Cardiovascular Pathology最新文献

Cardiac tamponade from ruptured intrathoracic organs can lead to sudden cardiac death. In rare circumstances, the pulmonary artery can be the source of hemopericardium. We describe a case of a 62-year-old woman with no significant past medical history, who presented with sudden unexpected death. A forensic autopsy revealed 500 ml of hemopericardium. Further dissection demonstrated a saccular aneurysm in the pulmonary artery trunk, along with the evidence of prior dissection, i.e., neointimal layer. Persistent ductus arteriosus (PDA) was also present. Pulmonary artery aneurysms (PAA) are rare and often associated with congenital heart disease (CHD). PDA is the most common CHD related to PAA. Secondary pulmonary hypertension makes the pulmonary artery vulnerable to medial degeneration and increases the risk of dissection and rupture. Careful inspection of the great vessels and congenital anomalies are essential in the forensic autopsies for sudden death investigation.

Over the years, advancements in the field of oncology have made remarkable strides in enhancing the efficacy of medical care for patients with cancer. These modernizations have resulted in prolonged survival and improved the quality of life for these patients. However, this progress has also been accompanied by escalation in mortality rates associated with anthracycline chemotherapy.

Anthracyclines, which are known for their potent antitumor properties, are notorious for their substantial cardiotoxic potential. Remarkably, even after 6 decades of research, a conclusive solution to protect the cardiovascular system against doxorubicin-induced damage has not yet been established. A comprehensive understanding of the pathophysiological processes driving cardiotoxicity combined with targeted research is crucial for developing innovative cardioprotective strategies.

This review seeks to explain the mechanisms responsible for structural and functional alterations in doxorubicin-induced cardiomyopathy.

Hamartoma of mature cardiac myocytes (HMCM) is an extremely rare cardiac tumor characterized by benign growth of differentiated mature striated cardiac myocytes, and usually involves the ventricular myocardium. We describe the case of a 15-year-old female who presented with a short history of atrial fibrillation and a polypoid epicardial tumor that was attached to the interatrial groove by a short pedicle. The resected specimen showed features consistent with HMCM. Although these tumors are not associated with any known molecular or cytogenetic abnormalities, we identified fusions transcripts along with complex copy number anomalies of chromosome 7.

Dilated cardiomyopathy (DCM) is defined as left ventricular enlargement accompanied by systolic dysfunction not explained by abnormal loading conditions or coronary heart disease. The DCM clinical spectrum is broad, ranging from subclinical to severe presentation with progression to end stage heart failure. To date, different genetic loci have been found to have moderate/definitive evidence for causality in DCM and pathogenic variants in the TTN gene represent the main genetic determinant.

Here, we describe a family in which the co-occurrence of two genetic hits, one in the TTN and one in the BAG3 gene, was associated with heterogeneous clinical presentation ranging from subclinical phenotypes to acute cardiogenic shock mimicking fulminant myocarditis. We hypothesize that at least some specific BAG3 genotypes could be related to DCM presenting with acute heart failure and suggest that patients and relatives carrying BAG3 pathogenic variants should be addressed to a tertiary-level heart care center.

The potential of the pericardial space as a therapeutic delivery tool for cardiac fibrosis and heart failure (HF) treatment has yet to be elucidated. Recently, miRNAs and exosomes have been discovered to be present in human pericardial fluid (PF). Novel studies have shown characteristic human PF miRNA compositions associated with cardiac diseases and higher miRNA expressions in PF compared to peripheral blood. Five key studies found differentially expressed miRNAs in HF, angina pectoris, aortic stenosis, ventricular tachycardia, and congenital heart diseases with either atrial fibrillation or sinus rhythm. As miRNA-based therapeutics for cardiac fibrosis and HF showed promising results in several in vivo studies for multiple miRNAs, we hypothesize a potential role of miRNA-based therapeutics delivered through the pericardial cavity. This is underlined by the favorable results of the first phase 1b clinical trial in this emerging field. Presenting the first human miRNA antisense drug trial, inhibition of miR-132 by intravenous administration of a novel antisense oligonucleotide, CDR132L, established efficacy in reducing miR-132 in plasma samples in a dose-dependent manner. We screened the literature, provided an overview of the miRNAs and exosomes present in PF, and drew a connection to those miRNAs previously elucidated in cardiac fibrosis and HF. Further, we speculate about clinical implications and potential delivery methods.

Background

Aortic stenosis (AS) and transthyretin (ATTR) cardiac amyloidosis (CA) share the same clinical profiles and cardiac phenotype. Amyloid deposits have been frequently reported in aortic valves of patients with severe AS referred for surgical aortic valve replacement (SAVR). The aim of this study was to determine the clinical and myocardial status of patients with aortic valve amyloidosis after aortic valve surgery.

Methods and results

We performed a retrospective descriptive study of 46 patients who underwent SAVR for severe AS with amyloid deposits upon histological analysis. All patients were screened for cardiac involvement. Amyloid deposits typing was successful in 35 (76%) patients and 28 (80%) were ATTR. Two (4%) had positive bone scintigraphy and among the 5 myocardial biopsies performed during surgery, 80% were positive for ATTR deposits.

Conclusion

ATTR is the predominant type in the presence of amyloid deposits on the aortic valve after surgery for severe AS but is only rarely accompanied by cardiac uptake on bone scintigraphy. Early stages of myocardial involvement are frequent and myocardial biopsy is more sensitive for detection of mild amyloid deposits than bone scintigraphy

Background

Pericardial fluid (PF) contains cells, proteins, and inflammatory mediators, such as cytokines, chemokines, growth factors, and matrix metalloproteinases. To date, we lack an adequate understanding of the inflammatory response that acute injury elicits in the pericardial space.

Objective

To characterize the inflammatory profile in the pericardial space acutely after ischemia/reperfusion.

Methods

Pigs were used to establish a percutaneous ischemia/reperfusion injury model. PF was removed from pigs at different time points postanesthesia or postischemia/reperfusion. Flow cytometry was used to characterize the immune cell composition of PF, while multiplex analysis was performed on the acellular portion of PF to determine the concentration of inflammatory mediators. There was a minimum of 3 pigs per group.

Results

While native PF mainly comprises macrophages, we show that neutrophils are the predominant inflammatory cell type in the pericardial space after injury. The combination of acute ischemia/reperfusion (IR) and repeatedly accessing the pericardial space significantly increases the concentration of interleukin-1 beta (IL-1β) and interleukin-1 receptor antagonist (IL-1ra). IR significantly increases the pericardial concentration of TGFβ1 but not TGFβ2. We observed that repeated manipulation of the pericardial space can also drive a robust pro-inflammatory response, resulting in a significant increase in immune cells and the accumulation of potent inflammatory mediators in the pericardial space.

Conclusion

In the present study, we show that both IR and surgical manipulation can drive robust inflammatory processes in the pericardial space, consisting of an increase in inflammatory cytokines and alteration in the number and composition of immune cells.