Association Between Stable Coronary Artery Disease and Hospital Readmissions Following Catheter Ablation for Atrial Fibrillation.

OBJECTIVE: To evaluate the association of stable coronary artery disease (CAD) with readmission following hospitalization for catheter ablation (CA) for atrial fibrillation (AF). PATIENTS AND METHODS: Using the Nationwide Readmissions Database, we identified all hospitalizations from the last quarter of 2015 through 2019 with a Medicare Severity-Diagnosis Related Group designation for a percutaneous intracardiac procedure, a procedure code for CA, and a primary discharge diagnosis of AF. Cases of acute coronary syndrome (ACS) at index hospitalization were excluded to define stable CAD. The primary outcome was all-cause 90-day hospital readmission; secondary end points included readmissions for AF, repeated CA, ACS, and heart failure (HF). RESULTS: Among 28,466 hospitalizations for CA for AF identified, 3171 (11.1%) involved patients with stable CAD. No hospitalizations included patients with HF diagnosis codes. The incidence of 90-day all-cause readmission was higher in patients with stable CAD (18.4% [400 of 2172] vs 14.4% [2549 of 17,667]; P=.006), as was the incidence of subsequent hospitalization with ACS (5.3% [21] vs 1.1% [28]; P<.001) or HF (17.0% [68] vs 10.2% [260]; P=.007). The incidence of readmission within 90 days with recurrent AF did not differ for those with or without stable CAD (21.9% [88] vs 26.5% [675]; P=.217). Pooled analysis of 90-day HF readmissions revealed a higher incidence among older patients, those with chronic kidney or pulmonary disease, and those with persistent and chronic AF subtypes. CONCLUSION: Results of this large-scale analysis suggest that among patients hospitalized for CA for AF, stable CAD is associated with hospital readmissions within 90 days, including admissions for ACS and decompensated HF.

HeartMate-3 Ventricular Assist Devices Versus the Total Artificial Heart for Biventricular Support: A Single-Center Series.

INTRODUCTION: The SynCardia total artificial heart (TAH) is the only device approved for biventricular support. Continuous flow ventricular assist devices (VAD) in a biventricular configuration (BiVAD) have been used with variable results. The purpose of this report was to examine differences in patient characteristics and outcomes between two HeartMate-3 (HM-3) VADs in comparison with TAH support. METHODS: All patients who received durable biventricular mechanical support from November 2018 to May 2022 at The Mount Sinai Hospital (New York) were considered. Baseline clinical, echocardiographic, hemodynamic, and outcome data were extracted. Primary outcomes were postoperative survival and successful bridge-to-transplant (BTT). RESULTS: A total of 16 patients received durable biventricular mechanical support during the study period, of which 6 (38%) patients received two HM-3 VAD pumps as BiVAD support and 10 (62%) patients received a TAH. Overall, TAH patients had a lower median lactate ( p < 0.05) at baseline compared to those on HM-3 BiVAD support yet had higher operative morbidity, lower 6-month survival ( p < 0.05), and a higher rate of renal failure (80 vs . 17%; p = 0.03). However, survival declined to the same rate at 1 year (50%) and was largely because of extracardiac adverse events related to underlying comorbidities (particularly, renal failure and diabetes, p < 0.05). Successful BTT was achieved in 3 out of 6 HM-3 BiVAD patients and in 5 out of 10 TAH patients. CONCLUSION: In our single center experience, similar outcomes were observed among patients BTT with HM-3 BiVAD compared to those BTT on TAH support despite lower Interagency Registry for Mechanically Assisted Circulatory Support level.

Vitamin D attenuates HMGB1-mediated neointimal hyperplasia after percutaneous coronary intervention in swine.

Intracoronary stenting is a common procedure in patients with coronary artery disease (CAD). Stent deployment stretches and denudes the endothelial layer, promoting a local inflammatory response, resulting in neointimal hyperplasia. Vitamin D deficiency associates with CAD. In this study, we examined the association of vitamin D status with high mobility group box 1 (HMGB1)-mediated pathways (HMGB1, receptor for advanced glycation end products [RAGE], and Toll-like receptor-2 and -4 [TLR2 and TLR4]) in neointimal hyperplasia in atherosclerotic swine following bare metal stenting. Yucatan microswine fed with a high-cholesterol diet were stratified to receive vitamin D-deficient (VD-DEF), vitamin D-sufficient (VD-SUF), and vitamin D-supplemented (VD-SUP) diet. After 6 months, PTCA (percutaneous transluminal balloon angioplasty) followed by bare metal stent implantation was performed in the left anterior descending (LAD) artery of each swine. Four months following coronary intervention, angiogram and optical coherence tomography (OCT) were performed and swine euthanized. Histology and immunohistochemistry were performed in excised LAD to evaluate the expression of HMGB1, RAGE, TLR2, and TLR4. OCT analysis revealed the greatest in-stent restenosis area in the LAD of VD-DEF compared to VD-SUF or VD-SUP swine. The protein expression of HMGB1, RAGE, TLR2, and TLR4 was significantly higher in the LAD of VD-DEF compared to VD-SUF or VD-SUP swine. Vitamin D deficiency was associated with both increased in-stent restenosis and increased HMGB1-mediated inflammation noted in coronary arteries following intravascular stenting. Inversely, vitamin D supplementation was associated with both a decrease in this inflammatory profile and in neointimal hyperplasia, warranting further investigation for vitamin D as a potential adjunct therapy following coronary intervention.

Comorbidity burden on receipt of adjuvant immunotherapy and survival in patients with stage III melanoma: an analysis of the National Cancer Database.

BACKGROUND: Comorbidity burden is associated with development of cancer, stage at diagnosis, and treatment outcomes. We evaluated the association between comorbidity burden, receipt of adjuvant immunotherapy, and survival in patients with stage III melanoma. METHODS: Using the National Cancer Database, we identified 16,906 patients with stage III melanoma who underwent surgery of the primary site. Outcomes included receipt of adjuvant immunotherapy and overall survival; independent variables included Charlson/Deyo comorbidity index (CDI) and receipt of adjuvant immunotherapy. RESULTS: Patients with CDI scores of two or more averaged 30.0% and 30.9% lower adjusted odds of receiving adjuvant immunotherapy relative to patients with a CDI score of zero or one, respectively (P = 0.001 and 0.002, respectively). Longer survival was associated with lower CDI scores (all P < 0.001) and receipt of adjuvant immunotherapy (P < 0.001). Patients who received adjuvant immunotherapy averaged 16.0% lower adjusted risk of death compared to patients who did not (P < 0.001), which was constant within all CDI cohorts. Patients with a CDI score of two or more averaged 53.4% and 39.1% higher adjusted risk of death relative to patients with a CDI score of zero or one (both P < 0.001). CONCLUSION: Greater comorbidity burden was associated with lower receipt of adjuvant immunotherapy; however, adjuvant immunotherapy provided similar survival benefit for patients' irrespective comorbidity burden. Our findings suggest that patients with stage III melanoma who have a greater comorbidity burden may benefit from adjuvant immunotherapy but should not replace careful patient selection by the clinician.

Dual alternate access sites for the treatment of an ostial left common iliac artery chronic total occlusion.

Growing endovascular strategies with TASC D lesions in aortoiliac disease reflect increasing technical success with evidenced safety and efficacy. In cases of failed transfemoral access, revascularization of iliac chronic total occlusions has prompted the utilization of other alternate access sites (e.g. transradial and transbrachial approaches) as important options in aortoiliac TASC D lesions. We describe a case of successful revascularization of an occluded ostial left common iliac artery in an 81-year-old man using a dual ulnar and tibioperoneal approach (absent radial artery). A Controlled Antegrade and Retrograde Tracking technique was performed where a balloon was advanced from the peroneal artery into the distal cap of the chronic total occlusion in the proximal common femoral artery. Balloon inflation was performed and a glidewire from transulnar access was advanced and re-entered into the true lumen in the common femoral artery. The wire was then snared and externalized out the transpedal access site creating a continuous true lumen from the ulnar artery to the peroneal artery. To reconstruct the aortic bifurcation, kissing balloon inflations were performed from the peroneal as well as the ulnar artery approaches. A 10 mm × 59 mm balloon expandable stent was placed in the ostial left common iliac artery and a 8 mm × 60 mm self-expanding stent was placed in the left external iliac artery successfully.

Atherothrombosis and the NLRP3 inflammasome - endogenous mechanisms of inhibition.

Recently, the CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) showed the successful anti-inflammatory benefit of canakinumab, a monoclonal antibody targeting interleukin-1ß (IL-1ß) toward major cardiovascular events (MACE) in patients with a previous myocardial infarction (MI). The magnitude of reduction in MACE was directly attributed to a reduction witnessed in IL-6 and C-reactive protein (CRP) and highlighted the therapeutic potential of selectively targeting IL-1ß for atherosclerotic disease, a notion previously introduced in animal models. IL-1ß is involved in the downstream activation of the IL-6 receptor, which itself has been previously implicated as a target for atherothrombosis from Mendelian randomization studies. Further support has been garnered with the results of CIRT (Cardiovascular Inflammation Reduction Trial), which showed the inability of low-dose methotrexate to reduce IL-1ß, IL-6, or high-sensitivity CRP (hsCRP) in addition to MACE among patients with prior MI or multivessel coronary artery disease (CAD) but with normal hsCRP levels. Therefore, elucidation of therapeutic targets against the IL-1ß pathway is of immense interest currently in treating atherothrombosis. Upstream and serving as an activator of IL-1ß lies the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome that has been well described in animal models to be activated by cholesterol crystals or hypoxia to promote cleavage and secretion of IL-1ß and IL-18 that lead to atherosclerotic deposition in arteries. Given the direct implication of an atherogenic role to the NLRP3 inflammasome in generating these cytokines, NLRP3 inhibitors are of interest with the consideration to move upstream from the initial success of anti-IL-1ß therapy. With further discussion of the existing knowledge on the proinflammatory relationship of the NLRP3 inflammasome with atherosclerosis, this review summarizes and critically evaluates the preclinical and interventional findings of endogenous NLRP3 inflammasome inhibition in attempts to elucidate anti-inflammatory mechanisms, and therapeutic targets against atherothrombosis. Further investigation focusing on the endogenous mechanisms of inhibition of the NLRP3 inflammasome would uncover diagnostic routes from defective means in inflammatory resolution. Specifically, pro-resolving lipid mediators, autophagy, and phosphorylation/dephosphorylation mechanisms are 3 points of worthy investigation from existing evidence.

Modulation of Cathepsin L Expression in the Coronary Arteries of Atherosclerotic Swine.

INTRODUCTION: Neointimal hyperplasia (NIH) and restenosis after percutaneous transluminal coronary angioplasty (PTCA) and intravascular stenting remain a problem on a long-term basis by causing endothelial denudation and damage to the intima and media. Vascular sterile inflammation has been attributed to the formation of NIH. Cathepsin L (CTSL), a lysosome protease, is associated with diet-induced atherogenesis. Vitamin D regulates the actions and regulatory effects of proteases and protease inhibitors in different cell types. Objectives of this study are to evaluate the modulatory effect of vitamin D on CTSL activity in post-PTCA coronary arteries of atherosclerotic swine. METHODS: Yucatan microswine were fed with high-cholesterol atherosclerotic diets. The swine were stratified to receive three diets: (1) vitamin D-deficient diet, (2) vitamin D-sufficient diet, and (3) vitamin D-supplement diet. After 6 mo, PTCA was performed in the left circumflex coronary artery (LCx). After 1 y, angiography and optical coherence tomography imaging were performed, and swine was euthanized. Coronary arteries were embedded in paraffin. Tissue sections were stained with hematoxylin and eosin. Expression of Ki67 and CTSL were evaluated by immunofluorescence. RESULTS: Increased number of Ki67 + cells were observed in the postangioplasty LCx in vitamin D-deficient compared with vitamin D-sufficient or vitamin D-supplemented swine. Notably, the expression of CTSL was significantly increased in postangioplasty LCx of vitamin D-deficient swine compared with the vitamin D-sufficient or vitamin D-supplemented animal groups. CONCLUSIONS: Increased expression of CTSL correlates with the formation of NIH in the PTCA-injured coronary arteries. However, in the presence of sufficient or supplemented levels of vitamin D in the blood, CTSL expression was significantly reduced.

Left Ventricular Thrombus After Acute Decompensated Heart Failure in the Setting of Ischemic Cardiomyopathy.

A 70-year-old male with a medical history significant for long-standing ischemic cardiomyopathy (ICM) and heart failure with reduced ejection fraction (HFrEF) was admitted to the hospital with shortness of breath (SOB) five days after an acute heart failure (HF) exacerbation. He had non-radiating chest pressure now at rest, but without evidence of an acute coronary syndrome (ACS). Diagnostic work-up on readmission included a transthoracic echocardiogram (TTE), which revealed worsening left ventricular (LV) systolic dysfunction with new wall motion abnormalities and an incidental echo density in the LV apex, suggestive of an LV thrombus. These findings were unseen on imaging 20 months prior. The patient was initiated on warfarin to be maintained for three months, and discharged in stable condition after optimization of his anginal symptoms. Cardiac catheterization was not attempted secondary to the patient's chronic kidney disease (CKD). The incidental finding of an LV thrombus occurred despite compliance with guideline-directed medical therapy of HFrEF and ICM, including adjunctive use of clopidogrel. With the poor survival associated with thromboembolism, the prevention, risk stratification and appropriate therapeutic approach to LV thrombus are poorly delineated in patients with HFrEF in sinus rhythm. Currently, the screening guidelines for the identification of LV thrombus in patients with HFrEF are also unknown. Given mixed evidence regarding prophylactic anticoagulation, we present this case of an incidental LV thrombus found during an episode of acute decompensated HF in the setting of long-standing ICM to emphasize the need to suspect LV thrombus formation after such presentations with closer follow-up for prompt detection and timely treatment.

Stenotrophomonas maltophilia Endocarditis of an Implantable Cardioverter Defibrillator Lead.

Stenotrophomonas maltophilia (S. maltophilia) is a nosocomial pathogen and a rare cause of infective endocarditis (IE). Given the intrinsic resistance to many classes of antibiotics, IE due to S. maltophilia carries significant morbidity and mortality among the cases described. Prompt identification of risk factors, particularly the use of medical devices, is necessary for the timely identification of this organism and prompt medical management. We report a case of an implantable cardioverter defibrillator (ICD) lead associated IE due to S. maltophilia and discuss the diagnosis, treatment and outcomes in relation to existing evidence.

Pro-inflammatory and pro-resolving mechanisms in the immunopathology of arteriovenous fistula maturation.

Introduction: With high rates of arteriovenous fistula (AVF) failure, there is a continued need to predict other factors and mechanisms associated with maturation deficits. Given the central association of inflammation with AVF failure, with neointimal hyperplasia (NIH) as one such mechanism, inflammation must be considered in two endogenous ways, either pro-inflammatory or pro-resolving, resulting in inward or outward vascular remodeling. Areas covered: This review summarizes and critically evaluates the preclinical and interventional data underlying AVF failure in attempts to elucidate the necessary balance between inflammation and its resolution. Expert opinion: Understanding the pro-inflammatory and pro-resolving mechanisms underlying inward and outward vascular remodeling and NIH prevention with AVF maturation is a necessary effort to develop key diagnostic and therapeutic interventions towards the ongoing issue of long-term AVF patency. The ability for clinical application has progressed but is limited to the identification of key targets and pathways with little understanding of how they are related synergistically or antagonistically. Likewise, the balance between acute inflammation and pro-resolution requires pertinent temporal considerations necessary for timely therapeutic application and predictive measurement.

Adipokine Dysregulation and Insulin Resistance with Atherosclerotic Vascular Disease: Metabolic Syndrome or Independent Sequelae?

Adipokine dysregulation and insulin resistance are two hallmark sequelae attributed to the current clinical definition of metabolic syndrome (MetS) that are also linked to atherosclerotic vascular disease. Here, we critically discuss the underlying pathophysiological mechanisms and the interplay between the two sequelae. Adipokine dysregulation is involved with decreased nitric oxide, vascular inflammation, and insulin resistance in itself to promote atherosclerosis. Insulin resistance is involved with endothelial dysfunction by direct and indirect mechanisms that also promote vascular inflammation and atherosclerosis. These mechanisms are discussed in atherosclerosis irrespective of MetS, and to evaluate the possibility of synergism in MetS. High retinol-binding protein-4 (RBP-4) and low cholesterol efflux in MetS may provide evidence of possible synergism and elevated atherosclerotic risk. An adverse adipokine panel that includes fetuin-A and adiponectin can potentially assess atherosclerotic risk in even those without MetS. Genetic possibilities may exist in atherosclerotic vascular diseases secondary to insulin resistance.

Treatment of an external iliac artery chronic total occlusion using alternate access sites.

BACKGROUND: With the advent of endovascular techniques, alternate sites such as the pedal and radial arteries can now be accessed when treating peripheral arterial disease to reduce procedural complications, shorten recovery time, and improve patient comfort. However, a paucity of literature exists on the availability of support devices that can be utilized during challenging cases. CASE PRESENTATION: A 70 year-old female patient presented for evaluation of severe lifestyle-limiting left-sided claudication refractory to maximal medical therapy. Angiography revealed a chronic total occlusion of the left external iliac artery, which was treated successfully by percutaneous intervention via a primary transpedal approach and with the assistance of the Outback® Elite re-entry device. The patient was discharged 2 h after the procedure and reported significant symptom improvement at follow-up. CONCLUSION: This case highlights a newly adopted endovascular approach through an alternate access site and illustrates how the Outback® Elite device can be used as an adjunctive tool in the treatment of complex lower-extremity vascular lesions.

Trends in use of echocardiography in hospitalized patients with syncope.

PURPOSE: We sought to assess the trends in use, predictors of echocardiography, and its impact on in-hospital mortality in patients admitted with syncope using a large national database. METHODS: Utilizing the Nationwide Inpatient Sample (NIS) database from 2001 to 2014, we identified adult patients (>18 years) with a primary discharge diagnosis of syncope and use of echocardiogram was ascertained. RESULTS: A total of 3 174 619 patients with a primary discharge diagnosis of syncope were identified, of which 184 167 (5.8%) underwent an echocardiogram. The rate of syncope hospitalization remained constant between 2001 and 2009 (1.1/1000 US population) but has since decreased steadily to about 0.5/1000 US population in 2014. After adjusting for patient and hospital characteristics, the rate of echocardiogram use increased significantly from 5.1% in 2001 to 6.8% in 2014 (2.7% relative increase per year [Ptrend  = 0.024]). Predictors of use were cardiac disorders, hypertension, diabetes, peripheral vascular disease, and renal failure. After adjusting for baseline risk, use of echocardiography was not associated with in-hospital mortality (OR = 0.827, P = 0.155), but was associated with a 14.6% increase in adjusted length of stay and a 22.6% increase in adjusted hospital cost compared to no echocardiography use (both P < 0.001). CONCLUSIONS: The admission rates for syncope are decreasing and use of echocardiography in hospitalized patients with syncope is appropriately low. Given the lack of any favorable impact on mortality and the association with increased costs, there is a continued need to emphasize evidence-based use of echocardiography in patients presenting with syncope.

Pro-resolving lipid mediators in the resolution of neointimal hyperplasia pathogenesis in atherosclerotic diseases.

INTRODUCTION: Despite advances in drug eluting technologies, neointimal hyperplasia (NIH) and restenosis still plagues endovascular therapy in atherosclerotic diseases. By appreciating atherosclerosis and NIH as complex inflammatory processes, specialized pro-resolving mediators (SPMs) are a superfamily of endogenous unsaturated fatty-acid derived lipids with the potential for inflammatory resolution. Areas covered: Inquiry into SPMs in this context is a novel approach and is the focus of this review, with emphasis on our understanding with NIH. Prior mechanistic understandings of SPM deficiency with atherosclerosis has offered insight, as well as the complexity and diversity of the SPM superfamily. Therapeutic investigation using SPMs to combat NIH is also evaluated here. Expert commentary: Endogenous deficiency of SPMs synthesis by 12/15-lipoxygenase underlies resolution deficits in atherosclerosis and NIH. Upstream PDGF inhibition by SPMs, most notably RvD1 and LXA4, confers a multifactorial attenuation of NIH that involves interconnected anti-inflammatory efforts, most notably switch pro-resolving smooth muscle cells (vSMCs) and macrophages. The ALX/FPR2 is one receptor system identified on vSMCs that interacts with these SPMs to promote NIH resolution. Therapeutically, while shown to be promising with less stent burden or cytotoxicity, SPMs must be balanced by necessary mechanistic, pharmacokinetic and anatomical considerations.