Monodeep Biswas

Cardiovascular outcomes of sodium-glucose cotransporter 2 inhibitors: A comprehensive review of clinical and preclinical studies

Diabetes is a leading cause of morbidity and mortality worldwide. Management of diabetes is changing at a rapid pace. Three new classes of antidiabetic drugs including GLP-1 (Glucagon-like peptide 1), DPP-IV (Dipeptidyl peptidase IV) and SGLT2 (Sodium glucose cotransporter 2) inhibitors have been approved in the last few years. Treating diabetes with the antidiabetic drug does not always reduce the cardiovascular complications of diabetes. On the contrary, there was a huge controversy regarding the effect of rosiglitazone on cardiovascular risk reduction a few years ago. Since then, submission of postmarketing cardiovascular outcome study data has been mandated by US FDA and other drug regulatory agencies for newer antidiabetic medications. This is to avoid further premature claims regarding cardiovascular harm or safety of the newer classes. We already have some cardiovascular safety data available on DPP-IV and GLP-1 groups of medications. Dapagliflozin, canagliflozin, and empagliflozin are currently approved SGLT2 inhibitors. We do not have sufficient cardiovascular outcome data available for this novel class. However, this group of drugs, which act by increasing renal glucose excretion, have also shown some non-glycemic benefits including weight reduction, blood pressure control, diuretic action, renal protection, decrease in arterial stiffness and uric acid reduction. Empagliflozin, a new member of SGLT2 class, showed significant cardiovascular morbidity and mortality benefit in recently published EMPA-REG OUTCOME trial. The authors summarize all the published clinical and preclinical cardiovascular outcome data of SGLT2 inhibitors, including recently completed and ongoing major clinical trials in this comprehensive review.

Clinical Significance of Markers of Collagen Metabolism in Rheumatic Mitral Valve Disease

Background Rheumatic Heart Disease (RHD), a chronic acquired heart disorder results from Acute Rheumatic Fever. It is a major public health concern in developing countries. In RHD, mostly the valves get affected. The present study investigated whether extracellular matrix remodelling in rheumatic valve leads to altered levels of collagen metabolism markers and if such markers can be clinically used to diagnose or monitor disease progression. Methodology This is a case control study comprising 118 subjects. It included 77 cases and 41 healthy controls. Cases were classified into two groups- Mitral Stenosis (MS) and Mitral Regurgitation (MR). Carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), total Matrix Metalloproteinase-1(MMP-1) and Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) were assessed. Histopathology studies were performed on excised mitral valve leaflets. A p value <0.05 was considered statistically significant. Results Plasma PICP and PIIINP concentrations increased significantly (p<0.01) in MS and MR subjects compared to controls but decreased gradually over a one year period post mitral valve replacement (p<0.05). In MS, PICP level and MMP-1/TIMP-1 ratio strongly correlated with mitral valve area (r = −0.40; r = 0.49 respectively) and pulmonary artery systolic pressure (r = 0.49; r = −0.49 respectively); while in MR they correlated with left ventricular internal diastolic (r = 0.68; r = −0.48 respectively) and systolic diameters (r = 0.65; r = −0.55 respectively). Receiver operating characteristic curve analysis established PICP as a better marker (AUC = 0.95; 95% CI = 0.91−0.99; p<0.0001). A cut-off >459 ng/mL for PICP provided 91% sensitivity, 90% specificity and a likelihood ratio of 9 in diagnosing RHD. Histopathology analysis revealed inflammation, scarring, neovascularisation and extensive leaflet fibrosis in diseased mitral valve. Conclusions Levels of collagen metabolism markers correlated with echocardiographic parameters for RHD diagnosis.

Spontaneous coronary artery dissection: Case report and review of literature

Spontaneous coronary artery dissection (SCAD) is an unusual cause of acute coronary syndrome or sudden cardiac death. SCAD has most frequently been described as presenting as an acute coronary syndrome in females during the peripartum period. It may also be associated with autoimmune and collagen vascular diseases, Marfans syndrome, chest trauma, and intense physical exercise. The most common presentation of SCAD is the acute onset of severe chest pain associated with autonomic symptoms. This condition has a high mortality rate if not identified and treated promptly. Here, we present a case of SCAD presenting with stroke, followed by a brief review.

Scattering of μ-mesons

SummaryThe scattering of μ-mesons is investigated by means of a rectangular cloud chamber with copper and lead plates placed alternately inside the chamber. μ-mesons after traversing thick layers of iron and lead absorber placed above and below the chamber are made to stop in 7.6 cm of iron layer by an anticoincidence method. The momenta of the scattered μ-mesons are thus well-defined in the region of (1.18±.05) GeV/c. The observed angular distribution coincides with the point-charge model of the nucleus given byMolière in the case of lead, and in the case of copper the distribution is just above the Molière curve.RiassuntoSi è analizzato lo scattering dei mesoni μ con una camera a nebbia rettangolare con piastre di rame e piombo poste alternate nell’interno della camera. I mesoni μ dopo aver attraversato grossi spessori di assorbitori di ferro e piombo posti sopra e sotto la camera vengono arrestati in uno spessore di ferro di 7.6 cm col metodo della anticoincidenza. Le quantità di moto dei mesoni μ di scattering sono così ben definite e comprese nella regione di (1.18±.05) GeV/c. La distribuzione angolare osservata nel caso del piombo coincide con il modello a carica puntiforme del nucleo dato daMolière, mentre nel caso del rame la distribuzione è appena al di sopra della curva di Molière.

Circulating carboxy-terminal propeptide of type I procollagen is increased in rheumatic heart disease

Mitral valve is mostly affected in rheumatic heart disease which is prevalent in developing countries [1–3] and thousands of new cases are being diagnosed worldwide every year [1–3]. It is known that extensive fibrosis occurs in the rheumatic valve [4]. Serum carboxyterminal propeptide of type I procollagen (PICP), the marker of collagen synthesis was reported as a marker of extracellular matrix (ECM) remodelling in various heart diseases [5–8]. We therefore, measured the levels of circulating PICP to explore the severity of ECM remodelling in rheumatic heart disease.

A conservative surgical approach for management of iatrogenic pulmonary artery perforation.

Accidental malposition of a chest tube in the pulmonary artery is a potentially fatal complication. Here we describe a 66 year-old obese woman with prior cardiac transplantation, intubated for respiratory failure and felt to have a large left pleural effusion. A chest tube was inserted using a trocar tube, and resulted in near-exsanguinating hemorrhage immediately, with development of hypovolemic shock. Prompt clamping of the tube proved life-saving, and CT scan confirmed placement of the tube in the main pulmonary artery. Initial stabilization, followed by a planned surgical approach, resulted in successful removal of the tube.

OS 01-07 CLINICAL IMPORTANCE OF COLLAGEN METABOLISM MARKERS IN RHEUMATIC HEART VALVE DISEASE IN INDIAN SUBPOPULATION.

Objective: Rheumatic Heart Disease (RHD), a chronic acquired heart disorder results from Acute Rheumatic Fever. RHD is mostly prevalent in developing nations which is mainly diagnosed by transthoracic echocardiography. Till date, there is no biochemical marker for disease management. In the present study we aim to investigate whether mitral valve remodeling contributes to altered levels of circulating biomarkers of collagen metabolism in rheumatic heart disease. Design and Method: The study involved RHD subjects with before and after valve replacement surgery which includes age and sex matched controls. Subjects were evaluated by 2-dimensional transthoracic echocardiography. Subjects were classified into two groups- Mitral Stenosis (MS) and Mitral Regurgitation (MR). Carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), total Matrix Metalloproteinase-1(MMP-1) and Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) were assessed. Histopathological studies were performed in excised mitral valve sections.. A p value < 0.05 was considered statistically significant. Results: Plasma PICP and PIIINP concentrations increased significantly (p < 0.01) in MS and MR subjects compared to controls but decreased gradually over a one year period post mitral valve replacement (p < 0.05). In MS, PICP level and MMP-1/TIMP-1 ratio strongly correlated with mitral valve area (r = −0.40; r = 0.49 respectively) and pulmonary artery systolic pressure (r = 0.49; r = −0.49 respectively); while in MR they correlated with left ventricular internal diastolic (r = 0.68; r = −0.48 respectively) and systolic diameters (r = 0.65; r = −0.55 respectively). Receiver operating characteristic curve analysis established PICP as a better marker (AUC = 0.95; 95% CI = 0.91 – 0.99; p < 0.0001). Histopathology analysis revealed inflammation, neovascularisation and extensive leaflet fibrosis in diseased mitral valve. Conclusions: Monitoring plasma PICP may guide new strategies to disease management and can be clinically used to diagnose or monitor disease progression in Rheumatic heart disease.