Plaque Rupture and Thrombosis: the Value of the Atherosclerotic Rabbit Model in Defining the Mechanism.

Persistent inflammation and mechanical injury associated with cholesterol crystal accretion within atherosclerotic plaques typically precedes plaque disruption (rupture and/or erosion) and thrombosis--often the terminal events of atherosclerotic cardiovascular disease. To elucidate the mechanisms of these events, the atherosclerotic rabbit model provides a unique and powerful tool that facilitates studies of atherogenesis starting with plaque buildup to eventual disruption. Examination of human coronary arteries obtained from patients who died with myocardial infarction demonstrates evidence of cholesterol crystals perforating the plaque cap and intimal surface of the arterial wall that can lead to rupture. These observations were made possible by omitting ethanol, an avid lipid solvent, from the tissue processing steps. Importantly, the atherosclerotic rabbit model exhibits a similar pathology of cholesterol crystals perforating the intimal surface as seen in ruptured human plaques. Local and systemic inflammatory responses in the model are also similar to those observed in humans. The strong parallel between the rabbit and human pathology validates the atherosclerotic rabbit model as a predictor of human pathophysiology of atherosclerosis. Thus, the atherosclerotic rabbit model can be used with confidence to evaluate diagnostic imaging and efficacy of novel anti-atherosclerotic therapy.

Genotype-Phenotype Correlation of a Rare Transthyretin Variant Causing Amyloidosis.

Left ventricular hypertrophy is a common entity with a broad differential diagnosis. We present a case of a middle-aged woman with left ventricular hypertrophy and neuropathy caused by a rare transthyretin variant in the absence of a family history or regional reports of hereditary transthyretin amyloidosis. This report outlines the diagnosis and management of patients with a mixed phenotype of hereditary transthyretin amyloidosis and enriches clinical data supporting the pathogenicity of a rare variant of transthyretin.

L'hypertrophie ventriculaire gauche est une entité clinique fréquente pour laquelle le diagnostic différentiel est vaste. Nous décrivons le cas d'une femme d'âge moyen présentant une hypertrophie ventriculaire gauche et une neuropathie, causées par un variant rare de la transthyrétine en l'absence d'antécédents familiaux ou de cas régionaux déclarés d'amylose héréditaire à transthyrétine. Le présent article décrit le diagnostic et la prise en charge des patients qui présentent un phénotype mixte d'amylose héréditaire à transthyrétine, et il alimente le bassin de données cliniques sur la pathogénicité d'un variant rare de la transthyrétine.

Emerging Pharmacologic Therapies for Heart Failure With Reduced Ejection Fraction.

The global burden of heart failure has reached epidemic proportions with tremendous health and economic consequences. Sodium glucose cotransporter 2 inhibitors, vericiguat, and omecamtiv mecarbil are novel agents that promise to blunt the high residual risk of heart failure with reduced ejection fraction. We review the vast knowledge base that has rapidly materialized for these agents and is poised to shape the current and future trends and recommendations in heart failure pharmacotherapy.

Le fardeau planétaire que représente l'insuffisance cardiaque (IC) a atteint des proportions épidémiques en plus d'avoir d'énormes répercussions sur la santé et l'économie. Le vericiguat et l'omécamtiv mécarbil sont des inhibiteurs du cotransporteur sodium-glucose de type 2 (SGLT2) novateurs et prometteurs qui donnent de l'espoir dans la réduction du risque résiduel élevé d'insuffisance cardiaque avec fraction d'éjection réduite. Nous examinons à l'heure actuelle la vaste base de connaissances qui s'est rapidement constituée pour ces agents et qui s'apprête à façonner les tendances et recommandations actuelles et futures relatives à la pharmacothérapie de l'IC.