Systolic Impairment Research Articles

Cardiac resynchronization therapy: association between genetically determinated dilated cardiomyopathy and dissinchronopathy

Abstract Background Patients with non-ischemic dilated cardiomyopathy (DCM) and left bundle branch block (LBBB) often undergoes cardiac resynchronization therapy (CRT). Despite CRT only a small group of patients restore normal left ventricular geometry and function. Many predictors of response to CRT have been described, but there are still insufficient data on the role of genetic mutations in sarcomere, cytoskeletal or desmosomal genes. Purpose To asses the role of genetic background as predictor of response after CRT in patient DCM and LBBB. Methods We retrospectively analyzed DCM patients with successful CRT implantation and available genetic testing consecutively included in the CRT-Registry of our Institution. DCM was defined by the presence of left ventricular or biventricular dilatation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease sufficient to cause global systolic impairment. Changes in main echocardiographic parameters: left ventricular ejection fraction (LVEF), LV End Systolic and End Diastolic Volume (LVESV and LVEDV), where compared between basal and 24–48 months of follow up. LV remodeling was defined by relative changes (Δ) in LV End Systolic Volume (LVESV) [(follow-up LVESV − PRE LVESV) / PRE LVESV × 100)]. Patients were considered super-responders (SR) if LVEF at 24–48 months was>50%. Genetic testing was done by Next Generation DNA and all variants were validated with bidirectional Sanger sequencing. Variants of uncertain significance (VUS) were excluded from the analysis. Patients being carrier of pathogenic (P) or likely pathogenic (LP) variants were considered affected by genetic DCM (GEN+ DCM). Patients non carrier of P/LP variants and with no evidence of familial disease were considered affected by non-genetically determined DCM (GEN− DCM). Results 73 patients met the inclusion criteria, 23 patients were GEN+ DCM, the remaining 50 patients had negative genetic test and no family history of DCM. Baseline characteristics were similar between groups. GEN− group was characterized by a greater improvement in LVEF (39±12 vs 29±12, p=0,006) and a greater relative reduction in LVESV (ΔLVESV 43% vs 18%, p=0,007). GEN− patients had a 33 ml higher mean LVESV reduction at 24–48 months after CRT, indipendently of their respective baseline values. 20 patients (27% of the total population) suffered of heart failure related death, heart transplantation or left ventricular assistance device implantation during follow up and the prevalence was significantly higher in GEN+ group (43% vs 20%, p=0,037). Coherently, patients in the GEN+ group showed a lower prevalence of super responders (4%, vs 24%, p=0,02) after CRT. Conclusions Non-genetically determined DCM DCM is associated with a better clinical and instrumental response to CRT and a higher probability of being super responders. Furthermore, our data support the hypothesis about dyssyncronopathy as a specific clinical entity inside DCM diseases. Funding Acknowledgement Type of funding sources: None.

Paediatric pulmonary arterial hypertension following congenital heart defect repair: enhanced risk stratification and outcomes in a national cohort

Abstract Introduction Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease (CHD). PAH following CHD repair (repaired PAH-CHD) is an emerging population with increased morbidity and mortality [1–3]. Risk scores that are widely used in the adult PAH population have not been validated and may not be applicable in young children with repaired PAH-CHD. Purpose To characterize the 20-year cohort of the UK National Paediatric PH Service, focusing on peri-operative characteristics and outcomes of children with repaired PAH-CHD, and develop a tailored risk stratification tool. Methods We included consecutive children presenting to our specialist service between 2001 and 2021 with a diagnosis of repaired PAH-CHD. Patients with univentricular physiology, segmental pulmonary hypertension (PH), and PH primarily due to abnormal development of the pulmonary vasculature were excluded. Univariable Cox regression analysis was performed in children with PAH present ≥3 months after CHD repair, with an outcome of death or transplantation. Time-dependent ROC analysis was used to evaluate the risk model. Results Overall, 178 patients were included (age 3.2 [1.3–7.9] years, 58.4% female). Most children (73.0%) were referred following CHD repair. Complex CHD was present in 61.2%, and 48.9% had combined pre- and post-tricuspid shunts. Down syndrome was present in 33.1%. At the first post-operative PH assessment, 53.1% of patients had symptoms, mainly breathlessness. On echocardiographic evaluation, 30.9% had moderate-severe right ventricular dilatation and 23.7% had right ventricular systolic impairment. Over a median follow-up of 6.0 [2.4–11.0] years, 30 (19.2%) patients died and 5 (3.2%) patients underwent lung transplantation. Transpant-free survival at 1, 5, and 10 years was 94.7% (95% CI: 91.2–98.3%), 85.9% (95% CI: 80.3–91.9%), and 80.1% (95% CI: 73.1–87.7%), respectively. Cox analysis identified several clinical variables associated with death or transplantation, of which the following variables assessed post-repair were used to develop the risk score: absence of pre-operative PH, breathlessness, right ventricular dysfunction, and pulmonary vascular resistance index >14 WU m2 or lesion at high risk of causing PH (Figure 1). This novel, simple risk score performed well (AUC >80% at 1, 3, 5 and 10 years) and was well-calibrated in our cohort (Figure 2, D'Agostino-Nam p=0.76). Conclusions In this national cohort of children with repaired PAH-CHD, mortality is significant. This novel, simple risk score performed well in our population and could be used in clinical practice at the time of post-operative assessment to predict outcome and direct management but requires further validation. Funding Acknowledgement Type of funding sources: None.

Impact of cardiac resynchronisation therapy in patients with cardiac sarcoidosis

Abstract Background Implantation of a device is usually required in cardiac sarcoidosis (CS) patients presenting with advanced conduction abnormalities or ventricular arrhythmias. A cardiac resynchronisation therapy (CRT) device is often chosen in patients with concomitant left ventricular systolic impairment. The role of CRT in CS is not well established. Purpose To describe the cohort of CS patients with CRT device in situ in our hospital focusing on the short-term effect in serial echocardiography and long-term outcomes on morbidity and mortality. Methods All consecutive CS patients with a CRT device in situ were identified in our CS database (2005–2022). A confident CS diagnosis was provided after review of all relevant clinical and imaging baseline data in our CS multi-disciplinary meeting and a consensus decision for CRT-D implantation was made based on international guidelines. All patients were followed up for at least 6 months with serial echocardiography. Serial data regarding symptoms, rhythm disturbance and echocardiographic parameters were obtained and comparisons were performed using Wilcoxon signed rank test. Results A total of 51 CS patients with CRT-D were identified (mean age: 57±10 years old). Patients were male predominant (64.7%) and Caucasian in origin (86.2%). Extra-cardiac sarcoidosis was confirmed histologically in 33 (64.7%) patients. The prevalence of smoking, diabetes, hypertension and ischaemic heart disease was 27.5%, 21.6%, 49.0% and 7.8% respectively. At the time of device implantation or during follow-up, 43 (84.3%) patients were found to have active cardiac sarcoidosis on cardiac PET. Post CRT implantation there was a significant difference in LV ejection fraction (35.9±15.0% vs 42.2±14.1%, p<0.001), LV end-systolic diameter (4.90±1.46 cm vs 4.62±1.32 cm, p=0.012) and LV end-diastolic diameter (5.99±1.18 cm vs 5.66±1.06 cm, p<0.001). No significant changes were observed in the right ventricular function (p=0.09) and severity of mitral regurgitation (p=0.40). There was one patient who experienced acute heart failure decompensation admission within six months of CRT-D implantation. The New York Heart Association (NYHA) class improved in 26 patients (51.0%), worsened in 4 (7.8%) patients and remained the same in 21 (41.2%) patients at 6 months post CRT-implantation. During the mean follow up of 47.6 months, the composite end-point of death and cardiac transplantation was reached in 9 (17.6%) patients (8 deaths and 1 cardiac transplantation). 5 patients had major complications including a large haematoma, a small atrio-septal defect, haemothorax, device associated endocarditis and lead fracture. Minor wound infections were seen in 3 patients and 4 patients received inappropriate shock or anti-tachycardia pacing. Conclusions CRT in cardiac sarcoidosis patients is associated with short-term improvement in LV remodelling and functional status but over a four year follow up, morbidity and mortality are common. Funding Acknowledgement Type of funding sources: None.

3D-echocardiography for evaluation of the right ventricle in patients with repaired Tetralogy of Fallot: a comparison study with cardiac magnetic resonance

Abstract Background Patients with repaired Tetralogy of Fallot (ToF) need periodic instrumental assessments, due to complications they can meet during lifetime. Right ventricle (RV) dilation and dysfunction are some examples that explain why those patients regularly undergo Cardiac Magnetic Resonance (CMR), currently the gold standard method to detect these complications. Purpose 3D-echocardiography is an emerging tool to study RV, but there is little data supporting its use in congenital heart diseases. This study aimed at evaluating its accuracy in assessing RV dimensions and systolic function in ToF patients, in comparison to CMR. Methods 34 patients were prospectively enrolled after CMR performance. They all underwent standard 2D-echocardiography and Multi-Beat-ECG-triggered 3D Full-Volume acquisition. RV End Diastolic Volume (RV-EDV), End Systolic Volume and Ejection Fraction (RV-EF) were defined both in 3D-echocardiography and CMR. Results Post-hoc analysis of 3D images was performed through a vendor-independent software in 30 patients, resulting in a feasibility of 88%. A Bland-Altman analysis was performed, showing that 3D-echocardiography underestimates the RV-EDV/BSA of −27.39 mL/m2 on average (CI 95%: −29.46; −25.31, SD: 5.68 mL/m2), compared to CMR, as expected. However, when compared to normality reference, 3D-echocardiography identified RV dilatation with a significant correlation to CMR (V=0.66, p<0.001). Moreover, ROC curves showed that 3D-echo-RV-EDV/BSA is the echocardiographic measure that best correlates to CMR in detecting RV dilatation (AUC 1, CI 95%: 1.00; 1.00), followed by RVOT diameter in PLAX (AUC 0.89, CI 95%: 0.69; 0.99). Youden analysis suggested 77 mL/m2 (Se 95%, Sp 100%; J 0,95) as optimal limit to define RV dilatation in 3D-echocardiography. Regarding the RV-EF, the Bland-Altman analysis showed that 3D-echocardiography overestimates the RV-EF by 1,97% on average (CI 95%: 0.01; 3.95, SD: 5.43), compared to CMR. Secondly, accuracy of different echocardiographic parameters (both 2D and 3D) in detecting a RV systolic impairment was analyzed: ROC curves showed that RV-EF in 3D echocardiography is the measurement that best correlates to CMR in detecting RV dysfunction (AUC 0.92, CI 95%: 0.79–1.00), followed by Fractional Area Change (FAC) (AUC 0.78, CI 95%: 0.60; 0.96). Tricuspid Annular Plane Systolic Excursion (TAPSE) and tricuspid valve annular motion velocities in systole (S'-TDI), instead, showed very poor correlation. Conclusions 3D-echocardiography showed good agreement with CMR in defining RV dimensions and systolic function in ToF patients, even more than the bidimensional measurements cardiologists are used to. This could lead to a wider use of this tool in daily clinical practice, involving a reduction in the execution of the numerous CMR patients usually undergo. Moreover, it could be a valid instrument in patients with contraindication to CMR. Funding Acknowledgement Type of funding sources: None.

Telomere Shortening in Hypertensive Heart Disease Depends on Oxidative DNA Damage and Predicts Impaired Recovery of Cardiac Function in Heart Failure.

Heart failure (HF) coincides with cardiomyocyte telomere shortening. Arterial hypertension is the most prominent risk factor for HF. Both HF and arterial hypertension are associated with dysregulation of the neurohormonal axis. How neurohormonal activation is linked to telomere shortening in the pathogenesis of HF is incompletely understood. Cardiomyocyte telomere length was assessed in a mouse model of hypertensive HF induced by excess neurohormonal activation (AngII [angiotensin II] infusion, high salt diet, and uninephrectomy), in AngII-stimulated cardiomyocytes and in endomyocardial biopsies from patients with HF. Superoxide production, expression of NOX2 (NADPH oxidase 2) and PRDX1 (peroxiredoxin 1) and HDAC6 (histone deacetylase 6) activity were assessed. Telomere shortening occurred in vitro and in vivo, correlating with both left ventricular (LV) dilatation and LV systolic function impairment. Telomere shortening coincided with increased superoxide production, increased NOX2 expression, increased HDAC6 activity, loss of the telomere-specific antioxidant PRDX1, and increased oxidative DNA-damage. NOX2 knockout prevented PRDX1 depletion, DNA-damage and telomere shortening confirming this enzyme as a critical source of reactive oxygen species. Cotreatment with the NOX inhibitor apocynin ameliorated hypertensive HF and telomere shortening. Similarly, treatment with the HDAC6 inhibitor tubastatin A, which increases PRDX1 bioavailability, prevented telomere shortening in adult cardiomyocytes. To explore the clinical relevance of our findings, we examined endomyocardial biopsies from an all-comer population of patients with HF with reduced ejection fraction. Here, cardiomyocyte telomere length predicted the recovery of cardiac function. Cardiomyocyte telomere shortening and oxidative damage in heart failure with reduced ejection fraction induced by excess neurohormonal activation depends on NOX2-derived superoxide and may help to stratify HF therapy.

Postsystolic shortening and early systolic lengthening for early detection of myocardial involvement in patients with systemic lupus erythematosus.

Cardiac involvement predicts a poor prognosis in patients with systemic lupus erythematosus (SLE). Two-dimensional speckle-tracking echocardiography (2D-STE) are used to identify subclinical myocardial involvement in various diseases. This study objected to evaluate postsystolic shortening (PSS) and early systolic lengthening (ESL) by 2D-STE for early detection of myocardial involvement in patients with SLE. A total of 121 patients with preserved left ventricular ejection fraction (LVEF) in SLE and 30 healthy controls underwent standard 2D-STE in our study. According to SLE disease activity index (SLEDAI), we divided SLE patients into two groups: the group of inactive disease (SLEDAI ≤ 4) and active disease (SLEDAI ≥ 5). The maximum of postsystolic strain index (PSImax ) and early systolic strain index (ESImax ) were acquired from 17 segments of left ventricular (LV). We also compared the PSImax and ESImax of basal, medial, and apical segments between SLE patients and controls. Compared with healthy controls and the group of SLEDAI ≤ 4, the group of SLEDAI ≥ 5 had higher PSImax and ESImax value of global LV and basal segments. The absolute value of global longitudinal strain (GLS) had no difference between the group of active disease and inactive disease. Multivariate analysis demonstrated that PSS was independently associated with SLEDAI and diabetes mellitus. Detection of PSS and ESL enable to identify LV systolic impairment in SLE patients at an early stage.

Subclinical left ventricular systolic dysfunction and incident stroke in the elderly: long-term findings from Cardiovascular Abnormalities and Brain Lesions.

Heart disease is associated with an increased risk for ischaemic stroke. However, the predictive value of reduced left ventricular ejection fraction (LVEF) for stroke is controversial and only observed in patients with severe reduction. LV global longitudinal strain (LV GLS) can detect subclinical LV systolic impairment when LVEF is normal. We investigated the prognostic role of LV GLS for incident stroke in a predominantly elderly cohort. Two-dimensional echocardiography with speckle tracking was performed in the Cardiac Abnormalities and Brain Lesions (CABL) study. Among 708 stroke-free participants (mean age 71.4 ± 9.4 years, 60.9% women), abnormal LV GLS (>-14.7%: 95% percentile of the subgroup without risk factors) was detected in 133 (18.8%). During a mean follow-up of 10.8 ± 3.9 years, 47 participants (6.6%) experienced an ischaemic stroke (26 cardioembolic or cryptogenic, 21 other subtypes). The cumulative incidence of ischaemic stroke was significantly higher in participants with abnormal LV GLS than with normal LV GLS (P < 0.001). In multivariate stepwise logistic regression analysis, abnormal LV GLS was associated with ischaemic stroke independently of cardiovascular risk factors including LVEF, LV mass, left atrial volume, subclinical cerebrovascular disease at baseline, and incident atrial fibrillation [hazard ratio (HR): 2.69, 95% confidence interval (CI): 1.47-4.92; P = 0.001]. Abnormal LV GLS independently predicted cardioembolic or cryptogenic stroke (adjusted HR: 3.57, 95% CI: 1.51-8.43; P = 0.004) but not other subtypes. LV GLS was a strong independent predictor of ischaemic stroke in a predominantly elderly stroke-free cohort. Our findings provide insights into the brain-heart interaction and may help improve stroke primary prevention strategies.

Serial Assessment of Cardiac Function and Pulmonary Hemodynamics in Infants With Down Syndrome

There is a dearth of longitudinal data describing the evolution of cardiopulmonary hemodynamics in infants with Down syndrome (DS) beyond infancy. We hypothesized that babies with DS, independent of the presence of congenital heart disease (CHD), demonstrate biventricular systolic and diastolic impairment and sustained elevation of pulmonary pressures compared with controls over the first 2years of age. This was a prospective observational cohort study of 70 infants with DS (48 with CHD and 22 without CHD) and 60 controls carried out in 3 tertiary neonatal intensive care units in Dublin, Ireland. Infants with DS with and without CHD and non-DS controls underwent serial echocardiograms at birth, 6months, 1year, and 2years of age to assess biventricular systolic and diastolic function using deformation analysis. Pulmonary vascular resistance was assessed using pulmonary artery acceleration time and left ventricular (LV) eccentricity index. Infants with DS exhibited smaller LV (birth: 27±4 vs 31±2mm, P&lt;.01; 2years: 43±5 vs 48±4mm, P&lt;.01) and right ventricular (birth: 28±3 vs 31±2mm, P&lt;.01; 2years: 40±4 vs 44±3mm, P&lt;.01) lengths and lower LV (birth: -19%±3% vs -22%±2%, P&lt;.01; 2years: -24%±2% vs -26%±2%, P&lt;.01) and right ventricular (birth: -19%±4% vs -22%±3%, P&lt;.01; 2years: -29%±6% vs -33%±4%, P&lt;.01) systolic strain over the 2-year period. Pulmonary artery acceleration time was lower in the DS group throughout the study period (birth: 44±10 vs 62±14ms, P&lt;.01; 2years 71±12 vs 83±11ms, P&lt;.01). No differences were observed between DS infants with and without CHD (all P&gt;.05). Infants with DS exhibit impaired maturational changes in myocardial function and pulmonary vascular resistance. Such novel findings provide valuable insights into the pathophysiology affecting cardiorespiratory morbidity in this population.

Pulmonary artery acceleration time accuracy for systolic pulmonary artery pressure estimation in critically ill patients

BackgroundEstimation of pulmonary pressures is of key importance in acute cardiovascular and respiratory failure. Pulmonary artery acceleration time (PAAT) has emerged as reliable parameter for the estimation of systolic pulmonary artery pressure (sPAP) in cardiological population with preserved right ventricular function. We sought to find whether PAAT correlates with sPAP in critically ill patients with and without right ventricular (RV) systolic dysfunction.MethodsObservational study. We measured sPAP using continuous-wave Doppler analysis of tricuspid regurgitation velocity peak method and we assessed the validity of PAAT in estimating sPAP in patients admitted to adult intensive care unit (ICU) for acute cardiovascular and respiratory failure.ResultsWe enrolled 236 patients admitted to cardiothoracic ICU for cardiovascular and respiratory failure (respectively: 129, 54.7% and 107, 45.3%). 114 (48.3%) had preserved RV systolic function (defined as TAPSE ≥ 17 mm), whilst 122 (51.7%) had RV systolic impairment (defined as TAPSE < 17 mm). A weak inverse correlation between PAAT and sPAP (ρ–0.189, p 0.0035) was observed in overall population, which was confirmed in those with preserved RV systolic PAAT and sPAP (ρ–0.361, p 0.0001). In patients with impaired RV systolic function no statistically significant correlation between PAAT and sPAP was demonstrated (p 0.2737). Adjusting PAAT values for log10, heart rate and RV ejection time did not modify the abovementioned correlations.ConclusionsPAAT measurement to derive sPAP is not reliable in cardiothoracic critically ill patients, particularly in the coexistence of RV systolic impairment.

Detection of early signs of right ventricular systolic impairment in unoperated Ebstein's anomaly by cardiac magnetic resonance feature tracking.

Cardiovascular magnetic resonance feature-tracking analysis (CMR-FT) provides a quantitative assessment of myocardial contraction with potential for diagnostic and prognostic ability in a wide spectrum of diseases. Ebstein's anomaly (EA) is a rare congenital heart disease characterized by apical displacement of the tricuspid valve. However, it is also considered a disorder of development affecting the global right ventricular myocardium. Aim of our study is to describe the complex contractile mechanics of the functional right ventricle (RV) in patients affected by EA through CMR-FT. Fifty surgery-free EA patients who had undergone a complete CMR protocol at our institution between January 2017 and December 2020 were selected for the retrospective study. A historical control group of twenty-five healthy subjects was also included. CMR-FT analysis was performed at a dedicated workstation by manually tracing RV endo- end epicardial borders on steady-state-free-precession (SSFP) cine images. Strain values were calculated. Apical displacement of the tricuspid valve (TV) was measured on a 4-chamber cine image from the right atrio-ventricular junction to the functional annulus of the TV. EA patients presented significantly impaired RV global radial strain (GRS) and global circumferential strain (GCS) compared to controls (P<0.0001 and P=0.0008, respectively). In a subgroup analysis, GRS was significantly compromised in patients with a severely displaced TV (>16 mm/m2) compared to milder forms (P=0.03) and to controls (P<0.0001). Among EA patients with a preserved ejection fraction, 12 (48%) vs. 6 (24%) controls had reduced both GRS and GCS. The contractile pattern of the functional RV in EA is characterised by prevalent alterations in the short-axis direction as indicated by reduced GRS and GCS. Strain values might be reduced prior to routine used functional parameters like RV ejection fraction (RVEF) and can possibly serve as an early predictor of myocardial dysfunction in EA patients.

P419 CARDIAC SARCOIDOSIS IN A CARRIER OF TTR GENE MUTATION

Abstract Abstract A 39–year–old man came to our attention after being identified as a carrier of the mutation lle68Leu in the transthyretin (TTR) gene, following his father’s diagnosis of cardiac amyloidosis. From then on, the patient underwent periodical follow–up for early detection of target organs involvement, with normal echocardiographic results of blood test and echocardiography. At the age of 41, he was hospitalized after a transient loss of consciousness (TLS) episode while riding a bicycle. The echocardiogram showed normal systolic function with an akinetic basal septum. A coronary angiogram excluded the presence of coronary artery disease. One year later, ECG abnormalities developed, with a new–onset right bundle branch block and posterior fascicular block. The echocardiogram showed a dilated cardiomyopathy with severe left systolic function impairment (ejection fraction 30%). SPECT with bisphosphonate ruled out cardiac amyloidosis. Cardiac MRI was significant for patchy areas of late gadolinium enhancement in the left ventricle. Before the following cardiological evaluation for a possible ICD implantation the patient was again hospitalized after a resuscitated cardiac arrest.Thoracic CT, performed in the emergency department, was significant for hilar lymphadenopathies and pulmonary nodules highly suggestive for sarcoidosis. FDG–PET showed multiorgan phlogistic–infiltrative involvement, including the myocardium. A subsequent hepatic CT–guided biopsy eventually confirmed the diagnosis of sarcoidosis. In secondary prevention, the patient underwent ICD implantation but continued to experience arrhythmic events.

Galectin-3 as a Marker of Cardiorenal Syndrome in Patients with Chronic Heart Failure

Aim. To assess the effect of renal dysfunction on the galectin-3 level in patients with chronic heart failure (HF) with preserved, intermediate and reduced left ventricular ejection fraction (EF).Material and methods. Along with a clinical examination, 69 patients with HF (NYHA class II-IV) underwent tests for the level of NT-proBNP and galectin-3 in serum using enzyme immunoassay.Results. Study participants were divided into 3 groups: 23 patients with preserved EF (HFpEF), 26 patients with midrange EF (HFmrEF), 20 patients with reduced EF (HFrEF). There was a trend to increase the concentration of galectin-3 with increase in NT-proBNP level. Correlation analysis showed significant feedback (r=−0.41, p&lt;0.05) between galectin-3 and EF only in patients with preserved systolic function. In the same group of HFpEF patients, the maximum serum galectin-3 level was 10.5 [6.5; 14.5] ng/ml. Serum galectin-3 level showed negative correlated with the GFR in patients with CHF (r=−0.513, p&lt;0.05). In patients with HF and glomerular filtration rate (GFR) &lt;60 ml/min/1.73 m2 it was higher than in patients with GFR&gt;60 ml/min/1.72 m2 (9 [5.3; 12.6] ng/mL vs 11.8 [6.2; 15.3] ng/mL, p&lt;0.05). According to the ROC-analysis data, galectin-3 level &gt;10.3 ng/ml indicates a high risk of chronic kidney disease stage 3-4 stage development (sensitivity 60%, specificity 75%) and can be considered as a risk factor for development of cardiorenal syndrome in HF patients.Conclusion. Galectin-3 level in patients with HF is more influenced by the degree of reduction in GFR rather than the left ventricular systolic function impairment.

A Comprehensive Assessment of Cardiomyopathies through Cardiovascular Magnetic Resonance: Focus on the Pediatric Population.

Cardiomyopathies (CMPs) are a heterogeneous group of diseases that involve the myocardium and result in systolic or diastolic impairment of the cardiac muscle, potentially leading to heart failure, malignant arrhythmias, or sudden cardiac death. Occurrence in pediatric age is rare but has been associated with worse outcomes. Non-invasive cardiac imaging techniques, integrated with clinical, genetic, and electrocardiographic data, have shown a pivotal role in the clinical work-up of such diseases by defining structural alterations and assessing potential complications. Above all modalities, cardiovascular magnetic resonance (CMR) has emerged as a powerful tool complementary to echocardiography to confirm diagnosis, provide prognostic information and guide therapeutic strategies secondary to its high spatial and temporal resolution, lack of ionizing radiation, and good reproducibility. Moreover, CMR can provide in vivo tissue characterization of the myocardial tissue aiding the identification of structural pathologic changes such as replacement or diffuse fibrosis, which are predictors of worse outcomes. Large prospective randomized studies are needed for further validation of CMR in the context of childhood CMPs. This review aims to highlight the role of advanced imaging with CMR in CMPs with particular reference to the dilated, hypertrophic and non-compacted phenotypes, which are more commonly seen in children.

Too Much Too Soon? The Catch-22 of Catching COVID-19

IntroductionMyocarditis has become a well-recognised cardiac complication of SARS-CoV-2 infection. Now, there are growing reports of rare incidences of myocarditis following receipt of mRNA COVID-19 vaccines.Case ReportA previously healthy 35-year-old male tested positive for COVID-19 on 8/12/21. He never required hospitalisation and was thought to have cleared the infection by 9/5/21. Three weeks later he received the first dose of Pfizer-BioNTech BNTT162b2/Comirnaty mRNA COVID-19 vaccine. Five days later he presented to emergency with chest pain alongside myalgia, headache and cough. His troponin-T was below reference range (RR), electrocardiogram showed sinus rhythm with mild, diffuse T-wave flattening, and no evidence of pericardial effusion was seen on bedside transthoracic echocardiogram (TTE) so was discharged. Two days later he represented to hospital with fevers, vomiting, diarrhea and a maculopapular rash. His subsequent admission was complicated by rapid deterioration and his management reflected a diagnostic dilemma with wide differentials. On day 2 of admission he became haemodynamically unstable requiring vasopressor therapy with a high sensitivity (hs) troponin-I of 103ng/L (RR <26ng/L). On day 4 he developed atrial fibrillation, worsening respiratory distress, peak hs troponin-I of 1474ng/L and required intubation, direct-current cardioversion and venoarterial extracorporeal membrane oxygenation (ECMO) for intractable heart failure. TTE here showed severe global systolic impairment with a left ventricular ejection fraction of 15% and small pericardial effusion. His subsequent treatment targeted possible multiorgan sepsis with antibiotics, vaccine-induced myocarditis with immunosuppressive therapy including anakinra and parental corticosteroids, or delayed COVID-19 myocarditis with supportive care. He was later extubated and successfully decannulated from 5 days on ECMO on day 11. Cardiac magnetic resonance imaging on day 12 showed elevated T1 and T2 values consistent with ongoing myocardial edema, but normal ventricular volume, thickness and function.SummaryThis is a case of fulminant myocarditis whereby the aetiology is unclear considering recent COVID-19 infection and mRNA vaccination. This raises questions as to the ideal timing of vaccine, type of vaccine and requirement for cardiac screening prior to vaccination in patients who have recovered from COVID-19.

The heart after surviving twin-to-twin transfusion syndrome

The persistent changes in cardiac structure and function in children who survived twin-to-twin transfusion syndrome remain a matter of concern and controversy. Current fetal echocardiographic parameters and their postnatal evolution can help improve our understanding of the subject. To describe the echocardiographic changes of monochorionic fetuses affected by twin-to-twin transfusion syndrome, the recipient and the donor, before and after laser photocoagulation and to determine their evolution in the third trimester and during their first year of life. An observational study was conducted including 55 uncomplicated monochorionic diamniotic twins and 78 pairs with twin-to-twin transfusion syndrome, 44 stage I-II and 34 stage III-IV, prospectively enrolled from 2015 until 2018. Comprehensive echocardiography was performed at 4 time periods: before laser photocoagulation, at 24 to 72 hours after surgery, at 28 to 30 weeks of gestation, and at 6 to 12 months after birth. Echocardiographic parameters were transformed to z-scores or indexed for heart area, estimated fetal weight, or body mass surface. At diagnosis, recipients in all stages presented larger hearts (cardiothoracic ratio z-score: 2.77 [0.8] vs controls:-0.03 [0.5]; P<.001) and signs of ventricular hypertrophy (left end-diastolic ventricle wall thickness: 2.68 [0.7] vs controls-0.03 [0.7]; P<.001), along with systolic (cardiac index recipients: 317 [114] mL/min/kg vs controls: 400 [120] mL/min/kg, P<.001) and diastolic impairment (isovolumetric relaxation time z-score: 2.76 [0.6] vs controls: 0.05 [0.6]; P<.001). Donors presented smaller ventricular areas and diameters when compared with controls (left end-diastolic ventricle area z-score:-1.48 [1] vs 0.03 [0.9]; P<.001), along with decreased longitudinal motion (tricuspid annular plane systolic excursion z-score:-0.9 [1] vs controls-0.04 [1]; P<.001) and shorter ejection time z-score (-1.5 [0.7] vs controls: 0.0 [0.7]; P<.001). After surgery, an improvement in functional parameters was observed in both fetuses, whereas most morphometric changes prevailed in donors and recipients in the prenatal period. Postnatally, cardiac remodeling persisted in recipients (left relative wall thickness: 0.34 [0.02] vs controls: 0.30 [0.02]; P<.001), whereas donors mainly presented a decreased longitudinal motion in infancy (tricuspid annular plane systolic excursion z-score:-0.72 [0.7] vs controls: 0.23 [0.9]; P<.05). Cardiac remodeling is present in both fetuses at the twin-to-twin transfusion syndrome diagnosis, whereas diastolic dysfunction is only significant in the recipient. Fetal therapy improves most echocardiographic parameters, although postnatally, the echocardiographic changes persist in both fetuses.

Hypoglycemia-Exacerbated Mitochondrial Connexin 43 Accumulation Aggravates Cardiac Dysfunction in Diabetic Cardiomyopathy.

BackgroundDiabetic cardiomyopathy (DCM) is a complex multifaceted disease responsible for elevated heart failure (HF) morbidity and mortality in patients with diabetes mellitus (DM). Patients with DCM exhibit subclinical diastolic dysfunction, progression toward systolic impairment, and abnormal electrophysiology. Hypoglycemia events that occur spontaneously or due to excess insulin administration threaten the lives of patients with DM—with the increased risk of sudden death. However, the molecular underpinnings of this fatal disease remain to be elucidated.Methods and ResultsHere, we used the established streptozotocin-induced DCM murine model to investigate how hypoglycemia aggravates DCM progression. We confirmed connexin 43 (Cx43) dissociation from cell–cell interaction and accumulation at mitochondrial inner membrane both in the cardiomyocytes of patients with DM and DCM murine. Here, we observed that cardiac diastolic function, induced by chronic hyperglycemia, was further aggravated upon hypoglycemia challenge. Similar contractile defects were recapitulated using neonatal mouse ventricular myocytes (NMVMs) under glucose fluctuation challenges. Using immunoprecipitation mass spectrometry, we identified and validated that hypoglycemia challenge activates the mitogen-activated protein kinase kinase (MAPK kinase) (MEK)/extracellular regulated protein kinase (ERK) and inhibits phosphoinositide 3-kinase (PI3K)/Akt pathways, which results in Cx43 phosphorylation by Src protein and translocation to mitochondria in cardiomyocytes. To determine causality, we overexpressed a mitochondrial targeting Cx43 (mtCx43) using adeno-associated virus serotype 2 (AAV2)/9. At normal blood glucose levels, mtCx43 overexpression recapitulated cardiac diastolic dysfunction as well as aberrant electrophysiology in vivo. Our findings give support for therapeutic targeting of MEK/ERK/Src and PI3K/Akt/Src pathways to prevent mtCx43-driven DCM.ConclusionDCM presents compensatory adaptation of mild mtCx43 accumulation, yet acute hypoglycemia challenges result in further accumulation of mtCx43 through the MEK/ERK/Src and PI3K/Akt/Src pathways. We provide evidence that Cx43 mislocalization is present in hearts of patients with DM hearts, STZ-induced DCM murine model, and glucose fluctuation challenged NMVMs. Mechanistically, we demonstrated that mtCx43 is responsible for inducing aberrant contraction and disrupts electrophysiology in cardiomyocytes and our results support targeting of mtCx43 in treating DCM.

Cardiovascular subphenotypes in patients with COVID-19 pneumonitis whose lungs are mechanically ventilated: a single-centre retrospective observational study.

SummaryUnsupervised clustering methods of transthoracic echocardiography variables have not been used to characterise circulatory failure mechanisms in patients with COVID‐19 pneumonitis. We conducted a retrospective, single‐centre cohort study in ICU patients with COVID‐19 pneumonitis whose lungs were mechanically ventilated and who underwent transthoracic echocardiography between March 2020 and May 2021. We performed latent class analysis of echocardiographic and haemodynamic variables. We characterised the identified subphenotypes by comparing their clinical parameters, treatment responses and 90‐day mortality rates. We included 305 patients with a median (IQR [range]) age 59 (49–66 [16–83]) y. Of these, 219 (72%) were male, 199 (65%) had moderate acute respiratory distress syndrome and 113 (37%) did not survive more than 90 days. Latent class analysis identified three cardiovascular subphenotypes: class 1 (52%; normal right ventricular function); class 2 (31%; right ventricular dilation with mostly preserved systolic function); and class 3 (17%; right ventricular dilation with systolic impairment). The three subphenotypes differed in their clinical characteristics and response to prone ventilation and outcomes, with 90‐day mortality rates of 22%, 42% and 73%, respectively (p < 0.001). We conclude that the identified subphenotypes aligned with right ventricular pathophysiology rather than the accepted definitions of right ventricular dysfunction, and these identified classifications were associated with clinical outcomes.

Prognostic implications of staging cardiac remodeling in patients undergoing cardiac resynchronization therapy

BackgroundCardiac resynchronization therapy (CRT) candidates often present with significant mitral and tricuspid regurgitation, pulmonary hypertension and right ventricular dysfunction when referred for device implantation. This study investigated the prognostic value of a novel cardiac staging system, based on the extent of cardiac remodeling prior to implantation. MethodsData were collected from an ongoing registry of CRT recipients. Patients were divided into 4 groups according to the extent of cardiac remodeling: group 1: left ventricular systolic dysfunction, group 2: left atrial dilatation and/or significant mitral regurgitation, group 3: pulmonary arterial hypertension and/or significant tricuspid regurgitation and group 4: right ventricular systolic impairment. Patients were followed up for the occurrence of all-cause mortality. ResultsA total of 844 patients (age 65 ± 10 years, 77% men) were included. Of the overall population, 145 (17%) patients were in group 1, 161 (19%) in group 2, 157 (19%) in group 3 and 381 (45%) in group 4. After a median follow-up of 95 (51–145) months, 517 (61%) patients died. Patients in groups 2, 3 and 4 had significantly higher mortality rates than those in group 1 (p = 0.025, p < 0.001 and p < 0.001, respectively). On multivariable analysis, groups 3 (HR 1.415; 95% CI 1.024–1.957; p = 0.032) and 4 (HR 1.599; 95% CI 1.204–2.123; p = 0.001) were independently associated with all-cause mortality. ConclusionsMost CRT candidates already present with extensive cardiac remodeling at the time of referral. Detection of the extent of cardiac remodeling before CRT implantation results in improved risk-stratification, and underscores the need for early referral.

Speckle tracking echocardiography strain analysis for the assessment and monitoring of myocardial mechanics after pediatric cardiac surgery

Abstract Funding Acknowledgements Type of funding sources: None. Background. Speckle-tracking echocardiography (STE) is a relatively new ultrasound technique that exploits acoustic reflections and artifacts within the ultrasonic window, with the aim of analyzing global myocardial deformation and segmenting. STE has proved to be more sensitive in identifying a myocardial dysfunction so gained increasing value in the evaluation of congenital heart diseases (CHD) even though its use, in pediatric cardiac surgery, is still limited. The present study aims to evaluate the global and left ventricular (LV) systolic impairment after pediatric cardiac surgery by STE strain (ε) analysis. Methods We prospectively enrolled 120 children undergoing cardiac surgery for CHD. Echocardiography was performed at four different times: pre-operatively, 12-36 hours (Time-1), 3-5 days (Time-2), 6-8 days (Time-3). Images were obtained in the 4-2-and 3 apical chamber’s views to derive LV global and regional (basal/mid/apical) ε values. Results. We collected data from 332 examinations in 120 children (mean age: 2.33 ±3.91, range: 0-16 years) at different post-operative times. 120 age-matched healthy children (3.1 ± 4.2 years) served as controls. All global, basal, and mid LVε values reduced after surgery; the lowest values were at Time-1 (p &amp;lt; 0.0001) but increased thereafter. At discharge, all global, basal, and mid LVε values persisted lower than pre-operatively and healthy children (p &amp;lt; 0.05). Instead, apical segments (lowest at baseline), increased after surgery (p &amp;lt; 0.0001), but remained lower compared to controls. LV ejection fraction (LVEF) decreased at Time-1 (p = 0.0003) but promptly recovered to Time-2, to standardize at Time-3. Conclusions. Despite LVEF was normalized by the discharge, STE ε has shown a systolic impairment after cardiac surgery that disclosed a gradual improvement but still uncomplete normalization at discharge. Regional STE differences revealed a discrepancy base-apex: apical segments, contrary to all the other regions, showed hypercontractility after surgery. The slower recovery of LVε values compared to LVEF, suggests that STE ε analysis may be more accurate in the follow-up of mild LV post-surgical impairment. Abstract Figure. LV ventricular ε values

Diastolic dysfunction worsen prognosis in patients with dilated cardiomyopathy independently of left ventricular systolic dysfunction

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The heart failure (HF) symptoms and prognosis in patients with HF with reduced ejection fraction (LVEF; HFrEF) is mostly associated with left ventricle (LV) remodelling and systolic dysfunction. However, in HFrEF patients the LV diastolic function is usually also impaired and worsen the prognosis. The significance of LV dysfunction in dilated cardiomyopathy (DCM) is well recognised, but not the diastolic dysfunction. Aim The analysis of diastolic function in DCM with different systolic impairment and its impact on the prognosis. Methods Between 2010 and 2020 we retrospectively analysed out- and in-hospital records of 567 DCM patients (age 52 ± 13 years, 78% male, NYHA 2.4 ± 0.8) with complete echocardiographic and outcome data. Patients were divided into 3 groups based on LVEF (EF1 &amp;lt;20%, EF2 20-29%, EF3 ≥30%) and into 3 groups according to diastolic function based on the ASE/EACVI 2016 recommendations. Results Most patients had no or mildly impaired diastolic function, however nearly 50% of EF1 patients had abnormal diastolic function (Table 1). During observation of 41 ± 27 months, 88 (16%) patients died (Table 1). Impaired diastolic function (G2 or G3) was found to be significant prognostic factor independently of LVEF (G2-3: HR 2.44 [95%CI 1.59-3.70], p &amp;lt; 0.001; LVEF: HR 0.10 [95%CI 0.09-0.10] for every 10%, p = 0.002) (Figure 1). Conclusion Most DCM patients had severely impaired LV systolic function and no or mildly impaired diastolic function. In DCM patients the diastolic dysfunction significantly worsens the prognosis independently of LVEF. Abstract Table 1. Abstract Figure 1.