A man in his seventies with fatigue and renal failure. / En mann i 70-årene med utmattelse og nyresvikt.

A man in his seventies underwent routine heart examinations as part of workup for kidney transplantation. Unexpected findings led to more extensive investigations and revealed two rare systemic diseases as causes of his heart failure.

First Norwegian case of hereditary ATTR amyloidosis with a novel transthyretin variant.

An earlier healthy 64-year-old man with previous surgery for bilateral carpal tunnel syndrome (CTS) in his 50s, presented with dyspnoea on exertion. Cardiac amyloidosis was suspected due to "red flag" signs and symptoms. Further investigations with scintigraphy and genetic testing confirmed the diagnosis of hereditary ATTR variant (ATTRv) amyloidosis. This is the first case report of ATTRv amyloidosis in a patient of Norwegian origin and is caused by the mutation E54A (p.E74A) in the transthyretin (TTR) gene. This mutation is previously not reported in international databases. Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed disease with a poor prognosis. Early recognition remains essential to afford the best treatment efficacy.

Glucose associated NETosis in patients with ST-elevation myocardial infarction: an observational study.

BACKGROUND: Neutrophil extracellular traps (NETs) have recently been identified as mediators in atherothrombosis. Although NETosis in general has been suggested to be glucose dependent, the transferability to patients with acute ST-elevation myocardial infarction (STEMI) is unclear. We assessed whether the NETs markers double-stranded deoxyribonucleid acid (dsDNA) and myeloperoxidase-DNA (MPO-DNA) associated with plasma glucose and the glucometabolic status in the acute phase and 3 months after a STEMI. We also explored whether an acute glucose load resulted in upregulated NETosis by assessment of peptidylarginine deiminase 4 (PAD4) gene expression. METHODS: In total, 224 STEMI patients were prospectively enrolled and underwent blood sampling acutely (median 16.5 h after PCI) and after 3 months. Glucometabolic status was defined based on the results of an oral glucose tolerance test (OGTT) as normal glucose regulation (NGR), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or type 2 diabetes (T2DM). dsDNA and MPO-DNA were measured in serum, while PAD4 mRNA was measured in circulating leukocytes by RT-PCR. RESULTS: dsDNA levels were significantly correlated to plasma glucose both acutely and after 3 months (r = 0.12 and r = 0.17, both p < 0.02), whereas MPO-DNA was not. No associations with the glucometabolic status were encountered for dsDNA and MPO-DNA acutely, but after 3 months dsDNA levels were elevated in patients with IFG and T2DM vs. NGR (428 vs. 371 ng/ml and 408 vs. 371 ng/ml, both p < 0.045). During the acute glucose load after 3 months, dsDNA and MPO-DNA remained unchanged while PAD4 mRNA increased significantly (RQ 0.836 vs. 0.920, p = 0.02). CONCLUSIONS: In this cohort of STEMI patients, levels of dsDNA associated with plasma glucose both in the acute and stable condition. The glucometabolic status was not substantially related to the selected NETs markers, however, an acute glucose load by OGTT performed after 3 months resulted in increased PAD4 expression, suggestive of enhanced NETosis in the aftermath of STEMI. TRIAL REGISTRATION: www.clinicaltrials.gov, NCT00926133 . Registered June 23, 2009.

IgM antibodies against phosphorylcholine measured early after acute ST-elevation myocardial infarction in relation to atherosclerotic disease burden and long-term clinical outcome.

PURPOSE: Studies have reported an association between low levels of natural immunoglobulin M antibodies against phosphorylcholine(IgM anti-PC) and worse prognosis in patients with coronary artery disease (CAD). The aims of the present study were, in patients with ST-elevation myocardial infarction (STEMI); 1) to compare serum levels of IgM anti-PC measured acutely and after 3 months; 2) to study an association between levels of IgM anti-PC and the severity ofCAD, and; 3) to investigate whether IgM anti-PC levels are associated with long-term clinical outcome. METHODS: A total of 213 patients without known diabetes (median age 59 years) with a PCI treated STEMI were enrolled. IgM anti-PC was measured in-hospital and after 3 months. Median follow-up time was 6.5 years (all-cause mortality, non-fatal myocardial re-infarction, recurrent ischemia causing hospital admission, heart failure and stroke). The severity of CAD was evaluated by coronary angiograms and patients were classified as having single- or multi-vessel disease and by SYNTAX score (SXscore). RESULTS: IgM anti-PC levels were stable over time when measured acutely and after 3 months. Patients with multi-vessel disease and high SXscore had significantly lower levels of IgM anti-PC in the acute phase of STEMI. Low levels of IgM anti-PC (the 25 percentile) measured acutely were associated with a 2-fold increase in the odds of having multi-vessel disease (adjusted OR 2.28 (95% CI 1.17, 4.44), p = 0.016), but not with high SXscore (Crude OR 2.20 (95% CI 0.96, 5.07), p = 0.06). Fifty-three patients experienced a new clinical event during long-term follow-up. Low levels of IgM anti PC were not associated with worse prognosis, (crude HR 1.54 (0.87-2.76), p = 0.14). CONCLUSION: STEMI patients with multi-vessel disease or high SXscore had significantly lower levels of IgM anti-PC in the acute phase and low levels were associated with multi-vessel disease, but not with worse clinical outcome during long-term follow-up.

Elevated serum osteoprotegerin levels measured early after acute ST-elevation myocardial infarction predict final infarct size.

BACKGROUND: Increased serum osteoprotegerin has been shown to be associated with increased mortality and heart failure development in patients with acute coronary syndromes. The aim of the present study was to elucidate a possible association between serum osteoprotegerin measured acutely in patients with ST-elevation myocardial infarction (STEMI) and final infarct size. METHODS Serum osteoprotegerin was measured in fasting blood samples from 199 patients with acute STEMI, sampled at a median time of 16 h after primary percutaneous coronary intervention (PCI). After 3 months, final infarct size (in percentage of left ventricular mass; LVM) was assessed by single-photon emission CT. The outcome variable final infarct size was dichotomised using the 75th percentile as the cutoff value (large infarct size ≥ 29.0%). A multivariable analysis was performed adjusting for multiple clinical and biochemical covariates. RESULTS: Median (IQR) osteoprotegerin concentration was 1.4 (1.0, 2.1) ng ml⁻¹ and patients with high osteoprotegerin level (> median) at baseline had larger infarct size at 3 months compared with patients with low osteoprotegerin levels (< median) (25 (8, 40) vs 6 (0, 19)% of LVM, respectively, p < 0.0001). A high osteoprotegerin level was also associated with an approximately sevenfold increase in the odds of developing a large myocardial infarct (OR 7.0; 3.2, 15.5, p < 0.001). After adjustment for potential confounders including peak troponin T, the adjusted OR was 5.2 (2.0, 13.1) p < 0.001. CONCLUSION: High levels of circulating osteoprotegerin measured the first morning after a PCI-treated acute STEMI were strongly associated with final infarct size.

[Impaired glucose tolerance in patients with acute myocardial infarction]. / Nedsatt glukosetoleranse hos pasienter med akutt hjerteinfarkt.

BACKGROUND: Diabetes and impaired glucose tolerance are associated with increased mortality in patients with acute myocardial infarction. We have used standardised oral glucose tolerance tests shortly after a myocardial infarction. METHODS: 109 patients admitted with acute myocardial infarction were prospectively enrolled in the study. An oral glucose tolerance test was performed the first morning the patients were stable, without pain, nausea or hyperglycaemia. The patients were classified into normal glucose tolerance, impaired glucose tolerance or diabetes, according to the results of the oral glucose tolerance test and fasting plasma glucose levels. RESULTS: 109 patients (25 women) were included. Eight patients were previously diagnosed with diabetes type 2. Oral glucose tolerance was tested for 90 patients, usually the day after admission. The test was positive in 47 patients; 32 of them had 2-h plasma glucose levels between 7.8 and 11.0 mmol/L and were classified as having impaired glucose tolerance, and 15 had 2-h plasma glucose > or = 11.1 mmol/L and were classified as newly diagnosed diabetes patients. Similar body mass indexes and lipid values were found in patients with different glycometabolic states. Smoking was associated with a positive oral glucose tolerance test. INTERPRETATION: More than half of the patients with acute myocardial infarction had undiagnosed impaired glucose tolerance or diabetes type 2, as determined by an oral glucose tolerance test. The test could easily be performed shortly after a myocardial infarction in most of the patients. Oral glucose tolerance testing should be considered in all patients with coronary heart disease without a history of diagnosed diabetes.