Critical Assessment of the Management of Unstable Angina in a Specialized Cardiology Emergency Room. / Avaliação Crítica do Manejo da Angina Instável em Pronto-Socorro Terciário de Cardiologia.

BACKGROUND: The management of unstable angina (UA) presents a challenge due to its subjective diagnosis and limited representation in randomized clinical trials that inform current practices. OBJECTIVES: This study aims to identify key factors associated with the indication for invasive versus non-invasive stratification in this population and to evaluate factors associated with stratification test results. METHODS: This retrospective cohort study included patients hospitalized with UA over a consecutive 20-month period. To assess factors associated with stratification strategies, patients were divided into invasive stratification (coronary angiography) and non-invasive stratification (other methods) groups. For the analysis of factors related to changes in stratification tests, patients were categorized into groups with or without obstructive coronary artery disease (CAD) or ischemia, as per the results of the requested tests. Comparisons between groups and multiple logistic regression analyses were performed, with statistical significance set at a 5% level. RESULTS: A total of 729 patients were included, with a median age of 63 years and a predominance of males (64.6%). Factors associated with invasive stratification included smoking (p = 0.001); type of chest pain (p < 0.001); "crescendo" pain (p = 0.006); TIMI score (p = 0.006); HEART score (p = 0.011). In multivariate analysis, current smokers (OR 2.23, 95% CI 1.13-4.8), former smokers (OR 2.19, 95% CI 1.39-3.53), and type A chest pain (OR 3.39, 95% CI 1.93-6.66) were independently associated. Factors associated with obstructive CAD or ischemia included length of hospital stay (p < 0.001); male gender (p = 0.032); effort-induced pain (p = 0.037); Diamond-Forrester score (p = 0.026); TIMI score (p = 0.001). In multivariate analysis, only chest pain (type B chest pain: OR 0.6, 95% CI 0.38-0.93, p = 0.026) and previous CAD (OR 1.42, 95% CI 1.01-2.0, p = 0.048) were independently associated. CONCLUSION: The type of chest pain plays a crucial role not only in the diagnosis of UA but also in determining the appropriate treatment. Our results highlight the importance of incorporating pain characteristics into prognostic scores endorsed by guidelines to optimize UA management.

FUNDAMENTO: O manejo da angina instável (AI) é um desafio devido ao seu diagnóstico subjetivo e à sua escassa representação em ensaios clínicos randomizados que determinem as práticas atuais. OBJETIVOS: O objetivo deste estudo é identificar os principais fatores associados à indicação de estratificação invasiva ou não nessa população e avaliar os fatores associados às alterações nos exames de estratificação. MÉTODOS: Coorte retrospectiva de pacientes internados por AI, em um período de 20 meses consecutivos. Para avaliar os fatores associados à estratégia de estratificação, os pacientes foram divididos em estratificação invasiva (cinecoronariografia) e não invasiva (demais métodos). Para análise de fatores relacionados às alterações nos exames de estratificação, os pacientes foram divididos em grupos com ou sem doença arterial coronariana (DAC) obstrutiva ou isquemia, conforme resultados dos exames solicitados. Foram realizadas comparações entre grupos e análise de regressão logística múltipla, com significância estatística definida em um nível de 5%. RESULTADOS: 729 pacientes foram incluídos, com mediana de idade de 63 anos e predomínio do sexo masculino (64,6%). Estiveram associados à estratificação invasiva: tabagismo (p = 0,001); tipo de dor torácica (p < 0,001); dor "em crescendo" (p = 0,006); escore TIMI (p = 0,006); escore HEART (p = 0,011). Na análise multivariada, tabagistas (OR 2,23, IC 95% 1,13-4,8), ex-tabagistas (OR 2,19, IC 1,39-3,53) e dor torácica tipo A (OR 3,39, IC 95% 1,93-6,66) estiveram associados de forma independente. Estiveram associados à DAC obstrutiva ou isquemia: tempo de internação hospitalar (p < 0,001); sexo masculino (p = 0,032); dor desencadeada por esforço (p = 0,037); Diamond-Forrester (p = 0,026); escore TIMI (p = 0,001). Na análise multivariada, apenas dor torácica (dor torácica tipo B: OR 0,6, IC 95% 0,38-0,93, p = 0,026) e DAC prévia (OR 1,42, IC 95% 1,01-2,0, p = 0,048) estiveram associadas de maneira independente. CONCLUSÕES: O tipo de dor torácica desempenha um papel crucial não apenas no diagnóstico da AI, mas também na definição do tratamento adequado. Nossos resultados destacam a importância de incorporar características da dor aos escores prognósticos endossados pelas diretrizes, para otimização do manejo da AI.

Association Between Diagnosis-to-Limb Revascularization Time and Clinical Outcomes in Outpatients With Chronic Limb-Threatening Ischemia: Insights From the CLIPPER Cohort.

BACKGROUND: The extent and consequences of ischemia in patients with chronic limb-threatening ischemia (CLTI) may change rapidly, and delays from diagnosis to revascularization may worsen outcomes. We sought to describe the association between time from diagnosis to endovascular lower extremity revascularization (diagnosis-to-limb revascularization [D2L] time) and clinical outcomes in outpatients with CLTI. METHODS AND RESULTS: In the CLIPPER cohort, comprising patients between 66 and 86 years old diagnosed with CLTI betweeen 2010 and 2019, we used Medicare claims data to identify patients who underwent outpatient endovascular revascularization within 180 days of diagnosis. We described the risk-adjusted association between D2L time and clinical outcomes. Among 1 130 065 patients aged between 66 and 86 years with CLTI, 99 221 (8.8%) underwent outpatient endovascular lower extremity revascularization within 180 days of their CLTI diagnosis. Among patients with D2L time <30 days, there was no association between D2L time and all-cause death or major lower extremity amputation. However, among patients with D2L time >30 days, each additional 10-day increase in D2L time was associated with a 2.5% greater risk of major amputation (hazard ratio, 1.025 [95% CI, 1.014-1.036]). There was no association between D2L time and all-cause death. CONCLUSIONS: A delay of >30 days from CLTI diagnosis to lower extremity endovascular revascularization was associated with an increased risk of major lower extremity amputation among patients undergoing outpatient endovascular revascularization. Improving systems of care to reduce D2L time could reduce amputations.

Evaluation of short-term mortality in patients with Medicare undergoing endovascular interventions for chronic limb-threatening ischemia.

INTRODUCTION: Patients with chronic limb-threatening ischemia (CLTI) have high mortality rates after revascularization. Risk stratification for short-term outcomes is challenging. We aimed to develop machine-learning models to rank predictive variables for 30-day and 90-day all-cause mortality after peripheral vascular intervention (PVI). METHODS: Patients undergoing PVI for CLTI in the Medicare-linked Vascular Quality Initiative were included. Sixty-six preprocedural variables were included. Random survival forest (RSF) models were constructed for 30-day and 90-day all-cause mortality in the training sample and evaluated in the testing sample. Predictive variables were ranked based on the frequency that they caused branch splitting nearest the root node by importance-weighted relative importance plots. Model performance was assessed by the Brier score, continuous ranked probability score, out-of-bag error rate, and Harrell's C-index. RESULTS: A total of 10,114 patients were included. The crude mortality rate was 4.4% at 30 days and 10.6% at 90 days. RSF models commonly identified stage 5 chronic kidney disease (CKD), dementia, congestive heart failure (CHF), age, urgent procedures, and need for assisted care as the most predictive variables. For both models, eight of the top 10 variables were either medical comorbidities or functional status variables. Models showed good discrimination (C-statistic 0.72 and 0.73) and calibration (Brier score 0.03 and 0.10). CONCLUSION: RSF models for 30-day and 90-day all-cause mortality commonly identified CKD, dementia, CHF, need for assisted care at home, urgent procedures, and age as the most predictive variables as critical factors in CLTI. Results may help guide individualized risk-benefit treatment conversations regarding PVI.

Implanted blood vessel external support device for the treatment of distal hypoperfusion ischemic syndrome in arteriovenous fistulas and high-frame-rate Vector Flow quality assessment.

INTRODUCTION: Distal hypoperfusion ischemic syndrome (DHIS) is a complication occurring after arteriovenous fistula (AVF) creation. Different surgical alternatives haves been proposed in case of severe DHIS. Aim of the present paper is to present a new technique for DHIS treatment. MATERIAL AND METHODS: Between the 1st of January 2021 and the 31st December 2021 all the patients referred to our center for DHIS grade 2-4 were treated with a new surgical technique. It consists of AVF remodeling using an external nitinol support (VasQ®) to reduce the risk of outflow vein enlargement and DHIS recurrence. To better appreciate the hemodynamic effects of the surgery, a new ultrasound technique called high-frame-rate Vector Flow (HiFR-VF) was used. RESULTS: Seven patients (M:F 1:3; mean age 43 ± 12 years, range 29-65) were included in this study. Central line was never necessary, and technical success was 100% at 12 months. The comparison with historical data demonstrated lower recurrence of symptoms in comparison to simple artery-to-vein redo (p 0.50). The HiFR-VF showed flow with limited turbulent characteristics at the anastomosis site. DISCUSSION AND CONCLUSION: The new technique proposed demonstrated to be safe and effective for treatment of DHIS, preventing symptoms recurrence. Ultrasound examination and HiFR-VF can be considered a valuable method to evaluate complex flows at the levels of vascular anastomosis.

Patients living farther from a tertiary care center are more likely to undergo peripheral arterial bypass for acute and chronic limb-threatening ischemia.

OBJECTIVE: The aim of this study was to assess the association between the proximity to the tertiary care hospital and the severity of peripheral arterial disease (PAD) at the time of lower extremity bypass (LEB) in a rural-urban mix region. METHODS: Patients undergoing LEB from 2010 to 2020 at Penn State Milton S. Hershey Medical Center were reviewed and stratified into two study groups based on a median distance from hospital (ie, Group I: ≥34 miles and Group II: <34 miles). Patients' demographic features, preoperative data including comorbidities, and medications were analyzed. A univariate analysis for the patient characteristics between the two study groups, along with evaluation of postoperative outcomes, and a multivariate predictive modeling to study the PAD stage as the indication of LEB was performed. A P-value of < .05 was set as a significant difference between the groups for all the analyses. RESULTS: There were 175 patients (49.9%) in Group I and 176 patients (50.1%) in Group II with a mean age of 65 ± 11.92 years (median, 64.61 years). No significant difference was observed in gender (P = .530), age (P = .906), and functional status (P = .830) between study groups. It was observed that patients in Group I were more likely to be overweight or obese (71.3% vs 57%; P = .007) and had a prior history of myocardial infarction (24.3% vs 15.3%; P = .036) in comparison to Group II. No postoperative outcomes were found to be statistically different between the study groups. The multivariate analyses based on various confounders displayed that patients in Group I had 56% higher likelihood of LEB for chronic limb-threatening ischemia (adjusted odds ratio, 1.56; 95% confidence interval, 0.92-2.62; P = .042). Group I patients also had five times higher odds of LEB for acute limb ischemia (adjusted odds ratio, 5.07; 95% confidence interval, 1.42-18.13; P = .012) as compared with those in the Group II. CONCLUSIONS: Patients' proximity to a major tertiary hospital may have implications on the disease progression for patients with PAD and could also be related to inadequate vascular services in primary and secondary hospitals. Lack of preventive care and disease management in regions afar from a tertiary hospital could be other implicating factors and highlights the need for outreach programs, along with distribution of vascular specialists, to reduce geographical disparities and ensure equity in access to care.

Diagnostic Accuracy of Pre-Transcatheter Aortic Valve Replacement Nitroglycerin-Free Fractional Flow Reserve-Computed Tomography-Based Physiological Assessment in Patients With Severe Aortic Stenosis for Predicting Post-Transcatheter Aortic Valve Replacement Ischemia.

BACKGROUND: Fractional flow reserve-computed tomography (FFRCT) has not been validated in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) for coronary artery disease due to theoretical difficulties in using nitroglycerin for such patients.Methods and Results: In this single-center study, we prospectively enrolled 21 patients (34 vessels) and performed pre-TAVR FFRCTwithout nitroglycerin, pre-TAVR invasive instantaneous wave-free ratio (iFR) measurements, and post-TAVR FFR measurements using a pressure wire. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of pre-TAVR FFRCT≤0.80 to predict post-TAVR invasive FFR ≤0.80 were 82%, 83%, 82%, 71%, and 90%, respectively. A receiver operating characteristic analysis demonstrated an optimal cutoff of 0.78 for pre-TAVR FFRCTto indicate post-TAVR FFR ≤0.80, with an area under the curve (AUC) of 0.84, and the counterpart cutoff of pre-TAVR iFR was 0.89 with an AUC of 0.86. CONCLUSIONS: FFRCTwithout nitroglycerin could be a useful non-invasive imaging modality for assessing the severity of coronary artery lesions in patients with severe AS.

Incidence, Risk Factors and Management of Postoperative Complications in Horizontal Strabismus Surgery.

OBJECTIVE: To report the incidence, risk factors and management of postoperative complications after horizontal strabismus surgery. DESIGN: Retrospective Cohort study. PARTICIPANTS: The study assessed 1,273 patients with 1,035 cases of exotropia and 238 cases of esotropia, with a minimum 18-month follow-up. METHODS: Retrospective review of strabismus operation patients' medical records included baseline demographics, age at surgery, pre/postoperative visual acuity, and deviation. Complications were categorized as surgical site (infection, scarring, cyst, granuloma, ischemia) and strabismus-related (recurrence, diplopia), with analysis of incidence, risk factors, and management. RESULTS: Among surgical site complications, the incidence of infection, pyogenic granuloma, and anterior segment ischemia were similar between the exotropia (0.3%, 0.3%, 0.2%) and esotropia (0.8%, 0%, 0.4%) groups (p = .221, 0.406, 0.515). In contrast, the esotropia group presented a higher risk of conjunctival inclusion cyst and conjunctival scar than the exotropia group, with incidences of 5.0% vs 2.2% and 6.3% vs 1.3%, respectively (p = .004, <0.001). Regarding strabismus complications, the incidence of early recurrence was not significant between the two groups, with 10.0% in the exotropia group and 10.5% in the esotropia group (p = .553). Older age and poor initial visual acuity were associated with early recurrence (p < .001). The esotropia group had a higher risk of persistent diplopia than the exotropia group, with incidences of 4.2% vs 2.0%, respectively (p = .003). CONCLUSION: Esotropia carries a higher risk of conjunctival inclusion cysts, conjunctival scarring, and persistent diplopia compared to the exotropia group, while both groups exhibit similar rates of early recurrence and other surgical site complications.

Role of Hemodynamic Assessment and Limitations in Ankle-Brachial Pressure Index, Toe- Brachial Pressure Index to Predict Wound Healing After Revascularization.

Chronic limb-threatening ischemia (CLTI) represents one of the most severe forms of peripheral arterial disease implying impaired wound healing and tissue loss at the same time posing a significant impact on the quality of life of patients and a serious economic burden on healthcare systems around the world. A major challenge in the management of patients with CLTI is the validity and role of non-invasive hemodynamic parameters in assessing their clinical status before and after revascularization. Traditionally, the diagnosis of CLTI is routinely based on clinical symptoms and confirmed by measurements of non-invasive limb hemodynamics including ankle-brachial pressure index (ABPI) and toe-brachial pressure index (TBPI). However, whether these indices alone can provide definitive treatment or be used as adjunctive tool along with the implementation of novel techniques to help guide revascularization for CLI patients still remains unclear.

Impact of Intensity of Vascular Care Preceding Major Amputation Among Patients With Chronic Limb-Threatening Ischemia.

BACKGROUND: Lower-limb amputation rates in patients with chronic limb-threatening ischemia vary across the United States, with marked disparities in amputation rates by gender, race, and income status. We evaluated the association of patient, hospital, and geographic characteristics with the intensity of vascular care received the year before a major lower-limb amputation and how intensity of care associates with outcomes after amputation. METHODS: Using Medicare claims data (2016-2019), beneficiaries diagnosed with chronic limb-threatening ischemia who underwent a major lower-limb amputation were identified. We examined patient, hospital, and geographic characteristics associated with the intensity of vascular care received the year before amputation. Secondary objectives evaluated all-cause mortality and adverse events following amputation. RESULTS: Of 33 036 total Medicare beneficiaries undergoing major amputation, 7885 (23.9%) were due to chronic limb-threatening ischemia; of these, 4988 (63.3%) received low-intensity and 2897 (36.7%) received high-intensity vascular care. Mean age, 76.6 years; women, 38.9%; Black adults, 24.5%; and of low income, 35.2%. After multivariable adjustment, those of low income (odds ratio, 0.65 [95% CI, 0.58-0.72]; P<0.001), and to a lesser extent, men (odds ratio, 0.89 [95% CI, 0.81-0.98]; P=0.019), and those who received care at a safety-net hospital (odds ratio, 0.87 [95% CI, 0.78-0.97]; P=0.012) were most likely to receive low intensity of care before amputation. High-intensity care was associated with a lower risk of all-cause mortality 2 years following amputation (hazard ratio, 0.79 [95% CI, 0.74-0.85]; P<0.001). CONCLUSIONS: Patients who were of low-income status, and to a lesser extent, men, or those cared for at safety-net hospitals were most likely to receive low-intensity vascular care. Low-intensity care was associated with worse long-term event-free survival. These data emphasize the continued disparities that exist in contemporary vascular practice.

A Pilot Study of Ratiometric Creatine CEST MRI Assessment of Rabbit Skeletal Muscle Energy Metabolism at 3 T.

BACKGROUND: pH MRI may provide useful information to evaluate metabolic disruption following ischemia. Radiofrequency amplitude-based creatine chemical exchange saturation transfer (CrCEST) ratiometric MRI is pH-sensitive, which could but has not been explored to examine muscle ischemia. PURPOSE: To investigate skeletal muscle energy metabolism alterations with CrCEST ratiometric MRI. STUDY TYPE: Prospective. ANIMAL MODEL: Seven adult New Zealand rabbits with ipsilateral hindlimb muscle ischemia. FIELD STRENGTH/SEQUENCE: 3 T/two MRI scans, including MRA and CEST imaging, were performed under two B1 amplitudes of 0.5 and 1.25 µT after 2 hours of hindlimb muscle ischemia and 1 hour of reperfusion recovery, respectively. ASSESSMENT: CEST effects of two energy metabolites of creatine and phosphocreatine (PCrCEST) were resolved with the multipool Lorentzian fitting approach. The pixel-wise CrCEST ratio was quantified by calculating the ratio of the resolved CrCEST peaks under a B1 amplitude of 1.25 µT to those under 0.5 µT in the entire muscle. STATISTICAL TESTS: One-way ANOVA and Pearson's correlation. P < 0.05 was considered statistically significant. RESULTS: MRA images confirmed the blood flow loss and restoration in the ischemic hindlimb at the ischemia and recovery phases, respectively. Ischemic muscles exhibited a significant decrease of PCr at the ischemia (under both B1 amplitudes) and recovery phases (under B1 amplitude of 0.5 µT) and significantly increased CrCEST from normal tissues at both phases (under both B1 levels). Specifically, CrCEST decreased, and PCrCEST increased with the CrCEST ratio. Significantly strong correlations were observed among the CrCEST ratio, and CrCEST and PCrCEST under both B1 levels (r > 0.80). DATA CONCLUSION: The CrCEST ratio altered substantially with muscle pathological states and was closely related to CEST effects of energy metabolites of Cr and PCr, suggesting that the pH-sensitive CrCEST ratiometric MRI is feasible to evaluate muscle injuries at the metabolic level. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 1.

Integrated myocardial flow reserve (iMFR) assessment: diffuse atherosclerosis and microvascular dysfunction are more strongly associated with mortality than focally impaired perfusion.

BACKGROUND AND AIMS: Although treatment of ischemia-causing epicardial stenoses may improve symptoms of ischemia, current evidence does not suggest that revascularization improves survival. Conventional myocardial ischemia imaging does not uniquely identify diffuse atherosclerosis, microvascular dysfunction, or nonobstructive epicardial stenoses. We sought to evaluate the prognostic value of integrated myocardial flow reserve (iMFR), a novel noninvasive approach to distinguish the perfusion impact of focal atherosclerosis from diffuse coronary disease. METHODS: This study analyzed a large single-center registry of consecutive patients clinically referred for rest-stress myocardial perfusion positron emission tomography. Cox proportional hazards modeling was used to assess the association of two previously reported and two novel perfusion measures with mortality risk: global stress myocardial blood flow (MBF); global myocardial flow reserve (MFR); and two metrics derived from iMFR analysis: the extents of focal and diffusely impaired perfusion. RESULTS: In total, 6867 patients were included with a median follow-up of 3.4 years [1st-3rd quartiles, 1.9-5.0] and 1444 deaths (21%). Although all evaluated perfusion measures were independently associated with death, diffusely impaired perfusion extent (hazard ratio 2.65, 95%C.I. [2.37-2.97]) and global MFR (HR 2.29, 95%C.I. [2.08-2.52]) were consistently stronger predictors than stress MBF (HR 1.62, 95%C.I. [1.46-1.79]). Focally impaired perfusion extent (HR 1.09, 95%C.I. [1.03-1.16]) was only moderately related to mortality. Diffusely impaired perfusion extent remained a significant independent predictor of death when combined with global MFR (p < 0.0001), providing improved risk stratification (overall net reclassification improvement 0.246, 95%C.I. [0.183-0.310]). CONCLUSIONS: The extent of diffusely impaired perfusion is a strong independent and additive marker of mortality risk beyond traditional risk factors, standard perfusion imaging, and global MFR, while focally impaired perfusion is only moderately related to mortality.

Dynamic assessment of brain perfusion in a middle cerebral artery occlusion rat model by contrast-enhanced ultrasound imaging: a pilot study.

BACKGROUND: The middle cerebral artery occlusion model (MCAo) is a commonly used animal model for cerebral ischemia studies but lacks accessible imaging techniques for the assessment of hemodynamic changes of the model. PURPOSE: The study aims to explore the value of contrast-enhanced ultrasound (CEUS) in evaluating brain perfusion in the early stages after MCAo surgery. MATERIAL AND METHODS: In total, 18 adult male Sprague-Dawley rats were subjected to right MCAo using an intraluminal filament model, and CEUS was performed at the three following timepoints: before (T0), immediately after (T1), and 6 h after permanent MCAo (T2). Twelve rats successfully completed the study, and their brains were removed and stained using 2, 3, 5-triphenyltetrazolium chloride (TTC). CEUS video images were visualized offline, and the time-intensity curves (TICs) were analyzed. Different cerebrovascular patterns and manifestations of the contrast enhancement in rat ischemic hemispheres were observed. Semi-quantitative parameters of TICs in ischemic areas (ROIi) and the surrounding normal- or hypo-perfused areas (ROIn) were calculated and compared between T0, T1, and T2, and also between ROIi and ROIn. RESULTS: A significant correlation was found between the lesion volume (%) determined by TTC and CEUS parameters (r = -0.691, P = 0.013 for peak intensity; r = -0.742, P = 0.006 for area under the curve) at T2. After the same occlusion, there were differences in contrast perfusion in each group. CONCLUSION: This study suggests that CEUS could be an effective imaging tool for studying cerebral ischemia and perfusion in small animals as long as the transcranial acoustic window allows it.

The Impact of Age on the Physiological Assessment of Borderline Coronary Stenoses.

Background and Objectives: Coronary angiography is the gold standard for diagnosing coronary artery disease (CAD). In the case of borderline changes, patients require further diagnosis through ischemia assessment via one of the recommended methods of invasive evaluation. This study aimed to assess whether clinical factors influence the risk of a positive result in invasive myocardial ischemia assessment and if these potential factors change with the patient's age and the consistency of ischemia assessment. Materials and Methods: Data were collected retrospectively on all consecutive patients hospitalized in the University Hospital in Krakow between 2020 and 2021, on whom physiological assessments of coronary circulation were performed. Patients were divided into two groups: patients aged 60 or younger and patients older than 60. Results: Despite the older patients having more risk factors for CAD, their physiological assessment results of borderline lesions were similar to those of the younger patients. Positive fractional flow reserve (FFR) assessments were obtained from almost 50% of vessels. In the younger patients, cigarette use and type 2 diabetes mellitus increased the risk of a positive FFR result by 3.5 and 2.5 times, respectively. In the older patients, male gender and peripheral vascular disease significantly increased the risk of a positive FFR by 2.5 and 2 times, respectively. Conclusions: Clinical characteristics of patients undergoing physiological assessment of borderline coronary stenosis varied significantly by age. Refining the definition of borderline lesions to include age, gender, and other factors may improve the identification of patients who would benefit from physiological assessment and coronary revascularization.

Characteristics and outcomes in patients with a prior myocardial infarction treated with extended dual antiplatelet therapy with ticagrelor 60 mg: findings from ALETHEIA, a multi-country observational study.

BACKGROUND: Guidelines recommend extended dual antiplatelet therapy, including ticagrelor 60 mg twice daily, in high-risk post-myocardial infarction (MI) patients who have tolerated 12 months and are not at high bleeding risk. The real-world utilization and bleeding and ischaemic outcomes associated with long-term ticagrelor 60 mg in routine clinical practice have not been well described. METHODS: Register and claims data from the USA (Optum Clinformatics, IBM MarketScan, and Medicare) and Europe (Sweden, Italy, UK, and Germany) were extracted. Patients initiating ticagrelor 60 mg ≥12 months after MI, meeting eligibility criteria for the PEGASUS-TIMI (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin - Thrombolysis in Myocardial Infarction 45) 54 trial, were included. The cumulative incidence of the composite of MI, stroke, or all-cause mortality and that of bleeding requiring hospitalization were calculated. Meta-analyses were performed to combine estimates from each source. RESULTS: A total of 7035 patients treated with ticagrelor 60 mg met eligibility criteria. Median age was 67 years and 29% were females; 12% had a history of multiple MIs. The majority (95%) had been treated with ticagrelor 90 mg prior to initiating ticagrelor 60 mg. At 12 months from initiation of ticagrelor 60 mg, the cumulative incidence [95% confidence interval (CI)] of MI, stroke, or mortality was 3.33% (2.73-4.04) and was approximately three-fold the risk of bleeding (0.96%; 0.69-1.33). CONCLUSIONS: This study provides insights into the use of ticagrelor 60 mg in patients with prior MI in clinical practice. Observed event rates for ischaemic events and bleeding generally align with those in the pivotal trials, support the established safety profile of ticagrelor, and highlight the significant residual ischaemic risk in this population.Clinical Trials.gov Registration NCT04568083.

Report of a phase 1 clinical trial for safety assessment of human placental mesenchymal stem cells therapy in patients with critical limb ischemia (CLI).

BACKGROUND: Critical limb ischemia (CLI) is associated with increased risk of tissue loss, leading to significant morbidity and mortality. Therapeutic angiogenesis using cell-based treatments, notably mesenchymal stem cells (MSCs), is essential for enhancing blood flow to ischemic areas in subjects suffering from CLI. The objective of this study was to evaluate the feasibility of using placenta-derived mesenchymal stem cells (P-MSCs) in patients with CLI. METHODS: This phase I dose-escalation study investigated P-MSCs in nine CLI patients who were enrolled into each of the two dosage groups (20 × 106 and 60 × 106 cells), delivered intramuscularly twice, two months apart. The incidence of treatment-related adverse events was the primary endpoint. The decrease in inflammatory cytokines, improvement in the ankle-brachial pressure index (ABI), maximum walking distance, vascular collateralization, alleviation of rest pain, healing of ulceration, and avoidance of major amputation in the target leg were the efficacy outcomes. RESULTS: All dosages of P-MSCs, including the highest tested dose of 60 × 106 cells, were well tolerated. During the 6-month follow-up period, there was a statistically significant decrease in IL-1 and IFN-γ serum levels following P-MSC treatment. The blood lymphocyte profile of participants with CLI did not significantly differ, suggesting that the injection of allogeneic cells did not cause T-cell proliferation in vivo. We found clinically substantial improvement in rest pain, ulcer healing, and maximum walking distance after P-MSC implantation. In patients with CLI, we performed minor amputations rather than major amputations. Angiography was unable to demonstrate new small vessels formation significantly. CONCLUSION: The observations from this phase I clinical study indicate that intramuscular administration of P-MSCs is considered safe and well tolerated and may dramatically improve physical performance and minimize inflammatory conditions in patients with CLI. TRIAL REGISTRATION: IRCT, IRCT20210221050446N1. Registered May 09, 2021.

Influence of sex on the functional assessment of myocardial ischemia.

BACKGROUND: Fractional flow reserve (FFR) and non-hyperemic resting pressure ratios, such as instantaneous wave-free ratio (iFR) and resting full-cycle ratio (RFR), are recommended for evaluating the significance of angiographically intermediate coronary stenoses. Despite their usefulness, approximately 20% of assessed lesions exhibit discordance between FFR and iFR/RFR. AIMS: The role of sex in this discrepancy remains uncertain; thus, we aimed to investigate its impact on the discordance between FFR and iFR/RFR. METHODS: We reviewed 417 consecutive intermediate stenotic lesions from 381 patients, stratified by sex and assessed with both FFR and iFR/RFR. FFR ≤0.80 and iFR/RFR ≤0.89 were considered positive for ischemia. RESULTS: Of the 381 patients, 92 (24.1%) were women. Women were older, had a lower estimated glomerular filtration rate (eGFR), higher ejection fraction, and were more likely to have peripheral artery disease than men. Median FFR and iFR/RFR values were lower in men than in women (FFR 0.86 vs. 0.80; P <0.001; iFR 0.92 vs. 0.90; P = 0.049). However, overall discordance prevalence was similar for both sexes (20.6% vs. 15.1%; P = 0.22). In men, eGFR, insulin-treated diabetes mellitus, and arterial hypertension were predictors of positive FFR | negative iFR/RFR discordance, while eGFR, insulin-treated diabetes mellitus, atrial fibrillation, and chronic obstructive pulmonary disease were predictors of negative FFR | positive iFR/RFR discordance. No factors associated with either discordance were identified in women. CONCLUSIONS: FFR and iFR/RFR results indicating significant ischemia were more common in men than women when assessing intermediate coronary stenoses. Nevertheless, sex did not predict discordant results.

Early peripheral vascular interventions for claudication are associated with higher rates of late interventions and progression to chronic limb threatening ischemia.

OBJECTIVE: Despite societal guidelines that peripheral vascular intervention (PVI) should not be the first-line therapy for intermittent claudication, a significant number of patients will undergo PVI for claudication within 6 months of diagnosis. The aim of the present study was to investigate the association of early PVI for claudication with subsequent interventions. METHODS: We evaluated 100% of Medicare fee-for-service claims to identify all beneficiaries with a new diagnosis of claudication from January 1, 2015 to December 31, 2017. The primary outcome was late intervention, defined as any femoropopliteal PVI performed >6 months after the claudication diagnosis (through June 30, 2021). Kaplan-Meier curves were used to compare the cumulative incidence of late PVI for claudication patients with early (≤6 months) PVI vs those without early PVI. A hierarchical Cox proportional hazards model was used to evaluate the patient- and physician-level characteristics associated with late PVIs. RESULTS: A total of 187,442 patients had a new diagnosis of claudication during the study period, of whom 6069 (3.2%) had undergone early PVI. After a median follow-up of 4.39 years (interquartile range, 3.62-5.17 years), 22.5% of the early PVI patients had undergone late PVI vs 3.6% of those without early PVI (P < .001). Patients treated by high use physicians of early PVI (≥2 standard deviations; physician outliers) were more likely to have received late PVI than were patients treated by standard use physician of early PVI (9.8% vs 3.9%; P < .001). Patients who had undergone early PVI (16.4% vs 7.8%) and patients treated by outlier physicians (9.7% vs 8.0%) were more likely to have developed CLTI (P < .001 for both). After adjustment, the patient factors associated with late PVI included receipt of early PVI (adjusted hazard ratio [aHR], 6.89; 95% confidence interval [CI], 6.42-7.40) and Black race (vs White; aHR, 1.19; 95% CI, 1.10-1.30). The only physician factor associated with late PVI was a majority of practice in an ambulatory surgery center or office-based laboratory, with an increasing proportion of ambulatory surgery center or office-based laboratory services associated with significantly increased rates of late PVI (quartile 4 vs quartile 1; aHR, 1.57; 95% CI, 1.41-1.75). CONCLUSIONS: Early PVI after the diagnosis of claudication was associated with higher late PVI rates compared with early nonoperative management. High use physicians of early PVI for claudication performed more late PVIs than did their peers, especially those primarily delivering care in high reimbursement settings. The appropriateness of early PVI for claudication needs critical evaluation, as do the incentives surrounding the delivery of these interventions in ambulatory intervention suites.

Area Deprivation Index is not predictive of worse outcomes after open lower extremity revascularization.

OBJECTIVE: Prior research has shown that socioeconomic status (SES) is associated with higher rates of diabetes, peripheral vascular disease, and amputation. We sought to determine whether SES or insurance type increases the risk of mortality, major adverse limb events (MALE), or hospital length of stay (LOS) after open lower extremity revascularization. METHODS: We conducted a retrospective analysis of patients who underwent open lower extremity revascularization at a single tertiary care center from January 2011 to March 2017 (n = 542). SES was determined using state Area Deprivation Index (ADI), a validated metric determined by income, education, employment, and housing quality by census block group. Patients undergoing amputation in this same time period (n = 243) were included to compare rates of revascularization to amputation by ADI and insurance status. For patients undergoing revascularization or amputation procedures on both limbs, each limb was treated individually for this analysis. We performed a multivariate analysis of the association between ADI and insurance type with mortality, MALE, and LOS using Cox proportional hazard models, including confounding variables such as age, gender, smoking status, body mass index, hyperlipidemia, hypertension, and diabetes. The cohort with an ADI quintile of 1, meaning least deprived, and the Medicare cohort were used for reference. P values of <.05 were considered statistically significant. RESULTS: We included 246 patients undergoing open lower extremity revascularization and 168 patients undergoing amputation. Controlling for age, gender, smoking status, body mass index, hyperlipidemia, hypertension, and diabetes, ADI was not an independent predictor of mortality (P = .838), MALE (P = .094), or hospital LOS (P = .912). Controlling for the same confounders, uninsured status was independently predictive of mortality (P = .033), but not MALE (P = .088) or hospital LOS (P = .125). There was no difference in the distribution of revascularizations or amputations by ADI (P = .628), but there was higher proportion of uninsured patients undergoing amputation compared with revascularization (P < .001). CONCLUSIONS: This study suggests that ADI is not associated with an increased risk of mortality or MALE in patients undergoing open lower extremity revascularization, but that uninsured patients are at higher risk of mortality after revascularization. These findings indicate that individuals undergoing open lower extremity revascularization at this single tertiary care teaching hospital received similar care, regardless of their ADI. Further study is warranted to understand the specific barriers that uninsured patients face.