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1.  Atrial antitachycardia pacing and managed ventricular pacing in bradycardia patients with paroxysmal or persistent atrial tachyarrhythmias: the MINERVA randomized multicentre international trial 
European Heart Journal  2014;35(35):2352-2362.
Atrial fibrillation (AF) is a common comorbidity in bradycardia patients. Advanced pacemakers feature atrial preventive pacing and atrial antitachycardia pacing (DDDRP) and managed ventricular pacing (MVP), which minimizes unnecessary right ventricular pacing. We evaluated whether DDDRP and MVP might reduce mortality, morbidity, or progression to permanent AF when compared with standard dual-chamber pacing (Control DDDR).
Methods and results
In a randomized, parallel, single-blind, multi-centre trial we enrolled 1300 patients with bradycardia and previous atrial tachyarrhythmias, in whom a DDDRP pacemaker had recently been implanted. History of permanent AF and third-degree atrioventricular block were exclusion criteria. After a 1-month run-in period, 1166 eligible patients, aged 74 ± 9 years, 50% females, were randomized to Control DDDR, DDDRP + MVP, or MVP. Analysis was intention-to-treat.
The primary outcome, i.e. the 2-year incidence of a combined endpoint composed of death, cardiovascular hospitalizations, or permanent AF, occurred in 102/385 (26.5%) Control DDDR patients, in 76/383 (19.8%) DDDRP + MVP patients [hazard ratio (HR) = 0.74, 95% confidence interval 0.55–0.99, P = 0.04 vs. Control DDDR] and in 85/398 (21.4%) MVP patients (HR = 0.89, 95% confidence interval 0.77–1.03, P = 0.125 vs. Control DDDR). When compared with Control DDDR, DDDRP + MVP reduced the risk for AF longer than 1 day (HR = 0.66, 95% CI 0.52–0.85, P < 0.001), AF longer than 7 days (HR = 0.52, 95% CI 0.36–0.73, P < 0.001), and permanent AF (HR = 0.39, 95% CI 0.21–0.75, P = 0.004).
In patients with bradycardia and atrial tachyarrhythmias, DDDRP + MVP is superior to standard dual-chamber pacing. The primary endpoint was significantly lowered through the reduction of the progression of atrial tachyarrhythmias to permanent AF. Identifier
PMCID: PMC4163193  PMID: 24771721
Pacemaker; Bradycardia; Atrial fibrillation; Atrial antitachycardia pacing; Managed ventricular pacing
2.  Cost-effectiveness of implantable cardioverter-defibrillator in today's world 
Indian Heart Journal  2014;66(Suppl 1):S101-S104.
The implantable cardioverter-defibrillator (ICD) is an example of an effective intervention with high up-front costs and delayed benefits. It has become a proven and well-accepted therapy not only for secondary but also for primary prevention of sudden cardiac death in patients with ischemic and non-ischemic heart disease. In recent years, the international guidelines have extended the indications to the prophylactic ICD, increasing the number of eligible patients and, together, the financial challenges of a widespread implementation. In this article, we review the available economic tools that can help address the ICD cost issue. We think that the awareness of such knowledge may facilitate dialogues between physicians, administrators and policy-makers, and help foster rational decision making.
PMCID: PMC4237288  PMID: 24568820
Implantable cardioverter-defibrillator; Costs; Cost-effectiveness; Heart failure; Sudden cardiac death
3.  Device-detected atrial fibrillation and risk for stroke: an analysis of >10 000 patients from the SOS AF project (Stroke preventiOn Strategies based on Atrial Fibrillation information from implanted devices) 
European Heart Journal  2013;35(8):508-516.
The aim of this study was to assess the association between maximum daily atrial fibrillation (AF) burden and risk of ischaemic stroke.
Cardiac implanted electronic devices (CIEDs) enhance detection of AF, providing a comprehensive measure of AF burden.
Design, setting, and patients
A pooled analysis of individual patient data from five prospective studies was performed. Patients without permanent AF, previously implanted with CIEDs, were included if they had at least 3 months of follow-up. A total of 10 016 patients (median age 70 years) met these criteria. The risk of ischaemic stroke associated with pre-specified cut-off points of AF burden (5 min, 1, 6, 12, and 23 h, respectively) was assessed.
During a median follow-up of 24 months, 43% of 10 016 patients experienced at least 1 day with at least 5 min of AF burden and for them the median time to the maximum AF burden was 6 months (inter-quartile range: 1.3–14). A Cox regression analysis adjusted for the CHADS2 score and anticoagulants at baseline demonstrated that AF burden was an independent predictor of ischaemic stroke. Among the thresholds of AF burden that we evaluated, 1 h was associated with the highest hazard ratio (HR) for ischaemic stroke, i.e. 2.11 (95% CI: 1.22–3.64, P = 0.008).
Device-detected AF burden is associated with an increased risk of ischaemic stroke in a relatively unselected population of CIEDs patients. This finding may add to the basis for timely and clinically appropriate decision-making on anticoagulation treatment.
PMCID: PMC3930873  PMID: 24334432
Atrial fibrillation; Anticoagulation; Implantable defibrillator; Pacemaker; Stroke
4.  The MOnitoring Resynchronization dEvices and CARdiac patiEnts (MORE-CARE) Randomized Controlled Trial: Phase 1 Results on Dynamics of Early Intervention With Remote Monitoring 
Remote monitoring (RM) in patients with advanced heart failure and cardiac resynchronization therapy defibrillators (CRT-D) may reduce delays in clinical decisions by transmitting automatic alerts. However, this strategy has never been tested specifically in this patient population, with alerts for lung fluid overload, and in a European setting.
The main objective of Phase 1 (presented here) is to evaluate if RM strategy is able to reduce time from device-detected events to clinical decisions.
In this multicenter randomized controlled trial, patients with moderate to severe heart failure implanted with CRT-D devices were randomized to a Remote group (with remote follow-up and wireless automatic alerts) or to a Control group (with standard follow-up without alerts). The primary endpoint of Phase 1 was the delay between an alert event and clinical decisions related to the event in the first 154 enrolled patients followed for 1 year.
The median delay from device-detected events to clinical decisions was considerably shorter in the Remote group compared to the Control group: 2 (25th-75th percentile, 1-4) days vs 29 (25th-75th percentile, 3-51) days respectively, P=.004. In-hospital visits were reduced in the Remote group (2.0 visits/patient/year vs 3.2 visits/patient/year in the Control group, 37.5% relative reduction, P<.001). Automatic alerts were successfully transmitted in 93% of events occurring outside the hospital in the Remote group. The annual rate of all-cause hospitalizations per patient did not differ between the two groups (P=.65).
RM in CRT-D patients with advanced heart failure allows physicians to promptly react to clinically relevant automatic alerts and significantly reduces the burden of in-hospital visits.
Trial Registration NCT00885677; (Archived by WebCite at
PMCID: PMC3758044  PMID: 23965236
cardiac resynchronization therapy; heart failure; alerts; remote monitoring; telemedicine
5.  Assessing the outcomes of implantable cardioverter defibrillator treatment in a real world setting: results from hospital record data 
A plethora of clinical studies have assessed the benefits of implantable cardioverter defibrillators (ICDs) and supported their use in clinical practice. However, evidence on the safety and efficacy of ICDs appears insufficient to support expansion of their use in clinical practice, and more information on their impact in real life settings is warranted. This paper aims to investigate the impact of ICDs using a large administrative dataset reflecting actual clinical practice.
Data were obtained from the hospital discharge database of the Friuli Venezia Giulia region in Italy containing patient-level information on 169,488 cases. Data on mortality outside hospital were obtained from regional sources. Exact matching method was used to estimate the outcomes associated with ICDs: mortality, length of stay, re-hospitalization and regional expenditure. The method was applied in two steps. First, patients with ICDs were matched with those without using the following: age class (by 5 years), gender, year of admission, type of admission (day hospital vs. ordinary) and primary diagnosis. In the second step, matching included also Charlson Comorbidities Index. Exact matching average treatment effect on the treated (ATT) was used as a main measure of impact.
Compared with matched controls, treatment with ICDs was associated with lower mortality (absolute risk reduction 10.6% at 1 year and 8.3% at 2 and 8.4% at 3 years, p < 0.001 and hazard ratio 0.80, p < 0.001), greater regional expenditure at index hospitalization (ATT: €9459.64, p < 0.001) and during follow up (ATT: €1707.29, p < 0.001) and higher re-hospitalization rate (ATT: 0.53, p < 0.001). No significant difference was found for length of stay (9.07 vs. 8.86 days). The results were maintained after more restrictive matching was applied.
Assessing the impact of innovative, expensive medical technologies on the basis of real world data is warranted, especially when there are barriers to implementation. Hospital administrative datasets can be of great value when a technology such as the ICD is implemented in a relatively small sample of patients, to allow use of exact matching techniques.
PMCID: PMC3602059  PMID: 23496994
Technology assessment; High cost technology; Matched paired analysis; Implantable cardioverter defibrillators
6.  Comprehensive risk reduction in patients with atrial fibrillation: emerging diagnostic and therapeutic options—a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference 
Europace  2011;14(1):8-27.
While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF.
PMCID: PMC3236658  PMID: 21791573
atrial fibrillation; management; outcomes; antithrombotic therapy; rate control; rhythm control; risk factors; early therapy
8.  Influence of time between last myocardial infarction and prophylactic implantable defibrillator implant on device detections and therapies. “Routine Practice” data from the SEARCH MI registry 
A multicenter European Registry, SEARCH-MI, was instituted in the year 2002 in order to assess patients’ outcomes and ICD interventions in patients with a previous MI and depressed LV function, treated with an ICD according to MADIT II results. In this analysis, we evaluate the influence of the time elapsed between last myocardial infarction (MI) and prophylactic cardioverter defibrillator (ICD) implant on device activations.
643 patients with left ventricular dysfunction (mean LVEF 26 ± 5%) and NYHA class I-III were prospectively followed for 1.8 ± 1.2 years in a multicenter registry. The population was divided into 3 groups according to the time between last MI and ICD implant: [1] from 40 days to less than 1.5 years; [2] from 1.5 to less than 7 years and [3] at least 7 years.
The cumulative incidence of ventricular tachyarrhymias and appropriate device therapy (ATP or shock) were higher in patients implanted longer time from last MI (Gray’s Test p = 0.002 and p = 0.013 respectively). No significant differences were seen in all cause mortality (Gray’s Test p = 0.618) or sudden cardiac death across the MI stratification groups (Gray’s Test p = 0.663).
Patients implanted with an ICD longer after the MI have a higher chance of presenting ventricular tachyarrhythmias and appropriate ICD therapy, while no differences were seen in overall mortality. These observations may be important for improving patient targeting in sudden death prevention.
PMCID: PMC3504521  PMID: 22966862
Cardioverter defibrillator; Myocardial infarction; Registry; Sudden death; Ventricular tachyarrhythmias.
9.  The empowerment of translational research: lessons from laminopathies 
The need for a collaborative approach to complex inherited diseases collectively referred to as laminopathies, encouraged Italian researchers, geneticists, physicians and patients to join in the Italian Network for Laminopathies, in 2009. Here, we highlight the advantages and added value of such a multidisciplinary effort to understand pathogenesis, clinical aspects and try to find a cure for Emery-Dreifuss muscular dystrophy, Mandibuloacral dysplasia, Hutchinson-Gilford Progeria and forms of lamin-linked cardiomyopathy, neuropathy and lipodystrophy.
PMCID: PMC3458975  PMID: 22691392
Laminopathies; Emery-Dreifuss Muscular Dystrophy; Dilated Cardiomyopathy with Conduction Defects; Mandibuloacral Dysplasia; Familial Partial Lipodystrophy Type 2; Hutchinson-Gilford Progeria Syndrome; Rare Diseases; Networking activity; interdisciplinary approach to diseases
10.  QRS pattern and improvement in right and left ventricular function after cardiac resynchronization therapy: a radionuclide study 
Predicting response to cardiac resynchronization therapy (CRT) remains a challenge. We evaluated the role of baseline QRS pattern to predict response in terms of improvement in biventricular ejection fraction (EF).
Consecutive patients (pts) undergoing CRT implantation underwent radionuclide angiography at baseline and at mid-term follow-up. The relationship between baseline QRS pattern and mechanical dyssynchrony using phase analysis was evaluated. Changes in left and right ventricular EF (LVEF and RVEF) were analyzed with regard to baseline QRS pattern.
We enrolled 56 pts, 32 with left bundle branch block (LBBB), 4 with right bundle branch block (RBBB) and 20 with non-specific intraventricular conduction disturbance (IVCD). A total of 48 pts completed follow-up. LBBB pts had significantly greater improvement in LVEF compared to RBBB or non-specific IVCD pts (+9.6 ± 10.9% vs. +2.6 ± 7.6%, p = 0.003). Response (defined as ≥ 5% increase in LVEF) was observed in 68% of LBBB vs. 24% of non-specific IVCD pts (p = 0.006). None of the RBBB pts were responders. RVEF was significantly improved in LBBB (+5.0 ± 9.0%, p = 0.007), but not in non-specific IVCD and RBBB pts (+0.4 ± 5.8%, p = 0.76). At multivariate analysis, LBBB was the only predictor of LVEF response (OR, 7.45; 95% CI 1.80-30.94; p = 0.006), but not QRS duration or extent of mechanical dyssynchrony.
Presence of a LBBB is a marker of a positive response to CRT in terms of biventricular improvement. Pts with non-LBBB pattern show significantly less benefit from CRT than those with LBBB.
PMCID: PMC3352038  PMID: 22494365
Cardiac resynchronization therapy; Left ventricular ejection fraction; Right ventricular ejection fraction; Dyssynchrony; Nuclear angiography; QRS morphology
11.  Treatment of atrial fibrillation with a dual defibrillator in heart failure patients (TRADE HF): protocol for a randomized clinical trial 
Trials  2011;12:44.
Heart failure(HF) and atrial fibrillation(AF) frequently coexist in the same patient and are associated with increased mortality and frequent hospitalizations. As the concomitance of AF and HF is often associated with a poor prognosis, the prompt treatment of AF in HF patients may significantly improve outcome.
Recent implantable cardiac resynchronization (CRT) devices allow electrical therapies to treat AF automatically. TRADE-HF (trial registration: NCT00345592; is a prospective, randomized, double arm study aimed at demonstrating the efficacy of an automatic, device-based therapy for treatment of atrial tachycardia and fibrillation(AT/AF) in patients indicated for CRT. The study compares automatic electrical therapy to a traditional more usual treatment of AT/AF: the goal is to demonstrate a reduction in a combined endpoint of unplanned hospitalizations for cardiac reasons, death from cardiovascular causes or permanent AF when using automatic atrial therapy as compared to the traditional approach involving hospitalization for symptoms and in-hospital treatment of AT/AF.
CRT pacemaker with the additional ability to convert AF as well as ventricular arrhythmias may play a simultaneous role in rhythm control and HF treatment. The value of the systematic implantation of CRT ICDs with the capacity to deliver atrial therapy in HF patients at risk of AF has not yet been explored. The TRADE-HF study will assess in CRT patients whether a strategy based on automatic management of atrial arrhythmias might be a valuable option to reduce the number of hospital admission and to reduce the progression the arrhythmia to a permanent form.
Trial registration
PMCID: PMC3049181  PMID: 21324118
12.  A simplified biventricular defibrillator with fixed long detection intervals reduces implantable cardioverter defibrillator (ICD) interventions and heart failure hospitalizations in patients with non-ischaemic cardiomyopathy implanted for primary prevention: the RELEVANT [Role of long dEtection window programming in patients with LEft VentriculAr dysfunction, Non-ischemic eTiology in primary prevention treated with a biventricular ICD] study 
European Heart Journal  2009;30(22):2758-2767.
To investigate the efficacy and safety of a cardiac resynchronization therapy with cardioverter–defibrillator (CRT-D) device with simplified ventricular tachycardia management in patients with non-ischaemic heart failure (HF) and primary prevention implantable cardioverter defibrillator (ICD) indication.
Methods and results
Prospective, controlled, parallel, multicentre, non-randomized study enrolling 324 primary prevention non-ischaemic HF patients implanted with CRT-D devices from 2004 to 2007: Protect group, 164 patients implanted with a Medtronic Insync III Protect device and Control group, 160 patients utilizing other Medtronic CRT-D devices.
Efficacy was assessed by computing appropriate and inappropriate detections and therapies during follow-up; safety compared hospitalizations and syncopal events between groups. Ninety per cent of both ventricular and supraventricular tachyarrhythmias terminated within the 13–29 beat detection interval with the Protect algorithm. The Protect group showed a significantly better event-free survival to first delivered therapy for total (P = 0.0001), appropriately treated (P = 0.002), and inappropriately treated episodes (P = 0.017). The total number of delivered shocks was significantly lower in the Protect group (22 vs. 59, P < 0.0001). In the Protect group, a significantly reduced HF hospitalization (hazard ratio 0.38, 95% CI 0.15–0.98, P = 0.044) was observed without any increase of syncope or death.
A simplified CRT-D device with fixed long detection reduced overall ICD therapy burden and HF hospitalizations without entailing any additional adverse events in primary prevention non-ischaemic HF patients.
PMCID: PMC2777026  PMID: 19567380
Cardiac resynchronization therapy; Implantable; Defibrillators; Non-ischaemic; Tachyarrhythmias
13.  Effectiveness of cardiac resynchronization therapy in heart failure patients with valvular heart disease: comparison with patients affected by ischaemic heart disease or dilated cardiomyopathy. The InSync/InSync ICD Italian Registry 
European Heart Journal  2009;30(18):2275-2283.
To analyse the effectiveness of cardiac resynchronization therapy (CRT) in patients with valvular heart disease (a subset not specifically investigated in randomized controlled trials) in comparison with ischaemic heart disease or dilated cardiomyopathy patients.
Methods and results
Patients enrolled in a national registry were evaluated during a median follow-up of 16 months after CRT implant. Patients with valvular heart disease treated with CRT (n = 108) in comparison with ischaemic heart disease (n = 737) and dilated cardiomyopathy (n = 635) patients presented: (i) a higher prevalence of chronic atrial fibrillation, with atrioventricular node ablation performed in around half of the cases; (ii) a similar clinical and echocardiographic profile at baseline; (iii) a similar improvement of LVEF and a similar reduction in ventricular volumes at 6–12 months; (iv) a favourable clinical response at 12 months with an improvement of the clinical composite score similar to that occurring in patients with dilated cardiomyopathy and more pronounced than that observed in patients with ischaemic heart disease; (v) a long-term outcome, in term of freedom from death or heart transplantation, similar to patients affected by ischaemic heart disease and basically more severe than that of patients affected by dilated cardiomyopathy.
In ‘real world’ clinical practice, CRT appears to be effective also in patients with valvular heart disease. However, in this group of patients the outcome after CRT does not precisely overlap any of the two other groups of patients, for which much more data are currently available.
PMCID: PMC2742782  PMID: 19515689
Cardiac resynchronization therapy; Heart failure; Valvular heart disease; Remodelling
14.  Clinical and arrhythmic outcomes after implantation of a defibrillator for primary prevention of sudden death in patients with post-myocardial infarction cardiomyopathy: The Survey to Evaluate Arrhythmia Rate in High-risk MI patients (SEARCH-MI) 
Europace  2009;11(4):476-482.
To evaluate clinical and arrhythmic outcomes in post-infarction cardiomyopathy patients implanted with a defibrillator (ICD) for primary prevention of sudden death.
Methods and results
The SEARCH-MI registry is a European multi-centre, prospective, observational study enrolling patients after myocardial infarction, chronic left ventricular dysfunction and an ICD implanted for primary prevention of sudden death. Data on 556 patients with at least one recorded follow-up are presented. Survey to Evaluate Arrhythmia Rate in High-risk MI (SEARCH-MI) patients were sicker than those enrolled in MADIT-II with higher New York Heart Association class and left bundle branch block. Total mortality was 10.4%. Close to one-third (30%) of patients experienced episodes of sustained ventricular arrhythmia. One-quarter (23%) received at least one appropriate therapy and 10% inappropriate therapy. Gender (25% males vs. 5% females, P = 0.0009) and history of non-sustained ventricular tachycardia (24% with vs. 18% without P = 0.037) were predictive of appropriate ventricular therapy.
SEARCH-MI represents the current clinical management of post-MI patients with left ventricular dysfunction indicated to defibrillator implant for primary prevention. European routine clinical practice was influenced by landmark trials and guidelines which impacted on the implantation of cardiac resynchronization therapy in over 25% of such patients. Non-sustained ventricular tachycardia identifies subjects with a higher incidence of appropriate ICD therapy.
PMCID: PMC2659601  PMID: 19136492
Post-infarction cardiomyopathy; Ventricular arrhythmias; Sudden death; Implantable cardioverter defibrillator
15.  Cardiac resynchronization therapy during rest and exercise: comparison of two optimization methods 
Europace  2008;10(10):1161-1169.
Optimal exercise programming of cardiac resynchronization therapy (CRT) devices is unknown. We aimed to: (i) investigate variations in optimal atrioventricular (AV) and interventricular (VV) delays from rest to exercise, assessed by both echocardiography and an automated intracardiac electrogram (IEGM) method; (ii) evaluate the acute haemodynamic impact of CRT optimization performed during exercise.
Methods and results
Twenty-four heart failure patients, previously implanted with a CRT defibrillator, underwent AV and VV delay optimization, by echocardiography and IEGM methods, both at rest and during supine bicycle exercise. Rest-to-exercise variations in optimal VV delay were observed in 58% of patients. Conversely, optimal AV delay did not change during exercise compared with rest. Substantial agreement of AV and VV delays was observed between both the optimization methods. Exercise optimization of VV delay by either method improved intraventricular dyssynchrony and increased aortic velocity time integral compared with the resting setting (P < 0.001).
In patients implanted with a CRT device, optimal VV delay varied considerably from rest to exercise, while AV delay did not change. Re-assessment of the optimal pacing configuration during supine exercise, by echocardiography as well as IEGM methods, yielded an additional haemodynamic benefit to that provided by resting optimization.
PMCID: PMC2552406  PMID: 18753213
Cardiac resynchronization therapy; Optimization; Exercise; Echocardiography; Intracardiac electrogram
16.  Telecardiology and Remote Monitoring of Implanted Electrical Devices: The Potential for Fresh Clinical Care Perspectives 
Journal of General Internal Medicine  2007;23(Suppl 1):73-77.
Telecardiology may help confront the growing burden of monitoring the reliability of implantable defibrillators/pacemakers. Herein, we suggest that the evolving capabilities of implanted devices to monitor patients’ status (heart rhythm, fluid overload, right ventricular pressure, oximetry, etc.) may imply a shift from strictly device-centered follow-up to perspectives centered on the patient (and patient-device interactions). Such approaches could provide improvements in health care delivery and clinical outcomes, especially in the field of heart failure. Major professional, policy, and ethical issues will have to be overcome to enable real-world implementation. This challenge may be relevant for the evolution of our health care systems.
PMCID: PMC2150639  PMID: 18095049
defibrillator; devices; heart failure; monitoring; pacemaker; telemedicine; telecardiology
17.  Telecardiology and Remote Monitoring of Implanted Electrical Devices: The Potential for Fresh Clinical Care Perspectives 
Journal of General Internal Medicine  2007;23(Suppl 1):73-77.
Telecardiology may help confront the growing burden of monitoring the reliability of implantable defibrillators/pacemakers. Herein, we suggest that the evolving capabilities of implanted devices to monitor patients’ status (heart rhythm, fluid overload, right ventricular pressure, oximetry, etc.) may imply a shift from strictly device-centered follow-up to perspectives centered on the patient (and patient-device interactions). Such approaches could provide improvements in health care delivery and clinical outcomes, especially in the field of heart failure. Major professional, policy, and ethical issues will have to be overcome to enable real-world implementation. This challenge may be relevant for the evolution of our health care systems.
PMCID: PMC2150639  PMID: 18095049
defibrillator; devices; heart failure; monitoring; pacemaker; telemedicine; telecardiology

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