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Background: Hypertensive disorders of pregnancy (HDP), including gestational hypertension, preeclampsia, and eclampsia, are risk factors for cardiovascular (CV) disease. Guidelines recommend that women with HDP be screened for the development of hypertension (HTN) within 6-12 months postpartum. However, the extent to which this early blood pressure (BP) screening is being performed and the impact on detection of CV risk factors is unknown., Methods: Women with HDP and without pre-existing hypertension (HTN) who had at least 6 months of clinical follow-up were categorized by postpartum BP screening status: early BP screen (6-12 months after delivery) or late BP screen (≥12 months after delivery). Multivariable logistic regression identified factors associated with early screening. Multivariable Cox proportional hazards modeling examined the association between early screening and detection of incident CV risk factors: HTN, prediabetes, diabetes mellitus type 2, or hyperlipidemia., Results: Among 4194 women with HDP, 1172 (28%) received early BP screening. Older age, pre-existing hyperlipidemia, diabetes, sickle cell disease, hypothyroidism, gestational diabetes, and delivery during or after 2014 were independently associated with early BP screening, whereas Hispanic ethnicity was associated with late BP screening. Early BP screening was most commonly performed at a primary care visit. After a median follow-up of 3.7 years, 1012 (24%) women had at least 1 new risk factor detected. Even after adjustment for baseline risk, women receiving early BP screening had a significantly higher rate of incident CV risk factor detection than women receiving late BP screening (56% vs 28%; adj. HR 2.70, 95%CI: 2.33-3.23, P < .001)., Conclusions: Early postpartum BP screening was performed in a minority of women with HDP, but was associated with greater detection of CV risk factors. More intensive postpartum CV screening and targeted interventions are needed to optimize CV health in this high-risk population of women with HDP., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Data collected via wearables may complement in-clinic assessments to monitor subclinical heart failure (HF)., Objectives: Evaluate the association of sensor-based digital walking measures with HF stage and characterize their correlation with in-clinic measures of physical performance, cardiac function and participant reported outcomes (PROs) in individuals with early HF., Methods: The analyzable cohort included participants from the Project Baseline Health Study (PBHS) with HF stage 0, A, or B, or adaptive remodeling phenotype (without risk factors but with mild echocardiographic change, termed RF-/ECHO+) (based on available first-visit in-clinic test and echocardiogram results) and with sufficient sensor data. We computed daily values per participant for 18 digital walking measures, comparing HF subgroups vs stage 0 using multinomial logistic regression and characterizing associations with in-clinic measures and PROs with Spearman's correlation coefficients, adjusting all analyses for confounders., Results: In the analyzable cohort (N=1265; 50.6% of the PBHS cohort), one standard deviation decreases in 17/18 walking measures were associated with greater likelihood for stage-B HF (multivariable-adjusted odds ratios [ORs] vs stage 0 ranging from 1.18-2.10), or A (ORs vs stage 0, 1.07-1.45), and lower likelihood for RF-/ECHO+ (ORs vs stage 0, 0.80-0.93). Peak 30-minute pace demonstrated the strongest associations with stage B (OR vs stage 0=2.10; 95% CI:1.74-2.53) and A (OR vs stage 0=1.43; 95% CI:1.23-1.66). Decreases in 13/18 measures were associated with greater likelihood for stage-B HF vs stage A. Strength of correlation with physical performance tests, echocardiographic cardiac-remodeling and dysfunction indices and PROs was greatest in stage B, then A, and lowest for 0., Conclusions: Digital measures of walking captured by wearable sensors could complement clinic-based testing to identify and monitor pre-symptomatic HF., (Copyright © 2024 Verily Life Sciences LLC. Published by Elsevier Inc. All rights reserved.)

Background: Low stroke volume index <35 ml/m 2 despite preserved ejection fraction (paradoxical low flow [PLF]) is associated with adverse outcomes in patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). However, whether the risk associated with PLF is similar in both sexes is unknown., Objectives: The purpose of this study was to analyze the risk associated with PLF in severe aortic stenosis for men and women randomized to TAVR or SAVR., Methods: Patients with ejection fraction ≥50% from the PARTNER (Placement of Aortic Transcatheter Valves) 2 and 3 trials were stratified by sex and treatment arm. The impact of PLF on the 2-year occurrence of the composite of death or heart failure hospitalization (primary endpoint) and of all-cause mortality alone (secondary endpoint) was analyzed. Analysis of variance was used to assess baseline differences between groups. Multivariate Cox regression analysis was used to identify predictors of the endpoint., Results: Out of 2,242 patients, PLF was present in 390 men and 239 women (30% vs 26%, P  = 0.06). PLF was associated with a higher rate of NYHA functional class III to IV dyspnea (60% vs 54%, P  < 0.001) and a higher prevalence of atrial fibrillation (39% vs 24%, P  < 0.001). PLF was a significant predictor of the primary endpoint among women undergoing SAVR in multivariate analysis (adjusted HR: 2.25 [95% CI: 1.14-4.43], P  = 0.02) but was not associated with a worse outcome in any of the other groups (all P  > 0.05)., Conclusions: In women with PLF, TAVR may improve outcomes compared to SAVR. PLF appears to have less impact on outcomes in men., Competing Interests: Statistical analyses were performed by employees of Edwards Lifesciences. Dr Carter-Storch has received a travel grant from AstraZeneca. Dr Hahn has received speaker fees from Abbott Structural, Baylis Medical, Edwards Lifesciences, and Philips Healthcare; has institutional consulting contracts for which she receives no direct compensation with Abbott Structural, Edwards Lifesciences, Medtronic, and Novartis; and is Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored tricuspid valve trials, for which she receives no direct industry compensation. Dr Abbas has received research support from and consulting for Edwards Lifesciences. Dr Mack has served as co-primary investigator for the PARTNER Trial for Edwards Lifesciences and the COAPT trial for Abbott; and has served as study chair for the APOLLO trial for Medtronic; no direct compensation for any of these activities. Dr Leon has received institutional research support from Edwards Lifesciences, Medtronic, Boston Scientific, and Abbott; and consulting/advisory board participation for Medtronic, Boston Scientific, Gore, Meril Lifescience, and Abbott. Dr Pibarot has received funding from Edwards Lifesciences, Medtronic, Pi-Cardia, and Cardiac Phoenix for echocardiography core laboratory analyses and research studies in the field of transcatheter valve therapies, for which he received no personal compensation; and has received lecture fees from Edwards Lifesciences and Medtronic. Dr Clavel has received core laboratory contract with Edwards Lifesciences; and research grants with Edwards Lifesciences and Medtronic, both without direct compensation. The PARTNER trials were funded by Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Achieving optimal cardiovascular health in rural populations can be challenging for several reasons including decreased access to care with limited availability of imaging modalities, specialist physicians, and other important health care team members. Therefore, innovative solutions are needed to optimize health care and address cardiovascular health disparities in rural areas. Mobile examination units can bring imaging technology to underserved or remote communities with limited access to health care services. Mobile examination units can be equipped with a wide array of assessment tools and multiple imaging modalities such as computed tomography scanning and echocardiography. The detailed structural assessment of cardiovascular and lung pathology, as well as the detection of extracardiac pathology afforded by computed tomography imaging combined with the functional and hemodynamic assessments acquired by echocardiography, yield deep phenotyping of heart and lung disease for populations historically underrepresented in epidemiological studies. Moreover, by bringing the mobile examination unit to local communities, innovative approaches are now possible including engagement with local professionals to perform these imaging assessments, thereby augmenting local expertise and experience. However, several challenges exist before mobile examination unit-based examinations can be effectively integrated into the rural health care setting including standardizing acquisition protocols, maintaining consistent image quality, and addressing ethical and privacy considerations. Herein, we discuss the potential importance of cardiac multimodality imaging to improve cardiovascular health in rural regions, outline the emerging experience in this field, highlight important current challenges, and offer solutions based on our experience in the RURAL (Risk Underlying Rural Areas Longitudinal) cohort study., Competing Interests: Disclosures None.

Innovations in cardiac imaging have fundamentally advanced the understanding and treatment of cardiovascular disease. These advances in noninvasive cardiac imaging have also expanded the role of the cardiac imager and dramatically increased the demand for imagers who are cross-trained in multiple modalities. However, we hypothesize that there is significant variation in the availability of cardiac imaging expertise and a disparity in the adoption of advanced imaging technologies across the United States. To evaluate this, we have brought together the leaders of cardiovascular imaging societies, imaging trainees, as well as collaborated with national imaging accreditation commissions and imaging certification boards to assess the state of cardiac imaging and the diversity of the imaging workforce in the United States. Aggregate data confirm the presence of critical gaps, such as limited access to imaging and imaging expertise in rural communities, as well as disparities in the imaging workforce, notably among women and underrepresented minorities. Based on these results, we have proposed solutions to promote and maintain a robust and diverse community of cardiac imagers and improve equity and accessibility for cardiac imaging technologies., Competing Interests: Disclosures Dr Douglas reports research grant to the institution HeartFlow; research support to Caption Health-in Kind; honoraria to Wolters Kluwer; and Foresite Labs scientific advisory board. Dr Hahn reports speaker fees from Abbott Structural, Baylis Medical, Edwards Lifesciences, Medtronic, Philips Healthcare, and Siemens Healthineers; Dr Hahn has institutional consulting contracts for which she receives no direct compensation with Abbott Structural, Edwards Lifesciences, Medtronic, and Novartis; she is Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored tricuspid valve trials, for which she receives no direct industry compensation. Dr Lang reports grants from Philips Imaging and Ultrasight. Dr Chareonthaitawee reports Clario and Ionetix; royalties from UpToDate. Dr Srichai reports consulting from Clario and royalties from UpToDate. Dr Burroughs is a member of medical advisory board in Bristol Myers Squibb, Health Kit, and Lantheus and conducted clinical research in Cytokinetic. Dr Blankstein reports research support in Novartis, Inc, and Amgen Inc; consultant in Caristo, Inc, Elucid, Inc, Heartflow, Inc, Nanox AI. The other authors report no conflicts.

Infiltrative cardiomyopathies comprise a broad spectrum of inherited or acquired conditions caused by deposition of abnormal substances within the myocardium. Increased wall thickness, inflammation, microvascular dysfunction, and fibrosis are the common pathological processes that lead to abnormal myocardial filling, chamber dilation, and disruption of conduction system. Advanced disease presents as heart failure and cardiac arrhythmias conferring poor prognosis. Infiltrative cardiomyopathies are often diagnosed late or misclassified as other more common conditions, such as hypertrophic cardiomyopathy, hypertensive heart disease, ischemic or other forms of nonischemic cardiomyopathies. Accurate diagnosis is also critical because clinical features, testing methodologies, and approach to treatment vary significantly even within the different types of infiltrative cardiomyopathies on the basis of the type of substance deposited. Substantial advances in noninvasive cardiac imaging have enabled accurate and early diagnosis. thereby eliminating the need for endomyocardial biopsy in most cases. This scientific statement discusses the role of contemporary multimodality imaging of infiltrative cardiomyopathies, including echocardiography, nuclear and cardiac magnetic resonance imaging in the diagnosis, prognostication, and assessment of response to treatment.

Background: Clinical and echocardiographic features may carry diverse information about the development of heart failure (HF). Therefore, we determined heterogeneity in clinical and echocardiographic phenotypes and its association with exercise capacity., Methods: In 2036 community-dwelling individuals, we defined echocardiographic profiles of left and right heart remodeling and dysfunction. We subdivided the cohort based on presence (+) or absence (-) of HF risk factors (RFs) and echocardiographic abnormalities (RF-/Echo-, RF-/Echo+, RF+/Echo-, RF+/Echo+). Multivariable-adjusted associations between subgroups and physical performance metrics from 6-minute walk and treadmill exercise testing were assessed., Results: The prevalence was 35.3% for RF-/Echo-, 4.7% for RF-/Echo+, 39.3% for RF+/Echo-, and 20.6% for RF+/Echo+. We observed large diversity in echocardiographic profiles in the Echo+ group. Participants with RF-/Echo+ (18.6% of Echo+) had predominantly echocardiographic abnormalities other than left ventricular (LV) diastolic dysfunction, hypertrophy and reduced ejection fraction, whereas their physical performance was similar to RF-/Echo-. In contrast, participants with RF+/Echo+ presented primarily with LV hypertrophy or dysfunction, features that related to lower 6-minute walking distance and lower exercise capacity., Conclusions: Subclinical echocardiographic abnormalities suggest HF pathogenesis, but the presence of HF risk factors and type of echo abnormality should be considered so as to distinguish adverse from benign adaptation and to stratify HF risk., Competing Interests: Disclosures All authors acknowledge institutional research grants from Verily Life Sciences. FH received an institutional research grant from Actelion within the past 2 years and an institutional research grant from Precordior. KM reports grants from Verily, Afferent, AHA, Cardiva Medical, Gilead, Luitpold, Medtronic, Merck, Eidos, Ferring, Apple, Sanifit, and St. Jude; grants and personal fees from Amgen, AstraZeneca, Bayer, CSL Behring, Johnson & Johnson, Novartis, and Sanofi; and personal fees from Anthos, Applied Therapeutics, Elsevier, Inova, Intermountain Health, Medscape, Mount Sinai, Mundi Pharma, Myokardia, Novo Nordisk, Otsuka, Portola, SmartMedics, and Theravance outside the submitted work. AH reports grants from Verily; grants and personal fees from AstraZeneca, Amgen, Bayer, Merck, and Novartis, and personal fees from Boston Scientific outside the submitted work. NC reports grants from the Research Foundation Flanders. GB reports grants from the National Institutes of Health (U01-HL146382-03, Rx01-MD013493-03, D43TW009337, U01-HL123336-06, U01-HL142099-03, and D43 TW011625-01) and royalties or licensing fees from UpToDate. The other authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Hypertensive disorders of pregnancy (HDP) are rising in prevalence and associated with adverse maternal and infant health outcomes. Current guidelines recommend labetalol, nifedipine, and methyldopa as acceptable first-line agents to treat HDP in outpatient settings. However, the current practice regarding antihypertensive medication usage and selection remain unclear. A retrospective, observational cohort study was conducted in 1,641 patients with a physician diagnosis of HDP who delivered at two academic medical centers in North Carolina from 2014 to 2017. Use of any antihypertensive medication, and the agent selected, at any encounter during pregnancy or on the delivery date was collected from the electronic health record. Proportions were compared across HDP diagnosis (eclampsia/severe preeclampsia, chronic hypertension with superimposed preeclampsia, preeclampsia, gestational hypertension) by Chi-square tests and multivariable logistic regression. Antihypertensive medications were used in 1,276 (77.8%) patients overall. Among treated patients, labetalol (74.9%) was the most frequently used medication followed by nifedipine (29.6%) and hydralazine (20.5%). Methyldopa was used infrequently (4.4%). HDP type was the strongest factor associated with use of an antihypertensive agent. Relative to gestational hypertension, antihypertensive use was significantly more likely [odds ratio (95% CI)] in patients with severe preeclampsia [5.94 (3.85-9.16)], chronic hypertension with superimposed preeclampsia [4.99 (3.46-7.19)], and preeclampsia [2.13 (1.61-2.82)]. In a real-world setting, antihypertensive medication use among HDP patients was common, labetalol, nifedipine, and hydralazine were the most commonly selected agents, and increasing HDP severity was associated with a higher likelihood of antihypertensive use. Future studies comparing medication effectiveness in pregnant patients with distinct HDP diagnoses are needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Garcia, Mulrenin, Nguyen, Loop, Daubert, Urrutia and Lee.)

Background: We sought to determine whether circulating modifiers of endothelial function are associated with cardiac structure and clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF)., Methods: We measured 25 proteins related to endothelial function in 99 patients from the GUIDE-IT study. Protein levels were evaluated for association with echocardiographic parameters and the incidence of all-cause death and hospitalization for heart failure (HHF)., Results: Higher concentrations of angiopoietin 2 (ANGPT2), vascular endothelial growth factor receptor 1 (VEGFR1) and hepatocyte growth factor (HGF) were significantly associated with worse function and larger ventricular volumes. Over time, decreases in ANGPT2 and, to a lesser extent, VEGFR1 and HGF, were associated with improvements in cardiac size and function. Individuals with higher concentrations of ANGPT2, VEGFR1 or HGF had increased risks for a composite of death and HHF in the following year (HR 2.76 (95% CI 1.73-4.40) per 2-fold change in ANGPT2; HR 1.76 (95% CI 1.11-2.79) for VEGFR1; and HR 4.04 (95% CI 2.19-7.44) for HGF)., Conclusions: Proteins related to endothelial function associate with cardiac size, cardiac function and clinical outcomes in patients with HFrEF. These results support the concept that endothelial function may be an important contributor to the progression to and the recovery from HFrEF., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The relationship between body size and cardiovascular events is complex. This study utilized the ADVANCE (Assessing Diagnostic Value of Noninvasive FFR CT in Coronary Care) Registry to investigate the association between body mass index (BMI), coronary artery disease (CAD), and clinical outcomes., Methods: The ADVANCE registry enrolled patients undergoing evaluation for clinically suspected CAD who had >30% stenosis on cardiac computed tomography angiography. Patients were stratified by BMI: normal <25 kg/m 2 , overweight 25-29.9 kg/m 2 , and obese ≥30 kg/m 2 . Baseline characteristics, cardiac computed tomography angiography and computed tomography fractional flow reserve (FFR CT ), were compared across BMI groups. Adjusted Cox proportional hazards models assessed the association between BMI and outcomes., Results: Among 5014 patients, 2166 (43.2%) had a normal BMI, 1883 (37.6%) were overweight, and 965 (19.2%) were obese. Patients with obesity were younger and more likely to have comorbidities, including diabetes and hypertension (all P <0.001), but were less likely to have obstructive coronary stenosis (65.2% obese, 72.2% overweight, and 73.2% normal BMI; P <0.001). However, the rate of hemodynamic significance, as indicated by a positive FFR CT , was similar across BMI categories (63.4% obese, 66.1% overweight, and 67.8% normal BMI; P =0.07). Additionally, patients with obesity had a lower coronary volume-to-myocardial mass ratio compared with patients who were overweight or had normal BMI (obese BMI, 23.7; overweight BMI, 24.8; and normal BMI, 26.3; P <0.001). After adjustment, the risk of major adverse cardiovascular events was similar regardless of BMI (all P >0.05)., Conclusions: Patients with obesity in the ADVANCE registry were less likely to have anatomically obstructive CAD by cardiac computed tomography angiography but had a similar degree of physiologically significant CAD by FFR CT and similar rates of adverse events. An exclusively anatomic assessment of CAD in patients with obesity may underestimate the burden of physiologically significant disease that is potentially due to a significantly lower volume-to-myocardial mass ratio., Competing Interests: Disclosures Dr Lowenstern reports consulting for Edwards Lifesciences. Dr Takagi reports speaking fees from HeartFlow Japan GK and consulting fee from HeartFlow Inc. Dr Koweek reports a research grant from HeartFlow. Dr Douglas reports a research grant from HeartFlow. Dr Pontone reports grants from GE Healthcare and HeartFlow and personal fees from GE, Bracco, and Medtronic. Dr Berman reports research support from HeartFlow. Dr de Bruyne reports grants from Abbott, St Jude Medical, and Medtronic, and other support from St Jude Medical, Boston Scientific, Opsens, Omega Pharma, Siemens, Edwards, GE, Sanofi, HeartFlow, and Bayer. Dr Bax reports grants from Boston Scientific, Medtronic, Biotronik, and Edwards Lifesciences. T. Akasaka reports grants from Daiichi-Sankyo, St. Jude Medical Japan, Boehringer Ingelheim Japan, Bayer, Pfizer Inc, Foundation for Biomedical Research and Innovation, Otsuka Pharmaceutical Co, Astellas Pharma, Terumo, Abbott Vascular Japan, Goodman Co, and Boston Scientific Japan and has served as a consultant for Daiichi-Sankyo, St. Jude Medical Japan, Boehringer Ingelheim Japan, Bayer, Pfizer Inc, Otsuka Pharmaceutical Co, Astellas Pharma Inc, Terumo, Abbott Vascular Japan, Goodman Co, Boston Scientific Japan, and HeartFlow Japan. Dr Nieman reports support from the National Institutes of Health (NIH R01–HL141712; NIH R01–HL146754) and reports unrestricted institutional research support from Siemens Healthineers, Bayer, HeartFlow Inc, Novartis unrelated to this work, consulting for Siemens Medical Solutions USA, and equity in Lumen Therapeutics. Dr Rogers reports receiving salary and equity in HeartFlow and is a full-time employee of HeartFlow; Dr Fairbairn is on the speaker’s bureau for HeartFlow. S. Mullen reports being an employee of and owning equity in HeartFlow. Dr Norgaard reports an unrestricted institutional research grant from HeartFlow Inc. Dr Patel reports research grants from Bayer, Janssen, HeartFlow, Novartis, the National Heart, Lung, and Blood Institute, and the Advisory Board/Consulting for Bayer, Janssen, HeartFlow, and Novartis. Dr Leipsic reports being a consultant and having stock options for Circle CVI and HeartFlow. The other authors report no conflicts.

Abstract: Prospective head-to-head comparison of coronary calcium scores between standard computed tomography (CT) and photon-counting CT show no significant differences, while photon-counting CT administers substantially lower radiation dose., Competing Interests: J.C.R.-G. is an employee of Siemens Healthineers. The remaining authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Coronary artery calcium (CAC) and left ventricular diastolic dysfunction (LVDD) are strong predictors of cardiovascular events and share common risk factors. However, their independent association remains unclear., Methods: In the Project Baseline Health Study (PBHS), 2082 participants underwent cardiac-gated, non-contrast chest computed tomography (CT) and echocardiography. The association between left ventricular (LV) diastolic function and CAC was assessed using multidimensional network and multivariable-adjusted regression analyses. Multivariable analysis was conducted on continuous LV diastolic parameters and categorical classification of LVDD and adjusted for traditional cardiometabolic risk factors. LVDD was defined using reference limits from a low-risk reference group without established cardiovascular disease, cardiovascular risk factors or evidence of CAC, (n ​= ​560). We also classified LVDD using the American Society of Echocardiography recommendations., Results: The mean age of the participants was 51 ​± ​17 years with 56.6% female and 62.6% non-Hispanic White. Overall, 38.1% had hypertension; 13.7% had diabetes; and 39.9% had CAC >0. An intertwined network was observed between diastolic parameters, CAC score, age, LV mass index, and pulse pressure. In the multivariable-adjusted analysis, e', E/e', and LV mass index were independently associated with CAC after adjustment for traditional risk factors. For both e' and E/e', the effect size and statistical significance were higher across increasing CAC tertiles. Other independent correlates of e' and E/e' included age, female sex, Black race, height, weight, pulse pressure, hemoglobin A1C, and HDL cholesterol. The independent association with CAC was confirmed using categorical analysis of LVDD, which occurred in 554 participants (26.6%) using population-derived thresholds., Conclusion: In the PBHS study, the subclinical coronary atherosclerotic disease burden detected using CAC scoring was independently associated with diastolic function., Gov Identifier: NCT03154346., Competing Interests: Declaration of competing interest All authors acknowledge institutional research grants from Verily Life Sciences. FH received an institutional research grant from Actelion Ltd. Within the last 2 years and an institutional research grant from Precordior Ltd. KM reports grants from Verily, Afferent, the American Heart Association (AHA), Cardiva Medical Inc, Gilead, Luitpold, Medtronic, Merck, Eidos, Ferring, Apple Inc, Sanifit, and St. Jude; grants and personal fees from Amgen, AstraZeneca, Bayer, CSL Behring, Johnson & Johnson, Novartis, and Sanofi; and personal fees from Anthos, Applied Therapeutics, Elsevier, Inova, Intermountain Health, Medscape, Mount Sinai, Mundi Pharma, Myokardia, Novo Nordisk, Otsuka, Portola, SmartMedics, and Theravance outside the submitted work. AH reports grants from Verily; grants and personal fees from AstraZeneca, Amgen, Bayer, Merck, and Novartis; and personal fees from Boston Scientific outside the submitted work. RC reports grants from Verily Life Sciences and Google Health, and personal fees from Cytokinetics Inc. And Centessa Inc. NC reports grants from the Research Foundation Flanders. FR reports equity from HealthPals and Carta, and advisory board and consulting fees from NovoNordisk, HealthPals, and Novartis. JB reports grants from the National Institutes of Health (U01-HL146382–03, R01-MD013493-03, D43TW009337, U01-HL123336–06, U01-HL142099-03, and D43 TW(01)1625-01) and royalties or licensing fees from UpToDate. The other authors have no conflicts of interest to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Importance: In patients with severe aortic stenosis and left ventricular ejection fraction (LVEF) less than 50%, early LVEF improvement after transcatheter aortic valve replacement (TAVR) is associated with improved 1-year mortality; however, its association with long-term clinical outcomes is not known., Objective: To examine the association between early LVEF improvement after TAVR and 5-year outcomes., Design, Setting, and Participants: This cohort study analyzed patients enrolled in the Placement of Aortic Transcatheter Valves (PARTNER) 1, 2, and S3 trials and registries between July 2007 and April 2015. High- and intermediate-risk patients with baseline LVEF less than 50% who underwent transfemoral TAVR were included in the current study. Data were analyzed from August 2020 to May 2021., Exposures: Early LVEF improvement, defined as increase of 10 percentage points or more at 30 days and also as a continuous variable (ΔLVEF between baseline and 30 days)., Main Outcomes and Measures: All-cause death at 5 years., Results: Among 659 included patients with LVEF less than 50%, 468 (71.0%) were male, and the mean (SD) age was 82.4 (7.7) years. LVEF improvement within 30 days following transfemoral TAVR occurred in 216 patients (32.8%) (mean [SD] ΔLVEF, 16.4 [5.7%]). Prior myocardial infarction, diabetes, cancer, higher baseline LVEF, larger left ventricular end-diastolic diameter, and larger aortic valve area were independently associated with lower likelihood of LVEF improvement. Patients with vs without early LVEF improvement after TAVR had lower 5-year all-cause death (102 [50.0%; 95% CI, 43.3-57.1] vs 246 [58.4%; 95% CI, 53.6-63.2]; P = .04) and cardiac death (52 [29.5%; 95% CI, 23.2-37.1] vs 135 [38.1%; 95% CI, 33.1-43.6]; P = .05). In multivariable analyses, early improvement in LVEF (modeled as a continuous variable) was associated with lower 5-year all-cause death (adjusted hazard ratio per 5% increase in LVEF, 0.94 [95% CI, 0.88-1.00]; P = .04) and cardiac death (adjusted hazard ratio per 5% increase in LVEF, 0.90 [95% CI, 0.82-0.98]; P = .02) after TAVR. Restricted cubic spline analysis demonstrated a visual inflection point at ΔLVEF of 10% beyond which there was a steep decline in all-cause mortality with increasing degree of LVEF improvement. There were no statistically significant differences in rehospitalization, New York Heart Association functional class, or Kansas City Cardiomyopathy Questionnaire Overall Summary score at 5 years in patients with vs without early LVEF improvement. In subgroup analysis, the association between early LVEF improvement and 5-year all-cause death was consistent regardless of the presence or absence of coronary artery disease or prior myocardial infarction., Conclusions and Relevance: In patients with severe aortic stenosis and LVEF less than 50%, 1 in 3 experience LVEF improvement within 1 month after TAVR. Early LVEF improvement is associated with lower 5-year all-cause and cardiac death.

Coronary artery calcium (CAC) is a specific marker of coronary atherosclerosis that can be used to measure calcified subclinical atherosclerotic burden. The Agatston method is the most widely used scoring algorithm for quantifying CAC and is expressed as the product of total calcium area and a quantized peak calcium density weighting factor defined by the calcification attenuation in HU on noncontrast computed tomography. Calcium density has emerged as an important area of inquiry because the Agatston score is upweighted based on the assumption that peak calcium density and atherosclerotic cardiovascular disease (ASCVD) risk are positively correlated. However, recent evidence demonstrates that calcium density is inversely associated with lesion vulnerability and ASCVD risk in population-based cohorts when accounting for age and plaque area. Here, we review calcium density by focusing on 3 main areas: 1) CAC scan acquisition parameters; 2) pathophysiology of calcified plaques; and 3) epidemiologic evidence relating calcium density to ASCVD outcomes. Through this process, we hope to provide further insight into the evolution of CAC scoring on noncontrast computed tomography., Competing Interests: Funding Support and Author Disclosures Dr Blaha has received grants from the National Institutes of Health, U.S. Food and Drug Administration, AHA, Amgen, Novo Nordisk, and Bayer; and is on the advisory boards for Amgen, Sanofi, Regeneron, Novartis, Novo Nordisk, Bayer, 89Bio, Kaleido, Roche, Inozyme, emocha, VoxelCloud, and Kowa. Dr Dzaye has received support from National Institutes of Health grant T32 HL007227. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The GUIDE-IT trial was, a multicenter, randomized, parallel group, unblinded study that randomized patients to having heart failure therapy titrated to achieve an NT-proBNP <1000 pg/mL or to usual clinical care., Methods and Results: We performed pre-specified subgroup analysis to look for the race and ethnicity-based differences in clinical outcomes of patients who were able to achieve GDMT or target NT-proBNP concentration of ≤1000 pg/mL at 90 days of follow-up. There were 894 patients enrolled in GUIDE-IT study. Of these, 733 participants had available data on 90-day guideline directed triple therapy and 616 on NT-proBNP. 35% of the patients were Black and 6% were Hispanic. Black patients were younger, had more comorbidities, lower EF, and higher NYHA class compared with non-Black. Adjusting for 90-day NT-proBNP and important baseline covariates, Black patients were at a higher risk than non-Black patients for HF hospitalization [HR, 2.19; 95% CI, 1.51-3.17; p < 0.0001], but at a similar risk for mortality [HR, 0.85.; 95% CI, 0.44-1.66; p = 0.64]. Similar results were seen adjusting for 90-day GDMT [HF hospitalization: Black vs non-Black, HR: 1.97; 1.41-2.77, P < 0.0001; mortality: HR: 0.70; 0.39-1.26, p = 0.23]. There were no significant differences between Hispanic and non-Hispanic patients with respect to heart failure hospitalization, cardiovascular or all-cause mortality. Over the study period, Black and Hispanic patients experienced smaller changes in physical function and quality of life as measured by the Kansas City Cardiomyopathy Questionnaire overall score., Conclusion: Compared to non-Black patients, Black patients in GUIDE-IT study had a higher risk of heart failure hospitalization, but a comparable risk of mortality, despite improved use of GDMT and achievement of similar biomarker targets., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Hypertensive disorders of pregnancy (HDP) are rising in prevalence, and increase risk of adverse maternal and fetal outcomes. Physiologic changes occur during pregnancy that alter drug pharmacokinetics. However, antihypertensive drugs lack pregnancy-specific dosing recommendations due to critical knowledge gaps surrounding the extent of gestational changes in antihypertensive drug pharmacokinetics and underlying mechanisms., Areas Covered: This review (1) summarizes currently recommended medications and dosing strategies for non-emergent HDP treatment, (2) reviews and synthesizes existing literature identified via a comprehensive PubMed search evaluating gestational changes in the maternal pharmacokinetics of commonly prescribed HDP drugs (notably labetalol and nifedipine), and (3) offers insight into the metabolism and clearance mechanisms underlying altered HDP drug pharmacokinetics during pregnancy. Remaining knowledge gaps and future research directions are summarized., Expert Opinion: A series of small pharmacokinetic studies illustrate higher oral clearance of labetalol and nifedipine during pregnancy. Pharmacokinetic modeling and preclinical studies suggest these effects are likely due to pregnancy-associated increases in hepatic UGT1A1- and CYP3A4-mediated first-pass metabolism and lower bioavailability. Accordingly, higher and/or more frequent doses may be needed to lower blood pressure during pregnancy. Future research is needed to address various evidence gaps and inform the development of more precise antihypertensive drug dosing strategies.

Background NT-proBNP (N-terminal pro-B-type natriuretic peptide) is a prognostic biomarker in heart failure (HF) with reduced ejection fraction. However, it is unclear whether there is a sex difference in NT-proBNP response and whether the therapeutic goal of NT-proBNP ≤1000 pg/mL has equivalent prognostic value in men and women with HF with reduced ejection fraction. Methods and Results In a secondary analysis of the GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment) trial we analyzed trends in NT-proBNP and goal attainment by sex. Differences in clinical characteristics, HF treatment, and time to all-cause death or HF hospitalization were compared. Landmark analysis at 3 months determined the prognostic value of early NT-proBNP goal achievement in men and women. Of the 286 (32%) women and 608 (68%) men in the GUIDE-IT trial, women were more likely to have a nonischemic cause and shorter duration of HF. Guideline-directed medical therapy was less intense over time in women. The absolute NT-proBNP values were consistently lower in women; however, the change in NT-proBNP and clinical outcomes were similar. After adjustment, women achieving the NT-proBNP goal had an 82% reduction in death or HF hospitalization compared with a 59% reduction in men. Conclusions Men and women with HF with reduced ejection fraction had a similar NT-proBNP response despite less intensive HF treatment among women. However, compared with men, the early NT-proBNP goal of ≤1000 pg/mL had greater prognostic value in women. Future efforts should be aimed at intensifying guideline-directed medical therapy in women, which may result in greater NT-proBNP reductions and improved outcomes in women with HF with reduced ejection fraction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01685840.

Background: Left ventricular assist devices (LVAD) are increasingly used for durable mechanical circulatory support in advanced heart failure. While LVAD therapy provides substantial improvement in mortality and quality of life, long-term therapy confers increased risk for device complications. We evaluated if cardiac computed tomography (CCT) improves the detection of cardiomechanical complications among patients with LVAD and suspected device malfunction., Methods: In this study, we compared the diagnostic performance of CCT and transthoracic echocardiography (TTE) for the identification of cardiomechanical LVAD complications, including thrombus or neointimal hyperplasia, inflow cannula malposition with dynamic obstruction, fixed outflow obstruction, device infection, and severe aortic regurgitation. Complications were confirmed with surgical evaluation, pathologic assessment, or response to therapeutic intervention., Results: Among 58 LVAD patients, who underwent CCT and TTE for suspected LVAD dysfunction, there were 49 confirmed cardiomechanical LVAD complications among 43 (74.1%) patients. The most common LVAD complication was thrombus or neointimal hyperplasia (65.3%), followed by dynamic obstruction (26.5%). Individually, CCT identified 29 of the 49 (59.2%) confirmed LVAD cardiomechanical complications, whereas TTE alone identified a complication in 11 cases (22.4%). However, diagnostic performance was greatest when the two modalities were used in combination, yielding a sensitivity of 67%, specificity of 93%, PPV of 97%, NPV of 47% and diagnostic accuracy of 73%., Conclusion: The novel and complementary use of CCT with TTE for the evaluation of suspected device malfunction improves the accurate identification of cardiomechanical LVAD complication compared to either modality alone., Competing Interests: Declaration of competing interest Priyesh Patel's research fellowship was funded by T32 HL007101. Chetan B. Patel is a consultant for Medtronic and Abbott. All other authors have no relevant disclosures or competing interests., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Cardiovascular imaging has significantly evolved since the turn of the century. Progress in the last two decades has been marked by advances in every modality used to image the heart, including echocardiography, cardiac magnetic resonance, cardiac CT and nuclear cardiology. There has also been a dramatic increase in hybrid and fusion modalities that leverage the unique capabilities of two imaging techniques simultaneously, as well as the incorporation of artificial intelligence and machine learning into the clinical workflow. These advances in non-invasive cardiac imaging have guided patient management and improved clinical outcomes. The technological developments of the past 20 years have also given rise to new imaging subspecialities and increased the demand for dedicated cardiac imagers who are cross-trained in multiple modalities. This state-of-the-art review summarizes the evolution of multimodality cardiac imaging in the 21st century and highlights opportunities for future innovation.

Purpose: Quantifying stenosis in cardiac computed tomography angiography (CTA) images remains a difficult task, as image noise and cardiac motion can degrade image quality and distort underlying anatomic information. The purpose of this study was to develop a computational framework to objectively assess the precision of quantifying coronary stenosis in cardiac CTA. Approach: The framework used models of coronary vessels and plaques, asymmetric motion point spread functions, CT image blur (task-based modulation transfer functions) and noise (noise-power spectrums), and an automated maximum-likelihood estimator implemented as a matched template squared-difference operator. These factors were integrated into an estimability index ( e ' ) as a task-based measure of image quality in cardiac CTA. The e ' index was applied to assess how well it can to predict the quality of 132 clinical cases selected from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain trial. The cases were divided into two cohorts, high quality and low quality, based on clinical scores and the concordance of clinical evaluations of cases by experienced cardiac imagers. The framework was also used to ascertain protocol factors for CTA Biomarker initiative of the Quantitative Imaging Biomarker Alliance (QIBA). Results: The e ' index categorized the patient datasets with an area under the curve of 0.985, an accuracy of 0.977, and an optimal e ' threshold of 25.58 corresponding to a stenosis estimation precision (standard deviation) of 3.91%. Data resampling and training-test validation methods demonstrated stable classifier thresholds and receiver operating curve performance. The framework was successfully applicable to the QIBA objective. Conclusions: A computational framework to objectively quantify stenosis estimation task performance was successfully implemented and was reflective of clinical results in the context of a prominent clinical trial with diverse sites, readers, scanners, acquisition protocols, and patients. It also demonstrated the potential for prospective optimization of imaging protocols toward targeted precision and measurement consistency in cardiac CT images., (© 2021 The Authors.)

Background: The evolution and clinical impact of cardiac remodeling after large ST-elevation myocardial infarction (STEMI) is not well delineated in the current therapeutic era., Methods: The PRESERVATION I trial longitudinally assessed cardiac structure and function in STEMI patients receiving primary percutaneous coronary intervention (PCI). Echocardiograms were performed immediately post-PCI and at 1, 3, 6 and 12 months after STEMI. The extent of cardiac remodeling was assessed in patients with ejection fraction (EF) ≤ 40% after PCI. Patients were stratified by the presence or absence of reverse remodeling, defined as an increase in end-diastolic volume (EDV) of ≤10 mL or decrease in EDV at 1 month, and evaluated for an association with adverse events at 1 year., Results: Of the 303 patients with large STEMI enrolled in PRESERVATION I, 225 (74%) had at least moderately reduced systolic function (mean EF 32 ± 5%) immediately after primary PCI. In the following year, there were significant increases in EF and LV volumes, with the greatest magnitude of change occurring in the first month. At 1 month, 104 patients (46%) demonstrated reverse remodeling, which was associated with a significantly lower rate of death, recurrent myocardial infarction and repeat cardiovascular hospitalization at 1 year (HR 0.44; 95% CI: 0.19-0.99)., Conclusion: Reduced EF after large STEMI and primary PCI is common in the current therapeutic era. The first month following primary reperfusion is a critical period during which the greatest degree of cardiac remodeling occurs. Patients demonstrating early reverse remodeling have a significantly lower rate of adverse events in the year after STEMI., Competing Interests: Disclosures Duke Clinical Research Institute was the recipient of research funding from Bellerophon Therapeutics Inc. Dr Zeymer has received honoraria for participation at steering committee meetings of PRESERVATION I. Dr Kasprzak has received investigator fees from Bellerophon Therapeutics Inc. Drs Rao, Krucoff and Douglas have received research grant support from Bellerophon Therapeutics Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Importance: Patients with abnormal (positive) exercise electrocardiography, but normal stress echocardiography (+ECG/-Echo) are commonly encountered in clinical practice; however, the prognostic significance of this discordant result is unclear., Objective: To determine whether patients with +ECG/-Echo have a higher rate of adverse clinical events and a poorer prognosis than patients with negative exercise ECG and normal stress Echo imaging (-ECG/-Echo)., Design, Setting, and Participants: Between January 1, 2000, and February 28, 2014, a total of 47 944 consecutive patients without known coronary artery disease who underwent exercise stress Echo at Duke University Medical Center were evaluated for inclusion in this observational cohort study. Data analysis was conducted from January 1, 2000, to December 31, 2016., Interventions/exposures: Patients were categorized as having -ECG/-Echo, +ECG/-Echo, or +Echo (-ECG/+Echo and +ECG/+Echo)., Main Outcomes and Measures: The primary outcome was a composite end point of death, myocardial infarction, hospitalization for unstable angina, and coronary revascularization. Secondary outcomes included individual adverse events and downstream testing., Results: After excluding submaximal tests and nondiagnostic ECG or stress imaging results, 15 077 patients (mean [SD] age, 52 [13] years; 6228 [41.3%] men) were classified by stress test results. Of these, 12 893 patients (85.5%) had -ECG/-Echo, 1286 patients (8.5%) had +ECG/-Echo, and 898 patients (6.0%) had +Echo. Through a median follow-up of 7.3 (interquartile range, 4.4-10.0) years, the composite end point occurred in 794 patients with -ECG/-Echo (8.5%), 142 patients with +ECG/-Echo (14.6%), and 297 patients with +Echo (37.4%). Death occurred in 425 patients with -ECG/-Echo (4.8%), 50 patients with +ECG/-Echo (5.9%), and 70 patients with +Echo (11.2%). Myocardial infarction occurred in 195 patients with -ECG/-Echo (2.2%), 31 patients with +ECG/-Echo (3.6%), and 59 patients with +Echo (8.7%). The addition of stress ECG findings to clinical and exercise data yielded incremental prognostic value. Patients with -ECG/-Echo imaging results had the least downstream testing (2.3%), followed by +ECG/-Echo (12.8%), and +Echo (33.6%) (P < .001)., Conclusions and Relevance: The presence of +ECG results with normal stress Echo imaging may identify a population of patients who are at slightly increased risk for adverse cardiac events, which was not previously recognized. Further study is needed to determine whether these patients will benefit from intensification of medical management.

The incidence of heart failure (HF) is increasing, particularly among women, and constitutes a rapidly growing public health problem. The primary prevention of HF in women should involve targeted, sex-specific strategies to increase awareness, promote a heart healthy lifestyle, and improve treatments that optimally control the risk factors for HF with reduced ejection fraction and HF with preserved ejection fraction. Epidemiological and pathophysiological differences in both HF subtypes strongly suggest that sex-specific preventive strategies and risk factor reduction may be particularly beneficial. However, significant gaps in sex-specific knowledge exist and are impeding preventive efforts. To overcome these limitations, women need to be adequately represented in HF research, sex differences must be prospectively investigated, and effective sex-specific interventions should be incorporated into clinical practice guidelines. This review summarizes the existing evidence that supports the primary prevention of HF in women and identifies potential strategies that are most likely to be effective in reducing the burden of HF among women., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aims to assess the association between biomarker-guided therapy and left ventricular (LV) remodeling., Background: In patients with heart failure with reduced ejection fraction (HFrEF), it is unclear if lowering natriuretic peptides reflects structural and functional changes in the heart. This study aims to assess the association between biomarker-guided therapy and left ventricular (LV) remodeling., Methods: The GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) Echo Substudy was a multicenter study that randomized 268 patients with HFrEF (EF ≤40%) to either pro-B-type natriuretic peptide (NT-proBNP)-guided treatment or usual care. Echocardiograms were performed at baseline and 12 months in 124 patients. Remodeling indices and clinical outcomes were compared between treatment arms and by achievement of the NT-proBNP goal of <1,000 pg/ml at 12 months., Results: At 12 months, the changes in EF and LV volumes were similar between the biomarker-guided and usual care arms with no difference in clinical outcomes; however, lowering NT-proBNP to <1,000 pg/ml, regardless of treatment strategy, was associated with a significantly greater increase in EF compared with those not reaching goal (9.9 ± 8.8% vs. 2.9 ± 7.9%; p < 0.001) and lower LV volumes. The extent of reverse remodeling correlated with the change in NT-proBNP: a decrease of 1,000 pg/ml was associated with an increase in EF of 6.7% and a reduction in systolic and diastolic volumes of 17.3 ml/m 2 and 15.7 ml/m 2 , respectively. Adverse events were significantly lower among patients achieving the NT-proBNP goal (p < 0.001)., Conclusions: Among patients with HFrEF, lowering NT-proBNP to <1,000 pg/ml by 12 months was associated with significant reverse remodeling and improved outcomes. A greater reduction in NT-proBNP was associated with more extensive reverse remodeling. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment [GUIDE-IT]; NCT01685840)., (Copyright © 2019 American College of Cardiology Foundation. All rights reserved.)

Background: Although sex differences exist in the management of acute coronary syndromes, less is known about the management and outcomes of women and men with suspected coronary artery disease being evaluated with noninvasive testing (NIT)., Methods: We investigated sex-based differences in NIT results and subsequent clinical management in 4,720 women and 4,246 men randomized to CT angiography versus stress testing in the PROMISE trial. Logistic regression models assessed relationships between sex and referral for catheterization, revascularization, and aspirin or statin use. Cox regression models assessed the relationship between sex and the composite of all-cause death, myocardial infarction, or unstable angina., Results: Women more often had normal NITs than men (61.0% vs 49.6%, P < .001) and less often had mild (29.3% vs 35.4%, P < .001), moderate (4.0% vs 6.8%, P < .001), or severe abnormalities (5.7% vs 8.3%, P < .001) found on NIT. Women were less likely to be referred for catheterization than men (7.6% vs 12.6%, adjusted OR 0.75 [0.62-0.90]; P = .002). Of those who underwent catheterization within 90 days of randomization (358 women, 534 men), fewer women than men had obstructive coronary artery disease (40.8% vs 60.9%, P < .001). At a 60-day visit, women were significantly less likely than men to report statin use when indicated (adjusted OR 0.81 [0.73-0.91]; P < .001) but were similarly likely to report aspirin use when indicated (adjusted OR 0.78 [0.56-1.08]; P = .13). Over a median follow-up of 25 months, women had better outcomes than men (adjusted OR 0.73 [0.57-0.94]; P = .017)., Conclusions: Although women more frequently had normal NITs compared with men, those with abnormalities on NIT were less likely to be referred for catheterization or to receive statin therapy. The high rates of negative NIT in women, coupled with the better outcomes compared with men, strongly support the need for a sex-specific algorithm to guide NIT and chest pain management., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Sleep-disordered breathing (SDB), including central and obstructive sleep apnea, is a marker of poor prognosis in heart failure (HF) and may worsen cardiac dysfunction over time. Treatment of SDB with adaptive servoventilation (ASV) may reverse pathologic cardiac remodeling in HF patients., Methods: The Cardiovascular Improvements with Minute Ventilation-targeted Adaptive Servo-Ventilation Therapy in Heart Failure (CAT-HF) trial randomized patients with acute decompensated HF and confirmed SDB to either optimal medical therapy (OMT) or treatment with ASV and OMT. Patients with reduced ejection fraction (HFrEF) or preserved EF (HFpEF) were included. Echocardiograms, performed at baseline and 6 months, assessed cardiac size and function and evaluated cardiac remodeling over time. The CAT-HF trial was stopped early in response to the SERVE-HF trial, which found increased mortality among HFrEF patients with central sleep apnea treated with ASV., Results: Of the 126 patients enrolled prior to trial cessation, 95 had both baseline and 6-month echocardiograms (77 HFrEF and 18 HFpEF). Among HFrEF patients, both treatment arms demonstrated a significant increase in EF: +4.3% in the ASV group (.0004) and +4.6% in OMT alone (P = .007) and a significant decrease in LV end-systolic volume index: -9.4 mL/m 2 in the ASV group (P = .01) and -8.6 mL/m 2 in OMT alone (P = .003). Reductions in left atrial (LA) volume and E/e' were greater in the ASV arm, whereas patients receiving OMT alone demonstrated more improvement in right ventricular function. HFpEF patients treated with ASV also had a decrease in LA size that was greater than those receiving OMT alone. Although there were significant intragroup changes within the ASV + OMT and OMT-alone groups, there were no significant intergroup differences at 6 months., Conclusions: Significant reverse LV remodeling was seen among HFrEF patients with SDB regardless of treatment allocation. Substantial reductions in LA volume among HFrEF and HFpEF patients receiving ASV suggest that ASV treatment may also improve diastolic function and warrant further investigation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Mitochondrial dysfunction and energy depletion in the failing heart are innovative therapeutic targets in heart failure management. Elamipretide is a novel tetrapeptide that increases mitochondrial energy; however, its safety, tolerability, and therapeutic effect on cardiac structure and function have not been studied in heart failure with reduced ejection fraction., Methods and Results: In this double-blind, placebo-controlled, ascending-dose trial, patients with heart failure with reduced ejection fraction (ejection fraction, ≤35%) were randomized to either a single 4-hour infusion of elamipretide (cohort 1 [n=8], 0.005; cohort 2 [n=8], 0.05; and cohort 3 [n=8], 0.25 mg·kg -1 ·h -1 ) or placebo control (n=12). Safety and efficacy were assessed by clinical, laboratory, and echocardiographic assessments performed at pre-, mid- and end-infusion and 6-, 8-, 12- and 24-hours postinfusion start. Peak plasma concentrations of elamipretide occurred at end-infusion and were undetectable by 24 hours postinfusion. There were no serious adverse events. Blood pressure and heart rate remained stable in all cohorts. Compared with placebo, a significant decrease in left ventricular end-diastolic volume (-18 mL; P =0.009) and end-systolic volume (-14 mL; P =0.005) occurred at end infusion in the highest dose cohort., Conclusions: This is the first study to evaluate elamipretide in heart failure with reduced ejection fraction and demonstrates that a single infusion of elamipretide is safe and well tolerated. High-dose elamipretide resulted in favorable changes in left ventricular volumes that correlated with peak plasma concentrations, supporting a temporal association and dose-effect relationship. Further study of elamipretide is needed to determine long-term safety and efficacy., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02388464., (© 2017 American Heart Association, Inc.)

Objectives: The aim of this study was to evaluate the long-term performance of transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) through longitudinal echocardiographic analysis., Background: The long-term performance of the SAPIEN TAVR is not well-described. Therefore, we examined the hemodynamic and valvular profile of the SAPIEN TAVR over 5 years., Methods: All patients receiving TAVR or SAVR with first post-implant (FPI) and 5-year echoes were analyzed for aortic valve (AV) peak velocity, AV mean gradient, AV area, peak left ventricular (LV) outflow tract and in-stent velocities, Doppler velocity index, aortic regurgitation (AR), LV mass index, stroke volume index, and cardiac index. The FPI and 5-year data were compared using a paired t test or McNemar's analyses., Results: There were 86 TAVR and 48 SAVR patients with paired FPI and 5-year echocardiograms. Baseline characteristics were similar between groups. The AV area did not change significantly 5 years after TAVR (p = 0.35). The AV mean gradient also remained stable: 11.5 ± 5.4 mm Hg at FPI to 11.0 ± 6.3 mm Hg at 5 years (p = 0.41). In contrast, the peak AV and LV outflow tract velocities decreased (p = 0.03 and p = 0.008, respectively), as did in-stent velocity (p = 0.015). Correspondingly, the TAVR Doppler velocity index was unchanged (p = 0.07). Among TAVR patients, there was no change in total AR (p = 0.40), transvalvular AR (p = 0.37), or paravalvular AR (p = 0.26). Stroke volume index and cardiac index remained stable (p = 0.16 and p = 0.25, respectively). However, there was a significant regression of LV mass index (p < 0.0001). The longitudinal evaluation among SAVR patients revealed similar trends. There was a low rate of adverse events among TAVR and SAVR patients alive at 5 years., Conclusions: Longitudinal assessment of the PARTNER I trial (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial) demonstrates that valve performance and cardiac hemodynamics are stable after implantation in both SAPIEN TAVR and SAVR in patients alive at 5 years. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: There is no broadly accepted standard method for assessing the quality of echocardiographic measurements in clinical research reports, despite the recognized importance of this information in assessing the quality of study results., Methods: Twenty unique clinical studies were identified reporting echocardiographic data quality for determinations of left ventricular (LV) volumes (n = 13), ejection fraction (n = 12), mass (n = 9), outflow tract diameter (n = 3), and mitral Doppler peak early velocity (n = 4). To better understand the range of possible estimates of data quality and to compare their utility, reported reproducibility measures were tabulated, and de novo estimates were then calculated for missing measures, including intraclass correlation coefficient (ICC), 95% limits of agreement, coefficient of variation (CV), coverage probability, and total deviation index, for each variable for each study., Results: The studies varied in approaches to reproducibility testing, sample size, and metrics assessed and values reported. Reported metrics included mean difference and its SD (n = 7 studies), ICC (n = 5), CV (n = 4), and Bland-Altman limits of agreement (n = 4). Once de novo estimates of all missing indices were determined, reasonable reproducibility targets for each were identified as those achieved by the majority of studies. These included, for LV end-diastolic volume, ICC > 0.95, CV < 7%, and coverage probability > 0.93 within 30 mL; for LV ejection fraction, ICC > 0.85, CV < 8%, and coverage probability > 0.85 within 10%; and for LV mass, ICC > 0.85, CV < 10%, and coverage probability > 0.60 within 20 g., Conclusions: Assessment of data quality in echocardiographic clinical research is infrequent, and methods vary substantially. A first step to standardizing echocardiographic quality reporting is to standardize assessments and reporting metrics. Potential benefits include clearer communication of data quality and the identification of achievable targets to benchmark quality improvement initiatives., (Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Clinical core laboratories, such as Echocardiography core laboratories, are increasingly used in clinical studies with imaging outcomes as primary, secondary, or surrogate endpoints. While many factors contribute to the quality of measurements of imaging variables, an essential step in ensuring the value of imaging data includes formal assessment and control of reproducibility via intra-observer and inter-observer reliability. There are many different agreement/reliability indices in the literature. However, different indices may lead to different conclusions and it is not clear which index is the preferred choice as an overall indication of data quality and a tool for providing guidance on improving quality and reliability in a core lab setting. In this paper, we pre-specify the desirable characteristics of an agreement index for assessing and improving reproducibility in a core lab setting; we compare existing agreement indices in terms of these characteristics to choose a preferred index. We conclude that, among the existing indices reviewed, the coverage probability for assessing agreement is the preferred agreement index on the basis of computational simplicity, its ability for rapid identification of discordant measurements to provide guidance for review and retraining, and its consistent evaluation of data quality across multiple reviewers, populations, and continuous/categorical data., (© The Author(s) 2014.)

Background: Although risk stratification is an important goal of cardiac noninvasive tests (NITs), few contemporary data exist on the prognostic value of different NITs according to patient sex., Objectives: The goal of this study was to compare the results and prognostic information derived from anatomic versus stress testing in stable men and women with suspected coronary artery disease., Methods: In 8,966 patients tested at randomization (4,500 to computed tomography angiography [CTA], 52% female; 4,466 to stress testing, 53% female), we assessed the relationship between sex and NIT results and between sex and a composite of death, myocardial infarction, or unstable angina hospitalization., Results: In women, a positive CTA (≥70% stenosis) was less likely than a positive stress test result (8% vs. 12%; adjusted odds ratio: 0.67). Compared with negative test results, a positive CTA was more strongly associated with subsequent clinical events than a positive stress test result (CTA-adjusted hazard ratio of 5.86 vs. stress-adjusted hazard ratio of 2.27; adjusted p = 0.028). Men were more likely to have a positive CTA than a positive stress test result (16% vs. 14%; adjusted odds ratio: 1.23). Compared with negative test results, a positive CTA was less strongly associated with subsequent clinical events than a positive stress test result in men, although this difference was not statistically significant (adjusted p = 0.168). Negative CTA and stress test results were equally likely to predict an event in both sexes. A significant interaction between sex, NIT type, and test result (p = 0.01) suggests that sex and NIT type jointly influence the relationship between test result and clinical events., Conclusions: The prognostic value of an NIT result varies according to test type and patient sex. Women seem to derive more prognostic information from a CTA, whereas men tend to derive similar prognostic value from both test types., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to determine whether presentation, risk assessment, testing choices, and results differ by sex in stable symptomatic outpatients with suspected coronary artery disease (CAD)., Background: Although established CAD presentations differ by sex, little is known about stable, suspected CAD., Methods: The characteristics of 10,003 men and women in the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial were compared using chi-square and Wilcoxon rank-sum tests. Sex differences in test selection and predictors of test positivity were examined using logistic regression., Results: Women were older (62.4 years of age vs. 59.0 years of age) and were more likely to be hypertensive (66.6% vs. 63.2%), dyslipidemic (68.9% vs. 66.3%), and to have a family history of premature CAD (34.6% vs. 29.3) (all p values <0.005). Women were less likely to smoke (45.6% vs. 57.0%; p < 0.001), although their prevalence of diabetes was similar to that in men (21.8% vs. 21.0%; p = 0.30). Chest pain was the primary symptom in 73.2% of women versus 72.3% of men (p = 0.30), and was characterized as “crushing/pressure/squeezing/tightness” in 52.5% of women versus 46.2% of men (p < 0.001). Compared with men, all risk scores characterized women as being at lower risk, and providers were more likely to characterize women as having a low (<30%) pre-test probability of CAD (40.7% vs. 34.1%; p < 0.001). Compared with men, women were more often referred to imaging tests (adjusted odds ratio: 1.21; 95% confidence interval: 1.01 to 1.44) than nonimaging tests. Women were less likely to have a positive test (9.7% vs. 15.1%; p < 0.001). Although univariate predictors of test positivity were similar, in multivariable models, age, body mass index, and Framingham risk score were predictive of a positive test in women, whereas Framingham and Diamond and Forrester risk scores were predictive in men., Conclusions: Patient sex influences the entire diagnostic pathway for possible CAD, from baseline risk factors and presentation to noninvasive test outcomes. These differences highlight the need for sex-specific approaches for the evaluation of CAD.

Background: Therapies that reverse pathologic left ventricular (LV) remodeling are often associated with improved outcomes. The incidence and impact of reverse LV remodeling after high-risk percutaneous coronary intervention (PCI) are unknown., Methods: The PROTECT II study was a multicenter trial in patients with complex, multivessel coronary artery disease and reduced ejection fraction (EF) that revealed an increase in visual EF after high-risk PCI. Among patients with quantitative echocardiography (LV volumes and biplane EF), we assessed the extent and predictors of reverse LV remodeling, defined as improved systolic function with an absolute increase in EF ≥5% and correlated these findings with clinical events., Results: Quantitative echocardiography was performed in 184 patients at baseline and longest follow-up. Mean EF at baseline was 27.1%. Ninety-three patients (51%) demonstrated reverse LV remodeling with an absolute increase in EF of 13.2% (P < .001). End-systolic volume decreased from 137.7 to 106.6 mL (P = .002). No significant change in EF or end-systolic volume was seen among non-remodelers. Reverse LV remodeling occurred more frequently in patients with more extensive revascularization (odds ratio, 7.52; 95% CI [1.31-43.25]) and was associated with significantly fewer major adverse events (composite of death/myocardial infarction/stroke/transient ischemic attack): 9.7% versus 24.2% (P = .009). There was also a greater reduction in New York Heart Association class III/IV heart failure among reverse LV remodelers (66.7% to 24.0%) than non-remodelers (56.3% to 34.4%), P = .045., Conclusions: Reverse LV remodeling can occur after high-risk PCI in patients with complex coronary artery disease and reduced EF and is associated with improved clinical outcomes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Interpretative variability can adversely affect echocardiographic reliability, but there is no widely accepted method to minimize variability and improve reproducibility., Methods: A continuous quality improvement process was devised that involves testing reproducibility by assessment of measurement differences followed by robust review, retraining, and retesting. Reproducibility was deemed acceptable if ≥80% of all interreader comparisons were within a prespecified acceptable difference. Readers not meeting this standard underwent retraining and retesting until acceptable reproducibility was achieved for the following parameters: left ventricular end-diastolic volume, biplane ejection fraction, mitral and aortic regurgitation, left ventricular outflow tract diameter, peak and mean aortic valve gradients, and aortic valve area. Eight hundred interreader comparisons for evaluation of reproducibility were generated from five readers interpreting 10 echocardiograms per testing cycle. The applicability and efficacy of this method were then evaluated by testing a second larger group of 10 readers and reevaluating reproducibility 1 year later., Results: All readers demonstrated acceptable reproducibility for biplane ejection fraction, mitral regurgitation, and peak and mean aortic valve gradients. Acceptable reproducibility for left ventricular end-diastolic volume, aortic regurgitation, and aortic valve area was achieved by four of five readers. No readers attained acceptable reproducibility on initial evaluation of left ventricular outflow tract diameter. After review and retraining, all readers demonstrated acceptable reproducibility, which was maintained on subsequent testing 1 year later. A second larger group of 10 readers was also evaluated and yielded similar results., Conclusions: A continuous quality improvement process was devised that successfully reduced interpretative variability in echocardiography and improved reproducibility that was sustained over time., (Copyright © 2015 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)