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Objective To assess allograft function over time after the Ross procedure. Design Prospective multicentre registry. Setting 10 cardiac surgery departments in Germany and the Netherlands. Patients Among 1775 consecutive adult patients (mean age 43.7±12.0) who underwent the Ross procedure, 1645 (93%) received an allograft (pulmonary=1612, aortic=12, unknown=21), 120 (6%) a bioprosthesis, and 5 (0.3%) a bovine jugular vein for right ventricular outflow tract reconstruction. Intervention Ross procedure. Main outcome measures Using non-linear longitudinal models, serial echocardiographic records (N=6950) were studied to assess pulmonary conduit function over time in patients who had undergone the Ross procedure, with a maximum echocardiographic follow-up of 22.4 years (5.5±4.3 years). Results A slight increase in pulmonary conduit regurgitation grade was observed during follow-up. Freedom from regurgitation grade ≥2+ was 95% after 14 years. Female patient gender, allograft use (compared to bioprosthesis), male donor gender, antibiotic treatment of the allograft, and specific surgical adjustments were associated with a significantly higher regurgitation grade. Mean conduit gradient increased from 4.7 mm Hg at 1 month to 10 mm Hg by 14 years, while peak gradient increased from 8.4 to 18.5 mm Hg. Smaller conduit diameter, male patient gender, younger patient age, younger donor age, and use of a bioprosthesis were associated with a significantly higher mean and peak gradient. During follow-up, 76 reinterventions were required on the pulmonary conduit in 67 patients. Freedom from pulmonary conduit reintervention or dysfunction was 90.6% (95% CI 87.7% to 93.6%) and 79.5% (95% CI 75.2% to 84.0%) at 15 years, respectively. Conclusions Echocardiographic follow-up of pulmonary conduits shows good conduit durability. Clinically important conduit regurgitation and stenosis are rare in adult patients after the Ross operation.

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). 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. 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. 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.

Aims Left ventricular assist device therapy has become the cornerstone in the treatment of end‐stage heart failure and is increasingly used as destination therapy next to bridge to transplant or recovery. HeartMate 3 (HM3) and HeartWare (HVAD) are centrifugal continuous flow devices implanted intrapericardially and most commonly used worldwide. No randomized controlled trials have been performed yet. Analysis based on large registries may be considered as the best alternative but has the disadvantage of different standard of care between centres and missing data. Bias is introduced, because the decision which device to use was not random, even more so because many centres use only one type of left ventricular assist device. Therefore, we performed a propensity score (PS)‐based analysis of long‐term clinical outcome of patients that received HM3 or HVAD in a single centre. Methods and results Between December 2010 and December 2019, 100 patients received HVAD and 81 patients HM3 as primary implantation at the University Medical Centre Utrecht. We performed PS matching with an extensive set of covariates, resulting in 112 matched patients with a median follow‐up of 28 months. After PS matching, survival was not significantly different (P = 0.21) but was better for HM3. The cumulative incidences for haemorrhagic stroke (P = 0.01) and pump thrombosis (P = 0.02) were significantly higher for HVAD patients. The cumulative incidences for major bleeding, ischaemic stroke, right heart failure, and driveline infection were not different between the groups. We found no interaction between the surgeon who performed the implantation and survival (P = 0.59, P = 0.78, and P = 0.89). Sensitivity analysis was performed, by PS matching without patients on preoperative temporary support resulting in 74 matched patients. This also resulted in a non‐significant difference in survival (P = 0.07). The PS‐adjusted Cox regression showed a worse but non‐significant (P = 0.10) survival for HVAD patients with hazard ratio 1.71 (95% confidence interval 0.91–3.24). Conclusions Survival was not significantly different between both groups after PS matching, but was better for HM3, with a significantly lower incidence of haemorrhagic stroke and pump thrombosis for HM3. These results need to be interpreted carefully, because matching may have introduced greater imbalance on unmeasured covariates. A multicentre approach of carefully selected centres is recommended to enlarge the number of matched patients.

Background: There is growing evidence that ergot dopamine agonists may induce cardiac valve regurgitation (CVR) in persons with Parkinson’s disease. It is unclear whether the CVR risk is increased with ergot-dopamine agonist use in persons with hyperprolactinaemia, in whom the dose is much lower. Objective: The aim of the study was to explore the association between different dopamine agonists and CVR in patients with Parkinson’s disease or hyperprolactinaemia. Design: Nested case-control studies conducted separately in cohorts of Parkinson’s disease and hyperprolactinaemia patients. Cases were patients who developed newly diagnosed CVR. Controls were CVR-free patients from the same cohorts and were matched to cases by age, sex, database and calendar year. Setting and Patients: Study patients were identified from over 4.5 million persons in The Health Improvement Network (THIN; UK), Health Search (Italy), and Integrated Primary Care Information (IPCI; the Netherlands) general practice databases in the years 1996–2007. The Parkinson’s disease cohort included new users of dopamine agonists or levodopa, while the hyperprolactinaemia cohort included new users or non-users of dopamine agonists. Main Outcome Measure: Risk of newly diagnosed CVR with dopamine agonist use compared with levodopa use in the Parkinson’s disease cohort, and dopamine agonist-naïve patients in the hyperprolactinaemia cohort. Results: In the Parkinson’s disease cohort (7893 dopamine agonist users, 11 766 levodopa users), 85 incident CVR cases were identified. Increased CVR risk was observed for ergot dopamine agonists (adjusted OR [OR adj ] 3.82; 95% CI 2.14, 6.81), but not for non-ergot dopamine agonists (OR adj 1.20; 95% CI 0.63, 2.29). In the hyperprolactinaemia cohort (6740 dopamine agonist users and 14299 dopamine agonist-naïve patients), 37 CVR cases were identified during a mean follow-up of 4.5 years and 3.5 years for new users and non-users of dopamine agonists, respectively. However, no association with ever use of ergot dopamine agonists was observed (OR adj 0.47; 95% CI 0.20,1.19). Conclusion: Ergot-derived dopamine agonists are associated with an increased risk of CVR in Parkinson’s disease but not in hyperprolactinaemia patients.

ObjectiveThe outcome of female patients after adult cardiac surgery has been reported to be less favourable compared with the outcome of male patients. This study compares men with women with respect to patient and procedural characteristics and early mortality in a contemporary national cohort of patients who underwent aortic valve (AV) and combined aortic valve/coronary (CABG/AV) surgery.MethodsAll patients who underwent AV (n=8717, 56% male) or a combined CABG/AV surgery (n=5867, 67% male) in the Netherlands between January 2007 and December 2011 were included.ResultsIn both groups, women were generally older than men (p<0.001) and presented with higher logistic EuroSCORES. In isolated AV surgery, men and women had comparable in-hospital mortality (OR 1.20, 95% CI 0.90 to 1.61; p=0.220). In concomitant CABG/AV surgery, in-hospital mortality was higher in women compared with men (OR 2.00, 95% CI 1.44 to 2.79; p<0.001). The area under the curve for logistic EuroSCORE 1 was systematically higher for men versus women in isolated AV surgery 0.82 (95% CI 0.78 to 0.86) vs 0.75 (95% CI 0.69 to 0.80) and in concomitant CABG/AV surgery 0.78 (95% CI 0.73 to 0.82) vs 0.69 (95% CI 0.63 to 0.74). Finally, (the weight of) risk factors associated with in-hospital mortality differed between men and women.ConclusionsThere are substantial male-female differences in patient presentation and procedural aspects in isolated AV and concomitant CABG/AV surgery in the Netherlands. Further studies are necessary to explore the mechanisms underlying the observed differences. In addition, the observation that standard risk scores perform worse in women warrants exploration of male-female specific risk models for patients undergoing cardiac surgery.Brief title:

The introduction of the Duke criteria and transesophageal echocardiography has improved early recognition of infective endocarditis but patients are still at high risk for severe morbidity or death. Whether an exclusively antibiotic regimen is superior to surgical intervention is subject to ongoing debate. Current guidelines indicate when surgery is the preferred treatment, but decisions are often based on physician preferences. Surgery has shown to decrease the risk of short-term mortality in patients who present with specific symptoms or microorganisms; nevertheless even then it often remains unclear when surgery should be performed. In this review we i) systematically reviewed the current literature comparing medical to surgical therapy to evaluate if surgery is the preferred option, ii) performed a meta-analysis of studies reporting propensity matched analyses, and iii), briefly summarized the current indications for surgery.

ObjectiveThere is uncertainty about surgical procedures for adult patients aged 18–60 years undergoing aortic valve replacement (AVR). Options include conventional AVR (mechanical, mAVR; tissue, tAVR), the pulmonary autograft (Ross) and aortic valve neocuspidisation (Ozaki). Transcatheter treatment may be an option for selected patients. We used formal consensus methodology to make recommendations about the suitability of each procedure.MethodsA working group, supported by a patient advisory group, developed a list of clinical scenarios across seven domains (anatomy, presentation, cardiac/non-cardiac comorbidities, concurrent treatments, lifestyle, preferences). A consensus group of 12 clinicians rated the appropriateness of each surgical procedure for each scenario on a 9-point Likert scale on two separate occasions (before and after a 1-day meeting).ResultsThere was a consensus that each procedure was appropriate (A) or inappropriate (I) for all clinical scenarios as follows: mAVR: total 76% (57% A, 19% I); tAVR: total 68% (68% A, 0% I); Ross: total 66% (39% A, 27% I); Ozaki: total 31% (3% A, 28% I). The remainder of percentages to 100% reflects the degree of uncertainty. There was a consensus that transcatheter aortic valve implantation is appropriate for 5 of 68 (7%) of all clinical scenarios (including frailty, prohibitive surgical risk and very limited life span).ConclusionsEvidence-based expert opinion emerging from a formal consensus process indicates that besides conventional AVR options, there is a high degree of certainty about the suitability of the Ross procedure in patients aged 18–60 years. Future clinical guidelines should include the option of the Ross procedure in aortic prosthetic valve selection.

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.

Consensus regarding optimal cerebral protection strategy in aortic arch surgery is lacking. We therefore performed a systematic review and meta-analysis to assess outcome differences between unilateral antegrade cerebral perfusion (ACP), bilateral ACP, retrograde cerebral perfusion (RCP) and deep hypothermic circulatory arrest (DHCA). A systematic literature search was performed in Embase, Medline, Web of Science, Cochrane and Google Scholar for all papers published till February 2021 reporting on early clinical outcome after aortic arch surgery utilizing either unilateral, bilateral ACP, RCP or DHCA. The primary outcome was operative mortality. Other key secondary endpoints were occurrence of postoperative disabling stroke, paraplegia, renal and respiratory failure. Pooled outcome risks were estimated using random-effects models. A total of 222 studies were included with a total of 43 720 patients. Pooled postoperative mortality in unilateral ACP group was 6.6% [95% confidence interval (CI) 5.3–8.1%], 9.1% (95% CI 7.9–10.4%), 7.8% (95% CI 5.6–10.7%), 9.2% (95% CI 6.7–12.7%) in bilateral ACP, RCP and DHCA groups, respectively. The incidence of postoperative disabling stroke was 4.8% (95% CI 3.8–6.1%) in the unilateral ACP group, 7.3% (95% CI 6.2–8.5%) in bilateral ACP, 6.4% (95% CI 4.4–9.1%) in RCP and 6.3% (95% CI 4.4–9.1%) in DHCA subgroups. The present meta-analysis summarizes the clinical outcomes of different cerebral protection techniques that have been used in clinical practice over the last decades. These outcomes may be used in advanced microsimulation model. These findings need to be placed in the context of the underlying aortic disease, the extent of the aortic disease and other comorbidities. Prospero registration number: CRD42021246372 METC: MEC-2019-0825

ObjectiveLongitudinal data on age-related changes in the diameters of the thoracic aorta are scarce. To better understand normal variation and to identify factors influencing this process, we aimed to report male-female-specific and age-specific aortic growth rate in the ageing general population and identify factors associated with growth rate.MethodsFrom the prospective population-based Rotterdam Study, 943 participants (52.0% females, median age at baseline 65 years (62–68)) underwent serial non-enhanced cardiac CT. We measured the diameters of the ascending (AA) and descending aorta (DA) at two time points and expressed absolute and relative differences. Linear mixed effects analysis was performed to identify determinants associated with change in aortic diameters.ResultsMean AA diameter at baseline was 37.3±3.6 mm in male population and 34.7±3.2 mm in female population, mean DA diameter was 29.6±2.3 in male population and 26.9±2.2 mm in female population. The median absolute change in diameters during follow-up (mean scan interval 14.1±0.3 years) was 1 mm (0–2) for both the AA and DA. Absolute change per decade in AA diameter was significantly larger in males than in females (0.72 mm/decade (0.00–1.43) vs 0.70 mm/decade (0.00–1.41), p=0.006), as well as absolute change in AD diameter (0.71 mm/decade (0.00–1.42) vs 0.69 mm/decade (0.00–1.36), p=0.008). There was no significant difference between male and female population in relative change of their aortic diameters during follow-up. Age, male sex, higher body mass index (BMI) and higher diastolic blood pressure (DBP) showed a statistically significant independent association with increase in AA and DA diameters over time.ConclusionsSome degree of increase in thoracic aortic diameters is typical in both men and women of an aging population. Factors associated with this change in thoracic aortic diameters were sex, age, BMI and DBP.