Design of the Dutch multicentre study on opportunistic screening of geriatric patients for atrial fibrillation using a smartphone PPG app: the Dutch-GERAF study.

BACKGROUND: Screening of high-risk patients is advocated to achieve early detection and treatment of clinical atrial fibrillation (AF). The Dutch-GERAF study will address two major issues. Firstly, the effectiveness and feasibility of an opportunistic screening strategy for clinical AF will be assessed in frail older patients and, secondly, observational data will be gathered regarding the efficacy and safety of oral anticoagulation (OAC). METHODS: This is a multicentre study on opportunistic screening of geriatric patients for clinical AF using a smartphone photoplethysmography (PPG) application. Inclusion criteria are age ≥ 65 years and the ability to perform at least three PPG recordings within 6 months. Exclusion criteria are the presence of a cardiac implantable device, advanced dementia or a severe tremor. The PPG application records patients' pulse at their fingertip and determines the likelihood of clinical AF. If clinical AF is suspected after a positive PPG recording, a confirmatory electrocardiogram is performed. Patients undergo a comprehensive geriatric assessment and a frailty index is calculated. Risk scores for major bleeding (MB) are applied. Standard laboratory testing and additional laboratory analyses are performed to determine the ABC-bleeding risk score. Follow-up data will be collected at 6 months, 12 months and 3 years on the incidence of AF, MB, hospitalisation, stroke, progression of cognitive disorders and mortality. DISCUSSION: The Dutch-GERAF study will focus on frail older patients, who are underrepresented in randomised clinical trials. It will provide insight into the effectiveness of screening for clinical AF and the efficacy and safety of OAC in this high-risk population. TRIAL REGISTRATION: NCT05337202.

Elderly patients benefit from minimally invasive mitral valve surgery: perioperative risk management matters.

OBJECTIVES: The goal was to assess the single-centre results of minimally invasive mitral valve surgery (MIMVS) in the elderly population. METHODS: All patients referred for minimally invasive valve surgery underwent a standardized preoperative screening. We performed a retrospective analysis of 131 consecutive elderly patients (≥75 years) who underwent endoscopic MIMVS through a right mini-thoracotomy. Survival and postoperative course were assessed in 2 groups: a repair group and a replacement group. RESULTS: Eighty-five patients underwent mitral valve repair, and 46 had mitral valve replacement. The mean age was 79 ± 2.9 years, and the median follow-up duration was 3.8 years. The cardiopulmonary bypass time (128.7 min vs 155.9 min, P = 0.012) and the cross-clamp time (84.9 min vs 124.1 min, P = 0.005) were significantly longer in the replacement group. Except for more reinterventions for bleeding in the replacement group (10.9% vs 0%, P = 0.005), there were no significant differences in the postoperative course between the 2 groups. Low mortality rates at the midterm follow-up were observed in both groups, and no differences were observed between the 4-and the 12-month follow-up. Survival rates after 1 year and 5 years were 97.6% and 88.6%, respectively, with no significant differences between the 2 groups. CONCLUSIONS: MIMVS is an excellent treatment option in vulnerable elderly patients with excellent short- and long-term results. Although other studies suggest that repair could be superior to replacement even in older patients, our experience suggests that replacement is equivalent to repair in terms of mortality and major adverse cardiac and cerebrovascular events. Experience and standardized preoperative screening are mandatory to achieve optimal results.

The evolution of technical prerequisites and local boundary conditions for optimization of mitral valve interventions-Emphasis on skills development and institutional risk performance.

This viewpoint report describes how the evolution of transcatheter mitral valve intervention (TMVI) is influenced by lessons learned from three evolutionary tracks: (1) the development of treatment from mitral valve surgery (MVS) to transcutaneous procedures; (2) the evolution of biomedical engineering for research and development resulting in predictable and safe clinical use; (3) the adaptation to local conditions, impact of transcatheter aortic valve replacement (TAVR) experience and creation of infrastructure for skills development and risk management. Thanks to developments in computer science and biostatistics, an increasing number of reports regarding clinical safety and effectiveness is generated. A full toolbox of techniques, devices and support technology is now available, especially in surgery. There is no doubt that the injury associated with a minimally invasive access reduces perioperative risks, but it may affect the effectiveness of the treatment due to incomplete correction. Based on literature, solutions and performance standards are formulated with an emphasis in technology and positive outcome. Despite references to Heart Team decision making, boundary conditions such as hospital infrastructure, caseload, skills training and perioperative risk management remain underexposed. The role of Biomedical Engineering is exclusively defined by the Research and Development (R&D) cycle including the impact of human factor engineering (HFE). Feasibility studies generate estimations of strengths and safety limitations. Usability testing reveals user friendliness and safety margins of clinical use. Apart from a certification requirement, this information should have an impact on the definition of necessary skills levels and consequent required training. Physicians Preference Testing (PPT) and use of a biosimulator are recommended. The example of the interaction between two Amsterdam heart centers describes the evolution of a professional ecosystem that can facilitate innovation. Adaptation to local conditions in terms of infrastructure, referrals and reimbursement, appears essential for the evolution of a complete mitral valve disease management program. Efficacy of institutional risk management performance (IRMP) and sufficient team skills should be embedded in an appropriate infrastructure that enables scale and offers complete and safe solutions for mitral valve disease. The longstanding evolution of mitral valve therapies is the result of working devices embedded in an ecosystem focused on developing skills and effective risk management actions.

Nitrous oxide abuse leading to extreme homocysteine levels and thrombosis in young adults: a case series.

BACKGROUND: Neurologic complications from recreational use of nitrous oxide (N2O), which are attributed to vitamin B12 deficiency, have been well documented. With increasing dosages and frequency of N2O use, an additional association with thromboembolisms is becoming apparent. OBJECTIVES: To assess thrombotic complications of recreational N2O use. METHODS: All medical charts at the largest hospital in Amsterdam were searched for N2O use and subsequent neurologic and/or thrombotic events. For patients with thrombotic events, we extracted data on the risk factors for arterial and venous thrombosis as well as serum vitamin B12 and homocysteine concentrations. RESULTS: Between January 2015 and May 2021, 326 patients who reported recreational use of N2O were identified; of these, 17 (5%) patients presented with severe thrombotic events associated with N2O (71% men; median age, 26 years [range, 18-53 years]), 5 patients presented with arterial thrombosis (3 with acute coronary syndrome, 1 with femoral artery thrombosis, and 1 with middle cerebral artery thrombus), and 12 patients presented with venous thromboembolisms (10 with pulmonary embolisms, 1 with portal vein thrombosis and 1 with cerebral vein thrombosis). Additionally, homocysteine were concentrations severely increased (median, 125 µmol/L [range, 22-253 µmol/L]; reference, <15 µmol/L). Patients reported use of 400 to 6000 g (ie, 50-750 balloons) of N2O in 1 day. Fifty percent of these patients had experienced neurologic symptoms before the thrombotic event. CONCLUSION: We describe an alarming incidence of serious thrombotic events among young adults after excessive recreational use of N2O, accompanied by extremely high homocysteine concentrations. The upward trend in the recreational use of N2O warrants more awareness of its dangers among both users and medical professionals. Furthermore, these findings could reopen the discussion on possible associations between hyperhomocysteinemia and thrombosis mediated through N2O.

The quest for determination of standard reference values of right ventricular longitudinal systolic strain: a systematic review and meta-analysis.

Right ventricular function is strongly associated with clinical outcomes in many conditions, and the evaluation of right ventricle (RV) structure and function in patients with cardiopulmonary disorders is an essential component of clinical management. The objective of this study was to determine the normal ranges of right ventricular longitudinal strain (RVLS) measurements derived by two-dimensional (2D) speckle tracking echocardiography (STE) through a systematic review and meta-analysis. A systematic review was performed using PubMed, Cochrane, ClinicalKey, and CINAHL. Search terms covered the concepts of right ventricle, strain, speckle-tracking, and 2D echocardiography with additional filtering for humans and adults over the last decade. The RV four-chamber longitudinal strain (RV4CLS), RV free wall longitudinal strain (RVFWLS), and free wall longitudinal segmental strain values of healthy individuals without cardiopulmonary diseases from 28 studies were assessed. Weighted means were estimated using random-effects models in a meta-analysis. The results show for RV4CLS -24,91%[CI - 25.94; - 23.88, I2 98%], for RVFWLS -27.63%[CI - 28.78; - 26.48, I2 98%], for basal RVFWLS -26.65%[CI - 30.57; - 22.73, I2 99%], mid RVFWLS -27.61%[CI - 30.99; - 24.22, I2 99%] and apical RVFWLS -24.54%[CI - 26.70; - 22.38, I2 98%]. This systematic review and meta-analysis showed longitudinal strain values of 2D STE derived RV. No clear reference value for RV strain can be distilled from the literature search due to high statistical heterogeneity between the studies. However, all results of our analysis suggest that the lower reference values for RVLS in the current recommendations with a cut-off value of - 20% is underestimated.

Recreational drug use among young, hospitalized patients with acute coronary syndrome: A retrospective study.

Background: Cocaine use is a well-established risk factor for acute coronary syndrome (ACS) although other recreational drugs (RD), are increasingly considered as potential cardiac risk factors. Compared to ACS without RD use, worse outcomes have been described for RD-associated ACS. Objective: The aim of this study was to explore the use of RD in a contemporary cohort of young ACS patients. Methods: Between June 2016 and October 2019, ACS patients aged 18-50 years, admitted to OLVG Hospital in Amsterdam, were retrospectively analysed. Medical chart review was performed to obtain patient and clinical characteristics, RD use, cardiac risk factors, outcome and follow up. Results: A total of 229 patients were included in the study. Recreational drug use prior to ACS was present in 24.9% of all patients, with cannabis (16.2%), cocaine (4.8%), or both (2.6%) most commonly observed. RD users were predominantly young men (87.7%) and had a significantly higher tobacco use compared to non-RD users (89.5% vs. 62.8%, P < 0.001), also after adjusting for age and sex. RD use was associated with larger myocardial infarctions with significantly higher CK-MB levels (104 ± 116 U/L vs 62 ± 96, P = 0.040) and poorer left ventricular function measured by echocardiography as compared to non-users (P = 0.007). Conclusion: Recreational drug use was present in almost 25% of all young ACS patients evaluated for drug use and was associated with larger myocardial infarction resulting in poorer left ventricular function as compared to non-users. Additionally, RD-users were younger and were more often tobacco users, compared to non-users.

4-Fluoroamphetamine (4-FA) intoxication results in exaggerated blood pressure effects compared to MDMA and amphetamine: A retrospective analysis.

Objective: 4-Fluoroamphetamine (4-FA) is an amphetamine-type stimulant, with effects comparable to amphetamine and 3,4-methylenedioxymethamphetamine (MDMA). Severe 4-FA-related complications, such as cardiomyopathy, myocardial infarction, and cerebral hemorrhage, have been described. The aim of this study was to explore the cardiovascular symptoms and complications in 4-FA and compare them to MDMA and amphetamine in intoxicated patients who presented to the emergency department (ED). Methods: Between November 2015 and March 2020, all self-reported 4-FA, MDMA, and amphetamine-intoxicated adult patients that presented at the ED of an inner-city hospital in Amsterdam, were retrospectively analyzed for cardiovascular symptoms, vital parameters, cardiovascular complications, interventions, admission rate, and Poisoning Severity Score (PSS). Results: A total of 582 patients were included, of which 31 (5.3%) with 4-FA intoxication (10/31 mono-intoxications, 32.3%), 406 (69.8%) with MDMA (59/406 mono-intoxications, 14.5%), 100 (17.2%) with amphetamine (10/100 mono-intoxications, 10.0%), and 45 (7.7%) with a cross intoxication of these drugs. 4-FA mono-intoxicated patients experienced more headache (n = 8; 80.0%) compared to MDMA (n = 2; 3.3%; P < 0.001) and amphetamine mono-intoxicated patients (n = 0; 0.0%; P < 0.001) and their systolic blood pressure was higher (164 mm Hg ± 31 vs 139 mm Hg ± 19; P = 0.031 vs 135 mm Hg ± 22; P = 0.033, respectively). Severe 4-FA-related cardiovascular complications included Takotsubo cardiomyopathy (n = 1; 3.2%), subarachnoid hemorrhage (n = 1; 3.2%), and hypertensive urgency (n = 2; 6.5%). Conclusions: 4-FA intoxication-related ED symptoms resemble MDMA and amphetamine complications, although patients presented more often with headache and hypertension. Severe 4-FA-related cardiovascular complications occurred in 40% of mono-intoxications.

At the Crossroads of Minimally Invasive Mitral Valve Surgery-Benching Single Hospital Experience to a National Registry: A Plea for Risk Management Technology.

Almost 30 years after the first endoscopic mitral valve repair, Minimally Invasive Mitral Valve Surgery (MIMVS) has become the standard at many institutions due to optimal clinical results and fast recovery. The question that arises is can already good results be further improved by an Institutional Risk Management Performance (IRMP) system in decreasing risks in minimally invasive mitral valve surgery (MIMVS)? As of yet, there are no reports on IRMP and learning systems in the literature. (2) Methods: We described and appraised our five-year single institutional experience with MIMVS in isolated valve surgery included in the Netherlands Heart Registry (NHR) and investigated root causes of high-impact complications. (3) Results: The 120-day and 12-month mortality were 1.1% and 1.9%, respectively, compared to the average of 4.3% and 5.3% reported in the NHR. The regurgitation rate was 1.4% compared to 5.2% nationwide. The few high-impact complications appeared not to be preventable. (4) Discussion: In MIMVS, freedom from major and minor complications is a strong indicator of an effective IRMP but remains concealed from physicians and patients, despite its relevance to shared decision making. Innovation adds to the complexity of MIMVS and challenges surgical competence. An IRMP system may detect and control new risks earlier. (5) Conclusion: An IRMP system contributes to an effective reduction of risks, pain and discomfort; provides relevant input for shared decision making; and warrants the safe introduction of new technology. Crossroads conclusions: investment in machine learning and AI for an effective IRMP system is recommended and the roles for commanding and operating surgeons should be considered.

Thrombosis within the left anterior descending coronary artery and left ventricle after high-dose nitrous oxide use.

We present a man in his 30s with acute anterior myocardial infarction due to thrombotic occlusion of the left anterior descending artery and subsequent left ventricular thrombus formation after high-dose recreational use of nitrous oxide (N2O). Initial questioning for use of illicit substances was negative, but low vitamin B12 levels and severely elevated homocysteine levels prompted us to interrogate for the use of laughing gas. On questioning, the patient admitted to have used this substance, which he presumed to be innocent. Neither percutaneous coronary intervention with balloon dilatation nor intravenous glycoprotein IIb/IIIa receptor antagonist, nor continuous use of anticoagulation and double antiplatelet therapy resulted in thrombus resolution. Due to a severely reduced left ventricular function, despite 3 months on heart failure therapy, the patient is being counselled for intracardiac defibrillator implantation. We conclude that N2O, notably when consumed in conjunction with other proatherogenic substances, is associated with thrombosis: a relation possibly mediated by severe hyperhomocysteinaemia.

Surgery and outcome of infective endocarditis in octogenarians: prospective data from the ESC EORP EURO-ENDO registry.

PURPOSE: High mortality and a limited performance of valvular surgery are typical features of infective endocarditis (IE) in octogenarians, even though surgical treatment is a major determinant of a successful outcome in IE. METHODS: Data from the prospective multicentre ESC EORP EURO-ENDO registry were used to assess the prognostic role of valvular surgery depending on age. RESULTS: As compared to < 80 yo patients, ≥ 80 yo had lower rates of theoretical indication for valvular surgery (49.1% vs. 60.3%, p < 0.001), of surgery performed (37.0% vs. 75.5%, p < 0.001), and a higher in-hospital (25.9% vs. 15.8%, p < 0.001) and 1-year mortality (41.3% vs. 22.2%, p < 0.001). By multivariable analysis, age per se was not predictive of 1-year mortality, but lack of surgical procedures when indicated was strongly predictive (HR 2.98 [2.43-3.66]). By propensity analysis, 304 ≥ 80 yo were matched to 608 < 80 yo patients. Propensity analysis confirmed the lower rate of indication for valvular surgery (51.3% vs. 57.2%, p = 0.031) and of surgery performed (35.3% vs. 68.4%, p < 0.0001) in ≥ 80 yo. Overall mortality remained higher in ≥ 80 yo (in-hospital: HR 1.50[1.06-2.13], p = 0.0210; 1-yr: HR 1.58[1.21-2.05], p = 0.0006), but was not different from that of < 80 yo among those who had surgery (in-hospital: 19.7% vs. 20.0%, p = 0.4236; 1-year: 27.3% vs. 25.5%, p = 0.7176). CONCLUSION: Although mortality rates are consistently higher in ≥ 80 yo patients than in < 80 yo patients in the general population, mortality of surgery in ≥ 80 yo is similar to < 80 yo after matching patients. These results confirm the importance of a better recognition of surgical indication and of an increased performance of surgery in ≥ 80 yo patients.

The Impact of Biomedical Engineering on the Development of Minimally Invasive Cardio-Thoracic Surgery.

(1) We describe the boundary conditions for minimally invasive cardiac surgery (MICS) with the aim to reduce procedure-related patient injury and discomfort. (2) The analysis of the MICS work process and its demand for improved tools and devices is followed by a description of the relevant sub-specialties of bio-medical engineering: electronics, biomechanics, and materials sciences. (3) Innovations can represent a desired adaptation of an existing work process or a radical redesign of procedure and devices such as in transcutaneous procedures. Focused interaction between engineers, industry, and surgeons is always mandatory (i.e., a therapeutic alliance for addressing 'unmet patient or professional needs'. (4) Novel techniques in MICS lean heavily on usability and safe and effective use in dedicated hands. Therefore, the use of training and simulation models should enable skills selection, a safe learning curve, and maintenance of proficiency. (5) The critical technical steps and cost-benefit trade-offs during the journey from invention to application will be explained. Business considerations such as time-to-market and returns on investment do shape the cost-benefit room for commercial use of technology. Proof of clinical safety and effectiveness by physicians remains important, but establishing the technical reliability of MICS tools and warranting appropriate surgical skills come first.

The Effect of the Timing of Invasive Management on Cardiac Function in Patients with NSTE-ACS, Insights from the OPTIMA-2 Randomized Controlled Trial.

The timing of coronary angiography in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) remains a matter of debate. The relationship between the timing of invasive management and left ventricular function (LVF) is largely unknown. The An Immediate or Early Invasive Strategy in Non-ST-Elevation Acute Coronary Syndrome trial (OPTIMA-2) was a randomized controlled prospective open-label multicenter trial that randomized 249 NSTE-ACS patients to either an immediate (<3 h) invasive treatment strategy or an early strategy (12-24 h). Patients were pre-treated with a combination of aspirin, ticagrelor and fondaparinux. The aim of this prespecified sub-analysis was to assess (the recovery of) left ventricular function by analysing echocardiography data obtained <72 h after admission and at 30-day follow-up, for patients with a confirmed diagnosis of acute coronary syndrome. LVF was determined using ejection fraction (EF) and global longitudinal strain (GLS). Inter-observer variability was tested. No difference in the recovery of EF was found between an immediate and early strategy if the follow-up echocardiograms were compared to baseline: 2.5% (standard deviation (SD): 7.9) and 3.3% (SD: 8.5), p = 0.51, nor was there any difference in GLS recovery between the study groups: -0.8% (SD: 2.5) vs. -0.7% (SD 2.8) p = 0.82. If baseline and follow-up echocardiograms were compared, there was a similar but significant improvement in both EF and GLS in both separate study groups. An immediate invasive strategy in NSTE-ACS patients did not result in an improved left ventricular EF or GLS recovery compared with an early strategy.

One-year mortality in NSTEMI patients is unaffected by timing of PCI within the first week of admission: Results of a real-world cohort analysis.

OBJECTIVES: We aimed to explore the impact of time to percutaneous coronary intervention (PCI) (T2P) on 1-year mortality in non-ST-elevation myocardial infarction (NSTEMI) patients. BACKGROUND: The current guidelines recommend an early invasive strategy for NSTEMI patients. However, impact of an early invasive strategy on mortality is a matter of debate. For that reason, real world data are of great value to determine the optimal treatment window. METHODS: This retrospective single center cohort study was performed in a high-volume PCI center in Amsterdam, The Netherlands. Intermediate- and high-risk NSTEMI patients undergoing PCI were included. The main discriminant was timing of PCI after admission (T2P), stratified according to different time windows (<24 h, 24-72 h, 72 h-7 days or >7 days). We analyzed 1-year mortality and the time distribution of overall survival. RESULTS: In total, 848 patients treated between January 1, 2016 and January 1, 2018 were included in the analysis. T2P was <24 h in 145 patients, 24-72 h in 192 patients, 72 h-7 days in 275 patients, and >7 days in 236 patients. The mean GRACE-risk score was 127.1 (SD 28.7), 130.0 (33.1), 133.8 (32.1), and 148.7 (34.6) respectively, p = <0.001. After adjusting for confounders, 1-year mortality in patients with T2P <24 h did not significantly differ when compared with T2P 24-72 h (OR = 1.08; 95% CI = 0.33-3.51) and T2P 72 h-7 days (OR 1.72; 95% CI = 0.57-5.21) but was significantly higher in T2P >7 days (OR = 3.20; 95% CI = 1.06-9.68). CONCLUSIONS: In an unselected cohort of patients with NSTEMI, treatment by PCI <24 h did not lead to improved survival as compared to aT2P <7 days strategy. Delay in PCI >7 days after admission resulted in worse outcome.

Non-bacterial thrombotic endocarditis manifested by ventricular fibrillation in a patient with low grade ovarian carcinoma: case report and literature review.

BACKGROUND: Non-bacterial thrombotic endocarditis (NBTE) is a rare form of endocarditis notably described in patients with advanced malignancy and auto-immune diseases. It is characterized by the formation of sterile, fibrin-containing vegetations on cardiac endothelium, in the absence of positive blood cultures. It is predominantly located on the mitral- and aortic valve (AV). Vegetations in NBTE are prone to embolize. Trousseau syndrome (TS) is defined as unexplained thrombotic events that precede the diagnosis of malignancy. CASE SUMMARY: A 49-year-old pre-menopausal woman with a history of visual disturbances, recurrent deep vein thrombosis (DVT) with concurrent pulmonary emboli (PE), and uterine myomas with dysfunctional uterine bleeding was resuscitated for ventricular fibrillation. While echocardiography revealed vegetations on the AV, blood cultures remained negative. Additional work-up for the aetiology of sterile vegetations revealed a low-grade ovarian carcinoma. Cardiac analysis showed evidence of myocardial infarction in the absence of coronary atherosclerosis as a cause for ventricular fibrillation. DISCUSSION: Unexplained thrombotic events (venous, arterial, or both) warrant further investigation, e.g., with regard to TS. NBTE is a potential source of thromboembolism in TS and a rare ante-mortem finding, which prompts additional investigation of the underlying cause. In our patient, a triad of (suspected) (i) arterial/systemic embolization (i.e. visual disturbances, splenic infarction, coronary embolism), (ii) peripheral thrombophlebitis/hypercoagulability (i.e. DVT and PE), and (iii) malignancy (i.e. gynaecological abnormalities) raised suspicion of NBTE in the setting of TS. Early diagnosis and treatment of NBTE is of importance due to the high incidence of embolization, with possible fatal outcome.

[Thromboembolisms due to recreational use of nitrous oxide]. / Trombo-embolieën door recreatief lachgasgebruik.

Nitrous oxide (N2O) is increasingly used as a recreational drug, and is presumed relatively safe and innocent. The risks for neurological complications are often known, however the risks of serious thromboembolic events are not. We describe three cases of acute thromboembolic events resulting in serious cardiovascular complications after N2O abuse: one case of myocardial infarction that resulted in a reduced ejection fraction, one case of peripheral arterial occlusion that led to limb amputation and one case of pulmonary embolism that resulted in hemodynamic instability requiring extracorporeal membrane oxygenation (ECMO) and surgical removal. All patients were young adults with a low cardiovascular risk profile. N2O inactivates vitamin B12, leading to vitamin B12 deficiency and subsequent to hyperhomocysteinemia, which is associated with the formation of fibrinolysis-resistant blood thrombi. In conclusion, we contest the safety and innocence of recreational N2O (ab)use. Our three cases illustrate that, next to previously described neurological complications, the use of nitrous oxide is associated with thromboembolic cardiovascular complications, presumably mediated by hyperhomocysteinemia.

Case report of an acute myocardial infarction after high-dose recreational nitrous oxide use: a consequence of hyperhomocysteinaemia?

BACKGROUND: Nitrous oxide (N2O, laughing gas) is increasingly used as a recreational drug and is presumed relatively safe and innocent. It is often being used in combination with other substances, such as cannabis. CASE SUMMARY: A young adult attended the emergency room because of chest pain after recreational use of very high-dose nitrous oxide in combination with cannabis. Electrocardiography demonstrated ST-elevation in the anterior leads. Coronary angiography showed thrombus in the proximal and thrombotic occlusion of the distal left anterior descending coronary artery for which primary percutaneous coronary intervention was attempted. Thrombus aspiration was unsuccessful and the patient was further treated with a glycoprotein IIb/IIIa in addition to dual platelet therapy. Blood results showed low vitamin B12 and folic acid status with concomitant hyperhomocysteinaemia, a known cause of hypercoagulation. Transthoracic echocardiogram showed a moderately reduced left ventricular ejection fraction (LVEF). Three months later, an improvement in LVEF and no recurrent angina or symptoms of heart failure were noticed. DISCUSSION: We report a case of acute myocardial infarction secondary to very high-dose nitrous oxide abuse in combination with cannabis and possible hypoxia. We propose that severe hyperhomocysteinaemia secondary to nitrous oxide-induced vitamin B12 deficiency together with the vasoconstrictive effects of cannabis might pose a seriously increased risk for intracoronary, among others, thrombus formation. In conclusion, we contest the safety and innocence of recreational nitrous oxide (ab)use, notably in the context of other factors increasing the risk of coagulation.

An immediate or early invasive strategy in non-ST-elevation acute coronary syndrome: The OPTIMA-2 randomized controlled trial.

BACKGROUND: In intermediate- and high-risk non-ST elevated acute coronary syndrome (NSTE-ACS) patients, a routine invasive approach is recommended. The timing of coronary angiography remains controversial. To assess whether an immediate (<3 hours) invasive treatment strategy would reduce infarct size and is safe, compared with an early strategy (12-24 hours), for patients admitted with NSTE-ACS while preferably treated with ticagrelor. METHODS: In this single-center, prospective, randomized trial an immediate or early invasive strategy was randomly assigned to patients with NSTE-ACS. At admission, the patients were preferably treated with a combination of aspirin, ticagrelor and fondaparinux. The primary endpoint was the infarct size as measured by area under the curve (AUC) of CK-MB in 48 hours. Secondary endpoints were bleeding outcomes and major adverse cardiac events (MACE): composite of all-cause death, MI and unplanned revascularization. Interim analysis showed futility regarding the primary endpoint and trial inclusion was terminated. RESULTS: In total 249 patients (71% of planned) were included. The primary endpoint of in-hospital infarct size was a median AUC of CK-MB 186.2 ng/mL in the immediate group (IQR 112-618) and 201.3 ng/mL in the early group (IQR 119-479). Clinical follow-up was 1-year. The MACE-rate was 10% in the immediate and 10% in the early group (hazard ratio [HR] 1.13, 95% CI: 0.52-2.49). CONCLUSIONS: In NSTE-ACS patients randomized to either an immediate or an early-invasive strategy the observed median difference in the primary endpoint was about half the magnitude of the expected difference. The trial was terminated early for futility after 71% of the projected enrollment had been randomized into the trial.