Coronary spasm and vasomotor dysfunction as a cause of MINOCA.

Increasing evidence has shown that coronary spasm and vasomotor dysfunction may be the underlying cause in more than half of myocardial infarctions with non-obstructive coronary arteries (MINOCA) as well as an important cause of chronic chest pain in the outpatient setting. We review the contemporary understanding of coronary spasm and related vasomotor dysfunction of the coronary arteries, the pathophysiology and prognosis, and current and emerging approaches to diagnosis and evidence-based treatment.

Ischemic or Coronary Evaluations in Patients With Monomorphic VT Electrical Storm Undergoing VT Ablation.

BACKGROUND: Monomorphic ventricular tachycardia (VT) electrical storm (ES) in patients with coronary artery disease is dependent on scarred myocardium. The role of routine ischemic or coronary evaluations before ablation in patients presenting with monomorphic VT storm, without acute coronary syndrome (ACS), remains unknown. OBJECTIVES: This study sought to assess the impact of ischemic or coronary evaluations on procedural outcomes and post-ablation mortality in monomorphic VT storm patients. METHODS: All patients undergoing VT ablation at the Cleveland Clinic from 2014 to 2020 after presenting with monomorphic VT storm were enrolled in a prospectively maintained registry. The associations among ischemic or coronary evaluations and short-term procedural efficacy, acute outcomes, and mortality during follow-up were assessed. RESULTS: A total of 97 consecutive patients with monomorphic VT storm in the absence of ACS underwent VT ablations. This cohort was characterized by severe LV systolic dysfunction (mean left ventricular ejection fraction 30.3%, 67% with known ischemic cardiomyopathy) with moderately severe heart failure (median NYHA functional class II); 45% of patients underwent ischemic or coronary evaluations via coronary angiography (10%), noninvasive myocardial perfusion (26%), or both (9%). The yield of these evaluations was low: No acute coronary occlusions were identified. There was no association between ischemic evaluation and acute ablation outcomes or mortality during follow-up. Similarly, in a secondary analysis, the yield of ischemic or coronary evaluations in patients with monomorphic VT storm and known coronary disease (regardless of ablation status) was found to be low. CONCLUSIONS: Ischemic evaluations in patients with monomorphic VT storm without ACS may not improve procedural outcomes or mortality after ablation.

Antegrade wire escalation in chronic total occlusions: State of the art review.

Coronary chronic total occlusion percutaneous coronary intervention treatment algorithms have helped to standardize crossing strategy sequence to improve efficacy and efficiency of CTO interventions based on angiographic criteria. Unfortunately, advanced crossing techniques such as a retrograde and subintimal guidewire tracking and reentry that have accelerated procedural success in more difficult lesions are associated with higher major adverse cardiac event rates as compared with traditional antegrade and intimal guidewire tracking. In this regard, antegrade wire escalation (AWE) remains the most common CTO crossing strategy. In this state of the art review, we outline the techniques employed to maximize the clinical utility of AWE crossing strategy for both novice operators as well as those experienced with the advanced crossing strategies. For the less experienced operator, these techniques may provide a framework to treat more patients safely and effectively without the need to refer to a more advanced operator. Whereas these same techniques may be employed by an advanced operator to improve the technical success in procedures requiring more advanced crossing strategies.

5-Year Outcomes After Bioresorbable Coronary Scaffolds Implanted With Improved Technique.

BACKGROUND: Bioresorbable vascular scaffolds (BVS) were designed to improve late event-free survival compared with metallic drug-eluting stents. However, initial trials demonstrated worse early outcomes with BVS, in part due to suboptimal technique. In the large-scale, blinded ABSORB IV trial, polymeric everolimus-eluting BVS implanted with improved technique demonstrated noninferior 1-year outcomes compared with cobalt chromium everolimus-eluting stents (CoCr-EES). OBJECTIVES: This study sought to evaluate the long-term outcomes from the ABSORB IV trial. METHODS: We randomized 2,604 patients at 147 sites with stable or acute coronary syndromes to BVS with improved technique vs CoCr-EES. Patients, clinical assessors, and event adjudicators were blinded to randomization. Five-year follow-up was completed. RESULTS: Target lesion failure at 5 years occurred in 216 (17.5%) patients assigned to BVS and 180 (14.5%) patients assigned to CoCr-EES (P = 0.03). Device thrombosis within 5 years occurred in 21 (1.7%) BVS and 13 (1.1%) CoCr-EES patients (P = 0.15). Event rates were slightly greater with BVS than CoCr-EES through 3-year follow-up and were similar between 3 and 5 years. Angina, also centrally adjudicated, recurred within 5 years in 659 patients (cumulative rate 53.0%) assigned to BVS and 674 (53.3%) patients assigned to CoCr-EES (P = 0.63). CONCLUSIONS: In this large-scale, blinded randomized trial, despite the improved implantation technique, the absolute 5-year rate of target lesion failure was 3% greater after BVS compared with CoCr-EES. The risk period for increased events was limited to 3 years, the time point of complete scaffold bioresorption; event rates were similar thereafter. Angina recurrence after intervention was frequent during 5-year follow-up but was comparable with both devices.(Absorb IV Randomized Controlled Trial; NCT02173379).

Multi-ancestry genome- and phenome-wide association studies of diverticular disease in electronic health records with natural language processing enriched phenotyping algorithm.

OBJECTIVE: Diverticular disease (DD) is one of the most prevalent conditions encountered by gastroenterologists, affecting ~50% of Americans before the age of 60. Our aim was to identify genetic risk variants and clinical phenotypes associated with DD, leveraging multiple electronic health record (EHR) data sources of 91,166 multi-ancestry participants with a Natural Language Processing (NLP) technique. MATERIALS AND METHODS: We developed a NLP-enriched phenotyping algorithm that incorporated colonoscopy or abdominal imaging reports to identify patients with diverticulosis and diverticulitis from multicenter EHRs. We performed genome-wide association studies (GWAS) of DD in European, African and multi-ancestry participants, followed by phenome-wide association studies (PheWAS) of the risk variants to identify their potential comorbid/pleiotropic effects in clinical phenotypes. RESULTS: Our developed algorithm showed a significant improvement in patient classification performance for DD analysis (algorithm PPVs ≥ 0.94), with up to a 3.5 fold increase in terms of the number of identified patients than the traditional method. Ancestry-stratified analyses of diverticulosis and diverticulitis of the identified subjects replicated the well-established associations between ARHGAP15 loci with DD, showing overall intensified GWAS signals in diverticulitis patients compared to diverticulosis patients. Our PheWAS analyses identified significant associations between the DD GWAS variants and circulatory system, genitourinary, and neoplastic EHR phenotypes. DISCUSSION: As the first multi-ancestry GWAS-PheWAS study, we showcased that heterogenous EHR data can be mapped through an integrative analytical pipeline and reveal significant genotype-phenotype associations with clinical interpretation. CONCLUSION: A systematic framework to process unstructured EHR data with NLP could advance a deep and scalable phenotyping for better patient identification and facilitate etiological investigation of a disease with multilayered data.

Prescriber Adoption of SLCO1B1 Genotype-Guided Simvastatin Clinical Decision Support in a Clinical Pharmacogenetics Program.

Pharmacogenetic implementation programs are increasingly feasible due to the availability of clinical guidelines for implementation research. The utilization of these resources has been reported with selected drug-gene pairs; however, little is known about how prescribers respond to pharmacogenetic recommendations for statin therapy. We prospectively assessed prescriber interaction with point-of-care clinical decision support (CDS) to guide simvastatin therapy for a diverse cohort of primary care patients enrolled in a clinical pharmacogenetics program. Of the 1,639 preemptively genotyped patients, 298 (18.2%) had an intermediate function (IF) OATP1B1 phenotype and 25 (1.53%) had a poor function (PF) phenotype, predicted by a common single nucleotide variant in the SLCO1B1 gene (c.521T>C; rs4149056). Clinicians were presented with CDS when simvastatin was prescribed for patients with IF or PF through the electronic health record. Importantly, 64.2% of the CDS deployed at the point-of-care was accepted by the prescribers and resulted in prescription changes. Statin intensity was found to significantly influence prescriber adoption of the pharmacogenetic-guided CDS, whereas patient gender or race, prescriber type, or pharmacogenetic training status did not significantly influence adoption. This study demonstrates that primary care providers readily adopt pharmacogenetic information to guide statin therapy for the majority of patients with preemptive genotype data.

Impact of radiographer immediate reporting of X-rays of the chest from general practice on the lung cancer pathway (radioX): a randomised controlled trial.

The National Optimal Lung Cancer Pathway recommends rapid progression from abnormal chest X-rays (CXRs) to CT. The impact of the more rapid reporting on the whole pathway is unknown. The aim of this study was to determine the impact of immediate reporting of CXRs requested by primary care by radiographers on the time to diagnosis of lung cancer. METHOD: People referred for CXR from primary care to a single acute district general hospital in London attended sessions that were prerandomised to either immediate radiographer (IR) reporting or standard radiographer (SR) reporting within 24 hours. CXRs were subsequently reported by radiologists blind to the radiographer reports to test the reliability of the radiographer report. Radiographer and local radiologist discordant cases were reviewed by thoracic radiologists, blinded to reporter. RESULTS: 8682 CXRs were performed between 21 June 2017 and 4 August 2018, 4096 (47.2%) for IR and 4586 (52.8%) for SR. Lung cancer was diagnosed in 49, with 27 (55.1%) for IR. The median time from CXR to diagnosis of lung cancer for IR was 32 days (IQR 19, 70) compared with 63 days (IQR 29, 78) for SR (p=0.03).8258 CXRs (95.1%) were reported by both radiographers and local radiologists. In the 1361 (16.5%) with discordance, the reviewing thoracic radiologists were equally likely to agree with local radiologist and radiographer reports. CONCLUSIONS: Immediate reporting of CXRs from primary care reduces time to diagnosis of lung cancer by half, likely due to rapid progress to CT. Radiographer reports are comparable to local radiologist reports for accuracy. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number ISRCTN21818068. Registered on 20 June 2017.

Interaction Between Race and Income on Cardiac Outcomes After Percutaneous Coronary Intervention.

Background Compared with White Americans, Black Americans have a greater prevalence of cardiac events following percutaneous coronary intervention. We evaluated the association between race and neighborhood income on post-percutaneous coronary intervention cardiac events and assessed whether income modifies the effect of race on this relationship. Methods and Results Consecutive patients (n=23 822) treated with percutaneous coronary intervention from January 1, 2000, to December 31, 2016, were included. All-cause mortality and major adverse cardiac event were assessed at 3 years. Extended 10-year follow-up was performed for those residing locally (n=1285). Neighborhood income was derived using median adjusted annual gross household income reported within the patient's zip code. We compared differences in treatment and outcomes, adjusting for race, income, and their interaction. In total, 3173 (13.3%) patients self-identified as Black Americans, and 20 649 (86.7%) self-identified as White Americans. Black Americans had a worse baseline cardiac risk profile and lower neighborhood income compared with White Americans. Although risk profile improved with increasing income in White Americans, no difference was observed across incomes among Black Americans. Despite similar long-term outpatient cardiology follow-up and medication prescription, risk profiles among Black Americans remained worse. At 3 years, unadjusted all-cause mortality (18.0% versus 15.2%; P<0.001) and major adverse cardiac event (37.3% versus 34.6%; P<0.001) were greater among Black Americans and with lower income (both P<0.001); race, income, and their interaction were not significant predictors in multivariable models. At 10-year follow-up, increasing income was associated with improved outcomes only in White Americans but not Black Americans. In multivariable models for major adverse cardiac event, income (hazard ratio [HR], 0.97 [95% CI, 0.96-0.98]; P=0.005), Black race (HR, 1.77 [95% CI, 1.58-1.96]; P=0.006), and their interaction (HR, 0.98 [95% CI, 0.97-0.99]; P=0.003) were significant predictors. Similar findings were observed for cardiac death. Conclusions Early 3-year post-percutaneous coronary intervention outcomes were driven by worse risk factor profiles in both Black Americans and those with lower neighborhood income. However, late 10-year outcomes showed an independent effect of race and income, with improving outcomes with greater income limited to White Americans. These findings illustrate the importance of developing novel care strategies that address both risk factor modification and social determinants of health to mitigate disparities in cardiac outcomes.

Radiation reduction in a modern catheterization laboratory: A single-center experience.

BACKGROUND: Measures were undertaken at the Cleveland Clinic to reduce radiation exposure to patients and personnel working in the catheterization laboratories. We report our experience with these improved systems over a 7-year period in patients undergoing diagnostic catheterization (DC) and percutaneous coronary interventions (PCIs). METHODS: Patients were categorized into preinitiative (2009-2012) and postinitiative (2013-2019) groups in the DC and PCI cohorts. Propensity score matching was done between the pre- and postinitiative groups for both cohorts based on age, sex, body surface area, total fluoroscopy time, and total acquisition time. The effectiveness of radiation reduction measures was assessed by comparing the total air kerma (Ka,r ), and fluoroscopy- and acquisition-mode air kerma in patients in the two groups. RESULTS: In the DC cohort, there was a significant reduction in Ka,r in the postinitiative group in comparison to the preinitiative group (median, 396 vs. 857 mGy; p < 0.001). In the PCI cohort, Ka,r in the postinitiative group was 1265 mGy, which was significantly lower than the corresponding values in the preinitiative group (1994 mGy; p < 0.001). We also observed a significant reduction in fluoroscopy- and acquisition-based air kerma rates, and air kerma area product in the postinitiative group in comparison to the preinitiative group in both matched and unmatched DC and PCI cohorts after the institution of radiation reduction measures. CONCLUSION: There was a significant and sustained reduction in radiation exposure to patients in the catheterization laboratory with the implementation of advanced protocols. Similar algorithms can be applied in other laboratories to achieve a similar reduction in radiation exposure.

Coronary intravascular brachytherapy for in-stent restenosis: A review of the contemporary literature.

Intracoronary stent restenosis (ISR) is a clinically relevant challenge in the modern era. Heterogeneity in patient- and lesion-specific factors can further compound this clinical challenge. Coronary intravascular brachytherapy (IVBT) was the standard therapeutic approach for ISR prior to the advent of drug-eluting stents (DES). Despite prospective data describing the superiority of DES over IVBT for treating de novo ISR, IVBT remains a treatment option for patients with complex disease. The purpose of this review is to evaluate the historical and contemporary literature surrounding IVBT in order to elucidate its role in modern cardiac care and to describe opportunities for future investigations to improve patient selection. Herein, we provide a review of the contemporary literature describing IVBT as a safe and effective treatment option for patients with recurrent, refractory ISR after multilayer DES and no good surgical or mechanical option. Combination therapy with emerging technologies such as DCBs may further increase efficacy.

A Phase 1 study of ADI-PEG20 (pegargiminase) combined with cisplatin and pemetrexed in ASS1-negative metastatic uveal melanoma.

Metastatic uveal melanoma (UM) is a devastating disease with few treatment options. We evaluated the safety, tolerability and preliminary activity of arginine depletion using pegylated arginine deiminase (ADI-PEG20; pegargiminase) combined with pemetrexed (Pem) and cisplatin (Cis) chemotherapy in a phase 1 dose-expansion study of patients with argininosuccinate synthetase (ASS1)-deficient metastatic UM. Eligible patients received up to six cycles of Pem (500 mg/m2 ) and Cis (75 mg/m2 ) every 3 weeks plus weekly intramuscular ADI (36 mg/m2 ), followed by maintenance ADI until progression (NCT02029690). Ten of fourteen ASS1-deficient patients with UM liver metastases and a median of one line of prior immunotherapy received ADIPemCis. Only one ≥ grade 3 adverse event of febrile neutropenia was reported. Seven patients had stable disease with a median progression-free survival of 3.0 months (range, 1.3-8.1) and a median overall survival of 11.5 months (range, 3.2-36.9). Despite anti-ADI-PEG20 antibody emergence, plasma arginine concentrations remained suppressed by 18 weeks with a reciprocal increase in plasma citrulline. Tumour rebiopsies at progression revealed ASS1 re-expression as an escape mechanism. ADIPemCis was well tolerated with modest disease stabilisation in metastatic UM. Further investigation of arginine deprivation is indicated in UM including combinations with immune checkpoint blockade and additional anti-metabolite strategies.

Outcomes of Interventional Management of Coronary Artery Disease in Kidney Transplant Recipients.

BACKGROUND: Cardiovascular disease is the most common cause of death among kidney transplant (KT) recipients. Trials routinely exclude patients with end-stage renal disease when assessing the effect of coronary artery revascularization. We looked to compare long-term outcomes in patients who underwent percutaneous coronary intervention (PCI) before KT with those managed medically. METHODS: We identified all patients who underwent coronary artery catheterization before KT from January 2008 to November 2019 at the Cleveland Clinic. The primary endpoint was all-cause mortality. RESULTS: A total of 272 patients were included, of whom 52 (19.11%) underwent PCI, and the remaining 220 patients were managed medically. The median age in the PCI group was 57.4 years (interquartile range [IQR], 46.9-61.2 years), whereas it was 53.9 years (IQR, 44.6-61 years) in the group medically managed. Baseline characteristics including sex, race, hypertension, diabetes, smoking, and hyperlipidemia were comparable in both groups. The median time to KT was 2.4 years (IQR, 1-5 years) in the PCI group vs 1.2 years (IQR, 0.6-3.3 years) in the medically managed group (P = .001). Among patients who underwent PCI, 40.4% had single vessel disease and 59.6% had multivessel disease compared with 16.8% and 28.6%, respectively, in the medically managed group (P < .001). Overall, there was no difference in mortality in the PCI group compared with the medically managed group after 10 years of follow-up (P = .416). CONCLUSIONS: Patients with coronary artery disease can be safely treated with PCI before KT and have comparable outcomes to those who are managed medically.

Effects of Testing and Disclosing Ancestry-Specific Genetic Risk for Kidney Failure on Patients and Health Care Professionals: A Randomized Clinical Trial.

IMPORTANCE: Risk variants in the apolipoprotein L1 (APOL1 [OMIM 603743]) gene on chromosome 22 are common in individuals of West African ancestry and confer increased risk of kidney failure for people with African ancestry and hypertension. Whether disclosing APOL1 genetic testing results to patients of African ancestry and their clinicians affects blood pressure, kidney disease screening, or patient behaviors is unknown. OBJECTIVE: To determine the effects of testing and disclosing APOL1 genetic results to patients of African ancestry with hypertension and their clinicians. DESIGN, SETTING, AND PARTICIPANTS: This pragmatic randomized clinical trial randomly assigned 2050 adults of African ancestry with hypertension and without existing chronic kidney disease in 2 US health care systems from November 1, 2014, through November 28, 2016; the final date of follow-up was January 16, 2018. Patients were randomly assigned to undergo immediate (intervention) or delayed (waiting list control group) APOL1 testing in a 7:1 ratio. Statistical analysis was performed from May 1, 2018, to July 31, 2020. INTERVENTIONS: Patients randomly assigned to the intervention group received APOL1 genetic testing results from trained staff; their clinicians received results through clinical decision support in electronic health records. Waiting list control patients received the results after their 12-month follow-up visit. MAIN OUTCOMES AND MEASURES: Coprimary outcomes were the change in 3-month systolic blood pressure and 12-month urine kidney disease screening comparing intervention patients with high-risk APOL1 genotypes and those with low-risk APOL1 genotypes. Secondary outcomes compared these outcomes between intervention group patients with high-risk APOL1 genotypes and controls. Exploratory analyses included psychobehavioral factors. RESULTS: Among 2050 randomly assigned patients (1360 women [66%]; mean [SD] age, 53 [10] years), the baseline mean (SD) systolic blood pressure was significantly higher in patients with high-risk APOL1 genotypes vs those with low-risk APOL1 genotypes and controls (137 [21] vs 134 [19] vs 133 [19] mm Hg; P = .003 for high-risk vs low-risk APOL1 genotypes; P = .001 for high-risk APOL1 genotypes vs controls). At 3 months, the mean (SD) change in systolic blood pressure was significantly greater in patients with high-risk APOL1 genotypes vs those with low-risk APOL1 genotypes (6 [18] vs 3 [18] mm Hg; P = .004) and controls (6 [18] vs 3 [19] mm Hg; P = .01). At 12 months, there was a 12% increase in urine kidney disease testing among patients with high-risk APOL1 genotypes (from 39 of 234 [17%] to 68 of 234 [29%]) vs a 6% increase among those with low-risk APOL1 genotypes (from 278 of 1561 [18%] to 377 of 1561 [24%]; P = .10) and a 7% increase among controls (from 33 of 255 [13%] to 50 of 255 [20%]; P = .01). In response to testing, patients with high-risk APOL1 genotypes reported more changes in lifestyle (a subjective measure that included better dietary and exercise habits; 129 of 218 [59%] vs 547 of 1468 [37%]; P < .001) and increased blood pressure medication use (21 of 218 [10%] vs 68 of 1468 [5%]; P = .005) vs those with low-risk APOL1 genotypes; 1631 of 1686 (97%) declared they would get tested again. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, disclosing APOL1 genetic testing results to patients of African ancestry with hypertension and their clinicians was associated with a greater reduction in systolic blood pressure, increased kidney disease screening, and positive self-reported behavior changes in those with high-risk genotypes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02234063.

Evaluation and optimisation of a footwear assessment tool for use within a clinical environment.

Footwear has been documented as a significant factor in the aetiology of foot pain in the general population. Assessing footwear in a clinical setting continues to be practitioner specific and there is limited guidance to direct advice. Health professionals must have access to clinically appropriate and reliable footwear assessment tools to educate patients on healthier footwear choices. The primary aim of this study was to critique what elements should be in a footwear assessment tool with a secondary aim of testing the agreed tool for validity.A combined Nominal Group Technique and then a Delphi technique from purposively sampled experts of foot health professions were employed to critique elements of footwear assessment. The agreed tool was then tested by practising podiatrists on 5 different shoes to assess the validity and reliability of the measures.Twelve test evaluation criteria were identified receiving significant ratings to form the final footwear assessment tool consisting of five footwear themes. Application of the tool in a clinical setting validated the themes of footwear characteristics, footwear structure, motion control and wear patterns. However, the assessment of footwear fit was not reliable.The footwear tool was refined based on the collective consensus achieved from the rounds creating a more clinically appropriate tool. The validity of this tool was assessed as high in some of the themes but for those that were lower, a training need was identified.

A Validated Model to Identify Patients With Low Likelihood of High-Risk Coronary Artery Disease Anatomy.

In stable coronary artery disease (CAD), revascularization improves outcomes only for patients with high-risk coronary anatomy (HRCA). We sought to derive and validate a prediction model, incorporating clinical and exercise stress test characteristics, to identify patients with HRCA. We conducted a retrospective analysis of patients undergoing exercise stress testing at Cleveland Clinic (2005 to 2014), followed by invasive coronary angiography within 3 months. We excluded patients with acute coronary syndrome, known CAD or ejection fraction <50%. HRCA was defined as left main, 3-vessel, or 2-vessel disease involving the proximal left anterior descending artery. Clinical and stress test predictors of HRCA were identified in a multivariable logistic regression model, internally validated with 1,000-fold bootstrapping. The model was then externally validated at the University of Pittsburgh Medical Center (2017 to 2019). The model was derived from 2,758 patients with complete data. HRCA was identified in 418 patients (15.2%) in the derivation cohort. The model consisted of 10 variables: age, male gender, hypertension, hypercholesterolemia, diabetes mellitus, family history of premature CAD, high-density lipoprotein, chest pain, exercise time, and Duke Treadmill Score. Bias-corrected c-statistic was 0.79 (95% confidence interval 0.77 to 0.81) with excellent calibration. In all, 762 patients (27.6%) had a predicted probability and observed prevalence of HRCA <5%. In the validation cohort, the model had a c-statistic of 0.79 (95% confidence interval 0.74 to 0.85) and 210 patients had an observed prevalence of HRCA <5% (40%). In conclusion, an externally validated prediction model, based on clinical characteristics and exercise stress test variables, can identify stable patients with CAD who have HRCA.