Risk Of Aortic Dissection Research Articles

Fluoroquinolones Are Associated With Increased Risk of Aortic Aneurysm or Dissection: Systematic Review and Meta-analysis

Fluoroquinolone use has been associated with collagen disease events, raising safety concerns. We hypothesized that the use of fluoroquinolones is associated with aortic aneurysm (AA) and aortic dissection or aortic rupture (AD/AR). We performed a systematic review with meta-analysis on studies published until March 2019. Seven observational studies were included, comprising 2,851,646 participants. The studies were evaluated regarding their risk of bias. Results on fluoroquinolone use risk comparing with nontreatment and with beta-lactam antibiotic use were extracted. The estimates were pooled through a random-effects model meta-analysis and heterogeneity assessed through the I2 statistic. Sensitivity analysis were performed, grouping studies per design and with exclusion of studies with critical risk of bias. Fluoroquinolone use was associated with a higher risk of AA/AD/AR, comparing with a nontreatment intervention (odds ratio = 2.26; 95%CI 1.93-2.65; I2 = 30%) and comparing with a beta-lactam intervention (odds ratio = 1.56; 95%CI 1.37-1.79; I2 = 0%). This harm effect remained significant when pooling the results for the AD/AR outcome only and across various study designs. Studies comparing with beta-lactam intervention were considered to have a moderate risk of bias, while the remaining ones were classified as having at least a serious risk of bias. All evaluated outcomes had very low Grading of Recommendation, Assessment, Development and Evaluation evidence. Fluoroquinolone use was associated with a significant risk of AA/AD/AR.

Family screening in patients with isolated bicuspid aortic valve in a general hospital, yield and subgroup analysis

Abstract Background Bicuspid aortic valve (BAV) may frequently lead to aortic dilatation with risk of aortic dissection. In patients with BAV both familial clustering and aortic dilatation in first-degree relatives (FDR) without BAV has been demonstrated. Based on these findings the ESC Aortic Guidelines recommend to consider screening of FDR, while the ACC/AHA Guidelines on Valvular Heart Diseases consider screening of FDR only if the index patient has associated aortopathy. Currently, no data about the effectiveness of screening is available. Purpose To investigate the yield of screening FDR of patients with isolated BAV and to explore subgroups with FDR of patients who had needed surgery or of patients with aortic dilatation. We hypothesized that aortic dilatation (>40mm) in the index patient is not a risk factor for BAV in FDR. Methods From 2012, patients with BAV visiting the outpatient clinic of a teaching hospital, received information advising cardiac screening of FDR. FDR of patients with isolated BAV who were referred, were included. From the 10 index patients from other hospitals, information was retrieved. [Fig.1] Results Referred were FDR from 118 index patients (mean age 60 years, standard deviation [SD] 14, range 15–90 years, 82 males [70%]). Of all index patients 63 (53%) had undergone aortic valve replacement, including concomitant ascending aorta replacement in 25 (21%). In the non-operated index patients, 31 (26%) had dilatation (>40mm) of sinus of Valsalva and/or tubular ascending aorta. Screened were 257 FDR (median 2 per index patient) comprising 20 parents (8%), 103 siblings (40%) and 134 offspring (52%). Mean age of FDR was 48 years (SD16, range 4–83 years) and 89 subjects (42%) were male. The diagnostic imaging modality was echocardiography in 240 cases (93%) and MRI in 17 cases. Ten FDR had an already known BAV and were not included in the screening. Among the 257 FDR, we diagnosed 12 new BAV (4.7%, 95% confidence interval [CI]2.9–8.0%) (mean age 44 years, 50% male). Additionally, we diagnosed 23 new isolated aorta dilatations (8.9%; 95% CI 6.0–13%) at level of sinus of Valsalva and/or tubular ascending aorta (mean age 57 years, 18 [78%] were male) [Fig. 1]. Among them, 11 had hypertension. FDR (n=147) of index patients with BAV and previous aortic valve surgery (n=63), had a risk ratio (RR) of 2.25 (95% CI 0.62–8.10) of having a BAV. FDR (n=126) of index patients with BAV and repaired or unrepaired aortic dilatation (n=56) had RR 0.35 (95% CI 0.10–1.25) of having a BAV. Conclusions Screening FDR of patients with isolated BAV resulted in a reasonable yield of 14% new cases with BAV or isolated aortic dilatation. The RR of the subgroup with aorta dilatation did not justify the limitation of the FDR as suggested in the ACC/AHA Guidelines. Figure 1. Flowchart of screening and result Funding Acknowledgement Type of funding source: None

Aortic wall stiffness and microcalcification in inherited thoracic aortopathies

Abstract Background Inherited thoracic aortic diseases are at substantially increased risk of aneurysm formation, aortic dissection or rupture. Importantly, up to 70% of dissections occur in aortas with a diameter below the threshold for prophylactic surgical replacement. Increased aortic stiffness and microcalcification have previously been identified as features of aortopathy and both indicate worsening vessel wall health. Improvement in our understanding of the disease processes that underpin high risk thoracic aortic aneurysms would be a major clinical advance. Purpose To investigate aortic wall microcalcification in a group of patients with inherited thoracic aortopathy and examine its relationship to both aortic stiffness and aortic diameter. Methods As part of an ongoing clinical study, 26 patients with thoracic aortopathy (14 congenital bicuspid aortic valve [BAV], 6 Marfan syndrome [MFS], 6 Turner syndrome [TS]) underwent aortic magnetic resonance imaging (MRI). Ascending aortic diameter and circumferential strain were determined by MRI at the level of the right pulmonary artery. Aortic pulse pressure was determined using applanation tomography. Aortic stiffness was calculated as circumferential aortic distensibility (circumferential strain/aortic pulse pressure). Microcalcification activity was measured using 18F-sodium fluoride positron emission tomography/computed tomography (18F-NaF PET/CT). 18F-NaF uptake was deemed “positive” if it was above the 95th centile of blood pool. A volume of interest was drawn around the ascending aorta and the volume of “positive” signal was indexed to patient height (indexed aortic microcalcification [iAMC] score). Results Distensibility differed between subgroups (BAV 0.06 [0.03], MFS 0.13 [0.07], TS 0.19 [0.09] mm/mmHg, p=0.011) was associated with body-mass index (r=0.46, p=0.025), and was inversely associated with age (R=−0.45, p=0.024) and aortic diameter (R=−0.61, p=0.001), but did not differ between sex, hypertension, hypercholesterolaemia or smoking status (all p>0.05). 18F-NaF uptake co-localised with the aortic wall of ascending thoracic aneurysms (Figure). The iAMC score was associated with aortic diameter (R=0.43, p=0.033), and aortic distensibility (R=−0.42, p=0.048), and appeared to carry a borderline association with age (R=0.39, p=0.064). There was no difference in iAMC between aortopathy subtypes, hypertension, smoking status, hypercholesterolaemia, or sex (all p>0.05). Conclusion In patients with inherited thoracic aortopathy, increased aortic wall stiffness and diameters, but not cardiovascular risk factors, are associated with increased aortic wall microcalcification. Further longitudinal and ex vivo studies are required to corroborate and validate these findings and determine if 18F-NaF uptake can predict disease progression and prognosis. Distensibility and Microcalcification Funding Acknowledgement Type of funding source: Other. Main funding source(s): British Heart Foundation clinical research training fellowship

Risk of aortic disease in long-distance cross-country skiers; a study of 209,226 patients

Abstract Background/Introduction Aneurysmal dilatation and dissection of the aorta are two facets of aortic disease that can lead to major disability and death. Some risk factors for aortic disease are also risk factors for atherosclerotic disease, but the overall causes of aortic disease are diverse and largely unknown. Persons with aortic aneurysms are advised to limit their physical activity, but associations of physical activity with subsequent incidence of aortic disease are little known. Earlier studies have shown strong association of performance in Vasaloppet with incidence of hypertension, a major risk factor for aortic disease. Aim To investigate associations of high levels of physical activity with incidence of aortic disease. Methods We studied 209,226 participants in a 30–90 km cross-country skiing event (Vasaloppet) and 536,038 persons from the general population, matched to the skiers on age, sex and residence. The number of completed races during the study period and the fastest relative finishing time in a race was recorded. The main outcomes were: 1) aortic disease (defined as thoracic and abdominal aortic aneurysm and/or aortic dissection); and 2) aortic dissection. Results During a median time at risk of 8.8 years, 1,442 aortic disease events and 265 aortic dissections occurred. Skiers had lower incidence of aortic disease than non-skiers (Cox proportional hazards ratio [HR] 0.42; 95% confidence interval [CI] 0.36–0.50). An association of better finishing time with aortic disease was observed, with a dose-response gradient from the fastest third (HR 0.25; 95% CI 0.18–0.35), via the slowest third (HR 0.64; 95% CI 0.49–0.82) to the non-skiers (reference group). Among skiers the number of completed races was not associated with incidence of aortic disease. Skiers also had lower incidence of acute aortic dissection (HR 0.61; 95% CI 0.44–0.85) than non-skiers. Low event rate among skiers made conclusions in subgroups unreasonable. All results are adjusted for age, sex, education and income. Results were similar in models accounting for use of antihypertensive and cholesterol-lowering medicines and genetic syndromes associated with aortic disease. Conclusion Participation in a long-distance skiing event was associated with lower risk of aortic disease and aortic dissection. Faster completion of the race was strongly associated with lower incidence of aortic disease. If causal, this study suggests that high physical activity and exercise may be protective against aortic disease. Kaplan-Meier Aorta disease Funding Acknowledgement Type of funding source: None

The contribution of X-chromosome genomic imprinting to the bicuspid aortic valve and aortic coarctation prevalence in women with Turner syndrome

Abstract Introduction Turner syndrome (TS) is caused by the absence or structural abnormality of X chromosome. Compared with the general population, the prevalence of congenital heart defects is significantly higher in women with TS, especially with 45,X karyotype. Moreover, congenital heart defects represent the major risk for aortic dissection in TS individuals. Purpose There is a lack of reliable evidence whether the extremely variable cardiovascular phenotype including presence of aortic coarctation (CoA) and bicuspid aortic valve (BAV) in TS women may be influenced by the parental origin of the retained X chromosome. Methods DNA samples were collected from peripheral lymphocytes of 48 women with non-mosaic 45,X karyotype and from buccal swab of their biological parents' cheek. Subsequently, the single normal X-chromosome origin was identified. Based on genetic evaluation, patients were divided into two subgroups according to the parenteral original of X chromosome - maternal (XM), and paternal (XP). Complete cardiovascular examination (echocardiography, MRI of the heart and great vessels) was performed in each of our study patient. Differences between the prevalence of BAV and CoA in two above mentioned subgroups were tested by Student's t-test using R Statistical Software version 2.15.3. Results The origin of the single X chromosome was as follows: in 14 (29.2%) individuals was proved paternal and in 34 (70.8%) maternal origin of X chromosome. The prevalence of BAV in the whole group was 47.9%, in XP 58%, in XM 44.1%; the prevalence of CoA in the whole group was 8.3%, in XP 7.1%, in XM 8.8%. There was no statistically significant difference identified between the prevalence of BAV and CoA in XP and XM subgroups. Conclusions Our study confirmed an extremely high prevalence of BAV and CoA in non-mosaic women with X chromosome monosomy but no clear evidence for X-linked genomic imprinting effect on the CoA and BAV development in TS individuals was found. However, further studies of larger numbers of TS patients are crucial to finally clarify the real relationship of genomic imprinting and cardiovascular disease in TS. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Supported by the grant from Ministry of Health of the Czech Republic VES 2017

Clinical characteristics and rate of dilatation in Turner syndrome patients treated for aortic dilatation.

Turner syndrome is associated with an increased risk of aortic aneurysms and dissection. Recent 2017 clinical care guidelines recommend medical therapy to treat aortic dilatation, although whether this slows dilatation is unknown. We aimed to describe a pre-guideline cohort of Turner syndrome patients with aortic dilatation, the rate of dilatation following diagnosis, and post therapy dilatation rates. We conducted a retrospective review of Turner syndrome patients with a dilated aortic root or ascending aorta by current definitions. In total, 40 patients were included with 22 treated patients. Most patients had 45,X karyotype, were white, non-Hispanic, and received both growth hormone and estrogen. Except for hypertension, there were no differences in risk factors among treated and untreated groups. Bicuspid aortic valve was very common. Treatment group patients had significantly more dilated ascending aortas by absolute measurements and aortic size index. In an adjusted model, there was minimal change in aortic measures over time and this was not associated with medication use. In conclusion, in this cohort, Turner syndrome patients with aortic dilatation were more likely to be treated if they had hypertension and if they met multiple dilatation criteria. Further study is needed to establish medical therapy efficacy on dilatation progression.

Clinical Features and Outcomes of Pregnancy-Related Acute Aortic Dissection

Women with aortopathy conditions are at risk for pregnancy-related aortic dissection, and these conditions may not be recognized until after the aortic dissection occurs. To examine the clinical characteristics, imaging features, and outcomes in women with pregnancy-related acute aortic dissection. A cohort study, comprising data from the International Registry of Acute Aortic Dissection (IRAD) (February 1, 1998, to February 28, 2018). The multicenter referral center study included 29 women with aortic dissection during pregnancy or less than 12 weeks post partum in IRAD from 1998 to 2018. Clinical features of pregnancy-related aortic dissection to be studied included underlying aortopathy, aortic size, type of aortic dissection, timing of dissection, hypertension, and previous aortic surgery. A total of 29 women (mean [SD] age, 32 [6] years) had pregnancy-related aortic dissection, representing 0.3% of all aortic dissections and 1% of aortic dissection in women in the IRAD. Among women younger than 35 years, aortic dissection was related to pregnancy in 20 of 105 women (19%). Thirteen women (45%) had type A aortic dissection, and 16 women (55%) had type B. Aortic dissection onset was known in 27 women (93%): 15 during pregnancy, 4 in the first trimester, and 11 in the third trimester; 12 were post partum, occurring a mean (SD) of 12.5 (14) days post partum. At type A aortic dissection diagnosis, the mean (SD) aortic diameters were sinus of Valsalva, 54.5 (5) mm and ascending aorta, 54.7 (6) mm. At type B aortic dissection diagnosis, the mean (SD) descending aortic diameter was 32.5 (5) mm. Twenty women (69%) had an aortopathy condition or a positive family history: 13 women (65%) with Marfan syndrome, 2 women (10%) with Loeys-Dietz syndrome, 2 women (10%) with bicuspid aortic valves, 2 women (10%) with a family history of aortic disease, and 1 woman (5%) with familial thoracic aortic aneurysm. Aortopathy was not recognized until after aortic dissection in 47% of the women. Twenty-eight women (97%) survived aortic dissection hospitalization. Aortic dissection complicating pregnancy is rare. Most pregnancy-related aortic dissection is due to an aortopathy often not diagnosed until after aortic dissection. In this study, type A aortic dissections were associated with a dilated aorta, and type B aortic dissections often were not. Recognition of underlying conditions and risks for aortic dissection may improve management of pregnancy in women with aortopathy.

Ciprofloxacin accelerates aortic enlargement and promotes dissection and rupture in Marfan mice

ObjectiveAortic aneurysm and dissection are major life-threatening complications of Marfan syndrome. Avoiding factors that promote aortic damage is critical in managing the care of these patients. Findings from clinical and animal studies raise concerns regarding fluoroquinolone use in patients at risk for aortic aneurysm and dissection. Therefore, we examined the effects of ciprofloxacin on aortic aneurysm and dissection development in Marfan mice. MethodsEight-week-old Marfan mice (Fbn1C1041G/+) were given ciprofloxacin (100 mg/kg/d; n = 51) or vehicle (n = 59) for 4 weeks. Mice were monitored for 16 weeks. Aortic diameters were measured by using ultrasonography, and aortic structure was examined by using histopathologic and immunostaining analyses. ResultsVehicle-treated Fbn1C1041G/+ mice showed progressive aortic enlargement, with aortic rupture occurring in 5% of these mice. Compared with vehicle-treated Fbn1C1041G/+ mice, ciprofloxacin-treated Fbn1C1041G/+ mice showed accelerated aortic enlargement (P = .01) and increased incidences of aortic dissection (25% vs 47%, P = .03) and rupture (5% vs 25%, P = .005). Furthermore, ciprofloxacin-treated Fbn1C1041G/+ mice had higher levels of elastic fiber fragmentation, matrix metalloproteinase expression, and apoptosis than did vehicle-treated Fbn1C1041G/+ mice. ConclusionsCiprofloxacin accelerates aortic root enlargement and increases the incidence of aortic dissection and rupture in Marfan mice, partially by suppressing lysyl oxidase expression and further compromising the inherited defect in aortic elastic fibers. Our findings substantiate that ciprofloxacin should be avoided in patients with Marfan syndrome.

Association of Infections and Use of Fluoroquinolones With the Risk of Aortic Aneurysm or Aortic Dissection

Prior observational studies have suggested that fluoroquinolone use may be associated with more than 2-fold increased risk of aortic aneurysm or aortic dissection (AA/AD). These studies, however, did not fully consider the role of coexisting infections and the risk of fluoroquinolones relative to other antibiotics. To estimate the risk of AA/AD associated with infections and to assess the comparative risk of AA/AD associated with fluoroquinolones vs other antibiotics with similar indication profiles among patients with the same types of infections. This nested case-control study identified 21 651 176 adult patients from a nationwide population-based health insurance claims database from January 1, 2009, to November 30, 2015. Each incident case of AA/AD was matched with 10 control individuals by age, sex, and follow-up duration in the database using risk-set sampling. Analysis of the data was conducted from April 2019 to March 2020. Infections and antibiotic use within a 60-day risk window before the occurrence of AA/AD. Conditional logistic regression was used to estimate the odds ratios (ORs) and 95% CIs comparing infections for which fluoroquinolones are commonly used with no infection within a 60-day risk window before outcome occurrence, adjusting for baseline confounders and concomitant antibiotic use. The adjusted ORs comparing fluoroquinolones with antibiotics with similar indication profiles within patients with indicated infections were also estimated. A total of 28 948 cases and 289 480 matched controls were included (71.37% male; mean [SD] age, 67.41 [15.03] years). Among these, the adjusted OR of AA/AD for any indicated infections was 1.73 (95% CI, 1.66-1.81). Septicemia (OR, 3.16; 95% CI, 2.63-3.78) and intra-abdominal infection (OR, 2.99; 95% CI, 2.45-3.65) had the highest increased risk. Fluoroquinolones were not associated with an increased AA/AD risk when compared with combined amoxicillin-clavulanate or combined ampicillin-sulbactam (OR, 1.01; 95% CI, 0.82-1.24) or with extended-spectrum cephalosporins (OR, 0.88; 95% CI, 0.70-1.11) among patients with indicated infections. The null findings for fluoroquinolone use remained robust in different subgroup and sensitivity analyses. These results highlight the importance of accounting for coexisting infections while examining the safety of antibiotics using real-world data; the findings suggest that concerns about AA/AD risk should not deter fluoroquinolone use for patients with indicated infections.

Association of Fluoroquinolones With the Risk of Aortic Aneurysm or Aortic Dissection

Previous observational studies have suggested that fluoroquinolones are associated with aortic aneurysm or dissection, but these studies may be subject to confounding by indication or surveillance bias. To assess the association of fluoroquinolones with risk of aortic aneurysm or aortic dissection (AA/AD) while accounting for potential confounding by fluoroquinolone indication and bias owing to differential surveillance. In an observational cohort study using a US commercial claims database, 2 pairwise 1:1 propensity score-matched cohorts were identified: patients aged 50 years or older with a diagnosis of pneumonia 3 days or less before initiating treatment with a fluoroquinolone or azithromycin and patients aged 50 years or older with a urinary tract infection (UTI) diagnosis 3 days or less before initiating a fluoroquinolone or combined trimethoprim and sulfamethoxazole. Hazard ratios (HRs) and 95% CIs were estimated controlling for 85 baseline confounders. In a secondary analysis, patients receiving fluoroquinolones were compared with those receiving amoxicillin, both with and without considering baseline aortic imaging, to address differences in detection of AA/AD before antibiotic use. Data on patients within the database from January 1, 2003, through September 30, 2015, were analyzed. Data analysis was conducted from July 23, 2019, to July 6, 2020. Hospitalization for AA/AD occurring within 60 days following treatment initiation. After propensity score matching, patient characteristics were well balanced, with 279 554 patients (mean [SD] age, 63.66 [10.93] years; 149 976 women [53.6%]) in the pneumonia cohort and 948 364 patients (mean [SD] age, 62.06 [10.33] years; 823 667 women [86.9%]) in the UTI cohort. Initiators of fluoroquinolones (n = 139 772 pairs in the pneumonia cohort and n = 474 182 pairs in the UTI cohort) had an increased rate of AA/AD compared with initiators of azithromycin (HR, 2.57; 95% CI, 1.36-4.86; incidence, 0.03% for fluoroquinolones vs 0.01% for azithromycin) but no increased rate compared with initiators of combined trimethoprim and sulfamethoxazole (HR, 0.99; 95% CI, 0.62-1.57; incidence, <0.01% in both UTI groups). Secondary analysis using amoxicillin as a comparator (n = 3 976 162 pairs) produced results consistent with those from earlier studies (HR, 1.54; 95% CI, 1.33-1.79; incidence, <0.01% in both groups). Requiring baseline imaging in this cohort (n = 542 649 pairs) to address surveillance bias attenuated the increased rate (HR, 1.13; 95% CI, 0.96-1.33; incidence, 0.06% for fluoroquinolones vs 0.05% for amoxicillin). The findings of this nationwide cohort study of adults with pneumonia or UTI suggest an increased relative rate of AA/AD associated with fluoroquinolones within the pneumonia cohort but not within the UTI cohort. In both cohorts, the absolute rate of AA/AD appeared to be low (<0.1%). The increased relative rate observed in the pneumonia cohort may be due to residual confounding or surveillance bias.

Predictive Factors of Operative Need in Medically Managed Type B Aortic Dissections

Aneurysmal degeneration of medically managed type B aortic dissection (TBAD) can be a life-threatening condition. Preventive thoracic endovascular aorta repair (TEVAR) in patients at risk could potentially be beneficial. The aim of this study was to examine the predictors for late aneurysmal dilatation after TBAD. A retrospective study was conducted on 82 patients with medically managed acute TBAD for a minimum of 14days. Relevant demographic, biochemical, and radiographic variables at presentation were studied. The aortic dissection risk calculator tool developed by Sailer etal., predicting the risk of adverse events after aortic dissection based on demographic and radiographic variables at presentation, was tested retrospectively. With a median follow-up of 36months (range 13-68), 25 (30.5%) patients underwent surgery (92% TEVAR). A larger initial aortic and false lumen diameter as well as a greater distal extension of the dissection was associated with higher need for surgery (respectively, P=0.003, P=0.004, and P=0.001). We observed higher growth rates of maximum aortic diameter in patients with a greater distal extension of the dissection, larger false lumen diameters and false lumen outflow, and entry tears located at the inner aortic arch (respectively, P=0.001, P=0.005, P=0.001 and P=0.014). No significant correlations could be found for the risks provided by the calculator tool. The initial maximum aortic diameter of TBAD is a key predictor for aortic growth. Furthermore, the distal extension of the dissection also seems to play an important role in late aneurysmal degeneration. However, we were not able to confirm the added value of the risk calculator tool in our study group.

Increased Risk of Aortic Dissection Associated With Pregnancy in Women With Turner Syndrome: A Systematic Review.

Turner syndrome (TS) is one of the most common chromosomal abnormalities in women. The condition is characterized by gonadal dysgenesis and is associated with structural cardiac abnormalities. Assisted reproductive technology with oocyte donation may be successful but places women with TS at increased risk of aortic dissection and death. To summarize all cases of aortic dissection associated with pregnancy in women with TS and provide guidance regarding the safety of pregnancy. Systematic review of PubMed for reports of women with TS, aortic dissection, and pregnancy. There are 14 total reported cases of aortic dissection associated with pregnancy in women with TS. Ten of these cases occurred during pregnancy or in the first month postpartum. The majority of affected pregnancies resulted from oocyte donation, 2 of which were multiple gestations. Two women had a documented history of hypertension, and 3 pregnancies were complicated by preeclampsia. Bicuspid aortic valve and coarctation of the aorta were the most common associated cardiac anomalies. More than half of women had some degree of aortic dilatation. Two women had no identifiable risk factors. Women with TS who desire pregnancy must be thoroughly counseled regarding the increased risk of aortic dissection during pregnancy and postpartum. Preconception consultation with maternal-fetal medicine, reproductive endocrinology, and cardiology is necessary along with a comprehensive physical evaluation. If women with TS choose to pursue pregnancy, they require rigorous cardiac monitoring each trimester during pregnancy and postpartum.

Impact of thoracic aortic aneurysm on outcomes of transcatheter aortic valve replacement: A nationwide cohort analysis.

The use of transcatheter aortic valve replacement (TAVR) has expanded to patient populations of varying surgical risk in light of recent clinical trials, yet its role in patients with aortic stenosis and coexisting thoracic aortic aneurysm (TAA) is not well-delineated. We aimed to evaluate whether risk factors and in-hospital outcomes vary between TAVR patients with and without an unruptured TAA. The Nationwide Readmissions Database was queried for patients hospitalized between January 2012 and December 2017 who underwent TAVR with and without an unruptured TAA. In-hospital outcomes were compared between cohorts after adjusting for sex, comorbidities, and TAVR approach, and in a subgroup analysis that excluded those with bicuspid aortic valves. Among 171,011 TAVR patients, 1,677 (1%) presented with TAA. Patients with TAA were younger (median age 80 vs. 82 years, p < .001) and more likely to have bicuspid aortic valves (9.3% vs. 0.9%, p < .001). Among patients with aneurysm, 2.6% died, 2.2% developed stroke, 1% developed aortic dissection, and 1.4% experienced cardiac tamponade while hospitalized. After adjusting for age, sex, bicuspid aortic valve, and all comorbidities, TAA was associated with significantly higher risk of post-TAVR aortic dissection (OR = 2.117, 95% CI [1.304-3.435], p = .002) and cardiac tamponade (OR = 1.682, 95% CI [1.1-2.572], p = .02). While the overall incidence of post-TAVR complications is low, patients with an unruptured TAA should be carefully considered by the Heart Team in weighing the additional risks of aortic dissection and cardiac tamponade after TAVR with those associated with surgery.

Is primary aldosteronism a potential risk factor for aortic dissection? A case report and literature review

BackgroundPrimary aldosteronism (PA) increases the risk of cardiovascular morbidity, including stroke, coronary artery disease, atrial fibrillation, and heart failure. The relationship between primary aldosteronism and aortic dissection has rarely been reported. We report a case of aortic dissection caused by secondary hypertension from PA and review similar cases in the literature.Case presentationA 56-year-old woman with a history of surgery for aortic dissection presented for follow-up of hypertension and a left adrenal mass. She had been diagnosed with hypertension and hypokalemia in 2003. Blood pressure had been controlled by antihypertensive medications. In 2009, she presented with chest and back pain; she was diagnosed with aortic dissection by computed tomography (CT). She underwent placement of an endovascular aortic stent graft. CT at that time showed a left adrenal mass with a diameter of 1 cm. In 2017, CT reexamination revealed that the left adrenal mass had grown to 3 cm in diameter. Laboratory data showed blood potassium 2.4 mmol/L (reference range: 3.5–5.3 mmol/L). The plasma aldosterone/renin ratio was elevated because of suppressed plasma renin and elevated serum aldosterone levels. Plasma aldosterone levels were not suppressed after taking captopril. Positron emission tomography/CT showed that the left adrenal tumor radiographic uptake was slightly increased (maximum standardized uptake value of 2.2), and metastasis was not detected. Laparoscopic adrenalectomy was performed, and an adrenocortical adenoma was confirmed histopathologically. After surgery, blood pressure and laboratory findings were within their reference ranges without any pharmacological treatment.ConclusionsOur patient and the literature suggest that PA is a potential cause of aortic dissection. Diagnosing PA in the early stages of the disease and early treatment are important because affected patients may be at increased risk of aortic dissection.

Effect of Glycation on Interlamellar Bonding of Arterial Elastin.

Interlamellar bonding in the arterial wall is often compromised by cardiovascular diseases. However, several recent nationwide and hospital-based studies have uniformly reported reduced risk of thoracic aortic dissection in patients with diabetes. As one of the primary structural constituents in the arterial wall, elastin plays an important role in providing its interlamellar structural integrity. The purpose of this study is to examine the effects of glycation on the interlamellar bonding properties of arterial elastin. Purified elastin network was isolated from porcine descending thoracic aorta and incubated in 2 M glucose solution for 7, 14 or 21 days at 37 °C. Peeling and direct tension tests were performed to provide complimentary information on understanding the interlamellar layer separation properties of elastin network with glycation effect. Peeling tests were simulated using a cohesive zone model (CZM). Multiphoton imaging was used to visualize the interlamellar elastin fibers in samples subjected to peeling and direct tension. Peeling and direct tension tests show that interlamellar energy release rate and strength both increases with the duration of glucose treatment. The traction at damage initiation estimated for the CZM agrees well with the interlamellar strength measurements from direct tension tests. Glycation was also found to increase the interlamellar failure strain of arterial elastin. Multiphoton imaging confirmed the contribution of radially running elastin fibers to resisting dissection. Nonenzymatic glycation reduces the propensity of arterial elastin to dissection. This study also suggests that the CZM effectively describes the interlamellar bonding properties of arterial elastin.

Novel loss of function mutation in NOTCH1 in a family with bicuspid aortic valve, ventricular septal defect, thoracic aortic aneurysm, and aortic valve stenosis

BackgroundBicuspid aortic valve is the most common congenital valvular heart defect in the general population. BAV is associated with significant morbidity due to valve failure, formation of thoracic aortic aneurysm, and increased risk of infective endocarditis and aortic dissection. Loss of function mutations in NOTCH1 (OMIM 190198) has previously been associated with congenital heart disease involving the aortic valve, left ventricle outflow tract, and mitral valve that segregates in affected pedigrees as an autosomal dominant trait with variable expressivity.MethodsWe performed whole‐exome sequencing in four members of a three‐generational family (three affected and one unaffected subject) with clinical phenotypes including aortic valve stenosis, thoracic aortic aneurysm, and ventricular septal defect.ResultsWe identified 16 potentially damaging genetic variants (one stop variant, one splice variant, and 14 missense variants) cosegregating with the phenotype. Of these variants, the nonsense mutation (p.Tyr291*) in NOTCH1 was the most deleterious variant identified and the most likely variant causing the disease.ConclusionInactivating NOTCH1 mutations are a rare cause of familial heart disease involving predominantly left ventricular outflow tract lesions and characterized by the heterogeneity of clinical phenotype.

Thoracic aortic aneurysm gene dictionary.

Thoracic aortic aneurysm is typically clinically silent, with a natural history of progressive enlargement until a potentially lethal complication such as rupture or dissection occurs. Underlying genetic predisposition strongly influences the risk of thoracic aortic aneurysm and dissection. Familial cases are more virulent, have a higher rate of aneurysm growth, and occur earlier in life. To date, over 30 genes have been associated with syndromic and non-syndromic thoracic aortic aneurysm and dissection. The causative genes and their specific variants help to predict the disease phenotype, including age at presentation, risk of dissection at small aortic sizes, and risk of other cardiovascular and systemic manifestations. This genetic "dictionary" is already a clinical reality, allowing us to personalize care based on specific causative mutations for a substantial proportion of these patients. Widespread genetic sequencing of thoracic aortic aneurysm and dissection patients has been and continues to be crucial to the rapid expansion of this dictionary and ultimately, the delivery of truly personalized care to every patient.

Male-female differences in quality of life and coping style in patients with Marfan syndrome and hereditary thoracic aortic diseases.

Hereditary thoracic aortic diseases (HTAD) such as Marfan syndrome (MFS) affect multiple organ systems and provide a risk of acute aortic dissection, which causes lifelong uncertainties. Although health‐related quality of life (HRQOL) was found to be reduced in HTAD patients, no studies have evaluated male–female‐specific aspects of HRQOL and coping in this population. This study aims to evaluate HRQOL in HTAD patients compared to the general population; assess male–female differences in HRQOL and factors associated with HRQOL; evaluate coping styles in male and female HTAD patients and identify factors associated with acceptance. All consecutive adult patients who visited the specialized HTAD outpatient clinic between 2013 and 2018 were asked to complete three HRQOL questionnaires: the Short Form 36 (SF‐36), the Hospital Anxiety and Depression Scale (HADS), and the Nijmegen Clinical Screening Instrument (NCSI). In total, 142 patients were included (mean age 42.1 years, 65 females, 123 MFS). Compared to the general population, HTAD patients scored significantly lower on multiple SF‐36 sub‐domains (males: General Health 54.5 ± 18.8 vs. 71.6 ± 20.6, p < .001; Vitality 58.3 ± 20.4 vs. 71.9 ± 18.3, p < .001; females: Physical Functioning 67.5 ± 23.8 vs. 80.4 ± 24.2, p = .003; Role Physical 58.3 ± 45.1 vs. 73.8 ± 38.5, p = .047; General Health 49.4 ± 24.3 vs. 69.9 ± 20.6, p < .001; Social Functioning 73.5 ± 22.0 vs. 82.0 ± 23.5, p = .027). Females scored significantly lower than males on the SF‐36 physical component score (41.6 [IQR 35.5–53.1] vs. 49.3 [IQR 42.3–54.6], p = .035). Males scored significantly higher on the coping style denial than females (2.75 [IQR 2.00–3.25] vs. 2.25 [IQR 1.75–3.25], p = .018). High scores on acceptance were found in 38 (26.8%) of HTAD patients, and these patients showed significantly better scores on the NCSI, SF‐36, and HADS, except on NCSI Satisfaction Relationships and SF‐36 Physical Functioning and Mental Health. Acceptance was associated with more medication use (beta blocker use, p = .008; angiotensin receptor blocker use, p = .003) and less hypertension (p = .001). In patients with MFS, employment was strongly associated with better scores on the NCSI. In conclusion, HTAD patients showed subnormal HRQOL, especially females. Interestingly, in both males and females factors such as employment, coping style, and disease acceptance seem more important for HRQOL than disease‐related factors. This highlights the importance of genetic counseling and guidance for HTAD patients, and offers valuable leads for HRQOL improvement.

Aortopathy in Congenital Heart Disease.

Aortic dilatation is common in patients with congenital heart disease and is seen in patients with bicuspid aortic valve and those with conotruncal congenital heart defects. It is important to identify patients with bicuspid aortic valve at high risk for aortic dissection. High-risk patients include those with the aortic root phenotype and those with syndromic or familial aortopathies including Marfan syndrome, Loeys-Dietz syndrome, and Turner syndrome. Aortic dilatation is common in patients with conotruncal congenital heart defects and rarely results in aortic dissection.

Expanding the cerebrovascular phenotype of the p.R258H variant in ACTA2 related hereditary thoracic aortic disease (HTAD)

Heterozygous variants in smooth muscle alpha-actin gene (ACTA2) are the most frequent cause of autosomal dominant hereditary thoracic aortic disease (HTAD). Several genotype-phenotype associations have been described, including a severe multisystemic smooth muscle disorder associated with de novo ACTA2 p.R179 variants, characterized by highly penetrant and early onset vascular disease, involvement of smooth muscle cell (SMC)-dependent organs and a distinct cerebrovascular phenotype. Missense variants at position 258 (p.R258C and p.R258H) have also been reported to have a more severe presentation including an increased risk for aortic dissection and a high risk of stroke. It has previously been suggested that the cerebrovascular phenotype of patients with p.R258 variants could represent a mild presentation of the cerebrovascular phenotype associated with p.R179 variants. Here we report on a five generation HTAD family with the p.R258H variant and describe the cerebrovascular findings seen in three family members, to expand on the previously reported phenotype associated with variants at this codon.