The Canadian Women's Heart Health Alliance ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women - Chapter 8: Knowledge Gaps and Status of Existing Research Programs in Canada.

Despite significant progress in medical research and public health efforts, gaps in knowledge of women's heart health remain across epidemiology, presentation, management, outcomes, education, research, and publications. Historically, heart disease was viewed primarily as a condition in men and male individuals, leading to limited understanding of the unique risks and symptoms that women experience. These knowledge gaps are particularly problematic because globally heart disease is the leading cause of death for women. Until recently, sex and gender have not been addressed in cardiovascular research, including in preclinical and clinical research. Recruitment was often limited to male participants and individuals identifying as men, and data analysis according to sex or gender was not conducted, leading to a lack of data on how treatments and interventions might affect female patients and individuals who identify as women differently. This lack of data has led to suboptimal treatment and limitations in our understanding of the underlying mechanisms of heart disease in women, and is directly related to limited awareness and knowledge gaps in professional training and public education. Women are often unaware of their risk factors for heart disease or symptoms they might experience, leading to delays in diagnosis and treatments. Additionally, health care providers might not receive adequate training to diagnose and treat heart disease in women, leading to misdiagnosis or undertreatment. Addressing these knowledge gaps requires a multipronged approach, including education and policy change, built on evidence-based research. In this chapter we review the current state of existing cardiovascular research in Canada with a specific focus on women.

En dépit des avancées importantes de la recherche médicale et des efforts en santé publique, il reste des lacunes dans les connaissances sur la santé cardiaque des femmes sur les plans de l'épidémiologie, du tableau clinique, de la prise en charge, des résultats, de l'éducation, de la recherche et des publications. Du point de vue historique, la cardiopathie a d'abord été perçue comme une maladie qui touchait les hommes et les individus de sexe masculin. De ce fait, la compréhension des risques particuliers et des symptômes qu'éprouvent les femmes est limitée. Ces lacunes dans les connaissances posent particulièrement problème puisqu'à l'échelle mondiale la cardiopathie est la cause principale de décès chez les femmes. Jusqu'à récemment, la recherche en cardiologie, notamment la recherche préclinique et clinique, ne portait pas sur le sexe et le genre. Le recrutement souvent limité aux participants masculins et aux individus dont l'identité de genre correspond au sexe masculin et l'absence d'analyses de données en fonction du sexe ou du genre ont eu pour conséquence un manque de données sur la façon dont les traitements et les interventions nuisent aux patientes féminines et aux individus dont l'identité de genre correspond au sexe féminin, et ce, de façon différente. Cette absence de données a mené à un traitement sous-optimal et à des limites de notre compréhension des mécanismes sous-jacents de la cardiopathie chez les femmes, et est directement reliée à nos connaissances limitées, et à nos lacunes en formation professionnelle et en éducation du public. Le fait que les femmes ne connaissent souvent pas leurs facteurs de risque de maladies du cœur ou les symptômes qu'elles peuvent éprouver entraîne des retards de diagnostic et de traitements. De plus, le fait que les prestataires de soins de santé ne reçoivent pas la formation adéquate pour poser le diagnostic et traiter la cardiopathie chez les femmes les mène à poser un mauvais diagnostic ou à ne pas traiter suffisamment. Pour pallier ces lacunes de connaissances, il faut une approche à plusieurs volets, qui porte notamment sur l'éducation et les changements dans les politiques, et qui repose sur la recherche fondée sur des données probantes. Dans ce chapitre, nous passons en revue l'état actuel de la recherche existante sur les maladies cardiovasculaires au Canada, plus particulièrement chez les femmes.

The Canadian Women's Heart Health Alliance ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women - Chapter 9: Summary of Current Status, Challenges, Opportunities, and Recommendations.

This final chapter of the Canadian Women's Heart Health Alliance "ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women" presents ATLAS highlights from the perspective of current status, challenges, and opportunities in cardiovascular care for women. We conclude with 12 specific recommendations for actionable next steps to further the existing progress that has been made in addressing these knowledge gaps by tackling the remaining outstanding disparities in women's cardiovascular care, with the goal to improve outcomes for women in Canada.

Dans ce chapitre final de l'ATLAS sur l'épidémiologie, le diagnostic et la prise en charge de la maladie cardiovasculaire chez les femmes de l'Alliance canadienne de santé cardiaque pour les femmes, nous présentons les points saillants de l'ATLAS au sujet de l'état actuel des soins cardiovasculaires offerts aux femmes, ainsi que des défis et des occasions dans ce domaine. Nous concluons par 12 recommandations concrètes sur les prochaines étapes à entreprendre pour donner suite aux progrès déjà réalisés afin de combler les lacunes dans les connaissances, en s'attaquant aux disparités qui subsistent dans les soins cardiovasculaires prodigués aux femmes, dans le but d'améliorer les résultats de santé des femmes au Canada.

Performance of Computed Tomographic Angiography-Based Aortic Valve Area for Assessment of Aortic Stenosis.

Background A total of 40% of patients with severe aortic stenosis (AS) have low-gradient AS, raising uncertainty about AS severity. Aortic valve calcification, measured by computed tomography (CT), is guideline-endorsed to aid in such cases. The performance of different CT-derived aortic valve areas (AVAs) is less well studied. Methods and Results Consecutive adult patients with presumed moderate and severe AS based on echocardiography (AVA measured by continuity equation on echocardiography <1.5 cm2) who underwent cardiac CT were identified retrospectively. AVAs, measured by direct planimetry on CT (AVACT) and by a hybrid approach (AVA measured in a hybrid manner with echocardiography and CT [AVAHybrid]), were measured. Sex-specific aortic valve calcification thresholds (≥1200 Agatston units in women and ≥2000 Agatston units in men) were applied to adjudicate severe or nonsevere AS. A total of 215 patients (38.0% women; mean±SD age, 78±8 years) were included: normal flow, 59.5%; and low flow, 40.5%. Among the different thresholds for AVACT and AVAHybrid, diagnostic performance was the best for AVACT <1.2 cm2 (sensitivity, 85%; specificity, 26%; and accuracy, 72%), with no significant difference by flow status. The percentage of patients with correctly classified AS severity (correctly classified severe AS+correctly classified moderate AS) was as follows; AVA measured by continuity equation on echocardiography <1.0 cm2, 77%; AVACT <1.2 cm2, 73%; AVACT <1.0 cm2, 58%; AVAHybrid <1.2 cm2, 59%; and AVAHybrid <1.0 cm2, 45%. AVACT cut points of 1.52 cm2 for normal flow and 1.56 cm2 for low flow, provided 95% specificity for excluding severe AS. Conclusions CT-derived AVAs have poor discrimination for AS severity. Using an AVACT <1.2-cm2 threshold to define severe AS can produce significant error. Larger AVACT thresholds improve specificity.

Catheter-Induced Postextrasystolic Potentiation in the Assessment of Severity of Low-Gradient Aortic Valve Stenosis.

BACKGROUND: Deciphering which patients with low-gradient aortic valve disease have severe stenosis can be difficult. We aimed to correlate the postextrasystolic potentiation (PESP) with dobutamine stress echocardiography and multidetector computed tomography in patients with low-gradient aortic valve stenosis. METHODS: Patients with an aortic valve area ≤1 cm2 and a mean gradient <40 mm Hg were included. Aortic valve stenosis severity was assessed by a core lab with dobutamine stress echocardiography, followed by a multidetector computed tomography aortic valve score if indeterminate. A premature ventricular contraction was induced by intentional catheter contact with the myocardium within the left ventricle. PESP was calculated as a percent change of pre-to-post mean gradient. Multidetector computed tomography was used to measure the aortic valve calcification score, and subsequently, aortic valve calcification density. RESULTS: Twenty-eight patients (age, 77±10 years; 19 female) were included. Dobutamine stress echocardiography increased mean gradient from baseline of 25±7 mm Hg to 36±11 mm Hg; pre-premature ventricular contraction mean gradient was 25±7 mm Hg and increased to post-premature ventricular contraction mean gradient of 32±10 mm Hg, representing a PESP of 24±11%. A ≥20% in PESP resulted in 100% sensitivity, 77% specificity, 83% positive predictive value, and 100% negative predictive value for diagnosing severe aortic valve stenosis. There was a significant correlation between PESP and projected aortic valve area and aortic valve calcification density (R=-0.64, P=0.0003; R=0.057, P=0.014, respectively). CONCLUSIONS: In patients with low-gradient aortic valve stenosis, catheter-induced premature ventricular contractions during cardiac catheterization causing ≥20% PESP has a 100% sensitivity for severe aortic valve stenosis. Validation of this 20% cutoff in larger groups with correlation to clinical end points is required.

The Canadian Women's Heart Health Alliance Atlas on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women - Chapter 6: Sex- and Gender-Specific Diagnosis and Treatment.

This chapter summarizes the sex- and gender-specific diagnosis and treatment of acute/unstable presentations and nacute/stable presentations of cardiovascular disease in women. Guidelines, scientific statements, systematic reviews/meta-analyses, and primary research studies related to diagnosis and treatment of coronary artery disease, cerebrovascular disease (stroke), valvular heart disease, and heart failure in women were reviewed. The evidence is summarized as a narrative, and when available, sex- and gender-specific practice and research recommendations are provided. Acute coronary syndrome presentations and emergency department delays are different in women than they are in men. Coronary angiography remains the gold-standard test for diagnosis of obstructive coronary artery disease. Other diagnostic imaging modalities for ischemic heart disease detection (eg, positron emission tomography, echocardiography, single-photon emission computed tomography, cardiovascular magnetic resonance, coronary computed tomography angiography) have been shown to be useful in women, with their selection dependent upon both the goal of the individualized assessment and the testing resources available. Noncontrast computed tomography and computed tomography angiography are used to diagnose stroke in women. Although sex-specific differences appear to exist in the efficacy of standard treatments for diverse presentations of acute coronary syndrome, many cardiovascular drugs and interventions tested in clinical trials were not powered to detect sex-specific differences, and knowledge gaps remain. Similarly, although knowledge is evolving about sex-specific difference in the management of valvular heart disease, and heart failure with both reduced and preserved ejection fraction, current guidelines are lacking in sex-specific recommendations, and more research is needed.

Ce chapitre présente un résumé sur le diagnostic et le traitement des tableaux cliniques aigus/instables et non aigus/stables des maladies cardiovasculaires chez les femmes, et les différences propres à chacun des deux sexes. Les lignes directrices, les énoncés scientifiques, les revues systématiques/méta-analyses et les études de recherche originale sur le diagnostic et le traitement des coronaropathies, des maladies vasculaires cérébrales (AVC), des valvulopathies cardiaques et de l'insuffisance cardiaque chez les femmes ont été examinés. Les données probantes sont résumées sous forme narrative et, lorsqu'elles sont disponibles, des recommandations en matière de pratique et de recherche pour chacun des deux sexes sont présentées. Les tableaux cliniques du syndrome coronarien aigu et les délais d'attente à l'urgence sont différents selon qu'une femme ou un homme en est atteint. L'angiographie coronarienne reste l'examen de référence pour le diagnostic des coronaropathies obstructives. D'autres examens d'imagerie diagnostique (p. ex. la tomographie par émission de positons, l'échocardiographie, la tomographie d'émission à photon unique, la résonance magnétique cardiovasculaire, l'angiographie coronarienne par tomodensitométrie) se sont avérés utiles pour la détection des cardiopathies ischémiques chez les femmes. Le recours à ces modalités dépend de l'objectif de l'évaluation personnalisée et des ressources disponibles. La tomodensitométrie sans agent de contraste et l'angiographie par tomodensitométrie sont utilisées pour le diagnostic des AVC chez les femmes. Malgré les différences entre les sexes quant à l'efficacité des traitements de référence des divers tableaux cliniques du syndrome coronarien aigu, bon nombre des médicaments et des interventions cardiovasculaires qui ont fait l'objet d'essais cliniques n'avaient pas la puissance statistique nécessaire pour détecter des différences selon les sexes, de sorte que les connaissances restent fragmentaires sur ce sujet. De même, malgré l'évolution des connaissances sur les différences sexuelles quant à la prise en charge des valvulopathies cardiaques et de l'insuffisance cardiaque avec fraction d'éjection réduite ou préservée, on ne trouve pas de recommandations pour chaque sexe dans les lignes directrices actuelles, d'où la pertinence d'études supplémentaires portant sur cette question.

The Canadian Women's Heart Health Alliance Atlas on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women - Chapter 5: Sex- and Gender-Unique Manifestations of Cardiovascular Disease.

This Atlas chapter summarizes sex- and some gender-associated, and unique aspects and manifestations of cardiovascular disease (CVD) in women. CVD is the primary cause of premature death in women in Canada and numerous sex-specific differences related to symptoms and pathophysiology exist. A review of the literature was done to identify sex-specific differences in symptoms, pathophysiology, and unique manifestations of CVD in women. Although women with ischemic heart disease might present with chest pain, the description of symptoms, delay between symptom onset and seeking medical attention, and prodromal symptoms are often different in women, compared with men. Nonatherosclerotic causes of angina and myocardial infarction, such as spontaneous coronary artery dissection are predominantly identified in women. Obstructive and nonobstructive coronary artery disease, aortic aneurysmal disease, and peripheral artery disease have worse outcomes in women compared with men. Sex differences exist in valvular heart disease and cardiomyopathies. Heart failure with preserved ejection fraction is more often diagnosed in women, who experience better survival after a heart failure diagnosis. Stroke might occur across the lifespan in women, who are at higher risk of stroke-related disability and age-specific mortality. Sex- and gender-unique differences exist in symptoms and pathophysiology of CVD in women. These differences must be considered when evaluating CVD manifestations, because they affect management and prognosis of cardiovascular conditions in women.

Dans le présent chapitre d'Atlas sont récapitulés les aspects et les manifestations uniques, associés au sexe et certains associés au genre, des maladies cardiovasculaires (MCV) chez les femmes. Les MCV sont la cause principale de décès prématurés chez les femmes au Canada. De nombreuses différences quant aux symptômes et à la physiopathologie existent entre les sexes. Nous avons réalisé une revue de la littérature pour déterminer les différences entre les sexes dans les symptômes et la physiopathologie, et les manifestations uniques des MCV chez les femmes. Bien que les femmes atteintes d'une cardiopathie ischémique puissent éprouver des douleurs thoraciques, la description des symptômes, le délai entre l'apparition des symptômes et l'obtention de soins médicaux, et les symptômes prodromiques sont souvent différents de ceux des hommes. Les causes de l'angine et de l'infarctus du myocarde non liées à l'athérosclérose telles que la dissection spontanée de l'artère coronaire sont principalement observées chez les femmes. La coronaropathie obstructive et non obstructive, l'anévrisme aortique et la maladie artérielle périphérique montrent de plus mauvaises issues chez les femmes que chez les hommes. Des différences entre les sexes sont observées dans la cardiopathie valvulaire et les cardiomyopathies. Le diagnostic d'insuffisance cardiaque avec fraction d'éjection préservée est plus souvent posé chez les femmes qui présentent un meilleur taux de survie après un diagnostic d'insuffisance cardiaque. L'accident vasculaire cérébral (AVC) pourrait survenir tout au long de la vie des femmes, qui sont exposées à un risque plus élevé d'incapacités liées à l'AVC et de mortalité par âge. Il existe des différences uniques entre les sexes et les genres pour ce qui est des symptômes et de la physiopathologie des MCV chez les femmes. Lors de l'évaluation des manifestations des MCV, il faut tenir compte de ces différences puisqu'elles influencent la prise en charge et le pronostic des maladies cardiovasculaires chez les femmes.

The Canadian Women's Heart Health Alliance ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women-Chapter 2: Scope of the Problem.

BACKGROUND: This Atlas chapter summarizes the epidemiology of cardiovascular disease (CVD) in women in Canada, discusses sex and gender disparities, and examines the intersectionality between sex and other factors that play a prominent role in CVD outcomes in women, including gender, indigenous identity, ethnic variation, disability, and socioeconomic status. METHODS: CVD is the leading cause of premature death in Canadian women. Coronary artery disease, including myocardial infarction, and followed by stroke, accounts for the majority of CVD-related deaths in Canadian women. The majority of emergency department visits and hospitalizations by women are due to coronary artery disease, heart failure, and stroke. The effect of traditional cardiovascular risk factors and their association with increasing cardiovascular morbidity is unique in this group. RESULTS: Indigenous women in Canada experience increased CVD, linked to colonization and subsequent social, economic, and political challenges. Women from particular racial and ethnic backgrounds (ie, South Asian, Afro-Caribbean, Hispanic, and Chinese North American women) have greater CVD risk factors, and CVD risk in East Asian women increases with duration of stay in Canada. CONCLUSIONS: Canadians living in northern, rural, remote, and on-reserve residences experience greater CVD morbidity, mortality, and risk factors. An increase in CVD risk among Canadian women has been linked with a background of lower socioeconomic status, and women with disabilities have an increased risk of adverse cardiac events.

CONTEXTE: Ce chapitre de l'Atlas condense l'épidémiologie des maladies cardiovasculaires (MCV) chez les femmes au Canada, aborde les disparités entre les sexes et les genres, et examine l'interrelation entre le sexe et d'autres facteurs qui jouent un rôle important dans l'émergence des MCV chez les femmes, notamment le genre, l'identité autochtone, les variations ethniques, le handicap et le statut socio-économique. MÉTHODES: Les MCV sont la principale cause de décès prématuré chez les femmes canadiennes. Les maladies coronariennes, y compris l'infarctus du myocarde, suivies des accidents vasculaires cérébraux, sont à l'origine de la majorité des décès liés aux MCV chez les femmes canadiennes. La majorité des visites aux urgences et des hospitalisations des femmes sont dues à des maladies coronariennes, des insuffisances cardiaques et des accidents vasculaires cérébraux. L'effet des facteurs de risque cardiovasculaire traditionnels et leur association avec l'augmentation de la morbidité cardiovasculaire est unique dans ce groupe. RÉSULTATS: Les femmes autochtones du Canada connaissent un accroissement des maladies cardiovasculaires, liée à la colonisation et aux défis sociaux, économiques et politiques qui en découlent. Les femmes d'origines raciales et ethniques spécifiques (par exemple les femmes sud-asiatiques, afro-caribéennes, hispaniques et chinoises d'Amérique du Nord) présentent des facteurs de risque de MCV plus importants, et le risque de MCV chez les femmes d'Asie de l'Est augmente avec la durée de leur séjour au Canada. CONCLUSIONS: Les canadiens qui vivent dans les régions nordiques, rurales, éloignées et dans les réserves présentent une morbidité, une mortalité et des facteurs de risque de MCV plus élevés. L'augmentation du risque de MCV chez les femmes canadiennes a été associée à un statut socio-économique plus bas, et les femmes handicapées ont un risque accru de survenue d'événements cardiaques indésirables.

Contrast-enhanced computed tomography assessment of aortic stenosis.

OBJECTIVES: Non-contrast CT aortic valve calcium scoring ignores the contribution of valvular fibrosis in aortic stenosis. We assessed aortic valve calcific and non-calcific disease using contrast-enhanced CT. METHODS: This was a post hoc analysis of 164 patients (median age 71 (IQR 66-77) years, 78% male) with aortic stenosis (41 mild, 89 moderate, 34 severe; 7% bicuspid) who underwent echocardiography and contrast-enhanced CT as part of imaging studies. Calcific and non-calcific (fibrosis) valve tissue volumes were quantified and indexed to annulus area, using Hounsfield unit thresholds calibrated against blood pool radiodensity. The fibrocalcific ratio assessed the relative contributions of valve fibrosis and calcification. The fibrocalcific volume (sum of indexed non-calcific and calcific volumes) was compared with aortic valve peak velocity and, in a subgroup, histology and valve weight. RESULTS: Contrast-enhanced CT calcium volumes correlated with CT calcium score (r=0.80, p<0.001) and peak aortic jet velocity (r=0.55, p<0.001). The fibrocalcific ratio decreased with increasing aortic stenosis severity (mild: 1.29 (0.98-2.38), moderate: 0.87 (1.48-1.72), severe: 0.47 (0.33-0.78), p<0.001) while the fibrocalcific volume increased (mild: 109 (75-150), moderate: 191 (117-253), severe: 274 (213-344) mm3/cm2). Fibrocalcific volume correlated with ex vivo valve weight (r=0.72, p<0.001). Compared with the Agatston score, fibrocalcific volume demonstrated a better correlation with peak aortic jet velocity (r=0.59 and r=0.67, respectively), particularly in females (r=0.38 and r=0.72, respectively). CONCLUSIONS: Contrast-enhanced CT assessment of aortic valve calcific and non-calcific volumes correlates with aortic stenosis severity and may be preferable to non-contrast CT when fibrosis is a significant contributor to valve obstruction.

Effect of Regional Upper Septal Hypertrophy on Echocardiographic Assessment of Left Ventricular Mass and Remodeling in Aortic Stenosis.

BACKGROUND: Transthoracic echocardiography (TTE) is the reference method for evaluation of aortic stenosis (AS), and it is extensively used to quantitate left ventricular (LV) mass and volumes. Regional upper septal hypertrophy (USH) or septal bulge is a frequent finding in patients with AS and may lead to overestimation of LV mass when using linear measurements. The objective of this study was to compare estimates of LV mass obtained by two-dimensional transthoracic echocardiographic LV dimensions measured at different levels of the LV cavity with those obtained by cardiovascular magnetic resonance (CMR). METHODS: One hundred six patients (mean age, 63 ± 15 years; 68% men) with AS were included in this subanalysis of the PROGRESSA study. Two-dimensional transthoracic echocardiographic measurements of LV dimensions were obtained at the basal level (BL; as recommended in guidelines), immediately below the septal bulge (BSB), and at a midventricular level (ML). Regional USH was defined as a basal interventricular septal thickness ≥ 13 mm and >1.3 times the thickness of the septal wall at the ML. Agreement between transthoracic echocardiographic and CMR measures was evaluated using Bland-Altman analysis. RESULTS: The distribution of AS severity was mild in 23%, moderate in 57%, and severe in 20% of patients. Regional USH was present in 28 patients (26%). In the whole cohort, two-dimensional TTE overestimated LV mass (bias: BL, +60 ± 31 g; BSB, +59 ± 32 g; ML, +54 ± 32 g; P = .02). The biplane Simpson method slightly but significantly underestimated LV end-diastolic volume (bias -10 ± 20 mL, P < .001) compared with CMR. Overestimation of LV mass was more marked in patients with USH when measuring at the BL and was significantly lower when measuring LV dimensions at the ML (P < .025 vs BL and BSB). CONCLUSIONS: Two-dimensional TTE systematically overestimated LV mass and underestimated LV volumes compared with CMR. However, the bias between TTE and CMR was less important when measuring at the ML. Measurements at the BL as suggested in guidelines should be avoided, and measurements at the ML should be preferred in patients with AS, especially in those with USH.

Sex-differences in echocardiographic assessment of aortic valve in young adult LDLr-/-/ApoB100/100/IGF-II+/- mice.

BACKGROUND: LDLr-/-/ApoB100/100/IGF-II+/- mice are used as a calcific aortic valve disease (CAVD) model. However, normal aortic valve hemodynamics i.e. remotely from CAVD onset and the sex-related differences are poorly known. METHODS AND RESULTS: Four groups of mice, intact males (IM, n = 49) and females (IF, n = 50), castrated males (CxM, n = 79) and ovariectomized females (OxF: 73), underwent a Doppler-echocardiography at 12 weeks of age. Gonadectomy was performed at 8 weeks. Aortic valve assessment using effective orifice area (EOA, using the continuity equation) and peak aortic transvalvular velocity (VPeak) was feasible in 89% of the mice with good to excellent reliability (intraclass correlation coefficients ranging from 0.90 to 0.98, p < 0.001). Mean VPeak was 104 ± 17 cm/s and mean EOA was 1.18*10-2 ± 0.22*10-2 cm2. EOA indexed to body surface area was 1.5 ± 0.3 cm2/m2. The 95th percentile of Vpeak was 132 cm/s and the 5th percentile of indexed EOA was 1.0 cm2/m2. Interestingly, IM had the highest VPeak (114 ± 14 cm/s) vs each of the other groups (CxM: 106 ± 19 cm/s, OxF: 97 ± 13 cm/s and IF: 96 ± 12 cm/s, ANOVA and corrected p < 0.001). This was mostly explained by a higher stroke volume (ANOVA and corrected p < 0.001) in IM compared to other groups. There were no major sex-differences in ventricular systolic function parameters. CONCLUSION: In LDLr-/-/ApoB100/100/IGF-II CAVD mice model, an aortic EOA <0.8*10-2 cm2 (or indexed EOA <1.0cm2/m2), and a peak aortic valve velocity > 132 cm/s may be proposed as thresholds to define CAVD. Intact male mice appear to have higher velocities.

Age, Sex, and Valve Phenotype Differences in Fibro-Calcific Remodeling of Calcified Aortic Valve.

Background In calcific aortic valve disease on tricuspid aortic valves (TAVs), men have higher aortic valve calcification and less fibrosis than women. However, little is known in bicuspid aortic valves (BAV). We thus aimed to investigate the impact of age, sex, and valve phenotype (TAVs versus BAVs) on fibro-calcific remodeling in calcific aortic valve disease. Methods and Results We included 2 cohorts: 411 patients who underwent multidetector computed tomography (37% women) for aortic valve calcification density assessment and 138 explanted aortic valves (histological cohort; 50% women). The cohorts were divided in younger (<60 years old) or older patients with BAV (≥60 years old), and TAV patients. In each group, women and men were matched. Women presented less aortic valve calcification density than men in each group of the multidetector computed tomography cohort (all P≤0.01). Moreover, in women, younger patients with BAV had the lowest aortic valve calcification density (both P=0.02). In multivariate analysis, aortic valve calcification density correlated with age (ß estimate±standard error: 6.5±1.8; P=0.0004) and male sex (109.2±18.4; P<0.0001), and there was a trend with TAVs (41.5±23.0; P=0.07). Women presented a higher collagen content than men (77.8±10.8 versus 69.9±12.9%; P<0.001) in the entire cohort. In women, younger patients with BAV had denser connective tissue than TAV and older patients with BAV (both P≤0.05), while no difference was observed between men. Conclusions In calcific aortic valve disease, women had less calcification and more fibrotic remodeling than men, regardless of the phenotype of the valve or age of the patient. Moreover, younger women with BAVs had less valve calcification. Thus, mineralization/fibrosis of the aortic valve is likely to have sex/age-specific mechanisms and be influenced by the valve morphology.

Characteristics and usefulness of unintended premature ventricular contraction during invasive assessment of aortic stenosis.

BACKGROUND: Postextrasystolic potentiation (PESP)-associated augmentation in left ventricular-aorta pressure gradient (LVAoG) observed after incidental premature ventricular contraction (PVC) during resting echocardiography is similar to dobutamine stress echocardiography (DSE)-associated augmentation in LVAoG in patients with low-flow, low-gradient (LF-LG) aortic stenosis (AS). What is not known is whether a similar relationship exists when unintended PVC causes PESP during cardiac catheterization in patients with AS. METHODS: We retrospectively reviewed all catheterizations performed for patients with at least moderate AS who had LVAoG assessment. Univariate and multivariate analyses were conducted to determine the predictors of pre- and post-PVC mean LVAoG ≥ 40 mmHg. RESULTS: Between September 2015 to September 2017, of 140 individuals undergoing cardiac catheterization, 34 met study criteria. Mean pre-PVC gradient was 38.9 ± 22.8 mmHg. All patients exhibited PESP-associated augmentation of LVAoG by an average of 28 ± 12%. In multivariate analysis, the only significant predictor of post-PVC mean LVAoG ≥ 40 mmHg was preserved LV function (OR 6.81; 95% CI 1.41-32.82, p = 0.02). Inability to generate ≥ 40 mmHg of mean LVAoG post-PVC had 100% specificity for nonsevere AS in our observational cohort. CONCLUSIONS: Unintended but interpretable PVCs occurred in one in four patients with AS undergoing cardiac catheterization with measurable hemodynamics. All of our patients with PVCs, regardless of underlying LVEF, exhibited PESP-associated augmentation of LVAoG. Our exploratory analysis suggests that inability to generate ≥40 mmHg of mean LVAoG post-PVC is highly specific for nonsevere AS.

Sex-Related Differences in the Extent of Myocardial Fibrosis in Patients With Aortic Valve Stenosis.

OBJECTIVES: The aim of this study was to assess the effect of sex on myocardial fibrosis as assessed by using cardiac magnetic resonance (CMR) imaging in aortic stenosis (AS). BACKGROUND: Previous studies reported sex-related differences in the left ventricular (LV) remodeling response to pressure overload in AS. However, there are very few data regarding the effect of sex on myocardial fibrosis, a key marker of LV decompensation and adverse cardiac events in AS. METHODS: A total of 249 patients (mean age 66 ± 13 years; 30% women) with at least mild AS were recruited from 2 prospective observational cohort studies and underwent comprehensive Doppler echocardiography and CMR examinations. On CMR, T1 mapping was used to quantify extracellular volume (ECV) fraction as a marker of diffuse fibrosis, and late gadolinium enhancement (LGE) was used to assess focal fibrosis. RESULTS: There was no difference in age between women and men (age 66 ± 15 years vs 66 ± 12 years; p = 0.78). However, women presented with a better cardiovascular risk profile than men with less hypertension, dyslipidemia, diabetes, and coronary artery disease (all, p ≤ 0.10). As expected, LV mass index measured by CMR imaging was smaller in women than in men (p < 0.0001). Despite fewer comorbidities, women presented with larger ECV fraction (median: 29.0% [25th to 75th percentiles: 27.4% to 30.6%] vs. 26.8% [25th to 75th percentiles: 25.1% to 28.7%]; p < 0.0001) and similar LGE (median: 4.5% [25th-75th percentiles: 2.3% to 7.0%] vs. 2.8% [25th-75th percentiles: 0.6% to 6.8%]; p = 0.20) than men. In multivariable analysis, female sex remained an independent determinant of higher ECV fraction and LGE (all, p ≤ 0.05). CONCLUSIONS: Women have greater diffuse and focal myocardial fibrosis independent of the degree of AS severity. These findings further emphasize the sex-related differences in LV remodeling response to pressure overload.

Assessment of Aortic Stenosis Severity: A Multimodality Approach.

Severe aortic stenosis (AS) is associated with a progressive cardiac remodeling that ultimately leads to heart failure and death if the valve is not replaced. The confirmation of AS severity is therefore crucial to adequately manage patients with AS. Transthoracic echocardiography is the first-line examination to confirm AS severity, but it may be inconclusive in discordant cases. In this setting, AS severity should be confirmed using a multimodality imaging approach. This review gives an overview of how to assess and/or confirm AS severity, especially in case of discordance.

Incidence, risk factors, clinical impact, and management of bioprosthesis structural valve degeneration.

PURPOSE OF REVIEW: Structural valve deterioration is the major cause of bioprosthesis failure and is increasing over time. We present an overview of incidence, mechanisms, predictors, clinical impact, and management of bioprosthetic valve structural degeneration. RECENT FINDINGS: Early degeneration caused by calcification and destruction of connective tissue of the prosthesis is controlled by multiple mechanisms, from mechanical stress to infiltration of lipids and inflammatory cells, and activation of the immune system. Despite major improvements in valve design and surgical procedures, the pathology is still the main limiting factor to the long-term durability. Appropriate selection of the model and size of bioprosthesis as well as proper medical management and follow-up after valve replacement are essential for optimal prevention, detection, and management of structural valve deterioration. Currently, redo open-heart surgery is the most frequently used approach to treat structural valve deterioration. The transcatheter valve-in-valve procedure, however, is a valuable alternative to surgery for high-risk patients. SUMMARY: Structural valve deterioration is responsible for significant morbidity and mortality after valve replacement. This multifactorial pathology is the main cause of valve re-intervention during follow-up. Although redo surgery is still the most frequently used intervention to treat valve structural failure, the transcatheter valve-in-valve procedure is rapidly expanding.