Real World Research Articles

Echocardiographic and clinical features of patients developing prosthesis-patient mismatch after TAVI: insights from an international multicenter registry

Abstract Background The impact of prosthesis-patient mismatch (PPM) after transcatheter aortic valve implantation (TAVI) is controversial. Purpose Our study aims to evaluate the impact of PPM on mortality and clinical-echocardiographic progression of cardiac damage in a "real world" cohort of patients at intermediate and low surgical risk and to characterize its main predictors. Methods 963 patients who underwent TAVI procedure between 2017 and 2021, from an international multicenter observational registry, were included in this analysis. Multiparametric echocardiographic data were analyzed at 1-year follow-up (FU). Clinical and echocardiographic features were stratified by presence of PPM and PPM severity, as per the most current international recommendations (VARC-3 criteria). Results 18% of patients developed post-TAVI PPM, (7.7% of the whole cohort severe). At baseline, 50.3% of patients with PPM were male (vs 46.2% in the cohort without PPM, p=0.33), aged 82y (interquartile range (IQR) 79-85y) vs 82y (IQR 78-86y; p=0.46), and 55.6% had Balloon-Expandable valves implanted (vs 46.8% of patients without PPM, p=0.04); they had smaller left ventricular outflow tract (LVOT) diameter (20mm, IQR 19-21 vs 20mm, IQR 20-22, p=0.02), reduced Stroke Volume index (SVi) (34.2 vs 38 ml/m2, p<0.01) and transaortic flow rate (190.6 vs 211 ml/s, p<0.01). At pre-discharge FU patients with PPM had more paravalvular aortic regurgitation (AR) (moderate/severe AR 15.8% vs 9.2%, p<0.01). At a median FU of 1.46 years (IQR 1-4), there was no evidence of a significant impact of PPM on overall mortality (15.3% vs 13.1%, p=0.46) nor on rehospitalization rate for heart failure (4.3% vs 8.0%, p=0.10). At 1-year FU, maladaptive alterations of left ventricular parameters were found in patients with PPM, with a significant increase in endsystolic diameter (ESD) (33 vs 28mm, p=0.03) and a statistically non-significant increase in LV mass index (121 vs 106g/m2, p=0.07). Interestingly, trajectory parameters of patients with PPM from baseline to 1-year FU showed a reduced cardiac remodeling compared to patients without PPM, including no LVEF improvement (p=0.88), absent reduction of LV end-diastolic volume (p=0.70), indexed LV mass (p=0.31), ESD (p=0.48) and pulmonary artery systolic pressure (p=0.82), and an increase of basal RV diameter (p<0.001). Patients with moderate/severe PPM had worse NYHA functional class at 1 year (NYHA III-IV 13% vs 7.8%, p=0.03). Independent predictor of PPM at multivariable logistic regression was male gender (OR=1.93, p=0.04); while SVi (OR=0.86, p<0.001), prosthetic size >23mm (OR=0.62, p=0.03) and LVOT diameter (OR=0.79, p=0.02) had protective effect. Conclusions There was no evidence of a short- or medium-term impact of PPM on mortality. However, clinical-echocardiographic evaluations demonstrated a PPM-related pattern of early ventricular maladaptive alterations associated with a significant deterioration in NYHA class at 1 year.

Comparative outcomes between empagliflozin and dapagliflozin in heart failure: real world multi-center cohort study

Abstract Introduction Heart failure (HF) is a significant global health concern, and sodium-glucose cotransporter-2 (SGLT2) inhibitors, such as dapagliflozin and empagliflozin, have emerged as important therapeutic options. However, their comparative effectiveness in a real-world population remains uncertain. Purpose The purpose of this multicenter, population-based cohort study was to investigate and compare the outcomes associated with dapagliflozin and empagliflozin use in patients with heart failure. We sought to understand whether these SGLT2 inhibitors had differential effects on cardiovascular events in a real-world setting. Methods We analysed data from a clinical data warehouse encompassing seven medical centers. Subjects diagnosed with heart failure between January 2021 and November 2023, who were prescribed dapagliflozin or empagliflozin, were included. We conducted one-to-one propensity-score matching, ensuring that the dapagliflozin and empagliflozin groups were comparable in baseline characteristics. The primary outcome was a composite of cardiovascular (CV) death or hospitalization for HF, analysed as the first event occurring after starting each medication. Secondary outcomes included individual components, all-cause death, and CV hospitalization. Results Propensity-score matching made a balanced cohort of 6,281 patients (3,111 in the dapagliflozin group and 3,170 in the empagliflozin group). The median follow-up duration was 16.0 months. In the propensity-score matched cohort, dapagliflozin and empagliflozin showed no significant difference in the primary outcome (8.8% versus 7.8%, hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.77-1.08, p=0.276). Similar findings were observed in secondary outcomes. Subgroup analysis revealed potential benefits of empagliflozin in patients with diabetes mellitus (DM) (7.8% versus 5.6%, HR 0.73, 95% CI 0.55-0.98, p=0.039). Conclusion This study suggests that dapagliflozin and empagliflozin have similar clinical outcomes in the management of heart failure in a real-world setting. However, empagliflozin showed result in improving outcomes for HF patients with DM. Further research is warranted to validate these findings and guide clinical decision-making in the individualized management of heart failure.Baseline characteristicsSubgroup analysis

Guideline-directed medical therapy titration for heart failure with ischaemic aetiology and its effect on cardiac remodelling and cardiovascular mortality-from a real world perspective

Abstract Background Contemporary Heart Failure (HF) pharmacological treatment has been reshaped by several landmark trials in recent years, and available evidence strongly encourages treatment up-titration to target doses. Recent literature regarding treatment sequencing demonstrated positive effects of up-titration on major outcomes regardless of HF aetiology. Purpose We investigated a contemporary Heart Failure with Reduced Ejection Fraction (HFrEF) patient cohort and ischaemic aetiology and sought to understand the effects both in terms of echocardiographic remodelling and upon mortality for cardiovascular (CV) causes of contemporary ESC guideline-directed medical therapy (GDMT) on a real-world level. Methods We retrospectively analysed data of consecutive patients with HFrEF and ischaemic genesis followed in our tertiary HF clinic between January 2019 and January 2022. Eligible patients were stratified into two groups: patients treated or not with full doses of ESC GDMT [including angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) or angiotensin receptor-neprilysin inhibitors (ARNI), beta-blockers, mineralocorticoid receptor antagonists (MRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i)]. Results Overall, 203 patients (mean age 70.1±12.3 years, 165 males) were included into the analysis. Over a mean follow-up of 1223±221.2 days, 115 (56.6) patients achieved the full recommended doses of each drug. Patients with an unsuccessful up-titration had higher end-diastolic volume at transthoracic echocardiography (p for difference at first and second follow-up <0.001; figure 1, panel A), lower left ventricular ejection fraction (40.1±4.3% vs 44.3±7.8 and 38.7±4.9% vs 42.3±5.6% at the first and second follow-up, respectively) and higher CV mortality rates compared to those treated with the maximal doses (figure 1, panel B). Conclusions Up-titration of pharmacotherapy in our real-world cohort of patients with HFrEF and ischaemic aetiology demonstrated a positive effect both on pivotal echocardiographic parameters and on CV mortality. Our data suggest that timely identification and referral of patients with coronary artery disease who fail to achieve complete positive remodelling after an acute event (or during chronic disease course) for HF contemporary treatment implementation should be envisaged.Figure 1

A survey of availability and affordability of polypills for primary and secondary prevention of cardiovascular diseases in selected countries

Abstract Background/Introduction The recent inclusion of polypills—fixed-dose combinations of two or more antihypertensive drugs and statin with or without aspirin—in the World Health Organization’s Essential Medicines List (EML) reiterates the potential of this approach to improve global treatment coverage for primary or secondary prevention of cardiovascular diseases (CVDs). Although there exists extensive evidence on efficacy, safety, and acceptability of polypills, there is no research to-date assessing the "real world" availability and affordability of polypills globally. Purpose We conducted a cross-sectional survey of public and private sector facilities in 13 countries from around the world to evaluate the availability and affordability of polypills. Methods In the surveyed countries, we first ascertained whether any polypill was authorized for marketing and/or included in the national EMLs and clinical guidelines. The facility survey employed a modified WHO/Health Action International methodology. In each country, we collected retail and price data for polypills from at least one public sector facility and three private pharmacies using convenience sampling. Polypills were considered unaffordable in a given country if the lowest paid worker spends more than a days’ wage to purchase monthly supply. Results Polypills were approved for marketing in four of the 13 surveyed countries: Spain, India, Mauritius, and Argentina. None of these countries included polypills in national guidelines, formularies, or EMLs. Further, none of the surveyed public pharmacies in any of the four countries stocked any polypills. Among the surveyed private sector facilities, availability ranged from 0% in India (out-of-stock on the survey day but listed for sale) to 100% in Argentina and Spain. In the private sector, we identified seven unique polypill combinations, marketed by eight different companies. Although not in stock, India had a wider range of various combinations (n=5). Many combinations (63%) found in this survey were affordable in the local context, but these were limited to India and Spain. A lowest paid government worker would spend between 0.2 (India)–2.8 (Mauritius) days’ wages to pay the price for one month’s supply of the polypills. Polypills were likely to be affordable in countries that locally manufactured them. Further, two-pill combinations (one antihypertensive and a statin) were stocked by private pharmacies in Argentina, Bangladesh, Cameroon, India, Nepal, and Spain, with affordability ranging from 0.2 (India)–7.1 (Cameroon) days’ wages. Conclusion Low availability and affordability of polypills in both public and private sectors suggest that the implementation and overall uptake of polypills remains poor globally. Context-specific multi-disciplinary health system research is required to understand factors affecting polypill implementation and to design and evaluate appropriate implementation strategies.

Evaluation of clinical need, effectiveness, and safety of the first myosin inhibitor mavacamten in real world patients

Abstract Background Hypertrophic cardiomyopathy has a high burden of heart failure if obstruction in the left-ventricular outflow tract (HOCM) is present. Mavacamten is the first available myosin inhibitor specifically addressing the underlying pathophysiology of hypercontractility in HOCM. Based on positive results of respective approval studies, mavacamten is recommended for therapy of HOCM in recent ESC guidelines but clinical real world data are lacking. Methods In this ongoing study, consecutive patients with current or previous diagnosis of HOCM presenting at a single referral centre for hypertrophic cardiomyopathy from March 2023 to February 2024 were included and analysed by treatment modality. In patients initiating mavacamten therapy, clinical data of 4 weekly follow ups were assessed, including efficacy (NYHA class, LVOT gradient and biomarkers) and adverse events. Results A total of 72 patients were included (59.1 ± 13.0 years, 68% male). Mavacamten treatment was started in 30/72 (41.7%) patients, 3/72 (4.1%) were referred for transcatheter septal reduction therapy (SRT), and 39/72 (54.2%) did not require any escalation in their treatment due to low gradient with current treatment or few symptoms. Of the latter, 3/39 (7.7%) had previous SRT, 36/39 (92.3%) were stable on negative inotropic medication. The average age of patients selected for mavacamten therapy was 58.0 ± 13.0 years, 80% were male, and the average thickness of the interventricular septum was 18.8 ± 2.8 mm. 22/30 (73.3%) were on baseline therapy with beta-blockers, 3/30 (10.0%) with calcium channel blockers, 2/30 (6.7%) with both, and 4/30 (13.3%) had additional treatment with disopyramide. As shown in table 1, there was a significant decrease in the LVOT gradient under Valsalva maneuver observed 4 weeks after initiation of mavacamten treatment (p=0.006), while the reduction in peak exercise LVOT gradient was statistically significant after 8 weeks (p=0.02). Simultaneously, a significant decrease in Nt-pro-BNP levels was observed after 4 weeks of therapy (p<0.001). A significant drop in troponin T levels compared to baseline was only noted after 20 weeks of treatment (p=0.02). At baseline, 66.7% patients were classified as NYHA class III/IV, and 12.5% after 20 weeks of treatment. 75% of the patients improved ≥1 NYHA class after 20 weeks. Regarding adverse events, there was one case of ejection fraction dropping to <50%, which resolved after halting treatment. Additionally, there were two reports of dizziness and one reported syncope, all of which resolved without taking any actions. Conclusion In this real-world single centre HOCM cohort, 41.7% of patients had an indication for myosin inhibitor therapy. The safety and effectiveness in lowering the LVOT gradient and improving NYHA class were consistent with findings from the approval studies.

Blood pressure and renal function changes in patients with severe chronic kidney disease undergoing radiofrequency renal denervation: 12 months outcomes from the Global SYMPLICITY Registry DEFINE

Abstract Background Radiofrequency renal denervation (RF RDN) lowers blood pressure (BP) in patients with uncontrolled hypertension (HTN). The impact of renal function on safety and efficacy of RDN is unknown. Purpose To assess BP and renal function in patients with HTN following RDN. Methods All patients treated with RF RDN (n=3332) from the observational Global SYMPLICITY Registry Denervation Findings in Real World (GSR DEFINE) were included. Patients were categorized into CKD stages by the corresponding estimated glomerular filtration rate (eGFR; mL/min/1.73m2): <45 (CKD stage 3b and higher; n=339), 45-59 (CKD stage 3a; n=467), ≥60 (CKD stage 2 and lower; n=2334). BP (office, 24h ambulatory BP), eGFR changes from baseline through 12 months were compared between groups. Comparisons between groups were made after adjusting for baseline BP and change in number of antihypertensive drug classes from baseline. Results At baseline, office systolic SBP (OSBP) in eGFR groups <45, 45-59, and ≥60 ml/min/1.73 m2 was: 164±25, 163±26 and 165±25 mmHg, respectively (p=0.083). 24-h ambulatory systolic BP (ASBP) was: 156±19, 153±20 and 154±19 mmHg, respectively (p=0.082). Mean eGFR was: 32.5±11.2, 53.6±4.4, and 86.8±18.6 ml/min/1.73 m2, respectively. A total of 1.1% of patients were on dialysis. Patients in eGFR group <45 ml/min/1.73 m2 were significantly older, had higher rates of ischemic heart disease, heart failure, diabetes, on more antihypertensive drug classes compared to higher eGFR groups. Patients were on 5.0±1.3, 4.6±1.3, and 4.5±1.4 antihypertensive drugs in eGFR <45, 45-59 and ≥60 ml/min/1.73 m2 groups, respectively (p<0.001). At 12 months, all had significant OSBP drop from baseline within the different eGFR groups (p<0.001). OSBP changed by -10.8±27.8, -10.5±25.9 and -14.7±26.6 mmHg in eGFR <45, 45-59 and ≥60 ml/min/1.73 m2 groups, respectively (adjusted p=0.095; Figure 1A). Similarly at 12 months, all patients had significant ASBP reductions from baseline across the eGFR groups (p<0.01). ASBP changed by -5.2±18.0, -6.9±18.8, and -8.5±18.8 mmHg in eGFR <45, 45-59 and ≥60 ml/min/1.73 m2 subgroups, respectively (adjusted p=0.16). At 12 months, eGFR did not significantly change from baseline in eGFR <45 and 45-59 ml/min/1.73 m2 groups (Figure 1B): 0.1±14.6 (p=0.92) and -0.6±12.8 ml/min/1.73 m2 (p=0.45), respectively. Estimated GFR changed from baseline by -5.6±15.5 ml/min/1.73 m2 in eGFR ≥60 ml/min/1.73 m2 group (p<0.001). Between group differences in eGFR changes were statistically significant (adjusted p<0.001), but by a numerically small difference. The no. of antihypertensive drug classes changed by -0.2±1.3, -0.1±1.0 and -0.1±1.0 in eGFR <45 and 45-59 ml/min/1.73 m2 groups, respectively. Conclusion Patients with uncontrolled HTN with different CKD severity including those with eGFR <45 ml/min/1.73 m2 had significant SBP reductions from baseline through 12 months, whilst renal function was preserved.Figure 1

Bringing interactive elements into classes: Augmented reality-based learning media development for electrical measurement subjects in vocational education

This study aims to develop and evaluate Augmented Reality (AR)-based learning media to improve student interest at SMKN 1 Kuantan Mudik. AR, which integrates virtual objects into the real world, is expected to enrich the learning experience through innovative visual and interactive elements. This research employs a Research and Development (R&D) which includes preliminary research, prototype creation, student response assessment, and systematic reflection. The AR-based learning media prototype was developed using Assemblr Edu software and evaluated by media experts, content specialists, and students. The validation results indicate that the media is highly viable, receiving a score of 92.7% from content experts and media specialists. Student trials produced ratings of 88.9% for effectiveness and 90.3% for engagement. The findings demonstrate that AR-based learning media significantly enhance student interest and involvement in the learning process. This study concludes that augmented reality learning media substantially improve educational experiences in vocational settings, showing potential for broader implementation across various subjects. However, this research is limited to expert validation processes and primarily focuses on student responses rather than measuring learning outcomes. This study is anticipated to provide a foundation for developing more comprehensive and effective learning media.

Measuring Minds: How Scientists Study How People Understand Others

In this article, we explore the science of understanding others’ minds. Specifically, we discuss how scientists try to study the processes of understanding the thoughts and feelings of other people (known as mentalizing) and of sharing other people’s emotions (known as empathizing). Understanding others is important because it helps people to build strong social connections with their friends, family, and people in their community. However, when people struggle with understanding others it might negatively impact their mental health or cause difficulties in their daily lives. Scientists are working hard to measure how people understand others—in the laboratory and in the real world. They use questionnaires and tests, observe people, track behaviors with mobile phones, and even image the brain. We will describe these methods and discuss how researching the understanding of others might help improve the lives of young people like you.

Undiagnosed Diabetes Mellitus is an important risk factor in secondary prevention after an acute coronary syndrome and warrants active screening

Abstract Background/Introduction Previous studies have shown that patients with Diabetes Mellitus (DM) undergoing percutaneous coronary intervention (PCI) for an acute coronary syndrome (ACS) have an increased ischemic risk compared to non-diabetics. This has led to the recommendation to take DM into account when considering extended dual antiplatelet therapy (DAPT) to prevent ischemic events. Although screening for DM can simply be conducted by measuring HbA1c values, the ACS guidelines do not yet recommend to screen for DM de novo. This may lead to undertreatment. Purpose We aimed to determine the ischemic risk of previously diagnosed DM and of DM de novo compared to patients without DM in a real world ACS population. Methods We included patients from the South East (Zuid Oost) Netherlands Heart Registry (ZON-HR) undergoing PCI for ACS without using oral anticoagulants and compared outcomes between DM and non-DM patients. In a subgroup of patients without previously diagnosed DM with available HbA1c measurements at baseline, we compared outcomes between patients with or without DM de novo (HbA1c ≥48 mmol/mol). All analyses were performed using Cox regression analysis. We used multivariate analysis to adjust for known ischemic risk factors. Results Of the 2406 patients included, 426 were previously diagnosed with DM. Additional ischemic risk factors, such as a history of myocardial infarction (MI), multivessel disease and kidney disease, were significantly more often present in patients with DM. Patients with DM showed numerically more major adverse cardiac and cerebral events (MACCE). However, this was not significant (HR: 1.24, 95% CI: 0.92-1.66). All-cause mortality was higher in patients with DM at 30 days (HR: 1.51, 95% CI 1.00-2.29) and 1 year (HR: 1.55, 95% CI 1.10-2.18), which remained significant at 1 year when corrected for additional risk factors. The HbA1c values at baseline were available in 387 patients without previously diagnosed DM. In this subgroup, 69 (18%) patients showed an elevated HbA1c level of ≥48 mmol/mol. Outcomes within this subgroup are presented in table 1. Patients with de novo DM showed significant more ischemic events after one month and one year follow-up compared to patients without DM de novo. Figure 1 depicts the survival from MACCE over time in these subgroups. Conclusion In our real world population of ACS patients undergoing PCI, we found no significant difference in ischemic risk between patients with previously diagnosed DM compared to non-DM. However, all-cause mortality was significant higher in DM patients. Active screening for DM resulted in a large proportion of patients with DM de novo who showed a major increase in ischemic risk. These results demonstrate the importance of screening for DM in ACS patients undergoing PCI.

Real-life experience with rilonacept for the treatment of recurrent pericarditis

Abstract Background Rilonacept, a soluble Interleukin-1 (IL-1) receptor fusion protein that neutralizes IL-1α and IL-1β, has shown efficacy in symptom resolution, weaning of standard-of-care therapies, and reducing the frequency of recurrent pericarditis (RP) episodes in clinical trials. Purpose We aimed to review the efficacy, safety, and duration of treatment with Rilonacept reliance in managing RP in our practice. Methods We analyzed 22 patients with RP treated with Rilonacept, 55 [43-69] years, 11 (50%) females. We reviewed clinical characteristics and outcomes, including the time since initial diagnosis of pericarditis, the presence of pericardial effusion/thickening, the duration of Rilonacept treatment, the ability to wean off steroids, and the recurrence of pericarditis symptoms attempting discontinuation. Results The length of time from the initial diagnosis of pericarditis to Rilonacept initiation was 9 [4-32] months. Fifteen patients out of 22 (68%) had pericardial effusion, 3 (20%) with tamponade requiring pericardiocentesis. Median length of treatment with Rilonacept was 14 [6-23] months, with 17/22 (77%) of patients being treated for ≥ 6 months. All patients who were on steroids (14/22, 64%) were able to discontinue their usage 1 [1-9] months after starting Rilonacept. Of the seventeen who were treated for 6 months or more, 12 (70%) remained on Rilonacept 160 mg weekly at the most recent assessment, 3 (18%) continued treatment with Rilonacept 160 mg every 2 or 4 weeks, and 2 (12%) discontinued Rilonacept treatment after 6 and 50 months. Of the 12 patients who remained on weekly treatment after a period of 6 months, 8 (67%) required Rilonacept for symptom control, 1 (8%) had recurrent symptoms after treatment every 2 weeks, and the remaining 3 (25%) preferred to continue despite a lack of symptoms (Figure 1). Conclusions The efficacy of Rilonacept in treating patients with RP and the ability to stop steroid therapy in the real world is in line with the efficacy data from clinical trials.Figure 1

Survival Improvement of StageIV Non-small Cell Lung Cancer in the Immunotherapy Era: A Retrospective Cohort Study in a US Population.

Immune checkpoint inhibitors (ICIs) greatly improved outcomes of stageIV non-small cell lung cancer (NSCLC) in randomized clinical trials. Limited data exists regarding the survival improvement of ICI use at the population level. Clinical data of patients with pathologically confirmed stageIV NSCLC diagnosed in 2013 and 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Survival outcomes were compared before and after ICI use to assess the survival improvement in the immunotherapy era in the real world. A total of 19,433 patients with stageIV NSCLC were included. Being female, age < 60years, of American Indian and Asian or Pacific Islander race, married, non-squamous histology, without bone, brain, or liver metastases, and receiving chemotherapy were significantly associated with better prognosis in multivariable analyses. Propensity score matching (PSM) based on associated factors resulted in 8743 patients each in the non-immunotherapy and immunotherapy groups (1:1 ratio). After PSM, both overall survival (OS) (p < 0.001) and cancer-specific survival (CSS) (p < 0.001) were significantly improved in the immunotherapy group. The median OS (mOS) was 6.0months in the non-immunotherapy group and 8.0months in the immunotherapy group. The 1-, 2-, and 3-year OS rate was 29.0%, 14.2%, and 8.5% in the non-immunotherapy group, and 37.8%, 23.5%, and 16.7% in the immunotherapy group, respectively. Patients who were male, under 60years old, married, white, had adenocarcinoma, had no bone or liver metastases, and received chemotherapy or radiation therapy were more likely to benefit from immunotherapy. Survival outcomes of patients with stageIV NSCLC were significantly improved in the immunotherapy era. Population-level benefits of survival varied among subgroups, and not all the increase in OS meant a clinically meaningful benefit.

Real-world evidence on pulmonary arterial hypertension: interim analysis from the Italian observational study INSPECTIO

Abstract Background Pulmonary arterial hypertension (PAH) is a rare, progressive disease leading to right-sided heart failure. The interest in risk assessment based on non-invasive parameters is growing, and insights from clinical practice are needed in this regard. INSPECTIO is an Italian observational study aimed at filling this knowledge gap. The results of an interim analysis at month 12 are presented below. Purpose The primary objective was to assess the change from baseline to month 12 in the number of the non-invasive low-risk parameters among World Health Organization functional class, 6-minutes walking distance, Brain Natriuretic Peptide (BNP) or N-terminal proBNP. Secondary objectives are the evaluation of echocardiographic and haemodynamic parameters, and the proportion of patients in which the therapy was optimized according to the guidelines. Methods Prospective, multicentre study on PAH patients at low/intermediate mortality risk treated with macitentan and/or selexipag as part of the oral combination therapy. Results Among 177 patients who were enrolled in 29 centres, 148 patients [median age 63.0 years (Q1/Q3: 53.5/73.0), 76.4% females] completed the 12-month follow up and were considered for this analysis. The median time from PAH diagnosis was 22.6 months (4.9/60.1). Sixty-four (43.2%) patients had idiopathic PAH; 4 (2.7%) heritable; 80 (54.1%) associated with other diseases [58 (72.5%) connective tissue disease, 11 (13.8%) congenital heart disease corrected for at least one year, 5 (6.3%) portal hypertension, 5 (6.3%) human immunodeficiency virus infection, 1 (1.3%) drug and toxins]. At baseline, 45.9% patients and 28.4% were in double and triple oral combination therapy, respectively. Primary objective: at month 12, the number of noninvasive low-risk parameters increased in 43 (29.1%) patients and remained stable in 80 (54.1%) patients [mean change 0.16 (p=0.017)]. The values at baseline, at month 12 and the change from baseline for each noninvasive parameter are shown in Table 1. Mean right atrial (RA) area (end-systole) and tricuspid annular plane systolic excursion (TAPSE) remained unchanged while a reduction of systolic pulmonary artery pressure (sPAP) was observed. Regarding the haemodynamic parameters, the mean pulmonary arterial pressure decreased [median change -4.5, (p=0.0346)], while cardiac index, pulmonary vascular resistance, and RA pressure remained stable (Table 2). The number of patients on triple therapy increased from 42 to 51 (+21.4%). Conclusions This study confirms that a noninvasive low-risk profile can be achieved with current combination PAH therapy. The modest or absent changes in echocardiographic and hemodynamic parameters suggest that treatment of PAH in real world is yet to be improved; on the other hand, the optimization of therapy in a significant portion of patients can possibly account for the improvement or stabilization observed.Noninvasive parametersEcho and hemodynamic parameters

Transcatheter mitral replacement: what are the outcomes of un-eligible patients compared to treated?

Abstract Background/Introduction Transcatheter mitral valve replacement (TMVR) is emerging in recent years as a promising tool to treat mitral regurgitation, however its applicability in the real world remains limited. Purpose The aim of the study is to assess the real-world screening success rate of TMVR in native anatomy and the 1-year outcomes of both accepted and refused patients as well as clinical results. Methods Retrospective analysis was performed on all patients screened for TMVR at our Valve Center, eligible for 1-year follow-up. In-hospital data of all patients admitted to our Department are prospectively collected. Follow-up was done through outpatient visits and/or telephone calls. Results Out of 3400 patients referred to mitral treatment at our department between January 2016-January 2022, 92 were submitted to screening for TMVR. Among these, 48 patients (49%) were accepted and treated with TMVR while 44 (44.8%) were refused (RG). The main reasons for rejection were anatomy unfeasibility in 25 patients (59%) and frailty in 5(11%). Main reasons for anatomy unfeasibility were risk LVOT obstruction (n=15; 60%), annular dimension (n=8; 33%) and ventricular dimension (n=2; 8,3%).Major baseline characteristics between groups were similar including age (85 vs 84), STS (12 vs 13), ejection fraction and LVEDD. However, refused patients had higher filtration rate than TMVR (80 vs 45 ml/min respectively (p=0.001)).All patients accepted were treated with TMVR: 7 patients received Tiara and 24 Tendyne. Procedure success in the TMVR group was 96% (46/48). Patients refused from TMVR were treated with Mitraclip in 5(11%) cases, 37(84%) were left in medical therapy and 2 (4,5%) underwent surgery. 1-year overall survival 65.2±51.3 vs 54.8±36.5 in TMVR and refused group respectively (p=0.002)(Figure 1). 6 deaths (2 cardiac, 33%) occurred in the TMVR compared to 37 (32 cardiac, 86%) in the refused group. Freedom from Cardiac death was 98±19% TMVR vs 75±65% (p&amp;lt;0.001)(Figure 2). NYHA class improved in 98% of cases in TMVR group but worsened in 80% in refused group, (p&amp;lt;0.001). TMVR screening failure is associated with increased cardiac death (HR 12 [1,51;95], p&amp;lt;0,019) and death for any causes (HR 17,5 [6,02;51], p&amp;lt;0,001). Conclusion(s) In the present experience, approximately 50% of patients screened for TMVR were accepted. The most frequent reasons for screening failure were anatomical issues. With a baseline similar clinical profile, treatment with TMVR provided significant 1-year survival and symptoms improvement compared to those of patients refused, whose prognosis is indeed remarkably poor. These data underline the importance of proper patient selection for TMVR to achieve good outcomes but also the need for technological improvement of devices to expand the proportion of patients who can be treated. Given the small numbers currently available, more data are needed to confirm the present findings, which must be considered hypothesis-generating.Figure 1Figure 2

Connections and choice for high schoolers

Chronic absenteeism is a symptom of a lack of student engagement. Many students feel that schools are not welcoming places and that what they learn in the classroom is not applicable in the real world. Schools like Metropolitan Regional Career and Technical Center (the Met) in Rhode Island offer an alternative to educating high school students that taps into their need for connection to adults and the world outside the classroom. The Met is the first school founded by Big Picture Learning, which has grown into a network of public schools across the country and internationally. Its interest-based learning approach gives students opportunities to explore internships and projects based on their interests and passions. The students devote two days a week to internships during the school year.

A retrospective study on real world, 2-stent left main bifurcation PCI using DK crush technique with IVUS guidance - a single center experience

Abstract Objectives The aim of this study is to investigate clinical outcome of the IVUS guided 2-stent bifurcation strategy using DK crush technique performed in a complex Left Main (LM) bifurcation lesions defined according to DEFINITION study in our local setting. We seek to assess the composite endpoint of target vessel failure (TVF) at 9-12 months. Methods All patients underwent IVUS guided 2-stent Bifurcation PCI with DK crush technique for complex LM bifurcation lesions defined by the DEFINITION criteria performed in a heart institute from 1.1.2019 to 31.7.2023 were included..Patient baseline characteristics, post-procedural and 12-months follow-up outcomes including cardiac death,myocardial infarction (MI),rate of target vessel failure (TVF),rate of stent thrombosis (ST) and major adverse coronary event (MACE) were analysed.Exclusion criteria are patients age &amp;lt;18 years and previous stenting in the target vessel Results A total of 50 patients were included in this analysis. Mean age was 64.3±9.1 years with predominant males (n= 38, 76%).Majority were hypertensive (n=37, 74%) and diabetes mellitus accounted for 32 (64%) cases.Patients with pre-existing coronary artery disease were 39 (78%) cases. 40% presented with history of recent myocardial infarction (MI), 12% had new onset angina and 6% had heart failure. Pre-existing chronic renal failure (18%) and history of CVA (2%). Among chronic renal failure cases, 50% had eGFR &amp;lt;50 during index procedure.Additionally, previous PCI was performed in 22 cases (44%) and 2 previous CABG cases included (4%).Majority of the cases were performed as staged elective procedure ( n=45, 90%) and others were indicated for ACS ( n=5, 10%). Radial approach was predominantly preferred with 25 cases (50%), where additional 5 cases (10%) were converted to femoral approach due to severe radial spasm. Among these 50 cases, 1 case required additional PCI to CTO LAD and mid LCX, while 7 cases (14%) had calcified lesions requiring scoring / cutting balloons and atherectomy device utilization for adequate lesion preparation prior to bifurcation stenting.All 50 patients received combination of both aspirin and a P2Y12 inhibitors for 12 months. Follow up done at at 30-day, 60-days and 1 year after the index procedure.Clinical follow-up were available in 46 (92%) patients only.4 cases were lost to follow up due to logistic reasons. At 1 year follow-up, cardiac death occurred in 5 (10.9%) patients, out of which 3 (6.5%) cases were cardiac related and 2 (4.4%) are non-cardiac. Major adverse cardiac events (MACE) and target vessel failure (TVF) occurred in total 4 (8.7%) cases, where 3 (6.5%) cases resulted in cardiac death and 1 (2.2%) case had MI and clinically driven target lesion revascularization. Conclusion Our experience demonstrates that IVUS guided, upfront 2-stent Bifurcation PCI using DK crush technique for complex bifurcation lesions is effective and safe with a low MACE and TLR rate at 1 year follow-up.

HiCorr: an influenza surveillance model using over-the-counter sales from community pharmacies

Abstract Background In large-scale community transmission, such as seasonal influenza, monitoring geographic trends and estimating the transmission intensity are critical to support public health decision-making. Previous studies have successfully used sales data from over-the-counter (OTC) products in community pharmacies to detect and monitor different epidemiological outbreaks, developing surveillance systems that are able to anticipate the load on primary care services and hospitals by up to 3 weeks. Methods The subset of OTC products sold in Portuguese community pharmacies was selected by correlating sales data to primary care attendance in previous flu seasons. This data pertained to daily coded episodes of influenza-like-illness (International Classification of Primary Care, 2nd Edition, code R80) in the Portuguese health cluster Oeste Sul. By fitting a moving epidemic method to historical sales data and then applying it to daily collected sales data, the developed index was used to anticipate the relative load to the primary care system as well as the start and the peak of epidemic activity for the current flu season. Results were compared to the public health data available on respiratory infections in Portugal. Results The model pinpointed the onset of the 2023-2024 flu epidemic in week 47 and its peak in week 52. The index curve showed a high correlation with the data published by the Portuguese national health service, with no time lag. However, the availability of consolidated public data was delayed, on average, by approximately two weeks. Discussion and conclusions Data from community pharmacies significantly enhance the early detection of seasonal flu trends, while reflecting population distribution. This underscores their invaluable contribution to public health assessments and the potential for improving the timeliness and accuracy of seasonal flu surveillance. Key messages • Community pharmacy data significantly enhance the early detection of seasonal flu trends. • Real world sales data maybe useful to support epidemic surveillance in public health.

Efficacy of online japanese intensive cardiac rehabilitation for secondary prevention for coronary artery disease: a comprehensive program including exercise, nutrition, mindfulness, and group support

Abstract Background/Introduction While comprehensive programs for cardiac rehabilitation are recommended for patients with coronary artery disease (CAD), systematic programs including nutrition, stress-management, and behavior change have not been clearly established. Purpose To comprehensively change the lifestyle of patients with CAD as secondary prevention, we developed an online based educational program "intensive cardiac rehabilitation for Japanese patients with CAD (J-ICR)" modifying ICR, a regimen covered by health insurance in the United States, to the program that has affinity with Japanese. Methods Online J-ICR program is set up as sessions for maintenance-phase CAD patients using an online application. J-ICR has 12 sessions held weekly for 3 hours per session, total 36 hours, aimed to integrate 4 components: 1) exercise guidance based on exercise prescription which contain aerobic exercise, resistance training, and multi-component exercise through online platforms, 2) dietary education focusing on "the Japan Diet", 3) stress management utilizing mindfulness, and 4) group support to enhance patient and medical-staff interaction. Twenty-two participants were randomly separated to Early Phase group and Late phase group. For verification of the efficacy of this program, we survey the adherence to the program and compared the changes in risk factor of CAD at 3 months defining Early phase group as intervention group and Late phase group as control. (Fig.1). Results After excluding 3 participants who withdrawn to participate, the remaining 19 participants were conducted the evaluation and 10 participants were in intervention group and 9 participants in control group, respectively. As for patient characteristics, the mean age was 66 years old, and all participants were male. History of CVD was comprising 8 cases of myocardial infarction and 15 cases of angina pectoris. As for the risk factors of CVD, there were not significant differences in mean low density lipoprotein (LDL) cholesterol (Intervention group 71.5mg/dl vs Control group 83.4mg/dl; p=0.12) or systolic blood pressure (SBP) (126mmHg vs 130mmHg; p=0.40) at base line between two groups. The average participating rate in program was 93.8% and there was no dropped out participant during the program in investigation group. After 3months, LDL cholesterol was not significantly decreased in both groups (mean reduction of Intervention group -0.3mg/dl, p=0.93 and control group -3.8mg/dl, p=0.43, respectively). However, there was significant reduction of SBP in intervention group (mean reduction 5.6mmHg, p=0.02) but in control group (mean reduction 2.4mmHg, p=0.42). (Fig.2). Conclusions This randomized controlled study showed the good adherence of J-ICR program and it suggested that J-ICR program has the effect on lowering systolic blood pressure at 3 months. Longer follow up data and the results of more participants are warranted to clarify the efficacy in real world prevention of CVD.

Complex versus non-complex, should we adjust the antiplatelet strategy to the type of percutaneous coronary intervention? Results from a real world PCI population

Abstract Background/introduction Personalized dual antiplatelet treatment (DAPT) using risk stratification is key to minimize bleeding- and ischemic events after percutaneous coronary intervention (PCI). Known ischemic risk factors include complex procedures which are integrated in the recommendation for extended DAPT in patients with additional ischemic risk factors. Purpose We aimed to provide insight whether a complex PCI (CPCI) should be regarded as an individual risk factor, regardless of other risk factors, to adjust the antiplatelet strategy. Also, we determined the effect of DAPT duration and choice of P2Y12 inhibitor on outcomes. Methods We included patients from the South East (Zuid Oost) Netherlands Heart Registry (ZON-HR) and excluded patients using oral anticoagulants. This PCI registry prospectively collects baseline-, procedural- and follow-up data including medication use and the intended DAPT duration. Patients were stratified to non-CPCI or CPCI comprising of bifurcation lesions with two stents, venagraft PCI, chronic total occlusion (CTO) or ≥ 60mm stent. Analyses were conducted using Cox regression analysis. Multivariate analysis was performed to adjust for risk factors and baseline differences. Results We included 3691 patients (842 CPCI). Table 1 demonstrates the baseline characteristics and DAPT strategy. CPCI was more often required in patients with a high ischemic risk profile based on the extensiveness of atherosclerosis and comorbidities. Non-CPCI patients more often underwent PCI for acute coronary syndrome. Outcomes are presented in table 2. Compared to non-CPCI, CPCI increased the risk of major adverse cardiac and cerebral events (MACCE) in the second half of the year as opposed to bleeding events, which more often occurred in the first months after CPCI, driven by access site bleedings (73% in CPCI versus 56% in non-CPCI, p=0.01). All-cause mortality was higher during the overall follow-up period after a CPCI compared to non-CPCI. These findings remain significant when corrected for additional risk factors in both groups. In patients with CPCI, treatment with ticagrelor or prasugrel strongly reduced MACCE between 6-12 months when compared to clopidogrel (multivariate HR: 0.28, 95% CI: 0.08-0.98), but did not influence bleeding events or all-cause mortality. No effect of extended DAPT was observed. Conclusions A CPCI is an important ischemic risk factor that could be used for risk stratification to guide antiplatelet strategy. Treatment with ticagrelor or prasugrel strongly diminished the risk of MACCE without increasing the bleeding risk in patients with a CPCI. As the risk of MACCE increases between 6-12 months after PCI while the risk of bleeding events diminishes in this period, extended DAPT from 6 to 12 months could also be considered to provide extended protection.Table 1.Table 2

Safety and effectiveness of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: insights from the SPUM-ACS study

Abstract Aims Data on Glycoprotein IIb/IIIa inhibitors (GPI) use in real world ACS patients following the introduction of potent P2Y12 inhibitors and newer generation stents are scant. Here, we aimed to assess the utilization, effectiveness, and safety of GPI in a large prospective cohort of contemporary ACS patients. Methods SPUM-ACS is a prospective, multicentre study in which ACS patients between 2009 and 2017 were recruited. The primary endpoint of the present study was major adverse cardiovascular events (MACE), a composite of all-cause death, non-fatal myocardial infarction (MI) and non-fatal stroke at one year. Any bleeding events, BARC 3-5 bleeding, and net adverse cardiovascular events (NACE) comprised the secondary endpoints. Results A total of 4395 ACS patients were included in the analysis. GPI-treated patients had more total coronary artery occlusion (56% vs 35%, p&amp;lt;0.001) and thrombus (60% vs 35%, p&amp;lt;0.001) at angiography. Among the propensity score matched (PSM) population (1992 patients equally split into two groups), GPI-treated patients showed lower MACE risk (PSM adjusted HR 0.70, 95% CI 0.49-0.99) but a higher risk of any (PSM adj HR 1.46, 95% CI 1.06-1.99) and major bleedings (PSM adj HR 1.73, 95% CI 1.09-2.76), resulting in a neutral effect on NACE (PSM adj HR 0.87, 95% CI 0.65-1.17). These results remained consistent across all subgroups. When including only patients treated with potent P2Y12, the incidence of MACE was not different between the two groups, (log rank p=0.50 and PSM adjusted HR 0.94, 95% CI 0.60-1.48). In the PSM population, GPI use (HR 0.76, 95% CI 0.59-0.99, p=0.04), TIMI 3 at the end of the procedure (HR 0.16, 95% CI 0.08-0.30, p&amp;lt;0.001) and potent P2Y12 inhibitor use (HR 0.70, 95% CI 0.49-0.99, p=0.04) were protective independent predictors of MACE at follow-up, while oral anticoagulation at discharge (4.48, 95% CI 2.10-9.52, p&amp;lt;0.001), multivessel disease (HR 1.95, 95% CI 1.09-3.48, p=0.02) and KILLIP class ≥ 2 at admission (HR 1.98, 95% CI 0.99-3.95, p=0.05) were adverse independent predictors. Conclusion In ACS patients undergoing PCI and broadly treated with potent P2Y12 inhibitors, GPI use reduced the risk of MACE at 1 year, while increasing the risk of major bleedings, with a neutral effect on NACE. The routine use of these pharmacological agents should be discouraged, while in selected patients GPI use should be considered following personalized balancing between ischaemic and bleeding risk.Events in PSM populationEvents in PSM population

Real world economic evaluation of CT-FFR in patients with suspected coronary artery disease

Abstract Background Incorporation of CT-derived fractional flow reserve (CT-FFR) enhances the precision of Coronary CT Angiography (CCTA) to detect hemodynamically significant coronary artery disease (CAD). However, the financial consequences remain unclear. Purpose Our objective is to assess the economic implications of CT-FFR in the Dutch Healthcare system. Methods This retrospective, single-center cost effectiveness analysis includes patient data of a previously published study assessing the impact of routine CT-FFR availability on clinical management. We collected medical resource use for both diagnostic and therapeutic cardiovascular care with a follow-up duration of 1 year. Costs of CT-FFR analysis were set at €1000, its current price for Dutch hospitals. Median total costs at were compared using the Wilcoxon rank sum test, including a sensitivity analysis in which cost estimations (without registered maximum tariffs) were increased or decreased with 10%. Results A total of 360 patients, classified as having low to intermediate risk of CAD, were enrolled in the study – 224 in the CCTA group and 136 in the CT-FFR group. In addition to undergoing more (invasive) diagnostic testing and revascularization procedures over the studied period, patients in the CCTA-group had more outpatient clinic consultations (p&amp;lt;0.001), presented more frequently to the emergency department (p=0.035) and spend more nights in the hospital (p=0.11). Median costs were €3.347 (IQR €1.066 – €4.862) in the CCTA-group and €1.436 (IQR €1.362 - €3.943) in the CT-FFR group (p=0.091). Increasing cost estimation with 10% revealed a median of €3.431 in the CCTA-group versus €1.479 in the CT-FFR group (p=0.078), decreasing with 10% showed median costs of €3.263 in the CCTA-group and €1.392 in the CT-FFR group (p=0.118). In our sample, CT-FFR guided care would have been significantly cheaper than CCTA-guided care at or below a market price of €770. Conclusion Despite the significant reduction in additional diagnostic testing and hospital visits in the CT-FFR group, CT-FFR guided care was not cheaper than CCTA-guided care at its current market price of €1.000. Economic cost-effectiveness would have occurred from a price of €770 per analysis. The large difference between medians suggests that the lack of significance might partially be attributed to insufficient power in this relatively small sample size. Additionally, this study did not account for costs associated with loss of productivity and quality of life. However, less additional diagnostic testing, less revascularization procedures and less hospital consultations and admissions leads to reduction in hospital resource consumption and patient burden, which is an important advantage of CT-FFR as the number of referred patients increases yearly.