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Cardiac neuroendocrine tumors (NETs) are particularly rare tumors that can lead to a very poor clinical outcome, partly because of metastases but mainly because of manifestations of the hormonal activity they exhibit. Prompt diagnosis is important in order to start the most effective treatment for their removal or management, with the fewest complications. They are often difficult to diagnose, especially in their early stages. One of the reasons for this is that the heart is an organ with a high rate of metabolism and is located in close proximity to other high-metabolism organs. In addition, the anatomic location and their small size render their diagnosis extremely challenging. In recent years, hybrid imaging methods have revolutionized the diagnostic approach to oncology patients and have established a place in the diagnosis of cardiac NETs, because they provide both anatomical and functional information at the same time. Positron emission tomography/computed tomography (PET/CT), PET/magnetic resonance imaging (PET/MRI) and single-photon emission computed tomography/CT (SPECT/CT) are widely used in clinical practice because of the very important metabolic information, the high sensitivity and specificity. However, prospective studies are needed to confirm the true clinical and prognostic value of various hybrid imaging diagnostic techniques in cardiac NETs.

The mortality of patients with non-ischemic dilated cardiomyopathy (NIDCM) remains substantial. We evaluated gene expression levels of myocardin, an early cardiac gene, in the peripheral blood cells of NIDCM patients as a prognostic biomarker in their long-term outcome and mortality from congestive HF (CHF). We retrospectively analyzed 101 consecutives optimally treated NIDCM patients of Cretan origin who were enrolled from the HF clinic of our hospital from November 2005 to December 2008. Our patient data were either taken from their medical files or recorded during visits to the HF unit or hospitalizations. Follow-up was carried out by telephone interview and by accessing information from general practitioners and cardiologists in private practice. The median follow-up period was 8 years (mean follow-up 7 ± 3.4 years). The overall mortality during follow-up was 61.4%, while mortality due to congestive heart failure (CHF) was 49.5%. Higher CHF and all-cause mortality were observed in patients with myocardin levels

Mitral commissural prolapse or flail, either isolated or combined with more extensive degenerative valve disease imposes several challenges both on its diagnosis and management whilst being a risk factor for valve reoperation after mitral valve repair. Accurate identification of the prolapsing segment is often not feasible with transthoracic 2D echocardiography, with transesophageal 3D imaging then required for correct diagnosis and surgical planning. Various surgical techniques employed alone or in combination, have yielded good results in the repair of commissural prolapse. Herein, we analyze the specific characteristics of commissural disease focusing our attention on 2D and 3D echocardiographic findings and we briefly comment on techniques employed for surgical correction of the disease.

Cardiac remodeling is recognized as an important aspect of cardiovascular disease (CVD) progression. Machine learning (ML) techniques were applied to basic clinical parameters and electrocardiographic features, in order to detect abnormal left ventricular geometry (LVG) even before the onset of left ventricular hypertrophy (LVH), in a population without established CVD. The authors enrolled 528 patients with and without essential hypertension, but no other indications of CVD. All patients underwent a full echocardiographic evaluation and were classified into 3 groups; normal geometry (NG), concentric remodeling without LVH (CR), and LVH. Abnormal LVG was identified as increased relative wall thickness (RWT) and/or left ventricular mass index (LVMi). The authors trained supervised ML models to classify patients with abnormal LVG and calculated SHAP values to perform feature importance and interaction analysis. Hypertension, age, body mass index over the Sokolow‐Lyon voltage, QRS‐T angle, and QTc duration were some of the most important features. Our model was able to distinguish NG from CR+LVH combined, with 87% accuracy on an unseen test set, 75% specificity, 97% sensitivity, and area under the receiver operating curve (AUC/ROC) equal to 0.91. The authors also trained our model to classify NG and CR (NG + CR) against those with LVH, with 89% test set accuracy, 93% specificity, 67% sensitivity, and an AUC/ROC value of 0.89, for a 0.4 decision threshold. Our ML algorithm effectively detects abnormal LVG even at early stages. Innovative solutions are needed to improve risk stratification of patients without established CVD, and ML may enable progress in this direction., We used machine learning techniques and found a combination of clinical and ECG features that enable prediction of abnormal left ventricular geometry or left ventricular hypertrophy (LVH). Concentric remodeling appears to be separable from LVH through a random forest method.

Aims Despite the existence of many studies, there are still limited data about the characteristics of myocarditis in Greece. This led to the creation of the Greek Myocarditis Registry aiming to document the different symptoms and treatment of myocarditis, assess possible prognostic factors, and find similarities and differences to what is already published in literature. This paper is a preliminary descriptive analysis of this Registry. Methods and results We analysed data for the hospitalization period of all patients included in the Registry from December 2015 until November 2017. Statistics are reported as frequency (%) or median and inter‐quartile range (IQR) as appropriate. In total, 146 patients were included; 83.3% of the patients reported an infection during the last 3 months. The most common symptom, regardless of the underlying infection, was chest pain (82.2%) followed by dyspnoea (18.5%), while the most common finding in clinical examination was tachycardia (26.7%). Presentation was more frequent in the winter months. ECG findings were not specific, with the repolarization abnormalities being the most frequent (60.3%). Atrial fibrillation was observed in two patients, both of whom presented with a reduced ventricular systolic function. Left ventricular ejection fraction changed significantly during the hospitalization [55% (IQR: 50–60%) on admission vs. 60% (IQR: 55–60%) on discharge, P = 0.0026]. Cardiac magnetic resonance was performed in 88 patients (61%), revealing mainly subepicardial and midcardial involvement of the lateral wall. Late gadolinium enhancement was present in all patients, while oedema was found in 39 of them. Only 11 patients underwent endomyocardial biopsy. Discharge medication consisted mainly of beta‐blockers (71.9%) and angiotensin‐converting enzyme inhibitors (41.8%), while 39.7% of the patients were prescribed both. Conclusions This preliminary analysis describes the typical presentation of myocarditis patients in Greece. It is a first step in developing a better prognostic model for the course of the disease, which will be completed after the incorporation of the patients' follow‐up data.

Paragangliomas are rare tumors of chromaffin cells arising from an extra-adrenal location. Unlike pheochromocytomas, they are seldom functional. We present a case of pericardial paraganglioma incidentally encountered on an echocardiographic study, focusing on the characteristic features the tumor demonstrates on different imaging modalities. (Level of Difficulty: Intermediate.)

Background: Early diagnosis of long QT type 3 (LQT3) syndrome during the neonatal period is of paramount clinical importance. LQT3 syndrome results in increased mortality and a mutation-specific response to treatment compared to other more common types of LQT syndrome. Mexiletine, a sodium channel blocker, demonstrates a mutation-specific QTc shortening effect in LQT3 syndrome patients.Case Presentation: A neonate manifested marked QTc prolongation after birth. An electrocardiogram (ECG) recording was performed due to positive family history of genetically confirmed LQT3 syndrome (SCN5A gene missense mutation Tyr1795Cys), and an association with sudden cardiac death was found in family members. The mexiletine QTc normalizing effect (QTc shortening from 537 to 443 ms), practical issues related to oral mexiletine treatment of our young patient, along with a literature review regarding identification and mexiletine treatment in infants with LQT3 syndrome are presented.Conclusions: Mexiletine could be considered in the treatment of high-risk LQT3 patients already in the neonatal period in addition to b-blocker therapy. Availability of standardized commercial mexiletine pediatric formulas, serum mexiletine level analyses, and future prospective studies are needed to evaluate the potential beneficial effect of early mexiletine treatment on the incidence of future acute cardiac events in these high-risk LQT syndrome patients.

Background Brugada syndrome (BrS) is a genetically heterogeneous channelopathy that may lead to sudden death. We report a novel mutation of the ankyrin-B gene that is probably related to the occurrence of BrS in two brothers. Case summary First, we present the case of a 27-year-old male who was admitted to the hospital with acute myocarditis. The patient showed left ventricular dysfunction and was given carvedilol. Six days later, while asymptomatic and afebrile, the patient exhibited an electrocardiogram (ECG) with repolarization ‘saddleback’ ST changes in V2. A procainamide provocative test was performed with a response for Type 1 Brugada ECG pattern. Genetic testing revealed a novel mutation, c.5418T>A (+/−) (p.His1806Gln), in the ankyrin-B gene encoding. His 34 years old brother had an ECG J point elevation in leads V1 and V2 of 1 mm not fulfilling diagnostic criteria for Brugada ECG pattern. He also experienced arrhythmia-related syncope. Flecainide provocation test changed ECG towards a Type 1 Brugada pattern. A subcutaneous implantable defibrillator (ICD) was implanted. Patient 1 remains asymptomatic while Patient 2 experienced an appropriate ICD shock during follow-up. Discussion In this case series, two brothers with BrS exhibited the same mutation of the ankyrin-B gene. Ankyrin-B is associated with the stability of plasma membrane proteins in the voltage-gated ion channels. Our finding provides a foundation for further investigation of this mutation in relation to BrS. Moreover, the timing of its presentation raises concerns as to whether myocarditis or beta-blockers are associated with the presentation of BrS ECG.

Heart failure (HF) with mid-range ejection fraction (HFmrEF) is a newly suggested entity in HF. Since it has been inadequately addressed, there is an urgent need to determine the profile of HFmrEF patients and the optimal approach to their management. The present study aimed to assess the long-term clinical outcomes of hypertensive patients with HFmrEF and the impact of blood pressure (BP) on their mortality and cardiovascular outcome. We performed a retrospective observational study that included 121 hypertensive patients with HFmrEF and 149 hypertensives with heart failure and preserved ejection fraction (HFpEF). The median follow-up was 84 months (22-122). Our analysis did not reveal any statistically significant difference between the two groups in total mortality (P = 0.34) or cardiovascular mortality (P = 0.54). The total mean survival time was 102.9 months (100.5-110.1), while the mean survival time was 105.3 months (80.4-90.2) in HFpEF and 97.6 months (92.7-102.6) in HFmrEF. An office systolic BP > 139 mm Hg and diastolic BP > 89 mm Hg were significantly associated with both all-cause mortality (P = 0.02 and P = 0.013, respectively) and cardiovascular mortality (P = 0.02 for both). In HFpEF patients, no significant association was found between outcome and office BP. HFpEF and HFmrEF have similar long-term outcomes. Suboptimal BP levels are a significant risk factor for an adverse outcome in HFmrEF. Our results emphasize the importance of good BP control in order to achieve better outcomes in hypertensives with impaired EF and HF symptomatology.

The effects of systemic hypertension on left ventricular function have been well described, as has been the response of the resulting alterations to antihypertensive treatment. However, hypertension effects on the right ventricle (RV) have not been sufficiently investigated; only in recent years, with the development of new imaging modalities, has its importance become widely recognized. Indeed, evidence from clinical trials suggestive of RV functional and structural impairment early in the course of arterial hypertension continues to accumulate. Newer imaging techniques, especially speckle-tracking-derived myocardial deformation imaging, have provided new insights into the effect of systemic hypertension on this previously neglected cardiac chamber. Two- and three-dimensional echocardiography, along with cardiac magnetic resonance imaging, forms the cornerstone of RV structural and functional assessment. This article provides an overview of the effect of longstanding hypertension on RV structure and function, the respective underlying mechanisms, and the potential therapeutic implications. It summarizes the available options for RV structural and functional assessment, and evaluates the existing evidence with respect to RV alterations in hypertensive disease, aiming to assess the current limits of scientific knowledge about a heart chamber that has only recently become the focus of greater interest.

Background: microRNAs (miRs) have emerged as important modulators of cardiovascular development and disease. Our aim was to determine whether cardiac-related miRs such as miR-21-5p and miR-1-3p were differentially expressed in acute viral myocarditis and whether any of them was related with the extent of myocardial damage and left ventricular dysfunction. Methods: We enrolled 40 patients with acute viral myocarditis. Blood samples were taken on admission and miRs expression levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. Results: miR-21-5p, miR-1-3p were significantly elevated in acute myocarditis. miR-21-5p levels showed a strong correlation with global longitudinal strain (r = 0.71, p &lt, 0.01), while miR-1-3p had significant correlations with troponin I (r = 0.79, p &lt, 0.01). Conclusions: The expression of miR-21-5p and miR-1-3p in peripheral blood is increased in acute viral myocarditis, and this increase is correlated with myocardial damage and indicative of left ventricular systolic dysfunction in these patients.

Purpose To associate the impact of aortic reconstruction using currently available grafts and endografts on pulse wave velocity in patients with abdominal aortic aneurysm (AAA) and to evaluate its effect on early cardiac systolic function indices. Materials and Methods Seventy-three consecutive patients with AAA (mean age 70±8 years; all men) who underwent open (n=12) or endovascular repair (EVAR; n=61) were prospectively enrolled in an observational cohort study. Left ventricular global longitudinal strain (GLS; an important diagnostic and prognostic index of early systolic dysfunction) and carotid-femoral pulse wave velocity (cf-PWV) were estimated 1 week preoperatively, as well as at 1 and 6 months postoperatively. Results A significant time effect was found for cf-PWV, which showed an increase at 1 month that remained through 6 months (p=0.007). Additionally, a deterioration in GLS values was revealed, with a significant change at 1 month that persisted 6 months later (pConclusion AAA repair leads not only to an increase in aortic stiffness, as measured by the increase in pulse wave velocity, but also to reduced cardiac systolic function. Our findings highlight the need for a more intense cardiac surveillance program after aortic reconstruction. Further studies are needed to investigate how this may translate into long-term manifestations of cardiovascular complications and symptomatology.

Cardiac remodeling is recognized as an important aspect of cardiovascular disease (CVD) progression. Machine learning (ML) techniques were applied on basic clinical parameters and electrocardiographic features for detecting abnormal left ventricular geometry (LVG), even before the onset of left ventricular hypertrophy (LVH), in a population without established CVD. After careful screening, we enrolled 528 subjects with and without essential hypertension, but no other indications of CVD. All patients underwent a full echocardiographic evaluation and were classified into 3 groups; normal geometry (NG), concentric remodeling without LVH (CR), and LVH. Abnormal LVG was identified as increased relative wall thickness (RWT) and/or left ventricular mass index (LVMi). We trained nonlinear predictive ML models, to classify subjects with abnormal LVG and calculated SHAP values to perform feature importance and interaction analysis. Hypertension, age, body mass index over the Sokolow-Lyon voltage, QRS-T angle, and QTc duration were some of the most important features. Our model was able to distinguish NG from all others (CR+LVH), with accuracy 86%, specificity 75%, sensitivity 95%, and area under the receiver operating curve (AUC/ROC) 0.89. We also trained our model to classify NG and CR (NG+CR) against those with established LVH, with accuracy 89%, specificity 97%, sensitivity 50%, and AUC/ROC 0.85. Our ML algorithm effectively detects abnormal LVG even at early stages. Innovative solutions are needed to improve risk stratification of patients without established CVD, especially in primary care settings, and ML may enable this direction.

Paragangliomas are rare tumors of chromaffin cells arising from an extra-adrenal location. Unlike pheochromocytomas, they are seldom functional. We present a case of pericardial paraganglioma incidentally encountered on an echocardiographic study, focusing on the characteristic features the tumor demonstrates on different imaging modalities. (Level of Difficulty: Intermediate.), Graphical abstract

Recent advances in Spatial Temporal Image Correlation (STIC) 4 D fetal echocardiography include the application of eSTIC based on electronic probe image acquisition. We aimed to directly compare the performance of conventional STIC versus eSTIC technique (B-Mode and color Doppler imaging) during off-line reconstruction of STIC/eSTIC fetal heart volume pairs.Pairs of B-Mode and Color Doppler STIC volumes were acquired sequentially by firstly conventional (STIC) followed by electronic (eSTIC) probes during 33 consecutive obstetric scans at median 23 (range 13-31) gestational weeks. The resulting 66 fetal heart volume pairs were assessed blindly off-line by a fetal cardiologist who documented feasibility of reconstruction, presence of motion artifacts, subjective image quality on a 4-level scale: 1-best to 4-non-diagnostic and morphological diagnosis, to enable a paired comparison of STIC and eSTIC in the same fetus under similar scanning conditions.eSTIC volumes had higher temporal resolution (37 vs. 24 frames per second,eSTIC was associated with more effective 4 D fetal heart reconstruction due to reduced motion artifacts and superior image quality in all planes, when compared to STIC. Early gestation reconstructions were not generally successful using either technology. Further study is needed to define the cost-effectiveness and diagnostic impact of eSTIC over conventional STIC and their role over, or in addition to, screening 2 D fetal echocardiography by appropriately trained sonographers.

Long non-coding RNAs (lncRNAs) participate in the modulation of cardiac hypertrophy, and they represent potential therapeutic targets in cardiovascular disease. We investigated the expression profiles of selected lncRNAs in peripheral blood mononuclear cells of patients with essential hypertension in relation to left ventricular hypertrophy. We assessed the expression levels of the lncRNAs MHRT, FENDRR and CARMEN using real-time reverse transcription polymerase chain reaction. Hypertensive patients showed significantly higher MHRT, FENDRR and CARMEN expression levels compared with healthy controls. In addition, we observed significant negative correlations of MHRT (r = -0.323, P = 0.003) and FENDRR (r = -0.380, P = 0.001) and a positive correlation of CARMEN (r = 0.458, P < 0.001) expression levels with left ventricular mass index. Our data reveal that the lncRNAs MHRT, FENDRR and CARMEN show distinct expression profiles in hypertensive patients and they possibly represent candidate therapeutic targets in hypertensive heart disease.

Anomalous origin of the left coronary artery arising from the pulmonary artery (ALCAPA or Bland-White-Garland syndrome) is a rare but serious congenital coronary artery anomaly, with a poor prognosis without surgical repair. There are two types of ALCAPA syndrome: infant type and adult type. We present a rare case of a 63-year-old female patient, with isolated left anterior descending artery origin from the pulmonary artery. Coronary computed tomography angiography revealed giant and tortuous coronary arteries with many collaterals between the left and right coronary system. The patient refused any surgical treatment.

The authors evaluated the effectiveness of percutaneous renal revascularization (PRR) with stenting for the treatment of atherosclerotic renal artery stenosis (ARAS) in patients with coronary artery disease and the usefulness of captopril renal scintigraphy for predicting clinical outcomes after PRR. Sixty‐four consecutive patients, referred for evaluation of suspected ARAS, after coronary angiography, underwent baseline captopril renal scintigraphy followed by renal angiography. Forty‐four patients (68.7%) were diagnosed with a significant ARAS≥ 60% and were treated with PRR plus medical therapy. Twenty‐four months after PRR, 86.4% and 73.3% of patients showed a hypertension and renal benefit, respectively. Captopril renal scintigraphy positivity had moderate sensitivity and high specificity in predicting a hypertension and renal benefit. In patients with ARAS≥ 70%, the sensitivity and specificity were 100% for both a hypertension and renal benefit. PRR for ARAS conferred a substantial benefit in patients with a high coronary artery disease burden. Captopril renal scintigraphy was highly accurate in predicting clinical outcomes.

Catecholamines play a major role in atherothrombotic mechanisms in essential hypertension. Alpha 2B -adrenergic receptors (α2B-ARs) are implicated in the pathophysiology of platelet aggregation. In this study, we evaluated platelet α2B-AR gene expression levels in patients with well-controlled essential hypertension compared with normal individuals and investigated their association with increased arterial stiffness. Fifty-nine patients with well-controlled essential hypertension (34 men, mean age 65 ± 9 years) and 26 normotensives (19 men, mean age 64 ± 8 years) were included in the study. For each patient, carotid-femoral pulse wave velocity (PWV) and carotid-radial PWV were evaluated. In addition, blood samples were obtained and platelets were isolated. The α2B-AR gene expression levels in platelets were examined by real-time polymerase chain reaction for each participant. Well-controlled hypertensive patients showed significantly higher gene expression levels of α2B-Rs in platelets compared with normotensives (34.7 ± 29.5 vs 17.6 ± 12.5, respectively, P = .005). Interestingly, we found that carotid-femoral PWV and carotid-radial PWV were positively correlated with platelet α2B-R gene expression levels (r = 0.59, P P = .002, respectively).Platelet α2B-R gene expression levels are increased in patients with well-controlled essential hypertension compared with normotensives and are correlated with increased PWV in those patients. Our data indicate an association of arterial stiffness and platelet α2B-Rs gene expression and indicate the need for further research.

Atrial fibrillation (AF) constitutes a relatively infrequent pregnancy complication, which may be a therapeutic Gordian knot. Indeed, sparse data exist regarding the prevalence, prognosis, and management of AF during pregnancy. In general, AF occurs as a benign, self-limited arrhythmia, but occasionally may have severe hemodynamic consequences in pregnant patients suffering from heart failure, congenital heart disease, or other comorbidities. Extra-cardiac causes of AF should always be meticulously excluded.Treatment decisions are difficult, since medications may cross the placental barrier and potentially affect fetal growth and organogenesis, or even result in fetal bradyarrhythmias. Treatment goals are not differentiated in comparison to those regarding AF occurring in the general population. Still, while maternal treatment is prioritized, issues regarding fetal health must deliberately be considered. Consequently, hemodynamic instability is to be promptly treated with synchronized electrical cardioversion. In contrast, in stable patients, pharmacologic cardioversion, under appropriate antithrombotic regimen, should be attempted. Selection of appropriate antithrombotic therapy, including novel oral anticoagulants, imposes further difficulties on therapeutic decision-making. Further clinical trials are warranted in order to assess the pathophysiology and prognosis of AF in pregnancy and ameliorate the evidence-based therapeutic strategy in this specific group of the population.

Background Although sacubitril/valsartan has recently shown its long-term benefits on morbidity and mortality in symptomatic patients with chronic heart failure with reduced ejection fraction (HFrEF), its short-term effects on diastolic function remain uncertain. We sought to assess 30-day effects of sacubitril/valsartan on left ventricular (LV) diastolic paremeters determined by speckle tracking and tissue Doppler imaging (STI and TDI respectively) as well as their association with functional capacity change evaluated by peak oxygen uptake (VO2max) in stable patients with symptomatic HFrEF. Methods A total of 35 patients (aged 61 ± 9 years) eligible for sacubitril/valsartan underwent a complete two-dimension (2D) echocardiographic study and a cardiopulmonary exercise test at baseline and 30 days after the initiation of therapy. Results Significant improvements in ratio of trans-mitral inflow early diastolic velocity E to mitral annulus early diastolic velocity E′ (ΔE/E′ = -35.9%, p = 0.001), peak early diastolic strain rate SRE (ΔSRE = +22.5%, p = 0.024) and ratio E/SRE (ΔE/SRE = -33.2%, p = 0.025) were observed after 1-month therapy. Compared with baseline, VO2max also increased significantly by 16.7 % (p = 0.001). Baseline E/SRE and ΔE/SRE were the strongest independent predictors of VO2max improvement (beta = -0.43, p = 0.004 and beta= 0.45, p =0.021 respectively) in the multivariate analysis. Conclusions Sacubitril/valsartan was associated with early improvement in LV diastolic function determined by TDI and 2D STI. Baseline E/SRE was stronger than standard echocardiographic parameters in predicting the early benefit of sacubitril/valsartan therapy.

Salt has been linked very closely to the occurrence and complications of arterial hypertension. A large percentage of patients with essential hypertension are salt-sensitive; that is, their blood pressure increases with increased salt intake and decreases with its reduction. For this reason, emphasis is placed on reducing salt intake to better regulate blood pressure. In day-to-day clinical practice this is viewed as mandatory for hypertensive patients who are judged to be salt-sensitive. Previous studies have highlighted the negative effect of high-salt diets on macrovascular function, which also affects blood pressure levels by increasing peripheral resistances. More recent studies provide a better overview of the pathophysiology of microvascular disorders and show that they are largely due to the overconsumption of salt. Microvascular lesions, which have a major impact on the functioning of vital organs, are often not well recognized in clinical practice and are not paid sufficient attention. In general, the damage caused by hypertension to the microvascular network is likely to be overlooked, while reversion of the damage is only rarely considered as a therapeutic target by the treating physician. The purpose of this review is to summarize the impact and the harmful consequences of increased salt consumption in the microvascular network, their significance and pathophysiology, and at the same time to place some emphasis on their treatment and reversion, mainly through diet.

Background Right ventricular (RV) apex has proven to induce abnormal left ventricular (LV) activation pattern leading to pacing-induced cardiomyopathy (PICM) in a substantial percentage of paced patients. This study assessed the impact of paced QRS duration on the expression in the peripheral blood of sarcoplasmic reticulum calcium ATPase (SERCA) and investigated whether its width is related to the extend of LV remodelling. Methods We enrolled 52 consecutive patients with preserved ejection fraction (EF) who underwent pacemaker implantation for bradycardic indications. Group A consisted of 24 patients paced for atrioventricular conduction disturbances with QRS = 142 ± 12 ms post-implant and group B of 28 patients paced for sinus node disease with QRS = 94 ± 2%ms post-implant. mRNA levels of SERCA were assesed at implantation, 3, 6 and 12 months follow-up, while echocardiographic parameters at implantation, 1, 2 and 4 years. Results In group A, mRNA levels of SERCA decreased significantly at 3 months and remained low at 6 and 12 months' follow-up and were associated to the deterioration of LV function and geometry. Paced QRS duration was associated to both the alteration in the expression of SERCA and to the extend of LV remodelling. In group B no statistically significant change was demonstrated. Conclusions Permanent RV pacing in patients with preserved EF and wide QRS post-implant is associated with a significant reduction of mRNA levels of SERCA. Paced QRS duration is associated to alterations in the expression of SERCA which precede adverse LV remodelling.

Aims Endothelial progenitor cells (EPCs) are bone marrow-derived cells that are mobilized into the circulation to migrate and differentiate into mature endothelial cells contributing to post-natal physiological and pathological neovascularization. In this study, we evaluated circulating EPCs in patients with hypertrophic cardiomyopathy (HCM) and examined a potential association with clinical parameters of the disease. Methods and results We included 40 HCM patients and 23 healthy individuals. Using flow cytometry we measured EPCs in peripheral blood as two subpopulations of CD45–/CD34+/VEGFR2+ and CD45–/CD34+/CD133+ cells. Circulating CD45–/CD34+/VEGFR2+ cells were significantly increased in HCM patients in comparison with the controls (0.000238 ± 0.0003136 vs. 0.000057 ± 0.0001316, respectively, P = 0.002). However, there was no significant difference in the number of circulating CD45–/CD34+/CD133+ cells (0.003079 ± 0.0033288 vs. 0.002065 ± 0.0022173, respectively, P = 0.153). The CD45–/CD34+/VEGFR2+ subpopulation revealed a moderate correlation with LV mass index (r = 0.35, P = 0.026), while both EPC subpopulation levels showed strong positive correlations with th E/e' ratio (r = 0.423, P = 0.007 for CD45–/CD34+/VEGFR2+ and r = 0.572, P

Platelets were traditionally considered to purely have a role in the maintenance of haemostasis. Recently their role in vasomotor function, inflammation and atherosclerosis has been very well-recognized. Endothelium which was originally considered as a simple passive barrier, it is now viewed as an organ whose normal functioning is crucial for maintaining vascular health. When endothelial balance is disturbed, vascular disease initiates. Platelet interactions with endothelium have an important contribution in this process. Low-grade inflammation, endothelial dysfunction, and platelet hyper-reactivity are all independently associated with an increased risk of cardiovascular events. Older antiplatelet agents like aspirin and clopidogrel and newer more potent agents like prasugrel and ticagrelor have been proven effective in all the clinical spectrum of coronary artery disease patients. Current antiplatelet medications and especially newer generation P2Y12 inhibitor ticagrelor, offer clinical benefits not only due to their well-recognized antithrombotic effect, but also via the attenuation of platelet inflammatory action, impediment of P2Y12 activation effects in other cells and through other complex and sometimes undefined pathways. Future research is expected to better define platelet-endothelium interactions and the multiple impact of current antiplatelet therapy on them.

Increased arterial stiffness has been related to altered cardiovascular hemodynamics, left ventricular hypertrophy, and a higher risk for cardiac events. Pulse wave velocity (PWV) has been used as a surrogate marker for arterial stiffness. Treatment of abdominal aortic aneurysms (AAAs) involves insertion of a rigid graft or endograft inside the arterial system which has been shown to increase arterial stiffness, but the cardiac implications of these alterations are mostly unknown. We report a case of a patient with a previous AAA surgical repair (>10 years ago) who developed a para-anastomotic pseudoaneurysm which was excluded with implantation of an endoluminal graft. From a cardiac perspective, this patient was asymptomatic and had a normal baseline preoperative evaluation. He had an initially high PWV (17 m/sec). Postprocedurally, the patient developed cardiac symptoms, and he underwent coronary angiography which indicated significant coronary artery disease, and he subsequently underwent bypass grafting. One week after the endovascular repair, the patient presented with an increased PWV at 21 m/sec. Echocardiographic indices were mostly unaltered (ejection fraction, left ventricular mass index, and left atrium volume index) compared with the preoperative evaluation, except for the global longitudinal strain which deteriorated from −25 to −21%. This case provides insight into hemodynamic alterations after implantation of an endograft which may result in deterioration of asymptomatic heart disease.

Platelets contain abundant microRNAs (miRs) that regulate gene expression and protein synthesis and may reflect platelet activation. We assessed platelet levels of miR-223, miR-126, and miR-22 in 82 patients with essential hypertension and 28 healthy individuals, using real-time reverse transcription polymerase chain reaction, and evaluated their relation with the patients’ clinical profile. Hypertensives had significantly lower platelet miR-22 and miR-223 levels (97.6 ± 170.3 in hypertensives versus 193.8 ± 228.9 in normotensives, p = 0.011, for miR-22; 91.3 ± 154.1 in hypertensives versus 189.9 ± 266.3 in normotensives, p = 0.022, for miR-223). Significant differences in platelet miR levels were also observed between hypertensives who had cardiovascular disease and those who did not (4.1 ± 3.6 versus 75.1 ± 85.2 for miR-126, 24.3 ± 62.9 versus 122.8 ± 187.9 for miR-22, and 10.1 ± 10.4 versus 119.3 ± 169.0 for miR-223, respectively; p

OBJECTIVES Adipose tissue plays a key role in cardiovascular physiology. Kinin receptors are important determinant of the effect of adiposity on endothelial function and cardiovascular function. We examined the gene expression levels of kinin receptors in the subcutaneous white adipose tissue (sWAT) of nondiabetic patients with and without coronary artery disease (CAD). PATIENTS AND METHODS We evaluated 21 patients with CAD (13 men, age: 68±8 years) and 23 patients without CAD (15 men, age: 66±5 years) who underwent catheterization through the femoral route. sWAT biopsies were obtained from the site of vessel puncture before the procedure and analyzed for bradykinin receptor type 1 (BKR1) and 2 (BKR2) gene expression by real-time quantitative PCR. RESULTS Although BKR2 expression levels did not differ significantly (413.12±532.41 in CAD patients vs. 378.33±534.45 in controls, P=NS), BKR1 expression in sWAT was significantly greater in patients with CAD (352.69±455.12 vs. 46.5±46.7, P

MicroRNAs regulate several aspects of physiological and pathologic cardiac hypertrophy, and they represent promising therapeutic targets in cardiovascular disease. We assessed the expression levels of the microRNAs miR-1, miR-133a, miR-26b, miR-208b, miR-499, and miR-21, in 102 patients with essential hypertension and 30 healthy individuals. All patients underwent two-dimensional echocardiography. MicroRNA expression levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. Hypertensive patients showed significantly lower miR-133a (5.06 ± 0.50 vs. 13.20 ± 2.15, P < .001) and miR-26b (6.76 ± 0.53 vs. 9.36 ± 1.40, P = .037) and higher miR-1 (25.99 ± 3.07 vs. 12.28 ± 2.06, P = .019), miR-208b (22.29 ± 2.96 vs. 8.73 ± 1.59, P = .016), miR-499 (10.06 ± 1.05 vs. 5.70 ± 0.91, P = .033), and miR-21 (2.75 ± 0.15 vs. 1.82 ± 0.20, P = .002) expression levels compared with healthy controls. In hypertensive patients, we observed significant negative correlations of miR-1 (r = -0.374, P < .001) and miR-133a (r = -0.431, P < .001) and significant positive correlations of miR-26b (r = 0.302, P = .002), miR-208b (r = 0.426, P < .001), miR-499 (r = 0.433, P < .001) and miR-21 (r = 0.498, P < .001) expression levels with left ventricular mass index. Our data reveal that miR-1, miR-133a, miR-26b, miR-208b, miR-499, and miR-21 show distinct expression profiles in hypertensive patients relative to healthy individuals and they are associated with clinical indices of left ventricular hypertrophy in hypertensive patients. Thus, they may be related to heart hypertrophy in hypertensive patients and are possibly candidate therapeutic targets in hypertensive heart disease.

This study examines the mobilization of mesenchymal stem cells (MSCs) in patients with hypertrophic cardiomyopathy (HCM) compared to healthy individuals. The pathogenesis of myocardial hypertrophy in HCM is not fully understood. MSCs are involved in the process of neovascularization, fibrosis, and ventricular wall remodeling.We included 40 patients with HCM and 23 healthy individuals. Using flow cytometry, we measured MSCs in peripheral blood, as a population of CD45-/CD34-/CD90+ cells and also as a population of CD45-/CD34-/CD105+ cells. The resulting MSC counts were expressed as percentages of the total cells. Patients with HCM were found to have a greater percentage of circulating CD45-/CD34-CD34-/CD90+ cells compared to controls (0.0041±0.005% vs. 0.0007±0.001%, respectively, P.001). No significant difference in circulating CD45-/CD34-/CD105+ cells in the peripheral blood was found between HCM patients and controls (0.016±0.018% vs. 0.012±0.014%, respectively, P=.4). Notably, circulating CD45-/CD34-/CD90+ cells were positively correlated with left ventricular mass index (r=0.54, P.001).Patients with HCM reveal an increased mobilization of MSCs compared to healthy individuals. Although further research is needed to reveal the clinical significance of our findings, our data open a new dimension in the pathophysiology of the disease and may indicate new future therapeutic possibilities.

To compare the peak global longitudinal myocardial strain (PGLS) and peak segmental longitudinal myocardial strain (PSLS) values by speckle-tracking echocardiography (STE) obtained using two different echocardiography devices. STE is an emerging quantitative ultrasound technique that allows an accurate evaluation of global and segmental myocardial function. However, there is a lack of standardization of the acquired data among different manufacturers. Sixty-three subjects, mean age 56.2±10.4 years, underwent complete echocardiographic studies with two different devices (Philips IE33 and General Electric VIVID E9) performed by the same operator. Thirty-one of them had known cardiac disease, with estimated left ventricular ejection fraction r=0.91, Pr=0.79, Pr=0.73, Pr=0.78, P

Catecholamines play a major role in atherothrombotic mechanisms in essential hypertension. Alpha

Cardiac muscle contraction occurs through an interaction of the myosin head with the actin filaments, a process which is regulated by the troponin complex together with tropomyosin and is Ca(2+) dependent. Mutations in genes encoding sarcomeric proteins are a common cause of familial hypertrophic and dilated cardiomyopathies. The scope of this review is to gather information from studies regarding the in vitro characterisation of six HCM and six DCM mutations on the cardiac TnC gene and to suggest, if possible, how they may lead to dysfunction. Since TnC is the subunit responsible for Ca(2+) binding, mutations in the TnC could possibly have a strong impact on Ca(2+) binding affinities. Furthermore, the interactions of mutant TnCs with their binding partners could be altered. From the characterisation studies available to date, we can conclude that the HCM mutations on TnC increase significantly the Ca(2+) sensitivity of force development or of ATPase activity, producing large pCa shifts in comparison to WT TnC. In contrast, the DCM mutations on TnC have a tendency to decrease the Ca(2+) sensitivity of force development or of ATPase activity in comparison to WT TnC. Furthermore, the DCM mutants of TnC are not responsive to the TnI phosphorylation signal resulting in filaments that preserve their Ca(2+) sensitivity in contrast to WT filaments that experience a decrease in Ca(2+) sensitivity upon TnI phosphorylation.

Bradykinin participates in various hypertensive processes, exerted via its type 1 and type 2 receptors (BKR1 and BKR2). The aim of the study was to investigate BKR1 and BK2R gene expression in peripheral monocytes in patients with essential hypertension compared with healthy individuals. Seventeen hypertensive patients (9 males, age 56 ± 7 years) and 12 healthy individuals (7 males, age 55 ± 6) participated. Mononuclear cells isolated using anti-CD14+ antibodies and mRNAs of BKR1 and BKR2 were estimated by real-time quantitative reverse transcription-PCR. Both BKR1 and BKR2 showed significantly upregulated gene expression in the group of hypertensive patients. Specifically, BKR1 gene expression was 142.1 ± 42.2 in hypertensives versus 20.2 ± 8 in controls (P = 0.024) and BKR2 was 1222.2 ± 361.6 in hypertensives versus 259.5 ± 99.1 in controls (P = 0.038). Antihypertensive treatment resulted in a decrease in BKR1 (from 142.1 ± 42.2 to 55.2 ± 17.1, P = 0.065) and in BKR2 (from 1222.2 ± 361.6 to 256.8 ± 81.8, P = 0.014) gene expression. BKR1 and BKR2 gene expression on peripheral monocytes is upregulated in essential hypertension. This may lead to functional changes in monocytes and contribute to the development of target organ damage in hypertensive patients.

A 61-year-old man with a history of smoking (30 pack-years) and dyslipidemia presented with inferior ST-segment elevation myocardial infarction 2 h after symptom onset and was transferred to the cardiac catheterization laboratory for primary percutaneous coronary intervention. Coronary angiography

Aims The aim of this study was to examine autonomic disorders in patients with different types of vasovagal syndrome by performing both a cardiac sympathetic innervation evaluation and a head-up tilt-test with heart rate variability (HRV) analysis. Methods and results We enrolled 60 patients with vasovagal syncope (32 women, mean age 40 ± 16 years), and 20 age-matched controls. We assessed the integrity and function of the myocardial pre-synaptic nerve endings and in the sympathovagal activity, using 123I-metaiodobenzylguanidine (MIBG) scintigraphy and time-domain indexes of HRV. A significantly lower heart/mediastinum ratio was found in the syncopal patients compared with the control group, both at 10 min (1.9 ± 0.25 vs. 3.6 ± 1.7, P = 0.02) and at 4 h (1.79 ± 0.12 vs. 2.07 ± 0.19, P = 0.04), whereas washout rate was significantly greater in syncopal patients (5.5 ± 3.7 vs. 2 ± 0.19, P = 0.04). There were no significant differences in any of the above parameters between patients with different types of syncope. In addition, the majority of the patients showed multiple adrenergic innervation defects in the left ventricular myocardium. No significant difference was found in any of the HRV time-domain indexes. However, a correlation was found between root-mean-square of the difference between successive RRs and washout rate in syncopal patients ( r = −0.256, P = 0.48). Conclusion Patients with vasovagal syncope induced by tilt testing reveal a high degree of disturbance of myocardial adrenergic innervation and multiple adrenergic innervation defects. This suggests a possible predominance of cardiac adrenergic activity in those with abnormal cardiac MIBG scintigraphy.

Aims To assess cardiac gene expression in peripheral blood cells of patients with idiopathic dilated cardiomyopathy (IDCM) and its relationship to echocardiographic left ventricular (LV) function. Methods and results A complete echocardiographic study and blood sampling were performed in 65 consecutive stable IDCM patients with LV ejection fraction (LVEF) 31.76 ± 10.07% and chronic mild to moderate heart failure (NYHA functional class II to III) for ≥9 months. Blood samples from 19 healthy individuals were included for comparison. Transcript levels of myocardin, GATA4, alpha- and beta-myosin heavy chain (MHC), sarcoplasmic reticulum calcium ATPase 2 (SERCA2), and phospholamban were determined by quantitative real-time reverse transcription-polymerase chain reaction. Myocardin (24.88 ± 4.93 vs. 3.98 ± 1.12, P = 0.0048) and GATA4 (17.85 ± 4.85 vs. 0.45 ± 0.15, P = 0.0069 × 10−5) were upregulated in IDCM patients compared with controls, whereas SERCA2 (5.11 ± 0.42 vs. 8.93 ± 1.07, P = 0.001) was downregulated. In IDCM patients, myocardin (r = 0.279, P = 0.025), GATA4 (r = 0.314, P = 0.011), beta-MHC (r = 0.444, P=0.0002), and alpha-MHC (r = 0.272, P = 0.034) showed positive correlations, whereas SERCA2 (r = −0.264, P = 0.034) exhibited a negative correlation with LVEF. Patients with elevated LV filling pressures had lower myocardin (15.06 ± 3.10 vs. 43.12 ± 12.03, P = 0.048), GATA4 (8.96 ± 2.17 vs. 34.38 ± 12.60, P = 0.026), beta-MHC (10.59 ± 4.05 vs. 16.43 ± 4.91, P = 0.013), and alpha-MHC (0.27 ± 0.08 vs. 0.79 ± 0.20, P = 0.033) and higher SERCA2 (5.65 ± 0.54 vs. 3.90 ± 0.61, P = 0.037) levels. Patients with atrial fibrillation (AF) had higher SERCA2 levels compared with sinus rhythm patients (6.75 ± 0.84 vs. 4.54 ± 0.45, P = 0.017). Conclusion Our data indicate that cardiac gene expression alterations in peripheral blood cells of IDCM patients may reflect alterations in LV function, whereas the presence of AF may be associated with increased SERCA2 levels in these patients.

Increased aortic stiffness has been found in heart failure (HF), but the underlying mechanisms remain to be elucidated. The aim of the present study was to examine the association between aortic stiffness and neurohumoral activation in patients with nonischemic dilated cardiomyopathy (NIDC).We examined 101 patients with NIDC, New York Heart Association Class II-III, LVEF 33.3 +/- 11.6%, and 33 controls. All subjects underwent blood sampling for plasma concentrations of renin, aldosterone, C-reactive protein (CRP), and brain natriuretic peptide (BNP). We evaluated the pulse wave velocity (PWV) of the proximal aorta in the region of the aortic arch with a new echo application. Patients showed increased PWV (P.001), and increased plasma levels of log-renin (P.001), log-aldosterone (P = .01), CRP (P = .01), and log-BNP (P = .01) compared with controls. PWV was correlated with log-BNP (r = 0.63, P.001) and log-aldosterone (r = 0.34, P.001) levels, with LV end-diastolic (r = 0.27, P = .01) and end-systolic (r = 0.33, P = 0.003) volumes, and the PW-tissue Doppler imaging systolic wave (r = -0.27, P = .006) and the E/e' ratio (r = 0.45, P.001). Linear regression analysis showed that log-BNP levels were independently associated with PWV.In patients with HF from NIDC, there is evidence of increased aortic stiffness that is correlated with LV shape and function. Although aldosterone levels seem to influence the aortic PWV, BNP levels are the best independent predictor of increased PWV.

We examined the relationship between proximal aortic stiffness and left ventricular (LV) diastolic function in patients with end-stage renal disease (ESRD). We studied 99 patients with ESRD with preserved LV ejection fraction greater than 50% and 83 controls. We assessed the aorta stiffness by measuring the pulse wave velocity (PWV) in the proximal aorta (PWVr) using a novel echo application and in the descending aorta (PWVcf) using a foot-to-foot method. Patients were classified according to LV diastolic filling pattern into normal, delayed relaxation, pseudonormal, and restrictive filing pattern groups. Patients with ESRD had increased PWVr, PWVcf, and LV mass index (LVMI) compared with controls (all P < .0001). Patients with advanced diastolic dysfunction showed increased PWVr (P < .001) and PWVcf (P = .007) compared with those with mild diastolic dysfunction. PWVr was correlated to PWVcf (r = 0.74, P < .001) in patients with ESRD. Multivariate linear regression analysis revealed that PWVr was independently correlated to both LVMI and LV diastolic filling pattern. Increased LVMI, advanced LV diastolic dysfunction, and generalized aortic stiffening were observed in patients with ESRD. Proximal aorta stiffness is associated with both increased LVMI and advanced LV diastolic dysfunction in those patients

Endothelial progenitor cells (EPCs) are bone marrow-derived cells that are mobilized into the circulation to migrate and differentiate into mature endothelial cells contributing to post-natal physiological and pathological neovascularization. In this study, we evaluated circulating EPCs in patients with hypertrophic cardiomyopathy (HCM) and examined a potential association with clinical parameters of the disease.We included 40 HCM patients and 23 healthy individuals. Using flow cytometry we measured EPCs in peripheral blood as two subpopulations of CD45-/CD34+/VEGFR2+ and CD45-/CD34+/CD133+ cells. Circulating CD45-/CD34+/VEGFR2+ cells were significantly increased in HCM patients in comparison with the controls (0.000238 ± 0.0003136 vs. 0.000057 ± 0.0001316, respectively, P = 0.002). However, there was no significant difference in the number of circulating CD45-/CD34+/CD133+ cells (0.003079 ± 0.0033288 vs. 0.002065 ± 0.0022173, respectively, P = 0.153). The CD45-/CD34+/VEGFR2+ subpopulation revealed a moderate correlation with LV mass index (r = 0.35, P = 0.026), while both EPC subpopulation levels showed strong positive correlations with th E/e' ratio (r = 0.423, P = 0.007 for CD45-/CD34+/VEGFR2+ and r = 0.572, P 0.001 for CD45-/CD34+/CD133+).HCM patients showed an increased mobilization of EPCs compared with healthy individuals that correlated with diastolic dysfunction. Our findings may open up new dimensions in the pathophysiology, prognostication, and treatment of HCM.

Left ventricular hypertrophy (LVH) is a strong predictor of adverse cardiovascular outcomes. It is the result of complex mechanisms that include not only an increase in protein synthesis and cell size but also proliferating cardiac progenitor cells and the influx of bone marrow-derived cells developing into cardiomyocytes. Stem and progenitor cells are known to contribute to the renewal of adult mammalian cardiomyocytes in case of myocardial injury or pressure and volume overload. They are activated in LVH and play a regulatory role in myocardial repair. They have high proliferative potential and secrete numerous cytokines, growth factors, and microRNAs that play important roles in cell differentiation, cardiac remodeling, and neovascularization. They are mobilized in response to either mechanical or chemical stimuli, hormones, or pharmacologic agents. Another important source of progenitor cells is the epicardial layer. It appears that precursor cells migrate from the epicardium to the myocardium in order to interact with myocardial cells. In addition, migratory cells participate in the formation of almost all cardiac structures in myocardial hypertrophy. Although the pathophysiological mechanisms are still obscure and further studies are required, their properties may open the door to regenerative cell therapy for the prevention of adverse remodeling.