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Heart failure, whether acute or chronic, remains a major health care crisis affecting almost 6 million Americans and over 23 million people worldwide. Roughly half of those affected will die within 5 years, and the annual cost exceeds $30 billion in the US alone. Although medical therapy has made some modest inroads in partially stemming the heart failure tsunami, there remains a significant population for whom medication is unsuccessful or has ceased being effective; such patients can benefit from heart transplantation or mechanical circulatory support. Indeed, in the past quarter century (and as covered in Cardiovascular Pathology over those years), significant improvements in pathologic understanding and in engineering design have materially enhanced the toolkit of options for such refractory patients. Mechanical devices, whether total artificial hearts or ventricular assist devices, have been reengineered to reduce complications and basic wear and tear. Transplant survival has also been extended through a better comprehension of and improved therapies for transplant vasculopathy and antibody-mediated rejection. Here we review the ideas and treatments from the last 25 years and highlight some of the new directions in nonpharmacologic heart failure therapy. [ABSTRACT FROM AUTHOR]

Abstract: Myocardium has long been considered a terminally differentiated tissue, with injury invariably leading to replacement with fibrosis. However, new reports suggest potential roles for circulating or endogenous stem cells in repopulating myocardium after irreversible injury. Unfortunately, these benefits may represent a double-edged sword. While offering exciting possibilities for therapy following myocardial infarction (MI), stem cells are also increasingly implicated in contributing to a number of vascular pathologies, including the formation of graft arterial disease (GAD) after cardiac transplantation. In this review, the function of stem cells in repopulating infarcted myocardium and their role in the pathogenesis of intimal hyperplastic lesions such as GAD will be discussed. [Copyright &y& Elsevier]

Allograft arteriopathy is a vascular intimal proliferative process that occurs in all solid organ transplants and stands as the single most significant obstacle to successful long-term solid organ transplantation; it shares a number of pathologic features with restenosis lesions and atherosclerosis. This article will review some of the newer developments in our understanding of the immunological and vascular biology underpinnings of the disease, including the roles played by cytokine and chemokine mediators in recruiting and activating both inflammatory cells, as well as smooth muscle cell precursors. [Copyright &y& Elsevier]

This article introduces the Second Special Issue of Cardiovascular Pathology (CVP), the official journal of the Society for Cardiovascular Pathology (SCVP). This CVP Special Issue showcases a series of commemorative review articles in celebration of the 25th anniversary of CVP originally published in 2016 and now compiled into a virtual collection with online access for the cardiovascular pathology community. This overview also provides updates on the major categories of cardiovascular diseases from the perspective of cardiovascular pathologists, highlighting publications from CVP , as well as additional important review articles and clinicopathologic references. • This article introduces the Second Special Issue of Cardiovascular Pathology (CVP), the official journal of the Society for Cardiovascular Pathology (SCVP). • This CVP Special Issue showcases a series of commemorative review articles commemorating the 25th anniversary of CVP originally published in 2016. • This overview also provides updates on the major categories of cardiovascular diseases from the perspective of cardiovascular pathologists. [ABSTRACT FROM AUTHOR]

Pericardial effusion can cause cardiac tamponade physiology with resultant cardiogenic shock and death. Myelofibrosis, the replacement of marrow cavity by fibrous connective tissue, is a secondary complication of a group of disorders known as myeloproliferative neoplasms, which are clonal processes characterized by abnormal proliferative growth of one or more hematopoietic lineages. One consequence of myelofibrosis is the development of hematopoiesis at other anatomic sites, most commonly the spleen and liver, a phenomenon known as extramedullary hematopoiesis (EMH). Herein we report a case of a man who died from pericardial tamponade due to a subacute pericardial effusion secondary to EMH in the pericardium in the setting of myelofibrosis. This case highlights an unusual etiology for pericardial effusion and tamponade that should be considered in cases of myelofibrosis and stimulates a discussion regarding the mechanisms and anatomic distribution of EMH. [ABSTRACT FROM AUTHOR]

Abstract Background The HeartWare HVAD (Medtronic, Minneapolis, MN) is a continuous-flow left ventricular assist device (LVAD) approved by the FDA in 2012 as a bridge to transplant in patients with end-stage left ventricular heart failure. The current inflow cannula has a smooth outer surface near the inflow edge and a sintered collar of titanium microspheres near the pump. A previous case series of HVAD patients bridged to transplant revealed thrombus on the outer surface of the inflow cannula in 8 of 8 patients, predominantly at the smooth-sintered interface, that was associated with a clinical stroke rate of 12.5%. Design Cases of HVAD devices removed at the time of heart transplant were identified in the surgical pathology database. The gross and microscopic findings were reviewed along with clinical data. Results A total of 22 patients with 24 HVAD implants diagnosed with dilated cardiomyopathy (13 patients), ischemic heart disease (4 patients), lymphocytic myocarditis (2 patients), hypertrophic cardiomyopathy (2 patients), and congenital valvular disease (1 patient) were included. Two patients received two HVADs to provide biventricular support. All patients received post-implantation anti-coagulation with an INR goal of 2 to 3. Gross pathologic examination revealed thrombi on the outer aspect of the HVAD inflow cannula in 23 of 24 devices (96%). The inflow cannula of the one device that did not develop thrombus was positioned such that the smooth-sintered interface was buried in the ventricular myocardium and not in contact with blood in the ventricular chamber. Complications during the period of device support included 9 thromboembolic events (41%) including 6 ischemic strokes (27%), 2 intracoronary thromboembolic events and 1 splenic infarct. Patients suffered strokes 4 to 174 days (mean 82) after HVAD placement and had thrombus on the inflow cannula ranging in size from 0.1–2.5 cm (axial), 0.4–4.5 cm (circumferential) and 0.1–0.5 cm (thickness). Histologic evaluation revealed bland, partially organized thrombi without evidence of infection. Other complications included driveline infections (9%), non-driveline related bacteremia (9%) and hemorrhage (5%). Conclusions We report here an extension of our original study to a total of 22 patients with 24 HVAD implants who were all successfully bridged to transplant. We validate the very high prevalence of thrombus around the HVAD inflow cannula, associated with a clinical thromboembolic event in over a third of the patients, the majority of which were strokes. The nidus for thrombus formation appears to be the smooth-sintered interface of the HVAD inflow cannula. Highlights • Thrombus occurred on the outside of the inflow cannula in nearly all HVAD devices. • Thromboembolic events occurred in 9 of 22 patients, including 6 ischemic strokes. • The nidus for thrombus formation appears to be the smooth-sintered interface. [ABSTRACT FROM AUTHOR]

• RNA and metabolite integrity are largely preserved up to 12 hours postmortem in cardiac samples. • Cardioplegic solution storage during the postmortem interval improves preservation of metabolite stability compared to storage in buffered saline. • We demonstrate the feasibility of pairing multiomics data from the exact same cardiac site to facilitate systems biology approaches to investigating cardiovascular disease. • Our approach broadens the availability of human cardiac tissue to be used in more research studies allowing for deep interrogation of multiple anatomic regions from the same heart. We sought to develop a rigorous, systematic protocol for the dissection and preservation of human hearts for biobanking that expands previous success in postmortem transcriptomics to multiomics from paired tissue. Existing cardiac biobanks consist largely of biopsy tissue or explanted hearts in select diseases and are insufficient for correlating whole organ phenotype with clinical data. We demonstrate optimal conditions for multiomics interrogation (ribonucleic acid (RNA) sequencing, untargeted metabolomics) in hearts by evaluating the effect of technical variables (storage solution, temperature) and simulated postmortem interval (PMI) on RNA and metabolite stability. We used bovine (n=3) and human (n=2) hearts fixed in PAXgene or snap-frozen with liquid nitrogen. Using a paired Wald test, only two of the genes assessed were differentially expressed between left ventricular samples from bovine hearts stored in PAXgene at 0 and 12 hours PMI (FDR q <0.05). We obtained similar findings in human left ventricular samples, suggesting stability of RNA transcripts at PMIs up to 12 hours. Different library preparation methods (mRNA poly-A capture vs. rRNA depletion) resulted in similar quality metrics with both library preparations achieving >95% of reads properly aligning to the reference genomes across all PMIs for bovine and human hearts. PMI had no effect on RNA Integrity Number or quantity of RNA recovered at the time points evaluated. Of the metabolites identified (855 total) using untargeted metabolomics of human left ventricular tissue, 503 metabolites remained stable across PMIs (0, 4, 8, 12 hours). Most metabolic pathways retained several stable metabolites. Our data demonstrate a technically rigorous, reproducible protocol that will enhance cardiac biobanking practices and facilitate novel insights into human CVD. Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Current biobanking practices insufficiently capture both the diverse array of phenotypes present in CVDs and the spatial heterogeneity across cardiac tissue sites. We have developed a rigorous and systematic protocol for the dissection and preservation of human cardiac biospecimens to enhance the availability of whole organ tissue for multiple applications. When combined with longitudinal clinical phenotyping, our protocol will enable multiomics in hearts to deepen our understanding of CVDs. [ABSTRACT FROM AUTHOR]

Surgical aortic specimens are usually examined in Pathology Departments as a result of treatment of aneurysms or dissections. A number of diseases, genetic syndromes (Marfan syndrome, Loeys–Dietz syndrome, etc.), and vasculopathic aging processes involved in vascular injury can cause both distinct and nonspecific histopathologic changes with degeneration of the media as a common denominator. Terminology for these changes has varied over time leading to confusion and inconsistencies. This consensus document has established a revised, unified nomenclature for the variety of noninflammatory degenerative aortic histopathologies seen in such specimens. Older terms such as cystic medial necrosis and medionecrosis are replaced by more technically accurate terms such as mucoid extracellular matrix accumulation (MEMA), elastic fiber fragmentation and/or loss, and smooth muscle cell nuclei loss. A straightforward system of grading is presented to gauge the extent of medial degeneration and synoptic reporting tables are provided. Herein we present a standardized nomenclature that is accessible to general pathologists and useful for future publications describing these entities. [ABSTRACT FROM AUTHOR]

Background Aortic valve replacement for calcific aortic valve stenosis is one of the more common cardiac surgical procedures. However, the underlying pathophysiology of calcific aortic valve stenosis is poorly understood. We therefore investigated the histologic findings of aortic valves excised for calcific aortic valve stenosis and correlated these findings with their associated clinical features. Results and Methods We performed a retrospective analysis on 6685 native aortic valves excised for calcific stenosis and 312 prosthetic tissue aortic valves with calcific degeneration at a single institution between 1987 and 2013. Patient demographics were correlated with valvular histologic features diagnosed on formalin-fixed, decalcified, and paraffin embedded hematoxylin and eosin stained sections. Of the analyzed aortic valves, 5200 (77.8%) were tricuspid, 1473 (22%) were bicuspid, 11 (0.2%) were unicuspid, and 1 was quadricuspid. The overall prevalence of osseous and/or chondromatous metaplasia was 15.6%. Compared to tricuspid valves, bicuspid valves had a higher prevalence of metaplasia (30.1% vs. 11.5%) and had an earlier mean age of excision (60.2 vs. 75.1 years old). In addition, the frequency of osseous metaplasia and/or chondromatous metaplasia increased with age at time of excision of bicuspid aortic valves, while tricuspid aortic valves showed the same incidence regardless of patient age. Males had a higher prevalence of metaplasia in both bicuspid (33.5% vs. 22.3%) and tricuspid (13.8% vs. 8.6%) aortic valves compared to females. Osseous metaplasia and/or chondromatous metaplasia was also more common in patients with bicuspid aortic valves and concurrent chronic kidney disease or atherosclerosis than in those without (33.6% vs. 28.3%). No osseous or chondromatous metaplasia was observed within the cusps of any of the prosthetic tissue valves. Conclusions Osseous and chondromatous metaplasia are common findings in native aortic valves but do not occur in prosthetic tissue aortic valves. Bicuspid valves appear to have an inherent proclivity for metaplasia, as demonstrated by their higher rates of osseous metaplasia and/or chondromatous metaplasia both overall and at earlier age compared to tricuspid and prosthetic tissue aortic valves. This predilection could be due to aberrant hemodynamic forces on bicuspid valves, as well as intrinsic genetic changes associated with bicuspid valve formation. Aortic valve interstitial cells may play a central role in this process. Calcification of prosthetic tissue valves is most likely a primarily dystrophic phenomenon. [ABSTRACT FROM AUTHOR]

Inflammatory diseases of the aorta include routine atherosclerosis, aortitis, periaortitis, and atherosclerosis with excessive inflammatory responses, such as inflammatory atherosclerotic aneurysms. The nomenclature and histologic features of these disorders are reviewed and discussed. In addition, diagnostic criteria are provided to distinguish between these disorders in surgical pathology specimens. An initial classification scheme is provided for aortitis and periaortitis based on the pattern of the inflammatory infiltrate: granulomatous/giant cell pattern, lymphoplasmacytic pattern, mixed inflammatory pattern, and the suppurative pattern. These inflammatory patterns are discussed in relation to specific systemic diseases including giant cell arteritis, Takayasu arteritis, granulomatosis with polyangiitis (Wegener’s), rheumatoid arthritis, sarcoidosis, ankylosing spondylitis, Cogan syndrome, Behçet’s disease, relapsing polychondritis, syphilitic aortitis, and bacterial and fungal infections. [ABSTRACT FROM AUTHOR]