Blood-threshold CMR volume analysis of functional univentricular heart.

PURPOSE: To validate a blood-threshold (BT) segmentation software for cardiac magnetic resonance (CMR) cine images in patients with functional univentricular heart (FUH). MATERIALS AND METHODS: We evaluated retrospectively 44 FUH patients aged 25 ± 8 years (mean ± standard deviation). For each patient, the epicardial contour of the single ventricle was manually segmented on cine images by two readers and an automated BT algorithm was independently applied to calculate end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), and cardiac mass (CM). Aortic flow analysis (AFA) was performed on through-plane images to obtain forward volumes and used as a benchmark. Reproducibility was tested in a subgroup of 24 randomly selected patients. Wilcoxon, Spearman, and Bland-Altman statistics were used. RESULTS: No significant difference was found between SV (median 57.7 ml; interquartile range 47.9-75.6) and aortic forward flow (57.4 ml; 48.9-80.4) (p = 0.123), with a high correlation (r = 0.789, p < 0.001). Intra-reader reproducibility was 86% for SV segmentation, and 96% for AFA. Inter-reader reproducibility was 85 and 96%, respectively. CONCLUSION: The BT segmentation provided an accurate and reproducible assessment of heart function in FUH patients.

Dietary Phytoestrogen Intake is Inversely Associated with Hypertension in a Cohort of Adults Living in the Mediterranean Area.

BACKGROUND: Dietary polyphenols, including phytoestrogens are abundantly present in a balanced diet. Evidence for their role in preventing non-communicable diseases is emerging. METHODS: We examined the association between estimated habitual intakes of dietary phytoestrogens and hypertension in a cohort study. The baseline data included 1936 men and women aged 18 years and older. Intakes of total phytoestrogens, isoflavones, and lignans were calculated from validated food frequency questionnaire. Data on the polyphenols content in foods were retrieved from the Phenol-Explorer database. RESULTS: Individuals in the highest quartile of dietary phytoestrogens intake were less likely to be hypertensive (OR: 0.66, 95% CI: 0.44-0.98); moreover, the association showed a significant decreasing trend. Isoflavones and lignans were not associated with lower odds of hypertension; however, some individual compounds, such as biochanin A and pinoresinol showed an independent inverse association with hypertension. CONCLUSIONS: Dietary phytoestrogens are associated with lower likelihood of hypertension in adults living in the Mediterranean area. Future studies are needed to confirm the present findings (i.e., prospective cohort studies) and to better understand the mechanisms underlying such associations.

Treatment of right ventricular outflow tract dysfunction: a multimodality approach.

The right timing to replace the pulmonary valve in a patient with dysfunction of the right ventricular outflow tract is unknown. Both percutaneous pulmonary valve and surgical prosthesis are suitable options. In every patient, the right ventricle (RV) remodels and recovers differently after pulmonary replacement. Therefore, it is difficult to identify the best treatment option and to predict the long-term results. In the last few years, we focused our research on optimizing the characterization of these patients through advanced cardiovascular imaging in order to find possible variables, parameters, and reproducible measurements that can help us in the decision-making process. The aim of the present article is to present our ongoing research lines that focus on the characterization and optimal treatment approach to the dysfunction of the RVOT.

Postmortem imaging in congenital heart disease: preliminary experience.

BACKGROUND: Despite the importance of the autopsy for quality improvement, autopsy rates have declined dramatically in recent decades due to poor acceptance by families and physicians and high costs to institutions. PURPOSE: To compare postmortem imaging (PMI) with autopsy in patients with congenital heart defects to see if PMI could substitute in some or all cases and to compare costs of the two methods. MATERIAL AND METHODS: Ten patients with congenital heart disease dying in hospital during the study period in whom an autopsy was planned underwent PMI using postmortem magnetic resonance imaging (PMMRI) (6 patients) and postmortem computed tomographic angiography (PMCTA) (10 patients) with permission of the family. Four patients were excluded from PMMR because of metal ECMO cannulas. PMI was interpreted before autopsy using an organ system checklist and results compared to autopsy. The costs of each method were tracked. RESULTS: When both PMMR and PMCTA were performed the PMI findings corresponded closely with autopsy. PMI correctly diagnosed the principal heart defects in all six cases and correctly imaged central vessels, heart valves and chambers, brain, abdominal organs, and bone. Weak points were visualization of the coronary arteries and distinguishing postmortem pulmonary atelectasis from lung pathology. The cause of death by PMI matched autopsy findings in 5/6 cases in which both PMMR and PMCTA were performed and was incomplete in the other five cases. The cost of PMI was about 15% lower than the cost of autopsy. CONCLUSION: PMI provided most gross anatomic cardiac diagnoses available by autopsy in our series of patients with congenital heart defects and the cost appears to be lower.

Resveratrol and anti-atherogenic effects.

The role of inflammation and oxidative stress in atherosclerosis development has been increasingly well recognized over the past decade. Inflammation has a significant role at all stages of atherosclerosis, including initiation, progression and plaque formation. Resveratrol is a naturally occurring polyphenolic compound found in grape products, berry fruits and red wine. Its ability to behave therapeutically as a component of red wine has attracted wide attention. Accumulating evidence suggests that it is a highly pleiotropic molecule that modulates numerous targets and molecular functions. Epidemiological studies indicate that the Mediterranean diet, rich in resveratrol, is associated with a reduced risk of atherosclerosis. Resveratrol is believed to decrease circulating low-density lipoprotein cholesterol levels, reduce cardiovascular disease risk; it reduces lipid peroxidation, platelet aggregation and oxidative stress. Resveratrol is considered a safe compound, since no significant toxic effects have been demonstrated after administration of a broad range of concentrations, and an effective anti-atherogenic agent.

QRS duration and QRS fractionation on surface electrocardiogram are markers of right ventricular dysfunction and atrialization in patients with Ebstein anomaly.

BACKGROUND: Ebstein anomaly is a rare and heterogeneous congenital heart defect affecting the tricuspid valve and right ventricular (RV) myocardium. Few studies have analysed the electrocardiographic features of Ebstein anomaly and none has addressed correlations with disease severity. METHODS: Patients with Ebstein anomaly who had undergone electrocardiography and cardiac magnetic resonance (CMR) within 6 weeks between 2001 and 2009 were included. Exclusion criteria were: associated congenital cardiac defect, previous RV myoplasty and/or reduction surgery, class I anti-arrhythmic drug therapy, and paced/pre-excited QRS. Standard electrocardiogram (ECG) findings were correlated with CMR-based RV measures and clinical profile. RESULTS: The mean age of the 63 study patients was 22 ± 13 years. An RV conduction delay (rsR' pattern in right precordial leads) was present in 45 patients (71%). The QRS duration correlated with anatomic RV diastolic volume (r = +0.56, P < 0.0001) and inversely with RV ejection fraction (EF; r = -0.62, P < 0.0001). The presence of QRS fractionation predicted greater atrialized RV volume (80 ± 31 vs. 45 ± 37 mL/m(2), P < 0.001). Normal QRS duration was associated with smaller anatomic RV diastolic volume (150 ± 57 vs. 256 ± 100 mL/m(2); P < 0.0001), higher RV EF (48 ± 6 vs. 34 ± 14%; P < 0.0001), higher oxygen consumption (VO(2)) at cardiopulmonary exercise (25.8 vs. 21.8 mL/kg/min, P = 0.05) and lower incidence of oxygen desaturation with exercise (25 vs. 65%, P = 0.02). CONCLUSION: Delayed and prolonged depolarization of the RV is common in patients with Ebstein anomaly. The QRS duration is a marker of RV enlargement and dysfunction. QRS fractionation is associated with a greater atrialized RV volume. A preserved surface ECG identifies a subset of patients with Ebstein anomaly with mild morphological and functional abnormalities and better clinical profile.

Coffee components and cardiovascular risk: beneficial and detrimental effects.

Coffee consists of several biological active compounds, such as caffeine, diterpenes, chlorogenic acids, and melanoidins, which may affect human health. The intake of each compound depends on the variety of coffee species, roasting degree, type of brewing method and serving size. The bioavailability and the distribution of each compound and its metabolites also contribute to coffee mechanisms of action. The health benefits of coffee consumption regarding cardiovascular system and metabolism mostly depend on its antioxidant compounds. In contrast, diterpenes and caffeine may produce harmful effects by raising lipid fraction and affecting endothelial function, respectively. Studying the mechanism of action of coffee components may help understanding whether coffee's impact on health is beneficial or hazardous. In this article, we reviewed the available information about coffee compounds and their mechanism of action. Furthermore, benefits and risks for cardiovascular system associated with coffee consumption will be discussed.

Heart failure patients with improved ejection fraction: Insights from the MECKI score database.

AIMS: Improvement of left ventricular ejection fraction is a major goal of heart failure (HF) treatment. However, data on clinical characteristics, exercise performance and prognosis in HF patients who improved ejection fraction (HFimpEF) are scarce. The study aimed to determine whether HFimpEF patients have a distinct clinical phenotype, biology and prognosis than HF patients with persistently reduced ejection fraction (pHFrEF). METHODS AND RESULTS: A total of 7948 patients enrolled in the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score database were evaluated (median follow-up of 1490 days). We analysed clinical, laboratory, electrocardiographic, echocardiographic, exercise, and survival data from HFimpEF (n = 1504) and pHFrEF (n = 6017) patients. The primary endpoint of the study was the composite of cardiovascular death, left ventricular assist device implantation, and urgent heart transplantation. HFimpEF patients had lower HF severity: left ventricular ejection fraction 44.0 [41.0-47.0] versus 29.7 [24.1-34.5]%, B-type natriuretic peptide 122 [65-296] versus 373 [152-888] pg/ml, haemoglobin 13.5 [12.2-14.6] versus 13.7 [12.5-14.7] g/dl, renal function by the Modification of Diet in Renal Disease equation 72.0 [56.7-89.3] versus 70.4 [54.5-85.3] ml/min, peak oxygen uptake 62.2 [50.7-74.1] versus 52.6 [41.8-64.3]% predicted, minute ventilation-to-carbon dioxide output slope 30.0 [26.9-34.4] versus 32.1 [28.0-38.0] in HFimpEF and pHFrEF, respectively (p < 0.001 for all). Cardiovascular mortality rates were 26.6 and 46.9 per 1000 person-years for HFimpEF and pHFrEF, respectively (p < 0.001). Kaplan-Meier analysis showed that HFimpEF had better a long-term prognosis compared with pHFrEF patients. After adjustment for variables differentiating HFimpEF from pHFrEF, except echocardiographic parameters, the Kaplan-Meier curves showed the same prognosis. CONCLUSIONS: Heart failure with improved ejection fraction represents a peculiar group of HF patients whose clinical, laboratory, electrocardiographic, echocardiographic, and exercise characteristics parallel the recovery of systolic function. Nonetheless, these patients remain at risk for adverse outcome.

Left ventricular aneurysm, aortic stenosis, and arcade mitral valve: coexistence of three rare congenital heart defects.

This report presents two fetuses with three rare congenital heart defects: congenital ventricular aneurysm, arcade mitral valve, and unicommissural aortic valve. Because interaction between the endocardium and the myocardium is essential for development of the myocardium and heart valves, the authors hypothesized that these three defects could be related to abnormal signaling between the endocardium and the myocardium during critical phases of cardiac development. This combination of defects might be incompatible with fetal survival to term.

Metabolic and Cardiovascular Effects of Switching Thiazides to Amlodipine in Hypertensive Patients With and Without Type 2 Diabetes (the Diuretics and Diabetes Control Study).

Background: Different studies have indicated that thiazide diuretics can increase the risk of developing type 2 diabetes (T2D). Therefore, in this study, we investigated whether switching from hydrochlorothiazide (HCTZ) to amlodipine resulted in ameliorating different cardiovascular and metabolic measures in hypertensive patients with or without T2D. Methods: This study [Diuretics and Diabetes Control (DiaDiC)] was a 6-week, single-blind, single-center randomized controlled trial. The first 20 normal glucose-tolerant, 20 prediabetic, and 20 T2D consecutive patients were randomized to continue the previous antihypertensive treatment with HCTZ (12.5-25 mg/day) or to switch from HCTZ to amlodipine (2.5-10 mg/day). The primary endpoints were the absolute change in 7-day continuous subcutaneous glucose monitoring (CSGM) glycemia, serum uric acid concentrations, and endothelial function [measured as flow-mediated dilation (FMD)]. Other secondary endpoints were investigated, including changes in glycated hemoglobin (HbA1c), glycemic variability from 7-day CSGM, and the estimated glomerular filtration rate (eGFR). Results: Amlodipine treatment was associated with a significant reduction in HbA1c (P = 0.03) for both 7-day CSGM glycemia (P = 0.01) and glycemic variability (coefficient of variability %: HCTZ +3%, amlodipine -2.8%), and a reduction in uric acid concentrations (P < 0.001), especially in participants with T2D or prediabetes. Following amlodipine treatment, a significant increase in both eGFR (P = 0.01) and FMD (P = 0.02) was also observed. Conclusions: This study demonstrates that the replacement of HCTZ with amlodipine has several metabolic and cardiovascular beneficial effects. However, further intervention studies are necessary to confirm the clinical effects of thiazides, especially in diabetic people and in those at risk of diabetes.

Right ventricular diameter predicts all-cause mortality in heart failure with preserved ejection fraction.

Left ventricular ejection fraction (EF) is helpful to differentiate heart failure (HF) phenotype in clinical practice. The aim of the study was to identify simple echocardiographic predictors of post-discharge all-cause mortality in hospitalized HF patients. Patients with acute HF (75 ± 9.8 years), classified in preserved (≥ 50%) and reduced (< 50%) EF (HFpEF and HFrEF, respectively), were enrolled. The mean follow-up period was of 25.4 months. Patients definitively analyzed were 135. At multivariate Cox model, right ventricular diameter (RVd), inferior vena cava diameter (IVCd) and blood urea nitrogen (BUN) resulted to be significantly associated with all-cause mortality in HFpEF (HR 2.4, p = 0.04; HR 1.06, p = 0.02; HR 1.02, p = 0.01), whereas, left atrial volume (LAV) was significantly associated with mortality in HFrEF (HR 1.06, p = 0.006). Excluding LAV from the model, only COPD remained an independent predictor of all-cause mortality (HR 2.15, p = 0.04) in HFrEF. At Kaplan-Meier analysis, no differences of survival between HFrEF and HFpEF were found, however, significantly increased all-cause mortality for higher values of basal-RVd, BUN, and IVCd (log-rank p = 0.0065, 0.0063, 0.0005) in HFpEF, and for COPD and higher LAV (log-rank p = 0.0046, p = 0.033) in HFrEF. These data are indicative that in patients hospitalized with HF, EF is not a suitable predictor of long-term all-cause mortality, whereas, right ventricular volumetric remodeling and IVCd have a prognostic role in HFpEF as well as LAV in HFrEF. Our study suggests that besides EF, other echocardiographic parameters are helpful to optimize the phenotyping and prognostic stratification of HF.

Prediction of stenting related adverse events through patient-specific finite element modelling.

Right ventricular outflow tract (RVOT) calcific obstruction is frequent after homograft conduit implantation to treat congenital heart disease. Stenting and percutaneous pulmonary valve implantation (PPVI) can relieve the obstruction and prolong the conduit lifespan, but require accurate pre-procedural evaluation to minimize the risk of coronary artery (CA) compression, stent fracture, conduit injury or arterial distortion. Herein, we test patient-specific finite element (FE) modeling as a tool to assess stenting feasibility and investigate clinically relevant risks associated to the percutaneous intervention. Three patients undergoing attempted PPVI due to calcific RVOT conduit failure were enrolled; the calcific RVOT, the aortic root and the proximal CA were segmented on CT scans for each patient. We numerically reproduced RVOT balloon angioplasty to test procedure feasibility and the subsequent RVOT pre-stenting expanding the stent through a balloon-in-balloon delivery system. Our FE framework predicted the occurrence of CA compression in the patient excluded from the real procedure. In the two patients undergoing RVOT stenting, numerical results were consistent with intraprocedural in-vivo fluoroscopic evidences. Furthermore, it quantified the stresses on the stent and on the relevant native structures, highlighting their marked dependence on the extent, shape and location of the calcific deposits. Stent deployment induced displacement and mechanical loading of the calcific deposits, also impacting on the adjacent anatomical structures. This novel workflow has the potential to tackle the analysis of complex RVOT clinical scenarios, pinpointing the procedure impact on the dysfunctional anatomy and elucidating potential periprocedural complications.

Impact of chocolate on the cardiovascular health.

The antioxidants such as polyphenols, especially flavonols, present in large quantitites in cocoa, cause vasodilation, modulate inflammatory markers and cardiovascular health, and possess a range of protective cardiovascular effects. On the other hand, overconsumption of chocolate can lead to tachyarrhythmias, supraventricular tachycardia, atrial fibrillation, ventricular tachycardia and ventricular fibrillation due to its caffeine content. This review describes both the cardioprotective and adverse effects of chocolate and its constituents.

Does Tetralogy of Fallot affect brain aging? A proof-of-concept study.

The impact of congenital heart disease on brain aging has not been extensively investigated. We evaluated cerebral microbleeds and white matter hyperintensities on brain magnetic resonance imaging in adult patients with tetralogy of Fallot (ToF). Ten ToF patients (6 women, 4 men; aged 21-58 years; New York Heart Association [NYHA] class 1-2) were prospectively enrolled and underwent a T1-weighted, a T2-weighted dark fluid, and a T2*-weighted scans. Ten age- and sex-matched controls were prospectively recruited and subjected to the same acquisition protocol. Cerebral microbleeds (CMBs) were manually counted while white matter hyperintensities (WMHs) were segmented using ITK-Snap. Wilcoxon signed-rank test, Spearman correlation, and Bland-Altman statistics were used. The median (interquartile range [IQR]) age was 45.0 (30.5-49.5) years in ToF patients and 46.0 (30.5-49.8) years in controls. The median (IQR) of the number of CMBs was 6.0 (4.0-7.8) in ToF patients and 0 (0.0-0.0) in controls (p = 0.002). The WMHs burden was 2,506 (1,557-2,900) mm3 for ToF patients and 2,212 (1,860-2,586) mm3 for controls (p = 0.160). Moreover, a positive significant correlation was found between the WMHs burden and the NYHA class (ρ = 0.80, p = 0.005). Inter-operator concordance rate for the presence/absence of CMBs was 90%; the reproducibility for the WMHs burden was 77%. In conclusion, we found more cerebral microbleeds and a higher WMHs burden in adult ToF patients than in controls. This preliminary comparison supports the hypothesis of an early brain aging in ToF patients. Larger studies are warranted.

Prevention of cardiovascular diseases with Carotenoids.

Oxidative stress is a key contributor to the development of cardiovascular diseases. Bioactive dietary elements including phytochemicals, and in particular, carotenoids display antioxidant effect and substantially reduce markers of oxidative stress. Carotenoids have been shown to prevent several chronic disorders including cardiovascular diseases by reducing the inflammatory responses. Here, we discuss the use of traditional and novel carotenoids in prevention of cardiovascular disease.

Effects of Polyphenols on Oxidative Stress-Mediated Injury in Cardiomyocytes.

Cardiovascular diseases are the main cause of mortality and morbidity in the world. Hypertension, ischemia/reperfusion, diabetes and anti-cancer drugs contribute to heart failure through oxidative and nitrosative stresses which cause cardiomyocytes nuclear and mitochondrial DNA damage, denaturation of intracellular proteins, lipid peroxidation and inflammation. Oxidative or nitrosative stress-mediated injury lead to cardiomyocytes apoptosis or necrosis. The reactive oxygen (ROS) and nitrogen species (RNS) concentration is dependent on their production and on the expression and activity of anti-oxidant enzymes. Polyphenols are a large group of natural compounds ubiquitously expressed in plants, and epidemiological studies have shown associations between a diet rich in polyphenols and the prevention of various ROS-mediated human diseases. Polyphenols reduce cardiomyocytes damage, necrosis, apoptosis, infarct size and improve cardiac function by decreasing oxidative stress-induced production of ROS or RNS. These effects are achieved by the ability of polyphenols to modulate the expression and activity of anti-oxidant enzymes and several signaling pathways involved in cells survival. This report reviews current knowledge on the potential anti-oxidative effects of polyphenols to control the cardiotoxicity induced by ROS and RNS stress.

Surgical mitral valve replacement with the Melody valve in infants and children: the Italian experience.

AIMS: Paediatric patients with mitral valve (MV) disease have limited options for prosthetic MV replacement. Based on long experience with the stented bovine jugular vein graft (Melody valve) in the right ventricular outflow tract, we aimed to test the use of the Melody valve as a surgical implant in the mitral position in a small group of infants with congenital mitral disease. METHODS AND RESULTS: Eight patients, aged from 3 months to 6.2 years, with congenital MV dysplasia underwent Melody valve implantation in the mitral position between March 2014 and October 2015. Once sutured to the MV annulus, the Melody valve was expanded through a balloon catheter to achieve the best diameter (12-20 mm). Two patients needed ECMO assistance after traditional MV repair and a Melody valve was successfully implanted as possible bail-out. However, neither of them recovered from multi-organ failure and both died, in spite of the well-functioning Melody prosthesis. During follow-up, only one patient underwent catheter-based balloon expansion of the valve. CONCLUSIONS: The medium-term results of this procedure are encouraging. The Melody valve opens up the opportunity to carry out MV replacement in more children at an earlier time point, and it has potential to revolutionise the treatment of MV disease.

Caffeic Acid Phenethyl Ester Regulates PPAR's Levels in Stem Cells-Derived Adipocytes.

Hypertrophic obesity inhibits activation of peroxisome proliferators-activated receptor gamma (PPARγ), considered the key mediator of the fully differentiated and insulin sensitive adipocyte phenotype. We examined the effects of Caffeic Acid Phenethyl Ester (Cape), isolated from propolis, a honeybee hive product, on Adipose Stem Cells (ASCs) differentiation to the adipocyte lineage. Finally we tested the effects of Cape on insulin-resistant adipocytes. Quantification of Oil Red O-stained cells showed that lipid droplets decreased following Cape treatment as well as radical oxygen species formation. Additionally, exposure of ASC to high glucose levels decreased adiponectin and increased proinflammatory cytokines mRNA levels, which were reversed by Cape-mediated increase of insulin sensitivity. Cape treatment resulted in decreased triglycerides synthesis and increased beta-oxidation. Exposure of ASCs to Lipopolysaccharide (LPS) induced a reduction of PPARγ, an increase of IL-6 levels associated with a well-known stimulation of lipolysis; Cape partially attenuated the LPS-mediated effects. These observations reveal the main role of PPARγ in the adipocyte function and during ASC differentiation. As there is now substantial interest in functional food and nutraceutical products, the observed therapeutic value of Cape in insulin-resistance related diseases should be taken into consideration.

Protocatechuic acid activates key components of insulin signaling pathway mimicking insulin activity.

SCOPE: Insulin resistance represents an independent risk factor for metabolic and cardiovascular diseases. Researchers have been interested in identifying active harmless compounds, as many insulin-sensitizing drugs have shown unwanted side-effects. It has been demonstrated that anthocyanins and one of their representative metabolites, protocatechuic acid (PCA), ameliorate hyperglycemia, and insulin sensitivity. This study investigated the mechanism of action of PCA responsible for the glucose uptake upregulation. METHODS AND RESULTS: In human visceral adipocytes, PCA stimulated insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation (+40% with respect to untreated cells) and the downstream events, i.e. phosphoinositide 3-kinase binding to IRS-1 and Akt phosphorylation (+100%, +180%, respectively, with respect to untreated cells). The insulin-like activity of PCA seemed to be mediated by insulin receptor since by inhibiting its autophosphorylation, the PCA effects were completely abolished. Furthermore, PCA was able to activate adenosine monophosphate-activated protein kinase, a serine/threonine kinase whose activation elicits insulin-sensitizing effects. CONCLUSION: This study showed that PCA stimulates the insulin signaling pathway in human adipocytes increasing GLUT4 translocation and glucose uptake. Decreasing insulin resistance is a most desirable aim to be reached for an effective therapeutic/preventive action against metabolic syndrome and type 2 diabetes. Identifying specific food/food components able to improve glucose metabolism can offer an attractive, novel, and economical strategy.