Electrocardiographic changes during sustained normobaric hypoxia in patients after myocardial infarction

Abstract The safety of prolonged high-altitude stays and exercise for physically fit post-myocardial infarction (MI) patients is unclear. Myocardial tissue hypoxia and pulmonary hypertension can affect cardiac function and electrophysiology, possibly contributing to arrhythmias. We included four non-professional male athletes, clinically stable after left ventricular MI (three with ST-segment elevation MI and one with non-ST-segment elevation MI) treated with drug-eluting stents for single-vessel coronary artery disease. Oxygen levels were reduced to a minimum of 11.8%, then restored to 20.9%. We conducted electrocardiography (ECG), ergometry, and echocardiography assessments in normoxic and hypoxic conditions. With an average age of 57.8 ± 3.3 years and MI history 37 to 104 months prior, participants experienced a significant increase in QTc intervals during hypoxia using Bazett’s (from 402 ± 13 to 417 ± 25 ms), Fridericia’s (from 409 ± 12 to 419 ± 19 ms), and Holzmann's formulas (from 103 ± 4 to 107 ± 6%) compared to normoxia. This effect partially reversed during recovery. Echocardiographic signs of pulmonary hypertension during normobaric hypoxia correlated significantly with altered QTc intervals (p < 0.001). Despite good health and complete revascularization following MI, susceptibility to hypoxia-induced QTc prolongation and ventricular ectopic beats persists, especially during physical activity. MI survivors planning high-altitude activities should consult cardiovascular specialists with high-altitude medicine expertise

Rate of venous thromboembolism in a prospective all-comers cohort with COVID-19

Abstract COVID-19 is associated with a variety of clinical complications including coagulopathy, which frequently results in venous thromboembolism (VTE). Retrospective analyses reported a markedly increased rate of VTEs in COVID-19. However, most recent studies on coagulopathy in COVID-19 were only focused on critically ill patients, and without suitable control groups. We aimed to evaluate the rate of VTEs in an all-comers cohort with suspected COVID-19 during a 30-days follow-up period. We also studied the level of D-dimers and their association with the course of disease. In our prospective single-center study (DRKS00021206, 03/30/2020), we analyzed 190 patients with suspected COVID-19 admitted to the emergency department between March and April 2020. Forty-nine patients were SARS-CoV-2 positive (25.8%). The 141 SARS-CoV-2-negative patients served as control group. After completion of a 30-days follow-up, VTE was diagnosed in 3 patients of the SARS-CoV-2-positive group (6.1%, amongst these 2 ICU cases) versus 5 patients in the SARS-CoV-2-negative group (3.5%), however the difference was not statistically significant (p = 0.427). 30-days mortality was similar in both groups (6.1% vs. 5%, p = 0.720). Disease severity correlated with the maximum level of D-dimers during follow-up in COVID-19. The rate of VTE was numerically higher in SARS-CoV-2 positive all-comers presenting with suspected COVID-19 as compared to well-matched controls suffering from similar symptoms. VTEs in the COVID-19 group predominantly occurred in ICU courses. The maximum level of D-dimers during follow-up was associated with disease severity in COVID-19, whereas the level of D-dimers at admission was not

Gender-specific diagnostic performance of a new high-sensitivity cardiac troponin I assay for detection of acute myocardial infarction

Background: The determination of cardiac troponin is essential for diagnosing myocardial infarction. A troponin I assay has recently been developed that provides the highest analytical sensitivity to date. Methods: The analysis included 1560 patients with chest pain, of whom 1098 were diagnosed with non-coronary chest pain, 189 with unstable angina pectoris and 273 with non-ST-segment elevation myocardial infarction. The troponin I concentration was determined on admission (0 hours) and 3 hours later. The diagnostic algorithm incorporated troponin I elevation above the gender-specific 99th percentile as well as predefined relative or absolute 3-hour changes in the troponin I concentration (delta). Results: The diagnostic criterion of troponin I above the 99th percentile resulted in a negative predictive value of 98.0% and 98.2% in men and women, respectively. For rule-in of non-ST-segment elevation myocardial infarction, the use of absolute deltas yielded higher positive predictive values and sensitivities compared to relative deltas. With detection rates of about 85% and 82% in men and women, respectively, non-ST-segment elevation myocardial infarction was diagnosed with a positive predictive value close to 84% in men and 80% in women. Conclusions: The investigational troponin I assay provides an excellent non-ST-segment elevation myocardial infarction rule out. With gender-specific differences, the application of absolute changes in troponin concentration was superior to relative changes to rule in patients with non-ST-segment elevation myocardial infarction

Development of nonfibrotic left ventricular hypertrophy in an ANG II-induced chronic ovine hypertension model

Hypertension is a major risk factor for many cardiovascular diseases and leads to subsequent concomitant pathologies such as left ventricular hypertrophy (LVH). Translational approaches using large animals get more important as they allow the use of standard clinical procedures in an experimental setting. Therefore, the aim of this study was to establish a minimally invasive ovine hypertension model using chronic angiotensin II (ANG II) treatment and to characterize its effects on cardiac remodeling after 8weeks. Sheep were implanted with osmotic minipumps filled with either vehicle control (n=7) or ANG II (n=9) for 8weeks. Mean arterial blood pressure in the ANG II-treated group increased from 87.4 +/- 5.3 to 111.8 +/- 6.9mmHg (P=0.00013). Cardiovascular magnetic resonance imaging showed an increase in left ventricular mass from 112 +/- 12.6g to 131 +/- 18.7g after 7weeks (P=0.0017). This was confirmed by postmortem measurement of left ventricular wall thickness which was higher in ANG II-treated animals compared to the control group (18 +/- 4mm vs. 13 +/- 2mm, respectively, P=0.002). However, ANG II-treated sheep did not reveal any signs of fibrosis or inflammatory infiltrates as defined by picrosirius red and H&E staining on myocardial full thickness paraffin sections of both atria and ventricles. Measurements of plasma high-sensitivity C-reactive protein and urinary 8-iso-prostaglandin F-2 were inconspicuous in all animals. Furthermore, multielectrode surface mapping of the heart did not show any differences in epicardial conduction velocity and heterogeneity. These data demonstrate that chronic ANG II treatment using osmotic minipumps presents a reliable, minimally invasive approach to establish hypertension and nonfibrotic LVH in sheep

Hemodynamics of self-expanding versus balloon-expandable transcatheter heart valves in relation to native aortic annulus anatomy

Objectives This study aimed to compare hemodynamic characteristics of different self-expanding (SE) and balloon-expandable (BE) transcatheter heart valves (THV) in relation to native aortic annulus anatomy. Background A patient centered THV selection becomes increasingly important as indications for transcatheter aortic valve replacement (TAVR) are extended towards lower risk populations. Methods Hemodynamic parameters including mean gradient (MG), effective orifice area (EOA), Doppler velocity index (DVI), degree of paravalvular regurgitation (PVR) and patient-prosthesis mismatch (PPM) were compared by valve type, label size and in relation to quintiles of native aortic annulus area. Results 2609 patients were treated at 3 centers in Germany with SAPIEN 3 (n = 1146), ACURATE Neo (n = 649), Evolut R (n = 546) or Evolut Pro (n = 268) THV. SE THVs provided superior hemodynamics in terms of larger EOA, higher DVI and lower MG compared to BE THV, especially in patients with small aortic annuli. Severe PPM was less frequent in SE treated patients. The rate of PVR >= moderate was comparable for SE and BE devices in smaller annular dimensions, but remarkably lower for BE TAVR in large aortic annular dimensions (> 547.64 mm(2)) (2% BE THV vs. > 10% for SE THV; p = moderate occurs less frequently

Complement system component dysregulation is a distinctive feature of COVID-19 disease: a prospective and comparative analysis of patients admitted to the emergency department for suspected COVID-19 disease

The complement system (CS) plays a pivotal role in Coronavirus disease 2019 (COVID-19) pathophysiology. The objective of this study was to provide a comparative, prospective data analysis of CS components in an all-comers cohort and COVID-19 patients. Patients with suspected COVID-19 infection admitted to the Emergency department were grouped for definite diagnosis of COVID-19 and no COVID-19 accordingly. Clinical presentation, routine laboratory and von Willebrand factor (vWF) antigen as well as CS components 3, 4 and activated 5 (C5a) were assessed. Also, total complement activity via the classical pathway (CH50) was determined. Levels of calprotectin in serum were measured using an automated quantitative lateral flow assay. We included 80 patients in this prospective trial. Of those 19 (23.7%) were tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with COVID-19 had higher levels of CS components 5a and 4 (54.79 [24.14-88.79] ng/ml vs. 35 [23.15-46.1] ng/ml; p = 0.0433 and 0.3772 [± 0.1056] g/L vs. 0.286 [0.2375-0.3748] g/L; p = 0.0168). COVID-19 patients had significantly higher levels of vWF antigen when compared to the control group (288.3 [± 80.26] % vs. 212 [151-320] %; p = 0.0469). There was a significant correlation between CS C3 and 5a with vWF antigen (

Impact of device landing zone calcification patterns on paravalvular regurgitation after transcatheter aortic valve replacement with different next-generation devices

Objective Residual paravalvular regurgitation (PVR) has been associated to adverse outcomes after transcatheter aortic valve replacement (TAVR). This study sought to evaluate the impact of device landing zone (DLZ) calcification on residual PVR after TAVR with different next-generation transcatheter heart valves. Methods 642 patients underwent TAVR with a SAPIEN 3 (S3; n=292), ACURATE neo (NEO; n=166), Evolut R (ER; n=132) or Lotus (n=52). Extent, location and asymmetry of DLZ calcification were assessed from contrast-enhanced CT imaging and correlated to PVR at discharge. Results PVR was >= moderate in 0.7% of S3 patients, 9.6% of NEO patients, 9.8% of ER patients and 0% of Lotus patients (p= moderate increased significantly over the tertiles of DLZ calcium volume (p=0.046). On multivariable analysis, calcification of the aortic valve cusps, LVOT calcification and the use of self-expanding transcatheter aortic valve implantation (TAVI) prostheses emerged as predictors of PVR. Conclusions The susceptibility to PVR depending on the amount of calcium was mainly observed in self-expanding TAVI prostheses. Thus, DLZ calcification is an important factor to be considered in prosthesis selection for each individual patient, keeping in mind the trade-off between PVR reduction, risk of new pacemaker implantation and unfavourable valve ha emodynamics

Transcatheter valve repair of tricuspid regurgitation with the PASCAL system: TriCLASP study 30-day results

Background Severe tricuspid regurgitation (TR) is independently associated with increased morbidity and mortality. Percutaneous transcatheter approaches may offer an alternative for patients not amenable to surgery. Methods TriCLASP is a prospective, single-arm, multicenter European post-market clinical follow-up study (NCT04614402) to evaluate the safety and performance of the PASCAL system (Edwards Lifesciences) in patients with severe or greater TR. At 30 days, a composite of major adverse events (MAEs) adjudicated by a clinical events committee, echocardiographic parameters adjudicated by core laboratory, and clinical, functional, and quality-of-life measures were evaluated. Results Mean age of the 74 enrolled patients was 80.3 years, with 58.1% female, 90.5% systemic hypertension, and 77.0% in New York Heart Association (NYHA) class III/IV. Mean Society for Thoracic Surgeons score (MV repair) was 9.0%. TR severity was significantly reduced at discharge (p < 0.001) and sustained at 30 days (p < 0.001), and 90.0% of patients achieved <= moderate TR. The composite MAE rate at 30 days was 3.0%, including 4 events in 2 patients: cardiovascular mortality 1.5%, stroke 1.5%, renal complications requiring unplanned dialysis or renal replacement therapy 1.5%, and severe bleeding 1.5%. There were no nonelective tricuspid valve reinterventions, major access site and vascular complications, major cardiac structural complications, or device embolizations. NYHA class I/II was achieved in 55.8%, 6-minute walk distance improved by 38.2 m (p < 0.001), and Kansas City cardiomyopathy questionnaire scores improved by 13.4 points (p < 0.001). Conclusion Experience with the PASCAL transcatheter valve repair system in a European post-market setting confirms favorable safety and effectiveness at 30 days. TR significantly reduced, and clinical, functional, and quality-of-life outcomes significantly improved. This study is ongoing. Clinical Trial Registration: The study is ongoing and registered on as NCT04614402. The current analysis is an interim report

Mimicking Clinical Trials with Synthetic Acute Myeloid Leukemia Patients Using Generative Artificial Intelligence

We used two different methodologies of generative artificial intelligence, CTAB-GAN+ and normalizing flows (NFlow), to synthesize patient data based on 1606 patients with acute myeloid leukemia that were treated within four multicenter clinical trials. The resulting data set consists of 1606 synthetic patients for each of the models. Data Dictionary NAME LABEL TYPE CODELIST AGE age num in years AMLSTAT AML status char de novo, sAML, tAML ASXL1 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' ATRX mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' BCOR mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' BCORL1 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' BRAF mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' CALR mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' CBL mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' CBLB mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' CDKN2A mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' CEBPA CEBPA mutation char 0 = 'no mutation', 1 = 'mutation' CGCX complex cytogenetic karyotype char 0 'No', 1 'Yes' CGNK cytogenetic normal karyotype char 0 'No', 1 'Yes' CR1 first complete remission char 0 = 'not achieved', 1 = 'achieved' CSF3R mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' CUX1 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' DNMT3A mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' EFSSTAT status variable for EFSTM num 0 'censored' 1 'event' EFSTM event free survival time num in months ETV6 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' EXAML extramedullary AML char 0 'No', 1 'Yes' EZH2 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' FBXW7 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' FLT3I FLT3-ITD mutation status char 0 = 'no mutation', 1 = 'mutation' FLT3T FLT3-TKD mutation status char 0 = 'no mutation', 1 = 'mutation' GATA2 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' GNAS mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' HB hemoglobin num in mmol/l HRAS mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' IDH1 IDH1 mutation status char 0 = 'no mutation', 1 = 'mutation' IDH2 IDH2 mutation status char 0 = 'no mutation', 1 = 'mutation' IKZF1 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' JAK2 Jak2 Mutation char 0 = 'no mutation', 1 = 'mutation' KDM6A mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' KIT mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' KRAS mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' MPL mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' MYD88 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' NOTCH1 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' NPM1 NPM1 mutation status char 0 = 'no mutation', 1 = 'mutation' NRAS mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' OSSTAT status variable for OSTM num 0 'censored' 1 'event' OSTM overall survival time num in months PDGFRA mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' PHF6 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' PLT platelet count num in 10⁶/l PTEN mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' PTPN11 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' RAD21 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' RUNX1 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' SETBP1 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' SEX sex char f 'female', m 'male' SF3B1 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' SMC1A mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' SMC3 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' SRSF2 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' STAG2 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' SUBJID subject identifier char TET2 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' TP53 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' U2AF1 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' WBC white blood count num in 10⁶/l WT1 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' ZRSR2 mutation indicator, NGS num 0 = 'no mutation', 1 = 'mutation' inv16_t16.16 mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' t8.21 mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' t.6.9..p23.q34. mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' inv.3..q21.q26.2. mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' minus.5 mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' del.5q. mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' t.9.22..q34.q11. mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' minus.7 mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' minus.17 mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' t.v.11..v.q23. mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' abn.17p. mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' t.9.11..p21.23.q23. mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' t.3.5. mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' t.6.11. mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' t.10.11. mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' t.11.19..q23.p13. mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' del.7q. mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' del.9q. mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' trisomy 8 mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' trisomy 21 mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' minus.Y mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation' minus.X mutation indicator, cytogenetics num 0 = 'no mutation', 1 = 'mutation