Hybrid imaging of neuroendocrine tumors in the heart: Union is strength.

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.

Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Cardiac Structural and Electrical Remodeling: From Myocardial Cytology to Cardiodiabetology.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have changed the clinical landscape of diabetes mellitus (DM) therapy through their favourable effects on cardiovascular outcomes. Notably, the use of SGLT2i has been linked to cardiovascular benefits regardless of DM status, while their pleiotropic actions remain to be fully elucidated. What we do know is that SGLT2i exert beneficial effects even at the level of the myocardial cell and that these are linked to an improvement in the energy substrate, resulting in less inflammation and fibrosis. SGLT2i ameliorates myocardial extracellular matrix remodeling, cardiomyocyte stiffness and concentric hypertrophy, achieving beneficial remodeling of the left ventricle with significant implications for the pathogenesis and outcome of heart failure. Most studies show a significant improvement in markers of diastolic dysfunction along with a reduction in left ventricular hypertrophy. In addition to these effects, there is electrophysiological remodeling, which explains initial data suggesting that SGLT2i have an antiarrhythmic action against both atrial and ventricular arrhythmias. However, future studies need to clarify not only the exact mechanisms of this beneficial functional, structural, and electrophysiological cardiac remodeling but also its magnitude to determine whether this is a class or a drug effect.

Electronic versus conventional spatiotemporal image correlation (STIC) fetal echocardiography: a direct comparison.

OBJECTIVES: 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. METHODS: 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. RESULTS: eSTIC volumes had higher temporal resolution (37 vs. 24 frames per second, p < .001), less motion during acquisition (12 vs. 20 cases, O.R. 7.0, p = .002) and better average image quality (1.9 vs. 2.2, p = .006) compared to STIC volumes. More diagnostic reconstructions were achieved by eSTIC (n = 55, 86%) than STIC (n = 52, 78.8%), p = .001), in a comparable analysis time (mean 4.96 vs. 4.94 min). During a comparison of image quality of the original acquisition (A) and reconstructed planes (B and C planes) e STIC was superior in 22 (33%), 39 (59%) and 21 (38%) volumes, respectively, with the remaining cases being of similar quality (<10% in each plane in favor of STIC). Imaging mode and gestational age had a similar impact on both eSTIC and STIC performance: diagnostically acceptable studies in 49 (75.8%) vs. 48 (72.2%) by B-Mode, 60 (90.9%) vs. 56 (84.8%) by Color Doppler Mode, 8 (62.5%) vs. 10 (50%) in early scans, 38 (95%) vs. 38 (95%) in mid-gestation scans, and 7 (70%) vs. 6 (60%) in third trimester scans. Eight obstetric scans identified a fetus with a cardiac variant or structural abnormality. Diagnostic concordance of the two STIC approaches was comparable (40/48 concordant interpretations, kappa 0.657) all confirmed by fetal and/or postnatal echocardiography. CONCLUSIONS: 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.

Mexiletine Treatment for Neonatal LQT3 Syndrome: Case Report and Literature Review.

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.

A case series of Brugada syndrome with a novel mutation in the ankyrin-B gene: an unusual unmasking in acute myocarditis.

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.

Cardiac Paraganglioma: Multimodality Imaging of a Rare Tumor.

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.).

Long-term prognostic value of myocardin expression levels in non-ischemic dilated cardiomyopathy.

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 < 14.26 (p < 0.001 for both CHF and all-cause mortality). A multivariate Cox regression analysis showed that myocardin level of expression had independent significant prognostic value for the risk of death from CHF (HR 14.5, 95% confidence interval (CI) 5.3-39) in those patients. Peripheral blood cells gene expression of myocardin, an early myocardial marker, may serve as prognostic biomarkers of the long-term outcome of patients with NIDCM. Our findings open new prospects in the risk stratification of these patients.

Peripheral Blood MicroRNAs as Potential Biomarkers of Myocardial Damage in Acute Viral Myocarditis.

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 < 0.01), while miR-1-3p had significant correlations with troponin I (r = 0.79, p < 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.

Mitral commissural prolapse.

Mitral commissural prolapse or flail, either isolated or combined with more extensive degenerative valve disease, imposes several challenges both on its diagnosis and management while 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.

Detection of abnormal left ventricular geometry in patients without cardiovascular disease through machine learning: An ECG-based approach.

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.

Early Left Ventricular Global Longitudinal Strain Deterioration After Aortic Aneurysm Repair: Impact of Aortic Stiffness.

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 (p<0.001). No significant group effect was observed between EVAR and open repair (p=0.98), and there was no significant interaction (p=0.96). Notably, the difference in GLS between baseline and 6 months significantly correlated with the corresponding changes in cf-PWV (r=0.494, p<0.001). CONCLUSION: 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.

HEllenic Registry on Myocarditis SyndromES on behalf of Hellenic Heart Failure Association: The HERMES-HF Registry.

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.

The impact of paced QRS duration on the expression of genes related to contractile function of the left ventricle in chronically paced patients from the right ventricular apex.

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.

Short-term effects of angiotensin receptor-neprilysin inhibitors on diastolic strain and tissue doppler parameters in heart failure patients with reduced ejection fraction: A pilot trial.

OBJECTIVE: 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' (ΔΕ//Ε' = -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. CONCLUSION: 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.

Long-term outcome of hypertensive patients with heart failure with mid-range ejection fraction: The significance of blood pressure control.

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.

Right ventricular dysfunction in arterial hypertension: still terra incognita?

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.

Salt-induced effects on microvascular function: A critical factor in hypertension mediated organ damage.

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.

Transient Lingual Ischemia Complicating Coronary Angiography.

Arterial embolism is a potential complication of coronary angiography and could theoretically affect the lingual circulation. However, the transient nature of clinical signs and symptoms suggests vasospasm as the most likely underlying mechanism of lingual ischemia in our case.