Alf Larsen | University of Bergen (original) (raw)

Papers by Alf Larsen

Trials, Jan 4, 2016

The application of therapeutic hypothermia (TH) for 12 to 24 hours following out-of-hospital card... more The application of therapeutic hypothermia (TH) for 12 to 24 hours following out-of-hospital cardiac arrest (OHCA) has been associated with decreased mortality and improved neurological function. However, the optimal duration of cooling is not known. We aimed to investigate whether targeted temperature management (TTM) at 33 ± 1 °C for 48 hours compared to 24 hours results in a better long-term neurological outcome. The TTH48 trial is an investigator-initiated pragmatic international trial in which patients resuscitated from OHCA are randomised to TTM at 33 ± 1 °C for either 24 or 48 hours. Inclusion criteria are: age older than 17 and below 80 years; presumed cardiac origin of arrest; and Glasgow Coma Score (GCS) <8, on admission. The primary outcome is neurological outcome at 6 months using the Cerebral Performance Category score (CPC) by an assessor blinded to treatment allocation and dichotomised to good (CPC 1-2) or poor (CPC 3-5) outcome. Secondary outcomes are: 6-month mor...

The American Journal of Cardiology, 2013

The clinical features and prognosis of patients with ST-segment elevation myocardial infarction (... more The clinical features and prognosis of patients with ST-segment elevation myocardial infarction (STEMI) and no significant coronary artery disease (CAD) have not been well studied. We examined the outcomes of patients with STEMI in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial according to the presence or absence of significant CAD. &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;No-CAD&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; was defined by the absence of any lesion with a diameter stenosis of ≥30% on quantitative coronary angiography of the baseline coronary angiogram. Of 3,602 patients, 127 (3.5%) had no-CAD. Of these, 86 (67.7%) had angiographically normal coronary arteries, and 41 (32.3%) had mild disease (diameter stenosis &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;30%). Eight patients had previously been treated with coronary artery bypass grafting. Compared to patients with CAD, patients with no-CAD were younger, had a lower body mass index, were more frequently black, had a lower prevalence of smoking and previous angina, and had a greater left ventricular ejection fraction. Cardiac enzymes were elevated in fewer patients with no-CAD than in those with CAD (63.2% vs 98.7%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). At 3 years of follow-up, the patients with no-CAD versus CAD had lower rates of major adverse cardiovascular events (7.7% vs 22.2%, p = 0.002), net adverse clinical events (major adverse cardiovascular events or major bleeding not related to coronary artery bypass grafting, 12.5% vs 26.9%, p = 0.005), and postprocedure coronary revascularization (0% vs 19.5%, p…

European Journal of Cardiovascular Nursing

Journal of Advanced Nursing, 2014

Resuscitation, 2010

Keywords: SCA PEA VF Coronary angiography PCI TIMI flow Coronary blood flow Coronary perfusion pr... more Keywords: SCA PEA VF Coronary angiography PCI TIMI flow Coronary blood flow Coronary perfusion pressure Mechanical chest compression LUCAS a b s t r a c t Patients with pulseless electrical activity or refractory ventricular fibrillation have a very bad prognosis. Coronary angiography and angioplasty may be required to restore an effective circulation, but this must be performed whilst chest compressions are continued. The LUCAS chest compression device is suitable for this purpose. So far there are no reports on the effect of this device on coronary circulation in humans. We monitored the coronary perfusion pressure assessed invasively as the difference between the diastolic pressures at the coronary ostium and right atrium, and compared these pressures with coronary flow graded using the TIMI scale in 6 patients. In 4 out of 6 we found a satisfactory coronary artery perfusion pressure and TIMI grade 3 flow (normal) on coronary angiography. Two of these patients survived the first 24 h. Two patients did not have a satisfactory perfusion pressure and adequate flow rate was not seen.

Thrombosis Journal, 2010

The pathophysiological pathways resulting in Late Stent Thrombosis (LST) remain uncertain. Findin... more The pathophysiological pathways resulting in Late Stent Thrombosis (LST) remain uncertain. Findings from animal studies indicate a role of the intrinsic coagulation pathway in arterial thrombus formation, while clinical studies support an association with ischemic cardiovascular disease. It is currently unknown whether differences in the state of the contact system might contribute to the risk of LST or Very Late Stent Thrombosis (VLST). We assessed the relation between levels of several components involved in the contact system and a history of LST and VLST, termed (V)LST in a cohort of 20 patients as compared to a matched control group treated with PCI. Activated factor XII (FXIIa), FXII zymogen (FXII), FXIIa-C1-esterase inhibitor (C1-inhibitor), Kallikrein-C1-inhibitor, FXIa-C1-inhibitor and FXIa-alpha1-antitrypsin (AT-inhibitor) complexes were measured by Enzyme-linked immunosorbent assy (ELISA) methodology.Cases and controls showed similar distributions in sex, age, baseline medications and stent type. Patients with a history of (V)LST had a significantly greater stent burden and a higher number of previous myocardial infarctions than the control patients.There were no significant between-group differences in the plasma levels of the components of the contact system. In a cohort of patients with a history of (V)LST, we did not observe differences in the activation state of the intrinsic coagulation system as compared to patients with a history of percutaneous coronary intervention without stent thrombosis.

International Journal of Cardiology - INT J CARDIOL, 2008

Exercise training improves functional parameters in patients with congestive heart failure (CHF).... more Exercise training improves functional parameters in patients with congestive heart failure (CHF). The aim of this study was to establish whether exercise training influence the elevated CgA levels in CHF patients. Plasma CgA was determined at baseline and at peak exercise before and after 12 weeks of training in 25 men (mean age 67±8 years) with CHF (NYHA functional class II and III). Plasma Chromogranin A (CgA) was significantly elevated in CHF, however without change after the 12 week exercise period. A positive correlation was obtained for CgA versus N-ANP and CgA versus TNFα for the patients with poor survival, indicating that in these patients the elevated plasma CgA was more closely connected to the myocardial release of natriuretic peptides and the inflammatory response than to activation of the sympathoadrenergic system.

Resuscitation, 2007

Mechanical chest compression may be necessary to make coronary intervention possible during resus... more Mechanical chest compression may be necessary to make coronary intervention possible during resuscitation. We report our experience using the Lund University Cardiac Arrest System (LUCAS, Jolife, Lund, Sweden) which is a gas-driven sternal compression device that incorporates a suction cup for active decompression. During the last 13 months LUCAS has been used in our catheterisation laboratory to maintain adequate organ perfusion pressure in 13 patients with cardiac arrest or severe hypotension and bradycardia (male/female ratio 1.6, mean age 59+/-19). The mean compression time was 105+/-60min (range 45-240), and the mean systolic and diastolic blood pressure obtained was 81+/-23 and 34+/-21mmHg, respectively. Angiography and eventually percutanous coronary intervention was possible in all cases during ongoing automatic chest compression. Three patients survived the procedure, but no patients were discharged alive. In two cases we found inadequate flow in the anterior descending artery, and in one case the invasive measurements revealed inadequate coronary perfusion pressure. There were no excessive intra-thoracic or intra-abdominal injuries. We conclude that the LUCAS device is suitable during cardiac catheterisation and intervention, and the device ensures an adequate systemic blood pressure in most patients without life-threatening injuries.

International Journal of Cardiology, 2008

Introduction: After changing our treatment regimen from thrombolytic therapy to primary percutane... more Introduction: After changing our treatment regimen from thrombolytic therapy to primary percutaneous intervention (PCI), we decided to perform a real-life retrospective comparison of the results obtained by thrombolytic therapy in 2000 with the results obtained by primary PCI in 2004 at our center which has no on-site cardiac surgery. Methods: All patients admitted with ST-elevation myocardial infarction (STEMI) during 2000 and 2004 were included in our study. The charts were scrutinized by one of the authors to ensure accurate information on diagnostics and timing. Relevant data, which were predefined, were noted and compared in patients treated during the two time-periods. Results: During the year of 2000, 197 patients were admitted with STEMI. Thrombolytics were administered to 138 of these patients. During 2004, 175 patients were admitted with STEMI and PCI was performed in 173 of these patients. Door-to-needle time was 28 min and door-toballoon time 80 min, respectively. In-hospital mortality was significantly reduced from 2000 to 2004 (19.3% vs 8.6%, p = 0.003). 30 daymortality was likewise reduced from 21.3% to 8.6%, (p = 0.0001), and this difference remained significant after excluding patients not receiving thrombolytics in the year 2000. In-hospital stay was reduced from 9.4 to 6.4 days, (p b 0.001). None of the patients required transfer to a tertiary center for acute coronary artery bypass grafting. Conclusion: Initiation of a primary PCI program at a center without on site cardiac surgery is associated with a substantial increase in number of patients offered reperfusion therapy and a significant reduction in morbidity and mortality.

International Journal of Cardiology, 2010

Variations in population-based levels of C-reactive protein, cardiovascular morbidity and all-cau... more Variations in population-based levels of C-reactive protein, cardiovascular morbidity and all-cause mortality ☆ An analysis of the relationship between C-reactive protein, Troponin-T, cardiovascular morbidity and death rates in an unselected population in Southwest Norway

International Journal of Cardiology, 2006

Subclavian artery occlusion causing an anterior non-ST-elevation myocardial infarction in a patie... more Subclavian artery occlusion causing an anterior non-ST-elevation myocardial infarction in a patient with a left internal mammary artery bypass to the left anterior descending artery. Presentation of a case not previously described in the literature to our knowledge. D

International Journal of Cardiology, 2002

Background: In patients with congestive heart failure (CHF) there is a shift from aerobic type I ... more Background: In patients with congestive heart failure (CHF) there is a shift from aerobic type I muscle fibres to less aerobic type II fibres. Exercise training has been shown to have beneficial effects on exercise performance, peripheral pathology and the neurohumoral profile in stable patients with CHF. This study evaluated the effect of a 3 month exercise training program on

European Journal of Heart Failure, 2006

Background: Natriuretic peptide levels reflect haemodynamics in patients with heart failure and m... more Background: Natriuretic peptide levels reflect haemodynamics in patients with heart failure and may serve as biochemical markers of cardiac filling pressures. The purpose of this study was to detect differences in the kinetic profile between atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and their N-terminal fragments N-ANP and N-BNP, in response to rapid and persistent vasodilatation. Methods: Sixteen men and four women aged 63.0 T 10.4 (mean T S.D.) with symptomatic congestive heart failure (NYHA III) and pulmonary capillary wedge pressure (PCWP) > 18 mm Hg, received a 24-h infusion of nitroglycerin (N = 8) or nicorandil (N = 12). A reduction of PCWP was achieved for the duration of the study. Natriuretic peptides were measured by radioimmunoassay at baseline, 1, 3, 6, 12 and 24 h. Results: PCWP and right atrial pressure fell rapidly and then increased modestly. ANP and N-ANP demonstrated a similar pattern. In contrast, BNP and N-BNP levels fell steadily throughout the observation period. This was accompanied by a continuous reduction of systemic vascular resistance (SVR). PCWP was highly correlated to the levels of all the natriuretic peptides. Using a longitudinal regression model evaluating responses over time, we found separate, significant relationships between all peptides and haemodynamic variables. Conclusion: The atrial natriuretic peptides reflect rapid changes in filling pressures while the B-type peptides respond much slower. Btype peptides are less sensitive to short-term changes in filling pressures, but should reflect changes in SVR better during vasodilator therapy.

European Journal of Heart Failure, 2009

The Cardiac Resynchronization Therapy (CRT) Survey II is a 6 months snapshot survey initiated by ... more The Cardiac Resynchronization Therapy (CRT) Survey II is a 6 months snapshot survey initiated by two ESC Associations, the European Heart Rhythm Association and the Heart Failure Association, which is designed to describe clinical practice regarding implantation of CRT devices in a broad sample of hospitals in 47 ESC member countries. The large volume of clinical and demographic data collected should reflect current patient selection, implantation, and follow-up practice and provide information relevant for assessing healthcare resource utilization in connection with CRT. The findings of this survey should permit representative benchmarking both nationally and internationally across Europe.

European Heart Journal, 2009

We studied the time-dependent relationships between microvascular obstruction (MO), infarct size,... more We studied the time-dependent relationships between microvascular obstruction (MO), infarct size, and left ventricular (LV) remodelling after acute myocardial infarction (MI). Forty-two consecutive patients with first-time ST-elevation MI, single-vessel disease, successfully treated with primary percutaneous coronary intervention (PCI) were included. Microvascular obstruction, infarct size, and LV remodelling were assessed by cardiac magnetic resonance. Cardiac magnetic resonance was performed at: 2 days, 1 week, 2 months, and 1 year following PCI. Microvascular obstruction was assessed by first-pass perfusion. Patients were divided into three groups according to the presence or absence of MO at 2 days and 1 week: no detectable MO at any time point (11 patients), MO detectable only at 2 days (16 patients), and MO detectable both at 2 days and 1 week (15 patients). In multivariable analysis adjusting for infarct size at 2 days, detectable MO at 1 week was an independent predictor (P = 0.003) of infarct size at 1 year follow-up, associated with adverse infarct healing, adverse LV remodelling, increased LV volumes, and lower ejection fractions when compared with the rest of the cohort. Microvascular obstruction is an important determinant of infarct healing. The effect of MO on infarct size translated into distinct patterns of LV remodelling during long-term follow-up.

Europace, 2013

We evaluated the effects of cardiac resynchronization therapy (CRT) on skeletal muscle pathology ... more We evaluated the effects of cardiac resynchronization therapy (CRT) on skeletal muscle pathology and inflammation in patients with heart failure. Stable patients (n = 21, 14 males, mean age 70 ± 7 years) with symptomatic heart failure (mean left ventricular ejection fraction 24 ± 6%) and an indication for CRT were included. Ergospirometry, skeletal muscle open biopsy, and blood sampling were performed prior to implantation and after 6 months of CRT. After CRT there was a reduction in both left ventricular end-diastolic diameter (LVEDD; 6.8 ± 0.8 vs. 6.3 ± 0.7 cm, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and native QRS duration (D) minus biventricular paced QRSD (172.9 ± 23 vs. 136.3 ± 23 ms, P ≤ 0.001). These changes were associated with an increase in peak slope oxygen uptake (consumption) (VO₂) (13.3 ± 2.2 vs. 14.5 ± 2.6 mL/kg/min, P = 0.07) and an improvement in the minute ventilation/carbon dioxide production slope (VE/VCO₂) slope (41.6 ± 7.4 vs. 39.1 ± 5.6, P = 0.012). There were no statistically significant changes in levels of pro-inflammatory cytokines, in mediators of mitochondrial biosynthesis or skeletal muscle pathology, except for an increase in skeletal muscle capillary density (4.5 ± 2.4 vs. 7.7 ± 3.3%, P = 0.002). Both the reduction of QRS duration and the increase in peak VO₂ correlated significantly with the change in mitochondrial density (r = 0.57, P = 0.008 and r = 0.54, P = 0.027, respectively). Cardiac resynchronization therapy, with improved functional status and reduced LVEDD resulted in increased peak VO₂, improvement in VE/VCO₂ slope and capillary density in skeletal muscle, with no reduction in systemic pro-inflammatory cytokines, increase in intramuscular levels of mediators of mitochondrial biosynthesis or improvement in skeletal muscle ultrastructure per se. ClinicalTrials.gov Identifier: NCT01019915.

Critical Care, 2013

Introduction: Therapeutic hypothermia (TH) after out-of-hospital cardiac arrest (OHCA) was adopte... more Introduction: Therapeutic hypothermia (TH) after out-of-hospital cardiac arrest (OHCA) was adopted early in Norway. Since 2004 the general recommendation has been to cool all unconscious OHCA patients treated in the intensive care unit (ICU), but the decision to cool individual patients was left to the responsible physician. We assessed factors that were associated with use of TH and predicted survival. Method: We conducted a retrospective observational study of prospectively collected cardiac arrest and ICU registry data from 2004 to 2008 at three university hospitals.

The American Journal of Cardiology, 2014

Statin therapy is indicated after ST-segment elevation myocardial infarction (STEMI) to reduce re... more Statin therapy is indicated after ST-segment elevation myocardial infarction (STEMI) to reduce recurrent ischemic events, but approximately 6% of patients with STEMI do not receive a statin prescription at discharge. This substudy aimed to define the clinical outcomes and patient characteristics associated with statin nonprescription after STEMI. We compared clinical, angiographic, and procedural characteristics and in-hospital, 30-day, 1-year, 2-year, and 3-year outcomes in 3,512 patients discharged after STEMI with and without (6%) statin prescriptions in the harmonizing outcomes with revascularization and stents in acute myocardial infarction trial (www.clinicaltrials.gov, NCT00433966). Statin nonprescription was associated with female sex, nonwhite race, previous bypass surgery, heart failure, renal impairment, anemia, thrombocytopenia, care in the United States, lower prescription rates of antiplatelets and neurohormonal antagonists, less percutaneous coronary intervention and stents, and, in 26% of cases, angiographically normal or nonobstructed coronary arteries. At every time point of follow-up after discharge, patients with no discharge statin prescription had significantly higher rates of net adverse clinical events, major adverse cardiac events, major bleeding unrelated to bypass surgery, and death. After multivariable adjustment, absence of a discharge statin prescription independently predicted 3-year major adverse cardiac event (hazard ratio 1.54, 95% confidence interval 1.15 to 2.07, p=0.0037) and death (hazard ratio 2.30, 95% confidence interval 1.41 to 3.77, p=0.0009). In conclusion, within the framework of this randomized trial of patients presenting with STEMI, approximately 6% of patients were discharged without statin therapy. Absence of a discharge statin prescription after STEMI was an independent predictor of ischemic events including death.