Acute Pericarditis LeWinter, Martin M
The New England journal of medicine,
12/2014, Letnik:
371, Številka:
25
Journal Article
Recenzirano
Acute pericarditis in the United States is usually idiopathic and presumed to be viral. A history and laboratory tests, a chest radiograph, and an echocardiogram are used in evaluation. Treatment ...usually includes an NSAID and colchicine.
Foreword
This
Journal
feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations.
Stage
A previously healthy 25-year-old man presents with pleuritic pain in the left side of the chest of 3 hours' duration, radiating to the left trapezius ridge and relieved by sitting forward. On physical examination, he appears anxious. His pulse is 104 beats per minute and regular, his blood pressure is 125/80 mm Hg without a paradoxical pulse, and his temperature is 37.8°C. A three-component friction rub is auscultated along the left sternal border. An electrocardiogram (ECG) reveals ST-segment elevations in multiple leads, which are consistent with acute pericarditis. How should this case be managed?
The Clinical Problem
Acute pericarditis . . .
Cardiac Titin: A Multifunctional Giant LEWINTER, Martin M; GRANZIER, Henk
Circulation (New York, N.Y.),
05/2010, Letnik:
121, Številka:
19
Journal Article
Pericardial Effusion Azarbal, Amir; LeWinter, Martin M
Cardiology clinics
35, Številka:
4
Journal Article
Recenzirano
The normal pericardial sac contains up to 50 mL of fluid, which consists of a plasma ultrafiltrate. Anything greater constitutes a pathologic effusion. The curvilinear pressure-volume relationship of ...the pericardial sac dictates hemodynamic consequences of a pericardial effusion and is responsible for rapidly accumulating fluid that causes cardiac tamponade. A variety of diseases and complications cause pericardial effusion. The most common are idiopathic pericarditis, cancer, connective tissue disorders, and hemorrhage. Management of pericardial effusion is dictated by whether tamponade is present or threatened. If it is, urgent/emergent pericardiocentesis is indicated. If not, a systematic approach to diagnosis and management should be undertaken.
Cardiac Titin and Heart Disease LeWinter, Martin M; Granzier, Henk L
Journal of cardiovascular pharmacology,
2014-March, Letnik:
63, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The giant sarcomeric protein titin is a key determinant of myocardial passive stiffness and stress-sensitive signaling. Titin stiffness is modulated by isoform variation, phosphorylation by protein ...kinases, and, possibly, oxidative stress through disulfide bond formation. Titin has also emerged as an important human disease gene. Early studies in patients with dilated cardiomyopathy (DCM) revealed shifts toward more compliant isoforms, an adaptation that offsets increases in passive stiffness based on the extracellular matrix. Similar shifts are observed in heart failure with preserved ejection fraction. In contrast, hypophosphorylation of PKA/G sites contributes to a net increase in cardiomyocyte resting tension in heart failure with preserved ejection fraction. More recently, titin mutations have been recognized as the most common etiology of inherited DCM. In addition, some DCM-causing mutations affect RBM20, a titin splice factor. Titin mutations are a rare cause of hypertrophic cardiomyopathy and also underlie some cases of arrhythmogenic right ventricular dysplasia. Finally, mutations of genes encoding proteins that interact with and/or bind to titin are responsible for both DCM and hypertrophic cardiomyopathy. Targeting titin as a therapeutic strategy is in its infancy, but it could potentially involve manipulation of isoforms, posttranslational modifications, and upregulation of normal protein in patients with disease-causing mutations.
Titin Is a Major Human Disease Gene LEWINTER, Martin M; GRANZIER, Henk L
Circulation (New York, N.Y.),
02/2013, Letnik:
127, Številka:
8
Journal Article
Patients with recurrent pericarditis were treated with the interleukin-1 trap rilonacept. Those who had a response were randomly assigned to receive continued rilonacept or placebo. Rilonacept led to ...a significantly lower risk of pericarditis recurrence than placebo.
BACKGROUND—The purpose of this study was to determine whether patients with heart failure and a preserved ejection fraction (HFpEF) have an increase in passive myocardial stiffness and the extent to ...which discovered changes depend on changes in extracellular matrix fibrillar collagen and cardiomyocyte titin.
METHODS AND RESULTS—Seventy patients undergoing coronary artery bypass grafting underwent an echocardiogram, plasma biomarker determination, and intraoperative left ventricular epicardial anterior wall biopsy. Patients were divided into 3 groupsreferent control (n=17, no hypertension or diabetes mellitus), hypertension (HTN) without (–) HFpEF (n=31), and HTN with (+) HFpEF (n=22). One or more of the following studies were performed on the biopsiespassive stiffness measurements to determine total, collagen-dependent and titin-dependent stiffness (differential extraction assay), collagen assays (biochemistry or histology), or titin isoform and phosphorylation assays. In comparison with controls, patients with HTN(–)HFpEF had no change in left ventricular end-diastolic pressure, myocardial passive stiffness, collagen, or titin phosphorylation but had an increase in biomarkers of inflammation (C-reactive protein, soluble ST2, tissue inhibitor of metalloproteinase 1). In comparison with both control and HTN(–)HFpEF, patients with HTN(+)HFpEF had increased left ventricular end-diastolic pressure, left atrial volume, N-terminal propeptide of brain natriuretic peptide, total, collagen-dependent, and titin-dependent stiffness, insoluble collagen, increased titin phosphorylation on PEVK S11878(S26), reduced phosphorylation on N2B S4185(S469), and increased biomarkers of inflammation.
CONCLUSIONS—Hypertension in the absence of HFpEF did not alter passive myocardial stiffness. Patients with HTN(+)HFpEF had a significant increase in passive myocardial stiffness; collagen-dependent and titin-dependent stiffness were increased. These data suggest that the development of HFpEF depends on changes in both collagen and titin homeostasis.
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