Angiotensin Receptor-Neprilysin Inhibitor Therapy and Cardiac Remodeling in Heart Failure: Consensus Statement from India

Adverse cardiac remodeling refers to progressive structural and functional modifications in the heart because of increased wall stress in the myocardium, loss of viable myocardium, and neurohormonal stimulation. The guideline-directed medical therapy for Heart failure (HF) includes Angiotensin receptor-neprilysin inhibitor (ARNI) (sacubitril/valsartan), ?-blockers, sodium-glucose co-transporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists (MRA). ARNI is under-prescribed in India despite its attractive safety and efficacy profile. Therefore, the consensus discusses objectives and topics related to ARNI in the management of cardiac remodeling, and experts shared their views on the early timely intervention of effective dosage of ARNI to improve the diagnosis and enhance mortality and morbidity benefits in cardiac reverse remodeling (CRR).

Role of Iron Therapy in Heart Failure: A Consensus Statement from India

Iron deficiency (ID) with or without anemia is frequently observed in patients with heart failure (HF). Uncorrected ID is associated with higher hospitalization and mortality in patients with acute HF (AHF) and chronic HF (CHF). Hence, in addition to chronic renal insufficiency, anemia, and diabetes, ID appears as a novel comorbidity and a treatment target of CHF. Intravenous (IV) ferric carboxymaltose (FCM) reduces the hospitalization risk due to HF worsening and improves functional capacity and quality of life (QOL) in HF patients. The current consensus document provides criteria, an expert opinion on the diagnosis of ID in HF, patient profiles for IV FCM, and correct administration and monitoring of such patients.

Unmet Need for Further LDL-C Lowering in India despite Statin Therapy: Lipid Association of India Recommendations for the Use of Bempedoic Acid

Lipid-lowering therapy plays a crucial role in reducing adverse cardiovascular (CV) events in patients with established atherosclerotic cardiovascular disease (ASCVD) and familial hypercholesterolemia. Lifestyle interventions along with high-intensity statin therapy are the first-line management strategy followed by ezetimibe. Only about 20–30% of patients who are on maximally tolerated statins reach recommended low-density lipoprotein cholesterol (LDL-C) goals. Several factors contribute to the problem, including adherence issues, prescription of less than high-intensity statin therapy, and de-escalation of statin dosages, but in patients with very high baseline LDL-C levels, including those with familial hypercholesterolemia and those who are intolerant to statins, it is critical to expand our arsenal of LDL-C-lowering medications. Moreover, in the extreme risk group of patients with an LDL-C goal of ?30 mg/dL according to the Lipid Association of India (LAI) risk stratification algorithm, there is a significant residual risk requiring the addition of non-statin drugs to achieve LAI recommended targets. This makes bempedoic acid a welcome addition to the existing non-statin therapies such as ezetimibe, bile acid sequestrants, and PCSK9 inhibitors. A low frequency of muscle-related side effects, minimal drug interactions, a significant reduction in high-sensitivity C-reactive protein (hsCRP), and a lower incidence of new-onset or worsening diabetes make it a useful adjunct for LDL-C lowering. However, the CV outcomes trial results are still pending. In this LAI consensus document, we discuss the pharmacology, indications, contraindications, advantages, and evidence-based recommendations for the use of bempedoic acid in clinical practice.

A novel approach for the prediction of treadmill test in cardiology using data mining algorithms implemented as a mobile application

Objective To develop a mobile app called “TMT Predict” to predict the results of Treadmill Test (TMT), using data mining techniques applied to a clinical dataset using minimal clinical attributes. To prospectively test the results of the app in realtime to TMT and correlate with coronary angiogram results. Methods In this study, instead of statistics, data mining approach has been utilized for the prediction of the results of TMT by analyzing the clinical records of 1000 cardiac patients. This research employed the Decision Tree algorithm, a new modified version of K-Nearest Neighbor (KNN) algorithm, K-Sorting and Searching (KSS). Furthermore, curve fitting mathematical technique was used to improve the Accuracy. The system used six clinical attributes such as age, gender, body mass index (BMI), dyslipidemia, diabetes mellitus and systemic hypertension. An Android app called “TMT Predict” was developed, wherein all three inputs were combined and analyzed. The final result is based on the dominating values of the three results. The app was further tested prospectively in 300 patients to predict the results of TMT and correlate with Coronary angiography. Results The accuracy of predicting the result of a TMT using data mining algorithms, Decision Tree and K-Sorting & Searching (KSS) were 73% and 78%, respectively. The mathematical method curve fitting predicted with 82% accuracy. The accuracy of the mobile app “TMT Predict”, improved to 84%. Age-wise analysis of the results show that the accuracy of the app dips when the age is more than 60 years indicating that there may be other factors like retirement stress that may have to be included. This gives scope for future research also. In the prospective study, the positive and negative predictive values of the app for the results of TMT and coronary angiogram were found to be 40% and 83% for TMT and 52% and 80% for coronary angiogram. The negative predictive value of the app was high, indicating that it is a good screening tool to rule out coronary artery heart disease (CAHD). Conclusion “TMT Predict” is a simple user-friendly android app, which uses six simple clinical attributes to predict the results of TMT. The app has a high negative predictive value indicating that it is a useful tool to rule out CAHD. The “TMT Predict” could be a future digital replacement for the manual TMT as an initial screening tool to rule out CAHD.

Reattachment of Fracture of Maxillary Anterior Tooth-An Aesthetic Approach

Fracture of anterior teeth is a very common form of dental injuries among children and young adolescents. Aesthetic rehabilitation of crown fractures of the maxillary anterior teeth is one of the greatest challenges to the dentist. Various treatment modalities have been practiced in past but reattachment of fracture is considered to be one of the most conservative, natural, and aesthetic approach. The restoration of natural teeth form, colour, and alignment in these patients create a positive social and emotional response in such patients. This paper discusses a case of 16-year-old male patient with fractured left central incisor (Ellis class 3 fracture). Reattachment of fracture was done along with single sitting endodontic treatment with fibre post using flow able composite resin cement. Evaluation at 6 weeks yields good reattachment, intact post, good aesthetics, and good periodontal health.

Novel STXBP2 Mutation Causing Familial Hemophagocytic Lymphohistiocytosis.

Familial Hemophagocytic Lymphohistiocytosis (FHL) is a rare autosomal recessive disorder. Diagnosis is established in presence of genetic mutation or positive family history in one of the siblings. Common genetic mutations associated with FHL are mutations in gene PRF-1 (also known as FHL 2), UNC13D (FHL 3) and STX11 (FHL 4). Recently mutation in STXBP2 encoding syntaxin binding protein 2 (Munc 18 -2) has been found to be associated with FHL type 5. Here we describe the first reported Indian patient with homozygous mutation in STX BP2 gene (c1697 G>A resulting in amino acid change p.G566D) causing FHL 5.

Validation of the children's depression rating scale- revised for adolescents in primary-care pediatric use in India.

Background: Adolescent depression needs to be identified and treated in the primary care settings. There is no clinician-rated measure validated in India for identifying depression among adolescents. Aim: We studied the diagnostic accuracy, reliability, and validity of Children's Depression Rating Scale - Revised (CDRS-R) for primary care pediatrics. Setting and Design: Prospective study in three schools in Southern India. Materials And Methods: Adolescents recruited were administered the CDRS-R by a pediatrician and clinical psychologist along with Beck Depression Inventory (BDI) for convergent validity. Impact of Event Scale (IES) for divergent validity and the ICD-10 clinical diagnosis of depressive disorders using modified Kiddie-SADS-Present and Lifetime Version (K-SADS-PL) interview as reference standard were administered by a psychiatrist independently. Appropriate statistical analyses for diagnostic accuracy, reliability, and validity were done. Results: A cut-off score of 30 (sensitivity = 83%, specificity = 84%; AUC in ROC = 87%) in CDRS-R is suggested for diagnosing depression. The inter-rater reliability (r = 0.73) and test-retest reliability (r = 0.98) was good. In addition to the adequate face and content validity, CDRS-R had good internal consistency (α = 0.76), high convergent (r = 0.71; P = 0.001), and divergent validity (r = 0.28; P = 0.20). There was moderate concordance with the reference standard of ICD-10 diagnosis (45.5%) in identifying depression and CDRS-R discriminated 80% of the other psychiatric morbidity. The six-factor structure explained 60.6% of variance. Conclusion: The CDRS-R showed strong psychometric properties and is now available for use in the primary-care pediatric practice in India.

Acute pancreatitis as the initial presentation in systemic lupus erythematosus.

It is exceptionally rare for acute pancreatitis to be the presenting manifestation of childhood systemic lupus erythematosus. We report a 14-year-old girl who presented with a history of fever, generalized rash, arthralgia and abdominal pain. Her serum amylase was 1472U/L and lipase 3316 U/L suggestive of acute pancreatitis. Other investigations revealed pancytopenia, low complement, high 24-hour urinary protein and elevated ANA and dsDNA. She was treated with IV methylprednisone, followed by oral steroids.

Efficacy and safety of tenecteplase in Indian patients with st-segment elevation myocardial infarction.

OBJECTIVE: To assess the efficacy and safety of tenecteplase in Indian patients with ST-segment elevation MI (STEMI). METHODS: Cardiologists/physicians who had used tenecteplase for management of STEMI, recorded safety and efficacy parameters from consecutively treated patients. Tenecteplase was administered as per the prescribing information. Adjunctive therapy which included clopidogrel and UFH/LMWH was administered as routinely practiced and indicated by guidelines. RESULTS: Five hundred and seven patients (male = 415, females = 92; mean age = 58.28 +/- 12.23 yrs; weight (kg) = 70.12 +/- 11.06) with STEMI were treated with weight-adjusted tenecteplase within median chest pain to drug interval of 120 minutes. Resolution of chest pain within median interval of 45 minutes occurred in 436 patients with median duration required for > or = 50% resolution of ST segment of 75 minutes. Clinically successful thrombolysis was reported in 80.67% patients. Five patients suffered intra-cranial hemorrhage (ICH), of which 3 patients had received Gp IIb/IIIa inhibitors. Incidence of intra-cranial hemorrhage attributable to tenecteplase was 0.39% (2 out of 507 patients). Incidence of myocardial re-infarction was 2.96% (15 out of 507 patients). There were 12 deaths (2.36%). CONCLUSION , This data shows that tenecteplase is safe and effective in Indian patients with STEMI and conforms to the international ASSENT-2 trial data.

Ocular manifestations of Behcet's disease.

Behcets disease is a systemic inflammatory vascular disorder characterized by recurrent oral and genital ulcers, eye lesion, arthritis and skin lesions. We report a case of Behcets disease with ocular manifestation in an 8 year old boy.

Paraneoplastic papilloedema in a child with neuroblastoma.

Non-metastatic neurological disease complicating neuroblastoma is well recognized. Gross papilloedema in the absence of intracranial disease as initial manifestation of neuroblastoma is reported in adults. We report for the first time a case of bilateral papilloedema in a child with neuroblastoma in the absence of intracranial disease and hypertension.

Scrub typhus.

Scrub typhus is being increasingly reported in adults in India.It should be considered a strong possibility in all undifferentiated fevers. Two children with this infection are being reported highlighting the wide variation in clinical presentation. Specific tests should be preferred over Weil Felix test wherever possible especially in areas reporting a high incidence of the infection.

Pulmonary aspergillosis in a child with hepatic failure.

Invasive aspergillosis is described more frequently as a complication of neoplastic disease and in immunocompromised patients. Hepatic failure is not a generally recognized risk for pulmonary aspergillosis. We report a 3-year-old boy who presented with hepatic failure and pneumonia and whose autopsy revealed liver cirrhosis and pulmonary aspergillosis.

Effect of diet on aflatoxin B1-DNA binding and aflatoxin B1-induced glutathione S-transferase placental form positive hepatic foci in the rat

Effects of diets on hepatic aflatoxin B1 (AFB1)- DNA binding and AFB1-induced glutathione S- transferase placental (GST-P) form positive hepatic foci have been examined in young male Fischer rats. Animals were fed either AIN-76A or Purina Chow (PC) diet for 1 wk before AFB1- DNA binding studies in vivo and in vitro. Animals were injected i.p. with AFB1 (1 mg/kg body wt) and 3 days later were given either AIN-76A or PC diet with or without 0.1% phenobarbital (PB) in their drinking water. All animals were sacrificed 10 wks after AFB1 dosing for analysis of AFB1-induced GST-P positive hepatic foci by immunochemistry. Two h after i.p. injection of AFB1, hepatic AFB1-DNA binding in AIN-76A fed rats was twice as much as those in PC fed animals without affecting GSH levels. There was no significant effect of diet on either cytochrome P-450 content, GSH levels or microsomal cytochrome P-450 mediated AFB1-DNA binding to exogenous DNA. There was a 40% increase in cytosolic GSH S-transferase activity with 1-chloro-2,4-dinitrobenzene as a substrate in PC fed animals compared to those given AIN- 76A diet. The number and area of AFB1-induced GST-P positive hepatic foci were twice and fivefold as much in AIN-76A fed compared to those in PC fed rats. The number of AFB1-induced GST-P positive foci was increased 5-10 fold in the presence of PB in both groups. In summary, the present data indicate that feeding of PC diet compared to AIN-76A diet inhibits the initiation phase whereas AIN-76A stimulates the promotion phase of AFB1 hepatocarcinogenesis in rats by inhibiting AFB1-DNA binding and increasing AFB1-induced hepatic foci respectively.

Non-01 Vibrio cholerae septicemia and meningitis in a neonate.

Non-O1 Vibrio cholerae is known to cause diarrhoea as well as extra-intestinal infections in adults and children. However meningitis in children is a rare occurrence. We report a neonate who developed septicemia and meningitis due to Non-O1 Vibrio cholerae.

Percutaneous transluminal mitral commissurotomy--experience with inoue balloon and over the wire technique.

OBJECTIVE: To compare the immediate and long-term results, safety and complication profile of inoue balloon technique (IBT) and over the wire technique (OWT) in the treatment of rheumatic mitral stenosis. METHODS: We have compared the IBT in 104 patients and OWT in 40 patients. Preprocedural, immediate post-procedure and follow-up echocardiograms of both groups of patients were done. RESULTS: There was no statistically significant difference in the success rates between IBT and OWT (97% vs. 95%; p > 0.05), nor was there a difference in reduction in mean left atrial pressure, mean pulmonary artery pressure, the occurrence of significant mitral regurgitation, or mortality (p > 0.05). The cost per procedure was cheaper with OWT but the occurrence of sustained ventricular tachycardia (VT) during the procedure was more common with OWT. OWT uses a stiff guidewire for positioning the balloon across the mitral valve, which is not done in IBT, hence there is the possibility of left ventricular perforation--which in fact occurred in one of our patients. During a mean follow up period of 12.9 months for IBT and 13.5 months for OWT, there was no significant restenosis in both the groups. The advantage of the OWT was the cheaper cost of the balloon and comparable results with IBT despite longer fluoroscopy and procedural times and the increased incidence of arrhythmias during the procedure. CONCLUSION: In a third world country like ours where escalating cost may be a deterrent in performing interventions, the OWT is a comparable alternative to IBT.

Valvuloplasty balloon detaching from the stem of a catheter.

A 12-year-old boy underwent pulmonary balloon valvotomy for isolated critical pulmonary stenosis. Following valvotomy, blood was found to be drawn into the syringe during deflation of the balloon, so a provisional diagnosis of a burst balloon was made. However, when the balloon catheter was withdrawn, the balloon got detached from the stem of the catheter at the level of the right atrium and was retained over the exchange guidewire. The balloon, when retrieved with a snare, was found to be intact. The balloon may have been partially detached at the junction of the proximal end of the balloon and the catheter; hence, blood was drawn from the catheter during deflation. In our institution balloons are reused following sterilization with ethylene oxide gas. We conclude that any balloon presumed to have burst inside the heart must be removed with great caution. In a third world country like India, where cost is an important factor, balloons can be reused, but with caution, keeping in mind complications such as in this case.

Isolated congenital left ventricular diverticulum in adults.

Isolated congenital ventricular diverticulum or aneurysm is rare and usually arises from the left ventricle. The presentation of this condition is diverse. We report three cases of isolated congenital left ventricular diverticula. The age range was 17-30 years. Chest X-ray provided the earliest clinical suspicion in these three cases of a cardiac anomaly which was diagnosed by echocardiography and confirmed by angiocardiography. The location of the congenital left ventricular diverticulum was the left ventricular apex in two cases and basal in the other. We conclude that congenital left ventricular diverticulum is a disease of protean presentations. A high index of suspicion is necessary while interpreting chest X-rays and echocardiographs to diagnose congenital left ventricular diverticulum. A contractile accessory chamber of the left ventricle with a narrow neck with or without midline defects and an electrocardiogram without Q waves is consistent with the diagnosis of congenital left ventricular diverticulum.