Left atrial strain parameters derived by echocardiography are impaired in patients with acute myocarditis and preserved systolic left ventricular function

Purpose: Data derived by cardiac magnetic resonance (CMR) feature tracking suggest that not only left ventricular but also left atrial function is impaired in patients with acute myocarditis. Therefore, we investigated the diagnostic value of speckle tracking echocardiography of the left ventricle and left atrium in patients with acute myocarditis and normal left ventricular ejection fraction (LVEF). Methods and results: 30 patients with acute myocarditis confirmed by CMR according to the Lake Louise criteria and 20 healthy controls were analyzed including global longitudinal strain (GLS) and left atrial (LA) strain parameters. Although preserved LVEF was present in both groups, GLS was significantly lower in patients with acute myocarditis (GLS − 19.1 ± 1.8% vs. GLS − 22.1 ± 1.7%, p < 0.001). Further diastolic dysfunction measured by E/e’ mean was significantly deteriorated in the myocarditis group compared to the control group (E/e’ mean 6.4 ± 1.6 vs. 5.5 ± 1.0, p = 0.038). LA reservoir function (47.6 ± 10.4% vs. 55.5 ± 10.8%, p = 0.013) and LA conduit function (-33.0 ± 9.6% vs. -39.4 ± 9.5%, p = 0.024) were significantly reduced in patients with acute myocarditis compared to healthy controls. Also left atrial stiffness index (0.15 ± 0.05 vs. 0.10 ± 0.03, p = 0.003) as well as left atrial filling index (1.67 ± 0.47 vs. 1.29 ± 0.34, p = 0.004) were deteriorated in patients with myocarditis compared to the control group. Conclusion: In patients with acute myocarditis and preserved LVEF not only GLS but also LA reservoir function, LA conduit function and left atrial stiffness index as well as left atrial filling index were impaired compared to healthy controls indicating ventricular diastolic dysfunction and elevated LV filling pressures

Association of Coronary Collaterals and Myocardial Salvage Measured by Serial Cardiac Magnetic Resonance Imaging after Acute Myocardial Infarction

Background: Coronary collateral flow in angiography has been linked with lower mortality rates in patients with coronary artery disease. However, the relevance of the underlying mechanism is sparse. Therefore, we tested the hypothesis that in patients with acute myocardial infarction (AMI), relevant coronary collateral flow is associated with more salvaged myocardium and lower risk of developing heart failure. Methods and Results: Patients with first AMI who received a percutaneous coronary intervention within 24 h after symptom onset were classified visually by assigning a Cohen–Rentrop Score (CRS) ranging between 0 (no collaterals) and 3 (complete retrograde filling of the occluded vessel). All 36 patients included in the analysis underwent cardiac magnetic resonance examination within 3 to 5 days after myocardial infarction and after 12 weeks. Patients with relevant collateral flow (CRS 2–3) to the infarct-related artery had significantly smaller final infarct size compared to those without (7 � 4% vs. 20 � 12%, p < 0.001). In addition, both groups showed improvement in left ventricular ejection fraction early after AMI, whereas the recovery was greater in CRS 2–3 (+8 � 5% vs. +3 � 5%, p = 0.015). Conclusion: In patients with first AMI, relevant collateral flow to the infarct-related artery was associated with more salvaged myocardium at 12 weeks, translating into greater improvement of systolic left ventricular function. The protective effect of coronary collaterals and the variance of infarct location should be further investigated in larger studies

Time to Recovery from Systolic Dysfunction Correlates with Left Ventricular Fibrosis in Arrhythmia-Induced Cardiomyopathy

Background: Arrhythmia-induced cardiomyopathy (AIC) is characterized by the reversibility of left ventricular (LV) systolic dysfunction (LVSD) after rhythm restoration. This study is a cardiac magnetic resonance tomography substudy of our AIC trial with the purpose to investigate whether left ventricular fibrosis affects the time to recovery (TTR) in patients with AIC. Method: Patients with newly diagnosed and otherwise unexplainable LVSD and tachyarrhythmia were prospectively recruited. LV ejection fraction (LVEF) was measured by echocardiography at baseline and 2, 4, and 6 months after rhythm control, and stress markers were assessed. After initial rhythm control, LV fibrosis was assessed through late gadolinium enhancement (LGE). Patients were diagnosed with AIC if their LVEF improved by ≥15% (or ≥10% when LVEF reached ≥50%). Non-responders served as controls (non-AIC). Results: The LGE analysis included 39 patients, 31 of whom recovered (AIC). LV end-systolic diameters decreased and LVEF increased during follow-up. LV LGE content correlated positively with TTR (r = 0.63, p = 0.003), with less LGE favoring faster recovery, and negatively with ΔLVEF (i.e., LVEF at month 2 compared to baseline) as a marker of fast recovery (r = −0.55, p = 0.012), suggesting that LV fibrosis affects the speed of recovery. Conclusion: LV fibrosis correlated positively with the time to recovery in patients with AIC. This correlation may help in the estimation of the recovery period and in the optimization of diagnostic and therapeutic strategies for patients with AIC

Central Sleep Apnea Is Associated with an Abnormal P-Wave Terminal Force in Lead V1 in Patients with Acute Myocardial Infarction Independent from Ventricular Function

Sleep-disordered breathing (SDB) is highly prevalent in patients with cardiovascular disease. We have recently shown that an elevation of the electrocardiographic (ECG) parameter P wave terminal force in lead V1 (PTFV1) is linked to atrial proarrhythmic activity by stimulation of reactive oxygen species (ROS)-dependent pathways. Since SDB leads to increased ROS generation, we aimed to investigate the relationship between SDB-related hypoxia and PTFV1 in patients with first-time acute myocardial infarction (AMI). We examined 56 patients with first-time AMI. PTFV1 was analyzed in 12-lead ECGs and defined as abnormal when ≥4000 µV*ms. Polysomnography (PSG) to assess SDB was performed within 3–5 days after AMI. SDB was defined by an apnea-hypopnea-index (AHI) >15/h. The multivariable regression analysis showed a significant association between SDB-related hypoxia and the magnitude of PTFV1 independent from other relevant clinical co-factors. Interestingly, this association was mainly driven by central but not obstructive apnea events. Additionally, abnormal PTFV1 was associated with SDB severity (as measured by AHI, B 21.495; CI [10.872 to 32.118]; p < 0.001), suggesting that ECG may help identify patients suitable for SDB screening. Hypoxia as a consequence of central sleep apnea may result in atrial electrical remodeling measured by abnormal PTFV1 in patients with first-time AMI independent of ventricular function. The PTFV1 may be used as a clinical marker for increased SDB risk in cardiovascular patients

Diet-Induced and Age-Related Changes in the Quadriceps Muscle: MRI and MRS in a Rat Model of Sarcopenia

Background: Knowledge about the molecular pathomechanisms of sarcopenia is still sparse, especially with regard to nutritional risk factors and the subtype of sarcopenic obesity. Objective: The aim of this study was to characterize diet-induced and age-related changes on the quality and quantity of the quadriceps muscle in a rat model of sarcopenia by different magnetic resonance (MR) techniques. Methods: A total of 36 6-month-old male Sprague-Dawley rats were randomly subdivided into 2 groups and received either a high-fat diet (HFD) or a control diet (CD). At the age of 16 months, 15 HFD and 18 CD rats underwent MR at 1.5 T. T1-weighted images as well as T2 relaxation time maps were acquired perpendicular to the long axis of the quadriceps muscles. Maximum cross-sectional area (CSA) of the quadriceps muscle was measured on T1-weighted images, and T2 relaxation times of muscle were assessed in a region without visible intramuscular fat (T2lean muscle) and across the complete CSA (T2muscle). Furthermore, 1H-MR spectroscopy was performed to evaluate the relative lipid content of the quadriceps muscles. These measurements were repeated 5 months later in the surviving 8 HFD and 14 CD rats. Results: HFD rats revealed significantly decreased CSA and CSA per body weight (BW) as well as prolonged T2 relaxation times of muscle. A higher weight gain (upper tertile during the first 6 months of diet in CD rats) resulted in a significant change of T2muscle, but had no relevant impact on CSA. Advancing age up to 21 months led to significantly decreased BW, CSA and CSA/BW, significantly prolonged T2muscle and T2lean muscle and enlarged lipid content in the quadriceps muscle. Conclusions: In an experimental setting a chronically fat-enriched diet was shown to have a relevant and age-associated influence on both muscle quantity and quality. By translational means the employed MR techniques give rise to the possibility of an early detection and noninvasive quantification of sarcopenia in humans, which is highly relevant for the field of geriatrics

Severe COVID-19 pneumonia: Perfusion analysis in correlation with pulmonary embolism and vessel enlargement using dual-energy CT data

Background Gas exchange in COVID-19 pneumonia is impaired and vessel obstruction has been suspected to cause ventilation-perfusion mismatch. Dual-energy CT (DECT) can depict pulmonary perfusion by regional assessment of iodine uptake. Objective The purpose of this study was the analysis of pulmonary perfusion using dual-energy CT in a cohort of 27 consecutive patients with severe COVID-19 pneumonia. Method We retrospectively analyzed pulmonary perfusion with DECT in 27 consecutive patients (mean age 57 years, range 21–73; 19 men and 8 women) with severe COVID-19 pneumonia. Iodine uptake (IU) in regions-of-interest placed into normally aerated lung, ground-glass opacifications (GGO) and consolidations was measured using a dedicated postprocessing software. Vessel enlargement (VE) within opacifications and presence of pulmonary embolism (PE) was assessed by subjective analysis. Linear mixed models were used for statistical analyses. Results Compared to normally aerated lung 106/151 (70.2%) opacifications without upstream PE demonstrated an increased IU, 9/151 (6.0%) an equal IU and 36/151 (23.8%) a decreased IU. The estimated mean iodine uptake (EMIU) in opacifications without upstream PE (GGO 1.77 mg/mL; 95%-CI: 1.52–2.02; p = 0.011, consolidations 1.82 mg/mL; 95%-CI: 1.56–2.08, p = 0.006) was significantly higher compared to normal lung (1.22 mg/mL; 95%-CI: 0.95–1.49). In case of upstream PE, EMIU of opacifications (combined GGO and consolidations) was significantly decreased compared to normal lung (0.52 mg/mL; 95%-CI: -0.07–1.12; p = 0.043). The presence of VE in opacifications correlated significantly with iodine uptake (p<0.001). Conclusions DECT revealed the opacifications in a subset of patients with severe COVID-19 pneumonia to be perfused non-uniformly with some being hypo- and others being hyperperfused. Mean iodine uptake in opacifications (both ground-glass and consolidation) was higher compared to normally aerated lung except for areas with upstream pulmonary embolism. Vessel enlargement correlated with iodine uptake: In summary, in a cohort of 27 consecutive patients with severe COVID-19 pneumonia, dual-energy CT demonstrated a wide range of iodine uptake in pulmonary ground-glass opacifications and consolidations as a surrogate marker for hypo- and hyperperfusion compared to normally aerated lung. Applying DECT to determine which pathophysiology is predominant might help to tailor therapy to the individual patient´s needs

Sleep-Disordered Breathing Is Associated With Reduced Left Atrial Strain Measured by Cardiac Magnetic Resonance Imaging in Patients After Acute Myocardial Infarction

Aims: Sleep disordered breathing (SDB) is known to cause left atrial (LA) remodeling. However, the relationship between SDB severity and LA dysfunction is insufficiently understood and may be elucidated by detailed feature tracking (FT) strain analysis of cardiac magnetic resonance images (CMR). After myocardial infarction (MI), both the left ventricle and atrium are subjected to increased stress which may be substantially worsened by concomitant SDB that could impair consequential healing. We therefore analyzed atrial strain in patients at the time of acute MI and 3 months after. Methods and Results: 40 patients with acute MI underwent CMR and polysomnography (PSG) within 3–5 days after MI. Follow-up was performed 3 months after acute MI. CMR cine data were analyzed using a dedicated FT software. Atrial strain (ε) and strain rate (SR) for atrial reservoir ([εs]; [SRs]), conduit ([εe]; [SRe]) and booster function ([εa]; [SRa]) were measured in two long-axis views. SDB was defined by an apnea-hypopnea-index (AHI) ≥15/h. Interestingly, LA εs and εe were significantly reduced in patients with SDB and correlated negative with AHI as a measure of SDB severity at both baseline and follow-up. Intriguingly, patients that exhibited a reduced AHI at follow-up were more likely to have developed improved atrial reservoir and conduit strain (linear regression, p=0.08 for εs and εe). Patients with improved SDB (ΔAHI + 5/h) showed a mean decrease of −5.3 ± 11.0% (p = 0.0131). Similarly, the difference for LA conduit function was +4.8 ± 5.9% (ΔAHI +5/h). Importantly, conventional volumetric parameters for atrial function (LA area, LA volume index) did not correlate with AHI at baseline or follow-up. Conclusion: Our results show that LA function measured by CMR strain but not by volumetry is impaired in patients with SDB during acute cardiac injury. Consistent with a mechanistic association, improvement of SBD at follow-up resulted in improved LA strain. LA strain measurement might thus provide insight into atrial function in patients with SDB

Multicenter Standardization of Phase-Resolved Functional Lung MRI in Patients With Suspected Chronic Thromboembolic Pulmonary Hypertension

BACKGROUND Detection of pulmonary perfusion defects is the recommended approach for diagnosing chronic thromboembolic pulmonary hypertension (CTEPH). This is currently achieved in a clinical setting using scintigraphy. Phase-resolved functional lung (PREFUL) magnetic resonance imaging (MRI) is an alternative technique for evaluating regional ventilation and perfusion without the use of ionizing radiation or contrast media. PURPOSE To assess the feasibility and image quality of PREFUL-MRI in a multicenter setting in suspected CTEPH. STUDY TYPE This is a prospective cohort sub-study. POPULATION Forty-five patients (64 ± 16 years old) with suspected CTEPH from nine study centers. FIELD STRENGTH/SEQUENCE 1.5 T and 3 T/2D spoiled gradient echo/bSSFP/T2 HASTE/3D MR angiography (TWIST). ASSESSMENT Lung signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between study centers with different MRI machines. The contrast between normally and poorly perfused lung areas was examined on PREFUL images. The perfusion defect percentage calculated using PREFUL-MRI (QDP$_{PREFUL}$ ) was compared to QDP from the established dynamic contrast-enhanced MRI technique (QDP$_{DCE}$ ). Furthermore, QDP$_{PREFUL}$ was compared between a patient subgroup with confirmed CTEPH or chronic thromboembolic disease (CTED) to other clinical subgroups. STATISTICAL TESTS t-Test, one-way analysis of variance (ANOVA), Pearson's correlation. Significance level was 5%. RESULTS Significant differences in lung SNR and CNR were present between study centers. However, PREFUL perfusion images showed a significant contrast between normally and poorly perfused lung areas (mean delta of normalized perfusion -4.2% SD 3.3) with no differences between study sites (ANOVA: P = 0.065). QDP$_{PREFUL}$ was significantly correlated with QDP$_{DCE}$ (r = 0.66), and was significantly higher in 18 patients with confirmed CTEPH or CTED (57.9 ± 12.2%) compared to subgroups with other causes of PH or with excluded PH (in total 27 patients with mean ± SD QDP$_{PREFUL}$  = 33.9 ± 17.2%). DATA CONCLUSION PREFUL-MRI could be considered as a non-invasive method for imaging regional lung perfusion in multicenter studies. LEVEL OF EVIDENCE 3 TECHNICAL EFFICACY: Stage 1

Dipeptidyl-peptidase 3 and IL-6: potential biomarkers for diagnostics in COVID-19 and association with pulmonary infiltrates

Coronavirus SARS-CoV-2 spread worldwide, causing a respiratory disease known as COVID-19. The aim of the present study was to examine whether Dipeptidyl-peptidase 3 (DPP3) and the inflammatory biomarkers IL-6, CRP, and leucocytes are associated with COVID-19 and able to predict the severity of pulmonary infiltrates in COVID-19 patients versus non-COVID-19 patients. 114 COVID-19 patients and 35 patients with respiratory infections other than SARS-CoV-2 were included in our prospective observational study. Blood samples were collected at presentation to the emergency department. 102 COVID-19 patients and 28 non-COVID-19 patients received CT imaging (19 outpatients did not receive CT imaging). If CT imaging was available, artificial intelligence software (CT Pneumonia Analysis) was used to quantify pulmonary infiltrates. According to the median of infiltrate (14.45%), patients who obtained quantitative CT analysis were divided into two groups (> median: 55 COVID-19 and nine non-COVID-19, ≤ median: 47 COVID-19 and 19 non-COVID-19). DPP3 was significantly elevated in COVID-19 patients (median 20.85 ng/ml, 95% CI 18.34–24.40 ng/ml), as opposed to those without SARS-CoV-2 (median 13.80 ng/ml, 95% CI 11.30–17.65 ng/ml; p < 0.001, AUC = 0.72), opposite to IL-6, CRP (each p = n.s.) and leucocytes (p < 0.05, but lower levels in COVID-19 patients). Regarding binary logistic regression analysis, higher DPP3 concentrations (OR = 1.12, p < 0.001) and lower leucocytes counts (OR = 0.76, p < 0.001) were identified as significant and independent predictors of SARS-CoV-2 infection, as opposed to IL-6 and CRP (each p = n.s.). IL-6 was significantly increased in patients with infiltrate above the median compared to infiltrate below the median both in COVID-19 (p < 0.001, AUC = 0.78) and in non-COVID-19 (p < 0.05, AUC = 0.81). CRP, DPP3, and leucocytes were increased in COVID-19 patients with infiltrate above median (each p < 0.05, AUC: CRP 0.82, DPP3 0.70, leucocytes 0.67) compared to infiltrate below median, opposite to non-COVID-19 (each p = n.s.). Regarding multiple linear regression analysis in COVID-19, CRP, IL-6, and leucocytes (each p < 0.05) were associated with the degree of pulmonary infiltrates, as opposed to DPP3 (p = n.s.). DPP3 showed the potential to be a COVID-19-specific biomarker. IL-6 might serve as a prognostic marker to assess the extent of pulmonary infiltrates in respiratory patients