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.

Myocardial Infarction in the ISCHEMIA Trial: Impact of Different Definitions on Incidence, Prognosis, and Treatment Comparisons.

BACKGROUND: In the ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), an initial invasive strategy did not significantly reduce rates of cardiovascular events or all-cause mortality in comparison with a conservative strategy in patients with stable ischemic heart disease and moderate/severe myocardial ischemia. The most frequent component of composite cardiovascular end points was myocardial infarction (MI). METHODS: ISCHEMIA prespecified that the primary and major secondary composite end points of the trial be analyzed using 2 MI definitions. For procedural MI, the primary MI definition used creatine kinase-MB as the preferred biomarker, whereas the secondary definition used cardiac troponin. Procedural thresholds were >5 times the upper reference level for percutaneous coronary intervention and >10 times for coronary artery bypass grafting. Procedural MI definitions included (1) a category of elevated biomarker only events with much higher biomarker thresholds, (2) new ST-segment depression of ≥1 mm for the primary and ≥0.5 mm for the secondary definition, and (3) new coronary dissections >National Heart, Lung, and Blood Institute grade 3. We compared MI type, frequency, and prognosis by treatment assignment using both MI definitions. RESULTS: Procedural MIs accounted for 20.1% of all MI events with the primary definition and 40.6% of all MI events with the secondary definition. Four-year MI rates in patients undergoing revascularization were more frequent with the invasive versus conservative strategy using the primary (2.7% versus 1.1%; adjusted hazard ratio [HR], 2.98 [95% CI, 1.87-4.73]) and secondary (8.2% versus 2.0%; adjusted HR, 5.04 [95% CI, 3.64-6.97]) MI definitions. Type 1 MIs were less frequent with the invasive versus conservative strategy using the primary (3.40% versus 6.89%; adjusted HR, 0.53 [95% CI, 0.41-0.69]; P<0.0001) and secondary (3.48% versus 6.89%; adjusted HR, 0.53 [95% CI, 0.41-0.69]; P<0.0001) definitions. The risk of subsequent cardiovascular death was higher after a type 1 MI than after no MI using the primary (adjusted HR, 3.38 [95% CI, 2.03-5.61]; P<0.001) or secondary MI definition (adjusted HR, 3.52 [2.11-5.88]; P<0.001). CONCLUSIONS: In ISCHEMIA, type 1 MI events using the primary and secondary definitions during 5-year follow-up were more frequent with an initial conservative strategy and associated with subsequent cardiovascular death. Procedural MI rates were greater in the invasive strategy and with the use of the secondary MI definition. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

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.

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.

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 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.

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 biochemical aspects of a non-ST-segment elevation acute coronary syndrome.

The clinical course of an acute coronary syndrome can vary from relatively benign to potentially fatal. The biomarkers of myocardial necrosis relate to the amount of myocardial damage and are closely linked to a patient's prognosis. They are measured to help guide management decisions. Recent interest in myocardial neurohumoral mechanisms has identified the natriuretic peptides as strong prognostic biomarkers following an ischemic event. During an acute event they provide information regarding the area of myocardium at risk. The biomarkers of inflammation, such as C-reactive protein, are related to both the development of atherosclerosis and the risk of acute ischemic events. The mechanism characterizing the pathophysiology of the syndrome is represented by these cardiac biomarkers. Assessing combinations of pathobiologically diverse biomarkers may provide a better risk evaluation method and further dictate subsequent therapy.

Gas embolism during hysteroscopic surgery using bipolar or monopolar diathermia: a randomized controlled trial.

OBJECTIVE: The objective of the study was to determine the incidence and amount of gas embolism during hysteroscopic surgery using either monopolar or bipolar diathermia and to investigate the relationship between the severity of gas embolism and the amount of intravasation of distension fluid. STUDY DESIGN: This was a randomized, observer-blinded trial. Fifty patients, scheduled for hysteroscopic surgery, were assigned to either monopolar or bipolar diathermia. Transesophageal echocardiography was used to detect and classify gas embolism (grade 0-IV). Intravasation of distension fluid was measured. RESULTS: Venous gas embolism was observed in all but 1 patient. A higher incidence of more extensive (grade IV) was seen during bipolar diathermia (42% vs 13%; P = .031). Paradoxical embolism was observed in 2 patients. When intravasation exceeded 1000 mL, significantly more grade IV venous gas embolism was seen (P = .049). CONCLUSION: During hysteroscopic surgery, gas embolism was equally observed irrespective of the type of diathermia. However, more extensive embolism was observed when intravasation of distension fluid exceeded 1 L. These results question the acceptance of up to 2500 mL intravasation of distension fluid if bipolar diathermia is used.

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.

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.

The value of N-terminal proB-type natriuretic peptide for early identification of myocardial infarction in patients with high-risk non-ST-elevation acute coronary syndromes.

BACKGROUND: N-terminal proB-type natriuretic peptide (NT-proBNP) is a marker of biomechanical strain, secreted by cardiomyocytes in response to ischemia. As necrosis occurs after prolonged ischemia, a rise in NT-proBNP concentration could precede a rise in markers of necrosis. METHODS: The aim of the study was to evaluate whether NT-proBNP is able to identify those patients with an evolving myocardial infarction (MI) with high-risk non-ST-elevation acute coronary syndromes (NSTE-ACS). Data were analyzed from a prospective cohort of 103 high-risk NSTE-ACS patients admitted within 6 h after onset of pain and treated with an early invasive strategy. NT-proBNP samples, obtained immediately upon admission, were related to the presence of an in hospital MI. The optimal cut-off value for NT-proBNP was determined using receiver-operating characteristics (ROC) curve analysis. RESULTS: Analyses was performed separately for creatinine kinase MB-mass (CKMB) and troponin T (TnT) based MI definitions. In both cases, a NT-proBNP concentration above 40 pmol/L (339 ng/L) at admission proved to be independently associated with the presence of MI. The diagnostic odds ratio (OR) for CKMB-MI was 4.9 (confidence interval 2.0-11.9, p<0.001). The diagnostic OR for TnT-MI was 4.9 (1.8-14.4, p=0.003). Adjusting for differences in baseline variables did not weaken the diagnostic OR. In addition, elevated NT-proBNP concentrations were related to unfavour-able demographic, physical and biochemical parameters. CONCLUSIONS: With a dichotomous cut-off value, a single elevated NT-proBNP (>40 pmol/L) at admission provides independent information about the presence of MI in high-risk NSTE-ACS patients.

The current practice for cocaine-associated chest pain in the Netherlands.

INTRODUCTION: Cocaine is considered a cardiovascular risk factor, yet it is not included in the frequently used risk stratification scores. Moreover, many guidelines provide limited advice on how to diagnose and treat cocaine-associated chest pain (CACP). This study aimed to determine the current practice for CACP patients in emergency departments and coronary care units throughout the Netherlands. METHODS: An anonymous online questionnaire-based survey was conducted among Dutch emergency physicians and cardiologists between July 2015 and February 2016. The questionnaire was based on the American Heart Association CACP treatment algorithm. RESULTS: A total of 214 subjects were enrolled and completed the questionnaire. All responders considered cocaine use a risk factor for developing acute coronary syndrome (ACS), nevertheless 74.4 % of emergency physicians and 81.1 % of cardiologists do not always question chest pain patients about drug use. Of all responders, 73.6 % never perform toxicology screening. Most responders (60 %) observe patients with CACP according to the European Society of Cardiology ACS guideline, and 24.3 % give these patients ß-blockers. CONCLUSION: The current practice for CACP patients in most emergency departments and coronary care units in the Netherlands is not in line with the AHA scientific statement. Emergency physicians and cardiologists should be advised to routinely question all chest pain patients on drug history and be aware that the risk stratifications scores are not validated for CACP. Despite the AHA scientific statement of 2008, many respondents utilize ß-blockers for CACP patients, which is supported by published evidence since the statement appeared.

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.

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.

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.

[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.

The association of depressive symptoms with survival in a Dutch cohort of patients with end-stage renal disease.

AIM: To evaluate the prevalence and the influence on survival of depressive symptoms in a European cohort of end-stage renal disease (ESRD) patients on renal replacement therapy (RRT). METHODS: In a prospective fashion, symptoms of depression were evaluated in ESRD patients on RRT using the depression subscore of the Hospital Anxiety and Depression Scale (HADS). Fatal and non-fatal clinical events were determined during a 1-year follow-up. RESULTS: Of 101 patients with ESRD, 42% showed manifest depressive symptoms, defined as a HADS-D score > or =7. No association was found between depressive symptoms and severity of somatic disease. During follow-up, all-cause mortality was significantly higher in patients with depressive symptoms above threshold (n = 42, mortality: 26%) compared to patients with depressive symptoms below threshold (n = 59, mortality 8%), (crude HR 3.3, CI 1.2-9.6, P = 0.02). The excess in mortality was mainly caused by a higher incidence of septicaemia (0 versus 12%, P = 0.01). After adjustment for clinical parameters, this association between depressive symptoms and mortality became even stronger. There was no significant difference observed in the incidence of cardiovascular events. CONCLUSIONS: Patients with ESRD treated with dialysis show a high level of depressive symptoms that is independently associated with poor survival. Future research should address appropriate therapeutic regimens.

A Perforated Mitral Valve Aneurysm: A Rare but Serious Complication of Aortic Valve Endocarditis Resulting From a Regurgitant Jet Lesion.

Infective endocarditis has high morbidity and mortality rates. The aortic valve is most often affected in native valve endocarditis. Complications of aortic valve endocarditis range from local abscess and fistula formation, systemic complications secondary to thromboembolism and septic embolization, to congestive heart failure resulting from conduction system involvement and valve damage. A rare complication of aortic valve endocarditis is the occurrence of a 'jet lesion' on the mitral valve. Such a lesion, caused by an impinging regurgitant jet stream from a damaged aortic valve, can become directly and indirectly inoculated and evolve into a local infected aneurysm which might eventually rupture causing acute severe congestive heart failure and/or peripheral thromboembolism. We present the case of a 63-year-old man who presented with aortic valve endocarditis complicated by a perforated mitral valve aneurysm, congestive heart failure, and peripheral thromboembolism.