En mann i 60-årene med dyspné og systolisk bilyd etter hjerteinfarkt.

Background: Ventricular septal rupture (VSR) following acute myocardial infarction is rare in the modern revascularisation era. Nevertheless, clinical awareness is paramount, as presentation may vary. Case presentation: A middle-aged male with no history of cardiovascular disease developed progressive heart failure symptoms while travelling abroad. Initial workup revealed a prominent systolic murmur, but findings were inconsistent with acute coronary syndrome. Transthoracic echocardiogram showed a small hypokinetic area in the basal septum, preserved left ventricular function and no significant valvulopathy. Despite the absence of chest pain, an invasive angiography revealed occlusion of a septal branch emerging from the left anterior descending artery, otherwise patent coronary arteries. Despite administration of diuretics, the patient remained symptomatic and presented two months later to his primary care provider with a persisting systolic murmur. He was subsequently referred to the outpatient cardiology clinic where echocardiography revealed a large VSR involving the basal anteroseptum of the left ventricle with a significant left-to-right shunt. After accurate radiological and haemodynamic assessment of the defect, he successfully underwent elective surgical repair. Interpretation: Although traditionally associated with large transmural myocardial infarctions, VSR may arise also from minor, subclinical events. A new-onset murmur is a valuable hint for the alert clinician.

Anti-PAD4 autoantibodies in rheumatoid arthritis: levels in serum over time and impact on PAD4 activity as measured with a small synthetic substrate.

Isoform 4 of the human peptidylarginine deiminase (hPAD4) enzyme may be responsible for the citrullination of antigens in rheumatoid arthritis (RA) and has been shown to be itself the target of disease-specific autoantibodies. Here, we have tested whether the level of serum anti-hPAD4 antibodies in RA patients is stable over a period of 10 years and whether the antibodies influence hPAD4-mediated deimination of the small substrate N-α-benzoyl-L-arginine ethyl ester. RA sera (n = 128) obtained at baseline and after 10 years were assessed for anti-hPAD4 antibodies by a specific immunoassay. For 118 RA patients, serum anti-hPAD4 IgG levels were stable over 10 years. Seven patients who were negative for anti-PAD4 IgG at baseline had become positive after 10 years. Further, total IgG from selected RA patients and controls were purified, and a fraction was depleted for anti-hPAD4 antibodies. Kinetic deimination assays were performed with total IgG and depleted fractions. The k ( cat ) and K ( m ) values of hPAD4-mediated deimination of N-α-benzoyl-L-arginine ethyl ester were not affected by the depletion of the anti-hPAD4 antibodies from the total IgG pool. In conclusion, RA patients remain positive for anti-hPAD4 antibodies over time and some patients who are initially anti-hPAD4 negative become positive later in the disease course. The anti-hPAD4 antibodies did not affect the enzymatic activity of hPAD4 when the small substrate N-α-benzoyl-L-arginine ethyl ester was used. However, this finding may not exclude an effect of these autoantibodies on citrullination of protein substrates in RA.