Peder Sörensson

Effect of postconditioning on infarct size in patients with ST elevation myocardial infarction

Background Small studies suggest that postconditioning reperfusion interrupted by brief repetitive cycles of reocclusions, may protect the myocardium in the clinical setting. Objective To test the hypothesis that postconditioning limits infarct size in relation to the area at risk in patients with ST elevation myocardial infarction (STEMI). Methods 76 patients (aged 37–87 years) eligible for primary percutaneous coronary intervention due to STEMI were randomised to standard percutaneous coronary intervention (n=38) or postconditioning, consisting of four cycles of 60 s reperfusion and 60 s of reocclusion before permanent reperfusion (n=38). Results The area at risk was determined from angiographic abnormally contracting segments. Infarct size was quantified from delayed enhancement MRI on days 6–9. Infarct size, expressed in relation to the area at risk, did not differ between the control group (44%; 30, 56) (median and quartiles) and the post-conditioned group (47%; 23, 63). The slope of the regression lines relating infarct size to the area at risk differed between the two groups. Infarct size was significantly (p=0.001) reduced by postconditioning in patients with large areas at risk. The area under the curve and peak troponin T release and CKMB during 48 h did not differ between patients in the control and postconditioning groups. Conclusions This prospective, randomised trial suggests that postconditioning does not reduce infarct size in patients with STEMI in the overall study group. The data indicate that postconditioning may be of value in patients with large areas at risk. Clinical trial registration information Karolinska Clinical Trial Registration (http://www.kctr.se). Unique identifier: CT20080014.

Circulating endothelial and platelet derived microparticles reflect the size of myocardium at risk in patients with ST-elevation myocardial infarction.

OBJECTIVES Microparticles (MP) are small membrane vesicles, released from activated, damaged and apoptotic endothelial cells (EMP) or platelets (PMP) that may actively modulate inflammation, coagulation and vascular function. We tested the hypothesis that the number of circulating EMP or PMP in acute myocardial infarction correlates with the myocardium at risk (MaR) and infarct size (IS). METHODS EMP were quantified in plasma samples of 36 patients (age: 63±10 years) with first time ST-elevation myocardial infarction (STEMI) using flow cytometry. EMP were defined as CD31(+)/CD42(-) MP and CD144(+) MP and PMP as CD31(+)/CD42(+) MP. MaR and IS was determined by cardiovascular magnetic resonance imaging one week after the index event. RESULTS Plasma levels of CD31(+)/CD42(-) EMP were 251.0±178.8/μl and CD144(+) 106.3±33.7/μl. PMP levels were 579.2±631.8/μl. MaR was 31.0±11.2% of the left ventricle and IS was 11.4±7.1% of the left ventricle. Patients with STEMI in the left anterior descending artery had higher levels of CD31(+)/CD42(-) EMP and PMP than those with other infarct-related arteries (p<0.05). The numbers of CD31(+)/CD42(-) EMP and PMP correlated to MaR, but not to IS. CONCLUSIONS Circulating EMP and PMP correlate to the size of MaR in patients with STEMI suggesting that they reflect the severity of the endothelial injury and platelet activation during myocardial ischemia.

Myocardial infarction with normal coronary arteries is common and associated with normal findings on cardiovascular magnetic resonance imaging: results from the Stockholm Myocardial Infarction with Normal Coronaries study

Myocardial infarction with angiographically normal coronary arteries (MINCA) is an important subtype of myocardial infarction; however, the prevalence, underlying pathophysiology, prognosis and optimal management of this condition are still largely unknown. Cardiovascular magnetic resonance (CMR) imaging has the potential to clarify the underlying pathology in patients with MINCA. The objective of this study was to investigate the diagnostic value of CMR imaging in this group of patients.

Assessment of myocardium at risk with contrast enhanced steady-state free precession cine cardiovascular magnetic resonance compared to single-photon emission computed tomography

BackgroundFinal infarct size following coronary occlusion is determined by the duration of ischemia, the size of myocardium at risk (MaR) and reperfusion injury. The reference method for determining MaR, single-photon emission computed tomography (SPECT) before reperfusion, is impractical in an acute setting. The aim of the present study was to evaluate whether MaR can be determined from the contrast enhanced myocardium using steady-state free precession (SSFP) cine cardiovascular magnetic resonance (CMR) performed one week after the acute event in ST-elevation myocardial infarction (STEMI) patients with total coronary occlusion.ResultsSixteen patients with STEMI (age 64 ± 8 years) received intravenous 99 m-Tc immediately before primary percutaneous coronary intervention. SPECT was performed within four hours. MaR was defined as the non-perfused myocardial volume derived with SPECT. CMR was performed 7.8 ± 1.2 days after the myocardial infarction using a protocol in which the contrast agent was administered before acquisition of short-axis SSFP cines. MaR was evaluated as the contrast enhanced myocardial volume in the cines by two blinded observers. MaR determined from the enhanced region on cine CMR correlated significantly with that derived with SPECT (r2 = 0.78, p < 0.001). The difference in MaR determined by CMR and SPECT was 0.5 ± 5.1% (mean ± SD). The interobserver variability of contrast enhanced cine SSFP measurements was 1.6 ± 3.7% (mean ± SD) of the left ventricle wall volume.ConclusionsContrast enhanced SSFP cine CMR performed one week after acute infarction accurately depicts MaR prior to reperfusion in STEMI patients with total occlusion undergoing primary PCI. This suggests that a single CMR examination might be performed for determination of MaR and infarct size.

Myocardium at risk by magnetic resonance imaging: head-to-head comparison of T2-weighted imaging and contrast-enhanced steady-state free precession.

Aims To determine the myocardial salvage index, the extent of infarction needs to be related to the myocardium at risk (MaR). Thus, the ability to assess both infarct size and MaR is of central clinical and scientific importance. The aim of the present study was to explore the relationship between T2-weighted cardiac magnetic resonance (CMR) and contrast-enhanced steady-state free precession (CE-SSFP) CMR for the determination of MaR in patients with acute myocardial infarction. Methods and results Twenty-one prospectively included patients with first-time ST-elevation myocardial infarction underwent CMR 1 week after primary percutaneous coronary intervention. For the assessment of MaR, T2-weighted images were acquired before and CE-SSFP images were acquired after the injection of a gadolinium-based contrast agent. For the assessment of infarct size, late gadolinium enhancement images were acquired. The MaR by T2-weighted imaging and CE-SSFP was 29 ± 11 and 32 ± 12% of the left ventricle, respectively. Thus, the MaR with T2-weighted imaging was slightly smaller than that by CE-SSFP (−3.0 ± 4.0%; P < 0.01). There was a significant correlation between the two MaR measures (r2= 0.89, P < 0.01), independent of the time after contrast agent administration at which the CE-SSFP was commenced (2–8 min). Conclusion There is a good agreement between the MaR assessed by T2-weighted imaging and that assessed by CE-SSFP in patients with reperfused acute myocardial infarction 1 week after the acute event. Thus, both methods can be used to determine MaR and myocardial salvage at this point in time.

Effect of remote ischemic conditioning on infarct size in patients with anterior ST-elevation myocardial infarction

BACKGROUND Previous studies indicate that remote ischemic conditioning performed before percutaneous coronary intervention (PCI) reduces infarct size in patients with ST-elevation myocardial infarction (STEMI). It remains unclear whether remote conditioning affords protection when performed in adjunct to primary PCI. We aimed to study whether remote ischemic per-postconditioning (RIperpostC) initiated after admission to the catheterization laboratory attenuates myocardial infarct size in patients with anterior STEMI. METHODS In this prospective multicenter trial 93 patients with anterior STEMI were randomized to RIperpostC or sham procedure as adjunct to primary PCI. RIperpostC was started on arrival in the catheterization laboratory by 5-minute cycles of inflation and deflation of a blood pressure cuff around the left thigh and continued throughout the PCI procedure. Infarct size and myocardium at risk were determined by cardiac magnetic resonance at day 4 to 7. The primary outcome was myocardial salvage index. RESULTS There was no significant difference in myocardial salvage index between the RIperpostC and control group (median 48.5% and interquartile range 30.9%-60.8% vs 49.2% [42.1%-58.8%]). Neither did absolute infarct size in relation to left ventricular myocardial volume differ significantly (RIperpostC 20.6% [14.1%-31.7%] vs control 17.9% [13.4%-25.0%]). The RIperpostC group had larger myocardial area at risk than the control group (43.1% (35.4%-49.7%) vs 37.0% (30.8%-44.1%) of the left ventricle, P=.03). Peak value and area under the curve for troponin T did not differ significantly between the study groups. CONCLUSIONS RIperpostC initiated after admission to the catheterization laboratory in patients with anterior STEMI did not confer protection against reperfusion injury.

Risk Factors and Markers for Acute Myocardial Infarction With Angiographically Normal Coronary Arteries.

Myocardial Infarction with normal coronary arteries (MINCA) is common with a prevalence of 1% to 12% of all myocardial infarctions. The pathogenic mechanisms of MINCA are still unknown, but endothelial dysfunction has been suggested as a possible cause. To investigate risk factors and markers for MINCA, we conducted a case-control study. Considering the reported low prevalence of classical risk factors for coronary heart disease (CHD) in some but not all studies, our hypothesis was that endothelial function and intima-media thickness (IMT) were better, respectively lower, than CHD controls. One hundred patients with MINCA fulfilling diagnostic criteria according to the European Society of Cardiology/American Collage of Cardiology/American Heart Association universal definition of myocardial infarction with myocarditis excluded by cardiac magnetic resonance imaging were investigated. Risk factors, endothelial function (EndoPAT), and IMT were compared to gender- and age-matched patients with myocardial infarction and CHD, respectively healthy controls. Smoking, hypertension, impaired glucose tolerance and diabetes mellitus, inflammatory disease, and psychiatric disorders were more common in patients with MINCA than in healthy controls. In contrast to patients with CHD, the lipid profile was antiatherogenic with low low-density lipoprotein and high high-density lipoprotein cholesterol. There were no major differences between the groups regarding endothelial function and IMT that were in the normal range. In conclusion, the present study showed that MINCA was associated with many established cardiovascular risk factors without major differences in atherosclerosis markers. MINCA patients recalled a high prevalence of emotional stress before admission that together with previous psychiatric vulnerability and female gender speaks strongly in favor of Takotsubo syndrome being an important cause of MINCA.

Height, weight and body mass index in adults with congenital heart disease

BACKGROUND High BMI is a risk factor for cardiovascular disease and, in contrast, low BMI is associated with worse prognosis in heart failure. The knowledge on BMI and the distribution in different BMI-classes in adults with congenital heart disease (CHD) are limited. METHODS AND RESULTS Data on 2424 adult patients was extracted from the Swedish Registry on Congenital Heart Disease and compared to a reference population (n=4605). The prevalence of overweight/obesity (BMI ≥ 25) was lower in men with variants of the Fontan procedure, pulmonary atresia (PA)/double outlet right ventricle (DORV) and aortic valve disease (AVD) (Fontan 22.0% and PA/DORV 15.1% vs. 43.0%, p=0.048 and p<0.001) (AVD 37.5% vs. 49.3%, p<0.001). Overt obesity (BMI ≥ 30) was only more common in women with AVD (12.8% vs. 9.0%, p=0.005). Underweight (BMI<18.5) was generally more common in men with CHD (complex lesions 4.9% vs. 0.9%, p<0.001 and simple lesions 3.2% vs. 0.6%, <0.001). Men with complex lesions were shorter than controls in contrast to females that in general did not differ from controls. CONCLUSION Higher prevalence of underweight in men with CHD combined with a lower prevalence of overweight/obesity in men with some complex lesions indicates that men with CHD in general has lower BMI compared to controls. In women, only limited differences between those with CHD and the controls were found. The complexity of the CHD had larger impact on height in men. The cause of these gender differences as well as possible significance for prognosis is unknown.

Cardiac involvement in Caucasian patients with pulmonary sarcoidosis

BackgroundCardiac sarcoidosis (CS) is a potentially life-threatening condition. At present, there is no consensus with regard to the optimal non-invasive clinical evaluation and diagnostic procedures of cardiac involvement in patients with sarcoidosis. The aim of this study in a large homogenous Scandinavian sarcoidosis cohort was therefore to identify risk factors of cardiac involvement in patients with sarcoidosis, and the value of initial routine investigation with ECG and cardiac related symptoms in screening for CS.MethodsIn this retrospective study a cohort of 1017 Caucasian patients with sarcoidosis were included. They were all screened with ECG at disease onset and investigated for CS according to clinical routine.ResultsAn abnormal ECG was recorded in 166 (16.3%) of the 1017 patients and CS was later diagnosed in 22 (13.2%) of them, compared to in one (0.1%) of the 851 sarcoidosis patients with a normal ECG (p < 0.0001). The risk for CS was higher in patients with a pathologic ECG combined with cardiac related symptoms (11/40) (27.5%) compared to those with pathologic ECG changes without symptoms (11/126) (8.7%) (p < 0.01). Furthermore, patients with Löfgren’s syndrome had a reduced risk for CS compared to those without (p < 0.05) the syndrome.ConclusionsThis study on an unusually large and homogenous sarcoidosis population demonstrate the importance of an abnormal ECG and cardiac related symptoms at disease onset as powerful predictors of a later diagnosis of cardiac sarcoidosis. In contrast, CS is very rare in subjects without symptoms and with a normal ECG. This knowledge is of importance, and may be used in a clinical algorithm, in identifying patients that should be followed and investigated extensively for the presence of CS.

HLA-alleles associated with increased risk for extra-pulmonary involvement in sarcoidosis.

Genetic factors influence the risk for disease as well as the clinical picture seen in sarcoidosis and especially the genes localized to the human leukocyte antigen (HLA) region on chromosome 6 are of importance. The aim of this study was to further investigate associations between HLA-DRB1 alleles and the risk for extra-pulmonary manifestations (EPMs), i.e. engagement of the skin, superficial lymph nodes, eyes, nervous system, kidneys, hypercalcemia, parotid and salivary glands, heart, liver, spleen and bone marrow in Scandinavian sarcoidosis patients. One thousand patients with together with a group of 2000 healthy individuals, matched for sex and age. HLA-DRB1 alleles were determined for all patients and controls. Excluding erythema nodosum and ankle arthritis, we found 288 of 1000 patients to have EPMs. There were 383 patients with Löfgrens syndrome (LS), and among them EPM were relatively uncommon and diagnosed in only 31 (8.1%) of the patients. In contrast, among the 617 non-LS patients, 257 (41.6%) had EPM (P < 0.0001). In LS patients, the absence of HLA-DRB1*03 substantially increased the risk factor for EPM (erythema nodosum and ankle arthritis excluded) (P < 0.0001). A distinct HLA allele combination, HLA-DRB1*04/*15, was identified as a risk factor for EPM in all patients (25 of 50 with DRB1*04/15 had EPM). In conclusion, EPM are common in non-LS sarcoidosis. Furthermore, HLA-typing of sarcoidosis patients can be used in the clinic to identify patients with an increased risk for EPM.