Isolated congenital absent aortic valve cusps in a fetus: A case report

Congenital absence of aortic valve cusps is an extremely rare congenital heart malformation. The absence of aortic valve cusps leads tosevere aortic regurgitation with resultant rapid and progressive heart failure and growth retardation in the fetus. Congenital absence ofthe aortic leaflets in association with other cardiac defects has been reported in the literature, but the isolated anomaly is not reportedyet. We present a case of a fetus with isolated congenital severe aortic regurgitation from absent aortic cusps and pathological specimenof this rare entity

Patent Foramen Ovale: Current Pathology, Pathophysiology, and Clinical Status

Patent foramen ovale (PFO) is experiencing increased clinical interest as a congenital cardiac lesion persisting into adulthood. It is implicated in several serious clinical syndromes, including stroke, myocardial infarction, and systemic embolism. The PFO is now amenable to percutaneous interventional therapies, and multiple novel technologies are either available or under development for lesion closure. The PFO should be better understood to take advantage of emerging percutaneous treatment options. This paper reviews PFO anatomy, pathology, pathophysiology, and clinical impact and discusses current therapeutic options

Prevalence, Clinical Profile, and Significance of Left Ventricular Remodeling in the End-Stage Phase of Hypertrophic Cardiomyopathy

Background— End stage (ES) is a recognized part of the hypertrophic cardiomyopathy (HCM) disease spectrum. Frequency, clinical profile and course, and treatment strategies in these patients remain incompletely defined. Methods and Results— Three HCM cohorts comprised 1259 patients, including 44 (3.5%) characterized as ES with systolic dysfunction (ejection fraction <50% at rest; range 15% to 49%). ES developed at a wide age range (14 to 74 years), with 45% of patients ≤40 years old. Although 29 patients (66%) died of progressive heart failure, had sudden death events, or underwent heart transplantation, 15 (34%) survived with medical management over 3±3 years. Duration from onset of HCM symptoms to ES identification was considerable (14±10 years), but ES onset to death/transplantation was brief (2.7±2 years). ES occurred with similar frequency in patients with or without prior myectomy ( P =0.84). Appropriate defibrillator interventions were 10% per year in patients awaiting donor hearts. Most ES patients (n=23; 52%) showed substantial left ventricular (LV) remodeling with cavity dilatation. Less complete remodeling occurred in 21 patients (48%), including 5 with persistence of a nondilated and markedly hypertrophied LV. Pathology and magnetic resonance imaging showed extensive (transmural) fibrosis in 9 of 11 ES patients. At initial evaluation, patients who developed ES were younger with more severe symptoms, had a larger LV cavity, and more frequently had a family history of ES than other HCM patients. Conclusions— ES of nonobstructive HCM has an expanded and more diverse clinical expression than previously appreciated, including occurrence in young patients, heterogeneous patterns of remodeling, frequent association with atrial fibrillation, and impaired LV contractility that precedes cavity dilatation, wall thinning, and heart failure symptoms. ES is an unfavorable complication (mortality rate 11% per year) and a sudden death risk factor; it requires vigilance to permit timely recognition and the necessity for defibrillator implantation and heart transplantation

Mutations with pathogenic potential in proteins located in or at the composite junctions of the intercalated disk connecting mammalian cardiomyocytes: a reference thesaurus for arrhythmogenic cardiomyopathies and for Naxos and Carvajal diseases

In the past decade, an avalanche of findings and reports has correlated arrhythmogenic ventricular cardiomyopathies (ARVC) and Naxos and Carvajal diseases with certain mutations in protein constituents of the special junctions connecting the polar regions (intercalated disks) of mature mammalian cardiomyocytes. These molecules, apparently together with some specific cytoskeletal proteins, are components of (or interact with) composite junctions. Composite junctions contain the amalgamated fusion products of the molecules that, in other cell types and tissues, occur in distinct separate junctions, i.e. desmosomes and adherens junctions. As the pertinent literature is still in an expanding phase and is obviously becoming important for various groups of researchers in basic cell and molecular biology, developmental biology, histology, physiology, cardiology, pathology and genetics, the relevant references so far recognized have been collected and are presented here in the following order: desmocollin-2 (Dsc2, DSC2), desmoglein-2 (Dsg2, DSG2), desmoplakin (DP, DSP), plakoglobin (PG, JUP), plakophilin-2 (Pkp2, PKP2) and some non-desmosomal proteins such as transmembrane protein 43 (TMEM43), ryanodine receptor 2 (RYR2), desmin, lamins A and C, striatin, titin and transforming growth factor-β3 (TGFβ3), followed by a collection of animal models and of reviews, commentaries, collections and comparative studies

Myocardial bridging, a frequent component of the hypertrophic cardiomyopathy phenotype, lacks systematic association with sudden cardiac death

Aims The clinical significance attributable to myocardial bridging of left anterior descending coronary artery in hypertrophic cardiomyopathy (HCM) remains controversial. Methods and results Prevalence and depth of coronary artery bridges (CBs) were assessed in 255 hearts, including 115 with HCM (median age 29, range 5\u201390; 75% male), and 140 controls. Coronary artery bridges were more common in HCM (47/115; 41%) than in patients who died of a variety of non-HCM-related causes (21/100; 21%; P = 0.002), or in patients with congenital aortic stenosis and left ventricular (LV) hypertrophy (5/40; 12%; P = 0.001). Among the HCM hearts, CBs were present in 33 of 77 patients (43%) with sudden death, in 10 of 27 (37%) with heart failure death (or heart transplantation), and in 4 of 11 (36%) with other modes of death (P = 0.826). Deeply embedded CBs ( 652 mm) occurred with similar frequency in HCM patients with sudden (21 of 77; 27%) or heart failure death (5 of 27; 13%; P = 0.191). In sudden death patients, the presence of CB was unrelated to gender (33% in women and 45% in men, P = 0.406) and age (41% <18 years vs. 44% 6518 years; P = 0.827). Conclusion In this morphological analysis of more than 250 hearts, CBs are a frequent component of phenotypically expressed HCM, and more common than in other disorders with or without LV hypertrophy. Although no systematic association with HCM-related sudden death is evident, our findings do not exclude the possibility that CB could contribute to increased risk in some individual patients, potentially impacting management decision-making on a case-by-case basis

Altered Desmosomal Proteins in Granulomatous Myocarditis and Potential Pathogenic Links to Arrhythmogenic Right Ventricular Cardiomyopathy

BACKGROUND: Immunoreactive signal for the desmosomal protein plakoglobin (γ-catenin) is reduced at cardiac intercalated disks in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), a highly arrhythmogenic condition caused by mutations in genes encoding desmosomal proteins. Previously, we observed a “false positive” case in which plakoglobin signal was reduced in a patient initially thought to have ARVC but who actually had cardiac sarcoidosis. Sarcoidosis can masquerade clinically as ARVC, but has not previously been associated with altered desmosomal proteins. METHODS AND RESULTS: We observed marked reduction in immunoreactive signal for plakoglobin at cardiac myocyte junctions in patients with sarcoidosis and giant cell myocarditis, both highly arrhythmogenic forms of myocarditis associated with granulomatous inflammation. In contrast, plakoglobin signal was not depressed in lymphocytic (non-granulomatous) myocarditis. To determine whether cytokines might promote dislocation of plakoglobin from desmosomes, we incubated cultures of neonatal rat ventricular myocytes with selected inflammatory mediators. Brief exposure to low concentrations of IL-17, TNFα and IL-6, cytokines implicated in granulomatous myocarditis, caused translocation of plakoglobin from cell-cell junctions to intracellular sites, whereas other potent cytokines implicated in non-granulomatous myocarditis had no effect, even at much high concentrations. We also observed myocardial expression of IL-17 and TNFα, and elevated serum levels of inflammatory mediators including IL-6R, IL-8, MCP1 and MIP1β in ARVC patients (all p<0.0001 compared with controls). CONCLUSIONS: These results suggest novel disease mechanisms involving desmosomal proteins in granulomatous myocarditis and implicate cytokines, perhaps derived in part from the myocardium, in disruption of desmosomal proteins and arrhythmogenesis in ARVC

Sudden cardiac death in the young: A consensus statement on recommended practices for cardiac examination by pathologists from the Society for Cardiovascular Pathology.

Sudden cardiac death is, by definition, an unexpected, untimely death caused by a cardiac condition in a person with known or unknown heart disease. This major international public health problem accounts for approximately 15-20% of all deaths. Typically more common in older adults with acquired heart disease, SCD also can occur in the young where the cause is more likely to be a genetically transmitted process. As these inherited disease processes can affect multiple family members, it is critical that these deaths are appropriately and thoroughly investigated. Across the United States, SCD cases in those less than 40 years of age will often fall under medical examiner/coroner jurisdiction resulting in scene investigation, review of available medical records and a complete autopsy including toxicological and histological studies. To date, there have not been consistent or uniform guidelines for cardiac examination in these cases. In addition, many medical examiner/coroner offices are understaffed and/or underfunded, both of which may hamper specialized examinations or studies (e.g., molecular testing). Use of such guidelines by pathologists in cases of SCD in decedents aged 1-39 years of age could result in life-saving medical intervention for other family members. These recommendations also may provide support for underfunded offices to argue for the significance of this specialized testing. As cardiac examinations in the setting of SCD in the young fall under ME/C jurisdiction, this consensus paper has been developed with members of the Society of Cardiovascular Pathology working with cardiovascular pathology-trained, practicing forensic pathologists

Sudden Cardiac Death in the Young: A Consensus Statement on Recommended Practices for Cardiac Examination by the Pathologist from the Society for Cardiovascular Pathology.

Sudden cardiac death is, by definition, an unexpected, untimely death caused by a cardiac condition in a person with known or unknown heart disease. This major international public health problem accounts for approximately 15-20% of all deaths. Typically more common in older adults with acquired heart disease, SCD also can occur in the young where the cause is more likely to be a genetically transmitted process. As these inherited disease processes can affect multiple family members, it is critical that these deaths are appropriately and thoroughly investigated. Across the United States, SCD cases in those less than 40 years of age will often fall under medical examiner/coroner jurisdiction resulting in scene investigation, review of available medical records and a complete autopsy including toxicological and histological studies. To date, there have not been consistent or uniform guidelines for cardiac examination in these cases. In addition, many medical examiner/coroner offices are understaffed and/or underfunded, both of which may hamper specialized examinations or studies (eg. molecular testing). Use of such guidelines by pathologists in cases of SCD in decedents aged 1 to 39 years of age could result in life-saving medical intervention for other family members. These recommendations also may provide support for underfunded offices to argue for the significance of this specialized testing. As cardiac examinations in the setting of SCD in the young fall under ME/C jurisdiction, this consensus paper has been developed with members of the Society of Cardiovascular Pathology working with cardiovascular pathology-trained, practicing forensic pathologists

Sudden cardiac death in the young: A consensus statement on recommended practices for cardiac examination by pathologists from the Society for Cardiovascular Pathology

Sudden cardiac death is, by definition, an unexpected, untimely death caused by a cardiac condition in a person with known or unknown heart disease. This major international public health problem accounts for approximately 15-20% of all deaths. Typically more common in older adults with acquired heart disease, SCD also can occur in the young where the cause is more likely to be a genetically transmitted process. As these inherited disease processes can affect multiple family members, it is critical that these deaths are appropriately and thoroughly investigated. Across the United States, SCD cases in those less than 40 years of age will often fall under medical examiner/coroner jurisdiction resulting in scene investigation, review of available medical records and a complete autopsy including toxicological and histological studies. To date, there have not been consistent or uniform guidelines for cardiac examination in these cases. In addition, many medical examiner/coroner offices are understaffed and/or underfunded, both of which may hamper specialized examinations or studies (e.g., molecular testing). Use of such guidelines by pathologists in cases of SCD in decedents aged 1-39 years of age could result in life-saving medical intervention for other family members. These recommendations also may provide support for underfunded offices to argue for the significance of this specialized testing. As cardiac examinations in the setting of SCD in the young fall under ME/C jurisdiction, this consensus paper has been developed with members of the Society of Cardiovascular Pathology working with cardiovascular pathology-trained, practicing forensic pathologists