Rationale and design of the ELEANOR trial early aortic valve surgery versus watchful waiting strategy in severe asymptomatic aortic regurgitation, ACRONYM: ELEANOR.

Background: The optimal treatment of patients with severe symptomatic aortic regurgitation (AR) is state-of-the-art surgery. Asymptomatic patients with advanced left ventricular (LV) dilatation and/or impaired ejection fraction should undergo surgical treatment, but there is no guidelines consensus on cut-off values for this recommendation. Multimodality imaging has brought new tools for the accurate selection of asymptomatic patients at risk of early clinical deterioration, however, prospective and randomized data are pending. Cardiac magnetic resonance (CMR)-derived AR quantification along with LV remodeling assessment appears to be the most accurate tool for a selection of such patients at risk. Trial design: The objective of our prospective and multicenter study is to determine whether patients at risk of early clinical deterioration as per CMR assessment will benefit from early surgical treatment. The study is designed as a superiority trial to demonstrate that early surgical treatment is safe and more effective than the standard treatment. A total of 217 asymptomatic patients with severe AR, but without current guidelines-based surgical indication, will be enrolled across all centers. We expect 24 % of patients identified as high clinical risk and therefore eligible for 1:1 randomization to early surgical treatment within 3 months or a watchful waiting strategy. Follow-up will be annual. We expect a complete restoration of LV size and function along with improved quality of life and physical performance in a short-term follow-up of 12 months. The primary endpoint will be a composite safety and efficacy with all criteria mandatory: 15 % or larger reduction of baseline CMR-derived LV end-diastolic volume index, LV ejection fraction >50 %, and no major adverse cardiovascular events. The annual follow-up will continue for a minimum of 4 years until the required number of endpoints is achieved to show a statistically significant difference in cardiovascular morbidity and mortality in early surgically treated patients. Conclusion: The ELEANOR trial is the first multicenter randomized controlled study to compare early surgical treatment with a watchful waiting strategy in asymptomatic patients with chronic severe AR at high risk of early clinical deterioration as per CMR assessment but without guidelines-based indications for surgical treatment.

Unicuspid Aortic Valve in Patients Undergoing the Ross Procedure.

BACKGROUND: The prevalence and outcomes of the unicuspid aortic valve (UAV) in patients undergoing the Ross procedure have been strongly underreported in the current literature. We sought to evaluate this in comparison with bicuspid (BAV) and tricuspid valve (TAV) in our Ross cohort. METHODS: This was a retrospective observational study of patients undergoing the Ross procedure at 2 dedicated centers between 2009 and 2020. Primary end points were the risks of midterm autograft reoperation and the onset of at least moderate aortic regurgitation during follow-up. The secondary end point was to compare the perioperative outcomes between the groups. RESULTS: Included in the analysis were 286 patients, of those 39% with UAV, 52% with BAV, and 9% with TAV. UAV patients were operated on at the youngest age (P < .001) and more often for a combined hemodynamic aortic valve pathology (P = .02). They had the largest aortic root dimensions: annulus (P = .01), Valsalva sinuses (P = .11), sinotubular junction (P = .001), and ascending aorta (P < .0001). The risks of reoperation (P = .86) and the onset of aortic regurgitation (P = .75) were comparable among the groups over the follow-up of 4.1 years. There was no difference in perioperative outcomes. CONCLUSIONS: UAV is a separate unit characterized by a distinct hemodynamic pathology and generated aortopathy. It is not associated with a higher risk of reoperation or new onset of aortic regurgitation after the Ross procedure in the midterm postoperatively. At the current state, UAV remains acceptable for the Ross procedure.

Comparison of bicuspidization and Ross procedure in the treatment of unicuspid aortic valve disease in adults - Insight from the AVIATOR registry.

Background: Unicuspid aortic valve (UAV) is the second most common underlying cause of aortic valve dysfunction in young adults after the bicuspid valve. The valve may be replaced (for example by pulmonary autograft) or repaired using the bicuspidization technique. The aim of our study was to compare short- and mid-term outcomes of Ross procedure with bicuspidization in patients with severe UAV dysfunction. Methods: This was a multi-center retrospective observational cohort study comparing data from two dedicated Ross centers in the Czech Republic with bicuspidization outcomes provided by AVIATOR registry. As for the Ross group, only the patients with UAV were included. Primary endpoint was mid-term freedom from reintervention. Secondary endpoints were mid-term freedom from major adverse events, endocarditis and pacemaker implantation. Results: Throughout the study period, 114 patients underwent the Ross procedure (years 2009-2020) and 126 patients underwent bicuspidization (years 2006-2019). The bicuspidization group was significantly younger and presented with a higher degree of dyspnea, a lower degree of aortic valve stenosis and more often with pure regurgitation. The primary endpoint occurred more frequently in the bicuspidization group than in the Ross group - 77.9 vs. 97.9 % at 5 years and 68.4 vs. 75.2 % at 10 years (p < 0.001). There was no difference in secondary endpoints. Conclusion: Ross procedure might offer a significantly lower mid-term risk of reintervention than bicuspidization in patients with UAV. Both procedures have comparable survival and risk of other short- and mid-term complications postoperatively.

Ross procedure provides survival benefit over mechanical valve in adults: a propensity-matched nationwide analysis.

OBJECTIVES: The choice of optimal surgical treatment for young and middle-aged adults with aortic valve disease remains a challenge. Mechanical aortic valve replacement (mAVR) is generally preferred despite promising recent outcomes of the Ross procedure. Our goal was to compare the strategies at a nationwide level. METHODS: This study was a retrospective analysis of prospectively recorded data from the National Registry of Cardiac Surgery of the Czech Republic. Using propensity score matching, we compared the outcomes of patients undergoing the Ross procedure in 2 dedicated centres with all mAVRs performed in country between 2009 and 2020. RESULTS: Throughout the study period, 296 adults underwent the Ross procedure and 5120 had an mAVR. We found and compared 291 matched pairs. There were no in-hospital deaths, and the risk of perioperative complications was similar in both groups. Over the average follow-up period of 4.1 vs 6.1 years, the Ross group had a lower all-cause mortality (0.7 vs 6.5%; P = 0.015). This result remained significant even when accounting for cardiac- and valve-related deaths only (P = 0.048). Unlike the Ross group, the mAVR group had a significantly lower relative survival compared with the age- and sex-matched general population. There was no difference in the risk of reoperation (4.5 vs 5.5%; P = 0.66). CONCLUSIONS: The Ross procedure offers a significant midterm survival benefit over mAVR. The procedures have a comparable risk of perioperative complications. Patients after mAVR have reduced survival. Thus, the Ross procedure should be the preferred treatment option for young and middle-aged adults with aortic valve disease in dedicated centres.

Personalized external aortic root support - how to implant it.

Personalized External Aortic Root Support (PEARS) is an evolving method of treatment for patients with a dilated aortic root or ascending aorta. This treatment is being adopted in an increasing number of centres. For the sake of the safety of the procedure a standardized surgical technique is necessary. The authors describe a surgical technique of implantation that is derived from their extensive experience.

Left Atrial Appendage Occlusion during Cardiac Surgery to Prevent Stroke.

BACKGROUND: Surgical occlusion of the left atrial appendage has been hypothesized to prevent ischemic stroke in patients with atrial fibrillation, but this has not been proved. The procedure can be performed during cardiac surgery undertaken for other reasons. METHODS: We conducted a multicenter, randomized trial involving participants with atrial fibrillation and a CHA2DS2-VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating greater risk of stroke) who were scheduled to undergo cardiac surgery for another indication. The participants were randomly assigned to undergo or not undergo occlusion of the left atrial appendage during surgery; all the participants were expected to receive usual care, including oral anticoagulation, during follow-up. The primary outcome was the occurrence of ischemic stroke (including transient ischemic attack with positive neuroimaging) or systemic embolism. The participants, research personnel, and primary care physicians (other than the surgeons) were unaware of the trial-group assignments. RESULTS: The primary analysis population included 2379 participants in the occlusion group and 2391 in the no-occlusion group, with a mean age of 71 years and a mean CHA2DS2-VASc score of 4.2. The participants were followed for a mean of 3.8 years. A total of 92.1% of the participants received the assigned procedure, and at 3 years, 76.8% of the participants continued to receive oral anticoagulation. Stroke or systemic embolism occurred in 114 participants (4.8%) in the occlusion group and in 168 (7.0%) in the no-occlusion group (hazard ratio, 0.67; 95% confidence interval, 0.53 to 0.85; P = 0.001). The incidence of perioperative bleeding, heart failure, or death did not differ significantly between the trial groups. CONCLUSIONS: Among participants with atrial fibrillation who had undergone cardiac surgery, most of whom continued to receive ongoing antithrombotic therapy, the risk of ischemic stroke or systemic embolism was lower with concomitant left atrial appendage occlusion performed during the surgery than without it. (Funded by the Canadian Institutes of Health Research and others; LAAOS III ClinicalTrials.gov number, NCT01561651.).

Long-Term Outcomes of Patients Undergoing the Ross Procedure.

BACKGROUND: Treatment of aortic-valve disease in young patients still poses challenges. The Ross procedure offers several potential advantages that may translate to improved long-term outcomes. OBJECTIVES: This study reports long-term outcomes after the Ross procedure. METHODS: Adult patients who were included in the Ross Registry between 1988 and 2018 were analyzed. Endpoints were overall survival, reintervention, and major adverse events at maximum follow-up. Multivariable regression analyses were performed to identify risk factors for survival and the need of Ross-related reintervention. RESULTS: There were 2,444 adult patients with a mean age of 44.1 ± 11.7 years identified. Early mortality was 1.0%. Estimated survival after 25 years was 75.8% and did not statistically differ from the general population (p = 0.189). The risk for autograft reintervention was 0.69% per patient-year and 0.62% per patient-year for right-ventricular outflow tract (RVOT) reintervention. Larger aortic annulus diameter (hazard ratio [HR]: 1.12/mm; 95% confidence interval [CI]: 1.05 to 1.19/mm; p < 0.001) and pre-operative presence of pure aortic insufficiency (HR: 1.74; 95% CI: 1.13 to 2.68; p = 0.01) were independent predictors for autograft reintervention, whereas the use of a biological valve (HR: 8.09; 95% CI: 5.01 to 13.08; p < 0.001) and patient age (HR: 0.97 per year; 95% CI: 0.96 to 0.99; p = 0.001) were independent predictors for RVOT reintervention. Major bleeding, valve thrombosis, permanent stroke, and endocarditis occurred with an incidence of 0.15% per patient-year, 0.07% per patient-year, 0.13%, and 0.36% per patient-year, respectively. CONCLUSIONS: The Ross procedure provides excellent survival over a follow-up period of up to 25 years. The rates of reintervention, anticoagulation-related morbidity, and endocarditis were very low. This procedure should therefore be considered as a very suitable treatment option in young patients suffering from aortic-valve disease. (Long-Term Follow-up After the Autograft Aortic Valve Procedure [Ross Operation]; NCT00708409).

Serum transferrin as a biomarker of hepatocyte nuclear factor 4 alpha activity and hepatocyte function in liver diseases.

BACKGROUND: Serum transferrin levels represent an independent predictor of mortality in patients with liver failure. Hepatocyte nuclear factor 4 alpha (HNF4α) is a master regulator of hepatocyte functions. The aim of this study was to explore whether serum transferrin reflects HNF4α activity. METHODS: Factors regulating transferrin expression in alcoholic hepatitis (AH) were assessed via transcriptomic/methylomic analysis as well as chromatin immunoprecipitation coupled to DNA sequencing. The findings were corroborated in primary hepatocytes. Serum and liver samples from 40 patients with advanced liver disease of multiple etiologies were also studied. RESULTS: In patients with advanced liver disease, serum transferrin levels correlated with hepatic transferrin expression (r = 0.51, p = 0.01). Immunohistochemical and biochemical tests confirmed reduced HNF4α and transferrin protein levels in individuals with cirrhosis. In AH, hepatic gene-gene correlation analysis in liver transcriptome revealed an enrichment of HNF4α signature in transferrin-correlated transcriptome while transforming growth factor beta 1 (TGFß1), tumor necrosis factor α (TNFα), interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6) negatively associated with transferrin signature. A key regulatory region in transferrin promoter was hypermethylated in patients with AH. In primary hepatocytes, treatment with TGFß1 or the HNF4α inhibitor BI6015 suppressed transferrin production, while exposure to TNFα, IL-1ß, and IL-6 had no effect. The correlation between hepatic HNF4A and transferrin mRNA levels was also seen in advanced liver disease. CONCLUSIONS: Serum transferrin levels constitute a prognostic and mechanistic biomarker. Consequently, they may serve as a surrogate of impaired hepatic HNF4α signaling and liver failure.

Personalized external aortic root support.

OBJECTIVES: Implantation of a personalized external aortic root support (PEARS) can prevent dilatation of the aortic root and ascending aorta in patients with aortopathy of various aetiologies. Because PEARS is an emerging technology, all aspects concerning indications, surgical technique and safety should be elucidated. Our goal was to summarize all of these aspects so that physicians and patients would have sufficient information to evaluate this alternative approach. METHODS: Between April 2004 and March 2020, 317 patients underwent PEARS operations at 25 surgical centres in 9 countries. RESULTS: The most common indication was Marfan syndrome (57%). The single perioperative death represented a mortality of 0.3%. The long-term experience comprises 871 patient/years with 1 patient living for 15 years and 19 patients living for more than 10 years. CONCLUSIONS: PEARS seems to be a promising method of treatment of dilatation of the aortic root and/or ascending aorta. Multicentre observational studies are needed to gain more experience because this operation is still uncommon and the number of operations per surgeon/centre is low.

Plasma Levels of Myocardial MicroRNA-133a Increase by Intraoperative Cytokine Hemoadsorption in the Complex Cardiovascular Operation.

BACKGROUND: Complex cardiovascular procedures may initiate a systemic inflammatory response syndrome (SIRS) with a massive cytokine release, which is involved in postoperative myocardial injury. Intraoperative cytokine hemoadsorption (HA) mitigates the inflammatory response. Micro ribonucleic acids (miRNAs) are emerging as a marker of myocardial injury. METHODS: This study evaluated if intraoperative cytokine reduction by HA modulates SIRS and affects myocardial injury as measured by miRNA-126, 223 and miRNA-1, 133a, respectively. Twenty-eight patients were assigned into HA (n = 15) and control (C) (n = 13) groups. HA was performed by integrating CytoSorb™ into the extracorporeal circuit. RESULTS: MiRNA-133a plasma levels were increased postoperatively in both groups but were much higher in the HA group than in the C group at 3 h (P = 0.037) and 18 h (P = 0.017) after reperfusion. MiRNA-1 and miRNA-223 plasma levels were significantly increased postoperatively, but did not differ between groups. The vascular miRNA-126 was not affected. CONCLUSION: Intraoperative cytokine HA in cardiovascular operations increased the plasma levels of miRNA-133a, suggesting higher myocardial injury.

Mitral bioprosthetic valve leaflet fusion treated by balloon valvuloplasty in patients on ECMO.

We present two patients who required extracorporeal membrane oxygenation (ECMO) support after bioprosthetic mitral valve replacement, who developed early structural valve failure due to leaflet fusion. Percutaneous balloon valvuloplasty restored normal leaflet motion and allowed discontinuation of ECMO support.

The First Manifestation of a Left Atrial Myxoma as a Consequence of Multiple Left Coronary Artery Embolisms.

A case of multiple embolisms in the left coronary artery as a rare first manifestation of left atrial myxoma is reported. A patient with embolic myocardial infarction and congestive heart failure was treated by percutaneous aspirations and balloon dilatations. Transesophageal echocardiography disclosed a villous myxoma with high embolic potential. Surgical resection of the tumour, suturing of a patent foramen ovale suture and an annuloplasty of the dilated tricuspid annulus was performed the third day after the admission. Recovery of the documented left ventricular systolic function can be explained by resorption of myxomatous material. The patient was discharged ten days after the surgery.

Monitoring of allograft vasculopathy by intravascular ultrasound one month and one year after heart transplantation: A single center study.

AIMS: The aim of this trial was to use intravascular ultrasound (IVUS) to determine whether cardiac allograft vasculopathy (CAV) starts progressing during the first year after heart transplantation (HTx). METHODS: We retrospectively analyzed 51 patients (11 women) who received heart transplants in our center between January 2010 and September 2013 and underwent coronary angiography as well as IVUS examination one month and one year after HTx. Patients with proven calcification and fibrotic plates in the IVUS examination one month after HTx constituted a group with defined donor-transmitted atherosclerosis (DTA). In patients without DTA, measurements of maximal intimal thickening (MIT) were made in two predetermined locations. RESULTS: Eight of the 51 patients had DTA, while 43 did not. These were divided based on maximal intimal thickness (MIT) into a group with MIT < 0.5 mm (27) and MIT ≥ 0.5 mm (16). No patient with MIT < 0.5 mm developed allograft vasculopathy within one year after HTx. CAV developed in three patients (P = 0.045) out of the 16 patients with MIT ≥ 0.5. In patients with DTA, a statistically significant deterioration in percent area stenosis (PAS) occurred in both artery sections (P = 0.01). CONCLUSION: Our trial showed that CAV progresses during the first year after HTx significantly more frequently in patients with DTA and MIT ≥ 0.5 mm. It is essential in these patients to implement an IVUS control examination one year after transplantation. The results can lead to a change in treatment strategy to prevent further progress of the disease.

[Surgical therapy of myocardial infarction]. / Místo chirurgické revaskularizace v lécbe akutního infarktu myokardu.

INTRODUCTION: Coronary artery bypass grafting (CABG) has been replaced by percutaneous coronary interventions in the treatment of myocardial infarction (MI) nowadays. The surgical repair is the only option for mechanical complications of MI. The aim of our study was to assess the results of surgical treatment of MI. PATIENTS AND METHODS: From January 2008 to December 2012 one thousand nine hundred fifty nine patients were operated on at Centre of cardiovascular surgery and transplantations in Brno for coronary artery disease, 103 (5.3 %) of them suffered from acute MI. The interval between MI and operations was longer than 24 hours in more than half of the patients. Nineteen patients underwent PCI before operation, 32 were in cardiogenic shock with intraaortic balloon pump in 12, twelve patients were after cardiopulmonary resuscitation and 18 were on ventilation. RESULTS: CABG alone was performed in 78 patients, in 25 patients mechanical complication of MI occurred; rupture of papillary muscle with mitral regurgitation in 8, rupture of interventricular septum in 11, rupture of free wall of left ventricle in 1 and evolving aneurysm of left ventricle in 5 patients. Several serious complications occurred in the postoperative period; disturbances of heart rhythm, syndrome of low cardiac output and pulmonary complications with the necessity of prolonged ventilation being the most frequent. Fourteen patients died during hospital stay (mortality 13.4 %). CONCLUSIONS: Patients after acute MI create the highest-risk group for surgical treatment. The reasons comprise serious preoperative status, delayed re-perfusion of ischemic area and serious hemodynamic effect of mechanical complications of MI. A lot of complications may occur during postoperative course and mortality is high. In the survivals the long term follow-up is promising.

Successful transplantation of a heart with an atrial septal defect caused by blunt trauma.

We report a case of a successful heart transplantation from a donor after multiple trauma. A traumatic atrial septal defect was repaired, and the postoperative course was uneventful.