Sharma, Anubhuti

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/Objectives: The peak oxygen consumption (VO2) during cardiopulmonary exercise testing (CPET) is a strong predictor of all-cause mortality. The cardiac output, a key determinant of VO2, can be assessed using resting echocardiographic parameters. The heart rate recovery and ventilatory efficiency (VE/VCO2 slope) from CPET offer additional insights into cardiovascular fitness. Methods: This study aimed to identify resting echocardiographic parameters that predict the percentage of predicted peak VO2, heart rate recovery, and VE/VCO2 slope in a general cardiology population. This retrospective analysis included 1909 patients who underwent echocardiography within 3 months of CPET from 2017 to 2022. Patients with potentially confounding co-morbid conditions were removed. Spearman correlations were used to compare 19 echocardiographic parameters to peak VO2, heart rate recovery, and the VE/VCO2 slope, followed by multiple linear regression of peak VO2. Results: Eleven echocardiographic parameters correlated with peak VO2, with the strongest correlations seen with the left ventricular stroke volume index (R = 0.284, p < 0.001), mitral valve medial annular a’ wave velocity (R = 0.142, p < 0.0001), and mitral E-to-e’ ratio (R = −0.117, p < 0.0001). The left ventricular diastolic parameters and mitral E/A ratio correlated strongly with the heart rate recovery and VE/VCO2 slope. The multiple linear regression analysis identified the left ventricular mass index, stroke volume index, mitral valve E wave velocity, tricuspid valve regurgitation peak systolic velocity, tricuspid lateral annular systolic velocity S’, and left atrial volume index as independent predictors of peak VO2 (R2 = 0.191). Conclusions: The left ventricular stroke volume, diastolic function, and RV systolic function markers are significant predictors of cardiopulmonary fitness, aiding clinical decision-making in patients without CPET data.

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: Cardiopulmonary Exercise Testing (CPET) analyzes physiologic information with gas exchange during exercise. Peak oxygen volume consumption (absolute peak VO2 and percent predicted peak VO2), minute ventilation divided by carbon dioxide volume (VE/VCO2 slope) and heart rate reduction after 1 minute of recovery (heart rate recovery, HRR) all have well-established prognostic cardiovascular implications. Aim: Given the wider use of echocardiography, we aimed to see if important CPET data could be determined from resting transthoracic echocardiography (TTE). Methods: In this retrospective study, cardiology patients above 18 years who underwent both resting TTE and a max-effort CPET within 3 months of each other (2017-2022) were included. Patients with a history of coronary artery bypass grafting, valve surgery, pacemakers, congenital heart disease, severe valve dysfunction and pulmonary hypertension were excluded before analysis. Univariate analysis with Spearman correlations was used to assess the relationship between 4 CPET measurements {absolute peak VO2 per kg, percent predicted peak VO2/kg (adjusted for age, sex and body surface area), HRR, and VE/VCO2}; and 22 quantitative TTE parameters. Bonferroni correction was applied within each set of correlations, with significance set at p-values <0.025. Multivariate linear regression models were built for all the related TTE measurements to assess relationship with the 4 CPET parameters, adjusting for age and sex. Results: Table 1 shows, out of 1909 patients analyzed, our regression model is strongest for absolute peak VO2/kg (R-squared=0.57), with 3 significantly associated TTE parameters. For percent-predicted peak VO2 per kg, 4 TTE variables were significantly associated. For heart rate recovery, only LV stroke-volume index was correlated. No TTE parameters were associated with VE/VCO2. Conclusion: Notably, echocardiographic stroke volume and tricuspid valve regurgitation peak velocity exhibited a strong correlation with absolute peak VO2/kg and percent predicted peak VO2/kg. LV stroke volume index was correlated with heart rate recovery. VE/VCO2 was not associated with any resting echocardiographic parameters, suggesting this parameter is truly exercise-dependent.

Introduction: Metabolic equivalents (METs), a measure of energy use during a specified exercise intensity, and volume of oxygen consumed (VO2) are key measurements in cardiopulmonary exercise tests (CPETs). METs are traditionally converted to VO2 via multiplying METs by 3.5 ml/kg/min when VO2 data is not available, due to the fact that the latter requires more-expensive, accurate measurements of volume of inspired and expired oxygen and CO2. However, it is unclear which populations have significant variation between peak METs and peak VO2. Research Question: In a general cardiology population, do older women have a weaker relationship between peak METs and peak VO2? Methods: We present a retrospective study analyzing the relationship of peak METs and peak VO2 achieved on a CPET. Patients presenting to the cardiology clinic who received a CPET from 2017-2022 were included. Patients with severe valvular dysfunction, congenital heart disease, prior coronary artery bypass grafting, or ejection fraction < 50% were removed to limit confounding. A Spearman correlation coefficient was calculated for the whole sample comparing peak METs and peak VO2. Subsequently, a subgroup of women age 65 or greater were compared to the general sample by a fisher’s z transformation. Results: 1907 patients were included. There was a strong positive correlation between peak VO2 and peak METs in the whole sample (r(1860) = 0.914), p<0,001), shown in Figure 1. Women age 65 or greater had a weaker correlation (r(190)=0.808, p<0.0001) compared to the those who were not (r(1668) = 0.915, p<0.0001; z = -5.656, p<0.001), shown in Figure 2. Conclusions: Peak METs and peak VO2 have an extremely strong positive correlation in a general cardiology population. However, these relationships weaken for women age 65 or greater. METs are an accurate, cost-effective proxy measurement of VO2 in a general population, however may lack reliability for certain demographics.

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.