Comparison of modes of failure and clinical outcomes between explanted porcine and bovine pericardial bioprosthetic valves.

Objective: To compare pathological and hemodynamic modes of failure and operative outcomes between explanted porcine and bovine pericardial bioprosthetic valves.

Methods: Patients who underwent explantation of their bioprosthetic valves at Toronto General Hospital from 2007 to 2019 were identified. Retrospective chart review was conducted to attain demographic information, operative outcomes, and echocardiography and pathology reports.

Valve-in-valve prosthesis-late morphological findings.

Since its implantation in 2002, transcatheter aortic valve implantation (TAVI) has become the preferred intervention for patients with severe aortic stenosis and significant co-morbidities. In 2007, it was adopted as a rescue procedure for failed bioprosthetic valves, now known as the valve-in-valve (VIV) procedure. Unlike other modes of treatment with a multitude of phase 4 post-marketing surveillance (PMS) data, use of these valves have increased rapidly even without long term durability data on this procedure and the near lack of information on the pathology of failed transcatheter aortic valve replacement (TAVR) bioprosthesis and especially after the VIV procedure.

Biomechanics of Aortic Dissection: A Comparison of Aortas Associated With Bicuspid and Tricuspid Aortic Valves.

Background Current methods for aortic dissection risk assessment are inadequate for patients with ascending aortic aneurysms associated with either bicuspid aortic valves (BAVs) or tricuspid aortic valves (TAVs). Biomechanical testing of aortic tissue may provide novel insights and biomarkers. Methods and Results From March 2017 to August 2019, aneurysmal ascending aortas (BAV=23, TAV=23) were collected from elective aortic surgery, normal aortas from transplant donors (n=9), and dissected aortas from surgery for aortic dissection (n=7).

A calcified chronic total occlusion preclinical model.

Objective: To create an experimental chronic total occlusion (CTO) model with calcification by dietary modification (cholesterol, calcium carbonate, vitamin D) and local injection of pro-calcification factors (dipotassium phosphate, calcium chloride, and bone morphogenetic protein-2 [BMP-2]).

Background: Percutaneous revascularization of CTOs frequently fails in heavily calcified occlusions. Development of novel approaches requires a reproducible preclinical model of calcified CTO.

Lipomatous hypertrophy of the interatrial septum is a pathologic, not an anatomic diagnosis.

Background And Aim: Lipomatous hypertrophy of the interatrial septum (LHIS), a fatty tumor, is usually diagnosed on both echo and CT/MRI imaging. Cases of LHIS located outside of the interatrial septum are extremely rare and rarer still are these cases large enough to cause symptoms. The clinical literature demonstrates a misunderstanding that fatty tumors outside the intra-atrial area represent lipomas.

Modes of bioprosthetic valve failure: a narrative review.

Purpose Of Review: A thorough understanding of the modes of bioprosthetic valve failure is critical as clinicians will be facing an increasing number of patients presenting with failed bioprostheses in coming years. The purpose of this article is to review modes of bioprosthestic valve degeneration, their management, and identify gaps for future research.

Recent Findings: Guidelines recommend monitoring hemodynamic performance of prosthetic valves using serial echocardiograms to determine valve function and presence of valve degeneration.

Protective role of Nrf2 against ischemia reperfusion injury and cardiac allograft vasculopathy.

Ischemia-reperfusion injury (IRI) and cardiac allograft vasculopathy (CAV) remain unsolved complications post-heart transplant (Tx). The antioxidant transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) has been suggested to inhibit reactive oxygen species-mediated NF-κB activation. We hypothesized that Nrf2 inhibits NF-κB activation post-Tx and suppresses IRI and the subsequent development of CAV.

Severely calcified bicuspid aortic valve stenosis after valve-sparing root replacement: A word of caution.

A 58-year-old man was admitted for reoperation for severe aortic stenosis in a previously preserved bicuspid aortic valve (BAV). He had undergone valve-sparing root replacement (VSSR) for dilated aortic root 6 years ago. Transesophageal echocardiography following VSSR showed good valve function with no aortic incompetence.

Fit-For-Purpose PD-L1 Biomarker Testing For Patient Selection in Immuno-Oncology: Guidelines For Clinical Laboratories From the Canadian Association of Pathologists-Association Canadienne Des Pathologistes (CAP-ACP).

Since 2014, programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) checkpoint inhibitors have been approved by various regulatory agencies for the treatment of multiple cancers including melanoma, lung cancer, urothelial carcinoma, renal cell carcinoma, head and neck cancer, classical Hodgkin lymphoma, colorectal cancer, gastroesophageal cancer, hepatocellular cancer, and other solid tumors. Of these approved drug/disease combinations, a subset also has regulatory agency-approved, commercially available companion/complementary diagnostic assays that were clinically validated using data from their corresponding clinical trials. The objective of this document is to provide evidence-based guidance to assist clinical laboratories in establishing fit-for-purpose PD-L1 biomarker assays that can accurately identify patients with specific tumor types who may respond to specific approved immuno-oncology therapies targeting the PD-1/PD-L1 checkpoint.

Developing a pan-cancer research autopsy programme.

Aims: Rapid procurement of a wide variety of metastatic and primary cancers and normal tissues after death through rapid autopsy opens largely unexplored avenues in cancer research. We describe a high-volume rapid research autopsy programme at a large academic medical centre.

Methods: Advanced-stage cancer patients, most commonly inpatients in palliative care facilities, were approached to participate in a cancer research autopsy programme with the goal of acquiring multidimensionally annotated tissue for cancer research.

Novel mediators of aneurysm progression in bicuspid aortic valve disease.

Bicuspid aortic valve (BAV) disease is a congenital abnormality that is associated with ascending aortic aneurysm yet many of the molecular mechanisms remain unknown. To identify novel molecular mechanisms of aneurysm formation we completed microarray analysis of the proximal (severely dilated) and distal (less dilated) regions of the ascending aorta from five patients with BAV. We identified 180 differentially expressed genes, 40 of which were validated by RT-qPCR.

Primary cardiac sarcomas: A multi-national retrospective review.

Background: Primary cardiac sarcoma (PCS) is a rare but often fatal disease. The current study aimed to analyze the impact of baseline demographics, local and systemic therapies in a contemporary cohort.

Methods: Clinical records of PCS across six institutions in three continents were reviewed.

Giant right atrial aneurysm.

Only a handful of congenital aneurysms of the right atrium have been reported in the literature. They are most commonly found in the third decade of life, and the differential diagnosis depends on the patient's age profile. They are associated with 5% risk of sudden cardiac death.

Antimalarial-induced Cardiomyopathy in Systemic Lupus Erythematosus: As Rare as Considered?

Objective: Antimalarials (AM) are recommended for all systemic lupus erythematosus (SLE) patients without specific contraindications. Their main adverse effect is retinal damage; however, heart disease has been described in isolated cases. The aim of our study is to describe 8 patients with AM-induced cardiomyopathy (AMIC) in a defined SLE cohort.

Adipose tumors of the heart.

Background: Primary cardiac adipose tumors are rare. There are two distinct pathologically defined entities that represent this tumor type: lipoma and lipomatous hypertrophy of the interatrial septum (LHIS). We present a single-center experience with these tumors and demonstrate that the location may not correspond to the pathologic diagnosis.

GLP-1 Receptor Expression Within the Human Heart.

Glucagonlike peptide-1 receptor (GLP-1R) agonists, which are used to treat type 2 diabetes and obesity, reduce the rates of myocardial infarction and cardiovascular death. GLP-1R has been localized to the human sinoatrial node; however, its expression in ventricular tissue remains uncertain. Here we studied GLP-1R expression in the human heart using GLP-1R-directed antisera, quantitative polymerase chain reaction (PCR), reverse transcription PCR to detect full-length messenger RNA (mRNA) transcripts, and in situ hybridization (ISH).

p53 and Mdm2 act synergistically to maintain cardiac homeostasis and mediate cardiomyocyte cell cycle arrest through a network of microRNAs.

Defining the roadblocks responsible for cell cycle arrest in adult cardiomyocytes lies at the core of developing cardiac regenerative therapies. p53 and Mdm2 are crucial mediators of cell cycle arrest in proliferative cell types, however, little is known about their function in regulating homeostasis and proliferation in terminally differentiated cell types, like cardiomyocytes. To explore this, we generated a cardiac-specific conditional deletion of p53 and Mdm2 (DKO) in adult mice.

Pancreatic Neuroendocrine Tumor Producing Insulin and Vasopressin.

The objective of the study is to report a rare case of pancreatic neuroendocrine tumor (pNET) producing insulin and vasopressin. We describe the clinical presentation and management of a metastatic pNET with refractory hypoglycemia and progressive severe hyponatremia. A 52-year-old patient had abdominal pain leading to the diagnosis of a tumor that was initially presumed to be splenic in origin.

A Matched Cohort Study of Patients With End-Stage Heart Failure from Anthracycline-Induced Cardiomyopathy Requiring Advanced Cardiac Support.

Anthracycline-induced cardiomyopathy (AIC) may progress to end-stage heart failure requiring mechanical circulatory support or orthotopic heart transplantation (OHT). Previous studies have described important clinical differences between AIC and nonischemic cardiomyopathy (NIC) cohorts requiring these advanced interventions. Therefore, we sought to extend this literature by comparing echocardiographic parameters, treatment strategies, and the prognosis between matched patients from these cohorts.