Safety and efficacy of atrial fibrillation ablation guided by Ablation Index module.

PURPOSE: Reconnection of pulmonary veins (PVs) remains common following radiofrequency catheter ablation for atrial fibrillation (AF). Ablation Index (AI) is a novel ablation quality marker that incorporates stability, contact force (CF), time, and power in a weighted formula. Its use seems to improve lesion durability. This is a prospective, single-arm registry to investigate on the safety and mid-term efficacy of AF ablation guided by the AI. METHODS: One hundred fifty-six consecutive patients (mean age 58 ± 10 years, 49% males, 44% with structural heart disease) referred for paroxysmal (124) or persistent (32) AF underwent antral PV isolation using a surround flow CF-sensing catheter guided by the AI. Radiofrequency was delivered targeting interlesion distance ≤ 6 mm and Ablation Index of 330-350 at posterior wall and 400-450 at anterior wall. RESULTS: Mean overall procedure time was 95 ± 30 min with a mean fluoroscopy time of 5 ± 6 min. Mean ablation time was 26 ± 10 min, 627/628 targeted PV were isolated. One pericardial effusion and two groin hematomas were reported; none required intervention. During a mean follow-up of 14 ± 6 months, 17 (10.8%) (9% paroxysmal AF vs 22% persistent AF, p = 0.09) patients had an atrial arrhythmia recurrence. CONCLUSIONS: PV ablation guided by AI resulted feasible, achieving a high rate of isolated PVs, with a low complication rate, and allowed a high single-procedure arrhythmia-free survival at 14 months.

Effectiveness of a management program for outpatient clinic or remote titration of beta-blockers in CRT patients: The RESTORE study.

BACKGROUND: Many patients fail to receive ß-blockers before cardiac resynchronization therapy defibrillator (CRT-D) implantation, or receive them at a suboptimal dose, and require optimization after implantation. We assessed the effectiveness of a structured program for ß-blocker titration in CRT-D patients followed up by means of conventional in-clinic visits or remote monitoring. METHODS AND RESULTS: 130 patients undergoing CRT implantation and treated according to the standard practice of the centers were included as a control group. A second group of 124 CRT-D candidates (Study Group) underwent up-titration visits every 2weeks after implantation (target dose: 10mg/day of bisoprolol or 50mg/day of carvedilol). In the Study Group, remote monitoring was undertaken in 66 patients, who received additional equipment for daily transmission of weight and blood pressure data, and scheduled titration telephone calls. In the Control Group, the maximal dose of ß-blockers was being administered to 12 (9%) patients on implantation and 21 (16%) on 6-month follow-up examination (p>0.05). In the Study Group, 25 (20%) patients were receiving the maximal dose of ß-blockers on implantation and 72 (58%) on follow-up examination (p<0.001). The 66 Study Group patients on remote monitoring underwent fewer in-clinic visits (p=0.034). Of these, 50 (76%) were on the maximal dose after remote up-titration (versus 38% of patients followed up conventionally, p<0.001). The decrease in left ventricular end-systolic volume was larger in the Study Group (p=0.040). CONCLUSIONS: The program for ß-blocker up-titration increased the number of patients reaching the target dose and improved the response to the therapy. The use of remote monitoring and daily transfer of weight and blood pressure data facilitated ß-blocker titration. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov/ Identifier: NCT02173028.

Atrial fibrillation detection using a novel three-vector cardiac implantable monitor: the atrial fibrillation detect study.

AIMS: Continuous rhythm monitoring is valuable for adequate atrial fibrillation (AF) management in the clinical setting. Subcutaneous leadless implantable cardiac monitors (ICMs) yield an improved AF detection, overcoming the intrinsic limitations of the currently available external recording systems, thus resulting in a more accurate patient treatment. The study purpose was to assess the detection performance of a novel three-vector ICM device equipped with a dedicated AF algorithm. METHODS AND RESULTS: Sixty-six patients (86.4% males; mean age 60.4 ± 9.4 years) at risk to present AF episodes, having undergone the novel ICM implant (BioMonitor, Biotronik SE&Co. KG, Berlin, Germany), were enrolled. External 48-h ECG Holter was performed 4 weeks after the device implantation. The automatic ICM AF classification was compared with the manual Holter arrhythmia recordings. Of the overall study population, 63/66 (95.5%) had analysable Holter data, 39/63 (62%) showed at least one true AF episode. All these patients had at least one AF episode stored in the ICM. On Holter monitoring, 24/63 (38%) patients did not show AF episodes, in 16 of them (16/24, 67%), the ICM confirmed the absence of AF. The AF detection sensitivity and positive predictive value for episodes' analysis were 95.4 and 76.3%, respectively. CONCLUSION: Continuous monitoring using this novel device, equipped with a dedicated detection algorithm, yields an accurate and reliable detection of AF episodes. The ICM is a promising tool for tailoring individual AF patient management. Further long-term prospective studies are necessary to confirm these encouraging results.

Fructose induces prothrombotic phenotype in human endothelial cells : A new role for "added sugar" in cardio-metabolic risk.

Intake of large amounts of added sweeteners has been associated with the pathogenesis of cardiometabolic risk. Several studies have shown that fructose increases the cardiovascular risk by modulating endothelial dysfunction and promoting atherosclerosis. Recently, a potential role for fructose in cardiovascular thrombosis has been suggested but with controversial results. Tissue factor (TF) plays a pivotal role in the pathophysiology of cardiovascular thrombosis by triggering the formation of intracoronary thrombi following endothelial injury. This study investigates the effects of fructose, in a concentration range usually observed in the plasma of patients with increased cardiovascular risk, on TF in human umbilical endothelial cells (HUVECs). Cells were stimulated with increasing concentrations of fructose (0.25, 1 and 2.5 mM) and then processed to evaluate TF-mRNA levels by real-time PCR as well as TF expression/activity by FACS analysis and procoagulant activity. Finally, a potential molecular pathway involved in modulating this phenomenon was investigated. We demonstrate that fructose induces transcription of mRNA for TF. In addition, we show that this monosaccharide promotes surface expression of TF that is functionally active. Fructose effects on TF appear modulated by the oxygen free radicals through activation of the transcription factor NF-κB since superoxide dismutase and NF-κB inhibitors suppressed TF expression. Data of the present study, although in vitro, indicate that fructose, besides promoting atherosclerosis, induces a prothrombotic phenotype in HUVECs, thus indicating one the mechanism(s) by which this sweetener might increase cardiometabolic risk.

Adipokines, vascular wall, and cardiovascular disease: a focused overview of the role of adipokines in the pathophysiology of cardiovascular disease.

Epidemiological evidence has shown that abdominal obesity is closely associated with the development of cardiovascular (CV) disease, suggesting that it might be considered as an independent CV risk factor. However, the pathophysiological mechanisms responsible for the association between these 2 clinical entities remain largely unknown. Adipocytes are considered able to produce and secrete chemical mediators known as "adipokines" that may exert several biological actions, including those on heart and vessels. Of interest, a different adipokine profile can be observed in the plasma of patients with obesity or metabolic syndrome compared with healthy controls. We consider the main adipokines, focusing on their effects on the vascular wall and analyzing their role in CV pathophysiology.

Effects of antihypertensive therapy on glucose, insulin metabolism, left ventricular diastolic dysfunction and renin system in overweight and obese hypertensives.

BACKGROUND: We attempted to test the hypothesis that the direct renin inhibitor aliskiren can improve diastolic dysfunction, glucose, and insulin metabolism (GIM) in overweight and obese hypertensive patients. METHODS AND RESULTS: Seventy-eight hypertensive patients were divided into two groups: 38 treated with aliskiren for six months, and 40 treated without aliskiren but with only traditional anti-hypertensive therapy, as controls. Doppler mitral flow velocity patterns were assessed before and after aliskiren during a six-month period. GIM (three-hour intravenous glucose tolerance test) was measured after four to six weeks of washout and six months of treatment. The mitral E/A ratio increased from 0.65 ± 0.11 to 0.75 ± 0.19. None of the indexes changed in the control group. In the control group, GIM parameters, fasting glucose levels (5.3 ± 0.9 to 6.0 ± 1.5 mmol/l; p = 0.003), fasting insulin levels (121 ± 121 to 189 ± 228 pmol/l; p = 0.03), and most other relevant metabolic measures (p < 0.05 for all) significantly worsened. Aliskiren did not affect GIM. In the control group LVM/height was not affected (119 ± 12 to 120 ± 17 g/m; p = 0.8), whereas aliskiren significantly reduced LVM/height (120 ± 13 to 111 ± 19 g/m; p = 0.04). CONCLUSIONS: Optimal target BP was achieved in the group as a whole and in both obese patient groups, while benefits to cardiac structure were of a smaller magnitude. In high-risk, overweight/obese patients with hypertension, traditional therapy provides significantly greater BP- versus aliskiren-lowering throughout the 24-hour dosing interval. Therefore in obese, hypertensive individuals, adequate and similar blood pressure control was achieved with aliskiren; however, the aliskiren group and not the control group was associated with a more favorable GIM profile and led to a significant regression of LVM; overall aliskiren-based treatment offers sustained control of PRA.

Cardiovascular disease and high-mobility group box 1--is a new inflammatory killer in town?

High-mobility group box 1 (HMGB-1) is a nuclear protein physiologically involved in the maintaining of DNA structure in the nucleus. When tissue damage occurs, necrotic cells as well as inflammatory cells, once activated, release this protein in circulating blood, where it seems to exert a direct proinflammatory action. Thus, HMGB-1 might be involved in the pathophysiology of several diseases, including cardiovascular disease. However, the experimental evidence has not yet clarified its cardiovascular role which is still debated. Specifically, it is still not completely resolved whether HMGB-1 plays a protective or detrimental role on cardiovascular function. In this review, we consider the role of HMGB-1 in pathological conditions and comment on the role of this protein in the cardiovascular disease.

The adipokine visfatin induces tissue factor expression in human coronary artery endothelial cells: another piece in the adipokines puzzle.

INTRODUCTION: Adipocytes are nowadays recognized as cells able to produce and secrete a large variety of active substances with direct effects on vascular cells, known as adipokines. Visfatin is a recently identified adipokine not yet completely characterized for its pathophysiological role in cardiovascular disease. Increased levels of visfatin are measurable in the plasma of patients with coronary artery disease and specifically in those with acute coronary syndromes (ACS). Several studies have indicated that Tissue Factor (TF) plays a pivotal role in the pathophysiology of ACS by triggering the formation of intracoronary thrombi following endothelial injury. This study investigates the effects of visfatin on TF in human coronary endothelial cells (HCAECs). METHODS: HCAECs were stimulated with visfatin in a concentration range usually measurable in plasma of patients with ACS and than processed to evaluate TF-mRNA levels as well as TF expression/activity. Finally, the role of NF-κB pathway was investigated. RESULTS: We demonstrate that visfatin induces transcription of mRNA for TF by Real Time PCR. In addition, we show that this adipokine promotes surface expression of TF that is functionally active since we measured increased procoagulant activity. Visfatin effects on TF appear modulated by the activation of the transcription factor, NF-κB, since NF-κB inhibitors suppressed TF expression. Finally, we show that the nicotinamide phopsphoribosyltransferase enzymatic activity of visfatin seems to play a pivotal role in modulating the NF-κB driven regulation of TF. DISCUSSION: Data of the present study, although in vitro, indicate that visfatin, at doses measurable in ACS patient plasma, induces a procoagulant phenotype in human coronary endothelial cells by promoting TF expression. These observations support the hypothesis that this adipokine might play a relevant role as an active partaker in athero-thrombotic disease.

[Obesity and ischemic heart disease. Is there a link between wellness' diseases?]. / Obesità e cardiopatia ischemica. Esiste un legame tra le malattie del benessere?

Obesity, the most common nutritional disorder in Western countries, is usually associated to cardiovascular diseases. However, the precise molecular pathways underlying this close association remain poorly understood. Nowadays, the adipose tissue is considered as an endocrine organ able to produce substances called adipo(cyto)kines that have different effects on lipid metabolism, closely involved in metabolic syndrome, and cardiovascular risk. The increased cardiovascular risk can be related also to peculiar dysfunction in the endocrine activity of adipose tissue observed in obesity responsible of vascular impairment (including endothelial dysfunction), prothrombotic tendency, and low-grade chronic inflammation. The present review aims at providing an up-dated overview on the adipocyte-derived molecules potentially involved in cardiovascular pathophysiology.

Neopterin: from forgotten biomarker to leading actor in cardiovascular pathophysiology.

Inflammation plays a role at all stages of atherosclerosis. Neopterin, a pteridine mainly synthesized by activated macrophages, is a marker of inflammation, immune system activation and an active participant in cardiovascular disease. Measurement of neopterin levels may help follow the evolution of specific inflammatory conditions (e.g. viral infection, renal transplant rejection, systemic inflammatory diseases, nephritic syndrome and autoimmune diseases). Serum levels of neopterin are elevated also in patients with coronary artery disease (CAD) and peripheral artery disease (PAD). Moreover, plasma levels of this molecule might predict adverse cardiovascular events in patients with CAD, acute coronary syndromes or severe PAD. In addition, neopterin levels are related to the development of heart failure. We provide an updated overview on neopterin and, its links with CAD, left ventricular dysfunction, and PAD. We also describe its potential role in cardiac regenerative strategies with using bone marrow cells.

Pro-atherothrombotic effects of leptin in human coronary endothelial cells.

Adipocytes are nowadays recognised as cells able to produce and secrete a large variety of active substances termed adipokines, which exert direct effects on vascular cells. Among these adipokines, leptin has been proposed to play a role in the pathophysiology of acute coronary syndromes, as well as in increasing cardiovascular risk. At the moment, however, the mechanisms linking leptin to cardiovascular disease are not completely understood. This study investigates the effects of leptin, in a concentration range usually observed in the plasma of patients with increased cardiovascular risk or measurable in patients with acute coronary syndromes, on tissue factor (TF) and cellular adhesion molecules (CAMs) expression in human coronary endothelial cells (HCAECs). We demonstrate that leptin induces transcription of mRNA for TF and CAMs by real-time PCR. In addition, we show that this adipokine promotes surface expression of TF and CAMs that are functionally active since we observed increased procoagulant activity and leukocyte adhesion on cell surface. Leptin effects appear modulated by eNOS-production of oxygen free radicals through the activation of the transcription factor, nuclear factor(NF)-kappaB, since L-NAME, Superoxide Dismutase and NF-kappaB inhibitors suppressed CAMs and TF expression. Data of the present study, although in vitro , indicate that leptin may exert direct effects on human coronary endothelial cells by promoting CAMs and TF expression and support the hypothesis that this adipokines, besides being involved in the pathophysiology of obesity, might play a relevant role as an active mediator linking obesity to cardiovascular disease.

Tissue Factor/Factor FVII Complex Inhibitors in Cardiovascular Disease. Are Things Going Well?

Blood coagulation is a complex biological mechanism aimed to avoid bleeding in which a highly regulated and coordinated interplay of specific proteins and cellular components respond quickly to a vascular injury. However, when this mechanisms occurs in the coronary circulation, it has not a "protective" effect, but rather, it plays a pivotal role in determining acute coronary syndromes. Coagulation recognizes Tissue Factor (TF), the main physiological initiator of the extrinsic coagulation pathway, as its starter.Since TF:VIIa complex is the critical point of the blood coagulation cascade, it is a pharmacological attractive issue for the development of agents with anti thrombotic properties that can exert their activity by inhibiting complex formation and/or its catalytic activity. In fact, it is intuitive that an antithrombotic agent able to inhibit this initial step of the coagulation pathway has several theoretical, extremely important, advantages if compared with drugs active downstream the coagulation pathway, such as FXa or thrombin. The present report gives a brief overview of TF pathophysiology, highlighting the most recent advances in the field of inhibitors of the complex TF/VIIa potentially useful in cardiovascular disease.