Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac involvement by sarcoidosis and concomitant deposition of AL amyloid is an uncommon association. We describe the case of a 53-year-old African-American man with a 7-year history of dilated nonischemic cardiomyopathy and severe cardiac failure who underwent orthotopic heart transplantation. His prior cardiac biopsies had only mild myocyte hypertrophy and minimal interstitial fibrosis. After surgery, numerous sarcoid granulomas and amyloid deposition were identified in the native heart. Six days after the transplant the patient died due to aspiration bronchopneumonia and acute renal failure. At autopsy, both sarcoidosis and immunoglobulin (Ig) lambda light-chain amyloidosis were present in the native atria, lungs, thyroid, liver, spleen, and kidneys. Sarcoid granulomas alone were present in the parathyroids, lymph nodes, and bone marrow. Amyloid deposition alone was present in the aorta, stomach, large bowel, and urinary bladder. There was no evidence of plasma cell dyscrasia, or underlying gammopathy. This unusual association was described in only two other cases in the medical literature. However, this is the first case of sarcoidosis and AL amyloidosis with successful sequencing and identification of Ig lambda light-chain amyloid, and in which there was no evidence of plasma cell dyscrasia.
 ...
PMID:Sarcoidosis and immunoglobulin lambda II light-chain amyloidosis diagnosed after orthotopic heart transplantation: a case report and review of the literature. 1571 64

The cardiac ryanodine receptor has become a subject of increasing interest as its role in the etiology of cardiac disease is becoming more apparent. In this article, we review the current knowledge of the structure and function of the cardiac ryanodine receptor and its implications in cardiac pathophysiology. Cardiac ryanodine receptors function by regulating calcium release from the sarcoplasmic reticulum in cardiomyocytes, thereby playing an integral role in excitation-contraction coupling. In heart failure, the myocardium remains in a chronic hyperadrenergic state. This leads to protein kinase A hyperphosphorylation of ryanodine receptors within cardiomyocytes, ultimately leading to calcium leakage from the sarcoplasmic reticulum into the cytosol and thus impairing excitation-contraction coupling. These mechanisms could partially explain the pathophysiology underlying the reduced cardiac output seen in heart failure. Beta-adrenergic blockade appears to correct the abnormality and reestablishes normal ryanodine receptor function. These calcium leaks can also generate delayed afterdepolarizations, which can lead to fatal arrhythmias. Two genetic diseases have been linked to mutations in the cardiac ryanodine receptor: arrhythmogenic right ventricular dysplasia type 2 and catecholaminergic polymorphic ventricular tachycardia or familial polymorphic ventricular tachycardia. As our understanding of this receptor and its modulators deepens, the possibility of clinical application draws near.
 ...
PMID:The cardiac ryanodine receptor (RyR2) and its role in heart disease. 1583 Nov 48

Left ventricular noncompaction (LVNC) has been recently proposed as a specific form of cardiomyopathy. There have been few pathological series describing gross and microscopic findings of this entity, especially in children. We present findings of 14 hearts (13 autopsy and 1 explant) with LVNC (isolated and associated with congenital heart disease), defined by poorly developed left ventricular (LV) papillary muscles and a noncompact inner LV myocardial layer comprising more than 50% of the LV thickness. The mean age at death/explant was 3.6 years (median, 2.5 months); there were 6 boys and 8 girls. The symptoms were sudden unexpected death (10) and heart failure (4). The diagnosis was suspected before death in only 1 of 13 autopsy cases. Right ventricular involvement (> 75% ventricular thickness comprised of noncompacted area with recess adjacent to tricuspid valve) was seen in 6 of 14 hearts. One patient had a sibling with pulmonary stenosis, but there was no other known familial cardiomyopathy. Endocardial fibroelastosis was a characteristic histological feature, as well as anastomosing or polypoid endocardial trabeculations, which resulted in staghorn-shaped, endocardial-lined recesses. There was a high rate of other cardiac anomalies, which often coexisted and were not clearly related to the LVNC, present in 8 cases (nonisolated LVNC): ventricular septal defect (4/14), anomalous venous pulmonary veins (1/14), coronary ostial stenosis (1/14), histiocytoid cardiomyopathy (1/14), polyvalvar dysplasia (2/14), and pulmonary stenosis (2/14). In the 6 isolated LVNC, there were 2 malformed atrioventricular valves (1 mitral and 1 tricuspid), which appeared part of the ventricular maldevelopment. There were no differences in histological or gross patterns of the noncompacted regions between the isolated and nonisolated LVNC. LVNC is frequently associated with other cardiac defects, especially when causing sudden death in infants and children. A clear-cut morphological distinction between "isolated" and "secondary" LVNC was not apparent. The pathologist should be aware of the entity because the diagnosis is often first established at autopsy.
 ...
PMID:Left ventricular noncompaction: a pathological study of 14 cases. 1636 Apr 27

We describe the cases of 2 infants aged 6 and 2 1/2 months, respectively, affected by mitral valve dysplasia that caused severe valvular insufficiency and heart failure in which a surgical correction was indicated because of critical general conditions. In both patients the anatomic characteristics of the valves were not suitable for repair, and an implant of a mechanical prosthesis was excluded because of the very young age of the infants and the impossibility of maintaining an adequate anticoagulant therapy. Therefore a Ross-Kabbani intervention was performed with an implant of a pulmonary autograft (in the mitral position) and an insertion of a pulmonary homograft. The postoperative course was free of major complications and good function of the autograft was present at short-term follow-up in both cases.
 ...
PMID:Pulmonary autograft for mitral valve replacement in infants: the Ross-Kabbani operation. 1591 34

The abnormally regulated release of Ca2+ from an intracellular Ca2+ store, the sarcoplasmic reticulum (SR), is the mechanism underlying contractile and relaxation dysfunctions in heart failure (HF). According to recent reports, protein kinase A (PKA)-mediated hyperphosphorylation of ryanodine receptor (RyR) in the SR has been shown to cause the dissociation of FK506 binding protein (FKBP) 12.6 from the RyR in heart failure. This causes an abnormal Ca2+ leak through the Ca2+ channel located in the RyR, leading to an increase in the cytosolic Ca2+ during diastole, prolongation of the Ca2+ transient, and delayed/slowed diastolic Ca2+ re-uptake. More recently, a considerable number of disease-linked mutations in the RyR have been reported in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) or arrhythmogenic right ventricular dysplasia type 2. An analysis of the disposition of these mutation sites within well-defined domains of the RyR polypeptide chain has led to the new concept that interdomain interactions among these domains play a critical role in channel regulation, and an altered domain interaction causes channel dysfunction in the failing heart. The knowledge gained from the recent literature concerning the critical proteins and the changes in their properties under pathological conditions has brought us to a better position to develop new pharmacological or genetic strategies for the treatment of heart failure or cardiac arrhythmia. A considerable body of evidence reviewed here indicates that abnormal RyR function plays an important role in the pathogenesis of heart failure. This review also covers some controversial issues in the literature concerning the involvement of phosphorylation and FKBP12.6.
 ...
PMID:Abnormal ryanodine receptor function in heart failure. 1595 Oct 21

Multinucleated epithelial giant cells (MEG) simulating viral cytopathic effect and/or dysplasia have been reported in the esophagus in association with inflammation, but the occurrence of similar cells in the colon has not been documented. Twenty-three colon specimens (22 biopsies and 1 partial colectomy) featuring MEG from 21 patients were evaluated for a variety of histologic features and correlated with clinical, endoscopic, and follow-up data. Patients included 9 males and 12 females (mean age, 64.9 years; range, 45-86 years). Eleven cases were obtained from 10 asymptomatic patients undergoing surveillance biopsies. Presenting symptoms in the remaining patients were dyspepsia, anemia, abdominal pain, and hematochezia. Over half (13 of 23) of the specimens were from descending and rectosigmoid colon, and almost all were visualized as polyps on endoscopy. Microscopically, all but 1 of the cases featured multiple MEG (range, 6 to >50 cells per biopsy) in the base and mid crypt zones of inflamed polyps with serrated architecture. Immunohistochemical stains for CMV, HSV, adenovirus, EBV, and polyoma virus were negative and no viral particles were identified on ultrastructural examination. Nuclear staining for hMLH1 and hMSH2, markers of microsatellite instability, was similar in distribution to adjacent serrated crypts, but reduced staining intensity was noted in occasional multinucleated cells. Expression of Ki-67 and cleaved caspase 3 was consistent with a quiescent or low proliferative state. Clinical follow-up was available for 9 patients (mean duration, 22.7 months). One patient died of heart failure; all others were well at last follow-up. Bizarre MEG may occasionally be seen within the crypts of inflamed polyps with serrated architecture, raising concern for dysplasia or viral infection. Immunohistochemical and ultrastructural studies fail to establish a viral etiology, and follow-up does not indicate clinically aggressive disease. These changes appear to represent a nonspecific, possibly degenerative response to inflammation and injury, and should be distinguished from dysplasia.
 ...
PMID:Multinucleated epithelial giant cells in colorectal polyps: a potential mimic of viropathic and/or dysplastic changes. 1595 56

A 70-year-old male patient with arrhythmogenic right ventricular dysplasia/cardiomyopathy demonstrating frequent attacks of ventricular tachycardia (VT) as well as heart failure underwent surgical treatment. Although the patient had severe regurgitation at the mitral and tricuspid valves, the contractility of the right and left ventricles was almost maintained. Annuloplasty of both valves abolished the regurgitation and very effectively controlled heart failure. Surgical cryoablation was performed on the lesion showing the earliest potential before the ORS complex during VT and the arrhythmia was terminated. However, a cardioverter defibrillator was implanted to prevent new VT caused by disease progression.
 ...
PMID:Successful surgical treatment of heart failure and ventricular tachycardia in a patient with arrhythmogenic right ventricular dysplasia with cardiomyopathy. 1604 Nov 75

Cardiomyopathies are primary disorders of cardiac muscle associated with abnormalities of cardiac wall thickness, chamber size, contraction, relaxation, conduction, and rhythm. They are a major cause of morbidity and mortality at all ages and, like acquired forms of cardiovascular disease, often result in heart failure. Over the past two decades, molecular genetic studies of humans and analyses of model organisms have made remarkable progress in defining the pathogenesis of cardiomyopathies. Hypertrophic cardiomyopathy can result from mutations in 11 genes that encode sarcomere proteins, and dilated cardiomyopathy is caused by mutations at 25 chromosome loci where genes encoding contractile, cytoskeletal, and calcium regulatory proteins have been identified. Causes of cardiomyopathies associated with clinically important cardiac arrhythmias have also been discovered: Mutations in cardiac metabolic genes cause hypertrophy in association with ventricular pre-excitation and mutations causing arrhythmogenic right ventricular dysplasia were recently discovered in protein constituents of desmosomes. This considerable genetic heterogeneity suggests that there are multiple pathways that lead to changes in heart structure and function. Defects in myocyte force generation, force transmission, and calcium homeostasis have emerged as particularly critical signals driving these pathologies. Delineation of the cell and molecular events triggered by cardiomyopathy gene mutations provide new fundamental knowledge about myocyte biology and organ physiology that accounts for cardiac remodeling and defines mechanistic pathways that lead to heart failure.
 ...
PMID:The genetic basis for cardiac remodeling. 1612 59

Natriuretic peptides are a family of structurally related but genetically distinct hormones/paracrine factors that regulate blood volume, blood pressure, ventricular hypertrophy, pulmonary hypertension, fat metabolism, and long bone growth. The mammalian members are atrial natriuretic peptide, B-type natriuretic peptide, C-type natriuretic peptide, and possibly osteocrin/musclin. Three single membrane-spanning natriuretic peptide receptors (NPRs) have been identified. Two, NPR-A/GC-A/NPR1 and NPR-B/GC-B/NPR2, are transmembrane guanylyl cyclases, enzymes that catalyze the synthesis of cGMP. One, NPR-C/NPR3, lacks intrinsic enzymatic activity and controls the local concentrations of natriuretic peptides through constitutive receptor-mediated internalization and degradation. Single allele-inactivating mutations in the promoter of human NPR-A are associated with hypertension and heart failure, whereas homozygous inactivating mutations in human NPR-B cause a form of short-limbed dwarfism known as acromesomelic dysplasia type Maroteaux. The physiological effects of natriuretic peptides are elicited through three classes of cGMP binding proteins: cGMP-dependent protein kinases, cGMP-regulated phosphodiesterases, and cyclic nucleotide-gated ion channels. In this comprehensive review, the structure, function, regulation, and biological consequences of natriuretic peptides and their associated signaling proteins are described.
 ...
PMID:Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions. 1629 70

Clinically, arrhythmogenic right ventricular dysplasia (ARVD) usually presents with ventricular arrhythmias, and unusual presentations were reported as acute coronary syndrome, heart failure and electrical storm. Taking all this different presentations and treatments in to account, we report a case of ARVD presenting with central cyanosis and clubbing simulating congenital heart disease. Besides this unusual presentation, the patient underwent also an unusual operation for this kind of abnormality, which cured the cyanosis completely.
 ...
PMID:Unusual presentation of a patient with arrhythmogenic right ventricular dysplasia treated with a Glenn shunt. 1633 97


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>