Ventricular Systolic Impairment Research Articles

Extra-domain A containing fibronectin in pulmonary hypertension and treatment effects of a function-blocking antibody.

Pulmonary vascular and right ventricular remodelling processes are important for development and progression of pulmonary hypertension (PH). The current study analyzed the functional role of the extra domain A containing fibronectin (ED-A+ Fn) for the development of PH by comparing ED-A+ Fn knockout (KO) and wild-type (WT) mice as well as the effects of an antibody-based therapeutical approach in a model of monocrotaline (MCT)-induced PH, which will be validated in a model of Sugen 5416/Hypoxia induced PH. PH was induced using monocrotaline (MCT) (PH mice). 69 mice were divided into the following groups: sham-treated controls (WT: n=7; KO: n=7), PH mice without specific treatment (WT: n=12; KO: n=10), PH mice treated with a dual endothelin receptor antagonist (MAC; WT: n=6; KO: n=11), WT PH mice treated with the F8 antibody, specifically recognizing ED-A+ Fn, (n=8) and WT PH mice treated with an antibody of irrelevant antigen specificity (KSF, n=8). Compared to controls, WT_PH mice showed a significant elevation of the right ventricular systolic pressure (RVPsys, p=0.04) and RV functional impairment including increased basal right ventricular (RVbasal, p=0.016) diameter or tricuspid annular plane systolic excursion (TAPSE, p=0.008). In contrast, KO PH did not show such effects compared to controls (p=n.s.). In WT_PH mice treated with F8, hemodynamic and echocardiographic parameters were significantly improved compared to untreated WT_PH mice or those treated with the KSF antibody (p<0.05). On the microscopic level, KO_PH mice showed significantly less tissue damage compared to the WT_PH mice (p=0.008). Furthermore, lung tissue damage could significantly be reduced after F8 treatment (p=0.04). Additionally, these findings could be verified in the Sugen 5416/Hypoxia mouse model, in which F8 significantly improved echocardiographic, hemodynamic and histologic parameters. ED-A+ Fn is of crucial importance for PH pathogenesis representing a promising therapeutic target in PH. We here show a novel therapeutic approach using antibody-mediated functional blockade of ED-A+ Fn capable to attenuate and partially reverse PH-associated tissue remodelling.

Two-dimensional speckle-tracking echocardiography in left ventricular systolic function in patients with systemic lupus erythematosus.

To investigate whether two-dimensional speckle-tracking echocardiography (2DSTE) can be considered a criterion for early left ventricular (LV) systolic impairment in patients with systemic lupus erythematosus (SLE) and to further explore the association with each other. We included 38 patients with SLE and assessed the degree of disease activity according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000 scoring criteria, together with 38 healthy controls who were matched by sex and age. Routine LV systolic function evaluation parameters were obtained by echocardiography as well as 2DSTE measurement of LV strain parameters to obtain global longitudinal strain (GLS) values, respectively. (I) On routine LV function parameters such as ejection fractions (EF) and left ventricular end-diastolic internal diameter (LVIDd), the SLE group and the control group did not reflect differences. In contrast, on the LV strain parameter obtained from 2DSTE measurements, the GLS values in all cardiac planes were lower in the SLE group than in the control group and showed statistically significant differences. (II) Correlation analysis showed that there was a correlation between SLEDAI and GLS, especially a meaningful correlation with GLS Avg and GLS A4C, with correlation coefficients of 0.35 and 0.47, respectively. The use of 2DSTE can detect early impaired LV systolic function in SLE patients, and GLS is progressively gaining attention as an indicator of subclinical myocardial injury and LV function in SLE patients. The correlation that exists between GLS and SLEDAI might contribute to a better assessment of cardiac involvement in SLE patients. Key Points • Cardiac involvement has become one of the major factors in the poor prognosis of SLE patients, which directly affects the mortality of SLE patients. Traditional echocardiography is difficult to detect early left ventricular function impairment, thus affecting clinicians' judgment and diagnosis. • 2DSTE can recognize subclinical myocardial injury in SLE patients at an early stage, and its derived strain parameters may be used as an indicator to evaluate myocardial involvement and reflect disease activity in SLE patients.

Heart rhythm complexity analysis in patients with inferior ST-elevation myocardial infarction

Heart rhythm complexity (HRC), a subtype of heart rate variability (HRV), is an important tool to investigate cardiovascular disease. In this study, we aimed to analyze serial changes in HRV and HRC metrics in patients with inferior ST-elevation myocardial infarction (STEMI) within 1 year postinfarct and explore the association between HRC and postinfarct left ventricular (LV) systolic impairment. We prospectively enrolled 33 inferior STEMI patients and 74 control subjects and analyzed traditional linear HRV and HRC metrics in both groups, including detrended fluctuation analysis (DFA) and multiscale entropy (MSE). We also analyzed follow-up postinfarct echocardiography for 1 year. The STEMI group had significantly lower standard deviation of RR interval (SDNN), and DFAα2 within 7 days postinfarct (acute stage) comparing to control subjects. LF power was consistently higher in STEMI group during follow up. The MSE scale 5 was higher at acute stage comparing to control subjects and had a trend of decrease during 1-year postinfarct. The MSE area under scale 1–5 showed persistently lower than control subjects and progressively decreased during 1-year postinfarct. To predict long-term postinfarct LV systolic impairment, the slope between MSE scale 1 to 5 (slope 1–5) had the best predictive value. MSE slope 1–5 also increased the predictive ability of the linear HRV metrics in both the net reclassification index and integrated discrimination index models. In conclusion, HRC and LV contractility decreased 1 year postinfarct in inferior STEMI patients, and MSE slope 1–5 was a good predictor of postinfarct LV systolic impairment.

A multimodality assessment of the protective capacity of statin therapy in a mouse model of radiation cardiotoxicity

PurposeDespite technological advances in radiotherapy (RT), cardiotoxicity remains a common complication in patients with lung, oesophageal and breast cancers. Statin therapy has been shown to have pleiotropic properties beyond its lipid-lowering effects. Previous murine models have shown statin therapy can reduce short-term functional effects of whole-heart irradiation. In this study, we assessed the efficacy of atorvastatin in protecting against the late effects of radiation exposure on systolic function, cardiac conduction, and atrial natriuretic peptide (ANP) following a clinically relevant partial-heart radiation exposure. Materials and MethodsFemale, 12-week old, C57BL/6j mice received an image-guided 16 Gy X-ray field to the base of the heart using a small animal radiotherapy research platform (SARRP), with or without atorvastatin from 1 week prior to irradiation until the end of the experiment. The animals were followed for 50 weeks with longitudinal transthoracic echocardiography (TTE) and electrocardiography (ECG) every 10 weeks, and plasma ANP every 20 weeks. ResultsAt 30–50 weeks, mild left ventricular systolic function impairment observed in the RT control group was less apparent in animals receiving atorvastatin. ECG analysis demonstrated prolongation of components of cardiac conduction related to the heart base at 10 and 30 weeks in the RT control group but not in animals treated with atorvastatin. In contrast to systolic function, conduction disturbances resolved at later time-points with radiation alone. ANP reductions were lower in irradiated animals receiving atorvastatin at 30 and 50 weeks. ConclusionsAtorvastatin prevents left ventricular systolic dysfunction, and the perturbation of cardiac conduction following partial heart irradiation. If confirmed in clinical studies, these data would support the use of statin therapy for cardioprotection during thoracic radiotherapy.

α7 nicotinic receptors play a role in regulation of cardiac hemodynamics.

The α7 nicotinic receptors (NR) have been confirmed in the heart but their role in cardiac functions has been contradictory. To address these contradictory findings, we analyzed cardiac functions in α7 NR knockout mice (α7-/-) in vivo and ex vivo in isolated hearts. A standard limb leads electrocardiogram was used, and the pressure curves were recorded in vivo, in Arteria carotis and in the left ventricle, or ex vivo, in the left ventricle of the spontaneously beating isolated hearts perfused following Langedorff's method. Experiments were performed under basic conditions, hypercholinergic conditions, and adrenergic stress. The relative expression levels of α and β NR subunits, muscarinic receptors, β1 adrenergic receptors, and acetylcholine life cycle markers were determined using RT-qPCR. Our results revealed a prolonged QT interval in α7-/- mice. All in vivo hemodynamic parameters were preserved under all studied conditions. The only difference in ex vivo heart rate between genotypes was the loss of bradycardia in prolonged incubation of isoproterenol-pretreated hearts with high doses of acetylcholine. In contrast, left ventricular systolic pressure was lower under basal conditions and showed a significantly higher increase during adrenergic stimulation. No changes in mRNA expression were observed. In conclusion, α7 NR has no major effect on heart rate, except when stressed hearts are exposed to a prolonged hypercholinergic state, suggesting a role in acetylcholine spillover control. In the absence of extracardiac regulatory mechanisms, left ventricular systolic impairment is revealed.

Assessment of Right Ventricular Systolic Function with 3-Dimensional Speckle Tracking Echocardiography in Isolated Mild Mitral Stenosis.

In rheumatic severe mitral stenosis, right ventricular mechanics deteriorate with the increasing severity of mitral stenosis. Therefore, we aimed to investigate right ventricular mechanics in patients with mild mitral stenosis using 3-dimensional speckle tracking echocardiography. In total, 40 patients with mild mitral stenosis and 36 age- and gender-matched healthy controls were included. Conventional echocardiographic examination was performed and 3-dimensional data sets were acquired for strain analysis. Besides conventional echocardiographic parameters, right ventricular volume and function and 3-dimensional speckle tracking echocardiography-derived right ventricular free wall longitudinal strain were compared between patients with mild mitral stenosis and healthy controls. Although 3-dimensional right ventricular volumes and ejection fraction were similar between the groups, 3-dimensional speckle tracking echocardiography-derived right ventricular free wall longitudinal strain was significantly lower in patients with mild mitral stenosis than in controls (25.57 ± 4.39% vs. 27.90 ± 4.71%, P =.028). Significant correlations were observed between right ventricular free wall longitudinal strain and mitral valve area and estimated systolic pulmonary artery pressure (r = 0.597, P <.001; r = -0.508, P =.003, respectively). Another significant positive correlation was observed between planimetric mitral valve area and 3-dimensional speckle tracking echocardiography-derived right ventricular free wall longitudinal strain (r = 0.597, P <.001). The degree of severity of mild mitral stenosis in terms of mitral valve area can help in the early detection of subclinical right ventricular systolic function impairment which can be easily detected by 3-dimensional speckle tracking echocardiography. Right ventricular contractile performance could decrease even in mild mitral stenosis.

Contemporary updates on ventricular arrhythmias: from mechanisms to management.

Ventricular arrhythmias (VAs) are a group of heart rhythm disorders that can be life-threatening and cause significant morbidity. VA in the presence of structural heart disease (SHD) has distinct prognostic implications and requires a comprehensive and multifaceted approach for investigation and management. Early specialist referral should be considered for all patients with VA. Particular urgency is recommended in patients with syncope, nonsustained/sustained VA on Holter monitor and SHD on cardiac imaging because ofthe heightened risk of sudden cardiac death. Comprehensive phenotyping is recommended for most patients with VA, encompassing noninvasive cardiac functional testing, multimodality imaging and genetic testing in select circumstances. Management of idiopathic VA is guided heavily by symptom burden and the presence of ventricular systolic impairment. In SHD, guideline-directed heart failure therapy and device implantation are critical considerations. Whilst commonly used and well-established, antiarrhythmic drugs can be hampered by toxicity and failure of adequate arrhythmia control. Catheter ablation is increasingly being considered a feasible first-line alternative to medical therapy, where outcomes are influenced by disease aetiology and scar burden in SHD. Catheter ablation is associated with reduced arrhythmia recurrence and burden and improved quality of life at follow-up.

Cardiomyopathy Associated with Right Ventricular Apical Pacing-Systematic Review and Meta-Analysis

Bradyarrhythmias are potentially life-threatening medical conditions. The most widespread treatment for slow rhythms is artificial ventricular pacing. From the inception of the idea of artificial pacing, ventricular leads were located in the apex of the right ventricle. Right ventricular apical pacing (RVAP) was thought to have a deteriorating effect on left ventricular systolic function. The aim of this study was to systematically assess results of randomized controlled trials to determine the effects of right ventricular apical pacing on left ventricular ejection fraction (LVEF). we systematically searched the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE databases for studies evaluating the influence of RVAP on LVEF. Pooled mean difference (MD) with a 95% confidence interval (CI) was estimated using a random effect model. 14 randomized controlled trials (RCTs) comprising 885 patients were included. In our meta-analysis, RVAP was associated with statistically significant left ventricular systolic function impairment as measured by LVEF. The mean difference between LVEF at baseline and after intervention amounted to 3.35% (95% CI: 1.80-4.91). our meta-analysis confirms that right ventricular apical pacing is associated with progressive deterioration of left ventricular systolic function.

Correlation of ECG changes at high altitude with findings on Coronary Angiogram.

Objective: To highlight association of coronary artery disease on angiograms and high altitude-related ECG abnormalities that is thought to be ischemic in origin.&#x0D; Place and Duration of Study: This was a cross sectional study done in Armed Force Institute of Cardiology/National Institute of Heart Disease from Oct 2016 to Oct 2021.&#x0D; Methodology: This was a cross sectional study done in AFIC/NIHD from Oct 2016–Oct 2021 (5years). A total of 103 patients at a range of 9000 to 22000 feet in altitude, with new ECG changes were selected via consecutive sampling. Data was analyzed by SPSS version-23. Descriptive statistics were run to present categorical data in frequencies and percentages. Chi-square and Fisher Exact Test was applied to find the association between study variables at 95% CI and 5% margin of error (α= 5%).&#x0D; Results: The data was collected from a total of 103 respondents, mean age (years) of the respondents was 30.57±6.27, and mean duration of stay (days) at high altitude was 64.8±68.3 (Table-I). ECG changes that were recorded were: T-wave inversion in anterior leads (V1, V2, V3) were reported in n=33(32%), T- wave inversion in Inferior leads (II, III, aVF) in 21(20.3%), T-wave inversion in lateral leads (V3-V6) 10(9.7%). Normal Ejection fraction was observed in 97% of the study participants while only 3% had mild left ventricular systolic impairment. Angiographic findings were found to be normal in n=92 (89.30%), minor coronary artery disease (CAD) in n=9 (8.70%), muscle bridge in LAD in n=2 (1.90%). Our results also showed that amongst other final diagnosis, of note were vasovagal syncope (n=5; 4.8%), pulmonary embolism (n=5; 4.8%) and pulmonary arterial hypertension (n=3; 2.9%).&#x0D; Conclusion: Our work leads us to the conclusion that ECG abnormalities at high altitude do not indicate coronary artery disease since they do not reflect a delay in electrical conduction or ischemia. These patients should be treated separately based on their high altitude disease symptoms (HAI).

Dynamic Change of Left Ventricular Mechanics in Patients with Acute Myocarditis with Preserved Left Ventricular Systolic Function: A 2-Year Follow-up Study.

Acute myocarditis mimics acute coronary syndrome due to its clinical course and presentation. This study aimed to evaluate left ventricular longitudinal and circumferential functions during the acute phase and late phase of acute myocarditis with preserved left ventricular ejection fraction using 2-dimensional speckle tracking echocardiography. Forty-one consecutive acute myocarditis patients with preserved left ventricular ejection fraction confirmed by cardiac magnetic resonance imaging underwent 2-dimensional speckle tracking echocardiography within the first week of hospital admission. Findings were compared with age and sex-matched 40 healthy controls. Left ventricular mechanics of the study group were reevaluated by 2-dimensional speckle tracking echocardiography during follow- up (23.85 ± 6.65 months later). Myocardial lesions with late gadolinium enhancement on cardiac magnetic resonance imaging were mostly localized in the subepicardial layer (91.40%) and commonly observed in the inferolateral wall (42.94%). Consistent with the cardiac magnetic resonance imaging findings, 2-dimensional speckle tracking echocardiography showed the localization of the involved myocardial segments with prominent impairment in global longitudinal peak systolic strain and global circumferential strain of the inferolateral wall of the left ventricle. In the acute phase, global longitudinal peak systolic strain (-17.32 ± 2.02 vs -20.59 ± 2.38) and global circumferential strain (-22.33 ± 2.27 vs -24.85 ± 3.19) were found to be lower in patients with acute myocarditis compared to healthy controls (both P &lt; .001). While global circumferential strain was improved in the late phase compared with the acute phase (from -22.28 ± 2.32 to -22.90 ± 2.65; P = .003). Global longitudinal peak systolic strain was not significantly changed during follow-up (from -17.30 ± 2.09 to -17.62 ± 2.19; P = .072). Subtle left ventricular systolic function impairment can be detected by the 2-dimensional speckle tracking echocardiography technique in patients with acute myocarditis with preserved left ventricular ejection fraction and improvement in circumferential function could be observed during follow-up.

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 &amp;gt;14 WU m2 or lesion at high risk of causing PH (Figure 1). This novel, simple risk score performed well (AUC &amp;gt;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.

Cardiomyopathy associated with right ventricular apical pacing – systematic review and meta-analysis

Abstract Aims Bradyarrhythmias are potentially life threatening medical conditions. The most widespread type of treatment of slow rhythms is artificial ventricular pacing. From the inception of the idea of artificial pacing, ventricular lead was located in the apex of the right ventricle. Right ventricular pacing (RVP) was thought to have deteriorating effect on left ventricular systolic function. The aim of this study was to systematically assess results of randomized controlled trials of the right ventricular pacing on left ventricular ejection fraction (LVEF). Methods We systematically searched the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE databases for studies evaluating the influence of the RVP on the LVEF. Pooled mean difference (MD) with a 95% confidence interval (CI) was estimated using a random effect model. Results 15 randomized controlled trials (RCTs) comprising 951 patients were included. The mean follow-up in the included studies ranged between 6 to 24 months. In our meta-analysis, RV pacing was associated with statistically significant (MD 2.91; 95% confidence interval (CI): 1.07–4.75) left ventricular systolic function impairment measured by LVEF. Conclusion Our meta-analysis confirms, that the right ventricular pacing is associated with progressive deterioration of the left ventricular systolic function. 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&amp;lt;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&amp;lt;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.

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.

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.

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.

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

Electrical Cardioversion for Persistent Atrial Fibrillation in the Era of Catheter Ablation: A Real-world Observational Study

Background: Electrical cardioversion (ECV) is frequently performed to treat persistent atrial fibrillation (AF). Although several large trials have suggested that rate control in AF may be non-inferior to rhythm-based strategies, individual patients may have better outcomes in terms of quality of life if sinus rhythm (SR) is achieved and maintained. This real-world, retrospective, observational study aimed to define the success rate and role of ECV in the management of persistent AF in the era of catheter ablation. Methods: All patients who underwent ECV for symptomatic persistent AF at our institution between January 2014 and August 2019 were analysed. Clinical and echocardiographic baseline characteristics were used to identify independent predictors for AF recurrence at 12 and 24 months using a Cox multivariate model. Results: We identified 1,028 consecutive patients with symptomatic persistent AF, 319 of whom were subsequently excluded from the study because they either spontaneously reverted to SR prior to ECV or declined ECV. We evaluated 701 patients (mean age 71 ± 10.8 years, male 70.2%). Acute success was achieved in 96.8% of patients. SR at 12 and 24 months was seen in 26.6% and 14.3% of patients (p&lt;0.0001), respectively. SR at 12 months was seen in 20.4% of patients with a left atrium (LA) diameter of ≤4 cm and in 6.2% of patients with an LA diameter of &gt;4 cm (p&lt;0.0001). At 24 months, SR was seen in 11.5% of patients with a LA diameter of ≤4 cm and in 2.8% with a diameter of &gt;4 cm (p&lt;0.0001). Predictors of SR at 12 months on univariate analysis were normal left ventricular systolic function and mild left ventricular systolic impairment (odds ratio [OR] 1.61, 95% confidence interval [CI] 1.08–2.45, p=0.021 and OR 0.5, 95% CI 0.24–0.94, p=0.043, respectively). In addition, flecainide and sotalol therapy improved the chances of SR at 12 months (OR 2.87, 95% CI 1.16–7.12, p=0.021 and OR 2.25, 95% CI 0.98–5.05, p=0.049, respectively). Multivariate analysis revealed no further positive predictors for SR maintenance in 24 months. Conclusion: ECV was not an effective long-term strategy for the maintenance of SR.

Self-assessment questions

In which of the following conditions should preconception counselling entail that pregnancy is not recommended?A.Mechanical prosthetic heart valveB.Hypertrophic obstructive cardiomyopathyC.Severe left ventricular systolic impairment (EF <30%)D.Previous peripartum cardiomyopathy with recovered cardiac functionE.Systemic right ventricle with normal systolic function.