Mikkel Malby Schoos

Exenatide Reduces Final Infarct Size in Patients With ST-Segment–Elevation Myocardial Infarction and Short-Duration of Ischemia

Background— Exenatide has been demonstrated to be cardioprotective as an adjunct to primary percutaneous coronary intervention in patients with ST-segment–elevation myocardial infarction (STEMI). The aim of the post hoc analysis study was to evaluate the effect of exenatide in relation to system delay, defined as time from first medical contact to first balloon. Methods and Results— Patients with STEMI and Thrombolysis In Myocardial Infarction flow 0/1 were randomly assigned to intravenous exenatide or placebo continuous infusion. Study treatment was commenced 15 minutes before intervention and maintained for 6 hours after the procedure. The patients were stratified according to median system delay (132 minutes). Final infarct size and myocardial area at risk were measured by cardiovascular magnetic resonance. Among patients with a system delay ⩽132 minutes (n=74), treatment with exenatide resulted in a smaller infarct size (9 grams [interquartile range (IQR), 4–13] versus 13 grams [IQR, 8–24], P=0.008, corresponding to 8% [IQR, 4–12] versus 11% [IQR, 7–17] of the left ventricle, P=0.015). In a regression analysis adjusting for myocardial area at risk the data points of the exenatide group lay significantly lower than for the placebo group (P=0.006). In the patients with system delay >132 minutes (n=74) no difference was observed in infarct size expressed as grams (P=0.49) or percentage (P=0.46). There was significant interaction between system delay (less than or equal to median versus greater than median) and treatment allocation in terms of infarct size (P=0.018). Conclusions— In this post hoc analysis, exenatide treatment was associated with a 30% decrease in final infarct size in patients with short system delay, whereas no cardioprotective effect in patients with long system delay was seen. However, this finding must be confirmed in larger studies. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00835848.

Prevalence, impact, and predictive value of detecting subclinical coronary and carotid atherosclerosis in asymptomatic adults: the BioImage study.

BACKGROUND Although recent studies suggest that measuring coronary artery calcification (CAC) may be superior to indirect atherosclerotic markers in predicting cardiac risk, there are limited data evaluating imaging-based biomarkers that directly quantify atherosclerosis in different vascular beds performed in a single cohort. OBJECTIVES The BioImage Study (A Clinical Study of Burden of Atherosclerotic Disease in an At-Risk Population) sought to identify imaging biomarkers that predict near-term (3-year) atherothrombotic events. METHODS The BioImage Study enrolled 5,808 asymptomatic U.S. adults (mean age: 69 years, 56.5% female) in a prospective cohort evaluating the role of vascular imaging on cardiovascular risk prediction. All patients were evaluated by CAC and novel 3-dimensional carotid ultrasound. Plaque areas from both carotid arteries were summed as the carotid plaque burden (cPB). The primary endpoint was the composite of major adverse cardiac events (MACE) (cardiovascular death, myocardial infarction, and ischemic stroke). A broader secondary MACE endpoint also included all-cause death, unstable angina, and coronary revascularization. RESULTS Over a median follow-up of 2.7 years, MACE occurred in 216 patients (4.2%), of which 82 (1.5%) were primary events. After adjustment for risk factors, and compared with individuals without any cPB, hazard ratios for MACE were 0.78 (95% confidence interval [CI]: 0.31 to 1.91), 1.45 (95% CI: 0.67 to 3.14), and 2.36 (95% CI: 1.13 to 4.92) with increasing cPB tertile, with similar results for CAC. Net reclassification significantly improved with either cPB (0.23) or CAC (0.25). MACE rates increased simultaneously with higher levels of both cPB and CAC. CONCLUSIONS Detection of subclinical carotid or coronary atherosclerosis improves risk predictions and reclassification compared with conventional risk factors, with comparable results for either modality. Cost-effective analyses are warranted to define the optimal roles of these complementary techniques. (BioImage Study: A Clinical Study of Burden of Atherosclerotic Disease in an At-Risk Population; NCT00738725).

Impact of system delay on infarct size, myocardial salvage index, and left ventricular function in patients with ST-segment elevation myocardial infarction.

BACKGROUND The association between reperfusion delay and myocardial damage has previously been assessed by evaluation of the duration from symptom onset to invasive treatment, but results have been conflicting. System delay defined as the duration from first medical contact to first balloon dilatation is less prone to bias and is also modifiable. The purpose was to evaluate the impact of system delay on myocardial salvage index (MSI) and infarct size in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention (PCI). METHODS In patients with ST-elevation myocardial infarction, MSI and final infarct size were assessed using cardiovascular magnetic resonance. Myocardial area at risk was measured within 1 to 7 days, and final infarct size was measured 90 ± 21 days after intervention. Patients were grouped according to system delay (0 to 120, 121 to 180, and >180 minutes). RESULTS In 219 patients, shorter system delay was associated with a smaller infarct size (8% [interquartile range 4-12%], 10% [6-16%], and 13% [8-17%]; P < .001) and larger MSI (0.77 [interquartile range 0.66-0.86], 0.72 [0.59-0.80], and 0.68 [0.64-0.72]; P = .005) for a system delay of up to 120, 121 to 180, and >180 minutes, respectively. A short system delay as a continuous variable independently predicted a smaller infarct size (r = 0.30, P < .001) and larger MSI (r = -0.25, P < .001) in multivariable linear regression analyses. Finally, shorter system delay (0-120 minutes) was associated with improved function (P = .019) and volumes of left ventricle (P = .022). CONCLUSIONS A shorter system delay resulted in smaller infarct size, larger MSI, and improved LV function in patients treated with primary PCI. Thus, this study confirms that minimizing system delay is crucial for primary PCI-related benefits.

Stroke After Transcatheter Aortic Valve Replacement: Incidence, Risk Factors, Prognosis, and Preventive Strategies

The first transcatheter aortisc valve replacement (TAVR) was performed in 2002, and has been proven beneficial in inoperable and high‐risk patients for open heart surgery. Stroke occurrence after TAVR, both periprocedure and at follow‐up, has not been well described. We sought to review incidence, pathophysiology, predictors, prognosis, and current preventive strategies of cerebrovascular accidents (CVAs) after TAVR. Studies were selected from a Medline search if they contained clinical outcomes data after TAVR. Acute and subacute CVAs after TAVR have been reported in 3% to 6% of patients. Approximately 45% of CVAs occur within 2 days after TAVR; 28% between 3 and 10 days; 4% between 10 and 30 days; and 10.5% occur from 1 month to 2 years. Clinically silent cerebral embolisms have been reported, with an incidence greatly exceeding that of overt CVAs. Underlying pathophysiologic mechanisms for CVAs can be broadly categorized into embolic and nonembolic causes, as well as procedural and postprocedural (early and late). Important predictors of early CVAs are small aortic valve area, atrial fibrillation, and balloon postdilation, whereas late CVAs are mostly influenced by chronic atrial fibrillation, prior cerebrovascular disease, and transapical approach. Following stroke, patients exhibit increased morbidity and mortality. A multilevel approach for the prevention of CVAs includes improved interventional techniques, embolic protection devices, antithrombotic treatment, close monitoring, and aggressive management of modifiable risk factors. Technology advances notwithstanding stroke morbidity and mortality remains steady. The significance of silent cerebral embolism on prognosis remains uncertain, and optimal medical treatment during and after TAVR should be further investigated.

Pre-hospital diagnosis and transfer of patients with acute myocardial infarction--a decade long experience from one of Europe's largest STEMI networks.

Early reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) is essential. Although primary percutaneous coronary intervention (pPCI) is the preferred revascularization technique, it often involves longer primary transportation or secondary inter-hospital transfers and thus longer system related delays. The current ESC Guidelines state that PCI should be performed within 120 minutes from first medical contact, and door-to-balloon time should be <60 minutes in order to reduce long term mortality. STEMI networks should be established with regionalization of pPCI treatment to address the challenges regarding pre-hospital treatment, triage and transport of STEMI patients and collaborations between hospitals and Emergency Medical Services (EMS). We report on a regional decade long experience from one of Europes largest STEMI networks located in Eastern Denmark, which serves a catchment area of 2.5 million inhabitants by processing ~4000 prehospital ECGs annually transmitted from 4 EMS systems to a single pPCI center treating 1100 patients per year. This organization has led to a significant improvement of the standard of therapy for acute myocardial infarction (MI) patients leading to historically low 30-day mortality for STEMI patients (<6%). About 70-80% of all STEMI patients are being triaged from the field and rerouted to the regional pPCI center. Significant delays are still found among patients who present to local hospitals and for those who are first admitted to a local emergency room and thus subject to inter-hospital transfer. In the directly transferred group, approximately 80% of patients can be treated within the current guideline time window of 120 minutes when triaged within a 185 km (~115 miles) radius. Since 2010, a Helicopter Emergency Medical Service has been implemented for air rescue. Air transfer was associated with a 20-30 minute decrease from first medical contact to pPCI, at distances down to 90 km from the pPCI center and with a trend toward better survival among air transported patients. The pPCI center also serves a small island in the Baltic Sea, where STEMI patients are rescued via air force helicopters. Based on data from more than 100 patients transferred over the past decade, we have found a similar in-hospital and long term mortality rate compared to the main island inhabitants. In conclusion, with the optimal collaboration within a STEMI network including local hospitals, university clinics, EMS and military helicopters using the same telemedicine system and field triage of STEMI patients, most patients can be treated within the time limits suggested by the current guidelines. These organizational changes are likely to contribute to the improved mortality rate for STEMI patients.

Usefulness of Pregnancy-Associated Plasma Protein A in Patients With Acute Coronary Syndrome

To investigate whether pregnancy-associated plasma protein-A (PAPP-A) is a prognostic marker in patients admitted with high-risk acute coronary syndrome. In patients admitted with high-risk non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and ST-segment elevation myocardial infarction (STEMI), risk stratification is primarily determined by the markers of myocardial necrosis and known demographic risk profiles. However, it has recently been proposed that the presence and extent of vulnerable plaques might influence the prognosis significantly. A marker for the vulnerable plaque could identify patients at high risk who would potentially benefit from intensive treatment and surveillance. Two populations of consecutive patients admitted with high-risk NSTE-ACS (n = 123) and STEMI (n = 314) were evaluated with serial measurements of PAPP-A. The incidence of mortality and nonfatal myocardial infarction was prospectively registered for 2.66 to 3.47 years. In the patients with high-risk NSTE-ACS, PAPP-A was related to the risk of nonfatal myocardial infarction (p = 0.02) and death (p = 0.03). This result was consistent on multivariate analysis of the combination of mortality or nonfatal myocardial infarction (odds ratio 2.65, 95% confidence interval 1.40 to 5.03) but not for mortality alone (p = NS). In patients with STEMI, PAPP-A was related to the risk of death (p = 0.01) but not the composite outcome of myocardial infarction and death. This was also true after adjustment for other univariate predictors of death (odds ratio 2.19, 95% confidence interval 1.16 to 4.16). In conclusion, PAPP-A seems to be valuable in predicting the outcomes of patients admitted with high-risk NSTE-ACS or STEMI.

Echocardiographic predictors of exercise capacity and mortality in chronic obstructive pulmonary disease

BackgroundChronic obstructive pulmonary disease (COPD) reduces exercise capacity, but lung function parameters do not fully explain functional class and lung-heart interaction could be the explanation. We evaluated echocardiographic predictors of mortality and six minutes walking distance (6MWD), a marker for quality of life and mortality in COPD.MethodsNinety COPD patients (GOLD criteria) were evaluated by body plethysmography, 6MWD and advanced echocardiography parameters (pulsed wave tissue Doppler and speckle tracking).ResultsMean 6MWD was 403 (± 113) meters. All 90 subjects had preserved left ventricular (LV) ejection fraction 64.3% ± 8.6%. Stroke volume decreased while heart rate increased with COPD severity and hyperinflation. In 66% of patients, some degree of diastolic dysfunction was present. Mitral tissue Doppler data in COPD could be interpreted as a sign of low LV preload and not necessarily an intrinsic impairment in LV relaxation/compliance. Tricuspid regurgitation (TR) increased with COPD severity and hyperinflation. Age (p < 0.001), BMI (p < 0.001), DLCO SB (p < 0.001) and TR (p 0.005) were independent predictors of 6MWD and a multivariable model incorporating heart function parameters (adjusted r2 = .511) compared well to a model with lung function parameters alone (adjusted r2 = .475). LV global longitudinal strain (p = 0.034) was the only independent predictor of mortality among all baseline, body plethysmographic and echocardiographic variables.ConclusionsAmong subjects with moderate to severe COPD and normal LVEF, GLS independently predicted all-cause mortality. Exercise tolerance correlated with standard lung function parameters only in univariate models; in subsequent models including echocardiographic parameters, longer 6MWD correlated independently with milder TR, better DLCO SB, younger age and lower BMI. We extended the evidence on COPD affecting cardiac chamber volumes, LV preload, heart rate, as well as systolic and diastolic function. Our results highlight lung-heart interaction and the necessity of cardiac evaluation in COPD.

Pregnancy-associated plasma protein-A, a marker for outcome in patients suspected for acute coronary syndrome.

OBJECTIVES To examine if pregnancy-associated plasma protein-A (PAPP-A) in patients with chest pain, could identify patients at risk for death or myocardial infarction. DESIGN AND METHODS Patients admitted with chest pain and both normal ECG and normal biomarkers were evaluated by serial measurement of PAPP-A. Main outcome measures were mortality and non-fatal myocardial infarction. RESULTS Median age of patients included (415) was 67years and 43% were women. The risk of death or non-fatal myocardial infarction after 3 months was 15% in the highest quartile of circulating PAPP-A compared with 3% in the lowest quartile (relative risk 3.7, p<0.01). Corresponding numbers after 1 year were 24% and 10% (relative risk 2.4, p=0.01). CONCLUSION In patients admitted with chest pain and both normal ECG and normal biomarkers PAPP-A seems to be valuable for predicting patients at high risk of death or non-fatal myocardial infarction.

Reperfusion delay in patients treated with primary percutaneous coronary intervention: insight from a real world Danish ST-segment elevation myocardial infarction population in the era of telemedicine:

Background: Reperfusion delay in ST-segment elevation myocardial infarction (STEMI) predicts adverse outcome. We evaluated time from alarm call (system delay) and time from first medical contact (PCI-related delay), where fibrinolysis could be initiated, to balloon inflation in a pre-hospital organization with tele-transmitted electrocardiograms, field triage and direct transfer to a 24/7 primary percutaneous coronary intervention (PPCI) center. Methods and results: This was a single center cohort study with long-term follow-up in 472 patients. The PPCI center registry was linked by person identification number to emergency medical services (EMS) and National Board of Health databases in the period of 2005–2008. Patients were stratified according to transfer distances to PPCI into zone 1 (0–25 km), zone 2 (65–100 km) and zone 3 (101–185 km) and according to referral by pre-hospital triage. System delay was 86 minutes (interquartile range (IQR) 72–113) in zone 1, 133 (116–180) in zone 2 and 173 (145–215) in zone 3 (p<0.001). PCI-related delay in directly referred patients was 109 (92–121) minutes in zone 2, but exceeded recommendations in zone 3 (139 (121–160)) and for patients admitted via the local hospital (219 (171–250)). System delay was an independent predictor of mortality (p<0.001). Conclusions: Pre-hospital triage is feasible in 73% of patients. PCI-related delay exceeded European Society of Cardiology (ESC) guidelines for patients living >100 km away and for non-directly referred patients. Sorting the PPCI centers catchment area into geographical zones identifies patients with long reperfusion delays. Possible solutions are pharmaco-invasive regiments, research in early ischemia detection, airborne transfer and EMS personnel education that ensures pre-hospital triage.

Association between lectin complement pathway initiators, C-reactive protein and left ventricular remodeling in myocardial infarction—A magnetic resonance study

BACKGROUND Lectin complement pathway (LP) activation is an important mechanism in myocardial ischemia reperfusion injury (IRI). LP is activated via the recognition molecules mannose-binding lectin (MBL), ficolins-2 and-3 and is regulated by MBL/Ficolin-associated Protein-1 (MAP-1). Also, C-reactive protein (CRP) and ficolin-2 interact in vitro, but the role of the ficolins in IRI is unknown. METHODS AND RESULTS In 55 patients with ST segment elevation myocardial infarction, we investigated the association of LP components and CRP in plasma samples with left ventricular (LV) end systolic and diastolic volumes (ESV and EDV) and infarct size, assessed by cardiac magnetic resonance early at 1-3 days after primary percutaneous coronary intervention and at 6 months follow-up. Opposed to MBL, ficolin-3 and MAP-1, ficolin-2 levels were low at baseline. At baseline, ficolin-2>median was associated with ESV and EDV increases by 7.83 ml/m(2) (p=0.004) and 14.04 ml/m(2) (p<0.001). MBL and MAP-1 were not associated with LV dilatation, yet ficolin-2 and MBL worked synergistically and the combination of their levels>median was associated with ESV (11.21 ml/m(2); p=0.017) and EDV increases (14.72 ml/m(2); p=0.006). MAP-1median had the greatest LV dilatation (17.61 ml/m(2)). The ficolin-2 × CRP interaction variable was positively associated with infarct size and inversely associated with EDV change over 6 months (p=0.006). There was no interaction between CRP and the other LP molecules. CONCLUSION The LP initiator molecule ficolin-2 and combinations of ficolin-2, MBL and MAP-1 are associated with LV dilatation after myocardial infarction. Interaction of ficolin-2 and CRP was associated with infarct size and LV remodeling, indicating a potential role for LP and LP-pentraxin cross-activation in IRI and LV remodeling.