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Dobutamine stress echocardiography (DSE) is a useful tool for assessing low-gradient significant aortic stenosis (AS) and contractile reserve (CR), but its prognostic utility has become controversial in recent studies. We evaluated the impact of DSE on aortic valve physiological, structural, and left ventricular parameters in low-gradient AS. Consecutive patients undergoing DSE for low-gradient AS evaluation from September 2010 to July 2016 were retrospectively studied, and DSE findings were divided into four groups: with and without severe AS and/or CR. Relationships between left ventricular chamber quantification, CR, aortic valve Doppler during DSE, and calcium score [by computerized tomography (CT)] were analyzed. There were 258 DSE studies performed on 243 patients, mean age 77.6 ± 10.8 yr and 183 (70.1%) were males. With increasing dobutamine dose, apart from systolic blood pressure, left ventricular ejection fraction, flow, cardiac power output, and longitudinal strain magnitude, along with aortic valve area and mean aortic gradient were all significantly increased ( P < 0.05). Flow and mean gradient increased in both the presence and absence of CR, whereas stroke volume and aortic valve area increased mainly in those with CR only. The aortic valve area increased in both patients with low and high calcium scores; however, the baseline area was lower in those with a higher calcium score. During DSE, aortic valve area increases with increase in aortic valve gradient. Higher calcium score is associated with lower baseline aortic valve area, but the aortic valve area still increases with dobutamine even in presence of a high calcium score. NEW & NOTEWORTHY We show that even in most severe aortic stenosis, there is some residual valve pliability. This suggests that a complete loss of pliability is not compatible with survival.

Objectives: To assess intermediate-term outcomes of aortic root replacement with valve-sparing reimplantation of bicuspid aortic valves (BAV), compared with tricuspid aortic valves (TAV)., Methods: From January 2002 to July 2017, 92 adults underwent aortic root replacement with BAV reimplantation and 515 with TAV reimplantation at the Cleveland Clinic. Balancing-score matching based on 28 preoperative variables yielded 71 well-matched BAV and TAV pairs (77% of possible pairs) for comparison of postoperative mortality and morbidity, longitudinal echocardiogram data, aortic valve reoperation, and survival., Results: In the BAV group, 1 hospital death occurred (1.1%); mortality among all reimplantations was 0.2%. Among matched patients, procedural morbidity was low and similar between BAV and TAV groups (1 stroke in TAV group; renal failure requiring dialysis, 1 patient each; red cell transfusion, 25% each). Five-year results: Severe aortic regurgitation was present in 7.4% of the BAV group and 2.9% of the TAV group (P = .7); 39% of BAV and 65% of TAV patients had none. Higher mean gradients (10 vs 7.4 mm Hg; P = .001) and left ventricular mass index (111 vs 101 g/m 2 ; P = .5) were present in BAV patients. Freedom from aortic valve reoperation was 94% in the BAV group and 98% in the TAV group (P = .10), and survival was 100% and 95%, respectively (P = .07)., Conclusions: Both BAV and TAV reimplantations can be performed with equal safety and good midterm outcomes; however, the constellation of higher gradients, less ventricular reverse remodeling, and more aortic valve reoperations with BAV reimplantations raises concerns requiring continued long-term surveillance., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Controversies remain in the management strategy for isolated tricuspid regurgitation (TR) because of adverse prognosis and uncertainties regarding the benefits of tricuspid valve surgery. We compared the characteristics and outcomes of a large cohort of patients with isolated TR, based on downstream tricuspid valve surgery versus medical management. Consecutive patients with isolated TR graded at least moderate-to-severe by echocardiography identified between January 2004 and December 2018 (n = 9,031, age 70 ± 15 years, 60% women) were retrospectively studied. The primary end point was time to all-cause mortality during follow-up. Outcomes were compared by management strategy using unadjusted and adjusted survival and multivariable regression analyses. Tricuspid valve surgery was performed in 632 of 9,031 of the cohort (7%), including 514 valve repairs and 118 valve replacements, with in-hospital mortality in 19 patients (2.9%). Overall, there were 3,985 all-cause deaths (44%) over mean follow-up of 2.6 ± 3.3 years. Tricuspid valve surgery was independently associated with lower mortality rate during follow-up, with hazard ratios (HRs) of 0.53 (95% confidence interval [CI] 0.45 to 0.64), and the association persisted in both primary and secondary TR subgroups. Tricuspid valve surgery also had a significantly higher rate of infective endocarditis and heart failure hospitalizations rates during follow-up, at HRs of 5.55 (95% CI 4.00 to 7.71) and 1.29 (95% CI 1.16 to 1.43), respectively. In conclusion, tricuspid valve surgery is rarely performed in isolated TR, but it is independently associated with greater survival for the overall cohort and both primary and secondary etiology subgroups. Increasing the utilization of this surgery at specialized centers is encouraged to try to improve the clinical outcomes for this challenging clinical entity., Competing Interests: Disclosures Dr. Desai has research and consultant agreements with Myokardia Inc, Medtronic, Silence therapeutics, and Caristo Diagnostics. Dr. Gillinov is consultant to AtriCure, Medtronic, Edwards, CryoLife, Abbott, Johnson and Johnson, and ClearFlow and has right to equity for ClearFlow. The other authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Risk models play important roles in stratification and decision-making towards cardiac surgery. Isolated tricuspid valve surgery is a high risk but increasingly performed the operation, however, the performance of risk models has not been externally evaluated in these patients. We compared the prognostic utility of contemporary risk scores for isolated tricuspid valve surgery., Methods: Consecutive patients undergoing isolated tricuspid valve surgery at Cleveland Clinic during 2004-2018 were evaluated in this cohort study. EuroSCORE II, Society of Thoracic Surgeon's tricuspid (STS-TVS) score, and the Model for End-stage Liver Disease (MELD) score were retrospectively calculated, and their performance for predicting operative mortality, postoperative complications, and mortality during follow-up was assessed., Results: Amongst 207 patients studied, the mean age was 54.1 ± 17.9 years, 116 (56.0%) were female, 92 (44.4%) had secondary tricuspid regurgitation, and 151 (72.9%) had a surgical repair. Mean EuroSCORE II, STS-TVS, and MELD scores were 6.3 ± 6.6%, 5.5 ± 6.2%, and 9.8 ± 4.7, respectively. C-statistics (95% confidence intervals) for operative mortality were 0.83 (0.74-0.93) for EuroSCORE II, 0.60 (0.45-0.75) for STS-TVS score, and 0.74 (0.58-0.89) for MELD score, while observed/expected ratios were 0.78 and 0.89 for the first two scores. All three scores were associated with mortality during follow-up and discriminated most postoperative complications., Conclusion: EuroSCORE II was superior to STS-tricuspid score for isolated TVS risk assessment. Although surgical risk scores traditionally underestimated operative mortality after isolated tricuspid valve surgery, they did not in our cohort, reflecting the excellent surgical results. The simple MELD score performed similarly to the EuroSCORE II, especially for discriminating morbidities., (© 2021 Wiley Periodicals LLC.)

Objective: To conduct a comprehensive systematic review and meta-analysis to compare mortality and other clinical outcomes associated with chili pepper (CP) consumption versus no/rare consumption of CP., Methods: A comprehensive search was performed using Ovid, Cochrane, Medline, EMBASE, and Scopus from inception till January 16, 2020. Observational studies and randomized controlled trials were included, while pediatric/animal studies, letters/case reports, reviews, abstracts, and book chapters were excluded. All-cause mortality was studied as the primary outcome. Cardiovascular mortality, cancer-related deaths and cerebrovascular accidents were studied as secondary outcomes., Results: From 4729 studies, four studies met the inclusion criteria. Random effects pooled analysis showed that all-cause mortality among CP consumers was lower, compared to rare/non-consumers, with a hazard ratio (HR) of 0.87 [95% CI: 0.85-0.90; p <0.0001; I 2 =1%]. HR for cardiovascular mortality was 0.83 [95% CI: 0.74-0.95; p  = 0.005, I 2 =66%] and for cancer-related mortality as 0.92 [95% CI: 0.87-0.97; p  = 0.001; I 2 =0%]. However, the HR for CVA was 0.78 [95% CI: 0.56-1.09; p  = 0.26; I 2 =60%]. The mode and amount of CP consumption varied across the studies, and data were insufficient to design an optimal strategy guiding its intake., Conclusion: Regular CP consumption was associated with significantly lower all-cause, cardiovascular, and cancer-related mortalities. However, based on current literature, it is difficult to derive a standardized approach to guide the optimal mode and amount of CP consumption. This warrants well-designed prospective studies to further investigate the potential health benefits of CP consumption., (© 2021 The Author(s).)

We sought to evaluate the outcomes of patients with severe mitral stenosis (MS) resulting from mitral annular calcification and assessed the prognostic impact of co-morbidities and frailty in guiding management. Among 6,915 patients with calcific MS who underwent echocardiography between January 2011 and March 2020, a total of 283 patients with severe calcific MS were retrospectively enrolled. We calculated the Charlson co-morbidity index (CCI). Frailty was scored from 0 to 3 points, with 1 point each assigned for reduced hemoglobin, reduced albumin, and inactivity. The primary end point was all-cause death. The mean age was 72 ± 11 years. The mean mitral valve (MV) area was 1.1 ± 0.4 cm 2 , and the mean transmitral gradient was 12 ± 4 mm Hg. Although 33% of the patients underwent MV intervention, 67% were conservatively managed. During a median follow-up of 360 days, 35% died. Patients who underwent MV intervention had an improved prognosis compared with those who were treated conservatively, even after propensity score matching. On multivariate Cox regression analysis, higher CCI (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.04 to 1.38, p = 0.011) and frailty score (HR 1.58, 95% CI 1.12 to 2.23, p = 0.01) were predictors of all-cause mortality, and MV intervention (HR 0.45, 95% CI 0.25 to 0.83, p = 0.011) and angiotensin converting enzyme inhibitor/angiotensin receptor blocker use (HR 0.39, 95% CI 0.20 to 0.79, p = 0.009) were associated with an improved prognosis. In conclusion, patients with severe calcific MS were often frail with multiple co-morbidities and were often managed conservatively. Higher CCI and worse frailty were associated with worse prognosis, regardless of the treatment strategy. MV intervention for select patients was associated with improved prognosis., Competing Interests: Disclosures Dr. Gillinov receives fees of ≥$5,000 per year as a paid consultant, speaker, or member of an advisory committee for Clear Catheter Systems, Inc., AtriCure, Inc., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Thoracic aortic dilatation often has an asymptomatic course but may present with lethal complications such as aortic rupture or dissection, particularly when the thoracic aorta is aneurysmally enlarged; therefore, appropriate diagnosis, surveillance, and management are vital. Recommendations regarding imaging and surgical management are outlined in contemporary clinical practice guidelines. Dedicated guidelines regarding medical therapies for the management of thoracic aortic dilatation are lacking. Most of the medical treatment strategies, especially recommendations regarding pharmacological medical therapies related to β-blockade and angiotensin receptor blockers, are derived from data on patients with Marfan syndrome. The main aims of medical therapies for the management of thoracic aortic dilatation are (1) to control the progression of the disease, and (2) to prevent complications related to the disease (such as aortic dissection and mortality). This paper reviews the contemporary evidence and highlights the gaps in evidence to be investigated in further studies., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature.)

Background Hypertrophic cardiomyopathy (HCM) and aortic stenosis can cause obstruction to the flow of blood out of the left ventricular outflow tract into the aorta, with obstructive HCM resulting in dynamic left ventricular outflow tract obstruction and moderate or severe aortic stenosis causing fixed obstruction caused by calcific degeneration. We sought to report the characteristics and longer-term outcomes of patients with severe obstructive HCM who also had concomitant moderate or severe aortic stenosis requiring surgical myectomy and aortic valve replacement. Methods and Results We studied 191 consecutive patients (age 67±6 years, 52% men) who underwent myectomy and aortic valve (AV) replacement (90% bioprosthesis) at our center between June 2002 and June 2018. Clinical and echo data including left ventricular outflow tract gradient and indexed AV area were recorded. The primary outcome was death. Prevalence of hypertension (63%) and hyperlipidemia (75%) were high, with a Society of Thoracic Surgeons score of 5±4, and 70% of participants had no HCM-related sudden death risk factors. Basal septal thickness and indexed AV area were 1.9±0.4 cm and 0.72±0.2 cm 2 /m 2 , respectively, while 100% of patients had dynamic left ventricular outflow tract gradient >50 mm Hg. At 6.5±4 years, 52 (27%) patients died (1.5% in-hospital deaths). One-, 2-, and 5-year survival in the current study sample was 94%, 91%, and 83%, respectively, similar to an age-sex-matched general US population. On multivariate Cox survival analysis, age (hazard ratio [HR], 1.65; 95% CI, 1.24-2.18), chronic kidney disease (HR, 1.58; 95% CI, 1.21-2.32), and right ventricular systolic pressure on preoperative echocardiography (HR, 1.28; 95% CI, 1.05-1.57) were associated with longer-term mortality, but traditional HCM risk factors did not. Conclusions In symptomatic patients with severely obstructive HCM and moderate or severe aortic stenosis undergoing a combined surgical myectomy and AV replacement at our center, the observed postoperative mortality was significantly lower than the expected mortality, and the longer-term survival was similar to a normal age-sex-matched US population.

Background: Isolated tricuspid regurgitation (TR) remains a management dilemma with poor outcomes. Echocardiography and cardiac magnetic resonance imaging (CMR) are valuable tools for evaluating TR, but their prognostic utility has rarely been studied together in this setting. We aimed to determine the prognostic value and thresholds for echocardiography and CMR parameters for isolated severe TR., Methods: Consecutive patients with isolated severe TR by echocardiography and undergoing CMR during January 2007 to June 2019 were studied. Echocardiography and CMR-derived quantitative parameters were analyzed for independent associations with and thresholds for predicting the primary end point of all-cause mortality during follow-up., Results: Among 262 patients studied, mean age was 62.8±15.6 years, 156 (59.5%) were females, 207 (79.0%) had secondary TR, and 87 (33.2%) underwent tricuspid valve surgery after CMR. There were 68 (26.0%) deaths during a mean follow-up of 2.5 years. Both CMR-derived tricuspid regurgitant fraction (per 5% increase) and right ventricle free wall longitudinal strain (per 1% decrease in magnitude) were independently associated with worse survival, with hazard ratios (95% CIs) of 1.15 (1.05-1.25) and 1.10 (1.04-1.17), respectively, along with right heart failure symptoms of 2.03 (1.14-3.60), while tricuspid valve surgery was borderline protective with 0.55 (0.31-0.997). Regurgitant fraction ≥30%, regurgitant volume ≥35 mL and right ventricle free wall longitudinal strain ≥-11% (by velocity vector imaging technique, which yields lower magnitude values than other conventional strain techniques) were the optimal thresholds for mortality during follow-up., Conclusions: TR quantification by CMR and right ventricle free wall longitudinal strain by echocardiography were the key imaging parameters independently associated with reduced survival in isolated TR, incremental to conventional clinical factors. Clinically significant thresholds for these parameters were determined and may help guide decision-making for TR management.

BACKGROUND. Echocardiography is the primary noninvasive technique for left ventricular (LV) strain measurement. MRI has potential advantages, although reference ranges and thresholds to differentiate normal from abnormal left ventricular global longitudinal strain (LVGLS), left ventricular global circumferential strain (LVGCS), and left ventricular global radial strain (LVGRS) are not yet established. OBJECTIVE. The purpose of our study was to determine the mean and lower limit of normal (LLN) of MRI-derived LV strain measurements in healthy patients and explore factors potentially influencing these measurements. EVIDENCE ACQUISITION. PubMed, Embase, and Cochrane Library databases were searched for studies published through January 1, 2020, that reported MRI-derived LV strain measurements in at least 30 healthy individuals. Mean and LLN measurements of LV strain were pooled using random-effects models overall and for studies stratified by measurement method (feature tracking [FT] or tagging). Additional subgroup and meta-regression analyses were performed. EVIDENCE SYNTHESIS. Twenty-three studies with a total of 1782 healthy subjects were included. Pooled means and LLNs for all studies were -18.6% (95% CI, -19.5% to -17.6%) and -13.3% (-13.9% to 12.7%) for LVGLS, -21.0% (-22.4% to -19.6%) and -15.6% (-17.0% to -14.3%) for LVGCS, and 38.7% (30.5-46.9%) and 20.6% (15.1-26.1%) for LVGRS. Pooled means and LLNs for LVGLS by strain measurement method were -19.4% (95% CI, -20.6% to -18.1%) and -13.1% (-14.2% to -12.0%) for FT and -15.6% (-16.2% to -15.1%) and -13.1% (-14.1% to -12.2%) for tagging. A later year of study publication, increasing patient age, and increasing body mass index were associated with more negative mean LVGLS values. An increasing LV end-diastolic volume index was associated with less negative mean LVGLS values. No factor was associated with LLN of LVGLS. CONCLUSION. We determined the pooled means and LLNs, with associated 95% CIs, for LV strain by cardiac MRI to define thresholds for normal, abnormal, and borderline strain in healthy patients. The method of strain measurement by MRI affected the mean LVGLS. No factor affected the LLN of LVGLS. CLINICAL IMPACT. This meta-analysis lays a foundation for clinical adoption of MRI-derived LV strain measurements, with management implications in both healthy patients and patients with various disease states.

Purpose: To evaluate the diagnostic and prognostic performance of the aortic valve calcium score (AVCS) with the Agatston method using CT in aortic stenosis (AS) and to assess mean AVCS according to AS severity., Materials and Methods: In this meta-analysis, PubMed, Embase, and Cochrane were searched from January 1, 1980, to December 31, 2020, for studies reporting sensitivity and specificity of AVCS using CT for severe AS, mean AVCS in severe and nonsevere AS, and/or hazard ratios for all-cause mortality in AS. Data were pooled using random effect models and meta-analysis software., Results: Twelve studies (six diagnostic, three prognostic, and 10 reporting mean AVCS by AS severity) were included for analysis. A total of 4101 patients (2255 with severe AS) were described in these 12 studies. Pooled sensitivity and specificity were 82% (95% CI: 80, 84) and 78% (95% CI: 75, 81), respectively. Pooled mean AVCS were 3219 (95% CI: 2795, 3643) for severe AS, compared with 1252 (95% CI: 863, 1640) for nonsevere AS, 1808 (95% CI: 1163, 2452) for moderate AS, and 584 (95% CI: 309, 859) for mild AS. Pooled hazard ratio for AVCS as a binary threshold to predict mortality was 2.11 (95% CI: 1.11, 4.12)., Conclusion: AVCS had moderate to high sensitivity and specificity for identifying severe AS and was also a useful prognostic imaging marker in AS. Mean AVCS categorized by AS severity may help guide clinical management. Keywords CT, Aortic Valve, Valves, Meta-Analysis© RSNA, 2021., Competing Interests: Disclosures of Conflicts of Interest: T.K.M.W. disclosed no relevant relationships. S.D.F. disclosed no relevant relationships. P.S. disclosed no relevant relationships. B.P.G. disclosed no relevant relationships. L.L.R. disclosed no relevant relationships. R.A.G. disclosed no relevant relationships. B.X. disclosed no relevant relationships., (2021 by the Radiological Society of North America, Inc.)

Background: Right ventricular (RV) systolic strain has recently demonstrated prognostic value in various cardiovascular diseases. Despite this, the reference range including the lower limit of normal (LLN) and factors associated with RV strain measurements are not well-established. This meta-analysis aimed to determine the mean and LLN of two- (2D) and three-dimensional (3D) right ventricular global (RVGLS), free wall (RVFWLS) and interventricular septal wall (IVSLS) longitudinal strains in healthy individuals and factors that affect strain measurements., Methods: In this meta-analysis, Pubmed, Embase and Cochrane databases were searched until 31 July 2020 for eligible studies reporting RVGLS, RVFWLS and/or IVSLS in at least 30 healthy subjects. We pooled the means and LLNs of RV strains by two- (2D) and three- (3D) dimensional echocardiography, and performed meta-regression analyses., Results: From 788 articles screened, 45 eligible studies totaling 4439 healthy subjects were eligible for analysis. Pooled means and LLNs with 95% confidence intervals for 2D- RV strains were RVGLS -23.4% (-24.2%, -22.6%) and -16.4% (-17.3%, -15.5%) in 27 studies; RVFWLS -26.9% (-28.0%, -25.9%) and -18.0% (-19.2%, -16.9%) in 32 studies; and IVSLS -20.4% (-22.0%, -18.9%) and -11.5% (-13.6%, -9.6%) in 10 studies, and similar results for 3D- RV strains. Right ventricular fractional area change and vendor software were associated with 2D-RVGLS and RVFWLS means and LLNs., Conclusion: We reported the pooled means and LLNs of RV systolic strains in healthy subjects, to define thresholds for abnormal, borderline and normal strains. Important factors associated with RV systolic strains include right ventricular fractional area change and vendor software., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The aims of this study were to characterize the interplay between mixed aortic valve disease (MAVD) phenotypes (defined by concomitant severities of aortic stenosis and aortic regurgitation) and left ventricular global longitudinal strain (LV-GLS), and to assess the prognostic utility of LV-GLS in MAVD., Background: Little is known about the way LV-GLS separates MAVD phenotypes and if it is associated with their outcomes., Methods: This observational cohort study evaluated 783 consecutive adult patients with left ventricular ejection fraction ≥50% and MAVD, which was defined as coexisting with at least moderate aortic stenosis and at least moderate aortic regurgitation. We measured the conventional echocardiographic variables and average LV-GLS from apical long, 2- and 4-chamber views. The primary endpoint was all-cause mortality., Results: Mean age of patients was 69 ± 15 years, and 58% were male. Mean LV-GLS was -14.7 ± 2.9%. In total, 458 patients (59%) underwent aortic valve replacement at a median period of 50 days (25th to 75th percentile range: 6 to 560 days). During a median follow-up period of 5.6 years (25th to 75th percentile range: 1.8 to 9.4 years), 391 patients (50%) died. When stratified patients into tertiles according to LV-GLS values, patients with worse LV-GLS had worse outcomes (p < 0.001). LV-GLS was independently associated with mortality (hazard ratio: 1.09; 95% confidential intervals: 1.04 to 1.14; p < 0.001), with the relationship between LV-GLS and mortality being linear., Conclusions: LV-GLS is associated with all-cause mortality. LV-GLS may be useful for risk stratification in patients with MAVD., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Mitral annular disjunction (MAD) is an increasingly recognized entity associated with mitral valve prolapse (MVP), ventricular arrhythmias and death. Few studies have investigated the utility of myocardial deformation analysis in MAD. We compared chamber quantification including strain by transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) between MVP patients with and without MAD., Methods: Forty-two patients with MVP (21 with MAD, 21 without MAD) and 21 controls were studied. Global, basal and basal inferolateral (BIL) segmental strains were measured and compared using velocity-vector imaging TTE and feature-tracking CMR., Results: Mean age was 54 ± 17 years, 19 (46%) were female, and 19 (46%) underwent surgical mitral valve repair with no deaths during follow-up in the 2 groups with MVP. Patients with MAD and MVP had lower basal longitudinal strain by TTE than those with MVP without MAD. Those with MAD and MVP had lower magnitude in BIL and basal segments by circumferential and radial strain by CMR compared to those with MVP without MAD and controls. Amongst global strain parameters, CMR-derived global circumferential strain was independently associated with MAD diagnosis odds ratio 1.49 (per 1%), 95% confidence interval 1.09-2.05, P = 0.014, with optimal threshold of -18.0% having 76% sensitivity and specificity for MAD., Conclusion: Abnormal circumferential and radial strain patterns in the basal segments by CMR may be useful for identifying regional LV dysfunction associated with MAD., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: A substantial proportion of infective endocarditis (IE) cases are complicated by local invasion. The purpose of this study was to identify patient and disease characteristics associated with local invasion in surgically treated IE patients., Methods: This was a nested case-control study. All episodes of IE for patients admitted to Cleveland Clinic from 1 January 2013 to 30 June 2016 were identified from the Cleveland Clinic IE Registry. Patients ≥18 years of age who underwent surgery for IE were included. Among these, cases were those with local invasion, controls were those without. Local invasion, defined as periannular extension, paravalvular abscess, intracardiac fistula or pseudoaneurysm, was ascertained from the surgical operative note. Associations of selected factors with local invasion were examined in a multivariable logistic regression model., Results: Among 511 patients who met inclusion criteria, 215 had local invasion. Mean age was 56 years; 369 were male. Overall 345 (68%) had aortic valve, 228 (45%) mitral valve, and 66 (13%) tricuspid or pulmonic valve involvement. Aortic valve involvement (OR 6.23, 95% CI 3.55-11.44), bioprosthetic valve (OR 3.88, 95% CI 2.36-6.44), significant paravalvular leak (OR 3.80, 95% CI 1.60-9.89), new atrioventricular nodal block (OR 3.77, 95% CI 1.87-7.90), infection with streptococci other than viridans group streptococci (OR 7.54, 95% CI 2.42-24.87) and presence of central nervous system emboli (OR 1.85, 95% CI 1.13-3.04) were associated with local invasion., Discussion: Intracardiac and microorganism factors, but not comorbid conditions, are associated with local invasion in IE., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Coronavirus disease (COVID-19), first identified in Wuhan, China, in December 2019, is now a pandemic, having already spread to 188 countries, with more than 28,280,000 infections worldwide. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the responsible infectious agent, and similar to other human coronaviruses, uses membrane-bound angiotensin-converting enzyme 2 (membrane-bound ACE2) for entry into the host cells. COVID-19 has important cardiovascular implications, especially for patients with pre-existing cardiovascular co-morbidities, potentially mediated through several mechanisms, including direct myocardial injury, worsening of those pre-existing cardiovascular co-morbidities, and adverse cardiovascular effects of potential therapies for COVID-19. The disease is causing a significant burden on health systems worldwide. Elective surgeries and procedures were postponed for a considerable period of time, and many patients with known cardiovascular disease (CVD) risk factors presented late to hospitals, for fear of contracting COVID-19, with serious adverse consequences. Significant negative impact on a population level is highlighted by prolonged isolation, decreased exercise and physical activity, and higher levels of depression and anxiety, all predisposing to elevated cardiovascular risk. This article provides a timely overview of COVID-19 and its impact on the cardiovascular system, focusing on the pathogenesis, potential adverse cardiovascular events, the potential treatment options, protection for health care providers and patients, and what the cardiovascular community could do to mitigate the impact of COVID-19., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt-20-779). The series “Heart Valve Disease” was commissioned by the editorial office without any funding or sponsorship. BX served as the unpaid Guest Editor of the series. Dr. LGS reports other from Posthorax GmbH, outside the submitted work. The authors have no other conflicts of interest to declare., (2021 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Background: Sinus of Valsalva aneurysms (SVAs) are rare. We assessed the role of multimodality imaging in guiding the contemporary management., Methods: A single-center retrospective cohort study over a 20-year period was performed., Results: Between January 1997 and June 2017, 103 patients were diagnosed with SVAs (median age: 58 years). Eighty patients presented with non-ruptured SVAs, and 23 with ruptured SVAs. Seventy-six patients underwent surgery, and 27 were conservatively managed. The median durations of follow-up were: 48 months (surgical group) vs. 37.5 months (conservative group). There was no mortality directly attributable to SVA surgery. There were no late complications in the conservative group. Transthoracic echocardiography (TTE) was the first-line imaging investigation (100.0% in surgical group vs. 92.6% in conservative group, P=0.019). Additional imaging studies included: (I) transesophageal echocardiography (TEE): 93.4% in surgical group vs. 22.2% in conservative group, P<0.001; (II) multi-detector cardiac computed tomography (MDCT): 61.8% in surgical group vs. 37.0% in conservative group, P=0.041; (III) cardiac magnetic resonance (CMR): 22.4% in surgical group vs. 14.8% in conservative group, P=0.579. At diagnosis, SVA diameters were: TTE: 4.80 cm (range, 3.30 cm); TEE: 5.40 cm (range, 4.00 cm); MDCT: 5.20 cm (range, 3.90 cm); CMR: 4.80 cm (range, 3.70 cm)., Conclusions: In a 20-year cohort, proper selection for surgery and conservative management resulted in excellent outcomes for SVAs. TTE was the first-line imaging investigation for assessment of SVAs, although many patients underwent an additional imaging investigation. The contemporary outcomes of imaging-guided SVA management were excellent., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt-20-630). The series “Heart Valve Disease” was commissioned by the editorial office without any funding or sponsorship. PS serves as the Editor- In-Chief of Cardiovascular Diagnosis and Therapy. BX served as the unpaid Guest Editor of the series. DK reports that she received a personal non-commercial grant from the Turkish Society of Cardiology, outside the submitted work. SDF reports personal fees from Renova Therapeutics, Inc., Precision Image Analysis, Inc. and serves in a fiduciary capacity, such as an elected officer, director, or chief medical officer, for Cryothermic Systems, Inc. and Precision Image Analysis, Inc., outside the submitted work. LGS reports to receive or have the right to receive royalty payments for inventions or discoveries commercialized through Posthorax GmbH, outside the submitted work. The authors have no other conflicts of interest to declare., (2021 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Background: Cardiac MRI is central to the evaluation of cardiac amyloidosis (CA). Native T 1 mapping and extracellular volume (ECV) are novel MR techniques with evolving utility in cardiovascular diseases, including CA., Purpose: To perform a meta-analysis of the diagnostic and prognostic data of native T 1 mapping and ECV techniques for assessing CA., Study Type: Systematic review and meta-analysis., Population: In all, 3520 patients including 1539 with CA from 22 studies retrieved following systematic search of Pubmed, Cochrane, and Embase., Field Strength/sequence: 1.5T or 3.0T/modified Look-Locker inversion recovery (MOLLI) or shortened MOLLI (shMOLLI) sequences., Assessment: Meta-analysis was performed for all CA and for light-chain (AL) and transthyretin (ATTR) subtypes. Thresholds were calculated to classify native T 1 and ECV values as not suggestive, indeterminate, or suggestive of CA., Statistical Analysis: Area under the receiver-operating characteristic curves (AUCs) and hazards ratios (HRs) with 95% confidence intervals (95% CI) were pooled using random-effects models and Open-Meta(Analyst) software., Results: Six studies were diagnostic, 16 studies reported T 1 and ECV values to determine reference range, and six were prognostic. Pooled AUCs (95% CI) for diagnosing CA were 0.92 (0.89-0.96) for native T 1 mapping and 0.96 (0.93-1.00) for ECV, with similarly high detection rates for AL- and ATTR-CA. Based on the pooled values of native T 1 and ECV in CA and control subjects, the thresholds that suggested the absence, indeterminate, or presence of CA were identified as <994 msec, 994-1073 msec, and >1073 msec, respectively, for native T 1 at 1.5T. Pooled HRs (95% CI) for predicting all-cause mortality were 1.15 (1.08-1.22) for native T 1 mapping as a continuous parameter, 1.19 (1.01-1.40) for ECV as a continuous parameter, and 4.93 (2.64-9.20) for ECV as a binary threshold., Data Conclusion: Native T 1 mapping and ECV had high diagnostic performance and predicted all-cause mortality in CA., Level of Evidence: 1 TECHNICAL EFFICACY STAGE: 2., (© 2020 International Society for Magnetic Resonance in Medicine.)

Objectives: This study was designed to compare the clinical and echocardiographic characteristics, management, and outcomes of severe atrial functional mitral regurgitation (AFMR) to primary mitral regurgitation (PMR)., Background: AFMR remains poorly defined clinically., Methods: Consecutive patients who underwent transesophageal echocardiography at our institution between 2011 and 2018 for severe mitral regurgitation with preserved left ventricular function were screened. We excluded patients with endocarditis, any form of cardiomyopathy, or prior mitral intervention. The absence of leaflet pathology defined AFMR. Outcomes included death and heart failure hospitalizations., Results: A total of 283 patients were included (AFMR = 14%, PMR = 86%). Compared to PMR, patients with AFMR had more comorbidities, including hypertension (94.9% vs. 76.2%; p = 0.015), diabetes mellitus (46.2% vs. 18.4%; p < 0.001), long-standing atrial fibrillation (28.2% vs. 13.1%; p = 0.015), prior nonmitral cardiac surgery (25.6% vs. 9.8%; p = 0.004), and pacemaker placement (33.3% vs. 13.5%; p = 0.002). They also had higher average E/e' (median [interquartile range]:16.04 [13.1 to 22.46] vs. 14.1 [10.89 to 19]; p = 0.036) and worse longitudinal left atrial strain peak positive value (16.86 ± 12.15% vs. 23.67 ± 14.09%; p = 0.002) compared to PMR. During follow-up (median: 22 months), patients with AFMR had worse survival (log-rank p = 0.009) and more heart failure hospitalizations (log-rank p = 0.002). They were also less likely to undergo mitral valve intervention (59.0% vs. 83.6%; p = 0.001), although surgery was associated with improved survival (log-rank p = 0.021). On multivariable regression analysis, AFMR was independently associated with mortality [adjusted odds ratio: 2.61, 95% confidence interval: 1.17 to 5.83; p = 0.02]., Conclusions: AFMR constitutes an under-recognized high-risk group, with significant comorbidities, limited therapeutic options, and poor outcomes., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Emerging research suggests that hormones found in anabolic implants interact with polyamine biosynthesis. The objective of this study was to determine the effects of steroidal hormones, polyamines and polyamine precursors on bovine satellite cell (BSC) differentiation and polyamine biosynthesis temporally. Primary BSCs were induced to differentiate in 3% horse serum (CON) and treated with 10 nM trenbolone acetate (TBA), 10 nM estradiol (E2), 10 nM TBA and 10 nM E2, 10 mM methionine, 8 mM ornithine, 2 mM putrescine, 1.5 mM spermidine, or 0.5 mM spermine. Total mRNA was isolated 0, 2, 4, 8, 12, 24, and 48 h post-treatment. Abundance of mRNA for genes associated with induction of BSC differentiation: paired box transcription factor 7, myogenic factor 5, and myogenic differentiation factor 1 and genes in the polyamine biosynthesis pathway: ornithine decarboxylase and S-adenosylmethionine-were analyzed. Overall, steroidal hormones did not impact ( p > 0.05) mRNA abundance of genes involved in BSC differentiation, but did alter ( p = 0.04) abundance of genes involved in polyamine biosynthesis. Polyamine precursors influenced ( p < 0.05) mRNA of genes involved in BSC differentiation. These results indicate that polyamine precursors and polyamines impact BSC differentiation and abundance of mRNA involved in polyamine biosynthesis, while steroidal hormones altered the mRNA involved in polyamine biosynthesis.

Background: Nonbacterial thrombotic endocarditis, or marantic endocarditis, is rare. Contemporary data on the etiology, echocardiographic evaluation, and management of nonbacterial thrombotic endocarditis are limited., Methods: A single-center retrospective cohort study was performed. Electronic medical records and echocardiographic records were searched for patients ages ≥18 years with a confirmed diagnosis of nonbacterial thrombotic endocarditis between January 1999 and November 2019. Demographic, echocardiographic, and management data were collected., Results: Of 600,577 transthoracic echocardiograms (TTEs) and 89,264 transesophageal echocardiograms (TEEs), 42 patients had nonbacterial thrombotic endocarditis (mean age: 54 ± 14.5 years; 66.7% were female). The median duration of follow-up was 8.2 (interquartile range 3.3-24.4) months. Seventeen patients (40.5%) had malignancy, 33.3% had systemic lupus erythematosus, and 35.7% had antiphospholipid antibody syndrome. Stroke was the most common presentation (59.5%). TTE enabled the diagnosis in 19 cases (45.2%), compared with TEE, which identified the condition in 33 of 34 (97.1%) cases in which it was utilized. Three-dimensional echocardiography was performed in 17 TEEs. The most common valves involved were mitral (61.9%), and aortic (23.8%) valves. Thirty-two patients were managed with anticoagulation. Ten patients underwent surgery. Sixteen (38.1%) patients died, most of whom had a diagnosis of advanced malignancy., Conclusion: In a contemporary 20-year cohort, TTE and TEE played important roles in diagnosis, with superior diagnostic performance of TEE for nonbacterial thrombotic endocarditis. Mortality was high, and advanced malignancy portended a worse prognosis. Management in most cases was therapeutic anticoagulation. In select cases, surgery provided favorable outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Patients with atrial fibrillation (AF) have risk factors that predispose to thoracic aneurysmal disease (TAD) and atherosclerosis. In this study in patients with AF, we assessed the occurrence of incidental TAD and assessed if a validated predictive score used to predict AF, the CHARGE-AF score, was associated with greater aortic dimensions. We also assessed the prevalence of coronary calcification. We conducted a cross-sectional study of 1,000 consecutive patients with AF undergoing chest multidetector CT during evaluation for pulmonary vein isolation. A dilated aortic root or ascending aorta (AA, dimension/ body surface area >2.05 cm/m 2 ) were found in 195 (20%). A total of 12 (1%) had significant aortic aneurysmal enlargement of > 5.0 cm. Advancing age, a bicuspid aortic valve, hypertension, and male gender were associated with increased aortic dimensions. Aortic root dimensions increased linearly (p < 0.001) and ascending aortic dimensions increased nonlinearly across CHARGE-AF deciles (p < 0.001). Nearly two-thirds (63%) had coronary calcification, 38% of whom were not on lipid-lowering therapy. In conclusion, in patients with AF undergoing gated chest CT, 1 in 5 had previously undetected TAD, with a small proportion having significantly aneurysmal dimensions approaching surgical thresholds. Risk factors previously established to increase the propensity to develop AF are also associated with increased TAD. These findings raise the need to consider a surveillance strategy for TAD in patients with AF, particularly in those with other risk factors for aortic disease. A high prevalence of coronary calcium was also detected, representing an opportunity to optimize statin therapy in patients with AF., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Surveillance of left ventricular function, part of current US Food and Drug Administration recommendations for anti-human epidermal growth factor receptor 2 (anti-HER2) chemotherapy, is based on historical data involving patients who received concomitant anthracycline therapy, a key enhancer of cardiac risk. More recent anti-HER2 treatment data suggest that cardiotoxicity detected by screening is rare and usually benign for patients who do not have cardiovascular risk factors and are not taking an anthracycline. Because of the burden of repetitive echocardiography required for surveillance and the risk of false-positive results, potentially leading to discontinuing lifesaving treatment, we advocate for a more focused cardiac surveillance strategy., (Copyright © 2021 The Cleveland Clinic Foundation. All Rights Reserved.)

Background: Concomitant TV repair during mitral valve (MV) surgery based on tricuspid valve annulus (TVA) dilation, rather than the degree of tricuspid regurgitation (TR), is beneficial and supported by the valve guidelines. We sought to determine TVA geometry and dimensions in controls and assess the changes that occur in patients with severe primary (PMR) and secondary (SMR) mitral regurgitation without TR., Methods: We analyzed cardiac computed tomographic angiography (CCTA) of 125 consecutive subjects: 50 controls with normal coronary CCTA and no valvular dysfunction, 50 PMR patients referred for robotic repair, and 25 SMR patients referred for transcatheter therapy. Patients with >2+ TR on echocardiography were excluded. Annular measurements were performed using dedicated software and compared. Correlations and determinants of TVA dimensions were analyzed., Results: Patients with SMR were older and had significantly more comorbidities. In controls, the TVA was larger and more planar and eccentric compared to the MV annulus (all P<0.01). Dimensions of both annuli correlated significantly (r≥0.5; P<0.001 for all dimensions) in controls and patients with severe MR. In both PMR and SMR, the TVA enlarged in all dimensions (P<0.01) with a trend towards becoming more circular. On multivariable regression, the MV annular area was the primary determinant of the TVA area (adjusted β=0.430, P<0.001)., Conclusions: Substantial changes in TVA dimensions are encountered in patients with severe MR even in the absence of severe TR such that TVA and MVA dimensions remain correlated. Close attention to the TVA in patients with severe MR is warranted., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form(available at: http://dx.doi.org/10.21037/cdt-20-903). Dr. PW reports being a consultant at Medtronic, Cryolife and Edwards LifeSciences, outside the submitted work. PS, MD serves as an Editor-in-Chief of Cardiovascular Diagnosis and Therapy. The other authors have no conflicts of interest to declare., (2021 Cardiovascular Diagnosis and Therapy. All rights reserved.)

To evaluate the temporal relations of cardiovascular disease in oncology patients referred to cardio-oncology and describe the impact of cardiovascular disease and cardiovascular risk factors on outcomes. All adult oncology patients referred to the cardio-oncology service at the Cleveland Clinic from January 2011 to June 2018 were included in the study. Comprehensive clinical information were collected. The impact on survival of temporal trends of cardiovascular disease in oncology patients were assessed with a Cox proportional hazards model and time-varying covariate adjustment for confounders. In total, 6,754 patients were included in the study (median age, 57 years; [interquartile range, 47 to 65 years]; 3,898 women [58%]; oncology history [60% - breast cancer, lymphoma, and leukemia]). Mortality and diagnosis of clinical cardiac disease peaked around the time of chemotherapy. 2,293 patients (34%) were diagnosed with a new cardiovascular risk factor after chemotherapy, over half of which were identified in the first year after cancer diagnosis. Patients with preexisting and post-chemotherapy cardiovascular disease had significantly worse outcomes than patients that did not develop any cardiovascular disease (p < 0.0001). The highest 1-year hazard ratios (HR) of post-chemotherapy cardiovascular disease were significantly associated with male (HR 1.81; 95% confidence interval 1.55 to 2.11; p < 0.001] and diabetes [HR 1.51; 95% confidence interval 1.26 to 1.81; p < 0.001]. In conclusion, patients referred to cardio-oncology, first diagnosis of cardiac events peaked around the time of chemotherapy. Those with preexisting or post-chemotherapy cardiovascular disease had worse survival. In addition to a high rate of cardiovascular risk factors at baseline, risk factor profile worsened over course of follow-up., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Winter moth, Operophtera brumata L. (Lepidoptera: Geometridae), causes widespread defoliation in both its native and introduced distributions. Invasive populations of winter moth are currently established in the United States and Canada, and pheromone-baited traps have been widely used to track its spread. Unfortunately, a native species, the Bruce spanworm, O. bruceata (Hulst), and O. bruceata × brumata hybrids respond to the same pheromone, complicating efforts to detect novel winter moth populations. Previously, differences in measurements of a part of the male genitalia called the uncus have been utilized to differentiate the species; however, the accuracy of these measurements has not been quantified using independent data. To establish morphological cutoffs and estimate the accuracy of uncus-based identifications, we compared morphological measurements and molecular identifications based on microsatellite genotyping. We find that there are significant differences in some uncus measurements, and that in general, uncus measurements have low type I error rates (i.e., the probability of having false positives for the presence of winter moth). However, uncus measurements had high type II error rates (i.e., the probability of having false negatives for the presence of winter moth). Our results show that uncus measurements can be useful for performing preliminary identifications to monitor the spread of winter moth, though for accurate monitoring, molecular methods are still required. As such, efforts to study the spread of winter moth into interior portions of North America should utilize a combination of pheromone trapping and uncus measurements, while maintaining vouchers for molecular identification., (© The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Limited data exist regarding the clinical characteristics and contemporary outcomes of patients with pulmonary valve (PoV) infective endocarditis (IE)., Methods: This is a retrospective cohort study of patients with a confirmed diagnosis of IE affecting the PoV at our centre between January 2002 and October 2018. Electronic medical records were reviewed to gather the clinical and echocardiographic variables. The population was subdivided according to risk factor profiles: group 1: miscellaneous risk factors; group 2: patients with congenital heart disease (CHD); and group 3: patients who inject drugs (PWID). The primary outcome was all-cause mortality., Results: Out of 2,124 cases of IE during the study period, 24 (1.1%) patients had PoV IE. The majority of cases of PoV IE occurred in patients with prosthetic valves (54.2%). Coagulase-negative Staphylococci species were the most common micro-organisms. Seventy-five per cent (75%) of the patients required surgical management. The median follow-up was 2.8 years (interquartile range: 0.2-5.3 years). Patients with miscellaneous risk factors were older (p<0.01), and had higher rates of hypertension (p=0.01) and hyperlipidaemia (p=0.04). There was a statistically significant difference in survival between the groups (p=0.03), mainly driven by better outcomes of patients with CHD, compared to those with miscellaneous risk factors., Conclusions: In a contemporary 16-year series, a high proportion of patients with PoV IE required surgical management. Patients with PoV IE and CHD had better survival, compared to patients with miscellaneous risk factors at a median follow-up of 2.8 years., (Copyright © 2020 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: Left ventricular global longitudinal strain (LVGLS), circumferential strain (LVGCS) and radial strain (LVGRS) are echocardiographic parameters with wide clinical applicability. However, the thresholds for abnormal left ventricular (LV) strains, particularly the lower limits of normal (LLN), are not well established. This meta-analysis determined the mean and LLN of two- (2D) and three-dimensional (3D) LV strain in healthy subjects and factors that influence strain measurements., Methods: We searched PubMed, Embase and Cochrane databases until 31 December 2019 for studies reporting left ventricular (LV) global strain in at least 50 healthy subjects. We pooled means and LLNs of 2D and 3D LV strain using random-effects models, and performed subgroup and meta-regression analysis for LVGLS., Results: Forty-four studies were eligible totaling 8,910 subjects. The pooled means and LLNs (95% confidence intervals) were -20.1% (-20.7%, -19.6%) and -15.4% (-16.0%, -14.7%) respectively for 2D-LVGLS; -21.9% (-23.4%, -20.3%) and -15.3% (-16.9%, -13.8%) respectively for 2D-LVGCS; and 48.4% (43.8%, 53.0%) and 25.5% (17.8%, 33.1%) respectively for 2D-LVGRS. All pooled analyses demonstrated significant heterogeneity, and means and LLNs of and 3D-LV strains differed marginally from 2D. Only vendor software was associated with differences in pooled means and LLN of 2D-LVGLS., Conclusions: In conclusion, pooled means and LLNs of 2D- and 3D-LV global strain parameters in healthy subjects were reported. Based on the pooled LLNs, thresholds for abnormal, borderline and normal strains can be defined, such as less negative than -14.7%, between -14.7% and -16.0% and more negative than -16.0% respectively for 2D-LVGLS, and 2D-LVGLS values are only affected by vendor software., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt-20-711). TKMW received a clinical and research fellowship grant from the National Heart Foundation of New Zealand (number 1775). The other authors have no conflicts of interest to declare., (2020 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Background: Mitral annular calcification (MAC) is prevalent in the aging population, with recent renewed interest regarding its associations with cardiovascular risk factors, outcomes, and influence on valvular heart disease and interventions. This meta-analysis aimed to report the relationships between MAC and cardiovascular mortality and morbidity events., Methods: Relevant studies were searched from PubMed, Cochrane, and Embase databases until November 30, 2019. Associations between MAC as a binary variable with death and cardiovascular events were pooled using random-effects models. The main outcomes of interest were all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, atrial fibrillation, and procedural outcomes., Results: Among 799 article abstracts and 122 full-text articles screened, 26 (16 prospective and 10 retrospective) studies totaling 35 070 subjects were analyzed. MAC was associated with higher all-cause death, hazard ratio (95% confidence interval) 1.76 (1.43-2.22), and cardiovascular mortality 1.85 (1.45-23.5). It also positively correlated with myocardial infarction 1.48 (1.22-1.79), stroke 1.51 (1.22-2.05), incidental heart failure 1.55 (1.30-1.84), atrial fibrillation 1.75 (1.43-2.15), and their composite, major adverse cardiovascular events (MACE). Finally, conversion to mitral valve replacement at time of cardiac surgery was more in patients with MAC than without MAC, with odds ratio (95% confidence interval) 2.82 (1.28-6.18)., Conclusion: Mitral annular calcification was overall associated with higher rates of death, and both individual and composite cardiovascular events. The presence of increasingly encountered MAC has significant clinical implications for cardiovascular risk assessment and valvular interventions., (© 2020 Wiley Periodicals LLC.)

The cobblestone tiger beetle, Cicindelidia marginipennis (Dejean, 1831) is a North American species specializing in riparian habitats from New Brunswick, Canada, to Alabama in the United States. In the United States, this species is state-listed as threatened or endangered range-wide and periodically receives consideration for federal listing, mostly due to habitat decline. Despite its conservation status, intraspecific genetic diversity for this species has not been explored and little is known about its natural history. To support further inquiry into the biology of C. marginipennis , this study provides the first look at range-wide genetic diversity using mitochondrial DNA (mtDNA), describes all three larval instars, and describes natural history characteristics from captive rearing and field observation. Based on mtDNA analyses, our results suggest that geographically based population structure may exist throughout the range, with individuals from Alabama possessing haplotypes not found elsewhere in our sampling. Further genetic analyses, particularly multi-locus analyses, are needed to determine whether the Alabama population represents a separate cryptic species. Our morphological analysis and descriptions of larval instars reveal a combination of characteristics that can be used to differentiate C. marginipennis from closely related and co-occurring species. Based on our field observations, we find that the larval "throw pile" of soil excavated from burrows is a key search image for locating larvae, and we provide descriptions and detailed photographs to aid surveys. Lastly, we find that this species can be successfully reared in captivity and provide guidelines to aid future recovery efforts., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Background: Cardiac computed tomography (CT) is emerging as an adjunctive modality to echocardiography in the evaluation of infective endocarditis (IE) and surgical planning. CT studies in IE have, however, focused on its diagnostic rather than prognostic utility, the latter of which is important in high-risk diseases like IE. We evaluated the associations between cardiac CT and transesophageal echocardiography (TEE) findings and adverse outcomes after IE surgery., Methods: Of 833 consecutive patients with surgically proven IE during May 1, 2014 to May 1, 2019, at Cleveland Clinic, 155 underwent both preoperative ECG-gated contrast-enhanced CT and TEE. Multivariable analyses were performed to identify CT and TEE biomarkers that predict adverse outcomes after IE surgery, adjusting for EuroSCORE II (European System for Cardiac operative Risk Evaluation II)., Results: CT and TEE were positive for IE in 123 (75.0%) and 124 (75.6%) of patients, respectively. Thirty-day mortality occurred in 3 (1.9%) patients and composite mortality or morbidities in 72 (46.5%). Pseudoaneurysm or abscess detected on TEE was the only imaging biomarker to show independent association with composite mortality or morbidities in-hospital, with odds ratio (95% CI) of 3.66 (1.76-7.59), P =0.001. There were 17 late deaths, and both pseudoaneurysm or abscess detected on CT and fistula detected on CT were the only independent predictors of total mortality during follow-up, with hazards ratios (95% CI) of 3.82 (1.25-11.7), P <0.001 and 9.84 (1.89-51.0), P =0.007, respectively., Conclusions: We identified cardiac CT and TEE features that predicted separate adverse outcomes after IE surgery. Imaging biomarkers can play important roles incremental to conventional clinical factors for risk stratification in patients undergoing IE surgery.

Background We sought to determine (1) long-term outcomes in patients presenting with documented Takotsubo syndrome (TS), (2) whether left ventricular global longitudinal strain (LV-GLS) provides incremental prognostic value, and (3) prognostic cutoffs of LV ejection fraction (LVEF) and LV-GLS during an acute TS episode. Methods and Results We studied 650 patients with TS (aged 66±14 years, 88% women) who were diagnosed clinically and angiographically between 2006 and 2018. Baseline LVEF and LV-GLS (using velocity vector imaging) were recorded. The primary end point was all-cause mortality. TS triggers were unknown (34%), emotional (16%), physical (41%), and neurologic (10%). Mean LVEF and LV-GLS were 36±10% and -11.6±0.4%; in addition, 94% patients had LVEF <52%, and 80% had apical ballooning. No patient had obstructive coronary artery disease. At a median of 2.2 years (interquartile range, 0.7-4.4), 175 (27%) had died (9% in-hospital deaths). Multivariate Cox survival analysis revealed that higher age (hazard ratio [HR], 1.35), male sex (HR, 1.75), lower baseline LVEF (HR, 1.02), worse LV-GLS (HR, 1.04), neurologic trigger (HR, 2.66), and physical trigger (HR, 2.64) were associated with mortality, whereas aspirin (HR, 0.70) and β-blockers (HR, 0.73) improved survival (all P <0.049). The addition of LVEF and LV-GLS to clinical markers (age, sex, cardiogenic shock at presentation, and peak troponin I) significantly increased log-likelihood ratios: clinical (-521.48), clinical plus LVEF (-511.32, P <0.001), and clinical plus LVEF and LV-GLS (-500.68, P <0.001). On penalized spline analysis, LVEF of 38% and LV-GLS of -10% were cutoffs below which survival was significantly worse. Conclusions Patients with TS with a neurologic or physical trigger had significantly worse survival than those without such a trigger, with baseline LVEF and LV-GLS providing incremental prognostic value.

Objectives: This study sought to evaluate the role of cardiac magnetic resonance (CMR) for the quantification of ischemic mitral regurgitation (IMR) and myocardial infarct size (MIS) in patients with ischemic cardiomyopathy (ICM). This study also sought to explore the interaction between IMR severity and MIS and its association with outcomes in patients with ICM., Background: IMR occurs secondary to a disease of the left ventricle and is associated with poor outcomes. The role of CMR for the evaluation and risk stratification of patients with ICM and IMR remains uncertain., Methods: Consecutive patients with ICM who underwent baseline CMR were included. MIS was quantified on late gadolinium enhancement imaging as the proportion of left ventricular mass. IMR was quantified with CMR by calculating the mitral regurgitant fraction (MRFraction). Cox proportional hazards models were built to assess the association of IMR and MIS quantification with the combined endpoint of all-cause death or heart transplant., Results: We evaluated 578 patients (mean age: 62 ± 11 years, 76% males). The mean left ventricular ejection fraction was 25 ± 11%, with an MIS of 24 ± 16% and MRFraction of 18 ± 17%. Over a median follow-up time of 4.9 years, 198 (34%) patients experienced death or cardiac transplant. On multivariable analysis, after comprehensive medical risk score, subsequent revascularization, implantable cardioverter-defibrillator insertion, and surgical mitral valve intervention were controlled for, the interaction of IMR severity and MIS emerged as a powerful predictor of adverse outcomes (p = 0.008). For patients with significant IMR (MRFraction: ≥35%), the hazard ratio comparing moderate MIS (15% to 29%) versus small MIS (<15%) was 1.51 (0.57 to 3.98), and the hazard ratio comparing large MIS (≥30%) versus small MIS was 5.41 (2.34 to 12.7)., Conclusions: Risk associated with IMR is more comprehensively described as an interaction between IMR severity and MIS. Further studies in patients IMR using comprehensive CMR evaluation are needed to verify whether this approach can improve patient selection and procedural outcomes to address IMR., (Copyright © 2020. Published by Elsevier Inc.)

Background: Prosthetic valve endocarditis (PVE) is a serious condition with high morbidity and mortality. This study investigated the association of surgical treatment with survival among patients with PVE., Methods: A retrospective cohort study was done of patients with PVE hospitalized over 8 years in a large referral center. Association of surgery with survival was evaluated with multivariable Cox proportional hazards regression, adjusting for propensity to be accepted for surgery, and analyzing surgery as a time-dependent covariate. Survival was also compared separately in a 1:1 propensity score-matched cohort of patients accepted for surgery and control patients consigned to nonsurgical treatment., Results: Of 523 patients (mean [SD] age, 61 [14] years; 370 [71%] men; 393 [75%] initially accepted for surgery), 404 ultimately underwent surgery and 119 received nonsurgical treatment alone. Surgical treatment was associated with significantly lower hazard of death in the entire cohort (hazard ratio [HR] = 0.32; 95% confidence interval [CI]: 0.22-0.48; P < .001) and in the 1:1 matched cohort (HR = 0.33; 95% CI: 0.19-0.57; P < .001). Initial acceptance for surgery was associated with significantly lower odds of in-hospital death (odds ratio [OR] = 0.26; 95% CI: 0.11-0.59; P < .001), death or readmission within 90 days (OR = 0.17; 95% CI: 0.07-0.43; P < .001), and death within 1 year (OR = 0.16; 95% CI: 0.08-0.34; P < .001)., Conclusions: Surgical treatment is associated with a large survival benefit in PVE. A decision to pursue nonsurgical treatment in PVE should entail close follow-up for any development of an indication for surgery., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

There has been a tidal wave of recent interest in artificial intelligence (AI), machine learning and deep learning approaches in cardiovascular (CV) medicine. In the era of modern medicine, AI and electronic health records hold the promise to improve the understanding of disease conditions and bring a personalized approach to CV care. The field of CV imaging (CVI), incorporating echocardiography, cardiac computed tomography, cardiac magnetic resonance imaging and nuclear imaging, with sophisticated imaging techniques and high volumes of imaging data, is primed to be at the forefront of the revolution in precision cardiology. This review provides a contemporary overview of the CVI imaging applications of AI, including a critique of the strengths and potential limitations of deep learning approaches., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background Concurrent presence of aortic stenosis and aortic regurgitation is termed mixed aortic valve disease (MAVD). Although multiple articles have addressed patients with "isolated" aortic stenosis or aortic regurgitation, the natural history, impact, and outcomes of MAVD are not well defined. Here, we evaluate long-term outcomes in patients with MAVD and cardiovascular adaptations to chronic MAVD. Methods and Results This observational cohort study evaluated 862 adult patients (56.8% male) with preserved left ventricular ejection fraction and at least moderate aortic regurgitation and moderate aortic stenosis. Primary outcome was all-cause mortality. Subgroup analysis was based on treatment modality (aortic valve replacement [AVR] versus medical management). A regression analysis of longitudinal echocardiographic parameters was performed to assess the natural history of MAVD. Mean age was 68±15 years, and mean left ventricular ejection fraction was 58±5%. At 4.6 years (25th-75th percentile range, 1.0-8.7), 58.6% of patients underwent an AVR and 48.8% patients died. In both unadjusted and adjusted Cox survival analysis, AVR was associated with improved survival (hazard ratio, 0.41; 95% CI, 0.34-0.51, P <0.001). Impact of AVR persisted when stratifying the cohort by symptom status and baseline aortic valve area (log rank, P <0.001 for both) and after propensity-score matching (hazard ratio, 0.40; 95% CI, 0.32-0.50; P <0.001). In the longitudinal analysis, there were statistically significant changes over time in aortic valve peak gradient ( P <0.001) and aortic valve area ( P <0.001) and only mild increases in left ventricular end-diastolic ( P <0.007) and -systolic ( P <0.001) volumes. Conclusions MAVD confers a high risk of all-cause mortality. However, AVR significantly reduces this risk independent of aortic valve area, symptom status, and after controlling for confounding variables.

Objectives: Tricuspid valve disease is increasingly encountered, but surgery is rarely performed in isolation, in part because of a reported higher operative risk than other single-valve operations. Although guidelines recommend valve repair, there is sparse literature for the optimal surgical approach in isolated tricuspid valve disease. We performed a meta-analysis examining outcomes of isolated tricuspid valve repair versus replacement., Methods: We searched Pubmed, Embase, Scopus and Cochrane from January 1980 to June 2019 for studies reporting outcomes of both isolated tricuspid valve repair and replacement, excluding congenital tricuspid aetiologies. Data were extracted and pooled using random-effects models and Review Manager 5.3 software., Results: There were 811 article abstracts screened, from which 52 full-text articles reviewed and 16 studies included, totalling 6808 repairs and 8261 replacements. Mean age ranged from 36 to 68 years and females made up 24%-92% of these studies. Pooled operative mortality rates and odds ratios (95% confidence intervals) for isolated tricuspid repair and replacement surgery were 8.4% vs 9.9%, 0.80 (0.64 to 1.00). Tricuspid repair was also associated with lower in-hospital acute renal failure 12.4% vs 15.6%, 0.82 (0.72 to 0.93) and pacemaker implantation 9.4% vs 21.0%, 0.37 (0.24 to 0.58), but higher stroke rate 1.5% vs 0.9%, 1.63 (1.10 to 2.41). There were no differences in rates of prolonged ventilation, mediastinitis, return to operating room or late mortality., Conclusion: Isolated tricuspid valve repair was associated with significantly reduced in-hospital mortality, renal failure and pacemaker implantation compared with replacement and is therefore recommended where feasible for isolated tricuspid valve disease, although its higher stroke rate warrants further research., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cardiovascular imaging has an important role in the assessment and management of aortic root and thoracic aorta ectasia and aneurysms. Sinus of Valsalva aneurysms are rare entities. Unique complications associated with sinus of Valsalva aneurysms make them different from traditional aortic root aneurysms. Established guidelines on the diagnosis and management of sinus of Valsalva aneurysms are lacking. This article reviews the applications of multimodality cardiovascular imaging (echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging) for the dedicated assessment and imaging-guided management of sinus of Valsalva aneurysms., (Copyright © 2019 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to determine whether baseline left ventricular global longitudinal strain (LV-GLS) and changes in left ventricular ejection fraction (LVEF) in a subgroup of subjects at post-operative follow-up added prognostic value in patients undergoing aortic valve (AV) surgery., Background: In patients with chronic severe aortic regurgitation (AR) and preserved LVEF, sensitive markers are needed to decide timing of AV surgery., Methods: This was an observational study in 865 patients (asymptomatic/mildly symptomatic, 52 ± 15 years of age, 79% men) with ≥3+ chronic AR and preserved LVEF of ≥50% who underwent AV surgery between 2003 and 2015. All patients had baseline echocardiography (and LV-GLS imaging), whereas 285 patients underwent post-operative echocardiography (including LV-GLS). Primary outcome was mortality., Results: Only 478 patients (56%) patients had preoperative LV-GLS values better than -19%, despite a mean LVEF of 57 ± 4%. At a median 38 days, 632 patients underwent AV replacement, whereas 233 patients had AV repair. At a median follow-up of 6.95 (interquartile range [IQR]: 5.2 to 9.1) years, 105 patients (12%) died (2% in-hospital deaths). A higher proportion of patients with baseline LV-GLS grades worse than -19% died versus those whose LV-GLS score was better (15% vs. 10%; p < 0.01), and worse LV-GLS value was independently associated with higher longer-term mortality (hazard ratio: 1.62; 95% confidence interval [CI]: 1.40 to 1.86]; p < 0.001). In the 285 patients who underwent echo at 3 to 12 months post-operatively, LVEF normalized in 91% patients; however, only 88 patients (31%) had LV-GLS values better than -19%. Patients whose follow-up LV-GLS value was better than -19% had significantly better longer-term survival than those whose LV-GLS was not (5% vs. 15%, respectively; p < 0.01). An absolute worsening of 5% of LV-GLS from baseline was associated with increased mortality., Conclusions: In patients with ≥3+ chronic AR and preserved LVEF undergoing AV surgery, a baseline LV-GLS value worse than -19% was associated with reduced survival. In a subgroup of patients who returned for 3- and 12-month follow-up examinations, persistently impaired LV-GLS was associated with increased mortality., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)