Consideration and Application of Lipoprotein(a) in the Risk Assessment of Atherosclerotic Cardiovascular Disease Risk in Adults.

Lipoprotein(a) (Lp[a]) is an low-density lipoprotein (LDL)-like particle in which apolipoprotein (apo) B is covalently bound to a plasminogen-like molecule called apo(a). A High level of Lp(a) has been demonstrated to be an independent, causal, and prevalent risk factor for atherosclerotic cardiovascular disease (ASCVD), as well as aortic valve disease, through mechanisms that promote atherogenesis, inflammation, and thrombosis. With reliable and accessible assays, Lp(a) level has been established to be associated linearly with the risk for ASCVD. The 2021 Canadian Cardiovascular Society Dyslipidemia Guidelines recommend measuring an Lp(a) level once in a person's lifetime as part of the initial lipid screening. The aim of this review is to provide an update and overview of the utility and application of Lp(a) level in the assessment and treatment of adults at risk for ASCVD, consistent with this guideline recommendation.

La lipoprotéine(a), ou Lp(a), est une lipoprotéine de basse densité dans laquelle l'apolipoprotéine B est liée de manière covalente à une molécule semblable au plasminogène, l'apolipoprotéine(a). On a démontré qu'un taux élevé de Lp(a) est un facteur de risque indépendant, causal et fréquent d'athérosclérose cardiovasculaire (ASCV) et de valvulopathie aortique, en raison de mécanismes qui favorisent l'athérogénèse, l'inflammation et la thrombose. Des épreuves fiables et accessibles ont permis d'établir que le taux de Lp(a) était associé de façon linéaire à un risque d'ASCV. Dans ses lignes directrices de 2021 sur la prise en charge de la dyslipidémie, la Société cardiovasculaire du Canada recommande de mesurer le taux de Lp(a) une fois au cours de la vie d'une personne, dans le cadre du dépistage initial des lipides. Le présent article vise à fournir une mise à jour et un compte rendu de l'utilité et de l'application du taux de Lp(a) dans l'évaluation et le traitement des adultes présentant un risque d'ASCV, conformément à cette recommandation issue des lignes directrices.

Do Heart Failure Biomarkers Influence Heart Failure Treatment Response?

PURPOSE OF REVIEW: Heart failure (HF) is one of the leading causes of cardiac morbidity and mortality around the world. Our evolving understanding of the cellular and molecular pathways of HF has led to the identification and evaluation of a growing number of HF biomarkers. Natriuretic peptides remain the best studied and understood HF biomarkers, with demonstrated clinical utility in the diagnosis and prognostication of HF. Less commonly understood is the utility of HF biomarkers for guiding and monitoring treatment response. In this review, we outline the current HF biomarker landscape and identify novel biomarkers that have potential to influence HF treatment response. RECENT FINDINGS: An increasing number of biomarkers have been identified through the study of HF mechanisms. While these biomarkers hold promise, they have not yet been proven to be effective in guiding HF therapy. A more developed understanding of HF mechanisms has resulted in an increased number of available pharmacologic HF therapies. In the past, biomarkers have been useful for the diagnosis and prognostication of HF. Future evaluation on their use to guide pharmacologic therapy is ongoing, and there is promise that biomarker-guided therapy will allow clinicians to begin personalizing treatment for their HF patients.

Anticoagulation in type 2 myocardial infarctions: Lessons learned from the rivaroxaban in type 2 myocardial infarctions feasibility trial.

Background: Type 2 myocardial infarction (T2MI) occurs when myocardial oxygen demand exceeds myocardial oxygen supply. T2MIs occur more frequently and have worse outcomes compared to Type 1 myocardial infarction caused by an acute plaque rupture. No clinical trial evidence is available to guide pharmacological therapies in this high-risk population. Methods: The Rivaroxaban in Type 2 Myocardial Infarction (R2MI) trial (NCT04838808) was a trainee-led, pragmatic, pilot study that randomised patients with a T2MI to either rivaroxaban 2.5 mg twice daily or placebo. The trial was stopped early due to low recruitment. Investigators explored the challenges of conducting the trial in this population. This was supplemented by a retrospective chart review of 10,000 consecutive troponin assays undertaken during the study period. Results: Over a 1-year period, 276 patients with T2MI were screened for inclusion of which only 7 (2.5%) were randomised in the trial. Study investigators identified trial design and participant population factors that limited recruitment. These included: heterogeneity of patient presentation, poor clinical prognosis, and lack of dedicated non-trainee study personnel. The major limitation to recruitment was the frequency of identified exclusion criterion. The retrospective chart review identified 1715 patients with an elevated high-sensitivity troponin level, of which 916 (53%) were adjudicated to be related to T2MI. Of these, 94.5% possessed an exclusion criterion for the trial. Conclusion: Patients with a T2MI are challenging to recruit into clinical trials involving oral anticoagulation. Future studies should account for only ∼1 in every 20 screened individuals being a candidate for study recruitment.

Comparing the Effectiveness of 2 Cardiac Rehabilitation Exercise Therapy Programs.

Cardiovascular diseases are among the leading causes of morbidity and mortality in Canada, highlighting the critical role of disease prevention and risk reduction programs. Cardiac rehabilitation (CR) is a key component of comprehensive cardiovascular care. Currently, more than 200 CR programs are established across the country, varying in duration, number of in-person supervised exercise sessions, and recommendations for exercise frequency at-home. In an increasingly cost-conscious healthcare environment, the effectiveness of healthcare services must be consistently reevaluated. This study evaluates the impact of 2 CR programs implemented by the Northern Alberta Cardiac Rehabilitation Program, by comparing peak metabolic equivalents achieved by study participants in each program. We hypothesize that our "hybrid" CR program, which is structured as an 8-week program with weekly in-person exercise sessions and a prescribed home exercise program, has patient outcomes similar to those of our "traditional" CR program, which required biweekly in-person exercise sessions over the course of 5 weeks. The results of this study may have implications for evaluating how to minimize barriers to both rehabilitation participation and long-term effectiveness of CR programs. The results may help inform the structuring and funding of future rehabilitation programs.

Les maladies cardiovasculaires (MCV) sont parmi les premières causes de morbidité et de mortalité au Canada d'où l'importance des programmes de prévention des MCV et de réduction du risque cardiovasculaire. La réadaptation cardiaque est un élément clé du continuum de soins cardiovasculaires. À l'heure actuelle, il existe plus de 200 programmes de réadaptation cardiaque au pays, qui diffèrent tant par leur durée, par le nombre de séances d'exercice supervisées en personne que par leurs recommandations sur la fréquence des exercices à domicile. Dans un contexte où le coût des soins de santé est de plus en plus préoccupant, l'efficience des services de santé doit constamment être réévaluée. Cette étude évalue les effets de deux programmes de réadaptation cardiaque instaurés par le Cardiac Rehabilitation Program du nord de l'Alberta en comparant l'équivalent métabolique maximal obtenu par les participants à l'étude pour chaque programme. L'hypothèse de départ était que notre programme de réadaptation cardiaque « hybride ¼, qui consiste d'une part en un programme de huit semaines de séances hebdomadaires d'exercices en personne et d'autre part en un programme d'exercices à domicile, donnerait des résultats semblables à ceux de notre programme « traditionnel ¼ de réadaptation cardiaque. Celui-ci se compose de deux séances d'exercices en personne par semaine, pendant cinq semaines. Les résultats de cette étude pourraient nous aider à réduire les obstacles qui nuisent à la participation aux programmes de réadaptation et à l'efficience à long terme de ces programmes. Nous espérons apporter un éclairage sur la structure et le financement des futurs programmes de réadaptation.

Simulation in cardiac critical care.

Medical simulation is a broad topic but at its core is defined as any effort to realistically reproduce a clinical procedure, team, or situation. Its goal is to allow risk-free practice-until-perfect, and in doing so, augment performance, efficiency, and safety. In medicine, even complex clinical situations can be dissected into reproducible parts that may be repeated and mastered, and these iterative improvements can add up to major gains. With our modern cardiac intensive care units treating a growing number of medically complex patients, the need for well-trained personnel, streamlined care pathways, and quality teamwork is imperative for improved patient outcomes. Simulation is therefore a potentially life-saving tool relevant to anyone working in cardiac intensive care. Accordingly, we believe that simulation is a priority for cardiac intensive care, not just a luxury. We offer the following primer on simulation in the cardiac intensive care environment.

Gastric metastases from primary breast cancers: rare causes of common gastrointestinal disorders.

We report two cases of gastric metastases from primary breast cancers. In case 1, a 31-year-old woman with right-sided ductal breast carcinoma presented with nausea, vomiting and frank haematemesis, 8 months after mastectomy and adjuvant chemotherapy. An esophagogastroduodenoscopy (EGD) revealed multiple ulcerated gastric lesions secondary to metastatic adenocarcinoma from primary breast tumour. In case 2, an 84-year-old woman with a history of left lobular carcinoma presented with early satiety, 17 years after initial mastectomy and adjuvant endocrine therapy. An EGD revealed unspecific gastric mucosa with thickened and erythematous folds and biopsies revealed adenocarcinoma from primary breast carcinoma. Our cases demonstrate how gastric metastases have variable, non-specific clinical and endoscopic presentations. Symptoms may include nausea, vomiting, early satiety and gastrointestinal (GI) bleeding. Endoscopic appearance may range from thickened gastric folds to ulcerating lesions. Our cases demonstrate that gastric metastases should be considered in patients with breast cancer history presenting with GI symptoms.

Characterization of the Genome Sequences of Enterovirus C109 from Two Respiratory Disease Cases in Florida, 2016.

The genomic sequences of two enterovirus C109 isolates (EV-C109 USA/FL/2016-21003 and EV-C109 USA/FL/2016-21002) were obtained during two separate case investigations of respiratory disease in two children. This marks the first description of EV-C109 genomes in the United States.

Effects of Scleral-lens Tear Clearance on Corneal Edema and Post-lens Tear Dynamics: A Pilot Study.

SIGNIFICANCE: The present study with small-diameter scleral lenses (SLs) revealed that post-lens tear thickness (PoLTT) was significantly associated with post-lens tear mixing, but not with central corneal edema, after short-term SL wear. PURPOSE: The aim of this study was to investigate the influence of SL tear clearance (PoLTT) on central corneal thickness and post-lens tear dynamics during 5-hour lens wear. METHODS: Neophytes with no active ocular disease were fitted bilaterally with SLs (hofocon A; 15.6-mm diameter; ~438-µm thickness; 97 Dk; 1.44 refractive index) with various initial PoLTT values ranging from 74 to 543 µm. Central corneal thickness and PoLTT were measured using optical coherence tomography during lens wear. Tear mixing was assessed using fluorogram and "out-in" method. RESULTS: The mean central corneal edema after 5-hour lens wear was 1.51% (95% confidence interval, 1.26 to 1.76%; P < .001), reached its peak at 2-hour post-lens insertion (1.65% [95% confidence interval, 1.45 to 1.85%]), and was independent of PoLTT. The fastest fluorescence decay of the post-lens tear film was observed superiorly. The fluorescence decay rate increased from center to periphery in all quadrants except superiorly. An inverse relationship was found between PoLTT and fluorescence decay rate at both 20-minute and 5-hour wear after lens insertion (P < .05). Excluding observations with out-in time exceeding 5 minutes, we found a direct relationship between PoLTT at 20 minutes after lens insertion and out-in time (P = .047). The % change in the PoLTT after 5-hour wear was greater with a thinner initial tear clearance than those with a thicker one (P = .034). CONCLUSIONS: Within our study parameters, a thinner PoLTT under a small-diameter SL was associated with faster PoLTT mixing. However, there was no relationship between PoLTT and central corneal thickness during 5-hour SL wear.

The Relationship of Lid Wiper Epitheliopathy to Ocular Surface Signs and Symptoms.

Purpose: There has been interest in determining whether lid wiper epitheliopathy (LWE) plays a key role in causing ocular discomfort. Conflicting reports have made it difficult to discern whether LWE is more prevalent in certain populations, what characteristics are associated with its severity, and what its role is in symptomology. This cross-sectional study on a large and diverse population attempts to answer these questions. Methods: Subjects were asked to complete questionnaires related to dry eye and to ocular discomfort. A comprehensive set of ocular surface parameters were assessed, including LWE length and width, tear-film lipid layer thickness, fluorescein tear breakup time (FTBUT), lid-parallel conjunctival folds (LIPCOF), and corneal staining. Results: A total of 287 subjects participated in the study. LWE was observed in 45% of the study cohort and was twice as prevalent in Asians than non-Asians (P < 0.005). LWE was more likely to present in contact lens wearers than non-contact lens wearers (P = 0.03). Decreased FTBUT was associated with increased LWE length and width (P < 0.005 and P = 0.01, respectively), although only a small effect size was noted. Presence of LIPCOF was linked with a 0.25-grade increase in LWE width (P = 0.01). Only LWE width was associated with greater symptoms in contact lens wearers. Conclusions: LWE was associated with decreased tear-film stability, contact lens wear, lid anatomy, and LIPCOF. LWE was not associated with symptoms in non-contact lens wearers. LWE width was associated with greater symptoms in contact lens wearers but was only clinically significant with moderate to severe LWE width.

Effects of Lens-Care Solutions on Hydrogel Lens Performance.

SIGNIFICANCE: Lens care multipurpose solutions (MPSs) can have varying effects on contact lens (CL) surface properties and the corneal epithelium. PURPOSE: The aim of this study was to investigate the short-term effects of newer MPS on CL comfort and dryness, prelens tear-film stability, and ocular-surface health. In vitro study was also performed to assess the effect of MPSs on CL surface properties. METHODS: Acuvue 2 CLs were soaked in control solution, Clear Care (CC), or test solutions: PureMoist, Biotrue, RevitaLens (RL), or saline solution (SS). Over four visits, subjects were exposed to control solution in one eye and to test solution in the contralateral eye for 2 hours using presoaked CLs. Contact lens comfort and dryness, ocular-surface health assessment, prelens noninvasive tear breakup time, and corneal epithelial permeability measured with fluorometry were assessed. Captive-sessile bubble technique evaluated CL wettability and viscous drag in vitro. RESULTS: At 10 minutes, mean comfort ± SD with PureMoist (76 ± 22) was lower than CC (86 ± 15, P = .02), Biotrue (92 ± 9, P < .005), RL (90 ± 13, P < .005), and SS (90 ± 14, P < .005). No other difference in comfort or dryness was noted. RevitaLens was associated with greater corneal epithelial permeability than CC (P = .020) and increased corneal staining compared with all MPSs (P < .005 for all). RevitaLens was also associated with longer prelens noninvasive tear breakup than CC (P < .005). In vitro results agreed with clinical findings of tear-film stability as RL reduced viscous drag. Contact lens surface wettability was enhanced by all MPSs in comparison to SS. CONCLUSIONS: Differences of MPSs on the ocular surface were found in vivo and in vitro. RL caused the greatest corneal epithelium disruption but also associated with higher tear-film stability. The effect of MPSs on CL surface properties in vitro seems to reflect how MPSs altered prelens tear stability.

Phenotypic analysis of arrhythmogenic cardiomyopathy in the Hutterite population: role of electrocardiogram in identifying high-risk desmocollin-2 carriers.

BACKGROUND: The p.Gln554X mutation in desmocollin-2 (DSC2) is prevalent in ≈10% of the Hutterite population. While the homozygous mutation causes severe biventricular arrhythmogenic right ventricular cardiomyopathy, the phenotypic features and prognosis of heterozygotes remain incompletely understood. METHODS AND RESULTS: Eleven homozygotes (mean age 32±8 years, 45% female), 28 heterozygotes (mean age 40±15 years, 50% female), and 22 mutation-negatives (mean age 43±17 years, 41% female) were examined. Diagnostic testing was performed as per the arrhythmogenic right ventricular cardiomyopathy modified Task Force Criteria. Inverted T waves in the right precordial leads on ECG were seen in all homozygotes but not in their counterparts (P<0.001). Homozygotes had higher median daily premature ventricular complex burden than did heterozygotes or mutation-negatives (1407 [IQR 1080 to 2936] versus 2 [IQR 0 to 6] versus 6 [IQR 0 to 214], P=0.0002). Ventricular tachycardia was observed in 60% of homozygotes but in none of the remaining individuals (P<0.001). On cardiac magnetic resonance imaging, homozygotes had significantly larger indexed end-diastolic volumes (right ventricular: 122±24 versus 83±17 versus 83±12 mL/m(2), P<0.0001; left ventricular: 93±18 versus 76±13 versus 80±11 mL/m(2), P=0.0124) and lower ejection fraction values compared with heterozygotes and mutation-negatives (right ventricular ejection fraction: 41±9% versus 59±9% versus 61±6%, P<0.0001; left ventricular ejection fraction: 53±8% versus 65±5% versus 64±5%, P<0.0001). Most affected individuals lacked right ventricular wall motion abnormalities. Thus, few met cardiac magnetic resonance imaging task force criteria. CONCLUSIONS: The ECG reliably identifies homozygous p.Gln554X carriers and may be useful as an initial step in the screening of high-risk Hutterites. The cardiac phenotype of heterozygotes appears benign, but further prospective follow-up of their arrhythmic risk is needed.

Overexpression of apolipoprotein F reduces HDL cholesterol levels in vivo.

OBJECTIVE: Apolipoprotein F (ApoF) is a protein component of several lipoprotein classes including HDL. It is also known as lipid transfer inhibitor protein (LTIP) based on its ability to inhibit lipid transfer between lipoproteins ex vivo. We sought to investigate the role of ApoF in HDL metabolism. METHODS AND RESULTS: Adeno-associated viruses (AAV) based on serotype 8, were used to overexpress either murine or human ApoF in mice. Overexpression of murine ApoF significantly reduced total cholesterol levels by 28% (P<0.001), HDL by 27% (P<0.001), and phospholipid levels by 19% (P<0.001). Overexpression of human ApoF had similar effects. Human ApoF was nearly exclusively HDL-associated in mice. In agreement with this finding, greater than 90% of the ApoF in human plasma was found on HDL(3), with only a small amount on LDL. Overexpression of mouse ApoF accelerated the plasma clearance of [(3)H]-cholesteryl ether labeled HDL. Plasma from mice overexpressing ApoF showed improved macrophage cholesterol efflux on a per HDL-C basis. CONCLUSIONS: ApoF overexpression reduces HDL cholesterol levels in mice by increasing clearance of HDL-CE. ApoF may be an important determinant of HDL metabolism and reverse cholesterol transport.