Angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker treatment and haemodynamic factors are associated with increased cardiac mRNA expression of angiotensin-converting enzyme 2 in patients with cardiovascular disease

Aims Coronavirus disease 2019 (COVID-19) is a widespread pandemic with an increased morbidity and mortality, especially for patients with cardiovascular diseases. Angiotensin-converting enzyme 2 (ACE2) has been identified as necessary cell entry point for SARS-CoV-2. Previous animal studies have demonstrated an increased ACE2 expression following treatment with either angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) that have led to a massive precariousness regarding the optimal cardiovascular therapy during this pandemic. Methods and results We have measured ACE2 mRNA expression using real-time quantitative polymerase chain reaction in atrial biopsies of 81 patients undergoing coronary artery bypass grafting and we compared 62 patients that received ACEi/ARB vs. 19 patients that were not ACEi/ARB-treated. We found atrial ACE2 mRNA expression to be significantly increased in patients treated with an ACEi or an ARB, independent of potential confounding comorbidities. Interestingly, the cardiac ACE2 mRNA expression correlated significantly with the expression in white blood cells of 22 patients encouraging further evaluation if the latter may be used as a surrogate for the former. Similarly, analysis of 18 ventricular biopsies revealed a significant and independent increase in ACE2 mRNA expression in patients with end-stage heart failure that were treated with ACEi/ARB. On the other hand, cardiac unloading with a left ventricular assist device significantly reduced ventricular ACE2 mRNA expression. Conclusion Treatment with ACEi/ARB is independently associated with an increased myocardial ACE2 mRNA expression in patients with coronary artery disease and in patients with end-stage heart failure. Further trials are needed to test whether this association is deleterious for patients with COVID-19, or possibly protective. Nevertheless, haemodynamic factors seem to be equally important for regulation of cardiac ACE2 mRNA expression

Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy

BackgroundHypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and beta -myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations.MethodsAs a part of the international multidisciplinary SILICOFCM project (www.silicofcm.eu) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography.ResultsThe most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p=0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p=0.085). Laboratory analyses revealed normal levels of creatinine (85.518.3 vs. 81.3 +/- 16.4 mu mol/l; p=0.487) and blood urea nitrogen (10.2 +/- 15.6 vs. 6.9 +/- 3.9 mmol/l; p=0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients carrying MYH7 mutation (33% vs. 10%; p=0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p=0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p=0.001). The difference in diastolic function, i.e. E/e ' ratio between the two groups was also noted (MYBPC3 8.8 +/- 3.3, MYH7 13.9 +/- 6.9, p=0.079).Conclusions Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3

Predictors of Nocturnal Hypoxemic Burden in Patients Undergoing Elective Coronary Artery Bypass Grafting Surgery

Nocturnal hypoxemia has been linked to increased cardiovascular morbidity and mortality. Several common diseases, such as sleep-disordered breathing (SDB), heart failure (HF), obesity, and pulmonary disease, coincide with an elevated nocturnal hypoxemic burden with and without repetitive desaturations. Research question: This study aimed to evaluate the association of relevant common diseases with distinctive metrics of nocturnal hypoxemic burden with and without repetitive desaturations in patients undergoing coronary artery bypass grafting surgery. Study design and methods: In this subanalysis of the prospective observational study, CONSIDER-AF (NCT02877745) portable SDB monitoring was performed on 429 patients with severe coronary artery disease the night before cardiac surgery. Pulse oximetry was used to determine nocturnal hypoxemic burden, as defined by total recording time spent with oxygen saturation levels < 90% (T90). T90 was further characterized as T90 due to intermittent hypoxemia (T90desaturation) and T90 due to nonspecific and noncyclic SpO2-drifts (T90non-specific). Results: Multivariable linear regression analysis identified SDB (apnea–hypopnea-index ≥ 15/h; B [95% CI]: 6.5 [0.4; 12.5], p = 0.036), obesity (8.2 [2.5; 13.9], p = 0.005), and mild-to-moderate chronic obstructive pulmonary disease (COPD, 16.7 [8.5; 25.0], p < 0.001) as significant predictors of an increased nocturnal hypoxemic burden. Diseases such as SDB, obesity and HF were significantly associated with elevated T90desaturation. In contrast, obesity and mild-to-moderate COPD were significant modulators of T90non-specific. Interpretation: SDB and leading causes for SDB, such as obesity and HF, are associated with an increased nocturnal hypoxemic burden with repetitive desaturations. Potential causes for hypoventilation syndromes, such as obesity and mild-to-moderate COPD, are linked to an increased hypoxemic burden without repetitive desaturations. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT02877745

Enhanced Cardiac CaMKII Oxidation and CaMKII-Dependent SR Ca Leak in Patients with Sleep-Disordered Breathing

Background: Sleep-disordered breathing (SDB) is associated with increased oxidant generation. Oxidized Ca/calmodulin kinase II (CaMKII) can contribute to atrial arrhythmias by the stimulation of sarcoplasmic reticulum Ca release events, i.e., Ca sparks. Methods: We prospectively enrolled 39 patients undergoing cardiac surgery to screen for SDB and collected right atrial appendage biopsies. Results: SDB was diagnosed in 14 patients (36%). SDB patients had significantly increased levels of oxidized and activated CaMKII (assessed by Western blotting/specific pulldown). Moreover, SDB patients showed a significant increase in Ca spark frequency (CaSpF measured by confocal microscopy) compared with control subjects. CaSpF was 3.58 ± 0.75 (SDB) vs. 2.49 ± 0.84 (no SDB) 1/100 µm−1s−1 (p < 0.05). In linear multivariable regression models, SDB severity was independently associated with increased CaSpF (B [95%CI]: 0.05 [0.03; 0.07], p < 0.001) after adjusting for important comorbidities. Interestingly, 30 min exposure to the CaMKII inhibitor autocamtide-2 related autoinhibitory peptide normalized the increased CaSpF and eliminated the association between SDB and CaSpF (B [95%CI]: 0.01 [−0.1; 0.03], p = 0.387). Conclusions: Patients with SDB have increased CaMKII oxidation/activation and increased CaMKII-dependent CaSpF in the atrial myocardium, independent of major clinical confounders, which may be a novel target for treatment of atrial arrhythmias in SDB

Interaktionen schlafbezogener Atmungsstörungen mit Vorhofflimmern

Background Atrial fibrillation (AF) is the most common cardiac arrhythmia. Central as well as obstructive sleep apnea interact with this condition. Intermittent hypoxia, oxidative stress, repeated awakening, intrathoracic pressure swings, and atrial remodeling as part of sleep-disordered breathing (SDB) can lead to AF. Objectives This article focuses on the complex relationship and recent research findings concerning SDB and AF, as well as the therapeutic options. Materials and Methods A literature search was conducted of original and review articles, as well as meta-analyses, published in the PubMed database between 1963 and 2020. Results The findings of the studies indicate a bidirectional relationship between SDB and AF. The pathophysiological consequences of obstructive and central sleep apnea vary. The studies evaluating the effects SDB treatment on the recurrence of AF after intervention (e.g., cardioversion and pulmonary vein isolation) do not yet provide a clear picture. Conclusions Previous studies suggest multiple interactions between SDB and AF. Considering the conflicting results on the effects of positive airway pressure treatment on the risk of recurrence of AF after intervention, further studies are needed

Interaktionen schlafbezogener Atmungsstörungen mit Vorhofflimmern - Pathophysiologie und Klinik

Background Atrial fibrillation (AF) is the most common cardiac arrhythmia. Central as well as obstructive sleep apnea interact with this condition. Intermittent hypoxia, oxidative stress, repeated awakening, intrathoracic pressure swings, and atrial remodeling as part of sleep-disordered breathing (SDB) can lead to AF. Objectives This article focuses on the complex relationship and recent research findings concerning SDB and AF, as well as the therapeutic options. Materials and Methods A literature search was conducted of original and review articles, as well as meta-analyses, published in the PubMed database between 1963 and 2020. Results The findings of the studies indicate a bidirectional relationship between SDB and AF. The pathophysiological consequences of obstructive and central sleep apnea vary. The studies evaluating the effects SDB treatment on the recurrence of AF after intervention (e.g., cardioversion and pulmonary vein isolation) do not yet provide a clear picture. Conclusions Previous studies suggest multiple interactions between SDB and AF. Considering the conflicting results on the effects of positive airway pressure treatment on the risk of recurrence of AF after intervention, further studies are needed. Hintergrund Vorhofflimmern (VHF) ist die häufigste Herzrhythmusstörung. Sowohl die zentrale als auch die obstruktive Schlafapnoe interagieren mit dieser Erkrankung. Intermittierende Hypoxie, oxidativer Stress, wiederkehrende Aufwachreaktionen, intrathorakale Druckveränderungen und atriales Remodeling können im Rahmen einer schlafbezogenen Atmungsstörung (SBAS) zu VHF führen. Ziel Dieser Artikel stellt die komplexen Zusammenhänge und Erkenntnisse jüngster Forschungen bezüglich SBAS und VHF sowie die Therapiemöglichkeiten dar. Material und Methoden Es erfolgten eine Literaturrecherche von Original- und Übersichtsartikeln sowie Metaanalysen, die zwischen 1963 und 2020 in der PubMed-Datenbank veröffentlicht wurden. Ergebnisse Die Erkenntnisse der Studien weisen auf einen bidirektionalen kausalen Zusammenhang zwischen SBAS und VHF hin. Die pathophysiologischen Auswirkungen der obstruktiven und zentralen Schlafapnoe auf VHF sind unterschiedlich. Die Studien, die die Effekte einer Therapie der SBAS auf das Rezidivrisiko von VHF nach Intervention (Kardioversion oder Pulmonalvenenisolation) untersuchen, ergeben bisher kein eindeutiges Bild. Diskussion Bisherige Studien bestätigen multiple Interaktionen zwischen SBAS und VHF. Aufgrund widersprüchlicher Ergebnisse hinsichtlich der Effekte einer positiven Atemwegsdrucktherapie auf das Rezidivrisiko von VHF nach Interventionen sind weitere Studien nötig

Interaktionen schlafbezogener Atmungsstörungen mit Vorhofflimmern

Background Atrial fibrillation (AF) is the most common cardiac arrhythmia. Central as well as obstructive sleep apnea interact with this condition. Intermittent hypoxia, oxidative stress, repeated awakening, intrathoracic pressure swings, and atrial remodeling as part of sleep-disordered breathing (SDB) can lead to AF. Objectives This article focuses on the complex relationship and recent research findings concerning SDB and AF, as well as the therapeutic options. Materials and Methods A literature search was conducted of original and review articles, as well as meta-analyses, published in the PubMed database between 1963 and 2020. Results The findings of the studies indicate a bidirectional relationship between SDB and AF. The pathophysiological consequences of obstructive and central sleep apnea vary. The studies evaluating the effects SDB treatment on the recurrence of AF after intervention (e.g., cardioversion and pulmonary vein isolation) do not yet provide a clear picture. Conclusions Previous studies suggest multiple interactions between SDB and AF. Considering the conflicting results on the effects of positive airway pressure treatment on the risk of recurrence of AF after intervention, further studies are needed

Frequency and Pattern of MRI Diffusion Restrictions after Diagnostic Catheter Neuroangiography

(1) Background: We investigated the frequency, location, and lesion size of diffusion restrictions (DR) in magnetic resonance imaging (MRI) of asymptomatic patients after diagnostic angiography and assessed risk factors for their occurrence. (2) Methods: We analyzed diffusion-weighted images (DWI) of 344 patients undergoing diagnostic angiographies in a neuroradiologic center. Only asymptomatic patients who received a magnetic resonance imaging (MRI) examination within seven days after the angiography were included. (3) Results: Asymptomatic infarcts on DWI were identified in 17% of the cases after diagnostic angiography. In these 59 patients, a total of 167 lesions were noted. The diameter of the lesions was 1–5 mm in 128 lesions, and 5–10 mm in 39 cases. Dot-shaped diffusion restrictions were found most frequently (n = 163, 97.6%). None of the patients had neurological deficits during or after angiography. Significant correlations were found between the occurrence of lesions and patient age (p p = 0.014), cerebral infarction (p = 0.026), or coronary heart disease/heart attack (p = 0.027); and the amount of contrast medium used (p = 0.047) and fluoroscopy time (p = 0.033). (4) Conclusions: With an incidence of 17%, we observed a comparatively high risk for asymptomatic cerebral ischemia after diagnostic neuroangiography. Further measures to reduce the risk of silent embolic infarcts and improve the safety of neuroangiography are warranted

Hypoxaemic burden in heart failure patients receiving adaptive servo-ventilation

Aims: This study aimed to assess the effectiveness of adaptive servo-ventilation (ASV) for lowering hypoxaemic burden components in heart failure with reduced ejection fraction (HFrEF) patients. Methods and results: Fifty-six stable HFrEF patients with left ventricular ejection fraction = 40 were randomized to receive either ASV (n = 27; 25 males) or optimal medical management or optimal medical management alone (n = 29; 26 males). Patients underwent overnight polysomnography at baseline and a 12 week follow-up visit. We quantified hypoxaemic as time spent at &lt;90% oxygen saturation (T90) decomposed into desaturation-related components (T90desaturation) and non-specific drifts (T90non-specific). In the ASV arm, T90 significantly shortened by nearly 60% from 50.1 ± 95.8 min at baseline to 20.5 ± 33.0 min at follow-up compared with 59.6 ± 88 and 65.4 ± 89.6 min in the control arm (P = 0.009). ASV reduced the apnoea-related component (T90desaturation) from 37.7 ± 54.5 to 2.1 ± 7.3 min vs. 37.7 ± 54.5 and 40.4 ± 66.4 min in the control arm (P = 0.008). A significant non-specific T90 component of 19.6 ± 31.8 min persisted during ASV. In adjusted multivariable regression, T90desaturation was significantly associated with the ratio of the forced expiratory volume in the first second to the forced vital capacity of the lungs (ß = 0.336, 95% confidence interval 0.080 to 0.593; P = 0.011) and T90non-specific with left ventricular ejection fraction (ß = -0.345, 95% confidence interval -0.616 to -0.073; P = 0.014). Conclusions: ASV effectively suppresses the sleep apnoea-related component of hypoxaemic burden in HFrEF patients. A significant hypoxaemic burden not directly attributable to sleep apnoea but related to the severity of heart failure remains and may adversely affect cardiovascular long-term outcomes