Frail patients who fall and their risk on major bleeding and intracranial haemorrhage. Outcomes from the Fall and Syncope Registry.

BACKGROUND: Major bleeding, and intracranial bleeding specifically, are severe complications related to the use of anticoagulation. To what extent the risk for major bleeding is elevated among frail older people is not well known because they are underrepresented in the randomized clinical trials (RCTs). This study investigates the risk for major bleeding (MB) and intra cranial haemorrhage (ICH) in frail older people who fall. METHODS: All patients 65 years and older visiting the Fall and Syncope Clinic, between November 2011 and January 2020, and underwent a MRI of the brain were eligible. Frailty was assessed with a Frailty Index, based on the accumulation of deficits model. Cerebral small vessel disease was described and evaluated as proposed in the position paper of Wardlaw and colleagues in 2013. RESULTS: 479 patients were included in this analysis. Mean follow-up was 7 years per patient (ranging from 1 month to 8 years and 5 months). 368 patients (77%) were frail. A total of 81 patients used oral anticoagulation (OAC). 17 extracranial MB of which 3 were traumatic and 14 gastrointestinal, and 16 ICH occurred. There was a total of 603.4 treatment years with OAC, and 8 MBs occurred among patients on OAC (bleeding rate 1.32 per 100 treatment years), of which 2 ICHs (bleeding rate 0.33 per 100 treatment years). The risk for extracranial MB was increased by the use of antiplatelet agents (APA) (adjusted OR 6.9, CI 95% 1.2-38.3), and by the use of OAC (adjusted OR 9.8, CI 95% 1.7-56.1). The risk for ICH was only heightened by white matter hyperintensities (WMH) (adjusted OR 3.8, CI 95% 1.0-13.4). The use of APA (adjusted OR 0.9, CI 95% 0.3-3.3) or OAC (adjusted OR 0.6, CI 95% 0.1-3.3) did not elevate the risk for ICH. CONCLUSION: In contrast to common belief, frail patients on OAC with repeated falls show a comparable bleeding rate as in the large RCTs, and the use of OAC did not increase the risk for ICH. However, the number of MBs was low, and of ICHs very low, despite extensive follow-up in this registry.

Sex-specific temporal evolution of circulating biomarkers in patients with chronic heart failure with reduced ejection fraction.

BACKGROUND: We aimed to assess differences in clinical characteristics, prognosis, and the temporal evolution of circulating biomarkers in male and female patients with HFrEF. METHODS: We included 250 patients (66 women) with chronic heart failure (CHF) between 2011 and 2013 and performed trimonthly blood sampling during a median follow-up of 2.2 years [median (IQR) of 8 (5-10) urine and 9 (5-10) plasma samples per patient]. After completion of follow-up we measured 8 biomarkers. The primary endpoint (PE) was the composite of cardiac death, cardiac transplantation, left ventricular assist device implantation, and hospitalization due to acute or worsened CHF. Joint models were used to determine whether there were differences in the temporal patterns of the biomarkers between men and women as the PE approached. RESULTS: A total of 66 patients reached the PE of which 52 (78.8%) were male and 14 (21.2%) were female. The temporal patterns of all studied biomarkers were associated with the PE, and overall showed disadvantageous changes as the PE approached. For NT-proBNP, HsTnT, and CRP, women showed higher levels over the entire follow-up duration and concomitant numerically higher hazard ratios [NT-proBNP: women: HR(95%CI) 7.57 (3.17-21.93), men: HR(95%CI) 3.14 (2.09-4.79), p for interaction = 0.104, HsTnT: women: HR(95%CI) 6.38 (2.18-22.46), men: HR(95%CI) 4.91 (2.58-9.39), p for interaction = 0.704, CRP: women: HR(95%CI) 7.48 (3.43-19.53), men: HR(95%CI) 3.29 [2.27-5.44], p for interaction = 0.106). In contrast, temporal patterns of glomerular and tubular renal markers showed similar associations with the PE in men and women. CONCLUSION: Although interaction terms are not statistically significant, the associations of temporal patterns of NT-proBNP, HsTnT, and CRP appear more outspoken in women than in men with HFrEF, whereas associations seem similar for temporal patterns of creatinine, eGFR, Cystatin C, KIM-1 and NAG. Larger studies are needed to confirm these potential sex differences.

[Capecitabine-induced ventricular fibrillation]. / Ventrikelfibrilleren door capecitabine.

BACKGROUND: Capecitabine is an orally-administered chemotherapeutic agent used in the treatment of colorectal, gastric and breast carcinoma. Capecitabine has relatively mild side effects. Less known are its potential severe cardiotoxic effects. CASE DESCRIPTION: We report a case of a 61-year-old man recently diagnosed with rectal cancer. Six days after starting with capecitabine, he developed a cardiac arrest due to ventricular fibrillation (VF). Extensive additional diagnostics did not explain the cardiac arrest nor VF. Given the observed time relation between initiation of capecitabine administration and the occurrence of VF, combined with the absence of other causes for VF, we suspect that VF is a likely consequence of capecitabine-induced coronary vasospasm. CONCLUSION: Capecitabine-induced VF is a rare occurrence. With the increasing use of capecitabine for the treatment of various cancers, health professionals should be aware of these potential cardiotoxic side effects.

ENerGetIcs in hypertrophic cardiomyopathy: traNslation between MRI, PET and cardiac myofilament function (ENGINE study).

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant heart disease mostly due to mutations in genes encoding sarcomeric proteins. HCM is characterised by asymmetric hypertrophy of the left ventricle (LV) in the absence of another cardiac or systemic disease. At present it lacks specific treatment to prevent or reverse cardiac dysfunction and hypertrophy in mutation carriers and HCM patients. Previous studies have indicated that sarcomere mutations increase energetic costs of cardiac contraction and cause myocardial dysfunction and hypertrophy. By using a translational approach, we aim to determine to what extent disturbances of myocardial energy metabolism underlie disease progression in HCM. METHODS: Hypertrophic obstructive cardiomyopathy (HOCM) patients and aortic valve stenosis (AVS) patients will undergo a positron emission tomography (PET) with acetate and cardiovascular magnetic resonance imaging (CMR) with tissue tagging before and 4 months after myectomy surgery or aortic valve replacement + septal biopsy. Myectomy tissue or septal biopsy will be used to determine efficiency of sarcomere contraction in-vitro, and results will be compared with in-vivo cardiac performance. Healthy subjects and non-hypertrophic HCM mutation carriers will serve as a control group. ENDPOINTS: Our study will reveal whether perturbations in cardiac energetics deteriorate during disease progression in HCM and whether these changes are attributed to cardiac remodelling or the presence of a sarcomere mutation per se. In-vitro studies in hypertrophied cardiac muscle from HOCM and AVS patients will establish whether sarcomere mutations increase ATP consumption of sarcomeres in human myocardium. Our follow-up imaging study in HOCM and AVS patients will reveal whether impaired cardiac energetics are restored by cardiac surgery.

The role of cardiac magnetic resonance imaging in differentiating the underlying causes of left ventricular hypertrophy.

The onset of sudden cardiac death and large inter- and intra-familial clinical variability of hypertrophic cardiomyopathy pose an important clinical challenge. Cardiac magnetic resonance imaging is a high-resolution imaging modality that has become increasingly available in the past decade and has the unique possibility to demonstrate the presence of fibrosis or scar using late gadolinium enhancement imaging. As a result, the diagnostic and prognostic potential of cardiac magnetic resonance imaging has been extensively explored in acute and chronic ischaemic cardiomyopathy, as well as in several nonischaemic cardiomyopathies.This review aims to provide a critical overview of recently published studies on hypertrophic cardiomyopathy and discusses the role of cardiac magnetic resonance imaging in differentiating underlying causes of hypertrophic cardiomyopathy, such as familial hypertrophic cardiomyopathy, cardiac involvement in systemic disease and left ventricular hypertrophy due to endurance sports. Also, it demonstrates the use of cardiac magnetic resonance in risk stratification for the onset of sudden cardiac death, and early identification of asymptomatic family members of hypertrophic cardiomyopathy patients who are at risk for the development of hypertrophic cardiomyopathy. (Neth Heart J 2010;18:135-43.).

Magnetic resonance imaging, pacemakers and implantable cardioverter-defibrillators: current situation and clinical perspective.

New developments and expanding indications have resulted in a significant increase in the number of patients with pacemakers and internal cardioverterdefibrillators (ICDs). Because of its unique capabilities, magnetic resonance imaging (MRI) has become one of the most important imaging modalities for evaluation of the central nervous system, tumours, musculoskeletal disorders and some cardiovascular diseases. As a consequence of these developments, an increasing number of patients with implanted devices meet the standard indications for MRI examination. Due to the presence of potential life-threatening risks and interactions, however, pacemakers and ICDs are currently not approved by the Food and Drug Administration (FDA) for use in an MRI scanner. Despite these limitations and restrictions, a limited but still growing number of studies reporting on the effects and safety issues of MRI and implanted devices have been published. Because physicians will be increasingly confronted with the issue of MRI in patients with implanted devices, this overview is given. The effects of MRI on an implanted pacemaker and/or ICDs and vice versa are described and, based on the current literature, a strategy for safe performance of MRI in these patients is proposed. (Neth Heart J 2010;18:31-7.).

Potential of [11C]acetate for measuring myocardial blood flow: Studies in normal subjects and patients with hypertrophic cardiomyopathy.

BACKGROUND: Measuring the rate of clearance of carbon-11 labelled acetate from myocardium using positron emission tomography (PET) is an accepted technique for noninvasively assessing myocardial oxygen consumption. Initial myocardial uptake of [(11)C]acetate, however, is related to myocardial blood flow (MBF) and several tracer kinetic models for quantifying MBF using [(11)C]acetate have been proposed. The objective of this study was to assess these models. METHODS: Eighteen healthy subjects and 18 patients with hypertrophic cardiomyopathy (HCM) were studied under baseline conditions with [(11)C]acetate and [(15)O]water. Four previously reported methods, including single- and multi-tissue compartment models, were used to calculate MBF from the measured [(11)C]acetate rate of influx K (1) and the (previously) reported relationship between K (1) and MBF. These MBF values were then compared with those derived from corresponding [(15)O]water studies. RESULTS: For all models, correlations between [(11)C]acetate and [(15)O]water-derived MBF ranged from .67 to .86 (all P < .005) in the control group and from .73 to .85 (all P < .001) in the HCM group. Two out of four models systematically underestimated perfusion with [(11)C]acetate, whilst the third model resulted in an overestimation. The fourth model, based on a simple single tissue compartment model with spillover, partial volume and recirculating metabolite corrections, resulted in a regression equation with a slope of near unity and an Y-intercept of almost zero (controls, K(1) = .74[MBF] + .09, r = .86, SEE = .13, P < .001 and HCM, K(1) = .89[MBF] + .03, r = .85, SEE = .12, P < .001). CONCLUSION: [(11)C]acetate enables quantification of MBF in fairly good agreement with actual MBF in both healthy individuals and patients with HCM. A single tissue compartment model with standardized correction for recirculating metabolites and with corrections for partial volume and spillover provided the best results.

The left bundle branch block revised with novel imaging modalities.

Left bundle branch block (LBBB) is related to abnormal cardiac conduction and mechanical asynchrony and is associated with hypertension and coronary artery disease. Improved evaluation of left ventricular (LV) mechanical asynchrony is needed, because of the increasing number of patients with LBBB and heart failure. In this paper, we describe tissue Doppler imaging (TDI), strain (rate) imaging and tissue tracking in LBBB patients. A variety of patterns of mechanical activation can be observed in LBBB patients. A recent development, referred to as tissue synchronisation imaging, colour codes TDI time-to-peak systolic velocities of segments and displays mechanical asynchrony. Furthermore, real-time 3D echocardiography provides new regional information about mechanical asynchrony. Contained in an LV model and projected on a bull's eye plot, this modality helps to display the spatial distribution of mechanical asynchrony. Finally, segmental time-to-peak circumferential strain curves, produced by cardiac magnetic resonance imaging, provide additional quantification of LV mechanical asynchrony. Effects of LBBB on regional and global cardiac function are impressive, myocardial involvement seems to play a role and with the help of these novel imaging modalities, new insights continue to develop.

Acute pulmonary congestion in patients with systolic heart failure versus diastolic heart failure: experience of a heart emergency unit.

BACKGROUND: Acute pulmonary congestion can be caused by systolic and diastolic heart failure. Whether this distinction is reflected in clinical outcome is unknown. AIM: To compare outcome after an episode of acute pulmonary congestion in patients with systolic heart failure and diastolic heart failure. METHODS: A retrospective, descriptive study was conducted on consecutive patients who presented with acute pulmonary congestion. Clinical outcome was evaluated based on mortality, number of hospital re-admissions, visits to the cardiology outpatient clinic and cardiovascular events. RESULTS: Altogether 86 patients were enrolled in this study: 59 patients (68%) had systolic dysfunction and 27 (32%) had diastolic dysfunction. Mean age was 75.6±11.0 in the systolic heart failure group and 80.1±9.4 years in the diastolic heart failure group. Mean follow-up was 427 days. Men and women were equally distributed between both patient groups. Re-admission and mortality rates were comparable between both groups. When combining cardiovascular events and mortality, patients with diastolic heart failure had more favourable outcome after acute pulmonary congestion than patients with systolic heart failure (37 vs. 70%, p=0.03). CONCLUSION: The proportions of patients presenting with acute pulmonary congestion due to diastolic heart failure were comparable with those found in literature. Patients were mainly elderly and as often male as female. Readmission and mortality rates were comparable between both patient groups. However, patients with diastolic heart failure had a more favourable prognosis when combining cardiovascular events and mortality.

The role of predicted intracranial bleeding risk in the choice of reperfusion strategy in patients with acute myocardial infarction.

OBJECTIVES: Intracranial haemorrhage after thrombolytic therapy for acute myocardial infarction occurs in 0.5-3% of patients. Prediction models have been developed to predetermine the intracranial bleeding risk, but have rarely been used for assigning the optimal reperfusion strategy. This might result in the use of thrombolytic therapy when primary PTCA would be preferable. METHODS: Prospective data were gathered in 1365 candidates for reperfusion therapy. Risk of intracranial haemorrhage was determined with a risk score derived from large-scale clinical trials. Patients were divided into three groups based on their risk of intracranial haemorrhage: <1%, 1-3% and >3% and stratified by age. RESULTS: An intracranial bleeding risk exceeding 3% was found in 120 patients (9%). These high-risk patients were often treated with thrombolysis (87%). Intracranial bleeding actually occurred in four out of 120 patients (3.3%) in this highest risk group, while no bleeding occurred in the other risk groups. CONCLUSION: The actual incidence of intracranial bleeding is similar to the predicted bleeding risk in high-risk patients. These high-risk patients are predominantly older than 70 years. Nearly all patients exceeding a 3% risk of intracranial haemorrhage were treated with thrombolytic therapy. Primary angioplasty should be preferred in patients aged over 70 years since success rates of direct PTCA are no worse in elderly compared with younger patients.