Exploring the Correlation Between Fibrosis Biomarkers and Clinical Disease Severity in PLN p.Arg14del Patients

Background: Pathogenic variants in phospholamban (PLN, like p. Arg14del), are found in patients diagnosed with arrhythmogenic (ACM) and dilated cardiomyopathy (DCM). Fibrosis formation in the heart is one of the hallmarks in PLN p.Arg14del carriers. During collagen synthesis and breakdown, propeptides are released into the circulation, such as procollagen type I carboxy-terminal propeptide (PICP) and C-terminal telopeptide collagen type I (ICTP).Aim: To investigate if PICP/ICTP levels in blood are correlative biomarkers for clinical disease severity and outcome in PLN p.Arg14del variant carriers.Methods: Serum and EDTA blood samples were collected from 72 PLN p.Arg14del carriers (age 50.5 years, 63% female) diagnosed with ACM (n = 12), DCM (n = 14), and preclinical variant carriers (n = 46). PICP levels were measured with an enzyme-linked immune sorbent assay and ICTP with a radio immuno-assay. Increased PICP/ICTP ratios suggest a higher collagen deposition. Clinical data including electrocardiographic, and imaging results were adjudicated from medical records.Results: No correlation between PICP/ICTP ratios and late gadolinium enhancement (LGE) was found. Moderate correlations were found between the PICP/ICTP ratio and end-diastolic/systolic volume (both rs = 0.40, n = 23, p = 0.06). PICP/ICTP ratio was significantly higher in patients with T wave inversion (TWI), especially in leads V4–V6, II, III, and aVF (p < 0.022) and in patients with premature ventricular contractions (PVCs) during an exercise tolerance test (p = 0.007).Conclusion: High PICP/ICTP ratios correlated with clinical parameters, such as TWI and PVCs. Given the limited size and heterogeneity of the patient group, additional studies are required to substantiate the incremental prognostic value of these fibrosis biomarkers in PLN p.Arg14del patients.

Correlation between echocardiographic parameters of left ventricle and glycosylated hemoglobin in children with type 1 Diabetes Mellitus

Introduction. Deterioration of left ventricular (LV) parameters in Diabetes Mellitus (DM) can occur in the absence of other heart problems. An association between glycosylated hemoglobin (HbA1c) and changes of the LV parameters in DM has been reported. However, data regarding this association model in children with Type 1 Diabetes Mellitus (T1DM) are limited. The purpose of the work was to investigate the association between HbA1c and the LV parameters in pediatric patients. Material and methods. The study was conducted on 28 children with T1DM ((aged 10 - 18 years, gender M (15)/F (13), duration ≥5 years). The clinical (standard medical examination) and paraclinical (biochemical dosage – HbA1c, echocardiography – LV functional and structural parameters) data was carried out. Statistical analysis used the SPSS version 20. Results. The correlational study between the HbA1c and the LV parameters revealed a statistically significant positive correlation coefficient with aortic root diameter (mm) (r=0.7**, p<0.001), left atrium (mm) (r=0.8**, p<0.001 LV diastolic diameter (mm) (r=0.7**, p<0.001), LV systolic diameter (mm) (r=0.7**, p<0.001), septal wall thickness (mm) (r=0.5*, p=0.036), posterior wall thickness (mm) (r=0.5*, p=0.032), LV diastolic volume (ml) (r=0.5*, p=0.025), LV systolic volume (ml) (r=0.6**, p=0.01), ejection fraction (%) (r=0.7**, p=0.001), fractional shortening (%) (r=0.6**, p=0.002). Conclusions. The results of the study show that in children with T1DM, the increase value of the HbA1c is associated with a consensual and proportional increase in the values of the parameters of the left ventricle.

Non-Invasive Myocardial Infarction Ischemic Area Estimation Through Four-Dimensional Ultrasound

Background/Objective: Following myocardial infarction, infarct size and cardiac function are significant predictors of long-term prognosis. Most echocardiography studies rely on two-dimensional analysis for estimation of left ventricular function and electrical activity analysis for estimation of infarct area. Other imaging modalities, such as cardiac magnetic resonance imaging, are limited by time, cost, availability, patient tolerance, and incompatible implantable devices. Using an experimental mouse model of myocardial infarction, we hypothesize that four-dimensional ultrasound offers a possible alternative for easy, quick, and reliable estimation of infarct size. Methods: A cohort of 10 mice underwent four-dimensional cardiac imaging at baseline using a small animal high frequency ultrasound. A thoracotomy was subsequently performed, and a suture placed to ligate the left coronary artery approximately midway down the left ventricle. Sequential four-dimensional ultrasound was performed at six time points over 28 days, following which the mice were euthanized. The hearts were then removed and sent for embedding and sectioning into seven uniform segments stained using both H&E and Masson’ s Trichrome. Results: Thus far, we have segmented the imaging and collected end diastolic volume, peak systolic volume, stroke volume, ejection fraction, transmural thickness, and circumferential strain. Additionally, four-dimensional models of the left ventricles have been rendered. Histological embedding, sectioning, and staining is still in progress, and therefore validation against the gold standard is still in process. Conclusion and Impact: Treatment and monitoring of myocardial infarction patients is reliant upon accurate assessment of patient status and prognosis. This study provides initial evidence for the validity of four-dimensional ultrasound as a tool for estimation of myocardial infarction size, providing an alternative to current two-dimensional methods that are less accurate and a more accessible alternative to highly specialized and costly equipment. Improved and accessible imaging methods have the potential to enhance patient care, ultimately improving overall health outcomes.

Correlation between Volumes Determined by Echocardiography and Cardiac MRI in Controls and Atrial Fibrillation Patients

Aims: We aimed to compare cardiac volumes measured with echocardiography (echo) and cardiac magnetic resonance imaging (MRI) in a mixed cohort of healthy controls (controls) and patients with atrial fibrillation (AF). Materials and methods: In total, 123 subjects were included in our study; 99 full datasets were analyzed. All the participants underwent clinical evaluation, EKG, echo, and cardiac MRI acquisition. Participants with full clinical data were grouped into 63 AF patients and 36 controls for calculation of left atrial volume (LA Vol) and 51 AF patients and 30 controls for calculation of left ventricular end-diastolic volume (LV EDV), end-systolic volume (ESV), and LV ejection fraction (LV EF). Results: No significant differences in LA Vol were observed (p > 0.05) when measured by either echo or MRI. However, echo provided significantly lower values for left ventricular volume (p < 0.0001). The echo LA Vol of all the subjects correlated well with that measured by MRI (Spearmen correlation coefficient r = 0.83, p < 0.0001). When comparing the two methods, significant positive correlations of EDV (all subjects: r = 0.55; Controls: r = 0.71; and AF patients: r = 0.51) and ESV (all subjects: r = 0.62; Controls: r = 0.47; and AF patients: r = 0.66) were found, with a negative bias for values determined using echo. For a subgroup of participants with ventricular volumes smaller than 49.50 mL, this bias was missing, thus in this case echocardiography could be used as an alternative for MRI. Conclusion: Good correlation and reduced bias were observed for LA Vol and EF determined by echo as compared to cardiac MRI in a mixed cohort of patients with AF and healthy volunteers. For the determination of volume values below 49.50 mL, an excellent correlation was observed between values obtained using echo and MRI, with comparatively reduced bias for the volumes determined by echo. Therefore, in certain cases, echocardiography could be used as a less expensive, less time-consuming, and contraindication free alternative to MRI for cardiac volume determination.

Age- and Sex-Specific Characteristics of Right Ventricular Compacted and Non-compacted Myocardium by Cardiac Magnetic Resonance

The age and sex-specific characteristics of right ventricular compacted (RV-CMi) and RV-trabeculated myocardial mass (RV-TMi) and the determinants of RV myocardium are less well-studied; however, in different conditions, these might provide additional diagnostic information. We aimed to describe the age- and sex-specific characteristics of RV-CMi, RV-TMi, and RV volumetric and functional parameters and investigate the determinants of RV myocardial mass with cardiac magnetic resonance (CMR). Two hundred healthy Caucasian volunteers free of known cardiovascular or systemic diseases were prospectively enrolled in this study. Four different age groups were established with equal numbers of males and females: Group A (n = 50, 20-29 years, mean age: 24.3 ± 3.2 years), Group B (n = 50, 30-39 years, mean age: 33.6 ± 2.6 years), Group C (n = 50, 40-49 years, mean age: 44.7 ± 2.7 years), and Group D (n = 50, ≥50 years, mean age: 55.1 ± 3.9 years). Left ventricular (LV) and RV volumetric, functional, CMi, and TMi values were measured with a threshold-based post-processing CMR method. The volumetric parameters, RV-CMi, and RV-TMi values were larger, and the ejection fraction (EF) was lower in males. The RV-CMi did not correlate with age in either of the sexes, while the RV-TMi decreased with age in females but remained stable in males. The RV-TMi and RV-CMi correlated positively with RV volumetric parameters, the LV-CMi, the LV-TMi, and each other in both sexes. LV-TMi, LV-CMi, RV end-systolic volume, and sex were independent predictors of RV-TMi. Understanding the characteristics of RV-trabeculated and RV-compacted myocardium might have additive value in diagnosing different conditions with RV hypertrophy or hypertrabeculation.

Association of Digoxin With Preserved Echocardiographic Indices in the Interstage Period: A Possible Mechanism to Explain Improved Survival?

Background For patients with hypoplastic left heart syndrome, digoxin has been associated with reduced interstage mortality after the Norwood operation, but the mechanism of this benefit remains unclear. Preservation of right ventricular (RV) echocardiographic indices has been associated with better outcomes in hypoplastic left heart syndrome. Therefore, we sought to determine whether digoxin use is associated with preservation of the RV indices in the interstage period. Methods and Results We conducted a retrospective cohort study of prospectively collected data using the public use data set from the Pediatric Heart Network Single Ventricle Reconstruction trial, conducted in 15 North American centers between 2005 and 2008. We included all patients who survived the interstage period and had echocardiographic data post‐Norwood and pre‐Glenn operations. We used multivariable linear regression to compare changes in RV parameters, adjusting for relevant covariates. Of 289 patients, 94 received digoxin at discharge post‐Norwood. There were no significant differences in baseline clinical characteristics or post‐Norwood echocardiographic RV indices (RV end‐diastolic volume indexed, RV end‐systolic volume indexed, ejection fraction) in the digoxin versus no‐digoxin groups. At the end of the interstage period and after adjustment for relevant covariates, patients on digoxin had better preserved RV indices compared with those not on digoxin for the ΔRV end‐diastolic volume (11 versus 15 mL, P =0.026) and the ΔRV end‐systolic volume (6 versus 9 mL, P =0.009) with the indexed ΔRV end‐systolic volume (11 versus 20 mL/BSA 1.3 , P =0.034). The change in the RV ejection fraction during the interstage period between the 2 groups did not meet statistical significance (−2 versus −5, P =0.056); however, the trend continued to be favorable for the digoxin group. Conclusions Digoxin use during the interstage period is associated with better preservation of the RV volume and tricuspid valve measurements leading to less adverse remodeling of the single ventricle. These findings suggest a possible mechanism of action explaining digoxin’s survival benefit during the interstage period.

Relationships between values of myocardial remodeling parameters and level of apoptosis biomarkers in patients with ischemic cardiomyopathy

The aim of the research. To study levels of the apoptosis biomarkers annexin A5 (AnxA5) and Bcl‑2 and to identify the presence of correlations of structural and functional parameters of the myocardium with the level of the studied biomarkers in patients with ischemic cardiomyopathy (ICMP).Materials and methods. Patients with ICMP (n = 47) were examined as the main group. The control group included 30 somatically healthy individuals. Bcl‑2 and APA5 levels were determined in the blood serum by the enzyme immunoassay.Results. It was found that in the group of patients with ICMP. The level of AnxA5 was statistically significantly higher (p < 0.001), and the level of Bcl‑2 was statistically significantly lower (p < 0.001) than in the control group. Based on the results of the correlation analysis a noticeable close relationship on the Cheddock scale was revealed between levels of the studied apoptosis biomarkers and the values of the sphericity index of in diastole and systole of left ventricle (LV), final diastolic and systolic volume of LV and ejection fraction of LV. Between the other parameters of myocardial remodeling and levels of the studied biomarkers of apoptosis, the closeness of relationships on the Cheddock scale were weak and moderate.

The effect of left ventricle ischemia severity on cardiac performance appeared on ejection fraction using radioactive TC 99m MIBI in comparison with echocardiography

Ischemic heart disease is a major causes of heart failure. Heart failure patients have predominantly left ventricular dysfunction (systolic or diastolic dysfunction, or both). Acute heart failure is most commonly caused by reduced myocardial contractility, and increased LV stiffness. We performed echocardiography and gated SPECT with Tc99m MIBI within 263 patients and 166 normal individuals. Left ventricular end systolic volume (LVESV), left ventricular end diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF) were measured. For all degrees of ischemia, there was a significant difference between ejection fraction values measured by SPECT and echocardiography, and there were no significant differences among end systolic volume and end diastolic volume value calculated by two methods for all cases. The mean value for EDV (ECHO)/EDV (SPECT) was 1.07 ± 0.31 for degree (1, 2); in the degree 3 the mean value was 1.02 ± 0.08, and 1.005 ± 0.07 for degree 4. The mean value for ESV (ECHO)/ESV (SPECT) was 1.08 ± 0.34 for degree (1, 2); while 1.03 ± 0.12, 1.021 ± 0.128 for degree 3 and 4 respectively. This study was showed a good relation between left ventricular size and ejection fraction measured by SPECT with Tc99m, and echocardiography.

25 Atrial remodelling in patients affected by chronic heart failure in therapy with sacubitril/valsartan

Aims Left atrial (LA) enlargement has been demonstrated to be a predictor of adverse cardiovascular outcomes, such as atrial fibrillation (AF), heart failure (HF), and cardiovascular death. Previous studies showed left ventricle ejection fraction (LVEF) improvement and reverse remodelling can be achieved after therapy with sacubitril/valsartan in real-world settings. We sought to investigate the association between left atrial (LA) structural and functional remodelling in patients with chronic HF after therapy with sacubitril/valsartan. Methods and results Patients affected by chronic HF with LV dysfunction (LVEF &lt; 35%), NYHA functional class II–III were followed up between September 2019 and March 2020. All patients underwent clinical and echocardiography Follow-up at baseline and after 6 months of therapy with sacubitril/valsartan. Measures of LA structure [LA end-systolic volume (LAESV)] and function [left atrial emptying fraction (LAEF), peak atrial longitudinal strain (PALS), LA conduit strain and peak atrial contraction strain (PACS)] were calculated. A total of 47 patients (median age 66 ± 7.97, male gender 85%, mean LVEF 28.33 ± 5.61%) were enrolled. The left atrial strain parameters (PALS and LA conduit) resulted higher at 6 months follow-up respect to baseline values, (14.68 ± 7.16 vs. 18.67 ± 8.03, P &lt; 0.001, and −7.61 ± 4.07 vs. −9.71 ± 5.23, P = 0.007, respectively). Conclusions Treatment with sacubitril/valsartan in patients with HFrEF is associated with an improvement in LA functional remodelling in a real-world scenario.

Direct mitral regurgitation quantification in hypertrophic cardiomyopathy using 4D flow CMR jet tracking: evaluation in comparison to conventional CMR

Background Quantitative evaluation of mitral regurgitation (MR) in hypertrophic cardiomyopathy (HCM) by cardiovascular magnetic resonance (CMR) relies on an indirect volumetric calculation. The aim of this study was to directly assess and quantify MR jets in patients with HCM using 4D flow CMR jet tracking in comparison to standard-of-care CMR indirect volumetric method. Methods This retrospective study included patients with HCM undergoing 4D flow CMR. By the indirect volumetric method from CMR, MR volume was quantified as left ventricular stroke volume minus forward aortic volume. By 4D flow CMR direct jet tracking, multiplanar reformatted planes were positioned in the peak velocity of the MR jet during systole to calculate through-plane regurgitant flow. MR severity was collected for agreement analysis from a clinical echocardiograms performed within 1 month of CMR. Inter-method and inter-observer agreement were assessed by intraclass correlation coefficient (ICC), Bland–Altman analysis, and Cohen’s kappa. Results Thirty-seven patients with HCM were included. Direct jet tracking demonstrated good inter-method agreement of MR volume compared to the indirect volumetric method (ICC = 0.80, p = 0.004) and fair agreement of MR severity (kappa = 0.27, p = 0.03). Direct jet tracking showed higher agreement with echocardiography (kappa = 0.35, p = 0.04) than indirect volumetric method (kappa = 0.16, p = 0.35). Inter-observer reproducibility of indirect volumetric method components revealed the lowest reproducibility in end-systolic volume (ICC = 0.69, p = 0.15). Indirect volumetric method showed good agreement of MR volume (ICC = 0.80, p = 0.003) and fair agreement of MR severity (kappa = 0.38, p < 0.001). Direct jet tracking demonstrated (1) excellent inter-observer reproducibility of MR volume (ICC = 0.97, p < 0.001) and MR severity (kappa = 0.84, p < 0.001) and (2) excellent intra-observer reproducibility of MR volume (ICC = 0.98, p < 0.001) and MR severity (kappa = 0.88, p < 0.001). Conclusions Quantifying MR and assessing MR severity by indirect volumetric method in HCM patients has limited inter-observer reproducibility. 4D flow CMR jet tracking is a potential alternative technique to directly quantify and assess MR severity with excellent inter- and intra-observer reproducibility and higher agreement with echocardiography in this population.