Subsequent Development Of Heart Failure Research Articles

Abstract 16532: Mosaic Loss of Y Chromosome in Leukocytes Predicts Death in Patients With Chronic Heart Failure Across the Whole Spectrum of Ejection Fraction

Aims: Mosaic loss of Y chromosome (LOY) in men increases with age and correlates with clonal expansion of myeloid cells. Experimental modeling demonstrated that LOY in hematopoietic cells leads to diffuse cardiac fibrosis and subsequent development of heart failure in mice. Cardiac fibrosis is an important pathogenic feature in heart failure irrespective of etiology. Therefore, we investigated the prognostic significance of LOY in men with chronic heart failure. Methods and Results: In a total of 705 male patients with chronic heart failure with reduced and preserved ejection fraction, LOY was determined by digital PCR of peripheral blood cells by assessing the 6bp sequence difference between the AMELX and AMELY genes. ROC analysis relating the extent of LOY to mortality revealed a LOY of 17% as the optimal cut-off value to predict death during follow-up. LOY >17% was observed in 18.6% of all patients, increased with age and was associated with increased mortality after three years (13,7% in patients without LOY compared to 29.0% in patients with LOY, p<0.001, Figure 1). LOY remained an independent predictor of death in multivariate analysis including, age, LVEF and nt-pro BNP serum levels (HR 1,67; 95% CI 1.08-2.57; p=0.017). Importantly, LOY was associated with increased mortality in patients with heart failure with reduced ejection fraction defined as LVEF < 50% (p<0.001) as well as in patients with preserved LVEF ≥ 50% (p=0.01). Conclusion: Among patients with heart failure, LOY in blood cells is associated with increased risk of death across the complete range of ejection fraction. Further studies are warranted to discern if LOY associates with cardiac fibrosis in men with heart failure and triggers increased profibrotic signaling. The results of this study may inform trials evaluating precision-targeted anti-fibrotic therapies in patients with chronic heart failure.

Diagnosis and management of patients with left ventricular hypertrophy: Role of multimodality cardiac imaging. A scientific statement of the Heart Failure Association of the European Society of Cardiology.

Left ventricular (LV) hypertrophy consists in an increased LV wall thickness. LV hypertrophy can be either secondary, in response to pressure or volume overload, or primary, i.e. not explained solely by abnormal loading conditions. Primary LV hypertrophy may be due to gene mutations or to the deposition or storage of abnormal substances in the extracellular spaces or within the cardiomyocytes (more appropriately defined as pseudohypertrophy). LV hypertrophy is often a precursor to subsequent development of heart failure. Cardiovascular imaging plays a key role in the assessment of LV hypertrophy. Echocardiography, the first-line imaging technique, allows a comprehensive assessment of LV systolic and diastolic function. Cardiovascular magnetic resonance provides added value as it measures accurately LV and right ventricular volumes and mass and characterizes myocardial tissue properties, which may provide important clues to the final diagnosis. Additionally, scintigraphy with bone tracers is included in the diagnostic algorithm of cardiac amyloidosis. Once the diagnosis is established, imaging findings may help predict future disease evolution and inform therapy and follow-up. This consensus document by the Heart Failure Association of the European Society of Cardiology provides an overview of the role of different cardiac imaging techniques for the differential diagnosis and management of patients with LV hypertrophy.

Idebenone attenuates ferroptosis by inhibiting excessive autophagy via the ROS-AMPK-mTOR pathway to preserve cardiac function after myocardial infarction

Cardiovascular diseases (CVDs) are the leading causes of mortality worldwide. As a type of CVDs, myocardial infarction (MI) induces ischemia hypoxia, which leads to excessive reactive oxygen species (ROS), resulting in multiple cell deaths and contributing to the subsequent development of heart failure or premature death. Recent evidence indicates that ROS-induced lipid peroxidation promotes autophagy and ferroptosis, leading to the loss of healthy myocardium and resulting in the dysfunction of cardiac tissue. Theoretically, cardiac function would be preserved after MI by inhibiting autophagy and ferroptosis. As an analog of coenzyme Q10 (CoQ10) and a clinically approved drug, idebenone would be used to inhibit ferroptosis and preserve cardiac function due to its capacity to improve mitochondrial physiology with antioxidant and anti-inflammatory properties. Here, we confirmed that the addition of idebenone inhibited H2O2-induced and RSL3-induced ferroptosis. Furthermore, the ROS-AMPK-mTOR pathway axis was identified as the signaling pathway that idebenone stimulated to prevent excessive autophagy and consequent ferroptosis. In the MI animal model, idebenone demonstrated a cardioprotective role by regulating ROS-dependent autophagy and inhibiting ferroptosis, which paves the way for the future clinical translation of idebenone in MI management.

Comparisons of serum non-transferrin-bound iron levels and fetal cardiac function between fetuses affected with hemoglobin Bart's disease and normal fetuses.

To compare the levels of Non-transferrin bound iron (NTBI) in fetuses with anemia, using Hb Bart's disease as a study model, and those in unaffected fetuses and to determine the association between fetal cardiac function and the levels of NTBI. A prospective study was conducted on pregnancies at risk of fetal Hb Bart's disease. All fetuses underwent standard ultrasound examination at 18-22 weeks of gestation for fetal biometry, anomaly screening and fetal cardiac function. After that, 2 ml of fetal blood was taken by cordocentesis to measure NTBI by Labile Plasma Iron (LPI), serum iron, hemoglobin and hematocrit. The NTBI levels of both groups were compared and the correlation between NTBI and fetal cardiac function was determined. A total of 50 fetuses, including 20 fetuses with Hb Bart's disease and 30 unaffected fetuses were recruited. There was a significant increase in the level of serum iron in the affected group (median: 22.7 vs. 9.7; p-value: 0.013) and also a significant increase in NTBI when compared with those of the unaffected fetuses (median 0.11 vs. 0.07; p-value: 0.046). In comparisons of fetal cardiac function, myocardial performance (Tei) index of both sides was significantly increased in the affected group (left Tei: p = 0.001, Right Tei: p = 0.008). Also, isovolumetric contraction time (ICT) was also significantly prolonged (left ICT: p = 0.00, right ICT: p = 0.000). Fetal LPI levels were significantly correlated inversely with fetal hemoglobin levels (p = 0.030) but not significantly correlated with the fetal serum iron levels (p = 0.138). Fetal LPI levels were also significantly correlated positively with myocardial performance index (Tei) of both sides (right Tei: R = 0.000, left Tei: R = 0.000) and right ICT (R = 0.013), but not significantly correlated with left ICT (R = 0.554). Anemia caused by fetal Hb Bart's disease in pre-hydropic stage is significantly associated with fetal cardiac dysfunction and increased fetal serum NTBI levels which are significantly correlated with worsening cardiac dysfunction. Nevertheless, based on the limitations of the present study, further studies including long-term data are required to support a role of fetal anemia as well as increased fetal serum NTBI levels in development of subsequent heart failure or cardiac compromise among the survivors, possibly predisposing to cardiovascular disease in adult life.

Impaired myocardial calcium handling in people with type 2 diabetes: an in vivo manganese-enhanced magnetic resonance imaging study

Abstract Background There is a high prevalence of subclinical cardiac dysfunction in people with type 2 diabetes (T2D) which is associated with subsequent development of heart failure. Dysregulated myocardial calcium handling has been demonstrated in animal models of T2D and may be a key mechanism driving the development of heart failure. Manganese-enhanced cardiac magnetic resonance imaging (MEMRI) provides a unique method to assess in vivo myocardial calcium handling. Purpose To determine whether myocardial calcium handling is perturbed in people with T2D with no history of cardiovascular disease. We hypothesised that myocardial manganese uptake would be reduced in people with T2D compared with healthy volunteers. Methods Cross-sectional case-control study, adults with (n=20) and without (n=9) T2D underwent both gadolinium-enhanced MRI and MEMRI. Standard gadolinium-enhanced MRI was used to assess cardiac structure, function and tissue characteristics. MEMRI scans were performed within two weeks of the initial scan. Native T1 maps were obtained in the mid-short axis slice position using a Modified Look-Locker Inversion recovery sequence. An intravenous infusion of manganese dipyridoxyl diphosphate (5 μmol/kg (0.1 mL/kg) at 1 mL/min) was administered and T1 maps at the same location were repetitively acquired every 2.5 min for 30 min. Regions of interest were drawn in the inferoseptal segment and blood pool for all T1 maps from 0 to 30 min by a single observer. The primary outcome was the rate of manganese uptake which was assessed by Patlak modelling as a measure of myocardial calcium handling. Manganese uptake constants were compared using analysis of co-variance, with age, sex and body mass index as co-variates. Results Subjects with T2D were older (62±7 vs. 57±5 years, p=0.046) but body mass index (29.0±4.5 vs. 26.2±3.4 kg/m2, p=0.106), systolic (135±16 vs. 134±17 mmHg, p=0.809) and diastolic (81±10 vs. 83±9 mmHg, p=0.736) blood pressures were similar. Compared to control subjects, participants with T2D had normal systolic function but more concentric left ventricular remodelling (mass/volume ratio 0.90±0.14 vs. 0.71±0.06 g/mL, p<0.001) and reduced peak early diastolic strain rate (0.64±0.17 vs. 0.91±0.26 s–1, p=0.002). Myocardial manganese uptake was substantially reduced in people with T2D compared with controls (6.51±1.46 vs. 8.45±2.52 ml/100 g of tissue/min, p=0.003) (Figure 1). Conclusions For the first time, we have demonstrated in vivo that despite no history of cardiovascular disease and normal systolic function, patients with T2D have marked impairment of myocardial calcium handling. This has potential major implications for the pathogenesis, diagnosis and treatment of diabetic cardiomyopathy. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation and National Institute for Health Research

Risk factors and prognosis for heart failure in atrial fibrillation subtypes in women and men

Abstract Background Atrial fibrillation (AF) and heart failure (HF) are common diseases that often co-exist and substantially impact both morbidity, mortality, and quality of life. Although there has been an increasing amount of research on HF in AF patients, there is limited knowledge on the association of AF subtypes (paroxysmal/persistent, permanent) with HF in women and men. Purpose To explore the sex-specific association between incident AF subtypes and HF risk factors and mortality in AF participants in a general population. Methods A total of 14,798 women and 13,197 men aged 25 years and older were enrolled from 1994 to 2008 and followed up for incident AF and HF through 2016. Cox proportional hazards regression analysis was conducted to provide sex- and AF subtype-specific hazard ratios (HRs) for the risk of HF, risk factors for HF and joint influence on mortality when AF precedes HF. Participants without AF and HF were used as reference. In the analysis of risk factors for HF we included only those who developed AF, and the follow-up period started at the date of first detected AF. Models were adjusted for systolic blood pressure, body mass index (BMI), total cholesterol, current smoking, physical activity, and history of myocardial infarction, angina pectoris, stroke, and diabetes mellitus, as well as age, with age as the time scale in the regression models. Results Over a median follow-up of 21.6 years, incident AF occurred in 856 women (471 with paroxysmal/persistent AF and 385 with permanent AF) and 1,036 men (587 with paroxysmal/persistent AF and 449 with permanent AF). Incident HF occurred in 761 women and 930 men. In both sexes, there was an increased risk of HF when AF was present. For permanent AF, women had a significantly higher risk of HF than men (HR 10.50, 95% CI 8.72–12.66 vs. HR 8.11, 95% CI 6.81–9.67). Permanent AF, current smoking, and prevalent myocardial infarction were significant risk factors for HF in AF participants in both sexes, while hypertension was only associated with increased risk of HF in women and BMI and prevalent stroke in men. Higher physical activity level was associated with reduced risk of AF in both sexes. The risk of death increased when HF succeeded AF. For women the risk of mortality was higher for permanent AF (HR 3.83, 95% CI 3.19–4.61 vs. HR 2.98, 95% CI 2.34–3.80), while in men it was highest for paroxysmal/persistent AF (HR 3.67, 95% CI 2.94–4.58 vs. HR 2.91, 95% CI 2.37–3.57), but there was no significant difference between sexes. Conclusions All AF subtypes were associated with an increased risk of HF in both sexes. For permanent AF, women had a significantly higher risk than men. Several risk factors for HF in AF participants were similar between sexes. However, hypertension was only a risk factor in women, whereas BMI and prevalent stroke were only risk factors in men. In AF participants, subsequent development of HF was associated with increased mortality in both sexes. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): UiT The Arctic University of Norway

Neuropeptide-Y Levels in ST-Segment-Elevation Myocardial Infarction: Relationship With Coronary Microvascular Function, Heart Failure, and Mortality.

BackgroundThe sympathetic cotransmitter, neuropeptide Y (NPY), is released into the coronary sinus during ST‐segment–elevation myocardial infarction and can constrict the coronary microvasculature. We sought to establish whether peripheral venous (PV) NPY levels, which are easy to obtain and measure, are associated with microvascular obstruction, myocardial recovery, and prognosis.Methods and ResultsNPY levels were measured immediately after primary percutaneous coronary intervention and compared with angiographic and cardiovascular magnetic resonance indexes of microvascular function. Patients were prospectively followed up for 6.4 (interquartile range, 4.1–8.0) years. PV (n=163) and coronary sinus (n=68) NPY levels were significantly correlated (r=0.92; P<0.001) and associated with multiple coronary and imaging parameters of microvascular function and infarct size (such as coronary flow reserve, acute myocardial edema, left ventricular ejection fraction, and late gadolinium enhancement 6 months later). We therefore assessed the prognostic value of PV NPY during follow‐up, where 34 patients (20.7%) developed heart failure or died. Kaplan‐Meier survival analysis demonstrated that high PV NPY levels (>21.4 pg/mL by binary recursive partitioning) were associated with increased incidence of heart failure and mortality (hazard ratio, 3.49 [95% CI, 1.65–7.4]; P<0.001). This relationship was maintained after adjustment for age, cardiovascular risk factors, and previous myocardial infarction.ConclusionsBoth PV and coronary sinus NPY levels correlate with microvascular function and infarct size after ST‐segment–elevation myocardial infarction. PV NPY levels are associated with the subsequent development of heart failure or mortality and may therefore be a useful prognostic marker. Further research is required to validate these findings.

New Progress in the Molecular Regulations and Therapeutic Applications in Cardiac Oxidative Damage Caused by Pressure Overload.

Chronic pressure overload is a key risk factor for mortality due to its subsequent development of heart failure, in which the underlying molecular mechanisms remain vastly undetermined. In this review, we updated the latest advancements for investigating the role and relevant mechanisms of oxidative stress involved in the pathogenesis of pressure-overload-induced cardiomyopathy and cardiac dysfunction, focusing on significant biological sources of reactive oxygen species (free radical) production, antioxidant defenses, and their association with the cardiac metabolic remodeling in the stressed heart. We also summarize the newly developed preclinical therapeutic approaches in animal models for pressure-overload-induced myocardial damage. This review aims to enhance the current understanding of the mechanisms of chronic hypertensive heart failure and potentially improve the development of better therapeutic strategies for the associated diseases.

Apical Sparing Strain Imaging In Patients With Hypertensive Emergency: A Study Of Patients Characteristics And Prognostic Value

<h3>Objective</h3> What are the clinical characteristics and prognostic values of patients with apical sparing strains compared to those with a normal strain pattern in hypertensive emergency? <h3>Background</h3> Differences in strain values among segments on the standard bull's eye model can give clues to different disease patterns. A pattern of apical sparing (AS) has been associated with cardiac amyloidosis, hypertrophic cardiomyopathy, hypertension, and aortic stenosis. Changes in longitudinal strain predict subsequent development of heart failure or reduction in left ventricular ejection fraction in patients undergoing cardiotoxic chemotherapy. <h3>Methods</h3> We conducted a historical cohort study of all patients with an admission diagnosis of hypertensive emergency who had an echocardiogram done with evaluation of the strain pattern. Patients with AS were compared to those without AS on the following characteristics: demographics (age, race, sex), comorbidities as measured by the Charlson Weighted Index of Comorbidity (CWIC), ejection fraction and laboratory values including creatinine and hemoglobin levels on admission, pro-BNP (if available), discharge disposition and readmission within 30 days. Patients were followed in time (via medical records) from the initial admission to collect any other ejection fraction data on echocardiogram that were in the medical records. <h3>Results</h3> There were 946 unique patients admitted with a diagnosis of hypertensive urgency or emergency. A total of 120 patients had an evaluation of the strain pattern on the echocardiogram. Approximately one-third [n=35] of patients admitted to the hospital with hypertensive emergency had apical sparing strain versus two-third [n=85] has non-apical sparing (figure 1). Forty percent and sixty percent of AS patients were males and females respectively, whereas, 55% and 45% of non-AS patients were males and females respectively. The mean age at admission was 58.2 ± 14.7 in AS and 60.6 ± 14.3 in non-apical sparing patients. A 97.1% of AS and 85.9% of non-AS patients were black p = 0.071. The mean baseline ejection fraction (EF) was 48.89% ± 12.55 and follow-up EF was 50.83% ± 12.63 in the apical sparing group p=0.58. On the other hand, the mean baseline EF was 53.47% ± 13.92, and follow-up EF% was 54.72% ± 14.83 in the non-apical sparing group p=0.39. The readmission rate within 30 days from discharge was 17.1% in AS versus 21.2% non-AS group. <h3>Conclusion</h3> The data showed a higher prevalence of AS strains in black patients and female patients. Patients with AS were younger than those without AS. The baseline and follow-up ejection fraction were similar in both study groups. Almost one-third of patients admitted to the hospital with hypertensive emergency/urgency have an apical sparing pattern. To summarize, the apical sparing pattern is not exclusive to cardiac amyloidosis and it is more commonly seen in hypertensive heart disease.

Abstract 12308: Stress-Related Neural Activity Predicts Subsequent Heart Failure

Introduction: Higher stress-related neural activity (SNA) associates with subsequent risk of cardiovascular disease. We investigated whether heightened SNA predicts subsequent heart failure (HF). Methods: Individuals (N=2,112; median age 69 years; 48% female) enrolled in the Mass General Brigham Biobank without baseline HF who underwent clinically indicated 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging were retrospectively identified. SNA was measured using validated methods, as amygdalar metabolic activity corrected for regulatory brain (i.e., medial prefrontal cortical) activity. Subsequent development of HF was determined via medical record review using International Classification of Diseases 10 (ICD-10) codes. Survival analyses using Cox and Kaplan-Meier models were performed. Results: Over a median follow-up period of 3.9 years after imaging, 210 individuals developed HF (57 systolic, 93 diastolic). Individuals with subsequent HF (versus no HF) had higher baseline SNA (mean Z-score 0.19 ± 1.07 versus -0.08 ± 0.99; p=0.005, adjusted for age and sex). SNA associated with subsequent HF when divided into tertiles (Figure) and as a continuous measure (standardized HR [95% CI]: 1.38 [1.11-1.70], p=0.003, adjusted for age, sex, hypertension, hyperlipidemia, diabetes and smoking). The association between SNA and HF subtype was stronger for diastolic HF (1.37 [1.00-1.88], p=0.047) than for systolic HF (1.14 [0.87-1.49], p=0.348) in models additionally adjusting for history of myocardial infarction. Conclusion: In this retrospective study of individuals with clinical FDG-PET/CT imaging, higher SNA predicted subsequent HF with a somewhat stronger association for diastolic HF. Understanding the link between heightened stress-associated neural activity and subsequent HF may provide important insights into better HF prevention and management strategies.

Is There a Sex Gap in Surviving an Acute Coronary Syndrome or Subsequent Development of Heart Failure?

We hypothesized that disparities between sexes in the management of myocardial infarction (MI) may have changed over time, and thus altered the prognoses after MI, especially the risk for the development of heart failure. Using a large population-based cohort of patients with MI between April 1, 2002, and March 31, 2016, we examined the incidence, angiographic findings, treatment (including revascularization), and clinical outcomes of patients with a first-time MI. To elucidate the differences between sexes, a series of multivariable models were created to explore all MI and non-ST-segment-elevation MI (NSTEMI) versus ST-segment-elevation MI (STEMI) over time. Between 2002 and 2016, 45 064 patients (13 878 [30.8%] women) were hospitalized with a primary diagnosis of first-time MI (54.9% NSTEMI and 45.1% STEMI). Women were older (median age, 72 versus 61 years), had more comorbidities, and had lower rates of diagnostic angiography than did men (women, 74%, versus men, 87%). When angiography was performed, women had a lower proportion of left main, 2-vessel disease with proximal left anterior descending or 3-vessel disease compared with men (33.4% versus 40.9%, P<0.0001), and a higher frequency of 1-vessel disease or nonobstructive coronary artery disease (39.6% versus 29.1%, P<0.0001). Women had a higher unadjusted rate of in-hospital mortality than did men in both patients with STEMI (women, 9.4%, versus men, 4.5%) and patients with NSTEMI (women, 4.7%, versus men, 2.9%). After adjustment, this difference remained significant in STEMI (adjusted odds ratio, 1.42 [95% CI, 1.24-1.64]) but not in NSTEMI (adjusted odds ratio, 0.97 [95% CI, 0.83-1.13]). After discharge, women developed heart failure after STEMI (women, 22.5%, versus men, 14.9%) as well as after NSTEMI (women, 23.2%, versus men, 15.7%). The adjusted relative risk for women versus men of developing the outcomes of mortality and heart failure remained similar across years, although the differences were nonsignificantly attenuated over 5 years of follow-up. Although some attenuation of differences in clinical outcomes over time has occurred, women remain at higher risk than men of dying or developing heart failure in the subsequent 5 years after STEMI or NSTEMI, even after accounting for differences in angiographic findings, revascularization, and other confounders.

Abstract 13311: Cyclocreatine Phosphate: A Novel Mechanism for Preventing Development of Heart Failure

Introduction: Demand ischemia causes irreversible myocardial injury (MI) through exhaustion of cellular adenosine triphosphate (ATP). We demonstrated that enhancing myocardial ATP stores during ischemia using Cyclocreatine Phosphate (CCrP), prevents myocardial injury and maintains cardiac contractility in a variety of models. The FDA has granted CCrP Orphan Drug Status with the designation of “ Prevention of Ischemic Injury to Enhance Cardiac Graft Recovery and Survival in Heart Transplantation ” . Hypothesis: CCrP administration will prevent ischemic injury and the subsequent development of heart failure in standard isoproterenol (ISO) rat model. Methods: 20 male Wistar rats (180-220 g) were used: ISO/saline (n=6), ISO/CCrP 0.8 gm/kg/day (n=5), control/saline (n=5), control/CCrP 0.8 gm/kg/day (n=4). Rats were injected S.C. with ISO for two consecutive days at doses of 85 and 170 mg/kg/day, respectively, then left for 2 weeks. CCrP and saline were injected IP (1 ml) 24 hours and 1 hour before ISO administration, then daily for 2 weeks. Serum CK-MB (U/L) measured 24 hours after last ISO injection. After 14 days, ECHO analysis for Ejection Fraction (EF%) was conducted, as well as heart weight (mg), fibrosis and deposition of collagen. Mean ± S.E.M and one-way ANOVA analysis were used. Results: Table I shows evidence of MI after 24 hours by high elevation of CK-MB in ISO rats, while significant protection was seen in ISO/CCrP rats. After 14 days, ISO/CCrP rats showed normal EF% and heart weight, while ISO/saline rats showed significant drop in EF% and an increase in heart weight. Blinded pathology indicated marked increase of fibrin and collagen deposition in ISO/saline rats, which were not seen in ISO/CCrP rats. Healthy rats treated with CCrP for 14 days, showed no toxicity in liver and renal function. Conclusions: The bioenergetic Cyclocreatine Phosphate is a promising first-in-class cardio-protective drug that prevents the development of heart failure due to ischemia.

Abstract 15431: Childhood Passive Smoke Exposure is Associated With Subclinical Left Ventricular Dysfunction in Adulthood - Childhood Determinants of Adult Health Study

Introduction: Prolonged childhood passive smoke exposure may affect adult cardiovascular health but there are few studies of cardiac function. Subclinical left ventricular dysfunction detected by global longitudinal strain (GLS) is predictive of the subsequent development of heart failure. We investigated the association of passive smoke exposure during childhood with GLS in adults. Methods: Data were from the Childhood Determinants of Adult Health (CDAH) study 34-year follow-up (2014-19). Three measures of passive smoking (severity of exposure index [SEI], cumulative years of exposure [CYE], total household smokers [THS]) were derived retrospectively from a validated questionnaire. GLS was measured in clinics using a Siemens Acuson SC2000 ultrasound machine and 4V1c transducer with speckle tracking analysis. Linear regression adjusted for confounding factors (age, gender, childhood socioeconomic position, childhood smoking, adult smoking status, parental education level) examined the association between childhood passive smoke exposure and GLS in adulthood. Results: Among 781 participants (mean age 45.2 ± 2.5 SD years, 52.6% females, 54.2% exposed to passive smoking), GLS showed a decrease (β adjusted -0.17% 95% CI -0.32%, -0.02%) per SD of SEI (range: 0-318, mean 24.2 ± 35.8 SD). CYE (range: 0-106, mean 10.4 ± 13.9 SD) was associated with a decrease in GLS (β adjusted -0.18% 95% CI -0.33%, -0.05%) per SD of exposure. For each THS in childhood (range: 0-5, mean 0.9 ± 1.0 SD), there was a decrease in GLS (β adjusted -0.20% 95% CI -0.36%, -0.05%). Conclusion: Childhood passive smoke exposure, independent of own smoking, was associated with a reduction in GLS, a measure of subclinical cardiac dysfunction. Each 1% decrease in GLS has been associated with 12% higher risk of cardiovascular morbidity and mortality in low-risk general population. There are potential long-term consequences to cardiac function from childhood passive smoke exposure.

Extracellular Superoxide Dismutase Is Associated With Left Ventricular Geometry and Heart Failure in Patients With Cardiovascular Disease.

BackgroundExtracellular superoxide dismutase (Ec‐SOD) is a major scavenger of reactive oxygen species. However, its relationships with abnormal left ventricular (LV) geometry patterns and heart failure (HF) are still unknown in patients with cardiovascular disease.Methods and ResultsA cross‐sectional study was carried out to evaluate the association of serum Ec‐SOD activity with LV geometry, as well as HF in 1047 patients with cardiovascular disease. All participants underwent standard echocardiography examination and measurement of serum Ec‐SOD activity. Overall, we found a significantly decreased trend of serum Ec‐SOD activity from subjects with normal geometry (147.96±15.94 U/mL), subjects with abnormal LV geometry without HF (140.19±20.12 U/mL), and subjects with abnormal LV geometry and overt HF (129.32±17.92 U/mL) after adjustment for potential confounders (P for trend <0.001). The downward trends remained significant in the concentric hypertrophy and eccentric hypertrophy groups after stratification by different LV geometry patterns. Multinomial logistic regression analysis showed that each 10 U/mL increase in serum Ec‐SOD activity was associated with a 16.5% decrease in the odds of concentric remodeling without HF (odds ratio [OR], 0.835; 95% CI, 0.736–0.948), a 40.4% decrease in the odds of concentric hypertrophy with HF (OR, 0.596; 95% CI, 0.486–0.730), a 16.1% decrease in the odds of eccentric hypertrophy without HF (OR, 0.839; 95% CI, 0.729–0.965) and a 34.0% decrease in the odds of eccentric hypertrophy with HF (OR, 0.660; 95% CI, 0.565–0.772).ConclusionsSerum Ec‐SOD activity was independently associated with abnormal LV geometry patterns with and without overt HF. Our results indicate that Ec‐SOD might be a potential link between LV structure remodeling and the development of subsequent HF in patients with cardiovascular disease.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier NCT03351907.

Atrial Fibrillation, Cancer and Echocardiography.

Nonvalvular atrial fibrillation (AF) is a relatively frequent arrhythmia in cancer patients; it is possibly due to direct effect of cancer or consequence of cancer therapies. AF creates important problems for both therapeutic management and prognosis in cancer patients. The anticoagulation of cancer patients presenting AF is a main issue because of the difficult balance between thromboembolic and bleeding risks, both elevated in this clinical setting. A comprehensive echo Doppler examination is mandatory to identify the eventual sources of emboli in left atrial (LA) cavity, mainly the transesophageal echocardiography (TEE), but also to predict the subsequent development of heart failure. This evaluation is particularly important to graduate anticoagulation and to prevent and manage symptoms/signs of heart failure. The performance of a TEE precardioversion is highly encouraged to detect possible thrombi in LA appendage. A careful assessment of LA size (LA volume index) and function (LA emptying fraction and/or LA strain) should always be planned to predict the possible recurrence of AF paroxysmal episodes. This is in fact a key action, not only from the cardiologic point of view but also for the oncologic perspectives in individual situations. Patients with larger left atrium and more impaired LA function should be addressed toward a less aggressive cancer treatment, with drugs which are not associated or are poorly related with the risk of AF development. A correct and comprehensive echocardiographic assessment could even induce the oncologist to change the cancer management balancing the oncologic and the cardiac risk.

Human Immunodeficiency Virus Increases the Risk of Incident Heart Failure.

Although the HIV can cause myocardial inflammation, the association of HIV infection with subsequent development of heart failure (HF) has not been extensively studied. This nationwide cohort study aimed to determine the risk of incident HF in people living with HIV/AIDS (PLWHA). We identified PLWHA using the Taiwan Centers for Disease Control and Prevention HIV Surveillance System. An age- and sex-matched control group without HIV infection was selected from the Taiwan National Health Insurance Research Database for comparison. All patients were followed up until December 2014 and were observed for a new diagnosis of HF. A time-dependent Cox proportional hazards model was used to determine the association of HIV and highly active antiretroviral therapy with incident HF, with death as a competing risk event. Of the 120,765 patients (24,153 PLWHA and 96,612 matched controls), 641 (0.53%) had incident HF during a mean follow-up period of 5.84 years, including 192 (0.79%) PLWHA and 449 (0.46%) controls. Time to diagnosis of incident HF was significantly shorter in PLWHA than in those without HIV infection (P < 0.001, the log-rank test). After adjusting for age, sex, and comorbidities, HIV infection was found to be an independent risk factor for incident HF (adjusted hazard ratio, 1.52; 95% confidence interval: 1.27 to 1.82). As the duration of highly active antiretroviral therapy increased, the risk of HF decreased (P = 0.014). HIV infection was an independent risk factor for incident HF. Clinicians need to be aware of the higher risk of HF in PLWHA.

Understanding the role of echocardiography in remodeling after acute myocardial infarction and development of heart failure with preserved ejection fraction.

Despite the use of reperfusion therapies in the last decades, acute myocardial infarction further remains one of the most frequentcauses of mortality. This is mainly caused by changes in the ventricular architecture leading to ventricular remodeling,followed by progressive development of heart failure. Transthoracic echocardiography is a non-invasive instrument whichcan provide information about the extent of the ischemic process and its consequences but can also predict the outcomes aftermyocardial infarction. Although standard echocardiographic parameters are currently used for risk stratification of these patients,they might not truly reflect left ventricular systolic dysfunction in acute myocardial infarct patients, since the detectionof subtle changes in the myocardial function is beyond their limits. The aim of this review is to underline the use of advancedechocardiographic parameters in identifying patients at risk for developing post-acute myocardial infarction heart failure andsubsequent adverse events. Advanced echocardiographic parameters derived from speckle tracking echocardiography providea detailed assessment on the global and regional left ventricular deformation. Therefore, speckle tracking echocardiographyhas a major role in predicting the prognosis of acute myocardial infarction patients and particularly in the development ofsubsequent heart failure, which might be prevented with early initiation of adequate therapy.

Community-Acquired Acute Kidney Injury as a Risk Factor of de novo Heart Failure Hospitalization

Objectives: Because patients with hospital-acquired acute kidney injury (AKI) are at risk for subsequent development of heart failure (HF) and little is known about the relation between community-acquired AKI (CA-AKI) and HF, we sought to determine if CA-AKI is a risk factor for incident HF hospitalization. Methods: We utilized Baylor Scott & White Health databases at the primary care and inpatient hospitalization levels to identify adults without a prior history of HF who had 2 or more serum creatinine measurements within 13 months in the primary care setting. We defined CA-AKI as a serum creatinine increase ≥0.3 mg/dL or ≥1.5 times the baseline for consecutive values within a 13-month period. We created a flag for de novo HF hospitalization at 90, 180, and 365 days following CA-AKI evaluation. Results: In the analyses, 210,895 unique adults were included, of whom 5,358 (2.5%) had CA-AKI. Those with CA-AKI had higher rates of comorbidities, higher rate of males (48 vs. 42%, p < 0.001), and were older (61.5 [50.3, 73.1] vs. 54.1 [42.8, 64.7] years, p < 0.001) than those who did not have CA-AKI. In total, 607 (0.3%), 833 (0.4%), and 1,089 (0.5%) individuals had an incident HF hospitalization in the 90, 180, and 365 days following the CA-AKI evaluation, respectively. After adjusting for demographic and clinical characteristics, patients with CA-AKI had >2 times the risk of de novo HF hospitalization compared with patients who did not have CA-AKI (90 days: 2.35 [1.83–3.02], p < 0.001; 180 days: 2.52 [2.04–3.13], p < 0.001; 365 days: 2.16 [1.77–2.64], p < 0.001). These multivariable models yielded strong predictive abilities, with the areas under the receiver-operating characteristic curve >0.90. Conclusion: After controlling for baseline and clinical characteristics, patients with CA-AKI were at approximately twofold the risk of de novo HF hospitalization (within 90, 180, and 365 days) compared with those who did not have CA-AKI. Hence, detecting CA-AKI may provide an opportunity for early intervention at the primary care level to possibly delay HF development.

Relationship between TRAIL and Left Ventricular Ejection Fraction in Patients with ST-Elevation Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention.

Background Apoptosis plays an important role in the myocardial injury after acute myocardial infarction and in the subsequent development of heart failure. Aim To clarify serum kinetics of apoptotic markers TRAIL and sFas and their relation to left ventricular ejection fraction (LVEF) in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Methods In 101 patients with STEMI treated with pPCI, levels of TRAIL and sFas were measured in series of serum samples obtained during hospitalization and one month after STEMI. LVEF was assessed at admission and at one month. Major adverse cardiovascular events (MACE, i.e., death, re-MI, and hospitalization for heart failure and stroke) were analysed during a two-year followup. Results Serum level of TRAIL significantly decreased one day after pPCI (50.5pg/mL) compared to admission (56.7pg/mL), subsequently increased on day 2 after pPCI (58.8pg/mL), and reached its highest level at one month (70.3pg/mL). TRAIL levels on days 1 and 2 showed a significant inverse correlation with troponin and a significant positive correlation with LVEF at baseline. Moreover, TRAIL correlated significantly with LVEF one month after STEMI (day 1: r=0.402, p<0.001; day 2: r=0.542, p<0.001). On the contrary, sFas level was significantly lowest at admission (5073pg/mL), increased one day after pPCI (6370pg/mL), and decreased on day 2 (5548pg/mL). Significantly highest sFas level was marked at one month (7024pg/mL). sFas failed to correlate with LVEF at baseline or at one month. Both TRAIL and sFas showed no ability to predict improvement of LVEF one month after STEMI or a 2-year MACE (represented by 3.29%). Conclusion In STEMI treated with pPCI, TRAIL reaches its lowest serum concentration after reperfusion. Low TRAIL level is associated with worse LVEF in the acute phase of STEMI as well as one month after STEMI. Higher TRAIL level appears to be beneficial and thus TRAIL seems to represent a protective mediator of post-AMI injury.

Influence of dietary eicosapentaenoic acid on the cardiac mechanical and mitochondrial functions during early sepsis

Sepsis triggers the failure of cardiac mitochondria and this deleterious effect could be prevented by omega-3 polyunsaturated fatty acids (PUFA). To evaluate the influence of eicosapentaenoic acid (C20: 5 omega-3 or EPA) on the mechanical and mitochondrial functions of the heart during early sepsis. Four month-old female Wistar rats were subdivided in 4 groups ( n = 8 per group) according to: (i) the 4-week diet given (deficient in omega-3 PUFA [DEF] or enriched with EPA); (ii) the surgery performed (caecal ligation at 1 cm of the apex of the heart and puncture in order to induce sepsis [CLP] or sham). The cardiac mechanical function was studied in vivo by NMR 48 h after the surgery. Immediately after, part of the myocardium was used in order to extract mitochondria and another part was frozen in order to subsequently analyse the fatty acid composition of cardiac phospholipids. The EPA groups display a large decrease in the omega-6/omega-3 PUFA ratio of cardiac phospholipids. Sepsis increases the mRNA expression of IL-1beta in the DEF group but not in the EPA one. The mechanical function is altered neither by the diets nor by the surgeries. The DEF/CLP animals have a deficient oxidative phosphorylation compared to the DEF/Sham rats: reduced mitochondrial oxygen consumption (−42%, P < 0.001) and ATP production (−37%, P < 0.05). The sepsis-induced mitochondrial damages in this group is due to an increase reactive oxygen species (ROS) release (+130 and +63% for the ROS/respiration and ROS/ATP ratios, P < 0.01 and P < 0.05, respectively). The dietary EPA prevents these damages ( P < 0.05). A sufficient EPA intake favours the upholding of the mitochondrial function during early sepsis, which could delay the subsequent development of heart failure. We plan to verify this beneficial effect of EPA in Humans affected by acute endocarditis.