Mean Difference Research Articles

Intracoronary nicardipine to induce hypaeremia

Abstract Background Several pharmacological agents and routes of administration have been used to induce transient maximal hyperaemia, but most suffer from shortcomings that limit their clinical usage. Nicardipine, a dihydropyridine calcium channel blocker, has been proposed as a coronary hyperaemic agent with the advantage of not causing any adverse effects. Purpose We compared intracoronary (IC) nicardipine with IC papaverine for obtaining fractional flow reserve (FFR) and pullback pressure gradient (PPG). Methods and results This is a prospective, single-center study enrolling stable patients presenting with intermediate coronary artery disease (CAD) undergoing invasive functional assessment. The lowest FFR, duration of the hyperemic plateau, and PPG were assessed after IC nicardipine (400 µg to the left coronary or 300 µg to the right coronary artery) and IC papaverine (12 mg to the left coronary artery and 8 mg to the right coronary artery). Results Overall, 107 patients with 108 vessels (216 FFR and 216 PPG paired measurements) were analyzed. The correlation in FFR between nicardipine and papaverine was r = 0.95 (95% CI 0.92 to 0.96, p < 0.001) with a mean difference of 0.02 FFR units (limit of the agreement [LOA]: -0.04 to 0.08). Similarly, the correlation in PPG between nicardipine and papaverine was r = 0.86 (95% CI 0.71 to 0.93, p < 0.001) with a mean difference of 0.01 PPG units (limit of the agreement [LOA]: -0.14 to 0.17). The hyperaemic plateau was significantly longer with nicardipine (101.4 ± 62.1 s nicardipine vs 41.5 ± 14.3 s papaverine, p < 0.001). No significant differences were observed in the magnitude of changes in blood pressure and heart rate (p=NS). No complications occurred with the administration of IC nicardipine or papaverine. Conclusion FFR and PPG values obtained following nicardipine administration exhibited excellent agreement with those obtained using papaverine. Moreover, the hyperaemic response induced by nicardipine led to a significantly prolonged steady state in comparison to papaverine. Given its widespread availability, cost-effectiveness, safety profile and frequent utilization in clinical settings, nicardipine emerges as the optimal vasodilator for coronary physiology testing.FFR by Nicardipine vs PapaverinePPG by Nicardipine vs Papaverine

Echocardiographic evaluation of right ventricle to pulmonary artery coupling in patients undergoing transcatheter aortic valve implantation: a systematic review and meta-analysis

Abstract Background Right Ventricle to Pulmonary Artery (RV/PA) uncoupling, which depicts the inability of RV contractility to match the increasing RV afterload, has recently gained recognition as a simple echocardiography parameter to aid prognosis judgment in patients with RV dysfunction. In Aortic Stenosis (AS) patients, the extent of RV dysfunction and Pulmonary Hypertension (PH) has been linked with poor outcomes, but the prognostic value of RV/PA uncoupling in AS patients undergoing TAVI has not been well-defined. Purpose To investigate the prognostic value of RV/PA uncoupling and its association with echocardiographic parameters in AS patients undergoing TAVI. Methods We conducted a systematic search through Pubmed and Embase to include studies up to February 2024. Studies were eligible if they evaluated the prognostic performance of RV/PA uncoupling in AS patients undergoing TAVI. Random-effects model were employed to pool the adjusted Hazard Ratio (aHR) with inverse-variance weighting method or Relative Risk (RR) with 95% Confidence Interval (95% CI) using Mantel-Haenszel test for categorical outcomes or Weighted Mean Difference (WMD) for numerical outcomes. Risk of bias assessment was conducted using the Newcastle Ottawa Scale (NOS). Results Thirteen studies were included. Out of 4,146 patients, 55.21% were reported to have RV-PA uncoupling prior to TAVI. RV/PA uncoupling was customarily assessed with TAPSE/PASP ratio, with threshold for uncoupling ranging between <0.31–<0.63 mm/mmHg. Follow-up period ranged between 6–65 months. Patients with baseline RV/PA uncoupling had lower LVEF (WMD -9.94% [-4.36– -15.53%]; I2 = 78%), lower TAPSE (WMD -4.98 mm [95% CI -1.15– -8.80]; I2 = 95%), and higher PASP (WMD 19.77 [95% CI 17.02–22.51]; I2 = 0%) compared to patients with RV/PA coupling at baseline. Baseline RV-PA uncoupling was an independent predictor of all-cause mortality (pooled aHR = 2.26 (95% CI 1.36–3.76); I2 = 77%) and composite endpoint of mortality and adverse cardiac or cerebrovascular events (pooled aHR = 2.07 (1.30–3.29); I2 = 24%). However, RV/PA uncoupling was not significantly associated with a higher risk of permanent pacemaker implantation after TAVI (pooled Risk Ratio 1.02 [0.70–1.47]; I2 = 0%). Conclusion Pre-procedural RV/PA uncoupling emerges as an independent predictor of worse prognosis in AS patients undergoing TAVI, contributing to a better understanding of the impact of this parameter on patient outcomes.

The efficacy of catheter ablation compared to medical therapy in heart failure patients with concomitant atrial fibrillation: A meta-analysis of randomized controlled trials

Abstract Introduction The management of atrial fibrillation in patients with heart failure continues to be a topic of ongoing debate. We conducted a meticulous comparison between two primary treatment modalities: catheter ablation versus medical therapy. Our aim is to assess the efficacy of these interventions in patients presenting with both atrial fibrillation and heart failure, drawing from the randomized controlled trials. Methods A comprehensive literature search was conducted up to February 2024, utilizing databases including PubMed, EMBASE, and Clinicaltrials.gov. A total of 10 randomized studies were identified and their data were extracted and analyzed. The primary outcomes assessed included the impact of catheter ablation on all-cause mortality, cardiovascular death, left ventricular ejection fraction (LVEF %), and 6-minute walk test (6MWT) in meters. Data were analyzed utilizing a random-effects model to calculate weighted mean differences for LVEF and 6MWT, and risk ratios for all-cause mortality and cardiovascular death on Review Manager 5.3 (RevMan 5.3) software. Results In totality, data from 1944 heart failure patients (N = 966 on catheter ablation; N = 978 on medical therapy) with concomitant atrial fibrillation were included. Patients in the catheter ablation group exhibited a significant reduction in all-cause mortality (RR 0.63 [95% CI 0.48, 0.83]; P=0.001; I2 = 17%). Moreover, there was a notable decrease in cardiovascular death among patients undergoing catheter ablation (RR 0.53 [95% CI 0.34, 0.81]; P=0.004; I2 = 20%). Patients who underwent catheter ablation demonstrated a marked improvement in LVEF (MD 5.79 [95% CI 3.13, 8.44]; P <0.0001; I2 = 82%). The 6MWT revealed superior outcomes in the catheter ablation group (MD 22.69 [95% CI 9.87, 35.50]; P=0.0005; I2 = 38%). Conclusion Heart failure patients with concomitant atrial fibrillation undergoing catheter ablation therapy exhibited notable improvements in LVEF and 6MWT, alongside a significantly reduced risk of all-cause mortality and cardiovascular death compared to those receiving solely medical therapy. These findings shed light on the potential advantages and superior outcomes associated with catheter ablation therapy in preserving cardiac chamber function and mitigating mortality in such a patient cohort. However, further investigations are warranted to understand the long-term benefits and optimal management strategies for such individuals.

Promoting a sustainable diet among office workers in Sweden: A pilot Study

Abstract Background Society is facing multiple challenges, including lifestyle-related diseases, alongside global climate change. Actions are needed to promote sustainable lifestyles advocating for healthy and environmentally friendly diets. This study aimed to assess how a sustainable lifestyle, compared to conventional healthy lifestyle education at work, affects participants’ energy intake, nutrient consumption, and diet-related CO2e. Methods An 8 week two-armed randomized trial was conducted, comprising a sustainable lifestyle arm (n = 21) and a healthy lifestyle arm (n = 16) based on the theoretical framework of the Behavioral Change Wheel, in total (n = 33) completed the trial. The office workers participated in 6 workshops during working hours. Linear mixed-effects models and analysis of variance tests were used for data analysis. Changes over time are presented as arms combined, along with their respective mean differences. Results A significant decrease in mean diet-related CO2e was observed (p < 0.001), with a decrease on average of 0.74 and 0.71 kg CO2e/day. The mean change in daily kilocalorie intake had a significant decrease over time (p = 0.008), on average of 192 and 386 Kcal. Moreover, a significant decrease in mean protein intake was observed (p < 0.001), with a decrease on average of 16 and 18 grams, possibly explaining the decrease in CO2e. No significant differences were observed between the arms at any timepoint. Conclusions Promoting sustainable lifestyle habits has a similar impact to advocating for a conventional healthy lifestyle regarding diet. This supports the new Nordic Nutrition Recommendations 2023. Despite the small sample size, insights into facilitating sustainable behaviors can influence public health policies across Europe and the workplace as an arena for health promotion. Key messages • The promotion of sustainable and healthy lifestyle habits at work can promote both individual and planetary health by decreasing diet-related CO2e emissions. • Here we demonstrate that the workplace has the potential to act as an arena to combat climate change.

Comparison of Surgical Techniques in Managing Craniosynostosis: Systematic Review and Bayesian Network Meta-Analysis

Open total cranial vault reconstruction (CVR) is the common procedure in managing craniosynostosis, yet more techniques have been introduced as alternatives, namely endoscopic suturectomy (ES), endoscopy-assisted craniectomy (EC), spring-assisted surgery (SAS), strip craniectomy with helmet (SC), Pi craniectomy (PiC), Pi plasty (PiP), and Renier’s “H” technique (RH). The aim of this study was to compare the effectiveness of craniosynostosis surgeries in improving the cephalic index of the patients. Studies published until 7 March 2024 reporting CVR, ES, SAS, SC, RH, and PiP as definitive craniosynostosis management with the cephalic index as the outcome were included. Bayesian network meta-analysis and pair-wise meta-analysis were performed using a random-effects model based on standardized mean difference (SMD) and 95% confidence interval (CI). Nine studies published in 2008–2024 recruiting a total of 464 craniosynostosis patients (age: 18–61 months) were included in this meta-analysis. EC (SMD = 0.23 [95%CI: −5.47 to 5.63]; p = 0.935), PiP (SMD = −0.07 [95%CI: −9.27 to 8.79]; p = 0.988), ES (SMD = −0.59 [95%CI: −6.07 to 4.94]; p = 0.834), PiC (SMD = −1.16 [95%CI: −8.89 to 6.35]; p = 0.765), RH (SMD = −0.96 [95%CI: −6.62 to 4.53]; p = 0.736), SAS (SMD = −0.86 [95%CI: −8.25 to 6.18]; p = 0.815), and SC (SMD = −1.79 [95%CI: −9.05 to 5.28]; p = 0.624) were found to be as effective as CVR in improving the cephalic index. Network meta-analysis suggests that PiP is the most effective among these techniques (rank 1 probability = 0.273). According to the rank probabilities of our model the order of techniques from the most to the least effective is as follows: EC > CVR > PiP > ES > SAS > RH > PiC > SC.

Efficacies of different treatment strategies for infants hospitalized with acute bronchiolitis.

: Acute bronchiolitis is a common cause of hospitalization during infancy that carries significant morbidity and mortality rates. : This study compared the efficacy of different treatment modalities for infants with bronchiolitis in terms of hospital stay and clinical severity scores. : The PubMed database was searched for re- levant studies. Eligibility criteria included double-blind randomized controlled trial design, assessment of the effect of treatment on bronchiolitis in infants under 2 years of age, and publication in English from inception through July 31, 2020. The primary efficacy outcome was the length of hospital stay, while the secondary outcome was the clinical severity score. The standardized treatment effect and standard error of the effect size were calculated. : We identified 45 randomized controlled trials of 24 pairwise comparisons. These 45 trials included 5,061 participants and investigated 13 types of interventions (12 active, 1 placebo). Inhalation therapy with epinephrine (standard mean difference [SMD], -0.41; 95% confidence interval [CI], -0.8 to -0.03) and hypertonic saline (SMD, -0.29; 95% CI, -0.55 to -0.03) reduced the length of hospital stay compared with normal saline. Hypertonic saline was the most effective at improving the clinical severity score (SMD, -0.52; 95% CI, -0.95 to -0.10). : Inhalation therapy with epinephrine and hypertonic saline reduced the length of hospital stay and the clinical severity of bronchiolitis among infants under 2 years of age.

Effectiveness of Digital Education on Human Papillomavirus Knowledge, Vaccination Intent and Completion Rates in Adolescents and Young Adults: A Meta-Analysis.

To examine the effects of digital educational intervention on HPV knowledge, vaccination intent and completion rates among adolescents and young adults. A systematic review and meta-analysis. The study followed PRISMA guidelines. Studies included randomised controlled trials assessing digital HPV educational interventions on individuals aged 9-26 years. Odds ratios (ORs), confidence intervals (CIs) and standardised mean differences (SMDs) were calculated and analysed with fixed- and random-effects models, depending on the degree of heterogeneity. Seven databases (Medline, PubMed, CINAHL, Cochrane Library, Web of Science, EMBASE and ASC) were searched from inception through April 9, 2024. Twelve studies enrolled 4925 participants were included. Six studies demonstrated that the intervention group significantly had higher HPV knowledge compared to the control group. Five studies reported a significant improvement on vaccination intent and vaccine completion rate. Subgroup analysis of the completion rates indicated that male participants demonstrated significantly greater vaccine competed rates. A tailored educational intervention was likely to effectively enhance HPV vaccine completion rates. Our findings confirmed that digital education was beneficial in enhancing adolescents and young adults' HPV knowledge, vaccination intention and vaccine completion rates. The tailored education might be considered prioritised in the design of interventions, while also considering the impact of gender on digital education. Digital interventions for HPV vaccinations require at least 7 months of follow-up, highlighting the vital role of tailored education for high-risk groups in designing effective interventions. The efficacy of digital interventions for HPV vaccination may differ across genders. There was no direct patient or public contribution, as this is a review of previous research. CRD-42023406919.

Family-based sexual health intervention for adolescents; A systematic review and meta-analysis

Abstract Background Family-based interventions are important in promoting adolescent sexual health outcomes. However, the effectiveness of these interventions in promoting adolescent sexual and reproductive health (ASRH) in Lower and middle-income countries (LMIC) has not been empirically evaluated. This review aimed to summarise the effectiveness of family-based sexual and reproductive health interventions in promoting ASRH in LMIC. Methods We conducted a systematic search for studies published in English from 2000 to October 2023 using MEDLINE, PsyINFO, CINAHL, Web of Science, and EMBASE databases. Studies were included if they involved adolescents aged 10-19 years, included family members in a key intervention component, evaluated the effectiveness of the interventions using an experimental or quasi-experimental design, assessed ASRH outcomes reported by adolescents and were conducted in LMIC setting. Standardized mean difference (SMD) and 95% confidence intervals were computed and meta-analyses were conducted using random effect models. Results Ten articles involving 2,246 participants were included in the review. The studies were nostly conducted in Africa. Across studies, there was no significant impact of family-based interventions in improving adolescent sexual health knowledge (SMD=0.5, 95%CI: -1.98 to 2.98), attitudes (SMD= -0.05, 95%CI: -1.92 to 1.82), practices (SMD=0.53, 95%CI: -0.69 to 1.75), or sexual communication with their family (SMD= 0.14, 95%CI: -0.42 to 0.7). Although individual studies reported a mixed effect of family-based interventions in improving sexual health outcomes, the pooled results from the meta-analysis showed no significant impact of family-based interventions. Conclusions Our review did not find any significant impact of family-based interventions in improving ASRH in LMIC. We recommend interventions using innovative approaches and novel strategies to align with the socio-cultural and economic background of the study setting. Key messages • This study found no significant impact of family-based interventions in improving ASRH in LMIC. • Additional studies, particularly from Asia, using culturally relevant interventions is required in this area.

Impact of age on health status after TAVI or SAVR in low risk patients with severe aortic stenosis: results from the PARTNER 3 Trial

Abstract Background Transcatheter aortic valve implantation (TAVI) results in similar 5-year survival and quality of life compared with surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS) and low surgical risk. Whether participants’ age at the time of intervention influences the health status benefit of TAVI vs. SAVR is unknown. Purpose To assess the relationship between age and both the short- and long-term health status outcomes of TAVI vs. SAVR among patients enrolled in the PARTNER 3 trial. Methods We used data from the PARTNER 3 randomized trial to compare health status outcomes between TAVI and SAVR, stratified by age (<70, 70-74, 75-79, ≥80 years). Health status was assessed at baseline, 1 month, 6 months, 12 months and annually through 5 years using the Kansas City Cardiomyopathy Questionnaire (KCCQ). The primary endpoint was the KCCQ overall summary score (KCCQ-OS) over the 5-year follow-up period (range 0-100; higher=better). The key secondary endpoint was an excellent outcome, defined as a KCCQ-OS>75 at 5-year follow-up without a decline of >10 points from baseline. Results Between March 2016 and October 2017, 1000 low-risk patients with severe AS were randomized in a 1:1 fashion to transfemoral TAVR using the balloon-expandable Sapien 3 valve or surgery in the PARTNER 3 trial. Among patients who underwent TAVI or SAVR (and had baseline health status available; TAVI: 494, SAVR: 449), 228 (24%) were <70, 284 (30%) were 70-74, 287 (31%) were 75-79, and 144 (15%) were ≥80 years old. Baseline health status was similar between the TAVI and SAVR groups as well as across age strata. At 30-day follow-up, health status was substantially better with TAVI than SAVR with similar differences across age strata (mean difference 13-18 points; Figure 1). At all other timepoints, there were no significant differences between TAVI and SAVR in any age group. The proportion of TAVI patients with an excellent outcome at 5-year follow-up ranged from 86% in the youngest subgroup to 73% in the oldest subgroup, with no significant differences compared with SAVR. Conclusions Among patients with severe AS at low surgical risk, TAVI using the SAPIEN 3 balloon-expandable valve resulted in substantially better health status in the early post-procedure period compared with SAVR across all age strata. Beyond the early recovery period, intermediate- and longer-term health status outcomes were similar with TAVI and SAVR, with no evidence of heterogeneity by age. Although longer term follow-up is necessary (and ongoing), these 5-year outcomes suggest that over the age range included in the PARTNER 3 trial, age alone should not play a dominant role in determining treatment recommendations for patients with severe AS.Health status by treatment and age group

Fractional flow reserve versus solely angiography-guided revascularisation in coronary artery disease, systematic review and meta-analysis

Abstract Objective Subsequent randomised controlled trials (RCTs) comparing the clinical outcomes of fractional flow reserve (FFR)-guided and angiography-guided revascularisation in patients with coronary artery disease (CAD) yielded inconsistent results. Moreover, recent European Society of Cardiology (ESC) guidelines lowered recommendation for FFR use in acute coronary syndorme (ACS). This study aimed to assess head to head whether FFR-guided revascularisation reduces the rates of hard clinical endpoints in comparison with the angiography-guided approach alone. Methods A systematic review was conducted through October 2023 at Embase, Clinicaltrials.gov, Cochrane Library, and EBSCO. Only RCTs that evaluated stable and unstable CAD and acute myocardial infarction (MI) were included. The trials selection was performed according to the latest ESC guidelines. Meta-regression analysis was performed to assess the impact of observation time on outcomes. Results Overall, 11 571 records were screened for relevant studies. Eight RCTs involving 4713 patients were included in the meta-analysis. FFR guidance was associated with a significant reduction of MI (RR, 0.75 [95% confidence interval {Cl}, 0.58–0.96], p=0.02) and lower rate of revascularisation (standardised mean difference - 0.12, [95% Cl, -0.14–-- 0.09], p<00001). There were no differences between FFR-guided and angio-guided revascularisation in MACE (RR, 0.84 [95% Cl, 0.69–1.02], p=0.08), all-cause mortality (RR, 1.00 [95% Cl, 0.58–1.74], p=0.99), and unplanned revascularisation (RR, 0.89 [95% Cl, 0.72–1.10], p=0.28). The meta-regression analysis revealed a significant impact of the duration of follow-up for MACE, all-cause mortality and MI, but not for unplanned revascularisation. Conclusions FFR-driven revascularisation was associated with a significantly lower rate of MI for entire population and also in the ACS subset. These results were achieved with a substantially less revascularisations compared with solely angiographic guidance.

Cangrelor versus no cangrelor during percutaneous coronary intervention in hemodynamically unstable patients: a cohort study on benefits and risks

Abstract Background Cangrelor is an intravenous P2Y12 inhibitor which, according to the European guidelines, may be considered for administration in acute coronary syndrome during percutaneous coronary intervention (PCI). Little is known regarding benefits and risks of such administration in hemodynamically unstable patients. Purpose To investigate the effects of cangrelor versus no cangrelor during PCI regarding major adverse cardiac events (MACE), in-hospital bleeding, and all-cause mortality in patients with cardiogenic shock and/or cardiac arrest. Methods The study population was extracted from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and included patients with cardiogenic shock or cardiac arrest undergoing PCI during the years 2016-2022. Propensity score matching (PSM) was used to create comparable groups. After matching, all variables used for calculating propensity score were balanced (standardized mean difference<0.1). Outcomes were MACE within 30 days, in-hospital bleeding, and all-cause mortality within 30 days. Risk ratios (RR) with 95% confidence intervals (CI) were calculated. When RR deviated from the null, the risk difference (RD) was determined. Results In all, 2,100 (66%) out of 3,206 patients with cardiogenic shock and/or cardiac arrest were included in the PSM analyses (median age: 69 years; 76% male; 78% ST-elevation myocardial infarction (STEMI)). Comparing cangrelor versus no cangrelor in this matched set of patients, the RR was 0.93 (95% CI: 0.84; 1.04) for MACE; 1.51 (1.02; 2.25) for in-hospital bleeding, with an RD of 1.9 percentage points (0.10; 3.7); and 0.93 (0.82; 1.04) for all-cause mortality (Table). In the PSM analysis regarding patients with cardiogenic shock, 1,098 (60%) out of 1,815 patients were included (median age: 71 years; 68% male; 82% STEMI). For these patients, RR was 0.85 (95% CI: 0.74; 0.97) for MACE, with an RD of -7.5 percentage points (-1.6; -13); 1.31 (0.82; 2.09) for in-hospital bleeding; and 0.83 (0.72; 0.95) for all-cause mortality, with an RD of -8.0 percentage points (-2.2; -14). In the PSM analysis regarding patients with cardiac arrest, 1,388 (76%) out of 1,827 patients were included (median age: 67 years; 81% male; 75% STEMI). RR was 0.98 (95% CI: 0.86; 1.12) for MACE; 1.53 (0.95; 2.49) for in-hospital bleeding; and 0.98 (0.86; 1.13) for all-cause mortality. Conclusion For patients with cardiogenic shock, but not for patients with cardiac arrest, administration of cangrelor versus no cangrelor during PCI was associated with a reduction in both MACE and all-cause mortality, with numbers needed to treat of 14 and 13, respectively. Overall, for patients with cardiogenic shock or cardiac arrest, administration of cangrelor versus no cangrelor during PCI was associated with an increased risk of in-hospital bleeding with a number needed to harm of 53.

Stimulation of the withdrawal reflex in gait training after stroke: A systematic review and meta-analysis.

After a stroke many people experience hemiparesis, resulting in walking difficulties which affects independence, mobility, and participation in activities of daily living. Activating the nociceptive withdrawal reflex (NWR) during gait training aims to support the initiation and facilitation of the swing phase of the paretic leg. The aim of this review is to investigate the orthotic and therapeutic effects of a NWR stimulation intervention to improve gait in patients after a stroke. We searched the databases CENTRAL, DORIS, MEDLINE, and PEDro, trial registers and reference lists. We selected randomized controlled trials using any type of stimulation of the NWR in people after stroke, comparing it to any control intervention, and reporting a change in gait performance assessed by means of any appropriate measurement method. We included three studies in this review, all of which used electrical stimulation to elicit the NWR during walking. The orthotic effect was investigated in one study, and the therapeutic effect in two studies, comparing walking with and without electrical stimulation-triggered NWR. The meta-analysis revealed a borderline statistical significance result for the therapeutic effect. The pooled mean difference between the treatment and control group (random-effects model) for walking speed was 0.13 m/s (95% CI -0.04 to 0.29; I2 = 72%) after treatment and 0.17 m/s (95% CI -0.03 to 0.37; I2 = 62%) at follow-up. Activating the NWR during gait training has not been investigated frequently so far. By using electrical stimulation-elicited NWR, severely affected hemiparetic patients may improve their walking speed.

Role of serum kisspeptin as a biomarker to detect miscarriage: a systematic review and meta-analysis.

Miscarriage is a common adverse pregnancy outcome with physical and emotional effects. Identifying predictive miscarriage biomarkers should improve early detection and management. Serum kisspeptin, known for its critical role in reproductive biology, has emerged as a potential biomarker for miscarriage. With this systematic review and meta-analysis, we aimed to assess the association between serum kisspeptin levels and the miscarriage risk. We systematically searched PubMed, Embase, and Cochrane Library databases for studies published up to February 2024, examining the association between serum kisspeptin levels and miscarriage. Eligible studies were observational designs that reported kisspeptin levels in women with and without miscarriage. We included 12 studies involving 2,050 participants. Pooled analysis demonstrated that low serum kisspeptin levels were significantly associated with an increased risk of miscarriage (standardized mean difference = -2.750; 95%CI: -4.357 to -1.143), with substantial heterogeneity (I2 = 98.7%). The pooled area under the curve from three studies indicated high diagnostic accuracy (AUC = 0.903; 95%CI: 0.860-0.946). Low serum kisspeptin levels are significantly associated with an increased miscarriage risk, suggesting that kisspeptin could serve as an effective biomarker for early detection. However, the significant heterogeneity among studies and the lack of standardized measurement protocols emphasize the necessity of further research before clinical implementation. SYSTEMATIC REVIEW REGISTRATION: (Registration ID: CRD42024520639).

Long-term outcomes of percutaneous coronary intervention versus coronary artery bypass grafting in women with severe coronary artery disease

Abstract Background The optimal revascularization strategy for severe coronary artery disease (CAD) in women remains controversial. Despite differences between women and men in the development of CAD, there remains a paucity of comparative real-world observational evidence comparing percutaneous coronary intervention (PCI) to coronary artery bypass grafting (CABG) in women. Purpose We evaluated short and long-term outcomes of PCI and CABG in women with severe CAD. Methods We conducted a propensity score-matched retrospective cohort study using linked clinical and administrative databases in Ontario, Canada to obtain records of women with left main, 3-vessel disease, or 2-vessel disease with proximal left anterior descending artery involvement undergoing PCI or CABG from April 1st, 2012 to December 31st, 2021. Patients who were >80 years of age and patients who underwent urgent or emergent procedures were excluded for the primary analysis. The primary outcome was a composite of myocardial infarction, stroke, repeat revascularization, and death (MACCE). Secondary outcomes included the individual components of MACCE and a composite of readmission for MI, heart failure, and stroke. Following multiple imputation and propensity score-matching, the Cox proportional hazards model and Fine-Gray sub-distribution hazard model with robust variance estimators accounting for death as a competing risk were used to evaluate long-term outcomes. Results In the primary cohort, 2469 patients underwent PCI and 3,721 patients underwent CABG. After propensity score matching, including by coronary disease territory, 2,033 well-balanced pairs were identified, with standardized mean differences <0.10 for all covariates. In-hospital death and stroke were significantly lower with PCI than with CABG (0.7% vs 1.5%, p=0.036) and (<0.2% vs 1.4%, p<0.001), respectively, and there was no difference in perioperative MI between PCI and CABG (1.1% vs 0.6%, p=0.121). At a median (IQR) of 5.1 (2.9-7.5) years, major adverse cardiac and cerebrovascular events (MACCE) was higher with PCI compared with CABG (37.7% vs 23.3%, HR 1.79, [95% CI: 1.66-1.91], p<0.001) (Figure 1). All-cause mortality was higher with PCI compared with CABG (17.8% vs 13.4%, HR 1.33, [95% CI: 1.21-1.45], p<0.001) (Figure 2). The composite readmission outcome (MI, heart failure, stroke) was higher with PCI compared with CABG (16.2% vs 11.2%, HR 1.42, [95% CI: 1.37-1.48], p<0.001). Conclusion In women with severe CAD, CABG appears to be associated with a long-term reduction in MACCE and mortality compared with PCI. Our findings provide evidence to suggest women with severe CAD may derive greater long-term benefit from CABG compared to PCI and suggest that the treatment recommendation should shift towards CABG in appropriately selected women.Figure 1.MACCE free survivalFigure 2.Overall survival

A meta-analysis of the efficacy and safety of exercise-based cardiac rehabilitation in patients with left ventricular assist devices

Abstract Background Left Ventricular Assist Devices (LVADs) and heart transplantation stand out as the two well-established and effective therapeutic approaches for managing patients with advanced heart failure. Exercise-based cardiac rehabilitation (EBCR) has been demonstrated to improve functional capacity in patients with LVAD. Purpose We aim to assess the efficacy and safety of EBCR in patients with LVAD. Also, to compare high-intensity (HIT) versus moderate-intensity (MIT) EBCR regimens in patients with LVAD. Methods A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) studies obtained from PubMed, Embase Cochrane, Scopus, and WOS until January 2024. We used the fixed-effects model to report dichotomous outcomes using risk ratio (RR) and continuous outcomes using standardized mean difference (SMD) with a 95% confidence interval (CI). Results Six RCTs with 160 patients were included. There was no significant difference between EBCR and standard care regarding peak VO2 change [SMD: 0.24 with 95% CI (-0.14, 0.62), P= 0.21] and six-minute walk distance (6-MWD) change [SMD: 0.28 with 95% CI (-0.11, 0.66), P= 0.16]. Also, there was no significant difference between HIT and MIT exercise regarding peak VO2 change [SMD: 0.20 with 95% CI (-0.41, 0.82), P= 0.52] and 6-MWD change [SMD: 0.07 with 95% CI (-0.54, 0.69), P= 0.81]. Moreover, EBCR was associated with a significant decrease in the incidence of any adverse events when compared to usual care with [RR: 0.80 with 95% CI (0.65, 0.99), P= 0.04], while there was no significant difference between HIT and MIT exercise regarding the incidence of any adverse events [RR: 0.38 with 95% CI (0.02, 9.22), P= 0.55]. Conclusion EBCR did not improve functional capacity in patients with LVAD, with no significant effect on peak VO2 or 6-MWD.

Subgroup results from KARDIA-2: impact of demographic and baseline disease characteristics on zilebesiran response in patients with hypertension uncontrolled by a standard oral antihypertensive

Abstract Background Zilebesiran is an investigational RNA interference therapeutic targeting hepatic angiotensinogen synthesis. In KARDIA-1, a single subcutaneous (SC) dose of zilebesiran monotherapy significantly reduced 24-hr mean ambulatory and office systolic blood pressure (SBP) from baseline to Months 3 and 6 versus placebo. The Phase 2 KARDIA-2 study assessed efficacy and safety of zilebesiran with a standard oral antihypertensive in patients with uncontrolled hypertension. Purpose Uncontrolled hypertension is a leading cause of cardiovascular morbidity and mortality, and medication non-adherence affects blood pressure control. Developing effective, long-lasting treatments is crucial for patients with hypertension uncontrolled by standard therapy. Methods KARDIA-2 enrolled adults with mild-to-moderate hypertension who were untreated or receiving stable therapy with ≤2 antihypertensives. Patients discontinued prior antihypertensive medication and were randomized 10:7:4 to open-label, once-daily oral treatment with 40 mg olmesartan, 5 mg amlodipine, or 2.5 mg indapamide. After ≥4 weeks on protocol-specified medication, patients with a 24-hr mean ambulatory SBP of 130–160 mmHg were randomized 1:1 in a double-blind manner to a single SC dose of zilebesiran 600 mg or placebo as add-on therapy. The primary endpoint was change from baseline to Month 3 in 24-hr mean ambulatory SBP versus placebo for each group. Efficacy and safety were also assessed in pre-specified subgroups: age (<65; ≥65 years), sex, race (Black; other), baseline 24-hr mean ambulatory SBP (<145; ≥145 mmHg), and baseline estimated glomerular filtration rate (≥60; <60 mL/min/1.73m2). Results The primary analysis included 667 patients (median age [range] 59 [27–75] years; 57% male, 28% Black). At Month 3, least-squares mean differences (LSMD) (95% confidence interval [CI]) between zilebesiran and placebo for the olmesartan, amlodipine, and indapamide groups were −4.0 (−7.6, −0.3), −9.7 (−12.9, −6.6), and −12.1 (−16.5, −7.6) mmHg, respectively, for 24-hr mean ambulatory SBP (all p<0.05). LSMD (95% CI) in office SBP for the same groups were −7.0 (−10.4, −3.6), −10.2 (−13.5, −6.9), and −18.5 (−22.8, −14.2) mmHg, respectively, (all p<0.001). SBP reductions were consistent across subgroups, except for a trend towards an attenuated response observed in Black patients (Figs 1, 2). More patients receiving zilebesiran (49–58%) than placebo (39–48%) experienced ≥1 adverse event through Month 6, with low rates of hyperkalaemia, hypotension, or acute kidney injury reported across all groups. Conclusion In KARDIA-2, a single dose of zilebesiran significantly reduced SBP versus placebo at Month 3 on top of a standard oral antihypertensive, with encouraging safety data. SBP reduction was consistent across most subgroups. Treatment with zilebesiran combined with standard antihypertensives may be effective for a broad population of patients with hypertension uncontrolled on monotherapy.

Use and associations with mortality/morbidity of guideline-directed medical therapy use in heart failure with improved ejection fraction: a PS-matched analysis from the swedish heart failure registry

Abstract Background Guideline-directed medical therapy reduces mortality/morbidity in heart failure (HF) with reduced ejection fraction (EF). However, evidence about its use and prognostic role once EF has improved is limited. Purpose To assess use and associations with mortality/morbidity of renin-angiotensin system inhibitors (RASi), angiotensin-receptor neprilysin inhibitors (ARNi), beta-blockers (BBL), and mineralocorticoid receptor antagonists (MRA) in patients with HF and improved EF (HFimpEF). Methods We analyzed patients with HFimpEF, defined as a first recorded EF <40% and a subsequent EF ≥40%, registered in the Swedish HF registry between 2004 and 2021. Index date was the SwedeHF registration reporting the second (i.e. improved) EF assessment. To reduce the bias related to the initial recommendation for MRA limited to more severe HF (NYHA III-IV), the assessment of MRA was restricted to patients with index date 2016 or later, when Swedish guidelines on HF included a recommendation for MRA in patients with NYHA class II–IV. The association between treatment use and the composite outcome cardiovascular mortality (CVM)/HF hospitalization (HHF) (with censoring >3 years) was assessed by Cox proportional hazard models in a 2:1 propensity score-matched cohort. Propensity scores for treatment use were calculated by a logistic regression model including 38 variables, achieving a standardized mean difference <0.1 for all evaluated variables. Since matching reduces the sample size and may limit generalizability, a Cox proportional hazard model was fitted in the overall cohort adjusting, rather than matching, for the propensity score (Overall HR). Results Of 4700 patients with HFimpEF (mean age 68±12 yrs, 70% male), 94%, 95%, and 50% received RASi/ARNi, BBL, and MRA, respectively. Regardless of the specific treatment, non-users had lower BMI, education level and use of other HF medications, but older age, higher EF at improvement, higher NT-proBNP, and more likely peripheral artery disease, anemia, and valvular disease. In the matched cohorts, RASi/ARNi use was associated with a statistically significant lower risk of CVM/HHF [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.53–0.95] (Figure). There was no statistically significant association between CVM/HHF and beta-blockers (HR 0.75, (95% CI 0.53-1.08), and MRA (HR 1.16, 95% CI 0.90-1.49). These results were consistent after adjustment for the propensity score in the overall cohort (Figure). Conclusion In patients with HFimpEF use of GDMT was high. Treatment with RASi/ARNi was associated with lower morbidity and mortality, whereas no statistically significant association was observed with beta-blockers which might be explained by limited statistical power.Composite outcome.

Influence of coronary plaque characteristics on lesion-specific ischemia assessed by coronary computed tomography angiography and fractional flow reserve - a systematic review and meta-analysis

Abstract Background Characterization of atherosclerotic plaque features by coronary computed tomography angiography (CCTA) carries profound prognostic value. Previous studies indicate that coronary plaque burden and certain plaque features are associated to lesion-specific ischemia by invasive fractional flow reserve (FFR). However, the existing literature is limited by small sample sizes, and provide inconsistent results. Purpose We performed a meta-analysis in order to delineate further the potential association between coronary plaque phenotype by CCTA and FFR. Methods A comprehensive systematic literature review and meta-analysis was conducted. PubMed and Embase databases were searched for studies that investigated the association between coronary plaque characteristics and FFR between January 2010 and August 2023. Study search, evaluation, and data extraction were performed independently by two researchers. Weighted mean difference (WMD) method for WMD was used for comparison of pooled per-lesion plaque parameters and presence of specific plaque features against presence of lesion-specific ischemia (FFR ≤0.80). Lesions with stenosis severity of 25-90% were included. Extracted data from eligible studies were analysed using random effects model for WMD and to estimate odds ratios (OR) with 95% confidence intervals (CI). Results A total of 12 studies were deemed eligible with 1,318 patients and available data on 1,915 coronary lesions. Of these, 626 lesions caused ischemia. Significantly greater total plaque volume (TPV) and non-calcified plaque volume (NCPV) occurred in lesions with abnormal FFR compared to normal FFR (WMD 83.0 mm3, 95% CI: 44.27; 121.81, p<0.001; WMD 83.63 mm3, 95% CI: 55.0; 112.24, p <0.001, respectively). Similar findings were observed for aggregate plaque volume (%APV) and plaque burden (%PB) with WMD 9.18, 95% CI: 6.08; 12.28, p<0.001; WMD 8.83, 95% CI: 4.32; 14.24, p=0.001, respectively. Napkin ring-sign and spotty calcification appeared more frequent in ischemia-causing lesions compared to those with FFR >0.80 (OR 4.25, 95% CI: 1.39; 13.00, p=0.011; OR 1.92, 95% CI: 1.33; 2.75, p=0.001, respectively). A summary of the meta-analysis findings regarding the association between plaque burden and plaque characteristics and FFR is provided in Figure 1 and 2. Conclusion CCTA-derived TPV and NCPV as well as %APV, %PB and the presence of napkin-ring sign and spotty calcification are associated with presence of lesion-specific ischemia. Coronary plaque assessment from CCTA images provide improved discrimination of lesion-specific ischaemia.

Short-term effects on sacubitril/valsartan therapy on right ventricle work and mechanics in patients with heart failure and reduced ejection fraction

Abstract Introduction In previous studies, sacubitril/valsartan (ARNI) therapy has been shown to have a positive effect on right ventricle (RV) function and on systolic pulmonary artery pressure in addition to improvement of left ventricle (LV) function in patients with heart failure and reduced ejection fraction (HFrEF). Recently, it was shown that a short-term ARNI therapy compared to valsartan-only therapy led to reduced systemic blood pressure and LV mechanical work, contributing to reduced LV myocardial perfusion and oxygen consumption. Purpose This paper aimed to study the effect of short-term ARNI therapy on RV mechanics and work and pulmonary and LV filling pressures compared to valsartan-only therapy in patients with HFrEF. Methods The study was a phase IV, prospective, randomized, double-blind, parallel-group study in patients with NYHA class II–III heart failure and LV ejection fraction (LVEF) <= 35 %. During a 6-week run-in period, all patients received valsartan therapy, which was up-titrated to the highest tolerated dose level (80 mg bid or 160 mg bid) and then randomized to either valsartan or sacubitril/valsartan. Myocardial oxygen consumption, energetic efficiency of cardiac work, and cardiac and systemic hemodynamics were quantified using echocardiography and 11C-acetate PET before and after 6 weeks of therapy (on stable dose) in 55 patients. The analyses were done with ANCOVA adjusting for pre-randomization values. Results The RV myocardial resting perfusion (mean difference of 0.056 (95% CI, 0.02 to 0.109) ml/g/min, p = 0.041) and RV myocardial oxygen consumption (0.005 (0.001 to 0.010) 1/min, p = 0.015) were significantly lower in the ARNI group compared with the valsartan-only group. The left atrial end-diastolic volume indexed to body surface area (geometric mean difference of 1.071 (95% CI, 0 to 1.148) ml/m2, p = 0.048) and the ratio of early mitral inflow velocity to medial mitral annular early diastolic velocity (mean difference of 2.467 (95% CI, 0.096 to 4.838), p = 0.042) were also significantly lower in the ARNI group compared with the control group. There was no difference between the groups in peak systolic right ventricle to right atrial pressure gradient. Still, the tricuspid annular plane systolic excursion was significantly higher in the valsartan-only group compared with the ARNI group (0.221 (0.039 to 0.404) cm, p = 0.018). There was no difference in RV free wall strain, fractional area change or systolic excursion velocity between the treatment arms (p> 0.262). Conclusions In addition to our earlier findings, sacubitril when added to valsartan appears to reduce also right ventricle myocardial perfusion and oxygen consumption. There was also a reduction in left atrial end-diastolic volume and in early mitral inflow to medial mitral annular early diastolic velocity in the sacubitril/valsartan group as compared to the valsartan-only group, which suggest decreased LV filling pressure.

Minimally invasive hysterectomy same-day discharge: systematic review and meta-analysis of predictors.

Same-day discharge (SDD) is increasingly prevalent following minimally invasive hysterectomy (MIH). However, consensus guidelines for selecting SDD eligibility criteria for MIH remain unexplored. This study aims to identify predictive factors for non-SDD following MIH (registered in PROSPERO CRD42022350373). PubMed, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials. All original studies that involve patients who were discharged on the same day are compared with those who were not (not failure to discharge / not intended to discharge). Categorical and continuous variables were reported as risk ratios with 95% confidence intervals and weighted mean differences with 95% CIs, respectively. Heterogeneity among the included studies was assessed using the I2 statistics. We conducted sensitivity analysis to identify the reason(s) for this heterogeneity. Ten studies (59,589 patients) were included, with a mean SDD rate of 20.28%. The predictors of overnight observation included factors such as American Society of Anesthesiologists classification (ASA) > II (P = .02; I2 = 92%), increased estimated blood loss (EBL) (P < 0.00001; I2 = 87%), surgeries starting later in the day (P < 0.00, I2 = 15%), and longer operation times (P = .002; I2 = 96%). In sensitivity and subgroup analyses, uterus weight emerged as a potential factor (P < 0.00; I2 = 50%), while the results concerning ASA, uterine weight, and EBL appeared to be homogeneous. However, the operation time remained heterogeneous. These factors could assist surgeons in the decision-making process regarding the performance of SDD subsequent to MIH procedures for patients.