Reduced incretin receptor trafficking upon activation enhances glycemic control and reverses obesity in diet-induced obese mice.

Activation of incretin receptors by their cognate agonist augments sustained cAMP generation both from the plasma membrane as well as from the endosome. To address the functional outcome of this spatiotemporal signaling, we developed a nonacylated glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor dual agonist I-M-150847 that reduced receptor internalization following activation of the incretin receptors. The incretin receptor dual agonist I-M-150847 was developed by replacing the tryptophan cage of exendin-4 tyrosine substituted at the amino terminus with the C-terminal undecapeptide sequence of oxyntomodulin that placed lysine 30 of I-M-150847 in frame with the corresponding lysine residue of GIP. The peptide I-M-150847 is a partial agonist of GLP-1R and GIPR; however, the receptors, upon activation by I-M-150847, undergo reduced internalization that promotes agonist-mediated iterative cAMP signaling and augments glucose-stimulated insulin exocytosis in pancreatic ß cells. Chronic administration of I-M-150847 improved glycemic control, enhanced insulin sensitivity, and provided profound weight loss in diet-induced obese (DIO) mice. Our results demonstrated that despite being a partial agonist, I-M-150847, by reducing the receptor internalization upon activation, enhanced the incretin effect and reversed obesity.NEW & NOTEWORTHY Replacement of the tryptophan cage (Trp-cage) with the C-terminal oxyntomodulin undecapeptide along with the tyrosine substitution at the amino terminus converts the selective glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 to a novel GLP-1R and GIPR dual agonist I-M-150847. Reduced internalization of incretin receptors upon activation by the GLP-1R and GIPR dual agonist I-M-150847 promotes iterative receptor signaling that enhances the incretin effect and reverses obesity.

Comparing Obtura Vascular Closure Device to Manual Compression for Achieving Hemostasis After Percutaneous Transfemoral Procedures: A Randomized Study.

PURPOSE: This trial was designed and aimed to compare safety and efficacy of Obtura™ vascular closure device (VCD) to manual compression (MC) among patients undergoing transfemoral catheterization. MATERIAL AND METHODS: This prospective, randomized, controlled, multicenter trial of Obtura VCD against MC randomized patients in 1:1 (n=268; 134:134) ratio. Safety and efficacy were measured by primary endpoints (time to hemostasis [TTH] and deployment success) and secondary endpoints which included technical success, device-related adverse events, and time to ambulation (TTA). RESULTS: The procedural access using right femoral artery was performed in 95.52% of patients in Obtura VCD versus 96.27% in standard MC method, whereas 2.99% of patients in each group underwent left femoral access. Bilateral access was performed in 1.49% (n=2) versus 0.75% (n=1) in Obtura VCD versus MC, respectively. Both the technical success and deployment success were 100%. Patients in Obtura VCD group had shorter TTH (3.26±3.39 vs 23.95±8.24 minutes; p<0.0001) and TTA (155.44±125.32 vs 723.84±197.98 minutes; p<0.0001) than MC group. No access site complications (re-bleeding, infection, arteriovenous fistula, and transient access site nerve injury) were noted at 2-week, 1-month, and 3-month follow-ups. There were 4 (3%) and 6 (4.5%) cases of hematoma, respectively, in Obtura VCD versus MC and 1 case (0.7%) of post-procedural arterial pseudoaneurysm each in both the groups which were successfully resolved and patients were discharged with no further complications. Further follow-up was without any adverse events. CONCLUSIONS: The study demonstrated favorable safety and efficacy of Obtura™ VCD with a significantly short TTH and TTA compared to MC. CLINICAL IMPACT: In patients undergoing cardiac catheterization, vascular closure devices (VCDs) can achieve hemostasis faster after successful implantation of the device with fewer complications such as bleeding and ambulation can be achieved faster. In terms of effectiveness, Obtura VCD was found to be better than manual compression in achieving early hemostasis and higher technical and deployment success was accomplished. Obtura VCD does not require enlargement of the route through the tissues, uses the same existing arterial sheath as its conduit, and does not cause patients' access sites to feel uncomfortable while it is being deployed.

A Novel TPM1 Mutation Causes Familial Hypertrophic Cardiomyopathy in an Indian Family: Genetic and Clinical Correlation.

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder characterised by unexplained left ventricular hypertrophy in the absence of abnormal loading conditions. The global prevalence of HCM is estimated to be 1 in 250 in the general population. It is caused due to mutations in genes coding for sarcomeric proteins. α-tropomyosin (TPM1) is an important protein in the sarcomeric thin filament which regulates sarcomere contraction. Mutations in TPM1 are known to cause hypertrophic cardiomyopathy, dilated cardiomyopathy and left ventricular non-compaction. Mutations in TPM1 causing hypertrophic cardiomyopathy are < 1%. However, some high-risk mutations causing sudden cardiac death are also known in this gene. We present a case of a novel heterozygous TPM1 mutation, NM_001018005.2:c.203A>G, p.Gln68Arg; co-segregating in an Indian family with hypertrophic cardiomyopathy. Our report expands the mutational spectrum of HCM due to TPM1 and provides the correlated cardiac phenotype.

Micro-Raman spectroscopy study of blood samples from myocardial infarction patients.

Acute myocardial infarction (MI) is found to be a major causative factor for global mortality and morbidity. This situation demands necessity of developing efficient and rapid diagnostic tools to detect acute MI. Raman spectroscopy is a non-destructive optical diagnostic technique, which has high potential in probing biochemical changes in clinical samples during initiation and progress of diseases. In this work, blood was taken as the sample to examine inflammation in acute MI patients using Raman spectroscopy. Ratio of Raman peak intensities that corresponds to phenylalanine (1000 cm-1) and tyrosine (825 cm-1) can facilitate indirect information about tetrahydrobiopterin (BH4) availability, which can indicate inflammatory status in patients. This ratio obtained was higher for MI patients in comparison with control subjects. The decrease in phenylalanine and tyrosine ratio (Phe-Tyr ratio) is attributed to the prognosis of standard of care (medications like antiplatelets including aspirin, statin and revascularisation) leading to inflammation reduction. Phe-Tyr ratio estimated from the Raman spectra of blood can be exploited as a reliable method to probe inflammation due to MI. The method is highly objective, require only microliters of sample and minimal sample preparation, signifying its clinical utility.

Effectiveness of ultrasonography-guided cardiac sympathetic denervation in acute control of electrical storm: A retrospective case series.

Background and Aims: Ultrasonography-guided left cardiac sympathetic denervation (LCSD) or bilateral cardiac sympathetic denervation (BCSD) may be a useful intervention in the electrical storm (ES) that persists despite pharmacological therapy. The aim of our study was to evaluate the effectiveness of ultrasonography-guided LCSD or BCSD in the acute control of ES. We conducted a retrospective case series of patients who underwent ultrasonography-guided CSD for control of ES at a tertiary care hospital. Material and Methods: Data of all patients who underwent unilateral or bilateral CSD were collected from January 2017 to December 2019. Eleven patients with ES refractory to standard antiarrhythmic therapy underwent ultrasonography-guided pharmacological CSD (eight underwent LCSD and three underwent BCSD). Quantitative data was expressed as mean and median with interquartile range (IQR). Non-quantitative data was expressed in proportions. Results: Eleven patients underwent ultrasonography-guided pharmacological CSD (eight underwent LCSD and three underwent BCSD). Six of the eleven patients were female (54.5%). Ischemia was the underlying substrate in nine patients (81.8%). Five patients (46%) had complete resolution of ventricular tachycardia (VT) after CSD and one had 90% reduction in episodes of VT. The median follow-up duration was 8 months inter-quartile range IQR (7-18). One patient succumbed to heart failure and one patient was lost to follow up. The other patients had no further events and were well at last follow up. Conclusion: Ultrasonography-guided pharmacological CSD is effective in the acute control of ES. It is easily performed with equipment that is readily available and relatively safe in terms of immediate complications and is an ideal second-line intervention when ES persists despite drug therapy.

Effectiveness of self-care educational programme on clinical outcomes and self-care behaviour among heart failure peoples-A randomized controlled trial: Study protocol.

AIM: To evaluate the effectiveness of a self-care education programme on clinical outcomes, self-care behaviour and knowledge on heart failure (HF) among peoples with HF. DESIGN: Randomized controlled trial. METHODS: The participants (N = 160) will be randomly assigned (1:1) to the intervention and the control arms using block randomization. The participants assigned to the intervention arm will receive educational intervention on HF self-care comprising video-assisted teaching with teach-back technique, tailored teaching at discharge and a guide on self-care followed by telephonic calls and text messages after discharge for 6 months along with standard care. The participants in the control arm will receive only a guide on self-care with standard care. The clinical outcomes such as health-related quality of life, hospital readmissions, N-terminal pro-brain natriuretic peptide levels, symptom perception, functional status, left ventricular ejection fraction, Seattle HF score, self-care behaviour and knowledge on HF will be measured at the baseline, after 1 and 6 months of the intervention. DISCUSSION: Several studies conducted on self-care education interventions have shown positive effects, whereas few studies have shown no effect on the people outcomes. Providing the printed self-care guide alone may not improve behaviour associated with self-care and clinical outcomes. These peoples need continuous reinforcement on self-care. If this self-care educational intervention shows beneficial effects, it will contribute to the clinical practice and improve clinical outcomes. IMPACT: This research will contribute to the evidence on the effectiveness of an educational intervention on self-care among peoples with HF. The results would assist the nurses caring for peoples with HF. They can also implement this intervention for improving the peoples' self-care behaviour. TRIAL REGISTRATION: The trial is registered with the Clinical Trial Registry India and the reference ID number CTRI/2019/10/021724.

The Asia-Pacific Society of Cardiology (APSC) Expert Committee Consensus Recommendations for Assessment of Suspected Acute Coronary Syndrome Using High-Sensitivity Cardiac Troponin T in the Emergency Department.

The Asia-Pacific Society of Cardiology (APSC) high-sensitivity troponin T (hs-TnT) consensus recommendations and rapid algorithm were developed to provide guidance for healthcare professionals in the Asia-Pacific region on assessing patients with suspected acute coronary syndrome (ACS) using a hs-TnT assay. Experts from Asia-Pacific convened in 2 meetings to develop evidence-based consensus recommendations and an algorithm for appropriate use of the hs-TnT assay. The Expert Committee defined a cardiac troponin assay as a high-sensitivity assay if the total imprecision is ≤10% at the 99th percentile of the upper reference limit and measurable concentrations below the 99th percentile are attainable with an assay at a concentration value above the assay's limit of detection for at least 50% of healthy individuals. Recommendations for single-measurement rule-out/rule-in cutoff values, as well as for serial measurements, were also developed. The Expert Committee also adopted similar hs-TnT cutoff values for men and women, recommended serial hs-TnT measurements for special populations, and provided guidance on the use of point-of-care troponin T devices in individuals suspected of ACS. These recommendations should be used in conjunction with all available clinical evidence when making the diagnosis of ACS.

Can Distal Radial Access Replace Conventional Radial Access for Coronary Catheterization? A Study Comparing Puncture Time, Attempts, Patient and Operator Comfort.

BACKGROUND: To compare distal (dTRA) and classical (cTRA) transradial approaches for coronary catheterization with respect to puncture attempts, puncture time, operator and patient comfort, and safety outcomes. METHODS: In this prospective observational study, patients undergoing coronary catheterization for standard indications via dTRA or cTRA approaches from July 2019 to May 2020 were included. Clinicodemographic and laboratory characteristics were recorded. Puncture time, number of puncture attempts, operator and patient comfort on the visual analogue scale (VAS), and access site complications like hematoma and radial artery occlusion were recorded. Patients were analyzed in the same group as the initial puncture, even if there was a cross-over. RESULTS: Of the 130 patients (40.8% women), 50.8% and 49.2% belonged to dTRA and cTRA groups, respectively. dTRA group required more than one puncture attempt more frequently than cTRA group (30.3% vs. 15.6%; P =.047); consequently, puncture time was longer (60s vs. 50s; P =.031, respectively). However, puncture time was comparable if the puncture was successful in the first attempt (47.5s vs. 45s; P =.492). Patient comfort was comparable (7.2 ± 0.9 vs. 7.2 ± 1.2; P =.852), but operator comfort was more with cTRA approach (8.3 ± 1.6 vs. 8.8 ± 1.2; P =.048). Post-procedure, cTRA had more minor bleeding than dTRA approach. There was no major bleeding in either group. The occurrence of radial artery occlusion was comparable in both groups. CONCLUSION: Although dTRA needed more attempts for successful puncture, puncture time was comparable with cTRA when puncture was successful on the first attempt. Therefore, one attempt at dTRA puncture could be a reasonable approach in patients undergoing coronary catheterization.

Efficacy of comprehensive structured exercise program on claudication pain and quality of life in type 2 diabetes mellitus with peripheral arterial disease.

Background: Peripheral arterial disease is one of the leading complications of type 2 diabetes mellitus. The primary symptom of peripheral arterial disease is claudication pain. Exercise is known to improve the claudication pain, thereby improving the quality of life. Methods: A total of 74 participants were recruited in each group and a detailed demographic assessment was done for all the participants. The study group received a comprehensive structured exercise program and standard care whereas the control group received only the standard care. Progression of the exercise was made at the 6th week of the protocol. All the outcome measures were reassessed after the 12th weeks for both study and control group. Results: The mean age of participants was 60.78 ± 11.29 (years) and 59.98 ± 11.42 (years) for the study and control group, respectively. There was a statistically significant difference in toe brachial index (p < 0.001), ankle brachial index (p < 0.001), 6-minute walk distance (p < 0.001), WHO-BREF quality of life questionnaire (p < 0.001), and walking ability ((p < 0.001) in the study group in comparison to the control group. Conclusion: In the present study we found that comprehensive structured exercise program improves the arterial indices, quality of life, walking ability and reduces claudication pain in type 2 diabetes mellitus with peripheral arterial disease. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01426-2.

Shepherd's Crook Curve: A Novel Technique for Angulated Side Branch Access in Bifurcation Angioplasty.

Coronary intervention involving the region of bifurcation remains a challenging issue for the cardiologist as well as a complication. A number of factors including the angulation of side branch with the main branch determines the success. Though provisional strategy remains the best option in bifurcation intervention, at times a two-stent strategy cannot be avoided. We report a case in which percutaneous coronary intervention was performed on the left anterior descending artery (LAD) at its bifurcation with a major diagonal branch (> 2.5 mm). The ostium of the diagonal was diseased, and the branch took off from the LAD at an unfavorable angle (> 120°). We describe the use of the "shepherd's crook wire curve" approach, a modification of the reverse wire technique, which allowed us to successfully wire, dilate, and protect the diagonal and so named to reflect its resemblance to the shape of a shepherd's crook.