The purpose of this study was to investigate the role of ivabradine in the treatment of symptomatic inappropriate sinus tachycardia using a double-blind, placebo-controlled, crossover design.
Due to ...its I(f) blocking properties, ivabradine can selectively attenuate the high discharge rate from sinus node cells, causing inappropriate sinus tachycardia.
Twenty-one patients were randomized to receive placebo (n=10) or ivabradine 5 mg twice daily (n=11) for 6 weeks. After a washout period, patients crossed over for an additional 6 weeks. Each patient underwent symptom evaluation and heart rate assessment at the start and finish of each phase.
After taking ivabradine, patients reported elimination of >70% of symptoms (relative risk: 0.25; 95% CI: 0.18 to 0.34; p<0.001), with 47% of them experiencing complete elimination. These effects were associated with a significant reduction of heart rate at rest (from 88±11 beats/min to 76±11 beats/min, p=0.011), on standing (from 108±12 beats/min to 92±11 beats/min, p<0.0001), during 24 h (from 88±5 beats/min to 77±9 beats/min, p=0.001), and during effort (from 176±17 beats/min to 158±16 beats/min, p=0.001). Ivabradine administration was also associated with a significant increase in exercise performance. No cardiovascular side effects were observed in any patients while taking ivabradine.
In this cohort, ivabradine significantly improved symptoms associated with inappropriate sinus tachycardia and completely eliminated them in approximately half of the patients. These findings suggest that ivabradine may be an important agent for improving symptoms in patients with inappropriate sinus tachycardia.
Objectives The purpose of this study was to investigate the role of ivabradine in the treatment of symptomatic inappropriate sinus tachycardia using a double-blind, placebo-controlled, crossover ...design. Background Due to its If blocking properties, ivabradine can selectively attenuate the high discharge rate from sinus node cells, causing inappropriate sinus tachycardia. Methods Twenty-one patients were randomized to receive placebo (n = 10) or ivabradine 5 mg twice daily (n = 11) for 6 weeks. After a washout period, patients crossed over for an additional 6 weeks. Each patient underwent symptom evaluation and heart rate assessment at the start and finish of each phase. Results After taking ivabradine, patients reported elimination of >70% of symptoms (relative risk: 0.25; 95% CI: 0.18 to 0.34; p < 0.001), with 47% of them experiencing complete elimination. These effects were associated with a significant reduction of heart rate at rest (from 88 ± 11 beats/min to 76 ± 11 beats/min, p = 0.011), on standing (from 108 ± 12 beats/min to 92 ± 11 beats/min, p < 0.0001), during 24 h (from 88 ± 5 beats/min to 77 ± 9 beats/min, p = 0.001), and during effort (from 176 ± 17 beats/min to 158 ± 16 beats/min, p = 0.001). Ivabradine administration was also associated with a significant increase in exercise performance. No cardiovascular side effects were observed in any patients while taking ivabradine. Conclusions In this cohort, ivabradine significantly improved symptoms associated with inappropriate sinus tachycardia and completely eliminated them in approximately half of the patients. These findings suggest that ivabradine may be an important agent for improving symptoms in patients with inappropriate sinus tachycardia.
Purpose
In patients with cancer, the safety of catheter ablation for non-valvular atrial fibrillation (AF) has not been evaluated, yet. The aim of this study was to assess the safety of AF ablation ...in cancer survivors.
Methods
Consecutively recruited patients undergoing catheter ablation of non-valvular AF at our center between March 2015 and March 2017 were evaluated. The primary outcome of the study was clinically relevant bleedings occurred within 30 ± 5 days after the procedure. Patients with cancer were propensity matched to patients without cancer in a 1:3 and 1:6 ratio after stratification by baseline clinical features.
Results
Overall, 184 patients were included in the study. Of them, 21 (11%) were cancer survivors. Cancer site was more frequently gastrointestinal (36%), breast (23%), and genitourinary (18%). At 30 ± 5 days, clinically relevant bleedings occurred in 14 patients. Crude odds ratio (OR) for clinically relevant bleedings was 3.60 (95% CI 1.02–12.7) higher in cancer than in non-cancer patients. This trend remained after propensity score–matched population (OR 3.48, 95% CI 0.76–15.90 for matched 1:3, OR 4.95, 95% CI 1.2–20.2 for matched 1:6). Type of anticoagulation was not associated with bleedings.
Conclusions
Preliminary results suggest that clinically relevant bleeding after catheter ablation for AF is more frequent in cancer survivors than in patients without cancer. Further studies are required to confirm the present data.
In patients with atrial fibrillation (AF) undergoing radiofrequency (RF) electrical disconnection of multiple pulmonary veins (PVs), the incidence of late conduction recurrences has not been ...systematically determined.
Using a prospectively designed, multistep approach, we aimed at assessing the correlation between acute achievement and chronic maintenance of electrical conduction block across RF lesions disconnecting the distal tract of the PV in 43 patients (52.3+/-8.2 years) with AF. Forty-one left superior (LS), 42 right superior (RS), 25 left inferior (LI), and 9 right inferior (RI) PVs were targeted during 108 EP procedures (2.6+/-0.5 per patient). Seventeen patients underwent 2 procedures, 23 patients underwent 3 procedures, and 3 patients underwent 4 procedures. During the first attempt, electrical disconnection was achieved in 112 PVs (95.7%). During a next procedure (time interval, 4.6+/-1.9 months), conduction recurrence was observed in 32 of 39 LSPVs (82.1%), 29 of 40 RSPVs (72.5%), 20 of 24 LIPVs (83.3%), and 7 of 9 RIPV (77.8%). After reablation at gap sites, a later procedure (time interval, 5.1+/-2.4 months) revealed a second recurrence in 13 of 22 LSPVs (59.1%) and 14 of 19 RSPVs (73.7%).
Conduction recurrence across disconnecting RF lesions can be observed in approximately 80% of cases 4 months after ablation. After reablation, similar recurrence rates are observed 5 months later. This high rate of late conduction recurrence may contribute significantly to AF recurrence in patients undergoing catheter ablation aiming at disconnection of multiple PVs.
Background
Inappropriate sinus tachycardia (IST) often causes palpitations, dyspnea, and exercise intolerance, that are generally treated with beta blockers and non-dihydropyridine calcium-channel ...antagonists. Ivabradine, a selective inhibitor of cardiac pacemaker I
f
current, has recently emerged as an effective and safe alternative to conventional drugs for IST.
Methods
We performed a systematic overview of clinical studies on the therapeutic yield of ivabradine in patients with inappropriate sinus tachycardia, published in MEDLINE database from January 2000 to March 2015.
Results
Overall, five case reports were found, all showing efficacy of ivabradine in subjects affected by IST. Eight non-randomized clinical studies demonstrated short- and medium-term safety and efficacy of ivabradine administration in IST, also in adjunction to or in comparison with metoprolol. One double-blind randomized crossover study also showed that ivabradine is superior to placebo for heart rate (HR) reduction and symptoms control in patients affected by IST.
Conclusions
Ivabradine is effective and safe in short- and medium-term treatment of IST. However, long-term follow-up studies and randomized studies comparing ivabradine with beta blockers are still lacking.
Abstract The recent advent of an entirely subcutaneous implantable defibrillator (ICD) has provided a relevant contribution to the debate concerning the use of ICD therapy in patients at high risk ...for death. Although conventional transvenous ICDs have proven very effective during the past 23 years, they still appear to be limited by nontrivial acute and long-term complications. This study delineates some of the historical and current issues characterizing the advent of the subcutaneous ICD system in daily clinical practice. Subcutaneous ICDs have proven effective in more than 1100 patients worldwide and appear to be competitive with transvenous ICD in all clinical conditions not requiring antibradycardia, antitachycardia, or cardiac resynchronization pacing.
Transvenous implantable cardioverter-defibrillators (ICD) for the primary and secondary prevention of sudden cardiac death due to ventricular tachycardia/fibrillation have led to a significant ...improvement in survival in high-risk populations. Although conventional transvenous ICD therapy is currently widely used, it is associated with severe intra- and perioperative complications related to the use of transvenous leads, mostly occurring late after implantation. The recent introduction of a new ICD system with fully subcutaneous sensing and shocking capabilities has provided a valuable therapeutic option for special patient groups, allowing to identify and stop malignant ventricular arrhythmias while discriminating them from high-rate supraventricular tachyarrhythmias. This has also given us the opportunity to analyze the advantages and limitations of both implantable lifesaving electrical therapies. In the present paper, the technical characteristics of subcutaneous ICDs are described along with the recent advances in clinical and experimental research that have led to the introduction of these devices into clinical practice (over 1000 patients have been treated worldwide since 2009). Subcutaneous ICDs are indicated for both primary and secondary prevention of cardiac arrest in patients at risk for acquired or congenital arrhythmogenic diseases, including those with an underlying genetic molecular mechanism, provided that they do not require antibradycardia or antitachycardia pacing or cardiac resynchronization therapy, which represent the main limitations of these new devices. A subcutaneous ICD system has the advantage of avoiding the need for transvenous leads, making its implantation or removal much simpler without requiring fluoroscopic guidance. In addition, subcutaneous ICDs can be used in children, young subjects and athletes, and in all patients for whom venous access may be difficult to achieve.
The brain can efficiently learn a wide range of tasks, motivating the search for biologically inspired learning rules for improving current artificial intelligence technology. Most biological models ...are composed of point neurons and cannot achieve state-of-the-art performance in machine learning. Recent works have proposed that input segregation (neurons receive sensory information and higher-order feedback in segregated compartments), and nonlinear dendritic computation would support error backpropagation in biological neurons. However, these approaches require propagating errors with a fine spatiotemporal structure to all the neurons, which is unlikely to be feasible in a biological network. To relax this assumption, we suggest that bursts and dendritic input segregation provide a natural support for target-based learning, which propagates targets rather than errors. A coincidence mechanism between the basal and the apical compartments allows for generating high-frequency bursts of spikes. This architecture supports a burst-dependent learning rule, based on the comparison between the target bursting activity triggered by the teaching signal and the one caused by the recurrent connections, providing support for target-based learning. We show that this framework can be used to efficiently solve spatiotemporal tasks, such as context-dependent store and recall of three-dimensional trajectories, and navigation tasks. Finally, we suggest that this neuronal architecture naturally allows for orchestrating "hierarchical imitation learning", enabling the decomposition of challenging long-horizon decision-making tasks into simpler subtasks. We show a possible implementation of this in a two-level network, where the high network produces the contextual signal for the low network.
Aims
In the EXPLORER‐HCM trial, mavacamten reduced left ventricular outflow tract obstruction (LVOTO) and improved functional capacity of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) ...patients. We sought to define the potential use of mavacamten by comparing real‐world HOCM patients with those enrolled in EXPLORER‐HCM and assessing their eligibility to treatment.
Methods and results
We collected information on HOCM patients followed up at 25 Italian HCM outpatient clinics and with significant LVOTO (i.e. gradient ≥30 mmHg at rest or ≥50 mmHg after Valsalva manoeuvre or exercise) despite pharmacological or non‐pharmacological therapy. Pharmacological or non‐pharmacological therapy resolved LVOTO in 1044 (61.2%) of the 1706 HOCM patients under active follow‐up, whereas 662 patients (38.8%) had persistent LVOTO. Compared to the EXPLORER‐HCM trial population, these real‐world HOCM patients were older (62.1 ± 14.3 vs. 58.5 ± 12.2 years, p = 0.02), had a lower body mass index (26.8 ± 5.3 vs. 29.7 ± 4.9 kg/m2, p < 0.0001) and a more frequent history of atrial fibrillation (21.5% vs. 9.8%, p = 0.027). At echocardiography, they had lower left ventricular ejection fraction (LVEF, 66 ± 7% vs. 74 ± 6%, p < 0.0001), higher left ventricular outflow tract gradients at rest (60 ± 27 vs. 52 ± 29 mmHg, p = 0.003), and larger left atrial volume index (49 ± 16 vs. 40 ± 12 ml/m2, p < 0.0001). Overall, 324 (48.9%) would have been eligible for enrolment in the EXPLORER‐HCM trial and 339 (51.2%) for treatment with mavacamten according to European guidelines.
Conclusions
Real‐world HOCM patients differ from the EXPLORER‐HCM population for their older age, lower LVEF and larger atrial volume, potentially reflecting a more advanced stage of the disease. About half of real‐world HOCM patients were found eligible to mavacamten.
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