Association of HbA1c and utilization of internal mammary arteries with wound infections in CABG.

Background: Deep sternal wound infection (DSWI) remains a serious complication after coronary artery bypass grafting (CABG). We herein aimed to stratify diabetic patients who underwent CABG using bilateral internal mammary artery (BIMA) for levels of glycated hemoglobin A1C (HbA1c) and compare postoperative outcomes. Methods: Between January 2010 and August 2020, 4,186 consecutive patients underwent isolated CABG at our center. In 3,229 patients, preoperative HbA1c levels were available. Primary endpoints were wound healing disorder (WHD), DSWI, and 30-day mortality. Patients were stratified according to preoperative HbA1c levels. Patients were further divided into subgroups according to utilization of BIMA. Results: After adjustment, no differences in mortality and stroke rates were seen between group 1 (HbA1c < 6.5%) vs. group 2 (HbA1c ≥ 6.5%). WHD was more frequent in group 2 [2.8 vs. 5.6%; adjusted p = 0.002; adjusted odds ratio (OR), 1.853 (1.243-2.711)] but not DSWI [1.0 vs. 1.5%; adjusted p = 0.543; adjusted OR, 1.247 (0.612-2.5409)]. BIMA use showed a higher rate of WHD [no BIMA: 3.0%; BIMA: 7.7%; adjusted p = 0.002; adjusted OR, 4.766 (1.747-13.002)] but not DSWI [no BIMA: 1.1%; BIMA: 1.8%; adjusted p = 0.615; adjusted OR, 1.591 (0.260-9.749)] in patients with HbA1c ≥ 6.5%. Conclusions: Intraoperative utilization of BIMA is not connected with an increase of DSWI but higher rates of WHD in patients with poor diabetic status and HbA1c ≥ 6.5%. Therefore, application of BIMA should be taken into consideration even in patients with poor diabetic status, while identification of special subsets of patients who are at particular high risk for DSWI is of paramount importance to prevent this serious complication.

Is Single LIMA-LAD Bypass Appropriate for OPCAB Training?

BACKGROUND: A significant impact of surgeons' experience on outcomes of off-pump coronary artery bypass (OPCAB) has been recognized through previous large-scale studies. However, a safe, effective, and concrete OPCAB training was yet to be identified. We evaluate a safety of our OPCAB training model with single left internal mammary artery (LIMA)-left anterior descending artery (LAD) as a reasonable first step. METHODS: Between January 2010 and June 2019, 180 patients with an isolated single coronary bypass of the LAD using LIMA as an in situ graft via median sternotomy fulfilled the inclusion criteria. Coronary arterial bypass under cardiopulmonary bypass (CPB), utilizing other graft material, minimal invasive direct coronary arterial bypass through left-sided thoracotomy, and multiple diseased coronary artery disease were excluded. The primary outcome is an early postoperative outcome (major adverse cardiac and cerebrovascular events [MACCEs]: myocardial infarction, coronary re-revascularization, stroke, acute renal failure, and all causes of death) between residents in training under supervision (group 1: n = 63) and experienced surgeons (group 2: n = 117). Trainees were already experienced in on-pump coronary artery bypass grafting. RESULTS: Preoperative variables were comparable. There was no significant difference in the rate of MACCEs between the two groups including hospital mortality (p = 1.000), perioperative myocardial infarction (p = 0.246), stroke (p = 0.655), and acute renal failure (p = 0.175). CONCLUSION: The early postoperative outcome of off-pump LIMA to the LAD performed by trainees was comparable to those by experienced surgeons. Single LIMA-LAD was safely performed by trainees under supervision without CPB. In order to master OPCAB technique, single LAD bypass might be a reasonable first step to get into touch with the technical characteristics of this special procedure.

Long-term survival after surgical treatment for post-infarction mechanical complications: results from the Caution study.

BACKGROUND AND AIMS: Mechanical complications (MCs) are rare but potentially fatal sequelae of acute myocardial infarction (AMI). Surgery, though challenging, is considered the treatment of choice. The authors sought to study early and long-term results of patients undergoing surgical treatment for post-AMI MCs. METHODS: Patients undergone surgical treatment for post-infarction MCs between 2001 through 2019 in 27 centers worldwide were retrieved from the database of CAUTION study. In-hospital and long-term mortality were the primary outcomes. Cox proportional hazards regression models were used to determine independent factors associated with overall mortality. RESULTS: The study included 720 patients. The median age was 70.0 [62.0-77.0] years, with a male predominance (64.6%). The most common MC encountered was ventricular septal rupture (VSR) (59.4%). Cardiogenic shock was seen on presentation in 56.1% of patients. In-hospital mortality rate was 37.4%; in more than 50% of cases, the cause of death was low cardiac output syndrome (LCOS). Late mortality occurred in 133 patients, with a median follow-up of 4.4 [1.0-8.6] years. Overall survival at 1, 5 and 10 years was 54.0%, 48.1% and 41.0%, respectively. Older age (p < 0.001) and postoperative LCOS (p < 0.001) were independent predictors of overall mortality. For hospital survivors, 10-year survival was 65.7% and was significant higher for patients with VSR than those with papillary muscle rupture (long-rank P = 0.022). CONCLUSIONS: Contemporary data from a multicenter cohort study show that surgical treatment for post-AMI MCs continues to be associated with high in-hospital mortality rates. However, long-term survival in patients surviving the immediate postoperative period is encouraging.Trial registration number: NCT03848429.

Impact of COVID-19 on incidence and outcomes of post-infarction mechanical complications in Europe.

OBJECTIVES: Post-acute myocardial infarction mechanical complications (post-AMI MCs) represent rare but life-threatening conditions, including free-wall rupture, ventricular septal rupture and papillary muscle rupture. During the coronavirus disease-19 (COVID-19) pandemic, an overwhelming pressure on healthcare systems led to delayed and potentially suboptimal treatments for time-dependent conditions. As AMI-related hospitalizations decreased, limited information is available whether higher rates of post-AMI MCs and related deaths occurred in this setting. This study was aimed to assess how COVID-19 in Europe has impacted the incidence, treatment and outcome of MCs. METHODS: The CAUTION-COVID19 study is a multicentre retrospective study collecting 175 patients with post-AMI MCs in 18 centres from 6 European countries, aimed to compare the incidence of such events, related patients' characteristics, and outcomes, between the first year of pandemic and the 2 previous years. RESULTS: A non-significant increase in MCs was observed [odds ratio (OR) = 1.15, 95% confidence interval (CI) 0.85-1.57; P = 0.364], with stronger growth in ventricular septal rupture diagnoses (OR = 1.43, 95% CI 0.95-2.18; P = 0.090). No significant differences in treatment types and mortality were found between the 2 periods. In-hospital mortality was 50.9% and was higher for conservatively managed cases (90.9%) and lower for surgical patients (44.0%). Patients admitted during COVID-19 more frequently had late-presenting infarction (OR = 2.47, 95% CI 1.24-4.92; P = 0.010), more stable conditions (OR = 2.61, 95% CI 1.27-5.35; P = 0.009) and higher EuroSCORE II (OR = 1.04, 95% CI 1.01-1.06; P = 0.006). CONCLUSIONS: A non-significant increase in MCs incidence occurred during the first year of COVID-19, characterized by a significantly higher rate of late-presenting infarction, stable conditions and EuroSCORE-II if compared to pre-pandemic data, without affecting treatment and mortality.

The current clinical practice for management of post-infarction ventricular septal rupture: a European survey.

Aims: Many historical and recent reports showed that post-infarction ventricular septal rupture (VSR) represents a life-threatening condition and the strategy to optimally manage it remains undefined. Therefore, disparate treatment policies among different centres with variable results are often described. We analysed data from European centres to capture the current clinical practice in VSR management. Methods and results: Thirty-nine centres belonging to eight European countries participated in a survey, filling a digital form of 38 questions from April to October 2022, to collect information about all the aspects of VSR treatment. Most centres encounter 1-5 VSR cases/year. Surgery remains the treatment of choice over percutaneous closure (71.8% vs. 28.2%). A delayed repair represents the preferred approach (87.2%). Haemodynamic conditions influence the management in almost all centres, although some try to achieve patients stabilization and delayed surgery even in cardiogenic shock. Although 33.3% of centres do not perform coronarography in unstable patients, revascularization approaches are widely variable. Most centres adopt mechanical circulatory support (MCS), mostly extracorporeal membrane oxygenation, especially pre-operatively to stabilize patients and achieve delayed repair. Post-operatively, such MCS are more often adopted in patients with ventricular dysfunction. Conclusion: In real-life, delayed surgery, regardless of the haemodynamic conditions, is the preferred strategy for VSR management in Europe. Extracorporeal membrane oxygenation is becoming the most frequently adopted MCS as bridge-to-operation. This survey provides a useful background to develop dedicated, prospective studies to strengthen the current evidence on VSR treatment and to help improving its currently unsatisfactory outcomes.

Impact of Surgeon Experience and Centre Volume on Outcome After Off-Pump Coronary Artery Bypass Surgery: Results From the European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG) Registry.

AIM: The aim of this study was to assess the impact of surgeon experience and centre volume on early operative outcomes in patients undergoing off-pump coronary artery bypass (OPCAB) surgery. METHOD: Of 7,352 patients in the European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG) registry, 1,549 underwent OPCAB and were included in the present analysis. Using adjusted regression analysis, we compared major early adverse events after procedures performed by experienced OPCAB surgeons (i.e., ≥20 cases per year; n=1,201) to those performed by non-OPCAB surgeons (n=348). Furthermore, the same end points were compared between procedures performed by OPCAB surgeons in high OPCAB volume centres (off-pump technique used in >50% of cases; n=894) and low OPCAB volume centres (n=307). RESULTS: In the experienced OPCAB surgeon group, we observed shorter procedure times (ß -43.858, 95% confidence interval [CI] -53.322 to -34.393; p<0.001), a lower rate of conversion to cardiopulmonary bypass (odds ratio [OR] 0.284, 95% CI 0.147-0.551; p<0.001), a lower rate of prolonged inotrope or vasoconstrictor use (OR 0.492, 95% CI 0.371-0.653; p<0.001), a lower rate of early postprocedural percutaneous coronary interventions (OR 0.335, 95% CI 0.169-0.663; p=0.002), and lower 30-day mortality (OR 0.423, 95% CI 0.194-0.924; p=0.031). In high OPCAB volume centres, we found a lower rate of prolonged inotrope use (OR 0.584, 95% CI 0.419-0.814; p=0.002), a lower rate of postprocedural acute kidney injury (OR 0.382, 95% CI 0.198-0.738; p=0.004), shorter duration of intensive care unit (ß -1.752, 95% CI -2.240 to -1.264; p<0.001) and hospital (ß -1.967; 95% CI -2.717 to -1.216; p<0.001) stays, and lower 30-day mortality (OR 0.316, 95% CI 0.114-0.881; p=0.028). CONCLUSIONS: Surgeon experience and centre volume may play an important role on the early outcomes after OPCAB surgery.

Antegrade axillary arterial perfusion in 3D endoscopic minimally-invasive mitral valve surgery.

Background: Minimally-invasive (MIS) mitral valve (MV) surgery has become standard therapy in many cardiac surgery centers. While femoral arterial perfusion is the preferred cannulation strategy in MIS mitral valve surgery, retrograde arterial perfusion is known to be associated with an increased risk for cerebral atheroembolism, particularly in atherosclerosis patients. Therefore, antegrade perfusion may be beneficial in such cases. This analysis aimed to compare outcomes of antegrade axillary vs. retrograde femoral perfusion in the MIS mitral valve surgery. Methods: This analysis includes 50 consecutive patients who underwent MIS between 2016 and 2020 using arterial cannulation of right axillary artery (Group A) due to severe aortic arteriosclerosis. Perioperative outcomes of the study group were compared with a historical control group of retrograde femoral perfusion (Group F) which was adjusted for age and gender (n = 50). Primary endpoint of the study was in-hospital mortality and perioperative cerebrovascular events. Results: Patients in group A had a significantly higher perioperative risk as compared to Group F (EuroSCORE II: 3.9 ± 2.5 vs. 1.6 ± 1.5; p = 0.001; STS-Score: 2.1 ± 1.4 vs. 1.3 ± 0.6; p = 0.023). Cardiopulmonary bypass time (group A: 172 ± 46; group F: 178 ± 51 min; p = 0.627) and duration of surgery (group A: 260 ± 65; group F: 257 ± 69 min; p = 0.870) were similar. However, aortic cross clamp time was significantly shorter in group A as compared to group F (86 ± 20 vs. 111 ± 29 min, p < 0.001). There was no perioperative stroke in either groups. In-hospital mortality was similar in both groups (group A: 1 patient; group F: 0 patients; p = 0.289). In group A, one patient required central aortic repair due to intraoperative aortic dissection. No further cardiovascular events occurred in Group A patients. Conclusion: Selective use of antegrade axillary artery perfusion in patients with systemic atherosclerosis shows similar in-hospital outcomes as compared to lower risk patients undergoing retrograde femoral perfusion. Patients with higher perioperative risk and severe atherosclerosis can be safely treated via the minimally invasive approach with antegrade axillary perfusion.

Circulating microRNAs in the prediction of BAV aortopathy: do the expression patterns correlate between blood and aortic tissue?

BACKGROUND: The limitation of aortic size-based criteria is gradually recognized in the prediction of aortic events especially in bicuspid aortic valve (BAV) cohorts, while most aortic events happen in patients with proximal aortic diameters <50 mm. Circulating microRNAs (miRs) have been addressed as a novel tool to improve risk stratification in patients with different aortopathies. We aimed to elucidate the correlation between peripheral whole blood and aortic tissue miRs in order to prove the potential availability as a biomarker in the clinical routine. METHODS: All patients who received elective aortic valve repair/replacement ± proximal aortic replacement to BAV disease (n = 65, 2013-2018) were prospectively included. The expression of 10 miRs (miR-1, miR-17, miR-18a, miR-19a, miR-20a, miR-21, miR-106a, miR-133a, miR-143 and miR-145) was analyzed in the intraoperatively acquired aortic tissue as well as in the peripheral blood before the surgery. RESULTS: We found a significant correlation between circulating miRs in the peripheral blood and aortic tissue levels of miR-21 (r = 0.293, p = 0.02), miR-133a (r = 0.43, p = 0.02), miR-143 (r = 0.68, p < 0.001), and miR-145 (r = 0.68, p < 0.001). Further, the multivariate logistic regression analysis revealed an association between blood and aortic tissue miR-143 levels each other (Odds Ratio [OR] 1.29, 95% Confidence Interval [CI] 1.11-1.67, p = 0.02; OR 1.36, 95% CI 1.19-2.01, p = 0.03, respectively) and a blood/aortic miR-143 level to dilated aorta (OR 3.61, 95% CI 1.62-9.02, p = 0.01; OR 2.92, 95% CI 1.81-7.05, p = 0.02, respectively). CONCLUSIONS: Our study demonstrates a significant correlation between peripheral whole blood and aortic tissue miRs, confirming the hypothesis that circulating miRs may reflect remodeling processes in the proximal aorta in bicuspid aortopathy patients.

Circulating microRNAs vs. aortic diameter in bicuspid aortic valve aortopathy.

There is growing clinical need and interest to implement novel risk prediction tools in bicuspid aortic valve-associated proximal aortic disease, so-called bicuspid aortic valve aortopathy. Inherent limitations of the diameter-based risk stratification for adverse aortic events in bicuspid aortic valve aortopathy patients have recently been recognized. Therefore, alternative diagnostic tools and subsequent adjustments in the treatment guidelines are urgently needed. Herein, we summarize the current evidence on recent diagnostic developments to improve risk stratification in bicuspid aortic valve aortopathy, including circulating microRNAs as biomarkers to predict the progression of aortic disease.

Neurological Complications in High-Risk Patients Undergoing Coronary Artery Bypass Surgery.

BACKGROUND: Coronary artery bypass grafting (CABG) without cardiopulmonary bypass and minimal or no aortic manipulation may be associated with a lower risk of neurological complications. We investigated this issue in patients with a high risk of perioperative stroke. METHODS: Data on 7352 patients who underwent isolated CABG from January 2015 to May 2017 were included in the multicenter study E-CABG (European Coronary Artery Bypass Grafting) registry. Of these, 684 patients had an increased risk of neurological complications, ie, previous stroke or transient ischemic attack, severe carotid artery stenosis or occlusion, or previous carotid artery intervention. In this subgroup, we analyzed the rates of the combined primary endpoint comprising any postoperative stroke or transient ischemic attack. A comparative analysis between CABG with and without aortic cross-clamping was performed. RESULTS: The primary endpoint was more often reached when aortic cross-clamping was used (propensity score matching, without vs with aortic cross-clamp: 0.9% vs 7.2%; P = .016). In comparison with all other revascularization techniques, off-pump CABG with avoidance of aortic manipulation was associated with the lowest rate of neurological complications (0.7%). CONCLUSIONS: In patients with increased risk of perioperative stroke, aortic manipulation including the use of cardiopulmonary bypass or partial clamping for central anastomoses is associated with higher rates of postoperative neurological complications. These patients may benefit from off-pump surgery without aortic manipulation if complete revascularization can be ensured.

Surgical Treatment of Postinfarction Ventricular Septal Rupture.

Importance: Ventricular septal rupture (VSR) is a rare but life-threatening mechanical complication of acute myocardial infarction associated with high mortality despite prompt treatment. Surgery represents the standard of care; however, only small single-center series or national registries are usually available in literature, whereas international multicenter investigations have been poorly carried out, therefore limiting the evidence on this topic. Objectives: To assess the clinical characteristics and early outcomes for patients who received surgery for postinfarction VSR and to identify factors independently associated with mortality. Design, Setting, and Participants: The Mechanical Complications of Acute Myocardial Infarction: an International Multicenter Cohort (CAUTION) Study is a retrospective multicenter international cohort study that includes patients who were treated surgically for mechanical complications of acute myocardial infarction. The study was conducted from January 2001 to December 2019 at 26 different centers worldwide among 475 consecutive patients who underwent surgery for postinfarction VSR. Exposures: Surgical treatment of postinfarction VSR, independent of the technique, alone or combined with other procedures (eg, coronary artery bypass grafting). Main Outcomes and Measures: The primary outcome was early mortality; secondary outcomes were postoperative complications. Results: Of the 475 patients included in the study, 290 (61.1%) were men, with a mean (SD) age of 68.5 (10.1) years. Cardiogenic shock was present in 213 patients (44.8%). Emergent or salvage surgery was performed in 212 cases (44.6%). The early mortality rate was 40.4% (192 patients), and it did not improve during the nearly 20 years considered for the study (median [IQR] yearly mortality, 41.7% [32.6%-50.0%]). Low cardiac output syndrome and multiorgan failure were the most common causes of death (low cardiac output syndrome, 70 [36.5%]; multiorgan failure, 53 [27.6%]). Recurrent VSR occurred in 59 participants (12.4%) but was not associated with mortality. Cardiogenic shock (survived: 95 [33.6%]; died, 118 [61.5%]; P < .001) and early surgery (time to surgery ≥7 days, survived: 105 [57.4%]; died, 47 [35.1%]; P < .001) were associated with lower survival. At multivariate analysis, older age (odds ratio [OR], 1.05; 95% CI, 1.02-1.08; P = .001), preoperative cardiac arrest (OR, 2.71; 95% CI, 1.18-6.27; P = .02) and percutaneous revascularization (OR, 1.63; 95% CI, 1.003-2.65; P = .048), and postoperative need for intra-aortic balloon pump (OR, 2.98; 95% CI, 1.46-6.09; P = .003) and extracorporeal membrane oxygenation (OR, 3.19; 95% CI, 1.30-7.38; P = .01) were independently associated with mortality. Conclusions and Relevance: In this study, surgical repair of postinfarction VSR was associated with a high risk of early mortality; this risk has remained unchanged during the last 2 decades. Delayed surgery seemed associated with better survival. Age, preoperative cardiac arrest and percutaneous revascularization, and postoperative need for intra-aortic balloon pump and extracorporeal membrane oxygenation were independently associated with early mortality. Further prospective studies addressing preoperative and perioperative patient management are warranted to hopefully improve the currently suboptimal outcome.

Narrative review of the contemporary surgical treatment of unicuspid aortic valve disease.

Unicuspid aortic valve disease (UAVD) is a frequent and long-lasting challenge for adult congenital heart disease centers. UAVD patients become usually symptomatic in their twenties or thirties and require a surgical treatment plan which should respect their complete lifespan combined with an adequate quality of life. Unfortunately, all current surgical strategies of congenital aortic valve disease bear some important limitations: (I) Aortic valve replacement using bioprosthetic valves is associated with early structural degeneration and leads frequently to re-operations. (II) Mechanical valves are commonly associated with lifelong risk of severe bleeding due to oral anticoagulation. (III) Using a pulmonary autograft (i.e., Ross procedure) for aortic valve replacement is associated with excellent long-term results in non-elderly patients. However, failure of pulmonary autograft or pulmonary homograft may require re-operations. (IV) Aortic valve repair or Ozaki procedure is only performed in a few heart centers worldwide and is associated with a limited reproducibility and early patch degeneration, suture dehiscence or increased risk of endocarditis. In contrast to degenerative tricuspid aortic valve disease, UAVD remains relatively understudied and reports on UAVD treatment are rare and usually limited to retrospective single-center observations. For this review, we searched PubMed for papers in the English language by using the search words unicuspid aortic valve, congenital aortic valve, Ross procedure, Ozaki procedure, aortic valve repair, mechanical/bioprosthetic aortic replacement, homograft. We read the abstracts of relevant titles to confirm their relevance, and the full papers were then extracted. References from extracted papers were checked for additional relevant reports. This review summarizes current surgical treatment strategies for UAVD including aortic valve replacement using bioprosthetic or mechanical valves, homografts, pulmonary autografts (i.e., Ross procedure) and aortic valve repair techniques for UAV. Furthermore, Ozaki procedure will be discussed.

Persistence of Reduced Left Ventricular Function after Aortic Valve Surgery for Aortic Valve Regurgitation: Bicuspid versus Tricuspid.

OBJECTIVE: Long-term prognosis of patients with aortic regurgitation (AR) and reduced left ventricular ejection fraction (LVEF) who undergo aortic valve surgery (AVS) is unknown. Due to the congenital origin, bicuspid aortic valve (BAV) morphotype might be associated with a more severe cardiomyopathy. We aimed to evaluate the LVEF recovery after aortic valve replacement (AVR) surgery in patients with AR and reduced preoperative LVEF. METHODS: This retrospective analysis included 1,170 consecutive patients with moderate to severe AR who underwent AVS at our institution between January 2005 and April 2016. Preoperative echocardiography revealed 154 (13%) patients with predominant AR and baseline LVEF < 50%. A total of 60 (39%) patients had a BAV (BAV group), while the remaining 94 (61%) patients had a tricuspid morphotype (tricuspid aortic valve [TAV] group). Follow-up protocol included clinical interview using a structured questionnaire and echocardiographic follow-up. RESULTS: A total of 154 patients (mean age 63.5 ± 12.4 years, 71% male) underwent AVS for AR in the context of reduced LVEF (mean LVEF 42 ± 8%). Fifteen (10%) patients had a severely reduced preoperative LVEF ≤ 30%. Mean STS (Society of Thoracic Surgeons) score was 1.36 ± 1.09%. Mean follow-up was comparable between both the study groups (BAV: 50 ± 40 months vs. TAV: 40 ± 38 months, p = 0.140). A total of 25 (17%) patients died during follow-up. Follow-up echocardiography demonstrated similar rate of postoperatively reduced LVEF in both groups (i.e., 39% BAV patients vs. 43% TAV patients; p = 0.638). Cox's regression analysis showed no significant impact of BAV morphotype (i.e., as compared with TAV) on the postoperative LVEF recovery (odds ratio [OR]: 1.065; p = 0.859). Severe left ventricular (LV) dysfunction at baseline (i.e., LVEF ≤ 30%) was a strong predictor for persistence of reduced LVEF during follow-up (OR: 3.174; 95% confidence interval: 1.517-6.640; p = 0.002). Survival was significantly reduced in patients with persisting LV dysfunction versus those in whom LVEF recovered (log rank: p < 0.001). CONCLUSION: Our study demonstrates that reduced LVEF persists postoperatively in 40 to 45% patients who present with relevant AR and reduced LVEF at baseline. Postoperative LVEF recovery is independent of aortic valve morphotype (i.e., BAV vs. TAV). Severe LV dysfunction (LVEF ≤ 30%) at baseline is a strong predictor for persistence of reduced LVEF in patients with AR and results in significantly reduced long-term survival.

Bicuspid aortopathy - molecular involvement of microRNAs and MMP-TIMP.

OBJECTIVES: We aimed to elucidate the correlation between expression patterns of aortic tissue microRNAs and the aortopathy formation in bicuspid aortic valve (BAV) disease. METHODS: All 65 patients who underwent elective aortic valve repair/replacement +/- proximal aortic replacement due to BAV disease with or without concomitant aortic aneurysm were identified from our BAV registry. Aortic tissue was collected intraoperatively from the ascending aorta at the greater and lesser curvature. Aortic tissue microRNAs analysis included 11 microRNAs (miR-1, miR-17, miR-18a, miR-19a, miR-20a, miR-21, miR-29b, miR-106a, miR-133a, miR-143 and miR-145). Furthermore, analysis of MMP2, TIMP1/2 mRNA and the protein expression was subsequently performed. The primary study endpoint was the correlation between microRNAs and MMP2, TIMP1/2 mRNA/protein expression. RESULTS: We found a significant association between miR-133a and TIMP1 mRNA (r = 0.870, p < 0.001), an inverse correlation between miR-143a and MMP2 protein expression (r= -0.614, p = 0.044) and a positive correlation between miR-133a and TIMP-2 protein expression (r = 0.583, p = 0.036) at the greater curvature. CONCLUSION: Our findings indicate that aortic tissue microRNAs may reflect remodelling processes of the proximal aorta in BAV aortopathy. Specific aortic tissue microRNAs may exert their regulatory effects on the aortopathy through their impact on MMPs/TIMPs homeostasis at the level of the greater curvature.

Focus on a rare clinical entity: unicuspid aortic valve disease.

INTRODUCTION: While the understanding of the pathophysiology and clinical implication of bicuspid aortic valves evolves rapidly, the natural history of unicuspid aortic valves is still poorly understood. Hence, a universally accepted diagnostic work-up process and therapy recommendations for UAV still have to be established. AREAS COVERED: This article aims to give an overview on the most recent literature addressing the pathophysiology, the diagnostic tools and appropriate surgical therapy options of unicuspid aortic valve. Due to the rare prevalence, the understanding of pathophysiology is still missing. Further, symptomatic aortic valve disease are seen much earlier life stage in this cohorts. Thus, it highlights the several surgical treatment options with pro and contra especially for the young adult cohorts. EXPERT OPINION: Large scale prospective observational studies using standardized diagnostic criteria are needed to reveal the clinical course. Further appropriate treatment strategies of unicuspid aortic valve patients is demanded.

Expression Patterns of Circulating MicroRNAs in the Risk Stratification of Bicuspid Aortopathy.

OBJECTIVE: Aortic size-based criteria are of limited value in the prediction of aortic events, while most aortic events occur in patients with proximal aortic diameters < 50 mm. Serological biomarkers and especially circulating microRNAs (miRNAs) have been proposed as an elegant tool to improve risk stratification in patients with different aortopathies. Therefore, we aimed to evaluate the levels of circulating miRNAs in a surgical cohort of patients presenting with bicuspid aortic valve disease and distinct valvulo-aortic phenotypes. METHODS: We prospectively examined a consecutive cohort of 145 patients referred for aortic valve surgery: (1) Sixty three patients (mean age 47 ± 11 years, 92% male) with bicuspid aortic valve regurgitation and root dilatation (BAV-AR), (2) thirty two patients (mean age 59 ± 11 years, 73% male) with bicuspid aortic valve stenosis (BAV-AS), and (3) fifty patients (mean age 56 ± 14 years, 55% male) with tricuspid aortic valve stenosis and normal aortic root diameters (TAV-AS) who underwent aortic valve+/-proximal aortic surgery at a single institution. MicroRNAs analysis included 11 miRNAs, all published previously in association with aortopathies. Endpoints of our study were (1) correlation between circulating miRNAs and aortic diameter and (2) comparison of circulating miRNAs in distinct valvulo-aortic phenotypes. RESULTS: We found a significant inverse linear correlation between circulating miRNAs levels and proximal aortic diameter in the whole study cohort. The strongest correlation was found for miR-17 (r = -0.42, p < 0.001), miR-20a (r = -0.37, p < 0.001), and miR-106a (r = -0.32, p < 0.001). All miRNAs were significantly downregulated in BAV vs. TAV with normal aortic root dimensions Conclusions: Our data demonstrate a significant inverse correlation between circulating miRNAs levels and the maximal aortic diameter in BAV aortopathy. When comparing miRNAs expression patterns in BAV vs. TAV patients with normal aortic root dimensions, BAV patients showed significant downregulation of analyzed miRNAs as compared to their TAV counterparts. Further multicenter studies in larger cohorts are needed to further validate these results.

Aortic valve-related aortopathy: assessing optimal timing of surgical intervention.

Introduction: Dilatation of the proximal aorta is often associated with an aortic valve disease (e.g. bicuspid aortic valve, aortic stenosis), so-called 'valve-related aortopathy.' The definition of optimal timing for surgical intervention in valve-related aortopathy remains incompletely clarified. The limited value of traditional diameter-based intervention criteria has been recognized and more sophisticated diagnostic tools are necessary.Areas covered: This article aims to give an overview on the most recent literature addressing the different forms of valve-related aortopathies and the optimal timing of surgical intervention. It highlights the valve morphotype-dependent (BAV vs TAV) and the valve lesion-dependent aortopathies (stenosis vs regurgitation) and outlines the current treatment options of those pathologies. Further, this review discusses novel serological and rheological markers, potentially helping in the decision-making process in valve-related aortopathy. Systematic literature searches were performed using PubMed and Embase up to July 2019.Expert opinion: The combination of serological biomarkers and quantitative rheological markers for transvalvular flow eccentricity might be an additional useful tool. A possible solution for the future could be a risk score which considers body-surface-adjusted aortic diameters, activity of certain circulating biomarkers, transvalvular flow patterns, possible connective tissue disorders, and the valve morphology to define an individualized treatment strategy.

Novel Approaches for BAV Aortopathy Prediction-Is There a Need for Cohort Studies and Biomarkers?

Bicuspid aortic valve (BAV) disease is the most common congenital malformation of the human heart with a prevalence of 1⁻2% in the general population. More than half of patients with a BAV present with a dilated proximal aorta (so-called bicuspid aortopathy) which is associated with an enhanced risk of life-threatening aortic complications. Up to now, the pathogenesis of bicuspid aortopathy as well as the risk stratification of aortic complications has not yet been sufficiently clarified. Recent findings have shown that bicuspid aortopathy features phenotypic heterogeneity. Two distinct valvulo-aortic phenotypes, the so-called root phenotype, as well as a dilation of the tubular ascending aorta, coincide with a significantly different risk for aortal complications. However, the phenotype-based classification that is only based on these two clinical forms is not sufficient to estimate the risk of aortal complications in a prognostically relevant way. Therefore, there is growing clinical interest to assess novel approaches in BAV research and to introduce circulating biomarkers as an elegant diagnostic tool to improve risk stratification in BAV aortopathy. A large scale epidemiological cohort study, ranking from apparently healthy individuals to disease patients, and comprehensive biobanks provide the opportunity to study BAV disease and its complications and to identify novel biomarkers for BAV aortopathy surveillance and prognosis. Firstly, the data indicate that several protein-based biomarkers and non-coding RNA molecules, in particular circulating microRNAs, can serve as relevant molecular biomarkers to predict the course of BAV-associated aortopathy. Here, we review the current literature and knowledge about BAV from a clinical point of view, and report about novel approaches in BAV biomarker research.

Evaluation of microribonucleic acids as potential biomarkers in the bicuspid aortic valve-associated aortopathy.

OBJECTIVES: We aimed to evaluate the impact of microRNAs to predict the bicuspid aortic valve (BAV)-associated aortopathy. METHODS: Sixty-three BAV patients (mean age 47 ± 11 years, 92% men) with root dilatation, who underwent aortic valve ± proximal aortic surgery (mean post-AVR follow-up 10.3 ± 6.9 years) were included. The BAV aortopathy entities were categorized in the 'less dilated' (aortic root <50 mm) and 'severely dilated' (aortic root ≥50 mm) aorta. Several microRNAs were assessed using polymerase chain reaction. End-points were the correlation between microRNAs and severity of aortopathy/prevalence of adverse aortic events. RESULTS: Circulating levels of miR-17 and miR-106a were strongly correlated (r = 0.84, P < 0.001). Our analysis yielded significantly higher values of miR-17 (delta Ct 2.09 ± 0.64 vs delta Ct 1.68 ± 0.64, P = 0.02) and miR-106a (delta Ct 5.88 ± 0.43 vs delta Ct 5.61 ± 0.60, P = 0.046) in BAV patients with the less dilated versus the severely dilated aorta. miR-17 (delta Ct 1.51 ± 0.73 vs delta Ct 2.00 ± 0.61, P = 0.02) and miR-106a (delta Ct 5.39 ± 0.69 vs delta Ct 5.85 ± 0.44, P = 0.007) were significantly downregulated in BAV patients who experienced adverse aortic events. CONCLUSIONS: Expression of circulating miR-17 and miR-106a in the BAV root phenotype patients correlates with the severity of aortopathy and the risk of adverse aortic events. MicroRNAs have the potential to serve as biomarkers in the BAV-associated aortopathy.