Real-World Experience With Antiplatelet Agents After Percutaneous Coronary Intervention in Patients With an Indication for an Oral Anticoagulant.

ABSTRACT: Patients undergoing percutaneous coronary intervention (PCI) with a clinical indication for oral anticoagulation (OAC) in addition to antiplatelet therapy (APT) necessitate rigorous evaluation of bleeding and ischemic risk to guide therapy. The optimal OAC/APT drug combination and duration of treatment is not known. This study aimed to evaluate the incidence of patients undergoing PCI with an OAC indication and the rationale for post-PCI combined OAC/APT selection in clinical practice. Consecutive patients undergoing PCI with an indication for combined OAC/APT were included in a 12-month retrospective case series. Patient demographics, clinical characteristics, prescribed OAC/APT regimens, and rationale for drug selection were reviewed. PCI was performed in 1650 patients during the study period, with an indication for OAC/APT in 133 (8.1%). A combination of aspirin, P2Y12 inhibitor, and OAC was the most frequently prescribed regime on discharge (n = 103, 81%). Dual antiplatelet therapy (DAPT) in combination with OAC was continued for a mean duration of 6.4 ± 4.4 weeks (range 3-52 weeks) before one antiplatelet was discontinued. There was no significant difference between the mean CHA2DS2-VASc or HAS-BLED score of patients with atrial fibrillation discharged on OAC/DAPT compared with alternate combinations (DAPT alone or OAC/single APT), 3.6 ± 1.3 versus 3.8 ± 1, P = 0.37 and 2.04 ± 0.7 versus 2.05 ± 1.0, P = 0.98, respectively. This case series identifies high variability in OAC/APT treatment duration and limited application of risk scoring systems and high-risk PCI characteristics in the selection of OAC/APT regimens. A more systematic patient assessment is needed to help standardize OAC/APT prescribing for this important patient cohort.

Establishing a Smartphone Ambulatory ECG Service for Patients Presenting to the Emergency Department with Pre-Syncope and Palpitations.

Background and Objectives: The Investigation of Palpitations in the ED (IPED) study showed that a smartphone-based event recorder increased the number of patients in whom an electrocardiogram (ECG) was captured during symptoms over five-fold to more than 55% at 90 days compared to standard care and concluded that this safe, non-invasive and easy-to-use device should be considered part of on-going care to all patients presenting acutely with unexplained palpitations or pre-syncope. This study reports the process of establishing a smartphone palpitation and pre-syncope ambulatory care Clinic (SPACC) service. Materials and Methods: A clinical standard operating procedure (SOP) was devised, and funding was secured through a business case for the purchase of 40 AliveCor devices in the first instance. The clinic was launched on 22 July 2019. Results: Between 22 July 2019 and 31 October 2019, 68 patients seen in the emergency departments (EDs) with palpitations or pre-syncope were referred to SPACC. Of those, 30 were male and 38 were female, and the mean age was 45.8 years old (SD 15.1) with a range from 18 years old to 80 years old. A total of 50 (74%) patients underwent full investigation. On the first assessment, seven (10%) patients were deemed to have non-cardiac palpitations and were not fitted with the device. All patients who underwent full investigation achieved symptomatic rhythm correlation most with sinus rhythm, ventricular ectopics, or bigeminy. A symptomatic cardiac dysrhythmia was detected in six (8.8%) patients. Three patients had supraventricular tachycardia (4%), two had atrial fibrillation (3%), and one had atrial flutter (2%). Qualitative feedback from the SPACC team suggested several areas where improvement to the clinic could be made. Conclusion: We believe a smartphone palpitation service based on ambulatory care is simple to implement and is effective at detecting cardiac dysrhythmia in ED palpitation patients.

Molecular basis for clinical heterogeneity in inherited cardiomyopathies due to myopalladin mutations.

Abnormalities in Z-disc proteins cause hypertrophic (HCM), dilated (DCM) and/or restrictive cardiomyopathy (RCM), but disease-causing mechanisms are not fully understood. Myopalladin (MYPN) is a Z-disc protein expressed in striated muscle and functions as a structural, signaling and gene expression regulating molecule in response to muscle stress. MYPN was genetically screened in 900 patients with HCM, DCM and RCM, and disease-causing mechanisms were investigated using comparative immunohistochemical analysis of the patient myocardium and neonatal rat cardiomyocytes expressing mutant MYPN. Cardiac-restricted transgenic (Tg) mice were generated and protein-protein interactions were evaluated. Two nonsense and 13 missense MYPN variants were identified in subjects with DCM, HCM and RCM with the average cardiomyopathy prevalence of 1.66%. Functional studies were performed on two variants (Q529X and Y20C) associated with variable clinical phenotypes. Humans carrying the Y20C-MYPN variant developed HCM or DCM, whereas Q529X-MYPN was found in familial RCM. Disturbed myofibrillogenesis with disruption of α-actinin2, desmin and cardiac ankyrin repeat protein (CARP) was evident in rat cardiomyocytes expressing MYPN(Q529X). Cardiac-restricted MYPN(Y20C) Tg mice developed HCM and disrupted intercalated discs, with disturbed expression of desmin, desmoplakin, connexin43 and vinculin being evident. Failed nuclear translocation and reduced binding of Y20C-MYPN to CARP were demonstrated using in vitro and in vivo systems. MYPN mutations cause various forms of cardiomyopathy via different protein-protein interactions. Q529X-MYPN causes RCM via disturbed myofibrillogenesis, whereas Y20C-MYPN perturbs MYPN nuclear shuttling and leads to abnormal assembly of terminal Z-disc within the cardiac transitional junction and intercalated disc.

Early after Discharge cardiac CT for low risk chest pain: The ED-CT study.

OBJECTIVES: An accelerated diagnostic pathway is created to aid the management of low risk patients presenting to the emergency room with chest pain. Records are taken of patient outcomes and factors influencing physician decision making between inpatient invasive angiography versus early outpatient cardiac CT angiography. METHODS: A cohort study at 30 days post discharge is undertaken over 1 year. Differences are observed between a population of patients who underwent early outpatient CT and a population of ambulatory haemodynamically stable patients who underwent inpatient fluoroscopic angiography. RESULTS: 369 underwent CT (F = 46%), 37 underwent angiography (F = 30%). Median outpatient CT was at 14 days. At 30 days 0 patients suffered mortality or myocardial infarction. 11% were recommended for invasive angiography. 2% of CT patients underwent coronary revascularisation. Median calcium score was 0. 20% of the CT population were commenced on high potency statin, or had their pre-existing statin dose intensified. Calcium score affected a composition of statin commencement, angiography, and revascularisation (OR 59, p < 0.001). Age, troponin, vascular disease, previous coronary revascularisation appeared to influence choice between CCTA and invasive angiography. CONCLUSION: An accelerated diagnostic pathway for outpatient cardiac CT for chest pain resulted in no mortality or myocardial infarction, with a low level of downstream testing and coronary revascularisation. ADVANCES IN KNOWLEDGE: At a median time to CCTA of 14 days post discharge from the emergency department there is no effect on patient major adverse cardiac events.

Reduced right ventricular myocardial strain in the elite athlete may not be a consequence of myocardial damage. "Cream masquerades as skimmed milk".

BACKGROUND: Latest research shows that the lower resting values of right ventricular (RV) myocardial % strain may represent a physiologic change rather than subclinical myocardial damage. Therefore, we assessed load-independent changes to the RV as a consequence of high intensity training by measuring the Isovolumic acceleration (IVA) of the free wall of the RV in conjunction with NT pro-BNP measured by an electrochemiluminescence assay. METHODS: Seventeen controls (mean age 27 ± 4), 24 soccer footballers (mean age 24 ± 4), and 18 elite rowers (mean age 22 ± 4) were studied. Left ventricular (LV) and RV % strain were measured using two-dimensional (2D) speckle based automated functional imaging (AFI) software. RV free wall IVA was measured using pulsed-wave tissue Doppler at the lateral tricuspid annulus. Standard 2D echo were used to measured RV parameters including the Tei index (systolic and diastolic function) and the total annular plane systolic excursion (TAPSE) of the RV annulus. NT pro-BNP was measured by an electrochemiluminescence assay. RESULTS: The RV diameter was increased in the footballers and elite rowers compared with controls (P < 0.001). RV wall size was greater in the elite rowers compared with controls and footballers (P = 0.002). The peak IVA of the RV was higher in the rowers, compared with the footballers and to controls (P < 0.001). The mean LV and RV % myocardial strain were lower in the elite athletes and the footballers compared with controls (P < 0.001). There was no difference in RV Tei index, levels of BNP, and TAPSE across all subjects. CONCLUSIONS: This study showed a significant increase in IVA of the RV of athletes despite reduced myocardial % strain and normal levels in NT-proBNP. This suggests that the decrease in % strain is not a consequence of myocardial damage, but may represents a part of the physiological response to endurance exercise. Therefore, a reduced IVA in a remodeled RV could herald a pathological response.

Myocardial strain: a clinical review.

BACKGROUND: Myocardial strain-change in myocardial fibre length over the cardiac cycle-is a measure of cardiac muscle function. It is obtained using conventional techniques such as echocardiography and magnetic resonance imaging, adding additional clinical information to augment the current techniques. METHODS: A narrative review of the current relevant literature with respect to myocardial strain, with a focus on strain measured by echocardiography. RESULTS: Myocardial strain identifies global and regional abnormalities in myocardial function and differentiates types of cardiomyopathy. It is an earlier marker of myocardial disease than ejection fraction and is predictive of cardiovascular adverse events. Accurate measurement requires high-quality images and experienced practitioners. CONCLUSION: This review explains advantages and disadvantages of myocardial strain imaging and explains why, through adding increased precision without additional burden, it should be a standard part of cardiac assessment.

Endomyocardial fibrosis with ischaemic stroke.

A Caucasian man in his mid-50s presented to the emergency department with sudden onset right-sided weakness and dysarthria. CT angiogram demonstrated a small volume of left middle cerebral artery territory infarction after which the patient underwent successful thrombolysis. Initial ECG showed diffuse T wave inversion. He was admitted to an acute stroke ward where 72 hours of telemetry demonstrated normal sinus rhythm without arrhythmia. Transthoracic echocardiogram showed a reduced ejection fraction of 47% in the absence of any regional wall motion abnormality. An echogenic mass was noted in the apical inferior septal wall. Cardiac MRI demonstrated circumferential mid to apical endocardial thickening with characteristic appearances consistent with endomyocardial fibrosis (EMF). Furthermore, a visible hypointensity in the apex confirmed left ventricular thrombus adherent to the area of EMF. The patient was started on anticoagulation and heart failure therapy. He has recovered from the ischaemic stroke and is currently under outpatient surveillance.

Long-term Outcomes for Drug-eluting Balloons versus Drug-eluting Stents in the Treatment of Small Vessel Coronary Artery Disease: A Systematic Review and Meta-analysis.

Background: This systematic review and meta-analysis compares long-term outcomes follow-up data comparing drug-eluting balloons (DEBs) and drug-eluting stents (DESs) in interventional treatment of small coronary artery disease (<3 mm). Methods: A systematic review was undertaken along with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome was 1-3-year performance of DEB versus DES in major adverse cardiac events. Secondary outcomes include all-cause mortality, MI, cardiac death, vessel thrombosis, major bleeding, target vessel revascularisation and target lesion revascularisation. Two independent reviewers extracted data. All outcomes used the Mantel-Haenszel and random effects models. ORs are presented with a 95% CI. Results: Of 4,661 articles, four randomised control trials were included (1,414 patients). DEBs demonstrated reduced rates of non-fatal MI at 1 year (OR 0.44; 95% CI [0.2-0.94]), and BASKET-SMALL 2 reported a significant reduction in 2-year bleeding rates (OR 0.3; 95% CI [0.1-0.91]). There was no significant difference in all other outcomes. Conclusion: Long-term follow-up of DEB and DES use in small coronary arteries demonstrates DEBs be comparable with DESs in all outcomes at 1, 2 and 3 years of follow-up. A significant reduction was found in rates of non-fatal MI at 1 year in the DEB arm, and a reduction in major bleeding episodes at 2 years in the BASKET-SMALL 2 trial. These data highlight the potential long-term utility of novel DEBs in small coronary artery disease revascularisation.

Cardiac dysfunction in solid tumours: scoping review.

Cardio-oncology is a dynamic field. Research has suggested that cancer itself can damage the heart, independent of cancer treatment-related cardiac dysfunction (CTRCD). The aim of this study was to establish the nature of cardiovascular abnormalities reported in cancer, excluding CTRCD. Scoping review search included cardiovascular abnormalities in adults with solid tumour malignancies, and excluded CTRCD and thrombotic events. Three databases (CINAHL, Embase, Medline) were searched, supplemented by a handsearch. All screening and data extraction was done by two researchers with consensus reached for any conflicts. Given the heterogeneous nature of the studies identified, data synthesis was narrative. The search identified 42 366 studies. Following deduplication and title/abstract screening, 195 studies were assessed for full-text eligibility. Forty-four studies are included in the final analysis. There are 19 prospective observational studies, 13 retrospective studies, 9 case reports and 3 cross-sectional studies. Types of abnormality identified include cardiomyopathy (16, including Takotsubo (9)), autonomic nervous system (ANS) dysfunction (10), biomarker disturbances (9), reduced myocardial strain (6) and others (3). Due to variable study design, the prevalence was not determined. Cardiovascular abnormalities were associated with morbidity (chest pain, dyspnoea, fatigue) and shortened prognosis. In conclusion: (1) There is evidence for cardiovascular dysfunction in patients with solid tumour malignancies, distinct from CTRCD. People with solid tumours have higher rates of cardiac disease, even when newly diagnosed and treatment naïve. (2) Abnormalities manifest mainly as cardiomyopathies, ANS dysfunction and raised biomarker levels and are associated with significant symptoms. (3) Treatment plans need to take account of these risks, and widen criteria for screening.

Predictive value of high-sensitivity troponin for significant coronary artery disease in new-onset atrial fibrillation with rapid ventricular response.

BACKGROUND: High-sensitivity troponin-T (HS-cTnT) levels are often measured in patients presenting with atrial fibrillation (AF), with many subjected to unnecessary invasive assessments. The significance of a normal or mildly raised HS-cTnT in this context is poorly understood. This study aimed to determine the predictive value of HS-cTnT for significant coronary artery disease (CAD) in new AF with rapid ventricular response. We also compared the discriminative ability of HS-cTnT to suspected angina for significant CAD. METHODS: We examined patients presenting with new AF to two tertiary Irish centers in a defined period. Those included had HS-cTnT taken at presentation and subsequent ischemic evaluation. RESULTS: Of 5350 cases screened for inclusion, 281 were deemed eligible. Of these, 148 and 133 patients had a positive and negative index HS-cTnT, respectively. Of those with negative HS-cTnT, 13 (9.8%) had significant CAD versus 51 (34.5%) with positive HS-cTnT (P < 0.001). Positive Hs-cTnT status remained significant upon multivariate analysis (OR, 2.9; 95% CI, 1.37-6.14; P = 0.005). A similar model where HS-cTnT was replaced with suspected angina produced an OR of 1.64 (95% CI, 0.75-3.59; P = 0.213). A logistic model determined optimal cutoff value for HS-cTnT to be less than 30 ng/l, producing a negative predictive value of 91.8% and area under the receiver operative curve of 83.36. CONCLUSION: HS-cTnT exhibits potential as an effective screening biomarker to predict nonsignificant CAD in new rapid AF, allowing more targeted and rationalized ischemic testing. HS-cTnT may also be a more accurate predictor of significant CAD than clinically suspected stable angina.Graphical abstract: http://links.lww.com/MCA/A540.

The use of deformation imaging in the assessment of patients pre and post transcatheter aortic valve implantation.

BACKGROUND: Deformation imaging represents a method of measuring myocardial function, including global longitudinal strain (GLS), peak atrial longitudinal strain (PALS) and radial strain. This study aimed to assess subclinical improvements in left ventricular function in patients undergoing transcatheter aortic valve implantation (TAVI) by comparing GLS, PALS and radial strain pre and post procedure. METHODS: We conducted a single site prospective observational study of 25 patients undergoing TAVI, comparing baseline and post-TAVI echocardiograms. Individual participants were assessed for differences in GLS, PALS and radial strain in addition to changes in left ventricular ejection fraction (LVEF) (%). RESULTS: Our results revealed a significant improvement in GLS (mean change pre-post of 2.14% [95% CI 1.08, 3.20] p = 0.0003) with no significant change in LVEF (0.96% [95% CI - 2.30, 4.22], p = 0.55). There was a statistically significant improvement in radial strain pre and post TAVI (mean 9.68% [95% CI 3.10, 16.25] p = 0.0058). There was positive trend towards improvements in PALS pre and post TAVI (mean change of 2.30% [95% CI - 0.19, 4.80] p = 0.068). CONCLUSION: In patients undergoing TAVI, measuring GLS and radial strain provided statistically significant information regarding subclinical improvements in LV function, which may have prognostic implications. The incorporation of deformation imaging in addition to standard echocardiographic measurements may have an important role in guiding future management in patients undergoing TAVI and assessing response.

Intravascular lithotripsy-assisted PCI for severely calcified coronary lesions: evaluating the impact on quality of life and outcomes.

BACKGROUND: Despite the increased uptake of intravascular lithotripsy (IVL) for treating severely calcified coronary lesions, there is limited patient-level data examining the effect of IVL on quality of life, symptomatology, and outcomes beyond 30 days. We sought to assess demographics, procedural characteristics, outcomes, and impact of IVL on patient-reported angina after a minimum of 6 months follow-up. METHODS: A retrospective single-center study was conducted of patients treated with coronary IVL between January and October 2020. Baseline demographics were obtained from electronic patient records and SYNTAX scores were calculated from index coronary angiograms. Technical success and complications were assessed along with clinical outcomes, which included all-cause mortality, myocardial infarction (MI), target lesion revascularization (TLR), and MACE (composite of death, stroke, MI, and TLR). Canadian Cardiovascular Society (CCS) angina classification was assessed at virtual clinical follow-up. RESULTS: Forty-seven consecutive patients were included. At a mean follow-up of 306 ± 74 days, the mean CCS angina score was reduced by 53% post-IVL-assisted PCI (2.9 vs 1.4, p < 0.001). Technical and procedural success were high (94% and 92%, respectively). One patient (2%) met the pre-specified criteria for in-hospital MACE and 4 (9%) met pre-specified MACE at follow-up, including 2 deaths and 2 TLR. Procedural complications included coronary dissection (11%) and coronary perforation (6%) and were managed either conservatively or with PCI. CONCLUSIONS: Coronary IVL is a safe and effective adjunctive therapy for treating heavily calcified coronary lesions. This cohort shows high procedural success and a significant reduction in CCS angina at follow-up.

Cancer treatment-related cardiac dysfunction.

OBJECTIVES: This paper describes cardiotoxicity and cancer treatment-related cardiac dysfunction (CTRCD). Long-term sequelae of treatment are important, and changing, and may manifest when a patient is under the care of a supportive care service. METHODS: Key messages for supportive and palliative care clinicians are outlined to facilitate identification and management of CTRCD. RESULTS: Not all cardiotoxicity is alike. Types of cardiotoxicity, cardiac complications of immunotherapy, the challenge of autonomic nervous system dysfunction in cancer and management of cardiotoxicity are highlighted. CONCLUSIONS: The key strategies are early detection of cardiotoxicity, monitoring for development of CTRCD during treatment and surveillance in survivorship.

Dyslipidaemia management in the cardiac rehabilitation clinic of a tertiary referral centre: analysis of the impact of new ESC guidance on LDL-C target achievement.

BACKGROUND: Optimisation of low-density lipoprotein cholesterol (LDL-C) targets is one component of cardiac rehabilitation (CR). The 2019 European Society of Cardiology (ESC) guidelines recommend lower LDL-C targets than those released in 2016. AIMS: To determine the proportion of patients who met 2019 LDL-C targets and compare these to international standards; examine the effect of the introduction of the recent ESC guidelines on target achievement. Examine the choice of lipid lowering therapy (LLT) used in our cohort. METHODS: Retrospective chart review of 163 patients who attended CR in 2019. Baseline LDL-C levels were calculated where applicable. Targets achieved were compared with the contemporary ESC guidance. Required LLT was estimated for those who were unable to meet their LDL-C target. RESULTS: Overall, 96/163 (59%) patients met their absolute LDL-C targets, which was favourable when compared to international standards. Fewer patients treated using the 2019 ESC guidelines met their absolute, (63% (70/112) vs. 51% (26/51)), or relative LDL-C 43% (22/51) targets. A high intensity statin was prescribed in 63% (89/163) of patients and only 9% (5/163) patients were prescribed ezetimibe therapy; increased use of these agents may have led to a further 20% (33/162) of patients meeting their LDL-C targets. 13% (22/163) of patients likely require PCSK9i therapy. CONCLUSIONS: Patients may be more likely to meet LDL-C targets while enrolled in CR compared to standard care. Following the introduction of lower absolute LDL-C targets and additional > 50% LDL-C reduction from baseline requirement, fewer patients are meeting the LDL-C targets set out in the 2019 ESC dyslipidaemia guidelines. Additionally, many patients are not on maximum statin therapy, ezetimibe is under-prescribed, and a guideline-reimbursement gap exists for those who require PCSK9i therapy.

Mechanical Non-ST-Segment Elevation Myocardial Infarction Secondary to Left Ventricular Outflow Tract Pseudoaneurysm: A Unique Entity.

We present a unique case of acute coronary syndrome (ACS) secondary to external coronary artery compression from a left ventricular outflow tract pseudoaneurysm in a postsurgical aortic valve replacement (AVR) patient, subsequently sealed with a pericardial patch. We highlight this rare presentation of ACS in postsurgical AVR patients and the importance of multimodality imaging and treatment of this unique, potentially serious sequela. (Level of Difficulty: Intermediate.).

Particle swarm optimization artificial intelligence technique for gene signature discovery in transcriptomic cohorts.

The development of gene signatures is key for delivering personalized medicine, despite only a few signatures being available for use in the clinic for cancer patients. Gene signature discovery tends to revolve around identifying a single signature. However, it has been shown that various highly predictive signatures can be produced from the same dataset. This study assumes that the presentation of top ranked signatures will allow greater efforts in the selection of gene signatures for validation on external datasets and for their clinical translation. Particle swarm optimization (PSO) is an evolutionary algorithm often used as a search strategy and largely represented as binary PSO (BPSO) in this domain. BPSO, however, fails to produce succinct feature sets for complex optimization problems, thus affecting its overall runtime and optimization performance. Enhanced BPSO (EBPSO) was developed to overcome these shortcomings. Thus, this study will validate unique candidate gene signatures for different underlying biology from EBPSO on transcriptomics cohorts. EBPSO was consistently seen to be as accurate as BPSO with substantially smaller feature signatures and significantly faster runtimes. 100% accuracy was achieved in all but two of the selected data sets. Using clinical transcriptomics cohorts, EBPSO has demonstrated the ability to identify accurate, succinct, and significantly prognostic signatures that are unique from one another. This has been proposed as a promising alternative to overcome the issues regarding traditional single gene signature generation. Interpretation of key genes within the signatures provided biological insights into the associated functions that were well correlated to their cancer type.

Cardiac Magnetic Resonance at 3.0 T in Patients With C282Y Homozygous Hereditary Hemochromatosis: Superiority of Radial and Circumferential Strain Over Cardiac T2* Measurements at Baseline and at Post Venesection Follow-up.

BACKGROUND: Iron-overload cardiomyopathy initially manifests with diastolic dysfunction and can progress to dilated cardiomyopathy if untreated. Previous studies have shown that patients with primary and secondary hemochromatosis can have subclinical left ventricle dysfunction with abnormalities on strain imaging. This study aimed to evaluate the relationship between cardiac T2* values and myocardial-wall strain in patients with hereditary hemochromatosis (HH) at the time of diagnosis and after a course of venesection treatment. MATERIALS AND METHODS: Baseline cardiac magnetic resonance (CMR) at 3 T was performed in 19 patients with newly diagnosed HH with elevated serum ferritin levels and repeated after a course of treatment with venesection. Quantitative T2* mapping and strain analysis were performed offline using dedicated relaxometry fitting and feature-tracking software. RESULTS: The majority (84%) of patients had normal baseline myocardial T2* values (mean 19.3 ms, range 8.9 to 31.2 ms), which improved significantly after venesection (mean 24.1 ms, range 11 to 38.1 ms) ( P =0.021). Mean global radial strain significantly improved from 25.0 (range: 15.6 to 32.9) to 28.3 (range: 19.8 to 35.8) ( P =0.001) and mean global circumferential strain improved, decreasing from -15.7 (range: -11.1 to -19.2) to -17.1 (range: -13.0 to -20.1) ( P =0.001). CONCLUSION: Patients with HH may have normal T2* values in the presence of subclinical left ventricle dysfunction, which can be detected by abnormal radial and circumferential strain. As strain imaging improves following venesection in HH, it may serve as a useful biomarker to guide treatment.

von Willebrand factor links primary hemostasis to innate immunity.

The plasma multimeric glycoprotein von Willebrand factor (VWF) plays a critical role in primary hemostasis by tethering platelets to exposed collagen at sites of vascular injury. Recent studies have identified additional biological roles for VWF, and in particular suggest that VWF may play an important role in regulating inflammatory responses. However, the molecular mechanisms through which VWF exerts its immuno-modulatory effects remain poorly understood. In this study, we report that VWF binding to macrophages triggers downstream MAP kinase signaling, NF-κB activation and production of pro-inflammatory cytokines and chemokines. In addition, VWF binding also drives macrophage M1 polarization and shifts macrophage metabolism towards glycolysis in a p38-dependent manner. Cumulatively, our findings define an important biological role for VWF in modulating macrophage function, and thereby establish a novel link between primary hemostasis and innate immunity.

Two-stage percutaneous closure of mitral periprosthetic valvular leak.

Periprosthetic valve leak can develop as a complication of valve replacement surgery and may manifest as symptomatic valvular regurgitation, heart failure, or haemolysis. We report a case of severe mitral periprosthetic valve leak requiring a two-stage percutaneous closure technique with multiple Amplatzer® III vascular plugs.

Postpartum multi-vessel spontaneous coronary artery dissection in the setting of cocaine and amphetamine use: a case report.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a recognized cause of acute coronary syndrome (ACS). Pregnancy, the postpartum period, and illicit drug use have all been reported as potential triggers. CASE SUMMARY: We describe the case of a 41-year-old patient who presented to the emergency department with chest pain in the setting of recent cocaine and amphetamine use. The patient was 4 months postpartum following an uncomplicated pregnancy. Past medical history was non-contributory, with no known risk factors for ischaemic heart disease. Electrocardiogram was normal but high-sensitivity troponin T was significantly elevated. Coronary angiography revealed multi-vessel SCAD. This was managed conservatively as the patient remained clinically stable and pain free without high-risk anatomy (left main stem or proximal two-vessel coronary artery dissection). DISCUSSION: Spontaneous coronary artery dissection must be considered in a postpartum patient presenting with ACS, particularly in the context of environmental stressors such as illicit drug use. Coronary angiography is key to determine diagnosis and guide management. Conservative therapy is favoured, except for patients with ongoing ischaemia, haemodynamic instability, and left main stem involvement. In this case, we suspect SCAD occurred due to the haemodynamic effects of cocaine and amphetamines in the context of structural arterial changes of the postpartum state.