Snigdha Jain

Inflammation and arterial stiffness in humans

Arterial stiffness is an established marker of cardiovascular morbidity and mortality and a potential therapeutic target. While hypertension and aging are established factors contributing to arterial stiffness, the role of inflammation in stiffening of the arteries is less well understood. We summarize existing literature regarding inflammation and arterial stiffness, including a discussion of the potential mechanisms by which inflammation may lead to arterial stiffening and studies assessing: (1) The association between subclinical inflammation and arterial stiffness in the general population; (2) The presence of increased arterial stiffness in primary inflammatory diseases; (3) The effect of anti-inflammatory therapy on arterial stiffness in primary inflammatory disease including the effect of statins; (4) Experimental evidence of immunization-induced arterial stiffening in normal adults. We discuss potential opportunities to assess the impact of anti-inflammatory interventions on arterial stiffness in subjects without primary inflammatory conditions. We also review the effect of inflammation on wave reflections.

Gender differences in the utilisation of surgery for congenital heart disease in India

Background Corrective surgery for congenital heart disease may be life-saving, but its utilisation depends upon several social and economic factors. Girls with cardiac defects may not receive equitable care in India, but this has not been systematically studied. Methods In this prospective study, parents or guardians of 405 consecutive children aged up to 12 years (mean±SD age 3.43±3.44 years; 271 boys) who had been advised to undergo elective paediatric cardiac surgery were interviewed using a validated questionnaire. The status of the patients was reviewed after a year and the factors associated with non-compliance with treatment were analysed. In a qualitative sub-study the parents of 20 children who had not undergone surgery were interviewed. Qualitative data were analysed using an inductive analytical approach. Results Of the 405 patients studied, 44% (59/134) of girls had undergone surgery at 1 year compared with 70% (189/271) of boys (χ2=24.97; p<0.001). Independent predictors for non-compliance with surgery included female gender (OR 3.46, 95% CI −2.06 to 5.80; p<0.0001), lower socioeconomic classes (lower-middle: OR 18.62, 95% CI −2.14 to 161.8, p=0.008; upper-lower: OR 34.27, 95% CI −3.72 to 316.0, p=0.002) and higher cost of surgery (OR 1.92, 95% CI −1.06 to 3.47, p=0.03). In the in-depth interviews, apprehensions about future matrimonial prospects of girls and lack of social support emerged as the major factors responsible for delays in undergoing surgery. Conclusions Female gender is an important determinant of non-compliance with paediatric cardiac surgery. Deep-seated social factors underlie this gender bias.

Interstitial Lung Disease in Systemic Sclerosis: Pathophysiology, Current and New Advances in Therapy

Systemic sclerosis is an autoimmune connective tissue disorder characterized by fibrosis of the skin and visceral organs. Interstitial lung disease (ILD) is a major complication of this disease and along with pulmonary arterial hypertension is the leading cause of mortality in scleroderma patients. The pathogenesis of pulmonary fibrosis is characterized by epithelial cell injury, activation of the coagulation pathway and inflammation, which create a profibrogenic environment in the lung in the setting of autoimmunity. The current standard of treatment for ILD in systemic sclerosis is cyclophosphamide. In view of the modest benefits in pulmonary function seen with cyclophosphamide in two recent trials and its significant toxicity, the search for alternative treatments is ongoing. With the advances in our understanding of the pathogenic mechanisms of pulmonary fibrosis, many promising therapeutic agents have come into view, but their efficacy needs to be evaluated before they can be recommended clinically. This review discusses the pathogenesis of pulmonary fibrosis with a focus on the potential target pathways, the current treatment options and recent advances in the treatment of ILD in systemic sclerosis.

Effect of Continuous Positive Airway Pressure, Weight Loss, or Continuous Positive Airway Pressure Plus Weight Loss on Central Hemodynamics and Arterial Stiffness

Obesity and obstructive sleep apnea tend to coexist. Little is known about the effects of obstructive sleep apnea, obesity, or their treatment on central aortic pressures and large artery stiffness. We randomized 139 adults with obesity (body mass index >30 kg/m2) and moderate-to-severe obstructive sleep apnea to (1) continuous positive airway pressure (CPAP) therapy (n=45), (2) weight loss (WL) therapy (n=48), or (3) combined CPAP and WL (n=46) for 24 weeks. We assessed the effect of these interventions on central pressures and carotid–femoral pulse wave velocity (a measure of large artery stiffness), measured with arterial tonometry. Central systolic pressure was reduced significantly only in the combination arm (−7.4 mm Hg; 95% confidence interval, −12.5 to −2.4 mm Hg; P=0.004), without significant reductions detected in either the WL-only (−2.3 mm Hg; 95% confidence interval, −7.5 to 3.0; P=0.39) or the CPAP-only (−3.1 mm Hg; 95% confidence interval, −8.3 to 2.0; P=0.23) arms. However, none of these interventions significantly changed central pulse pressure, pulse pressure amplification, or the central augmentation index. The change in mean arterial pressure (P=0.008) and heart rate (P=0.027) induced by the interventions was significant predictors of the change in carotid–femoral pulse wave velocity. However, after adjustment for mean arterial pressure and heart rate, no significant changes in carotid–femoral pulse wave velocity were observed in any group. In obese subjects with obstructive sleep apnea, combination therapy with WL and CPAP is effective in reducing central systolic pressure. However, this effect is largely mediated by changes in mean, rather than central pulse pressure. WL and CPAP, alone or in combination, did not reduce large artery stiffness in this population. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00371293.Obesity and obstructive sleep apnea tend to coexist. Little is known about the effects of obstructive sleep apnea, obesity, or their treatment on central aortic pressures and large artery stiffness. We randomized 139 adults with obesity (body mass index >30 kg/m 2 ) and moderate-to-severe obstructive sleep apnea to (1) continuous positive airway pressure (CPAP) therapy (n=45), (2) weight loss (WL) therapy (n=48), or (3) combined CPAP and WL (n=46) for 24 weeks. We assessed the effect of these interventions on central pressures and carotid–femoral pulse wave velocity (a measure of large artery stiffness), measured with arterial tonometry. Central systolic pressure was reduced significantly only in the combination arm (−7.4 mm Hg; 95% confidence interval, −12.5 to −2.4 mm Hg; P =0.004), without significant reductions detected in either the WL-only (−2.3 mm Hg; 95% confidence interval, −7.5 to 3.0; P =0.39) or the CPAP-only (−3.1 mm Hg; 95% confidence interval, −8.3 to 2.0; P =0.23) arms. However, none of these interventions significantly changed central pulse pressure, pulse pressure amplification, or the central augmentation index. The change in mean arterial pressure ( P =0.008) and heart rate ( P =0.027) induced by the interventions was significant predictors of the change in carotid–femoral pulse wave velocity. However, after adjustment for mean arterial pressure and heart rate, no significant changes in carotid–femoral pulse wave velocity were observed in any group. In obese subjects with obstructive sleep apnea, combination therapy with WL and CPAP is effective in reducing central systolic pressure. However, this effect is largely mediated by changes in mean, rather than central pulse pressure. WL and CPAP, alone or in combination, did not reduce large artery stiffness in this population. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00371293.

IMPACT OF TOTAL ARTERIAL COMPLIANCE, ASCENDING AND DESCENDING AORTIC WALL STIFFNESS ON LEFT VENTRICULAR MASS AND GEOMETRY

Impact of Total Arterial Compliance, Ascending and Descending Aortic Wall Stiffness on Left Ventricular Mass and Geometry The compliance of the arterial tree and aortic wall stiffness influence the pulsatile load of the left ventricle (LV). Limited data are available regarding the relationships

Readmissions of adults within three age groups following hospitalization for pneumonia: Analysis from the Nationwide Readmissions Database

Background While 30-day readmissions following hospitalization for pneumonia have been well-studied in the elderly, their burden in young adults remains poorly understood. Objective To study patterns of readmissions following hospitalization for pneumonia across age groups and insurance payers. Methods In the Nationwide Readmission Database for the years 2013 and 2014 we identified all adults (≥18 years) discharged alive after a hospitalization with the primary diagnosis of pneumonia, and examined rates of readmissions within 30-days of discharge. Using covariates included in the Center for Medicare & Medicaid Services risk-adjustment model for pneumonia readmissions in a multivariable regression model for survey data, we identified predictors of 30-day readmission. Results We identified 629,939 index pneumonia hospitalizations with a weighted estimate of 1,472,069 nationally. Overall, 16.2% of patients were readmitted within 30 days of their hospitalization for pneumonia, with 30-day readmission rates of 12.4% in the 18–44 year age-group, 16.1% in the 45–64 year age-group, and 16.7% in the ≥65-year age-group. In risk-adjusted analyses, compared with elderly, middle-aged adults were more likely to be readmitted (risk-adjusted OR 1.05, 95% CI 1.03–1.07). Mean cost per readmission was also highest for this age group at

MRI Assessment of Diastolic and Systolic Intraventricular Pressure Gradients in Heart Failure

15,976. Conclusion Middle-aged adults experience substantial rates of 30-day readmission that are comparable to those over 65 years of age, with a higher cost per readmission event. Future efforts are needed to identify potential interventions to alleviate the high burden of pneumonia readmissions in middle-aged adults.

TIME-RESOLVED LEFT VENTRICULAR MYOCARDIAL STRESS IN HEART FAILURE WITH REDUCED EJECTION FRACTION REVEALS A MARKED INCREASE IN LATE SYSTOLIC MYOCARDIAL LOAD

A deep phenotypic characterization of heart failure (HF) is important for a better understanding of its pathophysiology. In particular, novel noninvasive techniques for the characterization of functional abnormalities in HF with preserved ejection fraction are currently needed. While echocardiography is widely used to assess ventricular function, standard echocardiographic techniques provide a limited understanding of ventricular filling. The application of fluid dynamics theory, along with assessments of flow velocity fields in multiple dimensions in the ventricle, can be used to assess intraventricular pressure gradients (IVPGs), which in turn may provide valuable insights into ventricular diastolic and systolic function. Advances in imaging techniques now allow for accurate estimations of systolic and diastolic IVPGs, using noninvasive methods that are easily applicable in clinical research. In this review, we describe the basic concepts regarding intraventricular flow measurements and the derivation of IVPGs. We also review existing literature exploring the role of IVPGs in HF.

DIFFUSE MYOCARDIAL FIBROSIS IS GREATLY ELEVATED IN MALES WITH HEART FAILURE WITH REDUCED EJECTION FRACTION, BUT NOT HEART FAILURE WITH PRESERVED EJECTION FRACTION

Systolic myocardial wall stress (MWS) quantifies myocardial afterload. Despite its time-varying nature, little data exist regarding time-resolved MWS in systolic heart failure (HF). We studied 10 subjects with systolic HF (mean LV ejection fraction=40%). We assessed time-resolved LV volume and