Renin-angiotensin system inhibitors and mortality in patients with COVID-19.

Association of renin-angiotensin system inhibitors with risk of death in patients with hypertension (HTN) and coronavirus disease 2019 (COVID-19) is not well characterized. The aim of this study was to evaluate the outcomes of patients with HTN and COVID-19 with respect to different chronic antihypertensive drug intake. We performed a retrospective, observational study from a large cohort of patients with HTN and with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection admitted to the Emergency Rooms (ER) of the Piacenza Hospital network from February 21, 2020 to March 20, 2020. There were 1050 patients admitted to the ERs of the Piacenza Hospital network with COVID-19. HTN was present in 590 patients [median age, 76.2 years (IQR 68.2-82.6)]; 399 (66.1%) patients were male. Of them, 248 patients were chronically treated with ACEi, 181 with ARBs, and 161 with other drugs (O-drugs) including beta blockers, diuretics and calcium-channel inhibitors. With respect to the antihypertensive use, there was no difference between comorbid conditions. During a follow-up of 38 days (IQR 7.0-46.0), 256 patients (43.4%) died, without any difference stratifying for antihypertensive drugs. Of them, 107 (43.1%) were in ACEi group vs 67 (37%) in ARBs group vs 82 (50.7%) in O-drugs group, (log-rank test: p = 0.066). In patients with HTN and COVID-19, neither ACEi nor ARBs were independently associated with mortality. After adjusting for potential confounders in risk prediction, the rate of death was similar. Our data confirm Specialty Societal recommendations, suggesting that treatment with ACEIs or ARBs should not be discontinued because of COVID-19.

Clinical and epidemiological characteristics of 320 deceased patients with COVID-19 in an Italian Province: A retrospective observational study.

Studies have described clinical features of patients with coronavirus disease (COVID-19). However, limited data concerning the clinical characteristics of the Italian deaths are available. We aim to describe the clinical and epidemiological characteristics of 320 deceased from the Italian experience. We retrospectively collected all consecutive non-survivor patients with laboratory-confirmed COVID-19 infection admitted to the Emergency Rooms (ERs) Piacenza Hospital Network during the first month of COVID-19 pandemic in Italy. Clinical history, comorbidities, laboratory findings and treatment were recorded for each patient. A total of 1050 patients with confirmed COVID-19 pneumonia were admitted to the ERs between 24 February and 22 March 2020. Three hundred and twenty (30.5%) patients died with a median age of 78.0 years, 205 (64%) non-survivors were above 65 years old, 230 (71.9%) were male. Non-survivor patients showed frequently several coexisting medical conditions, with hypertension being the most common comorbidity (235 patients, 73.4%). The in-hospital mortality did not change during the progression of the pandemic. In this retrospective Italian study, most of COVID-19 deceased patients were elderly male aged over than 65 years. Hypertension was the most common coexisting disease. In-hospital mortality was high and showed no variation during the first month of the COVID-19 italian epidemic.

ALLiance for sEcondary PREvention after an acute coronary syndrome. The ALLEPRE trial: A multicenter fully nurse-coordinated intensive intervention program.

The main objective of cardiovascular disease prevention is to reduce morbidity and mortality by promoting a healthy lifestyle, reducing risk factors, and improving adherence to medications. Secondary prevention after an acute coronary syndrome has proved to be effective in reducing new cardiovascular events, but its limited use in everyday clinical practice suggests that there is considerable room for improvement. The short-term results of evidence-based studies of nurse-coordinated secondary prevention programs have been positive, but there is a lack of long-term outcome data. The Alliance for the Secondary Prevention of Cardiovascular Disease in the Emilia-Romagna region (ALLEPRE) is a multicenter, randomized, controlled trial designed to compare the effects of a structured nurse-coordinated intensive intervention on long-term outcomes and risk profiles after an acute coronary syndrome with those of the standard of care. All of the patients randomized to the intervention group take part in 9 one-to-one sessions with an experienced nurse from the participating centers with the aim at promoting healthy lifestyles, reducing risk factors, and increasing adherence to medication over a mean period of 5 years. The primary clinical end point is the reduction in the risk of the 5-year occurrence of major adverse events (a composite of cardiovascular mortality, nonfatal reinfarction, and nonfatal stroke). The primary surrogate end point is the achievement of prespecified targets relating to classical risk factors, lifestyle modifications, and adherence to pharmacological therapy after 2 years of follow-up. Coronary heart disease is a chronic degenerative disease, and patients who recover from an acute coronary syndrome (ACS) are at high risk of developing recurrent events.1 Although secondary prevention measures have proved to be effective and are strongly recommended by all of the international guidelines,2., 3. the 4 EUROASPIRE surveys4., 5., 6., 7., 8. showed that there was still a high prevalence of conventional risk factors, that secondary prevention measures were inadequately implemented, and that their main goals were often not reached. In addition, there were considerable discrepancy in secondary prevention practices between centers and countries, and a widespread underuse of cardiac prevention and rehabilitation programs despite their demonstrated effectiveness in reducing cardiovascular risk over time.9., 10. Over the last 10 years, nurses have been increasingly involved in successful cardiovascular risk management,11., 12., 13. but although this has improved levels of cardiovascular risk, no clear reduction in hard end points such as major cardiovascular adverse events and mortality has been demonstrated.10 The aim of the ALLEPRE trial is to evaluate the benefit of a homogeneous, structured, secondary prevention intervention program, fully coordinated by nurses from in- and outpatient clinics, in terms of cardiovascular risk profiles and major clinical events in ACS patients living in the large Emilia-Romagna region of Italy.

Physical activity intervention for elderly patients with reduced physical performance after acute coronary syndrome (HULK study): rationale and design of a randomized clinical trial.

BACKGROUND: Reduced physical performance and impaired mobility are common in elderly patients after acute coronary syndrome (ACS) and they represent independent risk factors for disability, morbidity, hospital readmission and mortality. Regular physical exercise represents a means for improving functional capacity. Nevertheless, its clinical benefit has been less investigated in elderly patients in the early phase after ACS. The HULK trial aims to investigate the clinical benefit of an early, tailored low-cost physical activity intervention in comparison to standard of care in elderly ACS patients with reduced physical performance. DESIGN: HULK is an investigator-initiated, prospective multicenter randomized controlled trial (NCT03021044). After successful management of the ACS acute phase and uneventful first 1 month, elderly (≥70 years) patients showing reduced physical performance are randomized (1:1 ratio) to either standard of care or physical activity intervention. Reduced physical performance is defined as a short physical performance battery (SPPB) score of 4-9. The early, tailored, low-cost physical intervention includes 4 sessions of physical activity with a supervisor and an home-based program of physical exercise. The chosen primary endpoint is the 6-month SPPB value. Secondary endpoints briefly include quality of life, on-treatment platelet reactivity, some laboratory data and clinical adverse events. To demonstrate an increase of at least one SPPB point in the experimental arm, a sample size of 226 patients is needed. CONCLUSIONS: The HULK study will test the hypothesis that an early, tailored low-cost physical activity intervention improves physical performance, quality of life, frailty status and outcome in elderly ACS patients with reduced physical performance. TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT03021044 , first posted January, 13th 2017.

Development of simulation combining a physical heart model and three-dimensional system for electrophysiology training.

BACKGROUND: A new three-dimensional heart anatomical simulator (3D HAS) has been created combining a physical heart model with an electroanatomic mapping (EAM) system. The aim of this study is to describe the development and the validation process of this device. METHODS: We developed the 3D HAS combining a physical heart model with an EAM system. This simulator was then validated by 10 electrophysiologists, subdivided in two groups based on their experience in electrophysiology procedures. The performance of the experts was compared to the one of the novices in achieving three different tasks: fluoroless reconstruction of the right atrium, coronary sinus cannulation, and deployment of a linear ablation lesion in the cavotricuspid isthmus. For each operator, a score was calculated based on objective parameter for each task and for the overall performance. RESULTS: The 3D HAS was located in an environment that allowed use of the main features of the EAM system including contact force sensing. No technical issue was encountered during the validation process. The experts' performance was significantly better than the one of the novices both overall (P = 0.009) and in each task (right atrium reconstruction, P = 0.016; coronary sinus cannulation, P = 0.008; ablation lesion, P = 0.03). CONCLUSIONS: The 3D HAS is reliable and allows use of the main features of an EAM system in the right atrium. The ability to discriminate different levels of experience suggests that this simulator is enough realistic and could be useful for electrophysiology training.

Community-based automated external defibrillator only resuscitation for out-of-hospital cardiac arrest patients.

BACKGROUND: Speed is the cornerstone of rescue for out-of-hospital cardiac arrest. As a consequence, community participation programs have been initiated to decrease response times. Even in the very best of these programs, however, short-term survival rates hover around 10% and long-term survival rates are half that. In most locales, survival is far worse. In Piacenza, Italy, responders have been trained for more than a decade to use publicly available automated external defibrillators (AEDs) and eschew the performance of cardiopulmonary resuscitation (CPR). It is known locally as "Progetto Vita." METHODS: From 2001 to 2014, we prospectively collected outcome data on all Progetto Vita-treated patients and all 3271 standard emergency medical services (EMS) patients. Progetto Vita rescuers simply accessed a public AED, turned it on, and only followed its instructions. Progetto Vita rescuers did not do CPR of any sort. If EMS arrived prior to initiation or even completion of the Progetto Vita protocol, EMS-supplanted Progetto Vita efforts and patients were not included in the Progetto Vita cohort. Follow-up was collected by each responder's data files, medical record review, and use of the Italian system death index. All cardiac arrest patients' death status was validated in 100% of patients through August 1, 2014. FINDINGS: Survival to hospital discharge occurred in 39 (41.4%) of the 95 patients treated by Progetto Vita and in 193 (5.9%) of the 3271 EMS patients. At 13-year follow-up, the Kaplan-Meier estimates of survival were 31.8% when AEDs only were used and 2.4% for standard EMS/CPR response. Estimates of survival are significantly better for Progetto Vita AED-only therapy when survival was stratified by time to respond, gender, location of cardiac arrest, and shockable rhythm. Relative to the 95 EMS patients with the fastest response times, Progetto Vita intervention was associated with a more than 2-fold increased rate of survival. INTERPRETATION: This is the first demonstration of excellent long-term survival from out-of-hospital cardiac arrest by promoting speed and ease of lay AED response without CPR.

Renal function and peak exercise oxygen consumption in chronic heart failure with reduced left ventricular ejection fraction.

BACKGROUND: Chronic kidney disease is associated with sympathetic activation and muscle abnormalities, which may contribute to decreased exercise capacity. We investigated the correlation of renal function with peak exercise oxygen consumption (V̇O2) in heart failure (HF) patients. METHODS AND RESULTS: We recruited 2,938 systolic HF patients who underwent clinical, laboratory, echocardiographic and cardiopulmonary exercise testing. The patients were stratified according to estimated glomerular filtration rate (eGFR). Mean follow-up was 3.7 years. The primary outcome was a composite of cardiovascular death and urgent heart transplantation at 3 years. On multivariable regression, eGFR was predictor of peakV̇O2(P<0.0001). Other predictors were age, sex, body mass index, HF etiology, NYHA class, atrial fibrillation, resting heart rate, B-type natriuretic peptide, hemoglobin, and treatment. After adjusting for significant covariates, the hazard ratio for primary outcome associated with peakV̇O2<12 ml·kg(-1)·min(-1)was 1.75 (95% confidence interval (CI): 1.06-2.91; P=0.0292) in patients with eGFR ≥60, 1.77 (0.87-3.61; P=0.1141) in those with eGFR of 45-59, and 2.72 (1.01-7.37; P=0.0489) in those with eGFR <45 ml·min(-1)·1.73 m(-2). The area under the receiver-operating characteristic curve for peakV̇O2<12 ml·kg(-1)·min(-1)was 0.63 (95% CI: 0.54-0.71), 0.67 (0.56-0.78), and 0.57 (0.47-0.69), respectively. Testing for interaction was not significant. CONCLUSIONS: Renal dysfunction is correlated with peakV̇O2. A peakV̇O2cutoff of 12 ml·kg(-1)·min(-1)offers limited prognostic information in HF patients with more severely impaired renal function.

Clinical characteristics, mortality, cardiac hospitalization, and ventricular arrhythmias in patients undergoing CRT-D implantation: results of the ACTION-HF study.

INTRODUCTION: The characteristics and outcomes of patients who undergo cardiac resynchronization therapy (CRT) device implantation in current clinical practice may differ from those of reference trial populations. Study objectives were to assess 2-year outcomes in a population implanted with a CRT plus defibrillator device in accordance with the standard of care and to evaluate any independent association between clinical variables and outcome. METHODS AND RESULTS: A total of 406 patients enrolled at 35 centers in Italy were followed up prospectively for 2 years. All patient management decisions were left to the treating physician's discretion, in accordance with clinical practice. ACTION-HF patients had a better baseline clinical status than patients enrolled in the COMPANION study: shorter HF history (1 vs 3.5 years, P < 0.01), less advanced NYHA functional class (III-IV: 73% vs 100%, P < 0.01), higher LVEF (26% vs 21%, P < 0.01), higher SBP (122 vs 112 mmHg, P < 0.01), and less diabetes (27% vs 41%, P < 0.01). This status was reflected in lower mortality (11.5% vs 26%) and a lower incidence of appropriate ICD shocks (12.1% vs 19.3%). AF history was an independent predictor of the combination of all-cause mortality and cardiac-cause hospitalization (HR: 3.31; P < 0.001). Recurrent or new atrial arrhythmias were independently associated with the development of ventricular arrhythmias (HR: 3.4; P < 0.001). CONCLUSIONS: This population appears clinically less compromised and had a lower incidence of adverse clinical outcomes than those of reference trials. However, we recorded a substantial burden of atrial arrhythmias, which was independently associated with a higher incidence of ventricular arrhythmias.

[Takotsubo syndrome during SARS-CoV-2 pneumonia: a possible cardiovascular complication]. / Sindrome Takotsubo in corso di polmonite da SARS-CoV-2: una possibile complicanza cardiovascolare.

Takotsubo syndrome (TTS) is one of the causes of myocardial infarction with non-obstructive coronary arteries, and is often triggered by physical events (e.g. acute respiratory failure), or emotional events (e.g. loss of a family member, cardiac stress induced by an acute illness). SARS-CoV-2 pneumonia currently represents a worldwide health problem; the correlations between cardiovascular disease, myocardial injury and SARS-CoV-2 infection are still unclear, but initial data show that myocardial damage represents a negative prognostic factor. Myocardial injury during SARS-CoV-2, as defined by a pathological rise in circulating troponin levels, is not an uncommon complication in hospitalized patients, and is significantly more frequent in intensive care unit patients and among those who died. In this setting, myocardial injury is mainly secondary to type 2 myocardial infarction (mismatch in myocardial oxygen supply and demand during respiratory failure); other causes include myocarditis, coronary thrombosis, sepsis or septic shock. At present, only few cases of TTS have been described during SARS-CoV-2. Here we report the case of a patient hospitalized for pneumonia and respiratory failure due to SARS-CoV-2 with subsequent onset of TTS triggered by both physical and emotional events.

[Late occurrence of pulmonary embolsim in SARS-CoV-2 pneumonia: a case series]. / L'embolia polmonare come complicanza tardiva della polmonite da SARS-CoV-2: una serie di casi clinici.

Several studies suggested that the acute phase of SARS-CoV-2 infection may be associated with a hypercoagulable state and increased risk for venous thromboembolism but the incidence of thrombotic complications in the late phase of the disease is currently unknown. The present article describes three cases of patients with SARS-CoV-2 pneumonia and late occurrence of pulmonary embolism. Case 1: a 57-year-old man diagnosed with pulmonary embolism and type B aortic dissection after 12 days from SARS-CoV-2 pneumonia. Laboratory panel at the time of pulmonary embolism showed no signs of ongoing inflammation but only an elevated D-dimer. Case 2: a 76-year-old man with a diagnosis of SARS-CoV-2 pneumonia followed by pulmonary embolism 20 days later, high-resolution computed tomography on that time showed a partial resolution of crazy paving consolidation. Case 3: a 77-year-old man with SARS-CoV-2 pneumonia who developed a venous thromboembolic event despite thromboprophylaxis with low molecular weight heparin. Also in this patients no markers of inflammation were present at the time of complication.The present cases raise the possibility that in SARS-CoV-2 infection the hypercoagulable state may persist over the active inflammation phase and cytokine storm. These findings suggest a role for medium-long term therapeutic anticoagulation started at the time of SARS-CoV-2 pneumonia diagnosis.

Left Atrial Function Predicts Cardiovascular Events in Patients With Chronic Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Heart failure (HF) is known to be the most widespread epidemic of cardiovascular disease. Among several factors with prognostic value for the clinical course of HF, left atrial (LA) function has not yet been fully examined. The aim of this prospective study was to evaluate LA function for the prediction of major cardiovascular outcomes in stable patients with chronic HF with reduced ejection fraction. Additionally, as secondary end points, cardiovascular mortality and atrial fibrillation were analyzed separately. METHODS: The predictive value of LA function evaluated by speckle-tracking echocardiography was assessed in a population of 286 outpatients referred to the authors' institution for routine evaluation of chronic HF. Global peak atrial longitudinal strain was measured at the end of the reservoir phase and calculated by averaging in all LA segments. RESULTS: During a median follow-up period of 48 ± 11 months, major adverse cardiac events occurred in 98 patients (34%). In a multivariate model, global peak atrial longitudinal strain (hazard ratio, 0.95; 95% CI, 0.94-0.96; P = .02), left ventricular ejection fraction (hazard ratio, 0.95; 95% CI, 0.93-0.97; P = .01), and renal failure (hazard ratio, 0.98; 95% CI, 0.97-0.99; P = .01) were independent predictors of an adverse outcome. Sixty-six patients (23%) died of cardiac causes. Fifty-four patients (19%) developed atrial fibrillation. Patients with lower global peak atrial longitudinal strain showed worse event-free survival and developed atrial fibrillation more frequently than those with higher levels. CONCLUSIONS: LA function assessed by speckle-tracking echocardiography is an independent prognostic marker in patients with HF with reduced ejection fraction.

Outcomes after sudden cardiac arrest in sports centres with and without on-site external defibrillators.

OBJECTIVE: Sudden cardiac arrest (SCA) is a rare but tragic event during amateur sports activities. Our aim is to analyse whether availability of automated external defibrillators (AEDs) in amateur sports centres could impact on SCA survival. METHODS: This is an observational study. During an 18-year period, data regarding exercise-related SCA in sports centres were prospectively collected. Survival rates and time to response were compared between centres with an AED already available and centres where an AED was not already present. RESULTS: Out of 252 sports facilities, 207 (82%) acquired an AED during follow-up while 45 (18%) did not. From 1999 to 2014, there were 26 SCAs (24 (92%) men, 54±17 years old) with 15 (58%) of them in centres with on-site AED. Neurologically intact survival rates were 93% in centres with on-site AED and 9% in centres without (P<0.001). Presence of on-site AED, presence of shockable rhythm, first assistance by a lay bystander and time to defibrillation were all related to neurological intact survival, but the presence of on-site AED was the only independent predictor in the multivariate analysis. The use of on-site AED resulted in a lower time to first shock when compared with emergency medical system-delivered AED (3.3±1.4min vs 7.3±3.2 min; P=0.001). CONCLUSIONS: The presence of on-site AEDs is associated with neurologically intact survival after an exercise-related SCA. Continuous efforts are recommended in order to introduce AEDs in sports and fitness centres, implement educational programmes and increase common awareness about SCA.

Pharmacogenomic Approach to Selecting Antiplatelet Therapy in Patients With Acute Coronary Syndromes: The PHARMCLO Trial.

BACKGROUND: Although clopidogrel is still frequently used in patients with acute coronary syndromes (ACS), its efficacy is hampered by interpatient response variability caused by genetic polymorphisms associated with clopidogrel's metabolism. OBJECTIVES: The goal of this study was to evaluate whether selecting antiplatelet therapy (clopidogrel, prasugrel, or ticagrelor) on the basis of a patient's genetic and clinical characteristics leads to better clinical outcomes compared with the standard of care, which bases the selection on clinical characteristics alone. METHODS: Patients hospitalized for ACS were randomly assigned to standard of care or the pharmacogenomic arm, which included the genotyping of ABCB1, CYP2C19*2, and CYP2C19*17 using an ST Q3 system that provides data within 70 min at each patient's bedside. The patients were followed up for 12 ± 1 month for the primary composite endpoint of cardiovascular death and the first occurrence of nonfatal myocardial infarction, nonfatal stroke, and major bleeding defined according to Bleeding Academic Research Consortium type 3 to 5 criteria. RESULTS: After enrolling 888 patients, the study was prematurely stopped. Clopidogrel was used more frequently in the standard-of-care arm (50.7% vs. 43.3%), ticagrelor in the pharmacogenomic arm (42.6% vs. 32.7%; p = 0.02), and prasugrel was equally used in both arms. The primary endpoint occurred in 71 patients (15.9%) in the pharmacogenomic arm and in 114 (25.9%) in the standard-of-care arm (hazard ratio: 0.58; 95% confidence interval: 0.43 to 0.78; p < 0.001). CONCLUSIONS: A personalized approach to selecting antiplatelet therapy for patients with ACS may reduce ischemic and bleeding events. (Pharmacogenetics of Clopidogrel in Patients With Acute Coronary Syndromes [PHARMCLO]; NCT03347435).

Exercise tolerance can explain the obesity paradox in patients with systolic heart failure: data from the MECKI Score Research Group.

AIMS: Obesity has been found to be protective in heart failure (HF), a finding leading to the concept of an obesity paradox. We hypothesized that a preserved cardiorespiratory fitness in obese HF patients may affect the relationship between survival and body mass index (BMI) and explain the obesity paradox in HF. METHODS AND RESULTS: A total of 4623 systolic HF patients (LVEF 31.5 ± 9.5%, BMI 26.2 ± 3.6 kg/m(2) ) were recruited and prospectively followed in 24 Italian HF centres belonging to the MECKI Score Research Group. Besides full clinical examination, patients underwent maximal cardiopulmonary exercise test at study enrolment. Median follow-up was 1113 (553-1803) days. The study population was divided according to BMI (<25, 25-30, >30 to ≤35 kg/m(2) ) and predicted peak oxygen consumption (peak VO2 , <50%, 50-80%, >80%). Study endpoints were all-cause and cardiovascular deaths including urgent cardiac transplant. All-cause and cardiovascular deaths occurred in 951 (28.6%, 57.4 per person-years) and 802 cases (17.4%, 48.4 per 1000 person-years), respectively. In the high BMI groups, several prognostic parameters presented better values [LVEF, peak VO2 , ventilation/carbon dioxide slope, renal function, and haemoglobin (P < 0.01)] compared with the lower BMI groups. Both BMI and peak VO2 were significant positive predictors of longer survival: both higher BMI and peak VO2 groups showed lower mortality (P < 0.001). At multivariable analysis and using a matching procedure (age, gender, LVEF, and peak VO2 ), the protective role of BMI disappeared. CONCLUSION: Exercise tolerance affects the relationship between BMI and survival. Cardiorespiratory fitness mitigates the obesity paradox observed in HF patients.

Reproducible efficacy of loading oral propafenone in restoring sinus rhythm in patients with paroxysmal atrial fibrillation.

This is the first study to demonstrate the reproducibility of an oral propafenone loading dose in converting paroxysmal atrial fibrillation in patients without significant cardiac disease or hypertension. This finding may support the development of the "pill-in-the-pocket" treatment strategy in this group of patients.

Management of oral chronic pharmacotherapy in patients hospitalized for acute decompensated heart failure.

Acute decompensated heart failure (ADHF) is the most common cause of cardiovascular hospitalization. The presentation is characterized by different clinical profiles due to various underlying causes, volume balance and tissue perfusion status. Currently, a variety of pharmacological therapies, including diuretics, beta-blockers, ACE-inhibitors, angiotensin receptor blockers and digoxin, are usually prescribed in order to treat chronic heart failure (HF) syndromes caused by left ventricular systolic dysfunction. Despite the large number of HF patients with frequent hospitalizations for decompensation, only a few studies have evaluated the management of oral chronic therapies in the clinical setting of ADHF. This article summarizes the information derived from the few published trials on this subject and a therapeutic approach is suggested with respect to the continuation, dose modification or suspension of oral medications.

Effect of cardiac resynchronization therapy on left atrial reverse remodeling: role of echocardiographic AV delay optimization.

BACKGROUND/OBJECTIVES: Cardiac resynchronization therapy (CRT) improves left ventricular (LV) function in patients with advanced heart failure (HF) and there are some evidences about beneficial effects also on left atrial (LA) dimension and function. The contribution of atrioventricular delay (AVD) optimization on LA changes has not been evaluated. The purpose of the present study was to further investigate the effect of CRT on LA reverse remodelling and to evaluate the contribution of AVD optimization. METHODS AND RESULTS: From the Cardiology Department of Piacenza Hospital and Modena University Hospital fifty one patients with refractory systolic HF and left bundle branch block were prospectively enrolled before CRT implantation. Patients were 1:1 randomized to either an optimized AVD (AV Opt group) determined by continuous wave Doppler aortic velocity-time integral (VTI) or an empiric AVD of 110 ms (AV Fixed group). Optimal AVD was defined as the AVD that yielded the largest aortic VTI at one of eight tested AV intervals (between 60 and 200 ms). LA volumes and emptying fractions were assessed by two-dimensional echocardiography at baseline and 6 months after CRT. At 6-month follow-up, CRT induced LA reverse remodeling in the whole population (maximal LA volume: 55.8 ± 16.4 ml/m² vs 50.3 ± 18.9 ml/m², p=0.006; pre-systolic LA volume: 47.0 ± 15.2 ml/m² vs 41.4 ± 17.4 ml/m², p=0.003; post-systolic LA volume: 36.4 ± 15.0 ml/m² vs 30.3 ± 18.0 ml/m(2), p=0.001); nevertheless, no substantial difference was observed about LA structural and functional remodeling between both AV Opt group and AV Fixed group. CONCLUSION: CRT induces LA reverse remodeling that appears independent from AVD optimization.