cAMP Imaging at Ryanodine Receptors Reveals ß2-Adrenoceptor Driven Arrhythmias.

[Figure: see text].

Hemodynamics and Diastolic Function after Native Aortic Valve Preserving vs. Replacing Surgery.

BACKGROUND: Alterations in left ventricular (LV) diastolic function following native tissue-preserving aortic valve (AV) procedures have not been systematically investigated. Furthermore, no comparisons have been made between these changes and those observed after prosthetic AV replacement. METHODS: From October 2017 to August 2020, 74 patients aged <65 years were referred to our institution for elective AV surgery. Preoperative and postoperative (i.e., discharge, 3-month and 1-year follow-up) transthoracic echocardiography was analyzed. RESULTS: Native tissue-preserving surgery was performed in 55 patients (AV repair: n = 42, Ross procedure: n = 13). The remaining 19 patients underwent prosthetic AV replacement. Preoperatively and at discharge, transvalvular hemodynamics and LV diastolic function were comparable in both groups. At 1-year follow-up, native valve (NV) patients showed significantly lower mean transvalvular gradient (7 ± 5 vs. 9 ± 3 mmHg, p = 0.046) and peak velocity (1.74 ± 0.51 vs. 2.26 ± 0.96 m/s, p = 0.004), and significantly better septal e' (9.1 ± 2.7 vs. 7.7 ± 2.5 cm/s, p = 0.043) and lateral e' (14.7 ± 3.1 vs. 11.7 ± 3.7 cm/s, p = 0.001). From preoperatively to 1-year postoperatively, septal and lateral e' and E/e' improved markedly after NV preservation (septal e': +0.7 cm/s, p = 0.075; lateral e': +2.3 cm/s, p < 0.001; E/e': -1.5, p = 0.001) but not after AV replacement (septal e': +0.2 cm/s, p = 0.809; lateral e': +0.8 cm/s, p = 0.574; E/e': -1.2, p = 0.347). Significant negative linear correlations between postoperative transvalvular gradients and absolute changes in lateral e' and E/e' were detected during follow-up. CONCLUSION: Preservation of native tissue in AV surgery results in superior transvalvular hemodynamics compared with prosthetic AV replacement. This may induce faster LV reverse remodeling and may explain more pronounced improvement in LV diastolic function.

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.

A novel technique to quantify aortic valve annulus deformation: A pilot study.

OBJECTIVES: We evaluated the potential of cardiac magnetic resonance (CMR)-derived strain to assess aortic valve (AV) annulus deformation during the cardiac cycle in regurgitant and well-functioning AVs. METHODS: Four patients with severe aortic regurgitation and seven healthy controls underwent CMR. Assessment of longitudinal strain was performed by hypothesizing the AV annulus would be the left ventricle in long-axis orientation. Longitudinal strain of the segments belonging to the muscular and fibrous AV annulus was weighted and averaged to obtain regional values (RLS). RESULTS: Comparison of RLS between regurgitant and well-functioning AVs showed a considerably different deformation of the muscular AV annulus (i.e., median RLS: 4.18 % [patients] vs. -10.41 % [controls], p = .024). The fibrous AV annulus demonstrated comparable deformational changes in both groups. CONCLUSION: CMR-derived strain allows for quantification of AV annulus deformation during the cardiac cycle and shows an altered RLS in the muscular AV annulus in patients with severe aortic regurgitation.

Mapping genetic changes in the cAMP-signaling cascade in human atria.

AIM: To obtain a quantitative expression profile of the main genes involved in the cAMP-signaling cascade in human control atria and in different cardiac pathologies. METHODS AND RESULTS: Expression of 48 target genes playing a relevant role in the cAMP-signaling cascade was assessed by RT-qPCR. 113 samples were obtained from right atrial appendages (RAA) of patients in sinus rhythm (SR) with or without atrium dilation, paroxysmal atrial fibrillation (AF), persistent AF or heart failure (HF); and left atrial appendages (LAA) from patients in SR or with AF. Our results show that right and left atrial appendages in donor hearts or from SR patients have similar expression values except for AC7 and PDE2A. Despite the enormous chamber-dependent variability in the gene-expression changes between pathologies, several distinguishable patterns could be identified. PDE8A, PI3Kγ and EPAC2 were upregulated in AF. Different phosphodiesterase (PDE) families showed specific pathology-dependent changes. CONCLUSION: By comparing mRNA-expression patterns of the cAMP-signaling cascade related genes in right and left atrial appendages of human hearts and across different pathologies, we show that 1) gene expression is not significantly affected by cardioplegic solution content, 2) it is appropriate to use SR atrial samples as controls, and 3) many genes in the cAMP-signaling cascade are affected in AF and HF but only few of them appear to be chamber (right or left) specific. TOPIC: Genetic changes in human diseased atria. TRANSLATIONAL PERSPECTIVE: The cyclic AMP signaling pathway is important for atrial function. However, expression patterns of the genes involved in the atria of healthy and diseased hearts are still unclear. We give here a general overview of how different pathologies affect the expression of key genes in the cAMP signaling pathway in human right and left atria appendages. Our study may help identifying new genes of interest as potential therapeutic targets or clinical biomarkers for these pathologies and could serve as a guide in future gene therapy studies.

Translational investigation of electrophysiology in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) patients are at increased risk of ventricular arrhythmias and sudden cardiac death, which can occur even in the absence of structural changes of the heart. HCM mouse models suggest mutations in myofilament components to affect Ca2+ homeostasis and thereby favor arrhythmia development. Additionally, some of them show indications of pro-arrhythmic changes in cardiac electrophysiology. In this study, we explored arrhythmia mechanisms in mice carrying a HCM mutation in Mybpc3 (Mybpc3-KI) and tested the translatability of our findings in human engineered heart tissues (EHTs) derived from CRISPR/Cas9-generated homozygous MYBPC3 mutant (MYBPC3hom) in induced pluripotent stem cells (iPSC) and to left ventricular septum samples obtained from HCM patients. We observed higher arrhythmia susceptibility in contractility measurements of field-stimulated intact cardiomyocytes and ventricular muscle strips as well as in electromyogram recordings of Langendorff-perfused hearts from adult Mybpc3-KI mice than in wild-type (WT) controls. The latter only occurred in homozygous (Hom-KI) but not in heterozygous (Het-KI) mouse hearts. Both Het- and Hom-KI are known to display pro-arrhythmic increased Ca2+ myofilament sensitivity as a direct consequence of the mutation. In the electrophysiological characterization of the model, we observed smaller repolarizing K+ currents in single cell patch clamp, longer ventricular action potentials in sharp microelectrode recordings and longer ventricular refractory periods in Langendorff-perfused hearts in Hom-KI, but not Het-KI. Interestingly, reduced K+ channel subunit transcript levels and prolonged action potentials were already detectable in newborn, pre-hypertrophic Hom-KI mice. Human iPSC-derived MYBPC3hom EHTs, which genetically mimicked the Hom-KI mice, did exhibit lower mutant mRNA and protein levels, lower force, beating frequency and relaxation time, but no significant alteration of the force-Ca2+ relation in skinned EHTs. Furthermore, MYBPC3hom EHTs did show higher spontaneous arrhythmic behavior, whereas action potentials measured by sharp microelectrode did not differ to isogenic controls. Action potentials measured in septal myectomy samples did not differ between patients with HCM and patients with aortic stenosis, except for the only sample with a MYBPC3 mutation. The data demonstrate that increased myofilament Ca2+ sensitivity is not sufficient to induce arrhythmias in the Mybpc3-KI mouse model and suggest that reduced K+ currents can be a pro-arrhythmic trigger in Hom-KI mice, probably already in early disease stages. However, neither data from EHTs nor from left ventricular samples indicate relevant reduction of K+ currents in human HCM. Therefore, our study highlights the species difference between mouse and human and emphasizes the importance of research in human samples and human-like models.

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.

Economic impact of enhanced recovery after surgery protocol in minimally invasive cardiac surgery.

BACKGROUND: ERAS (Enhanced Recovery After Surgery) is a multidisciplinary and integrative approach with the goal of optimizing the postoperative recovery. We aimed to analyze the economic impact of a newly established ERAS protocol in minimally invasive heart valve surgery at our institution. METHODS: ERAS protocol was implemented in 61 consecutive patients who were referred for elective minimally-invasive aortic or mitral valve surgery, between February 1, 2018 and March 31, 2019 (ERAS-group). Another 69 patients who underwent elective minimally-invasive heart valve surgery during the same time period were managed according to the hospital standards (Control-group). A detailed cost comparison analysis was carried out from a hospital perspective using a micro-costing approach. RESULTS: The total in-hospital stay was significantly shorter in the ERAS-group compared to the Control-group (6.1 ± 2.6 vs 7.7 ± 3.8 days; p = 0.008) resulting in significant cost savings of €1087.2 per patient (p = 0.003). Due to the intensified physiotherapy in the ERAS protocol, the costs for physiotherapy were €94.3 higher compared to the Control-group (p < 0.001). The total costs in the ERAS cohort were €11,200.0 ± 3029.6/patient compared to € 13,109.8 ± 4527.5/patient in the Control-Group resulting in cost savings of €1909.8 patient due to the implementation of the ERAS protocol (p = 0.006). CONCLUSION: Implementation of an ERAS-protocol in minimally-invasive cardiac surgery can be carried out safely with a fast postoperative recovery of the patient. ERAS results in a financial benefit of up to €1909 per patient and therefore will play a key role in modern cardiac surgery in the near future.

[Pneumomediastinum in Severe COVID-19-disease: a Case Series of Eight Patients]. / Pneumomediastinum bei schwerer COVID-19-Erkrankung: eine Fallserie von acht Patienten.

The most common cause of pneumomediastinum is trauma. However, in the context of COVID-19 pneumonia, this clinical picture is more often found in patients without underlying exogenous injury. Pathophysiologically, a cause analogous to the Macklin effect is suspected here, in which tears at the alveolar level lead to emphysema along the tracheobronchial tree with concentrating in the mediastinum. Here we present a case series of eight patients who were treated in our intensive care unit. In all patients, mediastinal emphysema could already be seen in the chest X-ray. Five patients also received a computed tomography scan of the thorax. Six patients had invasive ventilation. All patients received corticosteroids, anticoagulation and antibiotics. Pleural drainage was applied only in patients with an additional pneumothorax (n = 5). Bronchoscopy was performed only if there was a suspicion of iatrogenic injury to the tracheobronchial tree in relation to the appearance of the pneumomediastinum (n = 2). Three patients died during intensive care as part of the COVID-19 disease. A prognostic relationship between the occurrence of a pneumomediastinum and a fatal course of the disease is discussed.

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.

4D flow cardiovascular magnetic resonance for monitoring of aortic valve repair in bicuspid aortic valve disease.

BACKGROUND: Aortic valve repair has become a treatment option for adults with symptomatic bicuspid (BAV) or unicuspid (UAV) aortic valve insufficiency. Our aim was to demonstrate the feasibility of 4D flow cardiovascular magnetic resonance (CMR) to assess the impact of aortic valve repair on changes in blood flow dynamics in patients with symptomatic BAV or UAV. METHODS: Twenty patients with adult congenital heart disease (median 35 years, range 18-64; 16 male) and symptomatic aortic valve regurgitation (15 BAV, 5 UAV) were prospectively studied. All patients underwent 4D flow CMR before and after aortic valve repair. Aortic valve regurgitant fraction and systolic peak velocity were estimated. The degree of helical and vortical flow was evaluated according to a 3-point scale. Relative flow displacement and wall shear stress (WSS) were quantified at predefined levels in the thoracic aorta. RESULTS: All patients underwent successful aortic valve repair with a significant reduction of aortic valve regurgitation (16.7 ± 9.8% to 6.4 ± 4.4%, p < 0.001) and systolic peak velocity (2.3 ± 0.9 to 1.9 ± 0.4 m/s, p = 0.014). Both helical flow (1.6 ± 0.6 vs. 0.9 ± 0.5, p < 0.001) and vortical flow (1.2 ± 0.8 vs. 0.5 ± 0.6, p = 0.002) as well as both flow displacement (0.3 ± 0.1 vs. 0.25 ± 0.1, p = 0.031) and WSS (0.8 ± 0.2 N/m2 vs. 0.5 ± 0.2 N/m2, p < 0.001) in the ascending aorta were significantly reduced after aortic valve repair. CONCLUSIONS: 4D flow CMR allows assessment of the impact of aortic valve repair on changes in blood flow dynamics in patients with bicuspid aortic valve disease.

Rationale and Design of the Hamburg City Health Study.

The Hamburg City Health Study (HCHS) is a large, prospective, long-term, population-based cohort study and a unique research platform and network to obtain substantial knowledge about several important risk and prognostic factors in major chronic diseases. A random sample of 45,000 participants between 45 and 74 years of age from the general population of Hamburg, Germany, are taking part in an extensive baseline assessment at one dedicated study center. Participants undergo 13 validated and 5 novel examinations primarily targeting major organ system function and structures including extensive imaging examinations. The protocol includes validate self-reports via questionnaires regarding lifestyle and environmental conditions, dietary habits, physical condition and activity, sexual dysfunction, professional life, psychosocial context and burden, quality of life, digital media use, occupational, medical and family history as well as healthcare utilization. The assessment is completed by genomic and proteomic characterization. Beyond the identification of classical risk factors for major chronic diseases and survivorship, the core intention is to gather valid prevalence and incidence, and to develop complex models predicting health outcomes based on a multitude of examination data, imaging, biomarker, psychosocial and behavioral assessments. Participants at risk for coronary artery disease, atrial fibrillation, heart failure, stroke and dementia are invited for a visit to conduct an additional MRI examination of either heart or brain. Endpoint assessment of the overall sample will be completed through repeated follow-up examinations and surveys as well as related individual routine data from involved health and pension insurances. The study is targeting the complex relationship between biologic and psychosocial risk and resilience factors, chronic disease, health care use, survivorship and health as well as favorable and bad prognosis within a unique, large-scale long-term assessment with the perspective of further examinations after 6 years in a representative European metropolitan population.

Thrombelastometry guided blood-component therapy after cardiac surgery: a randomized study.

BACKGROUND: Significant bleeding is a well known complication after cardiac surgical procedures and is associated with worse outcome. Thrombelastometry (ROTEM®) allows point-of-care testing of the coagulation status but only limited data is available yet. The aim was to evaluate the ROTEM®-guided blood component therapy in a randomized trial. METHODS: In case of significant postoperative bleeding (> 200 ml/h) following elective isolated or combined cardiac surgical procedures (including 14% re-do procedures and 4% requiring circulatory arrest) patients were randomized to either a 4-chamber ROTEM®-guided blood-component transfusion protocol or received treatment guided by an algorithm based on standard coagulation testing (control). One hundred four patients (mean age: 67.2 ± 10.4 years, mean log. EuroSCORE 7.0 ± 8.8%) met the inclusion criteria. Mean CPB-time was 112.1 ± 55.1 min., mean cross-clamp time 72.5 ± 39.9 min. RESULTS: Baseline demographics were comparable in both groups. Overall there was no significant difference in transfusion requirements regarding red blood cells, platelets, plasma, fibrinogen or pooled factors and the re-thoracotomy rate was comparable (ROTEM®: 29% vs. control: 25%). However, there was a trend towards less 24-h drainage loss visible in the ROTEM®-group (ROTEM®: 1599.1 ± 834.3 ml vs. control: 1867.4 ± 827.4 ml; p = 0.066). In the subgroup of patients with long CPB-times (> 115 min.; n = 55) known to exhibit an increased risk for diffuse coagulopathy ROTEM®-guided treatment resulted in a significantly lower 24-h drainage loss (ROTEM®: 1538.2 ± 806.4 ml vs. control: 2056.8 ± 974.5 ml; p = 0.032) and reduced 5-year mortality (ROTEM®: 0% vs. control: 15%; p = 0.03). CONCLUSION: In case of postoperative bleeding following cardiac surgical procedures a treatment algorithm based on "point-of-care" 4-chamber ROTEM® seems to be at least as effective as standard therapy. In patients with long CPB-times ROTEM®-guided treatment may result in less bleeding, a marked reduction in costs and long-term mortality. TRIAL REGISTRATION: German Clinical Trials Register, TRN: DRKS00017367 , date of registration: 05.06.2019, 'retrospectively registered'.

Transapical tricuspid valve-in-ring implantation: An alternative approach to a challenging clinical scenario.

We report on a transapical tricuspid valve-in-ring implantation performed via right ventricular apex using the Sapien-XT-prosthesis. A 57-year-old woman with recurrent episodes of right heart failure and three previous sternotomies, including tricuspid valve repair with a 32 mm Carpentier-Edwards-Classic annuloplasty ring was admitted due to recurrent severe tricuspid regurgitation. Given the excessive surgical risk, a 29 mm Sapien-XT-prosthesis was selected for valve-in-ring implantation. Transapical valve-in-ring implantation procedure was uneventful. Predischarge echocardiography showed only trace paravalvular tricuspid regurgitation in the septal region. Transapical approach via right ventricular apex is a viable alternative for tricuspid valve-in-ring implantation in selected high-risk patients. © 2016 Wiley Periodicals, Inc.

The Value of Circulating Biomarkers in Bicuspid Aortic Valve-Associated Aortopathy.

Traditional risk stratification model of bicuspid aortic valve (BAV) aortopathy is based on measurement of maximal cross-sectional aortic diameter, definition of proximal aortic shape, and aortic stiffness/elasticity parameters. However, conventional imaging-based criteria are unable to provide reliable information regarding the risk stratification in BAV aortopathy, especially considering the heterogeneous nature of BAV disease. Given those limitations of conventional imaging, there is a growing clinical interest to use circulating biomarkers in the screening process for thoracic aortic aneurysms as well as in the risk-assessment algorithms. We aimed to systematically review currently available biomarkers, which may be of value to predict the natural evolution of aortopathy in individuals with BAV.

Update on bicuspid aortic valve aortopathy.

PURPOSE OF REVIEW: The appropriate treatment of bicuspid aortic valve (BAV)-associated aortopathy is still controversial. We aimed to summarize recent evidence from the literature that focused on the prediction of aortopathy progression and adverse aortic events. RECENT FINDINGS: Following the detailed description of valvulo-aortic phenotypes in BAV disease in the previous imaging studies, the most current research focused on the definition of hemodynamic markers that may affect the progression of BAV-associated aortopathy and search for blood-born biomarkers to improve the prediction of adverse aortic events. Furthermore, genetic analyses are ongoing and some preliminary data will be presented. SUMMARY: Serological biomarkers are a novel and promising diagnostic tool for screening thoracic aortic aneurysmal disease and prediction future adverse aortic events. In combination with rheological imaging as well as traditional risk factors diagnostic accuracy and cost-effectiveness of care in BAV-associated aortopathy will improve significantly. VIDEO ABSTRACT: http://links.lww.com/HCO/A44.

Comparison of Outcomes of Tricuspid Valve Surgery in Patients with Reduced and Normal Right Ventricular Function.

Background: To study the effect of tricuspid valve repair/replacement on outcomes of patients with reduced systolic right ventricular function. Methods: Between January 2012 and July 2016, 191 patients with isolated tricuspid valve regurgitation and/or in combination with other valve diseases were enrolled into this retrospective study. We compared early postoperative outcomes (i.e., 30 days after surgery) between patients' cohort with a preoperative reduced (i.e., at least moderately) versus normal (or mildly reduced) right ventricular function as defined by means of preoperative echocardiography. Results: A total of 82 (43%) patients had preoperatively reduced right ventricle function with tricuspid annular plane systolic excursion (TAPSE) of 13.3 ± 3.3 versus 20.2 ± 4.9 mm (p < 0.001). Ring annuloplasty was the most common surgical technique (i.e., 91% in both groups). Time of procedure (317 ± 123 vs. 262 ± 88 minutes, p < 0.01) and time on cardiopulmonary bypass (163 ± 77 vs. 143 ± 57 minutes, p = 0.036) were significantly longer in patients with impaired right ventricular function. Postoperative lactate (3.5 ± 3 vs. 2 ± 1 mmol/L, p = 0.001) and dose of catecholamines (epinephrine, 0.07 ± 0.15 vs. 0.013 ± 0.02 µg/kg/min, p = 0.001; norepinephrine, 0.18 ± 0.23 vs. 0.07 ± 0.09 µg/kg/min, p = 0.007) were also higher in this group. Postoperative rate of low cardiac output syndrome (10 vs. 27%, p = 0.005) and early mortality (n = 2 vs. n = 9, p = 0.018) were significantly increased in patients with reduced right ventricular function. Previous cardiac operation (p = 0.045), preoperative higher number of acute decompensations of heart failure (p < 0.001), reduced right ventricular function (p = 0.018), postoperative low cardiac output syndrome (p < 0.001), and renal replacement therapy (p < 0.001) were identified as risk factors for early mortality. Echocardiography at discharge revealed tricuspid valve regurgitation grade of 0.9 ± 0.7 versus 0.7 ± 0.6 (p = 0.052) and TAPSE of 12 ± 3 versus 15 ± 5 mm (p = 0.026) in patients with reduced right ventricular function. The New York Heart Association (NYHA) class improved to 1.7 ± 0.7 versus 1.3 ± 1 (p < 0.001) in this group of patients. Conclusion: Tricuspid valve repair/replacement effectively eliminated severe tricuspid regurgitation and improved clinical signs of heart failure. Although mortality and morbidity were increased in the group with reduced right ventricular function, even these patients benefitted from improved functional status and right ventricular systolic function early postoperatively.

Results of Contemporary Valve Surgery in Patients with Carcinoid Heart Disease.

BACKGROUND: Carcinoid tumor is a slow-growing type of neuroendocrine tumor, originating from enterochromaffin cells and secreting mainly serotonin. The diagnosis is based on clinical symptoms, hormone blood levels, radiological and nuclear imaging, and histological confirmation. However, most patients have metastases at the time of diagnosis because the clinical signs often remain unnoticed or are attributed to other abdominal conditions. In up to 50% of patients the endocardium is affected due to a hormonally active tumor profile. The study aim was to report the outcome of surgical treatment in patients with carcinoid heart disease, including the data of radiological and nuclear imaging, histological diagnosis, and follow up information. METHODS: Between 2008 and 2014, a total of 39 consecutive patients (28 males, 11 females; mean age 66 years; range: 28-84 years) with carcinoid heart syndrome were operated on at the authors' institution. Valvular heart disease was diagnosed with two-dimensional echocardiography. The study population included 26 patients (67%) with severe metastatic disease, who underwent radiotherapy preoperatively, and 13 patients (33%) who were metastasis-free and did not receive preoperative systemic therapy. Follow up was available for all hospital survivors, all of whom underwent serial echocardiographic follow up postoperatively. Adverse cardiac events were defined as cardiac-related death, a need for valvular reintervention, the occurrence of valve prosthesis-related complications, or echocardiographic evidence of new, high-degree valvular dysfunction during follow up. RESULTS: The majority of patients (n = 34; 87%) underwent isolated tricuspid valve replacement, while simultaneous pulmonary valve replacement was performed in five patients (13%). Postoperative complications included reoperation for bleeding in five patients (13%) and new heart block requiring pacemaker implantation in 10 (25%). The in-hospital mortality was 5% (n = 2). The overall survival was 43% at six years postoperatively. At the latest follow up, 12 of the 17 survivors were in NYHA class I, and five in NYHA class II. The adverse cardiac event rate was 71%. Echocardiographically, 46% of patients (6/13) showed at least stationary or mild improvement in the right ventricular ejection fraction at follow up, with no evidence of paravalvular leak, infective endocarditis, or progressive other native valvular carcinoid affection. Postoperatively, the right atrial dimensions were preserved as normal in 23 patients (59%), mildly dilated in six (15%), moderately dilated in three (8%), and severely dilated in seven (18%). Valve-in-valve transcatheter aortic valve implantation was performed in two patients (12%) due to structural degeneration of the valve bioprosthesis and native valve disease progression. CONCLUSIONS: Despite advanced systemic disease, the surgical treatment of patients with carcinoid heart syndrome is associated with an acceptable perioperative risk and satisfactory mid-term survival. Those patients who survived valve surgery benefited from a significant improvement in their functional capacity. Percutaneous procedures may represent a useful tool to reduce the risk of late valvular reinterventions.

Markers of Lipid Metabolism Do Not Correlate with the Expression of Aortopathy in Patients with Bicuspid Aortic Valve Disease.

BACKGROUND: Controversy exists regarding the potential effects of lipid metabolism on the expression of proximal aortopathy. The study aim was to compare the association between markers of lipid metabolism and the expression of proximal aortopathy in patients with either bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) disease. METHODS: A total of 458 consecutive patients (68% males) underwent aortic valve replacement (AVR) with or without concomitant aortic surgery between January 2008 and December 2014 at the authors' institution. All patients undergoing combined procedures were excluded. Attention was focused only on those patients who had aortic dimensions quantified by preoperative computed tomography/magnetic resonance imaging and/or transesophageal echocardiography. A correlation analysis was performed between markers of lipid metabolism (e.g., cholesterol, LDL, HDL, and triglyceride) and cross-sectional aortic diameters in BAV patients (n = 273) versus TAV patients (n = 185). Comparisons were also made of correlation patterns between markers of lipid metabolism and proximal aortic diameter in BAV regurgitation (n = 48) versus BAV stenosis (n = 225) cohorts. A logistic regression was performed to analyze predictors of proximal aortic diameter ≥40 mm in BAV and TAV subgroups. RESULTS: No significant correlation was found between maximal cross-sectional aortic diameters and parameters of lipid metabolism in the whole study population (n = 458). Only preoperative statin therapy was significantly associated with the proximal aortic diameter (OR = 0.64, p = 0.046). Neither was any significant correlation found between markers of lipid metabolism and proximal aortic diameter, separately in BAV and TAV cohorts. Logistic regression revealed a significant association between triglyceride levels and proximal aortic diameter ≥40 mm in the TAV-aortic stenosis (AS) subgroup (OR = 1.4, p = 0.026). Moreover, HDL levels were significantly associated with proximal aortic diameter ≥40 mm in the BAV-AS subgroup (OR = 0.5, p = 0.037). CONCLUSIONS: No significant correlation was identified between markers of lipid metabolism and proximal aortic diameter in surgical BAV and TAV cohorts. The observed correlation between statin use and proximal aortopathy must be addressed in subsequent studies.

Aortopathy in Bicuspid Aortic Valve Stenosis with Fusion of Right-Left versus Right-Non-Coronary Cusps: Are These Different Diseases?

BACKGROUND: The study aim was to prospectively analyze the impact of cusp fusion pattern on aortopathy severity in patients undergoing surgery for bicuspid aortic valve (BAV) stenosis. METHODS: A total of 137 consecutive patients with BAV stenosis (93 males, 44 females; mean age 61 ± 9 years) underwent aortic valve replacement with or without concomitant aortic surgery between January 2012 and March 2015. All patients underwent preoperative cardiac magnetic resonance imaging (cMRI) in order to evaluate morphological/functional parameters of the aortic root. Fusion of the right-left coronary cusps was identified in 99 patients (72%) (R/L group), while the remaining 38 patients (28%) had right-noncoronary cusp fusion (R/N group). cMRI data were used to guide sampling of the proximal aorta during surgery. The expression/severity of aortopathy was quantified by means of proximal aortic phenotype, indexed aortic diameter, and a histological sum-score. RESULTS: There were no significant differences in proximal aortic diameter between the R/L and R/N groups. Moreover, there was no significant difference in the prevalence of distinct aortic phenotypes between the study subgroups. The histological sumscore was comparable between the R/L and R/N groups (2.9 ± 1.5 versus 2.5 ± 1.1, p = 0.2). The angle LV/aorta was significantly larger in the R/L group than in the R/N group (52.1 ± 10.6° versus 45.1 ± 8.5°, p = 0.001). Logistic regression analysis demonstrated the angle LV/aorta and the angle jet/aorta to be predictive of a mid-ascending phenotype. The cusp fusion pattern had no significant impact on the occurrence of aortic phenotype. CONCLUSIONS: The study results demonstrated that cusp fusion morphotype has no significant impact on the expression and severity of bicuspid aortopathy in patients undergoing surgery for BAV stenosis.