Peripheral Artery Research Articles

Dual pathway inhibition in peripheral arterial disease

Despite its high worldwide prevalence and the intuitable negative prognostic connotation, for a long time peripheral artery disease (PAD) has not been the subject of particular interest by the cardiac scientific community. The availability of a new therapeutic strategy (low-dose rivaroxaban associated with acetylsalicylic acid) has reignited interest in PAD. The clear evidence derived from the COMPASS and VOYAGER PAD trials, with the possibility of using dual pathway inhibition, has given new energy to the therapeutic front against symptomatic PAD also associated with coronary artery disease. This review article aims to revisit the pathophysiological concepts underlying PAD and the path of the various clinical trials that have led to new scientific evidence.

What Is the Best Experimental Model for Developing Novel Therapeutics in Peripheral Artery Disease?

More than 200 million people worldwide have peripheral artery disease (PAD). PAD affects the quality of life and is associated with significant morbidity and mortality. Standard treatment for severe cases of PAD is surgical or endovascular revascularization. However, up to 30% of patients are not candidates for open or endovascular procedures, due to high operative risk or unfavorable vascular involvement. Furthermore, revascularization procedures may be insufficient to adequately improve microvascular tissue perfusion, wound healing, or limb salvage. Accordingly, regardless of advances in treatment modalities, outcomes of patients with PAD have remained unfavorable. Therefore, new medical therapeutic approaches are much needed. Small animal models are indispensable tools for the understanding of PAD physiopathology and the development of novel medical therapies. Development of animal models that more closely mimic the pathophysiology (with occlusive atherothrombosis and chronic development of limb ischemia) can incorporate the cardiovascular risk factors associated with this disease state, and focus on more clinically relevant outcomes is critical. In practice, this means using both animals that develop atherosclerosis and methods for the application of gradual arterial occlusion to induce hind limb ischemia. Doing so will likely help identify novel targets for intervention and overcome some principal challenges confronted by previous clinical trials. While various rodent models are discussed, the optimal animal model is yet to be defined.

Heel Raises and Calf Stretches Exercises Versus Medication Only in Ischemic Intermittent Claudication: A Randomized Controlled Trial.

Intermittent claudication is a primary symptom of peripheral artery disease (PAD). a chronic progressive disease caused primarily by atherosclerosis. It is usually characterized by leg pain, aches, cramps, or fatigue when walking, which improves with rest. Physical therapy, including a supervised exercise program, is often recommended as the first treatment for sprains. This study aims to evaluate the short-term effects of incorporating heel raise and calf stretch exercises with standard medical therapy compared to medical therapy alone in managing intermittent claudication. From May 2022 to November 2023, 160 patients with Stage II Fontaine PAD were randomly assigned to two equal groups. Group A (80 patients) received heel raise and calf stretch exercises in addition to medical treatment, while Group B (80 patients) received only medical treatment. Both groups underwent treadmill walking tests before and after three months to measure absolute walking distance (ACD), peak walking time (PWT), and Walking Impairment Questionnaire (WIQ) scores, including distance, speed, and symptom severity. At baseline, there were no significant differences between the groups in terms of ACD, peak walking time, ankle-brachial index, distance, speed, and symptoms. At follow-up, Group A showed significantly greater improvements in ACD (312.00 ± 45.43 m), peak walking time (8.54 ± 1.55 min), distance (29.46 ± 4.63 km), speed (20.01 ± 3.13 kph), and WIQ symptoms (22.10 ± 1.02) compared to Group B, which had ACD (276.55 ± 29.07 m), peak walking time (6.72 ± 1.70 min), distance (23.68 ± 3.89 km), speed (15.71 ± 2.71 kph), and WIQ symptoms (20.80 ± 1.47) (P < .001). The ankle-brachial index remained similar between the groups (P > .05). We concluded that integrating standard physical therapy exercises, such as calf raises and leg stretches, with medical therapy significantly enhances walking function in patients with ischemic intermittent claudication.

Clinical impact of systemic inflammation across the spectrum of different high-sensitivity CRP values in patients undergoing percutaneous coronary intervention

Abstract Background Systemic inflammation enhances atherosclerosis progression and is a well-established determinant of cardiovascular risk. High-sensitivity C-reactive protein (hsCRP), the most widely available biomarker of inflammation, has indeed been associated with the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) in patients undergoing percutaneous coronary intervention (PCI). However, some heterogeneity exists in the threshold to define high hsCRP associated with increased cardiovascular risk, with the 2 and 3 mg/L cut-offs being used more commonly. Purpose We aimed to evaluate the clinical impact of systemic inflammation in patients undergoing PCI across the spectrum of baseline hsCRP values. Methods We retrospectively evaluated consecutive patients undergoing PCI with drug-eluting stent implantation from 2012 to 2022 at Mount Sinai Hospital (NY, USA). We excluded patients presenting with acute myocardial infarction or active cancer and those for whom baseline hsCRP was not available or was above 10 mg/L. Patients were stratified into three groups according to baseline hsCRP levels: &amp;lt;2.0, 2.0 to 3.0, and &amp;gt;3.0 mg/L. We estimated the risk of 12-month adverse events using the lowest hsCRP group (&amp;lt;2.0 mg/L) as reference. The primary endpoint was MACCE, defined as the composite of all-cause death, myocardial infarction (MI), or stroke. Secondary endpoints were MACCE individual components, target vessel revascularization (TVR), stent thrombosis and bleeding. Results A total of 10,811 patients were included in the analysis. Of these, 6,210 (57.4%) had hsCRP &amp;lt;2.0 mg/L, 1,624 (15.0%) between 2 and 3 mg/L and 2,977 (27.6%) &amp;gt;3.0 mg/L. Incidence of anemia, diabetes mellitus, peripheral and cerebrovascular artery disease, atrial fibrillation and chronic kidney disease increased stepwise across hsCRP groups. Moreover, patients with higher hsCRP tended to present more frequently with unstable angina and higher baseline LDL cholesterol levels. As regards procedural variables, coronary artery disease severity and PCI complexity did not differ significantly across groups. When compared with patients with hsCRP &amp;lt; 2, hsCRP &amp;gt; 3 mg/L was associated with a greater adjusted risk of MACCE (4.9% vs 2.4%; HR 1.75 % CI 1.35 - 2.28), all-cause death (2.5% vs 0.9%, HR 2.34, 95%CI 1.57-3.47) and MI (2.5% vs 1.3%; HR 1.58 95%CI 1.11-2.26) (Figure 1). Risks of stroke, TVR, stent thrombosis and bleeding did not significantly differ across hsCRP groups (Table 1) Conclusions In patients undergoing PCI, elevated hsCRP values exceeding 3 mg/L exhibit a more robust association with the risk of MACCE and all-cause mortality, as compared with both hsCRP &amp;lt; 2.0 and between 2.0 and 3.0 mg/L. In this context, the use of hsCRP might improve the stratification of patients associated with higher inflammatory burden.

Preclinical assessment of transcatheter-delivered expandable endoluminal polymeric graft fabricated by electrospinning of microfiber

Abstract Background Matrix fabricated from electrospinning of micro fibre of polyester is porous and permeable to blood, facilitates cell infiltration and late resorption of the biodegradable material. This biomaterial opens an avenue of research in recreating a novel and favourable endoluminal lining in diseased vessel. Previous preclinical work has shown that implants in aorta of rodents generate layers of endoluminal elastin. In humans, one of the most impervious arteries to atherosclerosis is the intra-thoracic artery; therefore, an attempt to induce similar structures with an implantable device was made. Methods For this study, novel tissue-engineered vascular grafts (T-TEVGs) were used in a preclinical rabbit iliac artery model. It was made of resorbable polyester biomaterial processed into fibrous tubular conduits. These T-TEVGs were implanted percutaneously. In total, twelve T-TEVGs in iliac arteries of nine rabbits were implanted. Follow-up were conducted on five rabbits with eight T-TEVGs at three months, two rabbits with two T-TEVGs at six months, and two rabbits with two T-TEVGs at twelve months. At follow-up, percutaneous optical coherence tomography (OCT) was performed, and OCT-derived luminal vessel wall dimensions and fractional flow reserve (OFR) derived from OCT were assessed. Results The overall pooled analysis at different timepoints on follow-up, documented an average MLA of 1.74±0.48mm2, average of proximal and distal reference area of 4.55±0.99 mm2, average area stenosis of 61±12%, and mean OFR value of 0.96±0.03 (OFR ranging from 0.89 to 0.99). There was a moderate positive correlation between minimum lumen area and OFR (r=0.590, p&amp;lt; 0.01). There was a strong negative correlation between percentage area stenosis and OFR (r= - 0.846, p&amp;lt; 0.01). At no timepoint in follow-up and in every vessel analysed, OFR value was lower than 0.89, suggesting that none of these vessels exhibited flow-limiting narrowing. Our study has a few limitations. 1) The preclinical model is a non-atherosclerotic rabbit; 2) There was no barotrauma prior to the implantation of the device; 3) Limited sample size, short and medium follow-up duration, and pooling of assessment at different timepoints. Conclusion The current study shows the durability and favourable hemodynamics of this bioresorbable fibrillated scaffold at short and medium term follow-up, supporting the potential utility of T-TEVEGs for peripheral human artery revascularisation. Long-term follow-ups are mandatory to confirm the durability of these results. Histopathology of this preclinical model should confirm the endoluminal elastin as previously documented in rodents (rats) and will be presented at the time of the congress.

Deciphering postoperative hemodynamics in pediatric intensive care: insights from patient-specific computational fluid dynamics models for congenital heart disease

Abstract Purpose Precise hemodynamic control is imperative for optimizing outcomes in children undergoing cardiac surgery, particularly in the pediatric intensive care unit (PICU). Computational fluid dynamic (CFD) models tailored to individual pediatric patients following definitive repairs for congenital heart disease hold the potential to discern and analyze the intricacies of their hemodynamic systems. This study aims to explore the applicability of patient-specific CFD models in determining optimal treatment strategies to enhance patient hemodynamics. Methods Ten postoperative pediatric patients (6 females and 4 males, median age 4.5±3.6 months, median height 62.5±5.3 cm, and median weight 6.2±1.3 kg) diagnosed with ventricular septal defect (VSD, n=5), atrial septal defect (ASD, n=2), and atrioventricular septal defect (AVSD, n=3) were enrolled. Continuous radial arterial waveforms and sporadic arterial blood draws, including lactate levels, were recorded in the PICU postoperatively. Fluid dynamics equations were employed to model major and peripheral blood vessels, utilizing a 0–1-dimensional hemodynamic model validated in previous studies and refined for this investigation. Sensitivity analysis based on correlation coefficients identified significant parameters, adjusted for replicating pressure waveforms. Comparison and re-approximation was made with actual radial artery pressure waveforms from 78 arterial waveforms and blood draws. Updated parameters were then correlated with postoperative time and lactate levels in the ICU. Results Replicated waveforms demonstrated high agreement with original arterial waveforms, with mean, maximal, and minimal blood pressure percentages of 96.7±1.8%, 96.7±2.4%, and 95.8±2.4%, respectively. Notably, systemic vascular resistance and compliance exhibited a substantial relationship with time elapsed after admission to the PICU, with correlation coefficients (R) of 0.26 and 0.43, respectively. Lactate levels demonstrated a decrease with reduced peripheral vascular resistance and an increase in vascular compliance, with R of 0.23 and 0.32, respectively, aligning with expected clinical improvement and stability. Conclusion This study successfully attained precise replication of radial artery blood pressures and intricate pressure waveforms using patient-specific CFD models in pediatric patients following congenital heart disease repairs. The insights gained shed light on the pivotal hemodynamic parameters that impact both stability and instability. This research sets the stage for theoretically informed treatments by amalgamating real-time biological information with patient-specific CFD models.Re-approximation of arterial waveformCorrelation of hemodynamic parameters

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&amp;lt;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&amp;lt;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&amp;lt;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.

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 &amp;lt;5 years, 6-10 years, and &amp;gt;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 &amp;lt;5 years, 1,074 (22.4%) 5-10 years, and 1,831 (38.3%) &amp;gt;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 (&amp;lt;5 years, reference; 6-10 years, HR 1.25 [95% CI, 1.06-1.46]; &amp;gt;11 years, HR 1.33 [1.15-1.54]). The benefit of dapagliflozin on the primary outcome was consistent across T2D duration category: &amp;lt;5 years, HR 0.85 (95% CI, 0.69-1.04); 5-10 years, HR 0.65 (0.51-0.83); &amp;gt;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.

Factors associated with major adverse cardiovascular events among Arabs and Jews in Israel: a population-based cohort study

Abstract Introduction Arabs in Israel are at higher risk of cardiovascular mortality; however, there are no data on factors associated with disparities in major adverse cardiovascular events (MACE) incidence among Arabs and Jews. Purpose To study factors associated with MACE incidence among Arabs and Jews in Israel. Materials and Methods This is a cohort study carried out in urban localities of Hadera District in Israel. The study sample included 1,100 participants, stratified in equal numbers by ethnicity (Arab and Jewish), sex, and five 10-year age group (mean age: 51 years, range: 26-77). Data collected via in-person interviews conducted between 2001-2006 included socio-demographic characteristics and health-related behaviors (smoking, physical activity, and diet). Data on baseline diabetes, hypertension, dyslipidemia, and cardiovascular disease were collected from interviews and participants' health records. Information on MACE occurring during follow-up was determined based on hospital discharge diagnoses, recorded in the Israel Ministry of Health hospital admission database. MACE was defined as an acute coronary, cerebrovascular or peripheral artery event, or invasive procedure for its treatment. Factors associated with the time to first MACE were tested in Cox proportional hazards models. Sensitivity analysis included death from any cause as a competing risk, using Fine and Gray’s model. Results During a median follow-up period of 20 years, there were 221 first MACE during follow-up; 91 among Jewish participants and 130 among Arab participants, hazard ratio (HR) Arab vs. Jewish: 1.59; 95% confidence interval (CI) 1.22, 2.09, adjusted for age and sex. Arab ethnicity was no longer significantly associated with MACE, following further adjustment for years of education; HR: 1.32; 95%CI 0.95, 1.84. The HR (95%CI) associated with ethnicity after additional adjustment for health-related behaviors, body weight and baseline chronic morbidity was 1.02 (95%CI: 0.73, 1.42). A subgroup analysis among 950 participants, who did not have a baseline diagnosis of cardiovascular disease, produced similar results. These participants experience 147 first MACE during follow-up. The age and sex-adjusted HR (95%CI) associated with Arab ethnicity was 1.72 (1.23, 2.40), compared to 1.08 (0.72, 1.64) in a fully adjusted model. Competing risk analysis did not materially change these results. Conclusions Arabs in Israel are at higher risk for MACE. Lower socioeconomic position and higher prevalence of unhealthy lifestyle and cardiovascular risk factors may explain the excess risk of MACE among Arabs. Improving cardiovascular health among Arabs should consider social determinants of health and cultural aspects.

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&amp;lt;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.

Remnant cholesterol, not LDL cholesterol, explains peripheral artery disease risk conferred by apolipoprotein B: a cohort study

Abstract Background Elevated apolipoprotein B (apoB)-containing lipoproteins (=remnants + low-density lipoproteins [LDL]) are a major risk factor for atherosclerotic cardiovascular disease, including peripheral artery disease (PAD) and myocardial infarction. We tested the hypothesis that remnants and LDL both explain part of the increased risk of PAD conferred by elevated apoB-containing lipoproteins. For comparison, we also studied risk of chronic limb-threatening ischemia and myocardial infarction. Methods ApoB, remnant cholesterol, and LDL cholesterol were measured in 93,461 individuals without statin use at baseline from the Copenhagen General Population Study (2003-2015). During up to 15 years of follow-up, 1,207 had PAD, 552 had chronic limb threatening ischemia, and 2,022 had myocardial infarction in the national Danish Patient Registry. Remnant and LDL cholesterol were calculated from a standard-lipid profile. Remnant and LDL particle counts were additionally measured with nuclear magnetic resonance spectroscopy in 25,347 of the individuals. Results were replicated in 302,167 individuals without statin use from the UK Biobank (2004-2010). Results In the Copenhagen General Population Study, multivariable adjusted hazard ratios for risk of PAD per 1 mmol/L (39 mg/dL) increment in remnant and LDL cholesterol were 1.9 (95% confidence interval: 1.5-2.4) and 1.1 (1.0-1.2), respectively; corresponding results in the UK Biobank were 1.7 (1.4-2.1) and 0.9 (0.9-1.0), respectively. In the association from elevated apoB to increased risk of PAD, remnant and LDL cholesterol explained 73% (32-100%) and 8% (0-46%), respectively; corresponding results were 63% (30-100%) and 0% (0-33%) for risk of chronic limb-threatening ischemia, and 41% (27-55%) and 54% (38-70%) for risk of myocardial infarction; results for remnant and LDL particle counts corroborated these findings. Conclusions PAD risk conferred by elevated apoB-containing lipoproteins was explained mainly by elevated remnants, while myocardial infarction risk was explained by both elevated remnants and LDL.

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&amp;lt;0.01) and were more often females (57% vs 33%, respectively; p&amp;lt;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&amp;lt;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&amp;lt;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&amp;lt;0.01 for both). Non-retrievable SEVs required less radiation (14±7 vs. 18±10 mins, respectively; p&amp;lt;0.01), but still markedly more than BEVs (p&amp;lt;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

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) &amp;lt;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 &amp;lt;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 &amp;lt;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.

Lipid management among very-high-risk patients with atherosclerotic cardiovascular disease and type 2 diabetes

Abstract Background Patients with established atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes (DM2) often meet very-high-risk (VHR) criteria for recurrent ASCVD events and are recommended for aggressive low-density lipoprotein-cholesterol (LDL-C) lowering in guidelines. Purpose Our study aimed to evaluate the proportion of patients achieving guideline-based lipid goals and identify factors associated with achieving these goals among VHR patients with established ASCVD and DM2. Methods Electronic health record data were used to identify VHR patients with established ASCVD and DM2 across 14 large US healthcare systems between 1/1/2022-12/31/2022 with an available LDL-C measurement. We examined the percentage of patients achieving guideline-based lipid goals based on the 2018 AHA/ACC Multisociety Guideline, defined as either having an LDL-C &amp;lt;70 mg/dL or receiving maximal lipid-lowering therapy (i.e., on a PCSK9i monoclonal antibody (mAb)) at the time of the last LDL-C test, and performed multivariable logistic regression to evaluate factors associated with the achievement of those goals. Results Among 213,380 eligible VHR patients with ASCVD and DM2 (mean age 70.2 years, 42% women), 51.8% (110,452) patients achieved guideline-based lipid goals. This included 50.9% with an LDL-C &amp;lt;70 mg/dL and 1.7% on a PCSK9i mAb. Female sex (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.61-0.66), Black race (OR, 0.67; 95% CI, 0.63-0.72), Medicaid insurance (OR, 0.92; 95% CI, 0.86-0.97), and non-coronary artery disease forms of ASCVD including peripheral artery disease (OR, 0.67; 95% CI, 0.65-0.69) and cerebrovascular disease (OR, 0.80; 95% CI, 0.77-0.83) were associated with a lower likelihood of achieving guideline-based lipid goals. Conversely, having undergone percutaneous coronary intervention (OR, 1.31; 95% CI, 1.19-1.43) or coronary artery bypass graft (OR, 1.24; 95% CI, 1.06-1.45) in the previous year, and comorbidities including dialysis (OR, 1.38; 95% CI, 1.23-1.55), atrial fibrillation or flutter (OR, 1.09; 95% CI, 1.06-1.12), and systolic heart failure (OR, 1.11; 95% CI, 1.08-1.14) were associated with a higher likelihood of achieving these goals. Overall, 24.0% of patients were on no statin, 27.2% were on a low- or moderate-intensity statin, and only 5.8% were on a statin in combination with ezetimibe or a PCSK9i mAb. Conclusion Large gaps in care exist for VHR patients with ASCVD and DM2, particularly among women, Black individuals, and those with Medicaid. Targeted interventions are needed to improve the uptake of evidence-based secondary prevention therapies in these patients.

The risk factors for in-stent restenosis following drug-eluting stent implantation in end-stage renal disease patients receiving renal replacement therapy

Abstract Background Chronic renal disease is a recognized risk factor for in-stent restenosis (ISR) following percutaneous coronary intervention (PCI) with a drug-eluting stent (DES). However, the specific risk of ISR among individuals with end-stage renal disease (ESRD) remains unclear or insufficiently studied. Purpose It is imperative to identify the risk factors associated with ISR among patients with ESRD and coronary artery disease following the implantation of DES. This identification is crucial for generating evidence-based strategies aimed at preventing ISR. Methods ESRD patients undergoing renal replacement therapy with concomitant coronary artery disease who underwent PCI with their initial DES implantation at our hospital between January 2013 and December 2022 were included in the study cohort. Clinical data, laboratory test results, and PCI specifics were compared between patients with and without ISR. Univariate and multivariate analyses utilizing Cox proportional hazard regression were employed to identify independent risk factors for DES-ISR. Results Among the 321 patients with ESRD who underwent PCI with DES implantation, totaling 874.5 patient-years of follow-up, 53 cases of ISR occurred during this period, yielding an incidence rate of 6.1 per 100 patient-years. Several baseline characteristics, angiographic findings, and procedural details were found to elevate the risk of ISR significantly. These included underlying diabetes mellitus, peripheral artery disease (PAD), high serum parathyroid hormone levels, LDL-C levels, acute coronary syndrome as the clinical presentation, the presence of triple vessel disease, duration of dual antiplatelet therapy less than 1 year, target lesion involving the left main (LM) or left anterior descending (LAD) artery, target vessel size less than 3 mm, ostial lesion, bifurcation lesion, number of stents implanted equal to or more than 3, and stent size less than 3 mm. In the multivariate Cox proportional hazard model, bifurcation lesion (HR 14.70, 95% CI 4.66-46.38), PCI of LM or LAD (HR 5.29, 95% CI 1.14-24.60), target vessel size less than 3 mm (HR 4.10, 95% CI 1.77-9.50), PAD (HR 3.92, 95% CI 1.52-10.08), and ostial lesion (HR 2.92, 95% CI 1.16-7.38) were identified as independent risk factors for ISR (all p-values &amp;lt; 0.05). Conclusions Among ESRD patients with coronary artery disease, bifurcation lesion, PCI involving the LM or LAD, target vessel size less than 3 mm, PAD, and ostial lesion are identified as independent risk factors for ISR. These findings hold significance in enhancing risk stratification and decision-making concerning treatment planning for this population.Univariate analysis risk factors for ISR

Enhancing guidewire efficacy for transradial access: the EAGER randomised controlled trial

Abstract Background and Purpose The standard J tip peripheral guidewire used to perform coronary angiography was originally designed for transfemoral access and large vascular interventions over 70 years ago. The 3mm J tip on the standard wire is larger than the typical radial artery diameter and has limited ability to navigate smaller tortuous peripheral arteries increasing the risk of vessel spasm, and potentially reducing procedural success. We compared the efficacy and safety of a hydrophilic 1.5mm J tip guidewire (intervention - ‘baby J wire’) upfront versus the standard fixed core 0.035" J wire (‘control wire’). Methods Investigator initiated, blinded multicentre randomised trial conducted in Australia. Patients undergoing clinically indicated transradial coronary angiography were randomized 1:1 to either control or baby J peripheral guidewire use upfront. The primary endpoint was technical success defined as gaining access to the aortic root with the randomised guidewire. Secondary endpoints included total procedural time, time to aorta and coronary intubation, crossover rates to alternate wire or access site, fluoroscopy times, radial artery spasm, haematoma (EASY criteria), bleeding complications (BARC criteria) and vascular complications (VARC 2 criteria). Major adverse cardiac events (MACE) and clinical endpoints were adjudicated by a blinded independent clinical events committee. Results 330 patients were enrolled over a 9-month period from October 2022 to June 2023. The median age was 69 years (36% female), BMI 29kg/m2. The primary efficacy endpoint of technical success was achieved more frequently in the intervention group (96% v 85%; ARR 10.9% (95% CI 4.6 -17.2); P &amp;lt;0.001). Women were significantly more likely to benefit from the intervention related to higher failure rates with the control wire (69% vs 93% in men; P = &amp;lt; 0.001). Overall procedure times were similar between the groups (median 1135 vs 1354 seconds; P=0.094) but fluoroscopy time was lower in the baby J wire group (median 344 vs 491 seconds; P = 0.024). Radial completion of procedures was high and did not differ between groups (100% v 98%; P=0.2). Clinically significant bleeding (BARC2+) was more common in the control wire group (3% v 0%; P=0.017). There were no differences in MACE or vascular complications. Conclusion The hydrophilic 1.5mm J tip Baby J peripheral guidewire leads to greater upfront technical success and reduced fluoroscopy time for transradial coronary angiography compared to the standard 3mm J tip guidewire. The baby J hydrophilic guidewire is safe and may have key incremental benefits for the transradial approach particularly in patients with smaller diameter radial arteries including women.Primary Outcome

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 &amp;lt; 0.001), hs-Troponin T (β = 3.391, p &amp;lt; 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 &amp;lt; 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 &amp;lt; 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.

Peripheral artery disease, antithrombotic treatment and outcomes in European and Asian patients with atrial aibrillation: a report from 2 prospective observational registries

Abstract Background In patients with atrial fibrillation (AF), the impact of peripheral artery disease (PAD) on oral anticoagulant (OAC) therapy use and the risk of outcomes remains unclear. Objective To analyse the epidemiology of PAD in a large cohort of European and Asian AF patients, and the impact on treatment patterns and risks of adverse outcomes. Methods We analysed AF patients from two large prospective observational registries. We identified patients with PAD as reported by the investigators. Logistic regression analysis was used to assess factor associated with the presence of PAD at baseline. OAC prescription and risk of outcomes were analyzed according to the presence of PAD, using adjusted Logistic and Cox regression analyses. The primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). Interaction analyses were also performed according to different subgroups. Results 15,497 patients with AF (mean age 68.9, SD 11.6 years; 38.6% female, 30% from Asia) were included in the analysis. PAD was found in 941 patients (6.1%), with higher prevalence among European individuals compared to Asian (8.1% vs 1.2%, p&amp;lt;0.001). Patients with PAD were older, more likely with permanent AF, more symptomatic and with higher thromboembolic and bleeding risk. On logistic regression analysis, European patients had 6-fold higher odds of presenting with PAD compared with Asians (Figure 1, Panel A). Other comorbidities and increasing age were associated with higher odds of prevalent PAD (Figure 1 Panel A). Conversely, female sex was associated with lower odds of having PAD at baseline. With age modelled as a continuous variable, and odds of PAD at baseline, there was a non-linear relationship, with the odds of PAD increasing almost linearly until 70 years, plateauing afterwards (Figure 1 Panel B). After adjustments, PAD was associated with lower use of OAC (OR 0.69, 95% CI 0.57-0.85). On Cox regression analysis, PAD was associated with a higher risk of the primary composite outcome (HR 1.28, 95%CI: 1.08-1.52) and all-cause death (HR 1.40, 95%CI: 1.16-1.69). A significant interaction was observed between PAD and age, with greater risks of PAD found in younger patients (&amp;lt;65 years) for the primary outcome (pint=0.014, Figure 2, panel A). Consistent results were observed when we analysed the interaction between PAD and age, modelled as a restricted cubic spline, where the risk of the primary outcome followed a J-curve across age, while patients without PAD showed an approximately linear relationship (pint&amp;lt;0.001, Figure 2, Panel B). Conclusions In patients with AF, PAD is associated with lower use of OAC and higher risk of adverse outcomes, with a greater risk seen in younger patients.Figure 1Figure 2

Cardiovascular risk factors in poly-vascular vs isolated lower extremity peripheral arterial disease. analysis from the SOLACI peripheral registry

Abstract Introduction Atherosclerotic disease in more than one vascular bed (Polyvascular disease), is a strong independent risk factor for ischemic events and has worse clinical outcomes than those with disease in a single territory. Aims The objective of the present interim analysis is to describe the differences in cardiovascular risk factors and clinical presentation between patients with isolated infra-aortic peripheral artery disease (lower limb: "LL-PAD") and patients with Polyvascular Disease ("PD": simultaneuous coexistence of LL-PAD and affection of at least one more vascular bed) from a cohort of patients undergoing LL endovascular procedures in Latinamerica. Methods Our cohort included patients from The SOLACI Peripheral Registry from March 2021 to February 2024 (a prospective, multi-center, observational, and hospital-based registry of patients with LL- PAD, treated with endovascular interventions across 10 Latin American countries, 42 centers). Patients were considered to have PD if besides LL-PAD, they had a documented history of previous myocardial infarction (MI), coronary revascularization, cerebrovascular, aortic, and/or carotid artery disease. Results A total of 1438 patients were included in the analysis. PD was present in 506 patients(35.1%), of which 225(44.5%) had previous MI; 296(58.5%) previous coronary revascularization;265(52.4%) had aortic and / or carotid disease; and 121(23.9%) had cerebrovascular disease. Patients with PD were older than those with LL-PAD(70.5±9.76 vs 68.6±10.7). PD was more prevalent in men(69.6% vs 62.4%), former smokers(48.2% vs 32.8%), hypertension(92.1% vs 80.5%) and patients with dyslipidemia(75.3% vs 64%). The distribution of treated lesions in the PD group was: 15.4% ilio-femoral; 34 % femoropopliteal; 23.3% infrapopliteal; and 24% had multiple peripheral territories affected and treated at the same time-point. In the LL-PAD group, the distribution of treated lesions was: 12.5% ilio-femoral; 28.6% femoropopliteal; 31.5% infrapopliteal; and 24.8% had multiple peripheral territories affected simultaneously and treated during the same procedure. In general, the lesions were shorter in the PD group: ilio-femoral(53.5±29.2 vs 66.7±48.2mm); femoropopliteal(119±73.6 vs 122±81.7mm); and infrapopliteal(129±83.1 vs 147±93.1mm). In the PD group, a higher percentage of patients were treated with statins and antithrombotic agents: statins (87.5% vs 70.8%), aspirin (91.5% vs 81.1%), clopidogrel (60.9% vs 40.1%), and oral anticoagulants (13.8% vs 6.5%). The use of rivaroxaban was similar in both groups (3.4% vs 3.9%). The PD group had higher intrahospital complication rates: intrahospital death (2.2% vs 0.8%), cardiovascular intrahospital death (1.2% vs 0.4%), MI (0.8% vs 0.1%), stroke (0.4% vs 0%) and bleeding (0.8% vs 0.9%). Conclusions Patients with PD represent a very high-risk population. Systematic screening of multiple vascular beds in patients with LL-PAD may be warranted to prevent worse outcomes.