A Neuronal Network-Based Score Predicting Survival in Patients Undergoing Aortic Valve Intervention: The ABC-AS Score.

Background: Despite being the most commonly performed valvular intervention, risk prediction for aortic valve replacement in patients with severe aortic stenosis by currently used risk scores remains challenging. The study aim was to develop a biomarker-based risk score by means of a neuronal network. Methods: In this multicenter study, 3595 patients were divided into test and validation cohorts (70% to 30%) by random allocation. Input variables to develop the ABC-AS score were age, the cardiac biomarker high-sensitivity troponin T, and a patient history of cardiac decompensation. The validation cohort was used to verify the scores' value and for comparison with the Society of Thoracic Surgery Predictive Risk of Operative Mortality score. Results: Receiver operating curves demonstrated an improvement in prediction by using the ABC-AS score compared to the Society of Thoracic Surgery Predictive Risk of Operative Mortality (STS prom) score. Although the difference in predicting cardiovascular mortality was most notable at 30-day follow-up (area under the curve of 0.922 versus 0.678), ABC-AS also performed better in overall follow-up (0.839 versus 0.699). Furthermore, univariate analysis of ABC-AS tertiles yielded highly significant differences for all-cause (p < 0.0001) and cardiovascular mortality (p < 0.0001). Head-to-head comparison between both risk scores in a multivariable cox regression model underlined the potential of the ABC-AS score (HR per z-unit 2.633 (95% CI 2.156-3.216), p < 0.0001), while the STS prom score failed to reach statistical significance (p = 0.226). Conclusions: The newly developed ABC-AS score is an improved risk stratification tool to predict cardiovascular outcomes for patients undergoing aortic valve intervention.

Hypertrophic cardiomyopathy is characterized by alterations of the mitochondrial calcium uniporter complex proteins: insights from patients with aortic valve stenosis versus hypertrophic obstructive cardiomyopathy.

Introduction: Hypertrophies of the cardiac septum are caused either by aortic valve stenosis (AVS) or by congenital hypertrophic obstructive cardiomyopathy (HOCM). As they induce cardiac remodeling, these cardiac pathologies may promote an arrhythmogenic substrate with associated malignant ventricular arrhythmias and may lead to heart failure. While altered calcium (Ca2+) handling seems to be a key player in the pathogenesis, the role of mitochondrial calcium handling was not investigated in these patients to date. Methods: To investigate this issue, cardiac septal samples were collected from patients undergoing myectomy during cardiac surgery for excessive septal hypertrophy and/or aortic valve replacement, caused by AVS and HOCM. Septal specimens were matched with cardiac tissue obtained from post-mortem controls without cardiac diseases (Ctrl). Results and discussion: Patient characteristics and most of the echocardiographic parameters did not differ between AVS and HOCM. Most notably, the interventricular septum thickness, diastolic (IVSd), was the greatest in HOCM patients. Histological and molecular analyses showed a trend towards higher fibrotic burden in both pathologies, when compared to Ctrl. Most notably, the mitochondrial Ca2+ uniporter (MCU) complex associated proteins were altered in both pathologies of left ventricular hypertrophy (LVH). On the one hand, the expression pattern of the MCU complex subunits MCU and MICU1 were shown to be markedly increased, especially in AVS. On the other hand, PRMT-1, UCP-2, and UCP-3 declined with hypertrophy. These conditions were associated with an increase in the expression patterns of the Ca2+ uptaking ion channel SERCA2a in AVS (p = 0.0013), though not in HOCM, compared to healthy tissue. Our data obtained from human specimen from AVS or HOCM indicates major alterations in the expression of the mitochondrial calcium uniporter complex and associated proteins. Thus, in cardiac septal hypertrophies, besides modifications of cytosolic calcium handling, impaired mitochondrial uptake might be a key player in disease progression.

Transapical electrosurgical laceration and stabilization of mitral clips followed by transcatheter mitral valve replacement-A one-stop shop.

Objective: Electrosurgical laceration and stabilization of mitral clips (ELASTA-CLIP) is a bail-out technique to recreate a single-orifice mitral valve after transcatheter edge-to-edge repair (TEER) with subsequent transcatheter mitral valve replacement (TMVR). This technique is a novel option for patients with significant residual mitral regurgitation after TEER with high risk for conventional surgery. The original ELASTA CLIP procedure features a transseptal approach, whereas the TMVR with the Tendyne bioprosthesis has a transapical access. Hereby we tested the hypothesis that a modified transapical ELASTA CLIP technique can be safely applied transapically allowing a straightforward one-stop shop access strategy. Methods: We developed the procedural steps in a porcine passive-beating heart model and applied the modified technique with subsequent TMVR in 2 consecutive patients with severe mitral regurgitation after previous TEER. Patients were followed up to 30 days. Results: The modified transapical ELASTA CLIP procedure was successful in both patients. The mean total procedure time was 118 minutes, and the mean fluoroscopy duration 22 minutes. At 30 days' follow-up, both patients were alive without bleeding complications, reintervention, or prosthetic valve dysfunction. Conclusions: The modified transapical ELASTA CLIP procedure is technically feasible and safe at 30 days. Procedure times are lower compared with previous reports of the original transseptal approach.

The Presence of Ascending Aortic Dilatation in Patients Undergoing Transcatheter Aortic Valve Replacement Is Negatively Correlated with the Presence of Diabetes Mellitus and Does Not Impair Post-Procedural Outcomes.

Both relevant aortic valve stenosis (AS) and aortic valve insufficiency significantly contribute to structural changes in the ascending aorta (AA) and thus to its dilatation. In patients with severe AS undergoing transcatheter aortic valve replacement (TAVR), survival data regarding aortic changes and laboratory biomarker analyses are scarce. METHODS: A total of 179 patients with severe AS and an available computed tomography were included in this retrospective study. AA was measured, and dilatation was defined as a diameter ≥ 40 mm. Thirty-two patients had dilatation of the AA. A further 32 patients from the present population with a normal AA were matched to the aortic dilatation group with respect to gender, age, body mass index and body surface area, and the resulting study groups were compared with each other. In addition to echocardiographic and clinical characteristics, the expression of cardiovascular biomarkers such as brain natriuretic peptide (BNP), soluble suppression of tumorigenicity-2 (sST2), growth/differentiation of factor-15 (GDF-15), heart-type fatty-acid binding protein (H-FABP), insulin-like growth factor binding protein 2 (IGF-BP2) and soluble urokinase-type plasminogen activator receptor (suPAR) was analyzed. Kaplan-Meier curves for short- and long-term survival were obtained, and Pearson's and Spearman's correlations were calculated to identify the predictors between the diameter of the AA and clinical parameters. RESULTS: A total of 19% of the total cohort had dilatation of the AA. The study group with an AA diameter ≥ 40 mm showed a significantly low comorbidity with respect to diabetes mellitus in contrast to the comparison cohort with an AA diameter < 40 mm (p = 0.010). This result continued in the correlation analyses performed, as the presence of diabetes mellitus correlated negatively not only with the diameter of the AA (r = -0.404; p = 0.001) but also with the presence of aortic dilatation (r = -0.320; p = 0.010). In addition, the presence of AA dilatation after TAVR was shown to have no differences in terms of patient survival at 1, 3 and 5 years. There were no relevant differences in the cardiovascular biomarkers studied between the patients with dilated and normal AAs. CONCLUSION: The presence of AA dilatation before successful TAVR was not associated with a survival disadvantage at the respective follow-up intervals of 1, 3 and 5 years. Diabetes mellitus in general seemed to have a protective effect against the development of AA dilatation or aneurysm in patients with severe AS.

A Story of PA/BSA and Biomarkers to Diagnose Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis-The Rise of IGF-BP2 and GDF-15.

(1) Background: Currently, echocardiography is the primary non-invasive diagnostic method used to screen patients with severe aortic valve stenosis (AS) for pulmonary hypertension (PH) by estimating systolic pulmonary artery pressure (sPAP). Other radiological methods have been a focus of research in the past couple of years, as it was shown that by determining the pulmonary artery (PA) diameter, prognostic statements concerning overall mortality could be made in these patients. This study compared established and novel cardiovascular biomarkers with the PA/BSA value to detect PH in patients with severe AS. (2) Methods: The study cohort comprised 188 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR), who were then divided into two groups based on PA/BSA values obtained through CT-angiography. The presence of PH was defined as a PA/BSA ≥ 16.6 mm/m2 (n = 81), and absence as a PA/BSA < 16.6 mm/m2 (n = 107). Blood samples were taken before TAVR to assess cardiovascular biomarkers used in this study, namely brain natriuretic peptide (BNP), cardiac troponin I (cTnI), high-sensitive troponin (hsTN), soluble suppression of tumorigenesis-2 (sST2), growth/differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), insulin-like growth factor binding protein 2 (IGF-BP2), and soluble urokinase-type plasminogen activator receptor (suPAR). (3) Results: Patients with a PA/BSA ≥ 16.6 mm/m2 showed significantly higher levels of BNP (p = <0.001), GDF-15 (p = 0.040), and H-FABP (p = 0.007). The other investigated cardiovascular biomarkers did not significantly differ between the two groups. To predict a PA/BSA ≥ 16.6 mm/m2, cut-off values for the biomarkers were calculated. Here, GDF-15 (p = 0.029; cut-off 1172.0 pg/mL) and BNP (p < 0.001; cut-off 2194.0 pg/mL) showed significant results. Consequently, analyses of combined biomarkers were performed, which yielded IGF-BP2 + BNP (AUC = 0.721; 95%CI = 0.585−0.857; p = 0.004) as the best result of the two-way analyses and GDF-15 + IGF-BP2 + BNP (AUC = 0.727; 95%CI = 0.590−0.864; p = 0.004) as the best result of the three-way analyses. No significant difference regarding the 1-year survival between patients with PA/BSA < 16.6 mm/m2 and patients with PA/BSA ≥ 16.6 mm/m2 was found (log-rank test: p = 0.452). (4) Conclusions: Although PA/BSA aims to reduce the bias of the PA value caused by different body compositions and sizes, it is still a controversial parameter for diagnosing PH. Combining the parameter with different cardiovascular biomarkers did not lead to a significant increase in the diagnostic precision for detecting PH in patients with severe AS.

CT-Diagnosed Sarcopenia and Cardiovascular Biomarkers in Patients Undergoing Transcatheter Aortic Valve Replacement: Is It Possible to Predict Muscle Loss Based on Laboratory Tests?-A Multicentric Retrospective Analysis.

BACKGROUND: Patients with severe aortic valve stenosis (AS) often present with heart failure and sarcopenia. Sarcopenia, described as progressive degradation of skeletal muscle mass, has frequently been implicated as a cause of increased mortality, prolonged hospitalization and generalized poor outcome after transcatheter aortic valve replacement (TAVR). At present, sarcopenia is defined by the European Working Group on Sarcopenia in Older People (EWGSOP) based on clinical examination criteria and radiological imaging. The aim of the present study was to compare patients with Computed Tomography (CT)-diagnosed sarcopenia with regard to the expression of cardiovascular biomarkers in order to obtain additional, laboratory-chemical information. METHODS: A total of 179 patients with severe AS were included in this retrospective study. Sarcopenia was determined via CT by measurement of the psoas muscle area (PMA), which was indexed to body surface area (PMAi). According to previous studies, the lowest tertile was defined as sarcopenic. Patients with (59/179) and without sarcopenia (120/179) in the overall cohort were compared by gender-specific cut-offs with regard to the expression of cardiovascular biomarkers such as brain natriuretic peptide (BNP), soluble suppression of tumorigenicity-2 (sST2), growth/differentiation of factor-15 (GDF-15), heart-type fatty-acid binding protein (H-FABP), insulin like growth factor binding protein 2 (IGF-BP2) and soluble urokinase-type plasminogen activator receptor (suPAR). Additionally, binary logistic regression analyses were calculated to detect possible predictors of the presence of sarcopenia. RESULTS: No statistical differences regarding one-year survival could be detected between sarcopenic and non-sarcopenic patients in survival curves (log rank test p = 0.179). In the entire cohort, only BNP and hemoglobin (HB) showed a statistically significant difference, with only HB emerging as a relevant predictor for the presence of sarcopenia after binary logistic regression analysis (p = 0.015). No relevant difference in biomarker expression could be found in the male cohort. Regarding the female cohort, statistically significant differences were found in BNP, HB and hematocrit (HK). In binary logistic regression, however, none of the investigated criteria could be related to sarcopenia. CONCLUSION: Regardless of gender, patients with imaging-based muscle degradation did not demonstrate significantly different cardiovascular biomarker expression compared to those without it.

Myocarditis following mRNA COVID-19 vaccination: call for endomyocardial biopsy.

Acute myocarditis following mRNA COVID-19 vaccination was reported by the European Medicine Agency safety committee as a rare adverse event. We present a case series of three young male patients with suspected acute myocarditis following BNT162b2 mRNA COVID-19 vaccination including results of endomyocardial biopsies (EMB). Additionally, we analysed EMB of another 21 patients with clinically suspected acute myocarditis following vaccination to determine the pathohistological pattern. Overall, EMB revealed acute lymphocytic myocarditis in 5 (20.8%), chronic lymphocytic myocarditis in 6 (25%), cardiac sarcoidosis in 1 (4.2%), healed myocarditis in 6 (25%), and other diagnoses with cardiac damage of unclear aetiology in 6 (25%) cases. Our findings support the necessity of EMB in patients with suspected acute myocarditis following mRNA COVID-19 vaccination presenting with reduced EF to establish a correct and definite diagnosis. Concerns of these rare severe adverse events after COVID-19 immunization should not undermine its value for the global community.

Systolic Pulmonary Artery Pressure and Cardiovascular Biomarkers-New Non-Invasive Ways to Detect Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis Undergoing TAVR?

Background: Patients with severe aortic valve stenosis (AS) frequently present with pulmonary hypertension (PH). The gold standard for detection of pulmonary hypertension is right heart catheterization, which is not routinely performed as a preoperative standard in cardiology centers today, neither before surgical valve replacement nor before transcatheter aortic valve replacement (TAVR) procedure. Echocardiographic determination of systolic pulmonary artery pressure (sPAP) provides an opportunity to assess the presence or absence of PH. The aim of the present study was to investigate the extent to which plasma levels of common cardiovascular biomarkers behave in patients with severe AS and an sPAP < 40 mmHg in comparison to patients with an sPAP ≥ 40 mmHg. Methods: 179 patients with echocardiographic evidence of severe AS before TAVR procedure were divided into 2 groups based on sPAP. An sPAP of 40 mmHg was considered the cut-off value, with absence of PH defined by an sPAP < 40 mmHg (n = 82) and presence of PH defined by an sPAP ≥ 40 mmHg (n = 97). Directly before TAVR, a blood sample was drawn from each patient, and plasma concentrations of the cardiovascular biomarkers Soluble Suppression of Tumorigenicity-2 (sST2), Growth/Differentiation of Factor-15 (GDF-15), Heart-Type Fatty-Acid Binding Protein (H-FABP), Insulin Like Growth Factor Binding Protein 2 (IGF-BP2), Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR), Brain Natriuretic Peptide (BNP) and Cardiac Troponin I (cTnI) were determined. Results: Patients with an sPAP ≥ 40 mmHg had significantly higher sST2 (p = 0.010), GDF-15 (p = 0.005), IGF-BP2 (p = 0.029), suPAR (p = 0.018), BNP (p < 0.001) and cTnI (p = 0.039) plasma levels. Only for H-FABP (p = 0.069), no significant differences were discernible between the two groups. In addition, cut-off values were calculated to predict an sPAP ≥ 40 mmHg. Significant results were shown with 16045.84 pg/mL for sST2 (p = 0.010), with 1117.54 pg/mL for GDF-15 (p = 0.005), with 107028.43 pg/mL for IGF-BP2 (p = 0.029), with 3782.84 pg/mL for suPAR (p = 0.018), with 2248.00 pg/mL for BNP (p < 0.001) and with 20.50 pg/mL for cTnI (p = 0.002). Conclusions: sPAP as an echocardiographic parameter in combination with supplementary use of cardiovascular biomarkers presented here have the potential to provide more detailed information about the presence or absence of PH in a non-invasive way.

Tumor necrosis factor alpha-an underestimated risk predictor in patients undergoing transcatheter aortic valve replacement (TAVR)?

BACKGROUND: Systemic inflammation has been identified as a major cardiovascular risk factor in patients undergoing transcatheter aortic valve replacement (TAVR), yet currently, it is not adequately portrayed in scores for pre-interventional risk assessment. The aim of this study was to investigate the predictive ability of TNF-α in TAVR. METHODS: A total of 431 patients undergoing transfemoral TAVR were enrolled in this study. Blood samples were drawn prior to intervention, 24 h post-intervention, 4, 5, and 7 days post-intervention, and 1, 3, and 6 months post-TAVR. RESULTS: In a univariate Cox proportional hazard analysis, plasma concentrations of TNF-α after 24 h and after 5 days were associated with mortality after 12 months (after 24 h: HR 1.002 (1.000-1.004), p = 0.028; after 5d: HR 1.003 (1.001-1.005), p = 0.013). This association remained significant even after correction for confounders in a multivariate Cox regression analysis. Additionally, cut-offs were calculated. Patients above the cut-off for TNF-α after 5d had a significantly worse 12-month mortality than patients below the cut-off (18.8% vs. 2.8%, p = 0.046). CONCLUSION: Plasma levels of TNF-α after 24 h and 5 days were independently associated with 12-month mortality in patients undergoing TAVR. Thus, TNF-α could represent a novel biomarker for enhanced risk stratification in these patients.

Transapical off-pump mitral valve repair following prior mitral valve surgery: A case report.

RATIONALE: Redo surgeries after mitral valve repair are technically demanding. Procedures applying the NeoChord device (NeoChord Inc, St. Louis Park, MN) have proven to be safe and feasible in selected patients requiring mitral valve repair due to a leaflet prolapse or flail. However, its use for redo procedures after conventional surgical repair has not been well established yet. PATIENT CONCERNS: We report the case of a 57-year-old man who presented with dyspnea upon exertion. The patient had undergone a minimally invasive surgical mitral valve repair because of a flail leaflet of the segments segment 2 of the posterior mitral valve leaflet (P2)/segment 3 of the posterior mitral valve leaflet (P3) 4 years before. DIAGNOSES: Transesophageal echocardiography identified a relapse of severe mitral valve regurgitation. The recurring regurgitant jet was caused by a flail leaflet due to newly ruptured native chords. INTERVENTIONS: After discussion in an interdisciplinary heart team, we performed a minimally invasive off-pump redo procedure applying the NeoChord device under three-dimensional transesophageal echocardiographic guidance. OUTCOMES: The echocardiographic result with only trivial residual mitral regurgitation as well as the further clinical course of the patient were favorable. LESSONS: As redo surgery after minimally invasive mitral valve repair is challenging, the NeoChord device represents a novel treatment option that does not require cardiopulmonary bypass.

Safety of cryoballoon ablation for the treatment of atrial fibrillation: First European results from the cryo AF Global Registry.

BACKGROUND: Cryoballoon ablation for the treatment of patients with atrial fibrillation (AF) has been utilized in Europe for >15 years. OBJECTIVES: Report patient and procedural characteristics that influence the safety of cryoablation for the treatment of AF. METHODS: Patients enrolled in the prospective, multicenter Cryo AF Global Registry were treated at 38 European centers. Freedom from a ≥30s episode of AF/atrial flutter (AFL)/atrial tachycardia (AT) at 12-months and serious complications were analyzed. Univariate and multivariable models identified baseline patient and procedural characteristics that predicted a procedure-related complication. RESULTS: Of the 1418 subjects who completed an index procedure, the cohort was 62 ± 11 years of age, 37.7% female, and 72.2% paroxysmal AF (PAF). The mean procedure, left atrial dwell, and fluoroscopy times were 81 ± 34, 54 ± 25, and 14 ± 13 min, respectively. Among the 766 patients with 12-month follow-up, freedom from a ≥30 s AF/AFL/AT recurrence was 83.3% (95% CI: 79.8%-86.3%) and 71.6% (95% CI: 64.6%-77.4%) in patients with PAF and persistent AF. The serious procedure- and device-related adverse event rates were 4.7% and 2.0%. No baseline patient characteristic independently predicted a procedure-related adverse event; however, prolonged procedure duration (OR = 1.01 [95% CI: 1.00-1.01]), use of general anesthesia (OR = 1.71 [95% CI: 1.01-2.92]), and delivery of a cavotricuspid isthmus line (OR = 3.04 [95% CI: 1.01-9.20]) were each independently associated with the occurrence of a serious procedural safety event (all p < .05). CONCLUSIONS: Cryoballoon ablation is safe and effective in real-world use across a broad cohort of patients with AF.

Association of adipocytokines serum levels with left atrial thrombus formation in atrial fibrillation patients on oral anticoagulation (Alert) - A cross-sectional study.

BACKGROUND AND AIMS: Oral anticoagulation is effective for stroke prevention in atrial fibrillation (AF). However, strokes may still occur in high-risk individuals. We conducted a prospective trial to assess the association between adipocytokine serum levels and surrogate parameters for thromboembolic events. METHODS AND RESULTS: In this cross-sectional multicenter trial, we enrolled 189 patients with AF who were on oral anticoagulation. The primary endpoint was defined as either the presence of spontaneous echo contrast (SEC), a left atrial appendage (LAA), or a left atrial (LA) thrombus on transesophageal echocardiography. We investigated the association of adipocytokine serum levels with the combined endpoint using logistic regression analysis. Forty-eight individuals (25%) were assigned to group 1 (G1) due to the occurrence of at least one of the components of the combined endpoint (41 [21.7%] SEC, 3 [1.6%] LA thrombus, 13 [6.9%] LAA thrombus), whereas the remaining patients formed group 2 (G2). The BMI, logarithmized (loge) leptin (G1: 2.0 ± 1.3 µg/ml, G2: 2.0 ± 1.1 µg/ml, p = 0.746) and visfatin serum levels (G1: 3.4 ± 0.3 ng/ml, G2: 3.4 ± 0.5 ng/ml, p = 0.900) did not significantly differ between the groups. Conversely, logarithmized adiponectin (G1: 3.3 ± 0.6 ng/ml, G2: 3.1 ± 0.7 ng/ml, p = 0.036) and resistin levels (G1: 1.8 ± 0.5 ng/ml, G2: 1.6 ± 0.5 ng/ml, p = 0.009) were higher in patients with the primary endpoint. Multivariate logistic regression analysis using a score that combined the individual adiponectin and resistin values in each patient corroborated this association. CONCLUSIONS: Our results suggest that adiponectin and resistin may act as potential biomarkers to identify individuals with AF who are at high thromboembolic risk.

Cardiac Computed Tomography-Derived Left Atrial Volume Index as a Predictor of Long-Term Success of Cryo-Ablation in Patients With Atrial Fibrillation.

Patients with symptomatic, drug-refractory atrial fibrillation (AF) are frequently treated with catheter ablation. Cryo-ablation has been established as an alternative to radiofrequency ablation but long-term outcome data are still limited. This study aimed at elucidating the influence of the left atrial volume index (LAVI), derived from cardiac computed tomography (cCT) data, on the long-term outcome of ablation-naïve AF patients, after their first cryo-ablation. 415 patients (n = 290 [69.90%] male, 60.00 [IQR: 53.00 to 68.00] years old) who underwent a cCT and subsequent cryo-ablation index procedure were included in this single centre retrospective data analysis. A composite end point was defined (AF on electrocardiogram and/or electric cardioversion and/or re-do). Patients were closely followed for a year and then contacted for long-term follow-up after a median of 53.00 months (IQR: 34.50 to 73.00). Statistical analyses of the outcome and predictors of AF recurrence were conducted. In 224 patients (53.98%) no evidence of AF recurrence could be found. LAVI differed significantly between the positive and adverse (AF recurrence) outcome group (49.96 vs 56.07 ml/m2, p < 0.001). Cox regression analyses revealed cCT LAVI (HR: 1.022, 95% CI: 1.013 to 1.031, p < 0.001), BMI (HR: 1.044, 95% CI: 1.005 to 1.084, p < 0.05) and the type of AF (HR: 1.838 for nonparoxysmal AF, 95% CI: 1.214 to 2.781, p < 0.01) to be effective predictors of AF recurrence. A prognostic cCT LAVI cut-off value of 51.99 ml/m2 was calculated and must be validated in future prospective studies. In conclusion, LAVI is an accurate, yet underutilized predictor of AF recurrence after pulmonary vein isolation with cryo-energy and scores for calculating AF recurrence or progression risks might underemphasize the importance of CT-derived LAVI as a predictive factor.

Usefulness of the updated logistic clinical SYNTAX score after percutaneous coronary intervention in patients with prior coronary artery bypass graft surgery: Insights from the GLOBAL LEADERS trial.

OBJECTIVES: We aimed to investigate the prognostic utility of the anatomical CABG SYNTAX and logistic clinical SYNTAX scores for mortality after percutaneous coronary intervention (PCI) in patients with prior coronary artery bypass grafts (CABG). BACKGROUND: The anatomical SYNTAX score evaluated the anatomical complexity of coronary artery disease and helped predict the prognosis of patients undergoing PCI. The anatomical CABG SYNTAX score was derived from the anatomical SYNTAX score in patients with prior CABG, whilst the logistic clinical SYNTAX score was developed by incorporating clinical factors into the anatomical SYNTAX score. METHODS: We calculated the anatomical CABG SYNTAX score and logistic clinical SYNTAX score in 205 patients in the GLOBAL LEADERS trial. The predictive abilities of these scores for 2-year all-cause mortality were evaluated. RESULTS: Using the median scores as categorical thresholds between low and high score groups, the logistic clinical SYNTAX score was able to discriminate the risk of 2-year mortality, unlike the anatomical CABG SYNTAX score. The logistic clinical SYNTAX was significantly better at predicting 2-year mortality, compared to the anatomical CABG SYNTAX score, as evidenced by AUC values in receiver-operating characteristic curve analysis (0.806 vs. 0.582, p < .001) and integrated discrimination improvement (0.121, p < .001). CONCLUSIONS: The logistic clinical SYNTAX score was superior to the anatomical CABG SYNTAX score in predicting 2-year mortality.

Ticagrelor monotherapy beyond one month after PCI in ACS or stable CAD in elderly patients: a pre-specified analysis of the GLOBAL LEADERS trial.

AIMS: Antiplatelet treatment in the elderly post percutaneous coronary interventions (PCI) remains a complex issue. Here we report the results of the pre-specified subgroup analysis of the GLOBAL LEADERS trial evaluating the long-term safety and cardiovascular efficacy of ticagrelor monotherapy among patients categorised according to the pre-specified cut-off value of 75 years of age. METHODS AND RESULTS: This was a pre-specified analysis of the randomised GLOBAL LEADERS trial (n=15,991), comparing 23-month ticagrelor monotherapy (after one month of DAPT) with the reference treatment (12-month DAPT followed by 12 months of aspirin). Among elderly patients (>75 years; n=2,565), the primary endpoint (two-year all-cause mortality or new Q-wave core lab-adjudicated myocardial infarction [MI]) occurred in 7.2% and 9.4% of patients in the ticagrelor monotherapy and the reference group, respectively (hazard ratio [HR] 0.75, 95% confidence interval [CI]: 0.58-0.99, p=0.041; pint=0.23); BARC-defined bleeding type 3/5 occurred in 5.2% and 4.1%, respectively (HR 1.29, 95% CI: 0.89-1.86; p=0.180; pint=0.06). The elderly with stable CAD had a higher rate of BARC 3/5 type bleeding (HR 2.05, 95% CI: 1.18-3.55) with ticagrelor monotherapy versus the reference treatment (pint=0.02). Elderly patients had a lower rate of definite or probable stent thrombosis (ST) with ticagrelor monotherapy (0.4% vs 1.4%, p=0.015, pint=0.01), compared with the reference group. CONCLUSIONS: In this pre-specified, exploratory analysis of the overall neutral trial, there was no differential treatment effect of ticagrelor monotherapy (after one-month dual therapy with aspirin) found in elderly patients undergoing PCI with respect to the rate of the primary endpoint of all-cause death or new Q-wave MI. The lower rate of ST in the elderly with ticagrelor monotherapy is hypothesis-generating. ClinicalTrials.gov identifier: NCT01813435.

Perioperative beta-blockers for preventing surgery-related mortality and morbidity in adults undergoing cardiac surgery.

BACKGROUND: Randomized controlled trials (RCTs) have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and mortality. Thus routine prescription of these drugs in unselected patients remains a controversial issue. A previous version of this review assessing the effectiveness of perioperative beta-blockers in cardiac and non-cardiac surgery was last published in 2018. The previous review has now been split into two reviews according to type of surgery. This is an update and assesses the evidence in cardiac surgery only. OBJECTIVES: To assess the effectiveness of perioperatively administered beta-blockers for the prevention of surgery-related mortality and morbidity in adults undergoing cardiac surgery. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Biosis Previews and Conference Proceedings Citation Index-Science on 28 June 2019. We searched clinical trials registers and grey literature, and conducted backward- and forward-citation searching of relevant articles. SELECTION CRITERIA: We included RCTs and quasi-randomized studies comparing beta-blockers with a control (placebo or standard care) administered during the perioperative period to adults undergoing cardiac surgery. We excluded studies in which all participants in the standard care control group were given a pharmacological agent that was not given to participants in the intervention group, studies in which all participants in the control group were given a beta-blocker, and studies in which beta-blockers were given with an additional agent (e.g. magnesium). We excluded studies that did not measure or report review outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We assessed the certainty of evidence with GRADE. MAIN RESULTS: We included 63 studies with 7768 participants; six studies were quasi-randomized and the remaining were RCTs. All participants were undergoing cardiac surgery, and in most studies, at least some of the participants were previously taking beta-blockers. Types of beta-blockers were: propranolol, metoprolol, sotalol, esmolol, landiolol, acebutolol, timolol, carvedilol, nadolol, and atenolol. In twelve studies, beta-blockers were titrated according to heart rate or blood pressure. Duration of administration varied between studies, as did the time at which drugs were administered; in nine studies this was before surgery, in 20 studies during surgery, and in the remaining studies beta-blockers were started postoperatively. Overall, we found that most studies did not report sufficient details for us to adequately assess risk of bias. In particular, few studies reported methods used to randomize participants to groups. In some studies, participants in the control group were given beta-blockers as rescue therapy during the study period, and all studies in which the control was standard care were at high risk of performance bias because of the open-label study design. No studies were prospectively registered with clinical trials registers, which limited the assessment of reporting bias. We judged 68% studies to be at high risk of bias in at least one domain.Study authors reported few deaths (7 per 1000 in both the intervention and control groups), and we found low-certainty evidence that beta-blockers may make little or no difference to all-cause mortality at 30 days (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.47 to 1.90; 29 studies, 4099 participants). For myocardial infarctions, we found no evidence of a difference in events (RR 1.05, 95% CI 0.72 to 1.52; 25 studies, 3946 participants; low-certainty evidence). Few study authors reported cerebrovascular events, and the evidence was uncertain (RR 1.37, 95% CI 0.51 to 3.67; 5 studies, 1471 participants; very low-certainty evidence). Based on a control risk of 54 per 1000, we found low-certainty evidence that beta-blockers may reduce episodes of ventricular arrhythmias by 32 episodes per 1000 (RR 0.40, 95% CI 0.25 to 0.63; 12 studies, 2296 participants). For atrial fibrillation or flutter, there may be 163 fewer incidences with beta-blockers, based on a control risk of 327 incidences per 1000 (RR 0.50, 95% CI 0.42 to 0.59; 40 studies, 5650 participants; low-certainty evidence). However, the evidence for bradycardia and hypotension was less certain. We found that beta-blockers may make little or no difference to bradycardia (RR 1.63, 95% CI 0.92 to 2.91; 12 studies, 1640 participants; low-certainty evidence), or hypotension (RR 1.84, 95% CI 0.89 to 3.80; 10 studies, 1538 participants; low-certainty evidence).We used GRADE to downgrade the certainty of evidence. Owing to studies at high risk of bias in at least one domain, we downgraded each outcome for study limitations. Based on effect size calculations in the previous review, we found an insufficient number of participants in all outcomes (except atrial fibrillation) and, for some outcomes, we noted a wide confidence interval; therefore, we also downgraded outcomes owing to imprecision. The evidence for atrial fibrillation and length of hospital stay had a moderate level of statistical heterogeneity which we could not explain, and we, therefore, downgraded these outcomes for inconsistency. AUTHORS' CONCLUSIONS: We found no evidence of a difference in early all-cause mortality, myocardial infarction, cerebrovascular events, hypotension and bradycardia. However, there may be a reduction in atrial fibrillation and ventricular arrhythmias when beta-blockers are used. A larger sample size is likely to increase the certainty of this evidence. Four studies awaiting classification may alter the conclusions of this review.

Perioperative beta-blockers for preventing surgery-related mortality and morbidity in adults undergoing non-cardiac surgery.

BACKGROUND: Randomized controlled trials (RCTs) have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and mortality. Thus routine prescription of these drugs in an unselected population remains a controversial issue. A previous version of this review assessing the effectiveness of perioperative beta-blockers in cardiac and non-cardiac surgery was last published in 2018. The previous review has now been split into two reviews according to type of surgery. This is an update, and assesses the evidence in non-cardiac surgery only. OBJECTIVES: To assess the effectiveness of perioperatively administered beta-blockers for the prevention of surgery-related mortality and morbidity in adults undergoing non-cardiac surgery. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Biosis Previews and Conference Proceedings Citation Index-Science on 28 June 2019. We searched clinical trials registers and grey literature, and conducted backward- and forward-citation searching of relevant articles. SELECTION CRITERIA: We included RCTs and quasi-randomized studies comparing beta-blockers with a control (placebo or standard care) administered during the perioperative period to adults undergoing non-cardiac surgery. If studies included surgery with different types of anaesthesia, we included them if 70% participants, or at least 100 participants, received general anaesthesia. We excluded studies in which all participants in the standard care control group were given a pharmacological agent that was not given to participants in the intervention group, studies in which all participants in the control group were given a beta-blocker, and studies in which beta-blockers were given with an additional agent (e.g. magnesium). We excluded studies that did not measure or report review outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We assessed the certainty of evidence with GRADE. MAIN RESULTS: We included 83 RCTs with 14,967 participants; we found no quasi-randomized studies. All participants were undergoing non-cardiac surgery, and types of surgery ranged from low to high risk. Types of beta-blockers were: propranolol, metoprolol, esmolol, landiolol, nadolol, atenolol, labetalol, oxprenolol, and pindolol. In nine studies, beta-blockers were titrated according to heart rate or blood pressure. Duration of administration varied between studies, as did the time at which drugs were administered; in most studies, it was intraoperatively, but in 18 studies it was before surgery, in six postoperatively, one multi-arm study included groups of different timings, and one study did not report timing of drug administration. Overall, we found that more than half of the studies did not sufficiently report methods used for randomization. All studies in which the control was standard care were at high risk of performance bias because of the open-label study design. Only two studies were prospectively registered with clinical trials registers, which limited the assessment of reporting bias. In six studies, participants in the control group were given beta-blockers as rescue therapy during the study period.The evidence for all-cause mortality at 30 days was uncertain; based on the risk of death in the control group of 25 per 1000, the effect with beta-blockers was between two fewer and 13 more per 1000 (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.89 to 1.54; 16 studies, 11,446 participants; low-certainty evidence). Beta-blockers may reduce the incidence of myocardial infarction by 13 fewer incidences per 1000 (RR 0.72, 95% CI 0.60 to 0.87; 12 studies, 10,520 participants; low-certainty evidence). We found no evidence of a difference in cerebrovascular events (RR 1.65, 95% CI 0.97 to 2.81; 6 studies, 9460 participants; low-certainty evidence), or in ventricular arrhythmias (RR 0.72, 95% CI 0.35 to 1.47; 5 studies, 476 participants; very low-certainty evidence). Beta-blockers may reduce atrial fibrillation or flutter by 26 fewer incidences per 1000 (RR 0.41, 95% CI 0.21 to 0.79; 9 studies, 9080 participants; low-certainty evidence). However, beta-blockers may increase bradycardia by 55 more incidences per 1000 (RR 2.49, 95% CI 1.74 to 3.56; 49 studies, 12,239 participants; low-certainty evidence), and hypotension by 44 more per 1000 (RR 1.40, 95% CI 1.29 to 1.51; 49 studies, 12,304 participants; moderate-certainty evidence).We downgraded the certainty of the evidence owing to study limitations; some studies had high risks of bias, and the effects were sometimes altered when we excluded studies with a standard care control group (including only placebo-controlled trials showed an increase in early mortality and cerebrovascular events with beta-blockers). We also downgraded for inconsistency; one large, well-conducted, international study found a reduction in myocardial infarction, and an increase in cerebrovascular events and all-cause mortality, when beta-blockers were used, but other studies showed no evidence of a difference. We could not explain the reason for the inconsistency in the evidence for ventricular arrhythmias, and we also downgraded this outcome for imprecision because we found few studies with few participants. AUTHORS' CONCLUSIONS: The evidence for early all-cause mortality with perioperative beta-blockers was uncertain. We found no evidence of a difference in cerebrovascular events or ventricular arrhythmias, and the certainty of the evidence for these outcomes was low and very low. We found low-certainty evidence that beta-blockers may reduce atrial fibrillation and myocardial infarctions. However, beta-blockers may increase bradycardia (low-certainty evidence) and probably increase hypotension (moderate-certainty evidence). Further evidence from large placebo-controlled trials is likely to increase the certainty of these findings, and we recommend the assessment of impact on quality of life. We found 18 studies awaiting classification; inclusion of these studies in future updates may also increase the certainty of the evidence.

Potential mechanisms of endothelialisation in individuals implanted with a leadless pacemaker systems: An experimental in vitro study.

BACKGROUND: Leadless pacemaker technology is a promising upcoming field in clinical rhythmology. Today, the most commonly used system in the clinical setting is the Micra™ leadless pacemaker system (Medtronic). In autopsies of patients who witnessed non-pacemaker associated death, unexpected ingrowth/encapsulation within the wall of the right ventricle was reported. The occurrence of a complete encapsulation was not expected and the process of endothelialisation remains unclear. We hypothesized, that a local inflammatory response might be the cause of these findings. The aim of our experimental in-vitro study was to investigate the effect of the Micra™ system and its single components on inflammatory processes. METHODS: For this purpose, whole Micra™ pacemakers were incubated in heparin plasma from 25 healthy volunteers for 48 h at 37 °C. Furthermore, 1 g gold, steel, titanium, tungsten and nitinol wires were incubated in heparin plasma for 48 h at 37 °C as well (n = 10). To detect eventual inflammatory processes, interleukin- (IL) 1ß, IL-6, and tumor necrosis factor alpha (TNF-α), the chemokine IL-8 were measured using enzyme-linked immunosorbent assay (ELISA). Additionally, the level of transforming growth factor beta 1 (TGF-ß1) and vascular endothelial growth factor (VEGF) were analysed. RESULTS: ELISA analyses showed that the whole Micra system leads to a significant increase in the inflammatory cytokine IL-6 which correlates with the data gained by the incubation of whole blood with the different wires. In particular, 0.5 g of tungsten showed a significant rise of IL-6 which could also be found for IL-1ß and IL-8. CONCLUSIONS: The in vitro study of the Micra system showed that the material composition led to an onset of inflammatory processes in whole blood. Consequently, one may speculate that the composition of Micra pacemaker may have a local inflammatory, though subclinical, effects in patients implanted with a Micra™ pacemakers.

[Diabetes mellitus, coronary artery disease und heart disease (Update 2019)]. / Diabetes mellitus, koronare Herzkrankheit und Herzinsuffizienz (Update 2019).

Diabetes mellitus, cardiovascular disease and heart failure are interacting dynamically. Patients being diagnosed with cardiovascular disease should be screened for diabetes mellitus. Enhanced cardiovascular risk stratification based on biomarkers, symptoms and classical risk factors should be performed in patients with pre-existing diabetes mellitus. In patients with previously diagnosed arterosclerotic cardiovascular disease an agent proven to reduce major adverse cardiovascular events or cardiovascular mortality is recommended after therapy failure of metformin.

First in Man: Off-Pump Transapical Transcatheter Aortic Valve Implantation and Mitral Valve Repair.

We report the case of an 89-year-old man with severe aortic valve stenosis and concomitant severe mitral valve regurgitation. Due to his age and comorbidities, the patient was not accepted for open heart surgery. After interdisciplinary discussion with the heart team, the patient underwent a minimally invasive off-pump procedure combining aortic valve replacement with mitral valve repair. Cardiac surgeons performed a transapical aortic valve replacement, followed by mitral valve repair applying the NeoChord device (NeoChord Inc, St. Louis Park, MN) under three-dimensional transesophageal echocardiographic guidance by an interventional cardiologist. The patient's further clinical course was uneventful, and he did well on follow-up examinations.