[Leadless pacemakers: results of a survey from implanter centers in the Lombardy region]. / Pacemaker leadless: risultati di una survey condotta nei centri impiantatori della Regione Lombardia.

BACKGROUND: Transvenous pacing is nowadays the cornerstone of interventional management of bradyarrhythmias. It is still associated, however, with significant complications, mostly related to indwelling transvenous leads or device pocket. In order to reduce these complications, leadless pacemakers have been recently introduced into clinical practice, but no guidelines are yet available to indicate who are those patients that might benefit the most and whether leadless pacing should be preferred in the old or young population. This survey aims to describe the use of leadless pacemaker devices in a real-world setting. METHODS: Eleven arrhythmia centers in the Lombardy region (out of a total of 17 participating centers) responded to the proposed questionnaire regarding patient characteristics and indications to leadless pacing. RESULTS: Out of a total of 411 patients undergoing leadless pacing during 4.2 ± 0.98 years, the median age was 77 years, with 0.18% of patients having less than 18 years, 29.9% 18-65 years, 34.3% 65-80 years and 35.6% >80 years. The most common indication was slow atrial fibrillation (49% of patients), followed by atrioventricular block and sinoatrial dysfunction. Two centers reported in-hospital complications. CONCLUSIONS: Leadless pacemakers proved to be a safe pacing strategy actually destined mostly to elderly patients.

Contact-Force Guided Posterior Wall Isolation as an Adjunctive Ablation Strategy for Persistent Atrial Fibrillation.

BACKGROUND: The efficacy of posterior wall isolation (PWI) on top of pulmonary vein isolation (PVI) in patients affected by persistent atrial fibrillation (AF) is still controversial and little is known about the impact of contact-force (CF) technology. OBJECTIVE: In this retrospective study, we present our experience with PWI using CF sensing catheters and its efficacy and safety as an adjunctive ablation strategy on top of PVI for management of patients with persistent and longstanding persistent AF. METHODS: A total of 73 consecutive patients (20.5% female) affected by persistent atrial fibrillation (10.9% long-standing) underwent PWI as an adjunctive therapy to PVI using CF sensing catheters. Outcomes were reported as incidence of atrial arrhythmic recurrences (ARs) lasting >30 seconds at follow up and in addition, in patients provided with insertable cardiac monitors (ICM), as burden of AF or atrial tachycardias (AT) at relevant time points. RESULTS: PWI was successfully achieved in 65 (89.0%) patients. Two (2.7%) minor vascular procedural complications were observed. At 1 and 2-year follow-up, ARs free survival was observed in 80.5% and 64.1% of patients, respectively with 75.3% of patients off antiarrhythmic drugs at the last follow-up. Ten patients underwent repeat ablations during the follow-up. At multivariate analysis, early ARs within 3 months after procedure, were associated with a two-fold increased risk of late ARs at follow-up. Among patients provided with ICM, PWI on top of PVI was able to reduce the mean AT/AF burden of more than 50% compared with pre-ablation time, reporting very low levels (≤ 5%) over 2 years. CONCLUSIONS: In persistent atrial fibrillation, PWI on top of PVI using CF sensing catheters is safe and effective, providing great reduction of burden of ARs. Early ARs are associated with a greater risk of late recurrences.

Myotonic dystrophy type 1 and high ventricular vulnerability at the electrophysiological evaluation: ICD yes or not?

A significant number of sudden death (SD) is observed in myotonic dystrophy (DM1) despite pacemaker implantation and some consider the ICD to be the preferential device in patients with conduction disease. According to the latest guidelines, prophylactic ICD implantation in patients with neuromuscular disorder should follow the same recommendations of non-ischemic dilated cardiomyopathy, being reasonable when pacing is needed. We here report a case of DM1 patient who underwent ICD implantation even in the absence of conduction disturbances on ECG and ventricular dysfunction/fibrosis at cardiac magnetic resonance. The occurrence of syncope, non-sustained ventricular tachycardias at 24-Holter ECG monitoring and a family history of SD resulted associated with ventricular fibrillation inducibility at electrophysiological study, favouring ICD implantation. On our advice, DM1 patient with this association of SD risk factors should be targeted for ICD implantation.

Sex effect on efficacy of pulmonary vein cryoablation in patients with atrial fibrillation: data from the multicenter real-world 1STOP project.

PURPOSE: Pulmonary vein isolation (PVI) using cryoablation (PVI-C) is a widespread therapy for treating symptomatic, recurrent atrial fibrillation (AF). The impacts of sex on efficacy and safety of PVI-C in a real-world clinical practice is lacking. In a multicenter prospective project, we evaluated whether clinical characteristics, procedure parameters, procedural complications, long-term AF recurrence rates, and/or AF-related symptoms differed according to sex in patients treated with PVI-C. METHODS: Data from the study population were collected in the framework of the 1STOP ClinicalService® project, involving 47 Italian cardiology centers. Multivariable statistical analyses were conducted to determine if any baseline clinical characteristics impacted the efficacy of PVI-C. RESULTS: From April 2012, 2125 patients (27% female, 59 ± 11 years, 73% paroxysmal AF, and mean left atrial diameter = 42 ± 8 mm) underwent PVI-C. According to baseline characteristics, women were more likely to be older, with higher clinical risk scores (e.g., CHA2DS2-VASc), and a higher number of tested antiarrhythmic drugs before the index PVI-C procedure. Male and female cohorts showed comparable procedure time (mean = 107.7 ± 46.8 min) and a similar incidence of periprocedural complications (4.5% overall), even after adjustment for baseline characteristics (P = 0.880). The multivariable analyses demonstrated that the strongest predictor of AF recurrences was sex (0.74; 95% CI 0.58-0.93; P = 0.011). After propensity score adjustment, the hazard ratio from a multivariable model, which included age and AF type (persistent) as covariates, was 0.76 (0.60-0.97) (P = 0.025). CONCLUSIONS: According to the 1STOP project, in a real-world setting, PVI-C was relatively safe regardless of the patient's sex; however, when considering efficacy of the procedure, female patients had a lower long-term efficacy in comparison to males. CLINICAL TRIAL REGISTRATION: NCT01007474.

Contiguity Between Ablation Lesions and Strict Catheter Stability Settings Assessed by VISITAGTM Module Improve Clinical Outcomes of Paroxysmal Atrial Fibrillation Ablation　- Results From the VISITALY Study.

BACKGROUND: Our aim was to evaluate the clinical outcome of paroxysmal atrial fibrillation (AF) ablation with contact force technology, using an automated lesion tagging system (VISITAGTM module) with strict criteria of catheter stability.Methods and Results:We enrolled 200 consecutive patients who underwent pulmonary vein isolation (PVI) in 11 centers and were followed up for 12 months. The stability setting was within 3 mm for ≥10 s and for ≥15 s in 47% and 53% of patients, respectively. A mean of 67.2±21.9 VISITAGs was acquired. Freedom from atrial tachyarrhythmias at follow-up was 77.5% (155/200), and the contiguity between lesions was associated with a higher chronic success rate (96% vs. 77.1%; log-rank P=0.036). Radiofrequency (RF), fluoroscopy times, and recurrence rates at the 12-month follow-up were significantly lower than in a comparison group of 80 patients without VISITAGTM module (42.7±14.5 vs. 50.9±23.6 min; P=0.032; 11.6±7.8 vs. 18.4±12.8 min; P=0.003 and 22.5% vs. 41.2%; P=0.02). Two major complications (1 cardiac tamponade and 1 minor stroke) were observed only in the control group. CONCLUSIONS: Paroxysmal AF ablation with contact force technology and strict criteria of stability using the VISITAG module was a safe procedure, associated with an improvement in efficiency and a reduction of atrial tachyarrhythmia recurrence at the 12-month follow-up compared with manual annotation. Contiguity between lesions seemed to enhance effectiveness outcomes.

Influence of rs5065 atrial natriuretic peptide gene variant on coronary artery disease.

OBJECTIVES: The aim of this study was to investigate the impact of rs5065 atrial natriuretic peptide (ANP) gene variant on coronary artery disease (CAD) and its outcomes and to gain potential mechanistic insights on the association with CAD. BACKGROUND: Either modified ANP plasma levels or peptide structural alterations have been involved in development of cardiovascular events. METHODS: Three hundred ninety-three control subjects and 1,004 patients undergoing coronary angiography for suspected CAD (432 stable angina [SA], 572 acute coronary syndrome [ACS]) were genotyped for rs5065 ANP gene variant. Data in SA and ACS groups were replicated in an independent population of 482 stable angina patients (rSA) and of 675 ACS patients, respectively. Clinical follow-up was available for both SA and rSA patients. Plasma N-terminal-proANP, myeloperoxidase, lipoprotein-associated phospholipase A2, and oxidized low-density lipoprotein were assessed in a subgroup of rSA patients. RESULTS: rs5065 minor allele (MA) was an independent predictor of ACS (odds ratio: 1.90; 95% confidence interval: 1.40 to 2.58, p < 0.001). At follow-up, rs5065 MA was independently associated with a significantly higher rate of major adverse cardiovascular events in the SA group, p < 0.001. Data were replicated in the rSA group at follow-up (p = 0.008). Cox proportional hazard analysis tested by 4 models confirmed higher major adverse cardiovascular events risk in rs5065 MA carriers in both SA and rSA cohorts. Significantly higher myeloperoxidase levels were detected in rs5065 MA carriers (n = 597 [345 to 832 µg/l] vs. n = 488 [353 to 612 µg/l], p = 0.038). No association of rs5065 was observed with N-terminal-proANP levels. CONCLUSIONS: The MA of rs5065 ANP gene variant associates with increased susceptibility to ACS and has unfavorable prognostic value in CAD.

Femoral plaque echogenicity and cardiovascular risk in claudicants.

OBJECTIVES: The present study was designed to verify whether the evaluation of femoral plaque echogenicity might be a useful tool for cardiovascular risk assessment in patients affected by lower extremity peripheral arterial disease. BACKGROUND: Lower extremity peripheral arterial disease is a common manifestation of atherosclerosis and is associated with a high risk of developing major cardiovascular events. Vulnerable atherosclerotic plaque plays a central role in the occurrence of acute ischemic events in different vascular territories. Furthermore, atherosclerosis is a systemic disease, and the presence of an unstable atherosclerotic plaque in a certain vascular district, characterized by low echogenicity at B-mode ultrasound, is associated to a greater prevalence of unstable plaques in other vascular beds. METHODS: Femoral plaque echogenicity of 246 claudicants with ankle/brachial index ≤0.90 was evaluated at B-mode ultrasound by visual analysis and by calculating the grayscale median (GSM) value. In these patients, the occurrence of myocardial infarction and stroke was prospectively assessed. RESULTS: Femoral GSM values and plaque types assessed by visual analysis were highly correlated by Spearman analysis (rho = 0.905, p < 0.001). During a median follow-up of 30 months, 32 patients (13%) had a major cardiovascular event. Compared with patients without events, those who experienced an event during the follow-up had a lower femoral plaque GSM value (42.9 ± 26.2 vs. 58.8 ± 19.3, p = 0.002) and a higher prevalence of hypoechoic femoral plaque at visual analysis (68.8% vs. 19.6%, p < 0.001). At Cox analysis, femoral GSM showed an inverse relationship with cardiovascular risk, even after adjustment for possible confounders (hazard ratio: 0.96, 95% confidence interval [CI]: 0.95 to 0.98, p < 0.001). Furthermore, patients with hypoechoic femoral plaques at visual analysis had a 7.24-fold increased cardiovascular risk compared with patients with hyperechoic plaques after adjustment for possible confounders (95% CI: 3.23 to 16.22, p < 0.001). CONCLUSIONS: This study demonstrates that the presence of hypoechoic atherosclerotic femoral plaques is associated with higher cardiovascular risk in lower extremity peripheral arterial disease patients.

Carotid artery disease and stroke in patients with peripheral arterial disease. The role of inflammation.

Although during the last decade there have been great advances in our knowledge of the epidemiology and pathophysiology of multi-district atherosclerotic disease, little is known about the association between peripheral arterial disease and carotid artery disease. This review was conceived to cast some light on this topic, paying special attention to inflammation which plays a pivotal role in atherosclerosis. An aspect of pathophysiologic and clinical relevance is that the coexistence of carotid disease is more frequent in peripheral arterial disease than in coronary artery disease, not only in terms of carotid stenosis, but also with respect to the presence of hypoechoic unstable plaque. These latter plaques present a large infiltration of macrophages and are associated to high levels of inflammatory markers. In particular, the greater prevalence of hypoechoic carotid plaques in peripheral arterial disease compared to patients with carotid artery disease was poorly related to classic risk factors, but showed an independent association with an increased number of leukocyte and neutrophil cells, which are reliable markers of inflammation. The greater prevalence of hypoechoic unstable carotid plaques could explain why peripheral arterial disease portends higher risk of stroke than coronary artery disease.

Prevalence of hypoechoic carotid plaques in coronary artery disease: relationship with coexistent peripheral arterial disease and leukocyte number.

In coronary artery disease (CAD), a concomitant peripheral arterial disease (PAD) entails a more severe coronary atherosclerosis. We hypothesized that the severity of carotid artery disease is greater in CAD+PAD than in CAD alone. In 90 CAD and 79 CAD+PAD patients, carotid plaque echolucency was measured by gray-scale median (GSM), and the degree of carotid stenosis by routine Doppler criteria. Plaques were absent in 20 (22.2%) CAD and 8 (10.1%) CAD+PAD patients (p=0.035), while the prevalence of carotid stenosis>or=50% was 16.7% and 25.3%, respectively (p=0.166). The GSM score was 45.1 [21.7-67.7] in CAD+PAD vs 60.1 [44.9-83.1] in CAD alone (p<0.001). Consistently, hypoechoic plaques (GSM<25th percentile) were more common in CAD+PAD than in CAD patients (38.0% vs 11.4%, p<0.001). On multivariate analysis, CAD+PAD was the only variable significantly associated with hypoechoic plaques (OR=4.16, 95% CI 1.68-10.28). However, when the leukocyte count was added to the model, it showed the strongest association with hypoechoic plaques (OR=6.70, 95% CI 2.13-21.10). In conclusion, compared with CAD alone patients, those with concomitant PAD showed a greater prevalence of plaques with characteristics of instability. Thus, our data suggest that in CAD+PAD, evaluation of carotid plaque echogenicity could contribute to improve clinical decision-making and differentiate treatments for individual patients.

Echolucent femoral plaques entail higher risk of echolucent carotid plaques and a more severe inflammatory profile in peripheral arterial disease.

OBJECTIVE: Plaque instability is recognized as a multivessel phenomenon related to inflammation. This study examined if the morphology of femoral plaques was related to that of carotid plaques. METHODS: The echogenicity of femoral and carotid plaques of 102 patients with peripheral artery disease (PAD) was studied and classified as echolucent or echorich according to the gray-scale median (GSM) value, which was 53.6 for femoral plaques and 55.2 for carotid plaques. Serum C-reactive protein (CRP) levels and neutrophil count were also measured. RESULTS: Echolucent carotid plaques were more frequent in patients with echolucent than in those with echorich femoral plaques (55.8% vs 32.0%; P < .01). At multivariate analysis, femoral GSM lower than the median was the only significant predictor of echolucent carotid plaques (odds ratio [OR], 3.87; 95% confidence interval [CI], 1.53-9.83). Patients with echolucent femoral plaques had higher serum CRP levels (P < .01) and a higher neutrophil count (P = .029) than patients with echorich femoral plaques. However, univariate analysis showed that neutrophil count (OR, 3.48; 95% CI, 1.23-9.85) but not hs-CRP was associated with echolucent carotid plaques. At multivariate analysis, neutrophil count exceeding the median remained associated with echolucent carotid plaques (OR, 5.71; 95% CI, 1.37-23.85), whereas the association between femoral and carotid echolucency was attenuated (OR, 3.75; 95% CI, 0.98-4.43). CONCLUSIONS: In PAD, the presence of echolucent femoral plaques is associated with a greater prevalence of echolucent carotid plaques, probably as a consequence of a more pronounced inflammatory profile. This confirms and extends the finding that plaque echolucency is a multivessel phenomenon. Prospective studies are needed to assess whether carotid screening in PAD patients might contribute to improving clinical decision-making.

The prevalence of hypoechoic carotid plaques is greater in peripheral than in coronary artery disease and is related to the neutrophil count.

OBJECTIVE: Previous reports indicate that the prevalence and severity of carotid stenoses is greater in peripheral artery disease (PAD) than in coronary artery disease (CAD). To date, no study has compared these two populations with respect to plaque echogenicity, which is an independent risk factor for cerebrovascular events. METHODS: In 43 PAD patients without CAD and in 43 CAD patients without PAD, carotid plaques were studied with high-resolution B-mode ultrasound and by computerized measurement of the gray-scale median. RESULTS: At visual analysis, the prevalence of hypoechoic plaques was 39.5% in PAD and 18.6% in CAD (P = .033). The corresponding values for gray-scale median analysis were 34.9% and 14.0% (P = .024). At multivariate analysis, PAD patients showed a greater risk of having hypoechoic plaques than CAD patients at visual (odds ratio [OR], 4.39, 95% confidence interval [CI] 1.21-15.92, P = .025) and gray-scale median analysis (OR, 5.13; 95% CI, 1.27-20.67; P = .021). This association was no longer significant when neutrophil number was included among the covariates. In this model, only an increased neutrophil count was associated with hypoechoic plaques (P < .01 for both visual and gray-scale median analysis). Indeed, neutrophil count was greater in PAD than in CAD (4.4 +/- 1.0 vs 3.9 +/- 1.2 10(9)/L, P = .030). The concordance between visual typing of carotid plaques and gray-scale median measurement was good (rho = 0.714, P < .01). CONCLUSIONS: Compared with CAD patients, those with PAD, in addition to a greater atherosclerotic burden, may have characteristics of instability of carotid plaques that, in turn, may result in cerebrovascular events. Prospective studies are needed to assess specifically whether the greater prevalence of hypoechoic plaques in PAD vs CAD patients is associated with a greater risk of cerebrovascular events.

[Intermittent claudication in Italy. The Peripheral Arteriopathy and Cardiovascular Events (PACE) study]. / La claudicatio intermittens in Italia. lo studio Peripheral Arteriopathy and Cardiovascular Events (PACE).

BACKGROUND: The epidemiology of intermittent claudication in the primary care settings has been studied almost exclusively in northern European and northern American populations. This article compares the results of the Peripheral Arteriopathy and Cardiovascular Events (PACE) study, the first survey in Italy to assess the prevalence, comorbidity and natural history of intermittent claudication, with those observed in other western countries. METHODS: From the lists of seven general practitioners, all patients aged 40-80 years (n = 4352) received a Rose questionnaire. In those reporting leg pain while leg pain while walking (n = 760), Doppler examination was performed. Intermittent claudication was defined as an ankle/branchial index of < 0.90, or reduced flow velocity. For each claudicant, three age- and sex-matched controls were randomly selected from patients negative to the questionnaire. RESULTS: The prevalence of both intermittent claudication (1.6%) and associated cardiovascular disease (34%) tended to be lower in Italy than in the United Kingdom, Netherlands, and North America. Conversely, no between country difference was observed with respect to mortality, which was very high (relative risk 4.08; 95% confidence interval 1.50-10.84, p = 0.006) in the PACE claudicants. CONCLUSIONS: In this regard it is noteworthy that these patients, who were managed almost exclusively by their general practitioner were undertreated with respect to the use of antiplatelet therapy and correction of risk factors. There is need to alert them to this topic.

Peripheral arterial disease and cardiovascular risk in Italy. Results of the Peripheral Arteriopathy and Cardiovascular Events (PACE) study.

OBJECTIVE: Our knowledge about the natural history of peripheral arterial disease (PAD) is derived from studies carried out almost exclusively in northern European and northern American populations. This study was aimed at defining mortality and cardiovascular morbidity of PAD patients in Italy. METHODS: From the lists of seven general practitioners, we identified all subjects aged 40-80 years (n = 4352). Of those reporting leg symptoms while walking at the Rose Questionnaire (n = 760), 60 (1.6% of the general population) had PAD, as evidenced by an ankle-brachial index of < 0.90 or reduced Doppler flow velocity. For each PAD patient, three sex and age-matched controls negative to the Rose Questionnaire were randomly selected from the general practice lists. RESULTS: After 24 months of follow-up, 15% of PAD patients died, 8% from cardiovascular disease, and 25% developed a non-fatal cardiovascular event. At Cox analysis, the presence of PAD was associated with an increased risk of all-cause mortality (relative risk 4.03; 95% confidence interval 1.50-10.84; P = 0.006), cardiovascular mortality (relative risk 7.77; 95% confidence interval 1.51-40.16; P = 0.014), and non-fatal cardiovascular events (relative risk 3.11; 95% confidence interval 1.41-6.80; P = 0.005). CONCLUSIONS: This Italian study shows that, in general practice, symptomatic PAD is associated with a four-fold increased risk of mortality and a nearly eight-fold increased risk of cardiovascular mortality. These figures are quite similar to those reported in northern European and northern American populations. General practitioners, who are the clinicians primarily and largely responsible for the care of these patients, should be alerted to the consequences of PAD.

Metabolic syndrome in peripheral arterial disease: relationship with severity of peripheral circulatory insufficiency, inflammatory status, and cardiovascular comorbidity.

OBJECTIVE: Metabolic syndrome is defined by the clustering in the same person of at least three risk factors such as hyperglycemia, hypertriglyceridemia, low levels of high-density lipoprotein, hypertension, and abdominal obesity. In patients with peripheral arterial disease (PAD), we investigated the prevalence of metabolic syndrome and its relationship with the severity of peripheral circulatory insufficiency, inflammatory status, and cardiovascular comorbidity. METHODS: The presence of metabolic syndrome was assessed in 154 consecutive PAD patients (115 men, 39 women). Inflammatory status was assessed by measuring serum levels of C-reactive protein (CRP). RESULTS: Metabolic syndrome was present in 51.9% (42.7 % in men, 74.3% in women, P < .01). Patients with an ankle/brachial index (ABI) <0.64 (median) were more likely to have metabolic syndrome than those with less severe PAD (63.9% vs 42.8%, P < .02). The association between a low ABI and metabolic syndrome was maintained after adjustment for age and sex (odds ratio [OR], 2.19; 95% confidence interval [CI], 1.03 to 4.68). Compared with PAD patients without metabolic syndrome, those with the syndrome had greater body mass index (28.2 [25.6; 29.8] kg/m(2) vs 26.1 [24.2; 27.7] kg/m(2), P < .01) and higher levels of CRP (3.9 [1.6; 7.6] mg/L vs 2.0 [1.1; 3.7] mg/L, P < .02). A previous myocardial infarction was documented in 58.2% of patients with and in 37.5% of those without metabolic syndrome (P < .01). At multivariate analysis, metabolic syndrome was significantly associated with previous myocardial infarction also after adjustment for ABI (OR, 2.15; 95% CI, 1.06 to 4.38). CONCLUSIONS: Metabolic syndrome is present in >50% of PAD patients. The finding that well-established indicators of increased cardiovascular risk such as low ABI and increased CRP levels cluster with metabolic syndrome suggests that identification of this syndrome in these high-risk patients could indicate an even greater risk of cardiovascular events.

Functional status measured by walking impairment questionnaire and cardiovascular risk prediction in peripheral arterial disease: results of the Peripheral Arteriopathy and Cardiovascular Events (PACE) study.

The prognostic impact of the functional status of patients with intermittent claudication is still obscure. From the lists of seven general practitioners, we identified all subjects aged 40-80 years (n = 4352). Of those reporting leg symptoms while walking on the Rose questionnaire (n = 760), 60 had a qualifying diagnosis of peripheral arterial disease (PAD). All of them received the Walking Impairment Questionnaire (WIQ). For each patient affected by PAD, three sex- and age-matched controls were selected randomly. After a 24-month follow-up, survival curves showed that PAD patients with WIQ scores > median had a higher cardiovascular risk than controls, and patients with WIQ scores < median had an even poorer prognosis (p < 0.001 for all WIQ domains). In PAD, after adjustment for age, sex, ankle-brachial index and comorbidity, two WIQ domains (ie walking speed and stair-climbing) were associated with cardiovascular events. The cardiovascular risk of claudicants who had a score > median for at least three WIQ domains was intermediate versus the risk of controls and PAD patients with a WIQ score < median, also when adjusted for the covariates indicated above (RR = 3.26, p = 0.019). In intermittent claudication, a worse functional status entails a greater risk of ischemic events versus low functional impairment.