Reply to a letter to the editor written by Phansalkar et al, regarding publication entitled "Do we need a simplified model to predict outcomes in patients hospitalized with Acute Decompensated Heart Failure? Results from The Role of Sodium in Heart Failure Outcomes Prediction ('SHOUT-PREDICTION') study. Indian Heart J. 2021;73(4):458-463. doi:10.1016/j.ihj.2021.06.007".

This is the Reply to a letter to the Editor written by Phansalkar et al, regarding publication entitled "Do we need a simplified model to predict outcomes in patients hospitalized with Acute Decompensated Heart Failure? Results from The Role of Sodium in Heart Failure Outcomes Prediction ('SHOUT-PREDICTION') study. Indian Heart J. 2021; 73(4):458-463. doi: 10.1016/j.ihj.2021.06.007".

Do we need a simplified model to predict outcomes in patients hospitalized with Acute Decompensated Heart Failure? Results from The Role of Sodium in Heart Failure Outcomes Prediction ('SHOUT-PREDICTION') study.

CONTEXT: Hyponatremia is associated with high in-hospital mortality in patients with acute decompensated Heart Failure (ADHF) and is one of the components in various risk scores in heart failure (HF). However, some risk scores predict outcomes in these patients without using hyponatremia as its component. AIM: The study was aimed to evaluate the relationship between serum sodium levels at admission and clinical outcomes during the in-hospital course and three months' follow-up, in patients admitted in the intensive cardiac care unit (ICCU) with ADHF. METHODS AND MATERIAL: This was a single-center prospective, observational study in which 130 consecutive patients admitted with ADHF were observed for clinical characteristics and blood investigation at admission and their clinical outcomes during the in-hospital course and follow-up of 3 months. RESULTS: Hyponatremia and systolic blood pressure (SBP) both were found to be the independent predictor of in-hospital mortality. The SXS score (calculated as a product of SBP and serum sodium, divided by 1000) as a new prediction variable was significantly associated with in-hospital mortality and was compared with the Get with the guideline HF (GWTG-HF) score and ADHF national registry (ADHERE) score. The SXS score showed the best overall accuracy in predicting in-hospital mortality [area under the curve (AUC) = 0.899] as compared to the ADHERE (AUC = 0.780) and the GWTG (AUC = 0.815). CONCLUSIONS: A score derived from the product of serum sodium and SBP (SXS score) had a significant association with in-hospital mortality, and better predictive value as compared to GWTG and ADHERE risk score in these patients.

Prevalence of hypertension and prehypertension in schoolchildren from Central India.

BACKGROUND: Epidemiological transition with increasing burden of cardiovascular risk factors is evident not only in adults but also in children. The data on the prevalence of prehypertension and hypertension in children show large regional differences in India and such data are not available from Central India. We, therefore, conducted a large cross-sectional study in Indore to determine the distribution of blood pressure (BP) and the prevalence of hypertension and prehypertension among schoolchildren. METHODS: A total of 11,312 children (5305 girls, 6007 boys) aged 5-15 years, drawn from 80 government and private schools in equal proportion, were evaluated. Anthropometric measurements were obtained and BPs were measured using The Fourth Report on The Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents as reference standard. BP ≥90th to <95th percentile for given percentile of height was considered as prehypertension, whereas any BP ≥95th percentile was defined as hypertension. Multiple linear regression analysis was used to find out the determinants of hypertension in these children. RESULTS: Prehypertension was detected in 6.9% and 6.5% and hypertension was found in 6.8% and 7.0% of boys and girls, respectively. Height and weight were found to be a significant predictor of systolic and diastolic BP among both boys and girls. CONCLUSIONS: Our results show a high prevalence of prehypertension and hypertension in Indore schoolchildren with age and height being significant determinants. This highlights the need for routine BP measurements in children by pediatricians when they treat them for intercurrent illnesses or vaccinate them. It should also be mandatory as a part of school health checkup programs to detect childhood hypertension for further counseling and therapy.

Disseminated Cryptococcosis Mimicking Miliary Tuberculosis with Generalized Lymphadenopathy in Immunocompetent Host.

Cryptococcosis is a rare opportunistic infection in the immunocompromised host.1,2 Diagnosis of disseminated fungal infections is rarely thought of in immunocompetent hosts. In developing countries where tuberculosis is endemic, Cryptococcosis is often misdiagnosed as tuberculosis.3,4 A 14 year old girl, misdiagnosed as miliary tuberculosis with Koch's abdomen on ATT, presented with seizures. After extensive workup, she was found to have disseminated Cryptococcosis, not tuberculosis. This case report shows the similarity in presentation of tuberculosis and Cryptococcosis, and hence Cryptococcosis should always be kept as a differential diagnosis of tuberculosis.

Utility of physical examination and comparison to echocardiography for cardiac diagnosis.

OBJECTIVE: To find out the accuracy of cardiac auscultation using non-digital stethoscope in physical diagnosis of cardiac diseases. METHODS: We enrolled 104 consecutive patients with abnormal cardiac auscultatory findings attending cardiology clinic and not previously evaluated by echocardiography. One time detailed cardiac physical examination followed by echocardiography within 1 month was undertaken. Agreement between two methods was calculated using mean pair percentage agreement, kappa statistics (κ) and calculation of 95% confidence interval (CI) for kappa statistics. RESULTS: Using kappa statistics, there was almost perfect agreement between cardiac auscultation and echocardiography for the detection of mitral stenosis (κ=0.865; CI 0.76-0.97) and ventricular septal defect (κ=0.872; CI=0.73-1.01). Substantial agreement was noted for aortic stenosis (κ=0.752; CI=0.56-0.94), pulmonary stenosis (κ=0.647; CI=0.33-0.97) and atrial septal defect (κ=0.646; CI=0.32-0.97), while moderate agreement was found for mitral regurgitation (κ=0.470; CI=0.30-0.64), aortic regurgitation (κ=0.456; CI=0.25-0.66) and tricuspid regurgitation (κ=0.575; CI=0.38-0.77). For combined mitral stenosis and mitral regurgitation lesions, almost perfect agreement was found for mitral stenosis (κ=0.842; CI=0.691-0.993) while fair agreement noted for mitral regurgitation (κ=0.255; CI=-0.008 to 0.518). CONCLUSION: Careful clinical auscultation using a stethoscope remains a valuable tool for cardiac diagnosis. Decision on initial diagnosis and management of valvular and congenital heart diseases should be based on clinical examination and integrating such information with echocardiography as required.

Endothelium-dependent vasodilation is impaired in healthy offspring of hypertensive parents.

OBJECTIVES: Impaired endothelium-dependent vasodilation has been demonstrated in asymptomatic normotensive offspring of hypertensive parents in Caucasians and Chinese population. The study was designed to determine whether impaired endothelium-dependent vasodilation is present in Indian normotensive offspring with hypertensive parents. METHODS AND RESULTS: We conducted this study in non smoker, healthy, young volunteers with a positive (n = 45) or a negative parental history (n = 30) of essential hypertension in a case-control, blinded design. The subjects underwent a thorough clinical and routine laboratory evaluation. A high resolution ultrasound was used to assess endothelium-dependent brachial artery flow-mediated dilation by a single observer blinded to the family histories. The brachial artery diameters at baseline and after occlusion release, flow mediated dilatation %, brachial intima-media thickness/lumen diameter were obtained and compared between the two groups using student's t-test. There was no significant difference between the two groups in age, sex, body mass index, blood pressure and total cholesterol levels. However, there was a statistically significant impairment of flow mediated dilatation amongst subjects with parental history of hypertension compared to controls (6.87 SD 8.14 % vs 11.31 SD 5.17%, p < 0.01). Multiple regression analysis revealed no association of FMD with age, blood pressure, BMI or total cholesterol in those with or without parental hypertension. CONCLUSIONS: Our study demonstrated impaired brachial artery flow mediated dilatation amongst normotensive offspring with parental hypertension compared to controls. This suggests that endothelial dysfunction possibly precedes clinical hypertension and might have a role in the pathogenesis of essential hypertension.

Efficacy and safety of PDE-5 inhibitor tadalafil in pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a life threatening disease for which phosphodiesterase-5 inhibitor sildenafil is recently approved. We aimed to evaluate the efficacy and safety of tadalafil, a long acting congener of sildenafil, in treatment of PAH related to previous left to right shunt lesions. METHODS: In this blinded, cross over study, 11 patients with severe PAH related to congenital left to right shunt lesions (Eisenmenger syndrome) were randomly assigned to tadalafil (20 mg daily) or placebo for 4 weeks period, separated by a wash out period of at least 2 weeks. They were symptomatic with a six minute walk distance (6MWD)>or=50 m. The change in 6MWD, echo-Doppler determined pulmonary artery systolic pressure (PASP), WHO Class and modified Borg Dyspnea Index (BDI) were assessed after each therapy. RESULTS: Eight patients who completed the study protocol were analyzed. Tadalafil was associated with a significant increase in 6MWD (mean 409.25 SD 40.25 m vs 319.37 SD 42.39 m, p<0.0001), reduction in PASP (88.75 SD 23.26 mmHg vs 109.5 SD 23.78 mmHg, p<0.0001), improvement in BDI (4.62 SD 2.56 vs 6.37 SD 2.61, p=0.021) and WHO Class (6 patients vs 2 patients), compared to placebo. Tadalafil was well tolerated with no significant untoward effects. CONCLUSIONS: Tadalafil, in patients with PAH related to previous congenital left to right shunt lesions, lead to a significant improvement in exercise capacity (6MWD), PASP and WHO Class with reduced perceived exertion and was well tolerated.

Terminalia arjuna reverses impaired endothelial function in chronic smokers.

BACKGROUND: Smoking, largely through increased oxidative stress, causes endothelial dysfunction which is an early key event in atherosclerosis. Smoking cessation and antioxidant vitamin therapy are shown to have beneficial role by restoring altered endothelial physiology. The present study was aimed to determine whether Terminalia arjuna, an Indian medicinal plant with potent antioxidant constituents, would improve endothelial dysfunction in smokers. METHODS AND RESULTS: Eighteen healthy male smokers (age 28.16+/-9.45 years) and equal number of age-matched non-smoker controls participated in the study. The baseline brachial artery reactivity studies were performed using high frequency ultrasound according to standard protocol under identical conditions to determine endothelium-dependent, flow-mediated dilation and endothelium-independent nitroglycerine-mediated dilation. The two groups were matched regarding age, body mass index, blood pressure, serum cholesterol, mean resting vessel diameters and post-occlusion flow velocities (all p=NS). While flow-mediated dilation was significantly impaired amongst smokers compared to controls (4.71+/-2.22 v. 11.75+/-5.94%, p <0.005), the nitroglycerine-mediated dilation was similar in the two groups (20.35+/-3.89 v. 19.68+/-3.74%, p=NS). Subsequently the smokers were given Terminalia arjuna (500 mg q8h) or matching placebo randomly in a double blind cross-over design for two weeks each, followed by repetition of brachial artery reactivity studies to determine various parameters including flow-mediated dilation after each period. There was no significant difference as regards vessel diameter and flow velocities between the two therapies. However, the flow-mediated dilation showed significant improvement from baseline values after Terrminalia arjuna therapy but not with placebo (9.31+/-3.74 v. 5.17+/-2.42%, p <0.005). CONCLUSIONS: Smokers have impaired endothelium-dependent but normal endothelium-independent vasodilation as determined by brachial artery reactivity studies. Further, Terrminalia arjuna therapy for two weeks leads to significant regression of this endothelial abnormality amongst smokers.

The efficacy and tolerability of sildenafil in patients with moderate-to-severe pulmonary hypertension.

BACKGROUND: Pulmonary arterial hypertension is a life-threatening disease for which continuous intravenous infusion of prostacyclin has proved effective. However, it carries the risk of serious complications arising from the complex delivery system. Prostacyclin analogs, endothelin antagonists, and the phosphodiesterase-5 inhibitor sildenafil are emerging promising therapies. This study was aimed at evaluating the utility of oral sildenafil in patients with pulmonary hypertension of varied etiology, poorly controlled on conventional treatment. METHODS AND RESULTS: Ten consecutive patients with pulmonary hypertension, either primary or related to previous left-to-right shunts, thromboembolism, or interstitial lung disease, poorly controlled on conventional therapy such as warfarin, calcium antagonists, digitalis, and diuretics, were included. A thorough clinical, laboratory, and comprehensive echo Doppler evaluation was performed before enrollment in the trial to establish the diagnosis and obtain baseline data. Subjects received sildenafil 25 mg 8 hourly, or a matching placebo for two weeks each, in a randomized, double-blind, crossover design. A run-in period of two weeks was permitted between the two therapies during which patients continued to receive the conventional therapy without any vasodilator. At the end of each therapy period, the patients were evaluated for symptoms, New York Heart Association class, distance covered during the 6 min walk test, rating of modified Borg dyspnea score, and systolic pulmonary artery pressure using echo Doppler. The differences in the above variables at the end of sildenafil and placebo therapies were compared. Nine patients completed the study protocol. Sildenafil, compared to placebo, was associated with improved exercise tolerance as determined by the 6 min walk test (266.67+/-131.45 m v. 170+/-105 m; p<0.005), decrease in modified Borg dyspnea score (3.56+/-1.01 v. 5.11+/-1.45; p<0.01), decrease in Doppler-estimated pulmonary artery systolic pressures (55.33+/-16.52 mmHg v. 75.33+/-19.75 mmHg; p<0.005), improvement in New York Heart Association class (2 patients), and improvement in symptoms. Sildenafil was well tolerated with no untoward effects; further, no significant changes in heart rate or blood pressure occurred during the study period. CONCLUSIONS: Sildenafil improves exercise capacity and symptoms, and decreases pulmonary artery pressures in patients with primary or secondary pulmonary hypertension of varied etiology.

Efficacy of Terminalia arjuna in chronic stable angina: a double-blind, placebo-controlled, crossover study comparing Terminalia arjuna with isosorbide mononitrate.

BACKGROUND: Terminalia arjuna, an Indian medicinal plant, has been reported to have beneficial effects in patients with ischemic heart disease in a number of small, open studies. The need for a double-blind, randomized, placebo-controlled study with adequate sample size has long been felt. The bark extract (IPC-53) contains acids (arjunic acid, terminic acid), glycosides (arjunetin arjunosides I-IV), strong antioxidants (flavones, tannins, oligomeric proanthocyanidins), minerals. etc. and exhibits antifailure and anti-ischemic properties. METHODS AND RESULTS: Fifty-eight males with chronic stable angina (NYHA class II-III) with evidence of provocable ischemia on treadmill exercise test received Terminalia arjuna (500 mg 8 hourly), isosorbide mononitrate (40 mg/daily) or a matching placebo for one week each, separated by a wash-out period of at least three days in a randomized, double-blind, crossover design. They underwent clinical, biochemical and treadmill exercise evaluation at the end of each therapy which were compared during the three therapy periods. Terminalia arjuna therapy was associated with significant decrease in the frequency of angina and need for isosorbide dinitrate (5.69+/-6.91 mg/week v. 18.22+/-9.29 mg/week during placebo therapy, p<0.005). The treadmill exercise test parameters improved significantly during therapy with Terminalia arjuna compared to those with placebo. The total duration of exercise increased (6.14+/-2.51 min v. 4.76+/-2.38 min, p<0.005), maximal ST depression during the longest equivalent stages of submaximal exercise decreased (1.41+/-0.55 mm v. 2.21+/-0.56 mm, p<0.005), time to recovery decreased (6.49+/-2.37 min v. 9.27+/-3.39 min, p<0.005) and higher double products were achieved (25.75+/-4.81x10(3) v. 23.11+/-4.83x10(3), p<0.005) during Terminalia arjuna therapy. Similar improvements in clinical and treadmill exercise test parameters were observed with isosorbide mononitrate compared to placebo therapy. No significant differences were observed in clinical or treadmill exercise test parameters when Terminalia arjuna and isosorbide mononitrate therapies were compared. No significant untoward effects were reported during Terminalia arjuna therapy. CONCLUSIONS: Terminalia arjuna bark extract, 500 mg 8 hourly, given to patients with stable angina with provocable ischemia on treadmill exercise, led to improvement in clinical and treadmill exercise parameters as compared to placebo therapy. These benefits were similar to those observed with isosorbide mononitrate (40 mg/day) therapy and the extract was well tolerated. Limitations of this study include applicability of the results to only men with chronic stable angina but not necessarily to women, as they were not studied.