Therapy Research Articles

Estimated plasma volume in heart failure with reduced ejection fraction: ACE inhibitors versus angiotensin receptor/neprilysin inhibitor in follow up

Abstract Background Estimated plasma volume status (ePVs) has been considered a biological surrogate for congestion and has been shown to be associated with post-discharge outcomes in patients with heart failure with reduced ejection fraction (HFrEF). The plasma volume status can be easily estimated by the index of the PVs according to the haemoglobin and haematocrit levels. Purpose The aim of the study was to examine the change in ePVs and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels during the 12-month follow up of HFrEF patients treated with ACE inhibitors (ACEi) and angiotensin receptor/neprilysin inhibitor (ARNI). Methods We included all patients treated or diagnosed with HFrEF in our hospital from May 2021 to February 2022 and prescribed with either ACEi or ARNI among complete guideline-directed medical therapy (GDMT). We used Strauss-derived Duarte formula [ePVs= (100-Hct%) ÷ Hb] to estimate PVs during the initiation of GDMT and after 12-month follow up. Results This registry-based study included 619 patients with HFrEF, out of which 278 were prescribed with ACEi (ACEi group) and 273 with ARNI (ARNI group). There were no differences between the groups regarding age (ACEi 68 vs. ARNI 67 years, p=0.09), however, ACEi group had significantly more women (30% vs. 26% of patients, p=0.02). Patients in ACEi group were more likely to have ischemic cardiomyopathy (61 vs. 49%, p<0.01), higher estimated glomerular filtration rate (72 vs. 64 L/min/1.73m², p=0.01), while patients in ARNI group were more likely to be NYHA III class (40 vs. 48%, p=0.04). Initial ePVs (4.23 for ACEi vs. 4.20 for ARNI, p=0.46), NT-proBNP levels (3357.5 for ACEi vs. 2786 for ARNI, p=0.08), and left ventricular ejection fraction (median 35% for ACEi vs. 35% for ARNI, p=0.49) did not significantly differ between the groups. After the 12-month follow up, the change in ePVs was similar between the groups (-0.22 for ACEi vs. -0.19 for ARNI, p=0.93). Reduction of NT-proBNP levels was more prominent in ACEi group (1750.5 vs. 858.5 pg/mL, p=0.01). Mortality rate did not differ between the groups during 12-month follow up (9.71% in ACEi vs. 8.42% in ARNI, p=0.60). Conclusion In HFrEF patients both ACEi and ARNI reduced ePV and NTproBNP levels during 12-month follow up. ACEi were more potent in reducing NT-proBNP levels. Despite the more prominent reduction in NT-proBNP levels, no significant difference was observed in mortality rate during follow up between the groups.

The dynamic increment of epicardial adipose tissue is associated with reverse remodeling after guideline-directed medical treatment in dilated cardiomyopathy patients

Abstract Background/Introduction Epicardial adipose tissue (EAT) accumulation is associated with adverse prognosis in patients with HFpEF and a better prognosis in HFrEF patients. Whether EAT is playing a protective role in dilated cardiomyopathy (DCM) patients have been described sparingly. Purpose Aim to explore whether the epicardial fat would change along with the dynamic changes in cardiac function and volumes after receiving guideline-directed medical therapy (GDMT) in patients with DCM. Methods We prospectively enrolled 232 DCM patients who underwent complete baseline and follow-up Cardiac magnetic resonance (CMR) examinations. The measurement of the epicardial fat composition includes epicardial fat thickness, paracardial fat thickness, and paracardial fat volume, while the measurement of body fat composition includes subcutaneous and visceral abdominal fat, while We used univariable and multivariable logistic regression to evaluate the association between different body and cardiac fat depots with the changes in bi-ventricular structure (delta indexed EDV) and function (delta EF). Results The study included 232 patients (mean age 46.1±14.1 years, 157 (67.7%) males). After GDMT, we found that the visceral fat thickness and EAT (thickness and volume) tend to significantly increase. The increase in the (left ventricular reverse remodeling) LVRR group was significantly higher compared with the non-LVRR group. Independently with the changes of BMI and body fat depots, the increment of EAT was associated with the improvement in bi-ventricular function and volumes (significantly positively correlated with the improvement of LVEF (r = 0.499, p < 0.001), and RVEF (r = 0.482, p < 0.001), negatively correlated with delta LVEDVi (r = -0.407, p < 0.001), delta RVEDVi (r = -0.305, p < 0.001)). Conclusions After GDMT, the increment of EAT was positively correlated with the improvement of bi-ventricular structure and function, independent of the changes in BMI and body fat depots.Graphic Abstract

The association between elevated systemic inflammation response index and long-term mortality in patients with triple-vessel coronary disease

Abstract Background Inflammation is a critical factor in the development of coronary artery disease. The systemic inflammatory response index (SIRI) is a novel biomarker of inflammation. Studies have shown that SIRI is associated with the severity of coronary artery disease. However, there is currently a lack of research on the relationship between SIRI and adverse outcomes in patients with multivessel coronary artery disease. Our study aimed to investigate the correlation between SIRI and long-term mortality risk in patients with triple-vessel coronary disease (TVD) and explore the interaction between SIRI and treatment strategies. Methods After excluding patients with missing data or loss to follow-up, a total of 8559 patients with TVD were included in our study. Based on their SIRI levels during hospitalization, patients were evenly divided into three groups (SIRI-L, SIRI-M, and SIRI-H). All patients received appropriate treatment, including medical therapy alone (MT), percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG). The primary endpoint was all-cause death. SIRI was calculated by the formula: neutrophil counts × monocyte counts / lymphocyte counts. Results During a median follow-up of 6.58 years, a total of 1264 all-cause deaths (14.8%) were recorded. Elevated SIRI was significantly associated with increased mortality rates (11.1%, 14.6%, and 18.6% in the SIRI-L, SIRI-M, and SIRI-H groups, respectively). The risk of all-cause mortality was significantly higher in the SIRI-M and SIRI-H groups compared to the SIRI-L group (adjusted HR: 1.203, 95% CI: 1.037-1.395, p=0.015; adjusted HR: 1.400, 95% CI: 1.212-1.617, p<0.001; respectively). In elderly patients, the relationship between elevated SIRI and the risk of all-cause mortality was more pronounced, while it attenuated in younger patients. Additionally, it is noteworthy that there was an interaction between SIRI and treatment strategy (p=0.037). In patients of the SIRI-L group, there was no significant difference between PCI and CABG treatment. However, in patients of the SIRI-M and SIRI-H groups, CABG shows a significant survival advantage over PCI. Conclusion Evaluating SIRI may help identify high-risk groups among patients with triple-vessel coronary disease and guide the selection of treatment strategies.Kaplan-Meier curves

REDUCE-HF: a stronger heart go a long way

Abstract Introduction/Purpose Heart failure (HF) is a serious cardiovascular condition with a significant global health concern. The risk of heart failure rehospitalisation is high globally and locally, the 30-day HF readmission was about 32% from a local study (1). The study aims to adopt an intensive treatment strategy similar to Strong-HF trial (2) and evaluate rapid up-titration of guideline directed medical therapy (GDMT) and close follow-up will improve patients' outcomes after acute heart failure (AHF). Objectives The Reduction of Decompensation and Unnecessary Cardiac failure Emergency admissions: ambulatory Heart Failure service model (REDUCE-HF) is a non-randomised prospective study evaluating clinical outcome of patients discharged from AHF. Exclusion criteria included primary valvular disorders, end-stage renal failure and metastatic cancer. After HF discharge, eligible patients were recruited into our REDUCE-HF program irrespective of LVEF. They were subsequently managed in our ambulatory HF centre within two weeks, where intensive up-titration of GDMT and close follow-up would be proceeded. The data of our service model will be compared with our 5-year historical cohort. Primary outcome comprised of all-cause mortality and heart failure hospitalisation. Secondary outcome will be comparison of clinical and functional status at baseline and 3-month on follow up. Results Between October 2022, and December 2023, 245 patients were successfully recruited into our REDUCE-HF service model. Historical cohort of 6867 patients with primary diagnosis of acute heart failure were served as control (usual care pathway), data extracted from 2018 to 2022. Their mean age was 67.8+/-12.2 and 72.2%were male. 60% of them were HFrEF (EF<=40%) and 28% were ischaemic cardiomyopathy. The mean follow up period was 3 months. At 90 days, REDUCE-HF cohort group has shown much lower all-cause mortality than usual care group (2.5% vs 9.3%, HR 0.26, 95% CI 0.18-0.41, p<0.001). There was a much lower incidence of heart failure hospitalisation in REDUCE-HF group as compared to control (8.6% vs 13.1%, HR 0.65; 95% CI 0.55 to 0.74, p<0.01). In secondary outcome, there was significant reduction of NT-ProBNP of 45.2% (from 4229 to 2319pg/m, p<0.001), tremendous increment of 6-minute walk test (from 211 to 250m, p<0.001) and remarkable improvement of KCCQ score from 55.1 to 86.7, p<0.001. The overall LVEF was significantly increased from 39% to 44%, p<0.05. The positive outcome were attributed to good adherence to GDMT: ACEi/ARB/ARNI 91%, Betablocker 90.3%, MRA 72.4% and SGLT2i 95.5%. Conclusion The REDUCE-HF ambulatory service model has been proven effective in reducing mortality, decompensation and preventing unnecessary heart failure hospitalisation in this prospective study. By intervening proactively, this model not only enhances the quality of life but also hold promise in alleviating the burden of in-patient services on heart failure.

Guideline-Directed Medical Therapy Intolerance in Heart Failure.

This Teachable Moment discusses guideline-directed medical therapy intolerance in a woman in her 80s with heart failure with reduced ejection fraction and transthyretin amyloid cardiomyopathy.

Effects of empagliflozin on myocardial transcriptome in rats with aortic stenosis-induced heart failure

Abstract Introduction Aortic stenosis (AS) represents one of the most prevalent valvular heart diseases and an important cause of heart failure. Currently, no medical therapies influence the natural history of aortic stenosis. Although sodium glucose co-transporter 2 inhibitors (SGLT2i) have improved cardiovascular outcomes in heart failure patients with both reduced and preserved ejection fraction, their action mechanisms are not clear. Transcriptome analysis present great potential to identify biomarkers of disease and to gain insight into disease pathophysiology. In this study, we analyzed myocardial mRNA profile in aortic stenosis rats treated with empagliflozin. Methods Eighteen weeks after supra-aortic banding surgery, male Wistar rats were divided into 3 groups: Sham (n=15); aortic stenosis (AS, n=27); AS+empagliflozin (AS-EMP, n=27). Empagliflozin (10 mg/kg/day) was added to rat chow for 8 weeks. Transcriptome of left ventricle (LV) myocardium was studied by RNA-sequencing (sample size: 5 per group). Differential gene expression was analyzed in R environment using the DESeq2 package. Genes were considered differentially expressed (DEG) when they exhibited a log2 fold change (log2FC) higher than 1 (upregulated) or lower than -1 (downregulated), coupled with an adjusted p-value below 0.05. Functional enrichment analysis using gene ontology was performed by the online tool Enrich. Statistical analysis: ANOVA and Tukey. Results AS-EMP had lower LV diastolic diameter (Sham 8.39±0.57; AS 9.80±0.53*; AS-EMP 9.08±0.87# mm; p<0.05: * vs Sham; # vs AS), left atrium diameter (Sham 5.68±0.40; AS 9.67±1.00*; AS-EMP 8.97±1.36*# mm; p<0.05: * vs Sham; # vs AS), and LV mass (Sham 0.85±0.11; AS 2.19±0.27*; AS-EMP 1.76±0.34*# g; p<0.05: * vs Sham; # vs AS) than AS. A total of 1246 differentially expressed genes were identified, comprising 663 upregulated genes (70 genes in AS vs SHAM; 593 in AS-EMP vs AS) and 583 downregulated genes (35 genes in AS vs SHAM; 548 in AS-EMP vs AS). Most of the differentially expressed genes were enriched in processes such as extracellular matrix and structure organization, signal transduction regulation, and substrate-dependent cell migration (AS vs SHAM), as well as myocardial contraction, negative regulation of programmed cell death, and mitochondrial membrane organization (AS-EMP vs AS). The main upregulated genes were Loxl1, Mfap4, Postn, Col8a1, Pi16, and Nppa in AS vs SHAM; and Mxra8, Zfta, Pnisr, Thoc1, and Ralbp1 in AS-EMP vs AS comparison. The main downregulated genes were Mxra8, Ralbp1, and Tubgcp6 in AS vs SHAM; and Itgb5, Ltbp2, Tmem109, Plec, and Rorc in AS-EMP vs AS comparison. Conclusion We identified myocardial genes and biological processes that are potentially involved in aortic stenosis-induced heart failure. Empagliflozin attenuates cardiac remodeling and modulates myocardial genes involved with myocyte contraction, apoptosis, and mitochondrial organization in aortic stenosis rats.

Safety and efficacy of aspiration thrombectomy with intracoronary tirofiban VS aspiration thrombectomy alone in patients undergoing primary PCI: a systematic review and meta-analysis

Abstract Background Primary percutaneous coronary intervention (PPCI) may be complicated by intracoronary thrombus accumulation in ST elevation myocardial infarction (STEMI) leading to decrease in myocardial perfusion and increase in infarct size. The utilization of aspiration thrombectomy and intracoronary tirofiban in STEMI patients undergoing PPCI hold clinical relevance by removal of thrombus burden, potentially reducing distal embolization and improving myocardial perfusion and by targeting platelet aggregation to mitigate thrombotic complications, respectively. Given the paramount importance of achieving rapid and effective reperfusion in STEMI, the evaluation of these interventions is warranted to assess overall impact on patient outcomes in terms of safety and efficacy. Purpose The current meta-analysis aims to investigate the clinical outcomes of aspiration thrombectomy (AT) with intracoronary tirofiban versus AT alone during PPCI. Methods A systematic search for randomized controlled trials that evaluate the safety and efficacy of aspiration thrombectomy with intracoronary tirofiban in STEMI patients who underwent PPCI was done using PubMed, MEDLINE, Embase, Cochrane, Clinicaltrials.gov. and Herdin PH. Studies included those between 2010 - 2023 and involved human subjects. Search terms included "Aspiration Thrombectomy", "Intracoronary Tirofiban", "Primary Percutaneous Coronary Intervention" and "STEMI patients". Results Four RCTs (n: 490 participants) were included in this meta-analysis comparing aspiration thrombectomy with intracoronary tirofiban versus aspiration thrombectomy alone in STEMI patients undergoing PPCI. The results revealed no statistically significant difference in ST segment resolution (RR 1.02, 95%, CI: 0.97 - 1.08, P = 0.41, I2 = 0%), myocardial blush grade 2-3, (risk ratio of 1.04, 95%, CI: 0.97 – 1.12, P = 0.22, I2 = 62%) and TIMI 3 flow (risk ratio of 1.0, 95% CI: 0.95 - 1.04, P = 0.87). The occurrence of major adverse cardiovascular events did not significantly differ between the two groups (RR 0.46, 95% CI: 0.19 – 1.09, P = 0.08, I2 = 0%). There was no statistically significant difference in terms of bleeding when combining intracoronary tirofiban to standard medical therapy (RR 1.35, 95% CI: 0.64 – 2.84, P= 0.78, 4 trials [490 patients]). Conclusion In primary percutaneous coronary intervention, MACE outcomes of aspiration thrombectomy with intracoronary tirofiban were similar to that for aspiration thrombectomy alone in terms of improving myocardial perfusion in STEMI patients without increasing the risk for bleeding. Our meta-analysis suggests that AT alone may be the more acceptable standard during PPCI when encountering heavy thrombus burden. Future validated studies may help further investigate the strategy of adding tirofiban during aspiration thrombectomy.1. Primary Outcomes2. Secondary Outcomes

Secondary erythrocytosis / polycythemia due to sodium glucose co-transporter 2 inhibitors: a real world heart failure cohort

Abstract Background Sodium glucose co-transporter 2 inhibitors (SGLT2-i) are one of the four pillars of guideline-directed medical therapy in heart failure with reduced ejection fraction and preserved ejection fraction according to the current ESC and AHA/ACC heart failure guidelines 1,2. As a result, there has been a significant increase in their use worldwide. Although SGLT2 inhibitors are known to increase hemoglobin and hematocrit levels, there is a lack of data on the burden of erythrocytosis or polycythemia in pivotal trials 3,4. Purpose In this retrospective cohort study, we investigated the prevalence and clinical outcomes of SGLT2-i related erythrocytosis in a tertiary heart failure outpatient clinic. Methods We reviewed clinical data from heart failure patients treated with an SGLT2 inhibitor at our tertiary centre between September 2019 and October 2023. Patients were included if they were taking SGLT2-i continuously for more than one month. Data were collected on Hb/Hct levels at baseline before initiation of SGLT2-i, at peak levels during therapy and at the last follow-up. Erythrocytosis was defined according to the 2017 WHO classification as Hb> 10.3 mmol/L and/or Hct> 49% in men and Hb> 10.0 mmol/L and/or Hct> 48% in females. Results A total of 173 patients with heart failure were included (median age 58 [49-66] years, 65% male). One hundred and fifty-six patients (90%) were using dapagliflozin, while 16 patients (9%) were using empagliflozin. The overall prevalence of SGLT2i related erythrocytosis was 39/173 (22.5%; median age 60 and 82% males). Eleven (6.3%) patients had pre-existing erythrocytosis at baseline. During a mean follow-up of 14±10 months, 28/173 (16.2%) patients developed new onset erythrocytosis. The median time to the peak of the Hb/Hct level was 6.5 months. Although the group with erythrocytosis had significantly higher Hb and Hct at baseline compared to the group without erythrocytosis (Hb 9.7 mmol/L ± 1.0 vs. 8.5 mmol/L ± 1.0; p<0.001 in men and 9.1 mmol/L ± 0.8 mmol/L vs. 8.1 ± 0.8; p=0.006 in females), they also experienced a significantly greater median increase in Hb from baseline to peak (1.05 mmol/L vs. 0.60mmol/L; p=0.01) (see Figure 1) There were significantly more males (82% vs 60%; p=0.01) in the erythrocytosis group compared to the non-erythrocytosis group. In addition, the prevalence of OSAS was significantly higher in the group with erythrocytosis compared to the group without erythrocytosis (31% vs. 8%; p<0.001). Conclusion Secondary erythrocytosis or polycythemia is common in patients with chronic heart failure. It is particularly common in men and in patients with obstructive sleep apnoea syndrome (OSAS). There were no excess thrombotic or thromboembolic events, probably because of the routine use of anticoagulants/antiplatelets and limited follow-up. To avoid unnecessary haematological referrals and potential clinical adverse events, increased awareness among clinicians is needed.Table 1.Baseline and clinical outcomesFig1.Hemoglobin levels over time

Masked hypotension in patients with heart failure

Abstract Background Hypotension limits the up-titration of guideline-directed medical therapies (GDMTs) and correlates with poor prognosis in patients with heart failure. The value of ambulatory blood pressure monitoring (ABPM) in heart failure patients and its association with GDMTs optimization and clinical outcomes were undetermined. Methods REM-HF (Risk Evaluation and Management in Heart Failure) is a multicenter, prospective observational cohort. Our study screened patients from REM-HF who were hospitalized for incident HF and newly initiated GDMTs between April 2018 and December 2022. Eligible participants conducted a 24-hour ABPM before discharge and were followed-up as the cohort routine. GDMTs target dose achievement and dose trajectories were assessed at 3-month visit. The primary outcome was a composite of all-cause mortality and heart failure readmission. Results On adjusted restricted cubic spline analysis, office SBP demonstrated a U-shape relationship with the primary outcome (P for nonlinearity=0.003), while 24-hour SBP was linear (P for nonlinearity=0.338). The risk-related threshold of ambulatory and office systolic hypotension was defined as corresponding SBP < 120 mmHg accordingly. Combining these two measurements together, we described three blood pressure status as sustained hypotension (s-hypo, both SBP < 120 mmHg), masked hypotension (m-hypo, 24h SBP < 120 mmHg while office SBP ≥ 120mmHg), and non-hypotension (n-hypo). Among the 491 patients included, 124 (25.3%), 151 (30.8%) and 216 (44.0%) had s-hypo, m-hypo, and n-hypo, respectively. The m-hypo group showed similar clinical features as the s-hypo subjects, including more serious left ventricle remodeling and worse cardiac function. After the GDMTs dose titration, either patients with s-hypo or m-hypo were as unlikely to achieve target dose as the non-hypotensives (OR for s-hypo 0.42, 95%CI 0.19-0.95, P=0.038; OR for m-hypo 0.39, 95%CI 0.19-0.80, P=0.011). During a median follow-up of 693 days, the adjusted risk of primary outcome was higher in the s-hypo group and m-hypo group compared with the non-hypo group (HR for s-hypo 2.47, 95%CI 1.54-3.96, P<0.001; HR for m-hypo 1.68, 95%CI 1.06-2.65, P=0.027). No significant differences were found in target dose achievement and clinical outcomes between the s-hypo and m-hypo groups. Conclusion Masked systolic hypotension can occur in nearly one-third of new-onset HF patients. Patients with m-hypo and s-hypo exhibit similar clinical characteristics, both associated with GDMTs intolerance and adverse outcomes, suggesting m-hypo deserves recognition as a discrete entity. ABPM provides a more comprehensive view of patients’ blood pressure status by identifying this population.

Interventional treatment of patients with hypertrophic obstructive cardiomyopathy: the immediate and long-term results

Abstract Background Alcohol septal ablation (ASA) is a widely accepted and effective procedure for reducing septal thickness in patients with symptomatic hypertrophic obstructive cardiomyopathy (HOCM) who do not respond to medical treatment and have significant outflow tract gradients. Despite numerous studies confirming its safety and efficacy, as well as current guidelines from 2020 recommending ASA as a class 1 treatment option alongside surgical myectomy[1], the decision between these methods is still a subject of debate. Methods From 2009 to 2022 154 ASA performed in 145 patients (91 males, 54 females) with HOCM at our centre. Mean age of pts. was 42 [6;77] years. All pts. had right ventricle pacing lead with pacemaker backup and myocardial contrast ECHO(MCE) before procedure. Mean peak pressure gradient (PG) on LVOT was 93,5 ± 8,2 mm. Hg. Mitral valve regurgitation (MR) from moderate to severe was in all pts. Mean interventricular septum thickness was 2,5сm [1,6; 3,8]. Results Mean PG on LVOT decreased from 93,5 ± 8,2 mmHg to 31,7±4,3 mmHg. The grade of MR reduced from at least moderate to mild or even trivial. The procedure – related mortality was 1,3%. In 3 cases (2%) the procedure was aborted by he MCE data. Mean follow up for 145pts (100%)was 91±4,6 months. 112(77,3%) pts had PG reduction (to ≤30 mtmHg) – regarded as good result of procedure. 19 (13,1%) pts had PG > 30mmHg, but significant improvement in symptoms. Long term mortality in ASA pts. was 2.7%. 10(6.9%) pts needed redo procedure due to residual LVOTO, which was effective. 13(8,9%) patients had complete AV block and required permanent pacemaker. Mean interventricular wall thickness decreased from 2,5±0,3сm to 1,8±0,2cm. MR decreased from at least moderate to mild or complete disappearance. NYHA class reduced from 2,9 to 1,2. Conclusions ASA is effective and safe method of HOCM treatment. Accumulation of the experience can lead to a reduction in procedure time, a decrease in the number of complications, and an overall improvement in the outcomes of interventional HOCM treatment.

Efficacy and safety of dapagliflozin in non-diabetic patients with primary anterior ST-elevation myocardial infarction initiated in early hospital period

Abstract Background The effectiveness of SGLT2 inhibitors has been proven in all types of chronic heart failure (HFpEF, HFmrEF, and HFrEF), regardless of the presence of diabetes mellitus. There are still no clear recommendations regarding the timing of SGLT2 inhibitor administration after myocardial infarction (MI) and its influence on prognosis. It can be assumed that it is appropriate to consider the possibility that, if started quickly after the presentation of acute MI, SGLT inhibition might enhance outcomes in patients. Objective This study aims to investigate the efficacy and safety of the SGLT2 inhibitor Dapagliflozin in primary anterior ST-segment elevation myocardial infarction (STEMI) initiated in early hospital period, irrespective of heart failure manifestation. Methods The study includes 124 non-diabetic patients with primary anterior STEMI who underwent primary PCI and had left ventricular ejection fraction (LV EF) ≤45% and NT-proBNP > 900 pg/ml at symptom onset within 24 hours, regardless of heart failure symptom manifestation. Patients with cardiogenic shock were excluded. 62 patients received standard medical treatment including beta-blockers, ACE inhibitors (Control group), while the other 62 patients were administered the SGLT2 inhibitor Dapagliflozin 10 mg once a day during the first 48 hours of inpatient treatment, in addition to standard therapy (Dapa group). All patients were followed up for one year. Echocardiography was performed during the first 24 hours. Echocardiography and NT-proBNP were repeated at the end of the year. The primary endpoint was the one-year heart failure hospitalizations and secondary endpoints included one year cardiovascular mortality and changes in NT-proBNP, plasma creatinine and glycosylated hemoglobin levels. Results The study shows a significant difference in heart failure hospitalization between the groups. In the Control group, it was 25.8%, and in the Dapa group, it was 8.1% (p = 0.008). Initially, there were no significant changes in NT-proBNP levels; 1152.2 ± 222.4 pg/ml in the Control group and 1197.3 ± 279.8 pg/ml in the Dapa group (p= 0.33). At the end of a year, NT-proBNP increased in the Control group (1827.4 ± 317.8 pg/ml), whereas in the Dapa group, it significantly decreased (613.5 ± 215.6 pg/ml) (p < 0.01). One-year cardiovascular mortality in the Control and Dapa groups was 9.7% and 4.8%, respectively(p=0.491). Other blood markers did not differ, and side effects were comparable during the in-hospital period as well as at the end of the year. Conclusion Early administration of Dapagliflozin among non-diabetic patients with primary anterior STEMI is associated with a significant decreasing of heart failure hospitalization rate and NT-proBNP level. Additionally, early administration of dapagliflozin does not impact on safety indicators.

Development of a systematic referral model to primary care health interventions for patients with atrial fibrillation. a delphi study

Abstract Background The European Society of Cardiology (ESC) guidelines for the management of atrial fibrillation (AF) recommend integrated care in AF, combining medical treatment with lifestyle modifications and psychosocial management in a multi-disciplinary set-up. Research show that patients with AF can benefit from lifestyle interventions and psychosocial management, like patient education. According to World Health Organization recommendations, these health interventions are moving from hospitals to primary healthcare settings. Therefore, patients with AF should be systematically referred to these interventions. Yet, an evidence-based referral model that can support this transition is lacking. Purpose The purpose is to develop a systematic referral model for primary care health interventions for patients with AF. Methods We used the Delphi-technique with three rounds of questionnaires (figure 1). International and national clinical experts in AF across disciplines and health sectors were invited to participate. In the first round, the expert panel evaluated items that could be part of a referral model on relevance, improvability and self-reporting. In the second round, the expert panel evaluated each item as either an inclusion or exclusion criteria, important knowledge to have, or not relevant. In the third round, the expert panel evaluated the items according to data source and outcome status. A final model was drawn based on items reaching consensus. The study was reported according to the guidance on conducting and reporting Delphi studies (CREDES). Results In total, 69 of 139 invited experts accepted to participate (50%). These were mostly academics or clinicians (90%), stemming from primary sector (16%), secondary sector (35%) and research (32%). Most were medical doctors (36%) and nurses (35%). However physiotherapist, psychologists, dieticians, and other disciplines along with six patients with AF were also represented. The expert panel (60% females) had a mean age of 50 years, and 65% were from Denmark. For the final referral model (figure 2), AF symptom burden and impaired health-related quality of life, anxiety and poor medicine compliance combined with a risk factor profile were the main inclusion criteria. Furthermore, it was important to know about the patients’ mental well-being, self-management abilities and comorbidities. Conclusion Consensus was reached for a generic referral model, which can be further adjusted in the appropriate clinical context. The model includes inclusion criteria which closely correlate with guidelines for AF management focusing on reducing the patients’ symptom and risk factor burden. The referral model is expected to increase the number of patients with AF referred to primary care health interventions, which could lead to better quality of life, fewer hospital admissions and lowered health care costs in AF.

Coronary Computed Tomographic Angiography (CCTA) in non-ST elevation acute coronary syndromes

Abstract Background In patients presenting with an acute coronary syndrome (ACS), a diverse range of coronary artery disease is observed from structurally normal vessels to non-obstructive atherosclerosis and severe/obstructive coronary artery disease (CAD). In current clinical practice guidelines, the main diagnostic route for optimal management of patients with non-ST segment elevation acute coronary syndrome is invasive coronary angiography. However, in 30-40% of cases, no significant coronary lesions are evident. The purpose of this study is to describe the role of coronary computed tomographic angiography (CCTA) in non-ST elevation acute coronary syndromes in low and intermediate risk patients. Methods We describe the results of 504 patients evaluated with a protocol that includes the use of CCTA in patients with ACS. Patients over 18 years of age with a diagnosis of ACS without ST elevation who did not meet high-risk criteria (hemodynamic instability, dynamic changes in the ST segment or T wave, ventricular arrhythmia, GRACE score >140, refractory angina, heart failure or cardiorespiratory arrest) were included. They underwent CCTA as the initial coronary evaluation. Data collection was carried out between May 11, 2022 and February 20, 2024. Results 504 patients were included, with a mean age of 58 years, of which 44% were women and 56% men. Among the admission diagnoses, 26% were NSTEMI and 74% were unstable angina according to the 4th universal definition of acute myocardial infarction (AMI). The median high-sensitivity cardiac troponin T value was 7 nanograms per liter (interquartile range, 7 to 15) for the first troponin measurement. CCTA was performed in 93% of the patients. It was observed that 28% did not have any coronary lesions or plaques. 36% had non-obstructive coronary artery disease (plaques <50%). The rest had significant lesions in at least one vessel (27%), predominantly in the left anterior descending artery, or were nondiagnostic (9%). 31% had myocardial bridges, while in 13% of the patients a high-risk plaque was found. 38% of the patients included underwent invasive coronary angiography and 23% required revascularisation. Conclusion This study shows that the prevalence of ACS with coronary arteries without significant lesions by CCTA was 28%, which suggests CCTA could have a predominant role in the diagnostic algorithm of acute coronary syndromes without high-risk criteria, implying a decrease in the need of invasive studies in these patients. Only 38% required invasive coronary angiography, while revascularisation was performed in 23% of the patients. Furthermore, CCTA allowed a better detection of non-obstructive coronary artery disease (NOCAD) in 36% of the patients, and a more complete characterization of the atherosclerotic plaque, which could prompt to an initiation of preventive therapies or the optimization of medical treatment in these patients.Table 1CCTA findings

Prognostic impact of mitral valve geometry in patients with secondary mitral regurgitation: a secondary analysis of the MITRA-FR trial

Abstract Background Mitral valve (MV) transcatheter edge-to-edge repair (TEER) has emerged as a second line therapy on top of guidelines-directed medical treatment (GDMT) in heart failure (HF) patients with severe secondary mitral regurgitation (SMR). Following the disparate results of the COAPT and MITRA-FR pivotal trials, echocardiographic markers of LV remodeling and MR severity have been proposed to select patients most likely to benefit from MV-TEER. The characterization of MV geometry arises as a potential tool to stratify risk of outcomes in SMR patients, who underwent classical surgery or MV-TEER intervention. However, it remains unknown whether MV geometry parameters were associated with prognosis in MITRA-FR patients and whether MV-TEER could modulate their impact on outcomes. Purpose To evaluate the association between MV geometry and outcomes of HF patients with SMR in the MITRA-FR trial, as well as the impact of SMR treatment modality. Methods Thirteen MV geometry parameters were assessed from baseline transthoracic echocardiograms in patients from the MITRA-FR trial. The prognostic impact of MV geometry parameters was studied on top of the baseline clinical variables used in the primary analysis of MITRA-FR (i.e. age, atrial fibrillation [AF], ischemic cardiomyopathy, myocardial infarction, left ventricular ejection fraction [LVEF] and effective regurgitant orifice area [EROA]). The primary endpoint was the composite of all-cause mortality or HF hospitalization (HFH) within 2 years. The effect of treatment arms (MV-TEER plus GDMT vs. GDMT alone) on this association was also evaluated. Results Among the 307 patients included in the pivotal trial, 272 were analyzed in the present study (i.e. 135 from the GDMT group and 137 from the GDMT + MV-TEER group). Mean age was 70±10, 74% male. 50% had ischemic cardiomyopathy and 34% AF. LVEF was 33±7% and EROA was 31±11 mm². MV geometry parameters were presented for the whole population and according to the randomization group in the Table. Among these parameters, only MV tenting area remained independently associated with the primary endpoint (Hazard Ratio (HR) = 1.22 per 1 cm², Confidence Interval (CI) = 1.01-1.47; p=0.041) after multivariate analysis (Figure). Tenting height was independently associated with the risk of HFH (HR=1.07 per 1 mm, CI=1.00-1.14, p=0.037), but no MV geometry variable was associated with all-cause death. These findings remained consistent in both treatment arms (p>0.20 for interaction). Conclusion In HF patients with SMR included in the MITRA-FR trial, MV tenting area and MV tenting height were independently associated with the risk of HFH or all-cause mortality and HFH respectively, without any difference according to treatment arms. These data suggest that MV tethering provides an incremental prognostic value beyond classical echocardiographic variables, including EROA, and then should be considered in the risk stratification of patients with HF and SMR.Table of MV geometry parameters featuresMultivariate analysis (Forrest-plots)

Identifying prognostic factors in patients with cardiogenic shock undergoing VA-ECMO treatment: insights from ECLS-SHOCK using machine learning

Abstract Background/Introduction Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has not been shown to reduce short-term mortality in patients with acute myocardial infarction complicated by cardiogenic shock. However, whether some patients might benefit from VA-ECMO remains to be cleared. Purpose To identify the impact of VA-ECMO therapy on outcomes by leveraging the potential of machine learning. Methods The ECLS-SHOCK trial is a randomized controlled trial where patients with acute myocardial infarction complicated by cardiogenic shock for whom early revascularization was planned were randomly assigned to receive early VA-ECMO plus usual medical treatment or usual medical treatment alone. The primary outcome was death from any cause at 30 days. Extreme gradient boosting (XGBoost) was used to develop a model for the prediction of 30-day all-cause mortality and to assess the influence of VA-ECMO on outcomes. Results Overall, 209 patients were randomized to the VA-ECMO and 208 to control. Baseline characteristics between groups were well balanced (median age 63 years, 81% male, 67% presenting with ST-segment elevation myocardial infarction). At 30-days 100 patients in the VA-ECMO and 102 in the control group were dead. The final XGBoost model contained 27 variables and the 10 most influential variables are shown in Fig. 1. On derivation the model predicted mortality with an AUC of 1.00 and on validation with an AUC of 0.80 (95% CI 0.71 to 0.89), with a sensitivity of 95% (95% CI 88% to 100%) and a specificity of 55% (40% to 69%), resulting in a positive predictive value of 65% and a negative predictive value of 92% at a Youden-derived cut-off. Importantly, neither the VA-ECMO therapy nor its complications were among the most influential factors of the model with a relative importance of 1.1% for VA-ECMO therapy and 0.25% for peripheral vascular complications and bleeding complications even being discarded by the model. Conclusion In patients with acute myocardial infarction complicated by cardiogenic shock the influence of VA-ECMO therapy on 30-day mortality, even when investigated with complex machine learning models, is negligibly low.

Heart failure treatment in the last years of life - a nationwide study of 364,000 individuals

Abstract Background Heart failure treatment patterns towards the end of life have rarely been studied at large scale. Yet, this is important to assess, since heart failure is a chronic condition with patients on treatment for potentially many years. Purpose To investigate treatment patterns in the last years of life in patients with heart failure. Methods In a register-based study covering the whole Swedish population between 2007 and 2020, we investigated treatment patterns in the last years of life in 364,480 individuals who died with heart failure. We combined binomial models (to estimate proportion on treatment at death) and Poisson models (to estimate discontinuation rate), to estimate the proportion on each heart failure treatment up to 5 years prior to death, using penalized splines to allow for non-linearities. We also assessed comorbidity patterns over time. Results All heart failure treatments saw a gradual discontinuation closer to death, but the discontinuation rate of beta blockers decreased over time, resulting in an increasing proportion of patients on treatment at the time of death (Fig). Also, the pattern of comorbidities changed over time, with an increase in e.g., hypertension and atrial fibrillation, but a decline in ischemic heart disease (63% in 2007 gradually declining to 54% in 2020). Conclusions In this nationwide study, we observed a changing pattern of medical treatment of heart failure during the last years of life, most notably with an increasing use of beta blockers. Comorbidities and the shares of heart failure etiologies also changed over time, with an increase in several conditions but a decline in ischemic heart disease. Taken together, this may have important implications for planning and optimizing care for these patients.

Detection of chronic obstructive pulmonary disease and frequency of cardiopulmonary events in patients with a significant smoking history hospitalised for acute myocardial infarction

Abstract Background Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and also myocardial infarction (MI). Patients with COPD are more likely to have MI than those without and adequately treating COPD might improve cardiovascular outcomes. Reliable diagnosis is important for appropriate treatment. Prevalence of COPD in those hospitalised for MI has not been accurately established. Blood eosinophil count is an important guide to the benefit of inhaled corticosteroid (ICS) treatment in COPD. We aimed to accurately characterise lung function, symptom burden, eosinophil count and cardiopulmonary events in those with a significant smoking history hospitalised for acute MI. Methods Participants (n=216) with a smoking history of ≥10 pack-years currently hospitalised for acute MI were recruited at a single UK centre. Microspirometry and completion of the COPD Assessment Test (CAT) questionnaire were performed at enrolment. Presence and severity of COPD was graded using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. A high burden of COPD symptoms was defined as a CAT score of >10. Repeat CAT and assessment for relevant cardiopulmonary events was undertaken at 3 months and 1 year after enrolment. Results In the enrolled cohort, median age was 60 years (IQR 53-67), 26% were female, 57% were current smokers and median pack-year history was 32 (23-45). 41 of 216 (19 %, [95% CI 14-25]) had evidence of COPD, defined as FEV1/FEV6 <0.7 on best-attempt microspirometry, with 39 (95%) being GOLD2 or greater. Of the 41 with detected COPD, only 15 (37%, [22-53]) had a prior diagnosis. In those with evidence of COPD, a high burden of COPD symptoms was present in 63% of participants at enrolment, 40% at 3 months and 45% at 1 year. 20% [9-35] were receiving inhaled corticosteroids at enrolment. 63% [47-78] had eosinophil count ≥100 cells/mm3 and 17% [7-32] ≥300 cells/mm3. Among those with detected COPD, after 1 year 19.5% (95% CI 9-35%) had suffered a respiratory illness requiring prescription of medication, which was numerically but not statistically significantly higher than those without detected COPD (14.3% [10-20%]). In the COPD cohort, death, infection requiring hospitalisation, MI or unplanned coronary revascularisation, and bleeding requiring hospitalisation each occurred on two occasions (4.9%). Conclusions Based on these data, the prevalence of microspirometry-diagnosed COPD of any severity in patients with significant smoking history hospitalised for MI is around 19%. There is a high rate of undiagnosed and untreated disease, a significant burden of symptoms, including during convalescence, and around a 20% incidence of respiratory illness requiring medical treatment at 1 year. Gathering accurate data from this group is helpful in planning research and service improvement. Increasing detection of COPD in patients with MI would lead to improved cardiopulmonary outcomes.

Safe and favorable prognosis of thoracic endovascular aortic repair for the low-risk patients with non-acute type B aortic dissection

ObjectivePreemptive thoracic endovascular aortic repair (TEVAR) has the potential to improve the prognosis of Stanford type B aortic dissection (TBAD), however it is important to determine whether it could be safely performed as a prophylactic treatment. This study aimed to determine the short- and long-term outcomes of preemptive TEVAR for uncomplicated TBAD with a small aortic aneurysm.DesignRetrospective multicenter analysis.MethodsWe analyzed 212 patients with medically treated uncomplicated subacute TBAD between July 2004 and October 2019 in two Japanese academic centers. The short- and long-term prognosis of patients who underwent preemptive TEVAR and the changes in aortic diameter over time after TEVAR were analyzed. Aorta-related complications, aortic-related death and postoperative complications were recorded and analyzed. Analysis was performed on an intension-to-treat basis.ResultsDuring follow-up, patients were divided into two groups: optimal medical treatment [OMT; n = 185 (87%)] and preemptive TEVAR [n = 27 (13%)]. In all cases, aortic enlargement was the reason for therapeutic intervention in the preemptive TEVAR group. Propensity score matching yielded a cohort of 27 control patients with OMT (group A) and 27 patients who underwent preemptive TEVAR (group B). Preoperative characteristics were similar between groups. In group B, only one patient developed type A dissection at a late stage and died from aortic rupture. Freedom from aortic-related death at 1/5/10 years was 100%/92%/92% in group B. Overall growth (mm/year) of max aorta was significantly smaller in the TEVAR group than in the control group (−3.7 ± 2.9 vs. 0.4 ± 5.6, p < 0.01), and the diameter of the false lumen was reduced (−8 ± 4.8 vs. −1.3 ± 8.0, p < 0.001).ConclusionsShort- and long-term outcomes of TEVAR for uncomplicated TBAD with a small aortic aneurysm were excellent, with few postoperative complications. After TEVAR, aortic remodeling was observed in the short term, suggesting that it may contribute to the prevention of aortic-related death due to rupture.

Effect of catheter ablation in atrial fibrillation patients irrespective of their baseline heart failure: An updated meta-analysis

Abstract Introduction Patients with atrial fibrillation (AF) are associated with higher morbidity and mortality. Catheter ablation (CA) is supposed to improve outcomes in these patients. We aimed to update the evidence regarding CA in AF patients irrespective of their baseline heart failure. Methods We searched PubMed, Scopus, WOS, and Cochrane until February 2024 for relevant studies assessing the impact of CA compared to medical regimens in AF patients with and without heart failure. Outcomes of interest were all-cause mortality, cardiovascular mortality, hospitalization for HF, hospitalization for other cardiovascular causes, and stroke. Results 13 studies were included with a total of 18370 patients. In HF patients, irrespective to their ejection fraction, CA was associated with a significant reduction in all-cause mortality (RR 0.40, 95%CI [0.37 to 0.44], cardiovascular mortality (RR 0.36, 95%CI [0.32 to 0.42]), hospitalization from HF (RR 0.65, 95%CI [0.51 to 0.82]), hospitalization from other cardiovascular causes (RR 0.71, 95%CI [0.57 to 0.89]), and the incidence of stroke (RR 0.55, 95%CI [0.50 to 0.62]). Also, six studies with a total of 2015 patients compared CA to medical treatment in AF patients with HFrEF and HFpEF. CA showed a significant reduction in all-cause mortality in HFpEF patients compared to HFrEF (RR 0.46, 95%CI [0.25 to 0.85]) with no significant differences in terms of other studied outcomes. Moreover, six studies compared CA to medical treatment in HF vs no HF with a total of 2931 patients. Patients with AF and no HF had a significant reduction in all-cause mortality (RR .041, 95%CI [0.20 to 0.80]), with no significant differences in stroke or AF recurrence. Conclusion Current evidence supports the use of catheter ablation in atrial fibrillation patients, irrespective of their baseline heart failure, to achieve lower mortality and hospitalization rates.all-cause mortalitycardiovascular mortality

Prescribing contraceptives to minors without parental knowledge and consent

Abstract Background Sexually active adolescents may seek oral contraceptives without parental consent, posing challenges due to minors’ confidentiality and consent regulations. This is especially the case under the un-nuanced Israeli legal scheme regarding adolescents’ care. Methods Israeli OBGYNs were contacted through mailing lists and social media groups and asked to fill an online questionnaire regarding their experience and protocols concerning prescription of contraceptives to minors. They were also asked about their comprehension of the relevant legal obligations, the importance they ascribe to different ethical interests and considerations, as well as their training. Results Of the 177 responding gynecologists, 75% consulted minors about contraceptives during the past year, most of them without any training on providing care to adolescents. More than a third of respondents believed that parental involvement wasn’t legally required, while only 8% thought it mandatory for all minors under the age of 18. Most (75%) would ‘almost always’ prescribe contraceptives without parental knowledge upon request, while 20% never would. No correlation was found between respondents’ practices and their perception of the legal obligations. Participants agreed that the risk to the health of the minor due to having sex without contraceptives is of utmost importance. Those willing to prescribe gave greater weight to minor’s autonomy consideration, while those who do not prescribe were more concerned with the acts legal ramifications. The majority set the age of 15 as the threshold for consistently prescribing contraceptives to minors without parental involvement. Conclusions Access to contraceptives for mature minors without parental involvement is vital. There is great need for education and training for healthcare providers on providing medical treatment to adolescents, as well as for the development of policies and guidelines, addressing adolescents’ health disparities. Key messages • Israeli legal requirements challenge and hinder adolescents’ care as well contradict OBGYNs ethical and professional beliefs. • There is great need for education and training, as well as for the development of policies and guidelines, addressing adolescents’ health disparities.