Mean Difference Research Articles

Efficacy and safety of of SGLT2 ihibtors in post mi patients: a systematic review and meta-analysis of RCTs

Abstract Introduction Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have demonstrated a decrease in cardiovascular (CV) events, especially in diabetic patients. However, it remains unclear whether the early administration of SGLT2is confers cardioprotective benefits following acute myocardial infarction (AMI). Purpose Our objective is to explore the in-hospital and long-term prognoses of patients presenting with AMI who are treated with SGLT2is compared to non-SGLT2is users. Methods We conducted comprehensive searches across PubMed, CENTRAL, WOS, Scopus, and EMBASE until October 2023. Pooled data were reported using risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, along with a 95% confidence interval (CI). This systematic review and meta-analysis is registered with PROSPERO. Results We included 14 studies with a total of 37,038 patients. Compared to non-SGLT-2 inhibitors, SGLT-2 inhibitors were associated with a decreased incidence of major adverse cardiovascular events (MACE) (RR: 0.60 with 95% CI [0.45, 0.82], P< 0.01), all-cause mortality (RR: 0.67 with 95% CI [0.55, 0.81], P< 0.01), heart failure (RR: 0.68 with 95% CI [0.57, 0.80], P< 0.01), stroke (RR: 0.67 with 95% CI [0.45, 0.99], P= 0.04), increased left ventricular ejection fraction (MD: 2.45 with 95% CI [0.81, 4.09], P< 0.01), and decreased left ventricular end-systolic volume (MD: -5.72 with 95% CI [-10.76, -0.67], P= 0.03). Conclusion SGLT-2 inhibitors significantly decrease MACE, all-cause mortality, heart failure, left ventricular ejection fraction, and left ventricular end-systolic volume in myocardial infarction patients.Figure 1Figure 2

Safety and Efficacy of Moderate-intensity statin plus ezetimibe versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease: a meta-analysis

Abstract Background Atherosclerotic cardiovascular disease (ASCVD), affects approximately 18.6 million individuals worldwide, poses an important healthcare challenge. Despite the established efficacy of both high-intensity statin monotherapy (HIS) and moderate-intensity statin plus ezetimibe (MIS+EZT) in ASCVD management, the optimal treatment strategy remains unclear. Purpose This meta-analysis seeks to assess the impact of moderate-intensity statin plus ezetimibe (MIS+EZT) versus high-intensity statin monotherapy (HIS) on LDL < 70mg/dl; Total Cholesterol; LDL; High Density Cholesterol (HDL) and triglycerides levels. Our goal is to synthesize the existing evidence and pinpoint areas that warrant further investigation. Methods A thorough literature search was conducted across PubMed, Scopus, Web of Science, and the Cochrane databases, focusing on studies that compared the effects of moderate-intensity statins plus ezetimibe with high-intensity statin monotherapy in ASCVD patients. Results In the 13 included studies, involving 8,592 patients, of which 4,525 (52.67%) received moderate-intensity statin plus ezetimibe treatment. The follow-up period ranged from 12 to 219 weeks, with participant ages varying from 66 to 76.5 years in the MIS+EZT group and from 67 to 75.9 years in the HIS group. Analysis revealed significant MIS+EZT-associated with greater percentages in Low Density Lipoprotein (LDL) < 70 (Odds Ratio (OR) 1.76; 95% CI [1.26; 2.45]; p=0.001; I²=73%), LDL reduction (Mean Difference (MD) -5.05 mg/dL; 95% CI [-9.02;-1.07]; p<0.013; I²=56%;); Total Cholesterol reduction (MD -7.91 mg/ dL; 95% CI [-14.90; -0.91]; p<0.027; I²=60%); Triglycerides reduction (MD -8.20 mg/ dL; 95% CI [-13.05; -3.35]; p<0.001; I²=2%;); There was no statistical difference between groups in Drug Adverse reaction (Risk Ratio (RR) 1.19; 95% CI [0.79; 1.78]; p=0.404; I²=0%); and Drug intolerance (RR 0.78 ; 95% CI [0.32; 1.92]; p=0.584; I²=35%). Conclusions This meta-analysis underscores the effectiveness of MIS+EZT in enhancing significant clinical outcomes for ASCVD patients, as evidenced by improvements in a greater percentage of patients achieved the LDL <70 target, LDL, Total Cholesterol and Triglycerides levels . Importantly, there were no significant differences in the occurrence of overall adverse events and adverse drug reactions between the two groups.

Vericiguat in heart failure patients: analyzing safety, tolerability, and quality of life via meta-analysis of randomized controlled trials

Abstract Background Heart failure (HF) poses a significant burden on global healthcare systems, necessitating effective therapeutic interventions. Vericiguat, a novel agent targeting soluble guanylate cyclase, has emerged as a potential treatment for HF. Purpose To understand its impact on patient outcomes, including safety, tolerability, and quality of life (QoL). Methods A comprehensive meta-analysis was conducted, encompassing four randomized controlled trials (RCTs) identified through Cochrane CENTRAL, Ovid Medline R, Pubmed, and Web of Science databases up to December 1, 2023. The primary efficacy outcome, Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score (OSS), and the primary safety outcome, drug-related serious adverse events (AEs), were analyzed. Pooled mean differences (MD) and risk ratios (RR) were calculated using inverse variance common-effect model. Results The meta-analysis encompassed 5947 patients across the four RCTs. Our findings indicated that vericiguat did not demonstrate a significant beneficial effect on KCCQ-OSS (MD -0.13, 95% CI -1.32 to 1.05), suggesting no substantial impact on overall QoL, despite a statistically significant improvement in the KCCQ-Physical Limitation Score (PLS) (MD 3.74, 95% CI 0.24 to 7.24) compared to placebo. Notably, vericiguat exhibited a favorable safety and tolerability profile, with comparable risk for AEs leading to death (RR 1.32, 95%CI, 0.58 to 3.03), withdrawal due to AEs (RR 1.08, 95% CI 0.88 to 1.32) or serious AEs (RR 1,18, 95%CI, 0,50; 2,80), renal and urinary disorders (RR 0.99, 95% CI 0.88 to 1.11), symptomatic hypotension (RR 1.17, 95% CI 0.98 to 1.40), and acute kidney injury (RR 1.04, 95% CI 0.83 to 1.31) compared to placebo. Conclusion Vericiguat demonstrates promising safety and tolerability profiles in patients with HF. While our analysis reveals significant improvement in KCCQ-PLS, indicating enhanced physical limitation scores, the lack of statistically significant impact on overall QoL raises questions about its comprehensive efficacy. These findings underscore the need for further research to elucidate the holistic impact of vericiguat on patient-reported outcomes in heart failure management.Forest plot of quality of life outcomesForest plot of safety outcomes

Mini-open versus percutaneous surgical repair for acute Achilles tendon rupture: a systematic review and meta-analysis.

To compare the clinical outcomes and complications of mini-open (MOT) and percutaneous techniques (PT) in the surgical repair of acute Achilles tendon rupture (AATR). We systematically searched PubMed, Scopus, Web of Science, Clinical Trials, and the Cochrane Library for studies comparing MOT with PT for AATR. We assessed functional outcomes, complication rates, and operation time. Statistical analyses were performed using RevMan Web. Odds ratios (ORs) and mean difference (MD) with 95% confidence intervals (CIs) were pooled with a fixed-effects model for dichotomous and continuous endpoints, respectively. Heterogeneity was evaluated with I2 statistics. Eight studies, comprising 484 patients, were included, of whom 226 (46%) underwent MOT. MOT was associated with a significantly lower re-rupture rate (1.48% vs. 6.11%; OR 0.28; 95% CI 0.09-0.86; p = 0.03; I2 = 6%) and sural nerve injury rate (0.57% vs. 5.64%; OR 0.24; 95% CI 0.07-0.81; p = 0.02; I2 = 0%). No significant differences were observed in venous thrombosis (OR 0.81; 95% CI 0.17-3.94; p = 0.33; I2 = 0%), wound infection (OR 0.56; 95% CI 0.12-2.62; p = 0.46; I2 = 0%), or operation time (MD 1.83min; 95% CI -1.13-4.79; p = 0.23; I2 = 88%). Functional outcomes showed higher American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot scores in the MOT group (MD 1.52 points; 95% CI 0.62-2.42; p = 0.001; I2 = 3%), while (Achilles Tendon Total Rupture Score) ATRS, time to return to activities, and ankle plantar and dorsiflexion were comparable. MOT for AATR repair seems to reduce re-ruptures and sural nerve injuries while improving AOFAS scores, with no significant differences in other complications compared to PT. These findings suggest that the MOT may offer a safer and equally effective alternative to PT for AATR.

Efficacy of acetazolamide as adjunct therapy in improving fluid management in patients with acute congestive heart failure: a systematic review and meta-analysis of randomized controlled trials

Abstract Introduction Persistent congestion in acute congestive heart failure despite conventional treatments highlights the need for innovative therapeutic approaches. Evaluating acetazolamide as adjunctive therapy for reducing volume overload is significant. Our meta-analysis examines randomized clinical trials to assess acetazolamide's efficacy in improving fluid management in acute congestive heart failure. Methods We systematically searched Embase, PubMed, and the Cochrane Library in January 2024 for randomized controlled trials comparing the addition of acetazolamide to diuretic therapy versus standard diuretic therapy in patients with acute congestive heart failure. Article selection was conducted independently by two authors. Statistical analyses, including the weighted mean differences (MD) and assessment of heterogeneity using the I² statistic, were performed using R software version 5.4.1. Results Three studies comprising 596 patients were included. Of these, 297 (50%) received acetazolamide as adjunctive diuretic therapy, while 299 (50%) received standard diuretic therapy with a loop diuretic. Among participants, 385 (65%) were male, with a mean age of 72.76 years (±11.13). Acetazolamide adjunctive therapy led to an increase in natriuresis at day 2, expressed in milimoles (mmol), (MD 80.30; 95% CI [45.10-115.51]; p<0.00001; I2=29%), and a trend towards higher natriuresis volume, expressed in liters (L), at day 2 (MD 0.56; 95% CI [-0.37-1.48]; p=0.24; I2=87%), although the latter lacked statistical significance. Conclusions Our findings suggest that acetazolamide adjunctive therapy may have potential benefits in improving fluid management and possibly enhancing clinical outcomes in patients with acute congestive heart failure. Further research is warranted to validate these findings and explore the long-term effects of acetazolamide therapy.

DNA methylation in the TXNIP gene is associated with type 2 diabetes in Pacific Peoples living in NZ

Abstract Background Pacific Peoples living in Aotearoa New Zealand (NZ) have higher rates of type 2 diabetes (T2D) and have benefited less from improvements in cardiovascular health outcomes when compared with other populations in NZ. DNA methylation markers of T2D have been identified in non-Pacific populations and could be used to monitor the cumulative effects of T2D on cardiovascular disease risk. However, no study has yet investigated the relationships between T2D and DNA methylation in Pacific Peoples living in NZ. Purpose This study aimed to quantify the relationship between DNA methylation and T2D in two cohorts of Pacific Peoples living in NZ. Methods Whole-blood DNA methylation at over 850,000 loci was measured on Illumina MethylationEPIC arrays in 288 Pacific participants from the Pasifika Heart Study (PHS, n=191), a community cohort, and the Multi-Ethnic NZ Study of Acute Coronary Syndromes (MENZACS, n=97), a cohort of patients with acute coronary syndromes. In the PHS, the median age was 41 years, and 98 (51%) participants were female. In MENZACS, the median age was 53 years, and 18 (19%) participants were female. In both cohorts, T2D cases were defined by either previous diagnosis (n=58) or had an HbA1c measurement >58 mmol/mol (n=7). We compared 65 participants with T2D and 223 participants without T2D of Samoan (n=116), Tongan (n=66), Fijian (n=61), Cook Island Māori (n=22), Niuean (n=9), or of Other/Multiple Pacific (n=14) ethnicity in a meta epigenome-wide association study (EWAS). EWAS comparisons were adjusted for age, sex, and imputed blood cell composition. We compared the difference in means at differentially methylated loci between the European and Pacific MENZACS participants using a two-sample z statistic. For the 525 European participants, 85 had T2D, the median age was 57 years, and 149 (28%) were female. Results One locus cg19693031, in the thioredoxin interacting protein (TXNIP) gene, exhibited differential methylation between those with T2D and those without in the meta EWAS (false discovery rate =6.9x10-9). In the PHS we observed a mean reduction in cg19693031 methylation of 7.0% (95% CI, 5.0, 8.9) between those with T2D and those without. Similarly in the MENZACS Pacific participants we observed a mean reduction in cg19693031 methylation of 10.9% (95% CI, 7.6, 12.4) between those with T2D and those without. The MENZACS European participants with T2D had a mean reduction in cg19693031 methylation of 6.5% (95% CI, 5.3, 7.7, p<0.001) compared to those without T2D. The difference in means in T2D cases and controls between MENZACS Pacific and European participants was non-significant (p =0.08). Conclusion DNA methylation at cg19693031 is associated with T2D in Pacific Peoples living in NZ and may be a sensitive marker of T2D in Pacific Peoples with acute coronary syndromes. DNA methylation at this locus may provide valuable information on the relationship between T2D and cardiovascular disease.Miami plot of Pacific T2D EWAST2D methylation by population in MENZACS

AngioPy: an open-source, deep learning-driven tool for coronary artery segmentation

Abstract Background Quantitative coronary angiography (QCA) permits the objective assessment of coronary artery disease. However, traditional edge detection algorithms often struggle with accurate vessel segmentation due to the complexity and variable quality of angiographic images. As a result, manual correction is frequently needed, which is a major limitation of current QCA systems. Purpose We developed angioPy, a deep learning-driven tool for vessel segmentation that employs user-defined ground truth points to minimise manual correction. We compared its performance without correction with an established QCA system. Methods angioPy was developed using 2455 images from the Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2 (FAME 2) study. Deep learning models were constructed using the U-Net architecture with one of three popular backbones for image classification: ResNet101, DenseNet121, and InceptionResNet-v2. Critically, the model was constructed to integrate the user’s clinical expertise through the selection of a 5-10 ground-truth points along the length of the vessel of interest including the desired start and end point of vessel segmentation. These ground truth points were added to a separate channel of the input image. Five-fold cross validation was performed using proportions of 3:1:1 for training, validation, and test sets, respectively. External validation was performed on a separate dataset of 580 images not used for model development. For both datasets, ground truth segmentation masks were provided by interventional cardiologists using specialised in-house software. A separate analysis was performed in a cohort of 74 patients with mild/moderate stenoses that underwent vessel segmentation using both angioPy and an established commercial QCA package (Medis QFR®). Vessel dimensions at stenoses (proximal and distal reference, minimal luminal diameter) were extracted from both segmentation approaches and compared (609 diameters in total). Results The best performing model performed segmentation with an average F1 score of 0.927 (pixel accuracy 0.998, precision 0.925, sensitivity 0.930, specificity 0.999) with 99.2% of masks exhibiting an F1 score > 0.8 (Figure 1). Simliar results were achieved in the external validation set (F1 score 0.924, pixel accuracy 0.997, precision 0.921, sensitivity 0.929, specificity 0.999). Stenosis dimensions measured with angioPy (mean diameter 3.54 ±1.15 mm) exhibited excellent agreement with QCA (r=0.95 [95% CI 0.95-0.96], p<0.001; mean difference -0.18 mm [limits of agreement: -0.84 to 0.49]) (Figure 2). Minimal luminal diameter (mean 2.93 ±0.91 mm) also exhibited strong agreement (r=0.93 [95% CI 0.91-0.95], p<0.001; mean difference -0.06 mm [limits of agreement: -0.70 to 0.59]. Conclusion angioPy performs rapid and accurate coronary segmentation without the need for manual correction. Available as an open-source tool, angioPy has the potential to increase the efficiency and reliability of QCA.Figure 1.angioPy segmentationFigure 2.angioPy vs QCA (Medis)

Using Bland-Altman plot-based harmonization algorithm to optimize the harmonization for immunoassays.

Harmonization has been recommended by theInternational Organization for Standard (ISO) to achieve equivalent results across invitro diagnostic measurement devices (IVD-MDs). We aim to evaluate the effectiveness of Bland-Altman plot-based harmonization algorithm (BA-BHA) created in this study and compare it with weighted Deming regression-based harmonization algorithm (WD-BHA) proposed in ISO 21151:2020. Eighty patient sera were used as the harmonization reference material (HRM) to develop IVD-MD-specific harmonization algorithms. Another panel of 40 patient sera was used to validate the effectiveness of harmonization algorithms. We compared regression slopes, intercepts, Bland-Altman plot layouts, percent differences, limits of agreement (LoAs), between-method coefficients of variation (CV) before and after harmonization. After harmonization by WD-BHA, acceptable slopes and intercepts between measured values and HRM targets were observed in weighted Deming regression, but not in Passing-Bablok analysis. Mean differences were-5.5 to 5.0 % and differences at specific levels were-33.9 to 23.9 %. LoAs were-64.6 to 74.6 %. Between-method CV was 22.9 % (±12.9 %). However, after harmonization by BA-BHA, both weighted Deming and Passing-Bablok regressions equations presented harmonized results. Mean differences were-0.3 to 0.2 % and differences at specific levels were-1.1 to 1.6 %. LoAs were-23.3 to 23.2 %. Between-method CV was 8.4 % (±4.0 %). The data points were evenly distributed at both sides of the mean in Bland-Altman plots. The inequivalence of test results between different methods can be improved but unacceptable analytical differences at specific levels may be hidden in terms of an acceptable slope and intercept on WD-BHA. The new protocol BA-BHA may be a viable alternative to optimize the harmonization for immunoassays.

Combining Transcranial Direct Current Stimulation with Exercise to Improve Mobility, Stability, and Tremor Management in 25 Individuals with Parkinson’s Disease

Background/Objectives: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by tremors, balance impairments, and mobility limitations. Innovative approaches like combining transcranial direct current stimulation (tDCS) with exercise show promise in addressing these symptoms. This study investigates the effects of exercise combined with tDCS on mobility and tremor management in PD patients. Methods: Twenty-five individuals aged 60−75 (66.6 ± 7.33), diagnosed with PD (Hoehn and Yahr stage 2−3), were assigned to three groups in a randomized controlled design: exercise with active tDCS (n = 8), exercise with sham tDCS (n = 8), and a control group (n = 9). Dual-task training sessions focusing on walking speed, balance, and force control were conducted over ten sessions. Results: No significant differences were detected across the groups for grip strength or force control measures (p > 0.05). Significant improvements were observed in the intervention group: the Timed Up and Go (TUG) test showed a significant reduction in time (mean difference = 2.498 s, p < 0.001, ηp2 = 0.331); anterior–posterior displacement significantly increased (mean difference = 21.375 mm, p = 0.0269, ηp2 = 0.303); and force-tremor decoupling improved, with coherence in the 1−4 Hz band significantly decreasing (p = 0.0067). Finally, changes in TUG from post- to pre-treatment values were significantly positively correlated with the changes in coherence (R = 0.468, p = 0.018). Conclusions: Combining tDCS with exercise enhances mobility and tremor management in PD patients. These findings support the potential for such interventions to improve functional outcomes and quality of life for individuals with PD.

Core laboratory versus center-reported echocardiographic assessment of the native and bioprosthetic aortic valve

Abstract Background The use of a central echocardiographic core laboratory (ECL) is advised to minimize measurement variation and heterogeneity in clinical trials. Insights into quantitative differences between ECL and center-reported echocardiographic assessment of the native and bioprosthetic aortic valve are lacking. We aimed to explore clinically relevant differences between these evaluations. Methods Data were used from the PERIcardial SurGical AOrtic Valve ReplacemeNt (PERIGON) Pivotal Trial for the Avalus valve. In this trial, patients with an indication for surgical aortic valve replacement (SAVR) due to aortic stenosis or regurgitation (AR) were enrolled. Serial echocardiographic examinations were performed at each center and reanalyzed by an independent ECL. For the bioprosthetic valve analysis, postoperative data throughout 5-year follow-up were pooled. Differences between the ECL and the centers in continuous parameters were quantified in mean differences and intraclass correlation coefficients (ICCs). Between-center differences were illustrated by plotting standardized mean differences (SMDs) between centers and the ECL for the 10 sites that implanted the most prostheses. Agreement on AR, paravalvular leak (PVL), and prosthesis-patient mismatch (PPM) classification was investigated using Cohen’s kappa coefficients. Results The analysis on the native aortic valve was performed on 1118 patients. The relative mean difference was largest for the left ventricular outflow tract (LVOT) area, followed by stroke volume and effective orifice area (index), with center-reported values being 11-7% higher (Table 1). High ICCs of around 0.90 were observed for peak aortic jet velocity, mean pressure gradient, and the velocity-time integral across the aortic valve. More than 5000 echocardiograms were available for the bioprosthetic valve analysis. Therein, comparable results were observed. In Figure 1, differences in assessment on center level are illustrated. The SMDs for peak velocity were between 0 and 0.5 for all centers, while there was more heterogeneity between centers for other parameters. The kappa coefficient was 0.59 (95% confidence interval [CI] 0.56, 0.63) for agreement on native AR, 0.28 (95% CI 0.18, 0.37) for PVL, and 0.42 (95% CI 0.40, 0.44) for PPM. Conclusions For echocardiographic assessment of the native and bioprosthetic aortic valve, agreement between the ECL and the clinical centers varies by parameter and by center. There is high agreement on continuous-wave Doppler-related measurements. On the contrary, agreement is low for parameters that involve measurement of the LVOT diameter. These results provide important context for the interpretation of aortic valve performance in studies that lack central ECL evaluation.

Impact and determinants of depression in cardiac hospitalized patients

Abstract Depression increases cardiovascular risk and involves worse clinical outcomes. Little attention is paid to it in hospitalized patients. We studied prevalence and determinants of depression in this group, in order to select patients for further specific management. Methods Consecutive patients admitted to Cardiology wards were included. Cardiovascular risk factors, clinical and psychosocial data were collected. Self perceived mental and physical health quality were assesed by 12-item Short Form survey (SF-12), and Hospital Anxiety and Depression Scale (HADS) questionnaires were administered. Statistical analysis was performed using Spearman´s correlation, Mann-Whitney and Fisher tests, and Mantel-Cox, linear and logistic regression analyses. Results 170 consecutive patients, median age 74.5 (67.2-81.1), 59.4% male, were included. Most common pathologies were heart failure (44.7%) and coronary syndroms (28.8%). According to HADS results, depression was probable (score >10) in 10%, and at least possible (score > 8) in 27.1%. Both increased duration of hospitalization (Median 14 vs 7 days;p=0.016 and 11 vs 7 days;p=0.005 respectively). Anxiety was present in 16.5 % for probable case and 34.1% for possible case, with no significant change in median duration of hospitalization. 22.9% of patients were under antidepressant treatment, and 24% under anxiolytics, but they were added to treatment only in 1% and 7% respectively. No other not pharmacological measure was initiated. Self perceived mental health was diminished in probable depression (mean difference 14.9%;95%IC 9.7-20.2;p<0.001). Self perceived physical health was also lower (mean difference 6.4%;95%CI:1.1-11.8;p=0.016). Patients with depression were a mean of 5.6 years older (95%CI 1.4-9.8;p=0.032). Less than primary education (OR 5.69 (p 0.021), and Previous hospital admission OR 3.2 (1.0-10.3;p=0.034) increased the risk of depression in univariate analysis. By multivariate analysis, determinants of depression were anxiety (OR 22.5;95%CI 5.9-85.6;p<0.0001), need for surgery (OR 12.3;95%IC 2.1-73.2;p=0.009), need for intensive care unit surveillance (OR 4.2;95%CI 1.1-15.8;p=0.039), and age (OR 1.1;95%IC 1.0-1.2;p=0.001. AUC was 0.89;95%CI 0.81-0.96;p<0.0001. There was no difference in civil status, gender, income level, living accompanied, number of comorbidities, cardiovascular risk factor or reason for hospital admission. Conclusions Depression was prevalent in our hospitalized cardiac patients,in spite of previous pharmacological treatment. It prolongs duration of stay and impacts negatively in self perceived mental and physical health. Risk is increased in older people requiring intensive care surveillance or surgery, and specially by anxiety. These patients could benefit from a preventive multifactorial approach. Attention should also be paid to patients with a previous hospitalization and low educational level.ROC curve for multivariate model

Comparison of vessel-Fractional Flow Reserve (vFFR) and Quantitative Flow Ratio (QFR) using instantaneous wave-Free Ratio (iFR) or Resting Full-cycle Ratio (RFR) as reference

Abstract Background Angiography-based functional assessment remains the state of the art to assess the hemodynamic relevance of intermediate coronary stenoses. In addition to fractional flow reserve (FFR), adenosin free indices like instantaneous wave-free ratio (iFR) or resting full-cycle ratio (RFR) are widely used for the invasive evaluation. Although these methods are widely accepted, they are underused in clinical routine due to costs, their invasive nature, longer procedural times, and lack of availability. Vessel-fractional flow reserve (vFFR) and quantitative flow ratio (QFR) are new software-based methods for the evaluation of coronary-physiology. The aim of this study is to compare vFFR and QFR with the established invasive methods iFR or RFR. Methods We prospectively analyzed 95 Patients in our QFR-Registry vFFR- and QFR-computation was performed three-times by two certified, blinded, and independent experts using the QAngio XA 3D 3.2- and CAAS-software, respectively. Results: 101 main epicardial coronary arteries (52 LAD; 19 LCx; 30 RCA) were analyzed using vFFR, QFR and iFR or RFR. vFFR showed a good correlation with adenosine-free indices in all 3 measurements (AUC 0.883 with r=0.672, p<0.001; AUC 0.841 with r=0.618 p<0.001; AUC 0.840 with r=0.592, p<0.001 respectively). The diagnostic accuracy between the three vFFR-measurements and iFR/RFR was 83%; 81% and 79% respectively. QFR-computations showed a similar correlation with iFR/RFR (AUC 0.899 with r=0.720, p<0.001; AUC 0.919 with r=0.649, p<0.001; AUC 0.930 with r=0.703, p<0.001 respectively) with a diagnostic accuracy 88%, 89% and 88% respectively. The intra- and inter-observer reliability for vFFR (intra: mean difference 0.002±0.0568; inter: 0.024±0.054) and QFR (intra: mean difference 0.018±0.071; inter: 0.016±0.075) analyzed in a Bland-Altman Blot showed a good correlation between virtual assessments and invasive measurements with iFR/RFR. Conclusion The data show a good diagnostic agreement between vFFR and QFR and adenosine free invasive assessments. vFFR and QFR appear reasonable alternative approaches for the evaluation of intermediate stenoses. These data provide the rational to prospectively test for a clinical noninferiority of the non-invasive flow measurements.Diagnostic performance of vFFR/cQFR

Empagliflozin: unlocking new potentials in heart failure decongestion

Abstract Background Managing acute heart failure (AHF) remains a formidable challenge in cardiology, primarily due to the limitations of conventional decongestive therapies. This study explores the efficacy of Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, in decongestion management for AHF. Methods Conducted in a tertiary care setting, this prospective cohort study involved 450 patients, divided equally into an Empagliflozin group and a control group receiving standard care. The study assessed changes in body weight, clinical congestion scores, hematocrit levels, and NT-proBNP levels as primary outcomes over a period of 90 days. Safety and adverse events related to Empagliflozin were also monitored. Results Empagliflozin led to a significant reduction in body weight (mean difference at Day 15: −1.95 kg, P<0.0001), and clinical congestion scores (mean difference at Day 15: −0.35, P=0.0050). Hematocrit levels increased significantly (mean increase at Day 15: 1.65%, P<0.0001), and NT-proBNP levels showed a more substantial decrease in the Empagliflozin group compared to the placebo. Safety profiles were consistent with previous studies, showing no significant increase in adverse events. Conclusion Empagliflozin demonstrates a substantial improvement in decongestion management in AHF patients, offering a promising alternative to traditional therapies. The findings indicate potential broader applications in heart failure management and support the need for updated clinical guidelines incorporating Empagliflozin as a therapeutic option in AHF.

The effects of a dyadic empowerment-based heart failure management (De-HF) programme on self-care and HRQL : a randomized controlled trial

Abstract Background The ever-growing epidemiology of heart failure (HF) and its detrimental impacts on patients’ quality of life and healthcare cost urge for effective interventions to ameliorate the modifiable prognostic factors. As substantial evidence suggests ineffective self-care as an important candidate especially for the post-discharge outcomes, various care approaches are developed to optimize this behavioral outcome. However, even family carers are heavily involved in the self-care process, dyadic approach to improve the health outcomes of both interactive partners are least applied in the HF transitional care model. Purpose To evaluate the effects of a dyadic empowerment-based heart failure management program (De-HF) on dyadic health and hospital service utilization outcomes. Methods This double-blind RCT randomized 88 HF patient-carer dyads to receive the De-HF program or a dialectic education program, after hospital discharge. Based on the Theory of Dyadic Illness Management, the 16-week De-HF Program, comprising i) a dyadic assessment, ii) five online empowerment modules and iii) follow-up telecare, integrated explicit strategies (scenario-based training, teach-back and goal-setting) to actively engage the care dyads in collaborative disease management. Figure 1 is the graphical presentation of the De-HF Program. The primary outcome is health-related quality of life (HRQL) of the care dyads. Secondary outcomes include patients’ self-care as well as shared care and perceived control of the dyad. Results The mean age of the HF patients was 76.8 (9.4). The patients were in moderate disease severity [NYHA II/II: 56/44%; mean LVEF = 42.5%]. Figure 2 shows the consort flow diagram. After adjusting the socio-demographic characteristic, two-way analysis of covariance showed that patients in the De-HF program showed significantly greater improvement in patients’ self-care domains [Mean difference in change of score (95% CI): Self-care maintenance = 7.15 (1.82-12.46),Cohen’s d = 0.26, p=0.009; Self-care management = 10.04(3.29-16.79), Cohen’s d=0.65, p=0.004; symptom perception = 15.59 (8.20-22.98), Cohen’s d=0.928, p<0.001] and Minnesota Living with Heart Failure score [Mean different in the change of score (95% CI) = -11.45 (-18.24 - -4.66). Cohen’s d = -0.742, p=0.001]. The patient-carer dyads also have significantly greater improvement in perceived control (p=0.001) and collaborative disease management in terms of joint decision-making (p=0.001) and sense of reciprocity (p=0.026). Conclusion Dyadic science has evolved in self-care research for HF. This trial provides the first evidence to inform the positive effects of a theory-based dyadic transitional care program in improving the collaborative self-care management in a family context and patient health outcome. Longer-term evaluation on the effects of De-HF program on health service utilization outcomes and cost-effectiveness will be followed.The De-HF Managment ProgramThe Consort Flow Diagram

The upfront lipid-lowering combination therapy of statins and ezetimibe vs statin monotherapy in the reduction of cardiovascular outcomes. A meta-analysis.

Abstract Background Despite some data in last few years, there is still some inconsistency concerning the effectiveness and safety of the upfront intensive lipid lowering combination therapy (LLT; of moderate to high intensity statin therapy and ezetimibe) in comparison to high intensity statin therapy and recommended by some guidelines stepwise therapy approach. Purpose We sought to evaluate the efficacy of combination LLT compared with statin monotherapy for cardiovascular outcomes, LDL-C reduction, and associated adverse events. Methods A systematic literature search was conducted using PubMed, Embase, and ClinicalTrial.gov to identify relevant articles published from inception until 29th December 2023. The outcomes were assessed using pooled odds ratio (OR) for categorical data and mean difference (MD) for continuous data, with corresponding 95% confidence intervals (95% CI). Results A total of 11 studies (8 randomized controlled trials and 3 cohort studies) with 106,358 were involved in the analysis. The mean age of the patients in the combination LLT and statin monotherapy group was 65.3 and 65.7 years, respectively. Pooled analysis shows that combination LLT significantly reduces the LDL-C level from the baseline (MD, -12.13 mg/dl [0.31 mmol/l] (95%CI: -18.26 to -5.99 mg/dl), p<0.001), all-cause mortality (ACM) (OR, 0.75, 95%CI: 0.62 to 0.92, p=0.01), cardiovascular mortality (CVM) (OR 0.75, 95%CI: 0.66 to 0.84, p<0.001), major adverse cardiovascular events (MACE) (OR, 0.72 95%CI: 0.63 to 0.82, p<0.001), non-significant reduction in the incidence of stroke (OR 0.82, 95%CI: 0.66 to 1.01, p=0.06) when compared with statin monotherapy alone. Similarly, the therapy discontinuation rate was comparable between combination LLT and statin monotherapy groups (OR, 0.87 (95%CI: 0.53 to 1.40), p=0.56). The risk of adverse events related to the gastrointestinal tract (OR, 1.12 (95%CI: 0.93 to 1.36), p=0.23) and musculoskeletal system (OR, 0.88 (95%CI: 0.52 to 1.50), p=0.65) was comparable between both the groups of patients. Conclusion Combination LLT was associated with an overall greater reduction in LDL-C, a lower risk of ACM, MACE, and CVM compared to statin monotherapy alone.Forest Plot of desired outcomes.Central illustration with key findings.

Posterior wall isolation for persistent atrial fibrillation catheter ablation: an updated systematic review and meta-analysis

Abstract Background The ability of catheter ablation (CA) to prevent arrhythmic recurrences in patients with persistent atrial fibrillation (PeAF) remains suboptimal. In this context, the results of studies conducted with both thermal and non-thermal technologies, that evaluated the effect of adding electrical isolation of the posterior wall of the left atrium (PWI) to isolation of the pulmonary veins alone (PVI) have provided conflicting data. Purpose To compare the efficacy and safety of an ablative strategy with the addition of PWI to PVI versus PVI alone in patients with PeAF undergoing a first ablation procedure. Methods We searched electronic databases for observational studies and randomized controlled trials (RCTs) comparing PVI+PWI versus PVI alone as first CA procedure for PeAF, regardless of the technologies used. The efficacy outcomes were recurrence of any atrial tachyarrhythmias lasting more than 30 seconds, recurrence of atrial fibrillation (AF) and atrial flutter/atrial tachycardia (AFlu/AT). The safety outcome was relevant procedural complications defined as a composite of vascular complications, pericardial effusion or tamponade, phrenic nerve palsy, stroke, atrio-esophageal fistula, and death. The procedural time was compared between the ablation strategies studied. The software RevMan 5.4 was used to estimate the risk ratio (RR) and mean difference (MD) with the relative confidence intervals (CI), using a random-effect model. Results Thirteen studies (8 RCTs and 5 observational studies) counting a total of 2994 PeAF patients (1304 treated with PVI+PWI and 1690 with PVI alone; 1847 RF, 600 cryo and 547 PFA) were included in the analysis. Mean age was 65.2±4.1 years, and 26% were female. Mean follow-up period was 14.5±4.8 years. There were no significant differences in the risk of recurrence of any atrial tachyarrhythmias (RR 0.88; 95% CI 0.68-1.14) between the ablation strategies studied. Patients treated with PWI+PVI experienced a reduced risk of recurrence of AF (RR 0.67; 95% CI 0.48-0.94; p = 0.02) balanced by a trend towards increased risk of AFlu/AT (RR 1.74; 95% CI 0.99-3.06; p = 0.06) as compared with PVI alone strategy. No statistically significant differences in the risk of relevant procedural complication were identified between the studied groups (RR 0.94; 95% CI 0.50-1.78 – Fig. 2A). Procedural time was longer in the PWI+PVI group as compared with PVI alone (MD 30.63 min; 95% CI 8.60-52.65 min; p=0.006 – Fig. 2B). Conclusions Our metanalysis shows that, in patients with PeAF treated for the first time with CA, PWI+PVI versus PVI alone was not associated with a reduction of atrial tachyarrhythmias recurrence and required longer procedural times. Nonetheless, a reduction in the risk of AF recurrence and a trend towards an increased risk of AFlu/AT were identified. No differences in the risk of relevant procedural complications were found between the ablation strategies studied.Figure 2

Intermittent levosimendan infusions for advanced heart failure: a systematic review and meta-analysis of randomized controlled trials

Abstract Background Intermittent intravenous infusions of levosimendan have been shown to provide benefits in patients with advanced heart failure (AHF), preventing HF rehospitalization and mortality. Purpose We aim to investigate the efficacy of intermittent intravenous levosimendan infusion in patients with AHF. Methods A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and WOS until September 2023. We used the random-effects model to report dichotomous outcomes using risk ratio (RR) and continuous outcomes using mean difference (MD), with a 95% confidence interval (CI). Finally, we implemented a trial sequential analysis (TSA) to improve the reliability of our results. Results We included 15 RCTs with 1,181 patients. Intermittent levosimendan was significantly associated with an improved left ventricular ejection fraction (LVEF) compared to placebo (MD: 6,39, 95% CI [3.04, 9.73], P= 0.002; I2=75, P=0.0005), with cumulative Z-score of change after ≤ 1 week passing the monitoring boundaries favors the levosimendan but did not cross the required information size. Additionally, there was a significant improvement in the all-cause mortality rate favoring levosimendan (RR: 0.60, 95% CI [0.40, 0.90], P= 0.01; I2=9, P=0.36). However, There was no difference between intermittent levosimendan and placebo in all-cause rehospitalization rate (RR: 0.75, 95% CI [0.46, 1.22], P= 0.25; I2=70, P=0.04) or event-free survival rate (RR: 0.97, 95% CI [0.72, 1.30], P= 0.84; I2=63, P=0.03). Conclusion In patients with AHF, intermittent levosimendan significantly improved LVEF and all-cause mortality rate. However, there was no effect on rehospitalization or event-free survival.Figure 1.LVEF and TSAFigure 2.Mortality, Rehospital, Surviva

Cardioprotective role of statins in breast cancer patients treated with anthracyclines and/or trastuzumab: a systematic review and meta-analysis

Abstract Background Statins may have cardioprotective effects in patients undergoing cardiotoxic chemotherapy regimens. Yet, their role in mitigating anthracycline and/or trastuzumab-induced cardiotoxicity in patients with breast cancer remains unclear. Purpose To perform a systematic review and meta-analysis to evaluate the efficacy of statins in mitigating anthracycline and/or trastuzumab-induced cardiotoxicity among patients with breast cancer. Methods We systematically searched PubMed, Embase, and Cochrane databases until January 2024 for studies comparing the efficacy of statin therapy versus no statin therapy in breast cancer patients receiving either anthracyclines, trastuzumab, or both. Cardiotoxicity was defined as per the definition of each individual study. A random-effects model was used to assess pooled risk ratios (RR) and mean differences (MD) with corresponding 95% confidence intervals. Statistical analyses were performed using Review Manager version 5.4.1. Results We included five studies, of which two were randomised trials. The pooled population comprised 1,839 anthracyclines and/or trastuzumab-treated patients with breast cancer, of whom 864 (47%) received statin therapy. In the pooled analyses, cardiotoxicity was significantly lower in the statin therapy group as compared with the no statin therapy group (RR 0.45; 95% CI 0.27 to 0.72; p=0.001; Figure 1A), additionally statin therapy was associated with a significantly lower reduction in left ventricular ejection fraction as compared with no statin therapy (MD 4.11%; 95% CI 2.68 to 5.53; p<0.00001; Figure 1B). Conclusion In this meta-analysis, statin therapy in anthracyclines and/or trastuzumab-treated patients with breast cancer was associated with lower cardiotoxicity and decline in left ventricular ejection fraction.

Provisional stenting : drug-coated versus uncoated balloon for side branch in coronary bifurcation lesions: randomized study

Abstract Introduction The rePOT technique is a novel and easily applied approach for coronary bifurcations. Drug-Coated Balloon (DCB) angioplasty is increasingly being utilized in management of small vessels and coronary bifurcation lesions. Herein, we propose a new approach for treating coronary bifurcation lesions with the application of DCB to treat the side-branch in addition to the rePOT technique: the POT-sideDCB-POT technique. Materiel and Method: We described for the first time the POT-sideDCB-POT method for true bifurcation lesions (including the side-branch ostium), which is in line with the recommended management algorithm of the European Bifurcation Club8 consisting of a sequential approach to bifurcation stenting using the provisional strategy. The POT-sideDCB-POT is easy to perform and respects the geometry of all the three bifurcation segments. Results Overall, 100 patients with CBLs treated with provisional stenting using DES were included from our studie,50 with DCB side branche and 50 with UCB With a follow-up duration of 12 months, SB protection with DCB was associated with a lower degree of postoperative diameter stenosis (mean difference (MD): −10.35%, 95% confidence interval (CI): −13.17 to−8.53, p < 0.001; I2 = 0%) and less late lumen loss (MD: −0.18 mm, 95% CI:−0.28 to−0.10, p < 0.001; I2 = 69%) of SB compared to those with UCB. Moreover, SB protection with DCB was associated with reduced risks of target lesion revascularization (risk ratio [RR]: 0.45, 95% CI: 0.27 to 0.88, p = 0.02; I2 = 0%) and major adverse cardiovascular events (RR: 0.42, 95% CI: 0.27 to 0.66, p < 0.01; I2 = 0%). Subgroup analysis according to the study design showed similar results. Conclusions For patients with CBL treated with provisional stenting using DES, SB protection with DCB was associated with better angiographic and clinical outcomes than those with UCB.

Recent cardiac rehabilitation and its impact on cardiopulmonary exercise test variables in Brazilian cardiac transplant recipients

Abstract Introduction Heart transplantation (HTx) is an option for restoring the functional capacity of individuals with end-stage heart failure (HF). Cardiac rehabilitation (CR) plays an important role in improving variables related to cardiopulmonary exercise testing (CPET) in post-HTx patients. Purpose To evaluate whether CR is effective in improving CPET variables in Brazilian patients post-recent HTx compared to a Control Group (CG). Methods Retrospective comparative study composed of two groups: CR group (CRG) and CG. These recent HTx patients (aged 14 to 73 years) initiated CR within 150 days and were recruited from an HTx outpatient clinic at a south Brazilian public university hospital between 2014 and 2023. CPET was performed at three different times: pre-HTx (Time 01), post-recent HTx (Time 02), and post-CR or post-follow-up for CG (Time 03). This study was approved by the Institutional Review Board (protocol No. 20180651). Statistical analysis used Generalized Estimating Equations with alpha ≤ 0.05, and the mean difference (MD) data were presented along with 95% confidence interval (CI). Results CRG (n=18) had a mean age of 47.3±15.6 years and CG (n=11) 48.6±12.5 years (P=0.81). The mean time to start CRG was 62.2±9.6 days (minimum: 21; maximum: 147). There was an interaction for the Group*Time factor for the following CPET variables: VO2peak (P=0.039); VEmax (P=0.009); VO2 on second ventilatory threshold (P<0.001); HR on VT2 (P=0.030) and T½ (P=0.002). The main results are summarized in Table 1. We highlight that there was a difference in the comparison between groups at Time 03 for the variable VO2peak: MD: 5.16 ± 1.95 (95% CI: 1.3 to 9.0; P = 0.008), favorable to CRG. Conclusion Early CR after very recent HTx significantly increase peak VO2peak, VEmax, T½ and VO2 and HR at the VT2 compared to the control group (CG).