Alberto Balbarini

Transvenous removal of pacing and implantable cardiac defibrillating leads using single sheath mechanical dilatation and multiple venous approaches: high success rate and safety in more than 2000 leads

Aims The aim of the present study was to describe a 10 years single-centre experience in pacing and defibrillating leads removal using an effective and safe modified mechanical dilatation technique. Methods and results We developed a single mechanical dilating sheath extraction technique with multiple venous entry site approaches. We performed a venous entry site approach (VEA) in cases of exposed leads and an alternative transvenous femoral approach (TFA) combined with an internal transjugular approach (ITA) in the presence of very tight binding sites causing failure of VEA extraction or in cases of free-floating leads. We attempted to remove 2062 leads [1825 pacing and 237 implantable cardiac defibrillating (ICD) leads; 1989 exposed at the venous entry site and 73 free-floating] in 1193 consecutive patients. The VEA was effective in 1799 leads, the TFA in 28, and the ITA in 205; in the overall population, we completely removed 2032 leads (98.4%), partially removed 18 (0.9%), and failed to remove 12 leads (0.6%). Major complications were observed in eight patients (0.7%), causing three deaths (0.3%). Conclusion Mechanical single sheath extraction technique with multiple venous entry site approaches is effective, safe, and with a good cost effective profile for pacing and ICD leads removal.

Methods for evaluating endothelial function: a position statement from the European Society of Cardiology Working Group on Peripheral Circulation

The endothelium holds a pivotal role in cardiovascular health and disease. Assessment of its function was until recently limited to experimental designs due to its location. The advent of novel techniques has facilitated testing on a more detailed basis, with focus on distinct pathways. This review presents available in-vivo and ex-vivo methods for evaluating endothelial function with special focus on more recent ones. The diagnostic modalities covered include assessment of epicardial and microvascular coronary endothelial function, local vasodilation by venous occlusion plethysmography and flow-mediated dilatation, arterial pulse wave analysis and pulse amplitude tonometry, microvascular blood flow by laser Doppler flowmetry, biochemical markers and bioassays, measurement of endothelial-derived microparticles and progenitor cells, and glycocalyx measurements. Insights and practical information on the theoretical basis, methodological aspects, and clinical application in various disease states are discussed. The ability of these methods to detect endothelial dysfunction before overt cardiovascular disease manifests make them attractive clinical tools for prevention and rehabilitation.

Expression, pharmacology, and functional role of somatostatin receptor subtypes 1 and 2 in human macrophages

Somatostatin (SRIF)‐14 is recognized as an important mediator between the nervous and the immune system, although the functional role of its receptors (sst1–sst5) is poorly understood in humans. In our study, we demonstrate that human macrophages, differentiated from PBMC‐derived monocytes, express sst1 and sst2 mRNAs. sst1 and sst2 are mostly localized at the cell surface and display active binding sites. In particular, sst1/sst2 activation results in a weak internalization of sst1, and the sst2 internalization appears more efficient. At the functional level, the activation of SRIF receptors by the multiligand analogs SOM230 and KE108, but not by SRIF‐14 or cortistatin‐14, reduces macrophage viability. Their effects are mimicked by the selective activation of sst1 and sst2 using CH‐275 and SMS 201‐995/L‐779,976, respectively. Further, sst1‐ and sst2‐mediated effects are reversed by the sst1 antagonist SRA‐880 or the sst2 antagonist CYN 154806, respectively. CH‐275, SMS 201‐995, and L‐779,976, but not SRIF‐14, decrease mRNA expression and secretion of the MCP‐1. In addition, SRIF‐14, CH‐275, SMS 201‐995, and L‐779,976 decrease IL‐8 secretion, and they do not affect IL‐8 mRNA expression. In contrast, SRIF‐14 and sst1/sst2 agonists do not affect the secretion of matrix metalloproteinase‐9. Collectively, our results suggest that the SRIF system, through sst1 and sst2, exerts mainly an immunosuppressive effect in human macrophages and may, therefore, represent a therapeutic window that can be exploited for the development of new strategies in pharmacological therapy of inflammation.

Angiogenesis as Risk Factor for Plaque Vulnerability

Atherosclerosis is now generally accepted as an inflammatory disease, characterized by degenerative changes and extracellular accumulation of lipid and cholesterol. The evolving inflammatory reaction plays an important role in the initiation of atherosclerotic plaques and their destabilization, converting a chronic process into an acute disorder with an ensuing thrombo-embolism. Neovascularization has been, also, recognized as an important process for the progression of atherosclerotic plaques. In fact, vulnerable atherosclerotic plaque prone to rupture are characterized by an enlarged necrotic core containing an increased number of vasa vasorum, apoptotic macrophages, and more frequent intraplaque haemorrhage. Various functional roles have been assigned to intimal microvessels. This network of immature blood vessels is a viable source of intraplaque haemorrhage providing erythrocyte-derived phospholipids and free cholesterol. However, it is still challenging and controversial the relationship between the very process of angiogenesis and its causal association with the progression and complication of atherosclerosis. The selective targeting of neoangiogenesis poses a possible approach for the elimination of pre-existing and new growth of microvessels. The identification of target lesions is a critical issue, because current technologies have yet to achieve the goal of characterizing plaque morphology to the degree necessary to correctly identify rupture-prone lesions according to pathologic criteria. However, few imaging techniques can be used to detect the neovascularization within the atherosclerotic plaque in vivo. This review discusses the potential role of intraplaque angiogenesis as risk factor for plaque vulnerability.

Circulating endothelial progenitor cells and large artery structure and function in young subjects with uncomplicated Type 1 Diabetes

BackgroundCarotid intima-media thickness (IMT), indices of large artery stiffness and measures of endothelium function may be used as markers of early atherosclerosis in type 1 diabetes mellitus (T1DM). The aim of the present study was to compare the indices of large artery structure and function as well as endothelial function and regenerating capacity between adolescents with T1DM and healthy control of similar age. In addition, the associations of different vascular measures with endothelial progenitor cells (EPCs), glyco-metabolic control and serum levels of advanced glycation endproducts (AGEs), soluble receptors for AGEs (sRAGE) and adiponectin were evaluated.MethodsSixteen uncomplicated young T1DM patients (mean age 18 ± 2 years, history of disease 11 ± 5 years, HbA1c 7.7 ± 1.1%) and 26 controls (mean age 19 ± 2 years) were studied. A radiofrequency-based ultrasound system (Esaote MyLab 70) was used to measure carotid IMT and wave speed (WS, index of local stiffness), applanation tonometry (PulsePen) was applied to obtain central pulse pressure (PP) and augmentation index (AIx), and carotid-femoral pulse wave velocity (PWV, Complior) was used as index of aortic stiffness. Peripheral endothelium-dependent vasodilation was determined as reactive hyperemia index (RHI, EndoPAT). Circulating EPCs, glycometabolic profile, AGEs (autofluorescence method), sRAGE and adiponectin were also measured.ResultsAfter adjusting for age, sex and blood pressure, T1DM adolescents had significantly higher carotid IMT (456 ± 7 vs. 395 ± 63 μm, p < 0.005), carotid WS (p < 0.005), PWV (p = 0.01), AIx (p < 0.0001) and central PP (p < 0.01) and lower EPCs (p = 0.02) as compared to controls. RHI was reduced only in diabetic patients with HbA1c ≥7.5% (p < 0.05). In the overall population, EPCs were an independent determinant of carotid IMT (together with adiponectin), while fasting plasma glucose was an independent determinant of carotid WS, AIx and central PP.ConclusionsOur findings suggest that young subjects with relatively long-lasting T1DM have a generalized preclinical involvement of large artery structure and function, as well as a blunted endothelium regenerating capacity. Hyperglycemia and suboptimal chronic glycemic control seem to deteriorate the functional arterial characteristics, such as large arteries stiffness, wave reflection and peripheral endothelium-dependent vasodilation, whereas an impaired endothelium regenerating capacity and adiponectin levels seem to influence arterial structure.

Relationship between preclinical abnormalities of global and regional left ventricular function and insulin resistance in severe obesity: a Color Doppler Imaging Study

Background:The aim of this study was to evaluate the relationship between insulin resistance and preclinical abnormalities of the left ventricular structure and function detected in severe obesity by Color Doppler Myocardial Imaging (CDMI). Forty-eight consecutive severely obese patients (Group O) (11 males, 37 females, mean age 32.8±7 years) were enrolled. Forty-eight sex- and age-matched non-obese healthy subjects were also recruited as controls (Group C). All subjects underwent conventional 2D-Color Doppler echocardiography and CDMI. The homeostasis model assessment insulin resistance index (HOMA-IR) was used to assess insulin resistance results. Obese subjects had a greater left ventricular mass index (by height) (58.8±14 g/m2.7) than controls (37±8 g/m2.7) (P<0.0001), owing to compensation response to volume overload caused by a greater cardiac output (P<0.02). Preload reserve was increased in obese subjects, as demonstrated by a significant increase in left atrial dimension (P<0.0001). Obese patients had a slightly reduced LV diastolic function (transmitral E/A ratio: Group O, 1.1±0.8 vs Group C, 1.5 ±0.5; P<0.002). Cardiac deformation assessed by regional myocardial systolic strain and strain rate (SR) values was significantly lower (abnormal) in obese patients than in controls, both at the septum and lateral wall level. These strain and SR abnormalities were significantly related to body mass index. In addition, the early phase of diastolic function, evaluated using SR, was compromised in obese patients (P<0.001). The HOMA-IR values in obese patients were significantly higher (3.09±1.6) than those determined in the control group (0.92±0.5) (P<0.0001). The HOMA-IR values, in the obese group, were significantly related to systolic strain and SR values sampled at the septum level (P<0.0001).Conclusion:In conclusion, this study has demonstrated that obese patients pointed out systolic structural and functional abnormalities at a preclinical stage, in particular through strain and SR analysis; on the other hand, those altered CDMI parameters well distinguish obese subjects as compared with the control group. Furthermore, another main finding of the study was that myocardial deformation (systolic strain) could have a correlation with insulin resistance level.

Task force on: 'Early markers of atherosclerosis: influence of age and sex'.

Atherosclerosis and its complications are the most important causes of death all over the world, especially in Western countries. Diet habits, modern stress life, smoking, sedentary way of life and an involvement of genetic pattern of individuals lead to a sure degeneration of quality of life increasing the risk of atherosclerosis development. For this reason, the main purpose of actual medicine is to identify all the markers that could allow the physicians to evaluate the first moments of the development of this dangerous pathological process. The aim is to reduce the speed of its evolution, trying to delay indefinitely the risk coming from the morphological alterations of the vessels. ‘Endothelium function’ could allow physicians to detect the first moment of the natural history of atherosclerosis process. Its impairment is the first step in the degeneration of vascular structures. Many methods [flow-mediated vasodilatation (FMD); antero-posterior abdominal aorta diameter (APAO); intima-media thickness of the common carotid artery (CCA-IMT); arterial stiffness; and so on] try to evaluate its function, but many limitations come from general population characteristics. A standardization of the methods should take into account individuals’ peculiarities. Two elements, not modifiable, should be taken into account for vascular evaluation: age and sex. The aim of this review is to outline the linkage among age, sex and instrumental evaluation of patients considered for a noninvasive assessment of their cardiovascular risk profile.

Fibrin as a scaffold for cardiac tissue engineering

Fibrin is a natural biopolymer with many interesting properties, such as biocompatibility, bioresorbability, ease of processing, ability to be tailored to modify the conditions of polymerization, and potential for incorporation of both cells and cell mediators. Moreover, the fibrin network has a nanometric fibrous structure, mimicking extracellular matrix, and it can also be used in autologous applications. Therefore, fibrin has found many applications in tissue engineering, combined with cells, growth factors, or drugs. Because a major limitation of cardiac cell therapy is low cell engraftment, the use of biodegradable scaffolds for specific homing and in situ cell retention is desirable. Thus, fibrin‐based injectable cardiac tissue engineering may enhance cell therapy efficacy. Fibrin‐based biomaterials can also be used for engineering heart valves or cardiac patches. The aim of this review is to show cardiac bioengineering uses of fibrin, both as a cell delivery vehicle and as an implantable biomaterial.

Usefulness of Carotid Intima-Media Thickness Measurement and Peripheral B-Mode Ultrasound Scan in the Clinical Screening of Patients with Coronary Artery Disease

Previous observational studies have shown a relationship between carotid intima-media thickness (IMT) and coronary artery disease (CAD). In this study the authors evaluated the accuracy of the common carotid IMT measurement in predicting the presence and severity of CAD and the additional information offered by the detection of carotid, iliac, and lower limb plaques. One hundred and fifty consecutive patients were subjected to coronary angiography and carotid, iliac, and lower limb ultrasound scan. The mean value of six IMT measurements of the far wall of the common carotid artery was calculated in each patient. The mean IMT was significantly correlated to the number of stenosed coronary vessels (r = 0.43, p < 0.001), although the positive and negative predictive value of mean IMT in identifying patients with CAD was low (81% and 46%, respectively). The combined information offered by IMT measurements and peripheral (carotid, iliac, and lower limb) plaque detection was then used to obtain the best multivariate regression model able to predict CAD status. The multivariate model showed a highly significant multiple correlation coefficient (r = 0.60, p < 0.0001) and a sharp improvement in the negative predictive value (92%) with respect to the univariable model. B-mode ultra sound scan including common carotid IMT measurement and peripheral plaque detection may be of clinical value in the screening of patients with CAD.

The effects of acute passive smoke exposure on endothelium-dependent brachial artery dilation in healthy individuals

Passive smoking has both short-term and long-term vascular effects. It is not clear whether impairment of endothelial function reflects the acute effects of passive smoke exposure or the chronic effects. The purpose of this study was to assess the hypothesis that short-term exposure to passive smoke impairs endothelium-dependent vasodilation in healthy nonsmokers. Eighteen healthy young never smokers (12 men, 6 women) 21 to 55 years old (mean ± SD: 34 ±9 years) underwent ultrasonography measuring baseline brachial-artery diameter and brachial-artery diameter during hyperemia and after sublingual administration of nitroglycerin, twice: in a smoke-free environment, and then in the same environment polluted by 30 to 35 ppm carbon monoxide. Each subject served as his/her control. Carboxyhemoglobin was measured in blood samples of subjects tested. Mean value of carboxyhemoglobin was 0.6 ±0.5% in a smoke-free environment and 1.4 ± 0.5% in a smoking environment (p <0.02). Mean values of flow-mediated dilation (FMD) were 12.6% ± 7.8% in a smoke-free environment versus 6.8 ± 7.8% in a smoking environment (p <0.01). On the contrary, nitroglycerin-induced vasodilation did not show any statistical difference (21 ± 9.8% versus 23 ±1.4%). Finally, the increase of carboxyhemoglobin was related statistically to the impairment of flow-mediated dilation (r = 0.51; p <0.002). Passive smoking impaired flow-mediated vasodilation in healthy never smokers in a smoking environment. The impairment was strongly related to carboxyhemoglobin level.