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Background: Current guidelines recommend avoiding apical left ventricular (LV) pacing for cardiac resynchronization therapy (CRT)., Aims: We investigated the feasibility of nonapical pacing with the current quadripolar LV lead technology., Methods: We analyzed consecutive patients who received CRT with an LV quadripolar lead. The post--implantation position of each electrode of the LV lead was designated as basal, mid, or apical. The pacing capture threshold (PCT) and phrenic nerve stimulation (PNS) threshold were assessed for each electrode., Results: We enrolled 168 patients. A total of 8 CRT defibrillators were from Biotronik (with Sentus OTW QP leads), 98 were from Boston Scientific (with 21 Acuity X4 Spiral and 77 Acuity X4 Straight leads), and 62 from St. Jude Medical (with Quartet leads). The median (interquartile range) number of electrodes at nonapical segments per patient was 3 (1-4) with Biotronik Sentus leads, 4 (3-4) with spiral -design Boston Scientific leads, 4 (3-4) with straight Boston Scientific leads, and 3 (3-4) with St. Jude Medical Quartet leads (P = 0.045). Three patients (38%) with Biotronik Sentus leads, 21 (100%) with spiral -design Boston Scientific leads, 69 (90%) with straight -design Boston Scientific leads, and 49 (79%) with St. Jude Medical Quartet leads (P <0.001) had at least 1 electrode located at nonapical segments linked with a PNS -PCT safety margin of more than 2 V. During the 6-month follow -up, PNS was detected in 4 patients and was eliminated with reprogramming. No significant changes in PCT were detected during follow -up., Conclusions: Quadripolar leads allowed nonapical pacing with acceptable electrical parameters in the majority of CRT recipients, although differences were found among the currently available devices.

Aims: Dolichocarotids(DCs) represent a rare(2-6%) carotid imaging finding in the general population that may be free of clinical significance or be associated with cerebrovascular events. Their detection is traditionally assigned to carotid echo-color Doppler(ECD) and selective angiography(the standard method). The primary aim of this study was to estimate the sensitivity, specificity and accuracy of ECD in detecting DCs. Moreover, we monitored the DC curvature angle and the incidence of TIA, ischemic stroke, myocardial infarction and cardiovascular death over a five-year followup period., Methods: A total of 112 consecutive patients with DCs(80 men, mean age: 61±7 years) were recruited for carotid ECD and carotid angiography due to the persistence of neurological symptoms not well explained on ultrasound evaluations, according to the current guidelines., Results: ECD proved to have 100% sensitivity in detecting tortuosity and coiling and 96% sensitivity in detecting kinking, with an overall accuracy ranging from 92% to 100%. The specificity was 75% for tortuosity, 91% for kinking and 100% for coiling. During the five-year follow-up period, there was a statistically significant increase in tortuosity(61±11° at baseline versus 81±11° after five years, p＜0.001) and the kinking curvature angle(97±3° at baseline versus 100±3° at five years, p＜0.001), whilst no differences were observed with respect to coiling(136±10° at baseline versus 138±11° at five years, p=ns). Moreover, kinking was found to be more frequently statistically associated with cardiovascular death than tortuosity(p=0.005)., Conclusions: DCs predispose patients to potentially disabling and fatal events. ECD plays a primary role in the detection of DCs and therefore should be considered to be a secure and reproducible technique.

Obstructive sleep apnea syndrome (OSAS) in children can induce endothelial dysfunction, a well-known early marker of atherosclerosis. The study aimed to evaluate a link among endothelial function (measured by flow-mediated vasodilation (FMD)), obesity (evaluated by body mass index (BMI)), and sleep disordered breathing (SDB), assessed with apnoea/hypopnoea index (AHI), in a paediatric population. We demonstrated that our little OSAS patients showed an impaired endothelial function as compared to controls. In particular, the higher the AHI, the worst the FMD values and thus the endothelial function. Although the population sample is small, this study demonstrated that OSAS could impair endothelial function and worsen cardiovascular risk profile since childhood.

Background: Endothelial dysfunction has been already reported in inflammatory bowel diseases (IBD). However, case series so far examined were rather heterogeneous as for disease severity and subsets investigated., Objective: We evaluated endothelial dysfunction by brachial artery flow-mediated vasodilatation (FMD), and subclinical atherosclerosis by assessment of common carotid intima-media thickness (CCA-IMT) in a cohort of patients with Crohn's disease (CD) or Ulcerative colitis (UC) in active phase compared to healthy control subjects., Methods: Forty-nine patients (mean age 41±16 years), 25 with CD and 23 with UC, and forty controls (mean age 45±15 years) were enrolled. Diagnosis was based on the standard clinical, endoscopic and histological criteria. Disease activity was assessed by Crohn's Disease Activity Index or Disease Activity Index. All patients, were under medical treatment as appropriate., Results: FMD values were lower in IBD patients than controls (6.1±3.0 vs 8.2±3.4. p=0.003); no difference was seen between UC/CD groups (5.9±3.5 vs 6.3±2.6, p=0.67). No changes in statistical differences occurred after adjustment for age, gender, body mass index and family history of cardiovascular disease. Finally, no differences in IMT values were seen between IBD patients and controls. Disease duration and medical treatment did not affect endothelial function., Conclusions: Our study showed a lower FMD in IBD patients. Inflammation and immune response could explain endothelial dysfunction, which is the earliest stage of atherosclerotic process. IBD patients in active phase might therefore be at higher risk for atherosclerosis progression., (Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Purpose: According to the literature, estradiol has a direct vasodilator action by means of endothelium-derived relaxing factor synthesis. The present study aims to evaluate the acute hemodynamic effects of intranasal 17-β-estradiol on cerebral and lower limb arterial circulation in postmenopausal women., Methods: Sixteen healthy women in natural menopause (mean age: 54 ± 3 years) were investigated for at least 6 months, each receiving 300 µg of intranasal 17-β-estradiol. We evaluated the heart rate, systolic/diastolic blood pressure, peak systolic velocity, end-diastolic velocity, and velocity-time integral (VTI) at the level of internal carotid and posterior tibial arteries, before and after 30, 60, and 180 minutes of drug administration., Results: After intranasal 17-β-estradiol administration, the internal carotid artery VTI showed statistically significant (P < .05) variations at all the time intervals after administration of the drug (30, 60, and 180 minutes) when compared with "time zero" (T0, ie, the speed recorded at baseline before drug administration). No significant variation was found at the posterior tibial artery. The systolic/diastolic blood pressure and heart rate did not significantly differ before and after drug administration., Conclusions: The administration of a single intranasal dose of 17-β-estradiol in healthy postmenopausal women increased cerebral perfusions, whereas the effect on peripheral circulation was much more limited.

Introduction: Previous studies support the fact that extracorporeal shockwave (SW) induces angiogenesis and improves symptoms in patients affected by limb ischemia. The aim of this study was to evaluate the effects of SW therapy in patients with peripheral artery disease (PAD)., Methods: Twenty-two patients were enrolled in this study and were randomly assigned into two groups: SW treatment (12 patients, 67 ± 9 years) and control (10 patients, 68 ± 12 years). The inclusion criteria were the following: age over 40 years, PAD diagnosis, optimal medical therapy, and ankle-brachial index less than 0.9. SW therapy was administered using the Minilith® SL1 litotriptor with an ultrasound guide able to detect the target area using a B-mode technique and a 7.5 MHz convex probe emitting 2,000 impulses with an energy flux density of 0.03 mJ/mm(2)., Results: The variation in the degree of stenosis before and after treatment was statistically significant between the groups (-9% ± -10% vs. 0% ± 0%; P = 0.001). In addition, a significantly higher number of treated patients than controls showed a reduction in the Fontaine stage (12 [63%] vs. 0 [0%]; P < 0.001). This result was confirmed by analyzing the difference in patients' pain-free walking distance before and after SW therapy (76 ± 46 m vs. 0 ± 0 m for treated patients vs. controls; P < 0.001) and the difference in pain severity (measured on a pain scale; -1.4 ± 0.5 in the treated patients vs. -0.2 ± 0.4 in the controls; P < 0.001)., Conclusion: On the basis of these results the authors hypothesized a direct effect of SW on the ultrastructural composition of the vessel walls, inducing a reduction in artery stenosis. These data support the application of SW therapy as a new medical tool to improve the natural clinical course of PAD.

Aims: Patients at risk of sudden cardiac death (SCD) after myocardial infarction (MI) can be offered therapy with implantable cardioverter defibrillators (ICDs). Whether plasma biomarkers can help risk stratify for SCD and ventricular arrhythmias (VT/VF) is unclear., Methods and Results: The primary objective of the CAMI-GUIDE study is to assess the predictive role of C-reactive protein for SCD or VT/VF in ischaemic patients with the ejection fraction <30% and ICDs. Secondary endpoints included all-cause mortality, hospitalizations, and death from heart failure. Additional analyses incorporated cystatin-C and NT-ProBNP in multi-marker approach for the prediction of adverse outcomes. A total of 300 patients were enrolled. All-cause mortality at 2 years was 22.6%, mortality from heart failure was 8.3%. Primary endpoint occurred in 17.3%. At a competing risk multivariable analysis adjusted for baseline variables, no significant difference in primary endpoint was found between patients with C-reactive protein ≤3 vs. >3 mg/L [heart rate (HR) 0.91 (0.50-1.64) P = 0.76], while C-reactive protein >3 mg/L was strongly associated with mortality due to heart failure [HR: 3.17 (1.54-6.54) P = 0.002]. NT-proBNP above median was significantly associated with the primary endpoint [adjusted HR: 1.46 (1.020-2.129) P = 0.042]. A risk function, including the three biomarkers, NYHA class and resting HR, allowed stratification of patient mortality risk from 5 to 50%., Conclusion: C-reactive protein >3 mg/L is not associated with SCD or fast VT/VF, however, is a strong predictor of HF mortality. Biomarkers combined with clinical markers allow an excellent risk stratification of mortality at 2 years.

Venous echo-color-Doppler (ECD) showed that chronic cerebrospinal venous insufficiency (CCSVI) syndrome is related to multiple sclerosis (MS). Study aims were to assess interobserver variability in ultrasound evaluation of MS patients and to relate echo-markers to MS clinical symptoms and the disability degree. 277 MS patients (117 men, mean age 43.05+10.04 years) admitted to the Neurology Department of Bari University General Hospital, underwent clinical, Expanded Disability Status Scale (EDSS) evaluation, and a cerebro-venous system ECD evaluation. Two operators reevaluated 32 patients to calculate interobserver variability. McNemar test confirmed the procedure reproducibility between two operators (p=ns). Septa/membranes correlated with deep cerebral veins reflux [right: 16% absence vs. 58% presence, p < 0.0001; left: 26% vs. 50%, p < 0.0001]; their absence in Primary Progressive (PP) MS form [right: 11% vs. 2%, p < 0.001; left: 12% vs. 2%, p < 0.001]. Internal jugular veins (IJVs) reflux absence was in Relapsing-remitting (RR) form [right: 60% vs. 74%, p=0.036; left: 56% vs. 85%, p < 0.0001] like hemodynamically significant stenosis [right: 57% vs. 69%, p=0.033; left: 49% vs. 73%, p < 0.001] not present in PP [right: 11% vs. 2%, p < 0.001; left: 10% vs. 3%, p=0.009]. A supine IJVs blocked flow was related to the EDSS class [right: 4.8±1.5 vs. 5.4±1.4, p=0.006; left: 4.7±1.6 vs. 5.5±1.2, p < 0.0001]; its absence was linked to RR [right: 60% vs. 76%, p=0.016; left: 58% vs. 79%, p < 0.001]. ECD has an important value in MS patients with IJV anomalies detection and a good interobserver procedure reproducibility. MS is associated with CCSVI, although further studies are needed.

Background: Obstructive Sleep Apnea Syndrome (OSAS) is a common airways disease recognized as an independent cardiovascular risk factor. It is often associated with obesity, diabetes and dyslipidemia. Its pathophysiological consequences (hypoxia, hypercapnia, micro-arousals, sympathetic hyperactivity, oxidative stress, systemic inflammation and hyper-coagulability) are implicated in the development of hypertension, endothelial dysfunction and higher intima-media thickness (IMT) values, all elements known to lead to atherosclerosis. The study aim was to demonstrate a relationship between OSAS duration and IMT values and to confirm how OSAS severity could influence IMT (a marker of atherosclerosis)., Methods: We enrolled 156 patients (125 men, mean age: 60 ± 12 years) affected by OSAS of different severity: 111 (71%) were in CPAP therapy; some of the population were also affected by hypertension [102 (65%)], dyslipidemia [52 (33%)] and diabetes [38 (24%)]. Patients underwent evaluation of carotid artery IMT and answered a questionnaire investigating the time of onset (confirmed by a person aware of the patient's previous sleeping habits) and the duration of the disease., Results: We found a statistically significant higher IMT value in patients with longer-lasting disease (OSAS duration in IMT < 0.9 mm: 120 (60-192) months versus OSAS duration in IMT ≥ 0.9 mm: 200 (120-310) months; p < 0.001). OSAS severity is positively related to IMT values. We found a positive relationship between IMT and OSAS duration [r = 0.34; p < 0.001] and between AHI and IMT [r = 0.51; p < 0.001]., Conclusions: Our study shows that the duration of OSAS and its severity are important factor related with higher values of IMT and hence with a higher risk of atherosclerosis., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: To investigate endothelial dysfunction and morphological vascular changes in childhood obesity., Methods: 93 overweight/obese children (body mass index 26 ± 5 kg/m(2); median 26 kg/m(2); interquartile range 22-28 kg/m(2)), mean age 10.9 ± 2.7 years, underwent a check-up of total, high-density lipoprotein- and low-density lipoprotein-cholesterol, triglycerides, C-reactive protein, erythrocyte sedimentation rate, and white blood cell count, together with ultrasound measures of flow-mediated dilatation, carotid intima-media thickness, and anterior-posterior diameter of the abdominal aorta., Results: The body mass index of overweight/obese children had a statistically significant linear relationship (p < 0.05) with triglycerides, erythrocyte sedimentation rate, carotid intima-media thickness, anterior-posterior diameter of the abdominal aorta, and flow-mediated dilatation values., Conclusions: Overweight/obese children have an initial endothelial dysfunction and vascular damage, i.e., the first stage in the development of atherosclerosis.

Background and Aim: To establish, using echocardiography, color-flow Doppler and tissue doppler imaging (TDI), physiological values of systolic/diastolic indexes in healthy term/pre-term newborns, and to identify how different degrees of maturity influence morpho-functional cardiac alterations during the transitional period., Study Design and Subjects: 33 term newborns (M = 19, F = 14; gestational ages: 37th-41st week), and 20 pre-term infants (M = 11, F = 9; gestational ages: 31st-36th week) admitted to our department were studied. All infants underwent to clinical and Doppler ultrasound evaluations, carried out by the third to fourth day. Investigations included: M-mode echocardiography, color-flow Doppler and TDI., Outcome Measures and Results: Term and preterm neonates differed for: interventricular septum and left systolic/diastolic ventricle diameters (p<0.01 and <0.05 respectively); left ventricle posterior wall in systole (p<0.01); shortening and ejection fraction (p<0.05). Color-flow Doppler parameters on the tricuspid (peak E, peak A, ratio E/A; p<0.05) and on the mitral (peak E and E/A ratio; p<0.01) significantly differed between the two groups. Significant differences were also present for basal left ventricular lateral wall and right ventricular lateral wall in the Ew (p<0.01 and <0.05 respectively), Sw peak (p<0.01 and <0.05 respectively), and Ew/Aw (p<0.05). The isovolumetric relax time and the E/Ew measured on the medial mitral annulus also demonstrated significant differences (p<0.01) between the two groups., Conclusions: TDI is feasible in preterm neonates and enables assessment of myocardial velocities. With increasing gestational age, higher myocardial velocities and lower E/E' Œ ratios were found. TDI addition to standard neonatal echocardiography may provide further important information about cardiac function., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: There is a close link between heart failure and endothelial dysfunction. Brachial flow-mediated dilation (FMD) is a validated non-invasive measure of endothelial function. The aim of this study was to investigate the clinical correlates of FMD in patients with chronic heart failure (CHF)., Design, Setting, Patients: We evaluated 60 CHF outpatients (age 62 ± 14 years; 49 males, NYHA class 2.2 ± 0.7, left ventricular ejection fraction, LVEF, 33 ± 8%) taking conventional medical therapy (ACE-inhibitors and/or ARBs 93%, beta-blockers 95%) and in stable clinical conditions., Main Outcome Measures: The maximum recovery value of FMD was calculated as the ratio of the change in diameter (maximum-baseline) over the baseline value., Results: As compared with patients with a higher FMD, those with FMD below the median value (4.3%) were more frequently affected by ischemic cardiopathy (50 vs. 23%; p = 0.032) and diabetes mellitus (20 vs. 3%; p = 0.044), had a higher NYHA class (2.5 ± 0.5 vs. 1.9 ± 0.7; p < 0.001) and NT-proBNP (2,690 ± 3,690 vs. 822 ± 1,060; p = 0.001), lower glomerular filtration rate estimated by Cockcroft-Gault (GFRCG: 63 ± 28 vs. 78 ± 25; p = 0.001) and LVEF (29 ± 8 vs. 37 ± 9; p = 0.001), as well as more frequently showing a restrictive pattern (40 vs. 7%; p = 0.002). In a multivariate regression model (R (2) = 0.48; p < 0.001), FMD remained associated only with the NYHA class (p = 0.039) and diabetes mellitus (p = 0.024)., Conclusions: This study demonstrates that a better functional status and absence of diabetes mellitus are associated to higher FMD regardless of the etiology of the cardiac disease.

Introduction: Silent ischemia is an asymptomatic form of myocardial ischemia, not associated with angina or anginal equivalent symptoms, which can be demonstrated by changes in ECG, left ventricular function, myocardial perfusion, and metabolism. The aim of this study was to evaluate the prevalence of silent myocardial ischemia in a group of patients with asymptomatic carotid stenosis., Methods: A total of 37 patients with asymptomatic carotid plaques, without chest pain or dyspnea, was investigated. These patients were studied for age, sex, hypertension, diabetes, dyslipidemia, smoking, and family history of cardiac disease, and underwent technetium-99 m sestamibi myocardial stress-rest scintigraphy and echo-color Doppler examination of carotid arteries., Results: A statistically significant relationship (P=0.023) was shown between positive responders and negative responders to scintigraphy test when both were tested for degree of stenosis. This relationship is surprising in view of the small number of patients in our sample. Individuals who had a positive scintigraphy test had a mean stenosis degree of 35% ± 7% compared with a mean of 44% ± 13% for those with a negative test. Specificity of our detection was 81%, with positive and negative predictive values of 60% and 63%, respectively., Conclusion: The present study confirms that carotid atherosclerosis is associated with coronary atherosclerosis and highlights the importance of screening for ischemic heart disease in patients with asymptomatic carotid plaques, considering eventually plaque morphology (symmetry, composition, eccentricity or concentricity of the plaque, etc) for patient stratification., (© 2011 Ciccone et al, publisher and licensee Dove Medical Press Ltd.)

Purpose: Project Leonardo represented a feasibility study to evaluate the impact of a disease and care management (D&CM) model and of the introduction of "care manager" nurses, trained in this specialized role, into the primary health care system., Patients and Methods: Thirty care managers were placed into the offices of 83 general practitioners and family physicians in the Apulia Region of Italy with the purpose of creating a strong cooperative and collaborative "team" consisting of physicians, care managers, specialists, and patients. The central aim of the health team collaboration was to empower 1,160 patients living with cardiovascular disease (CVD), diabetes, heart failure, and/or at risk of cardiovascular disease (CVD risk) to take a more active role in their health. With the support of dedicated software for data collection and care management decision making, Project Leonardo implemented guidelines and recommendations for each condition aimed to improve patient health outcomes and promote appropriate resource utilization., Results: Results show that Leonardo was feasible and highly effective in increasing patient health knowledge, self-management skills, and readiness to make changes in health behaviors. Patient skill-building and ongoing monitoring by the health care team of diagnostic tests and services as well as treatment paths helped promote confidence and enhance safety of chronic patient management at home., Conclusion: Physicians, care managers, and patients showed unanimous agreement regarding the positive impact on patient health and self-management, and attributed the outcomes to the strong "partnership" between the care manager and the patient and the collaboration between the physician and the care manager. Future studies should consider the possibility of incorporating a patient empowerment model which considers the patient as the most important member of the health team and care managers as key health care collaborators able to enhance and support services to patients provided by physicians in the primary health care system.

Background: Atrial fibrillation (AF) induces loss of atrial contribution, heart rate irregularity, and fast ventricular rate., Objectives: The objectives of the study were to accurately measure AF incidence and to investigate the mutual temporal patterns of AF and heart failure (HF) in patients indicated to cardiac resynchronization therapy., Methods: Four hundred ten consecutive patients (70% male, age 69 +/- 11) with advanced HF (NYHA = 3.0 +/- 0.6), low ejection fraction (EF = 27 +/- 9%), and ventricular conduction delay (QRS = 165 +/- 29 ms) received a biventricular pacemaker. Enrolled patients were divided into two groups: G1 = 249 patients with no AF history, G2 = 161 patients with history of paroxysmal/persistent AF., Results: In a median follow-up of 13 months, AF episodes longer than 5 minutes occurred in 105 of 249 (42.2%) G1 patients and 76 of 161 (47.2%) G2 patients, while AF episodes longer than one day occurred in 14 of 249 (5.6%) G1 patients and in 36 of 161 (22.4%) G2 patients. Device diagnostics monitored daily values of patient activity, night heart rate (NHR), and heart rate variability (HRV). Comparing 30-day periods before AF onset and during persistent AF, significant (P < 0.0001) changes were observed in patient activity, which decreased from 221 +/- 13 to 162 +/- 12 minutes, and in NHR, which increased from 68 +/- 3 to 94 +/- 7 bpm. HRV significantly decreased (from 75 +/- 5 ms before AF onset to 60 +/- 6 ms after AF termination). NHR during AF was significantly (P < 0.01) and inversely correlated (R(2)= 0.73) with activity, with a significant lower activity associated with NHR >or= 88 bpm., Conclusion: AF is frequent in HF patients. Persistent AF is associated with statistically significant decrease in patient activity and HRV and NHR increase.

Objective: Cardiac resynchronisation therapy has proven to be effective in refractory heart failure (HF) patients with QRS >120-130 ms. Therefore, the aim of our study was to verify the long-term effectiveness of cardiac resynchronisation therapy in HF patients with echocardiographic evidence of mechanical asynchrony regardless of QRS duration., Methods: One hundred and six patients with New York Heart Association class II-IV HF and echocardiographic documentation of interventricular and intraventricular asynchrony underwent biventricular stimulation. A clinical and functional evaluation was performed at baseline, 1, 3, 6 months, and every 6 months thereafter., Results: After a median follow-up of 16 months, a significant improvement was noted in ejection fraction, left ventricular diameters, mitral regurgitation jet area, interventricular and intraventricular echocardiographic indexes of asynchrony, and the 6-min walking distance (P < 0.001 for all). Death rates for all causes and for cardiac causes were 18.2 (95% confidence interval 12.8-25.9) and 13.5 (95% confidence interval 9.0-20.3) per 100 person-years, respectively. Patients in New York Heart Association class IV had an almost three-fold increase in risk of dying as compared to class II-III (hazard ratio 2.97, 95% confidence interval 1.30-6.79)., Conclusions: Interventricular and intraventricular asynchrony at echocardiography may be useful in identifying HF patients suitable for cardiac resynchronisation therapy, with results comparable to those obtained with QRS duration selection criteria.

Aim: Gender related differences in epidemiology, treatment, and prognosis of heart failure (HF) have been reported. We examined the sex influence in patients treated with cardiac resynchronization therapy (CRT)., Methods and Results: Out of 334 consecutive HF patients (19.7% women) who underwent CRT, 195 patients reached clinical and echocardiographic evaluation at six and 12 months and were selected for analysis. A reduction in left ventricular (LV) end-diastolic volume/m(2) (EDVi) and end systolic volume/m(2) (ESVi) was evident in the overall population at six months (P < 0.001) and from six to 12 months (P < 0.001). Compared to men, women showed significantly greater changes in LV volumes at mid (P < 0.05) and long-term (P < 0.001) follow-up and a significantly higher LV ejection fraction (EF) (40.8 +/- 12.3 vs 34.1 +/- 10.1, P < 0.01) at one year. Multiple regression analysis, including several demographic and clinical parameters, revealed that female gender is independently associated with greater reduction in LV ESVi. At the 12-month follow-up, the proportion of responders (defined in terms of ESV reduction by at least 10%) was higher in women than in men (76.1% vs 59.3%, P < 0.05)., Conclusions: CRT induced a gender specific LV remodeling response.

Objective: To prospectively determine whether prespecified electrocardiographic, echocardiographic and tissue Doppler imaging (TDI) selection criteria may predict a positive response to cardiac resynchronisation therapy (CRT)., Methods: In this multicentre, prospective, non-randomised study, 96 heart failure patients with New York Heart Association class III-IV symptoms, an ejection fraction of < or =35%, and at least one marker of ventricular dyssynchrony according to prespecified electrocardiographic, echocardiographic or TDI criteria were enrolled. The primary endpoint was an improvement in the clinical composite score at 6 months., Results: At enrolment, 70 patients fulfilled the electrocardiographic criterion (QRS duration > or =150 ms), 77 patients showed echocardiographic signs of dyssynchrony, and 37 patients met the TDI dyssynchrony criteria. The overall responder rate was 78/96 (81%). In particular, the primary endpoint was reached in 68 patients who fulfilled the echocardiographic criteria as compared with 10 patients who did not (88 vs. 53%, P = 0.001). The patients who met the echocardiographic criteria showed a significant greater reduction in left ventricular end-systolic diameter (P = 0.029) and a higher improvement in quality of life (P = 0.017) than patients who did not. Neither electrocardiographic nor TDI criteria seemed to predict a positive response to CRT., Conclusions: In our patient population, mechanical indexes of dyssynchrony as assessed by echocardiography appeared to identify CRT responders. Although TDI is useful for evaluating ventricular dyssynchrony after CRT, the prespecified TDI inclusion criteria adopted in this investigation did not increase the number of CRT responders.

Aims: To assess the effects of cardiac resynchronization therapy (CRT) in > or =80-year-old patients vs. patients <80 years, in terms of clinical, functional, and echocardiographic parameters after 12 month of CRT, survival, and incidence of arrhythmic events., Methods and Results: The study population consisted of 1181 CRT patients (85 were > or =80 years old). They were enrolled in a national observational registry and underwent baseline evaluation and periodical follow-up visits. In the overall population, New York Heart Association class and ejection fraction (EF) improved and ventricular diameters decreased. Similar changes were observed in the two groups. In the study population, 157 patients died, 144 (13%) in the <80 years group and 13 (15%) in the > or =80 years group. There was a higher all-cause mortality (log-rank test, P = 0.015) among > or =80 years patients, with a trend towards higher sudden cardiac death (SCD) (P = 0.057), but similar non-SCD (P = 0.293). Using the combined endpoint of SCD or appropriate shock from a defibrillator for ventricular fibrillation, no significant differences resulted between groups (P = 0.455). In both groups, lower EF was associated with higher mortality., Conclusion: Cardiac resynchronization therapy demonstrated similar efficacy in patients aged > or =80 years and in those under 80, in terms of clinical and functional parameters and reverse remodelling. Similarly, CRT resulted in comparable effects on death for heart failure and on SCD.

Background: Patients at risk of sudden cardiac death (SCD) after myocardial infarction (MI) can currently be offered effective means of prevention, such as implantable cardioverter-defibrillators (ICD). However, predictors of SCD able to identify those patients who are at higher risk are still lacking. Whether C-reactive protein (CRP), a serum inflammatory marker with established prognostic accuracy after MI, can also be a predictor of SCD is unclear., Methods: The CAMI GUIDE study is designed to evaluate the prognostic role of CRP in patients undergoing ICD implantation after MI according to MADIT II criteria (i.e. left ventricular ejection fraction

Background: The aim of this study was to evaluate the ability of baseline clinical and echocardiographic parameters to predict a positive response to CRT., Methods: We analyzed 6-month data from the first 133 consecutive patients enrolled in a multicenter prospective study. These patients had symptomatic heart failure (HF) refractory to pharmacological therapy (NYHA class II-IV), left ventricular ejection fraction (LVEF) < or =35%, and prespecified electrocardiographic, echocardiographic or tissue Doppler imaging markers of left ventricular (LV) dyssynchrony., Results: After a follow-up period of 6 months, 1 patient died and 13 were hospitalized for worsening HF. There were significant (P < 0.01) clinical, functional, and echocardiographic improvements that included: New York heart Association Class, Quality-of-Life Score, QRS duration, LVEF, LV end-diastolic and end-systolic diameter (LVESD), and severity of mitral regurgitation A positive response was documented in 90/133 (68%) patients who presented an improved clinical composite score associated to an increase in LVEF > or = 5 units. A multivariate analysis identified that a smaller LVESD (OR = 0.957, 95% CI 0.920-0.996; P = 0.030) and longer interventricular mechanical delay (IVMD) (OR = 1.017, 95% CI 1.005-1.029, P = 0.007) as independent predictors of a positive response. Receiver-operating curve analysis showed that a positive response to CRT may be predicted in patients with IVMD > 44 ms (with a sensitivity of 66% and a specificity of 55%) or with LVESD < 60 mm (with a sensitivity of 66% and a specificity of 61%)., Conclusions: Our results confirm the limited value of QRS duration in the selection of patients for CRT. A less-advanced stage of disease and echocardiographic evidence of interventricular dyssynchrony demonstrated to predict response to CRT, while intraventricular dyssynchrony did not predict response.

Aims: Autocapture is an algorithm for automatic adaptation of ventricular output to capture threshold. The aim of this prospective study was to estimate the effects of ventricular Autocapture algorithm on DDD-DDDR pacemaker longevity., Methods and Results: Eighty-three patients implanted with a DDD-DDDR pacemaker (Affinity or Entity; St Jude Medical, USA) were enrolled and the Autocapture function was activated pre-discharge. Ventricular pulse duration was randomly programmed at 0.3 or 0.4 ms, with a cross-over at 8-12 weeks and again at 13-14 months. Diagnostic data were retrieved from device memory and by calculating battery current drain from long-term threshold recordings; device longevity was estimated at the following settings: Autocapture with a pulse duration of 0.3 and 0.4 ms, respectively, standard output (3.5 V, 0.4 ms) and conventional low output programming (2.5 V, 0.4 ms). According to a series of assumptions, Autocapture was associated with a 55-60% increase in estimated device longevity compared with standard output programming and a 6-7% increase in longevity compared with low output programming. No significant differences were found between Autocapture programmed with a pulse duration of 0.3 or 0.4 ms. In projections to a 10-year follow-up, use of the Autocapture function resulted in a 42% reduction in pacing-related estimated costs compared with standard output programming at 3.5 V, 0.4 ms., Conclusion: Pacing with constant adaptation of ventricular output in dual-chamber devices has the potential to increase generator longevity and to reduce sizeably pacing-related costs compared with standard programming.

The short-term prognosis of advanced refractory heart failure is extremely poor and closely correlated with progressive left ventricular dysfunction. The identification of the negative effects of conduction delay on cardiac performance, observed in almost 50% of heart failure patients, disclosed a new research field addressing the correction of electrical abnormalities in order to achieve an improvement in myocardial function. Biventricular stimulation, or cardiac resynchronization therapy, corrects the atrioventricular, inter- and intraventricular mechanical asynchrony and, to date, is indicated (class IIA, level of evidence A) for patients with NYHA class III-IV refractory heart failure regardless of its etiology, QRS interval > or = 130 ms, left ventricular end-diastolic diameter > or = 55 mm, and ejection fraction < or = 35%. To date, the completed trials demonstrated in patients undergoing biventricular pacing a significant improvement in left ventricular performance, quality of life and NYHA class with no significant effects on total mortality. The identification of non-responders (approximately 20-30% of the patient population in completed trials) represents an unresolved issue of cardiac resynchronization therapy. Tissue Doppler imaging evaluation of left ventricular dyssynchrony, which is being addressed by non-randomized prospective studies, should drastically decrease the percentage of these patients.

This article describes a case of cardiac resynchronization therapy (CRT) performed with dual site left ventricular pacing. The main clinical and functional long-term results are in agreement with the most recent data regarding traditional CRT. Furthermore, this innovative pacing modality allowed optimal inter- and intraventricular resynchronization.

Objectives: The aim of the study was to evaluate the effectiveness of cardiac resynchronization therapy (CRT) in patients with refractory heart failure (HF) and incomplete left bundle branch block ("narrow" QRS), together with echocardiographic evidence of interventricular and intraventricular asynchrony., Background: Cardiac resynchronization therapy has been proven effective in patients with HF and wide QRS by ameliorating contraction asynchrony., Methods: Fifty-two patients with severe HF received biventricular pacing. The patients were eligible in the presence of echocardiographic evidence of interventricular and intraventricular asynchrony, regardless of QRS duration. The patient population was divided into group 1 (n = 38), with a QRS duration >120 ms, and group 2 (n = 14), with a QRS duration < or =120 ms., Results: The baseline parameters considered in the study were similar in both groups. At follow-up, CRT determined narrowing of the QRS interval in the entire population and in group 1 (p < 0.001), whereas a small increase in QRS duration was observed in group 2 (p = NS); in all patients and within groups, we observed improvement of New York Heart Association functional class (p < 0.001 in all), left ventricular ejection fraction (p < 0.001 in all), left ventricular end-diastolic and end-systolic diameter (p < 0.05 within groups), mitral regurgitation area (p < 0.001 in all), interventricular delay (p < 0.001 in all), and deceleration time (group 1: p < 0.001, group 2: p < 0.05), with no significant difference between groups. The 6-min walking test improved in both groups (group 1: p < 0.001; group 2: p < 0.01)., Conclusions: Cardiac resynchronization therapy determined clinical and functional benefit that was similar in patients with wide or "narrow" QRS. Cardiac resynchronization therapy may be helpful in patients with echocardiographic evidence of interventricular and intraventricular asynchrony and incomplete left bundle branch block.

Background: Heart failure remains a major cause of morbidity and mortality despite advances in pharmacological treatment. Recently, multisite biventricular pacing has been used in the treatment of patients with heart failure., Objectives and Methods: The short and medium term effects of this treatment modality were assessed, and the association between baseline clinical characteristics and the positive response to treatment was investigated. Consecutive patients who received this treatment modality were included. They underwent comprehensive clinical and echocardiographic assessment including a 6 min walk at baseline, one month and three months., Results: Between January 1998 and June 1999, 95 patients received multisite biventricular pacing therapy in the three participating hospitals. In 63 patients with complete three-month follow-ups, there were improvements from baseline to three-month follow-up in New York Heart Association heart failure (3.3 +/- 0.5 to 2.2 +/- 0.6, P<0.001) and 6 min walk (305 +/- 120 to 403 +/- 113 m, P<0.001). Significant salutary changes in echocardiographic measurements were also observed in left ventricular (LV) diastolic dimension, ejection fractions (EFs), interventricular contraction delay and severity of mitral regurgitation (MR). The 63 patients were categorized into responders (n=42) and nonresponders (n=21) based on the clinical response. Clinical characteristics were similar between the two groups. The responders had a more pronounced decrease in QRS width. An increase in LVEF and a reduction in LV diastolic dimension, interventricular mechanical delay and severity of MR were observed in the responders but not in the nonresponders. Furthermore, there was a positive association between the reduction in QRS width and the increase in LVEF., Conclusions: Cardiac resynchronization by means of multisite pacing appears to be a promising therapy in the treatment of heart failure. The salutary clinical response is associated with echocardiographic improvement.

The evaluation of left ventricular ejection fraction (LVEF) may be troublesome in difficult clinical settings in patients with coronary artery disease (CAD). The aim of this study was to compare 2 simple geometrical and nongeometrical methods of LVEF evaluation that could overcome the typical technical limitations of ultrasound examination. The authors studied 26 patients with proven CAD (63+/-10 years) who underwent left ventricular (LV) catheterization and coronary angiography during the hospital stay. A complete 2D-Doppler echocardiography was performed and LVEF was evaluated with the formula by Wyatt (W-LVEF), which relates the left ventricle to a biplane ellipsoidal figure, and by the myocardial performance index (MPI) formula (MPI-LVEF), MPI being an index of systodiastolic function. Mean MPI-LVEF was 41+/-8% and was significantly lower with respect to contrast angiography (52+/-14%, p = 0.0003) and to W-LVEF (49+/-13%, p = 0.0009). There was no statistically significant correlation between MPI-LVEF and geometric (either angiographic or ultrasound) LVEF. Bland-Altman analysis showed lack of agreement between MPI-LVEF and any other method evaluated in the study. MPI-LVEF may not be reliable and accurate for the evaluation of systolic function in patients with CAD. Nonetheless, the evaluation of global LV function by means of MPI may represent a valuable and affordable alternative to expensive and time-consuming methods, especially in the presence of difficult technical settings.

Background: During the last decade single lead VDD pacing has been progressively affirmed as an electrotherapy of choice in patients with advanced atrioventricular block without alterations of the sinus function. It combines the benefits of P-synchronous ventricular pacing with an easy implant procedure when compared to the conventional DDD approach. The aim of this study was to evaluate the validity of such an approach in a large population of patients, all implanted in a single center., Methods: From 1987 up to now, 317 patients, all affected by advanced atrioventricular block and without sinus node dysfunction, were implanted in our center with a single lead VDD pacemaker. During follow-up the persistence of a proper atrioventricular synchronization was assessed and evaluated., Results: The mean follow-up was 3.9 +/- 2.7 years/patient (range 6-138 months). The 94.6% of implanted systems maintained the normal VDD pacing function. Permanent reprogramming in VVI mode was necessary in 17 patients (5.36%); in 12 (3.78%) because of chronic atrial fibrillation and in 5 (1.63%) for loss of atrial sensing. The percentage of atrial synchronization was optimal (> 98%) and acceptable (> 95%) in 81% and 19% of patients, respectively. Episodes of paroxysmal atrial fibrillation occurred in 3 patients. Neither inhibition by myopotentials nor occurrence of sinus node disease was observed during follow-up. These results are in accordance with those reported by previous studies, performed on a smaller population or on a multicenter basis, and are comparable with the results reported for conventional DDD pacemaker., Conclusions: Our results confirm the high reliability of the single lead VDD pacing system concerning the long-term persistence of a proper atrioventricular synchronization. Data showed above enforce our opinion that this pacing approach should be considered the treatment of choice in patients with advanced atrioventricular block and preserved sinus node function.

Background: The issue of DDD pacing as a therapeutic option for patients with obstructive hypertrophic cardiomyopathy is still under debate. Moreover, some authors stress the concept of the placebo effect of electrical therapy in this particular setting., Methods: We retrospectively evaluated 8 symptomatic patients with obstructive hypertrophic cardiomyopathy despite medical therapy, who underwent DDD pacemaker implantation as an adjunctive therapeutic strategy. All patients were evaluated with a two-dimensional/Doppler echocardiogram at baseline, shortly after the beginning of DDD pacing and at follow-up. In 3 patients dobutamine stimulation was necessary to elicit the intraventricular gradient., Results: At follow-up (21 +/- 19 months, range 1-54 months) the peak gradient declined from 86 +/- 27 to 34 +/- 27 mmHg (55.2%). In 4 patients the peak gradient sharply declined after pacemaker implantation with active pacing and remained stable throughout the follow-up. In 2 patients we noted a continuous reduction in the peak gradient during the follow-up, while in 2 patients it returned to baseline values after 1 year and 1 month, respectively, despite an early reduction with DDD pacing. All patients experienced symptomatic amelioration throughout the follow-up. Two patients developed angina at the end of our observation together with an increase in the peak gradient., Conclusions: We believe that DDD pacing may be considered as a practical therapeutic option for patients with obstructive hypertrophic cardiomyopathy who would otherwise be regarded as candidates for surgery.

The authors describe 3 cases of AMI occurring shortly after a negative bicycle ergometer stress test. These cases represent an unfortunate but extremely rare complication of a relatively safe diagnostic procedure. The authors also focus on the pathogenesis of the ischemic event, which may be attributed either to intraplaque hemorrhage or to platelet aggregation, both exercise-induced. The prevalence of AMI in this paper (0.06%) is similar to the data described in literature.