Background: The pathogenesis of idiopathic premature ventricular contractions (PVCs) may differ between patients with left- vs right- outflow tract (LVOT; RVOT) PVCs. We hypothesized that PVCs of LVOT origin would be associated with a higher prevalence of inflammatory conditions, such as coronary artery disease (CAD) and aortic sclerosis (AS), and elevation in the inflammatory biomarker, neutrophil-to-lymphocyte ratio (NLR). Research Question: Is NLR associated with LVOT PVCs? Aim: To compare clinical factors and NLR between patients with left- versus right-outflow tract origin of PVCs. Methods: We studied 140 patients undergoing idiopathic outflow tract PVC ablations at our institution. Patients with acute inflammatory conditions were excluded. NLR was calculated by dividing the absolute neutrophil by lymphocyte counts. Associations between clinical variables, NLR, and PVC site of origin at ablation were examined using logistic regression analysis. Results: An LVOT site of origin was present in 48 (35%) patients, with significant differences in clinical variables to RVOT patients. Independent predictors of LVOT (vs RVOT) PVCs were chronic kidney disease (CKD, odds ratio [OR]: 5.3, 95% CI: 1.3 - 22.1), age>50 (3.8, 1.6 - 8.6) and NLR (1.35, 0.9 - 1.9). An elevated NLR (≥3.92) was present in 14% of patients with LVOT PVCs vs 6.4% in those with RVOT PVCs (p<0.006). Conclusions: We found a significant difference in risk factors between otherwise idiopathic LVOT vs RVOT PVCs. In contrast to those with RVOT PVCs, patients with PVCs of LVOT origin are older and have a higher prevalence of CKD. NLR is an independent predictor for LVOT PVCs. Our findings highlight the potential importance of inflammation as a selective mediator of LVOT PVCs.

HomeJournal of the American Heart AssociationVol. 11, No. 5Long‐Term Outcomes are Similar Despite Sex Disparities in High‐Intensity Statin Use in Patients With Nonobstructive Coronary Artery Disease Diagnosed Via Invasive Coronary Angiography Open AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toOpen AccessLetterPDF/EPUBLong‐Term Outcomes are Similar Despite Sex Disparities in High‐Intensity Statin Use in Patients With Nonobstructive Coronary Artery Disease Diagnosed Via Invasive Coronary Angiography Edwin Lu, MD, Christopher Hanson, MD, George Beller, MD and Jamieson Bourque, MD, MHS Edwin LuEdwin Lu https://orcid.org/0000-0003-1671-9733 , Department of Medicine, , University of North Carolina Hospitals, , Chapel Hill, , NC, Search for more papers by this author , Christopher HansonChristopher Hanson https://orcid.org/0000-0002-8002-6213 , Sparrow Thoracic and Cardiovascular Institute, , Sparrow Hospitals, , Lansing, , MI, Search for more papers by this author , George BellerGeorge Beller , Division of Cardiovascular Medicine, , Department of Medicine, , University of Virginia, , Charlottesville, , VA, Search for more papers by this author and Jamieson BourqueJamieson Bourque * Correspondence to: Jamieson Bourque, MD, MHS, Department of Cardiology, University of Virginia Health System, 1215 Lee Street, Charlottesville, VA 22908. E‐mail: E-mail Address: [email protected] https://orcid.org/0000-0003-0727-199X , Division of Cardiovascular Medicine, , Department of Medicine, , University of Virginia, , Charlottesville, , VA, , Department of Radiology, , University of Virginia, , Charlottesville, , VA, Search for more papers by this author Originally published22 Feb 2022https://doi.org/10.1161/JAHA.121.022202Journal of the American Heart Association. 2022;11:e022202Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: February 22, 2022: Ahead of Print In current practice, high intensity statins are prescribed for patients diagnosed with obstructive or nonobstructive coronary artery disease (CAD). Studies have shown that women are commonly undertreated with statins.1, 2 We sought to determine medication usage patterns and outcomes by sex at long‐term follow‐up.The data that support the findings of this study are available from the corresponding author upon reasonable request. All patients who underwent index invasive coronary angiography (ICA) at the University of Virginia for high pretest probability of CAD between January 1, 2012 and December 31, 2013 were included (n=1579). Patients with known CAD, history of myocardial infarction, or emergent indications for invasive coronary angiography (ST‐elevation myocardial infarction, cardiogenic shock, postcardiac arrest) were excluded. Invasive coronary angiographies performed for preoperative evaluation for transplant or cardiothoracic surgery were also excluded. This study cohort included 925 patients. The University of Virginia institutional review board gave approval for the study protocol and rendered waiver of informed consent. At a median time of follow‐up at 6.0 years, complete long‐term follow‐up data were available for 850 patients (91.9%). There were no statistically significant differences between the initial 925 patients and the 850 patients comprising this follow‐up cohort (P>0.05 for all clinical characteristics across all stenosis groups). Patients were classified as having normal/near‐normal coronary arteries (≤20% stenosis, n=264), nonobstructive CAD (21%–49% stenosis, n=114), or obstructive CAD (≥50% stenosis, n=472). Outcomes (cardiac death, nonfatal myocardial infarction, and late revascularization) were gathered prospectively and compared between groups by Kaplan‐Meier survival analysis. We gathered baseline and follow‐up data on statin usage on the 850 patients with follow‐up data available and compared usage in the 3 groups by sex via chi‐square analysis and Fisher’s exact test where appropriate. The alpha level of significance was set at <0.05. All statistical analyses were performed using SAS (version 9.3; SAS Institute Inc, Cary, NC).Baseline mean low‐density lipoprotein cholesterol values were 103 in men and 113 in women (P<0.001). At a median follow‐up of 6.0 years, there was an increase in overall statin use regardless of sex (Table). No differences in aspirin, beta blocker, or overall statin usage by sex were seen across all stenosis groups (P>0.05 for all medications). No differences in high‐intensity statin use (atorvastatin 40/80 mg or rosuvastatin 20/40 mg) were seen between the sexes in patients with obstructive CAD (51.9% of men versus 51.5% of women, P=0.78). Interestingly, there was a significant difference in usage of high‐intensity statins by sex in patients with nonobstructive CAD (43.4% of men versus 20.0% of women, P=0.001). Yet, outcomes were similar between the sexes across all stenosis groups (P>0.05 for all groups).Table . Study Cohort Statin Usage Subdivided by Severity of Angiographic Coronary StenosisTotal cohort, n (%)Severity of coronary stenosis≤20%, n (%)21%–49%, n (%)≥50%, n (%)SexBaselineFollow‐upBaselineFollow‐upBaselineFollow‐upBaselineFollow‐upMale222 (46.9)350 (74.6)42 (34.7)64 (52.9)24 (45.3)37 (69.8)156 (52.2)249 (84.4)High intensity***23 (43.4)*153 (51.9)Female187 (49.5)253 (67.6)63 (44.1)73 (51.4)37 (60.7)40 (66.7)87 (50.0)140 (81.9)High intensity***12 (20.0)*88 (51.5)John Wiley & Sons, Ltd*High‐intensity statin usage data were not gathered in these groups.Fewer women with CAD are treated with statins compared with their male cohorts despite evidence showing similarly improved cardiovascular outcomes with statin therapy for primary or secondary prevention.3, 4 Commonly cited causes of this treatment disparity include a lower rate of statin prescribing by physicians, higher rates of declined statin therapy when offered, and higher rates of statin therapy discontinuation after starting.2 Our study demonstrated overall similar usage of statins across all stenosis groups and similar high‐intensity statin usage by sex in patients with obstructive CAD. This similarity in usage by sex in obstructive CAD could be explained by the patient population’s relatively high cardiovascular risk, leading to high rates of high‐intensity statin usage regardless of sex.5 However, there was a significant difference in statin usage between sexes in patients with nonobstructive CAD. Despite this disparity in treatment, we found that outcomes remained similar between sexes across all stenosis groups. One possible explanation for this could be differences in coronary anatomic features, where higher risk lesions were more aggressively treated with medical therapy. Unfortunately, this possibility was not assessed during our angiographic review. These similar outcomes could also be a result of a relatively low sample size, highlighting the need for further study, but could represent an area for optimization of medical therapy in female patients with nonobstructive CAD.Sources of FundingThis work was supported by National Institutes of Health 5T32EB003841.DisclosuresDr Bourque is a consultant for Pfizer and GE Healthcare. The other authors have nothing to disclose.Footnotes* Correspondence to: Jamieson Bourque, MD, MHS, Department of Cardiology, University of Virginia Health System, 1215 Lee Street, Charlottesville, VA 22908. E‐mail: [email protected]eduFor Sources of Funding and Disclosures, see page 2.References1 Pagidipati NJ, Mudrick DW, Chiswell K, Brucker A, Peterson ED, Douglas PS. Sex differences in long‐term outcomes of patients across the spectrum of coronary artery disease. Am Heart J. 2018; 206:51–60. doi: 10.1016/j.ahj.2018.09.014CrossrefMedlineGoogle Scholar2 Nanna MG, Wang TY, Xiang Q, Goldberg AC, Robinson JG, Roger VL, Virani SS, Wilson PWF, Louie MJ, Koren A, et al. Sex differences in the use of statins in community practice: patient and provider assessment of lipid management registry. Circ Cardiovasc Qual Outcomes. 2019; 12:e005562. doi: 10.1161/CIRCOUTCOMES.118.005562LinkGoogle Scholar3 Ridker PM, MacFadyen JG, Fonseca FAH, Genest J, Gotto AM, Kastelein JJP, Koenig W, Libby P, Lorenzatti AJ, Nordestgaard BG, et al. Number needed to treat with rosuvastatin to prevent first cardiovascular events and death among men and women with low low‐density lipoprotein cholesterol and elevated high‐sensitivity C‐reactive protein: justification for the use of statins in prevention: an intervention trial evaluating rosuvastatin (JUPITER). Circ Cardiovasc Qual Outcomes. 2009; 2:616–623. doi: 10.1161/CIRCOUTCOMES.109.848473AbstractGoogle Scholar4 Cholesterol Treatment Trialists (CTT) Collaboration . Efficacy and safety of LDL‐lowering therapy among men and women: meta‐analysis of individual data from 174 000 participants in 27 randomised trials. Lancet. 2015; 385:1397–1405. doi: 10.1016/S0140‐6736(14)61368‐4CrossrefMedlineGoogle Scholar5 Ma J, Sehgal NL, Ayanian JZ, Stafford RS. National trends in statin use by coronary heart disease risk category. PLoS Medicine. 2005; 2:e123. doi: 10.1371/journal.pmed.0020123CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails March 1, 2022Vol 11, Issue 5Article InformationMetrics Copyright © 2022 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley BlackwellThis is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.https://doi.org/10.1161/JAHA.121.022202PMID: 35191316 Manuscript receivedJune 29, 2021Manuscript acceptedJanuary 6, 2022Originally publishedFebruary 22, 2022 Keywordshigh intensity statinnonobstructive coronary artery diseasedisparitiessex differencesPDF download SubjectsCardiovascular DiseaseQuality and OutcomesSecondary PreventionWomen, Sex, and Gender

BACKGROUND:Normal or near normal coronary arteries (NNCA) or nonobstructive coronary artery disease (CAD) are commonly found on invasive coronary angiography (ICA).HYPOTHESIS:We aimed to determine long-term outcomes by severity of CAD in a contemporary cohort of patients undergoing ICA for evaluation for ischemic heart disease.METHODS:We assessed a consecutive cohort of 925 patients who underwent non-emergent ICA over 24 months. Cardiac death (CD), nonfatal myocardial infarction (NFMI), late revascularization, and medication use were assessed.RESULTS:Follow-up data was available in 850 patients. Of patients without heart failure, at a median of 6.0 years, there was a significant decrease in survival free from CD or NFMI, and from all cardiac events, for those with obstructive CAD compared with patients with NNCAs or nonobstructive CAD (p < .001 for both). No differences between NNCA and nonobstructive CAD patients in rates of CD or NFMI (2.0% vs. 2.1%/year, p = .58) or all cardiac events (2.4% vs. 2.9%/year, p = .84) were observed.CONCLUSION:Long-term follow-up in a contemporary cohort of consecutive patients undergoing non-emergent ICA for detection of CAD showed no difference in annual rates of CD or NFMI, or total cardiac events, in patients with NNCAs versus those with nonobstructive CAD, whereas patients with obstructive CAD had significantly more events. Event rates were low and similar by gender. Use of aspirin, lipid lowering therapy, and beta-blockers increased in all subgroups after ICA. We speculate this may explain the low incidence of subsequent cardiac events, and similar event rates in patients with NNCA and nonobstructive CAD, even in patients presenting with non-ST-elevation MI.

Introduction: In current practice, high intensity statins are prescribed for patients diagnosed with CAD. However, studies have shown that women are commonly undertreated with statins. We compared long-term outcomes and medication usage patterns related to gender in a contemporary cohort of patients who underwent invasive coronary angiography (ICA) for index evaluation of suspected CAD for an abnormal stress test, stable or unstable angina, following an NSTEMI, or as part of their evaluation for heart failure. Methods: A cohort of 850 consecutive patients who underwent ICA for suspected CAD was classified as having normal/near-normal coronary arteries (≤20% stenosis, n=264), nonobstructive CAD (21-49% stenosis, n=114), or obstructive CAD (≥50% stenosis, n=472). We prospectively determined outcomes (cardiac death, nonfatal MI, and late revascularization) via Kaplan-Meier analysis in these 3 groups. We also obtained baseline and follow up data on statin use, and compared usage in the 3 groups related to gender by Chi-square analysis. Results: Baseline mean LDL values were 103 in men and 113 in women (p<0.001). At a median follow up of 6.0 years, there was an increase in statin use (51.5% at baseline vs 85.0% at follow up in obstructive CAD group; 54.0% vs 67.3% for nonobstructive CAD group). There were no differences in aspirin, beta-blocker, or overall statin usage by gender across all groups (p>0.05 for all medications). No difference in high intensity statin use (atorvastatin 40/80 mg or rosuvastatin 20/40 mg) was seen between genders in patients with obstructive CAD (61.4% of men vs 62.9% of women, p=0.78). Interestingly, there was a significant difference in usage of high intensity statins between genders in patients with nonobstructive CAD (63.9% of men vs 26.8% of women, p =0.001). Yet, outcomes were similar between genders across all stenosis groups (p>0.05 for all groups). Conclusions: Our study shows that fewer women with nonobstructive CAD are treated with high intensity statins compared to their male cohorts. Despite this disparity in treatment, outcomes remained similar between genders. This discrepancy warrants the need for further study and could represent an area for optimization of medical therapy in female patients with nonobstructive CAD.

BACKGROUND:Selective fusion of double curves in patients with scoliosis is considered to spare fusion levels. In 2011, we studied the lumbosacral takeoff angle, defined as the angle between the center-sacral vertical line and a line through the centra of S1, L5, and L4. The lumbosacral takeoff angle was shown to moderately correlate with the lumbar Cobb angle, and a predictive equation was developed to predict the lumbar Cobb angle after selective fusions. The purposes of the present study were to validate that equation in a separate cohort and to assess differences in outcomes following selective and nonselective fusion. METHODS:Patients with Lenke 1B, 1C, 3B, or 3C curve patterns undergoing fusion (both selective and nonselective) with pedicle screw constructs and a minimum of 2 years of follow-up were included. Selective fusion was defined as a lowest level of fixation cephalad to or at the apex of the lumbar curve. To validate the previously derived equation, we used this data set and analysis of variance to check for differences between the actual and calculated postoperative lumbar Cobb angles. Pearson correlation, multiple linear regression, and t tests were used to explore relationships and differences between the selective and nonselective fusion groups. RESULTS:The mean calculated postoperative lumbar Cobb angle (and standard deviation) (22.35° ± 3.82°) was not significantly different from the actual postoperative lumbar Cobb angle (21.08° ± 7.75°), with an average model error of -1.268° (95% confidence interval, -2.649° to 0.112°). The preoperative lumbar Cobb angle was larger in patients with deformities that were chosen for nonselective fusion (50.2° versus 38.9°; p < 0.001). Performing selective fusion resulted in a 3.5° correction of the lumbosacral takeoff angle (p < 0.001), whereas nonselective fusion resulted in a 9.3° correction (p < 0.001). CONCLUSIONS:The lumbosacral takeoff angle can be used to predict the residual lumbar Cobb angle and may be used by surgeons to aid in the decision between selective and nonselective fusion. The change in the lumbosacral takeoff angle following selective fusion is small. Improvement in the lumbosacral takeoff angle and coronal balance is greater in association with nonselective fusion. LEVEL OF EVIDENCE:Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Phase change contrast agents (PCCAs) are fluorocarbon liquid droplets that convert into microbubbles when exposed to high acoustic pressures. Given their small size, PCCAs can exit leaky blood vessels and provide exogenous contrast outside of the vascular system, thereby circumventing one of the primary limitations of microbubbles. However, a limitation of PCCAs is the high acoustic pressure required for conversion to gaseous phase, which may restrict their use as a diagnostic imaging agent. The incorporation of solid nanoparticles into the liquid perfluorocarbon phase has been suggested as a means to reduce the pressures required to convert PCCAs, however, this has not been confirmed through rigorous empirical observation. In this work, we sought to determine whether the presence of solid nanoparticles contained within the liquid perfluorocarbon core of PCCAs effects the pressure required for acoustic conversion into a gaseous microbubble.