Persisting IL-18 levels after COVID-19 correlate with markers of cardiovascular inflammation reflecting potential risk of CVDs development.

COVID-19 manifestation is associated with a strong immune system activation leading to inflammation and subsequently affecting the cardiovascular system. The objective of the study was to reveal possible interconnection between prolongated inflammation and the development or exacerbation of long-term cardiovascular complications after COVID-19. We investigated correlations between humoral and cellular immune system markers together with markers of cardiovascular inflammation/dysfunction during COVID-19 onset and subsequent recovery. We analyzed 22 hospitalized patients with severe COVID-19 within three timepoints (acute, 1 and 6 months after COVID-19) in order to track the impact of COVID-19 on the long-term decline of the cardiovascular system fitness and eventual development of CVDs. Among the cytokines dysregulated during COVID-19 changes, we showed significant correlations of IL-18 as a key driver of several pathophysiological changes with markers of cardiovascular inflammation/dysfunction. Our findings established novel immune-related markers, which can be used for the stratification of patients at high risk of CVDs for further therapy.

Lower ventricular and atrial strain in patients who recovered from COVID-19 assessed by cardiovascular magnetic resonance feature tracking.

Introduction: One of the most common complications of coronavirus disease 2019 (COVID-19) is myocardial injury, and although its cause is unclear, it can alter the heart's contractility. This study aimed to characterize the ventricular and atrial strain in patients who recovered from COVID-19 using cardiovascular magnetic resonance feature-tracking (CMR-FT). Methods: In this single-center study, we assessed left ventricle (LV) and right ventricular (RV) global circumferential strain (GCS), global longitudinal strain (GLS), global radial strain (GRS), left atrial (LA) and right atrial (RA) longitudinal strain (LS) parameters by CMR-FT. The student's t-test and Wilcoxon rank-sum test were used to compare the variables. Results: We compared seventy-two patients who recovered from COVID-19 (49 ± 16 years) to fifty-four controls (49 ± 12 years, p = 0.752). The patients received a CMR examination 48 (34 to 165) days after the COVID-19 diagnosis. 28% had LGE. Both groups had normal LV systolic function. Strain parameters were significantly lower in the COVID-19 survivors than in controls. Discussion: Patients who recovered from COVID-19 exhibited significantly lower strain in the left ventricle (through LVGCS, LVGLS, LVGRS), right ventricle (through RVGLS and RVGRS), left atrium (through LALS), and right atrium (through RALS) than controls.

Myocardial native T1 mapping and extracellular volume quantification in asymptomatic female carriers of Duchenne muscular dystrophy gene mutations.

BACKGROUND: Female carriers of dystrophin gene mutations (DMD-FC) were previously considered non-manifesting, but in recent decades, cardiomyopathy associated with muscular dystrophy and myocardial fibrosis has been described. Our study aimed to assess prospectively myocardial fibrosis in asymptomatic DMD-FC compared to a sex-matched control group (CG) with similar age distribution using native T1 mapping and extracellular volume (ECV) quantification by cardiovascular magnetic resonance (CMR) imaging. MATERIALS AND METHODS: 38 DMD-FC with verified genetic mutation and 22 healthy volunteers were included. Using CMR, native T1 relaxation time and ECV quantification were determined in each group. Late gadolinium enhancement (LGE) was assessed in all cases. RESULTS: There were 38 DMD-FC (mean age 39.1 ± 8.8 years) and 22 healthy volunteers (mean age 39.9 ± 12.6 years) imagined by CMR. The mean global native T1 relaxation time was similar for DMD-FC and CG (1005.1 ± 26.3 ms vs. 1003.5 ± 25.0 ms; p-value = 0.81). Likewise, the mean global ECV value was also similar between the groups (27.92 ± 2.02% vs. 27.10 ± 2.89%; p-value = 0.20). The segmental analysis of mean ECV values according to the American Heart Association classification did not show any differences between DMD-FC and CG. There was a non-significant trend towards higher mean ECV values of DMD-FC in the inferior and inferolateral segments of the myocardium (p-value = 0.075 and 0.070 respectively). CONCLUSION: There were no statistically significant differences in the mean global and segmental native T1 relaxation times and the mean global or segmental ECV values. There was a trend towards higher segmental mean ECV values of DMD-FC in the inferior and inferolateral walls of the myocardium.

News in diagnostics and treament of cardiomyopathies.

Cardiomyopathies are defined as myocardial disorders in which the heart muscle is structurally and functionaly abnormal in the absence of a disease sufficient to cause this abnormality such as coronary artery disease, hypertension, valvular or congenital heart disease. According to the phenotype expresion cardiomyopathies are divided into dilated, hypertrophic, restrictive, arrhytmogenic and unclassified cardiomyopathies (noncompaction and tako-tsubo cardiomyopathy). The same phenotypic expression may include etiologically different forms of the disease, and at the same time phenotypic expression may change in many cardiomyopathies in the course of illness. For each type of cardiomyopathy, we further distinguish the familial (genetic) form and the acquired form. The clinical manifestation of the disease includes symptoms of heart failure, with reduced, mildly reduced or preserved ejection fraction, symptoms resulting from a number of arrhythmias and extracardiac symptoms, but in some cases symptoms may not be presented for a relatively long time. The disease can lead to significant morbidity and mortality if not detected and treated early, especially in young people who are frequently affected. Significant developments in diagnostic and treatment methods have led to an improvement in the prognosis of patients with cardiomyopathies in recent years.

Hepcidin and ferritin levels as markers of immune cell activation during septic shock, severe COVID-19 and sterile inflammation.

Introduction: Major clinically relevant inflammatory events such as septic shock and severe COVID-19 trigger dynamic changes in the host immune system, presenting promising candidates for new biomarkers to improve precision diagnostics and patient stratification. Hepcidin, a master regulator of iron metabolism, has been intensively studied in many pathologies associated with immune system activation, however these data have never been compared to other clinical settings. Thus, we aimed to reveal the dynamics of iron regulation in various clinical settings and to determine the suitability of hepcidin and/or ferritin levels as biomarkers of inflammatory disease severity. Cohorts: To investigate the overall predictive ability of hepcidin and ferritin, we enrolled the patients suffering with three different diagnoses - in detail 40 patients with COVID-19, 29 patients in septic shock and eight orthopedic patients who were compared to nine healthy donors and all cohorts to each other. Results: We showed that increased hepcidin levels reflect overall immune cell activation driven by intrinsic stimuli, without requiring direct involvement of infection vectors. Contrary to hepcidin, ferritin levels were more strongly boosted by pathogen-induced inflammation - in septic shock more than four-fold and in COVID-19 six-fold in comparison to sterile inflammation. We also defined the predictive capacity of hepcidin-to-ferritin ratio with AUC=0.79 and P = 0.03. Discussion: Our findings confirm that hepcidin is a potent marker of septic shock and other acute inflammation-associated pathologies and demonstrate the utility of the hepcidin-to-ferritin ratio as a predictor of mortality in septic shock, but not in COVID-19.

Left atrium phasic impairments in paroxysmal atrial fibrillation patients assessed by cardiovascular magnetic resonance feature tracking.

Atrial fibrillation (AF) is an abnormal and irregular heartbeat caused by uncoordinated electrical impulses in the left atrium (LA), which could induce lasting changes in the heart tissue or could be a consequence of underlying cardiac disease. This study aimed to assess the left atrial phasic function and deformation in paroxysmal AF (PAF) patients-who had not received radiofrequency ablation and had no signs of permanent AF-using the cardiovascular magnetic resonance (CMR) feature-tracking (FT) technique. Fifty subjects (27 PAF patients and 23 controls) were included and examined with CMR. Their LA volume, LA function, LA longitudinal strain (LS) and LA strain rate were assessed in the LA reservoir, conduit, and contractile phases. PAF patients exhibited higher LA volumes than controls, while their LA emptying fraction and LA LS was significantly lower in all three phases. In contrast, the corresponding emptying volumes (total, passive and active) were similar in both groups. The LA volumetric rates from CMR-derived volume curves differed significantly in PAF patients vs controls in the reservoir and contractile phases. In contrast, the equivalent LV volumetric rates were similar. This study suggests that assessing the LA phasic function could offer insight into early LA impairments for PAF patients.

Stress pulmonary circulation parameters assessed by a cardiovascular magnetic resonance in patients after a heart transplant.

Rest pulmonary circulation parameters such as pulmonary transit time (PTT), heart rate corrected PTT (PTTc) and pulmonary transit beats (PTB) can be evaluated using several methods, including the first-pass perfusion from cardiovascular magnetic resonance. As previously published, up to 58% of patients after HTx have diastolic dysfunction detectable only in stress conditions. By using adenosine stress perfusion images, stress analogues of the mentioned parameters can be assessed. By dividing stress to rest biomarkers, potential new ratio parameters (PTT ratio and PTTc ratio) can be obtained. The objectives were to (1) provide more evidence about stress pulmonary circulation biomarkers, (2) present stress to rest ratio parameters, and (3) assess these biomarkers in patients with presumed diastolic dysfunction after heart transplant (HTx) and in childhood cancer survivors (CCS) without any signs of diastolic dysfunction. In this retrospective study, 48 patients after HTx, divided into subgroups based on echocardiographic signs of diastolic dysfunction (41 without, 7 with) and 39 CCS were enrolled. PTT was defined as the difference between the onset time of the signal intensity increase in the left and the right ventricle. PTT in rest conditions were without significant differences when comparing the CCS and HTx subgroup without diastolic dysfunction (4.96 ± 0.93 s vs. 5.51 ± 1.14 s, p = 0.063) or with diastolic dysfunction (4.96 ± 0.93 s vs. 6.04 ± 1.13 s, p = 0.13). However, in stress conditions, both PTT and PTTc were significantly lower in the CCS group than in the HTx subgroups, (PTT: 3.76 ± 0.78 s vs. 4.82 ± 1.03 s, p < 0.001; 5.52 ± 1.56 s, p = 0.002). PTT ratio and PTTc ratio were below 1 in all groups. In conclusion, stress pulmonary circulation parameters obtained from CMR showed prolonged PTT and PTTc in HTx groups compared to CCS, which corresponds with the presumption of underlying diastolic dysfunction. The ratio parameters were less than 1.

Assessment of late cardiotoxic effects in patients treated for cancer in childhood.

Graphical AbstractThe aim was to assess the late cardiotoxic effects in young adults treated for various cancer types in childhood using echocardiography and 24-h ECG Holter monitoring.

Assessment of left ventricular volumes and ejection fraction using ultra-low-dose thallium-201 SPECT on a CZT camera: a comparison with magnetic resonance imaging.

BACKGROUND: Cadmium-Zinc-Telluride (CZT) technology allows use of low activities of radiopharmaceuticals. The aim was to verify the values of left ventricular volume parameters, obtained via ultra-low-dose thallium Single Photon Emission Computed Tomography (SPECT) using a CZT camera. METHODS AND RESULTS: Forty-five patients referred for an assessment of myocardial perfusion or viability imaging were examined using CZT-SPECT and 1.5 T magnetic resonance (MRI) scanner. The ultra-low-dose protocol with 0.5 Mbq 201-Tl per kg of body weight was used. The values of end-systolic (ESV) and end-diastolic volumes (EDV), left ventricular ejection fraction (EF) and myocardial mass (MM) were assessed using both techniques. A very good correlation was found between the EF, ESV, and EDV values assessed with CZT-SPECT and cardiac magnetic resonance MRI; the Pearson coefficients were 0.86, 0.95, and 0.91, respectively. A moderate correlation was found for myocardial mass, r = 0.57. Compared to MRI, SPECT systematically overestimated ESV and MM, while it underestimates the EF, with P ≤ .001 in all cases. There was no difference in EDV estimation. CONCLUSIONS: Left ventricular volumes and ejection fraction assessed via ultra-low-dose CZT-SPECT showed very good correlation with the values obtained by MRI. A moderate correlation was found for myocardial mass.

Stress and Rest Pulmonary Transit Times Assessed by Cardiovascular Magnetic Resonance.

Acquiring pulmonary circulation parameters as a potential marker of cardiopulmonary function is not new. Methods to obtain these parameters have been developed over time, with the latest being first-pass perfusion sequences in cardiovascular magnetic resonance (CMR). Even though more data on these parameters has been recently published, different nomenclature and acquisition methods are used across studies; some works even reported conflicting data. The most commonly used circulation parameters obtained using CMR include pulmonary transit time (PTT) and pulmonary transit beats (PTB). PTT is the time needed for a contrast agent (typically gadolinium-based) to circulate from the right ventricle (RV) to the left ventricle (LV). PTB is the number of cardiac cycles the process takes. Some authors also include corrected heart rate (HR) versions along with standard PTT. Besides other methods, CMR offers an option to assess stress circulation parameters, but data are minimal. This review aims to summarize the up-to-date findings and provide an overview of the latest progress on this promising, dynamically evolving topic.

Left ventricular myocardial deformation assessment in asymptomatic patients with recently diagnosed sarcoidosis of the respiratory tract and/or extrapulmonary sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease affecting different organs including the heart. Myocardial strain analysis could potentially detect the early stages of cardiac dysfunction in sarcoidosis patients. The present study aims to assess the use of cardiac magnetic resonance (CMR) strain analysis using feature tracking (FT) in the detection of early cardiac involvement in asymptomatic patients with sarcoidosis. METHODS: One hundred and thirteen CMR studies of patients with sarcoidosis of the respiratory tract and/or extrapulmonary sarcoidosis without pre-existing known cardiovascular disease were included in the study and analysed using FT and compared to 22 age and gender-matched controls. Global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS) of the left ventricle (LV) were measured. RESULTS: The sarcoidosis patients did not significantly differ from the controls in basic demographic data and had normal global and regional systolic LV function-LV ejection fraction (EF) 66 ± 7% vs 65 ± 5% in the controls (p = NS). No statistically significant differences were found in all strain parameters between patients and controls: GLS (- 13.9 ± 3.1 vs. - 14.2 ± 2.5), GCS (- 23.4 ± 4.0 vs. - 22.2 ± 2.9) and GRS (53.4 ± 13.5 vs. 51.2 ± 13.6%) (p = NS). CONCLUSION: Patients with sarcoidosis of the respiratory tract and/or extrapulmonary sarcoidosis had normal myocardial deformation measured by CMR-FT derived global strain.

Extracellular volume quantification using synthetic haematocrit assessed from native and post-contrast longitudinal relaxation T1 times of a blood pool.

BACKGROUND: In terms of cardiovascular magnetic resonance are haematocrit values required for calculation of extracellular volume fraction (ECV). Previously published studies have hypothesized that haematocrit could be calculated from T1 blood pool relaxation time, however only native T1 relaxation time values have been used and the resulting formulae had been both in reciprocal and linear proportion. The aim of the study was to generate a synthetic haematocrit formula from only native relaxation time values first, calculate whether linear or reciprocal model is more precise in haematocrit estimation and then determine whether adding post-contrast values further improve its precision. METHODS: One hundred thirty-nine subjects underwent CMR examination. Haematocrit was measured using standard laboratory methods. Afterwards T1 relaxation times before and after the application of a contrast agent were measured and a statistical relationship between these values was calculated. RESULTS: Different linear and reciprocal models were created to estimate the value of synthetic haematocrit and ECV. The highest coefficient of determination was observed in the combined reciprocal model "- 0.047 + (779/ blood native) - (11.36/ blood post-contrast)". CONCLUSIONS: This study provides more evidence that assessing synthetic haematocrit and synthetic ECV is feasible and statistically most accurate model to use is reciprocal. Adding post-contrast values to the calculation was proved to improve the precision of the formula statistically significantly.

Quantitative assessment of left ventricular longitudinal function and myocardial deformation in Duchenne muscular dystrophy patients.

BACKGROUND: Duchenne muscular dystrophy (DMD) manifests in males mainly by skeletal muscle impairment, but also by cardiac dysfunction. The assessment of the early phases of cardiac involvement using echocardiography is often very difficult to perform in these patients. The aim of the study was to use cardiac magnetic resonance (CMR) strain analysis and mitral annular plane systolic excursion (MAPSE) in the detection of early left ventricular (LV) dysfunction in DMD patients. METHODS AND RESULTS: In total, 51 male DMD patients and 18 matched controls were examined by CMR. MAPSE measurement and functional analysis using feature tracking (FT) were performed. Three groups of patients were evaluated: A/ patients with LGE and LV EF < 50% (n = 8), B/ patients with LGE and LVEF ≥ 50% (n = 13), and C/ patients without LGE and LVEF ≥ 50% (n = 30). MAPSE and global LV strains of the 3 DMD groups were compared to controls (n = 18). Groups A and B had significantly reduced values of MAPSE, global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) in comparison to controls (p < 0.05). The values of MAPSE (11.6 ± 1.9 v 13.7 ± 2.7 mm) and GCS (- 26.2 ± 4.2 v - 30.0 ± 5.1%) were significantly reduced in group C compared to the controls (p < 0.05). CONCLUSION: DMD patients had decreased LV systolic function measured by MAPSE and global LV strain even in the case of normal LV EF and the absence of LGE. FT and MAPSE measurement provide sensitive assessment of early cardiac involvement in DMD patients.

Myocardial T1 mapping using SMART1 Map and MOLLI mapping in asymptomatic patients with recent extracardiac sarcoidosis.

INTRODUCTION: Sarcoidosis is a systemic granulomatous disease affecting in particular the respiratory tract. Cardiac magnetic resonance (CMR), including a measurement of T1 relaxation time, could potentially detect early stadia of sarcoidosis of the heart. The study aims to assess T1 mapping in the detection of early cardiac involvement in asymptomatic patients with sarcoidosis. METHODS: One hundred and twenty patients with extracardiac sarcoidosis and without any heart disease history were included. One hundred and thirteen of them underwent a CMR examination. The mean time from the diagnosis of sarcoidosis was 0.8 (0.2-3.3) years. Cine images for the assessment of left ventricular (LV) functional parameters and pre- and post-contrast saturation method using adaptive recovery times for cardiac T1 mapping (SMART1 Map) and modified Look-Locker inversion recovery (MOLLI) images were acquired for the assessment of native T1 relaxation time and extracellular volume (ECV). The measured parameters were compared between sarcoidosis patients and 22 controls. RESULTS: The sarcoidosis patients had normal global and regional systolic LV function-LV ejection fraction 65 ± 5% versus 66 ± 7% (p NS). The mean native T1 relaxation times were not prolonged-1465 ± 93 ms versus 1480 ± 88 ms (p NS) measured by SMART1 Map and 1317 ± 60 ms versus 1313 ± 83 ms (p NS) measured using a MOLLI sequence. Similarly, the mean ECV values did not increase-16.9 ± 3.9% versus 17.9 ± 3.7% (p NS) measured by SMART1 Map and 30.9 ± 2.9% versus 31.6 ± 8.3% (p NS) measured using a MOLLI sequence. CONCLUSION: Myocardial native T1 relaxation times were not prolonged and ECV was not increased in asymptomatic patients with extracardiac sarcoidosis.