Daid, Simranpreet Singh

Background: Chronic right ventricular pacing (RVP) can lead to electrical dyssynchrony, often resulting in pacemaker-induced cardiomyopathy (PICM). Although biventricular pacing (BiVP) is a standard upgrade strategy, it is associated with notable rates of non-response and procedural limitations. Conduction system pacing (CSP), including His bundle pacing (HBP) and left bundle branch pacing (LBBP), offers a more physiological approach by directly engaging the native conduction system. Emerging evidence supports the role of His-Purkinje conduction system pacing (HPCSP) in reversing adverse remodeling and improving clinical outcomes in PICM patients. Methods: A comprehensive literature search was performed across PubMed, Embase, Cochrane Library, and ClinicalTrials.gov through January 2025. Studies were included if they evaluated outcomes in patients with PICM who had been chronically paced in the right ventricle and subsequently upgraded to HPCSP. Key endpoints included changes in left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class. Results: Six studies comprising 144 patients were included. Over an average follow-up of 17.9 ± 10.5 months, significant improvement in LVEF was observed, increasing from 35 ± 8% prior to upgrade to 48 ± 12% following HPCSP (P < 0.001). Similarly, NYHA class improved from a baseline of 2.7 ± 0.8 to 1.9 ± 0.8 (P < 0.001), indicating meaningful symptomatic relief. Conclusion: Upgrading to His-Purkinje conduction system pacing is a safe and effective strategy in patients with PICM. It offers significant improvements in cardiac function and quality of life by restoring physiologic electrical activation. HPCSP represents a promising alternative to BiVP in this population and should be considered in clinical decision-making for pacing upgrades.

Introduction: Hypercholesterolemia drives atherosclerotic cardiovascular disease. Bempedoic acid (BA) lowers low-density-lipoprotein cholesterol (LDL-C) by inhibiting ATP-citrate-lyase, providing a non-statin option for patients who need additional lipid control. Hypothesis: We expected BA to improve atherogenic lipids and major adverse cardiovascular events (MACE) without raising cardiovascular (CV) mortality and with an acceptable safety profile. Aims: To measure the pooled effect of BA on (1) LDL-C, (2) non-HDL-C, (3) high-sensitivity C-reactive protein (hsCRP) and to compare clinical outcomes for (4) MACE, (5) CV mortality, and (6) hyperuricemia versus placebo. Methods: A systematic search of PubMed, Embase, MEDLINE, Google Scholar and ClinicalTrials.gov through 1 April 2025 identified randomized controlled trials (RCTs) of BA versus placebo in adults with hypercholesterolemia. Data were extracted into a spreadsheet, and analyses were performed with RevMan 5.4. Results: 13 RCT's with 22345 patients met the inclusion criteria. BA produced robust lipid and inflammatory improvements. LDL-C fell by 24.3 % (95 % CI −27.8 to −20.9), non-HDL-C by 19.8 % (95 % CI −25.0 to −14.6), and hsCRP by 26.7 % (95 % CI −39.6 to −13.7). These changes translated into a 19 % relative reduction in MACE (RR 0.81, 95 % CI 0.68–0.96), while CV mortality was unchanged (RR 0.87, 95 % CI 0.53–1.43). As anticipated, hyperuricemia risk almost doubled with BA (RR 1.93, 95 % CI 1.75–2.14). Conclusion: BA consistently lowers LDL-C, non-HDL-C and systemic inflammation and reduces MACE without affecting CV mortality. The main safety concern is higher hyperuricemia, which appears manageable with monitoring. These findings support BA as an effective add-on therapy for patients who are statin-intolerant or need further lipid reduction, while highlighting the need for longer trials to assess mortality benefits and long-term safety.

Introduction: Dyslipidemia remains a major driver of cardiovascular disease. Monoclonal antibodies (mAb) that block angiopoietin-like protein 3 (ANGPTL3) lower atherogenic lipids by a mechanism distinct from statins. Earlier evidence centred on the Evinacumab. A new trial now evaluate the investigational antibody SHR-1918. Hypothesis: We hypothesized that treatment with ANGPTL3 mAbs whether evinacumab or SHR-1918 would significantly improve lipid parameters compared to placebo without increasing adverse events. Aims: To Quantify the pooled effect of ANGPTL3 mAbs on low-density lipoprotein cholesterol (LDL-C), Triglycerides, apolipoprotein B (ApoB) and non-high-density lipoprotein cholesterol (non-HDL-C) and Compare efficacy and safety between Evinacumab and SHR-1918 subgroups. Methods: A systematic search of Pubmed, Google Scholar MEDLINE, Embase, and ClinicalTrials.gov untill 1 April 2025 was done and relevant randomised controlled trials (RCT's) comparing ANGPTL3 mAbs with placebo in dyslipidaemic patients were included. Data was extracted on spreadsheet and Data analysis was done in RevMan 5.4. Results: 5 RCT's comprising of 603 patients met inclusion criteria. The pooled analysis showed marked reductions in atherogenic lipids with ANGPTL3 monoclonal antibodies versus placebo, including low-density lipoprotein cholesterol (SMD = –2.73, 95 % CI –4.16 to –1.31, P < 0.001), triglycerides (SMD = –3.54, 95 % CI –4.71 to –2.37, P < 0.001), apolipoprotein B (SMD = –1.98, 95 % CI –2.97 to –1.00, P < 0.001) and non-HDL-C (SMD = –2.89, 95 % CI –4.00 to –1.78, P < 0.001). Sub-group analyses demonstrated directionally consistent lipid lowering for both evinacumab and the newer agent SHR-1918. Adverse-event due to treatment evaluation revealed no significant increase in Adverse events due to treatment (RR = 1.05, 95 % CI 0.87 to 1.27, P = 0.63) or serious events (RR = 1.37, 95 % CI 0.54 to 3.44, P = 0.49), indicating good overall tolerability. Conclusion: monoclonal antibodies targeting ANGPTL3 encompassing both evinacumab and the newer agent SHR-1918 consistently reduced LDL-C, triglycerides, and related lipid markers with a favourable tolerability profile. Further large, long-term studies are needed to fully establish their safety, clinical effectiveness, and potential to improve cardiovascular outcomes.

Background: Pneumocystis pneumonia (PCP) is an opportunistic fungal infection, which is frequently observed in immunocompromised patients. Although T-cell immunity is classically related to Pneumocystis defense, recent data support roles for B lymphocytes in the development of PCP in animals, and we have observed several cases of PCP in patients receiving rituximab. These observations prompted a systematic review and meta-analysis of our experience to see the efficacy of PCP prophylaxis (TMP-SMX) in lymphoma patients receiving rituximab. The efficacy of PCP prophylaxis in this population remains a subject of clinical interest. Research Question: To evaluate the effect of PCP prophylaxis compared to no prophylaxis on the risk of developing PCP in lymphoma patients receiving rituximab. Methods: We conducted meta-analysis including six retrospective cohort studies that compared the incidence of PCP in lymphoma patients receiving rituximab with and without prophylaxis. The cohort studies with incept up to January 2023 were retrieved from databases including PubMed, Google Scholar, EMBASE, PLOS ONE, Cochrane, and ClinicalTrials.gov. Data extraction was done using a spreadsheet, and data analysis was done using RevMan 5.4.1 for meta-analysis. Results: The analysis included 2304 patients, with 571 receiving PCP prophylaxis and 1733 did not receive prophylaxis. Studies reporting results of PCP prophylaxis were included. Enrolled studies were quality assessed with Newcastle-Ottawa Scale. The incidence of PCP was significantly lower in the prophylaxis group (3 out of 571) compared to the no prophylaxis group (67 out of 1733). The pooled risk ratio (RR) was 0.23 [95% CI, 0.09 to 0.58], indicating a 77% reduction in the risk of PCP with prophylaxis. Conclusion: The clinical course of cases of PCP in patients treated with rituximab can be quite fulminant, with significant mortality. Primary prophylaxis should be considered in patients at risk. PCP prophylaxis significantly decrease the risk of PCP in lymphoma patients receiving rituximab-based therapies, with a pooled risk ratio of 0.23.

Background: Antithrombotic regimens play a pivotal role in averting complications and ischemic incidents post-percutaneous coronary intervention (PCI) in MI (myocardial infarction) patients. Bivalirudin stands as a viable alternative to unfractionated heparin in this cohort, demonstrating the efficacy and safety profiles. Aim: We aimed to compare the efficacy and safety of bivalirudin versus unfractionated heparin in post-percutaneous coronary intervention (PCI) in MI (myocardial infarction) patients. Research Question : What is the efficacy and safety of Bivalirudin compared to unfractionated heparin in patients with MI undergoing PCI, specifically in terms of major bleeding, cardiovascular mortality, and other major adverse cardiovascular events? Methods: We systematically searched PubMed, including MEDLINE, Embase, Cochrane Library, Google Scholar, ClinicalTrials.gov, and EBSCOhost/CINAHL, from January 1, 2000, through May 29, 2024, for randomized controlled trials (RCTs) that evaluated Bivalirudin versus unfractionated heparin and with a study population of patients with MI undergoing PCI. Data extraction was done using a spreadsheet, and data analysis was done using RevMan 5.4.1 for meta-analysis. The primary efficacy and safety endpoints were major bleeding, major cardiovascular events, cardiovascular mortality, all-cause mortality, myocardial infarction, stent thrombosis, and stroke. Results: Our analysis included 11 RCTs, encompassing a total of 40,919 participants. When compared with unfractionated heparin, bivalirudin was associated with a significant reduction in major bleeding events (RR 0.66 [0.55 to 0.80]; p < 0.0001) and cardiovascular mortality (RR 0.79 [0.67 to 0.92]; p < 0.003). However, there were no significant differences between Bivalirudin and unfractionated heparin in terms of major adverse cardiovascular events (RR 1.02 [0.91 to 1.13]; p = 0.76), all-cause mortality (RR 0.89 [0.78 to 1.01]; p = 0.08), MI (RR 0.99 [0.85 to 1.15]; p = 0.90), stent thrombosis (RR 1.12 [0.53 to 2.40]; p = 0.76), or stroke (RR 0.96 [0.73 to 1.26]; p = 0.75). Conclusion: Our meta-analysis indicates that in patients with MI undergoing PCI, Bivalirudin is associated with lower rates of major bleeding and cardiovascular mortality compared to unfractionated heparin. However, there were no significant differences observed in major adverse cardiovascular events, all-cause mortality, MI, stroke, or stent thrombosis between the two treatment groups.

Background: Persistent atrial fibrillation (AF) presents a significant management challenge, particularly in patients with concurrent heart failure. The effectiveness of catheter ablation compared to medical therapy for these patients remains under debate. Aim: This meta-analysis aims to evaluate the outcomes of catheter ablation versus medical therapy for managing persistent AF. Research Question: How does catheter ablation compare to medical therapy in managing persistent AF considering outcomes like arrhythmia recurrence, hospitalizations, cardiac function, exercise capacity, and mortality? Methods: We performed a meta-analysis of randomized controlled trials (RCTs) comparing catheter ablation with medical therapy in patients with persistent AF. Data sources included PubMed, Embase, Cochrane Library, Clinicaltrial.gov, Google Scholar, and CINAHL/EBSCOHOST, with studies selected based on predefined inclusion criteria. Primary outcomes assessed were recurrence of atrial arrhythmias, hospitalizations, changes in left ventricular ejection fraction (LVEF), changes in 6-minute walk test (6MWT) distance, and all-cause mortality. The data extraction was done using a spreadsheet, and the data analysis was done using RevMan 5.4.1: for meta-analysis Results: A total of 10 RCTs involving 1812 patients were included in the analysis. Compared to medical therapy, catheter ablation significantly reduced the recurrence of atrial arrhythmias (risk ratio [RR] = 0.43, 95% confidence interval [CI]: 0.29-0.63, P < 0.0001). Hospitalization rates due to heart failure were also lower in the ablation group (RR = 0.57, 95% CI: 0.44-0.73, P < 0.001). Improvements in LVEF were observed with a mean difference (MD) of 5.98% (95% CI: 3.81% to 8.15%, P < 0.00001). The performance on the 6MWT was better in the catheter ablation group, with an MD of 28.83 meters (95% CI: 8.61 to 49.05 meters, P = 0.005). Additionally, catheter ablation was associated with a reduction in all-cause mortality (RR = 0.60, 95% CI: 0.45-0.80, P = 0.00006). Conclusion: This meta-analysis demonstrates that catheter ablation is superior to medical therapy in managing persistent atrial fibrillation. Catheter ablation offers significant benefits in reducing atrial arrhythmia recurrence, lowering hospitalization rates, improving cardiac function and exercise capacity, and reducing mortality. These findings support the consideration of catheter ablation as a preferred treatment strategy for patients with persistent AF.