Long-Term Health-Related Quality of Life following Acute Type A Aortic Dissection with a Focus on Male-Female Differences: A Cross Sectional Study.

Objectives: Acute type A aortic dissection (ATAAD) is a life-threatening cardiovascular emergency, of which the long-term impact on health-related quality of life (HRQoL) and male-female-specific insights remain inadequately clarified. Methods: Consecutive adult ATAAD patients who underwent surgery were retrospectively included between 2007 and 2017 in four referral centers in the Netherlands, and baseline data were collected. The 36-Item Short-Form (SF-36) Health Survey was sent to all survivors between 2019 and 2021 and compared to validated SF-36 scores of the Dutch general population stratified by age group and sex. Results: In total, 324/555 surviving patients returned the SF-36 questionnaire (response rate 58%), of which 40.0% were female; the median follow-up was 6.5 years (range: 1.7-13.9, IQR: 4.0-9.4) after surgery for ATAAD. In comparison to the general population, ATAAD patients scored significantly lower on 6/8 SF-36 subdomains and higher on bodily pain. Differences in HRQoL domains compared to the sex-matched data were largely comparable between sexes, apart from bodily pain. In the age-matched subgroups impaired HRQoL was most pronounced in younger patients aged 41-60 (5/8 impaired domains). Female ATAAD patients scored significantly worse on 5/8 SF-36 subdomains and the physical component summary (PCS) scores than male patients. Age at ATAAD, female sex, hypertension, COPD, and prior thoracic aortic aneurysm were associated with worse PCS scores. Conclusions: Long-term HRQoL was impaired in both male and female ATAAD patients when compared to the general population. Further studies on the nature of this impairment and on interventions to improve HRQoL after ATAAD are clearly warranted, with special attention to females and younger patients.

Blood and Imaging Biomarkers in the Long-term Follow-up of Bicuspid Aortic Valve Patients.

Background: Bicuspid aortic valve (BAV) is a common congenital heart defect. Patients with BAV are at risk for long-term complications such as valve stenosis and regurgitation. This study aimed to investigate sex differences in blood and imaging biomarkers and to describe the long-term prognostic value of blood and echocardiographic biomarkers. Methods: Patients were included from 2 prospective observational cohort studies; they underwent venous blood sampling and transthoracic echocardiography including speckle tracking. Analyzed blood biomarkers were red-cell distribution width (RDW), creatinine, C-reactive protein (CRP), troponin T, N-terminal pro B-type natriuretic peptide (NT-proBNP), and transforming growth factor-beta (TGF-ß). Sex differences were analyzed at baseline. Associations between biomarkers and arrhythmia-free and intervention-free survival were determined by Cox regression, adjusted for age and sex. Results: A total of 182 patients with BAV were included: median age 34; interquartile range [IQR]: 23-46 years; 55.5% male. CRP, NT-proBNP, and RDW were higher in women, whereas creatinine, troponin T and TGF-ß were higher among men. After a median follow-up time of 6.9 (IQR: 6.5-9.9) years, arrhythmia-free and intervention-free survival was, 81.0% and 73.1%, respectively. NT-proBNP was associated with both arrhythmia-free and intervention-free survival (hazard ratio [HR], 1.94, P = 0.005 and HR, 2.06, P = 0.002, respectively). On echocardiography higher left atrial (LA) size, left ventricular end-diastolic diameter (LVEDD), left ventricular (LV) mass index and E/e' ratio were associated with lower arrhythmia-free survival, whereas higher LA size, LV mass index, aortic valve peak velocity, and aortic regurgitation were associated with lower intervention-free survival. Conclusions: Differences were observed in blood biomarkers between men and women with BAV. Besides LV systolic parameters, diastolic LV function and NT-proBNP should have a more prominent role as prognostic markers in clinical care.

Contexte: La bicuspide valvulaire aortique (BVA) est une anomalie cardiaque congénitale fréquente. Les patients atteints d'une BVA présentent des risques de complications à long terme, comme la sténose valvulaire ou la régurgitation valvulaire. Cette étude visait 1) à évaluer les différences entre les sexes en ce qui concerne les biomarqueurs sanguins et les biomarqueurs à l'imagerie; et 2) à décrire la valeur pronostique à long terme des biomarqueurs sanguins et échocardiographiques. Méthodologie: Des patients de 2 études de cohortes observationnelles prospectives ont été inclus dans l'analyse. Des échantillons de sang veineux ont été prélevés, et des échocardiographies transthoraciques, y compris le suivi des marqueurs acoustiques, ont été effectuées. Les biomarqueurs sanguins analysés étaient les suivants : indice de distribution des globules rouges (IDR), créatinine, protéine C-réactive (CRP), troponine T, propeptide natriurétique de type B N-terminal (NT-proBNP) et facteur de croissance transformant ß (TGF-ß). Les différences entre les sexes ont été analysées au départ. Les liens entre les biomarqueurs et la survie sans arythmie et sans intervention ont été déterminés par la régression de Cox, avec correction en fonction de l'âge et du sexe. Résultats: Cent quatre-vingt-deux patients présentant une BVA étaient inclus (âge médian de 34 [écart interquartile : 23-46] ans, 55,5 % hommes). La CRP, la NT-proBNP et l'IDR étaient plus élevées chez les femmes, alors que la créatinine, la troponine T et le TGF-ß étaient plus élevés chez les hommes. Après une période de suivi médiane de 6,9 (écart interquartile : 6,5-9,9) ans, les taux de survie sans arythmie et sans intervention étaient respectivement de 81,0 % et de 73,1 %. La NT-proBNP a été associée à la survie sans arythmie (rapport des risques instantanés [RRI] : 1,94, p = 0,005) et à la survie sans intervention (RRI : 2,06, p = 0,002). À l'échocardiographie, des valeurs élevées pour la taille de l'oreillette gauche, le diamètre télédiastolique du ventricule gauche (VG), l'indice de masse du VG et le rapport E/e' étaient associées à un faible taux de survie sans arythmie, alors que des valeurs élevées pour la taille de l'oreillette gauche, l'indice de masse du VG, la vitesse maximale aortique et la régurgitation aortique étaient associées à un faible taux de survie sans intervention. Conclusions: Les biomarqueurs sanguins variaient en fonction du sexe des personnes présentant une BVA. Outre les paramètres systoliques du VG, la fonction VG diastolique et la NT-proBNP devraient être davantage utilisées comme marqueurs pronostiques en soins cliniques.

Long-term surgical outcomes of congenital supravalvular aortic stenosis: a systematic review, meta-analysis and microsimulation study.

OBJECTIVES: Congenital supravalvular aortic stenosis (SVAS) is a rare form of congenital outflow tract obstruction and long-term outcomes are scarcely reported. This study aims to provide an overview of outcomes after surgical repair for congenital SVAS. METHODS: A systematic review of published literature was conducted, including observational studies reporting long-term clinical outcome (>2 years) after SVAS repair in children or adults considering >20 patients. Early risks, late event rates and time-to-event data were pooled and entered into a microsimulation model to estimate 30-year outcomes. Life expectancy was compared to the age-, sex- and origin-matched general population. RESULTS: Twenty-three publications were included, encompassing a total of 1472 patients (13 125 patient-years; pooled mean follow-up: 9.0 (6.2) years; median follow-up: 6.3 years). Pooled mean age at surgical repair was 4.7 (5.8) years and the most commonly used surgical technique was the single-patch repair (43.6%). Pooled early mortality was 4.2% (95% confidence interval: 3.2-5.5%) and late mortality was 0.61% (95% CI: 0.45-0.83) per patient-year. Based on microsimulation, over a 30-year time horizon, it was estimated that an average patient with SVAS repair (mean age: 4.7 years) had an observed life expectancy that was 90.7% (95% credible interval: 90.0-91.6%) of expected life expectancy in the matched general population. The microsimulation-based 30-year risk of myocardial infarction was 8.1% (95% credible interval: 7.3-9.9%) and reintervention 31.3% (95% credible interval: 29.6-33.4%), of which 27.2% (95% credible interval: 25.8-29.1) due to repair dysfunction. CONCLUSIONS: After surgical repair for SVAS, 30-year survival is lower than the matched-general-population survival and the lifetime risk of reintervention is considerable. Therefore, lifelong monitoring of the cardiovascular system and in particular residual stenosis and coronary obstruction is recommended.

Male-Female Differences in Acute Type B Aortic Dissection.

BACKGROUND: Acute type B aortic dissection is a cardiovascular emergency with considerable mortality and morbidity risk. Male-female differences have been observed in cardiovascular disease; however, literature on type B aortic dissection is scarce. METHODS AND RESULTS: A retrospective cohort study was conducted including all consecutive patients with acute type B aortic dissection between 2007 and 2017 in 4 tertiary hospitals using patient files and questionnaires for late morbidity. In total, 384 patients were included with a follow-up of 6.1 (range, 0.02-14.8) years, of which 41% (n=156) were female. Women presented at an older age than men (67 [interquartile range (IQR), 57-73] versus 62 [IQR, 52-71]; P=0.015). Prior abdominal aortic aneurysm (6% versus 15%; P=0.009), distally extending dissections (71 versus 85%; P=0.001), and clinical malperfusion (18% versus 32%; P=0.002) were less frequently observed in women. Absolute maximal descending aortic diameters were smaller in women (36 [IQR: 33-40] mm versus 39 [IQR, 36-43] mm; P<0.001), while indexed for body surface area diameters were larger in women (20 [IQR, 18-23] mm/m2 versus 19 [IQR, 17-21] mm/m2). No male-female differences were found in treatment choice; however, indications for invasive treatment were different (P<0.001). Early mortality rate was 9.6% in women and 11.8% in men (P=0.60). The 5-year survival was 83% (95% CI, 77-89) for women and 84% (95% CI, 79-89) for men (P=0.90). No male-female differences were observed in late (re)interventions. CONCLUSIONS: No male-female differences were found in management, early or late death, and morbidity in patients presenting with acute type B aortic dissection, despite distinct clinical profiles at presentation. More details on the impact of age and type of intervention are warranted in future studies.

Circulating biomarkers associated with aortic diameter in male and female patients with thoracic aortic disease: a cross-sectional study.

OBJECTIVE: As thoracic aortic disease (TAD) is generally asymptomatic, biomarkers are needed to provide insight into early progression. We aimed to examine the association between circulating blood biomarkers and the maximal thoracic aortic diameter (TADmax). METHODS: In this cross-sectional study, consecutive adult patients with a thoracic aortic diameter ≥40 mm and/or genetically proven hereditary TAD (HTAD) visiting our specialised outpatient clinic between 2017 and 2020 were prospectively included. Venous blood sampling and CT angiography and/or transthoracic echocardiography of the aorta were performed. Linear regression analyses were performed and estimates were presented as mean difference in TADmax in mm per doubling of standardised biomarker level. RESULTS: In total, 158 patients were included (median age 61 (50.3-68.8) years, 37.3% female). HTAD diagnosis was confirmed in 36 of 158 (22.7%) patients. TADmax was 43.9±5.2 mm in men vs 41.9±5.1 in women (p=0.030). In unadjusted analysis, significant associations with TADmax were found for interleukin-6 (1.15 (95% CI 0.33 to 1.96), p=0.006), growth differentiation factor-15 (1.01 (95% CI 0.18 to 1.84), p=0.018), microfibrillar-associated protein 4 (MFAP4) (-0.88 (95% CI -1.71 to 0.05), p=0.039) and triiodothyronine (T3) (-2.00 (95%CI -3.01 to 0.99), p<0.001). The association of MFAP4 with TADmax was stronger in women (p for interaction=0.020) and for homocysteine, an inverse association with TADmax was observed when compared with men (p for interaction=0.008). When adjusted for age, sex, hyperlipidaemia and HTAD, total cholesterol (1.10 (95% CI 0.27 to 1.93), p=0.010) and T3 (-1.20 (95% CI -2.14 to 0.25), p=0.014) were significantly associated with TADmax. CONCLUSIONS: Circulating biomarkers indicative of inflammation, lipid metabolism and thyroid function might be associated with TAD severity. Possible distinct biomarker patterns for men and women warrant further investigation.

Long Term Health Related Quality of Life After Acute Type B Aortic Dissection: a Cross Sectional Survey Study.

OBJECTIVE: Acute type B aortic dissection (ATBD) is a rare yet serious cardiovascular event that potentially has an impact on health related quality of life (HRQoL). However, long term follow up data on this topic are scarce. This study aimed to review the long term HRQoL among patients treated for ATBD. METHODS: In this multicentre, cross sectional survey study, consecutive treated patients with ATBD between 2007 and 2017 in four referral centres in the Netherlands were retrospectively included and baseline data were collected. Between 2019 and 2021 the 36 Item Short Form Survey (SF-36) was sent to all surviving patients (n = 263) and was compared with validated SF-36 scores in the Dutch general population stratified by age and sex. RESULTS: In total, 144 of 263 surviving patients completed the SF-36 (response rate 55%). Median (IQR) age was 68 (61, 76) years at completion of the questionnaire, and 40% (n = 58) were female. Initial treatment was medical in 55% (n = 79), endovascular in 41% (n = 59), and surgical in 4% (n = 6) of ATBD patients. Median follow up time was 6.1 (range 1.7-13.9; IQR 4.0, 9.0) years. Compared with the general population, patients scored significantly worse on six of eight SF-36 subdomains, particularly physical domains. Apart from bodily pain, there were no substantial differences in HRQoL between male and female ATBD patients. Compared with sex matched normative data, females scored significantly worse on five of eight subdomains, whereas males scored significantly lower on six subdomains. Younger patients aged 41-60 years seemed more severely impaired in HRQoL compared with the age matched general population. Treatment strategy did not influence HRQoL outcomes. Follow up time was associated with better Physical and Mental Component Summary scores. CONCLUSION: Long term HRQoL was impaired in ATBD patients compared with the Dutch general population, especially regarding physical status. This warrants more attention for HRQoL during clinical follow up. Rehabilitation programmes including exercise and physical support might improve HRQoL and increase patients' health understanding.

Elective Ascending Aortic Aneurysm Surgery in the Elderly.

BACKGROUND: No clear guidelines exist for performing preventive surgery for ascending aortic (AA) aneurysm in elderly patients. This study aims to provide insights by: (1) evaluating patient and procedural characteristics and (2) comparing early outcomes and long-term mortality after surgery between elderly and non-elderly patients. METHODS: A multicenter retrospective observational cohort-study was performed. Data was collected on patients who underwent elective AA surgery in three institutions (2006-2017). Clinical presentation, outcomes, and mortality were compared between elderly (≥70 years) and non-elderly patients. RESULTS: In total, 724 non-elderly and 231 elderly patients were operated upon. Elderly patients had larger aortic diameters (57.0 mm (IQR 53-63) vs. 53.0 mm (IQR 49-58), p < 0.001) and more cardiovascular risk factors at the time of surgery than non-elderly patients. Elderly females had significantly larger aortic diameters than elderly males (59.5 mm (55-65) vs. 56.0 mm (51-60), p < 0.001). Short-term mortality was comparable between elderly and non-elderly patients (3.0% vs. 1.5%, p = 0.16). Five-year survival was 93.9% in non-elderly patients and 81.4% in elderly patients (p < 0.001), which are both lower than that of the age-matched general Dutch population. CONCLUSION: This study showed that in elderly patients, a higher threshold exists to undergo surgery, especially in elderly females. Despite these differences, short-term outcomes were comparable between 'relatively healthy' elderly and non-elderly patients.

Aortic dilation and growth in women with Turner syndrome.

OBJECTIVE: Women with Turner syndrome (TS) are at increased risk of aortic dissection, which is a life-threatening event associated with aortic dilation. Knowledge on the development of aortic dilation over time remains limited. This study aims to describe the prevalence of aortic dilation, to find associated factors and to study aortic growth in women with TS. METHODS: In this prospective multicentre cohort study, consecutive adult women with genetically proven TS included between 2014 and 2016 underwent ECG-triggered multiphase CT angiography at baseline and after 3 years. Aortic diameters were measured at seven levels of the thoracic aorta using double oblique reconstruction and indexed for body surface area. Ascending aortic dilation was defined as an aortic size index >20 mm/m2. Aorta-related and cardiovascular events were collected. Statistical analysis included linear and logistic regression and linear mixed effects models. RESULTS: The cohort consisted of 89 women with a median age of 34 years (IQR: 24-44). Ascending aortic dilation was found in 38.2% at baseline. At baseline, age (OR: 1.08 (95% CI 1.03 to 1.13), p<0.001), presence of bicuspid aortic valve (BAV) (OR: 7.09 (95% CI 2.22 to 25.9), p=0.002) and systolic blood pressure (OR: 1.06 (95% CI 1.02 to 1.11), p=0.004) were independently associated with ascending aortic dilation. During a median follow-up of 3.0 (2.4-3.6) years (n=77), significant aortic growth was found only at the sinotubular junction (0.20±1.92 mm, p=0.021). No aortic dissection occurred, one patient underwent aortic surgery and one woman died. CONCLUSIONS: In women with TS, ascending aortic dilation is common and associated with age, BAV and systolic blood pressure. Aortic diameters were stable during a 3-year follow-up, apart from a significant yet not clinically relevant increase at the sinotubular junction, which may suggest a more benign course of progression than previously reported.

Male-female differences in acute thoracic aortic dissection: a systematic review and meta-analysis.

OBJECTIVES: This study aims to systematically review published literature on male-female differences in presentation, management and outcomes in patients diagnosed with acute thoracic aortic dissection (AD). METHODS: A systematic literature search was conducted for studies published between 1 January 1999 and 19 October 2020 investigating mortality and morbidity in adult patients diagnosed with AD. Patient and treatment characteristics were compared with odds ratios (ORs) and standardized mean differences and a meta-analysis using a random-effects model was performed for early mortality. Overall survival and reoperation were visualized by pooled Kaplan-Meier curves. RESULTS: Nine studies investigating type A dissections (AD-A), 1 investigating type B dissections (AD-B) and 3 investigating both AD-A and AD-B were included encompassing 18 659 patients. Males were younger in both AD-A (P < 0.001) and AD-B (P < 0.001), and in AD-A patients males had more distally extended dissections [OR 0.57, 95% confidence interval (CI) 0.46-0.70; P < 0.001]. Longer operation times were observed for males in AD-A (standardized mean difference 0.29, 95% CI 0.17-0.41; P < 0.001) while male patients were less often treated conservatively in AD-B (OR 0.65, 95% CI 0.58-0.72; P < 0.001). The pooled early mortality risk ratio for males versus females was 0.94 (95% CI 0.84-1.06, P = 0.308) in AD-A and 0.92 (95% CI 0.83-1.03, P = 0.143) in AD-B. Pooled overall mortality in AD-A showed no male-female difference, whereas male patients had more reinterventions during follow-up. CONCLUSIONS: This systematic review shows male-female differences in AD patient and treatment characteristics, comparable early and overall mortality and inconsistent outcome reporting. As published literature is scarce and heterogeneous, large prospective studies with standardized reporting of male-female characteristics and outcomes are clearly warranted. Improved knowledge of male-female differences in AD will help shape optimal individualized care for both males and females. CLINICAL REGISTRATION NUMBER: PROSPERO, ID number: CRD42020155926.