Marc D. Cohen

2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative

Objective The 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. Methods A joint working group from the ACR and the European League Against Rheumatism developed, in three phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease—this being the appropriate current paradigm underlying the disease construct ‘RA’. Results In the new criteria set, classification as ‘definite RA’ is based on the confirmed presence of synovitis in at least one joint, absence of an alternative diagnosis better explaining the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in four domains: number and site of involved joints (range 0–5), serological abnormality (range 0–3), elevated acute-phase response (range 0–1) and symptom duration (two levels; range 0–1). Conclusion This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimise the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct ‘RA’.

Isolated atrial septal defect with pulmonary vascular obstructive disease--long-term follow-up and prediction of outcome after surgical correction.

UNLABELLED We examined the cases of 702 patients found to have isolated atrial septal defect of the secundum or sinus venosus type at catheterization from 1953 to 1978. Forty patients (6%), 34 women and six men, had pulmonary vascular obstructive disease, with a total pulmonary resistance greater than 7 U/m2; of these patients 26 (mean age 47 years) underwent surgical closure and 14 (mean age 44 years) received medical treatment. All patients were followed for at least 4 years, with a median follow-up of 12 years. At the most recent follow-up, 17 of the 40 patients were dead. Of the 22 surgically treated patients with total pulmonary resistance less than 15 U/m2, 19 were alive with significant regression of symptoms. All four surgically treated patients with total pulmonary resistance greater than or equal to 15 U/m2 were dead. Of the five medically treated patients with total pulmonary resistance less than 15 U/m2, four had died, and one was alive with significant progression of symptoms. Of the nine medically treated patients with total pulmonary resistance greater than or equal to 15 U/m2, six had died and the three survivors had progression of symptoms. In the surgically treated group, the following variables correlated with survival: total pulmonary resistance (p less than .00001), pulmonary arteriolar resistance (p less than .00001), pulmonary-to-systemic resistance ratio (p = .004), systemic arterial oxygen saturation (p = .005), and pulmonary arterial oxygen saturation (p = .007). IN CONCLUSION (1) Atrial septal defect with high total pulmonary resistance is uncommon and predominates in adult female patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Sustained ventricular tachycardia associated with sarcoidosis: Assessment of the underlying cardiac anatomy and the prospective utility of programmed ventricular stimulation, drug therapy and an implantable antitachycardia device

The presentation, cardiac anatomy and utility of programmed ventricular stimulation in seven patients with sustained ventricular tachycardia associated with sarcoidosis are described. The mean patient age was 38 +/- 8 years. Pulmonary involvement was apparent in three patients and no systemic manifestations of sarcoidosis were present in one patient. All patients had electrocardiographic abnormalities at rest and six had a left ventricular ejection fraction less than 45%. All seven patients had left ventricular wall motion abnormalities and five had mitral valve dysfunction. Sustained ventricular tachycardia was easily induced in all patients. Spontaneous sustained ventricular tachycardia was not prevented with corticosteroid administration. Despite antiarrhythmic drug therapy, two patients had sudden cardiac death and an additional four had recurrence of ventricular tachycardia. Four patients had an automatic cardioverter-defibrillator implanted and received drug therapy; all four received appropriate shocks. This report represents the largest descriptive series of consecutive patients with sustained ventricular tachycardia associated with sarcoidosis. Antiarrhythmic drug therapy of ventricular tachycardia in patients with sarcoidosis, even when guided with programmed ventricular stimulation, is associated with a high rate of arrhythmia recurrence or sudden death, or both. Thus, implantation of an automatic antitachycardia device (cardioverter-defibrillator) should be considered as primary therapy in such patients. Furthermore, sarcoidosis should be excluded, with Kveim skin testing if necessary, in any patient with sustained ventricular tachycardia of unknown origin.

Rheumatoid Arthritis–Interstitial Lung Disease–associated Mortality

RATIONALE Mortality rates from rheumatoid arthritis-associated interstitial lung disease (RA-ILD) are largely unknown. OBJECTIVES We sought to determine mortality rates from rheumatoid arthritis-associated interstitial lung disease in the United States from 1988 through 2004. METHODS Using data from the National Center for Health Statistics, we calculated age-adjusted mortality rates from the deaths of persons with rheumatoid arthritis-associated interstitial lung disease, determined the prevalence of interstitial lung disease in all decedents with rheumatoid arthritis, and compared the age and underlying cause of death in these two cohorts of decedents. MEASUREMENTS AND MAIN RESULTS From 1988 to 2004, there were 39,138,394 deaths in U.S. residents and 162,032 rheumatoid arthritis-associated deaths. Of these deaths, 10,725 (6.6%) met criteria for rheumatoid arthritis-associated interstitial lung. Mortality rates from rheumatoid arthritis fell over the course of this study in both women and men. However, mortality rates from rheumatoid arthritis-associated interstitial lung disease increased 28.3% in women (to 3.1 per million persons in 2004) and declined 12.5% in men (to 1.5 per million persons in 2004). Because the rate of decline in rheumatoid arthritis outpaced rheumatoid arthritis-associated interstitial lung disease in men, the prevalence of rheumatoid arthritis-associated interstitial lung disease increased in both sexes over time. CONCLUSIONS Clinically significant RA-ILD occurs in nearly 10% of the RA population, and is associated with shortened survival and more severe underlying disease. Whereas overall mortality rates for RA have fallen, those associated with RA-ILD have increased significantly in older age groups.

The Churg Strauss Syndrome (allergic granulomatous angiitis): review and update

OBJECTIVES Review the clinical and physiopathologic aspects of the Churg-Strauss syndrome (CSS), including recent data regarding treatment and possible etiologic and triggering factors. METHODS A search of the Medline database was conducted between 1966 and 2002, regarding CSS and related vasculitic conditions. Original articles were reviewed as well as major vasculitis textbooks, which were also examined for original references. RESULTS CSS has been increasingly recognized during the past few decades, but remains an uncommon disease of unknown cause. The disorder had been traditionally classified as a variant of polyarteritis nodosa until its updated description by Churg and Strauss in 1951. Although it shares various clinical laboratory and pathologic characteristics with polyarteritis nodosa and Wegener granulomatosis, a distinct combination of features makes it a separate entity. The presence of asthma, usually of adult onset, along with other allergic symptoms, peripheral and tissue eosinophilia, and systemic vasculitis should prompt the clinician to consider the diagnosis, seek potential confirmation with a tissue biopsy, and begin therapy to minimize complications and prevent permanent organ damage. The treatment of CSS has been mainly extrapolated from other vasculitides, and the literature addressing drug therapy for this specific syndrome is limited. CONCLUSIONS CSS is a distinct entity that should be recognized and distinguished from other forms of vasculitis to provide the appropriate early treatment, which could prevent permanent organ damage.

Platelet inhibitor agents in cardiovascular disease: An update

Platelets interact with the coagulation and fibrinolytic systems in the maintenance of hemostasis. However, these physiologic mechanisms may become pathologic, requiring prevention and treatment. In this review, the following clinical developments are analyzed: 1) the role of platelets in thrombogenesis; 2) the pharmacology of platelet inhibitory agents; and, most important, 3) the results of recent randomized trials of platelet inhibitor agents in different cardiovascular disorders. Aspirin reduces mortality and infarction rates in unstable angina and significantly decreases vascular mortality in acute myocardial infarction. Platelet inhibitors decrease mortality and recurrent cardiovascular events in the chronic phase after myocardial infarction. They also decrease vein graft occlusion rates after coronary bypass surgery. Although platelet inhibitors are beneficial in preventing acute vessel occlusion during coronary angioplasty, they are ineffective in preventing chronic restenosis. Antiplatelet agents, combined with warfarin, reduce thromboembolic events in patients with a mechanical prosthesis. Platelet inhibitors are also effective in secondary prevention of vascular events in patients with cerebrovascular disease. Finally, the use of aspirin for primary prevention of cardiovascular disease is still evolving, particularly in individuals at high risk. In conclusion, platelet inhibitors are effective in patients with a variety of cardiovascular disorders. The best studied, most inexpensive and least toxic agent is aspirin at a daily dose of 160 to 325 mg. Studies using new platelet inhibitor agents with different mechanisms of action are currently underway.

Determinants of collateral filling observed during sudden controlled coronary artery occlusion in human subjects

Higher grades of collateral circulation limit the extent of myocardial ischemia observed during balloon inflation in patients with single vessel coronary disease undergoing coronary angioplasty. However, the grade of collateral filling during sudden coronary occlusion varies from patient to patient. To assess which characteristics may predict a high grade of collateral filling, baseline clinical and angiographic variables were correlated with the grade of filling during coronary occlusion in 67 patients (whose angina ranged from 1 week to 36 months in duration) undergoing left anterior descending or right coronary artery angioplasty. A second contralateral arterial catheter was used to assess the collateral filling that reached the vessel dilated before and during transient total occlusion by the angioplasty balloon. Thirty-six patients had a proximal stenotic lesion ranging in severity from 65 to 99%. On a 0 to 3 scale, mean collateral filling grade before inflation was 0.4 versus 1.8 during inflation (p = 0.001). All 19 patients with 95 to 99% stenosis had at least grade 2 collateral filling during inflation. In contrast, 18 of 21 patients with less than or equal to 80% stenosis had only grade 0 or 1 collateral filling during inflation. There were significant positive correlations between collateral grade during inflation and 1) baseline lesion severity (r = 0.76), 2) baseline collateral filling grade (r = 0.50), and 3) vessel dilated. There was no relation between collateral filling during inflation and age, gender, risk factors, duration of angina or proximal versus distal location of the lesion. Lesion severity was the only independent variable associated with collateral filling grade.(ABSTRACT TRUNCATED AT 250 WORDS)

Hematologic malignancies and the use of methotrexate in rheumatoid arthritis: A retrospective study

PURPOSE To evaluate the relationship between use of methotrexate in rheumatoid arthritis patients and development of hematologic malignancies. PATIENTS AND METHODS We retrospectively analyzed all patients registered at the Mayo Clinic from 1976 through 1992 with rheumatoid arthritis (n = 16,263) cross-indexed with patients registered during the same period with a hematologic malignancy (n = 21,270). Adult patients were selected who had rheumatoid arthritis, were treated with a disease-modifying antirheumatic drug, and subsequently developed a hematologic malignancy. RESULTS Thirty-nine patients met the selection criteria. Twelve of them had been given methotrexate. The characteristics of those who received methotrexate, including the type of hematologic malignancy, did not differ from those of patients who received other disease-modifying antirheumatic drugs. CONCLUSIONS Hematologic malignancies are uncommon in patients with rheumatoid arthritis treated with disease-modifying antirheumatic drugs, including methotrexate. There does not appear to be a relationship between the peak or cumulative dose or the duration of methotrexate therapy and the subsequent development of hematologic malignancy. The histologic types of hematologic malignancy seen in the methotrexate-treated patients did not differ from those of patients treated with other disease-modifying antirheumatic drugs.

Usefulness of antithrombotic therapy in resting angina pectoris or non-Q-wave myocardial infarction in preventing death and myocardial infarction (a pilot study from the antithrombotic therapy in acute coronary syndromes study group)

In a prospective pilot trial of antithrombotic therapy in the acute coronary syndromes (ATACS) of resting and unstable angina pectoris or non-Q-wave myocardial infarction, 3 different antithrombotic regimens in the prevention of recurrent ischemic events were compared for efficacy. Ninety-three patients were randomized to receive aspirin (325 mg/day), or full-dose heparin followed by warfarin, or the combination of aspirin (80 mg/day) plus heparin and then warfarin. Trial antithrombotic therapy was added to standardized antianginal medication and continued for 3 months or until an end point was reached. Analysis, by intention-to-treat, of the 3-month end points, revealed the following: recurrent ischemia occurred in 7 patients (22%) after aspirin, in 6 patients (25%) after heparin and warfarin, and in 16 patients (43%) after aspirin combined with heparin and then warfarin; coronary revascularization occurred in 12 patients (38%) after aspirin, in 12 patients (50%) after heparin and warfarin, and in 22 patients (60%) after aspirin combined with heparin and then warfarin; myocardial infarction occurred in 1 patient (3%) after aspirin, in 3 patients (13%) after heparin and warfarin, and in no patient after aspirin combined with heparin and then warfarin; no deaths occurred after aspirin or after aspirin combined with heparin and then warfarin, but 1 patient (4%) died after warfarin alone; major bleeding occurred in 3 patients (9%) after aspirin, in 2 patients (8%) after heparin and warfarin, and in 3 patients (8%) after aspirin combined with heparin and then warfarin. Recurrent myocardial ischemia occurred at 3 +/- 3 days after randomization.(ABSTRACT TRUNCATED AT 250 WORDS)

Reversal of chronic ischemic myocardial dysfunction after transluminal coronary angioplasty

From a cohort of patients referred for elective transluminal coronary angioplasty, a subset of patients was evaluated to determine whether revascularization using coronary angioplasty could salvage chronically ischemic myocardium. Reversible chronic ischemic left ventricular dysfunction was identified by a severe wall motion abnormality at rest and at least one of the following: 1) persistent angina pectoris; 2) postextrasystolic ventricular contraction potentiation of motion in the asynergic zone on baseline ventriculogram; and 3) thallium-201 uptake in the asynergic zone. Twelve patients were identified as having reversible chronic ischemia and underwent coronary angioplasty. Their mean age was 63 +/- 11 years and duration of symptoms 8.3 +/- 9.7 weeks. Immediate pre- and postangioplasty left ventriculograms were obtained. Regional wall motion was analyzed using a radial axis model, and global ejection fraction was calculated. After angioplasty, tension development (heart rate-systolic pressure product) increased in the absence of an increase in left ventricular end-diastolic pressure. Global ejection fraction increased from 46 +/- 20 to 62 +/- 19% (p less than 0.005). The percent of left ventricular diastolic perimeter showing asynergy decreased from 29 +/- 11 to 10 +/- 13% (p less than 0.005). During follow-up ranging from 6 to 51 months, sudden death occurred in one patient who had had no improvement in wall motion after angioplasty, repeat angioplasty was performed in three patients and eight patients remained asymptomatic. Application of easily obtainable clinical data identifies a subset of patients with chronically ischemic myocardium. Coronary angioplasty in such patients is useful in salvaging hibernating myocardium.