Evolving cardiovascular uses of direct-acting oral anticoagulants: a paradigm shift on the horizon?

Direct-acting oral anticoagulants (DOACs), by virtue of pharmacological properties perceived as innovative, are changing the therapeutic scenario of patients requiring short- and long-term anticoagulation. The evidence gathered so far (from pre-approval pivotal trials to real-world post-marketing observational data) consistently confirms that DOACs are overall comparable to vitamin-K antagonists (VKAs) in terms of safety, efficacy, effectiveness and unequivocally documents a clinically relevant reduced risk of intracranial bleeding in the settings of non-valvular atrial fibrillation (AF) and venous thromboembolism. The following issues are attracting considerable clinical interest: (a) identifying specific subpopulations of patients with AF most likely to benefit from one of these agents (the so-called tailored therapy), and (b) expanding therapeutic indications in emerging diseases characterized by arterial and venous thromboembolic risk. In these scenarios, the risk-benefit profile of DOACs, as compared to VKAs or heparins, is still incompletely characterized. In cardiology, the challenging task of selecting a suitable or even the most appropriate DOAC for patients with AF and a particular phenotype prompted experts to provide suggestions based on careful review of subgroups of patients from pivotal RCTs. However, in the past few months, variegated multicenter trials have been published (RE-CIRCUIT, PIONEER-AF-PCI, GEMINI-ACS-1), with potential influence on clinical practice. Therefore, this review aims to update the latest evidence on the evolving therapeutic uses of DOACs in the cardiovascular area, addressing potential impact for clinicians.

Long term follow-up of "full metal jacket" of de novo coronary lesions with new generation Zotarolimus-eluting stents.

BACKGROUND: Diffuse coronary artery disease treatment still remains a challenge for interventional cardiologists and cardiac surgeons. There are few data on full metal jacket (FMJ) stenting, especially with new-generation drug-eluting stents. We aimed to assess the efficacy and safety of FMJ with new-generation Zotarolimus-eluting stents (n-ZES). METHODS AND RESULTS: All patients who underwent FMJ with n-ZES (≥60mm stent length) in eleven Italian interventional centers participating in the Clinical Service® project were included in this analysis. The project population consisted of 120 patients and 122 lesions. Mean age was 67±10years and 95 (79.2%) patients were male. A chronic total occlusion was present in 34 lesions (27.9%). The number of stents implanted per lesion was 2.9±0.8, and the diameter of the stents was 3.0±0.5mm. Predilation and post-dilatation were performed in 107 (87.7%) and 92 (75.4%) patients, respectively. At 41±21month follow-up there were 2 patients with subacute definite stent thrombosis, 6 patients (5.0%) had cardiac death and 5 patients (4.2%) had non-fatal myocardial infarction. Seven patients (5.8%) underwent clinically-driven target lesion revascularization. Fourteen patients (11.7%) had at least one major adverse cardiac event. CONCLUSION: The treatment of diffuse coronary artery disease with FMJ stenting with n-ZES appears to be effective and safe. Late and very-late ST does not seem to be an issue and the rate of restenosis and of major cardiac adverse events after more than 3-year follow-up is rather low.

Prospective multicentre clinical performance evaluation of second and third generation zotarolimus-eluting stents to treat patients with bifurcated coronary lesions.

AIM: To assess the "real world" clinical outcome of patients with bifurcated lesions undergoing percutaneous coronary intervention with implantation of second and third generations of zotarolimus-eluting stent. METHODS AND RESULTS: Nine Italian centres participated in a prospective multicentre clinical project evaluating the outcome of patients receiving zotarolimus-eluting Resolute stent and Resolute Integrity stents. Patients with bifurcated lesions entered this evaluation. Clinical characteristics and angiographic and procedural details were prospectively recorded. Clinical outcome was prospectively assessed to evaluate the occurrence of major adverse cardiac events (MACE). A total of 577 patients were enrolled. The target lesion was distal left main in 11.1% and left anterior descending artery in 52.8%, and 30.3% of lesions were Medina 1,1,1. At a mean follow-up time of 27.0 ± 13.5 months, the survival free from MACE was 91.8%. Survival free from MACE was similar in patients grouped according to different bifurcated lesion complexity. On the contrary, patients receiving a single stent had better survival free from MACE as compared with those with double stent (P = 0.005). At multivariable analysis, double stenting (but not bifurcated lesion complexity) was found to be a significant predictor of MACE (hazard ratio, 2.52; 95% confidence interval, 1.28-4.94; P = 0.007). Of note, patients receiving the second stent as a bail-out had worse survival free from MACE compared with those who received it as a planned technique (P = 0.045). CONCLUSION: The treatment of patients with bifurcated lesions with second and third generation zotarolimus-eluting stents is associated with good long-term clinical outcomes. Clinical outcome seems to be independent of lesion complexity, but may be influenced by the stenting technique (single or double stenting as well as elective or bail-out double stenting). © 2015 Wiley Periodicals, Inc.

[Major epidemiological changes and clinical variables in patients undergoing a program of heart rehabilitation after cardiac surgery - MEPHISTOPHELES]. / Major epidemiological changes and clinical variables in patients undergoing a program of heart rehabilitation after cardiac surgery - MEPHISTOPHELES.

BACKGROUND: Recent observational studies show an increase of more complex and critically ill patients referred to Italian cardiac rehabilitation (CR) departments; the exact mechanisms underlying this phenomenon, however, have not been clearly identified. The aim of our study was to evaluate the epidemiological and clinical changes that occurred over the last decade in patients hospitalized in CR departments with high admittance rates. METHODS: We have retrospectively evaluated all patients admitted between 2002 and 2009 to our division of CR (n = 3340, 1155 female, mean age 66.4 ± 11 years) after recent cardiac surgery. The study population was divided into two homogeneous groups: the four-year period 2002-2005, group A (n = 1614, 540 female, mean age 66.1 ± 10 years) and the four-year period 2006-2009, group B (n = 1726, 615 female, mean age 67.4 ± 11 years). Data were compared using specific indicators of clinical complexity. RESULTS: Patients aged >75 years were more in group B compared to A (26.3 vs 19.8%, p<0.0001), as well as patients with recent complex surgical interventions, such as combined coronary artery bypass grafting and heart valve surgery (16.4 vs 10.2%, p<0.0001). An increased incidence of cardiovascular death (1.4 vs 0.6%, p=0.02), acute coronary syndrome (1.5 vs 0.7%, p=0.02) and persistent atrial fibrillation/flutter (13.5 vs 7.1%, p<0.0001) was observed in group B, as well as an increased prevalence of systolic heart failure (18.3 vs 9.0%, p<0.0001). Similarly, the incidence of acute respiratory failure episodes (1.0 vs 0.4%, p=0.05), the prevalence of patients admitted with a tracheostomy tube (2.6 vs 0.2%, p<0.0001) and the incidence of acute renal failure (1.1 vs 0.5%, p=0.05) were significantly increased in group B. Postoperative infections and surgical wound complications were 4-fold higher in group B (13.9 vs 3.1%, p<0.0001, and 12.8 vs 2.3%, p<0.0001, respectively). Compared to group A, patients of group B showed a significantly lower physical performance, as expressed by the Rivermead motility index (3.8 ± 1.1 vs 5.2 ± 0.8, p<0.001); moreover, the number of subjects able to perform an incremental training program was significantly lower in group B than group A (14.8 vs 60.6%, p<0.0001). Mean hospital stay was longer in group B than group A (25.4 ± 13 vs 22.1 ± 9 days, p<0.001). CONCLUSIONS: Our study, by collecting data from a CR division in northern Italy with high admittance rates, demonstrates a dramatic increase in clinical complexity over the last few years. This points to the need for new expertise and major resources to be allocated to CR departments.

Predictors for restoration of normal left ventricular function in response to cardiac resynchronization therapy measured at time of implantation.

There are no parameters predicting the individual probability of "full response" to cardiac resynchronization therapy (CRT). The aim of this work was to find prognostic factors of full clinical and echocardiographic responses (i.e., ≥50% left ventricular ejection fraction [LVEF] and New York Heart Association class I) after 1 year of CRT. This was a prospective follow-up study that involved 2 hospitals. Patients (n = 75) with advanced heart failure (64 ± 9 years of age, 87% men, LVEF 24 ± 7%) who received CRT were followed for 17 ± 9 months. Univariate and multivariate regression analyses were used to identify predictors of full CRT response. A nomogram predicting the individual probability of full CRT response during follow-up was calculated. There were 13 patients with restoration of normal LVEF versus 62 without (mean LVEF 56% ± 5% vs 31% ± 8%, respectively, p <0.001). Predictors of full response included cause of heart disease, baseline QRS width, and degree of QRS shortening in response to CRT. Patients with nonischemic heart disease, baseline QRS width ≤150 ms, and QRS shortening ≥40 ms in response to CRT had a >75% probability of restoration of normal LVEF. In conclusion, our nomogram using a combination of cause, baseline QRS width, and degree of QRS shortening in response to CRT allows assessment of individual probability of full response. This observation awaits further confirmation from larger series.

In vivo assessment of coronary stents with 64-row multidetector computed tomography: analysis of metal artifacts.

OBJECTIVE: To evaluate stent-induced artifacts by 64-row multidetector computed tomography (MDCT). METHODS: We studied 26 stented patients with MDCT before conventional coronary angiography (CCA). The CT values were measured. Stents were classified as occluded, with significant stenosis, with nonsignificant stenosis, or patent. For the patent stents, mean in-stent and out-stent CT values were compared; stents 3 mm or smaller were compared with stents larger than 3 mm. Multidetector CT was compared with CCA. RESULTS: We analyzed 42 stents. At CCA, 34 stents were patent, 5 were nonsignificantly stenosed, 1 was significantly stenosed, and 2 were occluded. At MDCT, 33 of 34 patent stents, 2 occluded stents, and 1 stent with significant stenosis were correctly diagnosed; nonsignificant stenoses were undetected, 1 patent stent was misdiagnosed as occluded (κ = 0.727). The out-stent CT value was lower than in-stent CT value both in stents 3 mm or smaller (P = 0.001) and stents larger than 3 mm (P < 0.001). The in-stent CT value of stents 3 mm or smaller was higher (P = 0.011) than that of stents larger than 3 mm. CONCLUSIONS: Metal artifacts cause overlooking of nonsignificant stenosis.

Low-risk profile for malignant ventricular arrhythmias and sudden cardiac death after surgical ventricular reconstruction.

BACKGROUND: Although it has been recently demonstrated that there was no significant difference in total survival and clinical outcomes between patients who underwent coronary artery bypass grafting (CABG) with or without surgical ventricular reconstruction (SVR), the question of whether or not SVR decreases the arrhythmic risk profile in this population has not been clarified yet. OBJECTIVE: To determine the real incidence of sudden cardiac death (SCD) and sustained ventricular tachycardia/ventricular fibrillation (sustained VT/VF) in patients following CABG added to SVR and to define their clinical and echocardiographic parameters predicting in-hospital and long-term arrhythmic events (SCD + sustained VT/VF). METHODS: Pre- and postoperative clinical and echocardiographic values as well as postoperative electrocardiogram Holter data of 65 patients (21 female, 63 ± 11 years) who underwent SVR + CABG were retrospectively evaluated. RESULTS: Mean follow-up was 1,105 ± 940 days. At 3 years, the SCD-free rate was 98% and the rate free from arrhythmic events was 88%. Multivariate logistic analysis identified a preoperative left ventricular end-systolic volume index (LVESVI) > 102 mL/m(2) (odds ratio [OR] 1.4, confidence interval [CI] 1.073-1.864, P = 0.02; sensitivity 100%, specificity 94%) and a postoperative pulmonary artery systolic pressure (PASP) > 27 mmHg (OR 2.3, CI 1.887-4.487, P = 0.01; sensitivity 100%, specificity 71%) as independent predictors of arrhythmic events. CONCLUSIONS: Our and previous studies report a low incidence of arrhythmic events in patients following SVR added to CABG, considering the high-risk profile of the study population. A preoperative LVESVI > 102 mL/m(2) and a postoperative PASP > 27 mmHg had a good sensitivity and specificity in predicting arrhythmic events.

Sex-related differences in patients undergoing percutaneous unprotected left main stenting.

AIMS: Percutaneous coronary intervention (PCI) is increasingly being used for unprotected left main (ULM) disease. Limited data are available on sex-related differences in this setting. We investigated gender-associated differences in patients undergoing stent-based PCI for ULM. METHODS AND RESULTS: We analysed baseline, procedural and long-term data of patients with ULM undergoing stent-based PCI at participating centres. The primary end-point was the long-term rate of major cardiovascular events rate (MACE, i.e., the composite of death, myocardial infarction, or target lesion revascularisation). The study population included 1,452 cases, with 27.8% females and 72.2% males. Women were older, more frequently diabetic, hypertensive or presenting with an acute coronary syndrome, and thus with a higher EuroSCORE, but were less commonly treated with drug-eluting stents (DES), in comparison to men (all p<0.01). After a median follow-up of 18 months, women showed an unadjusted higher risk of death (p=0.040), cardiac death (p=0.033), and the death/myocardial infarction (p=0.012). However, after multivariable adjustment, gender was no longer an independent predictor of death (hazard ratio=1.119 [0.804-1.558]), cardiac death (hazard ratio=1.045 [0.697-1.567]), or death/myocardial infarction (hazard ratio=0.531 [0.192-1.465]), given the predominant role of age, diabetes and EuroSCORE as independent predictors and confounders of the gender-based comparison. CONCLUSIONS: Women undergoing PCI for ULM present more often with an acute coronary syndrome, are treated less frequently with DES, and have more adverse events, but these gender biases are not confirmed after adjusting for confounders. Thus, stent-based PCI for ULM offers similarly favourable clinical results in women as well as in men.

[ST-elevation myocardial infarction: reperfusion strategy based on the results from large clinical trials]. / Strategie riperfusive nell'infarto miocardico acuto: cosa dicono i trial.

The efficacy of reperfusion therapy, both pharmacological and mechanical, in patients with ST-elevation myocardial infarction (STEMI) is time-dependent. The relation is closer the earlier we are from symptom onset and is valid for thrombolysis within 6h and for primary angioplasty till to at least the twelfth hour. Benefits of reperfusion bring to an advantage both in terms of myocardial salvage and left ventricular systolic function and in terms of quality of life and long-term survival. Although mortality and morbidity of STEMI patients have been greatly reduced in the last 20 years, the need for guideline revision and implementation remains urgent, mostly because mortality of real-world STEMI patients keeps to be always much higher compared to what reported in big randomized controlled trials. The most important indications from big trials and guidelines regarding both pharmacological and non-pharmacological reperfusion strategy in STEMI patients are discussed.

The embolic storm: dramatic peripheral complications of left ventricular thrombosis after myocardial infarction.

Left ventricular thrombus is a common complication after acute myocardial infarction. Although anticoagulant treatment has an established role in reducing the rate of thrombus formation and embolic phenomena during acute myocardial infarction, prior studies showed that left ventricular thrombus and systemic embolization may develop irrespective of adequate anticoagulant therapy. We present a descriptive case of a patient with left ventricular thrombus who experienced dramatic peripheral embolic events soon after the onset of anterior myocardial infarction despite full anticoagulation, and we discuss possible pathogenesis.

Arrhythmic risk evaluation during exercise at high altitude in healthy subjects: role of microvolt T-wave alternans.

BACKGROUND: Altitude-induced sympathetic hyperactivity can elicit rhythm disturbances in healthy subjects, in particular during exercise. AIM: To asses the real susceptibility of healthy myocardium to malignant ventricular arrhythmias during exercise at high altitude using microvolt T-wave alternans (MTWA). METHODS: We evaluated eight healthy trained participants (one female, 42 +/- 9 years) during a mountain climbing expedition on Gashembrum II (Pakistan, 8,150 m). MTWA and heart rate variability (HRV) were measured in each subject at sea level and at high altitude, both under rest conditions and during exercise. MTWA was determined with the modified moving average method. HRV was expressed as root mean square of successive differences. RESULTS: Rest HRV at high altitude was significantly lower compared to rest HRV at sea level (36 +/- 5 vs 56 +/- 9 ms, P = 0.003). HRV during exercise was significantly lower with respect to rest condition both in normoxia (46 +/- 7 vs 56 +/- 9 ms, P = 0.0001) and hypoxia (27 +/- 4 vs 36 +/- 5 ms, P = 0.005). Moreover, HRV was significantly lower during exercise at high altitude compared to exercise at sea level (27 +/- 4 vs 46 +/- 7 ms, P = 0.0002) and arrhythmias were more frequent during exercise in hypoxia. Nevertheless, MTWA was absent under rest conditions both at sea level and at high altitude and minimally evoked during exercise in both conditions (22 +/- 3 microV and 23 +/- 3 microV, respectively, P = 0.2). CONCLUSIONS: In spite of an enhanced sympathetic activity, MTWA testing during exercise at high altitude was negative in all participants. Healthy trained subjects during exercise under hypoxia seem to be at low risk for dangerous arrhythmias.

Clip-based arterial haemostasis after antegrade common femoral artery puncture.

BACKGROUND: Given the frequent involvement of infra-popliteal arteries, an ipsilateral antegrade common femoral artery puncture (ACFAP) is usually preferred to a contralateral retrograde femoral access for percutaneous transluminal angioplasty (PTA) in patients with critical limb ischemia (CLI). Because of the frequent difficulty to get a sufficient manual pressure on the puncture site, ACFAP is burdened by a high number of bleeding local complications, including retroperitoneal haematoma. We report a series of patients who consecutively received a clip-based arterial closure device after ACFAP and ipsilateral PTA for CLI. METHODS: Thirty patients (73+/-6 years; 18 men; 100% diabetes) admitted to our hospital because of CLI consecutively underwent peripheral PTA after an ACFAP and received a clip-based arterial closure device. Time to haemostasis was defined as the interval elapsed between clip deployment and first observed haemostasis. All patients were mobilized after 6 h. Follow-up was 30 days. RESULTS: All patients were on double anti-platelet therapy. At the end of the procedure, Activation Clotting Time was 226+/-37 s. Procedural success in delivering the clip was 100%. Time to haemostasis was 21+/-19 s. No major local vascular complications and in particular no retroperitoneal bleeding were documented. All patients could be discharged within the following 3 days. No major complications were noted during a 30 days follow-up. CONCLUSIONS: The use of a clip-based arterial closure device after ACFAP for peripheral PTA in CLI seems to be safe and effective.

Long-term survival in patients undergoing cardiac resynchronization therapy: the importance of performing atrio-ventricular junction ablation in patients with permanent atrial fibrillation.

AIMS: To investigate the effects of cardiac resynchronization therapy (CRT) on survival in heart failure (HF) patients with permanent atrial fibrillation (AF) and the role of atrio-ventricular junction (AVJ) ablation in these patients. METHODS AND RESULTS: Data from 1285 consecutive patients implanted with CRT devices are presented: 1042 patients were in sinus rhythm (SR) and 243 (19%) in AF. Rate control in AF was achieved by either ablating the AVJ in 118 patients (AVJ-abl) or prescribing negative chronotropic drugs (AF-Drugs). Compared with SR, patients with AF were significantly older, more likely to be non-ischaemic, with higher ejection fraction, shorter QRS duration, and less often received ICD back-up. During a median follow-up of 34 months, 170/1042 patients in SR and 39/243 in AF died (mortality: 8.4 and 8.9 per 100 person-year, respectively). Adjusted hazard ratios were similar for all-cause and cardiac mortality [0.9 (0.57-1.42), P = 0.64 and 1.00 (0.60-1.66) P = 0.99, respectively]. Among AF patients, only 11/118 AVJ-abl patients died vs. 28/125 AF-Drugs patients (mortality: 4.3 and 15.2 per 100 person-year, respectively, P < 0.001). Adjusted hazard ratios of AVJ-abl vs. AF-Drugs was 0.26 [95% confidence interval (CI) 0.09-0.73, P = 0.010] for all-cause mortality, 0.31 (95% CI 0.10-0.99, P = 0.048) for cardiac mortality, and 0.15 (95% CI 0.03-0.70, P = 0.016) for HF mortality. CONCLUSION: Patients with HF and AF treated with CRT have similar mortality compared with patients in SR. In AF, AVJ ablation in addition to CRT significantly improves overall survival compared with CRT alone, primarily by reducing HF death.

Endovascular repair of thoracic aortic disease with the EndoFit stent-graft: short and midterm results from a single center.

PURPOSE: To analyze the outcomes of endovascular treatment of thoracic aortic pathologies performed at a single center with the EndoFit thoracic stent-graft system. METHODS: From January 2002 to January 2007, 41 patients (33 men; mean age 69.3+/-9.7 years, range 48-84) were treated for thoracic aortic disease with the EndoFit stent-graft system. Patient data were retrieved from a retrospective review of hospital records. Indications for treatment were progression of aneurysm size in atherosclerotic aneurysms (n = 24, mean aneurysm diameter 7.19+/-1.48 cm), acute contained aortic rupture (n = 5), aortic dissection (n = 6), penetrating atherosclerotic ulcers (n = 4), post-traumatic pseudoaneurysm (n = 1), and post coarctation repair aneurysm (n = 1). RESULTS: The EndoFit stent-graft was successfully deployed in all 41 patients. The in-hospital and 30-day mortality rate was 7.3% (3 patients). Three (7.3%) postoperative endoleaks were recorded: a proximal type Ia and a distal Ib both resolved spontaneously at 1 and 3 months, respectively. The third patient had a persistent type Ia endoleak; conversion was necessary after 1 year. There was only 1 case of spinal ischemia, with consequent lower extremity weakness; no paraplegia was observed. During a mean 24.8-month follow-up, 2 secondary type Ia endoleaks were treated with additional stent-grafts. There were 7 (17%) deaths during follow-up. At 2 years, overall patient survival by Kaplan-Meier analysis was 70%; aneurysm-related survival was 89%. CONCLUSION: Endovascular treatment of vascular disease involving the descending thoracic aorta can be safely performed with the EndoFit thoracic stent-graft system.

Long-term outcome in diabetic heart failure patients treated with cardiac resynchronization therapy.

BACKGROUND: Diabetes mellitus is an independent risk factor for increased morbidity and mortality in heart failure (HF) patients. AIMS: To compare functional and structural improvement, as well as long-term outcome, between diabetic and non-diabetic HF patients treated with cardiac resynchronization therapy (CRT). METHODS: We compared response to CRT in 141 diabetic and 214 non-diabetic consecutive patients. Major events were; death from any cause, urgent heart transplantation and implantation of a left ventricular (LV) assist device. Frequencies of hospitalisation and defibrillator (CRT-D) discharges were also analyzed. RESULTS: CRT was able to significantly improve functional capacity, ventricular geometry and neurohumoral imbalance in both diabetic and non-diabetic patients over a median follow-up time of 34 months. Overall event-free survival was similar in diabetic and non-diabetic patients (HR 1.23, p=0.363), as was survival free from CRT-D interventions (HR 1.72; p=0.115) and hospitalisations (HR 1.12; p=0.500). On multivariable analysis, NYHA class IV (p=0.002), low LV ejection fraction (p=0.002), absence of beta-blocker therapy (p<0.001), impaired renal function (p=0.003), presence of an epicardial lead (p=0.025), but not diabetes (p=0.821) were associated with a poor outcome after CRT. CONCLUSIONS: Diabetic HF patients treated with CRT had a very favourable functional and survival outcome, which was comparable to non-diabetic patients.

Stent-graft treatment of late stenosis of the left common carotid artery following thoracic graft placement.

We report the case of a patient with subtotal occlusion of the origin of the left common carotid artery (CCA) following thoracic graft placement. Retrograde endovascular placement of a stent-graft by minimal cervical access was undertaken to repair the occlusive lesion of the left CCA and prevent future complications of endoluminal thoracic reconstruction. The retrograde endovascular repair of CCA lesions, as other authors have already suggested, may be the treatment of choice in "high-surgical-risk" patients. In these cases where the ostium of supra-aortic trunks is compromised following thoracic aorta stent-graft migration, endoluminal placement of a stent-graft in the CCA can guarantee both maintenance of carotid flow and thoracic stent-graft fixation.

Dipyridamole stress echocardiography stratifies outcomes of asymptomatic patients with recent myocardial revascularization.

BACKGROUND: Patients with previous myocardial revascularization, even if symptom-free, remain at risk of subsequent cardiac events, so that a non-invasive tool able to stratify this population is wishful. OBJECTIVES: To assess the prognostic value of dipyridamole stress echocardiography (DipSE) in a population of asymptomatic patients following complete myocardial revascularization, either by coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). METHODS: We retrospectively evaluated 104 consecutive symptom-free patients (mean age 67+/-9.3 years, 75 males) with recent (<12 months) complete myocardial revascularization (48% PCI, 52% CABG) undergoing DipSE. Ischemia was defined as the onset of a new or worsening wall motion abnormality during DipSE. The composite end point of the study was cardiac death and non-fatal acute coronary syndrome. RESULTS: Myocardial ischemia was identified in 23 patients (22.1%). During a mean follow up of 21 months, 7 (30.4%) out of these patients suffered cardiac events. Among the remaining 81 patients (77.9%) with negative DipSE results, 7 (8.6%) experienced cardiac events. At multivariable analysis only a positive DipSE (odds ratio 3.9, P=0.03), wall motion score index at peak of stress (OR 3.6, P=0.04) and a prior myocardial infarction (odds ratio 3.5, P=0.04) achieved statistical significance for cardiac events. Moreover, DipSE effectively stratified patients into a high and low risk group according to presence of inducible ischemia (event rate per year 16% vs 4.8%, P=0.02). CONCLUSIONS: DipSE yields appropriate risk stratification and provides incremental prognostic value over clinical variables even in asymptomatic patients with prior complete myocardial revascularization. A negative DipSE portends a benign prognosis (<5% event rate/year) in such population.

Activity monitoring in heart failure patients with cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves functional capacity in heart failure patients. This study aimed to prospectively analyze long-term device-based monitoring of physical activity in patients undergoing CRT. METHODS AND RESULTS: The Activity Log Index (ALI), calculated by CRT devices, represents the percentage of time when acceleration exceeds a threshold and monitors the physical activity. Data from 178 CRT patients (New York Heart Association III 91%, left ventricular ejection fraction 21+/-6%, left ventricular end-diastolic diameter 69+/-9 mm, QRS 159+/-27 ms, sinus rhythm 81%) were retrieved. The ALI increased from a baseline value of 3.6+/-2.0 to 11.2+/-4.6 (p<0.005) 104 weeks after initiation of CRT. A plateau was reached at approximately 12 weeks and thereafter ALI remained stable for up to 2 years. The magnitude of the changes in ALI was similar in patients with different etiologies and underlying rhythms. Despite similar values at baseline, elderly patients (>or=65 years) exhibited significantly lower ALI values than younger patients during the follow-up and at the plateau (9.5+/-4.2 vs 13.3+/-4.8, p<0.001). CONCLUSIONS: Device-based monitoring of physical activity in CRT patients is feasible. CRT resulted in a large and long-term increase in physical activity.

Long-term survival of patients with heart failure and ventricular conduction delay treated with cardiac resynchronization therapy.

This multicenter longitudinal observational trial was designed to analyze the long-term outcome of patients with heart failure (HF) treated with cardiac resynchronization therapy (CRT) alone or with implantable cardioverter-defibrillator (ICD) backup in a daily practice scenario. It is unknown whether the magnitude of survival benefits conferred by CRT in a daily practice scenario is comparable to what has been observed in randomized controlled trials and whether this benefit is sustained over the long term. The outcome of 1,303 consecutive patients with ischemic or nonischemic cardiomyopathy on optimal pharmacologic therapy treated from August 1, 1995 to August 1, 2004 at 4 European centers with CRT alone (44%) or with ICD backup for symptomatic HF and prolonged QRS duration was assessed. Cumulative event-free survival was evaluated for a combined end point, defined as death from any cause, urgent transplantation, or implantation of a left ventricular assist device. The cumulative incidence of competing events, HF, sudden cardiac death, and noncardiac death, was also assessed. Event-free survival was similar across the different centers. At 1 and 5 years, cumulative event-free survivals were 92% (95% confidence interval [CI] 91 to 94) and 56% (95% CI 48 to 64), respectively. The cumulative incidence of HF deaths was 25.1% (95% CI 19 to 31.7), whereas that of sudden death was 9.5% (95% CI 5.1 to 15.7). Using multivariate analysis, CRT with an ICD backup was associated with a nonsignificant decrease in mortality by 20% (hazard ratio 0.83, 95% CI 0.58 to 1.17, p = 0.284), with a highly significant protective effect against sudden cardiac death (hazard ratio 0.04, 95% CI 0.04 to 0.28, p <0.002). In conclusion, patients with advanced HF and a wide QRS complex routinely treated with CRT have a favorable long-term outcome that was reproducible at different centers. The leading cause of death in these patients remained HF, and this mode of death was competing with other causes in determining outcome. Total mortality was 20% lower with ICD backup (95% CI 42% lower to 17% higher) due to a protective effect against sudden cardiac death.