Variations in current clinical practice of postoperative pericardial effusion: a questionnaire study.

OBJECTIVE: Postoperative pericardial effusion (PPE) occurs frequently after cardiac surgery, potentially leading to life-threatening cardiac tamponade. Specific treatment guidelines are currently lacking, possibly leading to variations in clinical practice. Our goal was to assess clinical PPE management and evaluate variation between centres and clinicians. METHODS: A nationwide survey was sent to all interventional cardiologists and cardiothoracic surgeons in the Netherlands, regarding their preferred diagnostic and treatment modality of PPE. Clinical preferences were explored utilising four patient scenarios, each with a high/low echocardiographic and clinical suspicion of cardiac tamponade. Scenarios were also stratified by three PPE sizes (<1 cm, 1-2 cm, >2 cm). RESULTS: In total, 46/140 interventional cardiologists and 48/120 cardiothoracic surgeons responded (27/31 contacted centres). Cardiologists favoured routine postoperative echocardiography in all patients (44%), whereas cardiothoracic surgeons preferred routine imaging after specific procedures, especially mitral (85%) and tricuspid (79%) valve surgery. Overall, pericardiocentesis (83%) was preferred over surgical evacuation (17%). Regarding all patient scenarios, cardiothoracic surgeons significantly preferred evacuation compared with cardiologists (51% vs 37%, p<0.001). This was also observed with cardiologists employed in surgical centres compared with non-surgical centres (43% vs 31%, p=0.02). Inter-rater analysis varied from poor to near-excellent (к 0.22-0.67), suggesting varying PPE treatment preferences within one centre. CONCLUSION: There is significant variation in the preferred management of PPE between hospitals and clinicians, even within the same centre, possibly due to the lack of specific guidelines. Therefore, robust results of a systematic approach to PPE diagnosis and treatment are needed to formulate evidence-based recommendations and optimise patient outcome.

Neuroinflammation in cognitive decline post-cardiac surgery (the FOCUS study): an observational study protocol.

INTRODUCTION: Postoperative cognitive dysfunction occurs frequently after coronary artery bypass grafting (CABG). The underlying mechanisms remain poorly understood, but neuroinflammation might play a pivotal role. We hypothesise that systemic inflammation induced by the surgical trauma could activate the innate immune (glial) cells of the brain. This could lead to an exaggerated neuroinflammatory cascade, resulting in neuronal dysfunction and loss of neuronal cells. Therefore, the aims of this study are to assess neuroinflammation in vivo presurgery and postsurgery in patients undergoing major cardiac surgery and investigate whether there is a relationship of neuroinflammation to cognitive outcomes, changes to brain structure and function, and systemic inflammation. METHODS AND ANALYSIS: The FOCUS study is a prospective, single-centre observational study, including 30 patients undergoing elective on-pump CABG. Translocator protein (TSPO) positron emission tomography neuroimaging will be performed preoperatively and postoperatively using the second generation tracer 18F-DPA-714 to assess the neuroinflammatory response. In addition, a comprehensive cerebral MRI will be performed presurgery and postsurgery, in order to discover newly developed brain and vascular wall lesions. Up to 6 months postoperatively, serial extensive neurocognitive assessments will be performed and blood will be obtained to quantify systemic inflammatory responses and peripheral immune cell activation. ETHICS AND DISSEMINATION: Patients do not benefit directly from engaging in the study, but imaging neuroinflammation is considered safe and no side effects are expected. The study protocol obtained ethical approval by the Medical Research Ethics Committee region Arnhem-Nijmegen. This work will be published in peer-reviewed international medical journals and presented at medical conferences. TRIAL REGISTRATION NUMBER: NCT04520802.

Cardiac Troponin Composition Characterization after Non ST-Elevation Myocardial Infarction: Relation with Culprit Artery, Ischemic Time Window, and Severity of Injury.

BACKGROUND: Troponin composition characterization has been implicated as a next step to differentiate among non-ST elevation myocardial infarction (NSTEMI) patients and improve distinction from other conditions with troponin release. We therefore studied coronary and peripheral troponin compositions in relation to clinical variables of NSTEMI patients. METHODS: Samples were obtained from the great cardiac vein (GCV), coronary sinus (CS), and peripheral circulation of 45 patients with NSTEMI. We measured total cTnI concentrations, and assessed both complex cTnI (binary cTnIC + all ternary cTnTIC forms), and large-size cTnTIC (full-size and partially truncated cTnTIC). Troponin compositions were studied in relation to culprit vessel localization (left anterior descending artery [LAD] or non-LAD), ischemic time window, and peak CK-MB value. RESULTS: Sampling occurred at a median of 25 hours after symptom onset. Of total peripheral cTnI, a median of 87[78-100]% consisted of complex cTnI; and 9[6-15]% was large-size cTnTIC. All concentrations (total, complex cTnI, and large-size cTnTIC) were significantly higher in the CS than in peripheral samples (P < 0.001). For LAD culprit patients, GCV concentrations were all significantly higher; in non-LAD culprit patients, CS concentrations were higher. Proportionally, more large-size cTnTIC was present in the earliest sampled patients and in those with the highest CK-MB peaks. CONCLUSIONS: In coronary veins draining the infarct area, concentrations of both full-size and degraded troponin were higher than in the peripheral circulation. This finding, and the observed associations of troponin composition with the ischemic time window and the extent of sustained injury may contribute to future characterization of different disease states among NSTEMI patients.

Exercise and myocardial injury in hypertrophic cardiomyopathy.

OBJECTIVE: Troponin and high signal intensity on T2-weighted (HighT2) cardiovascular magnetic resonance imaging (CMRi) are both markers of myocardial injury in hypertrophic cardiomyopathy (HCM). The interplay between exercise and disease development remains uncertain in HCM. We sought to assess the occurrence of postexercise troponin rises and its determinants. METHODS: Multicentre project on patients with HCM and mutation carriers without hypertrophy (controls). Participants performed a symptom limited bicycle test with hs-cTnT assessment pre-exercise and 6 hours postexercise. Pre-exercise CMRi was performed in patients with HCM to assess measures of hypertrophy and myocardial injury. Depending on baseline troponin (< or >13 ng/L), a rise was defined as a >50% or >20% increase, respectively. RESULTS: Troponin rises occurred in 18% (23/127) of patients with HCM and 4% (2/53) in mutation carriers (p=0.01). Comparing patients with HCM with and without a postexercise troponin rise, maximum heart rates (157±19 vs 143±23, p=0.004) and maximal wall thickness (20 mm vs 17 mm, p=0.023) were higher in the former, as was the presence of late gadolinium enhancement (85% vs 57%, p=0.02). HighT2 was seen in 65% (13/20) and 19% (15/79), respectively (p<0.001). HighT2 was the only independent predictor of troponin rise (adjusted odds ratio 7.9; 95% CI 2.7 to 23.3; p<0.001). CONCLUSIONS: Postexercise troponin rises were seen in about 20% of patients with HCM, almost five times more frequent than in mutation carriers. HighT2 on CMRi may identify a group of particularly vulnerable patients, supporting the concept that HighT2 reflects an active disease state, prone to additional injury after a short episode of high oxygen demand.

Association between Lifelong Physical Activity and Disease Characteristics in HCM.

PURPOSE: Hypertrophic cardiomyopathy (HCM) is characterized by inappropriate left ventricular (LV) wall thickness. Adaptations to exercise can occasionally mimic certain HCM characteristics. However, it is unclear whether physical activity affects HCM genotype expression and disease characteristics. Consequently, we compared lifelong physical activity volumes between HCM gene carriers with and without HCM phenotype, and compared disease characteristics among tertiles of physical activity in phenotypic HCM patients. METHODS: We enrolled n = 22 genotype positive/phenotype negative (G+/P-) HCM gene carriers, n = 44 genotype positive/phenotype positive (G+/P+) HCM patients, and n = 36 genotype negative/phenotype positive (G-/P+) HCM patients. Lifelong physical activity was recorded using a questionnaire and quantified as metabolic equivalent of task hours per week. RESULTS: We included 102 participants (51 ± 16 yr, 49% male). Lifelong physical activity volumes were not different between G+/P+ and G+/P- subjects (16 [10-29] vs 14 [6-26] metabolic equivalent of task-hours per week, P = 0.33). Among phenotypic HCM patients, there was no difference in LV wall thickness, mass, and late gadolinium enhancement across physical activity tertiles. Patients with the highest reported physical activity volumes were younger at the time of diagnosis (tertile 1: 52 ± 14 yr, tertile 2: 49 ± 15 yr, tertile 3: 41 ± 18 yr; P = 0.03), and more often had a history of nonsustained ventricular tachycardia (4% vs 30% vs 30%, P = 0.03). CONCLUSIONS: Lifelong physical activity volumes are not associated with genotype-to-phenotype transition in HCM gene carriers. We also found no difference in LV wall thickness across physical activity tertiles. However, the most active HCM patients were younger at the time of diagnosis and had a higher arrhythmic burden. These observations warrant further exploration of the role of exercise in HCM disease development.

Prediction of Extensive Myocardial Fibrosis in Nonhigh Risk Patients With Hypertrophic Cardiomyopathy.

In nonhigh risk patients with hypertrophic cardiomyopathy (HC), the presence of extensive late gadolinium enhancement (LGEext) at cardiovascular magnetic resonance (CMR) imaging has been proposed as a risk modifier in the decision process for implantable cardioverter defibrillator implantation. With a pretest risk of about 10%, a strategy that alters the likelihood of LGEext could markedly affect efficacious CMR imaging. Our aim was to study the potential of clinical variables and biomarkers to predict LGEext. In 98 HC patients without any clear indication for implantable cardioverter defibrillator implantation, we determined the discriminative values of a set of clinical variables and a panel of biomarkers (hs-cTnT, NTproBNP, GDF-15, and Gal-3, CICP) for LGEext, that is, LGE ≥15% of the left ventricular mass. LGEext was present in 10% (10/98) of patients. The clinical prediction model contained a history of nonsustained ventricular tachycardia, maximal wall thickness and reduced systolic function (c-statistic: 0.868, p <0.001). Of all biomarkers, only hs-cTnT was associated with LGEext, in addition to the improved clinical model of diagnostic accuracy (p = 0.04). A biomarker-only strategy allowed the exclusion of LGEext in half of the cohort, in case of a hs-cTnT concentration less than the optimal cutoff (Youden index; 8 ng/L-sensitivity 100%, specificity 54%). In conclusion, in this nonhigh risk HC cohort, the pretest likelihood of LGEext can be altered using clinical variables and the addition of hs-cTnT. The promising findings with the use of hs-cTnT only call for new initiatives to study its impact on efficacious CMR imaging in a larger HC population, either with or without additional use of clinical variables.

A multi-site coronary sampling study on CRP in non-STEMI: Novel insights into the inflammatory process in acute coronary syndromes.

BACKGROUND AND AIMS: Inflammation has become a key element in cardiovascular disease, and recently, new anti-inflammatory interventions have shown promising results. In this context, CRP levels have been thoroughly studied in vitro and in animals, but studies in humans are scarce and insights into its release, site(s) of production and uptake are not uniform. METHODS: We performed a biomarker study with multi-site sampling in the coronary circulation, in non-ST elevation MI (NSTEMI) patients with coronary angiography and right-sided catheterisation. Trans-lesional gradients were obtained by sampling distal to the culprit lesion, in patients with a suitable anatomy. To asses trans-cardiac gradients, blood was sampled from the systemic circulation, coronary sinus (CS) and great cardiac vein. Concentrations of CRP were measured with a high-sensitivity assay. RESULTS: In 42 patients, a median systemic venous CRP concentration of 4.97 mg/L was observed. There was no evidence of a trans-lesional gradient (4.59 mg/L versus 4.56 mg/L, p = 0.278; n = 14). A significant decrease in CRP concentration was observed between systemic arterial and CS samples (4.88 mg/L versus 4.44 mg/L; p < 0.001; n = 42). This trans-cardiac gradient was irrespective of time of presentation, infarct size and culprit lesion location. The gradient was not only driven by blood that ran through the injured myocardium, but also by lower CRP concentrations in the coronary veins that drain non-infarcted myocardium. CONCLUSIONS: In the context of NSTEMI, we observed a trans-cardiac decrease in CRP, which may indicate the first human in vivo proof of a net CRP uptake by the myocardium, with a role for CRP both in the injured and adjacent myocardium.

High T2-weighted signal intensity for risk prediction of sudden cardiac death in hypertrophic cardiomyopathy.

In search of improved risk stratification in hypertrophic cardiomyopathy (HCM), CMR imaging has been implicated as a potential tool for prediction of sudden cardiac death (SCD). In follow-up of the promising results with extensive late gadolinium enhancement (LGE), high signal-intensity on T2-weighted imaging (HighT2) has become subject of interest given its association with markers of adverse disease progression, such as LGE, elevated troponin and non-sustained ventricular tachycardia. In lack of follow-up cohorts, we initiated an exploratory study on the association between HighT2 and the internationally defined risk categories of SCD. In a cohort of 109 HCM patients from a multicenter study on CMR imaging and biomarkers, we estimated the 5-year SCD risk (HCM Risk-SCD model). Patients were categorized as low (< 4%), intermediate (≥ 4-<6%) or high (≥ 6%) risk. In addition, risk categorization according to the ACC/AHA guidelines was performed. HighT2 was present in 27% (29/109). Patients with HighT2 were more often at an intermediate-high risk of SCD according to the European (28 vs. 10%, p = .032) and American guidelines (41 vs. 18%, p = .010) compared to those without HighT2. The estimated 5-year SCD risk of our cohort was 1.9% (IQR 1.3-2.9%), and projected SCD rates were higher in patients with than without HighT2 (2.8 vs. 1.8%, p = .002). In conclusion, HCM patients with HighT2 were more likely to be intermediate-high risk, with projected SCD rates that were 1.5 fold higher than in patients without HighT2. These pilot findings call for corroborative studies with more intermediate-high risk HCM patients and clinical follow-up to assess whether HighT2 may have additional value to current risk stratification.

High T2-weighted signal intensity is associated with elevated troponin T in hypertrophic cardiomyopathy.

OBJECTIVE: Areas of high signal intensity (HighT2) on T2-weighted cardiovascular magnetic resonance (CMR) imaging have been demonstrated in hypertrophic cardiomyopathy (HCM). It has been hypothesised that HighT2 may indicate active tissue injury in HCM. In this context, we studied HighT2 in relation to cardiac troponin. METHODS: Outpatient HCM patients without a history of coronary artery disease underwent CMR imaging at 1.5 T using T2-weighted, cine and late gadolinium enhancement (LGE) imaging to assess HighT2, left ventricular (LV) function, LV mass and the presence and extent of LGE. Highly sensitive cardiac troponin T (hs-cTnT) was assessed as a marker of injury, with hs-cTnT ≥14 and >3 ng/L defined as an elevated and detectable troponin. RESULTS: HighT2 was present in 28% of patients (28/101). An elevated hs-cTnT was present in 54% of patients with HighT2 (15/28) compared with 14% of patients without HighT2 (10/73) (p<0.001). Hs-cTnT was detectable in 96% of patients with HighT2 (27/28) compared with 66% of patients without HighT2 (48/73) (p=0.002). In case of an undetectable hs-cTnT, HighT2 was only seen in 4% (1/26). In addition, the extent of HighT2 was related with increasing hs-cTnT concentrations (Spearman's ρ: 0.42, p<0.001). CONCLUSIONS: In this CMR study of patients with HCM, we observed HighT2 in a quarter of patients, and demonstrated that HighT2 was associated with an elevated hs-cTnT. This observation, combined with the very high negative predictive value of an undetectable hs-cTnT for HighT2, provides supportive evidence for the hypothesis that HighT2 is indicative of recently sustained myocyte injury.

Audiometric Characteristics of a Dutch DFNA10 Family With Mid-Frequency Hearing Impairment.

OBJECTIVES: Mutations in EYA4 can cause nonsyndromic autosomal dominant sensorineural hearing impairment (DFNA10) or a syndromic variant with hearing impairment and dilated cardiomyopathy. A mutation in EYA4 was found in a Dutch family, causing DFNA10. This study is focused on characterizing the hearing impairment in this family. DESIGN: Whole exome sequencing was performed in the proband. In addition, peripheral blood samples were collected from 23 family members, and segregation analyses were performed. All participants underwent otorhinolaryngological examinations and pure-tone audiometry, and 12 participants underwent speech audiometry. In addition, an extended set of audiometric measurements was performed in five family members to evaluate the functional status of the cochlea. Vestibular testing was performed in three family members. Two individuals underwent echocardiography to evaluate the nonsyndromic phenotype. RESULTS: The authors present a Dutch family with a truncating mutation in EYA4 causing a mid-frequency hearing impairment. This mutation (c.464del) leads to a frameshift and a premature stop codon (p.Pro155fsX). This mutation is the most N-terminal mutation in EYA4 found to date. In addition, a missense mutation, predicted to be deleterious, was found in EYA4 in two family members. Echocardiography in two family members revealed no signs of dilated cardiomyopathy. Results of caloric and velocity step tests in three family members showed no abnormalities. Hearing impairment was found to be symmetric and progressive, beginning as a mid-frequency hearing impairment in childhood and developing into a high-frequency, moderate hearing impairment later in life. Furthermore, an extended set of audiometric measurements was performed in five family members. The results were comparable to those obtained in patients with other sensory types of hearing impairments, such as patients with Usher syndrome type IIA and presbyacusis, and not to those obtained in patients with (cochlear) conductive types of hearing impairment, such as DFNA8/12 and DFNA13. CONCLUSIONS: The mid-frequency hearing impairment in the present family was found to be symmetric and progressive, with a predominantly childhood onset. The results of psychophysical measurements revealed similarities to other conditions involving a sensory type of hearing impairment, such as Usher syndrome type IIA and presbyacusis. The study results suggest that EYA4 is expressed in the sensory cells of the cochlea. This phenotypic description will facilitate counseling for hearing impairment in DFNA10 patients.

Effect of metformin pretreatment on myocardial injury during coronary artery bypass surgery in patients without diabetes (MetCAB): a double-blind, randomised controlled trial.

BACKGROUND: During coronary artery bypass graft (CABG) surgery, ischaemia and reperfusion damage myocardial tissue, and increased postoperative plasma troponin concentration is associated with a worse outcome. We investigated whether metformin pretreatment limits cardiac injury, assessed by troponin concentrations, during CABG surgery in patients without diabetes. METHODS: We did a placebo-controlled, double-blind, single-centre study in an academic hospital in Nijmegen (Netherlands) in adult patients without diabetes undergoing an elective on-pump CABG procedure. We randomly assigned patients (1:1) in blocks of ten via a computer-generated randomisation sequence to either metformin hydrochloride (500 mg three times per day) or placebo (three times per day) for 3 days before surgery. The last dose was given roughly 3 h before surgery. Patients, investigators, trial staff, and the statistician were all masked to treatment allocation. The primary endpoint was the plasma concentration of high-sensitive troponin I at 6, 12, and 24 h postreperfusion after surgery, analysed in the per-protocol population with a mixed-model analysis using all these timepoints. Secondary endpoints included the occurrence of clinically relevant arrhythmias within 24 hours after reperfusion, the need for inotropic support, time to detubation, duration of stay in the intensive-care unit, and postoperative use of insulin. This study is registered with ClinicalTrials.gov, number NCT01438723. FINDINGS: Between Nov 8, 2011, and Nov 22, 2013, we randomly assigned 111 patients to treatment (57 to metformin and 54 to placebo). Five patients dropped out from the metformin group, and six from the placebo group. 52 patients in the metformin group and 48 patients in the placebo group were included in the per-protocol analysis. Geometric mean high-sensitivity troponin I increased from 0 µg/L to 3·67 µg/L (95% CI 3·06-4·41) with metformin and to 3·32 µg/L (2·75-4·01) with placebo at 6 h after reperfusion; 2·84 µg/L (2·37-3·41) and 2·45 µg/L (2·02-2·96), respectively, at 12 h; and to 1·77 µg/L (1·47-2·12) and 1·60 µg/L (1·32-1·94) at 24 h. The concentrations did not differ significantly between the groups (difference 12·3% for all timepoints [95% CI -12·4 to 44·1] p=0·35). Occurrence of arrhythmias did not differ between groups (three [5·8%] of 52 patients who received metformin vs three [6·3%] of 48 patients who received placebo; p=1·00). There was no difference between groups in the need for inotropic support, time to detubation, duration of stay in the intensive-care unit, or postoperative use of insulin. No patients died within 30 days after surgery. Occurrence of gastrointestinal discomfort (mostly diarrhoea) was significantly higher with metformin than with placebo (11 [21·2%] of 52 vs two [4·2%] of 48 patients; p=0·01). INTERPRETATION: Short-term metformin pretreatment, although safe, does not seem to be an effective strategy to reduce periprocedural myocardial injury in patients without diabetes undergoing CABG surgery. FUNDING: Netherlands Organisation for Health Research and Development and Netherlands Heart Foundation.

Pre-hospital triage for primary angioplasty: direct referral to the intervention center versus interhospital transport.

OBJECTIVES: We sought to study the impact of direct referral to an intervention center after pre-hospital diagnosis of ST-segment elevation myocardial infarction (STEMI) on treatment intervals and outcome. BACKGROUND: Primary angioplasty has become the preferred reperfusion strategy in STEMI. Ambulance diagnosis and direct referral to an intervention center is an attractive treatment option that has not been studied extensively. METHODS: Consecutive pre-hospital patients with STEMI, who were referred to our intervention center for primary angioplasty between 2005 and 2007, were studied. After pre-hospital diagnosis, patients were either directly transported to our center or referred through a nonintervention center. The catheterization laboratory was activated before transport to the intervention center. RESULTS: Of the 581 patients referred, 454 (78%) came with direct transport and 127 (22%) through a nonintervention center. Direct transport was associated with a higher proportion of patients treated within the 90-min time window of the STEMI guidelines: 82% versus 23% (p < 0.01). Patients directly transported had a significantly shorter median symptom-to-balloon time of 149 min (Interquartile range: 118 to 197 min) versus 219 min (interquartile range: 178 to 315 min), p < 0.01, a higher post-procedural Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 rate (92% vs. 84%; p = 0.03), and a lower 1-year mortality rate (7% vs. 13%; p = 0.03). Direct transport to the intervention center was independently associated with the symptom-to-balloon time, which in turn was an independent predictor of post-procedural TIMI flow grade 3, a strong prognosticator of outcome. CONCLUSIONS: After ambulance-based diagnosis of STEMI, direct transport to an intervention center with pre-hospital notification of the catheterization laboratory more than triples the proportion of patients treated within the time window of the guidelines. Time to balloon was an independent predictor of post-procedural TIMI flow grade 3, which underscores the need to reduce treatment delays.

Sustained coronary patency after fibrinolytic therapy as independent predictor of 10-year cardiac survival Observations from the Antithrombotics in the Prevention of Reocclusion in COronary Thrombolysis (APRICOT) trial.

BACKGROUND: Whether late coronary patency after myocardial infarction has prognostic impact independent of left ventricular function remains a matter of debate. Reocclusion rates in the first year after fibrinolysis vary between 20% and 30%. Of all reocclusions, about 30% present as clinical reinfarction, associated with a 2-fold-increased risk of mortality. The clinical impact of reocclusion that presents without reinfarction has not been studied; but an association has been demonstrated with impaired contractile recovery of left ventricular function, the strongest prognosticator of long-term outcome. We therefore studied the impact of 3-month coronary patency after successful fibrinolysis on 10-year cardiac survival. METHODS: In the APRICOT-1 trial, 248 ST-elevation myocardial infarction patients with an open infarct artery 24 hours after fibrinolysis had 3-month repeated angiography. Ten-year clinical follow-up was complete in 99.6%. RESULTS: The reocclusion rate was 29% (71/248). Of these reocclusions, 24% presented as clinical reinfarction (17/71). Cardiac survival at 10 years was 73% in patients with a reoccluded infarct artery and 88% in patients with sustained patency (P < .01). This difference was also present in patients in whom reocclusion was only detected as a result of systematic repeated angiography, that is, in the absence of reinfarction or ischemic symptoms between angiograms (70% vs 86%, P < .03). Multivariable analysis identified sustained patency at 3-month angiography as independent predictor of 10-year cardiac survival (hazard ratio 2.10, 95% CI 1.10-4.02) together with left ventricular ejection fraction. CONCLUSIONS: Sustained infarct artery patency in the first 3 months after successful fibrinolysis is a strong predictor of 10-year cardiac survival, independent of left ventricular function. Notably, this also holds true when reocclusion occurs without signs of clinical reinfarction or recurrent ischemia. Therefore, future preventive strategies should also focus on "clinically silent" reocclusions. Additional studies on better antithrombotic regimens and the combination with a routine invasive strategy early after successful fibrinolysis are warranted.

Reperfusion therapy in out-of-hospital cardiac arrest: current insights.

Although early care in out-of-hospital cardiac arrest has been improved over the past decades, survival remains poor and neurological performance after survival is often impaired. Consequently, new therapies are needed to improve outcome. As thrombotic processes such as acute myocardial infarction or pulmonary embolism are frequent causes of cardiac arrest, therapies like fibrinolysis or percutaneous coronary intervention are of interest. Both therapies can restore coronary and pulmonary perfusion in cardiac arrest patients and, additionally, fibrinolysis might prevent microthrombi to the brain. In this review, the rationale, safety and efficacy of reperfusion therapy in patients with out-of-hospital cardiac arrest will be discussed.

Antiplatelet therapy and progression of coronary artery disease: a placebo-controlled trial with angiographic and clinical follow-up after myocardial infarction.

INTRODUCTION: In patients after ST-elevation myocardial infarction (STEMI), antiplatelet therapy reduces subsequent cardiac events, which are often attributed to recurrent thrombosis with (sub)total occlusion in the infarct-related artery. Whether antiplatelet therapy influences the often subclinical process of coronary disease progression in noninfarct arteries has not been reported. METHODS: Quantitative coronary angiography of noninfarct arteries was performed on paired cine-angiograms of 149 patients from fibrinolytic trials who had a patent infarct-related artery 3 to 4 weeks following STEMI and who were randomized to either continue the daily combination of 50-mg aspirin and 400-mg dipyridamole or to matching placebo. Follow-up angiography was scheduled at 1 year. RESULTS: On a per-patient basis, the change in minimal luminal diameter (MLD) was 0.00 mm in the aspirin/dipyridamole group (n = 76) and was 0.01 mm in the placebo group (n = 73). There was no difference between these groups in the changes in MLD (-0.02 mm; 95% CI -0.09 to 0.05), neither were there significant differences in mean luminal diameter and diameter stenosis. Progression (1 segment/patient with > or = 0.40 mm decrease in MLD) was seen in two thirds of patients and did not independently predict long-term death and/or reinfarction. CONCLUSION: In this placebo-controlled trial after STEMI, the combination of aspirin and dipyridamole did not affect noninfarct artery disease progression. Progression did not predict long-term clinical outcome.

Transport for abciximab facilitated primary angioplasty versus on-site thrombolysis with a liberal rescue policy: the randomised Holland Infarction Study (HIS).

AIMS: As of to date, the only large transportation trial comparing on-site fibrin-specific thrombolysis with transfer for primary angioplasty in patients presenting in a referral centre is the DANAMI-2 trial, with only 3% rescue angioplasty. The Holland Infarction Study (HIS) compared abciximab facilitated primary angioplasty (FP) with on-site fibrin-specific thrombolytic therapy (TT) with a liberal protocol-driven rescue angioplasty (transport to intervention centre in case < 50% ST resolution at 60 min). METHODS AND RESULTS: Patients in a referral centre without shock and < 4.5 h of chest pain presenting with ST-elevation having > or = 12 mm ST-segment shift were randomised to either strategy. Of the originally planned 900 patients only 48 were included due to suspension of financial funding. Death, recurrent MI and stroke at one year was 8% for the FP-group and 22% for the TT-group (p = 0.2). Two hours after randomisation the rates of complete ST-segment resolution (> or =70%) were 52% and 35%, respectively (p = 0.2). CONCLUSION: This prematurely discontinued randomised transportation trial shows favorable trends with respect to long-term clinical outcome and early ST-resolution for abciximab facilitated primary angioplasty. In view of the real world delays associated with interhospital transport for primary angioplasty, treatment strategies focusing on early fibrin-specific lysis with a liberal selective rescue policy are warranted.