Prevalence and Clinical Significance of Electrocardiographic Complete Right Bundle Branch Block in Young Individuals.

BACKGROUND AND AIMS: There is limited information on the clinical significance of complete right bundle branch block (CRBBB) in young individuals. The aim of this study was to determine the prevalence and significance of CRBBB in a large cohort of young individuals aged 14-35 years old. METHODS: From 2008 to 2018, 104,369 consecutive individuals underwent a cardiovascular assessment with a health questionnaire, electrocardiogram, clinical consultation, and selective echocardiography. Follow-up was obtained via direct telephone consultations. Mean follow-up was 7.3 ± 2.7 years. RESULTS: CRBBB was identified in 154 (0.1%) individuals and was more prevalent in males compared with females (0.20% vs. 0.06%; p<0.05) and in athletes compared with non-athletes (0.25% vs. 0.14%; p<0.05). CRBBB-related cardiac conditions were identified in 7 (5%) individuals (4 with atrial septal defect, 1 with Brugada syndrome, 1 with progressive cardiac conduction disease and 1 with atrial fibrillation). Pathology was more frequently identified in individuals with non-isolated CRBBB compared with individuals with isolated CRBBB (14% vs 1%; p < 0.05) and in individuals with a QRS duration of ≥130 milliseconds (ms) compared with individuals with a QRS of <130ms (10% vs 1%; p<0.05). CONCLUSION: The prevalence of CRBBB in young individuals was 0.1% and was more prevalent in males and athletes. CRBBB-related conditions were identified in 5% of individuals and were more common in individuals with non-isolated CRBBB and more pronounced intraventricular conduction delay (QRS duration of ≥130ms). Secondary evaluation should be considered for young individuals with CRBBB with symptoms, concerning family history, additional electrocardiographic anomalies or significant QRS prolongation (≥130ms).

There is limited information on the clinical significance of complete right bundle branch block (CRBBB) in young people (aged 14 to 35 years old). CRBBB is a rare finding in young individuals and is more common in male and athletic individuals. CRBBB related-conditions are found in 5% of young individuals with this electrocardiogram finding and are more common in those with additional heart symptoms, family history of premature heart disease, other abnormal electrocardiographic (ECG) findings and more pronounced forms of CRBBB (≥ 130 milliseconds). Further investigation, including at least an ultrasound of the heart (echocardiogram), is recommended for all young individuals with CRBBB with concerning symptoms, family history of heart disease, additional ECG anomalies or more pronounced CRBBB (≥130milliseconds).

Magnetic resonance coronary angiography in the era of multimodality imaging.

Cardiovascular magnetic resonance is currently the reference standard for non-invasive measurements of ventricular dimensions and ejection fraction, and may offer a comprehensive assessment of all myocardial tissue properties (including oedema, fibrosis, fat, iron, and protein deposition), as well as of stress perfusion, conveniently as part of a single examination. It also has a well-established role for coronary assessment in paediatric patients, especially with congenital heart disease and vasculitides, such as Kawasaki disease, and it should be considered as a first-line technique in these cases. Despite being recognised as a safe, non-radiating, and non-contrast technique, it is yet to be implemented widely in clinical use as an efficient alternative to computed tomography coronary angiography. Currently impressive progress is being made in the development of sequences and overcoming technical challenges, which are thoroughly discussed in this article, while further development is required to convert this into a robust, non-invasive technique for routine clinical decision-making in cardiovascular disease, particularly in adult patients. In this review, we will summarise current clinical applications of magnetic resonance coronary imaging, both in adult and paediatric populations, with reference to currently established imaging techniques, focusing also on ongoing research and future development.

Assessing the Impact of Frailty on Cognitive Function in Older Adults Receiving Home Care.

It is commonly accepted that frailty and dementia-related cognitive decline are strongly associated. However, degree of this association is often debated, especially in homebound elders with disabilities. Therefore, this study aimed to investigate the association of frailty on cognitive function in older adults receiving homecare. A screening for frailty and cognitive function was conducted at 12 primary healthcare settings of the nationally funded program "Help at Home" in Heraklion Crete, Greece. Cognitive function and frailty were assessed using the Montreal Cognitive Assessment questionnaire and the SHARE-f index, respectively. Barthel-Activities of Daily Living and the Charlson Comorbidity Index were also used for the identification of disability and comorbidity, respectively. The mean age of the 192 participants (66% female) was 78.04 ± 8.01 years old. In depth-analysis using multiple linear regression, revealed that frailty was not significantly associated with cognitive decline (frail vs. non-frail (B'=-2.39, p=0.246) even after adjusting for depression and multi-comorbidity. Importantly, as protective factors for cognitive decline progression and thus dementia development, was scientifically correlated with annual individual income >4500 (B'=2.31, p=0.005) -poverty threshold-compared to those with <4500 and, higher education level as compared to Uneducated (B'=2.94, p=0.019). However, depression was associated with cognitive decline regardless of socioeconomic variables. In conclusion, our results suggest that health professionals caring for frail people with cognitive impairment, must focus on early recognition and management of depression.

Renal Effects of SGLT-2 Inhibitors and Other Anti-diabetic Drugs: Clinical Relevance and Potential Risks.

Type 2 diabetes mellitus (T2DM) is a metabolic disease affecting an increasing percentage of general population worldwide. Patients with T2DM are frequently characterized by impaired renal function, primarily as a result of diabetic kidney injury, but also by other contributing factors, such as hypertension, atherosclerosis, and medications. Sodium-glucose cotransporter (SGLT)-2 inhibitors have emerged as a new, promising class of antidiabetic agents with actions that seem to extend beyond their hypoglycemic effect.

Improving the detection of preclinical organ damage in newly diagnosed hypertension: nocturnal hypertension versus non-dipping pattern.

The clinical relevance of nocturnal hypertension (NH) in comparison with non-dipping status has not been clarified yet, as regards subclinical target organ damage. We aimed to elucidate whether NH or dipping status reflects better organ damage. The study population included 319 newly diagnosed hypertensive patients. Subclinical organ damage was evaluated to all participants. On the basis of nocturnal blood pressure (BP) levels the population was divided into two groups: NH and nocturnal normotension. Also, individuals were defined as dippers and non-dippers according to systolic BP fall. Patients with NH were characterized by increased arterial pulse wave velocity (PWV; 9.1±1.7 vs 8.4±1.5 m s(-1), P=0.0001) and carotid intima-media thickness (0.77±0.18 vs 0.69±0.15 mm, P=0.016) compared with normotensive subjects. Notably, they also exhibited higher values of left ventricular mass index (88.1±22.9 vs 82.8±16.6 g m(-)(2) P=0.043). On the contrary, non-dipping status was associated only with differences in PWV (9.26±0.2 vs 8.64±0.2 m s(-1), P=0.031, 8) and in creatinine clearance (95±3 vs 106±4, P=0.025) in the group of NH. The presence of NH is accompanied by subclinical atherosclerosis, as well as structural abnormalities of the left ventricle. Therefore, NH rather than non-dipping status could be preferably integrated with the risk of organ damage.

Clinical utility of biomarkers in premature atherosclerosis.

Atherosclerosis is a very complex procedure responsible for the development of coronary artery disease which is the leading cause of death in the civilized world. The obvious pandemic character of atherosclerosis augments the need to discover an ideal biomarker, which will be able to facilitate the clinical diagnosis of the atherosclerosis from the physicians especially in the early stages of the atherosclerotic process. Among the biomarkers that are already used there are classical ones, such as c-reactive protein, interleukins, tumour necrosis factor, apolipoproteins, fibrinogen, homocysteine, and novel promising ones such as lipoprotein-associated phospholipase, asymmetric dimethylarginine, myeloperoxidase, cathepsins and cystatin C. The possibility of combining circulating biomarkers with other methods such as non-invasive and invasive imaging is clinically attractive because this could contribute to the improved diagnosis and understanding of premature atherosclerosis pathogenesis.

Assessment of acute coronary syndromes: focus on novel biomarkers.

Coronary artery disease (CAD) is the leading cause of mortality in Western Societies and several developing countries. Recent evidence suggests that most detrimental clinical manifestations of CAD, such as acute coronary syndromes (ACS), are the outcome of inflammatory processes that lead to plaque formation and rupture and eventually to ischemia and potentially myocardial necrosis. Neither of the traditionally used biomarkers is thought to be the gold standard in detection of myocardial ischemia or necrosis. A biomarker that could detect quite early the ischemic myocardium as well as define the risk of a future event with high sensitivity and specificity is still lacking. Several biomarkers, implicated in the pathogenesis and clinical evolution of atherosclerosis, have emerged as potent biomarkers for early detection of myocardial ischemia. In the current review, we summarize recent evidence of the most promising biomarkers and discuss their potential role in clinical practice in patients suffering from ACSs.

Monitoring calcific aortic valve disease: the role of biomarkers.

Calcific aortic valve disease is a common disease in the elderly associated with significant morbidity and mortality. It was once described as a passive degenerative process during which serum calcium attaches to the valve surface and binds to the leaflet. However, during the last decade mounting evidence demonstrated that this disease has an active biologic process with numerous signaling pathways. The histological hallmarks seem to be inflammation, oxidized lipids-also detectable in aortic valve lesions-and a remodeling of the extracellular matrix leading to bone formation. Over the years, growing evidence has indicated the risk factors for calcific aortic stenosis including lipids, hypertension, male gender, renal failure, and diabetes. Additional monitoring tools, such as molecular imaging, could improve risk stratification, while assessment of severity and prognosis of patients with chronic aortic regurgitation, is desirable. Also, several studies have investigated the role of biomarkers regarding their utility in the screening of calcific aortic valve disease and their putative clinical value, though their role still remains undetermined.

Circulating endothelial progenitor cells as biomarkers for prediction of cardiovascular outcomes.

Experimental studies suggest that bone marrow-derived endothelial progenitor cells (EPCs) play an important role in the maintenance of endothelial integrity and hemostasis. The number of circulating EPC has been shown to be inversely correlated with cardiovascular risk factors and vascular function and to predict cardiovascular events independent of both traditional and non-traditional risk factors. Thus, EPCs provide a clinical advantage over the use of other biomarkers as their measurement is directly associated with endothelial function, and available evidence suggests that they are consistently and significantly associated with a spectrum of cardiovascular complications, such as acute coronary syndromes and coronary artery disease. However, many issues in the field of EPC isolation and identification, particularly in regards to the effective and unequivocal molecular characterization of these cells still remain unresolved. In addition, simple EPC counts do not adequately describe cardiovascular disease risk. This limitation is attributable to variation in the definition of EPCs, the number of existing cardiovascular risk factors in different patients as well as a difference in the interaction between EPCs and other hematopoietic progenitor, inflammatory cells or platelets.

The role of microRNAs in cardiovascular disease.

Cardiovascular disease, which is multifactorial and can be influenced by a multitude of environmental and heritable risk factors, remains a major health problem, even though its pathophysiology is far from been elucidated. Discovered just over a decade ago, microRNAs comprise short, non-coding RNAs, which have evoked a great deal of interest, due to their importance for many aspects of homeostasis and disease. Hundreds of different microRNAs are constantly being reported in various organisms. According to a growing body of literature, they have been implicated in the regulation of human physiological processes. More specifically, miRNAs are expressed in the cardiovascular system and could have crucial roles in normal development and physiology, as well as in disease development. Furthermore, they have been shown to participate in cardiovascular disease pathogenesis including atherosclerosis, coronary artery disease, myocardial infarction, heart failure and cardiac arrhythmias. In contrast to our original thought, miRNAs exist in circulating blood and are relatively stable, thus, they could be proved useful as biomarkers in that state. Understanding the underlying mechanisms, in which these major regulatory gene families are implicated, will provide novel opportunities for diagnosis and therapy of cardiovascular diseases.

Estimation and variable selection via frailty models with penalized likelihood.

The penalized likelihood methodology has been consistently demonstrated to be an attractive shrinkage and selection method. It does not only automatically and consistently select the important variables but also produces estimators that are as efficient as the oracle estimator. In this paper, we apply this approach to a general likelihood function for data organized in clusters, which corresponds to a class of frailty models, which includes the Cox model and the Gamma frailty model as special cases. Our aim was to provide practitioners in the medical or reliability field with options other than the Gamma frailty model, which has been extensively studied because of its mathematical convenience. We illustrate the penalized likelihood methodology for frailty models through simulations and real data.

Functional imaging of tumours with 99Tcm-sestamibi pinhole scintigraphy.

This study presents the advantages of pinhole over parallel-hole scintigraphy in the assessment of 99Tcm-sestamibi-related tumour biology. Twenty-five patients with malignancies underwent 99Tcm-sestamibi scintigraphy (Cardiolite, Dupont) before radiotherapy, 10 of whom had repeat scintigrams after the delivery of 25 Gy and at the end of radiotherapy. A total of 45 scintigrams with parallel-hole and pinhole collimation were evaluated for tumour avidity and ability to provide images for differential biological analysis within the tumour (areas of different uptake) or beyond the main mass (multifocality, satellite tumoral foci). The pinhole collimator was located with precision over the tumour area using a radiotherapy simulator. In 19 of 45 (42%) parallel-hole scintigrams the tumours were non-avid, whereas in 13 of 45 (29%) the tumours could be identified but the image quality was very poor. In contrast, tumour avidity was assessed in all 25 cases (100%) using pinhole scintigraphy and all pinhole images were evaluable for assessment of 99Tcm-sestamibi biology. The tumour-to-normal tissue (T/N) count ratio for the tumoral centre ranged from 1.71 to 4.36 (median 3.07) vs 1.54 to 3.20 (median 2.18) at the periphery, as assessed by pinhole imaging. Of 10 cases followed up with repeated scintigrams during radiotherapy, 2 showed an increasing T/N ratio during radiotherapy, both of whom did not respond to treatment. In the other eight cases, the T/N ratio decreased progressively during radiation treatment and all eight cases showed a varying degree of response on computed tomography or magnetic resonance imaging carried out 2 months after radiotherapy. It is concluded that 99Tcm-sestamibi tumour avidity can be successfully assessed with pinhole scintigraphy. Pinhole scintigraphy provides tumour images suitable for the evaluation of biological features related to radiolabelled pharmaceuticals. The premature observation that tumours showing increased 99Tcm-sestamibi uptake during radiotherapy correlated with poor therapeutic outcome requires further investigation.