Sex and Gender Aspects in Vascular Ageing - Focus on Epidemiology, Pathophysiology, and Outcomes.

Sex and gender are important modifiers of cardiovascular system physiology, pathophysiology, and disease development. The atherosclerosis process, together with the progressive loss of arterial elasticity with age, is a major factor influencing the development of overt cardiovascular, renal, and cerebrovascular disease. While differences between women and men in epidemiology and pathophysiology of vascular ageing are increasingly reported, sex-disaggregated data are still scarcely available for prospective studies. A better knowledge of sex differences in physiological ageing as well as in disease-related changes in vascular ageing trajectories is crucial to avoid misdiagnosis and mistreatment. This review presents key concepts and knowledge gaps identified in vascular ageing due to gonadal function, vascular physiology, pathophysiology, psychosocial factors, pregnancy, and prognostic relevance. Gender roles determine the effectiveness of any cardiovascular preventive strategy and acceptance for non-invasive or invasive diagnostics and therapeutics. Gender differences in health behaviour, also due to sociocultural norms conditioned by society, contribute to behaviours that may lead to premature arterial vascular ageing. These include differences in risk behaviours like smoking, diet, exercise, and in stress, but also conditions such as housing, noise pollution, poverty, disability, and any kind of stigmatisation. The VascAgeNet Gender Expert Group aims to advance the use of non-invasive vascular ageing measures in routine clinical settings by providing facts to fill in the gaps concerning sex and gender differences at each step of this process, and to search for solutions.

Higher pulse pressure/stroke volume index is associated with impaired outcome in hypertensive patients with left ventricular hypertrophy the LIFE study.

We tested the prognostic impact of a marker of arterial stiffness, pulse pressure/stroke volume index (PP/SVi), in patients with hypertension and left ventricular (LV) hypertrophy. We used data from 866 patients randomized to losartan or atenolol-based antihypertensive treatment, over a median of 4.8 years, in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. The association of PP/SVi with outcomes was tested in Cox regression analyses and reported as hazard ratio (HR) and 95% confidence intervals (CI). In multivariate regression, reduction of PP/SVi was independently associated with male gender, reduction in systolic blood pressure (BP) and relative wall thickness and with an increase in left ventricular ejection fraction (all p < .05). After adjusting for confounders, higher baseline PP/SVi predicted a 38% higher hazard of combined major fatal and non-fatal cardiovascular events (95% CI 1.04-1.84), and higher hazard of cardiovascular mortality (HR 2.35 (95% CI 1.59-3.48) and stroke (HR 1.45 (95% CI 1.06-1.99) (all p < .05). Higher PP/SVi also predicts higher rate of hospitalization for HF (HR 2.15 (95% CI 1.48-3.12) and a 52% higher hazard of all-cause mortality (95% CI 1.10-2.09) (both p < .05). In hypertensive patients with electrocardiographic LV hypertrophy, higher PP/SVi was associated with increased cardiovascular morbidity and mortality.

Giant right ventricular outflow tract thrombus in hereditary spherocytosis: a case report.

BACKGROUND: In hereditary spherocytosis with severe anemia, splenectomy is a recommended treatment. However, the spleen carries an important role both in immune function and coagulation. The increased risk of bacterial infections associated with splenectomy is well known. Recently, hypercoagulation disorders have also been linked to splenectomy through loss of regulation of platelet activity, loss of filtering function and post-splenectomy thrombocytosis. CASE PRESENTATION: A 28 year-old smoking women who had previously undergone splenectomy due to hereditary spherocytosis with a moderate thrombocytosis (platelet count 553-635*10(9)/L), presented with recurrent episodes of pulmonary embolisms. Further examination by multimodality cardiac imaging demonstrated a giant chronic thrombus in the right ventricular outflow tract, which eventually had to be surgically removed. CONCLUSIONS: The present case highlights the increased risk of severe thromboembolic complications following therapeutic splenectomy in hereditary spherocytosis, and emphasis the important role of multimodality cardiac imaging in recurrent pulmonary embolism, diagnosing a giant chronic thrombus in the right ventricular outflow tract.

The association of hypertension with asymptomatic cardiovascular organ damage in rheumatoid arthritis.

BACKGROUND: The association of hypertension with asymptomatic cardiovascular organ damage in patients with rheumatoid arthritis (RA) has been little studied by echocardiography. METHODS: Echocardiography was done in 134 RA patients and 102 healthy controls. Left ventricular (LV) geometry was considered abnormal if LV mass index or relative wall thickness was increased. LV diastolic dysfunction was considered present if septal early diastolic tissue velocity <8 cm/s. Systemic arterial compliance (SAC) was assessed from stroke volume index/pulse pressure ratio. RESULTS: The hypertensive RA patients (n = 72) had higher inflammatory activity, older age and more diabetes than the normotensive RA patients (n = 62) (all p < 0.05). Rates of abnormal LV geometry, LV diastolic dysfunction and lower SAC were higher among the hypertensive RA patients (p < 0.05), but similar between normotensive RA patients and controls. Hypertension was associated with a 3-fold higher prevalence both for abnormal LV geometry (odds ratio 2.89 [95% confidence interval 1.09-7.63], p = 0.03) and for diastolic LV dysfunction (odds ratio 2.92 [95% confidence interval 1.14-7.46], p = 0.03) as well as lower SAC (ß = 0.31, p = 0.001) independent of age, gender, diabetes and inflammatory activity measured by erythrocyte sedimentation rate. CONCLUSION: The presence of asymptomatic cardiovascular organ damage in RA patients is closely associated with hypertension independent of inflammatory activity.

Obesity-associated metabolic changes influence resting and peak heart rate in women and men.

OBJECTIVES: To study the relationship between obesity and heart rate (HR) in women and men. DESIGN: We studied 241 overweight and obese subjects without known heart disease. All subjects underwent ergospirometry during maximal exercise testing on treadmill and recording of body composition, electrocardiogram and clinic and ambulatory blood pressure. RESULTS: Women (n = 132) were slightly older and had higher fat mass, but lower weight, blood pressure and prevalence of metabolic syndrome (MetS) than men (n = 109) (all p < 0.05), while prevalences of obesity and hypertension did not differ. A significant interaction between sex and HR was demonstrated (p < 0.05). In multivariate analysis, female sex (ß = 0.99, p < 0.01) predicted higher resting HR independent of confounders. Higher resting HR was particularly associated with presence of MetS, hypertension, higher insulin resistance and lower relative muscle mass in men (all p < 0.05). Female sex also predicted higher peak exercise HR (ß = 0.48, p < 0.01) independent of confounders. Higher peak exercise HR was particularly associated with higher exercise capacity and lower age and self-reported physical activity in men, while lower HbA1c and absence of obesity were the main covariates in women in multivariate analyses (all p < 0.05). CONCLUSIONS: In our study population, obesity and obesity-associated metabolic changes influenced both resting and peak exercise HR.

Determinants of systolic blood pressure response during exercise in overweight subjects.

AIM: Higher systolic exercise blood pressure (BP) is associated with increased cardiovascular risk in hypertension. We aimed at identifying covariates of systolic exercise BP in overweight subjects. METHODS: 77 subjects with body mass index (BMI) > 27 kg/m(2) and without known heart disease were tested. BP was measured by sphygmomanometry before and at all exercise stages during maximal exercise capacity testing on a treadmill. High peak systolic exercise BP was defined as ≥ 200 mmHg. RESULTS: The study population was 48 ± 10 years and included 60% women and 42% with known hypertension. Average BMI was 32.6 ± 4.8 kg/m(2) and clinic BP 132/82 ± 17/8 mmHg. High systolic exercise BP was found in 32%. Subjects with high systolic exercise BP had higher systolic clinic and 24-h ambulatory BP (ABP), as well as lower peak oxygen uptake, compared with subjects with normal systolic exercise BP (all p < 0.05). In multiple regression analysis known hypertension (ß = 0.33), higher systolic ABP (ß = 0.22) and high-density lipoprotein (HDL)-cholesterol level (ß = 0.23, all p < 0.05) predicted higher systolic exercise BP independent of sex and peak oxygen uptake (multiple R(2) = 0.32, p < 0.001). CONCLUSION: Among overweight subjects, known hypertension, higher systolic ABP and HDL-cholesterol level were the most important factors predicting higher systolic exercise BP.

Impact of isolated systolic hypertension on normalization of left ventricular structure during antihypertensive treatment (the LIFE study).

OBJECTIVE: We tested the impact of isolated systolic hypertension (ISH) on normalization of left ventricular (LV) structure during antihypertensive treatment. METHODS: Baseline and annual echocardiograms were recorded in 873 hypertensive patients with electrocardiographic signs of LV hypertrophy during 4.8 years randomized losartan- or atenolol-based antihypertensive treatment in the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study and classified as having ISH (n = 128) if systolic BP ≥ 160 mmHg and diastolic BP < 90 mmHg, or non-ISH divided into two groups by systolic BP ≥ 160 mmHg (non-ISH ≥ 160 mmHg) (n = 645) and systolic BP < 160 mm Hg (n = 100) (non-ISH < 160 mmHg), respectively. RESULTS: Patients with ISH were older, with higher prevalence of diabetes than non-ISH groups and higher pulse pressure/stroke volume index (all p < 0.05). Baseline systolic blood pressure (BP) differed between groups and was highest in the non-ISH ≥ 160 mmHg group (p < 0.05). Systolic BP reduction was less in the ISH group (p < 0.05). LV geometry did not differ between ISH and non-ISH ≥ 160 mmHg groups at baseline, but ISH had more residual LV hypertrophy of concentric type at the last study visit (p < 0.05). In multivariate analysis, less reduction of LV mass was predicted by ISH (ß = - 0.07) independent of significant associations with baseline LVMi (ß = 0.52) and atenolol-based treatment (ß = - 0.08) and clinical confounders (all p < 0.05). CONCLUSIONS: ISH is associated with impaired normalization of LV mass during systematic antihypertensive treatment. The findings may help explain the higher cardiovascular event rate previously reported in ISH patients.

Compositional plaque progression in women and men with non-obstructive coronary artery disease.

Background: In coronary artery disease (CAD), plaque progression and plaque composition are associated with cardiovascular risk. Whether compositional plaque progression in non-obstructive CAD differs between women and men is less studied. Methods: We included 31 patients (42% women) with chronic non-obstructive CAD from the Norwegian Registry of Invasive Cardiology, undergoing serial coronary computed tomography angiography (CCTA) on clinical indication (median inter-scan interval 1.8 [1.5-2.2] years). We performed quantitative and qualitative plaque analysis of all coronary artery segments. Results: Women were older compared to men (65 ± 8 years vs. 55 ± 12 years, p = 0.019), while there was no difference in the prevalence of hypertension, diabetes, smoking or statin treatment between groups. At baseline, women had a higher total plaque burden, more calcified plaques, and less fibro-fatty and necrotic core plaques compared to men (all p < 0.05). During follow-up, men showed faster progression of fibro-fatty plaques (4.0 ± 5.4 % per year vs. -0.6 ± 3.1 % per year, p = 0.019) and a greater reduction of fibrous plaques (-7.3 ± 6.1 % per year vs. 2.1 ± 7.2 % per year, p = 0.003) compared to women even after age adjustment. At follow-up, total plaque burden remained higher in women compared to men (24.9 ± 3.3 % vs. 21.1 ± 2.6 %, p = 0.001), while men had an increase in fibro-fatty (21.2 ± 9.3 % vs. 28.6 ± 9.8 %, p = 0.004) and necrotic core plaques (5.6 ± 3.6 % vs. 10.8 ± 7.2 %, p = 0.006), and a decrease in fibrous plaques (69.0 ± 11.9 % vs. 54.7 ± 13.7 %, p < 0.001). Women's plaque composition remained unaltered. Conclusion: In non-obstructive CAD, serial CCTA demonstrated a higher total plaque burden and a stable plaque composition in women, while men had a faster progression of unstable low-attenuating fibro-fatty plaques.Clinical trial registration: ClinicalTrials.gov: Identifier NCT04009421.

Developing technologies to assess vascular ageing: a roadmap from VascAgeNet.

Vascular ageing is the deterioration of arterial structure and function which occurs naturally with age, and which can be accelerated with disease. Measurements of vascular ageing are emerging as markers of cardiovascular risk, with potential applications in disease diagnosis and prognosis, and for guiding treatments. However, vascular ageing is not yet routinely assessed in clinical practice. A key step towards this is the development of technologies to assess vascular ageing. In this Roadmap, experts discuss several aspects of this process, including: measurement technologies; the development pipeline; clinical applications; and future research directions. The Roadmap summarises the state of the art, outlines the major challenges to overcome, and identifies potential future research directions to address these challenges.

Magnetic Resonance Imaging and Computed Tomography for the Noninvasive Assessment of Arterial Aging: A Review by the VascAgeNet COST Action.

Magnetic resonance imaging and computed tomography allow the characterization of arterial state and function with high confidence and thus play a key role in the understanding of arterial aging and its translation into the clinic. Decades of research into the development of innovative imaging sequences and image analysis techniques have led to the identification of a large number of potential biomarkers, some bringing improvement in basic science, others in clinical practice. Nonetheless, the complexity of some of these biomarkers and the image analysis techniques required for their computation hamper their widespread use. In this narrative review, current biomarkers related to aging of the aorta, their founding principles, the sequence, and postprocessing required, and their predictive values for cardiovascular events are summarized. For each biomarker a summary of reference values and reproducibility studies and limitations is provided. The present review, developed in the COST Action VascAgeNet, aims to guide clinicians and technical researchers in the critical understanding of the possibilities offered by these advanced imaging modalities for studying the state and function of the aorta, and their possible clinically relevant relationships with aging.

Epicardial adipose tissue volume, plaque vulnerability and myocardial ischemia in non-obstructive coronary artery disease.

Background: Epicardial adipose tissue (EAT) accumulation has been associated with inflammation, atherosclerosis and microvascular dysfunction. Whether increased EAT volume is associated with coronary plaque vulnerability and demand myocardial ischemia in patients with non-obstructive coronary artery disease (CAD) is less explored. Methods: In 125 patients (median age 63[58, 69] years and 58% women) with chest pain and non-obstructive CAD, EAT volume was quantified on non-contrast cardiac CT images. EAT volume in the highest tertile (>125 ml) was defined as high EAT volume. Total coronary plaque volume and plaque vulnerability were quantified by coronary CT angiography (CCTA). Demand myocardial ischemia was detected by contrast dobutamine stress echocardiography. Results: High EAT volume was more common in men and associated with higher BMI, hypertension, increased left ventricular mass index (LVMi), C-reactive protein (CRP) and positive remodelling (all p < 0.05). There was no difference in age, coronary calcium score, total and non-calcified plaque volume or presence of demand myocardial ischemia between groups (all p ≥ 0.34). In a multivariable model, obesity (p = 0.006), hypertension (p = 0.007) and LVMi (p = 0.016) were independently associated with high EAT volume. Including plaque vulnerability in an alternative model, positive remodelling (p = 0.038) was independently associated with high EAT volume. Conclusion: In non-obstructive CAD, high EAT volume was associated with cardiometabolic risk factors, inflammation and plaque vulnerability, while there was no association with demand myocardial ischemia or coronary plaque volume. Following our results, the role of EAT volume as a biomarker in non-obstructive CAD remains unclear.

Vascular function in hypertension: does gender dimension matter?

Blood pressure and vascular ageing trajectories differ between men and women. These differences develop due to sex-related factors, attributable to sex chromosomes or sex hormones, and due to gender-related factors, mainly related to different sociocultural behaviors. The present review summarizes the relevant facts regarding gender-related differences in vascular function in hypertension. Among sex-related factors, endogenous 17ß-estradiol plays a key role in protecting pre-menopausal women from vascular ageing. However, as vascular ageing (preceding and inducing hypertension) has a steeper increase in women than in men starting already from the third decade, it is likely that gender-related factors play a prominent role, especially in the young. Among gender-related factors, psychological stress (including that one related to gender-based violence and discrimination), depression, some psychological traits, but also low socioeconomic status, are more common in women than men, and their impact on vascular ageing is likely to be greater in women. Men, on the contrary, are more exposed to the vascular adverse consequences of alcohol consumption, as well as of social deprivation, while "toxic masculinity" traits may result in lower adherence to lifestyle and preventive strategies. Unhealthy diet habits are more prevalent in men and smoking is equally prevalent in the two sexes, but have a disproportional negative effect on women's vascular health. In conclusion, given the major and complex role of gender-related factors in driving vascular alterations and blood pressure patterns, gender dimension should be systematically integrated into future research on vascular function and hypertension and to tailor cardiovascular prevention strategies.

Global left ventricular load in asymptomatic aortic stenosis: covariates and prognostic implication (the SEAS trial).

INTRODUCTION: Valvuloarterial impedance (Zva) is a measure of global (combined valvular and arterial) load opposing left ventricular (LV) ejection in aortic stenosis (AS). The present study identified covariates and tested the prognostic significance of global LV load in patients with asymptomatic AS. METHODS: 1418 patients with mild-moderate, asymptomatic AS in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study were followed for a mean of 43±14 months during randomized, placebo-controlled treatment with combined simvastatin 40 mg and ezetimibe 10 mg daily. High global LV load was defined as Zva >5 mm Hg/ml/m2. The impact of baseline global LV load on rate of major cardiovascular (CV) events, aortic valve events and total mortality was assessed in Cox regression models reporting hazard ratio (HR) and 95% Confidence Intervals (CI). RESULTS: High global LV load was found in 18% (n=252) of patients and associated with female gender, higher age, hypertension, more severe AS and lower ejection fraction (all p<0.05). A total of 476 major CV events, 444 aortic valve events and 132 deaths occurred during follow-up. In multivariate Cox regression analyses, high global LV load predicted higher rate of major CV events (HR 1.35 [95% CI 1.08-1.71], P=0.010) and aortic valve events (HR 1.41 [95% CI 1.12-1.79], P=0.004) independent of hypertension, LV ejection fraction, female gender, age, abnormal LV geometry and AS severity, but failed to predict mortality. CONCLUSION: In asymptomatic AS, assessment of global LV load adds complementary information on prognosis to that provided by hypertension or established prognosticators like AS severity and LV ejection fraction.

Paradoxical sinus deceleration during dobutamine stress echocardiography: case series and review of the literature.

Background: Dobutamine stress echocardiography is an established diagnostic modality for assessing myocardial ischaemia in patients with known or suspected coronary artery disease. Dobutamine infusion causes dose-dependent increase in heart rate and contractility. However, in some cases, it induces paradoxical sinus deceleration, whose underlying mechanism and clinical significance are not fully understood. Case summary: We present episodes of paradoxical sinus deceleration observed during dobutamine stress echocardiography in six (four males and two females) patients and described its patterns of occurrence and clinical and echocardiographic characteristics. Discussion: Paradoxical sinus deceleration occurred mostly at maximal dobutamine infusion was accompanied with a decline in blood pressure and resolved spontaneously following cessation of dobutamine infusion. Individuals experiencing paradoxical sinus deceleration had in common abnormal left ventricle geometry but differed with regard to age, sex, and cardiometabolic risk factors.

Relationship between hypertension and non-obstructive coronary artery disease in chronic coronary syndrome (the NORIC registry).

BACKGROUND: The burden of non-obstructive coronary artery disease (CAD) in the society is high, and there is currently limited evidence-based recommendation for risk stratification and treatment. Previous studies have demonstrated an association between increasing extent of non-obstructive CAD and cardiovascular events. Whether hypertension, a modifiable cardiovascular risk factor, is associated with extensive non-obstructive CAD in patients with symptomatic chronic coronary syndrome (CCS) remains unclear. METHODS: We included 1138 patients (mean age 62±11 years, 48% women) with symptomatic CCS and non-obstructive CAD (1-49% lumen diameter reduction) by coronary computed tomography angiography (CCTA) from the Norwegian Registry for Invasive Cardiology (NORIC). The extent of non-obstructive CAD was assessed as coronary artery segment involvement score (SIS), and extensive non-obstructive CAD was adjudicated when SIS >4. Hypertension was defined as known hypertension or use of antihypertensive medication. RESULTS: Hypertension was found in 45% of patients. Hypertensive patients were older, with a higher SIS, calcium score, and prevalence of comorbidities and statin therapy compared to the normotensive (all p<0.05). There was no difference in the prevalence of hypertension between sexes. Univariable analysis revealed a significant association between hypertension and non-obstructive CAD. In multivariable analysis, hypertension remained associated with extensive non-obstructive CAD, independent of sex, age, smoking, diabetes, statin treatment, obesity and calcium score (OR 1.85, 95% CI [1.22-2.80], p = 0.004). CONCLUSION: In symptomatic CCS, hypertension was associated with extensive non-obstructive CAD by CCTA. Whether hypertension may be a new treatment target in symptomatic non-obstructive CAD needs to be explored in future studies. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: Identifier NCT04009421.

Even chained acylcarnitines predict long-term cardiovascular prognosis in patients with chest pain and non-obstructive coronary artery disease.

Background: Acylcarnitines are essential for mitochondrial fatty acid oxidation. Earlier studies suggest that impaired energy metabolism may be implicated in the pathogenesis of microvascular angina. We explored metabolites from the carnitine pathway as predictors of cardiovascular disease (CVD) - and all-cause mortality among patients with non-obstructive coronary artery disease (NOCAD). Methods: A total of 1046 patients with suspected stable coronary syndrome underwent coronary angiography during 2000-2004, with findings of NOCAD. Serum levels of 8 selected carnitine metabolites were analyzed through liquid chromatography tandem mass spectrometry. Associations with CVD- and all-cause mortality were assessed by multivariable Cox regression models. Results: Median age at inclusion was 57 years. 51.5% were men. During median (25th- 75th percentiles), 14.1 (13.2-15.4) years of follow-up, 5.7% of the participants died from CVD and the incidence of all-cause mortality was 17.3%. Serum acetyl, octanoyl- and palmitoylcarnitine predicted CVD mortality with multivariable HR and 95% CI (per SD increment log transformed) of 1.36 (1.01-1.83), 1.49 (1.15-1.93) and 2.07 (1.49-2.85), p ≤ 0.04, respectively. Higher serum acetyl- and palmitoylcarnitines were also associated with increased risk of all-cause mortality (HR (95% CI): 1.27 (1.01-1.50), and 1.51 (1.26-1.81), p ≤ 0.007. Baseline levels of the precursors trimethyllysine and Æ´-butyrobetaine, carnitine or the odd chained propionylcarnitine and (iso)valerylcarnitine were not associated with adverse outcomes. Conclusion: Elevated serum even-chained acylcarnitines predicted adverse long-term prognosis in NOCAD. The strongest risk estimates were observed for palmitoylcarnitine, which predicted both CVD- and all-cause mortality after extensive multivariable adjustments. Underlying pathomechanisms should be further elucidated.

Contrast stress echocardiography in hypertensive heart disease.

Hypertension is associated with atherosclerosis and cardiac and vascular structural and functional changes. Myocardial ischemia may arise in hypertension independent of coronary artery disease through an interaction between several pathophysiological mechanisms, including left ventricular hypertrophy, increased arterial stiffness and reduced coronary flow reserve associated with microvascular disease and endothelial dysfunction. The present case report demonstrates how contrast stress echocardiography can be used to diagnose myocardial ischemia in a hypertensive patient with angina pectoris but without significant obstructive coronary artery disease. The myocardial ischemia was due to severe resistant hypertension complicated with concentric left ventricular hypertrophy and increased arterial stiffness.

Total coronary atherosclerotic plaque burden is associated with myocardial ischemia in non-obstructive coronary artery disease.

AIM: Whether the total coronary atherosclerotic plaque burden is independently associated with myocardial ischemia in non-obstructive coronary artery disease (CAD) is not well established. We aimed to test the association of total plaque burden quantified by coronary computed tomography angiography (CCTA) with myocardial ischemia in patients with chronic coronary syndrome and non-obstructive CAD. METHODS: We included 125 patients (age 62 ± 9 years, 58% women) with chronic coronary syndrome and non-obstructive CAD (stenosis < 50%) by CCTA, who were grouped according to presence or absence of myocardial ischemia by myocardial contrast stress echocardiography. Total plaque burden was quantified by CCTA as the total plaque volume in the main coronary arteries, and positive remodelling was defined as remodelling index > 1.10. RESULTS: Patients with myocardial ischemia (n = 66) had higher total plaque burden (847 ± 245 mm3 vs. 758 ± 251 mm3, p = 0.049) and higher left ventricular (LV) mass index (42.1 ± 9.9 g/m2.7 vs. 37.3 ± 8.0 g/m2.7, p = 0.004), while age, sex, prevalence of hypertension, diabetes, calcium score and positive remodelling did not differ between the groups (all p > 0.05). In multivariable regression analysis, total plaque burden remained associated with presence of myocardial ischemia (OR 1.02, 95% CI 1.00-1.04, p = 0.045) independent of age, sex, hypertension, diabetes, LV mass index, coronary calcium score and positive remodelling. CONCLUSION: Total coronary artery plaque burden by CCTA was independently associated with myocardial ischemia in patients with non-obstructive CAD. Whether plaque quantification is useful for clinical management of patients with non-obstructive CAD should be tested in prospective studies.ClinicalTrials.gov: Identifier NCT01853527.

An unusual location of a papillary fibroelastoma.

A 72-year-old woman was hospitalized with recurrent acute coronary syndrome after initial successful treatment of acute ST-elevation myocardial infarction with percutaneous coronary intervention. Echocardiography demonstrated unexpectedly a 9 x 8 mm pendulating structure attached to the anterior, proximal interventricular septum in the left ventricular outflow tract 6 mm beneath the aortic valve annulus. Magnetic resonance imaging of the heart yielded the same findings. The patient underwent coronary artery bypass grafting and tumour excision. The histopathological findings were typical for papillary fibroelastoma (PFE) with a central zone of connective tissue and some elastic fibres without blood vessels and covered by endocardium. PFE is the third most common type of primary cardiac tumours, second to myxoma and lipoma. PFEs are avascular papillomas that predominantly occur on the aortic and mitral valves (90%). However, the present case demonstrates that PFE occasionally can be attached to the ventricular wall endocardium.