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1.
Heart Lung Circ ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38811293

ABSTRACT

BACKGROUND: Diabetic patients with coronary artery disease may benefit from elective coronary artery bypass graft (CABG) surgery. It is unknown whether this merit is transferable to patients with acute myocardial infarction (AMI) undergoing surgery. METHOD: A total of 1,427 patients underwent CABG within 48 hours of being diagnosed with AMI at the current institution between 2001 and 2019. Of these patients, 206 (14.4%) had insulin-dependent diabetes mellitus (IDDM) and 148 (10.4%) had non-insulin dependent diabetes mellitus (NIDDM). Retrospective data analysis was performed. RESULTS: Patients with NIDDM showed the highest perioperative risk profile, with a EuroScore II of 11.6 (±10.3) compared with 7.8 (±8.0) in non-diabetic patients and 8.4 (±7.8) in patients with IDDM (p<0.001). Sub-analysis demonstrated a higher proportion of non-ST-elevation myocardial infarction patients in the NIDDM cohort compared with the IDDM cohort (70.9% vs 56.8%; p=0.005). Postoperatively, NIDDM patients had more sepsis (p<0.01) and longer ventilation times (p<0.001) compared with non-DM and IDDM patients (p<0.01). Wound healing complications were rare, but almost twice as high in NIDDM patients compared with non-DM and IDDM patients (4.7% vs 0.9% vs 2.4%, respectively). The 30-day mortality was highest in the NIDDM cohort (18.3% vs 11.3% vs 7.8%; p=0.012). Analysis of survival for up to 15 years revealed a significantly reduced survival of diabetic patients compared with non-diabetic patients, with lowest survival rates in NIDDM patients (p<0.001). CONCLUSIONS: Non-insulin dependent diabetes mellitus patients undergoing CABG within 48 hours of being diagnosed with AMI are at increased risk of short-term and long-term complications. Therefore, this particular group should undergo a careful evaluation concerning the expected risks and benefits of CABG in this setting.

3.
Cardiol J ; 30(6): 1003-1009, 2023.
Article in English | MEDLINE | ID: mdl-37964645

ABSTRACT

BACKGROUND: Patients with complex coronary artery disease (CAD) may benefit from surgical myocardial revascularization but weighing the risk of peri-operative complications against the expected merit is difficult. Minimally invasive direct artery bypass (MIDCAB) procedures are less invasive, provide the prognostic advantage of operative revascularization of the left anterior descending artery and may be integrated in hybrid strategies. Herein, the outcomes between patients with coronary 1-vessel disease (1-VD) and patients with 2-VD and 3-VD after MIDCAB procedures were compared in this single-center study. METHODS: Between 1998 and 2018, 1363 patients underwent MIDCAB at the documented institution. 628 (46.1%) patients had 1-VD, 434 (31.9%) patients 2-VD and 300 (22.0%) patients suffered from 3-VD. Data of patients with 2-VD, and 3-VD were pooled as multi-VD (MVD). RESULTS: Patients with MVD were older (66.2 ± 10.9 vs. 62.9 ± 11.2 years; p < 0.001) and presented with a higher EuroScore II (2.10 [0.4; 34.2] vs. 1.2 [0.4; 12.1]; p < 0.001). Procedure time was longer in MVD patients (131.1 ± 50.3 min vs. 122.2 ± 34.5 min; p < 0.001). Post-operatively, MVD patients had a higher stroke rate (17 [2.3%] vs. 4 [0.6%]; p = 0.014). No difference in 30-day mortality was observed (12 [1.6%] vs. 4 [0.6%]; p = 0.128). Survival after 15 years was significantly lower in MVD patients (p < 0.01). Hybrid procedures were planned in 295 (40.2%) patients with MVD and realized in 183 (61.2%) cases. MVD patients with incomplete hybrid procedures had a significantly decreased long-term survival compared to cases with complete revascularization (p < 0.01). CONCLUSIONS: Minimally invasive direct coronary artery bypass procedures are low-risk surgical procedures. If hybrid procedures have been planned, completion of revascularization should be a major goal.


Subject(s)
Coronary Artery Disease , Humans , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/surgery , Coronary Artery Bypass/methods , Follow-Up Studies , Treatment Outcome , Myocardial Revascularization/methods
4.
Article in English | MEDLINE | ID: mdl-37341633

ABSTRACT

OBJECTIVES: Pulmonary valve regurgitation is a common problem after relief of right ventricular outflow tract (RVOT) obstruction with a transannular patch. Pulmonary valve replacement with a homograft or xenograft is the routine treatment. Longevity of biological valves and the availability of homografts are limited. Alternatives to restore RVOT competence are evaluated. The goal of this study was to present intermediate-term results for pulmonary valve reconstruction (PVr) in patients with severe regurgitation. METHODS: PVr was performed in 24 patients (August 2006‒July 2018). We analysed perioperative data, pre- and postoperative cardiac magnetic resonance (CMR) imaging studies, freedom from valve replacement and risk factors for pulmonary valve dysfunction. RESULTS: The underlying diagnoses were tetralogy of Fallot (n = 18, 75%), pulmonary stenosis (n = 5, 20.8%) and the double outlet right ventricle post banding procedure (n = 1, 4.2%). The median age was 21.5 (14.8-23.7) years. Main (n = 9, 37.5%) and branch pulmonary artery procedures (n = 6, 25%) and surgery of the RVOT (n = 16, 30.2%) were often part of the reconstruction. The median follow-up after the operation was 8.0 (4.7-9.7) years. Freedom from valve failure was 96% at 2 and 90% at 5 years. The mean longevity of the reconstructive surgery was 9.9 years (95% confidence interval: 8.8-11.1 years). CMR before and 6 months after surgery showed a reduction in the regurgitation fraction [41% (33-55) vs 20% (18-27) P = 0.00] and of the indexed right ventricular end-diastolic volume [156 ml/m2 (149-175) vs 116 ml/m2 (100-143), P = 0.004]. Peak velocity across the pulmonary valve (determined by CMR) half a year after surgery was 2.0, unchanged. CONCLUSIONS: PVr can be achieved with acceptable intermediate-term results and may delay pulmonary valve replacement.

5.
J Cardiovasc Med (Hagerstown) ; 23(8): 519-523, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35905002

ABSTRACT

AIMS: Patients with pulmonary embolism (PE) and contraindications for or failed thrombolysis are at the highest risk for PE-related fatal events. These patients may benefit from surgical embolectomy, but data concerning this approach are still limited. METHODS: The method used here was retrospective data analysis of 103 patients who underwent surgical embolectomy from 2002 to 2020 at our department. RESULTS: Mean age was 58.4 (±15.1) years. Fifty-eight (56.3%) patients had undergone recent surgery; the surgery was tumor associated in 32 (31.1%) cases. Thirty (29.1%) patients had to be resuscitated due to PE, and 13 (12.6%) patients underwent thrombolysis prior to pulmonary embolectomy. Fifteen (14.5%) patients were placed on extra corporeal membrane oxygenation (ECMO) peri-operatively. Five patients (4.9%) died intra-operatively. Neurological symptoms occurred in four patients (3.9%). Thirty-day mortality was 23.3% ( n  = 24). Re-thoracotomy due to bleeding was necessary in 12 (11.6%) patients. This parameter was also identified as an independent risk factor for mortality. CONCLUSION: Surgical pulmonary embolectomy resulted in survival of the majority of patients with PE and contraindications for or failed thrombolysis. Given the excessive mortality when left untreated, an operative approach should become a routine part of discussions concerning alternative treatment options for these patients.


Subject(s)
Pulmonary Embolism , Thrombolytic Therapy , Acute Disease , Embolectomy/adverse effects , Embolectomy/methods , Humans , Middle Aged , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/surgery , Retrospective Studies , Thrombolytic Therapy/adverse effects , Treatment Outcome
6.
Eur J Cardiothorac Surg ; 62(3)2022 08 03.
Article in English | MEDLINE | ID: mdl-35138350

ABSTRACT

OBJECTIVES: There are disparities in the adherence to guideline-recommended therapies after coronary artery bypass graft (CABG). We therefore sought to evaluate the effect of guideline-adherent medical secondary prevention on 1-year outcome after CABG. METHODS: Data were taken from the randomized 'Ticagrelor in CABG' trial. From April 2013 until April 2017, patients who underwent CABG were included. For the present analysis, we compared patients who were treated with optimal medical secondary prevention with those where 1 or more of the recommended medications were missing. RESULTS: Follow-up data at 12 months were available in 1807 patients. About half (54%) of them were treated with optimal secondary prevention. All-cause mortality [0.5% vs 3.5%, hazard ratio (HR) 0.14 (0.05-0.37), P < 0.01], cardiovascular mortality [0.1% vs 1.7%, HR 0.06 (0.01-0.46), P = 0.007] and major adverse events [6.5% vs 11.5%, HR 0.54 (0.39-0.74), P < 0.01] were significantly lower in the group with optimal secondary prevention. The multivariable model for the primary end point based on binary concordance to guideline recommended therapy identified 3 independent factors: adherence to guideline recommended therapy [HR 0.55 (0.39-0.78), P < 0.001]; normal renal function [HR 0.99 (0.98-0.99), P = 0.040]; and off-pump surgery [HR 2.06 (1.02-4.18), P = 0.045]. CONCLUSIONS: Only every second patient receives optimal secondary prevention after CABG. Guideline adherent secondary prevention therapy is associated with lower mid-term mortality and less adverse cardiovascular events after 12 months.


Subject(s)
Coronary Artery Bypass , Coronary Artery Disease , Coronary Artery Bypass/adverse effects , Coronary Artery Disease/surgery , Humans , Prognosis , Secondary Prevention , Ticagrelor , Treatment Outcome
7.
Thorac Cardiovasc Surg ; 70(2): 126-132, 2022 Mar.
Article in English | MEDLINE | ID: mdl-33540424

ABSTRACT

BACKGROUND: Mitral valved stents tend to migrate or to develop paravalvular leakage due to high-left ventricular pressure in this cavity. Thus, this study describes a newly developed mitral valved stent anchoring technology. METHODS: Based on an existing mitral valved stent, four anchoring units with curved surgical needles were designed and fabricated using three-dimensional (3D) software and print technology. Mitral nitinol stents assembled with four anchoring units were successively fixed on 10 porcine annuli. Mechanical tests were performed with a tensile force test system and recorded the tension forces of the 10 nitinol stents on the annulus. RESULTS: The average maximum force was 28.3 ± 5.21 N, the lowest was 21.7 N, and the highest was 38.6 N until the stent lost contact with the annulus; for the break force (zero movement of stent from annulus), the average value was 18.5 ± 6.7 N with a maximum value of 26.9 N and a minimum value of 6.07 N. It was additionally observed that the puncture needles of the anchoring units passed into the mitral annulus in all 10 hearts and further penetrated the myocardium in only one additional heart. The anchoring units enhanced the tightness of the mitral valved stent and did not destroy the circumflex coronary artery, coronary sinus, right atrium, aortic root, or the left ventricular outflow tract. CONCLUSION: The new anchoring units for mitral nitinol stents were produced with 3D software and printing technology; with this new type of anchoring technology, the mitral valved stent can be tightly fixed toward the mitral annulus.


Subject(s)
Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Mitral Valve Insufficiency , Animals , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/methods , Humans , Mitral Valve/diagnostic imaging , Mitral Valve/surgery , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/surgery , Stents , Swine , Technology , Treatment Outcome
8.
Rev Cardiovasc Med ; 23(7): 237, 2022 Jul.
Article in English | MEDLINE | ID: mdl-39076918

ABSTRACT

Objective: Acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) remains associated with a high rate of mortality and disabling morbidity. Coronary artery bypass grafting (CABG) is seldom considered in this setting due to the fear of peri-operative complications. Here, we analysed the outcome of CS patients undergoing CABG within 48 hours after diagnosed with AMI. Methods: A single-center, retrospective data analysis was performed in 220 AMI patients with CS that underwent CABG within 48 hours between 01/2001 and 01/2018. Results: 141 patients were diagnosed with ST-elevation myocardial infarction (STEMI), 79 with non-STEMI (NSTEMI). Median age was 67 (60; 72) for STEMI, and 68 (60.8; 75.0) years for NSTEMI patients (p = 0.190). 52.5% of STEMI patients and 39.2% of NSTEMI patients had suffered from cardiac arrest (CA) pre-operatively (p = 0.049). Coronary 3-vessel disease was present in most patients (78.0% STEMI vs 83.5% NSTEMI; p = 0.381). Percutaneous coronary interventions (PCI) were performed in 32.6% STEMI and 27.8% NSTEMI patients (p = 0.543) prior to surgery. Time from diagnosis to surgery was shorter in STEMI patients (3.92 (2.67; 5.98) vs 7.50 (4.78; 16.74) hours; p < 0.001). A complete revascularization was achieved in 82.3% of STEMI and 73.4% of NSTEMI cases (p = 0.116). Post-operative low cardiac output occurred in 14.2% of STEMI vs 8.9% of NSTEMI patients (p = 0.289). The rate of cerebrovascular injury-including hypoxic brain damage was 12.1% for STEMI and 10.1% among NSTEMI patients. (p = 0.825). 30-day mortality was 32.6% after STEMI vs 31.6% in NSTEMI cases (p = 0.285). Conclusions: In contrast to the discouraging data concerning the role of PCI in AMI patients with CS and complex coronary artery disease, CABG may represent a treatment option worth considering.

9.
Circ Cardiovasc Imaging ; 14(10): e012468, 2021 10.
Article in English | MEDLINE | ID: mdl-34610753

ABSTRACT

BACKGROUND: The status of the systemic right ventricular coronary microcirculation in hypoplastic left heart syndrome (HLHS) is largely unknown. It is presumed that the systemic right ventricle's coronary microcirculation exhibits unique pathophysiological characteristics of HLHS in Fontan circulation. The present study sought to quantify myocardial blood flow by cardiac magnetic resonance imaging and evaluate the determinants of microvascular coronary dysfunction and myocardial ischemia in HLHS. METHODS: One hundred nineteen HLHS patients (median age, 4.80 years) and 34 healthy volunteers (median age, 5.50 years) underwent follow-up cardiac magnetic resonance imaging ≈1.8 years after total cavopulmonary connection. Right ventricle volumes and function, myocardial perfusion, diffuse fibrosis, and late gadolinium enhancement were assessed in 4 anatomic HLHS subtypes. Myocardial blood flow (MBF) was quantified at rest and during adenosine-induced hyperemia. Coronary conductance was estimated from MBF at rest and catheter-based measurements of mean aortic pressure (n=99). RESULTS: Hyperemic MBF in the systemic ventricle was lower in HLHS compared with controls (1.89±0.57 versus 2.70±0.84 mL/g per min; P<0.001), while MBF at rest normalized by the rate-pressure product, was similar (1.25±0.36 versus 1.19±0.33; P=0.446). Independent risk factors for a reduced hyperemic MBF were an HLHS subtype with mitral stenosis and aortic atresia (P=0.017), late gadolinium enhancement (P=0.042), right ventricular diastolic dysfunction (P=0.005), and increasing age at total cavopulmonary connection (P=0.022). The coronary conductance correlated negatively with systemic blood oxygen saturation (r, -0.29; P=0.02). The frequency of late gadolinium enhancement increased with age at total cavopulmonary connection (P=0.014). CONCLUSIONS: The coronary microcirculation of the systemic ventricle in young HLHS patients shows significant differences compared with controls. These hypothesis-generating findings on HLHS-specific risk factors for microvascular dysfunction suggest a potential benefit from early relief of frank cyanosis by total cavopulmonary connection.


Subject(s)
Coronary Circulation/physiology , Hypoplastic Left Heart Syndrome/physiopathology , Microcirculation/physiology , Myocardial Ischemia/physiopathology , Child , Child, Preschool , Echocardiography, Doppler , Female , Follow-Up Studies , Humans , Hypoplastic Left Heart Syndrome/complications , Hypoplastic Left Heart Syndrome/diagnosis , Magnetic Resonance Imaging, Cine , Male , Myocardial Ischemia/diagnosis , Myocardial Ischemia/etiology , Myocardial Perfusion Imaging/methods , Oxygen Saturation , Prospective Studies
10.
Int J Cardiol ; 323: 65-67, 2021 01 15.
Article in English | MEDLINE | ID: mdl-32991943

ABSTRACT

INTRODUCTION: The descending aorta (DAo) in patients with hypoplastic left heart syndrome (HLHS) after Norwood procedure is frequenty enlarged and exhibits increased stiffness. Such findings of previous studies still remain unexplained given the fact that the DAo is not involved in the Norwood operation. METHODS: We studied five HLHS patients with DAo dilatation (aged: 2.9-15.1 years (y), median 9.0 y), four HLHS patients without DAo dilatation (aged: 3.5-9.7 years, median 6.45 y) and 7 healthy controls (aged 6.3-41.6 y, median 26.0 y) using cardiovascular magnetic resonance imaging with acquisition of cine images, contrast-enhanced angiograms and 4D flow. 4D flow data were analyzed based on in-house developed analysis software to quantify vortical flow patterns in terms of vorticity. RESULTS: All patients with DAo dilatation presented with a caliber reduction between the proximal and distal aortic arch of more than 40% (median reduction 71%, range 43%-79%) and with increased z-scores of the DAo. Vorticity in the DAo of patients with DAo dilatation (median: -24 s-1, range: -26 s-1 - -8 s-1) was significantly increased in magnitude compared to controls (median: 0 s-1, range: -2 - +2) (p < 0.01). Vorticity in the DAo of patients without DAo dilatatation was not significantly increased compared to controls. DAo z-scores were associated with increased vorticity. CONCLUSIONS: The findings of signficiantly increased vorticity and its association with increased DAo z-scores can potentially explain vascular alterations in the DAo of HLHS patients. This study gives motivation for further investigations and may ultimately lead to future Norwood procedure modifications.


Subject(s)
Aortic Diseases , Hypoplastic Left Heart Syndrome , Norwood Procedures , Adolescent , Adult , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/surgery , Child , Child, Preschool , Dilatation , Humans , Hypoplastic Left Heart Syndrome/diagnostic imaging , Hypoplastic Left Heart Syndrome/surgery , Young Adult
11.
Eur Heart J Case Rep ; 4(5): 1-4, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33204949

ABSTRACT

BACKGROUND: Loeys-Dietz syndrome (LDS) is a genetic connective tissue disorder, which is characterized by rapid development of aortic and peripheral arterial aneurysms. Loeys-Dietz syndrome has some overlapping phenotypic features with other inherited aortopathies such as Marfan syndrome. However, LDS has a more aggressive vascular course with patient morbidity and mortality occurring at an early age. CASE SUMMARY: We present the rare case of an 11-year-old girl with LDS who underwent valve sparing aortic root replacement at the age of 2.9 years with good results. She had routine follow-up cardiovascular magnetic resonance imaging and was found to have a large aneurysm of the right subclavian artery. After multidisciplinary team discussion, successful surgical resection with prosthetic graft replacement of the right subclavian artery was performed. DISCUSSION: This case illustrates that large aneurysms of aortic branches can already develop in childhood and underlines the need for frequent follow-ups including cross-sectional imaging and multidisciplinary team management.

12.
Eur J Cardiothorac Surg ; 57(2): 380-387, 2020 02 01.
Article in English | MEDLINE | ID: mdl-31302680

ABSTRACT

OBJECTIVES: The right ventricular outflow tract reconstruction is a common necessity in congenital cardiac surgery. As homograft availability is limited, alternatives need to be evaluated. The Labcor® conduit consists of a porcine tricomposite valve assembled inside a bovine pericardium tube. This study presents intermediate-term results for its utilization for right ventricular outflow tract reconstruction. METHODS: Labcor conduits were implanted in 53 patients (February 2009-July 2016). We analysed perioperative data, freedom from conduit failure and risk factors for conduit dysfunction. RESULTS: The most common diagnosis was Tetralogy of Fallot (n = 20, 37.7%). The median age at surgery was 10.0 [interquartile range (IQR) 4.9-14.3] years. Pulmonary artery plasty (n = 37, 69.8%) and augmentation of the right ventricular outflow tract (n = 16, 30.2%) were often part of the procedure. The median conduit size was 21 (range 11-25) mm. There was no in-hospital death. The median follow-up after surgery was 4.6 (IQR 3.4-5.6) years. Fourteen patients (27.5%) developed conduit failure with stenosis being the main cause. Freedom from conduit failure was 98.0% at 2 and 80.5% at 5 years. The median longevity of the conduit was 7.4 years (95% confidence interval 5.1-9.8 years). Younger age and smaller conduit size were related to conduit failure. CONCLUSIONS: Utilization of the Labcor conduit revealed acceptable intermediate-term results. The conduit appeared to be functioning sufficiently well within the first 5 years in the majority of patients. The higher rate of failure concerning smaller conduits might be associated with somatic outgrowth; however, conduit degeneration as common and long-term outcome still needs to be evaluated.


Subject(s)
Bioprosthesis , Heart Defects, Congenital , Heart Valve Prosthesis , Ventricular Outflow Obstruction , Adolescent , Animals , Cattle , Child , Child, Preschool , Heart Defects, Congenital/surgery , Heart Ventricles/surgery , Humans , Infant , Reoperation , Retrospective Studies , Swine , Treatment Outcome , Ventricular Outflow Obstruction/surgery
13.
Thorac Cardiovasc Surg ; 68(2): 124-130, 2020 03.
Article in English | MEDLINE | ID: mdl-29975967

ABSTRACT

BACKGROUND: The impact of patient-prosthesis mismatch (PPM) after aortic valve replacement (AVR) on long-term survival and quality of life (QoL) remains controversial. The objective of this study was to evaluate the impact of PPM on long-term survival and QoL in a large cohort of patients treated with isolated stented biological AVR in a single-center experience. METHODS: We analyzed data of 632 consecutive patients following isolated stented biological AVR between 2007 and 2012 at our institution. We evaluated the QoL (393 evaluable patients) using the Short Form 12-item Health Survey (SF-12) questionnaire via telephone call and the impact of PPM on long-term survival (533 evaluable patients) by Kaplan-Meier's estimate. RESULTS: Severe PPM (<0.65 cm2/m2) had a negative impact on physical component summary (PCS) score (SF-12) compared with patients with moderate or no PPM (p = 0.014), while the mental component summary (MCS) score (SF-12) was not affected by the degree of PPM (p = 0.133). Long-term survival was not different among the three different PPM groups investigated (p = 0.75). CONCLUSION: Severity of PPM demonstrated no influence on long-term survival and MCS score (SF-12), but it was associated with a lower PCS score (SF-12) in patients with severe PPM.


Subject(s)
Aortic Valve Stenosis/surgery , Aortic Valve/surgery , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis , Quality of Life , Aged , Aged, 80 and over , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/mortality , Aortic Valve Stenosis/physiopathology , Female , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/mortality , Hemodynamics , Humans , Male , Middle Aged , Prosthesis Design , Recovery of Function , Severity of Illness Index , Time Factors , Treatment Outcome
14.
Clin Epigenetics ; 11(1): 89, 2019 06 11.
Article in English | MEDLINE | ID: mdl-31186048

ABSTRACT

BACKGROUND: Cardiac disease modelling using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) requires thorough insight into cardiac cell type differentiation processes. However, current methods to discriminate different cardiac cell types are mostly time-consuming, are costly and often provide imprecise phenotypic evaluation. DNA methylation plays a critical role during early heart development and cardiac cellular specification. We therefore investigated the DNA methylation pattern in different cardiac tissues to identify CpG loci for further cardiac cell type characterization. RESULTS: An array-based genome-wide DNA methylation analysis using Illumina Infinium HumanMethylation450 BeadChips led to the identification of 168 differentially methylated CpG loci in atrial and ventricular human heart tissue samples (n = 49) from different patients with congenital heart defects (CHD). Systematic evaluation of atrial-ventricular DNA methylation pattern in cardiac tissues in an independent sample cohort of non-failing donor hearts and cardiac patients using bisulfite pyrosequencing helped us to define a subset of 16 differentially methylated CpG loci enabling precise characterization of human atrial and ventricular cardiac tissue samples. This defined set of reproducible cardiac tissue-specific DNA methylation sites allowed us to consistently detect the cellular identity of hiPSC-CM subtypes. CONCLUSION: Testing DNA methylation of only a small set of defined CpG sites thus makes it possible to distinguish atrial and ventricular cardiac tissues and cardiac atrial and ventricular subtypes of hiPSC-CMs. This method represents a rapid and reliable system for phenotypic characterization of in vitro-generated cardiomyocytes and opens new opportunities for cardiovascular research and patient-specific therapy.


Subject(s)
DNA Methylation , Heart Atria/cytology , Heart Defects, Congenital/pathology , Heart Ventricles/cytology , Myocytes, Cardiac/cytology , Cells, Cultured , CpG Islands , Female , Heart Atria/chemistry , Heart Defects, Congenital/genetics , Heart Ventricles/chemistry , Humans , Induced Pluripotent Stem Cells/chemistry , Induced Pluripotent Stem Cells/cytology , Male , Models, Biological , Myocytes, Cardiac/chemistry , Organ Specificity , Sequence Analysis, DNA , Tissue Engineering
15.
Eur Heart J ; 40(29): 2432-2440, 2019 08 01.
Article in English | MEDLINE | ID: mdl-31145798

ABSTRACT

AIMS: The antiplatelet treatment strategy providing optimal balance between thrombotic and bleeding risks in patients undergoing coronary artery bypass grafting (CABG) is unclear. We prospectively compared the efficacy of ticagrelor and aspirin after CABG. METHODS AND RESULTS: We randomly assigned in double-blind fashion patients scheduled for CABG to either ticagrelor 90 mg twice daily or 100 mg aspirin (1:1) once daily. The primary outcome was the composite of cardiovascular death, myocardial infarction (MI), repeat revascularization, and stroke 12 months after CABG. The main safety endpoint was based on the Bleeding Academic Research Consortium classification, defined as BARC ≥4 for periprocedural and hospital stay-related bleedings and BARC ≥3 for post-discharge bleedings. The study was prematurely halted after recruitment of 1859 out of 3850 planned patients. Twelve months after CABG, the primary endpoint occurred in 86 out of 931 patients (9.7%) in the ticagrelor group and in 73 out of 928 patients (8.2%) in the aspirin group [hazard ratio 1.19; 95% confidence interval (CI) 0.87-1.62; P = 0.28]. All-cause mortality (ticagrelor 2.5% vs. aspirin 2.6%, hazard ratio 0.96, CI 0.53-1.72; P = 0.89), cardiovascular death (ticagrelor 1.2% vs. aspirin 1.4%, hazard ratio 0.85, CI 0.38-1.89; P = 0.68), MI (ticagrelor 2.1% vs. aspirin 3.4%, hazard ratio 0.63, CI 0.36-1.12, P = 0.12), and stroke (ticagrelor 3.1% vs. 2.6%, hazard ratio 1.21, CI 0.70-2.08; P = 0.49), showed no significant difference between the ticagrelor and aspirin group. The main safety endpoint was also not significantly different (ticagrelor 3.7% vs. aspirin 3.2%, hazard ratio 1.17, CI 0.71-1.92; P = 0.53). CONCLUSION: In this prematurely terminated and thus underpowered randomized trial of ticagrelor vs. aspirin in patients after CABG no significant differences in major cardiovascular events or major bleeding could be demonstrated. CLINICALTRIALS.GOV IDENTIFIER: NCT01755520.


Subject(s)
Aspirin/therapeutic use , Coronary Artery Bypass/methods , Platelet Aggregation Inhibitors/therapeutic use , Ticagrelor/therapeutic use , Aged , Double-Blind Method , Early Termination of Clinical Trials , Female , Humans , Male , Postoperative Complications/drug therapy , Postoperative Complications/prevention & control , Postoperative Hemorrhage/chemically induced , Postoperative Hemorrhage/epidemiology , Treatment Outcome
16.
Congenit Heart Dis ; 14(3): 427-437, 2019 May.
Article in English | MEDLINE | ID: mdl-30604917

ABSTRACT

OBJECTIVES: Neonates and infants undergoing surgery for congenital heart disease are at risk for developmental impairment. Hypoxic-ischemic brain injury might be one contributing factor. We aimed to investigate the perioperative release of the astrocyte protein S100B and its relation to cerebral oxygenation. METHODS: Serum S100B was measured before and 0, 12, 24, and 48 hours after surgery. Cerebral oxygen saturation was derived by near-infrared spectroscopy. S100B reference values based on preoperative samples; concentrations above the 75th percentile were defined as elevated. Patients with elevated S100B at 24 or 48 hours were compared to cases with S100B in the normal range. Neonates (≤28 days) and infants (>28 and ≤365 days) were analyzed separately due to age-dependent release of S100B. RESULTS: Seventy-four patients underwent 94 surgical procedures (neonates, n = 38; infants, n = 56). S100B concentrations were higher in neonates before and after surgery at all time points (P ≤ .015). Highest values were noticed immediately after surgery. Postoperative S100B was elevated after 15 (40.5%) surgeries in neonates. There was no difference in pre-, intra-, or postoperative cerebral oxygenation. In infants, postoperative S100B was elevated after 23 (41.8%) procedures. Preoperative cerebral oxygen saturations tended to be lower (53 ± 12% vs 59 ± 12%, P = .069) and arterial-cerebral oxygen saturation difference was higher (35 ± 11% vs 28 ± 11%, P = .018) in infants with elevated postoperative S100B. In the early postoperative course, cerebral oxygen saturation was lower (54 ± 13% vs 63 ± 12%, P = .011) and arterial-cerebral oxygen saturation difference was wider (38 ± 11% vs 30 ± 10%, P = .008). Cerebral oxygen saturation was also lower for the entire postoperative course (62 ± 18% vs 67 ± 9%, P = .047). CONCLUSIONS: Postoperative S100B was elevated in about 40% of neonates and infants undergoing cardiac surgery. Infants with elevated postoperative S100B had impaired perioperative cerebral tissue oxygenation. No relation between S100B and cerebral oxygenation could be demonstrated in neonates.


Subject(s)
Astrocytes/metabolism , Brain/blood supply , Cardiac Surgical Procedures , Cardiopulmonary Bypass , Cerebrovascular Circulation , Heart Defects, Congenital/surgery , Oxygen/blood , S100 Calcium Binding Protein beta Subunit/blood , Age Factors , Biomarkers/blood , Cardiac Surgical Procedures/adverse effects , Cardiopulmonary Bypass/adverse effects , Female , Heart Defects, Congenital/blood , Heart Defects, Congenital/diagnosis , Heart Defects, Congenital/physiopathology , Humans , Infant , Infant, Newborn , Male , Oxygen Consumption , Prospective Studies , Risk Factors , Time Factors , Treatment Outcome , Up-Regulation
17.
Thorac Cardiovasc Surg ; 67(S 04): e11-e18, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31893463

ABSTRACT

BACKGROUND: Neonates undergoing surgery for complex congenital heart disease are at risk of developmental impairment. Hypoxic-ischemic brain injury might be a contributing factor. We aimed to investigate the perioperative release of the astrocyte cytoskeleton component glial fibrillary acid protein and its relation to cerebral oxygenation. METHODS: Serum glial fibrillary acid protein levels were measured before and 0, 12, 24, and 48 hours after surgery. Reference values were based on preoperative samples; concentrations above the 95th percentile were defined as elevated. Cerebral oxygenation was derived by near-infrared spectroscopy. RESULTS: Thirty-six neonates undergoing 38 surgeries utilizing cardiopulmonary bypass were enrolled (complete data available for 35 procedures). Glial fibrillary acid protein was elevated after 18 surgeries (arterial switch: 7/12; Norwood: 5/15; others: 6/8; p = 0.144). Age at surgery was higher in cases with elevated serum levels (6 [4-7] vs. 4 [2-5] days, p = 0.009) and intraoperative cerebral oxygen saturation was lower (70 ± 10% vs. 77 ± 7%, p = 0.029). In cases with elevated postoperative glial fibrillary acid protein, preoperative cerebral oxygen saturation was lower for neonates undergoing the arterial switch operation (55 ± 9% vs. 64 ± 4%, p = 0.048) and age at surgery was higher for neonates with a Norwood procedure (7 [6-8] vs. 5 [4-6] days, p = 0.028). CONCLUSIONS: Glial fibrillary acid protein was elevated after ∼50% of neonatal cardiac surgeries and was related to cerebral oxygenation and older age at surgery. The potential value as a biomarker for cerebral injury after neonatal cardiac surgery warrants further investigation; in particular, the association with neurodevelopmental outcome needs to be determined.


Subject(s)
Cardiac Surgical Procedures/adverse effects , Cerebrovascular Circulation , Glial Fibrillary Acidic Protein/blood , Heart Defects, Congenital/surgery , Hypoxia-Ischemia, Brain/blood , Hypoxia-Ischemia, Brain/etiology , Oxygen/blood , Age Factors , Biomarkers/blood , Cardiopulmonary Bypass/adverse effects , Heart Defects, Congenital/diagnosis , Humans , Hypoxia-Ischemia, Brain/diagnosis , Hypoxia-Ischemia, Brain/physiopathology , Infant, Newborn , Pilot Projects , Prospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Up-Regulation
18.
Eur J Cardiothorac Surg ; 54(6): 1013-1021, 2018 12 01.
Article in English | MEDLINE | ID: mdl-30052908

ABSTRACT

OBJECTIVES: Transcatheter mitral valved stent implantation provides an off-pump treatment option for mitral valve regurgitation, especially for secondary mitral valve regurgitation. The aim of this study was to evaluate novel fixation strategies: direct fixation (SUPRA) and subvalvular fixation (sub-VALV) to successfully implement alternative fixation methods at the mitral annulus and to reduce radial stent and apical tether forces. METHODS: Specific concepts were developed for the supra-annular hook-shaped fixation (SUPRA) and the subvalvular fixation (sub-VALV). These prototypes were compared with the sole apical tether fixation (AP) methods. Thirty-three pigs underwent mitral valved stent implantation accompanied by standardized transoesophageal echocardiographic and haemodynamic evaluation of heart function and the stent performance 1 h after implantation. Additionally, animals were followed up for 3 months. RESULTS: Secure deployment and correct positioning with low transvalvular gradients were achieved in all cases with mitral valved stent implantation. Nevertheless, 2 pigs died due to rhythm disturbances during dissection and pre-transcatheter mitral valve implantation. Paravalvular leakages were trace or less in prototypes with supra-annular fixation and sole apical fixation. In contrast, moderate paravalvular leakages were observed in the sub-VALV group (P < 0.001). In addition, the effect of a specific stent design on heart function was demonstrated: an increased rate of ischaemia and arrhythmia (P = 0.037) and a small left ventricular ejection fraction reduction (P < 0.05) were observed in the group with subvalvular fixation. In all but 1 case, gross evaluation demonstrated a good ingrowth of the valved stents of between 36% and 100% tissue coverage after a follow-up of 1 month or longer. CONCLUSIONS: The low degree of paravalvular leakages in the supra-annular and apical fixation groups and the normal longitudinal function highlight the good alignment of these new mitral valved stent designs within the native anatomy. The novel, hook-shaped, supra-annular fixation elements were well tolerated in the hearts resulting in excellent health of the animals at long-term follow-up times of up to 3 months.


Subject(s)
Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Mitral Valve , Animals , Echocardiography, Transesophageal , Equipment Design , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis Implantation/methods , Mitral Valve/diagnostic imaging , Mitral Valve/surgery , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/surgery , Prosthesis Design , Stents , Swine
19.
Ann Thorac Surg ; 105(5): 1447-1454, 2018 05.
Article in English | MEDLINE | ID: mdl-29288017

ABSTRACT

BACKGROUND: Optimal pulmonary perfusion is crucial for a well-functioning Fontan circulation in patients with hypoplastic left heart syndrome (HLHS). To obtain an adequate size of the left pulmonary artery (LPA), patch enlargement is a routine part of the hemi-Fontan procedure in our center. However, LPA patch enlargement at the time of the modified Norwood procedure may have surgical advantages. Therefore, the aim of this study was to evaluate whether anatomic and functional effects of the new approach are superior. METHODS: A total of 51 consecutive HLHS patients underwent a cardiovascular magnetic resonance imaging study including assessment of LPA anatomy and lung perfusion. The LPA of 20 patients was enlarged during the modified Norwood procedure (group N) and of 31 patients during the hemi-Fontan procedure (group HF). RESULTS: The median indexed cross-sectional area of the LPA in group N was significantly higher than in group HF (49.5 versus 27.9 mm2/m2, p < 0.0001). The regional pulmonary perfusion as measured by first-pass, contrast-enhanced signal intensity upslope was significantly improved in group N (left side 0.67 s-1 versus 0.40 s-1, p = 0.002; right side 0.84 s-1 versus 0.52 s-1, p = 0.01). The total hemi-Fontan bypass and procedure times were significantly shorter in group N (both p < 0.001). CONCLUSIONS: These first magnetic resonance imaging data show that HLHS patients after LPA patch enlargement during the modified Norwood procedure have significantly higher LPA cross-sectional areas and show improved lung perfusion and shorter overall procedure time as compared with LPA patching during second stage (hemi-Fontan). Therefore, this promising surgical technique may improve blood flow dynamics of the Fontan circulation in the long run.


Subject(s)
Hypoplastic Left Heart Syndrome/surgery , Norwood Procedures/methods , Pulmonary Artery/surgery , Pulmonary Circulation/physiology , Child, Preschool , Female , Humans , Hypoplastic Left Heart Syndrome/diagnostic imaging , Hypoplastic Left Heart Syndrome/physiopathology , Infant , Magnetic Resonance Imaging , Male , Retrospective Studies , Treatment Outcome
20.
J Am Heart Assoc ; 6(10)2017 Oct 03.
Article in English | MEDLINE | ID: mdl-28974496

ABSTRACT

BACKGROUND: The optimal timing of coronary artery bypass grafting (CABG) in clinically stable patients with acute myocardial infarction who are unsuitable for percutaneous coronary intervention is unclear. We report our experience with early CABG in these patients. METHODS AND RESULTS: Between January 2001 and May 2015, 766 patients with ST-segment-elevation myocardial infarction (STEMI, n=305) or non-STEMI (NSTEMI, n=461) not including cardiogenic shock underwent CABG within 48 hours at our department. STEMI patients were younger than non-STEMI patients (age 65 years [range: 58-72] versus 70 years [range: 62-75], P<0.001) with a lower EuroSCORE II (4.12 [range: 2.75-5.81] versus 4.58 [range: 2.80-7.74], P=0.009). STEMI patients had undergone preoperative percutaneous coronary intervention more often (20.3% versus 7.8%, P<0.001). Time to surgery was shorter in STEMI compared with non-STEMI patients (5.0 hours [range: 3.2-8.8] versus 11.7 hours [range: 6.4-22.0], P<0.001). No significant differences concerning arterial graft use (93.8% versus 94.8%, P=0.540) or complete revascularization (87.5% versus 83.4%, P=0.121) were observed. The rate of strokes did not differ between the groups (2.0% versus 3.9%, P=0.134). Thirty-day mortality was lower in STEMI patients (2.7% versus 6.6% P=0.018), especially when CABG was performed within 6 hours (1.8% versus 7.1%, P=0.041). Survival of STEMI and non-STEMI patients was 94% versus 88% after 1 year (P<0.001), 87% versus 73% after 5 years (P<0.001), and 74% versus 57% after 10 years (P<0.001). Independent predictors of 30-day and long-term mortality included preoperatively increased lactate values, age, atrial fibrillation, and reduced left ventricular function. CONCLUSIONS: Stable STEMI patients showed a lower rate of perioperative complications and better survival compared with non-STEMI patients when CABG was performed within 48 hours.


Subject(s)
Coronary Artery Bypass , Non-ST Elevated Myocardial Infarction/surgery , ST Elevation Myocardial Infarction/surgery , Time-to-Treatment , Aged , Coronary Artery Bypass/adverse effects , Coronary Artery Bypass/mortality , Female , Germany , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Non-ST Elevated Myocardial Infarction/diagnosis , Non-ST Elevated Myocardial Infarction/mortality , Non-ST Elevated Myocardial Infarction/physiopathology , Postoperative Complications/etiology , Proportional Hazards Models , Retrospective Studies , Risk Factors , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/mortality , ST Elevation Myocardial Infarction/physiopathology , Time Factors , Treatment Outcome
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