Jens Kristensen

Routine thrombectomy in percutaneous coronary intervention for acute ST-segment-elevation myocardial infarction: a randomized, controlled trial.

Background— Distal embolization during primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction may result in reduced myocardial perfusion, infarct extension, and impaired prognosis. Methods and Results— In a prospective randomized trial, we studied the effect of routine thrombectomy in 215 patients with ST-segment–elevation myocardial infarction lasting <12 hours undergoing primary PCI. Patients were randomized to thrombectomy pretreatment or standard PCI. The primary end point was myocardial salvage measured by sestamibi SPECT, calculated as the difference between area at risk and final infarct size determined after 30 days (percent). Secondary end points included final infarct size, ST-segment resolution, and troponin T release. Baseline variables, including ST-segment elevation and area at risk, were similar. Salvage was not statistically different in the thrombectomy and control groups (median, 13% [interquartile range, 9% to 21%] and 18% [interquartile range, 7% to 25%]; P=0.12), but 24 patients in the thrombectomy group and 12 patients in the control group did not have an early SPECT scan, mainly because of poor general or cardiac condition (P=0.04). In the thrombectomy group, final infarct size was increased (median, 15%; [interquartile range, 4% to 25%] versus 8% [interquartile range, 2% to 18%]; P=0.004). Conclusions— Thrombectomy performed as routine therapy in primary PCI for ST-elevation myocardial infarction does not increase myocardial salvage. The study suggests a possible deleterious effect of thrombectomy, resulting in an increased final infarct size, and does not support the use of thrombectomy in unselected primary PCI patients.

Hypothermia during reperfusion does not reduce myocardial infarct size in pigs.

AbstractWe previously described a method for regional myocardial cooling that reaches the target temperature within 4 min. The present study evaluated whether this method for regional myocardial cooling during reperfusion reduces myocardial infarct size (IS) in 75–kg pigs. Myocardial infarction was induced by inflation of an angioplasty balloon in the left anterior descendent artery for 45 min followed by 3 h reperfusion. First, 15 pigs were randomized to regional myocardial cooling during reperfusion (n = 8) or control (n = 7). As further control experiments, systemic hypothermia was induced prior to ischemia (n = 3) and during reperfusion (n = 3). IS and area at risk (AAR) were evaluated in vivo by single photon emission cardiac tomography (SPECT) and by standard histochemical staining.Regional cooling during reperfusion did not reduce IS/AAR as assessed by histochemistry (cooling: 0.71 ± 0.8; control: 0.68 ± 0.10; p = ns) and SPECT (cooling: 0.90 ± 0.20; control: 0.88 ± 0.32; p = ns). Systemic hypothermia during ischemia reduced IS/AAR (histochemistry: 0.09 ± 0.11; SPECT: 0.25 ± 0.22; p < 0.001 and p = 0.01 vs control, respectively). Induction of systemic hypothermia during reperfusion had no significant effect on IS/AAR (histochemistry: 0.63 ± 0.07; SPECT: 0.74 ± 0.09; p = ns vs control for both comparisons).In conclusion, hypothermia during ischemia is strongly myocardioprotective while hypothermia during reperfusion does not reduce myocardial infarct size in human–sized pigs.

Lack of cardioprotection from subcutaneously and preischemic administered Liraglutide in a closed chest porcine ischemia reperfusion model

BackgroundGlucagon-like peptide 1 (GLP1) analogues are promising new treatment options for patients with type 2 diabetes, but may have both potentially beneficial and harmful cardiovascular effects. This may also be the case for the analogues of GLP1 for clinical use. The present study examined the effect of treatment with Liraglutide, a long-acting GLP1 analogue, on myocardial ischemia and reperfusion in a porcine model.MethodsDanish Landrace Pigs (70–80 kg) were randomly assigned to Liraglutide (10 μg/kg) or control treatment given daily for three days before ischemia-reperfusion. Ischemia was induced by balloon occlusion of the left anterior descending artery for 40 minutes followed by 2.5 hours of reperfusion. The primary outcome parameter was infarct size in relation to the ischemic region at risk. Secondary endpoints were the hemodynamic parameters mean pulmonary pressure, cardiac output, pulmonary capillary wedge pressure as measured by a Swan-Ganz catheter as well as arterial pressure and heart rate.ResultsThe infarct size in relation to ischemic risk region in the control versus the Liraglutide group did not differ significantly: 0.46 ± 0.14 and 0.54 ± 0.12) (mean and standard deviation (SD), p = 0.21). Heart rate was significantly higher in the Liraglutide group during the experiment, while the other hemodynamic parameters did not differ significantly.ConclusionLiraglutide has a neutral effect on myocardial infarct size in a porcine ischemia-reperfusion model.

Lack of acute cardioprotective effect from preischaemic erythropoietin administration in a porcine coronary occlusion model

Background:  Recombinant human erythropoietin (rhEPO) has been proposed to possess important tissue protective, apart from haematopoietic, effects. Cardioprotective effects have thus been reported in rodents exposed to myocardial ischaemia. Pathways common to the mediation of ischaemic preconditioning may be involved. Before clinical testing such possible cardioprotective effects needs assessment in an experimental large animal model with closer similarity to human ischaemic pathophysiology.

Multimodality imaging-guided left ventricular lead placement in cardiac resynchronization therapy: a randomized controlled trial.

Left ventricular (LV) lead position at the latest mechanically activated non‐scarred myocardial LV region confers improved response to cardiac resynchronization therapy (CRT). We conducted a double‐blind, randomized controlled trial to evaluate the clinical benefit of multimodality imaging‐guided LV lead placement in CRT.

Myocardial perfusion imaging with 99mTc sestamibi early after reperfusion reliably reflects infarct size reduction by ischaemic preconditioning in an experimental porcine model.

ObjectiveReliable methods for assessment of tissue reperfusion early after revascularizing therapy for acute myocardial infarction are needed. Myocardial perfusion imaging with 99mTc sestamibi (MIBI MPI) may serve this purpose. Usage during early reperfusion may be problematic e.g. due to ischaemic preconditioning (IP), which is important in inducing ischaemic tolerance. It is mediated through the opening of mitochondrial K+ ATP channels, reducing mitochondrial membrane potential. This may, as well as ischaemia per se, affect cellular uptake of 99mTc sestamibi. We therefore studied the reliability of MIBI MPI during early reperfusion as a measure of infarct size and its reduction by ischaemic preconditioning. Methods and resultsWe compared MIBI MPI (cut-off, 45% of maximum pixel count) with a histochemical method in a porcine model, nine controls and eight IP pigs, using 45 min catheter based coronary occlusion of the left anterior descending artery. Infarct size (IS) was determined relative to the area at risk (AAR). The relative infarct size (IS/AAR) after 120 min reperfusion estimated by MPI was 0.83 (0.17) in controls vs 0.07 (0.12) in the IP group (mean (SD), P<0.001). The corresponding values for histochemistry were controls 0.77 (0.19) vs IP 0.07 (0.11), P<0.001. IS/AAR measured by MPI and histochemistry were correlated significantly (r=0.93, P<0.001). Furthermore, IS relative to left ventricular mass (IS/LV) determined by autoradiography and histochemistry correlated (r=0.93, P<0.001). MPI overestimated IS/LV and AAR/LV by approximately a factor of 2 compared with histochemistry or autoradiography. ConclusionMIBI MPI during early reperfusion is a reliable measure of relative infarct size reduction after ischaemic preconditioning, supporting use for stratification for adjunctive therapy and for assessment of prognosis.

Nationwide experience of catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations

Objective The aim of this study was to characterise disease penetrance, course of disease and use of antiarrhythmic medication and implantable cardioverter-defibrillator (ICD) therapy in a Danish nationwide cohort of patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) due to mutations in the ryanodine receptor-2 (RyR2) gene. Methods The study population was identified through the national hereditary heart disease database (Progeny). The study population was divided into three groups: probands, symptomatic and asymptomatic relatives. Results We identified 23 symptomatic probands, 18 symptomatic and 10 asymptomatic relatives with a RyR2 mutation. Twenty (87%) probands and 10 (36%) relatives had severe presenting symptoms (sudden cardiac death (SCD), aborted SCD (ASCD) or syncope). As compared with symptomatic relatives, probands had lower age at onset of symptoms (16 years (IQR, 10–33) vs 43 years (IQR, 25–54), p<0.0001) and were more prone to fatal or near-fatal events (ASCD, SCD) (16vs5, p<0.0001). Twenty-eight patients had an ICD implanted, and eight experienced appropriate ICD therapy during follow-up (65 months (IQR, 43–175)). Electrical storm was seen in two of the 28 ICD treated patients (7%). No patients receiving treatment died during follow-up (57 months (IQR, 32–139)). Multifocal atrial tachycardia was the predominant symptom in five patients. Conclusions In a national cohort of RyR2 mutation-positive CPVT patients, SCD, ASCD and syncope were presenting events in the majority of probands and also occurred in 36% of relatives identified through family screening. Probands were younger at disease onset and more prone to fatal or near-fatal events than relatives.

Can new pulmonary gas exchange parameters contribute to evaluation of pulmonary congestion in left-sided heart failure?

BACKGROUND Assessment of pulmonary congestion in left-sided heart failure is necessary for guiding anticongestive therapy. Clinical examination and chest x-ray are semiquantitative methods with poor diagnostic accuracy and reproducibility. OBJECTIVES To establish reference values, describe reproducibility, and investigate the diagnostic and monitoring properties in relation to pulmonary congestion of new pulmonary gas exchange parameters describing ventilation/perfusion mismatch (variable fraction of ventilation [fA2] or the drop in oxygen pressure from the mixed alveolar air of the two ventilated compartments to the nonshunted end-capillary blood [DeltaPO(2)]) and pulmonary shunt. METHODS Sixty healthy volunteers and 69 patients requiring an acute chest x-ray in a cardiac care unit were included. The gas exchange parameters were estimated by analyzing standard bedside respiratory and circulatory measurements obtained during short-term exposure to different levels of inspired oxygen. Nine patients were classified as having pulmonary congestion using a reference diagnosis and were followed during 30 days of anticongestive therapy. Diagnostic and monitoring properties were compared with chest x-ray, N-terminal probrain natriuretic peptide (NT-proBNP), spirometry values, arterial oxygen tension, alveolar-arterial oxygen difference and venous admixture. RESULTS The 95% reference intervals for healthy subjects were narrow (ie, fA2 [0.75 to 0.90], DeltaPO(2) [0.0 kPa to 0.5 kPa] and pulmonary shunt [0.0% to 8.2%]). Reproducibility was relatively good with small within subject coefficients of variation (ie, fA2 [0.05], DeltaPO(2) [0.4 kPa] and pulmonary shunt [2.0%]). fA2, DeltaPO(2) and NT-proBNP had significantly better diagnostic properties, with high sensitivities (100%) but low specificities (30% to 40%). During successful anticongestive therapy, fA2, DeltaPO(2), NT-proBNP and spirometry values showed significant improvements. CONCLUSIONS The gas exchange parameter for ventilation/perfusion mismatch but not pulmonary shunt can have a possible role in rejecting the diagnosis of pulmonary congestion and in monitoring anticongestive therapy.

The α-MSH analogue AP214 attenuates rise in pulmonary pressure and fall in ejection fraction in lipopolysaccharide-induced systemic inflammatory response syndrome in pigs

Background:  The effect of an α‐melanocyte stimulating hormone (α‐MSH) analogue (AP214) on experimentally endotoxin‐induced systemic inflammatory response syndrome (SIRS) was studied, because α‐MSH in rodent models has shown promise in attenuating inflammatory response markers and associated organ damage in SIRS. SIRS is associated with considerable morbidity and mortality. Consequently, new treatment modalities are still warranted to address the different aspects of the pathophysiological process.

A phase of increased ST elevation during coronary occlusion following ischemic preconditioning

AbstractATP–sensitive potassium channels are opened during the course of ischemic preconditioning (IP). As experimental data suggest that opening of sarcolemmal ATP–sensitive potassium channels underlie ST elevation during myocardial ischemia, one would expect to observe increased ST elevation during ischemia following IP. However, clinical studies have reported IP to attenuate ST elevation during repeated brief coronary occlusions. The objective of this study was to characterize the temporal course of ST elevation during coronary occlusion following IP. Twenty–eight closed–chest pigs were subject to catheter–based left anterior descending coronary artery occlusion/ reperfusion for 45/120 minutes. Thirteen animals were preconditioned by two occlusion/reperfusion cycles of 10/30 minutes. Fifteen pigs served as controls. The electrocardiographic ST vector magnitude was continuously monitored. IP reduced the infarct size normalized for area at risk (IP 9.6 ± 15.8%; control 71.2 ± 14.7%; p < 0.001). IP increased the time between coronary artery occlusion and appearance of significant rise in ST vector magnitude from 51 ± 17 to 94 ± 33 seconds (p < 0.01). IP reduced the rise in ST vector magnitude after 120 seconds of occlusion from 202 ± 85 µV to 68 ± 28 µV (p < 0.001) and increased the rise in ST vector magnitude after 600 seconds from 265 ± 106 µV to 427 ± 232 µV (p < 0.001).ConclusionIschemic preconditioning reduced and delayed early ST elevation during subsequent coronary artery occlusion, but increased late ST elevation. Thus, ischemic preconditioning causes a dynamic and critically time-dependent biphasic pattern of ST elevation during repeated coronary occlusions.