An insight into the hepatoprotective role of Velpatasvir and Sofosbuvir per se and in combination against carbon tetrachloride-induced hepatic fibrosis in rats.

Hepatitis C is a global health issue. Hepatitis C Virus (HCV) induces fibrosis by redox reactions, which involve the deposition of collagen in extracellular matrix (ECM). This study aimed to examine the antifibrotic effect of direct-acting antivirals; Sofosbuvir and Velpatasvir, per se and in combination against carbon tetrachloride (CCl4)-induced fibrosis in rats. Carbon tetrachloride (intraperitoneal; 0.5 ml/kg) twice weekly for six weeks was used to induce hepatic fibrosis in rats. After two weeks of CCl4, oral administration of Sofosbuvir (20 mg/kg/d) and Velpatasvir (10 mg/kg/d) was administered to rats for the last four weeks. Liver function tests (LFTs), renal function tests (RFTs), oxidative stress markers, and the levels of TNF-a, NF-κB, and IL-6 were measured through ELISA and western blotting at the end of the study. CCl4 significantly ameliorated the values of RFTs, LFTs and lipid profiles in the diseased group, which were normalized by the SOF and VEL both alone and in combination. These drugs produced potent antioxidant effects by significantly increasing antioxidant enzymes. From the histopathology of hepatic tissues of rats treated with drugs, the antifibrotic effect was further manifested, which showed suppression of hepatic stellate cells (HSCs) in treated rats, as compared to the disease control group. The antifibrotic effect was further demonstrated by significantly decreasing the levels of TNF-a, NF-κB and IL-6 in serum and hepatic tissues of treated rats as compared to the disease control group. Sofosbuvir and Velpatasvir alone and in combination showed marked inhibition of fibrosis in the CCl4-induced non-HCV rat model, which was mediated by decreased levels of TNF-a/NF-κB and the IL-6 signaling pathway. Thus, it can be concluded that Sofosbuvir and Velpatasvir might have an antifibrotic effect that appears to be independent of their antiviral activity.

A Fatal Case of Native Valve Endocarditis with Multiple Embolic Phenomena and Invasive Methicillin-Resistant Staphylococcus aureus Bacteremia: A Case Report from the Maldives.

Infective endocarditis (IE) is a life-threatening condition caused by infection within the endocardium of the heart and commonly involves the valves. The subsequent cascading inflammation leads to the appearance of a highly friable thrombus that is large enough to become lodged within the heart chambers. As a result, fever, fatigue, heart murmurs, and embolization phenomena may be seen in patients with IE. Embolization results in the seeding of bacteria and obstruction of circulation, causing cell ischemia. Of concern, bacteria with the potential to gain pan-drug resistance, such as methicillin-resistant Staphylococcus aureus (MRSA), are increasingly being identified as the causative agent of IE in hospitals and among intravenous drug abusers. We retrospectively reviewed de-identified clinical data to summarize the clinical course of a patient with MRSA isolated using an automated blood culture system. At the time of presentation, the patient showed a poor consciousness level, and the calculated Glasgow scale was 10/15. A high-grade fever with circulatory shock indicated an occult infection, and a systolic murmur was observed with peripheral signs of embolization. This case demonstrated the emerging threat of antimicrobial resistance in the community and revealed clinical findings of IE that may be helpful to clinicians for the early recognition of the disease. The management of such cases requires a multi-specialty approach, which is not widely available in small-island developing states such as the Maldives.

Retrograde percutaneous coronary intervention in a calcified and dissected left anterior descending artery using single catheter - To lose the patience is to lose the battle.

Percutaneous coronary intervention (PCI) after iatrogenic coronary dissection in a heavily calcified vessel is technically challenging and a retrograde approach helps in that scenario. "Reverse rota wiring" shortens the procedure time in retrograde PCI whenever rotational atherectomy is planned. A 70-year-old male patient with previous PCI to diagonal and left circumflex arteries and attempted PCI to left anterior descending (LAD) and right coronary arteries, presented with exertional angina. After documenting ischemia, PCI to LAD was scheduled. After failed initial antegrade attempts, retrograde wiring through the diagonal was done. Then reverse rota wiring and rotational atherectomy (RA) to LAD using 1.25 mm burr was done. Since the 1.25 mm rota burr was entrapped, the entire system was manually pulled back. Repeat retrograde wiring and RA using 1.5 burr was done since the intravascular ultrasound showed >270° calcium. After multiple balloon dilatations, stenting was done using two drug-eluting stents. Coronary perforation with cardiac tamponade occurred after stenting. After pericardiocentesis, perforation was sealed with a guidezilla-II assisted covered stent implantation and final thrombolysis in myocardial infarction (TIMI) 3 flow was achieved. The patient remained symptom-free at one-year follow-up. Operator skills and perseverance are essential for good outcome in complex PCIs. Learning objectives: 1.Retrograde percutaneous coronary intervention is useful in iatrogenic coronary dissection, when antegrade attempts to enter the true lumen fail.2.'Reverse rota wiring' is an alternative method to do rotational atherectomy after retrograde wire crossing. It shortens the procedure time and it is useful in heavily calcified lesions where balloon uncrossability is anticipated.

Absolute zero-contrast percutaneous coronary intervention under intravascular ultrasound guidance in chronic kidney disease patients - From despair to hope?

Background: Zero contrast percutaneous coronary intervention (PCI) reduces contrast induced acute kidney injury (CI-AKI), and it improves the outcome of chronic kidney disease (CKD) patients undergoing PCI. Objectives: We sought to assess the safety and short-term outcomes of 'absolute' zero-contrast PCI under intravascular ultrasound (IVUS) guidance in CKD patients. Methods: Data from all consecutive CKD patients who were included for absolute zero contrast PCI during the period of June 2020 to March 2021 were included in this analysis. Clinical characteristics, angiographic, IVUS and procedural data, and follow-up data were analyzed. Results: Totally 42 patients (66 vessels) with the mean age of 69.04 ± 11.9 years, were included for absolute zero-contrast PCI. The mean serum creatinine and estimated glomerular filtration rate (eGFR) were 2.67 ± 1.46 mgs% and 30.67 ± 12.26 ml/min/1.73 m2 respectively. The most common presentation was acute coronary syndrome (ACS) and the mean left ventricular ejection fraction (LVEF) and SYNTAX score were 43.7 ± 11.9% and 27.7 ± 14.1 respectively. Complex PCI including 14 (21.2%) left main coronary artery (LMCA) PCI (seven LMCA bifurcation PCI) and three chronic total occlusion (CTO) PCI were also done. Technical success was 92.4% without any major complications. Two patients died of non cardiac causes on follow up (3-12 months), and all the remaining were symptom free. Conclusion: IVUS guided 'absolute' zero-contrast PCI is feasible and safe CKD patients. Even in complex lesion morphologies, the procedure can be completed without any contrast and complications.

Percutaneous coronary intervention in unprotected left main coronary artery stenosis: Mid-term outcomes of a single-center observational study.

BACKGROUND: Percutaneous coronary intervention (PCI) is an appropriate alternative to coronary artery bypass grafting (CABG) for revascularization of unprotected left main coronary artery (ULMCA) disease in patients with low-to-intermediate anatomic complexity or when the patient refuses CABG even after adequate counselling by heart team. We assessed the safety, in-hospital and mid-term outcomes of ULMCA stenting with drug-eluting stents (DES) in Indian patients. METHODS: Our study was a retrospective analysis of patients who had undergone ULMCA PCI at a tertiary center, between March 2011 and February 2020. Clinical characteristics, procedural data, and follow-up data were analyzed. The primary outcome was a composite of major adverse cardiovascular and cerebrovascular events (MACCE) during the hospital stay and at follow-up. The median follow-up was 2.8 years (interquartile range: 1.5-4.1 years). RESULTS: 661 patients (mean age, 63.5 ± 10.9 years) had undergone ULMCA PCI. The mean SYNTAX score was 27.9 ± 10.4 and the mean LVEF was 58.0 ± 11.1%. 3-vessel disease and distal lesions were noted in 54% and 70.6% patients, respectively. The incidence of in-hospital MACCE was 1.8% and the MACCE during follow-up was 11.5% (including 48 [8.4%] cardiac deaths). The overall survival rates after one, three, five, and nine years were 94%, 88%, 84%, and 82%, respectively. The multivariate analysis revealed that age >65 years and high SYNTAX scores were independent predictors of mid to long-term mortality. CONCLUSION: ULMCA PCI with DES is safe and has acceptable in-hospital and mid-term outcomes among patients with low-to-intermediate SYNTAX score.

Retrograde chronic total occlusion percutaneous coronary intervention using single catheter: A single centre registry.

OBJECTIVES: To analyse the feasibility, safety and procedural outcomes of percutaneous coronary intervention (PCI) for chronic total occlusions (CTO) through retrograde approach using single catheter. METHODS: Our study was a retrospective observational study that enrolled patients who underwent retrograde CTO PCI using a single catheter between June 2016 and February 2020. Clinical success was defined as successful completion of CTO PCI without associated in-hospital major clinical complications like death, myocardial infarction, stroke or urgent revascularisation. Technical success was defined as successful completion of CTO PCI using single catheter and minimum diameter stenosis of <30% with thrombolysis in myocardial infarction (TIMI) flow grade 3, without significant side branch occlusion, flow-limiting dissection, distal embolization, or angiographic thrombus. RESULTS: Totally 102 patients underwent retrograde CTO PCI during the study period. Out of which, 15 cases were attempted using single catheter. Mean age of the population was 59.1 ± 8.9 years (males: 86.7%) and the left ventricular ejection fraction (LVEF) was (61% ± 9.1%). Mean number of diseased arteries was 2.1 ± 0.7, length of the CTO was 25.5 ± 7.4 mm and J-CTO score was 2.3 ± 0.7. We achieved a technical success rate of 73.3% using single catheter, and the overall clinical success (Including single catheter and ping pong) was obtained in 86.7% cases. One patient (6.7%) developed cardiac tamponade and none of study population required dialysis for contrast induced acute kidney injury (CI-AKI) CONCLUSIONS: Retrograde CTO PCI using single catheter is a technically challenging procedure when compared with other CTO PCI. Our study demonstrated acceptable outcomes which is comparable to other antegrade and retrograde CTO PCI registries.

Discordant responses to his refractory premature ventricular beats (PVBs) during a regular narrow QRS tachycardia. What is the mechanism.

A 32-year-old lady was evaluated for recurrent episodes of palpitation. During one of the palpitation episodes a regular narrow QRS tachycardia was documented, and it got terminated with the administration of IV adenosine. The baseline 12 lead electrocardiogram (ECG) did not show any manifest preexcitation. There was no evidence of structural heart disease by echocardiogram. Patient underwent an electrophysiology (EP) study after informed consent. Quadripolar catheters were placed at the His region and right ventricular (RV) apex. A decapolar catheter was placed in the coronary sinus (CS) with CS 9, 10 dipoles at CS OS region and CS 1, 2 dipoles at CS distal region. A mapping & ablation catheter was positioned at right atrial (RA) appendage. Baseline atrial and ventricular pacing protocols could not be performed as both atrial and ventricular pacing were easily inducing a regular narrow QRS tachycardia. His refractory premature ventricular beats [PVBs] were delivered from RVRV apex and left ventricular [LV] free wall. Discordant responses were obtained. What is the mechanism?