Left Ventricular Function Ejection Research Articles

Clinical Course and Outcomes in Patients with Left Ventricular Dysfunction Due to Myocardial Infarction After Kawasaki Disease.

Long-term outcomes of patients with left ventricular dysfunction after Kawasaki disease (KD) remain unknown. The clinical course of 37 patients (29 males 8 females) with left ventricular ejection function (LVEF) less than 45% after KD since 1978 was retrospectively investigated. Cardiac events in this study were defined as admissions because of heart failure, fatal ventricular arrhythmias, heart transplantation, and death. Their ages when evaluated ranged from 1 to 70years (median 35years). The onset of KD ranged from 2months to 20years (median 21months). All patients had bilateral coronary artery lesions, and multi-vessel occlusion occurred in 31 patients (84%). Previous myocardial infarction (MI) was found in 28 patients (76%). The interval from the onset of acute KD to the initial MI ranged from 15days to 25years (median 3months). Reperfusion therapy was successful in 6 patients (30%), and coronary artery bypass grafting was performed in 23 patients (62%). Non-sustained ventricular tachycardia and fatal ventricular arrhythmias were detected in 11 patients and 22 patients, respectively. There were 15 deaths (41%). The 20-year and 50-year survival rates after KD were 84% (95% CI 67-92) and 54% (34-73), respectively (n = 37). The 30-year cardiac event-free rate after the detection of low LVEF was 42% (95% CI 27-59). The cutoff point of the left ventricular end-diastolic dimension for cardiac events was 65mm. Patients with low LVEF had fatal ventricular arrhythmias and a worsening of their ischemic cardiomyopathy after 30years of age and their outcomes were poor.

Early recruitable coronary collaterals preserve miocardial viability in late presentation infarctions.

Previous studies showed conflicting results regarding the contribution of coronary collateral circulation (CCC) to myocardial perfusion and function in the setting of myocardial infarction (MI). In the primary angioplasty era, the role of CCC in these studies may have been influenced by the effect of early reperfusion. The true impact of CCC could be clarified by studying its effect on nonreperfused patients. The aim of our study was to evaluate the effect of CCC on myocardial viability of late presentation MI. Between 2008 and 2019, we included 167 patients with a late presentation MI who had a complete angiographic occlusion in a major coronary artery in which myocardial viability of the culprit territory was assessed. Patients were divided according to the presence of angiographic early recruited CCC (ERCC) (Rentrop 2-3) or poor CCC (PCC) (Rentrop 0-1). A lower left ventricular ejection function (LVEF) at discharge (54.2 ± 9 vs. 47.9 ± 12; <0.01) and a more severe left ventricular wall motion abnormalities in the culprit territory were observed in PCC patients. The presence of ERCC was the main independent predictor of myocardial viability in late presentation MI (hazard ratio, 4.24; 95% confidence interval, 1.68-10.6; P < 0.001). At follow-up, wall motion score increased significantly (2.05 ± 0.16; P = 0.02) in patients with ERCC but not in PCC patients (0.07 ± 0.16; P = 0.4), and LVEF improvement was significantly higher in ERCC than in PCC patients (9.7 ± 2.6 vs. 3.8 ± 4.2; P = 0.02). The presence of ERCC was the main independent predictor of myocardial viability in late presentation MI.

The comparative effects of sacubitril/valsartan versusenalapril on pulmonary hypertension due to heart failure with a reduced ejection fraction.

The purpose of this study was to investigate the effects of sacubitril/valsartan on right ventricular (RV) function in patients with pulmonary hypertension (PH) due to heart failure with reduced ejection fraction (HFrEF). We prospectively enrolled patients with HFrEF‐induced PH admitted to the Department of Cardiology between August 2018 and December 2019. Patients were randomized to receive oral treatment with sacubitril/valsartan or enalapril. Epidemiological data were recorded before treatment. Echocardiography was performed at admission and 6 months of follow‐up, and all parameters were compared. Major adverse cardiac events (MACEs) were compared between baseline and 6 months follow‐up. There were no significant differences in the baseline characteristics between the two groups. After 6 months of treatment, both treatment groups improved the following parameters from baseline (mean ± SD): left atrium, left ventricle, the left ventricular ejection function (LVEF), RV systolic function (the tricuspid annular plane systolic excursion [TAPSE], the systolic pulmonary artery pressure [sPAP], and TAPSE/sPAP). After 6 months, sacubitril/valsartan improved significantly the following parameters compared with enalapril (all p < 0.05): LVEF (47.07 ± 6.93% vs. 43.47 ± 7.95%); TAPSE (15.33 ± 1.31 vs. 14.78 ± 1.36 mm); sPAP (36.76 ± 14.32 vs. 42.26 ± 12.07 mmHg); and TAPSE/sPAP ratio (0.50 ± 0.23 vs. 0.39 ± 0.14), respectively. There was no difference in readmissions due to recurrent heart failure. Sacubitril/valsartan seems to provide more beneficial effects among patients with HFrEF‐induced PH to improve RV function, along with a decrease in pulmonary pressure.

Role of TLR4 signaling on Porphyromonas gingivalis LPS-induced cardiac dysfunction in mice.

Oral infections, particularly periodontitis, are a well-established risk factor for cardiovascular diseases, although the molecular mechanisms involved remain elusive. The aims of the present study were to investigate the effects of lipopolysaccharide derived from Porphyromonas gingivalis (PG-LPS) on cardiac function in mice, and to elucidate the underlying mechanisms. Mice (C57BL/6) were injected with PG-LPS (0.8 mg/kg/day) with or without an inhibitor of Toll-like receptor 4 (TLR4) signaling (TAK-242, 0.8 mg/kg/day) for 4 weeks. Left ventricular ejection function was significantly decreased at 1 week (from 67 ± 0.5 to 58 ± 1.2%) and remained low at 4 weeks (57 ± 1.0%). The number of apoptotic myocytes was increased (approximately 7.4-fold), the area of fibrosis was increased (approximately 3.3-fold) and the number of 8-hydroxydeoxyguanosine-positive myocytes, a sensitive indicator of oxidative DNA damage, was increased (approximately 7.6-fold) at 4 weeks in the heart of PG-LPS treated mice. However, levels of various serum pro-inflammatory cytokines in PG-LPS-treated mice were similar to those in control mice. The impairment of cardiac function in PG-LPS-treated mice appears to involve activation of TLR4-NADPH oxidase (NOX) 4 signaling, leading to abundant production of reactive oxygen species and Ca2+ leakage from sarcoplastic reticulumn induced by calmodulin kinase II (CaMKII)-mediated phosphorylation of phospholamban (at Thr-17) and ryanodine receptor 2 (at Ser-2448). Pharmacological inhibition of TLR4 with TAK-242 attenuated the changes in cardiac function in PG-LPS-treated mice. Our results indicate that TLR4-NOX4 signaling may be a new therapeutic target for treatment of cardiovascular diseases in patients with periodontitis.

P228 WEARABLE DEFIBRILLATOR IN CLINICAL PRACTICE. MULTIANNUAL MULTI–CENTER EXPERIENCE

Abstract Introduction Heart failure with reduced left ventricular ejection function (LVEF) represents a life–threatening condition for patients (pts). A period of time of 40–90 days, in optimal medical therapy, is indicated to evaluate the recovery of the LVEF and the indication to ICD implantation. In this period, from 1% to 5% of pts can experience sudden death. We evaluated the usefulness of the wearable cardioverter defibrillator (WCD) as a temporary antiarrhythmic therapy in the interval from discharge to the three–month follow–up. Methods From December 2015 to December 2021, 174 consecutive pts (141 M (81%); mean age 62 years ± 11.6 years) were discharged with reduced FE &amp;lt; 35% in OMT, with WCD and were re–evaluated within 3 months to establish indication for ICD implantation. Results 110 pts (63.2%) recovered LVEF at 3 months and left the indication to ICD. 9 pts refused and/or returned the WCD due to poor compliance (5.2%); 52 pts (29.9%) did not recover LVEF and were implanted with ICD. The WCD was worn continuously by the majority of pts with good compliance for 87.4 ± 52.0 days (range 1 ÷ 303 days), for 22.08 hours / day. 23 episodes of AF were correctly recognized; 10 TVNS&amp;gt; 10 sec; 1 episode of VF in 1 patient in which 1 shock was correctly delivered. 1 inappropriate shock was delivered on tachycardic AF. During the WCD wearing period, 3 deaths occurred (1.7%): in 2 pts due to refractory HF (one of these pts had VF correctly recognized and treated by the WCD but degenerated into pulseless activities); 1 death for terminal cancer). The use of WCD has progressively increased over the years (from 4.5 LV / yy in 2015–16 to 45 LV / yy in 2020–21). Conclusions The use of WCD has gradually increased in clinical practice for patients who have not yet developed clear indications for ICD implantation. In the majority of them, ventricular dysfunction is transient. Wearable cardioverter defibrillator represents additional security during this period. Continuous monitoring makes it possible to identify supraventricular and ventricular arrhythmias, improving therapeutic appropriateness and in general the patients have excellent compliance with the device. Further studies are needed to substantiate this strategy.

P26 “FUNCTION FOLLOWS FORM”: THE ROLE OF THE CARDIAC MAGNETIC RESONANCE IN THE ARRHYTHMIC RISK STRATIFICATION IN PATIENTS WITH CARDIAC SARCOIDOSIS

Abstract Background Sarcoidosis is an inflammatory disorder characterized by non–caseating granulomatous infiltration in multiple organs, including the heart. The presence of granulomas within the myocardium can cause heart failure, atrio–ventricular block, ventricular arrhythmias (VA) and sudden cardiac death (SCD). Due to the patchy pattern of sarcoid infiltration, endomyocardial biopsy has a poor sensitivity and cardiac magnetic resonance (CMR) is becoming the gold standard imaging, detecting small area of myocardial fibrosis and scar using late gadolinium enhancement (LGE). The identification of LGE in patients with dilated cardiomyopathy is strongly associated with VA and SCD and similar findings were reported in cardiac sarcoidosis (CS) patients. Methods In order to assess the risk of VA and SCD related to LGE in the CS, we performed a meta–analysis including all the studies enrolling patients with suspected or confirmed CS undergoing CMR. We conducted a digital search in PubMed, Embase, Cochrane Database of Systematic Reviews, Web of Science, Scopus, and Google Scholar from inception through October 2021. Clinical outcomes of interest were arrhythmogenic events defined as VA (ventricular tachycardia or ventricular fibrillation), SCD or aborted SCD (appropriate ICD discharge) during follow–up. Results Eleven studies with a total of 1.123 CS patients (left ventricular ejection function [LVEF]: 59 ± 23%) with an appropriate follow–up were included in the final analysis. Overall, as depicted in the Figure 1, the identification of LGE at CMR was associated with a 13–fold increase risk in potentially lethal VA (R = 12.76, 95% CI [6.30–25.87]) than patients without LGE. Conclusions Our findings suggest that the presence of myocardial scarring as evidenced by the identification of LGE in CMR provides meaningful information about the arrhythmic risk stratification of CS patients.

Preventive Effect Observation of Dapagliflozin on Middle and Later Ventricular Remodeling in Patients with Acute ST Segment Elevation Anterior Wall Myocardial Infarction: A Single-Center, Retrospective Cohort Study.

Objective: This study aimed to observe the effect of dapagliflozin on left ventricular ejection function (LVEF) and left ventricular end-diastolic volume (LVEDV) in patients with acute anesthesia ST segment elevation myocardial infarction (ASTEMI) and explore the effect of prophylactic treatment on ventricular remodeling (VR). Methods. A retrospective cohort design was employed to collect 188 patients with anterior wall STEMI who received emergency percutaneous coronary intervention (PCI). The patients were divided into dapagliflozin group and control group. The baseline data, the results of echocardiography at 6 months and on admission, and the proportion of VR were compared between the two groups. Echocardiography followed up for the two groups for 6 months after PCI and VR (LVEDV increased ≥20%) were considered the main clinical outcomes. Single-factor and multifactor logistic regression was conducted to explore the preventive effect of dapagliflozin on VR in patients with anterior wall STEMI. Results. There were significant differences in gender, history of diabetes, glycosylated hemoglobin (Hb1AC), admission LVEF, Killip grade of heart failure, and brain natriuretic peptide (BNP) between the dapagliflozin group and the control group regarding the baseline data. Compared with the results of echocardiography at admission and 6 months, the decrease in LVEDV and the increase of LVEF at 6 months in the dapagliflozin group were significantly higher than those in the control group. During the follow-up of 6 months, the VR rate in the dapagliflozin group was significantly lower than that in the control group. Multifactor logistic regression analysis suggested that the risk of VR was reduced by taking dapagliflozin after the adjustment of the confounding factors. Additionally, the combined use of dapagliflozin, ACEI/ARB, and β-block can further reduce the risk. Conclusion. Regular taking of dapagliflozin has a positive effect on the improvement of middle and LVEF and left ventricular volume enlargement in patients with anterior wall STEMI, as well as the prevention of the occurrence of VR.

In-Hospital and Long-Term Outcomes of ST-Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention

Introduction: We evaluated in-hospital and long-term outcomes of patients who underwent primary percutaneous coronary intervention (PCI) in a tertiary center. Patients and Methods: We examined 1550 patients (mean age= 58.5 years, 83.1% male) admitted with acute ST-segment elevation myocardial infarction (AMI) who underwent primary PCI and were followed-up prospectively. The primary outcomes were in-hospital death and major adverse cardiac events (MACE) at follow-up. Results: The mean duration of ischemia at admission was 2.85 ± 2.49 hours; 10.3% of the patients were Killip class III or IV. The mean door-to-device time was 43 (29-52) minutes. During hospitalization, all-cause mortality occurred in 73 patients (4.7%). Multivariate analysis revealed that advanced age, impaired left ventricular ejection function, high Killip functional class, hemoglobin level at admission, ventricular arrhythmias, and advanced atrioventricular block were independent predictors of poor prognosis (OR= 1.07, 0.93, 15.34, 1.44, 3.79, and 4.26 respectively). Among discharged patients with a median 49.5 (25-73) months follow-up, 12.4% of them died, 12.5% had a recurrent myocardial infarction (MI), and 2.3% had a cerebrovascular accident. The strongest independent MACE predictors were impaired left ventricular function, poor glomerular filtration rate, low albumin level, and a history of cerebrovascular disease (HR= 0.97, 0.99, 0.65, and 2.50, respectively). Secondary outcomes were contrast-induced acute kidney injury (16.7%), ventricular arrhythmias (6.1%), advanced atrioventricular block (3.7%), atrial fibrillation (7.6%), and major bleeding (1.6%). Conclusion: AMI still has a poor long-term prognosis. These results emphasize the advantages of rapid, non-delayed revascularization. Patients should be followed-up closely after discharge in both the short- and long-term.

Carotid Reservoir Pressure Decrease After Prolonged Head Down Tilt Bed Rest in Young Healthy Subjects Is Associated With Reduction in Left Ventricular Ejection Time and Diastolic Length.

BackgroundThe arterial pressure waveform reflects the interaction between the heart and the arterial system and carries potentially relevant information about circulatory status. According to the commonly accepted ‘wave transmission model’, the net BP waveform results from the super-position of discrete forward and backward pressure waves, with the forward wave in systole determined mainly by the left ventricular (LV) ejection function and the backward by the wave reflection from the periphery, the timing and amplitude of which depend on arterial stiffness, the wave propagation speed and the extent of downstream admittance mismatching. However, this approach obscures the ‘Windkessel function’ of the elastic arteries. Recently, a ‘reservoir-excess pressure’ model has been proposed, which interprets the arterial BP waveform as a composite of a volume-related ‘reservoir’ pressure and a wave-related ‘excess’ pressure.MethodsIn this study we applied the reservoir-excess pressure approach to the analysis of carotid arterial pressure waveforms (applanation tonometry) in 10 young healthy volunteers before and after a 5-week head down tilt bed rest which induced a significant reduction in stroke volume (SV), end-diastolic LV volume and LV longitudinal function without significant changes in central blood pressure, cardiac output, total peripheral resistance and aortic stiffness. Forward and backward pressure components were also determined by wave separation analysis.ResultsCompared to the baseline state, bed rest induced a significant reduction in LV ejection time (LVET), diastolic time (DT), backward pressure amplitude (bP) and pressure reservoir integral (INTPR). INTPR correlated directly with LVET, DT, time to the peak of backward wave (bT) and stroke volume, while excess pressure integral (INTXSP) correlated directly with central pressure. Furthermore, Δ.INTPR correlated directly with Δ.LVET, and Δ.DT, and in multivariate analysis INTPR was independently related to LVET and DT and INTXSP to central systolic BP.ConclusionThis is an hypothesis generating paper which adds support to the idea that the reservoir-wave hypothesis applied to non-invasively obtained carotid pressure waveforms is of potential clinical usefulness.

Relationship Between Fragmented QRS Complex and Left Ventricular Fibrosis and Function in Patients With Danon Disease.

BackgroundFragmented QRS (f-QRS) complex on the surface ECG is a cardiac conduction abnormality that indicates myocardial scarring. The relationship between the f-QRS complex and cardiac status in patients with Danon disease (DD) remains unclear and will be explored in this study.MethodsPatients with genetically confirmed DD and cardiac magnetic resonance imaging (CMR) examinations were recruited from multiple centers. The number of leads, pattern, score, and segmental distribution of the f-QRS complex were assessed by surface 12-lead ECG. Cardiac status, such as left ventricular (LV) volume, function, and extent of late gadolinium enhancement (LGE), was demonstrated by CMR. The segmental distribution of LGE was also assessed. Correlations between the f-QRS and cardiac status were assessed.ResultsFifteen patients (14 men) with DD who underwent 12-lead ECG and CMR imaging were included. The f-QRS complex was documented in all patients (n = 15, 100%). Three patterns of f-QRS were found, with the notched R/S pattern (74%) being the most common, followed by fragmented QRS (16%) and various RSR' (11%). The fragmented QRS pattern showed an association with a higher level of myocardial fibrosis (LGE > 35%). The burden of f-QRS in each patient was assessed by the number of leads with f-QRS (median 7, range 2–12) and the f-QRS score (median 9, range 2–33). In the correlation analysis, the f-QRS score was positively correlated with LGE% (r = 0.726, p = 0.002), negatively correlated with LV ejection function (LVEF; r = −0.617, p = 0.014) as evaluated by CMR. In the local distribution, f-QRS score and LGE% were both predominant in the LV free wall but did not correlate well among the anterior, lateral, and inferior segments.ConclusionIn this DD cohort, the quantitative f-QRS was correlated well with myocardial fibrosis burden and LV dysfunction in general. This finding suggests that f-QRS can be used as a simple screening tool to assess cardiac status in patients with DD.

Prevalence and risk factors of trastuzumab induced cardiotoxicity in Tunisian HER2-positive breast cancer patients.

Cardiotoxicity is the most important side effect of Trastuzumab treatment. The purpose of this study is to evaluate the prevalence of Trastuzumab induced cardiotoxicity and to analyze risk factors associated with this side effect. A retrospective institutional study was carried out from June 2018 to December 2018 at the department of Medical Oncology of Salah Azaiz institute, Tunis, Tunisia. Demographic, clinical characteristics (menopausal status, breast cancer stage, anthracyclines exposure, comorbidities presence…) and left ventricular ejection function (LVEF) measurements, were collected from patient records. Twenty-three women (20%) had Trastuzumab induced cardiotoxicity.65.2% (N = 15) experienced a decrease in LVEF more than 10% with a decrease below normal value and 34.8% (N = 8) experienced a decrease in LVEF more than 20%. Obesity is a risk factor for the occurrence of Trastuzumab induced cardiotoxicity (adjusted odds ratio (OR) = 2.919 (95% confidence interval (CI) [1.0411-8.186]; p = 0.042). Our study highlighted that obesity is associated with a high risk of cardiotoxicity in women treated with Trastuzumab. Therefore, close monitoring of cardiac function is recommended especially for obese women during Trastuzumab administering.

Epicardial fat thickness in infants of diabetic mothers.

Epicardial fat thickness (EFT) in adults and children has been related to the metabolic syndrome and other cardiovascular risk factors; however, scarce studies have evaluated it in infants of diabetic mothers (IDM) in whom, alterations in the thickness of the interventricular septum have been reported. This study compares the EFT in IDM versus infants of non-diabetic mothers (INDM) and its association with others echocardiographic parameters. We performed a cross sectional study in 93 infants (64 IDM and 29 INDM). To evaluate EFT dimensions, an echocardiogram was performed within the first 24h of extrauterine life in both groups. In diabetic mothers, HbA1c was also determined. There was no significant difference in birth weight between the groups although gestational age was lower in IDM. The EFT (3.6 vs. 2.5 mm, p < 0.0001), the interventricular septum thickness (IVST) (6.2 vs. 5.2 mm, p < 0.0001) and the IVST / left ventricle posterior wall (1.3 vs. 1.1, p = 0.001) were higher in the IDM; while the left ventricular expulsion fraction [LVFE] (71.1 vs. 77.8; p < 0.0001) was lower than in the INDM, respectively. We found a positive correlation between EFT with IVST (r = 0.577; p = 0.0001), LVPW (r = 0.262; p = 0.011), IVST/LVPW index (r = 0.353; p = 0.001), and mitral integral early velocity (r = 0.313; p = 0.002), while a negative correlation with LVFE was observed (r = -0.376; p = 0.0001). The EFT is higher in IDM than in INDM. It was positively related with echocardiographic parameters of left ventricular thickness and negatively with left ventricular ejection function.

Abstract 9430: A Novel Soluble Epoxide Hydrolase Peptide Vaccine Attenuates Cardiac Remodeling After Myocardial Infarction Through Angiogenesis

Introduction: Vaccination therapy has long-lasting effects and solves medication non-adherence. However, vaccination therapy on myocardial infarction (MI) has not been developed. Epoxyeicosatrienoic acids (EETs) play an important role in cardio-protective mechanisms through angiogenesis. Here, we developed a soluble epoxide hydrolase (sEH) peptide vaccine to increase the level of EETs and assessed its therapeutic effect for MI-induced heart failure. Hypothesis: We predicted that neovascularization by a sEH vaccine would reduce infract size and prevent post-MI cardiac remodeling. Methods and Results: We made a sEH peptide vaccine based on the amino-acid sequences and administrated the vaccine to rats. ELISA showed that the vaccine induced anti-sEH antibody. Mass spectrometry also confirmed that the vaccine significantly increased blood EETs levels compared to the saline group (P=0.007). We evaluated the effects of the sEH vaccine in the rat model of MI. One week after the left anterior descending artery (LAD) ligation, the vaccinated group significantly suppressed the increase of left ventricular systolic diameter (LVDs) and prevented the decline in left ventricular anterior wall (LVAW), fractional shortening (FS), and ejection function (EF) in echocardiography (P&lt;0.001, P&lt;0.001, P=0.002, and P&lt;0.001 respectively). With the pathological evaluation of the hearts, it was clear that the number of micro-vessels increased in the vaccinated group by immunostaining for CD31 and α-SMA (P=0.015 and P=0.027 respectively). Azan staining showed that infarct-induced fibrosis was lower in the vaccinated group (P=0.029). Western blot showed higher vascular endothelial growth factor (VEGF) expressions of heart muscles in the vaccinated group (P=0.040). Conclusion: The sEH vaccine therapy for MI induces angiogenesis, which promotes reverse cardiac remodeling. This vaccine is expected to be a treatment option to prevent heart failure after MI.

Effects of chronic Porphylomonas gingivalis lipopolysaccharide infusion on cardiac dysfunction in mice

ObjectivePeriodontitis (PD) is a chronic inflammatory disease of tooth-supportive tissue. An association between PD and cardiovascular disease (CVD) has been established. Although PD is generally accepted as a risk factor for CVD, the existence of a relationship remains debatable. Possible mechanisms include the release of inflammatory mediators such as lipopolysaccharide (LPS), which may spread systemically and promote CVD. MethodsTo compare the effects of lipopolysaccharide derived from Porphylomonas gingivalis (PG-LPS) on cardiac muscle in mice, mice were treated for 1 week with/without PG-LPS at a dose equivalent to the circulating level in PD patients (0.8 mg/kg/day). ResultsCardiac function in terms of left ventricular ejection function was significantly decreased at 1 week compared to that in the control (from 66 ± 0.5% to 57 ± 1.1%). Compared to the controls, the number of apoptotic myocytes and the area of fibrosis were significantly increased by approximately 2.7-fold and 14-fold, respectively. The impairment of cardiac function appeared to involve the activation of cAMP/PKA signaling and cAMP/calmodulin kinase II signaling (CaMKII), leading to cardiac fibrosis, myocyte apoptosis and heart failure. ConclusionsOur results indicate that cAMP/PKA and cAMP/CaMKII signaling may be a new therapeutic target for the treatment of cardiovascular diseases in patients with periodontitis.

Maternal Fructose Intake Exacerbates Cardiac Remodeling in Offspring with Ventricular Pressure Overload.

Recent studies demonstrated that metabolic syndrome and cardiovascular diseases could be elicited by developmental programming, which is regulated by prenatal nutritional and environmental stress. In this study, we utilized a rat model to examine the effect of excessive maternal fructose intake during pregnancy and lactation on cardiac development and progression of pressure overload-induced cardiac hypertrophy in offspring. Transverse aortic constriction (TAC) was performed on 3-month-old male offspring to induce ventricular pressure overload. Four weeks post-TAC, echocardiographic assessment as well as histopathological and biochemical examinations were performed on the myocardium of the offspring. Echocardiographic and gross examinations showed that heart weight, interventricular septal thickness in diastole (IVD; d), and left ventricular posterior wall thickness in diastole (LVPW; d) were elevated in offspring with TAC and further increased by maternal fructose exposure (MFE). However, the left ventricular ejection function was not significantly affected. Myocardial histopathological examination revealed that the indices of fibrosis and oxidative stress were higher in offspring with MFE and TAC than those in animals receiving either treatment. Molecular examinations on the myocardium demonstrated an MFE-induced upregulation of p38-MAPK signaling. Next generation sequence (NGS) analysis indicated a modulation of the expression levels of several cardiac hypertrophy-associated genes, including GPR22, Myh7, Nppa, P2RX4, and Npy by MFE. Subsequent RT-PCR indicated that MFE regulated the expression levels of genes responsive to cardiac hypertrophy (i.e., Myh-7, ANP) and oxidative stress (i.e., GR, GPx, and NQO-1). In conclusion, MFE during pregnancy and lactation modulated myocardial gene expression, increased oxidative stress, and exacerbated ventricular pressure overload-induced cardiac remodeling in rat offspring.

Association of ICAM-1 with low left ventricular ejection fraction in patients with advanced coronary artery disease

Background and Aims: Decreased of left ventricular ejection function affects the quality of life and survival of patients with cardiovascular disease. The purpose of this study is to investigate the relationship between left ventricular dysfunction and the blood plasma ICAM-1 protein in patients with coronary artery disease.

Genetics of hypertrophic cardiomyopathy: Genotype-phenotype correlation

Hypertrophic cardiomyopathy (HCM) has a sarcomeric origin in more than half of cases. Correlations between a mutation presence and the clinical, electrical and echocardiographic phenotype are not clearly characterised. To determine the link for HCM patients between the genotype/phenotype, and the impact of a found mutation. We studied a group of 104 patients with a HCM diagnosis (average age: 56 ± 15 years). Clinical, echocardiographic, electrocardiographic as well as genetic data were evaluated and compared. Genotype-positive patients were more likely to be younger (50,9 ± 17.5 years versus 39,9 ± 17.6, P < 0.01), more often women (56% versus 27%, P < 0.01), had more family history of hypertrophic cardiomyopathy (51% versus 18%, P < 0.001) and an increased incidence of sudden death (2,99 ± 2,83 versus 1,97 ± 1,2, P = 0.03). Echocardiographically, they were less often obstructive ( P < 0.01) and had a reduced left ventricular ejection function ( P = 0.02). Electrically, there was no difference in left ventricular hypertrophy ECG variables or in repolarization problems between the two groups. Genotype-phenotype link for HCM patients is low and both the ECG and the echocardiography are not relevant. The presence of a mutation is associated with an increased risk of sudden death. Genetic testing for HCM patients remains essential considering the impact of non-genetic factors.

Cytoprotective effects of spirulina extract against doxorubicin‐induced cardiotoxicity: Biochemical evidences and translational perspectives in cardio-oncology.

e15042 Background: Spirulina, a blue-green algae used in the daily diet of natives of Africa and America, has antioxidant, anticancer, antiviral, hepatoprotective, immune enhancing and lipid-lowering effects. Considering that doxorubicin-induced cardiotoxicity involves myocardial inflammation, ferroptosis and overexpression of several cytokines involved in cell dead and apoptosis, the use of spirulina during exposure to doxorubicin could be an intriguing method to reduces myocardial injuries in cancer patients undergoing treatment with anthracyclines. Methods: Human fetal cardiomyocytes (HFC cell line) were exposed to doxorubicin (from 10 to 500 nM), alone or in combination with spirulina extract (from 10 to 100 µg/ml) for 24 and 48h. After the incubation period, we performed the following tests: determination of cell viability, through analysis of mitochondrial dehydrogenase activity, study of lipid peroxidation (quantifying cellular Malondialdehyde and 4-hydroxynonenal), intracellular Ca2+ homeostasis. Moreover, pro-inflammatory studied were also performed (activation of NLRP3 inflammasome; expression of TLR4/MyD88; mTORC1 Fox01/3a; transcriptional activation of p65/NF-κB and secretion of cytokines involved in cardiotoxicity (Interleukins 1β, 8, 6). Results: Spirulina extract, co-incubated with doxorubicin exerts cardioprotective effects, enhancing cell viability of 20-36.7 % compared to untreated cells (p&lt;0,01 for all); spirulina extract reduced significantly the cardiotoxicity through MyD88/NF-KB/cytokines axis and mTORC1 Fox01/3α mediated mechanisms and reduces oxidative damages of doxorubicin resulting in lower intracellular calcium content. Conclusions: For the first time, it was demonstrated that spirulina extract exert anti-inflammatory and cytoprotective properties in myocardial cells exposed to growing concentration of doxorubicin leading to preclinical studies in mice analyzing any effects on cardiac strain and left ventricular ejection function.

Asociación entre interleuquinas inflamatorias y la presencia de trastornos intraventriculares de la conducción en pacientes con serología positiva para enfermedad de Chagas y función ventricular conservada

Background: Intraventricular conduction disturbances are common in patients with Chagas disease and preserved left ventricular ejection fraction, but their association with higher inflammatory activity is unknown. Objectives: The aim of this study was to determine the presence of an association between interleukin levels and intraventricular conduction disturbances in patients with positive serology for Chagas disease and preserved left ventricular function. Methods: Twenty-two patients between 22 and 80 years of age with positive serology test for Chagas disease with more than 20 years progression and left ventricular ejection fraction ≥50% were included in the study and compared with a control group of 14 healthy individuals. Plasma levels of IFN-γ, IL-1β, IL-6, IL-10, IL-12 (p70), IL-15, IL-17A, MCP-1/CCL2, MIP-1 a/CCL3, TNF-a and IL-2 were measured in patients and controls. Right bundle branch block, left anterior hemiblock or left bundle branch block were considered intraventricular conduction disturbances. Results: Among the 22 patients with positive serology for Chagas disease, 10 presented intraventricular conduction disturbances (45.4%). This group had elevated levels of interleukins with high inflammatory effect such as INF-γ, IL-15, IL-2, IL-12, MIP-1 α, compared with the control group, and high levels of IL-10 as a regulatory mechanism of an excessive immune response. Conclusions: The association between elevated levels of inflammatory interleukins and intraventricular conduction disturbances suggests that chronic inflammation may play a role in the development of these abnormalities in patients with positive serology for Chagas disease and preserved left ventricular ejection function.

Aortic valve-sparing root replacement with Tirone E. David's reimplantation technique: single-centre 25-year experience.

Tirone E. David described aortic valve-sparing root reimplantion (AVSRR) almost 30 years ago. At our centre, we adopted this operation in 1993, and since then, we have performed >700 operations over a time period of >25 years. In this report, we present our single-centre experience. Between 1993 and 2019, a total of 732 patients underwent AVSRR at our centre. The mean age was 53 ± 15 and 522 (71%) were male. Marfan syndrome was present in 117 (16%) patients and bicuspid aortic valve in 81 (11%). The indication for surgery was aortic root aneurysm in 588 (80%) patients and acute aortic dissection in 144 (20%) patients. Mini-sternotomy was performed in 74 (10%) patients. A straight tube graft (David I) was used in 677 (92%) and a Valsalva-graft in 55 (8%) patients. Cusp plasty was done in 83 (11%) patients. Concomitant cardiac procedures were performed in 438 (60%) patients. Overall in-hospital mortality was 3.8% (n = 29) and 1.9% (n = 11) in elective cases. Postoperative echocardiography was available for 671 patients and showed aortic insufficiency (AI) ≤I° in 647 (96%) patients. The mean follow-up time was 10 ± 6.7 years and comprised a total of 7307 patient-years. The 1-, 5-, 10- and 15-year survival rates were: 93%, 88%, 77% and 65%, respectively. The rates for freedom from valve-related reoperation at 1, 5, 10 and 15 years after initial surgery were 97%, 93%, 88% and 85%, respectively. Cox regression analysis identified age [odds ratio (OR) = 0.975, 95% confidence interval (CI) = 0.955-0.995, P = 0.016], hyperlipidaemia (OR = 1.980, 95% CI = 1.175-3.335, P = 0.010), preoperative level of left ventricular ejection function (OR = 1.749, 95% CI = 1.024-2.987, P = 0.041) and postoperative degree of AI (OR = 1.880, 95% CI = 1.532-2.308, P ≤ 0.001) as risk factors for the future AI or reoperation. David procedure can be performed extremely safely, with low risks for perioperative morbidity and mortality, both in elective situations via minimally invasive access and in emergent settings for acute aortic type A dissection. Regarding long-term outcome, David's AVSRR seems to provide excellent clinical results and sustainable function of the aortic valve in the majority of patients almost 3 decades after its introduction.