History Of Peripheral Arterial Disease Research Articles

Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Male and Female Patients: A Secondary Analysis of the ADAPTABLE Randomized Clinical Trial.

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality in the US. Although aspirin is recommended for secondary prevention of ASCVD, there was no difference in safety and effectiveness of aspirin dosed daily at 81 mg or 325 mg in the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) randomized clinical trial. However, it is unknown whether differences by sex exist in the safety and effectiveness of the different aspirin doses. To evaluate sex-specific differences in the safety and effectiveness of 2 aspirin doses in the ADAPTAPLE trial. The ADAPTABLE study was an open-label, pragmatic, randomized clinical trial that randomly assigned participants with chronic, stable ASCVD to 81 mg vs 325 mg of aspirin daily. Using Cox proportional-hazard models, male and female participants were compared for outcomes. In addition, it was assessed whether sex was an effect modifier in the association between aspirin dose and outcomes. The ADAPTABLE trial was conducted at 40 medical centers and 1 health plan. Eligible patients were 18 years and older and had established ASCVD. Study data were analyzed from December 2021 to March 2024. Patients received 81 mg or 325 mg of aspirin daily for the secondary prevention of ASCVD. The primary effectiveness outcomes included all-cause death and hospitalization for myocardial infarction (MI) or stroke. The primary safety outcome was hospitalization for major bleeding requiring transfusion. A total of 15 076 patients (median [IQR] age, 67.6 [60.7-73.6] years; 10 352 male [68.7%]) were followed up for a median (IQR) of 26.2 (19.0-34.9) months. Overall, 4724 (31.3%) were female, and 2307 of the female participants (48.8%) received aspirin 81 mg. Compared with males, female participants were younger (median [IQR] age, 66.3 [59.4-72.6] years vs 68.2 (61.4-73.9) years, less likely to self-report White race (3426 [72.5%] vs 8564 [82.7%]), more likely to smoke (564 [12.9%] vs 818 [8.4%]), and more likely to have a history of peripheral arterial disease (1179 [25.7%] vs 2314 [23.0%]). The primary effectiveness outcome of all-cause death and hospitalization for MI or stroke occurred in 379 female participants (8.1%) and 780 male participants (7.1%). There was no significant interaction by sex for the primary effectiveness end point between the 2 aspirin doses (female adjusted hazard ratio [aHR], 1.01; 95% CI, 0.82-1.26 and male aHR, 1.06; 95% CI, 0.91-1.23; P interaction term for sex = .74). During the trial, female participants had fewer revascularization procedures (237 [5.0%] vs 680 [6.6%]; aHR, 0.79; 95% CI, 0.68-0.92; P = .002) but had a higher risk of hospitalization for stroke (aHR, 1.72; 95% CI, 1.27-2.33; P < .001). Among female participants, there was a slightly higher rate of bleeding in the 81-mg aspirin cohort compared with the 325-mg cohort (20 [0.83%] vs 13 [0.52%]; aHR, 2.21; 95% CI, 1.04-4.70; P interaction term for sex = .07). There were no significant differences between female and male participants regarding aspirin dose adherence. In this secondary analysis of the ADAPTABLE trial, there were no significant sex-specific differences in the effectiveness and safety of 2 aspirin doses for secondary prevention of ASCVD events. ClinicalTrials.gov Identifier: NCT02697916.

Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Male and Female Patients

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality in the US. Although aspirin is recommended for secondary prevention of ASCVD, there was no difference in safety and effectiveness of aspirin dosed daily at 81 mg or 325 mg in the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) randomized clinical trial. However, it is unknown whether differences by sex exist in the safety and effectiveness of the different aspirin doses. To evaluate sex-specific differences in the safety and effectiveness of 2 aspirin doses in the ADAPTAPLE trial. The ADAPTABLE study was an open-label, pragmatic, randomized clinical trial that randomly assigned participants with chronic, stable ASCVD to 81 mg vs 325 mg of aspirin daily. Using Cox proportional-hazard models, male and female participants were compared for outcomes. In addition, it was assessed whether sex was an effect modifier in the association between aspirin dose and outcomes. The ADAPTABLE trial was conducted at 40 medical centers and 1 health plan. Eligible patients were 18 years and older and had established ASCVD. Study data were analyzed from December 2021 to March 2024. Patients received 81 mg or 325 mg of aspirin daily for the secondary prevention of ASCVD. The primary effectiveness outcomes included all-cause death and hospitalization for myocardial infarction (MI) or stroke. The primary safety outcome was hospitalization for major bleeding requiring transfusion. A total of 15 076 patients (median [IQR] age, 67.6 [60.7-73.6] years; 10 352 male [68.7%]) were followed up for a median (IQR) of 26.2 (19.0-34.9) months. Overall, 4724 (31.3%) were female, and 2307 of the female participants (48.8%) received aspirin 81 mg. Compared with males, female participants were younger (median [IQR] age, 66.3 [59.4-72.6] years vs 68.2 (61.4-73.9) years, less likely to self-report White race (3426 [72.5%] vs 8564 [82.7%]), more likely to smoke (564 [12.9%] vs 818 [8.4%]), and more likely to have a history of peripheral arterial disease (1179 [25.7%] vs 2314 [23.0%]). The primary effectiveness outcome of all-cause death and hospitalization for MI or stroke occurred in 379 female participants (8.1%) and 780 male participants (7.1%). There was no significant interaction by sex for the primary effectiveness end point between the 2 aspirin doses (female adjusted hazard ratio [aHR], 1.01; 95% CI, 0.82-1.26 and male aHR, 1.06; 95% CI, 0.91-1.23; P interaction term for sex = .74). During the trial, female participants had fewer revascularization procedures (237 [5.0%] vs 680 [6.6%]; aHR, 0.79; 95% CI, 0.68-0.92; P = .002) but had a higher risk of hospitalization for stroke (aHR, 1.72; 95% CI, 1.27-2.33; P < .001). Among female participants, there was a slightly higher rate of bleeding in the 81-mg aspirin cohort compared with the 325-mg cohort (20 [0.83%] vs 13 [0.52%]; aHR, 2.21; 95% CI, 1.04-4.70; P interaction term for sex = .07). There were no significant differences between female and male participants regarding aspirin dose adherence. In this secondary analysis of the ADAPTABLE trial, there were no significant sex-specific differences in the effectiveness and safety of 2 aspirin doses for secondary prevention of ASCVD events. ClinicalTrials.gov Identifier: NCT02697916.

A REAL–WORLD PROTOCOL OF EARLY USE OF TRIPLE LIPID LOWERING THERAPY WITH I–PCSK9

Abstract Aim We evaluated the feasibility of an early triple lipid lowering therapy (LLT) with PCSK9 inhibitors in patients with acute coronary syndromes (ACS). Methods In this multicenter experience, we consecutively enrolled ACS patients from July to November 2023. The prescribed LLT was evaluated at discharge. Triple therapy with a high–intensity statin plus ezetimibe and PCSK9i was recommended in the following cases: patients already on statin or statin/ezetimibe therapy with LDL–C values &amp;gt; 70 mg/dl; patients not on LLT at admission with LDL–C values &amp;gt; 70 mg/dl and at least one of diabetes mellitus (DM), multivessel coronary artery disease (MV) or peripheral arterial disease (PAD); patients not on LLT at the time of admission and LDL–C values &amp;gt; 140 mg/dl even in the absence of DM, MV or PAD. A six–month follow–up was planned to determine LDL–C target attainment, compliance, side e!ects, and cardiovascular events. Results We consecutively enrolled 264 patients, 95% of whom were discharged with high–intensity statin plus ezetimibe and 29% discharged with in–hospital addition of PCSK9i (triple therapy). Of the 77 patients discharged in triple LLT, the median age was 71.4 years, 71% were male, 42% were current smokers, DM was present in 19%, and 48% had history of hypertension. The diagnosis at admission was ST–Elevation Myocardial Infarction in 66.2%, Non–ST–Elevation Myocardial Infarction in 29.5%, and unstable angina in 4.3% of cases; 63% of patients had history of coronary artery disease and 6.8% had history of peripheral artery disease (PAD); 19.6% were already on at least one statin therapy and the median LDL–C value at admission was 128 mg/dl. Conclusions In conclusion, the use of an early and strong lipid lowering approach in very high risk patients with in–hospital or at discharge PCSK9i administration is feasible and safe. The complete results of six–months follow–up and LDL–C values will be available for the congress.

Variability in the prevalence of depression among adults with chronic pain: UK Biobank analysis through clinical prediction models

BackgroundThe prevalence of depression among people with chronic pain remains unclear due to the heterogeneity of study samples and definitions of depression. We aimed to identify sources of variation in the prevalence of depression among people with chronic pain and generate clinical prediction models to estimate the probability of depression among individuals with chronic pain.MethodsParticipants were from the UK Biobank. The primary outcome was a “lifetime” history of depression. The model’s performance was evaluated using discrimination (optimism-corrected C statistic) and calibration (calibration plot).ResultsAnalyses included 24,405 patients with chronic pain (mean age 64.1 years). Among participants with chronic widespread pain, the prevalence of having a “lifetime” history of depression was 45.7% and varied (25.0–66.7%) depending on patient characteristics. The final clinical prediction model (optimism-corrected C statistic: 0.66; good calibration on the calibration plot) included age, BMI, smoking status, physical activity, socioeconomic status, gender, history of asthma, history of heart failure, and history of peripheral artery disease. Among participants with chronic regional pain, the prevalence of having a “lifetime” history of depression was 30.2% and varied (21.4–70.6%) depending on patient characteristics. The final clinical prediction model (optimism-corrected C statistic: 0.65; good calibration on the calibration plot) included age, gender, nature of pain, smoking status, regular opioid use, history of asthma, pain location that bothers you most, and BMI.ConclusionsThere was substantial variability in the prevalence of depression among patients with chronic pain. Clinically relevant factors were selected to develop prediction models. Clinicians can use these models to assess patients’ treatment needs. These predictors are convenient to collect during daily practice, making it easy for busy clinicians to use them.

Clinical characteristics associated with elevated levels of lipoprotein(a) in patients with vascular risk.

Lipoprotein(a) (Lp(a)) is increasingly used in the evaluation of patients with vascular risk due to its association with cardiovascular events. The purpose of this study was to identify the clinical characteristics of patients with elevated levels of Lp(a) attended in an outpatient vascular risk unit. An observational, retrospective study was conducted to assess the clinical characteristics of patients with elevated levels of Lp(a) (≥50 mg/dL), as compared to patients with normal values (<50 mg/dL). The sample was composed of 878 patients identified as having a high vascular risk due to a diagnosis of vascular disease, attended in a vascular risk unit between 2021 and 2022. The highest levels of Lp(a) were independently associated with a higher probability of having a history of peripheral arterial disease (p=0.024), polygenic familial hypercholesterolemia (PH, p=0.030) and combined familial hypercholesterolemia (CFH, p=0.015); and using PCSK9 inhibitor treatment (p=0.029) and combination therapy with statins and ezetimibe (p=0.018). In contrast, there were no significant differences in relation to familial history of early cardiovascular disease (p=0.143) or personal history of cardiovascular disease (p=0.063), which contrasts with other series. Elevated levels of Lp(a) were associated with a history of peripheral arterial disease, diagnosis of FHP and CFH, and need for more intense lipid-lowering treatments.

New-onset atrial fibrillation in chronic coronary syndrome outpatients. Insights from the international CLARIFY registry

Abstract Background and Aims Data on new-onset atrial fibrillation (NOAF) in patients with chronic coronary syndromes (CCS) are scarce. This study aims to describe the incidence, predictors and impact on cardiovascular outcomes of NOAF in CCS patients. Methods Data from the international (45 countries) CLARIFY registry (prospeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) were used. Among 29,001 CCS outpatients without previously reported AF at baseline, patients with at least one episode of AF/flutter diagnosed during 5-year follow-up were compared with patients in sinus rhythm throughout the study. Results The incidence rate of NOAF was 1.12 [95% confidence interval (CI) 1.06-1.18] per 100 patients-year (cumulative incidence at five years: 5.0%). Independent predictors of NOAF were increasing age, increasing body mass index, treated hypertension, history of peripheral artery disease, alcohol intake and low left ventricular ejection fraction, while high triglycerides were associated with lower incidence. NOAF was associated with a substantial increase in the risk of adverse outcomes, with adjusted hazard ratios of 2.52 (95%CI 2.11-3.01) for the composite of cardiovascular death, myocardial infarction or stroke, 3.22 (95%CI 2.63-3.94) for cardiovascular death, 1.55 (95%CI 1.08-2.22) for myocardial infarction, 2.80 (95%CI 2.0-3.91) for stroke, 2.64 (95%CI 2.23-3.11) for all cause death, 9.38 (95%CI 8.02-10.97) for hospitalization for heart failure and 4.33 (95%CI 2.94-6.39) for major bleeding. Conclusion Among CCS patients, NOAF is common and is strongly associated with worse outcomes. Whether more intensive preventive measures and more systematic screening for AF would improve prognosis in this population deserves further investigation.FlowchartGraphical Abstract

Abstract 15311: Predict Factors Affected With In-Hospital Clinical Outcomes Between Endovascular Therapy and Fogarty Thrombectomy for Patients With Acute Limb Ischemia: A Large Number Analysis Based on JROAD-DPC Database

Background: The etiology of acute limb ischemia (ALI) has been often reported to be embolism caused by atrial fibrillation (Af) and/or atrial flutter (AFL), and thrombosis caused by atherosclerosis. Although endovascular therapy (EVT) or fogarty thrombectomy (Fogarty) is recommended as a primary treatment for patients with ALI, which treatment should be chosen is still controversial. Aim: To evaluate differences of clinical outcomes between primary treatments for patients with ALI, and identify prognostic predictors. Methods: This was a retrospective study based on the database in the JROAD-DPC (Japanese Registry of All Cardiac and Vascular Diseases and the Diagnosis Procedure Combination). Figure.1 showed the flow chart of this study. Comparison with EVT-alone and Fogarty-alone group was analyzed using propensity score matching with 16 clinically relevant covariates. Clinical outcomes were death, major adverse cardiovascular events (MACE; myocardial infarction, coronary intervention, heart failure, stroke, cerebral hemorrhage), bleeding complications with bleeding academic research consortium (BARC) type 3-5, and any amputation. Results: Figure2-4 showed the results of this study. Figure.3 demonstrated that bleeding complications and any amputation in Fogarty-alone group were significantly less than EVT-alone group. Figure.4 revealed that Fogarty tended to decrease an amputation-free survival rate in ALI patients who had no history of peripheral artery disease (PAD) and not administered an antiplatelet before onset. Conclusions: Fogarty should be selected as the primary treatment as much as possible for ALI patients, especially those without PAD.

Abstract 114: “Failing” DAPT? Think Again

Introduction Bow Hunter’s Syndrome (BHS) is a rare etiology of vertebrobasilar insufficiency that usually occurs with head turn, which causes compression of the vertebral artery by an osteophyte. There is subsequent hypoperfusion of brain tissue, but thromboembolism and ischemic stroke is rare. Timely diagnosis is imperative, as decompressive surgery can be curative. This unique case highlights the diagnostic and therapeutic challenges of a patient with multiple vascular risk factors who suffered from strokes secondary to BHS. Methods A 79‐year‐old man with a past medical history of peripheral artery disease, abdominal aortic aneurysm, myocardial infarction with drug eluding stents (on dual antiplatelet therapy (DAPT)), complete heart block with pacemaker, heart failure with reduced ejection fraction, hypertension, hyperlipidemia, and diabetes mellitus presented to an outside hospital with recurrent episodes of right‐sided weakness every 1‐2 days over the previous 3 weeks. Episodes always occurred after activity and only upon sitting. He had previously undergone non‐contrasted head computed tomography (NCHCT) (magnetic resonance imaging (MRI) was unable to be performed secondary to pacemaker), which did not reveal strokes. His initial computed tomography angiogram (CTA) of the head and neck was unremarkable. However, CTA head and neck 4 days later demonstrated 90 percent stenosis of the mid left V2 at the C3‐4 level and a 75‐90 percent stenosis of the left mid V2 segment at the C5‐6 level (hard and soft plaque in these areas). He was switched from DAPT to aspirin and warfarin because he was considered a “DAPT failure.” He continued to have episodes, so he was transferred to our institution for a second opinion. Results On arrival, the exam was notable for right‐sided hemiparesis and dysmetria. Repeat CTA head and neck demonstrated multifocal intracranial atherosclerosis with marked stenosis of the left V4 segment. However, marked stenosis at V2 appeared to be owed to external compression from facet arthrosis rather than atherosclerosis. He also had moderate stenosis of the right V4 segment. Eventually, he underwent an MRI brain, which demonstrated acute to subacute infarcts in the left pons. He was taken for a cerebral angiogram on the same day, which demonstrated stenosis of the distal V2 segment of the left vertebral artery (at the level of C3‐C4) with interval development of marked stenosis following neck flexion and occlusion of the left vertebral artery following leftward head rotation. Findings were most consistent with rotational occlusion of the left vertebral artery, which is also known as BHS. The patient underwent surgery, but suffered from a gastrointestinal bleed and developed post‐operative atrial fibrillation; after a risks/benefits discussion, he was discharged on anticoagulation only. He had no further strokes. Conclusion This patient suffered from ischemic strokes, which occur in less than 10% of BHS cases. Contralateral vertebral artery stenosis, which is unable to supply retrograde flow during compression, is the likely etiology of this patient's strokes. Recurrent posterior circulation strokes in the setting of optimal medical management should clue clinicians to consider other etiologies of stroke. Dynamic angiography is the gold standard for BHS and decompressive surgery is often curative.

Predictors of Bleeding after Percutaneous Coronary Intervention

Background: Acute coronary syndrome patient outcomes have been improved using early invasive techniques. The aim of this study was to investigate the incidence, location, and severity of bleeding in PCI-treated cases to identify patient risk profiles and increased bleeding occurrences.&#x0D; Methods: This prospective observational study evaluated percutaneous coronary angiography in 80 patients with hypertension and diabetes mellitus who planned to undergo primary or elective PCI. The cases were separated into 2 groups; those who reported bleeding (n=11) and those who did not (n=69). All patients underwent physical examination, laboratory evaluation, 12-lead electrocardiography, and PCI.&#x0D; Results: In univariate regression analysis, age (OR: 1.09, 95% CI: 1.009 – 1.192), female gender (OR: 4.32, 95% CI: 1.157 – 16.131), history of peripheral arterial disease (OR: 7.31, 95% CI: 1.585 – 33.742), and femoral site of vascular access (OR: 9.6, 95% CI: 2.263 – 40.721) were independent predictors of major bleeding after PCI. In multivariate regression analysis, age (OR: 1.12, 95% CI:1.014 – 1.269), female gender (OR: 13.75, 95% CI: 1.983 – 161.2), history of peripheral arterial disease (OR: 43.38, 95% CI: 3.754 - 1042) and femoral site of vascular access (OR: 13.29, 95% CI: 2.233 – 128.5) were independent predictors of major bleeding after PCI.&#x0D; Conclusions: Patients who reported bleeding after PCI had a significantly higher age, prevalence of female sex, serum creatinine, and transfemoral intervention before and after intervention compared to patients who did not report bleeding, while haemoglobin and transradial intervention before and after intervention were significantly lower in the bleeding cases than in the non-bleeding cases.

515-P: Study to Evaluate the Relationship between Inpatient Glycemic Control as Measured by CGM and Wound Healing in Patients Admitted for Diabetic Foot Ulcer (DFU)

We performed a post-hoc analysis of hospitalized patients admitted with DFU enrolled in an inpatient continuous glucose monitor (CGM) study. Bivariate analysis was conducted between those with wound healing vs. non-healing over a 16-week period. Logistic regression was performed to assess the following CGM metrics and likelihood of wound healing: TIR (70-180 mg/dl), TAR (&amp;gt;180 mg/dl) and TBR (&amp;lt;70 mg/dl). Potential confounders included in the multivariate analysis were age, race and sex, history of peripheral arterial disease, renal failure, prior amputation, and ulcer duration. Results of patient characteristics are summarized in the Table. Of 230 patients enrolled in our CGM studies, 62 (27%) were admitted for DFU. Sixteen weeks after discharge, 9 (15%) patients were lost to follow-up, 13 (21%) had healed, and 39 (62%) had not healed. Of the non-healed, 10 (15%) had an amputation, 3 (4.7%) died, and 26 (41%) had a persistent ulcer. We did not find an association between the likelihood of healing and CGM derived glycemic metrics: fully adjusted models for TIR (OR 0.99, 95% CI 0.96-1.02), TAR (1.01 95% CI 0.98-1.04), and TBR (0.85; 95% CI 0.52-1.40). While glycemic control remains an important predictor of diabetes complications, we did not find an association between glycemic control in the hospital based on CGM metric and post-discharge healing. Disclosure K.K.Rogers: None. A.A.Rashied: None. M.Schechter: None. M.Fayfman: None. Funding Dexcom, Inc.

Subclinical coronary atherosclerosis, detected by computer tomography with coronary calcium score, and the occurrence of major cardiovascular events at 5 years of follow-up in a cohort of patients with systemic sclerosis

BackgroundSpreading data describe cardiovascular disease (CVD) as a growing cause of hospitalization in systemic sclerosis (SSc) patients. Although interstitial lung disease and pulmonary arterial hypertension (PAH) remain the principal causes of mortality, the presence of CVD has been shown to further increase mortality in SSc patients. Few and contrasting data are available on cardiovascular impairment, particularly of subclinical coronary arteries disease, in SSc patients. The aims of this study were: 1) to determine the demographic, clinical, and cardiovascular differences between the groups of SSc patients with and without subclinical coronary atherosclerosis (SCA) assessed by coronary calcium score; 2) to verify the performance of cardiovascular risk scores in SSc for detection of SCA major cardiovascular events (MCVE); 3) to evaluate the risk factors associated to MCVE in 5 years of follow-up in this study group of patients. MethodsSixty-seven SSc patients were enrolled in this study. SCA was assessed using quantification of coronary calcium score by computerized tomography, reported as Agatson. Evaluation of common cardiovascular risk scores, carotid plaques by Doppler ultrasonography, the history of peripheral artery disease (PAD), lipid profiles, and clinical and laboratiristic characteristics of SSc were assessed at baseline visits for each patient. Factors associated with the presence of SCA were assessed by multivariate logistic analysis. A five years prospective study was performed for the evaluation of MCVE occurrence and its possible predictors. ResultsThe prevalence of SCA was 42% (Agatston scores of 266.04 ± 455.9 units) in our group of SSc patients. Patients with SCA were principally older (p = 0.0001) and had higher rates of CENP-B antibodies (57% vs 26%; p = 0.009), pulmonary arterial hypertension (PAH) (25% vs 3%; p = 0.008), dysphagia (86% vs 61%; p = 0.027), and users of statins (36% vs 8%; p = 0.004), carotid plaque (82% vs 13%; p = 0.0001), PAD (79% vs 18%; p = 0.0001), and metabolic syndrome (25% vs 0%; p = 0.002) than patients without SCA. Metabolic syndrome (OR: 8.2, p = 0.0001), presence of a PAD (OR: 5.98, p = 0.031), and carotid plaque (OR: 5.49, p = 0.010) were the main factors associated with SCA in SSc patients, by multivariate regression analysis. MCVE occurred in 7 patients. By multivariate COX regression analysis unique predictor of MCVE in 5 years of follow-up in our SSc patients was the presence of PAH (HR: 10.33, p = 0.009). Of note, the contemporary presence of PAH and SCA (defined as "not pure" pattern of PAH) was observed in 71% of patients with the occurrence of MCVE ConclusionThis study evidenced the high presence of the new “not pure” pattern of PAH, which could worsen the outcome in SSc in a medium-term (5 years) observation period. Furthermore, our data confirmed a higher cardiovascular impairment in SSc due to the presence of both SCA, mainly associated with typical cardiovascular risk factors, and PAH, life-threatening complications of SSc, that is the principal cause of the occurrence of MCVE in our SSc patients. A careful assessment of cardiovascular involvement in SSc and a more aggressive therapeutic strategy for preventing CAD and treating PAH should be highly suggested to reduce MCVE in SSc patients.

Risk stratification for worsening renal function and renal decline in heart failure patients with reduced ejection fraction after sacubitril/valsartan treatment

BackgroundIn the real-world setting, data regarding renal decline following sacubitril/valsartan treatment are lacking. This study aimed to develop a scoring system to predict renal outcome in sacubitril/valsartan-treated patients. MethodsBetween 2017 and 2018, a total of 1505 heart failure patients with reduced ejection fraction (HFrEF) undergoing sacubitril/valsartan treatment were consecutively enrolled from 10 hospitals to serve as the derivation cohort. Another 1620 HFrEF patients receiving sacubitril/valsartan were included as the validation cohort. Worsening renal function (WRF) was defined as a serum creatinine increase of >0.3 mg/dL and/or >25 % at 8 months of sacubitril/valsartan treatment. The derivation cohort was used to identify independent predictive factors for WRF through multivariate analysis, which were then used to develop the risk score system. ResultsAmong the 3125 HFrEF patients, 689 (22.0 %) patients had WRF at 8 months following sacubitril/valsartan treatment. In the derivation cohort, six prognostic factors (age, functional class, history of peripheral arterial disease, diabetes mellitus, gout or hyperuricemia, and serum albumin level) were independently associated with WRF, and were combined into a risk predicting score. This score showed accurate discrimination in the derivation and validation cohorts (Harrell's concordance indexes 0.74 and 0.71, 95 % confidence intervals 0.71–0.78 and 0.69–0.74, respectively). Patients with a higher risk score experienced a more rapid decline in renal function, poorer clinical outcomes, and a higher rate of discontinuation of sacubitril/valsartan treatment. ConclusionsThis study developed a score for WRF after sacubitril/valsartan treatment, which may assist clinicians with risk stratification and therapeutic decision-making.

History of peripheral artery disease and cardiovascular risk of real-world patients with acute coronary syndrome: Role of inflammation and comorbidities

BackgroundPatients with acute coronary syndromes (ACS) remain at risk of cardiovascular disease (CVD) recurrences. Peripheral artery disease (PAD) may identify a very high risk (VHR) group who may derive greater benefit from intensified secondary prevention. MethodsAmong ACS-patients enrolled in the prospective multi-center Special Program University Medicine (SPUM), we assessed the impact of PAD on major cardiovascular events (MACE: composite of myocardial infarction, stroke and all-cause death) and major bleeding. Multivariate analysis tested the relation of each significant variable with MACE, as well as biomarkers of inflammation and novel markers of atherogenesis. ResultsOut of 4787 ACS patients, 6.0% (n = 285) had PAD. PAD-patients were older (p < 0.001), with established CVD and signs of increased persistent inflammation (hs-CRP; 23.6 ± 46.5 vs 10.4 ± 27.2 mg/l, p < 0.001 and sFlt-1; 1399.5 ± 1501.3 vs 1047.2 ± 1378.6 ng/l, p = 0.018). In-hospital-death (3.2% vs 1.4%, p = 0.022) and -MACE (5.6% vs 3.0%, p = 0.017) were higher in PAD-patients. MACE at 1 year (18.6% vs 7.9%,p < 0.001) remained increased even after adjustment for confounders (Adj. HR 1.53, 95% CI: 1.14–2.08, p = 0.005). Major bleeding did not differ between groups (Adj. HR 1.18; 95% CI 0.71–1.97, p = 0.512). Although PAD predicted MACE, PAD-patients were prescribed less frequently for secondary prevention at discharge. ConclusionsIn this real-world ACS patient cohort, concomitant PAD is a marker of VHR and is associated with increased and persistent inflammation, higher risk for MACE without an increased risk of major bleeding. Therefore, a history of PAD may be useful to identify those ACS patients at VHR who require more aggressive secondary prevention.

Predictors for the Development of Major Adverse Limb Events after Percutaneous Revascularization—Gender-Related Characteristics

Background and Objectives: Revascularization has been proven to be superior to medication for symptom improvement in patients with peripheral arterial disease (PAD). There are well known gender differences in therapeutic strategies for PAD. The influence of gender on post-angioplasty prognosis is not fully understood though. The present study aims to identify potential peculiarities between men and women undergoing peripheral angioplasty, as well as factors responsible for those differences. Material and methods: 104 consecutive subjects (50 women and 54 men) who underwent percutaneous angioplasty (PTA) between January and October 2019 for symptomatic PAD were included. Demographics, PAD history, cardiovascular risk factors, comorbidities, the associated coronary or cerebrovascular diseases, biological parameters, drug-treatment and PTA type and technique were taken into account. The follow-up period was 2 years, during which major adverse limb events (MALE) were documented. Results: The mean age was 67 ± 10 years. Women were 4 years older than the men (69 ± 10 years vs. 65 ± 9.2 years-p = 0.04). Smoking was more prevalent in men (p = 0.0004), while other cardiovascular risk factors did not differ significantly. The mean follow-up of the two groups was 21 ± 2.4 months. Women had infra-inguinal involvement more frequently (78%), while men exhibited mixed disease, with supra + infra-inguinal (37%) or solely supra-inguinal (20.3%) involvement (p = 0.0012). Rates of MALE were similar in the two groups (p = 0.914). Gender did not influence the incidence of PAD-related adverse events. The only parameter that proved to have a significant influence on the occurrence of MALE was the ankle-brachial index (ABI). A value below 0.5 was found to be an independent predictor for MALE (p = 0.001). Conclusions: There was no significant difference in the incidence rates of MALE between the two genders over a 2-year follow-up period post-PTA. Regardless of sex, an ankle-brachial index value below 0.5 was the sole independent predictor for limb-related adverse events.

The Independent Impact of Peripheral Arterial Disease on Mortality in Nonagenarians and Centenarians Who Were Treated in an Intensive Care Unit: A Consecutive Cohort of 1 108 Patients

To investigate the clinical characteristics, risk factors, and outcomes of inpatients with peripheral arterial disease (PAD) including lower extremity PAD, abdominal aortic aneurysm (AAA), and carotid artery disease in a large cohort of critically ill patients aged ≥ 90 years. A retrospective analysis was conducted of all adult patients aged ≥ 90 years consecutively admitted to the intensive care unit at a tertiary care centre in Hamburg, Germany, between 1 January 2008 and 30 April 2019. Multivariable regression and Kaplan-Meier methods were used to determine the independent impact of PAD on short and long term mortality endpoints. The analyses were adjusted for confounding by several sociodemographic and clinical parameters including Charlson Comorbidity Index (CCI) and established clinical risk scores. A total of 1 108 eligible patients were identified (92.3 years, 33% men). Of these, 24% had PAD (9% lower extremity PAD, 2% AAA, 15% coronary artery disease) and 76% did not have any history of PAD and were used as a comparison group. When compared with the comparison group, patients with PAD had a higher CCI (2 vs. 1, p < .001), more often had chronic kidney disease (28% vs. 21%, p= .019), and renal replacement therapy (5% vs. 2%, p= .016). Furthermore, they needed vasopressors (48% vs. 40%, p= .027) and parenteral nutrition (10% vs. 6%, p= .041) more often. After adjusting for confounding, PAD was independently associated with increased in hospital (hazard ratio [HR] 1.97, 95% confidence interval [CI] 1.39 - 2.81, p < .001) and long term mortality rates (HR 1.32, 95% CI 1.05 - 1.66, p= .019). One of four critically ill nonagenarians and centenarians in an ICU in Germany had PAD. PAD was associated with both higher short and long term mortality rates while its impact outweighed higher age. Future studies should address this increasingly important population beyond 89 years of age.

Management of large post-crossover inguinal lymphocele

A 73-year-old man with a history of peripheral arterial disease and previous bilateral common femoral artery reconstruction presented with left foot critical limb-threatening ischaemia and underwent right to left femoro-profunda crossover grafting. Postoperatively, he developed a left groin lymph leak that initially dried up but later re-presented as a very large lymphocele. Initial attempts with aspiration on three occasions and then surgical drainage with sac excision and ligation of long saphenous lymphatics did not lead to resolution. Subsequently, a hybrid approach using percutaneous lymphangiography and drainage, sclerotherapy (bleomycin, then absolute alcohol) and eventual identification and ligation of the afferent lymphatic channel resulted in resolution of the lymphocele without untoward side effects, sepsis or compromise of the revascularisation.

Clinical Predictors of Mortality and Heart Failure Hospitalization in Patients With Severe Tricuspid Regurgitation

BackgroundThere is an incomplete understanding of the predictors of morbidity and mortality in patients with severe tricuspid regurgitation (TR). This study sought to identify key risk factors for all-cause mortality and heart failure (HF) hospitalization among patients with severe TR. MethodsPatients with severe TR were identified from 2 centers, Oregon Health & Science University and Abrazo Health, from January 01, 2016 to December 31, 2018. Patients with any concomitant severe valvular diseases or prior valvular intervention were excluded. Multivariable regression was utilized to identify demographic, clinical, and echocardiographic variables independently associated with all-cause mortality or HF hospitalization. Results435 patients with severe TR were followed for a median of 2.8 years. The mean age of the population was 66.9 ± 18.5 years and 58% were female. All-cause mortality was identified in 20.5% of the population. Of the cohort, 35.4% of patients were hospitalized for HF. Isolated tricuspid valve intervention was performed in 2.5% of patients. Independent predictors of all-cause mortality included history of solid tumor (odds ratio [OR] 6.6, 95% confidence interval [CI] 2.1-19.1, p = 0.001), history of peripheral artery disease (OR 3.5, 95% CI 1.2-9.4, p = 0.013), and elevated international normalized ratio in the absence of anticoagulation (OR 1.9, 95% CI 1.2-3.2, p = 0.008). Predictors of HF hospitalization included history of diabetes mellitus (OR 2.2, 95% CI 1.1-4.0, p = 0.014) and history of reduced left ventricular ejection fraction (OR 5.7, 95% CI 2.9-11.7, p < 0.0001). ConclusionsSevere untreated TR is associated with high mortality and frequent HF hospitalizations. Understanding predictors of these outcomes is important to identify patients who may benefit from early tricuspid valve intervention to help improve outcomes in this patient population.

Association of Sex and Race With Incident Peripheral Artery Disease Among Veterans With Normal Ankle-Brachial Indices

Reported risk of incident peripheral artery disease (PAD) by sex and race varies significantly and has not been reported in national cohorts among individuals free of baseline PAD. To evaluate the association of sex and race, as well as prevalent cardiovascular risk factors, with limb outcomes in a national cohort of people with normal baseline ankle-brachial indices (ABIs). This cohort study was conducted using data from participants in the Veterans Affairs Birth Cohort Study (born 1945-1965), with follow-up data between January 1, 2000, and December 31, 2016. Baseline demographics were collected from 77 041 participants receiving care from the Veterans Health Administration with baseline ABIs of 0.90 to 1.40 and no history of PAD. Data were analyzed from October 2019 through September 2022. Sex, race, diabetes, and smoking status. Incident PAD, defined as subsequent ABI less than 0.90, surgical or percutaneous revascularization, or nontraumatic amputation. Of 77 041 participants with normal ABIs (73 822 [95.8%] men; mean [SD] age, 60.2 [5.9] years; 13 080 Black [18.2%] and 54 377 White [75.6%] among 71 911 participants with race and ethnicity data), there were 6692 incident PAD events over a median [IQR] of 3.9 [1.7-6.9] years. Incidence rates were lower for women than men (incidence rates [IRs] per 1000 person-years, 7.4 incidents [95% CI, 6.2-8.8 incidents] vs 19.2 incidents [95% CI, 18.7-19.6 incidents]), with a lower risk of incident PAD (adjusted hazard ratio [aHR], 0.49 [95% CI, 0.41-0.59]). IRs per 1000 person-years of incident PAD were similar for Black and White participants (18.9 incidents [95% CI, 17.9-20.1 incidents] vs 18.8 incidents [95% CI, 18.3-19.4]). Compared with White participants, Black participants had increased risk of total PAD (aHR, 1.09 [95% CI, 1.02-1.16]) and nontraumatic amputation (aHR, 1.20 [95% CI, 1.06-1.36]) but not surgical or percutaneous revascularization (aHR, 1.10 [95% CI, 0.98-1.23]) or subsequent ABI less than 0.90 (aHR, 1.04 [95% CI, 0.95-1.13]). Diabetes (aHR, 1.62 [95% CI, 1.53-1.72]) and smoking (eg, current vs never: aHR, 1.76 [95% CI, 1.64-1.89]) were associated with incident PAD. Incident PAD was rare among individuals without a history of smoking or diabetes (eg, among 632 women: IR per 1000 people-years, 2.1 incidents [95% CI, 1.0-4.5 incidents]) despite an otherwise-high-risk cardiovascular profile (eg, 527 women [83.4%] with hypertension). This study found that the risk of PAD was approximately 50% lower in women than men and less than 10% higher for Black vs White participants, while the risk of nontraumatic amputation was 20% higher among Black compared with White participants.

Neurologic outcomes of carotid and other emergent interventions for ischemic stroke over 6years with dataset enhanced by machine learning.

The current mainstays of ischemic stroke treatment include the use of thrombolysis (tissue plasminogen activator [tPA]), urgent carotid endarterectomy (uCEA) or urgent carotid artery stenting (uCAS), and mechanical endovascular reperfusion/thrombectomy (MER). Scarce data describe the presenting stroke severity and neurologic outcomes for these acute ischemic stroke interventions, alone or in combination. The authors hypothesize that patients undergoing carotid interventions experience better functional neurologic outcomes than other stroke interventions. A comprehensive stroke center dataset was combined with data for stroke-related procedures, comorbidities, complications, and physician documentation collected from electronic medical record data. A total of 10,975 patient encounter records from January 1, 2015, through July 31, 2021, were retrieved. The presenting stroke severity was determined by vascular/stroke neurologists using the National Institutes of Health Stroke Scale (NIHSS). Functional neurologic outcomes were reported using the modified Rankin scale (mRS) score, which quantifies the degree of neurologic disability. Because mRS values were only available for 3627 encounters in the original dataset, the authors developed a machine learning algorithm to analyze physician documentation and assign an mRS value. After the exclusion and machine learning analysis, a total of 5170 patient encounters were included for statistical analysis. Statistical analyses included the χ2 test, one-way analysis of variance and logistic regression on 30-day complications, stroke severity, and neurologic outcomes. Patients were divided into five cohorts: (1) uCEA or uCAS (n= 189), (2) tPA alone (n= 1053), (3) MER alone (n= 418), (4) tPA+ MER (n= 199), and (5) no intervention (n= 3311). Patients undergoing uCEA/uCAS were significantly more likely to be male, smokers, and have a history of peripheral arterial disease compared with other stroke cohorts. The length of stay was shortest for patients who only received tPA or no intervention (6days), followed by uCEA/uCAS (7.2days), MER (10.2days), and tPA+ MER (8.8days) cohorts (P< .001). The 30-day mortality was highest in the MER cohort (12.2%) and lowest in the uCEA/uCAS cohort (2.6%). The uCEA/uCAS cohort compared with other cohorts had the lowest presenting stroke severity (NIHSS 4.9 vs NIHSS 6.9-16.0), and best neurologic outcomes (mRS 1.7 vs mRS 1.8-2.6). After an ischemic stroke, patients undergoing urgent carotid interventions had the lowest presenting stroke severity (NIHSS) and highest rate of independent neurologic outcomes (mRS) compared with other stroke interventions. Incoming stroke severity correlates with functional neurologic outcomes, and patients who present with an NIHSS of 10 or less who undergo uCEA/uCAS have a high likelihood of independent neurologic functional outcome (mRS of ≤2).

Long-Term Risk of Carotid Stenosis and Cerebrovascular Disease after Radiation Therapy for Head and Neck Cancer

<h3>Purpose/Objective(s)</h3> The incidence of asymptomatic carotid artery stenosis (CAS) in the general population is ∼5%. CAS is a known toxicity of radiation therapy (RT) for head and neck cancer (HNC). CAS screening is not routinely performed after RT despite the increased risk of cerebrovascular disease (CVD) in this population. Here we report long-term incidence and associated risk factors for CAS and CVD after RT for HNC. <h3>Materials/Methods</h3> Records were retrospectively identified for all patients undergoing carotid ultrasound (U/S) screening following RT for HNC at a single institution between November 2000 and October 2020. Exclusion criteria included CAS or CVD prior to RT. Carotid U/S screening was obtained within 24 months of RT completion, then every three years in the absence of CAS or annually following CAS diagnosis. Asymptomatic CAS was defined as radiographic luminal narrowing ≥50%; CVD was defined as stroke or transient ischemic attack, and composite CAS was defined as asymptomatic CAS and/or CVD. Cumulative incidence estimates (CIE) of asymptomatic CAS, CVD, and composite CAS were estimated. Univariate and multivariable (MVA) Cox proportional hazards regression was used to study potential associations between clinical parameters and the CVD and composite CAS outcomes. <h3>Results</h3> Among 628 patients, median follow-up was 4.8 years (IQR 2.6 - 8.3 yr) with 97 patients followed beyond 10 yr. Median age was 61 yo. 56% of patients had a history of smoking. 61% had an oropharyngeal primary tumor (64% p16+). Squamous cell carcinoma was the most common histology (94%). 57% patients completed 70 Gy over 35 fractions, 69% received concurrent chemotherapy, and 28% were treated post-operatively. Asymptomatic CAS was identified in 111 (18%) with 50 (45%) prescribed CAS-related medication and 24 (22%) undergoing carotid endarterectomy or stenting. 5, 10, and 12-year CIE for asymptomatic CAS were 19.8%, 37.1%, and 50.2%, respectively. MVA showed that a history of peripheral arterial disease ([PAD]; HR 4.5, 95% CI 1.7 - 11.8) and myocardial infarction ([MI]; HR 3.3; 95% CI 1.1 - 9.8) were predictive of time to asymptomatic CAS. CVD events were observed in 45 (7.2%) patients, of whom 27 (60%) were found to have asymptomatic CAS. 5, 10, and 12-year CIE for CVD were 5.4%, 12.4%, and 21.7%, respectively. On MVA, male sex (HR 3.3, 95% CI 1.1 - 10) and type 2 diabetes mellitus ([DM2]; HR 2.3, 95% CI 1.2 - 4.6) were significantly associated with CVD. 5, 10, and 12-year CIE for composite CAS were 17.5%, 32.3%, and 43.6%, respectively. On MVA, male sex (HR 2.0, 95% CI 1.1 – 3.3), PAD (HR 3.1, 95% CI 1.2 - 7.8), and MI (HR 2.5, 95% CI 1.1 - 5.9) were significantly associated with composite CAS. <h3>Conclusion</h3> Long-term follow up shows a steady increase in the risk of asymptomatic CAS and CVD following RT for HNC. It is independently associated with sex, PAD, MI, and DM2. Ongoing analyses include dosimetric analysis of CAS and CVD per carotid artery and cost-effectiveness of carotid ultrasound screening.