Italian Association of Hospital Cardiologists Position Paper 'Gender discrepancy: time to implement gender-based clinical management'.

It has been well assessed that women have been widely under-represented in cardiovascular clinical trials. Moreover, a significant discrepancy in pharmacological and interventional strategies has been reported. Therefore, poor outcomes and more significant mortality have been shown in many diseases. Pharmacokinetic and pharmacodynamic differences in drug metabolism have also been described so that effectiveness could be different according to sex. However, awareness about the gender gap remains too scarce. Consequently, gender-specific guidelines are lacking, and the need for a sex-specific approach has become more evident in the last few years. This paper aims to evaluate different therapeutic approaches to managing the most common women's diseases.

Implantable defibrillator-detected heart failure status predicts ventricular tachyarrhythmias.

INTRODUCTION: The prediction of ventricular tachyarrhythmias among patients with implantable cardioverter defibrillators is difficult with available clinical tools. We sought to assess whether in patients with heart failure (HF) and reduced ejection fraction with defibrillators, physiological sensor-based HF status, as summarized by the HeartLogic index, could predict appropriate device therapies. METHODS: Five hundred and sixty-eight consecutive HF patients with defibrillators (n = 158, 28%) or cardiac resynchronization therapy-defibrillators (n = 410, 72%) were included in this prospective observational multicenter analysis. The association of both HeartLogic index and its physiological components with defibrillator shocks and overall appropriate therapies was assessed in regression and time-dependent Cox models. RESULTS: Over a follow-up of 25 (15-35) months, 122 (21%) patients received an appropriate device therapy (shock, n = 74, 13%), while the HeartLogic index crossed the threshold value (alert, HeartLogic ≥ 16) 1200 times (0.71 alerts/patient-year) in 370 (65%) subjects. The occurrence of ≥1 HeartLogic alert was significantly associated with both appropriate shocks (Hazard ratios [HR]: 2.44, 95% confidence interval [CI]: 1.49-3.97, p = .003), and any appropriate defibrillator therapies. In multivariable time-dependent Cox models, weekly IN-alert state was the strongest predictor of appropriate defibrillator shocks (HR: 2.94, 95% CI: 1.73-5.01, p < .001) and overall therapies. Compared with stable patients, patients with appropriate shocks had significantly higher values of HeartLogic index, third heart sound amplitude, and resting heart rate 30-60 days before device therapy. CONCLUSION: The HeartLogic index is an independent dynamic predictor of appropriate defibrillator therapies. The combined index and its individual physiological components change before the arrhythmic event occurs.

Combination of an implantable defibrillator multi-sensor heart failure index and an apnea index for the prediction of atrial high-rate events.

AIMS: Patients with atrial fibrillation frequently experience sleep disorder breathing, and both conditions are highly prevalent in presence of heart failure (HF). We explored the association between the combination of an HF and a sleep apnoea (SA) index and the incidence of atrial high-rate events (AHRE) in patients with implantable defibrillators (ICDs). METHODS AND RESULTS: Data were prospectively collected from 411 consecutive HF patients with ICD. The IN-alert HF state was measured by the multi-sensor HeartLogic Index (>16), and the ICD-measured Respiratory Disturbance Index (RDI) was computed to identify severe SA. The endpoints were as follows: daily AHRE burden of ≥5 min, ≥6 h, and ≥23 h. During a median follow-up of 26 months, the time IN-alert HF state was 13% of the total observation period. The RDI value was ≥30 episodes/h (severe SA) during 58% of the observation period. An AHRE burden of ≥5 min/day was documented in 139 (34%) patients, ≥6 h/day in 89 (22%) patients, and ≥23 h/day in 68 (17%) patients. The IN-alert HF state was independently associated with AHRE regardless of the daily burden threshold: hazard ratios from 2.17 for ≥5 min/day to 3.43 for ≥23 h/day (P < 0.01). An RDI ≥ 30 episodes/h was associated only with AHRE burden ≥5 min/day [hazard ratio 1.55 (95% confidence interval: 1.11-2.16), P = 0.001]. The combination of IN-alert HF state and RDI ≥ 30 episodes/h accounted for only 6% of the follow-up period and was associated with high rates of AHRE occurrence (from 28 events/100 patient-years for AHRE burden ≥5 min/day to 22 events/100 patient-years for AHRE burden ≥23 h/day). CONCLUSIONS: In HF patients, the occurrence of AHRE is independently associated with the ICD-measured IN-alert HF state and RDI ≥ 30 episodes/h. The coexistence of these two conditions occurs rarely but is associated with a very high rate of AHRE occurrence. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov/Identifier: NCT02275637.

Performance of a multi-sensor implantable defibrillator algorithm for heart failure monitoring in the presence of atrial fibrillation.

AIMS: The HeartLogic Index combines data from multiple implantable cardioverter defibrillators (ICDs) sensors and has been shown to accurately stratify patients at risk of heart failure (HF) events. We evaluated and compared the performance of this algorithm during sinus rhythm and during long-lasting atrial fibrillation (AF). METHODS AND RESULTS: HeartLogic was activated in 568 ICD patients from 26 centres. We found periods of ≥30 consecutive days with an atrial high-rate episode (AHRE) burden <1 h/day and periods with an AHRE burden ≥20 h/day. We then identified patients who met both criteria during the follow-up (AHRE group, n = 53), to allow pairwise comparison of periods. For control purposes, we identified patients with an AHRE burden <1 h throughout their follow-up and implemented 2:1 propensity score matching vs. the AHRE group (matched non-AHRE group, n = 106). In the AHRE group, the rate of alerts was 1.2 [95% confidence interval (CI): 1.0-1.5]/patient-year during periods with an AHRE burden <1 h/day and 2.0 (95% CI: 1.5-2.6)/patient-year during periods with an AHRE-burden ≥20 h/day (P = 0.004). The rate of HF hospitalizations was 0.34 (95% CI: 0.15-0.69)/patient-year during IN-alert periods and 0.06 (95% CI: 0.02-0.14)/patient-year during OUT-of-alert periods (P < 0.001). The IN/OUT-of-alert state incidence rate ratio of HF hospitalizations was 8.59 (95% CI: 1.67-55.31) during periods with an AHRE burden <1 h/day and 2.70 (95% CI: 1.01-28.33) during periods with an AHRE burden ≥20 h/day. In the matched non-AHRE group, the rate of HF hospitalizations was 0.29 (95% CI: 0.12-0.60)/patient-year during IN-alert periods and 0.04 (95% CI: 0.02-0.08)/patient-year during OUT-of-alert periods (P < 0.001). The incidence rate ratio was 7.11 (95% CI: 2.19-22.44). CONCLUSION: Patients received more alerts during periods of AF. The ability of the algorithm to identify increased risk of HF events was confirmed during AF, despite a lower IN/OUT-of-alert incidence rate ratio in comparison with non-AF periods and non-AF patients. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov/Identifier: NCT02275637.

[New frontiers in pacing: from myocardial pacing to conduction system pacing]. / Nuove frontiere dell'elettrostimolazione: dal pacing del miocardio comune al pacing del sistema di conduzione.

For many years, cardiac pacing has been based on the stimulation of right ventricular common myocardium to correct diseases of the conduction system. The birth and the development of cardiac resynchronization have led to growing interest in the correction and prevention of pacing-induced dyssynchrony. Many observational studies and some randomized clinical trials have shown that conduction system pacing (CSP) can not only prevent pacing-induced dyssynchrony but can also correct proximal conduction system blocks, with reduction of QRS duration and with equal or greater effectiveness than biventricular pacing. Based on these results, many Italian electrophysiologists have changed the stimulation target from the right ventricular common myocardium to CSP. The two techniques with greater clinical impact are the His bundle stimulation and the left bundle branch pacing. The latter, in particular, because of its easier implantation technique and better electric parameters, is spreading like wildfire and is representing a real revolution in the cardiac pacing field. However, despite the growing amount of data, until now, the European Society of Cardiology guidelines give a very limited role to CSP.

Association between amount of biventricular pacing and heart failure status measured by a multisensor implantable defibrillator algorithm.

Background: Achieving a high biventricular pacing percentage (BiV%) is crucial for optimizing outcomes in cardiac resynchronization therapy (CRT). The HeartLogic index, a multiparametric heart failure (HF) risk score, incorporates implantable cardioverter-defibrillator (ICD)-measured variables and has demonstrated its predictive ability for impending HF decompensation. Objective: This study aimed to investigate the relationship between daily BiV% in CRT ICD patients and their HF status, assessed using the HeartLogic algorithm. Methods: The HeartLogic algorithm was activated in 306 patients across 26 centers, with a median follow-up of 26 months (25th-75th percentile: 15-37). Results: During the follow-up period, 619 HeartLogic alerts were recorded in 186 patients. Overall, daily values associated with the best clinical status (highest first heart sound, intrathoracic impedance, patient activity; lowest combined index, third heart sound, respiration rate, night heart rate) were associated with a BiV% exceeding 99%. We identified 455 instances of BiV% dropping below 98% after consistent pacing periods. Longer episodes of reduced BiV% (hazard ratio: 2.68; 95% CI: 1.02-9.72; P = .045) and lower BiV% (hazard ratio: 3.97; 95% CI: 1.74-9.06; P=.001) were linked to a higher risk of HeartLogic alerts. BiV% drops exceeding 7 days predicted alerts with 90% sensitivity (95% CI [74%-98%]) and 55% specificity (95% CI [51%-60%]), while BiV% ≤96% predicted alerts with 74% sensitivity (95% CI [55%-88%]) and 81% specificity (95% CI [77%-85%]). Conclusion: A clear correlation was observed between reduced daily BiV% and worsening clinical conditions, as indicated by the HeartLogic index. Importantly, even minor reductions in pacing percentage and duration were associated with an increased risk of HF alerts.

[Gender discrepancy: time to implement gender-based clinical management]. / Position paper ANMCO: Differenze di genere nell'approccio farmacologico cardiovascolare.

It is well established that gender strongly influences cardiovascular risk factors, playing a crucial role in cardiovascular prevention, clinical pathways, diagnostic approach and treatment. Beyond the sex, which is a biological factor, gender entails a socio-cultural condition that impacts access and quality of care due to structural and institutional barriers. However, despite its great importance, this issue has not been adequately covered. Indeed sex and gender differences scarcely impact the clinical approach, creating a lot of disparities in care and outcomes of patients. Therefore, it becomes essential to increase the awareness of the importance of sex and gender influences on cardiovascular diseases. Moreover, new strategies for reducing disparities should be developed. Importantly, these differences should be taken into account in guideline recommendations. In this regard, it is crucial to include a greater number of women in clinical trials, since they are currently underrepresented. Furthermore, more women should be involved as member of international boards in order to develop recommendations and guidelines with more attention to this important topic.The aim of this ANMCO position paper is to shed light on gender differences concerning many cardiovascular drugs in order to encourage a more personalized therapeutic approach.

[Temporary cardiac pacing: 50 years old and still young]. / La stimolazione cardiaca temporanea: dopo 50 anni una metodica ancora giovane.

Temporary cardiac pacing (TCP) is a 50-year-old technique but it is still young. It is used in all cardiology departments for saving lives of patients with bradycardia and hemodynamic instability. The know-how of TCP cannot miss in clinical competence of cardiologists that work in the cardiac intensive care unit. However, despite its wide diffusion, the scientific evidence supporting TCP is not so strong and in Italian hospitals the management of some aspects of TCP is highly variable, including indications as well as antibiotic and anticoagulant prophylaxis. Due to the high risk of TCP-related complications, the 2021 European guidelines on cardiac pacing recommend whenever possible to avoid TCP before cardiac implantable electronic device implantation and, in all cases, TCP duration should be as short as possible. In the last years, if on the one hand, TCP indications have gradually decreased, on the other hand high-frequency TCP during aortic valvuloplasty or transcatheter aortic valve implantation procedures have progressively increased.

[Electrical storm management in the cardiac care unit]. / Gestione della tempesta aritmica in terapia intensiva cardiologica.

Electrical storm (ES) is characterized by at least three separate episodes of ventricular arrhythmia (VA) over 24 h that require treatment or an incessant VA lasting >12 h. The incidence is higher in patients with implantable cardioverter-defibrillators (ICDs) in secondary prevention and the main manifestation is monomorphic VA. ES onset represents a major event in the history of patients with cardiomyopathies that significantly worsens prognosis. The management of ES is complex and requires a multidisciplinary approach including a comprehensive clinical assessment, resuscitation and sedation management skills, ICD reprogramming, ablation, and neuromodulation procedures. ES early recognition and prompt treatment initiation increase the chances of therapeutic success. Each one of these aspects will be properly discussed in the present decalogue. Notably, ES management remains a challenge, with only limited available evidence from small retrospective series and a substantial lack/limited number of randomized or prospective trials. The spectrum of available antiarrhythmic drugs is limited, as well as their efficacy. The future hope is that larger prospective studies will be able to answer important questions, concerning the most effective pharmacologic strategies, the timing for the invasive treatment, the indications for acute neuromodulation strategies and for the circulatory support tools.

Performance of a multisensor implantable defibrillator algorithm for heart failure monitoring related to co-morbidities.

AIMS: The HeartLogic algorithm combines multiple implantable defibrillator (ICD) sensor data and has proved to be a sensitive and timely predictor of impending heart failure (HF) decompensation in cardiac resynchronization therapy (CRT-D) patients. We evaluated the performance of this algorithm in non-CRT ICD patients and in the presence of co-morbidities. METHODS AND RESULTS: The HeartLogic feature was activated in 568 ICD patients (410 with CRT-D) from 26 centres. The median follow-up was 26 months [25th-75th percentile: 16-37]. During follow-up, 97 hospitalizations were reported (53 cardiovascular) and 55 patients died. We recorded 1200 HeartLogic alerts in 370 patients. Overall, the time IN the alert state was 13% of the total observation period. The rate of cardiovascular hospitalizations or death was 0.48/patient-year (95% CI: 0.37-0.60) with the HeartLogic IN the alert state and 0.04/patient-year (95% CI: 0.03-0.05) OUT of the alert state, with an incidence rate ratio of 13.35 (95% CI: 8.83-20.51, P < 0.001). Among patient characteristics, atrial fibrillation (AF) on implantation (HR: 1.62, 95% CI: 1.27-2.07, P < 0.001) and chronic kidney disease (CKD) (HR: 1.53, 95% CI: 1.21-1.93, P < 0.001) independently predicted alerts. HeartLogic alerts were not associated with CRT-D versus ICD implantation (HR: 1.03, 95% CI: 0.82-1.30, P = 0.775). Comparisons of the clinical event rates in the IN alert state with those in the OUT of alert state yielded incidence rate ratios ranging from 9.72 to 14.54 (all P < 0.001) in all groups of patients stratified by: CRT-D/ICD, AF/non-AF, and CKD/non-CKD. After multivariate correction, the occurrence of alerts was associated with cardiovascular hospitalization or death (HR: 1.92, 95% CI: 1.05-3.51, P = 0.036). CONCLUSIONS: The burden of HeartLogic alerts was similar between CRT-D and ICD patients, while patients with AF and CKD seemed more exposed to alerts. Nonetheless, the ability of the HeartLogic algorithm to identify periods of significantly increased risk of clinical events was confirmed, regardless of the type of device and the presence of AF or CKD.

Predicting all-cause mortality by means of a multisensor implantable defibrillator algorithm for heart failure monitoring.

BACKGROUND: The HeartLogic algorithm (Boston Scientific) has proved to be a sensitive and timely predictor of impending heart failure (HF) decompensation. OBJECTIVE: The purpose of this study was to determine whether remotely monitored data from this algorithm could be used to identify patients at high risk for mortality. METHODS: The algorithm combines implantable cardioverter-defibrillator (ICD)-measured accelerometer-based heart sounds, intrathoracic impedance, respiration rate, ratio of respiration rate to tidal volume, night heart rate, and patient activity into a single index. An alert is issued when the index crosses a programmable threshold. The feature was activated in 568 ICD patients from 26 centers. RESULTS: During median follow-up of 26 months [25th-75th percentile 16-37], 1200 alerts were recorded in 370 patients (65%). Overall, the time IN-alert state was 13% of the total observation period (151/1159 years) and 20% of the follow-up period of the 370 patients with alerts. During follow-up, 55 patients died (46 in the group with alerts). The rate of death was 0.25 per patient-year (95% confidence interval [CI] 0.17-0.34) IN-alert state and 0.02 per patient-year (95% CI 0.01-0.03) OUT of the alert state, with an incidence rate ratio of 13.72 (95% CI 7.62-25.60; P <.001). After multivariate correction for baseline confounders (age, ischemic cardiomyopathy, kidney disease, atrial fibrillation), the IN-alert state remained significantly associated with the occurrence of death (hazard ratio 9.18; 95% CI 5.27-15.99; P <.001). CONCLUSION: The HeartLogic algorithm provides an index that can be used to identify patients at higher risk for all-cause mortality. The index state identifies periods of significantly increased risk of death.

Management of oral anticoagulant therapy after intracranial hemorrhage in patients with atrial fibrillation.

Intracranial hemorrhage (ICH) is considered a potentially severe complication of oral anticoagulants (OACs) and antiplatelet therapy (APT). Patients with atrial fibrillation (AF) who survived ICH present both an increased ischemic and bleeding risk. Due to its lethality, initiating or reinitiating OACs in ICH survivors with AF is challenging. Since ICH recurrence may be life-threatening, patients who experience an ICH are often not treated with OACs, and thus remain at a higher risk of thromboembolic events. It is worthy of mention that subjects with a recent ICH and AF have been scarcely enrolled in randomized controlled trials (RCTs) on ischemic stroke risk management in AF. Nevertheless, in observational studies, stroke incidence and mortality of patients with AF who survived ICH had been shown to be significantly reduced among those treated with OACs. However, the risk of hemorrhagic events, including recurrent ICH, was not necessarily increased, especially in patients with post-traumatic ICH. The optimal timing of anticoagulation initiation or restarting after an ICH in AF patients is also largely debated. Finally, the left atrial appendage occlusion option should be evaluated in AF patients with a very high risk of recurrent ICH. Overall, an interdisciplinary unit consisting of cardiologists, neurologists, neuroradiologists, neurosurgeons, patients, and their families should be involved in management decisions. According to available evidence, this review outlines the most appropriate anticoagulation strategies after an ICH that should be adopted to treat this neglected subset of patients.

Management of Patients Treated with Direct Oral Anticoagulants in Clinical Practice and Challenging Scenarios.

It is well established that direct oral anticoagulants (DOACs) are the cornerstone of anticoagulant strategy in atrial fibrillation (AF) and venous thromboembolism (VTE) and should be preferred over vitamin K antagonists (VKAs) since they are superior or non-inferior to VKAs in reducing thromboembolic risk and are associated with a lower risk of intracranial hemorrhage (IH). In addition, many factors, such as fewer pharmacokinetic interactions and less need for monitoring, contribute to the favor of this therapeutic strategy. Although DOACs represent a more suitable option, several issues should be considered in clinical practice, including drug-drug interactions (DDIs), switching to other antithrombotic therapies, preprocedural and postprocedural periods, and the use in patients with chronic renal and liver failure and in those with cancer. Furthermore, adherence to DOACs appears to remain suboptimal. This narrative review aims to provide a practical guide for DOAC prescription and address challenging scenarios.

[Management of infections in patients with cardiac implantable electronic devices]. / La gestione delle infezioni nei pazienti portatori di dispositivi impiantabili.

Implantation of pacemakers and cardiac defibrillators is a life-saving treatment but can put our patients at risk of infections, increasing morbidity and mortality and prolonging hospitalization with a significant financial healthcare burden. A preventive strategy is crucial but, while several strategies such as administration of intravenous antibiotic therapy before implantation are well recognized, other uncertainties remain. The main gaps regard the use of periprocedural measures, including antibacterial envelope to prevent device infection, the appropriate management of antithrombotic therapy before and after device implantation and timing of device reimplantation. To address these issues, some important randomized clinical trials and a European Heart Rhythm Association consensus document have recently been published. The aim of this article is to review current knowledge on the management of infections in patients with cardiac implantable electronic devices to help not only electrophysiologists, but also physicians in their daily practice.

Effects of COVID-19 lockdown on arrhythmias in patients with implantable cardioverter-defibrillators in southern Italy.

Background: The effects of lockdown on non-COVID patients are varied and unexpected. The aim is to evaluate the burden of cardiac arrhythmias during a lockdown period because of COVID-19 pandemics in a population implanted with cardiac defibrillators and followed by remote monitoring. Methods: In this retrospective, multicentre cohort study, we included 574 remotely monitored implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D) recipients implanted before January 1, 2019, at seven hospitals in the Campania region, comparing the burden of arrhythmias occurred during the lockdown period because of COVID-19 epidemics (from March 9 to May 1, 2020) with the arrhythmias burden of the corresponding period in 2019 (reference period). Data collection was performed through remote monitoring. Results: During the lockdown period, we observed ventricular tachyarrhythmias (ventricular tachycardia or fibrillation) in 25 (4.8%) patients while in seasonal reference period we documented ventricular tachyarrhythmias in 12 (2.3%) patients; the comparison between the periods is statistically significant (P < .04). Atrial arrhythmias were detected in 38 (8.2%) subjects during the lockdown period and in 24 (5.2%) during the reference period (P < .004). Conclusion: In seven hospitals in the Campania region, during the pandemic lockdown period, we observed a higher burden of arrhythmic events in ICD/CRT-D patients through device remote monitoring.

Implantable defibrillator-detected heart failure status predicts atrial fibrillation occurrence.

BACKGROUND: In heart failure (HF) patients, atrial fibrillation (AF) is associated with a worse prognosis. Implantable cardioverter-defibrillator (ICD) diagnostics allow continuous monitoring of AF and are equipped with algorithms for HF monitoring. OBJECTIVE: We evaluated the association between the values of the multisensor HF HeartLogic index and the incidence of AF, and assessed the performance of the index in detecting follow-up periods of significantly increased AF risk. METHODS: The HeartLogic feature was activated in 568 ICD patients. Median follow-up was 25 months [25th-75th percentile (15-35)]. The HeartLogic algorithm calculates a daily HF index and identifies periods of IN-alert state on the basis of a configurable threshold. The endpoints were daily AF burden ≥5 minutes, ≥6 hours, and ≥23 hours. RESULTS: The HeartLogic index crossed the threshold value 1200 times. AF burden ≥5 minutes/day was documented in 183 patients (32%), ≥6 hours/day in 118 patients (21%), and ≥23 hours/day in 89 patients (16%). The weekly time of IN-alert state was independently associated with AF burden ≥5 minutes/day (hazard ratio [HR] 1.95; 95% confidence interval [CI] 1.22-3.13; P = .005), ≥6 hours/day (HR 2.66; 95% CI 1.60-4.44; P <.001), and ≥23 hours/day (HR 3.32; 95% CI 1.83-6.02; P <.001), after correction for baseline confounders. Comparison of the episode rates in the IN-alert state with those in the OUT-of-alert state yielded HR ranging from 1.57 to 3.11 for AF burden from ≥5 minutes to ≥23 hours. CONCLUSIONS: The HeartLogic alert state was independently associated with AF occurrence. The intervals of time defined by the algorithm as periods of increased risk of HF allow risk stratification of AF according to various thresholds of daily burden.

[Arrhythmias and sudden death in neuromuscular disorders]. / Aritmie e morte improvvisa nelle malattie neuromuscolari.

Neuromuscular diseases (NMD) are a broadly defined group of disorders that all involve injury or dysfunction of peripheral nerves, neuromuscular junction or muscle, often with dominant or recessive pattern of inheritance. Cardiac involvement is uncommon, in particular with cardiomyopathies and brady/tachyarrhythmias. The causes of cardiac involvement are unclear: replacement fibrosis, alteration of membrane permeability, sympathetic hyperactivity, or accumulation of toxic metabolites can play a role in the pathogenesis of cardiac disorders. The early diagnosis is of pivotal importance to prevent evolution of the disease: electrocardiographic alterations and arrhythmias, particularly if associated with family history for cardiomyopathy or sudden death, can be an early signal of cardiomyopathy associated with NMD. Genetic analysis can improve prognostic stratification, particularly related to arrhythmic risk, and guide to a tailored therapy.

Design and rationale of the Impact of MultiPoint pacing in CRT patients with reduced RV-to-LV delay (IMAGE-CRT) study.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an established treatment in patients with heart failure and prolonged QRS duration. A biventricular device is implanted to achieve faster activation and more synchronous contraction of the ventricles. Despite the convincing effect of CRT, 30-40% of patients do not respond. We decided to investigate the role of multipoint pacing (MPP) in a selected group of patients with right ventricle (RV)-to-left ventricle (LV) intervals less than 80 ms that do not respond to traditional CRT. METHODS: We will enrol 248 patients in this patient-blinded, observational, clinical study aiming to investigate if MPP could decrease LV end-systolic volume (ESV) in patients with RV-to-LV interval less than 80 ms. MPP will be activated ON at implant in patients with RV-to-LV delay less than 80 ms and OFF in RV-to-LV at least 80 ms. At follow-up the activation of MPP will be related to CRT response. The primary study endpoint will be the responder rate at 6 months, defined as a decrease in LV ejection fraction, LV end-diastolic volume, LV end-systolic volume (LVESV) at least 15% from baseline. Secondary outcomes include 12 months relative percentage reduction in LVESV and a combined clinical outcome measure of response to CRT defined as the patient being alive, no hospitalization due to heart failure, and experiencing an improvement in New York Heart Association functional class (Composite-Score). CONCLUSION: Reducing the nonresponder rate continues to be an important goal for CRT.If an increase in reverse remodelling can be achieved by MPP, this study supports the conduct of larger trials investigating the role of MPP on clinical outcomes in selected patients treated, right now, only with traditional CRT. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02713308. Registered on 18 March 2016.

Effect of right ventricular apical pacing in survivors of myocardial infarction.

BACKGROUND: Much information is available regarding the possible negative effects of long-term right ventricular (RV) apical pacing, which may cause worsening of heart failure. However, very limited data are available regarding the effects of RV pacing in patients with a previous myocardial infarction (MI). METHODS AND RESULTS: We screened 115 consecutive post-MI patients and matched a group of 29 pacemaker (PM) recipients with a group of 49 unpaced patients, for age, left ventricular (LV) ejection fraction, and site of MI. During a median follow-up of 54 months, echocardiograms showed a decrease in LV ejection fraction in the paced group, from 51 +/- 10 to 39 +/- 11 (P < 0.01), and a minimal change in the unpaced group, from 57 +/- 8 to 56 +/- 7 (P = 0.98). Similar change was observed in systolic and diastolic diameters and volumes. CONCLUSIONS: The study showed that, in post-MI patients, RV apical pacing was associated with a worsening of LV function, suggesting that, among MI survivors, the need for a PM is a marker of worse outcome.

Presence of left ventricular contractile reserve, evaluated by means of dobutamine stress-echo test, is able to predict response to cardiac resynchronization therapy.

INTRODUCTION: We evaluated whether the dobutamine stress-echo test can select responders to cardiac resynchronization therapy (CRT). Up to 50% of patients do not respond to CRT. Lack of response may be due to a significant amount of scar or fibrotic tissue at myocardial level. METHODS AND RESULTS: We studied 42 CRT patients. After clinical and echocardiographic evaluation, all patients underwent a dobutamine stress-echo test to assess contractile reserve. Cut-off for the test was an increase of 25% of the left ventricular ejection fraction. Patients were implanted with a CRT-defibrillator and followed up at 6 months. Cut-off for CRT response was a reduction of 15% of left ventricular end-systolic volume. Twenty-five patients responded to CRT; all of them showed presence of contractile reserve. The test showed a sensitivity of 100% and a specificity of 88%. CONCLUSION: Contractile reserve was a strong predictive factor of response to CRT in the studied population.