Transesophageal echocardiography of cardiac function in Nile crocodiles - A novel tool for assessing complex hemodynamic patterns.

BACKGROUND: The crocodilian heart is unique among reptiles with its four-chambered structure and complete intracardiac separation of pulmonary and systemic blood flows and pressures. Crocodiles have retained two aortic arches; one from each ventricle, that communicate via Foramen of Panizza, immediately distally from the aortic valves. Moreover, crocodiles can regulate vascular resistance in the pulmonary portion of the right ventricular outflow tract (RVOT). These unique features allow for a complex regulation of shunting between the pulmonary and systemic circulations. Studies on crocodile shunting have predominantly been based on invasive measurements, but here we report on the use of echocardiography. METHODS: Experiments were performed on seven pentobarbital anaesthetized juvenile Nile crocodiles (length and mass of 192 ± 13 cm and 26 ± 5 kg, respectively). Echocardiographic imaging was performed using a transesophageal (TEE) approach. All images were EKG-gated. RESULTS: We obtain excellent views of cardiac structures and central vasculature through the esophagus. Standard imaging planes were defined for both long- and short axis views of the left ventricle and truncus arteriosus. For the RV, only a short axis view could be obtained. Color Doppler was used to visualize flow. Pulsed waved Doppler for measuring flow profiles across the atrioventricular valves, in the two RVOTs and the left ventricular outflow tract. Shunting across the Foramen of Panizza could be visualized and gated to the EKG. CONCLUSION: TEE can be used to image the unique features of the crocodile heart and allow for in-vivo imaging of the complex shunting hemodynamics, including timing of cardiac shunts.

High burden of coronary atherosclerosis in patients with cirrhosis.

BACKGROUND: Population studies report increased cardiovascular mortality in patients with cirrhosis. Coronary artery disease may be a trait of end-stage liver disease, but whether it is frequent or extensive in cirrhosis in general is unknown. Thus, we aimed to assess the prevalence and extent of coronary artery disease in unselected cirrhosis patients. MATERIALS AND METHODS: Using coronary computed tomography angiography, we investigated 52 patients from all Child-Pugh classes and aetiologies of cirrhosis without known cardiac disease for presence and severity of coronary artery disease in a cross-sectional design. Persons referred with new-onset chest pain served as controls. RESULTS: The prevalence of coronary artery disease was not significantly different between cirrhosis patients and controls (77% vs. 65%, P=0·19). However, cirrhosis patients had a markedly higher coronary artery calcification (Agatston) score than controls (120 [interquartile range, 0-345] vs. 5 [interquartile range, 0-86] HU, P=0·001). Likewise, patients with cirrhosis had a higher prevalence of extensive (≥5 coronary segments involved; 45% vs. 18%, P=0·01) and multivessel coronary disease (≥2 vessels involved; 75% vs. 53%, P=0·02). Furthermore, the total plaque volume whether noncalcified or calcified was higher in cirrhosis (117 [interquartile range, 0-310] vs. 36 [interquartile range, 0-148] mm3 , P=0·02). CONCLUSION: Coronary artery disease is equally prevalent in patients with cirrhosis and subjects with new-onset chest pain, but cirrhosis patients have more extensive and severe disease including several coronary high-risk features associated with myocardial ischaemia and a poor clinical outcome. The potential of preventive measures for coronary artery disease in cirrhosis needs attention.

Soluble receptor of advanced glycation end-products in patients with acute myocardial infarction treated with remote ischaemic conditioning.

BACKGROUND: Several studies have demonstrated that soluble receptor of advanced glycation end-products (sRAGE) is a valuable inflammatory biomarker in cardiovascular disease (CVD). Remote ischaemic conditioning may rescue myocardial tissue during acute myocardial infarction (AMI). In the present study, we evaluate whether sRAGE is a helpful biomarker in patients with AMI receiving remote ischaemic conditioning. METHODS: Plasma sRAGE levels were measured in 191 patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous intervention (pPCI) of which 97 patients were randomised to receive remote ischaemic conditioning. RESULTS: The sRAGE levels were not different when compared to the randomised controls. In 122 patients, measurement of myocardial salvage index (SI) was obtained. Patients who received remote ischaemic conditioning had significantly higher SI compared to the controls (p < 0.03), although this effect was not seen in sRAGE concentrations. However, sRAGE levels increased with higher New York Heart Association (NYHA) classification after 30 days of follow-up. CONCLUSIONS: sRAGE levels do not reflect increased SI in AMI patients who received remote ischaemic conditioning prior to hospital admission.

Improved long-term clinical outcomes in patients with ST-elevation myocardial infarction undergoing remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention.

AIMS: Remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction increases myocardial salvage. We investigated the effect of remote ischaemic conditioning on long-term clinical outcome. METHODS AND RESULTS: From February 2007 to November 2008, 333 patients with a suspected first acute ST-elevation myocardial infarction were randomized to receive primary percutaneous coronary intervention with (n = 166) or without (n = 167) remote ischaemic conditioning (intermittent arm ischaemia through four cycles of 5-min inflation followed by 5-min deflation of a blood-pressure cuff). Patient follow-up extended from the randomization date until an outcome, emigration or January 2012 (median follow-up = 3.8 years). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE)-a composite of all-cause mortality, myocardial infarction, readmission for heart failure, and ischaemic stroke/transient ischaemic attack. The individual components of the primary endpoint comprised the secondary endpoints. Outcomes were obtained from Danish nationwide medical registries and validated by medical record review and contact to patients' general practitioner. In the per-protocol analysis of 251 patient fulfilling trial criteria, MACCE occurred for 17 (13.5%) patients in the intervention group compared with 32 (25.6%) patients in the control group, yielding a hazard ratio (HR) of 0.49 (95% confidence interval: 0.27-0.89, P = 0.018). The HR for all-cause mortality was 0.32 (95% confidence interval: 0.12-0.88, P = 0.027). Although lower precision, the HRs were also directionally lower for all other secondary endpoints. CONCLUSION: Remote ischaemic conditioning before primary percutaneous coronary intervention seemed to improve long-term clinical outcomes in patients with ST-elevation myocardial infarction.

High osteoprotegerin levels predict MACCE in STEMI patients, but are not associated with myocardial salvage.

OBJECTIVES: High circulating levels of osteoprotegerin (OPG) carry prognostic impact in cohorts with various cardiovascular diagnoses. With the present study, we aim to investigate the role of OPG within the scale of myocardial damage. DESIGN: This study includes 219 consecutive patients with acute ST-elevation myocardial infarction randomized to primary percutaneous coronary intervention (pPCI) or pPCI and remote ischemic per-conditioning. Salvage index via myocardial single-photon emission CT assessment (data available in 61% of the patients) was performed, and derived from Day 1 (myocardial area at risk) and Day 30 (final infarct size). Plasma OPG levels were measured using an in-house immunoassay. A combined end-point of all-mortality, myocardial infarction, stroke, readmission for heart failure and ischemic stroke/transient ischemic attack (Major Adverse Cardiac and Cerebrovascular Events [MACCE]) was used for follow-up; 45 (38-48 months). RESULTS: High OPG levels were associated with the severity of cardiovascular disease. During follow-up, OPG was a predictor of MACCE (unadjusted, HR: 2.1, 95% CI: 1.14-3.85, P = 0.017). Adjustments for age, gender, and body mass index preserved the independent predictive power of OPG. However, OPG levels were neither associated with salvage index nor with the final infarct size. Remote ischemic per-conditioning had no effect on OPG levels. CONCLUSION: Despite absent association between OPG levels and the scale of myocardial damage, high OPG levels predict a significantly increased risk of MACCE.

Computed tomographic-based three-dimensional printing of giant coronary artery fistulas to guide surgical strategy: a case series.

Background: Coronary artery fistulas (CAFs) are abnormal communications between the coronary arteries and the heart chambers, arteries, or veins, potentially leading to significant shunting, myocardial ischaemia and heart failure. Computed tomographic (CT) angiography or conventional invasive angiography is the reference standard for the diagnosis of coronary fistulas. The fistula anatomy can become very complex, which makes surgical or interventional planning challenging. Case summary: We report two cases of hugely dilated and tortuous coronary circumflex artery fistulas draining into the coronary sinus. Both patients were followed up for more than 10 years because of very complex coronary fistula anatomy and mild symptoms. From two-dimensional (2D) sliced CT images alone it, was uncertain whether surgery was feasible. However, since both patients had symptom progression (Patient 1 developed heart failure, and Patient 2 had recurrent pericardial effusions), three-dimensional (3D) heart models were printed for better understanding of the complex fistula anatomy and improved surgical planning. Both patients had successful surgery and symptomatic relief at follow-up. Discussion: The delay in surgery, until clinical deterioration, may partly be a consequence of a general reluctance in performing complex surgery in patients with CAFs. As of now, CT-based 3D printing has primarily been used in isolated cases. However, 3D printing is evolving rapidly and supplementing 2D sliced CT images with a physical 3D heart model may improve the anatomical understanding and pre-surgical planning that could lead to better surgical outcome.

Pulmonary Valve Replacement in Tetralogy of Fallot: Procedural Volume and Durability of Bioprosthetic Pulmonary Valves.

BACKGROUND: Robust data on changes in pulmonary valve replacement (PVR) procedural volume and predictors of bioprosthetic pulmonary valve (BPV) durability in patients with tetralogy of Fallot (TOF) are scarce. OBJECTIVES: This study sought to assess temporal trends in PVR procedural volume and BPV durability in a nationwide, retrospective TOF cohort. METHODS: Data were obtained from patient records. Robust linear regression was used to assess temporal trends in PVR procedural volume. Piecewise exponential additive mixed models were used to estimate BPV durability, defined as the time from implantation to redo PVR with death as a competing risk, and to assess risk factors for reduced durability. RESULTS: In total, 546 PVR were performed in 384 patients from 1976 to 2021. The annual number of PVR increased from 0.4 to 6.0 per million population (P < 0.001). In the last decade, the transcatheter PVR volume increased by 20% annually (P < 0.001), whereas the surgical PVR volume did not change significantly. The median BPV durability was 17 years (Q1: 10-Q3: 10 years-not applicable). There was no significant difference in the durability of different BPV after adjustment for confounders. Age at PVR (HR: 0.78 per 10 years from <1 year; 95% CI: 0.63-0.96; P = 0.02) and true inner valve diameter (9-17 mm vs 18-22 mm HR: 0.40; 95% CI: 0.22-0.73; P = 0.003 and 18-22 mm vs 23-30 mm HR: 0.59; 95% CI: 0.25-1.39; P = 0.23) were associated with reduced BPV durability in multivariate models. CONCLUSIONS: The PVR procedural volume has increased over time, with a greater increment in transcatheter than surgical PVR during the last decade. Younger patient age at PVR and a smaller true inner valve diameter predicted reduced BPV durability.

Twenty years' experience at the Heart Transplant Center, Aarhus University Hospital, Skejby, Denmark.

OBJECTIVES: The Heart Transplantation Center, Aarhus University Hospital, Skejby, now has 20 years' experience with heart transplantation (HTX). This study aims to evaluate long-term outcome after HTX including incidences of cancer and severe renal dysfunction. DESIGN: Outcomes were reviewed using the transplant database of our department, the Scandiatransplant database, hospital medical records, and national database of biopsies. RESULTS: From December 31, 1992 to February 27, 2013, a total of 258 patients underwent index HTX. Survival for the whole patient cohort at 1 month and 1 year was 95% and 88%. Long-term survival estimates of 5, 10, 15, and 20 years were 80%, 70%, 55%, and 40%, respectively. Median survival time was 15.6 years. Significant improvement in survival was observed from the 1992-1998 vs. 1999-2005 era and the 1992-1998 vs. the 2006-2012 era. Three patients (1%) underwent renal transplantation, and 29 patients (11%) developed severe renal dysfunction requiring dialysis. Sixty-four (25%) patients developed cancer, with skin cancer being most common. CONCLUSION: HTX is an excellent treatment for selected patients with end-stage heart failure. The prognosis has improved in the latest transplantation eras. With balanced immunosuppressive treatment, severe renal dysfunction and cancer can be limited to an acceptable level.

Temporal changes in the surgical management of patients with tetralogy of Fallot in Denmark: a nationwide cohort study.

OBJECTIVES: To assess temporal changes in the surgical management of patients with tetralogy of Fallot including the timing of interventions, surgical techniques, reinterventions and survival in a nationwide cohort. METHODS: Patients with tetralogy of Fallot in Denmark were divided into 3 eras based on their year of birth: early (1977-1991), intermediate (1992-2006) and late (2007-2021). RESULTS: The cohort consisted of 745 patients. Median follow-up was 21.2 years (13.7-30.5). There was a temporal trend towards less shunt palliation (-0.3% per year, 95% CI -0.05 to -0.1). Median age at intracardiac repair was 2.9 years (1.8-5.0), 0.8 years (0.5-1.3) and 0.5 years (0.4-0.7) (P < 0.001) in the early, intermediate and late era, respectively. There was a temporal trend towards less valve-sparing repair (-0.7% per year, 95% CI -0.5 to -1.0) and more repair with transannular patches (0.7% per year, 95% CI 0.5-1.0). Survival at 10 years was 79% (64-76), 90% (87-93) and 95% (92-98) (P < 0.001) and pulmonary valve replacement within the first 10 years after intracardiac repair was performed in 3% (1-6), 12% (8-16) and 21% (13-29) (P < 0.001) in the early, intermediate and late era, respectively. CONCLUSIONS: There was a temporal trend towards less shunt palliation and intracardiac repair at a younger age with more use of transannular patches. While survival throughout childhood and adolescence has improved, more patients undergo pulmonary valve replacement during the first 10 years after intracardiac repair.

Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial.

BACKGROUND: Remote ischaemic preconditioning attenuates cardiac injury at elective surgery and angioplasty. We tested the hypothesis that remote ischaemic conditioning during evolving ST-elevation myocardial infarction, and done before primary percutaneous coronary intervention, increases myocardial salvage. METHODS: 333 consecutive adult patients with a suspected first acute myocardial infarction were randomly assigned in a 1:1 ratio by computerised block randomisation to receive primary percutaneous coronary intervention with (n=166 patients) versus without (n=167) remote conditioning (intermittent arm ischaemia through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff). Allocation was concealed with opaque sealed envelopes. Patients received remote conditioning during transport to hospital, and primary percutaneous coronary intervention in hospital. The primary endpoint was myocardial salvage index at 30 days after primary percutaneous coronary intervention, measured by myocardial perfusion imaging as the proportion of the area at risk salvaged by treatment; analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00435266. FINDINGS: 82 patients were excluded on arrival at hospital because they did not meet inclusion criteria, 32 were lost to follow-up, and 77 did not complete the follow-up with data for salvage index. Median salvage index was 0.75 (IQR 0.50-0.93, n=73) in the remote conditioning group versus 0.55 (0.35-0.88, n=69) in the control group, with median difference of 0.10 (95% CI 0.01-0.22; p=0.0333); mean salvage index was 0.69 (SD 0.27) versus 0.57 (0.26), with mean difference of 0.12 (95% CI 0.01-0.21; p=0.0333). Major adverse coronary events were death (n=3 per group), reinfarction (n=1 per group), and heart failure (n=3 per group). INTERPRETATION: Remote ischaemic conditioning before hospital admission increases myocardial salvage, and has a favourable safety profile. Our findings merit a larger trial to establish the effect of remote conditioning on clinical outcomes. FUNDING: Fondation Leducq.

Global longitudinal strain by speckle tracking for infarct size estimation.

AIMS: To assess the utility of speckle tracking global longitudinal systolic strain (GLS) compared with traditional echocardiographic indices including left ventricular ejection fraction (LVEF), wall motion score index (WMSI), and end-systolic volume index (ESVI), in estimating the infarct size (IS) following a ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: The study includes 227 patients with STEMI and day 1 and day 30 echocardiograms, and myocardial perfusion imaging (MPI) only at day 30 to assess IS. IS was modelled by linear regression with echocardiographic parameters using MPI as reference. Resulting echocardiographic IS estimates were compared by ratios of standard deviations of model residuals (RSD). To estimate the resultant day 30 IS 1 day after a STEMI, GLS was more precise than LVEF (RSD: 0.91, P = 0.014) and ESVI (RSD: 0.88, P = 0.002), and comparable with WMSI (RSD 0.99, P = 0.86). To estimate IS from a day 30 echocardiogram, GLS was comparable with LVEF (RSD: 0.98, P = 0.68) and ESVI (RSD: 1.04, P = 0.40), but WMSI was more precise (RSD: 0.89, P = 0.006). Multiple linear regression revealed that on day 1 after STEMI, GLS significantly complemented the standard parameters separately (P-values all models <0.001) or combined [multivariable model: GLS (P = 0.001), WMSI (P = 0.03), LVEF (P = 0.40)]. On day 30, GLS significantly complemented LVEF and ESVI, but when WMSI was in the model, GLS's association with IS was not significant. CONCLUSION: On day 1 after revascularization for STEMI, GLS contains additional information about final IS compared with standard echocardiographic systolic function indices. Studies are needed to clarify whether this has prognostic implications.

Takotsubo cardiomyopathy. An important differential diagnosis to acute myocardial infarction.

INTRODUCTION: Sparse information with regard to the electrocardiographic (ECG) changes in Takotsubo cardiomyopathy (TC) is available. The purpose of this study was to describe the clinical characteristics and electrocardiographic changes in a Danish cohort of patients with TC. We discuss the potential pathophysiological mechanisms of TC. METHODS: Cases were registered during a three year period. Patients who were hospitalized at Skejby Hospital suspected of acute myocardial infarction in whom coronary angiography was performed in the acute or subacute phase were registered. Data were obtained retrospectively from medical records and the hospitals laboratory database. RESULTS: Seven patients with TC were identified comprising six females and one male (mean age 70, range 53-81 years). In the acute phase all patients had ECG changes compatible with ST-elevation acute myocardial infarction (STEMI), as well as profound impaired left ventricular function with apical ballooning. At follow-up (range 1-82 weeks), both ECG and left ventricular function were normalized in all patients. CONCLUSION: In the acute phase symptoms and ECG changes resemble those in patients with STEMI, hence acute coronary angiography is indicated in most cases. Pathophysiological aspects are discussed.

Influence of preinfarction angina and coronary collateral blood flow on the efficacy of remote ischaemic conditioning in patients with ST segment elevation myocardial infarction: post hoc subgroup analysis of a randomised controlled trial.

OBJECTIVES: Remote ischaemic conditioning (RIC) confers cardioprotection in patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). We investigated whether preinfarction angina and coronary collateral blood flow (CCBF) to the infarct-related artery modify the efficacy of RIC. DESIGN: Post hoc subgroup analysis of a randomised controlled trial. PARTICIPANTS: A total of 139 patients with STEMI randomised to treatment with pPCI or RIC+pPCI. INTERVENTIONS: RIC was performed prior to pPCI as four cycles of 5 min upper arm ischaemia and reperfusion with a blood pressure cuff. PRIMARY OUTCOME MEASURE: Myocardial salvage index (MSI) assessed by single-photon emission computerised tomography. We evaluated the efficacy of RIC in subgroups of patients with or without preinfarction angina or CCBF. RESULTS: Of 139 patients included in the study, 109 had available data for preinfarction angina status and 54 had preinfarction angina. Among 83 patients with Thrombolysis In Myocardial Infarction flow 0/1 on arrival, 43 had CCBF. Overall, RIC+pPCI increased median MSI compared with pPCI alone (0.75 vs 0.56, p=0.045). Mean MSI did not differ between patients with and without preinfarction angina in either the pPCI alone (0.58 and 0.57; 95% CI -0.17 to 0.19, p=0.94) or the RIC+pPCI group (0.66 and 0.69; 95% CI -0.18 to 0.10, p=0.58). Mean MSI did not differ between patients with and without CCBF in the pPCI alone group (0.51 and 0.55; 95% CI -0.20 to 0.13, p=0.64), but was increased in patients with CCBF versus without CCBF in the RIC+pPCI group (0.75 vs 0.58; 95% CI 0.03 to 0.31, p=0.02; effect modification from CCBF on the effect of RIC on MSI, p=0.06). CONCLUSIONS: Preinfarction angina did not modify the efficacy of RIC in patients with STEMI undergoing pPCI. CCBF to the infarct-related artery seems to be of importance for the cardioprotective efficacy of RIC. TRIAL REGISTRATION NUMBER: NCT00435266, Post-results.

Remote ischaemic conditioning and healthcare system delay in patients with ST-segment elevation myocardial infarction.

OBJECTIVE: We investigated influence of remote ischaemic conditioning (RIC) on the detrimental effect of healthcare system delay on myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). METHODS: A post-hoc analysis of a randomised controlled trial in patients with STEMI randomised to treatment with pPCI or RIC+pPCI. RIC was performed as four cycles of intermittent 5 min upper arm ischaemia and reperfusion. Healthcare system delay was defined as time from emergency medical service call to pPCI-wire. Myocardial salvage index (MSI) was assessed by single photon emission computerised tomography. RESULTS: Data for healthcare system delay and MSI were available for 129 patients. MSI was negatively associated with healthcare system delay in patients treated with pPCI alone (-0.003 decrease in MSI/min of healthcare system delay; 95% CI -0.005 to -0.001, r(2)=0.11, p=0.008) but not in patients treated with RIC+pPCI (-0.0002 decrease in MSI/min of healthcare system delay; 95% CI -0.001 to 0.001, r(2)=0.002, p=0.74). In patients with healthcare system delay ≤120 min, RIC+pPCI did not affect median MSI compared with pPCI alone (0.75 (IQR: 0.49-0.99) and 0.70 (0.45-0.94), p=1.00). However, in patients with healthcare system delay >120 min, RIC+pPCI increased median MSI compared with pPCI alone (0.74 (0.52-0.93) vs 0.42 (0.22-0.68), p=0.02). Adjusting for potential confounders did not affect the results. CONCLUSIONS: RIC as adjunctive to pPCI attenuated the detrimental effect of healthcare system delay on myocardial salvage in patients with STEMI, suggesting that the cardioprotective effect of RIC increases with the duration of ischaemia. TRIAL REGISTRATION NUMBER: NCT00435266; post-results.

Cost-effectiveness of remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction.

AIMS: Remote ischaemic conditioning seems to improve long-term clinical outcomes in patients undergoing primary percutaneous coronary intervention. Remote ischaemic conditioning can be applied with cycles of alternating inflation and deflation of a blood-pressure cuff. We evaluated the cost-effectiveness of remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction from the perspective of the Danish healthcare system. METHODS AND RESULTS: Between February 2007 and November 2008, 251 patients with ST-elevation myocardial infarction were randomly assigned to remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention (n=126) or to primary percutaneous coronary intervention alone (n=125). During a 4-year follow-up period, we used data from Danish medical registries and medical records to estimate within-trial cardiovascular medical care costs and major adverse cardiac and cerebrovascular event-free survival. After 4 years of follow-up, mean cumulative cardiovascular medical care costs were €2763 (95% confidence interval 207-5318, P=0.034) lower in the remote ischaemic conditioning group than in the control group (€12,065 vs. €14,828), while mean major adverse cardiac and cerebrovascular event-free survival time was 0.30 years (95% confidence interval 0.03-0.57, P=0.032) higher in the remote ischaemic conditioning group than in the control group (3.51 vs. 3.21 years). In the cost-effectiveness plane, remote ischaemic conditioning therapy was economically dominant (less costly and more effective) in 97.26% of 10,000 bootstrap replications. CONCLUSION: Remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention appears to be a cost-effective treatment strategy in patients with ST-elevation myocardial infarction.

Cardiac Arrest following a Myocardial Infarction in a Child Treated with Methylphenidate.

The use of psychostimulants labeled to treat attention deficit/hyperactivity disorder increases. Among side effects these drugs raise blood pressure and heart rate, and the safety has been scrutinised in recent years. Data from large epidemiological studies, including over a million person-years, did not report any cases of myocardial infarction in current users of methylphenidate, and the risk of serious adverse cardiac events was not found to be increased. We present a case with an 11-year-old child, treated with methylphenidate, who suffered cardiac arrest and was diagnosed with a remote myocardial infarction. This demonstrates that myocardial infarction can happen due to methylphenidate exposure in a cardiac healthy child, without cardiovascular risk factors.

Impact of cardiovascular risk factors and medication use on the efficacy of remote ischaemic conditioning: post hoc subgroup analysis of a randomised controlled trial.

OBJECTIVES: Remote ischaemic conditioning (RIC) promotes cardioprotection in patients undergoing primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI). The effect of RIC may be modified by cardiovascular risk factors and their medications. We examined whether cardiovascular risk factors, lipid and glucose levels, and medication use influenced the efficacy of RIC in patients with STEMI treated with pPCI. DESIGN: Post hoc subgroup analysis of a single-centre randomised controlled trial. PARTICIPANTS: A total of 139 patients with STEMI, randomised during ambulance transport to hospital for pPCI with (n=71) or without (n=68) RIC, met the trial criteria and achieved data for a myocardial salvage index (MSI). INTERVENTIONS: RIC was administered through intermittent arm ischaemia with four cycles of 5 min inflation and 5 min deflation of a blood pressure cuff. PRIMARY OUTCOME MEASURES: MSI, estimated by single-photon emission CT. We evaluated the efficacy of RIC on the MSI in patient subgroups of cardiovascular risk factors, lipid and glucose levels, and medication use. RESULTS: We found no significant difference in the efficacy of RIC in subgroups of cardiovascular risk factors, lipid and glucose levels, and medication use. However, point estimates indicated a reduced effect of RIC among smokers (median difference in MSI between RIC and control groups: -0.02 (95% CI -0.32 to 0.28) in smokers vs 0.25 (95% CI 0.08 to 0.42) in non-smokers, p value for interaction=0.13) and an increased effect of RIC in statin users (median difference in MSI between RIC and control groups: 0.34 (95% CI 0.03 to 0.65) in statin users vs 0.09 (95% CI -0.11 to 0.29) in non-statin users, p value for interaction=0.19). CONCLUSIONS: RIC as an adjunct to pPCI seems to improve MSI in our trial population of patients with STEMI regardless of most cardiovascular risk factors and their medications. Our post hoc finding on a limited sample size calls for further investigation in large-scale multicentre trials. TRIAL REGISTRATION NUMBER: NCT00435266.

Fatal haemolytic crisis with microvascular pulmonary obstruction mimicking a pulmonary embolism in a young African man with glucose-6-phosphate dehydrogenase deficiency.

We report a fatal case of haemolytic crisis mimicking a pulmonary embolism in a previously healthy 42-year-old African man. The patient was admitted to hospital with fatigue, shortness of breath and jaundice lasting for 2 days. Laboratory tests were consistent with haemolysis and inflammation. The patient was treated as having a mycoplasma pneumonia. His condition deteriorated rapidly, with respiratory distress and circulatory failure. Echocardiography showed pulmonary hypertension and right heart dilation. Despite the fact that he was given fibrinolysis for suspected pulmonary embolism, he developed cardiac arrest and died after a long-lasting resuscitation attempt. Postmortem examinations revealed that the patient had a glucose-6-phosphate dehydrogenase deficiency and disseminated intravascular coagulation with pulmonary microthrombi. To the best of our knowledge, this is the first case of death caused by right heart failure due to microvascular obstruction resulting from multiple microvascular thrombosis in a patient with acute haemolysis due to glucose-6-phosphate dehydrogenase deficiency.

Association between endogenous complement inhibitor and myocardial salvage in patients with myocardial infarction.

BACKGROUND: Many pathogenic processes and diseases are the result of an erroneous activation of the complement cascade and a number of inhibitors of complement have thus been examined for anti-inflammatory actions. It was recently demonstrated that supraphysiological concentrations of the endogenous complement inhibitor MAp44 (also denoted MAP1) protect against myocardial reperfusion injury. In the present study, we examined the association between outcome after acute myocardial infarction (MI) and the plasma levels of MAp44 and its related proteins MASP-1 and MASP-3 in patients with first-time MI. In addition, we compared plasma levels of MAp44, MASP-1, and MASP-3 in MI patients to levels in a healthy control group. METHODS: A total of 192 MI patients and 140 control persons were included. Plasma samples were obtained and analysed with time-resolved immunofluorometric assays determining the plasma levels of MAp44, MASP-1, and MASP-3. The myocardial outcomes (salvage index and final infarct size) were measured by gated single-photon emission CT. RESULTS: MI patients had 18 % higher plasma levels of MAp44 (IQR 11-25%) as compared to the healthy control group (p<0.001. However, neither salvage index (Spearman rho -0.1, p=0.28) nor final infarct size (Spearman rho 0.02, p=0.83) correlated with plasma levels of MAp44. Likewise, MASP-1 and MASP-3 were elevated in MI patients (p=0.002 and p<0.001), but the levels were not correlated to outcome. CONCLUSIONS: Plasma levels of MAp44, MASP-1, and MASP-3 are significantly higher in patients with MI compared to healthy control persons, but are not associated with short-term outcome measured as salvage index and final infarct.