Combining home monitoring temporal trends from implanted defibrillators and baseline patient risk profile to predict heart failure hospitalizations: results from the SELENE HF study.

AIMS: We developed and validated an algorithm for prediction of heart failure (HF) hospitalizations using remote monitoring (RM) data transmitted by implanted defibrillators. METHODS AND RESULTS: The SELENE HF study enrolled 918 patients (median age 69 years, 81% men, median ejection fraction 30%) with cardiac resynchronization therapy (44%), dual-chamber (38%), or single-chamber defibrillators with atrial diagnostics (18%). To develop a predictive algorithm, temporal trends of diurnal and nocturnal heart rates, ventricular extrasystoles, atrial tachyarrhythmia burden, heart rate variability, physical activity, and thoracic impedance obtained by daily automatic RM were combined with a baseline risk-stratifier (Seattle HF Model) into one index. The primary endpoint was the first post-implant adjudicated HF hospitalization. After a median follow-up of 22.5 months since enrolment, patients were randomly allocated to the algorithm derivation group (n = 457; 31 endpoints) or algorithm validation group (n = 461; 29 endpoints). In the derivation group, the index showed a C-statistics of 0.89 [95% confidence interval (CI): 0.83-0.95] with 2.73 odds ratio (CI 1.98-3.78) for first HF hospitalization per unitary increase of index value (P < 0.001). In the validation group, sensitivity of predicting primary endpoint was 65.5% (CI 45.7-82.1%), median alerting time 42 days (interquartile range 21-89), and false (or unexplained) alert rate 0.69 (CI 0.64-0.74) [or 0.63 (CI 0.58-0.68)] per patient-year. Without the baseline risk-stratifier, the sensitivity remained 65.5% and the false/unexplained alert rates increased by ≈10% to 0.76/0.71 per patient-year. CONCLUSION: With the developed algorithm, two-thirds of first post-implant HF hospitalizations could be predicted timely with only 0.7 false alerts per patient-year.

Reactive atrial-based antitachycardia pacing therapy reduces atrial tachyarrhythmias.

BACKGROUND: Reactive atrial-based antitachycardia pacing (rATP) aims to terminate atrial tachyarrhythmia/atrial fibrillation (AT/AF) episodes when they spontaneously organize to atrial flutter or atrial tachycardia; however, its effectiveness in the real-world has not been studied. We used a large device database (Medtronic CareLink, Medtronic, Minneapolis, MN, USA) to evaluate the effects of rATP at reducing AT/AF. METHODS: Pacemaker, defibrillator, and resynchronization device transmission data were analyzed. Eligible patients had device detected AT/AF during a baseline period but were not in persistent AT/AF immediately preceding first transmission. Note that 1:1 individual matching between groups was conducted using age, sex, device type, pacing mode, AT/AF, and percent ventricular pacing at baseline. Risks of AT/AF events were compared between patients with rATP-enabled versus control patients with rATP-disabled or not available in the device. For matched patients, AT/AF event rates at 2 years were estimated by Kaplan-Meier method, and hazard ratios (HRs) were calculated by Cox proportional hazard models. RESULTS: Of 43,440 qualifying patients, 4,203 had rATP on. Matching resulted in 4,016 pairs, totaling 8,032 patients for analysis. The rATP group experienced significantly lower risks of AT/AF events lasting ≥1 day (HR 0.81), ≥7 days (HR 0.64), and ≥30 days (HR 0.56) compared to control (P < 0.0001 for all). In subgroup analysis, rATP was associated with reduced risks of AT/AF events across age, sex, device type, baseline AT/AF, and preventive atrial pacing. CONCLUSIONS: Among real-world patients from a large device database, rATP therapy was significantly associated with a reduced risk of AT/AF. This association was independent of whether the patient had a pacemaker, defibrillator, or resynchronization device.

Health care cost analysis of enhanced pacing modalities in bradycardia patients: Portuguese case study on the results of the MINERVA trial.

INTRODUCTION: The MINERVA trial established that atrial preventive pacing and atrial antitachycardia pacing (DDDRP) in combination with managed ventricular pacing (MVP) reduces progression to permanent atrial fibrillation (AF) in patients with paroxysmal or persistent AF and bradycardia who need cardiac pacing, compared to standard dual-chamber pacing (DDDR). It was shown that AF-related health care utilization was significantly lower in the DDDRP + MVP group than in the control group. Cost analysis demonstrated significant savings related to this new algorithm, based on health care costs from the USA, Italy, Spain and the UK. OBJECTIVE: To calculate the savings associated with reduced health care utilization due to enhanced pacing modalities in the Portuguese setting. METHODS: The impact on costs was estimated based on tariffs for AF-related hospitalizations and costs for emergency department and outpatient visits in Portugal. RESULTS: The MINERVA trial showed a 42% reduction in AF-related health care utilization thanks to the new algorithm. In Portugal, this represents a potential cost saving of 2323 euros per 100 patients in the first year and 17118 euros over a 10-year period. Considering the number of patients who could benefit from this new algorithm, Portugal could save a total of 75369 euros per year and 555410 euros over 10 years. Additional savings could accrue if heart failure and stroke hospitalizations were considered. CONCLUSION: The combination of atrial preventive pacing, atrial antitachycardia pacing and an algorithm to minimize the detrimental effect of right ventricular pacing reduces recurrent and permanent AF. The new DDDRP + MVP pacing mode could contribute to significant costs savings in the Portuguese health care setting.

[Appropriateness criteria for the management of anticoagulant therapy in complex patients with atrial fibrillation. The opinion of a group of expert Italian cardiologists]. / Criteri di appropriatezza nella gestione della terapia anticoagulante nel paziente complesso con fibrillazione atriale. L'opinione di un gruppo di esperti cardiologi italiani.

Atrial fibrillation (AF) is a common arrhythmia often associated with high thromboembolic risk. The purpose of this position paper is to provide clinicians with recommendations useful in managing some important issues regarding the use of anticoagulant therapy in patients with AF in particularly complex clinical situations.The RAND/UCLA appropriateness method, validated to combine the best available scientific evidence with the collective judgment of experts, was used to assess the judgment of an expert panel of cardiologists. To this purpose, the benefit-to-harm ratio of 37 clinical scenarios was rated. Each indication was classified as "appropriate", "uncertain", or "inappropriate" in accordance with the panelists' median score.The present document reports the results of this consensus process, which led to the development of recommendations for clinical practice on how to use anticoagulant therapy in patients with AF in complex clinical settings, including the presence of comorbidities, cardioversion, or ablation. Non-vitamin K oral anticoagulants are a valid alternative to vitamin K antagonists in preventing embolic events in patients with non-valvular AF, particularly in case of clinical complexity.

Center experience does not influence long-term outcome and peri-procedural complications after cryoballoon ablation of paroxysmal atrial fibrillation: Data on 860 patients from the real-world multicenter observational project.

BACKGROUND: The aim of this research was to evaluate whether the procedural data, the incidence of complications, and the long-term freedom from atrial fibrillation (AF) recurrences are influenced by center experience in a paroxysmal AF (PAF) population performing a first-time pulmonary vein isolation (PVI) by cryoballoon ablation (CBA). METHODS: A total of 860 patients underwent PVI by CBA. Center experience groups were predefined according to the quartiles of the distribution regarding the amount of performed procedures: 3.1%, 10.6%, 22.7% and 63.6% of patients were respectively followed in each group from 1st (less experienced) to 4th (more experienced) quartile of experience. RESULTS: In the entire population, median procedure and fluoroscopy time were 105 and 25 min, respectively. The median procedure time significantly decreased from 130 to 90 min (P < 0.001) as the center's experience increased. In 47 (5.5%) patients, a peri-procedural complication occurred. As the experience of centers increased, the acute intraprocedural PVI success rate increased (from 94.3% to 98.9%, P = 0.007), whereas there was a tendency towards a decreased incidence of peri-procedure complications (from 7.4% to 4.6%, P = 0.998). The mean 1-year freedom from AF recurrence probability was 78.3%, and the 18-month mean was 68.9% with no difference among the groups with different levels of experience. CONCLUSION: CBA is a safe and effective treatment for patients with PAF. Peri-procedural complications and procedural times were low in all the analyzed sub-groups, showing a decreasing trend in function of center expertise. The long-term freedom from AF recurrence was not influenced by the level of experience. (clinicaltrials.gov: NCT01007474).

Sick Sinus Syndrome.

The sick sinus syndrome includes symptoms and signs related to sinus node dysfunction. This can be caused by intrinsic abnormal impulse formation and/or propagation from the sinus node or, in some cases, by extrinsic reversible causes. Careful evaluation of symptoms and of the electrocardiogram is of crucial importance, because diagnosis is mainly based on these 2 elements. In some cases, the pathophysiologic mechanism that induces sinus node dysfunction also favors the onset of atrial arrhythmias, which results in a more complex clinical condition, known as "bradycardia-tachycardia syndrome."

Atrioventricular Nodal Conduction Disease.

This article describes the different anatomic structures involved in normal atrioventricular conduction and their pathologic states. It defines their effects on the electrocardiogram, and describes how to localize the level and evaluate the severity of conduction disease by electrocardiographic analysis. It illustrates the relevance of intracavitary recordings in the diagnosis of level of block.

Intraventricular Delay and Blocks.

From the atrioventricular node, electrical activation is propagated to both ventricles by a system of specialized conducting fibers, His Purkinje System (HPS), guaranteeing a fast, synchronous depolarization of both ventricles. From the predivisional common stem, a right and left branch separate, subdividing further in a fairly predictable fashion. Synchronous ventricular activation results in a QRS with specific characteristics and duration of less than 110 milliseconds. Block or delay in any part of the HPS changes the electrocardiographic (ECG) morphology. This article discusses the use and limitations of standard ECG in detecting abnormal ventricular propagation in specific areas of the HPS.

Role of Surface Electrocardiograms in Patients with Cardiac Implantable Electronic Devices.

Surface electrocardiograms, both resting 12-lead electrocardiographs and ambulatory electrocardiograph monitoring, play an essential role in establishing indications for cardiac implantable electronic devices (pacemakers, cardiac implantable defibrillators, and cardiac resynchronization therapies), and in the evaluation of patients already implanted. Current devices have prolonged memory capabilities (defined as Holter functions) and remote monitoring functions, to evaluate the electrical properties and the automatic detection of arrhythmias. Nonetheless, surface electrocardiography remains the critical tool to detect device malfunction, evaluate programming and function, verify the automatic arrhythmia analysis and the delivered electric therapy, and prevent inappropriate intervention.

Advanced Concepts of Atrioventricular Nodal Electrophysiology: Observations on the Mechanisms of Atrioventricular Nodal Reciprocating Tachycardias.

Atrioventricular node reentrant tachycardia (AVNRT) is a supraventricular arrhythmia easily diagnosed by 12-lead electrocardiogram. What is far more challenging, is the understanding of the reentrant circuit in its typical and atypical presentations. The function of the atrioventricular node is still incomplete and this knowledge gap is reflected in the reconstruction of the pathways used by AVNRT in its multiform presentations. This article illustrates the heterogeneous electrocardiographic manifestations of AVNRT. We reconstruct the reentrant circuits involved using more recent understanding of the anatomic and electrophysiologic characteristics of the atrioventricular node.

P Wave Analysis in the Era of Atrial Fibrillation Ablation.

The common arrhythmia atrial fibrillation (AF) is incompletely understood. The mechanism of initiation and the perpetuation of AF remain speculative. This article summarizes current knowledge of the complex relationship between arrhythmias triggering AF and their long-term effects on atrial tissue, leading to perpetuation of tachycardia. It focuses on the role of the electrocardiogram (ECG) from AF diagnosis to identification of sinus P wave abnormalities predicting future occurrences. The role of ambulatory ECG recordings in managing AF and the use of frequency analysis determining degree of organization and identification of AF triggers are discussed.

Peculiar Electrocardiographic Aspects of Wide QRS Complex Tachycardia: When Differential Diagnosis Is Difficult.

Wide complex tachycardia may represent a challenge for correct interpretation of standard electrocardiogram, which is crucial for proper patient management. For this reason, algorithms based on electrocardiographic criteria have been developed to guide interpretation in a step-by-step approach. Despite their greater accuracy, some cases of wide QRS complex tachycardia are a challenge. Some peculiar forms of ventricular tachycardia, and complex supraventricular substrate or particular clinical condition, may originate a challenging electrocardiographic pattern. In this article, a series of peculiar cases of wide QRS complex tachycardia is presented as paradigm of how important a comprehensive clinical approach is in these patients.

Cardiac resynchronization therapy: How did consensus guidelines from Europe and the United States evolve in the last 15 years?

Cardiac resynchronization therapy (CRT) was proposed around 20 years ago, and its clinical use rapidly moved from pioneering experiences to randomized controlled trials (RCT). Since 2002 recommendations for CRT have been included in international consensus guidelines that even in an early phase recommended CRT as an effective treatment for improving symptoms, reducing hospitalizations and mortality in well-selected patients with wide QRS, left ventricular dysfunction and moderate to severe heart failure (NYHA classes III-IV), on optimal medical therapy. Subsequently the indications were extended to mild (NYHA class II) heart failure (associated with left ventricular dysfunction and wide QRS) and more recently also to appropriately selected patients with conventional indications for pacing having a left ventricular ejection fraction of 50% or less and NYHA class I-III. While all the guidelines strongly recommend CRT in case of LBBB with QRS duration >150 ms, lower strength of recommendations, with some heterogeneity, appears when QRS duration is 130-150 ms, especially if not associated with LBBB. Of note, according to recent guidelines, CRT is not recommended in case of QRS duration <130 ms, which is now the lower limit for candidacy to CRT, differently from the 120 ms limit used before. Despite consensus guidelines, many data indicate that CRT is still underused, with great heterogeneity in its implementation, both in North America and Europe, thus requiring a more organized patient referral.

Arterial stiffness and left ventricular performance in elderly patients with persistent atrial fibrillation.

BACKGROUND: The prevalence of atrial fibrillation (AF) and arterial stiffness (AS) increases with age. AIMS: To evaluate if AS is correlated to longitudinal strain (LS), a marker of left ventricular (LV) function, in elderly AF patients with preserved ejection fraction (EF) undergoing external cardioversion. METHODS: AS was measured using the cardio-ankle vascular index (CAVI), LS was calculated from echocardiographic data of three consecutive cardiac cycles. RESULTS: We enrolled 38 patients (age 76 ± 8 years; men 60.5%; EF 65 ± 7%). LS and CAVI were, respectively, - 17.7 ± 3.7% and 9.7 ± 1.3. Multivariate analysis showed that LV performance was inversely related to height (p < 0.001) and to the presence of AF-related symptoms (p = 0.008). LS grew with increasing values of CAVI (p = 0.038). CONCLUSIONS: In elderly AF patients with preserved systolic function, LV performance is directly associated with AS. This link could influence atrium remodeling and the incidence of arrhythmia relapse.

Clinically oriented device programming in bradycardia patients: part 1 (sinus node disease). Proposals from AIAC (Italian Association of Arrhythmology and Cardiac Pacing).

: Modern pacemakers have an increasing number of programable parameters and specific algorithms designed to optimize pacing therapy in relation to the individual characteristics of patients. When choosing the most appropriate pacemaker type and programing, the following variables must be taken into account: the type of bradyarrhythmia at the time of pacemaker implantation; the cardiac chamber requiring pacing, and the percentage of pacing actually needed to correct the rhythm disorder; the possible association of multiple rhythm disturbances and conduction diseases; the evolution of conduction disorders during follow-up. The goals of device programing are to preserve or restore the heart rate response to metabolic and hemodynamic demands; to maintain physiological conduction; to maximize device longevity; to detect, prevent, and treat atrial arrhythmia. In patients with sinus node disease, the optimal pacing mode is DDDR. Based on all the available evidence, in this setting, we consider appropriate the activation of the following algorithms: rate responsive function in patients with chronotropic incompetence; algorithms to maximize intrinsic atrioventricular conduction in the absence of atrioventricular blocks; mode-switch algorithms; algorithms for autoadaptive management of the atrial pacing output; algorithms for the prevention and treatment of atrial tachyarrhythmias in the subgroup of patients with atrial tachyarrhythmias/atrial fibrillation. The purpose of this two-part consensus document is to provide specific suggestions (based on an extensive literature review) on appropriate pacemaker setting in relation to patients' clinical features.

Clinically oriented device programming in bradycardia patients: part 2 (atrioventricular blocks and neurally mediated syncope). Proposals from AIAC (Italian Association of Arrhythmology and Cardiac Pacing).

: The purpose of this two-part consensus document is to provide specific suggestions (based on an extensive literature review) on appropriate pacemaker setting in relation to patients' clinical features. In part 2, criteria for pacemaker choice and programming in atrioventricular blocks and neurally mediate syncope are proposed. The atrioventricular blocks can be paroxysmal or persistent, isolated or associated with sinus node disease. Neurally mediated syncope can be related to carotid sinus syndrome or cardioinhibitory vasovagal syncope. In sinus rhythm, with persistent atrioventricular block, we considered appropriate the activation of mode-switch algorithms, and algorithms for auto-adaptive management of the ventricular pacing output. If the atrioventricular block is paroxysmal, in addition to algorithms mentioned above, algorithms to maximize intrinsic atrioventricular conduction should be activated. When sinus node disease is associated with atrioventricular block, the activation of rate-responsive function in patients with chronotropic incompetence is appropriate. In permanent atrial fibrillation with atrioventricular block, algorithms for auto-adaptive management of the ventricular pacing output should be activated. If the atrioventricular block is persistent, the activation of rate-responsive function is appropriate. In carotid sinus syndrome, adequate rate hysteresis should be programmed. In vasovagal syncope, specialized sensing and pacing algorithms designed for reflex syncope prevention should be activated.

Sex-related differences in chronic heart failure.

The prevalence of chronic heart failure (CHF) is steadily increasing. Both sexes are affected, with significant differences in etiology, epidemiology and clinical presentation, prognosis, comorbidities, and response to treatment. Women tend to develop CHF at a more advanced age, present more often with HF with preserved ejection fraction, are more symptomatic, and have a worse quality of life than men, but also a better prognosis. In women, CHF has more frequently a non-ischemic etiology, and arterial hypertension and diabetes mellitus are leading comorbidities. Furthermore, many sex-related differences have been detected in the response to treatment, for example a greater prognostic benefit from angiotensin-receptor blockers in women, a higher incidence of complications after defibrillator implantation, and a greater response to cardiac resynchronization therapy. Furthermore, women are less likely to receive defibrillator therapy or heart transplantation. The significant underrepresentation of women in clinical trials limits our capacity to evaluate the extent of sex-related differences in CHF, although their characterization seems crucial in order to achieve the ultimate goal of a tailored therapy for this condition.

The prognostic benefit of cardiac resynchronization therapy is greater in concordant vs. discordant left bundle branch block in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT).

Aims: Discordant and concordant left bundle branch block (dLBBB/cLBBB) are characterized by negative or positive T waves, respectively, in lateral leads. We assessed if the two morphologies are associated with different clinical status and prognosis in patients with heart failure (HF) and current indication to Cardiac Resynchronization Therapy (CRT)/CRT-Defibrillator (CRT-D). Methods and results: Baseline electrocardiograms of 1270 patients with LBBB in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy cohort were analysed to identify dLBBB and cLBBB. The two groups were compared with respect to baseline clinical characteristics, primary endpoint (HF event or death), and secondary endpoint (ventricular tachycardia, ventricular fibrillation, or death) over a 3.5-year period, and benefit of CRT-D over implantable cardioverter defibrillator (ICD). dLBBB was identified in 909 (72%) patients, and cLBBB in 361 (28%). Patients with dLBBB were older, had more severe symptoms and systolic dysfunction, as well as higher brain natriuretic peptide. CRT-D was superior to ICD in patients with both LBBB morphologies. The occurrence of the primary outcome was significantly more frequent in patients with dLBBB than in those with cLBBB, both in the entire cohort (P = 0.005), and in the CRT-D arm (P = 0.002). There was a trend towards more frequent occurrence of the secondary endpoint in patients with dLBBB than in those with cLBBB, but statistical significance was not reached in the whole population or in the subgroup undergoing CRT-D. Among patients receiving CRT-D, dLBBB was an independent predictor of the primary endpoint. Conclusion: dLBBB morphology is associated with more severe HF clinical status and worse prognosis, even in patients receiving CRT-D, compared with cLBBB morphology.

Ventricular-arterial coupling in centenarians without cardiovascular diseases.

BACKGROUND: Ventricular-arterial (VA) coupling is a central determinant of cardiovascular system performance and cardiac energetics. This index is expressed by the Ea/Ees ratio, where the effective arterial elastance (Ea) indicates the net arterial load exerted on the left ventricle and the left ventricular end-systolic elastance (Ees) is a load-independent measure of left ventricular chamber performance. METHODS: Thirty-three centenarians (100.6 ± 1.2 years, range 99-105 years, 10 M) without cardiovascular diseases underwent a complete echocardiographic evaluation and an instantaneous arterial blood pressure measurement, to characterize the Ea/Ees ratio and its two determinants indexed to body surface area. RESULTS: VA coupling was markedly reduced (Ea/Ees ratio 0.40 ± 0.1), reflecting a disproportionate increase in Ees index (8.5 ± 2.2 mmHg/ml/m2) compared with Ea index (3.2 ± 0.8 mmHg/ml/m2). Notably, the coupling ratio was significantly lower in women (0.37 ± 0.1) than in men (0.45 ± 0.1, p = 0.0003), due to an increase in Ees index significantly greater in women (9.4 ± 1.9 mmHg/ml/m2) than in men (6.5 ± 1.5 mmHg/ml/m2, p = 0.0002). Using multivariate regression analysis, only female gender (ß coefficient -0.04, p = 0.01) and relative wall thickness (ß coefficient -0.49, p < 0.0001) showed a significant inverse correlation to VA coupling. CONCLUSIONS: Our analysis in a population of centenarians without overt cardiovascular disease revealed very low values of VA coupling, especially in women. Both a LV structural remodeling as well as a high aortic elastance might have contributed to a secondary disproportionate increase in myocardial stiffness.