, notably inflammation and malignancy, especially involving the lymph nodes, induce mediastinal inflammation and fibrosis. Many esophageal disorders can penetrate or produce a fistula usually with pneumopericardium. Rarely, primarily pericardial disorders like purulent pericarditis, malignancies, and rough pericardial calcifications affect the contiguous tissues. We discuss the many syndromes and disorders under each of these topics.

Pericardial involvement in diseases of the heart and other contiguous structures: part II: pericardial involvement in noncardiac contiguous disorders.

Active contiguous abnormalities can frequently involve the pericardium. Prominent among these are cardiac conditions which encroach on the pericardium, particularly transmural myocardial infarction (newly always with Q-waves). Complications of infarctions, notably myocardial pseudoaneurysm, have one wall which is pericardium. Furthermore, dissecting aneurysm of the aorta and the intramural aortic hemorrhage may rupture into the pericardium with tamponade, or, if limited, mimic acute pericarditis. Diseases of the lungs and pleura, including the diaphragmatic pleura, also result in pulmonary embolism which can produce several syndromes. Mediastinal diseases, notably inflammation and malignancy, especially involving the lymph nodes, induce mediastinal inflammation and fibrosis. Many esophageal disorders can penetrate or produce a fistula usually with pneumopericardium. Rarely, primarily pericardial disorders like purulent pericarditis, malignancies, and rough pericardial calcifications affect the contiguous tissues. We discuss the many syndromes and disorders under each of these topics.

Variations of left atrial activation patterns in congestive heart failure.

We report about a case of a patient admitted to the Intensive Cardiac Care Unit for severe congestive heart failure which showed modification of P-wave morphology and duration, correlated with the clinical evolution. In the case here described, we show that ECG analysis, specifically P wave, allow us to assess the hemodynamic evolution of the acute decompensated heart failure patient. Electrocardiographic examination is the first and the most simple and available diagnostic tool in the evaluation of patients with cardiac diseases. Usually, P-wave evaluation is not carefully assessed, in spite of very useful informations we can draw from its interpretation. We report about a patient admitted to our Intensive Cardiac Care Unit (ICCU) for severe congestive heart failure which showed peculiar modification of P-wave morphology and duration, well correlated with the clinical course.

Colchicine for recurrent pericarditis (CORP): a randomized trial.

BACKGROUND: Recurrence is the most common complication of pericarditis, affecting 10% to 50% of patients. OBJECTIVE: To evaluate the efficacy and safety of colchicine for the secondary prevention of recurrent pericarditis. DESIGN: Prospective, randomized, double-blind, placebo-controlled multicenter trial. (ClinicalTrials.gov registration number: NCT00128414) SETTING: 4 general hospitals in urban areas of Italy. PATIENTS: 120 patients with a first recurrence of pericarditis. INTERVENTION: In addition to conventional treatment, patients were randomly assigned to receive either placebo or colchicine, 1.0 to 2.0 mg on the first day followed by a maintenance dose of 0.5 to 1.0 mg/d, for 6 months. MEASUREMENTS: The primary study end point was the recurrence rate at 18 months. Secondary end points were symptom persistence at 72 hours, remission rate at 1 week, number of recurrences, time to first recurrence, disease-related hospitalization, cardiac tamponade, and rate of constrictive pericarditis. RESULTS: At 18 months, the recurrence rate was 24% in the colchicine group and 55% in the placebo group (absolute risk reduction, 0.31 [95% CI, 0.13 to 0.46]; relative risk reduction, 0.56 [CI, 0.27 to 0.73]; number needed to treat, 3 [CI, 2 to 7]). Colchicine reduced the persistence of symptoms at 72 hours (absolute risk reduction, 0.30 [CI, 0.13 to 0.45]; relative risk reduction, 0.56 [CI, 0.27 to 0.74]) and mean number of recurrences, increased the remission rate at 1 week, and prolonged the time to subsequent recurrence. The study groups had similar rates of side effects and drug withdrawal. LIMITATION: Multiple recurrences and neoplastic or bacterial causes were excluded. CONCLUSION: Colchicine is safe and effective for secondary prevention of recurrent pericarditis.

Transient Super-Himalayan P-waves in severe pulmonary emphysema.

Himalayan P-waves are classically associated with congenital heart diseases with right to left shunt where they indicate a dilated right atrium and tend to be persistent. We report a case of transient Himalayan P-waves of 9-mm amplitude associated with a severe emphysema exacerbation. Patient had a normal right atrial size. The giant P-waves were likely the result of severe pulmonary hyperinflation, right atrial hypoxia, and transient mechanical load on the right atrium directly resulting from the bronchospasm. Transient Himalayan P-waves of quite such amplitude have not been reported previously, which makes our case the first such report in literature.

Complete heart block--an underappreciated serious complication of central venous catheter placement.

Central venous catheter (CVC) placement is a common bedside procedure that is frequently performed in critically ill patients. More than 5 million CVCs are inserted annually across the United States alone. Procedure-related complications may vary from minor bleeding to life-threatening complications such as arterial perforation and pneumothorax. Cardiac arrhythmias can often occur during the guidewire placement, and bundle-branch blocks have also been reported. We herewith report a case of complete heart block during CVC placement, which is a rare but serious complication of this procedure. Because the patient had a preexisting left bundle-branch block, complete heart block likely resulted from a probable trauma to the right bundle branch during the guidewire insertion.

Hypothermia masquerading as pericarditis: an unusual electrocardiographic analogy.

Hypothermia is one of the most common environmental emergencies encountered by physicians that can be associated with a variety of electrocardiographic (ECG) abnormalities. The classic and well-known ECG manifestations of hypothermia include the presence of J (Osborne) waves, interval (PR, QRS, QT) prolongation, varied T-wave abnormalities, and atrial and ventricular arrhythmias. There are less well-defined and known ECG signs of hypothermia that, in fact, may simulate findings of acute coronary ischemia. We describe a case of hypothermia with associated ECG findings mimicking pericarditis. Especially interesting was the challenging presentation and several associated important learning points. Herewith, we also discuss some important ECG and clinical factors that may be used in differentiating the genesis of ST elevations.