Machine learning based detection of T-wave alternans in real ambulatory conditions.

BACKGROUND AND OBJECTIVE: T-wave alternans (TWA) is a fluctuation in the repolarization morphology of the ECG. It is associated with cardiac instability and sudden cardiac death risk. Diverse methods have been proposed for TWA analysis. However, TWA detection in ambulatory settings remains a challenge due to the absence of standardized evaluation metrics and detection thresholds. METHODS: In this work we use traditional TWA analysis signal processing-based methods for feature extraction, and two machine learning (ML) methods, namely, K-nearest-neighbor (KNN) and random forest (RF), for TWA detection, addressing hyper-parameter tuning and feature selection. The final goal is the detection in ambulatory recordings of short, non-sustained and sparse TWA events. RESULTS: We train ML methods to detect a wide variety of alternant voltage from 20 to 100 µV, i.e., ranging from non-visible micro-alternans to TWA of higher amplitudes, to recognize a wide range in concordance to risk stratification. In classification, RF outperforms significantly the recall in comparison with the signal processing methods, at the expense of a small lost in precision. Despite ambulatory detection stands for an imbalanced category context, the trained ML systems always outperform signal processing methods. CONCLUSIONS: We propose a comprehensive integration of multiple variables inspired by TWA signal processing methods to fed learning-based methods. ML models consistently outperform the best signal processing methods, yielding superior recall scores.

Subjective identification and ablation of drivers improves rhythm control in patients with persistent atrial fibrillation. The CHAOS-AF study.

INTRODUCTION AND OBJECTIVES: The optimal approach for persistent atrial fibrillation (AF) ablation remains unknown. In patients with persistent AF, we compared an ablation strategy based on pulmonary vein isolation (PVI) plus ablation of drivers (PVI+D), with a conventional PVI-only approach performed in a 1:1 propensity score-matched cohort. METHODS: Drivers were subjectively identified using conventional high-density mapping catheters (IntellaMap ORION, PentaRay NAV or Advisor HD Grid), without dedicated software, as fractionated continuous or quasicontinuous electrograms on 1 to 2 adjacent bipoles, which were ablated first; and as sites with spatiotemporal dispersion (the entire cycle length comprised within the mapping catheter) plus noncontinuous fractionation, which were only targeted in patients without fractionated continuous electrograms, or without AF conversion after ablation of fractionated continuous electrograms. Ablation included PVI plus focal or linear ablation targeting drivers. RESULTS: A total of 50 patients were included in each group (61±10 years, 25% women). Fractionated continuous electrograms were found and ablated in 21 patients from the PVI+D group (42%), leading to AF conversion in 7 patients. In the remaining 43 patients, 143 sites with spatiotemporal dispersion plus noncontinuous fractionation were targeted. Globally, AF conversion was achieved in 21 patients (42%). The PVI+D group showed lower atrial arrhythmia recurrences at 1 year of follow-up (30.6% vs 48%; P=.048) and at the last follow-up (46% vs 72%; P=.013), and less progression to permanent AF (10% vs 40%; P=.001). CONCLUSIONS: Subjective identification and ablation of drivers, added to PVI, increased 1-year freedom from atrial arrhythmia and decreased long-term recurrences and progression to permanent AF.

Bayesian analysis of the Substrate Ablation vs. Antiarrhythmic Drug Therapy for Symptomatic Ventricular Tachycardia trial.

BACKGROUND AND AIMS: Bayesian analyses can provide additional insights into the results of clinical trials, aiding in the decision-making process. We analysed the Substrate Ablation vs. Antiarrhythmic Drug Therapy for Symptomatic Ventricular Tachycardia (SURVIVE-VT) trial using Bayesian survival models. METHODS AND RESULTS: The SURVIVE-VT trial randomized patients with ischaemic cardiomyopathy and monomorphic ventricular tachycardia (VT) to catheter ablation or antiarrhythmic drugs (AAD) as a first-line strategy. The primary outcome was a composite of cardiovascular death, appropriate implantable cardioverter-defibrillator shocks, unplanned heart failure hospitalizations, or severe treatment-related complications. We used informative, skeptical, and non-informative priors with different probabilities of large effects to compute the posterior distributions using Markov Chain Monte Carlo methods. We calculated the probabilities of hazard ratios (HR) being <1, <0.9, and <0.75, as well as 2-year survival estimates. Of the 144 randomized patients, 71 underwent catheter ablation and 73 received AAD. Regardless of the prior, catheter ablation had a >98% probability of reducing the primary outcome (HR < 1) and a >96% probability of achieving a reduction of >10% (HR < 0.9). The probability of a >25% (HR < 0.75) reduction of treatment-related complications was >90%. Catheter ablation had a high probability (>93%) of reducing incessant/slow undetected VT/electric storm, unplanned hospitalizations for ventricular arrhythmias, and overall cardiovascular admissions > 25%, with absolute differences of 15.2%, 21.2%, and 20.2%, respectively. CONCLUSION: In patients with ischaemic cardiomyopathy and VT, catheter ablation as a first-line therapy resulted in a high probability of reducing several clinical outcomes compared to AAD. Our study highlights the value of Bayesian analysis in clinical trials and its potential for guiding treatment decisions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03734562.

Case Series of Ventricular Tachycardia Ablation With Pulsed-Field Ablation: Pushing Technology Further (Into the Ventricle).

Three cases of ventricular tachycardia ablation with pulsed-field ablation technology performed at 2 separate centers are reported, highlighting the advantages and disadvantages of this tool inside the ventricle: its dependence on proximity rather than contact makes it useful in sites with poor stability, while the speed of application and large scope of action provided by commercially available catheters could help with ablating large diseased areas of endocardium in a fast and hemodynamically well-tolerated fashion. However, lesion depth could be insufficient for guaranteeing efficacy in preventing ventricular tachycardias originating at an epicardial site, even in the right ventricle.

Machine Learning approach for TWA detection relying on ensemble data design.

Background and objective: T-wave alternans (TWA) is a fluctuation of the ST-T complex of the surface electrocardiogram (ECG) on an every-other-beat basis. It has been shown to be clinically helpful for sudden cardiac death stratification, though the lack of a gold standard to benchmark detection methods limits its application and impairs the development of alternative techniques. In this work, a novel approach based on machine learning for TWA detection is proposed. Additionally, a complete experimental setup is presented for TWA detection methods benchmarking. Methods: The proposed experimental setup is based on the use of open-source databases to enable experiment replication and the use of real ECG signals with added TWA episodes. Also, intra-patient overfitting and class imbalance have been carefully avoided. The Spectral Method (SM), the Modified Moving Average Method (MMA), and the Time Domain Method (TM) are used to obtain input features to the Machine Learning (ML) algorithms, namely, K Nearest Neighbor, Decision Trees, Random Forest, Support Vector Machine and Multi-Layer Perceptron. Results: There were not found large differences in the performance of the different ML algorithms. Decision Trees showed the best overall performance (accuracy 0.88 ± 0.04 , precision 0.89 ± 0.05 , Recall 0.90 ± 0.05 , F1 score 0.89 ± 0.03 ). Compared to the SM (accuracy 0.79, precision 0.93, Recall 0.64, F1 score 0.76) there was an improvement in every metric except for the precision. Conclusions: In this work, a realistic database to test the presence of TWA using ML algorithms was assembled. The ML algorithms overall outperformed the SM used as a gold standard. Learning from data to identify alternans elicits a substantial detection growth at the expense of a small increment of the false alarm.

Stabilization of unstable reentrant atrial tachycardias via fractionated continuous electrical activity ablation (CHAOS study).

BACKGROUND: Unstable reentrant atrial tachycardias (ATs) (i.e., those with frequent circuit modification or conversion to atrial fibrillation) are challenging to ablate. We tested a strategy to achieve arrhythmia stabilization into mappable stable ATs based on the detection and ablation of rotors. METHODS: All consecutive patients from May 2017 to December 2019 were included. Mapping was performed using conventional high-density mapping catheters (IntellaMap ORION, PentaRay NAV, or Advisor HD Grid). Rotors were subjectively identified as fractionated continuous (or quasi-continuous) electrograms on 1-2 adjacent bipoles, without dedicated software. In patients without detectable rotors, sites with spatiotemporal dispersion (i.e., all the cycle length comprised within the mapping catheter) plus non-continuous fractionation on single bipoles were targeted. Ablation success was defined as conversion to a stable AT or sinus rhythm. RESULTS: Ninety-seven patients with reentrant ATs were ablated. Of these, 18 (18.6%) presented unstable circuits. Thirteen (72%) patients had detectable rotors (median 2 [1-3] rotors per patient); focal ablation was successful in 12 (92%). In the other 5 patients, 17 sites with spatiotemporal dispersion were identified and targeted. Globally, and excluding 1 patient with spontaneous AT stabilization, ablation success was achieved in 16/17 patients (94.1%). One-year freedom from atrial arrhythmias was similar between patients with unstable and stable ATs (66.7% vs. 65.8%, p = 0.946). CONCLUSIONS: Most unstable reentrant ATs show detectable rotors, identified as sites with single-bipole fractionated quasi-continuous signals, or spatiotemporal dispersion plus non-continuous fractionation. Ablation of these sites is highly effective to stabilize the AT or convert it into sinus rhythm.

Automatic identification of areas with low-voltage fragmented electrograms for the detection of the critical isthmus of atypical atrial flutters.

INTRODUCTION: Critical isthmuses of atypical atrial flutters (AAFLs) are usually located at slow conduction areas that exhibit fractionated electrograms. We tested a novel software, intended for integration with a commercially available navigation system, that automatically detects fractionated electrograms, to identify the critical isthmus in patients with AAFL ablation. METHODS AND RESULTS: All available patients were analyzed; 27 patients with 33 AAFLs were included. The PentaRay NAV catheter (Biosense Webster) was used for mapping. The novel software was retrospectively applied; fractionated points with duration ≥80 ms and bipolar voltage between 0.05 and 0.5 mV were highlighted on the surface of maps. In 10 randomly chosen AAFLs, an expert electrophysiologist evaluated the positive predictive value of the algorithm to detect true fractionation: 74.4%. We tested the capacity of the software to identify areas of fractionation (defined as clusters of ≥3 adjacent points with fractionation) at the critical isthmus of the AAFLs (defined using conventional mapping criteria). An area of fractionation was identified at the critical isthmus in 30 cases (91%). Globally, 144 areas of fractionation (median number per AAFL 4 [3-6]) were identified. Duration of the fractionation or the surface of the areas was not different between areas at critical isthmuses and the rest. Setting the fractionation score filter of the software in nine provided best performance. CONCLUSIONS: The novel software detected areas of fractionation at the critical isthmus in most AAFLs, which may help identify the critical isthmus in clinical practice.

Characterization of high-power and very-high-power short-duration radiofrequency lesions performed with a new-generation catheter and a temperature-control ablation mode.

INTRODUCTION: High-power short-duration (HPSD) has been proposed to shorten procedure times while maintaining efficacy and safety. We evaluated the differences in size and geometry between radiofrequency lesions obtained with this method and conventional ones. METHODS AND RESULTS: Twenty-eight sets of 10 perpendicular radiofrequency applications were performed with two commercially available catheters: a temperature-controlled HPSD catheter (QDot-Micro) and a conventional power-controlled catheter (Thermocool SmartTouch) on porcine left ventricle. Different power settings (35, 40, 50, and 90 W), contact force (CF; 10 and 20 g), ablation index (AI; 400 and 550), and application times were combined to create conventional (35-40 W), HPSD (50 W) and very-high-power short-duration (VHPSD; 90 W) lesions, that were cross-sectioned and measured. About 4-s VHPSD lesions were smaller, shallower, and thinner than HPSD performed with the QDot-Micro catheter in any scenario of CF or AI (61 ± 7.8 mm3 , 6.1 ± 0.3 mm wide, and 2.9 ± 0.1 mm deep with 10 g; 72.2 ± 0.5 mm3 , 6.8 ± 0.3 mm wide, and 2.9 ± 0.2 mm deep with 20 g). Conventional and HPSD lesions performed with the temperature-controlled catheter were generally bigger, deeper, and wider than the ones obtained with the power-controlled catheter, as well as more consistent in size. This was especially true with the lower CF and AI scenario, while differences were less notable with other setting combinations. CONCLUSION: VHPSD lesions performed with QDot-Micro catheter were smaller than any other lesions, which is especially attractive for posterior left atrial wall ablation. On the contrary, conventional-powered and HPSD lesions performed with this catheter were equally sized (or even bigger with lower CF and AI objectives), as well as more consistent in size, which would guarantee transmurality in other locations.

Validity and Reliability of an Offline Ultrasound Measurement of Bladder Base Displacement in Women.

The effect of different exercises on the position of pelvic organs in women has not been sufficiently assessed. The objective was to analyze the validity and reliability of a new two-dimensional ultrasound algorithm to measure offline the displacement of the bladder base during abdominal exercises. This algorithm could be a useful method to future studies in determine the most appropriate exercises in sports and in rehabilitative program for the pelvic floor in women. All subjects were tested by transverse transabdominal ultrasound. The measurements were conducted offline using a customized code written in MATLAB (Ecolab) for image-processing, and manually on the ultrasound monitor using electronic calipers. The agreement was assessed with a paired t-test, Pearson's linear correlation coefficient (r), the Lin's concordance correlation coefficient (CCC), the intraclass correlation coefficient ICC (A,2) and a Bland-Altman plot. The reliability was confirmed by the interdays intra-rater ICC coefficient. The results were that Ecolab and ultrasound transducer measures did not differ statistically (p = 0.246). Furthermore, both methods showed a very strong relationship, and the Ecolab demonstrated to be a valid and reliable method. We concluded that Ecolab seemed to be a valid and reliable tool to assess the effect of abdominal contractions in the female pelvic floor.

Substrate Ablation vs Antiarrhythmic Drug Therapy for Symptomatic Ventricular Tachycardia.

BACKGROUND: In patients with ischemic cardiomyopathy and an implantable cardioverter-defibrillator (ICD), catheter ablation and antiarrhythmic drugs (AADs) reduce ICD shocks, but the most effective approach remains uncertain. OBJECTIVES: This trial compares the efficacy and safety of catheter ablation vs AAD as first-line therapy in ICD patients with symptomatic ventricular tachycardias (VTs). METHODS: The SURVIVE-VT (Substrate Ablation vs Antiarrhythmic Drug Therapy for Symptomatic Ventricular Tachycardia) is a prospective, multicenter, randomized trial including patients with ischemic cardiomyopathy and appropriated ICD shock. Patients were 1:1 randomized to complete endocardial substrate-based catheter ablation or antiarrhythmic therapy (amiodarone + beta-blockers, amiodarone alone, or sotalol ± beta-blockers). The primary outcome was a composite of cardiovascular death, appropriate ICD shock, unplanned hospitalization for worsening heart failure, or severe treatment-related complications. RESULTS: In this trial, 144 patients (median age, 70 years; 96% male) were randomized to catheter ablation (71 patients) or AAD (73 patients). After 24 months, the primary outcome occurred in 28.2% of patients in the ablation group and 46.6% of those in the AAD group (hazard ratio [HR]: 0.52; 95% CI: 0.30-0.90; P = 0.021). This difference was driven by a significant reduction in severe treatment-related complications (9.9% vs 28.8%, HR: 0.30; 95% CI: 0.13-0.71; P = 0.006). Eight patients were hospitalized for heart failure in the ablation group and 13 in the AAD group (HR: 0.56; 95% CI: 0.23-1.35; P = 0.198). There was no difference in cardiac mortality (HR: 0.93; 95% CI: 0.19-4.61; P = 0.929). CONCLUSIONS: In ICD patients with ischemic cardiomyopathy and symptomatic VT, catheter ablation reduced the composite endpoint of cardiovascular death, appropriate ICD shock, hospitalization due to heart failure, or severe treatment-related complications compared to AAD. (Substrate Ablation vs Antiarrhythmic Drug Therapy for Symptomatic Ventricular Tachycardia [SURVIVE-VT]: NCT03734562).

Exploring the role of the left DLPFC in fatigue during unresisted rhythmic movements.

Understanding central fatigue during motor activities is important in neuroscience and different medical fields. The central mechanisms of motor fatigue are known in depth for isometric muscle contractions; however, current knowledge about rhythmic movements and central fatigue is rather scarce. In this study, we explored the role of an executive area (left dorsolateral prefrontal cortex [DLPFC]) in fatigue development during rhythmic movement execution, finger tapping (FT) at the maximal rate, and fatigue after effects on the stability of rhythmic patterns. Participants (n = 19) performed six sets of unresisted FT (with a 3 min rest in-between). Each set included four interleaved 30 s repetitions of self-selected (two repetitions) and maximal rate FT (two repetitions) without rest in-between. Left DLPFC involvement in the task was perturbed by transcranial static magnetic stimulation (tSMS) in two sessions (one real and one sham). Moreover, half of the self-selected FT repetitions were performed concurrently with a demanding cognitive task, the Stroop test. Compared with sham stimulation, real tSMS stimulation prevented waning in tapping frequency at the maximal rate without affecting perceived levels of fatigue. Participants' engagement in the Stroop test just prior to maximal FT reduced the movement amplitude during this mode of execution. Movement variability at self-selected rates increased during Stroop execution, especially under fatigue previously induced by maximal FT. Our results indicate cognitive-motor interactions and a prominent role of the prefrontal cortex in fatigue and the motor control of simple repetitive movement patterns. We suggest the need to approach motor fatigue including cognitive perspectives.

Impact of power and contact force on index-guided radiofrequency lesions in an ex vivo porcine heart model.

PURPOSE: Lesion size index (LSI) and ablation index (AI) are markers of lesion quality that incorporate power, contact force (CF) and time in a weighted formula to estimate lesion size. Although accurate predicting lesion depth in vitro, their precision in lesion size estimation has not been well established for certain power and CF settings. We conducted an experimental ex vivo study to analyse the effect of power and CF in size and morphology of ablation lesions in a porcine heart model. METHODS: Twenty-four sets of 10 perpendicular epicardial radiofrequency applications were performed with two commercially available catheters (TactiCath, Sensor Enabled; and SmartTouch) on porcine left ventricle submerged in 37 °C saline, combining different power (25, 30, 35, 40, 50 and 60 W) and CF (10 and 20 g) settings, and aiming at a lower (LSI/AI of 5/400) or higher (LSI/AI of 6/550) index. After each application, lesions were cross-sectioned and measured. RESULTS: Four hundred eighty lesions were performed. For a given target index and CF, significant differences in lesion volume and depth with different power were observed with both catheters, generally with smaller lesions using higher power. Lesions performed with CF of 10 g were particularly smaller with TactiCath compared to SmartTouch; lesions with CF of 20 g aiming a low LSI/AI were, however, bigger; lesions with CF of 20 g aiming a high LSI/AI were similar. In general, high-power lesions were wider and shallower than low-power lesions, especially with SmartTouch. CONCLUSION: Size and morphology of index-guided radiofrequency lesions varied significantly with different power and CF settings.

High-density mapping with fragmentation analysis in patients with reentrant atrial tachycardias (MAP-FLURHY study).

PURPOSE: Reentrant atrial tachycardias (ATs) use areas of slow conduction that can be visualized as fragmented electrograms. We aimed to test an ablation strategy based on the identification and ablation of spots with fragmented electrograms in reentrant ATs, using Rhythmia navigation system. METHODS: All consecutive patients from June 2016 to June 2019 were included. The IntellaMap ORION Catheter was used to detect sites with fragmentation, arbitrarily defined as fragmented electrograms > 70 ms. Entrainment was used to check if these areas belonged to the AT circuit. Ablation targeted the longest fragmented electrogram within the circuit: focal ablation for microreentries and lines for macroreentries. Ablation success was defined from each AT as conversion to sinus rhythm or another AT. RESULTS: Twenty-seven consecutive patients with 44 mappable ATs were included. All ATs showed sites with fragmented electrograms (104 sites; 2.4 sites per AT); 43/44 ATs had fragmented electrograms within the circuit, which were the target of ablation. Ablation success: 34/36 ATs (94%); success could not be assessed in 8 circuits, in 6 due to mechanical conversion to sinus rhythm at the target fragmented site. Fragmented electrograms within the AT circuits were longer than electrograms outside the circuits (110 ± 30 vs 90 ± 15 ms, p < 0.001). A fragmentation duration > 100 ms/ > 40% of the AT cycle length predicted to be a successful site for ablation with 72.3%/73.8% specificity, respectively. Sixty-two percent of the patients were free from atrial arrhythmias at 1 year. CONCLUSIONS: Most ATs had detectable fragmented electrograms within the circuit, which could be the target of ablation with high efficacy.

Peripheral-central interplay for fatiguing unresisted repetitive movements: a study using muscle ischaemia and M1 neuromodulation.

Maximal-rate rhythmic repetitive movements cannot be sustained for very long, even if unresisted. Peripheral and central mechanisms of fatigue, such as the slowing of muscle relaxation and an increase in M1-GABAb inhibition, act alongside the reduction of maximal execution rates. However, maximal muscle force appears unaffected, and it is unknown whether the increased excitability of M1 GABAergic interneurons is an adaptation to the waning of muscle contractility in these movements. Here, we observed increased M1 GABAb inhibition at the end of 30 s of a maximal-rate finger-tapping (FT) task that caused fatigue and muscle slowdown in a sample of 19 healthy participants. The former recovered a few seconds after FT ended, regardless of whether muscle ischaemia was used to keep the muscle slowed down. Therefore, the increased excitability of M1-GABAb circuits does not appear to be mediated by afferent feedback from the muscle. In the same subjects, continuous (inhibitory) and intermittent (excitatory) theta-burst stimulation (TBS) was used to modulate M1 excitability and to understand the underlying central mechanisms within the motor cortex. The effect produced by TBS on M1 excitability did not affect FT performance. We conclude that fatigue during brief, maximal-rate unresisted repetitive movements has supraspinal components, with origins upstream of the motor cortex.

Effect of stimulation timing on testing voluntary muscle force generation.

BACKGROUND: The interpolated twitch technique (ITT) is a ubiquitous test for assessing the level of voluntary muscle force generation, in which muscle twitches are evoked via percutaneous electrical stimulation. Traditionally, the stimulation timing during the ITT is not computer-controlled and usually delivered from 5 to 10 s after the maximal voluntary contraction (MVC) of the potentiated muscle. METHODS: In this work, we evaluated the sizes of the evoked twitches in the lower limb with different controlled stimulation time delays with respect to the MVC of the ankle plantar flexors. Fifteen healthy participants were included. We recorded the un-potentiated muscle twitch amplitudes at rest in response to doublet supramaximal stimulation of the tibial nerve, superimposed twitches (SITs) at three different delays from the beginning of the MVC force plateau (0.1, 0.75, and 1.5 s), and resting twitches in the potentiated muscle at four different delays once the MVC was finished (0.1, 2.5, 5.0, and 10.0 s). RESULTS: The magnitude of the SITs did not vary among the delays tested but varied among the potentiated resting twitch (PRT) amplitudes, with 2.5 s being largest and 0.1 s being the smallest. Remarkably, the resting twitch amplitudes reduced during the session despite the long rest periods between MVCs (5 min). CONCLUSION: We conclude that proper control of the stimulation timing is mandatory to increase the sensitivity of the ITT, and a 2.5 s delay from the end of the MVC is recommended for the PRT. Controlling the development of fatigue, which can be intrinsic to testing with repeated MVCs, is also essential. We recommend reducing the number of MVC repetitions and increasing the rest periods between them.

Temporal dynamics of muscle, spinal and cortical excitability and their association with kinematics during three minutes of maximal-rate finger tapping.

We tested peripheral, spinal and cortical excitability during 3 minutes of unresisted finger tapping at the maximal possible rate, which induced fatigue. Subsequently, we studied the temporal dynamics of muscle fatigue, expressed in the tapping movement profile, and its relationship to neural systems using mixed model analyses. The tapping rate decreased by 40% over the duration of the task. The change in the amplitude of the range of motion was not significant. The excitability of the flexor and extensor muscles of the index finger was tested via evoked potentials obtained with various types of stimulation at various levels of the motor system. The change in spinal excitability with time was evaluated considering the simultaneous changes in muscle excitability; we also considered how spinal excitability changed over time to evaluate cortical excitability. Excitability in the flexor and extensor muscles at the different levels tested changed significantly, but similar excitability levels were observed at notably different tapping rates. Our results showed that only 33% of the decrease in the tapping rate was explained by changes in the excitability of the structures tested in the present work.

Heart failure hospitalization reduction and cost savings achieved by improved delivery of effective biventricular pacing: economic implications of the OLE study under the US setting.

Background: The hOLter for Efficacy analysis (OLE) study demonstrated that current device pacing diagnostics overestimate the amount of cardiac resynchronization therapy (CRT) pacing that effectively stimulates the cardiac tissue. Sub-optimal pacing increases mortality, hospitalizations, and associated health-care costs. We sought to estimate the expected number of hospital admissions due to heart failure (HF) and its respective financial impact in patients with maximized effective pacing versus conventional pacing. Methods: A Markov model was developed to project HF hospitalizations and quantify the costs that could be avoided if pacing was maximally effective. OLE data were used to inform the prevalence of ineffective pacing among CRT patients and and average loss of pacing by causes. Adaptive CRT trial data quantified the reduction in underlying hospitalization risk by increasing effective pacing delivered. Survival was informed by a meta-analysis of 5 randomized clinical trials. Costs were analyzed from a US payer perspective. Results: Projected average hospitalizations totaled 4.58 over a lifetime horizon for CRT patients with conventional pacing. Maximizing effective pacing delivery was projected to avoid 1.83 HF admissions/patient over the lifetime. This equates to a savings of 40% (US$22,802) compared with conventional pacing from the Medicare perspective. In a sensitivity analysis, CRT with effective pacing was projected to provide cost savings in all scenarios. Conclusions: Maximized effective pacing leads to a lower number of HF hospitalizations, thus allowing significant cost offsets in the US setting.