Impact of multiple sclerosis on employment and income: Insights from a random sample representative of private sector employees in France using longitudinal administrative data.

In France, few data sources are available to estimate the impact of multiple sclerosis (MS) on job retention and its consequences on the level of resources, especially in large representative samples. The aim of the present study was to measure impact of MS on employment rates, wages and income (including unemployment benefit, sickness benefit and disability pension) by comparing work trajectories of people living with MS with those of a matched control group. We used the HYGIE database, which is the result of the linkage of two administrative databases in the private sector for a random sample of over 900,000 people. In order to identify the causal effect of MS on employment after 1 to 20 years, the difference-in-differences method with matching (age, sex, career and health history) was used, overall and in subgroups. The year of entry in long-term disease status for MS was used to approximate the onset of MS. Overall, 946 people with MS were included. Their situation was fairly favorable before MS (88.1% in employment, resources higher than the median for the general population), but MS had strong and continuous negative effects. Indeed, at 10 years, the employment rate fell by 28.6 percentage points (pp) and the disability pension allowance increased by 50.5 pp; the wage percentile fell by 19.2 pp and the replacement income accounted for a growing share of total income (+ 39.7 pp). Although administrative data had several strengths, clinical information on the severity of the disease or on its therapeutic management was not available. In conclusion, this study shows that the effects of MS on the employed population in the private sector occur early in the disease course and are cumulative, and that replacement income helps to reduce the loss of resources thanks to the French health and social system.

Upper extremity versus lower extremity for secondary access during transcatheter aortic valve implantation: rationale and design of the randomised TAVI XS trial.

BACKGROUND: During transcatheter aortic valve implantation (TAVI), secondary access is required for angiographic guidance and temporary pacing. The most commonly used secondary access sites are the femoral artery (angiographic guidance) and the femoral vein (temporary pacing). An upper extremity approach using the radial artery and an upper arm vein instead of the lower extremity approach using the femoral artery and femoral vein may reduce clinically relevant secondary access site-related bleeding complications, but robust evidence is lacking. TRIAL DESIGN: The TAVI XS trial is a multicentre, randomised, open-label clinical trial with blinded evaluation of endpoints. A total of 238 patients undergoing transfemoral TAVI will be included. The primary endpoint is the incidence of clinically relevant bleeding (i.e. Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding) of the randomised secondary access site (either diagnostic or pacemaker access, or both) within 30 days after TAVI. Secondary endpoints include time to mobilisation after TAVI, duration of hospitalisation, any BARC type 2, 3 or 5 bleeding, and early safety at 30 days according to Valve Academic Research Consortium­3 criteria. CONCLUSION: The TAVI XS trial is the first randomised trial comparing an upper extremity approach to a lower extremity approach with regard to clinically relevant secondary access site-related bleeding complications. The results of this trial will provide important insights into the safety and efficacy of an upper extremity approach in patients undergoing transfemoral TAVI.

Mycotic aortic aneurysms: characteristic macroscopic findings in a case series.

Infected or mycotic aortic aneurysms (MAAs) are a rare type of aneurysms. Due to the high risk of rupture, MAAs are life-threatening conditions. Early diagnosis and treatment are necessary, yet MAAs are usually found coincidentally. We report 10 patients with MAAs in whom macroscopically, similar coined-sized lesions of the inner aortic wall were seen in all cases. When a coin-sized lesion in the inner aortic wall is seen during open surgical repair of an aortic aneurysm, the surgeon should consider an infectious cause. Microbiological tissue samples should be collected, and additional targeted antibiotic therapy should be started.

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.

Long-term outcomes after recurrent acute thoracic aortic dissection: Insights from the International Registry of Aortic Dissection.

OBJECTIVE: With an aging population and advancements in imaging, recurrence of thoracic aortic dissection is becoming more common. METHODS: All patients enrolled in the International Registry of Aortic Dissection from 1996 to 2023 with type A and type B acute aortic dissection were identified. Among them, initial dissection and recurrent dissection were discerned. The study period was categorized into 3 eras: historic era, 1996 to 2005; middle era, 2006 to 2015; most recent era, 2016 to 2023. Propensity score matching was applied between initial dissection and recurrent dissection. Outcome of interests included long-term survival and cumulative incidence of major aortic events defined by the composite of reintervention, aortic rupture, and new dissection. RESULTS: The proportion of recurrent dissection increased from 5.9% in the historic era to 8.0% in the most recent era in the entire dissection cohort. In patients with type A dissection, propensity score matching between initial dissection and recurrent dissection yielded 326 matched pairs. Kaplan-Meier curves showed similar long-term survival between the 2 groups. However, the cumulative incidence of major aortic events was significantly higher in the recurrent dissection group (40.3% ± 6.2% vs 17.8% ± 5.1% at 4 years in the initial dissection group, P = .02). For type B dissection, 316 matched pairs were observed after propensity score matching. Long-term survival and the incidence of major aortic events were equivalent between the 2 groups. CONCLUSIONS: The case volume of recurrent dissection or the ability to detect recurrent dissection has increased over time. Acute type A recurrent dissection was associated with a higher risk of major aortic events than initial dissection. Further judicious follow-up may be crucial after type A recurrent dissection.

Using Upper Arm Vein as Temporary Pacemaker Access Site: A Next Step in Minimizing the Invasiveness of Transcatheter Aortic Valve Replacement.

Background The femoral vein is commonly used as a pacemaker access site during transcatheter aortic valve replacement (TAVR). Using an upper arm vein as an alternative access site potentially causes fewer bleeding complications and shorter time to mobilization. We aimed to assess the safety and efficacy of an upper arm vein as a temporary pacemaker access site during TAVR. Methods We evaluated all patients undergoing TAVR in our center between January 2020 and January 2023. Upper arm, femoral, and jugular vein pacemaker access was used in 255 (45.8%), 191 (34.3%), and 111 (19.9%) patients, respectively. Clinical outcomes were analyzed according to pacemaker access in the overall population and in a propensity-matched population involving 165 upper arm and 165 femoral vein patients. Primary endpoint was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 pacemaker access site-related bleeding. Results In the overall population, primary endpoint was lowest for upper arm, followed by femoral and jugular vein access (2.4% vs. 5.8% vs. 10.8%, p = 0.003). Time to mobilization was significantly longer (p < 0.001) in the jugular cohort compared with the other cohorts. In the propensity-matched cohort, primary endpoint showed a trend toward lower occurrence in the upper arm compared with the femoral cohort (2.4% vs. 6.1%, p = 0.10). Time to mobilization was significantly shorter (480 vs. 1140 min, p < 0.001) in the upper arm cohort, with a comparable skin-to-skin time (83 vs. 85 min, p = 0.75). Cross-over from upper arm pacemaker access was required in 17 patients (6.3% of attempted cases via an upper arm vein). Conclusions Using an upper arm vein as a temporary pacemaker access site is safe and feasible. Its use might be associated with fewer bleeding complications and shorter time to mobilization compared with the femoral vein.

Abnormal Iron Status and Adverse Outcome After Elective Cardiac Surgery: A Prospective, Observational Multicenter Study.

OBJECTIVES: To investigate the incidence of preoperative abnormal iron status and its association with packed red blood cell (PRBC) transfusion, postoperative major complications, and new onset of clinically significant disability in patients undergoing elective cardiac surgery. DESIGN: A prospective, observational multicenter cohort study. SETTING: Three cardiac surgical centers in the Netherlands between 2019 and 2021. Recruitment was on hold between March and May 2020 due to COVID-19. PATIENTS: A total of 427 patients aged 60 years and older who underwent elective on-pump cardiac surgery. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was a 30-day PRBC transfusion. Secondary endpoints were postoperative major complications within 30 days (eg, acute kidney injury, sepsis), and new onset of clinically significant disability within 120 days of surgery. Iron status was evaluated before surgery. Abnormal iron status was present in 45.2% of patients (n = 193), and most frequently the result of iron deficiency (27.4%, n = 117). An abnormal iron status was not associated with PRBC transfusion (adjusted relative risk [ARR] 1.2; 95% CI 0.9-1.8: p = 0.227) or new onset of clinically significant disability (ARR 2.0; 95% CI 0.9-4.6: p = 0.098). However, the risk of postoperative major complications was increased in patients with an abnormal iron status (ARR 1.7; 95% CI 1.1-2.5: p = 0.012). CONCLUSIONS: An abnormal iron status before elective cardiac surgery was associated with an increased risk of postoperative major complications but not with PRBC transfusion or a new onset of clinically significant disability.

Mammals Achieve Common Neural Coverage of Visual Scenes Using Distinct Sampling Behaviors.

Most vertebrates use head and eye movements to quickly change gaze orientation and sample different portions of the environment with periods of stable fixation. Visual information must be integrated across fixations to construct a complete perspective of the visual environment. In concert with this sampling strategy, neurons adapt to unchanging input to conserve energy and ensure that only novel information from each fixation is processed. We demonstrate how adaptation recovery times and saccade properties interact and thus shape spatiotemporal tradeoffs observed in the motor and visual systems of mice, cats, marmosets, macaques, and humans. These tradeoffs predict that in order to achieve similar visual coverage over time, animals with smaller receptive field sizes require faster saccade rates. Indeed, we find comparable sampling of the visual environment by neuronal populations across mammals when integrating measurements of saccadic behavior with receptive field sizes and V1 neuronal density. We propose that these mammals share a common statistically driven strategy of maintaining coverage of their visual environment over time calibrated to their respective visual system characteristics.

Type A Aortic Dissection in a 24-Year-Old Patient With Kabuki Syndrome.

Our case report documents the first type A aortic dissection in a patient with Kabuki syndrome (KS) and emphasize the need for intensive cardiovascular risk monitoring in patients with KS. It stresses the importance of further research to establish a correlation and awareness for patients with KS.

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.

Male-female differences in contemporary elective ascending aortic surgery: insights from the Netherlands Heart Registration.

Background: Scientific research regarding male-female differences in ascending aortic surgery is scarce. The objective of this study was to identify male-female differences in presentation, treatment and peri-operative outcome in elective ascending aortic surgery. Methods: Elective ascending aortic surgery procedures that took place in the Netherlands between 01/01/2013-31/12/2017 were identified from the Netherlands Heart Registration. Male-female differences in presentation, treatment characteristics, and in-hospital mortality and morbidity were explored. Results: The study population consisted of 887 females (31%) and 1,972 males (69%). Females were older (median age 67 versus 62 years, P<0.001), more often had chronic lung disease (12.3% versus 9.1%, P=0.011), New York Heart Association (NYHA) class III-IV (21.5% versus 15.5%, P=0.003), and less often a history of percutaneous coronary intervention (PCI) (3.2% versus 5.0%, P=0.033). Isolated supracoronary aortic replacement was performed in 47.7% of females versus 30.6% of males (P<0.001), and ascending aorta with root replacement in 40.6% of females versus 56.7% of males (P<0.001). Females more often underwent concomitant interventions of the aortic arch (33.1% versus 20.2%, P<0.001) and the mitral valve (8.2% versus 5.2%, P=0.002), and less often concomitant coronary artery bypass grafting (CABG) (14.4% versus 19.1%, P=0.002). Overall, in-hospital mortality was significantly higher in females (5.1% versus 2.7%, P=0.003). In multivariable regression analysis, being female was an independent risk factor for in-hospital mortality [odds ratio (OR) 1.55, 95% confidence interval (CI): 1.02-2.37]. Conclusions: This nation-wide cohort shows clear differences between females and males in patient presentation, procedural characteristics, in-hospital outcomes, and risk factors for in-hospital mortality in elective ascending aortic surgery. Further exploration of these differences, and of modifiable within-male and within-female risk factors, may offer great opportunities in improving treatment and thereby outcomes for both males and females.

Surgical bypass to the left subclavian artery: an extra-anatomical transpleural approach.

A distal anastomosis in zone 3 is technically demanding during the frozen elephant trunk procedure. Proximalization of the distal anastomosis to zone 2 with subsequent revascularization of the left subclavian artery is an attractive alternative. This video tutorial describes the technique of an extra-anatomical bypass from the aortic prosthesis to the infraclavicular left subclavian (axillary) artery in arch replacement with the distal aortic graft anastomosis in zone 2.

How to reduce the complication rate of multiple burr holes surgery in moyamoya angiopathy.

PURPOSE: This study is aimed at analyzing clinical outcome, absence of stroke recurrence, revascularization, and complications and long-term follow-up in the surgical treatment of moyamoya angiopathy (MMA) using the multiple burr holes (MBH) technique with dura opening and arachnoid preservation as a single procedure. To the best of our knowledge, this is the first to describe an MBH technique with arachnoid preservation. METHOD: We retrospectively reviewed all patients operated from June 2001 to March 2021, for a symptomatic and progressive MMA operated with opening of the dura but arachnoid preservation. Clinical examinations were obtained in all patients, and radiological monitoring was performed by cerebral 3D-magnetic resonance angiography (MRA) with perfusion or single-photon emission computed tomography (SPECT) with acetazolamide. RESULTS: In total, 21 consecutive patients (6 children and 15 adults) were included with a mean age of 7.4 years in the pediatric group and 36.9 years in the adult group. Initial presentation was permanent ischemic stroke in 15 cases, transient ischemic attack (TIA) in 5 cases, and cerebral hemorrhage in one case. The MBH with dura opening and arachnoid preservation was performed bilaterally in 9 cases (43%) and unilaterally in 12 cases (57%). One patient died due to intraoperative bilateral ischemic stroke. Of the 20 other patients, 30% demonstrated clinical stability and 70% showed partial or complete recovery. Although one patient experienced a perioperative stroke, we did not observe any pseudomeningocele or postoperative ischemic stroke (IS) recurrence in all surviving cases during the average follow-up period of 55.5 months (range: 1-195). These outcomes emphasize the importance of preoperative monitoring to ensure the effectiveness and safety of the intervention. Postoperative angiography studies showed revascularization in 96.3% of treated hemispheres (100% in the adult group vs 80% in the pediatric group). CONCLUSIONS: Our results on this small cohort suggest that the MBH technique with opening of the dura and arachnoids preservation can prevent recurrent strokes and reduce the risk of pseudomeningocele.

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.

Adventitial adaptive immune cells are associated with ascending aortic dilatation in patients with a bicuspid aortic valve.

Background: Bicuspid aortic valve (BAV) is associated with ascending aorta aneurysms and dissections. Presently, genetic factors and pathological flow patterns are considered responsible for aneurysm formation in BAV while the exact role of inflammatory processes remains unknown. Methods: In order to objectify inflammation, we employ a highly sensitive, quantitative immunohistochemistry approach. Whole slides of dissected, dilated and non-dilated ascending aortas from BAV patients were quantitatively analyzed. Results: Dilated aortas show a 4-fold increase of lymphocytes and a 25-fold increase in B lymphocytes in the adventitia compared to non-dilated aortas. Tertiary lymphoid structures with B cell follicles and helper T cell expansion were identified in dilated and dissected aortas. Dilated aortas were associated with an increase in M1-like macrophages in the aorta media, in contrast the number of M2-like macrophages did not change significantly. Conclusion: This study finds unexpected large numbers of immune cells in dilating aortas of BAV patients. These findings raise the question whether immune cells in BAV aortopathy are innocent bystanders or contribute to the deterioration of the aortic wall.

Diastolic delta best predicts paravalvular regurgitation after transcatheter aortic valve replacement as assessed by cardiac magnetic resonance: the APPOSE trial.

AIMS: Paravalvular regurgitation (PVR) is a common complication after transcatheter aortic valve replacement (TAVR) that poses an increased risk of rehospitalization for heart failure and mortality. The aim of this study was to assess the accuracy of haemodynamic indices to predict relevant PVR. METHODS AND RESULTS: In this prospective single-centre clinical trial, four haemodynamic indices of PVR measured during TAVR were assessed for their correlation with gold standard cardiac magnetic resonance (CMR)-derived regurgitant fraction (CMR-RF) at 1 month follow-up: diastolic delta (DD), heart rate-adjusted diastolic delta (HR-DD), aortic regurgitation index (ARI), and aortic regurgitation index ratio (ARI ratio). These haemodynamic indices were analysed for their ability to predict relevant PVR (defined as CMR-RF > 20%) using receiver operating characteristic (ROC) curves with corresponding area under the ROC curves (AUCs). A total of 77 patients were included and had CMR performed 41 ± 14 days after TAVR. Mean CMR-RF was 12.4 ± 9.3%. Fifteen (19.5%) patients had CMR-RF > 20%. DD had the best correlation with CMR-RF and the highest AUC to predict relevant PVR (0.82; 95% CI, 0.72-0.92), followed by HR-DD (AUC 0.78; 95% CI, 0.67-0.89), ARI (AUC 0.78; 95% CI, 0.66-0.89), and ARI ratio (AUC 0.65; 95% CI, 0.49-0.81). The optimal cut-off value for DD was 32 mmHg, with sensitivity of 69% and specificity of 77% in predicting relevant PVR. CONCLUSION: DD measured during TAVR best predicts relevant PVR. Correction for heart rate (HR-DD) or systolic blood pressure (ARI, ARI ratio) did not improve this predictive value.

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.

Postoperative Inflammation and Fever After Elective Aortic Valve and Aortic Root Replacement: A Retrospective Cohort Study.

Background: Fever after cardiac surgery is common. More knowledge of postoperative fever could lead to better patient selection for diagnostic workup and empirical antibiotic treatment. We aimed to analyze the postoperative course of inflammation and fever after elective aortic valve and aortic root replacement. Methods: In a retrospective single-center cohort study, we included 3 groups of patients after elective cardiac surgery: aortic root with aortic valve replacement (Bentall procedure, from 2014 to 2021), valve-sparing root replacement (VSRR, from 2014 to 2021), and isolated surgical aortic valve replacement (SAVR, from 2018 to 2021). Exclusion criteria were age <18 years, cardiac surgery other than described, use of deep-hypothermic circulatory arrest, reoperations, and preexisting infections. Primary outcome measure was the number of patients per group with postoperative fever (≥38°C). Secondary outcome measures were the percentage of patients per group with infections and outcome. Results: Among 307 patients included (76 Bentall, 40 VSRR, 191 SAVR), 71% had postoperative fever. Fever occurred significantly more often in the Bentall (84%) and VSRR group (83%) compared with patients after SAVR (64%, P = .001). Seventeen patients had fever due to infection versus 202 with diagnoses of postoperative inflammation. In case of infection, fever was significantly higher (38.8°C vs 38.4°C, P = .03), and both the number of days with fever and hospital admission duration were significantly longer. Conclusions: Postoperative fever is more often observed after Bentall procedure and VSRR compared to SAVR. In diagnoses of infection, there is a higher and prolonged fever.

Cardiac safety of dual anti-HER2 blockade with pertuzumab plus trastuzumab in early HER2-positive breast cancer in the APHINITY trial.

BACKGROUND: Trastuzumab increases the incidence of cardiac events (CEs) in patients with breast cancer (BC). Dual blockade with pertuzumab (P) and trastuzumab (T) improves BC outcomes and is the standard of care for high-risk human epidermal growth factor receptor 2 (HER2)-positive early BC patients. We analyzed the cardiac safety of P and T in the phase III APHINITY trial. PATIENTS AND METHODS: Left ventricular ejection fraction (LVEF) ≥ 55% was required at study entry. LVEF assessment was carried out every 3 months during treatment, every 6 months up to month 36, and yearly up to 10 years. Primary CE was defined as heart failure class III/IV and a significant decrease in LVEF (defined as ≥10% from baseline and to <50%), or cardiac death. Secondary CE was defined as a confirmed significant decrease in LVEF, or CEs confirmed by the cardiac advisory board. RESULTS: The safety analysis population consisted of 4769 patients. With 74 months of median follow-up, CEs were observed in 159 patients (3.3%): 83 (3.5%) in P + T and 76 (3.2%) in T arms, respectively. Most CEs occurred during anti-HER2 therapy (123; 77.4%) and were asymptomatic or mildly symptomatic decreases in LVEF (133; 83.6%). There were two cardiac deaths in each arm (0.1%). Cardiac risk factors indicated were age > 65 years, body mass index ≥ 25 kg/m2, baseline LVEF between 55% and <60%, and use of an anthracycline-containing chemotherapy regimen. Acute recovery from a CE based on subsequent LVEF values was observed in 127/155 patients (81.9%). CONCLUSIONS: Dual blockade with P + T does not increase the risk of CEs compared with T alone. The use of anthracycline-based chemotherapy increases the risk of a CE; hence, non-anthracycline chemotherapy may be considered, particularly in patients with cardiovascular risk factors.