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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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: There is emerging evidence that localization and elimination of abnormal electric activity in the epicardial right ventricular outflow tract may be beneficial in patients with Brugada syndrome., Methods and Results: A total of 135 symptomatic Brugada syndrome patients having implantable cardiac defibrillator were enrolled: 63 (group 1) having documented ventricular tachycardia (VT)/ventricular fibrillation (VF) and Brugada syndrome-related symptoms, and 72 (group 2) having inducible VT/VF without ECG documentation at the time of symptoms. About 27 patients of group 1 experienced multiple implantable cardiac defibrillator shocks for recurrent VT/VF episodes. Three-dimensional maps before and after ajmaline determined the arrhythmogenic electrophysiological substrate (AES) as characterized by prolonged fragmented ventricular potentials. Primary end point was identification and elimination of AES leading to ECG pattern normalization and VT/VF noninducibility. Extensive areas of AES were found in the right ventricle epicardium, which were wider in group 1 ( P =0.007). AES increased after ajmaline in both groups ( P <0.001) and was larger in men ( P =0.008). The increase of type-1 ST-segment elevation correlated with AES expansion ( r =0.682, P <0.001). Radiofrequency ablation eliminated AES leading to ECG normalization and VT/VF noninducibility in all patients. During a median follow-up of 10 months, the ECG remained normal even after ajmaline in all except 2 patients who underwent a repeated effective procedure for recurrent VF., Conclusions: In Brugada syndrome, AES is commonly located in the right ventricle epicardium and ajmaline exposes its extent and distribution, which is correlated with the degree of coved ST-elevation. AES elimination by radiofrequency ablation results in ECG normalization and VT/VF noninducibility. Substrate-based ablation is effective in potentially eliminating the arrhythmic consequences of this genetic disease., Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT02641431., (© 2017 American Heart Association, Inc.)

Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia. The trigger for initiation of AF is generally an enhanced vulnerability of pulmonary vein cardiomyocyte sleeves to either focal or re-entrant activity. The maintenance of AF is based on a "driver" mechanism in a vulnerable substrate. Cardiac mapping technology is providing further insight into these extremely dynamic processes. AF can lead to electrophysiological and structural remodelling, thereby promoting the condition. The management includes prevention of stroke by oral anticoagulation or left atrial appendage (LAA) occlusion, upstream therapy of concomitant conditions, and symptomatic improvement using rate control and/or rhythm control. Nonpharmacological strategies include electrical cardioversion and catheter ablation. There are substantial geographical variations in the management of AF, though European data indicate that 80% of patients receive adequate anticoagulation and 79% adequate rate control. High rates of morbidity and mortality weigh against perceived difficulties in management. Clinical research and growing experience are helping refine clinical indications and provide better technical approaches. Active research in cardiac electrophysiology is producing new antiarrhythmic agents that are reaching the experimental clinical arena, inhibiting novel ion channels. Future research should give better understanding of the underlying aetiology of AF and identification of drug targets, to help the move toward patient-specific therapy., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Whether Brugada syndrome (BrS) depends on functional epicardial substrates, which may be definitively eliminated by radiofrequency ablation, remains unknown., Methods and Results: Patients with BrS underwent epicardial mapping to identify areas of abnormal electrograms as target for radiofrequency ablation. Substrate identification consisted in mapping right ventricle epicardial surface before and after flecainide (2 mg/kg per 10 minutes). After radiofrequency ablation, flecainide and remap confirmed elimination of abnormal substrate, BrS ECG pattern, and ventricular tachycardia/ventricular fibrillation inducibility. Flecainide testing was performed at each follow-up visits ≤6 months. Fourteen patients with BrS, median age 39 years (30.3-42.3) with implantable cardioverter-defibrillator were enrolled. Low-voltage areas (<1.5 mV) were commonly identified on the anterior right free wall and right ventricular outflow tract, which increased after flecainide from 17.6 cm(2) (12.1-24.2) to 28.5 cm(2) (21.6-30.2; P=0.001). Similarly, areas with abnormal electrograms increased after flecainide from 19.0 (17.5-23.6) to 27.3 cm(2) (24.0-31.2; P=0.001). After 23.8 minutes (18.1-28.5) of radiofrequency ablation, abnormal electrograms disappeared, whereas low-voltage areas were replaced by scar areas (<0.5 mV) of 25.9 cm(2) (19.6-31.0). Substrate elimination resulted in BrS ECG pattern disappearance and no ventricular tachycardia/ventricular fibrillation inducibility without complications. After a median follow-up of 5 months (3.8-5.3), ECG remained normal despite flecainide., Conclusions: In patients with BrS, there is a relationship between abnormal ECG pattern, the extent of abnormal epicardial substrate, and ventricular tachycardia/ventricular fibrillation inducibility. Ablation of the substrate identified in the presence of flecainide can eliminate the BrS phenotype and warrants further study., (© 2015 American Heart Association, Inc.)

Background: Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing (MultiPoint™ Pacing [MPP], St. Jude Medical) improves acute LV function and LV reverse remodeling at 3 months., Objective: The purpose of this study was to test the hypothesis that MPP can also improve LV function at 12 months., Methods: Consecutive patients receiving a CRT implant (Unify Quadra MP™ or Quadra Assura MP™ CRT-D and Quartet™ LV lead, St. Jude Medical) were randomized to receive pressure-volume (PV) loop optimized biventricular pacing with either conventional cardiac resynchronization therapy (CONV) or MPP. CRT response was defined by a reduction in end-systolic volume (ESV) ≥15% relative to BASELINE as determined by a blinded observer and alive status., Results: Forty-four patients (New York Heart Association class III, ejection fraction [EF] 29% ± 6%, QRS 152 ± 17 ms) were enrolled and randomized to either CONV (N = 22) or MPP (N = 22). During the observation period, 2 patients died of noncardiac causes and 2 patients were lost to follow-up. After 12 months, 12 of 21 patients (57%) in the CONV group and 16 of 21 patients (76%) in the MPP group were classified as CRT responders (P = .33). ESV reduction and EF increase relative to BASELINE were significantly greater with MPP than with CONV (ESV: median -25%, interquartile range [IQR] [-39% to -20%] vs median -18%, IQR [-25% to -2%], P = .03; EF: median +15%, IQR [8% to 20%] vs median +5%, IQR [-1% to 8%], P <.001)., Conclusion: Sustaining the trend observed 3 months postimplant, PV loop-guided multipoint LV pacing resulted in greater LV reverse remodeling and increased LV function at 12 months compared to PV loop-guided conventional CRT., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing in a single coronary sinus branch improves acute LV function. We hypothesized that multipoint pacing (MPP) can improve midterm echocardiographic and clinical response compared with conventional CRT., Methods and Results: Consecutive patients receiving a CRT implant (Unify Quadra MP™ or Quadra Assura MP™ CRT-D and Quartet™ LV lead, St. Jude Medical, Sylmar, CA, USA) were randomized to receive biventricular (BiV) pacing with either conventional LV pacing (CONV group) or MPP (MPP group). For each patient, an optimal pacing configuration for the assigned pacing mode was programmed based on intraoperative pressure-volume (PV) loop measurements. A clinical evaluation and transthoracic echocardiogram were performed before implant (BASELINE) and at 3 months postimplant and analyzed by a blinded observer. A reduction in end-systolic volume (ESV) of ≥15% relative to BASELINE was prospectively defined as response to CRT. Forty-four patients (NYHA Class III, EF 29 ± 6%, QRS duration 152 ± 17 milliseconds) were enrolled and randomized. One patient in the MPP group was lost to follow-up and excluded from further analysis. After 3 months, 11 of 22 (50%) CONV patients and 16 of 21 (76%) MPP patients were classified as responders. ESV reduction, EF increase, and NYHA class reduction relative to BASELINE were significantly greater in the MPP group than in the CONV group (ESV: -21.0 ± 13.9 vs. -12.6 ± 11.1%, P = 0.03; EF: +9.8 ± 5.1 vs. +2.0 ± 7.8 percentage points, P < 0.001; ΔNYHA: -1.05 ± 0.22 vs. -0.72 ± 0.46 functional classes, P = 0.006)., Conclusion: PV loop optimized BiV pacing with MPP resulted in an improved rate of response to CRT., (© 2014 Wiley Periodicals, Inc.)

Background: The management of Wolff-Parkinson-White is based on the distinction between asymptomatic and symptomatic presentations, but evidence is limited in the asymptomatic population., Methods and Results: The Wolff-Parkinson-White registry was an 8-year prospective study of either symptomatic or asymptomatic Wolff-Parkinson-White patients referred to our Arrhythmology Department for evaluation or ablation. Inclusion criteria were a baseline electrophysiological testing with or without radiofrequency catheter ablation (RFA). Primary end points were the percentage of patients who experienced ventricular fibrillation (VF) or potentially malignant arrhythmias and risk factors. Among 2169 enrolled patients, 1001 (550 asymptomatic) did not undergo RFA (no-RFA group) and 1168 (206 asymptomatic) underwent ablation (RFA group). There were no differences in clinical and electrophysiological characteristics between the 2 groups except for symptoms. In the no-RFA group, VF occurred in 1.5% of patients, virtually exclusively (13 of 15) in children (median age, 11 years), and was associated with a short accessory pathway antegrade refractory period (P<0.001) and atrioventricular reentrant tachycardia initiating atrial fibrillation (P<0.001) but not symptoms. In the RFA group, ablation was successful in 98.5%, and after RFA, no patients developed malignant arrhythmias or VF over the 8-year follow-up. Untreated patients were more likely to experience malignant arrhythmias and VF (log-rank P<0.001). Time-dependent receiver-operating characteristic curves for predicting VF identified an optimal anterograde effective refractory period of the accessory pathway cutoff of 240 milliseconds., Conclusions: The prognosis of the Wolff-Parkinson-White syndrome essentially depends on intrinsic electrophysiological properties of AP rather than on symptoms. RFA performed during the same procedure after electrophysiological testing is of benefit in improving the long-term outcomes., (© 2014 American Heart Association, Inc.)

There is evidence for a higher prevalence of atrial fibrillation (AF) in athletes engaged in long-term endurance sports training compared with the general population. Although atrial anatomic adaptations, alterations in autonomic nervous system, chronic systemic inflammation and fibrosis have been proposed as potential mechanisms, they remain speculative. Medical therapy with long-term antiarrhythmic agents or 'pill in the pocket' medications is hampered by limitations, such as sports eligibility and interference with exercise tolerance. AF ablation represents a valid therapeutic option with results similar to these achieved in other patients. Nevertheless, further clinical trials are needed to confirm whether endurance sport practice affects the maintenance of sinus rhythm following catheter ablation of AF.

Background: Conventional cardiac resynchronization therapy (CRT) improves acute cardiac hemodynamics., Objective: To investigate if CRT with multipoint left ventricular (LV) pacing in a single coronary sinus branch (MultiPoint Pacing [MPP], St Jude Medical, Sylmar, CA) can offer further hemodynamic benefits to patients., Methods: Forty-four consecutive patients (80% men, New York Heart Association III, end-systolic volume 180 ± 77 mL, ejection fraction 27% ± 6%, and QRS duration 152 ± 17 ms) receiving a CRT device implant (Unify Quadra MP or Quadra Assura MP and Quartet LV lead, St Jude Medical) underwent intraoperative assessment of LV hemodynamics by using a pressure-volume loop system (Inca, CD Leycom). A pacing protocol was performed, including 9 biventricular pacing interventions with conventional CRT (CONV) using distal and proximal LV electrodes and various MPP configurations. Each pacing intervention was performed twice in randomized order with right ventricular pacing (BASELINE) repeated after every intervention., Results: Evaluable recordings were obtained in 42 patients. Relative to BASELINE, the best MPP intervention significantly increased the rate of pressure change (dP/dtmax; 15.9% ± 10.0% vs 13.5% ± 8.8%; P < .001), stroke work (27.2% ± 42.5% vs 19.4% ± 32.2%; P = .018), stroke volume (10.4% ± 22.5% vs 4.1% ± 13.1%; P = .003), and ejection fraction (10.5% ± 20.9% vs 5.3% ± 13.2%; P = .003) as compared with the best CONV intervention. Moreover, the best MPP intervention improved acute diastolic function, significantly decreasing -dP/dtmin (-13.5% ± 10.2% vs -10.6% ± 6.8%; P = .011), relaxation time constant (-7.5% ± 9.0% vs -4.8% ± 7.2%; P = .012), and end-diastolic pressure (-18.2% ± 22.4% vs -8.7% ± 21.4%; P < .001) as compared with the best CONV intervention., Conclusions: CRT with MPP can significantly improve acute LV hemodynamic parameters assessed with pressure-volume loop measurements as compared with CONV., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Atrioesophageal fistula is an extremely rare but often fatal late complication of atrial fibrillation ablation procedures resulting from massive thermal injury to the esophagus and surrounding structures. Causes of death include cerebral air embolism, massive gastrointestinal bleeding, and septic shock. Because of its exceptionally low rate of occurrence, no predictors of lesion development have been found and there has not been an uniform approach to either early diagnosis or corrective therapy. Currently, preventive strategies include empirically reducing power titration during PVI and/or while ablating the posterior left atrial wall, limiting energy delivery time and number, avoiding overlapping ablation lines as well as monitoring intraluminal esophageal temperature. In addition, it has been suggested to use conscious sedation rather than general anesthesia for better pain perception, monitoring intraprocedural esophageal position in relation to the posterior left atrium and extensive patient education regarding signs and symptoms of esophageal injury. Early diagnosis is essential to enable an aggressive treatment including stenting and/or surgical intervention to minimize the excessive morbidity and mortality associated with this condition. Unfortunately, despite application of such preventive measures, cases of complete atrial-esophageal fistula have still been reported.

Background: Nonirrigated magnetic ablation may result in potential char, ineffective lesions, and longer procedure times., Objective: This study sought to report the safety and long-term efficacy of irrigated-tip magnetic ablation of atrial fibrillation (AF)., Methods: Catheter ablation was remotely performed using a new irrigated-tip magnetic catheter (ThermoCool NaviStar-RMT, Biosense Webster, Diamond Bar, CA) in 130 consecutive patients (mean age 59.7 ± 10.5 years) with symptomatic paroxysmal (81 patients) or persistent (49 patients) AF. The radiofrequency (RF) generator was set to fixed power of 30 W. The primary end point of the study was freedom from atrial tachycardia (AT)/AF off antiarrhythmic drugs., Results: The procedure was safely performed in all conventional ablation targets, but crossover to manual catheters was required in 12 patients to complete the mitral isthmus line. The total procedure time was 94.6 ± 15.3 minutes. Impedance values significantly decreased during RF applications (P < .001) and the maximum temperature on the catheter tip was 36.4°C ± 0.8°C. The follow-up duration was 15.3 ± 4.9 months. The primary end point was achieved in 66 of 81(81.4%) patients with paroxysmal AF and in 33 of 49 (67.3%) with persistent AF (P = .035, by log-rank test). Patients with paroxysmal AF had higher late AF recurrence (P =.044). Overall, postablation incessant left AT developed in 7 of 130 (5.4%) patients. Major complications were not observed. Left atrial diameter (P < .001) and heart failure (P = .032) predicted arrhythmia recurrence after remote irrigated-tip ablation., Conclusion: Remote ablation with irrigated-tip magnetic catheters can be safely and effectively performed in patients with AF, but longer follow-up periods are required to evaluate late AF recurrences., (Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Circumferential pulmonary vein ablation (CPVA) is an effective treatment for atrial fibrillation (AF). Accurate left atrial (LA) mapping is essential for creating lesions at the LA-pulmonary vein (PV) junction, avoiding PV stenosis., Objectives: The purpose of this study was to establish whether endocardial impedance varies within the LA and PVs and whether it is a useful tool for mapping and ablation., Methods: Pilot Phase: Three-dimensional LA maps were created using CARTO. Impedance (Z) was measured using a radiofrequency generator at multiple points in the LA, PV ostia (PVO), and deep PVs in 79 patients undergoing their first AF ablation (group 1) and 29 patients undergoing repeat CPVA (group 2). Prospective Phase: In an additional 20 patients, using pilot phase data, one operator defined catheter tip location as either LA or PVO based on CARTO and fluoroscopy. A second operator blinded to CARTO simultaneously did the same based on impedance at 15 +/- 4 points per patient., Results: Group 1: Z(LA) was 99.4 +/- 9.0 omega. Z(PVO) was higher (109.2 +/- 8.5 omega), rising further as the catheter advanced into deep PV (137 omega +/- 18). Z(PVO) differed from Z(LA) by 9 +/- 4 omega. Group 2 had a lower Z(LA) and Z(PVO) compared with group 1 (P <.05). Impedance monitoring differentiated between LA and PVO, with 91% specificity and sensitivity, 96% positive predictive value, and 81% negative predictive value. At 3-month follow-up, no patients had evidence of PV stenosis on magnetic resonance imaging., Conclusion: Impedance mapping reliably identifies the LA-PV transitional zone, facilitating AF ablation, and its use is associated with a low incidence of PV stenosis.

Objectives: Few data have been published on transcatheter ablation of atrial fibrillation (AF) in patients with mitral valve prostheses. Thus, we sought to report our experience., Background: Ablation is an effective treatment for AF. Patients with prosthetic mitral valves represent a special group because of an increased risk from the ablation procedure due to the possibility of damage to the prosthetic valve., Methods: Between July 2001 and July 2003, 26 patients with mitral valve prostheses (MVP) underwent circumferential pulmonary vein ablation for AF. A matched group of 52 ablated patients without MVP acted as control subjects. After a blanking period of three months, a follow-up of 12 months was considered for MVP patients and controls. Holter recordings were performed in all subjects at 3, 6, and 12 months., Results: Radiation exposure was higher in the MVP group, with fluoroscopy times of 35.3 +/- 21 min versus 20.9 +/- 15 min in controls. At the end of follow-up, 73% of MVP patients were in sinus rhythm, compared with 75% of controls. Atrial tachycardia occurred in six (23%) MVP patients, requiring repeat ablation in three, and one (2%) control subject, which settled without treatment. One transient ischemic attack and one femoral pseudoaneurysm occurred in the MVP group. No complications occurred in the control group., Conclusions: Ablation of AF in patients with MVP is feasible, with outcomes similar to those of standard patients. Complications were higher among MVP patients with a greater radiation exposure and a higher incidence of post-ablation atrial tachycardia.

In this clinical study, the authors refer to a thirty-six month treatment of Grades I and II haemorrhoids (pharmacological treatment) with a group of 75 patients (45 females and 30 males) and treatment for Grades III and IV haemorrhoids (Pharmacological and surgical treatment) on a second group of 23 patients for a total of 98 patients treated and observed. For the pharmacological treatment, a rectal cream containing 0.25% Oxethacaine chlorhydrate (Emoren, produced by Novasorel, srl) was used on all patients. The cream was applied intra-anally and on the external orifice twice a day, morning and evening, for ten days. In order to evaluate the therapeuctic effect, the following symptoms were monitored: pruritus, ematochezia, burning, tenesmus, and pain. The following results were demonstrated: a) in all patients: A reduction in pruritus, pain, blood and mucous loss, Elimination of tenesmus, Absence of peri-anal eczema, b) in 15 patients, haemorrhoids were reduced for 11 months. Therefore the results obtained reconfirm that local treatment with EMOREN demonstrated to be clinically efficient in the treatment of Grades I and II haemorrhoids as well as in post surgical treatment both for the attenuation and elimination of pain and the clinical objectives of the pathology in question.

Heart failure (HF) may complicate ischemic heart disease in both its acute and chronic manifestations, representing a prevalent health problem throughout the world. Development of therapies to improve heart function, relieve symptoms, reduce hospitalizations and improve survival is a high priority in cardiovascular medicine. The available pharmacological strategies, including angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, beta-blockers, and aldosterone receptor antagonists have recently been complemented by new electrical therapy, including implantable cardioverter-defibrillators for "MADIT II" patients and cardiac resynchronization for the 30% of HF patients with concomitant intraventricular conduction delay. The wide variety of available HF medications provides ample evidence that we have not yet succeeded in this effort. Safe and effective inotropic electrical therapy could be a useful addition to our therapeutic armamentarium in an attempt to correct Ca2+ fluxes abnormalities during the cardiac action potential. Cardiac contractility modulation (CCM) by means of non-excitatory electrical currents delivered during the action potential plateau has been shown to acutely enhance systolic function in humans with HF. Herewith, we report on our preliminary experience with CCM therapy for patients with HF, providing fundamental notions to characterize the rationale of this novel form of therapy. Briefly, CCM therapy appears to be safe and feasible. Proarrhythmic effects of this novel therapy seem unlikely. Preliminary data indicate that CCM gradually and significantly improves systolic performance, symptoms and functional status. The technique would appear to be attractive as an additive treatment for severe HF. Controlled randomized studies are needed to validate this novel concept.

Introduction: Conventional electrical therapies for heart failure (HF) encompass defibrillation and ventricular resynchronization for patients at high risk for lethal arrhythmias and/or with inhomogeneous ventricular contraction. Cardiac contractility modulation (CCM) by means of nonexcitatory electrical currents delivered during the action potential plateau has been shown to acutely enhance systolic function in humans with HF. The aim of this multicenter study was to assess the chronic safety and preliminary efficacy of an implantable device delivering this novel form of electrical therapy., Methods and Results: Thirteen patients with drug-resistant HF (New York Heart Association [NYHA] class III) were consecutively implanted with a device (OPTIMIZER II) delivering CCM biphasic square-wave pulses (20 ms, 5.8-7.7 V, 30 ms after detection of local activation) through two right ventricular leads screwed into the right aspect of the interventricular septum. CCM signals were delivered 3 hours daily over 8 weeks (3-hour phase) and 7 hours daily over the next 24 weeks (7-hour phase). Safety and feasibility of this novel therapy were regarded as primary endpoints. Preliminary clinical efficacy, -as expressed by changes in ejection fraction (EF), NYHA class, 6-minute walking test (6-MWT), peak O(2) uptake (peak VO(2)), and Minnesota Living with HF Questionnaire (MLWHFQ), was assessed at baseline and at the end of each phase. At the end of follow-up (8.8 +/- 0.2 months), all patients were alive, without heart transplantation or need for left ventricular assist device. Serial 24-hour Holter analysis revealed no proarrhythmic effect. No devices malfunctioned or failed for any reason other than end-of-battery life. Throughout the two study phases, EF improved from 22.7 +/- 7% to 28.7 +/- 7% and 37 +/- 13% (P = 0.004), 6-MWT from 418 +/- 99 m to 477 +/- 96 m and 510 +/- 107 m (P = 0.002), MLWHFQ from 36 +/- 21 to 18 +/- 12 and 7 +/- 6 (P = 0.002), peak VO(2) from 13.7 +/- 1.1 to 14.9 +/- 1.9 to 16.2 +/- 2.4 (P = 0.037), and NYHA class from 3 to 1.8 +/- 0.4 to 1.5 +/- 0.7 (P < 0.001)., Conclusion: CCM therapy appears to be safe and feasible. Proarrhythmic effects of this novel therapy seem unlikely. Preliminary data indicate that CCM gradually and significantly improves systolic performance, symptoms, and functional status. CCM therapy for 7 hours per day is associated with greater dispersion near the mean, emphasizing the need to individually tailor CCM delivery duration. The technique appears to be attractive as an additive treatment for severe HF. Controlled randomized studies are needed to validate this novel concept.

Background: There are no data to evaluate the relationship between autonomic nerve function modification and recurrent atrial fibrillation (AF) after circumferential pulmonary vein ablation (CPVA). This study assesses the incremental benefit of vagal denervation by radiofrequency in preventing recurrent AF in a large series of patients undergoing CPVA for paroxysmal AF., Methods and Results: Data were collected on 297 patients undergoing CPVA for paroxysmal AF. Abolition of all evoked vagal reflexes around all pulmonary vein ostia was defined as complete vagal denervation (CVD) and was obtained in 34.3% of patients. Follow-up ended at 12 months. Heart rate variability attenuation, consistent with vagal withdrawal, was detectable for up to 3 months after CPVA, particularly in patients with reflexes and CVD, who were less likely to have recurrent AF than those without reflexes (P=0.0002, log-rank test). Only the percentage area of left atrial isolation and CVD were predictors of AF recurrence after CPVA (P<0.001 and P=0.025, respectively)., Conclusions: This study suggests that adjunctive CVD during CPVA significantly reduces recurrence of AF at 12 months.

We assessed the feasibility of cardiac contractility modulation (CCM) by electric currents applied during the refractory period in patients with heart failure (HF). Extracellular electric currents modulating action potential and calcium transients have been shown to potentiate myocardial contractility in vitro and in animal models of chronic HF. CCM signals were biphasic square-wave pulses with adjustable amplitude, duration, and time delay from sensing of local electric activity. Signals were applied to the left ventricle through an epicardial vein (in 12 patients) or to the right ventricular (RV) aspect of the septum endocardially (in 6 patients). Simultaneous left ventricular (LV) and aortic pressure measurements were performed using a Millar catheter (Millar Instruments, Houston, Texas). Hemodynamics during RV temporary dual-chamber pacing was regarded as the control condition. Both LV and RV CCM stimulation increased dP/dt(max) to a similar degree (9.1 +/- 4.5% and 7.1 +/- 0.8%, respectively; p <0.01 vs controls), with associated aortic pulse pressure changes of 10.3 +/- 7.2% and 10.8 +/- 1.1% (p <0.01 vs controls). Regional systolic wall motion assessed quantitatively by color kinesis echocardiography was markedly enhanced near the CCM electrode, and the area of increased contractility involved 4.6 +/- 1.2 segments per patient. In 6 patients with HF with left bundle branch block, CCM signals delivered during biventricular pacing (BVP) produced an additional 16.1 +/- 3.7% increase in dP/dt(max) and a 17.0 +/- 7.5% increase in pulse pressure compared with BVP alone (p <0.01). CCM stimulation in patients with HF enhanced regional and global measures of LV systolic function, regardless of the varied delivery chamber or whether modulation was performed during RV pacing or BVP.

The dominance of the left atrium (LA) in the pulmonary vein (PV) regions for triggering and maintaining atrial fibrillation (AF) is now widely recognized. Radiofrequency (RF) PV isolation with electroanatomical guidance has recently emerged as a promising approach for AF treatment. We report the clinical outcome of the procedure in 251 consecutive patients with paroxysmal (n = 179) or permanent (n = 72) AF. Circular RF lesions were deployed transseptally during sinus rhythm or AF at 5 mm from PV ostia. Procedural and mapping times were 112 +/- 32 min and 75 +/- 27 min, respectively, with 29 +/- 11 min of fluoroscopy. Complete lesions (peak-to-peak bipolar electrogram amplitude < 0.1 mV inside the line and no double potentials) were achieved in 85% of the veins treated. Sinus rhythm was restored during RF delivery in 52% and by DC shock in the remaining. Major complications (cardiac tamponade) occurred in 3%. Extent of ablated area was 4.9 +/- 0.5 cm2, accounting for 28 +/- 9% of the total LA map surface. After 11 +/- 5 months, procedure success rates (freedom from AF without antiarrhythmic drugs) were 85% for paroxysmal and 68% for permanent AF. No PV stenoses were detected. By univariate analysis, an increased risk of recurrence was predicted by LA dilation (diameter > 50 mm), AF duration, and a low ablated area (< 15% of total LA surface). After adjustment, only the latter variable continued to be significant (odds ratio 3.5, 95% confidence interval, 1.6-5.8). In conclusion, RF PV isolation is safe and effective in either paroxysmal or permanent AF. Patients with enlarged left atrium may require wider lesions to achieve AF suppression.

Background: Acute left ventricular pacing has been associated with hemodynamic improvement in patients with congestive heart failure and wide QRS complex. We hypothesized that pacing two left ventricular sites simultaneously would produce faster activation and better systolic function than single-site pacing., Methods: We selected 14 heart failure patients (NYHA functional class III or IV) in normal sinus rhythm with left bundle branch block and QRS > 150 ms. An 8F dual micromanometer catheter was placed in the aorta for measuring +dP/dt (mmHg/s), aortic pulse pressure (mmHg), and end-diastolic pressure (mmHg). Pacing leads were positioned via coronary veins at the posterior base and lateral wall. Patients were acutely paced VDD at the posterior base, lateral wall, and both sites (dual-site) with 5 atrioventricular delays (from 8 ms to PR -30 ms). Pacing sequences were executed in randomized order using a custom external computer (FlexStim, Guidant CRM)., Results: Dual-site pacing increased peak +dP/dt significantly more than posterior base and lateral wall pacing. Dual-site and posterior base pacing raised aortic pulse pressure significantly more than lateral wall pacing. Dual-site pacing shortened QRS duration by 22 %, whereas posterior base and lateral wall pacing increased it by 2 and 12%, respectively (p = 0.006)., Conclusions: In heart failure patients with left bundle branch block, dual-site pacing improves systolic function more than single-site stimulation. Improved ventricular activation synchrony, expressed by paced QRS narrowing, may account for the additional benefit of dual- vs single-site pacing in enhancing contractility. This novel approach deserves consideration for future heart failure pacing studies.

Background: We treated paroxysmal recurrent atrial fibrillation (AF) with radiofrequency (RF) catheter ablation by creating long linear lesions in the atria. To achieve line continuity, a 3D electroanatomic nonfluoroscopic mapping system was used., Methods and Results: In 27 patients with recurrent AF, a catheter incorporating a passive magnetic field sensor was navigated in both atria to construct a 3D activation map. RF energy was delivered to create continuous linear lesions: 3 lines (intercaval, isthmic, and anteroseptal) in the right atrium and a long line encircling the pulmonary veins in the left atrium. After RF application, the atria were remapped to validate completeness of the block lines, demonstrated by late activation of the areas circumscribed by the lines. The mean procedure duration was 312+/-103 minutes (range, 187 to 495), with mean fluoroscopy time of 107+/-44 minutes (range, 32 to 185 minutes). No acute complications occurred, but 1 patient experienced early prolonged sinus pauses and received a pacemaker. During the first day, 17 patients (63%) had AF episodes, but at discharge, 25 patients were in sinus rhythm. After a follow-up of 6. 0 to 15.3 months (average, 10.5+/-3.0 months), 16 patients are asymptomatic, 3 have an almost complete disappearance of symptoms, 1 patient is improved, and 7 patients have their AF attacks unchanged., Conclusions: Paroxysmal recurrent drug-refractory AF can be treated by RF catheter ablation. Creation of long continuous linear lesions necessary to compartmentalize the atria is facilitated by a nonfluoroscopic electroanatomic mapping system.

Background: Percutaneous transluminal coronary angioplasty (PTCA) of chronic total coronary artery occlusions is associated with very high restenosis and reocclusion rates. Coronary stenting has been proposed as a means of improving outcome. However, the Wiktor device for chronic coronary occlusion has never been tested in a large patient sample. This study reports the first multicenter experience with the Wiktor stent for treatment of chronic occlusions., Methods: From January 1993 to December 1996, 89 consecutive patients with 91 chronic occlusions underwent Wiktor stent implantation after successful PTCA. Post-stenting regimen consisted of coumadin plus aspirin in the first 49 (55%) patients and aspirin plus ticlopidine in the following 40 (45%)., Results: Stenting was successful in 87 (98%) patients. At 1 month, 6% of patients had subacute stent thrombosis, 1% access-site complications and 3% major bleeding events. Stent thrombosis showed a univariate association with coumadin therapy (p = 0.009). Angiographic follow-up was obtained in 93% of 82 eligible patients. Restenosis rate was 32%, including 4% reocclusions. Through multiple logistic regression analysis, restenosis was independently associated with multiple stents (odds ratio-OR = 27.67, 95% confidence interval-CI = 4.25 to 79.95, p = 0.0008) and increasing values of occlusion length (OR = 1.23, 95% CI = 1.09 to 1.39, p = 0.001). Freedom from death, myocardial infarction or stented vessel revascularization was 87 and 72% at one and three years, respectively., Conclusions: Short- and long-term clinical and angiographic outcomes are favorable in patients undergoing Wiktor stent implantation for chronic coronary occlusion. Further technical refinements are needed to reduce restenosis rate in patients with long lesions and multiple stents.

Background: Emergency coronary angioplasty can be the treatment of choice in selected patients with acute myocardial infarction in centers with adequate facilities and organization., Methods: A multicenter observational study in patients with high-risk acute myocardial infarction was conducted to evaluate the quality of emergency angioplasty treatment according to process, acute and long-term outcome, and use of resources., Results: The RAI registry included 345 patients with high-risk acute myocardial infarction who were admitted to six participating centers over a thirteen-month period. Emergency coronary angiography was performed in 261 patients (76%) and was followed by immediate angioplasty in 236 of them (68%). Mean door-to-procedure time was 58 +/- 47 min. Severe left ventricular failure was present at admission in 35 (13%) of the 261 patients with emergency coronary angiography; and 29 of them were in cardiogenic shock (11%). Overall, in-hospital mortality for patients with angioplasty was 7.6%; i.e., 43% and 3.7% for patients with and without shock, respectively., Conclusions: Despite logistical limitation, in centers with emergency angioplasty programs this treatment can be performed with favorable process and acute outcome characteristics in patients with high-risk myocardial infarction.

Objectives: This study sought to investigate whether residual viability of infarcted myocardium may play a role in the pathogenesis of exercise-induced ventricular arrhythmias., Background: We previously showed that transient ischemia within partially infarcted areas often precipitates ventricular arrhythmias during exercise that are consistently obliterated by intravenous nitrates., Methods: We studied 60 patients with chronic stable angina and a previous myocardial infarction. All underwent at least two consecutive exercise stress tests, coronary angiography and stress/rest myocardial perfusion tomography by Tc-99m 2-methoxy isobutyl isonitrile (MIBI). In the last 26 consecutive patients, residual viability was assessed by single-photon emission computed tomography (SPECT) using fluorine (F)-18 fluorodeoxyglucose. Perfusion and metabolic data were evaluated qualitatively by three independent observers in blinded manner., Results: With exercise, 30 patients (group A) consistently developed ventricular arrhythmias (> 10 ventricular ectopic beats/min, couplets, nonsustained ventricular tachycardia); the remaining 30 patients (group B) did not. The severity of coronary artery disease (Gensini score) was similar in the two groups. Postexercise SPECT showed partial reperfusion of an infarcted area in 28 of 30 patients of group A but in only 9 of 30 of group B (p < 0.0001). Uptake of F-18 fluorodeoxyglucose was observed within the infarcted zone in 10 of 13 and 1 of 13 patients in groups A and B, respectively (p = 0.0003)., Conclusions: In patients with myocardial infarction, exercise-induced ventricular arrhythmias appear to be triggered by transient ischemia occurring within a partially necrotic area containing large amounts of viable myocardium. Therefore, occurrence of arrhythmias during exercise may represent a clue to the presence of residual viability within a previously infarcted area.

We studied 20 patients with ischaemic heart disease, who consistently developed complex ventricular arrhythmias during exercise testing. Treadmill exercise was performed twice, both during the placebo infusion and then during intravenous administration of nitroglycerin, titrated to reduce systolic blood pressure by 10 mmHg. Exercise duration in those administered placebo was 7.8 +/- 1.7 and 7.9 +/- 1.5 min, respectively (ns); angina developed in five patients and ischaemic ST changes in 10. In those administered nitroglycerin, exercise duration increased to 8.4 +/- 2 min (P less than 0.05). Diagnostic ST segment depression was observed in only two patients and only one had angina. Ventricular arrhythmias, consistently present during both tests on those administered placebo, were dramatically reduced by nitroglycerin in all 20 patients. There were 455 (mean 35.8 +/- 16.8) and 418 (mean 34.4 +/- 11.1) ventricular ectopic beats in the two exercise tests on those administered placebo and 11 in those receiving the nitroglycerin infusion (mean 0.6 +/- 0.1) (P less than 0.001). There were 28 and 29 couplets in those receiving placebo (ns) and none in those receiving nitroglycerin (P less than 0.001). Ventricular tachycardia was present in six and eight patients who received placebo but in none in those administered nitroglycerin (P less than 0.001). Abolition of exercise-induced arrhythmias was maintained during chronic treatment with oral coronary vasodilators. Prevention of exercise-related arrhythmias by nitroglycerin appears a good indicator of their ischaemic origin and may provide valuable information for long-term prophylaxis with oral vasodilators, thus avoiding antiarrhythmic agents with their potential side effects.

The endothelium-derived peptide, endothelin, has been shown to exert powerful constrictor activity in both isolated and in situ coronary arteries. Recent in vitro data on isolated cardiac myocytes suggest that the substance might also possess electrophysiologic properties. We investigated the possibility that endothelin (ET-1) may exert proarrhythmic effects when infused selectively in the coronary circulation of open-chest-anesthetized dogs. Animals were instrumented for the measurement of left anterior descending (LAD) or left circumflex (LCX) coronary artery blood flow, left systolic ventricular pressure (LSVP), dP/dtmax, mean arterial pressure (MAP), and epicardial electrocardiogram (ECG; three leads). Data were recorded during infusion (2 min) of saline (n = 5) or increasing doses of endothelin (5-80 pmol/kg) given selectively in either the LCX (n = 10) or the LAD (n = 10). When infused into the LCX, endothelin produced a dose-dependent decrease in flow (40 +/- 23% at 80 pmol/kg, mean +/- SD, p less than 0.01) with a concomitant increase in coronary resistance and a decrease in dP/dtmax and MAP. ECG changes typical of myocardial ischemia paralleled the decrease in flow and culminated in ventricular fibrillation at the highest dose (80% of dogs). Endothelin caused similar hemodynamic effects when infused in the LAD, but fatal arrhythmias occurred for lower doses and for little or no change in coronary blood flow. Thirty percent of the animals died at 10 and 60% died at 20 pmol/kg, doses that induced only a moderate decrease (8 +/- 7 and 21 +/- 12%, respectively) in LAD total blood flow. Ventricular tachycardia always preceded ventricular fibrillation and death.(ABSTRACT TRUNCATED AT 250 WORDS)

In patients with coronary artery disease, electrocardiographic signs of left atrial enlargement (LAE-negative P wave deflection greater than or equal to 1 mm2 in lead V1) are associated with increased left ventricular end diastolic pressure (LVEDP). We investigated the possibility that transient LAE could represent an additional criterion for diagnosing myocardial ischemia during exercise testing (EST). We studied 48 consecutive patients with chronic stable angina, positive EST and 201 Tl scintigraphy, and angiographically proven CAD; 200 other consecutive patients with atypical chest pain and normal stress/rest 201 Tl scintigraphy served as controls. During EST, transient LAE developed in 34/48 patients with CAD but in only 1/200 controls (p less than 0.001). When present, LAE preceded ST changes (6.1 +/- 1 min vs 8.2 +/- 2 min) and recovered earlier (4.7 +/- 4 min vs 5.8 +/- 3 min). The prevalence of 2-3 vessel CAD was significantly higher in patients with EST-induced LAE (54% vs 34%, p less than 0.05). In conclusion, transient ECG signs of LAE during EST represent a highly specific sign of reversible ischemia and are frequently associated with multivessel CAD. Although less sensitive than classical ST criteria, this sign may prove useful in patients exhibiting equivocal ST changes and in the presence of ventricular conduction disturbances.

In patients with ischemic heart disease and arrhythmias, selection of antiarrhythmic treatment is often difficult as it is hard to separate "primary" from ischemic arrhythmias. We studied 20 patients with ischemic heart disease, who developed ventricular arrhythmias consistently during exercise test. Exercise test was performed twice during infusion of placebo and then during intravenous administration of nitroglycerin, titrated to reduce systolic blood pressure by 10 mmHg. Exercise duration was 7.8 +/- 1.7 and 7.9 +/- 1.5 min, in the 2 placebo tests (NS). Angina developed in 5 patients and ischemic ST changes in 10. With nitroglycerin exercise duration increased to 8.4 +/- 20 min (p less than 0.05), diagnostic ST segment depression was observed in 2 patients and only 1 had angina. In all 20 patients, ventricular arrhythmias were consistently present during both tests on placebo, that were markedly reduced by nitroglycerin. In fact, ventricular ectopic beats were 455 (mean 35.8 +/- 16.8) and 418 (mean 34.4 +/- 11.1) in the 2 exercise tests with placebo, and 11 during nitroglycerin infusion (mean 0.6 +/- 0.1; p less than 0.001). Couplets were 28 and 29 during placebo (NS) and 0 during nitroglycerin (p less than 0.001). Ventricular tachycardia was present in 6 and 8 patients during placebo but in none during nitroglycerin (p less than 0.001). Reduction of exercise-induced arrhythmias was maintained during chronic treatment with oral vasodilators. Prevention of exercise-related arrhythmias by nitroglycerin infusion appears a good indicator of their ischemic origin and may provide valuable information for long-term profilaxis with oral vasodilators, then avoiding the use of antiarrhythmic agents and their potential side effects.

Blood viscosity and filtrability have been studied in 7 patients with ischemic heart disease and in 9 control subjects before and after maximal stress test on cycloergometer. The diagnosis of ischemic heart disease has been previously established on the basis of the clinical history, abnormal stress test or coronary arteriography. No significant differences were observed, at rest, in the two groups. On the contrary, after stress test blood filtrability resulted significantly reduced in ischemic patients when compared to controls. Blood viscosity resulted substantially unchanged in both groups. Our data may suggest the existence of an alteration in blood filtrability during stress test with a possible pathogenetic role.

Plasma beta-thromboglobulin (beta TG) was assayed in 10 insulin-dependent uncomplicated diabetic subjects and in 10 age- and sex-matched metabolically healthy controls, both at rest and after maximal physical exercise. Diabetic patients showed significantly higher (p less than 0.005) resting beta TG values as compared to the control group. After physical exercise, beta TG rose significantly (p less than 0.05) only in the control group, thus abolishing the difference (evaluated through beta TG values) between the two groups observed at rest. Platelet hyperactivity seems thus to be present even in uncomplicated diabetes, at rest, while exercise does not lead to a further increase in beta TG values contrary to what is observed in controls.

Technetium-99m labeled bis(1,2-diethylphosphino)ethane was evaluated as a cardiac perfusion agent in mice, dogs and normal human volunteers. The agent produced as a single cationic compound was prepared by a simple kit type method and had a rapid myocardial uptake in animals. The cardiac uptake of the agent in dogs averaged 4.6% of administered dose and delineated left and right ventricles by in vivo imaging. In dogs with experimental myocardial infarction, the agent was distributed according to the regional myocardial blood flow, had excellent correlation with myocardial distribution of 85Sr microspheres (r = 0.96, 0.93)] and 201Tl (r = 0.91 and 0.83), and enabled us to detect perfusion defects by in vivo scintigraphy. The agent, however, failed to have a useful degree of cardiac uptake in humans.

The biodistribution of the three cationic 99mTc complexes [99mTc(TMP)6]+, [99mTc(POM-POM)3]+, and [99mTc(TBIN)6]+--where TMP represents trimethylphosphite, POM-POM represents 1,2-bis(dimethyoxyphosphino)ethane, and TBIN represents t-butylisonitrile--have been evaluated in humans and dogs. Each agent was studied in three normal volunteers at rest, while [99mTc(POM-POM)3]+ and [99mTc(TBIN)6]+ were each studied in one normal volunteer at exercise. Even though all three agents yield good myocardial images in dogs, none appear suitable for clinical use as myocardial perfusion imaging radiopharmaceuticals. In humans, [99mTc(TMP)6]+ and [99mTc(POM-POM)3]+ clear very slowly from the blood and provide myocardial images only several hours after injection. [99mTc(TBIN)6]+ clears rapidly from the blood, but accumulation in the lung obscures the myocardial image for the first hour after injection; at later times, activity in the liver and spleen masks the apical wall. These results correlate with the blood-binding properties of the three complexes. [99mTc(TMP)6]+ and [99mTc(POM-POM)3]+ bind tightly to the plasma of human blood, but not to the plasma of dog blood; [99mTc(TBIN)6]+ does not bind tightly to the plasma of either dog or human blood. Among the Tc(I) complexes studied to date in humans, [99mTc(TBIN)6]+ appears to be unique in biodistribution pattern, blood-binding properties, and the fact that exercise improves the ultimate myocardial image. All the Tc(I) complexes appear to undergo myocardial accumulation by a mechanism different from that utilized by Tc(III) complexes. Animal studies alone are not adequate to evaluate the potential utility of 99mTc cationic complexes for myocardial perfusion studies.

Plasma beta-thromboglobulin concentration was measured in ten uncomplicated insulin-dependent diabetic subjects, in ten insulin-dependent patients with retinopathy and in ten age- and sex-matched healthy controls, both at rest and after cycloergometric exercise to exhaustion. Resting plasma beta-thromboglobulin was similar in the two patient groups and significantly higher than the control group. After exercising, plasma beta-thromboglobulin rose significantly only in the control group. Platelet hyperactivity is therefore present even in uncomplicated diabetes mellitus and is not influenced by the presence of complications. A chronic overstimulation of platelets could be responsible for the high basal plasma beta-thromboglobulin concentration in diabetes mellitus and for its abnormal behaviour after physical exercise.

Heart rate, blood pressure, and left ventricular ejection fraction (LVEF) were measured by means of Au 195 m first-pass angiocardiography, during maximal supine bicycle exercise in 20 young asymptomatic patients with insulin-dependent diabetes (IDD) (10 retinopathic and 10 uncomplicated) and in 10 control subjects. Five patients with retinopathic IDD also had mild subclinical autonomic neuropathy. Exercise capacity was diminished, although not significantly, in patients with retinopathic IDD. Heart rate and LVEF were similar in all groups at rest and at submaximal exercise. At peak exercise patients with retinopathic IDD had significantly lower heart rate (134 +/- 4 bpm) and LVEF (62.9 +/- 3.7%) than those with umcomplicated IDD (158 +/- 8 bpm and 76.6 +/- 2.4%, respectively) and control subjects (152 +/- 6 bpm and 73.5 +/- 1.9%, respectively). LVEF increased vs baseline in all control subjects and patients with uncomplicated IDD, but in only three with retinopathic IDD. Leg muscle blood flow (MBF) was also evaluated at rest and during exercise by 133Xe washout. Exercise MBF was significantly lower in patients with retinopathic IDD (40.5 +/- 2.23 ml X min-1 X 100 gm-1) than in control subjects (49.9 +/- 1.87 ml X min-1 X 100 gm-1) and in those with uncomplicated IDD (49.0 +/- 1.87 ml X min-1 X 100 gm-1). Diffuse microangiopathy, alone or in combination with neuropathy, might be responsible for the impairment of cardiovascular function in diabetes.

Left ventricular function (LVF) was studied in 25 obese patients (four males and 21 females) by serial poligraphic measurements, namely systolic time intervals (STI), during a short period of dieting (2721 kJ/day (650 kcal/day) as single daily meal regimen). In the same period, all the patients underwent also three standardized exercise tests at the cycloergometer. At the end of the study (20th day), statistically significant differences were obtained in weight loss (P less than 0.001); two main parameters of STI, namely pre-ejection period index (PEPI) and PEP/LVET ratio were lowered (P less than 0.001): furthermore, peak and recovery systolic blood pressure (SBP) and heart rate (HR) during exercising, were also significantly reduced. These data suggest that an improvement of LVF and cardiac performance are present since the early phases of caloric restriction in obesity.

Habitual smoking is one of the best established risk factors for cardiovascular disease. The pathogenesis of smoke-induced damage is not so well clarified, but it probably includes--among some other aspects--an activation of the hemostatic system. Recently it has been shown that smoking a single cigarette can significantly decrease the coronary blood flow in coronary patients as well as in normal subjects. We tested the hypothesis that the acute effects of smoke are mediated by the hemostatic system. Seven healthy male volunteers, aged 20-40 years (mean 32 +/- 6 years), entered the study. All were habitual smokers, but had abstained from smoking in the 12 hours preceding the test. After lying in absolute rest for about 30 minutes, each subject smoked a cigarette containing 1.2 mg of nicotine. Immediately before and after smoking, blood was drawn by clear venipuncture for the evaluation of the following hemostatic variables: collagen-induced platelet aggregation by the method of Born; thromboxane B2 (TxB2) production by platelets stimulated with collagen, radioimmunoassay (RIA); plasma beta thromboglobulin (TG) (RIA); plasma fibrinopeptide A (FPA) (RIA); plasma fibrinolytic activity in the euglobulin fraction (NEF) (fibrin plate method). The following results, respectively before and after smoking, were observed: collagen-induced platelet aggregation 55 +/- 3 vs. 57 +/- 6%; TxB2 100.5 +/- 5.9 vs. 90.3 +/- 9.0 ng/10(8) platelets; plasma beta-TG 20.8 +/- 2.2 vs. 19.2 +/- 2.3 ng/ml; plasma FPA 2.3 +/- 0.3 vs. 2.2 +/- 0.1 ng/ml; NEF, lysis diameter 16.8 +/- 1.6 vs. 16.7 +/- 1.7 mm; NEF + C1 inhibitor lysis diameter 8.8 +/- 0.7 vs. 9.1 +/- 0.7 mm.(ABSTRACT TRUNCATED AT 250 WORDS)