Suppression of circulating free fatty acids with acipimox in chronic heart failure patients changes whole body metabolism but does not affect cardiac function.

Circulating free fatty acids (FFAs) may worsen heart failure (HF) due to myocardial lipotoxicity and impaired energy generation. We studied cardiac and whole body effects of 28 days of suppression of circulating FFAs with acipimox in patients with chronic HF. In a randomized double-blind crossover design, 24 HF patients with ischemic heart disease [left ventricular ejection fraction: 26 ± 2%; New York Heart Association classes II (n = 13) and III (n = 5)] received 28 days of acipimox treatment (250 mg, 4 times/day) and placebo. Left ventricular ejection fraction, diastolic function, tissue-Doppler regional myocardial function, exercise capacity, noninvasive cardiac index, NH(2)-terminal pro-brain natriuretic peptide (NT-pro-BNP), and whole body metabolic parameters were measured. Eighteen patients were included for analysis. FFAs were reduced by 27% in the acipimox-treated group [acipimox vs. placebo (day 28-day 0): -0.10 ± 0.03 vs. +0.01 ± 0.03 mmol/l, P < 0.01]. Glucose and insulin levels did not change. Acipimox tended to increase glucose and decrease lipid utilization rates at the whole body level and significantly changed the effect of insulin on substrate utilization. The hyperinsulinemic euglycemic clamp M value did not differ. Global and regional myocardial function did not differ. Exercise capacity, cardiac index, systemic vascular resistance, and NT-pro-BNP were not affected by treatment. In conclusion, acipimox caused minor changes in whole body metabolism and decreased the FFA supply, but a long-term reduction in circulating FFAs with acipimox did not change systolic or diastolic cardiac function or exercise capacity in patients with HF.

Potential significance of spontaneous and interventional ST-changes in patients transferred for primary percutaneous coronary intervention: observations from the ST-MONitoring in Acute Myocardial Infarction study (The MONAMI study).

AIMS: In patients with ST-elevation myocardial infarction (STEMI) scheduled for primary percutaneous coronary intervention (primary PCI), acute risk-assessment may be valuable for tailoring of adjunctive therapy at the time of coronary intervention. The present study was designed to quantify pre-, per-, and post-interventional ST-changes, to evaluate whether a pre-specified continuous ST-monitoring classification provides potential prognostic information in the pre- and per-interventional phase, and to compare post-interventional ST-resolution parameters derived from continuous ST-monitoring and snapshot ECGs, respectively. METHODS AND RESULTS: In 92 STEMI patients, continuous ST-monitoring was initiated in the pre-hospital phase and continued during and 90 min following PCI. Patients were divided into three groups: (A) patients achieving spontaneous ST-resolution before PCI; (B) patients with preserved ST-elevation immediately before PCI and with no increase in ST-elevation during PCI; and (C) patients with preserved ST-elevation immediately before PCI and with increase in ST-elevation during PCI. Groups A (n=22), B (n=43), and C (n=27) differed in peak level of troponin-T (1.4, 4.7, and 7.2 microg/L, P<0.001), creatinine kinase MB isoenzyme (35, 150, and 325 microg/L, P<0.001), and N-terminal pro-brain natriuretic peptide (Nt-pro-BNP) (183, 175, and 269 pmol/L, P=0.084) during admission, and left ventricular ejection fraction evaluated within 2 h of PCI (0.53, 0.48, and 0.45, P=0.047) and after 3 months (0.58, 0.54, and 0.45, P<0.001). Groups B and C also differed in time from first balloon inflation to > or =70% resolution of ST-elevation (14 vs. 42 min, P=0.002), whereas no differences were observed in traditional 90 min ST-resolution analysis or angiographically assessed parameters. CONCLUSION: STEMI patients transferred for primary PCI are heterogeneous with respect to pre- and per-interventional ST-changes, and a pre-specified ST-monitoring classification seems useful for stratification of patients at time of PCI into groups with low, intermediate, and high risk profile. Furthermore, post-interventional ST-monitoring indicates that traditional 90 min ST-resolution analysis may have limited value in the era of primary PCI.

Reduction of treatment delay in patients with ST-elevation myocardial infarction: impact of pre-hospital diagnosis and direct referral to primary percutanous coronary intervention.

AIMS: The majority of patients with ST-elevation myocardial infarction (STEMI) are admitted to local hospitals without primary percutaneous coronary intervention (primary PCI) facilities. Acute transferral to an interventional centre is necessary to treat these patients with primary PCI. The present study assessed the reduction in treatment delay achieved by pre-hospital diagnosis and referral directly to an interventional centre. METHODS AND RESULTS: Two local hospitals without primary PCI facilities were serving the study region. Pre-hospital diagnoses were established with the use of telemedicine, by ambulance physicians, or by general practitioners. Primary PCI was accepted as the preferred reperfusion therapy in patients with STEMI. From 31 October 2002 to 31 January 2004 all patients transported by ambulance and transferred for primary PCI were registered. Patients with STEMI were divided into three groups: (A) patients diagnosed at a local hospital (n = 55), (B) patients diagnosed pre-hospitally and admitted to a local hospital (n = 85), and (C) patients diagnosed pre-hospitally and referred directly to the interventional centre (n = 21). When comparing group A with group B and C, no difference was found in age, sex, infarct location, or distance from the scene of event to the interventional centre, whereas the median time from ambulance call to first balloon inflation was 41 min shorter in group B compared with group A (P<0.001) and 81 min shorter in group C compared with group A (P<0.001). CONCLUSION: In a cohort of patients scheduled for admission to a local hospital and subsequent transferral to an interventional centre for primary PCI, those diagnosed pre-hospitally had shorter treatment delay compared with those diagnosed in hospital, both in the setting of initial admission to a local hospital, and to an even larger extent in the setting of referral directly to the interventional centre.

Mortality rates in patients with ST-elevation vs. non-ST-elevation acute myocardial infarction: observations from an unselected cohort.

AIMS: Acute myocardial infarction (AMI) is categorized, according to the presenting electrocardiogram, into non-ST-elevation myocardial infarction (non-STEMI), ST-elevation myocardial infarction (STEMI), or bundle branch block myocardial infarction (BBBMI). Data on the prognostic significance of these categories mainly originate from voluntary based registries or large-scale clinical trials and may be hampered by selection and information bias. The aim of this historical cohort study was to evaluate the prognostic significance of different categories of AMI in an unselected cohort. METHODS AND RESULTS: From 1 November 1999 to 31 October 2001, patient records were reviewed from all admissions to hospitals serving a study region with 139,000 inhabitants. An Endpoint Committee determined whether patients fulfilled the European Society of Cardiology criteria of AMI. A total of 654 patients with AMI were identified. The proportion having non-STEMI, STEMI, and BBBMI was 54, 39 and 6%, and the associated 1 year mortality was 31, 21, and 55%, respectively (log rank 54, P<0.001). The more favourable outcome observed in patients with STEMI remained significant according to multivariable analysis (P=0.044). CONCLUSION: In an unselected cohort of patients admitted with AMI, the mortality was considerably higher than expected from voluntary-based registries and large-scale clinical trials. The most favourable outcome is observed in patients with STEMI.