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AbstractBackgroundAortic stenosis (AS) is associated with myocardial ischemia through different mechanisms and may impair coronary arterial flow. However, data on the impact of moderate AS in patients with acute myocardial infarction (MI) is limited.AimsThis study aimed to investigate the impact of moderate AS in patients presenting with acute myocardial infarction (MI).MethodsWe conducted a retrospective analysis of all patients who presented with acute MI to all Mayo Clinic hospitals, using the Enterprise Mayo PCI Database from 2005 to 2016. Patients were stratified into two groups: moderate AS and mild/no AS. The primary outcome was all cause mortality.ResultsThe moderate AS group included 183 (13.3%) patients, and the mild/no AS group included 1190 (86.7%) patients. During hospitalization, there was no difference between both groups in mortality. Patients with moderate AS had higher in‐hospital congestive heart failure (CHF) (8.2% vs. 4.4%, p = 0.025) compared with mild/no AS patients. At 1‐year follow‐up, patients with moderate AS had higher mortality (23.9% vs. 8.1%, p < 0.001) and higher CHF hospitalization (8.3% vs. 3.7%, p = 0.028). In multivariate analysis, moderate AS was associated with higher mortality at 1‐year (odds ratio 2.4, 95% confidence interval [1.4–4.1], p = 0.002). In subgroup analyses, moderate AS increased all‐cause mortality in STEMI and NSTEMI patients.ConclusionThe presence of moderate AS in acute MI patients was associated with worse clinical outcomes during hospitalization and at 1‐year follow‐up. These unfavorable outcomes highlight the need for a close follow‐up of these patients and for timely therapeutic strategies to best manage these coexisting conditions.

Gastrointestinal (GI) amyloidosis can be acquired or genetic and is commonly caused by chronic inflammatory illnesses (AA amyloidosis), haematological malignancies (AL amyloidosis) and end-stage renal disease (beta-2 microglobulin amyloidosis). The accumulation of these aberrant proteins disrupts the structures and functions of many organs; the least common of which is the GI tract. GI presentations depend on the type, location and amount of amyloid deposition. Symptoms can range from nausea and vomiting to fatal GI bleeds. Pathological examination of the involved tissue with characteristic green birefringence under polarised light is used to confirm the diagnosis. Patients should be considered for further evaluation to rule out additional organ involvement, notably cardiac and renal. We present a patient with amyloidosis-induced gastroparesis, an under-recognised presentation of systemic amyloidosis in the gastroenterology system.

Background Endovascular thrombectomy (EVT) is a treatment option for acute ischemic stroke due to large vessel occlusion. The use of a balloon-guided catheter (BGC) for EVT via transradial access (TRA) has emerged as a treatment approach, but its efficacy and safety compared to existing practices are uncertain. Methods A systematic literature review was performed using Embase, PubMed, Scopus, Web of Science databases, and manual search. Studies reporting safety and efficacy metrics for TRA BGC EVT were included. Data regarding recanalization time, thrombolysis in cerebral infarction (TICI), modified Rankin scale (mRS), symptomatic intracranial hemorrhage (sICH), first pass effect (FPE), and additional complications was pooled using a random-effects model to calculate event rates and 95% confidence intervals (CI). Results The search yielded five studies (n = 117). The mean time from puncture to final recanalization was 34.5 (95% CI = 30.5 to 39.14, I 2 = 0%, P-value = 0.37) min. Successful recanalization (TICI 2b-3) and complete recanalization (TICI 3) occurred in 96.6% (95% CI = 91.24 to 98.71, I 2 = 0%, P-value = 0.99) and 55.2% (95% CI = 42.14 to 67.54, I 2 = 0%, P-value = 0.39) of cases, respectively. FPE occurred in 67.5% (95% CI = 51.73 to 80.10, I 2 = 0%, P-value = 0.56) of patients. mRS 0-2 was achieved in 41.2% (95% CI = 27.34 to 56.65, I 2 = 70%, P-value = 0.07) of patients. sICH occurred in 5.0% (95% CI = 1.25 to 17.91, I 2 = 0%, P-value = 1.00) of patients. Local complications of radial hematoma and radial vasospasm occurred in 5.0% (95% CI = 0.49 to 12.36, I 2 = 29%, P-value = 0.24) and 2.1% (95% CI = 1.25 to 17.91, I 2 = 71%, P-value = 0.03) of cases, respectively. Switch to femoral access was necessary in 3.7% (95% CI = 0.00 to 14.07, I 2 = 68%, P-value = 0.02) of procedures. The average number of passes per procedure was 1.6 (95% CI = 1.15 to 2.11, I 2 = 88%, P-value < 0.001). Conclusion TRA BGC EVT has potential as a safe and efficacious treatment option compared to existing methods. However, additional, prospective studies are necessary to inform clinical decision making.

Abstract Intestinal permeability may correlate with adverse outcomes during hematopoietic stem cell transplantation (HSCT), but longitudinal quantification with traditional oral mannitol and lactulose is not feasible in HSCT recipients because of mucositis and diarrhea. A modified lactulose:rhamnose (LR) assay is validated in children with environmental enteritis. Our study objective was to quantify peri-HSCT intestinal permeability changes using the modified LR assay. The LR assay was administered before transplant, at day +7 and +30 to 80 pediatric and young adult patients who received allogeneic HSCT. Lactulose and rhamnose were detected using urine mass spectrometry and expressed as an L:R ratio. Metagenomic shotgun sequencing of stool for microbiome analyses and enzyme-linked immunosorbent assay analyses of plasma lipopolysaccharide binding protein (LBP), ST2, REG3α, claudin1, occludin, and intestinal alkaline phosphatase were performed at the same timepoints. L:R ratios were increased at day +7 but returned to baseline at day +30 in most patients (P = .014). Conditioning regimen intensity did not affect the trajectory of L:R (P = .39). Baseline L:R ratios did not vary with diagnosis. L:R correlated with LBP levels (r2 = 0.208; P = .0014). High L:R ratios were associated with lower microbiome diversity (P = .035), loss of anaerobic organisms (P = .020), and higher plasma LBP (P = .0014). No adverse gastrointestinal effects occurred because of LR. Intestinal permeability as measured through L:R ratios after allogeneic HSCT correlates with intestinal dysbiosis and elevated plasma LBP. The LR assay is well-tolerated and may identify transplant recipients who are more likely to experience adverse outcomes.

Summary Background Patients with gastroparesis and related disorders have symptoms including early satiety, postprandial fullness and bloating. Buspirone, a 5‐HT 1 receptor agonist, may improve fundic accommodation. Aim To determine if buspirone treatment improves early satiety and postprandial fullness in patients with symptoms of gastroparesis. Methods This 4‐week multi‐centre clinical trial randomised patients with symptoms of gastroparesis and moderate‐to‐severe symptoms of fullness (Gastroparesis Cardinal Symptom Index [GCSI] early satiety/postprandial fullness subscore [ES/PPF]) to buspirone (10 mg orally) or placebo three times per day. The primary outcome was a change in the ES/PPF from baseline to 4 weeks. The primary analysis was per protocol intention‐to‐treat ANCOVA of between‐group baseline vs. 4‐week differences (DoD) in ES/PPF adjusted for baseline ES/PPF. Results are reported using both nominal and Bonferroni (BF) p values. Results and conclusions Ninety‐six patients (47 buspirone, 49 placeboes; 92% female, 50% delayed gastric emptying, 39% diabetic) were enrolled. There was no between‐groups difference in the 4‐week ES/PPF primary outcome: −1.16 ± 1.25 (SD) on buspirone vs −1.03 ± 1.29 (SD) on placebo (mean DoD: −0.11 [95% CI: −0.68, 0.45]; p = 0.69). Buspirone performed better than placebo in patients with severe‐to‐very severe bloating at baseline compared to patients with none to moderate: (ES/PPF DoD = −0.65 vs. 1.58, p TX*GROUP = 0.003; p BF = 0.07). Among individual GCSI symptoms, only bloating appeared to improve with buspirone vs. placebo. Conclusions Patients with moderate‐to‐severe early satiety/postprandial fullness and other symptoms of gastroparesis did not benefit from buspirone treatment to improve the ES/PPF primary outcome compared with placebo. There was a suggestion of the benefit of buspirone in patients with more severe bloating. Trial Registration: ClinicalTrials.gov NCT0358714285.

Purpose of review Advances in pharmacogenomics have paved the way for personalized medicine. The purpose of this review is to summarize the background, rationale, and evidence for pharmacogenomics in cardiovascular medicine. Recent findings Randomized clinical trials have supported the role of a genotype-guided approach for antiplatelet therapy in patients with coronary artery disease undergoing percutaneous coronary interventions. Additionally, there is increasing evidence supporting the association of certain genetic variants and risk of statin associated muscle symptoms. Furthermore, germline genetic variation is being used as a biomarker to target patients with specific therapy. Summary Pharmacogenomics has the potential to improve patient care by providing the right drug to the right patient and could guide the identification of novel drug therapies for cardiovascular disease.

Background Racial and ethnic disparities in outcomes exist following many cardiac procedures. Transcatheter mitral valve replacement (TMVR) has grown as an alternative to mitral valve surgery for patients at high surgical risk. The outcomes of TMVR by race and ethnicity are unknown. We aimed to evaluate racial and ethnic disparities in the outcomes of TMVR. Methods and Results We analyzed the National Inpatient Sample database from 2016 to 2020 to identify hospitalizations for TMVR. Racial and ethnic disparities in TMVR outcomes were determined using logistic regression models. Between 2016 and 2020, 5005 hospitalizations for TMVR were identified, composed of 3840 (76.7%) White race, 505 (10.1%) Black race, 315 (6.3%) Hispanic ethnicity, and 345 (6.9%) from other races (Asian, Pacific Islander, American Indian or Alaska Native, Other). Compared with other racial and ethnic groups, Black patients were significantly younger and more likely to be women (both P <0.01). There were no significant differences between White, Black, and Hispanic patients in in‐hospital mortality (5.2% versus 5.0% versus <3.5%; P =0.89) and procedural complications, including heart block ( P =0.91), permanent pacemaker ( P =0.49), prosthetic valve dysfunction ( P =0.45), stroke ( P =0.37), acute kidney injury ( P =0.32), major bleeding ( P =0.23), and blood transfusion ( P =0.92), even after adjustment for baseline characteristics. Adjusted vascular complications were higher in Black compared with White patients ( P =0.03). Trend analysis revealed a significant increase in TMVR in all racial and ethnic groups from 2016 to 2020 ( P trend <0.05). Conclusions Between 2016 and 2020, Black and Hispanic patients undergoing TMVR had similar in‐hospital outcomes compared with White patients, except for higher vascular complications in Black patients. Further comparative studies of TMVR in clinically similar White patients and other racial and ethnic groups are warranted to confirm our findings.

Abstract Background In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR‐Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR‐Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence‐based findings and recommendation from the full document. Methods ICAR‐Allergic Rhinitis 2023 employed established evidence‐based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. Results ICAR‐Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. Conclusion The ICAR‐Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.

Heart failure (HF) is a chronic, debilitating condition associated with significant morbidity, mortality, and socioeconomic burden. Patients with end-stage HF (ESHF) who are not a candidate for advanced therapies will continue to progress despite standard medical therapy. Thus, the focus of care shifts from prolonging life to controlling symptoms and improving quality of life through palliative care ( PC). Because the condition and prognosis of HF patients evolve and can rapidly deteriorate, it is imperative to begin the discussion on end-of-life (EOL) issues early during HF management. These include the completion of an advance directive, do-not-resuscitate orders, and policies on device therapy and discontinuation as part of advance care planning (ACP). ESHF patients who do not have indications for advanced therapies or those who wish not to have a left ventricular assist device (LVAD) or heart transplant (HT) often experience high symptom burden despite adequate medical management. The proper identification and assessment of symptoms such as pain, dyspnea, nausea, depression, and anxiety are essential to the management of ESHF and may be underdiagnosed and undertreated. Psychological support and spiritual care are also crucial to improving the quality of life during EOL. Caregivers of ESHF patients must also be provided supportive care to prevent compassion fatigue and improve resilience in patient care. In this narrative review, we compare the international guidelines and provide an overview of end-of-life and palliative care for patients with ESHF.

Cerebrovascular accident (CVA) is one of the leading causes of death in the United States. Von Willebrand factor plays an important role in platelet activation and adhesion. It remains unclear whether Von Willebrand disease (vWD) is associated with a decreased risk of developing CVA. The study aimed to compare the relative risk (RR) of CVA in patients with and without vWD. We queried the National Inpatient Sample from 2009 to 2014 for discharge data and records for vWD and CVA using International Classification of Diseases, Ninth-Revision codes. The unadjusted and adjusted RR of CVA in patients with and without vWD were estimated using log-binomial model. Descriptive measures including means, medians, standard deviations, and range were presented based on normality test of continuous data. The prevalence of CVA was lower in patients with vWD than in those without vWD (1.31% vs 2.04%), with a RR of 0.64 (95% confidence interval (CI): 0.60–0.68). After adjusting for common CVA risk factors, the RR remained lower in vWD patients: 0.81 (95% CI: 0.76–0.86). vWD is associated with a lower RR of developing CVA. This suggests that deficiency of Von Willebrand factor is potentially protective against the development of CVA. To the best of our knowledge, this is the first study in humans to compare the RR of CVA in patients with and without vWD. Future studies are needed to explore causal relationships and therapeutic benefits.