Peripheral Arterial Disease Research Articles

Association of telomeres length with cardiovascular risk factors and arterial stiffness

Abstract Background Leukocyte telomere length (LTL) has been explored as a marker of biological aging, with connections established to age-related diseases like atherosclerosis. Studies have particularly associated telomeres with conditions such as peripheral vascular disease, coronary heart disease, and cardiovascular mortality. Methods In this cross-sectional analysis we enrolled individuals from "Corinthia" study which was conducted in the homonym region in Greece. We measured LTL in individuals to obtain comparative metrics on the prevalence of cardiovascular risk factors as well as arterial stiffness. Carotid-femoral pulse wave velocity (cfPWV) was used to evaluate arterial stiffness. Results Our analysis included 419 individuals aged 62.4 ± 11.8 years with a median LTL at 6.78 (IQR: 5.08-8.72) bp. Using the median LTL as a cutoff, the cohort was divided into two groups, Group A: 208 patients with low LTL, Group B: 211 patients with high LTL. Group A exhibited a significantly higher proportion of males (52.4% vs. 34.1%, p < 0.01), higher body mass index (BMI) (29.3 ± 4.7 kg/m2 vs. 28.5 ± 4.4 kg/m2, p <0.05), and a higher prevalence of hypertension (78.8% vs. 67.8%, p = 0.01) and dyslipidemia (51% vs. 38.9%, p = 0.014). No significant difference was observed regarding the prevalence of diabetes mellitus, smoking habits, and established cardiovascular disease. In the analysis of the whole cohort, cfPWV was found significant higher in Group A (9.61 ± 3.46 m/s vs. 8.38 ± 2.49 m/s, p <0.01) compared to group B (Figure, Panel A). This association remained significant (β = -0.096, p = 0.038), even after adjustment for confounders in the multivariate regression analysis. Finally, a statistically significant negative correlation between LTL and cfPWV was observed (Figure, Panel B). Conclusion LTL plays a pivotal role in cardiovascular health, and lower LTL is associated with impaired cfPWV values and a heightened prevalence of obesity, hypertension, and dyslipidemia.Asociation of LTL with cfPWV values.

Nationwide trends in utilization and safety of ventricular arrythmia ablation in patients with hypertrophic cardiomyopathy

Abstract Background Catheter ablation for ventricular arrhythmias, including ventricular tachycardia (VT) and premature ventricular complexes (PVC) is increasingly utilized across the nation, while data on its safety in Hypertrophic Cardiomyopathy (HCM) patients is sparse. Purpose To analyze the nationwide trends in utilization and complications of inpatient ventricular arrhythmia ablations in patients with HCM. Methods This study is a retrospective analysis of hospitalizations, in HCM patients 18 years of age and older, who underwent an inpatient VA ablation in the U.S., between 2016 and 2020. We drew data from the National Inpatient Sample (NIS) database. Patients without HCM undergoing the CA for VA were used as controls. Baseline sociodemographic and clinical data, procedural complications, mortality and length of stay were analyzed. Multivariable analysis was performed to identify independent predictors of procedural complications. Results Among a weighted total of 2880 patients hospitalized between 2016 and 2020, who underwent VA ablations, the median age was 67 years (IQR 56-74), 60% were male, and 73% were white. The HCM group had similar age distribution but more women (64.5% vs 33.6%, p<0.001) and more African Americans (13.2% vs. 7.3%, p=0.03). The non-HCM cohort had significantly higher rates of prior myocardial infarction (22% vs 12.4%, p=0.026), ischemic cardiomyopathy (30.1% vs 0.8%, p<0.001), heart failure (70.5% vs 39.7%, p<0.001), and peripheral vascular disease (PVD, 42.9% vs 18.2%, p<0.001). This was reflected in higher Deyo Comorbidity Index in the non-HCM cohort (score of ≥ 2 in 66.6% vs 43%, p<0.001). Overall, the real-world peri-procedural complication rate in the entire cohort was 15.3%, including 6.4% hemorrhagic, 4.5% pericardial, and 2.3% vascular complications. There was a trend for lower complication rate in the HCM group (9.9% vs. 16.7%, p = 0.08). The in-hospital mortality didn’t defer (1.7% vs. 4.2%, p=0.28) and the length of stay was shorter in the HCM group (3.5 vs. 6.4 days, p < 0.001). Multivariable logistic regression analysis showed obesity (OR 2.06; 95%CI: 1.59 - 2.67; p<0.001) and PVD (OR 2.19; 95%CI: 1.34-3.53; p=0.001) to be independent predictors of complications while HCM was not (OR 0.76, 95% CI 0.51-1.14, p = 0.195). Conclusion Real-world data from a nationwide inpatient database shows comparable safety for VA ablation in HCM patients with similar mortality and lower length of stay, compared to non-HCM patients.

Sex differences in secondary prevention and outcomes post-myocardial infarction in Scotland

Abstract Background Sex differences in outcomes after myocardial infarction (MI) are of increasing interest. Differential receipt of evidence-based treatments may contribute to such disparities. Purpose In this study, we investigate sex differences in the burden of risk factors, in-hospital and long-term treatment and outcomes in contemporary practice in Scotland, by analysing a nationwide sample of consecutive MI admissions. Methods All MI admissions centrally recorded between 2010-2016 by Public Health Scotland were included and followed up until the end of 2021. Poisson regressions analysed in-hospital outcomes (percutaneous coronary intervention (PCI), mortality and post-discharge secondary prevention medication). Models were adjusted for age, co-morbidities and ST-elevation on the electrocardiogram. Royston-Parmar models analysed long-term outcomes (all-cause and cardiovascular mortality, major adverse cardiovascular events (MACE)) and were sequentially adjusted for confounders (age, comorbidities, secondary prevention medications). A 2:1 age and sex-matched general population were included as controls. Results Of a total 47,063 MI patients, 15,776 (33.5%) were women. They were matched with 81,641 controls free of major cardiovascular disease. Median (interquartile range) age was 64 (56-72) years for men and 69 (60-75) years for women. Obesity, hypertension and renal disease were the risk factors more prevalent amongst women, while men had higher rates of previous MI, peripheral vascular disease and atrial fibrillation. Compared to men, women were less likely to undergo PCI (risk ratio (95% confidence interval) – 0.87 (0.86-0.89)) or receive secondary prevention (0.94 (0.93-0.95)), but had similar in-hospital mortality (1.06 (0.99-1.13)), after multi-variable adjustment. Over a median follow-up of 8.4 (6.8-10.2) years, women had higher raw rates of adverse outcomes. However, after full confounder adjustment, this translated into lower risk for women of all cause-mortality 0.92 (0.89-0.95), cardiovascular mortality 0.82 (0.78-0.87) and MACE 0.92 (0.88-0.95) (Figure 1). The female survival advantage was attenuated post-MI in comparison to controls free of significant cardiovascular disease (Figure 2). Conclusions Women and men have different MI risk factor profiles. Women had overall worse crude outcome rates after MI, driven by age and comorbidities. This may have been driven further by undertreatment after MI, including PCI and secondary prevention. Urgent identification of drivers for such disparities in care is warranted in order to improve outcomes and ensure health equity.

Correlation analysis of self-rated health and net adverse clinical events in patients with acute myocardial infarction

Abstract Backgrounds Self-rated health (SRH） is a recognized standard risk factor for myocardial infarction, but its impact on prognosis remains uncertain. Purpose This study aims to investigate the impact of self-rated health on the long-term clinical outcomes of myocardial infarction patients. Methods The data for this study were derived from a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals from 2010 to 2023, Patients were divided into satisfied and unsatisfied groups based on their responses to an SRH questionnaire. Propensity score matching (PSM) was utilized to balance covariates between the two groups and analyze the relationship between SRH and clinical outcomes. The primary endpoint was net adverse clinical events (NACE), comprising cardiac death, recurrent myocardial infarction, revascularization, ischemic stroke, and bleeding events (BARC ≥3). The secondary endpoint comprised the individual components of the primary endpoint. Results The study included a total of 55,054 AMI patients, with 54,049 rating their health as satisfactory and 1,005 patients as unsatisfactory. In the satisfactory group, patients tended to be younger, had fewer females, better Killip classification, a higher proportion of STEMI cases, a higher rate of undergoing PCI, and a lower prevalence of concomitant disease such as diabetes, hypertension, chronic kidney disease, cerebrovascular disease, peripheral vascular disease, thyroid disease, and chronic lung disease. Additionally, patients in the satisfactory group had a higher proportion of antiplatelet therapy use (aspirin, ticagrelor). 1,005 pairs were well matched after PSM. After a median follow-up of 1626 days, the proportion of all-cause death, cardiac death, and recurrent myocardial infarction in the satisfied group was significantly lower than that in the unsatisfied group. Multivariable Cox regression analysis revealed that satisfactory SRH was associated with a reduced risk of NACE (aHR 0.809, 95%CI 0.704-0.930, P=0.002), cardiac death (aHR 0.790, 95%CI 0.665-0.939, P=0.007), and recurrent myocardial infarction (aHR 0.734, 95%CI 0.563-0.955, P=0.021). Conclusions Good SRH can decrease the risk of NACE in myocardial infarction patients, underscoring the importance of considering SRH in clinical assessment.

Risk factors of 30-day mortality following cardiac surgery in adults with congenital heart disease: analysis from the Japanese registry

Abstract Background With advancements in pediatric therapies, the adult congenital heart disease (ACHD) population has grown consistently. ACHD patients often face complications necessitating cardiac surgery, and understanding surgical risk factors is essential. Purpose This study aims to assess ACHD surgical risk factors using big data, addressing evidence gaps in previous research limited to univariate analysis due to few perioperative adverse events. Methods We analyzed the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC) database from April 2013 to March 2020. The JROAD-DPC database covers nearly all teaching hospitals with cardiovascular beds participation in JROAD. Our study included ACHD patients (>15 years) undergoing open-heart surgery. Our primary outcome was 30-day mortality. We assessed clinical backgrounds, admission status, treatment, and length of hospital stay. Results Out of 13,677 ACHD patients (mean age: 53 years, females 47%) undergoing cardiac surgery assessed for 30-day mortality, 13,516 (98.8%) patients were categorized into the survival group and 161 (1.2%) into the death group. Mortality rates varied by complexity of congenital heart disease (CHD): 0.8% for simple, 1.8% for moderate, and 0.9% for great. The figure shows that a significant increase in 30-day mortality rates with age was demonstrated in simple and moderate complexity (p<0.001 for trend analysis in both categories). In contrast, for cases of great complexity, the increase in 30-day mortality rates with aging was not statistically significant (p=0.443). The death group was significantly older and had higher rates of ambulance admissions, renal disease, and peripheral vascular disease. Intra-aortic balloon pumps (IABP), veno-arterial extracorporeal membrane oxygenation (VA-ECMO), and dialysis during hospitalization were significantly higher among deceased patients. Length of ICU stay was significantly longer in the death group (median [IQR]; 3 [2-4] vs. 6 [3-11], p<0.001). Cox proportional-hazards model showed that age, moderate complexity, emergency admission, hospital bed counts, renal disease, and use of IABP and VA-ECMO were independently associated with 30-day mortality (Table). Conclusions The present study, which utilizes the nationwide administrative DPC database, demonstrates that surgical outcomes for patients with ACHD, as measured by 30-day mortality rates, are generally favorable. These outcomes significantly depend on factors such as age, complexity of CHD, emergency admissions, hospital capacity, renal disease, and use of mechanical circulatory support.

Combination of moderate-intensity statins and ezetimibe versus high-intensity statins alone for primary prevention of cardiovascular events

Abstract Background Combination of a moderate-intensity statin with ezetimibe can lead to similar reductions in cardiovascular events as monotherapy with a high-intensity statin in patients with established atherosclerotic cardiovascular disease (ASCVD). The comparative effectiveness of these two cholesterol-lowering strategies in the primary prevention setting is unknown. Purpose To compare incident ASCVD events associated with a combination of moderate-intensity statin and ezetimibe versus monotherapy with a high-intensity statin in adults without prior history of cardiovascular disease. Methods We conducted a new-user active comparator retrospective population-based cohort study in Canada. We included all adults aged ≥ 67 years (eligible for drug coverage) with a first prescription of either a combination of moderate-intensity statin with ezetimibe ("combination therapy") or high-intensity statin alone between January 2010 and December 2022. Patients were excluded if they had not received any prior lipid lowering therapies or had a history of myocardial infarction (MI), stroke, heart failure, peripheral vascular disease or prior coronary revascularisation at any time before or within 3 months of treatment initiation. The primary outcome was a composite of all-cause death, hospitalization for MI or stroke, or coronary revascularization. An inverse probability of treatment weighting propensity score was used to account for confounding (demographics, comorbidities, laboratory tests, other medications). Results Among 67,884 patients (mean age: 74.0±5.5y; 53% females), 8,798 (13%) initiated combination therapy and 59,086 (87%) initiated a high-intensity statin. At 1 year, after weighting, the mean achieved LDL-C was ~1.9 mmol/L in both groups. The median follow-up was 6.5 years. The cumulative incidence of the primary outcome at 10 years in the weighted cohort was 32.7% in the combination therapy group and 36.1% in the high-intensity statin group (HR: 0.87; 95% CI: 0.82 to 0.92; p<0.001; absolute risk reduction: 3.5%; 95% CI: 0.8 to 6.1; Figure 1). This result was primarily driven by a lower risk of all-cause death (HR: 0.85; 95% CI: 0.80 to 0.91; p<0.001; Figure 2) and stroke (cause-specific [cs] HR: 0.86; 95% CI 0.74 to 0.99; p=0.04), whereas no differences were observed in the risk of MI (csHR: 0.97; 95% CI: 0.82 to 1.15) or coronary revascularization (csHR: 0.97; 95% CI 0.85 to 1.11). Conclusion The combination of moderate-intensity statins with ezetimibe was associated with a lower risk of incident ASCVD compared with high-intensity statins alone among primary prevention patients in a real-world setting. These results were driven by a lower risk of all-cause death and stroke, but not coronary events. The influence of statin intolerance on the allocated strategy and adherence to therapy cannot be addressed in this analysis, which, along with verifying these estimates, may be best determined in a prospective randomized trial.

Comprehensive risk factor management through a dedicated secondary prevention clinic: experience from hamilton, Ontario

Abstract Introduction and Background Atherosclerotic cardiovascular diseases (ASCVD) remain a major source of morbidity and mortality. Modifiable ASCVD risk factors can be effectively treated, however, there is a lack of systematic implementation of secondary prevention therapies in ASCVD patients. We established a comprehensive secondary prevention program for patients with ASCVD to provide care for all modifiable risk factors in an integrated manner. Methods Patients with established coronary artery disease (CAD), cerebrovascular disease (CVD) and peripheral vascular disease (PVD) who had one or more uncontrolled risk factors, were referred to the center(s). Patients were assessed between November 2022 and October 2023. Uncontrolled risk factors were defined as dyslipidemia (LDL > 70 mg/dL [1.8 mmol/L]), hypertension (defined as BP >130/80 mmHg), diabetes (HbA1c >6.5%), chronic kidney disease (eGFR <60 ml/min/1.73m2) obesity (BMI >30 kg/m2) and current tobacco use. Data was collected at the initial visit and subsequent follow-up visits. Results A total of 274 patients were seen, with 85% were referred for CAD. Median age was 62 years,72% were men. The most common uncontrolled modifiable risk factor was hypertension (62% of patients), followed by dyslipidemia (60%) and obesity (50%). 39% of patients had diabetes, with 57% on a SGLT2i, 16% on a GLP-1 agonist and with 23% with HbA1c >8%. Blood pressure was above 140/90 mm Hg in 41% of patients, 20% were current smokers and 75% of patients had two or more uncontrolled risk factors. At the first visit, 56% of patients had a pharmacological intervention. The most common was for management of dyslipidemia, followed by diabetes and then hypertension. 17.8%(n=49) patients had a change in statin,13.8% (n= 38) patients were started on Ezetmibe, 9.1%(n=25) on Icosapent Ethyl, and 16.4% (n= 45) on a PCSK9i inhibitor (monoclonal antibody or Inclisiran). Among patients with diabetes, 5.1%(n=14) patients were started on a GLP-1 agonist and 2.5%(n=7) were started on a SGLT2i. 2.9%(n=8) patients were started on Varenicline and 2.9%(n=8) were started on NRT. Mean LDL (with LDL >1.8 at baseline) at visit 1 was at 3.03 ± 1.1 (n=157) mmol/dl, which reduced to 2.05 ± 0.9 (n=77) mmol/dl by 2nd visit and to 1.90 ± 1.3 (n=32) mmol/dl by visit 3. Average SBP (SBP >130 at baseline) at visit 1 was 143.3 ± 13.4 (n=114) mm Hg, this was subsequently reduced to 126.4 ± 14.0 (n=58) mm Hg at visit 2 and further reduced to 123.2 ± 14.7 (n=31) mm Hg by visit 3. Discussion and Impact: In our tertiary Cardiac Care center there are a significant number of patients with established ASCVD that remain on inadequate treatment for secondary prevention. Addressing these risk factors in a timely and integrated fashion in one clinic improves the implementation of guideline directed therapies for management of secondary risk factors in ASCVD and is expected to result in improved outcomes.

Impact of procedural and patient-related risks on 1-year outcomes for patients with 1-month DAPT followed by P2Y12 inhibitor monotherapy after biodegradable-polymer drug-eluting stent implantation

Abstract Background While early de-escalation of dual antiplatelet therapy (DAPT) and P2Y12 inhibitor monotherapy following short DAPT are becoming standard treatments for patients after percutaneous coronary intervention (PCI), the impact of procedural and patient-related risks on clinical outcomes of PCI for patients receiving the above DAPT regimen has never been established. Purpose To evaluate the impact of procedural and patient-related risk factors on 1-year cardiovascular and bleeding outcomes in patients with 1-month DAPT followed by P2Y12 inhibitor monotherapy after biodegradable-polymer drug-eluting stent (BP-DES) implantation. Methods Using data from the multi-centre regional-wide REIWA registry, we assessed clinical outcomes according to each risk factor and compared between patients with and without either procedural or patient-related risk factors. The primary end point was net adverse clinical events (NACE), defined as a composite of cardiovascular outcomes (cardiovascular death, myocardial infarction, definite stent thrombosis, ischemic or hemorrhagic stroke) and bleeding outcomes (TIMI major or minor bleeding), which was same with that for STOPDAPT-2 trial. Procedural risk was defined as a factor of complex PCI which was previously published and included the follows: treatment of three vessels, three or more lesions, three or more stents, bifurcation with two stents, long stenting (total stent length >60 mm) and target of chronic total occlusion. Additionally, patient-related risk factors were defined as chronic kidney disease, anaemia, peripheral vascular disease, heart failure and advanced age (≧75 years). Results Among 1,202 patients treated BP-DES with 1-month DAPT, 276 patients (23.0%) had at least one procedural factors and 510 patients (42.4%) had one or more patient-related risks. Compared with each risk factor, patients with patient-related risk factor were more likely to have higher NACE rates, whereas low NACE rates were observed in patients with each procedural risk factor (Figure 1). In addition, during 1-year follow-up, patients with patient-related risk factors had a significantly higher incidence of NACE compared with patients without such risks (4.90 % vs. 1.73 %, p = 0.002) (Figure 2). However, no significant differences in NACE rates was observed between patients with and without procedural risk factors (2.54% vs. 3.24%, p = 0.555). Conclusion In patients undergoing BP-DES implantation and 1 month DAPT followed by P2Y12 inhibitor monotherapy, patient-related risk factors had an impact on 1-year clinical outcomes, while procedural risk factors no longer had small impact on those outcomes.

PIRCHE-II: a new tool to predict rejection in cardiac transplantation?

Abstract Aim This retrospective observational study aims to compare patients diagnosed with antibody-mediated or cell-mediated rejection with patients without episodes of rejection and study any predictors of rejection at follow-up with particular attention to PIRCHE-II scores. Materials and Methods We performed a retrospective evaluation of prospectively collected data of heart transplant patients from January 2022 to August 2023, at a single hospital. Preoperative, intraoperative and postoperative parameters are collected anonymously in our institutional database used for internal quality control. The primary endpoint was the incidence of rejection in one of three control endomyocardial biopsies. As pre-operative data, age, sex, BSA, blood group mismatch, risk such as dyslipidemia, hypertension, diabetes, peripheral vascular disease, COPD, previous cardiac surgery, PRA, ischemia time and post-operative infections. We evaluated patients at a mean follow-up of 106 (78 – 180) days. In patients who tested positive for cell-mediated or antibody-mediated rejection, the PIRCHE-II score was calculated. Results There were 45 patients with no diagnosis of rejection and they were aged 61 [50-65]; 22.2% were women, with a mean BSA of 1.87 ± 0.19. 22.2% had a blood type mismatch. They had a mean PIRCHE-II of 111.88 ± 43.6. There were 15 patients diagnosed with rejection and they were 63 years old [52 – 66]; 20.0% were women, with a mean BSA of 1.84 ± 0.23. 13.3% had a blood type mismatch. They had a mean PIRCHE-II of 113.70 ± 33.90. In multivariable analysis, the main predictors of rejection were plasma transfusions [OR 0.053, 95% CI, p=0.02], post-operative infections [OR 0.076, 95% CI, p=<0, 02] and the PIRCHE – II [OR 3.284, 95% CI, p=0.04]. The mean PIRCHE-II of patients who presented antibody-mediated or cell-mediated rejection was 113.70 ± 33.90 and that of patients who did not present any rejection was 111.88 ± 33.90; Conclusion According to the results obtained, the PIRCHE-II algorithm could be a tool in immunological risk stratification in patients undergoing cardiac transplantation. It is necessary, however, to apply PIRCHE-II to a larger number of patients and should also be considered in light of other factors such as the immunological status of the recipients, the immediate post-operative course (infections, CMV reactivation, blood component transfusions), which could constitute an immunological trigger and patient compliance in immunosuppressive therapy.Patients' featuresResuts

Long-term survival after coronary artery bypass grafting comparing bilateral versus single internal mammary artery in a women cohort

Abstract Introduction Although neutral results from the ART randomized controlled trial, observational studies have been supporting better survival after bilateral internal mammary artery (BIMA) vs single internal mammary artery (SIMA) coronary artery bypass grafting (CABG). However, for some specific subgroups, like women patients, more doubts remain about BIMA benefits. Aim To compare long-term survival and early results in women after SIMA vs BIMA. Methods Longitudinal, retrospective, single-center study including consecutive women with at least 2 left-coronary system (LCS) vessel disease who underwent primary isolated CABG with at least 1 internal mammary artery (IMA) conduit and a minimum of 2 conduits targeting the LCS, between 2004-2014. Emergent or salvage surgeries, on-pump beating-heart, BIMA in which 1 IMA targeted the right coronary artery territory were excluded. The primary outcome was all-causes mortality (checked on February 2023). Time-to-event outcomes were studied using Kaplan-Meier Curves, Log-Rank test and multivariable Cox Regression. Median follow-up was 11 years, maximum of 19 years. Results From 539 women selected for this study, BIMA CABG was performed in 30%. SIMA patient’s were older (mean age 68.95±8.39 vs 62.75±9.82 years, p<0.001), but the prevalence of cardiovascular risk factors were similar between groups (arterial hypertension, p=0.693; dyslipidemia, p=0.111; diabetes mellitus, p=0.462 and obesity, p=0.109). Peripheral artery disease (p=0.707), left ventricular dysfunction (p=0.727), cerebrovascular disease (p=0.730), active smoking habits (p=0.05) and chronic obstrutive pulmonary disease (p=0.537) were also similar. Severe chronic kidney disease (27% vs 14%, p<0.001) and Canadian Coronary Society - grade IV (74% vs 63%, p=0.011) were more frequent in SIMA group. In the univariable survival analysis, SIMA had worse survival results than BIMA (Log Rank test p<0.01). At 5-, 10- and 15- years of follow-up, cumulative survival for SIMA vs BIMA were 88% vs 90%, 68% vs 75%, 42% vs 58%, respectively. However, the multivariable Cox regression showed that BIMA was not associated with long-term survival (HR [95%CI]: 1.09 [0.75-1.59], p=0.6). Most of post-operative outcomes were similar between groups, with the exception of atrial fibrilation (25% vs 16%, p=0.031) and time to discharge (median days [min-max]: 7 [4-128] vs 7 [4-59]) that were higher in SIMA. No differences were found in immediate reexploration of thorax (sternal infection – 0.3% SIMA vs 1.2% BIMA, p=0.219; bleeding- 1.6% SIMA vs 0.6% BIMA, p=0.681). Redo CABG occurred in 1 SIMA and 1 BIMA women, at 41 and 84 months of follow-up, respectively. Conclusion In this study, revascularization with BIMA seems to be safe in women and provides similar results than SIMA. More studies in women are needed to establish the better approach for this specific subgroup.

Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists and cancer mortality. A real-world registry

Abstract Background Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1ra) reduce cardiovascular events through different mechanisms, nevertheless, their association with cancer remains unclear. Purpose We aim to compare the combined treatment (SGLT2i and GLP1ra) with monotherapy regarding hospitalization or/and death for cancer in a general population and a subgroup of patients with cardiovascular disease (CVD). Methods Retrospective observational study of patients who were prescribed SGLT2i, GLP1ra, or both drugs. Multinomial propensity score was performed in all the population and in a subgroup of patients with CVD (atrial fibrillation [AF], heart failure [HF], coronary artery disease [CAD], peripheral arterial disease [PAD], or cerebrovascular accident [CVA]). The following variables were included to adjust the three groups: Sex, Age, Obesity, diabetes mellitus (DM), high blood pressure (HBP), dyslipidemia (DLP), CAD, HF, AF, and CVA. The three primary outcomes were (i) hospitalization for any cancer, (ii) death for any cancer, and (iii) the combined event in the included population and the subgroup of patients with CVD. The multivariate Cox regression analysis determined the hazard rate (HR) of age, sex, risk factors, and treatment for each outcome. Results We included 14709 patients (11366 with SGLT2i, 1016 with GLP1ra, and 2327 with both treatments) from the treatment initiation. The subgroup with CVD included 4957 (33.7%) patients (Fig 1). After 33 months of median follow-up, the incidence of cancer events was similar between patients with and without CVD (3.4% or 3.7%, respectively). Sex (male) and age were the main risk factors for the 3 outcomes in both groups. Combined treatment and its duration had a protector role for cancer mortality regarding monotherapy with SGLT2i or GLP1ra in all population (HR [95%CI]) 0.2216 [0.106-0.459]; p<0.001 or 0.1928 [0.071-0.519]; p=0.001, respectively) (Fig 2a) and in the subgroup of patients with CVD (HR [95%CI]) 0.279 [0.078-0.994]; p<0.049 or 0.129 [0.024-0.668]; p=0.014, respectively) (Fig 2b), but these results were not found for the outcome of hospitalization for cancer. The combined therapy concerning SGLT2i and duration of treatment showed a protective role against the combined event (HR [95%CI]) 0.709 [0.521-0.967]; p=0.029) and (HR [95%CI]) 0.991 [0.983-0.999]; p=0.032) in the general population but not in the group of CVD. A higher survival rate for any cancer mortality was observed in those patients with the combined therapy respect to monotherapy (SGLT2i or GLP1ra) in the general population (Fig 2c) and the subgroup of patients with CVD (Fig 2d). Conclusions Initiation of combined therapy vs. monotherapy was associated with a lower rate of cancer mortality in the general population and patients with CVD. Future clinical trials and mechanistic studies will clarify the possible role of these drugs on carcinogenesis.Figure 1Figure 2

Effects of dapagliflozin in heart failure according to duration of type 2 diabetes: a patient-level meta-analysis of DAPA-HF and DELIVER

Abstract Introduction Type 2 diabetes (T2D) is a common comorbidity in heart failure (HF), and long-standing T2D is associated with worse outcomes. Purpose To investigate the efficacy and safety of dapagliflozin, compared with placebo, according to duration of T2D in patients with HF and established T2D. Methods We conducted a patient-level pooled analysis of the DAPA-HF and DELIVER trials, which evaluated the effects of dapagliflozin, compared with placebo, in patients with HF with reduced ejection fraction and HF with mildly reduced/preserved ejection fraction, respectively. T2D duration was categorized as <5 years, 6-10 years, and >11 years. The primary outcome was a composite of worsening HF or cardiovascular death. Results Of the 4,784 patients with a history of T2D, 1,879 (39.3%) had a T2D duration of <5 years, 1,074 (22.4%) 5-10 years, and 1,831 (38.3%) >11 years. Patients with longer-duration T2D were older, more often female, and White, and had a higher HbA1c, body mass index, and left ventricular ejection fraction. They were more likely to have ischaemic heart disease, peripheral artery disease, hypertension, and chronic kidney disease, but were less likely to have atrial fibrillation/flutter. Although patients with longer-duration T2D had longer duration of HF, they were not more likely to have a prior HF hospitalization or worse New York Heart Association functional class. Despite similar N-terminal pro-B-type natriuretic peptide levels, patients with longer-duration T2D had a higher risk of the primary outcome, even after adjustment for potential confounders (<5 years, reference; 6-10 years, HR 1.25 [95% CI, 1.06-1.46]; >11 years, HR 1.33 [1.15-1.54]). The benefit of dapagliflozin on the primary outcome was consistent across T2D duration category: <5 years, HR 0.85 (95% CI, 0.69-1.04); 5-10 years, HR 0.65 (0.51-0.83); >11 years, HR 0.84 (0.70-1.01) (Pinteraction=0.18). Dapagliflozin reduced the risk of secondary clinical outcomes and increased (improved) mean KCCQ scores from baseline to 8 months, regardless of T2D duration (Table). Adverse events and treatment discontinuation were not more frequent with dapagliflozin than with placebo irrespective of T2D duration. Conclusions Dapagliflozin reduced the risk of worsening HF or cardiovascular death, and improved symptoms, in patients with HF and T2D, irrespective of T2D duration.

Single arterial access versus standard access in TAVI: results from a large multicenter registry

Abstract Background The transfemoral approach has become the gold standard primary access for transcatheter aortic valve implantation (TAVI) due to low complication rates. An additional secondary access (ScA) is used for angiographic guidance of the procedure. Recently, small, single-center studies demonstrated feasibility of single-access for transfemoral TAVI without a secondary access. However, comparative and large-scale data are missing. Purpose We assessed vascular and bleeding complications of ScA and Single access (SA) approaches in a large multicenter registry to evaluate both strategies. Methods The PULSE registry (Plug or sUture based vascuLar cloSurE after TAVI) retrospectively evaluated data of 10,120 patients who underwent transfemoral TAVI at 10 high-volume German heart centers from 2016 to 2021. In 9,457 patients who qualified for analysis ScA (80.7% femoral, 19.3% radial) were performed in 8709 (92%) and SA in 748 (8%). Outcomes were evaluated in accordance with the Valve Academic Research Consortium (VARC-3) definitions. Results Median age was 81.9[IQR 78.2, 85.1] years and 48.9% of patients were female (median logistic EuroSCORE II: 3.3% [IQR 2.1, 5.6]). Peripheral artery disease was comparable between groups (13.5 vs. 14.0%, p=0.73). While overall major access-related vascular complications did not differ significantly (6.1% vs. 4.8%, p=0.20), there was a higher incidence of minor complications for ScA compared to SA (9.0% vs. 2.8%, p<0.001). Secondary access complications amounted to 2.7% in the ScA group and were mainly characterized as bleeding (1.2%) and pseudoaneurysms (1.2%) mostly treated conservatively (1.2%), yet in some cases surgical repair was needed (0.8%). No significant difference was observed regarding type III/IV bleeding (4.1% vs. 4.3%, p=0.91), stroke rate (2.4% vs. 3.6%, p=0.05), stage III/IV acute kidney injury (2.4% vs. 2.4%, p=1.00) or all-cause 30-day mortality (5.8% and 5.7%, p=0.99) for ScA compared to SA groups. Conclusion In patients treated with transfemoral TAVI, a single access approach was associated with lower rates of minor access-related vascular complications without compromising overall outcomes, suggesting potential benefits of a minimally-invasive TAVI approach with the omission of additional vascular access.

Systemic inflammation in patients with atherosclerotic cardiovascular and chronic kidney disease in Spain: a population-based study using electronic medical records from a primary care database

Abstract Background Systemic inflammation (SI) is recognized as a critical driver of atherosclerotic cardiovascular disease (ASCVD), and it is frequently observed in ASCVD patients with comorbid chronic kidney disease (CKD). Elevated C-reactive protein (CRP) levels, a common biomarker for SI, have been associated with poor prognosis in ASCVD and CKD patients, increased risk of major adverse cardiovascular events and renal disease progression, as well as greater mortality. Purpose To estimate the prevalence of SI in patients with ASCVD in Spain overall and by CKD status, and to describe patients’ clinical characteristics. Methods In this population-based observational study, data from THIN Spain, a database of electronic medical records from a large network of general practitioners, were used to identify adult patients with a diagnosis code of ASCVD (atherosclerotic coronary or cerebrovascular event, peripheral arterial disease, or other atherosclerotic vascular event) and ≥1 eligible CRP measurement between January 1st 2014 to July 31st 2023 (latest data available at time of data extraction).[Figure] SI was defined as CRP ≥ 2mg/L. Point prevalence of SI at the end of the study (among patients alive with ≥1 CRP in the prior 18 months) and the proportion of patients with evidence of SI during the study period (2014-2023) were estimated overall and by CKD status (defined as CKD stage 3+, or eGFR <60 mL/min/1.73m², or urinary albumin-to-creatinine ratio ≥30 mg/g). Patients’ comorbidities (defined using primary care diagnoses), and laboratory values were reported by SI status at first CRP measurement during the study period. Results Among 76,423 patients with ASCVD diagnosis, 15,798 patients (20.7%) were included in the study (mean age: 71.1 years; 43% females), of whom 5,111 (34%) had CKD at first eligible CRP (n=975 with unknown CKD status). Mean CRP in ASCVD patients with CKD was 24% higher than in those without CKD (4.36 vs 3.53 mg/L, p<0.001). The proportion of ASCVD patients with SI at first CRP measurement was 58% overall (65% among CKD patients; 55% among patients without CKD; p<0.001). The point prevalence of SI at the end of the study was 56% among ASCVD patients overall (62% among CKD patients; 52% among patients without CKD; p<0.001), while 64% of ASCVD patients had evidence of SI at any time during the study period (72% among CKD patients; 59% among patients without CKD; p<0.001). Compared to ASCVD patients without SI, higher proportion of SI patients were smokers and with comorbidities. Also, ASCVD patients with SI had lower baseline eGFR levels and higher levels of LDL-C and triglycerides than ASCVD patients without SI.[Table] Conclusions SI prevalence is high among patients with ASCVD in Spain, especially among patients with comorbid CKD. Strategies to target SI may have beneficial effects in prevention of cardiovascular events and mortality in ASCVD patients.

Procedure-related radiation and contrast use during TAVI procedures with balloon-expandable versus self-expanding devices

Abstract Background Transcatheter aortic valve implantation (TAVI) procedures show some fundamental differences, depending on the use of balloon-expandable (BEV) or self-expanding (SEV) devices. We aimed to assess, how it translates into contrast use and radiation exposure. Methods From five high volume European centers consecutive patients were included, who underwent transfemoral TAVI procedure. Patient- and procedural characteristics were recorded and compared in relation to the used TAVI device. Results In total 3131 patients were included. 53% were male and the mean age was 80±9 years. 1273 (41%) patients were treated with BEV, while 1858 (59%) with a SEV system. Patients, receiving SEV were older (81±9 vs 79±9 years, respectively; p<0.01) and were more often females (57% vs 33%, respectively; p<0.01). There was also a trend for less peripheral artery disease (14% vs 17%, respectively; p=0.06). Overall total radiation time was 15±9 min., that was markedly shorter for BEV than for SEV (13±8 vs. 17±10 min., respectively; p<0.01). On average 130±65 mL contrast media was used, that was less for BEV than for SEV (104±52 vs. 148±67 mL, respectively; p<0.01) In terms of contrast use, retrievable- and non-retrievable SEVs were comparable (148±71 vs. 146±63 mL, respectively; p=0.41), but both markedly higher, than for BEVs (p<0.01 for both). Non-retrievable SEVs required less radiation (14±7 vs. 18±10 mins, respectively; p<0.01), but still markedly more than BEVs (p<0.01). Conclusion TAVI procedures with BEV require shorter radiation exposure for the team and markedly less contrast, than with SEV. This might be reasonable to consider during patient-tailored procedure planning.Radiation and contrast usage during TAVI

Lipoprotein(a) and atherosclerotic cardiovascular disease in a Brazilian tertiary hospital population

Abstract Background/Introduction Elevated levels of lipoprotein(a) [Lp(a)] are a strong risk marker of atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction (MI), ischemic stroke, and peripheral arterial disease, as well as of aortic valve calcification and stenosis. However, few studies have assessed the prevalence of high Lp(a) levels in patients followed at a tertiary hospital specialized in cardiovascular diseases (CVD). In addition, there is scant information about Lp(a) concentrations in Brazilian individuals. Purpose The aim of the study was to describe the demographic characteristics and comorbidities of patients with at least one measure of Lp(a) at a tertiary treatment center for CVD in our city – Brazil. Methods Patients treated at a heart institute had their data extracted between the years 1999 and 2021. Data were obtained through direct electronic extraction of patients' medical records. The patients were categorized according to different Lp(a) cutoff levels (> 50 and < 70, > 70 and < 90, and > 90 mg/dL) and by quartiles. Results Of 4,970 unique patients included in the study, the mean age at baseline was 59.9 years (SD ± 14.5), 2,634 (53%) were male, and the median Lp(a) was 23.2 mg/dL (interquartile range 8.9 - 56.8 mg/dL). In the whole cohort, 460 (9.3%) had Lp(a) > 50 and < 70, 344 (6.9%) > 70 and < 90, 612 (12.3%) > 90 mg/dl and 138 (2.8%) > 150 mg/dL. Established ASCVD was reported in 1,223 (24%) of the individuals, with a progressively higher prevalence across the Lp(a) categories above (31.2%, 33.8%, 34.2%, respectively) (table 1). Moreover, the Lp(a) median (interquartile range) in mg/dL was significantly higher in those with baseline history of ASCVD (31.4 [10.8-71.2] vs 21.2 [8.3-52]), MI (27.8 [10.6-65.9] vs 22.3 [8.5-54.7]) and stroke (24.9 [10-69.5] vs 23.1 [8.9-56.5]), all p < 0.05 (table 2). Lp(a) was also significantly higher among those with LDL-C ≥ 100 mg/dL relative to LDL-C < 100 mg/dl (25.5[9.5-63.2] vs 21.4[8.4 vs 52.2] p < 0.05). Conclusions In this cohort of patients followed at a tertiary center specialized in CVD, approximately a third had Lp(a) levels above 50 mg/dL, a cutoff robustly associated with ASCVD. This finding likely represents an important source of cardiovascular residual risk, particularly in those with established ASCVD, exposing the need of further therapies.

Transferrin saturation is a superior prognostic biomarker for iron deficiency after acute decompensated heart failure: a retrospective clinical real-world cohort study

Abstract Background Iron deficiency (ID) is the most common extracardiac comorbidity in heart failure (HF) and associated with worse outcomes. While a uniform definition of ID in HF remains lacking, several biomarkers for ID, including ferritin and transferrin saturation (TSAT), are used in both clinical trials and clinical practice. However, which biomarker is a superior prognostic predictor for ID in HF remains unsettled. In addition, real-world clinical data on ID screening and intravenous (IV) iron treatment is largely missing. Purpose To determine which biomarker is a superior prognostic predictor for the composite endpoint of HF rehospitalisation (HHF) and all-cause mortality in a real-world cohort of patients with HF and coexisting ID, and to investigate frequency and predictors of ID screening and IV iron treatment. Methods In this retrospective cohort study, all patients aged 18-85 years hospitalised at a tertiary university hospital with new onset HF with reduced ejection fraction (HFrEF) in 2016-2020 were consecutively included from medical records by ICD-10 code I50.0-I50.9 and followed until 31 December 2021. Patient characteristics, comorbidities, medications, laboratory results and data on follow-up, including if ID was tested for, IV iron administration, HHF and all-cause mortality was collected. First available iron status after admission for index hospitalisation was used. Predictors for ID screening and IV iron use were identified with univariate logistic regression. The association between ID markers and the composite endpoint was analysed with Cox regression adjusted for age, sex, baseline anemia, estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and N-terminal pro-B type natriuretic peptide (NT-proBNP) below median value with median ferritin and TSAT values set as references respectively. Results In all, 753 patients were included (66.5 ± 12.7 years, 508 (67.5%) men, ejection fraction 29.5 ± 6.9% and mean NT-proBNP 6241 ± 7183 ng/L). Of these, 484 (64.3%) were screened for ID and 235 (48.6%) fulfilled criteria for ID. Of these, 94 (40.0%) received IV iron. Of screened patients, 28.6% had ID with anemia and 20.8% ID without anemia (Table 1). Factors associated with screening for ID were follow-up at hospital, anemia, eGFR <30 mL/min/1.73 m2 and ischemic heart disease, and for IV iron additionally chronic kidney disease and peripheral artery disease. Median ferritin was 140 µg/L and TSAT 0.2. Both ferritin and TSAT displayed an inversely linear association with outcomes, while TSAT <0.2 showed a stronger association with increased risk of HHF and all-cause mortality compared to median values (Figure 1-2). Conclusions In a real-world clinical setting, TSAT was a superior prognostic biomarker for worse outcomes compared to ferritin in patients hospitalised for acute HF. While both ID screening and IV iron use remained greatly underutilised in clinical practice, identification of a reliable biomarker for ID is critical.

Carbon dioxide (CO2) as an alternative contrast agent in percutaneous transluminal angioplasty procedures for chronic limb-threatening ischemia patients with chronic kidney disease

Background: Chronic limb-threatening ischemia (CLTI) is a very morbid illness that significantly reduces quality of life. The severity of this disease may necessitate revascularization or amputation. Arteriography is frequently performed for the planning of revascularization. Patients with compromised kidney function need alternative contrast agents. CO2 may be utilized in lower extremity vascular diagnostics and intervention, especially in patients at risk for contrast-induced nephropathy (CIN). Case Illustration: An 80-year-old female with bilateral leg pain and leg swelling had an ulcer on her toe for 2 weeks. She had a history of intermittent claudication for 1 year, hypertension for 5 years, kidney stones for 2 years, and chronic kidney disease for 1 year. She underwent an ECG, laboratory, USG, DUS, and CT-angiography examination. From her laboratory result, her initial creatinine was 5.02 mg/dL (eGFR 8 mL/m/1.73 m2). After good hydration, it became 1.28 mg/dL (eGFR 39 mL/m/1.73 m2). After a CT-angiography procedure, her creatinine level was increased (3.7 mg/dL; eGFR 10.9 mL/m/1.73 m2). She was diagnosed with CLTI Rutherford V Fontain 3 left lower extremity. She suggested doing an angioplasty procedure with a safer contrast agent. An angioplasty procedure was done at RSSA Malang with CO2 contrast. After the procedure, her leg pain improved, and her creatinine didn’t elevate. Conclusion: CO2 angiography might be used as a safe alternative contrast medium in patients with CLTI, which benefits the preservation of renal function and prevents limb amputations. Keyword: chronic limb-threatening, chronic kidney disease, CO2 angiography, contrast-induced nephropathy, peripheral artery disease

Estimation of individual lifetime cardiovascular disease risk and treatment benefit in patients with established atherosclerotic cardiovascular disease: the updated SMART-REACH2 model

Abstract Background The 2021 ESC Guidelines on Cardiovascular Disease (CVD) Prevention in Clinical Practice recommend using (lifetime) risk to guide preventive treatment intensification. Purpose Updating and systematically recalibrating the SMART-REACH lifetime prediction model for the estimation of lifetime risk of recurrent CVD in patients with established atherosclerotic CVD (ASCVD) to various European and international risk regions. Methods The updated SMART-REACH (i.e., SMART-REACH2) model was derived using data from 9,477 individuals between 40-90 years with coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysms included in the UCC-SMART cohort in whom 2,090 ASCVD events were observed during a median follow-up of 8.9 years (interquartile range 4.5–14.1). Coefficients for type of CVD, estimated glomerular filtration rate, non-high density lipoprotein cholesterol, systolic blood pressure, duration of CVD, C-reactive protein, current smoking, and presence of diabetes were derived using sex-stratified cause-specific Cox models with age as the time axis, adjusted for the competing risk of non-CVD mortality. Lifetables were used to estimate 10-year and lifetime CVD-risk and CVD-free life expectancy. The SMART-REACH2 model was externally validated in 121,701 patients from the NOR-COR, Nor-COAST, HUNT3, SWEDEHEART, Bialystok PLUS/Polaspire, REACH-EU, and REACH non-EU (Asia, Japan, Latin America, North America) covering 43 countries. The model was recalibrated to specific risk regions based on the expected-observed ratios from representative cohorts. Performance was assessed by calibration of predicted and observed risk and Harrel’s C-statistic for discrimination. Results 16,689ASCVD events were observed in the external validation cohorts. The model was visually well calibrated for the various risk regions. The pooled C-statistic across risk regions was 0.665 [95% confidence interval 0.640-0.691], with adequate performance in the separate regions (Figure 1). Using SMART-REACH2 to estimate potential gain in CVD-free life expectancy upon treatment initiation showed varying projections. For example, two comparable 55-year-old males from the low-risk region and very high-risk region would gain an estimated 2.2 and 3.9 CVD-free life years as a result of smoking cessation (Figure 2). Conclusion(s) By using larger and more contemporary data sources, considering geographical differences, and extending the age range, the updated SMART-REACH2 model provides an improved algorithm for the estimation of lifetime risk and CVD-free life expectancy for individuals with established ASCVD, facilitating shared decision-making for cardiovascular prevention as recommended by the 2021 ESC Prevention of CVD guidelines.C-statistics across global risk regionsCase vignette

Association of soluble ST2 with heart failure and other comorbidities in patients with severe coronary heart disease

Abstract Background Circulating levels of soluble suppression of tumorigenicity-2 (sST2) reflect vascular congestion, inflammation, and fibrosis. sST2 has been proposed as a useful biomarker to predict the mortality and hospitalization due to heart failure. However, there is limited evidence regarding the relationship between sST2 and heart failure, as well as other comorbidities, in severe coronary heart disease (CAD). Purpose This study aims to measure the circulating levels of soluble ST2 (sST2) in a large population of patients with severe CAD to determine its association with heart failure, cardiac function, inflammation, and other important comorbidities. Methods This subanalysis is part of the ongoing perspective observational study. Available serum samples from 520 patients undergoing elective coronary artery bypass grafting (CABG) were analysed for sST2 levels. The inclusion criteria were written informed consent and age between 18-85 years. Exclusion criteria for this analysis were severe valvular disease, severe chronic obstructive pulmonary disease, oxygen therapy, nocturnal positive airway pressure support or mechanical ventilation, and the need for catecholamines or circulatory assist devices. The circulating levels of human sST2 were measured from frozen serum (-80°C) using commercially available ELISA kits. The plasma was diluted 100 times to detect sST2 levels (assay range of 31.2 - 2,000 pg/mL). Two measurements were taken to account as means for intra-assay variabilities. Logarithmic transformation was used to convert non-normal distributed data. Student t' test and linear regression were applied to categorical or continuous variables as appropriate. Results sST2 levels (median 20.4 ng/ml, [IQR 15.5 – 28.8]) significantly predict worse left ventricular ejection fraction (β = -0.164, p = 0.006), and significantly correlate with levels of NT-proBNP (β = 3.263, p < 0.001), hs-Troponin T (β = 3.391, p < 0.001), high-sensitivity C-reactive protein (β = 2.472, p = 0.014) and heart failure (p= 0.002). Interestingly, common comorbidities such as chronic kidney disease (estimated glomerular filtration rate < 60 mL/min/1.73 m2, p = 0.004), diabetes mellitus (p = 0.001) and higher levels of glycated haemoglobin (HbA1c, β = 3.615, p < 0.001) showed also a significant association with sST2 levels. No significant association of sST2 was observed with arterial hypertension (p = 0.190), atrial fibrillation (p = 0.289), obesity (BMI ≥ 30 kg/m2, p = 0.302), sleep apnoea (apnoea-hypopnoea index ≥ 15/h, p = 0.068), peripheral artery disease (p = 0.823), or previous stroke (p = 0.861). Conclusion(s) Circulating levels of sST2 significantly correlate with heart failure, NT-proBNP, hs-TnT, and hs-CRP in patients with severe CAD. Additionally, sST2 levels were found to be elevated in patients with diabetes mellitus and chronic kidney disease.