Cardiovascular Pathology

Silver for the Society for Cardiovascular Pathology—SCVP Turns 25

Jagdish Butany, Avrum Gotlieb — 2010-04-02

It is 25 years since the inception of the society in 1985! Conceived in a conference room on the 6th floor of the Medical Sciences Building at the University of Toronto, the Society was officially born the following year at the United States and Canadian Academy of Pathology (USCAP) meeting. Since then, the Society has flourished. Educationally, it has been achieving its aims and goals, meeting annually at the USCAP and holding symposia of its own, and in conjunction with the USCAP. In the early years, the Society had an additional meeting at the American Heart Association. However, this was not very productive and was soon canceled. In the last 3 years, the Society has been putting on its own additional symposia on the Saturday evening preceding the USCAP annual meeting. These have covered contemporary topics and have been very successful under the able stewardship of Professor Gaetano Thiene.

Quo Vadis? The Society for Cardiovascular Pathology over the next 25 years and beyond

L. Maximilian Buja, Jagdish Butany — 2010-04-26

Those engaged in medicine, pathology, and biomedical science have experienced major developments, advances, opportunities, and challenges in a milieu of ever increasing pace of change in these fields commencing with the second half of the 20th century and continuing into the start of the current millennium. It was during this period of exciting and rapid technologic, diagnostic and therapeutic progress that the Society for Cardiovascular Pathology (SCVP) was founded 25 years ago. This signal event consolidated the maturation, significance and importance of the scientific discipline and clinical subspecialty of cardiovascular pathology.

Cardiovascular pathology: maturation of a discipline and the Society for Cardiovascular Pathology

Frederick J. Schoen — 2010-04-26

Abstract: This communication briefly summarizes the maturation of Cardiovascular Pathology, both as a subspecialty of Pathology and as an academic discipline, and the founding and contributions of the Society for Cardiovascular Pathology.

The Society for Cardiovascular Pathology celebrating 25 disruptively exciting years

Bruce McManus — 2010-02-05

Abstract: It was 25 years ago when the Society for Cardiovascular Pathology was first organized. The Society has since devoted itself to the advancement of understanding about heart and blood vessel disorders, especially their diagnosis, and for the improvement of prevention, management, and treatment. In this 25 year span, the Society has accomplished many goals and met its initial commitments as an organization, dedication to education and learning, and to collegiality. With the many exciting steps the Society has taken in the first 25 years, it is sure to move to new and significantly transformative endeavours in the coming decades.

Dr. Bruce McManus, 2010 SCVP Distinguished Achievement Award recipient

Jagdish Butany, Avrum Gotlieb — 2010-04-02

Dr. Bruce McManus is a professor in the Department of Pathology and Laboratory Medicine at the University of British Columbia, Vancouver, Canada. Since 2006, he has been the director of the James Hogg iCAPTURE Center of Cardiovascular and Pulmonary Research at St. Hall's Hospital–Providence Health Care, Vancouver, British Columbia, Canada. In September 2007, Dr. McManus was appointed inaugural director of the newly launched Providence Heart and Lung Institute at St. Paul's Hospital. Dr. McManus has served as the inaugural scientific director of the Institute of Circulatory and Respiratory Health, Canadian Institutes of Health Research (CIHR).

L. Maximilian Buja, M.D., 2009 SCVP Distinguished Achievement Award recipient

Jagdish Butany, Avrum Gotlieb — 2010-04-08

L. Maximilian Buja, M.D., has recently been appointed as Executive Director of the Houston Academy of Medicine-Texas Medical Center Library, while continuing as a Professor of Pathology and Laboratory Medicine at The University of Texas Medical School at Houston. He previously was Executive Vice President for Academic Affairs at The University of Texas Health Science Center at Houston, a position he assumed in July 2003 after serving as Dean of The University of Texas Medical School at Houston from April 1996.

Dr. William D. Edwards: 2008 SCVP Distinguished Achievement Award recipient

Jagdish Butany, Avrum Gotlieb — 2010-04-09

William D. Edwards is the Society for Cardiovascular Pathology 2008 Distinguished Achievement awardee. He received a BA in Chemistry from the University of Kansas. His medical school training was at the same University, and he subsequently completed pathology training at the University of Kansas, University of Cincinnati, and the University of Minnesota. The last was with Dr. Jesse Edwards at the United Hospital, Miller Division, in St. Paul, MN, USA. He has worked at the Mayo Clinic Rochester MN since 1978. Currently, he is Professor in Pathology and cross-appointed in cardiology. He is Medical Director of autopsy pathology, Director of the Mayo Tissue Registry, and Director of the Cardiovascular Pathology Fellowship Training Program. His role as a teacher and a diagnostic cardiovascular pathologist has been stellar. Dr. Edwards has written numerous manuscripts that many of us have found invaluable in learning cardiac pathology. His teaching skills are well recognized with a heavy teaching schedule for his local medical colleagues and students and numerous courses and invited lectures in North America and the world. His structured and organized approach to teaching pathology is valued. His teaching has been recognized by his colleagues with numerous Best Teacher awards. He has written on almost all types of cardiovascular pathologies and contributed to the original descriptions of several entities. Echocardiographic pathological correlation, medical photography, and congenital heart disease have remained an interest over the years. Bill has trained many cardiologists, cardiac surgeons, and pathologists, including many who have become cardiac pathologists. A compassionate physician, he is guided by his faith and values. His attitude and behaviour have been recognized by a Karis Award at the Mayo Clinic given to a physician who exemplifies compassionate patient care. Bill has been a role model and a mentor to many of us.

Prevention of sudden cardiac death in the young and in athletes: dream or reality?

Gaetano Thiene, Elisa Carturan, Domenico Corrado, Cristina Basso — 2009-06-17

Abstract: Cardiovascular diseases account for 40% of all deaths in the Western countries, and nearly two thirds of them occur suddenly. Young people (<35 years) are not spared from sudden death (SD) with a rate of 1/100,000 per year. Effort is a trigger with a threefold risk in athletes vs. nonathletes, and sports disqualification is by itself life-saving in people with underlying concealed cardiovascular diseases. Several culprits of cardiac SD may be identified at postmortem and atherosclerotic coronary artery disease is the leading cause (25% of SD cases in the young), mostly consisting of a single obstructive plaque with fibrocellular intimal proliferation. However, the spectrum of cardiovascular substrates is wide and include also congenital diseases of the coronary arteries (mainly anomalous origin), myocardium (arrhythmogenic and hypertrophic cardiomyopathies, myocarditis), valves (aortic stenosis and mitral valve prolapse), and conduction system (ventricular preexcitation, accelerated atrioventricular conduction and block). In up to 20% of cases, the heart is grossly and histologically normal at autopsy (unexplained SD or “mors sine materia”), and inherited ion channel diseases have been implicated (long and short QT syndromes, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia).Targets to treat and prevent SD in the young consist of the following: (a) avoid triggers like effort or emotion, (b) inhibit the onset of arrhythmias with drugs or ablation, (c) switch off arrhythmias with defibrillator, and (d) hinder the recurrence of the disease with genetic counseling and/or therapy. In vivo detection of cardiomyopathies is nowadays feasible by electrocardiogram and/or echocardiography, which resulted in a sharp decline of SD in the athletes in Italy, thanks to obligatory preparticipation screening for sport activity. Genetic screening could play a pivotal role in early detection of asymptomatic mutation carriers of cardiovascular diseases at risk of SD.

SDF-1α involved in mobilization and recruitment of endothelial progenitor cells after arterial injury in mice

2009-06-08

Abstract: Background: Endothelial progenitor cells (EPCs) can be mobilized by cytokines and recruited to sites of neovascularization and neointima, where they differentiate into mature endothelial cells. It is thought that stromal cell-derived factor-1α (SDF-1α) is involved in ischemia-mediated mobilization and homing of EPCs and in vascular injury-mediated mobilization and homing of vascular smooth muscle progenitor cells. It is unclear if SDF-1α plays a similar role in the mobilization and recruitment of EPCs after vascular injury.Methods and Results: SDF-1α was detected by reverse transcriptase–polymerase chain reaction and Western blot in the carotid arteries of mice at different times after wire-induced injury. SDF-1α expression was evident at 1 day and peaked at 3 days after arterial injury. In an ELISA test, a rise in the plasmatic concentration of SDF-1α and a significant reduction of SDF-1α bone marrow (BM) concentration were noticed at different times after injury (Days 1, 3, and 7). Fluorescence-activated cell sorting analysis revealed that the amount of circulating EPCs was increased shortly after induction of vascular injury and persisted for up to 7 days. In SDF-1α antibody-treated mice, only a small rise in the amount of circulating EPCs was noted at 1 day. En-face microscopy and immunohistochemical analysis showed that systemic injection of EPCs after vascular injury demonstrated their recruitment to the sites of endothelial denudation, where they could adopt an endothelium-like phenotype and accelerate reendothelialization of the injured arteries. Fewer CXCR4 (receptor of SDF-1)-blocked EPCs could home to the sites of endothelial denudation, and accelerated reendothelialization was not observed in this group. Treatment of mice after carotid injury with a neutralizing SDF-1α monoclonal antibody for 2 weeks reduced reendothelialization area.Conclusion: We demonstrated for the first time that SDF-1α plays an important role in reendothelialization after vascular injury in mice. This contribution appears to be attributable to SDF-1α-dependent mobilization and recruitment of circulating EPCs.

High prevalence of amyloid in 150 surgically removed heart valves—a comparison of histological and clinical data reveals a correlation to atheroinflammatory conditions

2009-06-08

Abstract: Introduction: The prevalence, pathophysiology, and clinical indicators of valvular amyloid deposition have not been clarified yet.Methods: One hundred fifty surgically resected heart valve specimens [67.4±1.0 years; aortic stenosis (AS), n=100; aortic regurgitation, n=19; mitral stenosis, n=7; mitral regurgitation, n=24] were qualitatively, semiquantitatively, and immunohistochemically analyzed and correlated with clinical data.Results: Amyloid was found in 83/150 specimens with highest prevalence in AS (74/100), intermediate prevalence in mitral stenosis (2/7) and regurgitation (7/24), and lowest prevalence in aortic regurgitation (2/19). Severe and polymorphic amyloid deposits were almost exclusively found in AS (35/100). Filamentous cloudy amyloid patterns occurred with the same frequency in AS (29/100). A combination of both was found only in AS (n=7/100). By immunohistochemistry, none of the most common amyloid proteins was identified except for a weak staining by the apolipoprotein AI antibody, but more intense adjacent to amyloid deposits. Amyloid correlated with valvular thickening (P<.05), hyperlipidemia (P=.07), coronary artery disease (P=.084), and obesity (P=.082).Conclusions: Localized valvular amyloid is predominantly found in stenotic aortic valves. It appears to depend on atheroinflammatory conditions and high shear-stress hemodynamics. Further studies are needed to identify the underlying protein.

Common pathogenic features of atherosclerosis and calcific aortic stenosis: role of transforming growth factor-β

Songyi Xu, Amber C. Liu, Avrum I. Gotlieb — 2009-11-30

Abstract: Calcific aortic stenosis and atherosclerosis have been investigated separately in experimental in vitro and in vivo studies and in clinical studies. The similarities identified in both diseases suggest that similar pathogenic pathways are involved in both conditions. Most current therapeutic studies are focused on statins. The evidence suggests that statin effects on valves may, in large part, be independent of the lipid lowering effects of the drug. There are several molecules that play significant regulatory roles on the development and progression of valve sclerosis and calcification and on growth and complications of atherosclerotic plaques. The purpose of this review is to discuss the pathogenic features of the two conditions, highlight the important similarities, and then review the data that suggest that transforming growth factor-β may play a key regulatory role in both diseases and that this is worthy of study as a potential therapeutic target for both conditions.

Segmental arterial mediolysis of varying phases affecting both the intra-abdominal and intracranial vertebral arteries: an autopsy case report

Ayako Ro, Norimasa Kageyama, Akihiro Takatsu, Tatsushige Fukunaga — 2009-04-17

Abstract: We report an autopsy case of segmental arterial mediolysis (SAM) of various phases occurring in both the intracranial vertebral artery (IVA) and intra-abdominal arteries. The patient was a 70-year-old male found dead in his house. The cause of death was massive intra-abdominal hemorrhage owing to a ruptured right gastroepiploic artery. Histopathological examination revealed that there was a broad arterial dissection as long as 20 cm in the right gastroepiploic artery associated with SAM in the injurious phase. In addition, SAM in the reparative phase was observed as organized arterial dissections in the left gastric artery. Furthermore, SAM in the reparative phase was detected as an arterial dissection in the right IVA undergoing an organizing process. These three lesions were considered to have developed at different times. SAM occurring in both the intra-abdominal and intracranial vertebral arteries is extremely rare. This coincidence may provide a clue to the relationship between SAM and spontaneous IVA dissection.

Professor Alan George Rose (1940–2009), the cardiovascular pathologist from Cabo de Buena Esperanza

Gaetano Thiene — 2010-03-12

In 1992, when the chair of the Jesse E. Edwards Cardiac Registry fell vacant, I was invited to be the reviewer of the application of Dr. Alan G. Rose, Chairman of the Department of Pathology at the University of Cape Town, known to me only from the literature as the cardiac pathologist of the Groote Schuur Hospital in Cape Town, where the first heart transplantation was performed in 1967 by Christian Barnard. He had the curriculum vitae of a scholar!

Alan George Rose: 1940–2009: in memoriam

Runjan Chetty — 2010-04-26

Professor Alan Rose was a graduate of the University of Cape Town, qualifying first as a medical doctor and then, in 1968, as an anatomical pathologist. At that time, he was a pathologist involved with cardiac research in association with the Barnard brothers. This research culminated in the world's first heart transplant, and Alan Rose ultimately conducted the autopsy on the recipient. So a famous and productive career in cardiovascular pathology was launched. His interest and contributions to the field of cardiovascular pathology grew exponentially and in a short time he was recognized as a pioneer, innovator, and major player in this area. His international reputation burgeoned, and he was invited to speak at several meetings overseas.

Sally Patricia Allwork (June 14, 1938–July 12, 2009)

Robert H. Anderson, Stephanie Taylor, Gaetano Thiene — 2009-11-20

After a short illness of rapid onset, Sally Allwork passed away on the July 12, 2009. Sally achieved her ultimate position as a morphologist despite the lack of an initial traditional university education. Her mother was Italian in origin. She left school at the age of 16 after taking her 'O' level examinations. She became an Almoners' Clerk at The Central Middlesex Hospital, continuing her studies in the evenings so as to obtain the necessary qualifications to become a laboratory technician. She was appointed as a student technician at The Hammersmith Hospital and eventually achieved a position as a technician working in the operating rooms. It was there that she met her life-long mentor, Professor Hugh Bentall. Under his subsequent tutelage, she began to prepare homograft heart valves, but technical work did not satisfy her inquiring mind. So, encouraged by Hugh, she studied anatomy under Professor Tony Glenister at The Charing Cross Hospital Medical School, passing an examination on basic anatomy and laboratory procedures which made her eligible to complete further studies. These produced a thesis qualifying for the degree of Master of Philosophy, and following this, another thesis on the functionally univentricular heart, which resulted in the award of Doctor of Philosophy from the University of London.

Reduced cyclic stretch, endothelial dysfunction, and oxidative stress: an ex vivo model

2009-09-07

Abstract: Background: The objective of this study was to investigate whether reduction of cyclic circumferential stretch will impair endothelial function and elevate basal levels of oxidative stress, both known risk factors linked to cardiovascular disease.Methods: Ex vivo and in vitro models were used to perfuse porcine carotid arteries and porcine endothelial cells, respectively, for 24 h. In both cases, one group was allowed to stretch naturally when exposed to a pulse shear stress (6±3 dynes/cm2) combined with a pulse pressure of 80±10 mmHg, yielding a physiological cyclic stretch of 4–5%. This group was compared to a reduced stretch group, achieved by wrapping the arterial segment with a silicon band or by seeding the endothelial cells inside less compliant tubes, decreasing cyclic stretch to 1%.Results: The experimentally reduced compliance caused a significant decrease in bradykinin-dependent vascular relaxation. Reduced compliance significantly decreased the phosphorylation of serine 1177 (Ser1177) on eNOS, suggesting the activity of eNOS was decreased. Overall production of reactive oxygen species was increased by reducing compliance, as visualized with DHE. Finally, p22-phox and p47-phox, key players in the superoxide-generating NAD(P)H oxidase, were also up-regulated by reduced compliance.Conclusions: These findings point out how reduced arterial compliance increases the risk of arterial disease by creating a less functional endothelium, interrupting the eNOS activation pathway, and increasing the vascular levels of oxidative stress.

Utility of immunofluorescence and electron microscopy in endomyocardial biopsies from patients with unexplained heart failure

Rosemary C. She, Elizabeth H. Hammond — 2009-06-08

Abstract: Background: With our increasing understanding of inflammatory heart disease, the relevance of Dallas criteria has come into question. Immunofluorescence (IF) and electron microscopy (EM) can potentially identify immune reactants and ultrastructural changes not visible by light microscopy (LM), particularly in cases not meeting Dallas criteria.Methods: This was a retrospective, descriptive study of native endomyocardial biopsies (MBx) performed 1981 to 2006, undertaken to assess the utility of these methods. All patients had decreased cardiac function but normal coronary angiographic studies. LM identified cases as myocarditis (Dallas+), borderline myocarditis (Dallas+/−), or cardiomyopathy (Dallas−). IF studies (human leukocyte antigen (HLA)-DR, IgG, IgM, IgA, C3d, C1q, and fibrinogen) reported interstitial, capillary, or heart-reactive, antibody-like staining patterns. EM findings were also reviewed.Results: Of 472 records from 429 patients (6 months–78 years old), 44 were Dallas+, 47 Dallas+/−, and 381 Dallas−. Significant IF and/or EM findings were identified in 421 cases (89%). By IF, 142 (37%) Dallas− cases had significant capillary HLA-DR expression. Thirty-four of 37 cases with vascular immune complex deposition were Dallas−. LM commonly failed to detect myofilament loss (138 cases) and endothelial cell changes (126 cases) that were observed by EM.Conclusions: IF is a useful strategy for defining inflammatory phenomenon as it revealed significant immune-related heart disease not demonstrable by LM. EM better defined myofilament loss, a finding previously found to be associated with adverse clinical outcome. We strongly recommend that a portion of tissue obtained from all MBx be routinely frozen for IF and fixed appropriately for EM studies. Future studies characterizing the inflammatory molecular profile of myocardial tissues may better define myocarditis.

Hypoplastic coronary artery disease causing sudden death. Report of two cases and review of the literature

2009-07-21

Abstract: Congenital coronary anomalies represent a condition often unrecognized in the living and in the dead. Investigating this condition is relevant for both clinicians and pathologists in order to identify potentially unrecognized coronary causes of sudden death.Hypoplastic coronary artery disease (HCAD) is a rare congenital abnormality reported to be associated with sudden death.We report two additional cases of previously apparently healthy people who died suddenly and were found to have HCAD at postmortem evaluation. The clinicopathologic findings are discussed along with a review of the literature.

Cellular pathology of mitral valve prolapse

Marco Prunotto, Philippe Primo Caimmi, Massimo Bongiovanni — 2009-04-17

Abstract: Background: Mitral valve prolapse (MVP) is the most frequent cause of chronic, pure, and isolated mitral regurgitation, and is estimated to affect more than 144 million individuals worldwide. This short review focuses in particular on the structural and cellular aspects of MVP in humans. The key microscopic change in MVP appears to occur in the fibrosa, on which the structural integrity of the entire valve depends. Recent discoveries showed that proteoglycans may play an active role in both MVP initiation and/or progression together with valvular interstitial cells. A full understanding of the cellular basis of MVP goes beyond a mere mechanicistic description of the disease, involving the transformation of resting fibroblasts into activated myofibroblasts.Conclusions: Mitral valve could represent therefore an ideal environment to study early transformation phases of fibroblasts toward a protomyofibroblast phenotype.

Unusual cardiovascular manifestations of sarcoidosis, a report of three cases: coronary artery aneurysm with myocardial infarction, symptomatic mitral valvular disease, and sudden death from ruptured splenic artery

Joel H. Barton, Fabio Tavora, Andrew Farb, Ling Li, Allen P. Burke — 2009-06-08

Abstract: Background: Cardiac and vascular involvement by sarcoid is only rarely recognized clinically. Involvement of muscular arteries such as epicardial coronaries or the splenic artery has not been previously reported in these patients, and valvular disease has been reported only rarely.Methods: We present herein clinical, imaging and pathologic documentation of three such patients, each displaying one of these unusual manifestations and enlarging the spectrum of cardiac sarcoid.Results: The presentations were life threatening, one with myocardial infarction caused by a coronary artery aneurysm, a second with splenic artery rupture and hemorrhage, and the third with severe mitral regurgitation. The clinical and histopathologic findings are described and a review of the literature is undertaken.

Second harmonic generation microscopy to investigate collagen configuration: a pericarditis case study

2009-07-27

Abstract: We have used second-harmonic-generation (SHG) to image collagen fibers in pericardial tissue removed from a patient with constrictive pericarditis and compared this to healthy pericardium. SHG imaging allowed for the visualization of collagen fibers without the need for staining or pretreatment. Images were compared to stained histology slides. Collagen fibers in SHG and histology images displayed the same structure and morphology. The mature collagen of the parietal pericardium was easily distinguishable from the new collagen accumulation due to the pericarditis. SHG imaging can provide a convenient and valuable architectural profile of collagen organization.

Recurrent cardiac amyloidosis following previous heart transplantation

Adriana Luk, Eric Ahn, Andrew Lee, Heather J. Ross, Jagdish Butany — 2009-09-10

Abstract: Recurrent cardiac amyloidosis has been reported in the literature. We present two cases, one at 41 months after heart transplant and autologous stem cell transplant, and the other, at 83 months following heart transplantation. The former is the first case ever reported of a patient with amyloid light chain amyloidosis with systemic recurrence following these two treatment modalities, and the latter is a patient with hereditary amyloidosis, whose interval to disease recurrence is the longest ever reported for this type.

Ultrastructural pathology of the nuclear envelope in familial lamin A/C cardiomyopathy

2009-04-17

Abstract: The LMNA gene encodes lamins A and C, two structural proteins of the nuclear lamina, a part of the nuclear envelope. LMNA gene mutations may cause familial cardiomyopathy. In this article, we describe an electron microscopic image of an endomyocardial biopsy specimen of a subject with familial cardiomyopathy with early onset cardiac fibrosis due to a deletion in LMNA, showing structural damage of the nuclear envelope.

Aspergillus endocarditis in a known case of allergic bronchopulmonary aspergillosis: an autopsy report

2009-02-12

Abstract: Invasive aspergillosis is an emerging infection mainly affecting immunocompromised patients. Aspergillus endocarditis remains a rare infection and usually occurs following cardiac surgery for prosthetic valves. This is an uncommon case of a 60-year-old asthmatic male who developed allergic bronchopulmonary aspergillosis during the course of his illness, and while receiving low dose oral steroids, he subsequently developed right-sided Aspergillus mural and native valvular endocarditis with extensive invasive pulmonary aspergillosis.

Editorial Board

2010-07-01