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Background Coronary microvascular dysfunction (CMD) is an early feature of diabetic cardiomyopathy, which usually precedes the onset of systolic and diastolic dysfunction (DDF). Continuous intracoronary thermodilution allows an accurate and reproducible assessment of absolute coronary blood flow and microvascular resistance thus allowing the evaluation of coronary flow reserve (CFR) and Microvascular Resistance Reserve (MRR), a novel index specific for microvascular function, which is independent from the myocardial mass. In the present study we compared absolute coronary flow and resistance, CFR and MRR assessed by continuous intracoronary thermodilution in diabetic versus non-diabetic patients. Left atrial reservoir strain (LASr), an early marker of DDF was compared between the two groups. Methods In this observational retrospective study, 108 patients with suspected angina and non-obstructive coronary artery disease (NOCAD) consecutively undergoing elective coronary angiography (CAG) from September 2018 to June 2021 were enrolled. The invasive functional assessment of microvascular function was performed in the left anterior descending artery (LAD) with intracoronary continuous thermodilution. Patients were classified according to the presence of DM. Absolute resting and hyperemic coronary flow (in mL/min) and resistance (in WU) were compared between the two cohorts. FFR was measured to assess coronary epicardial lesions, while CFR and MRR were calculated to assess microvascular function. LAS, assessed by speckle tracking echocardiography, was used to detect early myocardial structural changes potentially associated with microvascular dysfunction. Results The median FFR value was 0.83 [0.79–0.87] without any significant difference between the two groups. Absolute resting and hyperemic flow in the left anterior descending coronary were similar between diabetic and non-diabetic patients. Similarly, resting and hyperemic resistances did not change significantly between the two groups. In the DM cohort the CFR and MRR were significantly lower compared to the control group (CFR=2.4±0.6 and 2.9±0.8; MRR=2.8±0.9 and 3.5±1 for diabetic and non-diabetic patients respectively, [p Conclusions Compared with non-diabetic patients, CFR and MRR were lower in patients with DM and non-obstructive epicardial coronary arteries, while both resting and hyperemic coronary flow and resistance were similar. LASr was lower in diabetic patients, confirming the presence of a subclinical DDF associated to the microcirculatory impairment. Continuous intracoronary thermodilution-derived indexes provide a reliable and operator-independent assessment of coronary macro- and microvasculature and might potentially facilitate widespread clinical adoption of invasive physiologic assessment of suspected microvascular disease. Funding Acknowledgement Type of funding sources: None.

Background Sodium-glucose co-transporter 2 inhibitors (SGLT2-I) currently receive intense clinical interest in patients with and without diabetes mellitus (DM) with pleiotropic beneficial effects. Nowadays, the inflammation response in the setting of acute myocardial infarction (AMI) has been proposed as a potential pharmacological intervention target. In this setting, we tested the hypothesis that the SGLT2-I displays anti-inflammatory effect along with glucose-lowering properties. We investigated the relationship between stress hyperglycemia, inflammation burden and infarct size in a cohort of type 2 diabetic AMI patients treated with SGLT2-I versus other oral anti-diabetic (OAD) agents alone. Methods In this multicenter international registry, all diabetic patients with AMI treated with percutaneous coronary intervention (PCI) between 2018 and 2021 were enrolled. Based on the admission anti-diabetic therapy, patients were divided into those receiving SGLT2-I versus other OAD agents alone. Patients on insulin therapy alone or combined with OAD agents were excluded from the study. The following inflammatory markers were evaluated at different time points: total white blood cell, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and neutrophil-to-platelet ratio (NPR), C-reactive protein. Infarct size was assessed by peak troponin levels and echocardiographic parameters. Results The final study population consisted of 583 patients hospitalized for AMI (both STEMI and NSTEMI) classified as SGLT2-I users (n=98) versus other OAD agents alone (n=485). Admission hyperglycemia was more prevalent among the other OAD agents group. Reduced infarct size was detected in patients treated with SGLT2-I compared to those treated with other OAD agents alone. Both at admission, and after 24 hours, inflammatory indices were significantly higher in patients treated with other OAD agents alone, with a significant increase in neutrophils levels at 24 hours, compared to the SGLT2-I group. In multivariate analysis, SGLT2-I emerged as a significant predictor of reduced inflammatory response (OR 0.45, 95% CI 0.27–0.75, p=0.002), together with peak troponin values, independently of age, admission creatinine values and admission glycemia. Conclusions Type 2 Diabetic patients hospitalized for AMI and receiving SGLT2-I exhibited modest inflammatory response and myocardial damage/infarct size compared to other OAD agents alone, independently of glucose-metabolic control. Our findings pave the way for new pathophysiological and therapeutic insights regarding the cardioprotective effect of SGLT2-I in the setting of coronary artery disease. Funding Acknowledgement Type of funding sources: None.

Background Aortic Regurgitation (AR) may aggravate the clinical course in patients with heart failure and preserved ejection fraction (HFpEF) by increasing filling pressures and triggering LV remodelling. Objective To assess AR's prevalence and long-term prognostic implications in patients with HFpEF. Methods The study population consisted of 458 consecutive patients (age 77.5±9.2 y, 57.9% females) hospitalized with de novo or worsened HFpEF. Patients with more than moderate aortic and/or mitral valve disease were excluded. Data on cardiovascular death, HF re-hospitalization and their composite (MACE) were collected. Results Out of 309 (67.5%) patients with any AR, 156 (34.0%) and 153 (33.5%) had mild-AR and moderate-AR, respectively. The remaining 149 (32.5%) individuals had no-AR. Patients with versus without AR were significantly older with larger LV and LA volumes and a higher prevalence of diastolic dysfunction (all p Conclusions In patients with HFpEF, mild-to-moderate AR is highly prevalent, and it seems to identify individuals with worse long-term outcomes. This suggests that even mild AR should be considered a high-risk prognostic marker in patients with HFpEF. Funding Acknowledgement Type of funding sources: None.

Introduction The development of left ventricular hypertrophy in patients with severe aortic stenosis (AS) is accompanied by adaptive coronary flow regulation, both in epicardial and microvascular compartment, which ultimately lead to a chronic ischemic insult even in the absence of obstructive coronary artery disease. Intracoronary continuous thermodilution of saline through a dedicated infusion catheter is a novel tool that allows to measure absolute coronary flow and microvascular resistance at rest and during hyperemia and to calculate both coronary flow reserve (CFR) and Microvascular Resistance Reserve (MRR) Purpose We aimed to assess absolute coronary flow, microvascular resistance, CFR and MRR in patients with AS, by continuous intracoronary thermodilution, comparing these hemodynamic findings with a propensity-score matched contemporary cohort of patients without AS. Methods Absolute coronary blood flow and microvascular resistance were measured by continuous thermodilution in 29 patients with AS and compared to 15 controls matched for age, gender, diabetes mellitus and functional severity of epicardial coronary lesions. Myocardial work, total myocardial mass and LAD-specific mass were quantified by echocardiography and cardiac-CT. Results Patients with AS presented a significantly positive LV remodeling with lower global longitudinal strain and higher global work index compared to controls (p Conclusions In patients with severe aortic stenosis and non-obstructive coronary artery disease, with the progression of LVH, the compensatory mechanism of increased resting flow maintains an adequate perfusion at rest, but not during hyperemia (Figure 2). As consequence, both CFR and MRR are significantly impaired. Funding Acknowledgement Type of funding sources: None.

Introduction The bolus thermodilution-derived index of microcirculatory resistance (IMR) has emerged over years as the standard of reference to invasively define coronary microvascular dysfunction (CMD). However, the technique still presents some limitations, mainly related to the fact that manual injection of saline bolus accounts for some variance in the measurements. Continuous intracoronary thermodilution has been recently introduced as a tool to directly quantify absolute coronary flow and microvascular resistance both at rest and during hyperemia and has shown to be safe and operator independent. Microvascular resistance reserve (MRR), derived from continuous thermodilution, has been validated as novel index specific for microcirculation and independent from myocardial mass. Purpose To compare head-to-head the intra-observer repeatability of bolus and continuous thermodilution for assessing microvascular function. Methods Patients undergoing coronary angiography in the absence of obstructive coronary artery disease were prospectively enrolled. Bolus and continuous intracoronary thermodilution measurements were performed in duplicates in the left anterior descending artery (LAD). Patients were randomly assigned in a 1:1 ratio to undergo first bolus thermodilution or first continuous thermodilution assessment. Results A total of 102 patients were enrolled. Average FFR was 0.86±0.06. Coronary Flow Reserve (CFR) calculated with continuous thermodilution (CFRthermo) was significantly lower than bolus thermodilution-derived CFR (CFRbolus) (2.63±0.65 and 3.29±1.17, respectively, p Conclusion Continuous intracoronary thermodilution has a higher repeatability than bolus thermodilution in the assessment of CMD. Funding Acknowledgement Type of funding sources: None.

Background Myocardial infarction with non-obstructed coronary arteries (MINOCA) is common in current clinical practice and cardiac magnetic resonance (CMR) plays an important role in the present management of this group of patients. However, there are still a lot of controversies concerning the etiology behind the syndrome of MINOCA. Furthermore, the prognostic value of CMR in patients with MINOCA is still undetermined. Purpose We aimed to determine the diagnostic and prognostic value of CMR in the management of patients with MINOCA. Methods A systematic review was performed to identify studies reporting the results of CMR findings in MINOCA patients (non-obstructive CAD or normal coronary arteries). Random effects models were used to determine the prevalence of different disease entities – myocarditis, myocardial infarction, Takotsubo cardiomyopathy or normal CMR findings. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the prognostic value of CMR diagnosis in the subgroup of studies that reported clinical outcomes. Major adverse clinical events (MACE) were defined based on the specific study definitions and included cardiovascular death, non-fatal myocardial infarction, and cardiovascular hospitalization. Results 31 studies comprising 4119 patients were included. Mean age was 54.1±3.3, 59% were males. The pooled prevalence of myocarditis was 32% (95% CI 0.25 to 0.39), myocardial infarction (MI) - 21% (95% CI 0.17 to 0.24), Takotsubo cardiomyopathy −12% (95% CI 0.09 to 0.16). Normal findings were found in 23% (95% CI 0.14 to 0.35), figure 1. In a subgroup analysis of seven studies (900 patients) that reported clinical outcomes the prognostic value of the CMR was assessed. CMR diagnosis of myocarditis was not significantly associated with increased risk of MACE (pooled OR, 1.50; 95% CI, 0.46 to 4.87; p=0.459). However, both diagnosis of MI and Takotsubo were significantly associated with increased risk of combined clinical outcomes (pooled OR, 1.75; 95% CI, 1.12 to 3.59; p Conclusion In patients with MINOCA CMR brings important diagnostic and prognostic role. The pooled prevalence of myocarditis was 32%, of MI – 21% and of Takotsubo – 12%. The CMR diagnosis of MI and Takotsubo was associated with increased risk of MACE. Funding Acknowledgement Type of funding sources: None.

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Dr. Paolisso, Dr. Esposito, Dr. Fabbricatore are supported by a research grant from the CardioPaTh PhD Program of University of Naples Federico II Background Non-invasive myocardial work (MW) is a validated index of left ventricular (LV) systolic performance, incorporating afterload and myocardial metabolism. The role of MW in predicting the first hospitalization for de novo heart failure with preserved ejection fraction (HFpEF) is still unknown. Purpose To investigate the diagnostic performance of MW to predict the first de novo HFpEF hospitalization in ambulatory individuals with preserved LVEF. Methods Twenty-nine patients with trans-thoracic echocardiography performed at least 6 months before the first HFpEF hospitalization were compared with 29 matched controls. MW was derived as the area of pressure-strain loop using speckle-tracking and brachial artery blood pressure. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were collected. First HFpEF hospitalization and its combination with cardiovascular death (MACE) and all-cause of death (MAE) were assessed. Results At baseline, future HFpEF patients showed lower GWI, GCW, GWE and higher GWW than controls (all p 170 mmHg% was associated with a 4-fold increase of MACE (HR = 4.5, 95% CI 1.59–13.12, p = 0.005) and a 3-fold higher risk of MAE (HR = 2.9, 95% CI 1.24–6.6, p = 0.014). Conclusions In ambulatory patients with preserved LVEF and risk factors, GWW showed high accuracy to predict the first HFpEF hospitalization and its combination with mortality. The GWW routine assessment may be clinically helpful in patients with dyspnea. Abstract Figure 1: Serial changes of LARs, LV GLS Abstract Figure 2:Kaplan–Meier survival curves fo

Background Deferring percutaneous coronary intervention (PCI) in patients with non-ischemic coronary stenoses based on fractional flow reserve (FFR) and preserved left ventricular ejection fraction (LVEF) is associated with favorable long-term clinical outcomes. In patients with reduced LVEF, the role of reversible/residual ischemia in deferring revascularization is still debated. Purpose To investigate whether FFR provides additive clinical benefit compared to coronary angiography in deferring revascularization in patients with intermediate coronary stenoses and reduced LVEF. Methods Among 4577 coronary angiographies performed between 2002 and 2010, consecutive patients with reduced LVEF (≤50%) and at least one intermediate coronary stenosis [diameter stenosis (DS)% 40–70%] in whom revascularization was deferred based either on FFR (FFR-guided) or angiography (Angiography-guided) were screened. The primary endpoint of the study was cumulative incidence of death at 10 years. Results A total of 843 patients were included (209 in the FFR-guided and 634 in the Angio-guided group). Median clinical follow-up was 7.1 years (IQR 3.2–11.2 years). After 1:1 propensity score matching, baseline characteristics between the two groups were similar. All-cause death at 10 years was significantly lower in the FFR-guided compared with the Angiography-guided group (94 [45%] vs 115 [55%], HR 0.72 [95% CI 0.55–0.95], p Conclusions In patients with reduced LVEF and associated coronary artery disease, deferring revascularization of intermediate stenoses based on FFR is associated with lower incidence of death and MACCE at 10 years. Funding Acknowledgement Type of funding sources: None.

Background Percutaneous coronary interventions (PCI) in calcified coronary artery lesions is associated with impaired stent expansion, higher rate of periprocedural complications and cardiac mortality. Lesion preparation using dedicated calcium modifying techniques such as RA or IVL has been advocated. Studies comparing these technologies are lacking. Objectives To compare the in-stent pressure gradient, evaluated by virtual fractional flow-reserve, in calcific lesions treated using either rotational atherectomy (RA) or intravascular lithotripsy (IVL). Methods Patients undergoing either RA- or IVL-assisted PCI from two European centers were included. Propensity score matching (1:2) was performed to control for potential bias. Primary outcome was post- PCI in-stent pressure gradient calculated by virtual fractional flow reserve (vFFRgrad, calculated as the difference between the vFFR at the proximal minus distal edge of the stent). Secondary outcomes included the proportion of patients with complete functional revascularization defined as of distal vFFR post PCI (vFFRpost) ≥0.90. Results From a cohort of 210 patients, 105 matched patients (70 RA and 35 IVL) were included. Pre-PCI vFFR did not differ between groups (0,65±0,13 RA and 0,67±0,11 IVL). After PCI, in-stent pressure gradient was significantly lower in the IVL group (0.032±0.026 vs 0.043±0.026 in the RA group, p=0.024). The proportion of vessels with functional complete revascularization was similar between the two groups (32.9% vs. 37.1% in the RA and IVL group, respectively; p=0.669) Conclusions Calcific lesions preparation with IVL is effective and resulted in improved in-stent pressure gradient compared to RA. Approximately one third of the patients undergoing PCI for a severely calcified lesion achieved functional revascularization with no difference between rotational RA and IVL. Funding Acknowledgement Type of funding sources: None. In stent gradients after RA and IVL

Cardiac transplant-related vasculopathy remains a leading cause of morbidity and mortality in heart transplant (HTx) recipients. Recently, coronary angiography-derived vessel fractional flow reserve (vFFR) has emerged as a new diagnostic computational tool to functionally evaluate the severity of coronary artery disease. Although vFFR estimates have been shown to perform well against invasive FFR in atherosclerotic coronary artery disease, data on the use of vFFR in heart transplant recipients suffering from cardiac transplant-related arteriopathy are lacking. The aim of the presented study was to validate coronary angiography-derived vessel fractional flow reserve to calculate fractional flow reserve in HTx patients with and without cardiac transplant-related vasculopathy. A prospective, single center study of HTx patients referred for annual check-up, undergoing surveillance coronarography was conducted. Invasive FFR was measured using a motorized device at the speed of 1.0 mm/s in all three major coronary arteries. Angiography-derived pullback FFR was derived from the angiogram and compared with invasive FFR pullback curve. Overall, 18,059 FFR values were extracted from the FFR pullback curves from 23 HTx patients. The mean age was 59.3 ± 9.7 years, the mean time after transplantation was 5.24 years [IQR 1.20, 11.25]. A total of 39 vessels from 23 patients (24 LAD, 11 LCX, 4 RCA) were analyzed. Mean distal vFFR was 0.87 ± 0.14 whereas invasive distal FFR was 0.88 ± 0.17. An excellent correlation was found between invasive distal FFR and vFFR (r = 0.92; p < 0.001). The correlation of the pullback tracing was high, with a correlation coefficient between vFFR and invasive FFR pullback values of 0.72 (95% CI 0.71 to 0.73, p < 0.001). The mean difference between vFFR and invasive FFR pullback values was -0.01 with 0.06 of SD (limits of agreements -0.12 to 0.13). In HTx patients, coronary angiography-derived FFR correlates excellently with invasively measured wire-derived FFR. Therefore, angiography derived FFR could be used as a novel diagnostic tool to quantify the functional severity of graft vasculopathy. ispartof: DIAGNOSTICS vol:11 issue:10 ispartof: location:Switzerland status: published

Funding Acknowledgements Type of funding sources: None. Background Speckle Tracking Echocardiography (STE) provides a comprehensive and quantitative assessment of myocardial function. However, the accuracy of STE-derived indices to predict maintenance of sinus rhythm (SR) following radio-frequency catheter ablation (CA) is still under debate. Therefore, the aim of the present study is to define the accuracy of STE-derived parameters to predict long-term maintenance of SR in patients with paroxysmal AF undergoing CA. Methods We prospectively enrolled 218 consecutive patients (age: 62 ± 10 years, 30% females) with paroxysmal AF undergoing first-CA. All patients with preserved ejection fraction (EF ≥ 50%) underwent comprehensive transthoracic echocardiography at baseline, including assessment of left ventricular (LV) global longitudinal strain (GLS), left atrial (LA) reservoir strain (LASr), LA conduit strain (LAScd) and LA contractile strain (LASct) using two-dimensional STE in apical views. Results At 12 months follow up, a total of 39 (18%) patients had a documented recurrence of AF. Among imaging parameters, LASr > 23% showed the largest area under the curve (0.80) to predict long-term maintenance of SR with sensitivity of 79% and specificity of 72%. Other parameters of LA function, LA diameter, maximum or minimum LA volume index, LV GLS or ejection fraction, and indices of LV diastolic function had lower area under the curve (Figure 1). Using multi-variable logistic regression, LASr (OR 1.19, 95% CI 1.10-1.23, p Conclusion In patients with paroxysmal AF undergoing radio-frequency CA, preserved LA reservoir and contractile strain is independently associated with long-term maintenance of SR, whereas LA diameter or volumes were not. LA strain may therefore be useful in management of patients with paroxysmal AF. Figure 1: Receiver-operating characteristic curves of left atrial reservoir strain (LASr), LA conduit strain (LAScd), LA contractile strain (LASct), LA emptying fraction (LAEF), LA expansion index (LAEI), LA end-systolic (LAES) and end-diastolic (LAED) volume index (VI) to predict long-term maintenance of sinus rhythm. Abstract Figure.

Background Atrial structural and functional changes may develop as a result of catheter ablation (CA) in patients with paroxysmal and persistent atrial fibrillation (AF). However, the relation between AF recurrence and atrial performance following CA is still under debate. Our aim is to describe the long-term effects of CA on LA remodeling and its correlates to the maintenance of sinus rhythm (SR). Methods We prospectively enrolled 178 consecutive patients (age: 63±9 years, 35% females) with paroxysmal AF undergoing first-CA (67%) or redo-CA (22%), and 20 individuals (11%) with long-standing persistent AF (PAF) undergoing first CA. All patients underwent comprehensive transthoracic echocardiography at baseline and at 12-month follow-up, including the assessment of reservoir and contractile strain (LAS) using two dimensional speckle tracking echocardiography in all three apical views. The study population was divided in two sub-groups according to AF recurrence during follow-up. Results During one-year follow-up, 144 (81%) patients maintained SR whereas 34 (19%) patients had AF recurrence [first-CA group 16 (13%), redo-CA group 8 (20%) and PAF group 10 (50%)]. Improvement of LAS was observed only in patients with paroxysmal and long-standing persistent AF who underwent the first CA and who remained in SR (Figure 1A, 1C). In contrast, recurrent AF was associated with absence of LAS improvement (Figure 1A, 1C). Different time course of LA performance was observed in the redo-CA group, i.e. LAS remained unchanged from baseline regardless of long-term maintenance of SR (Figure 1B). Moreover, at follow-up, no significant differences in LAS between redo-CA patients with SR versus AF were observed. Of note, in patients with long-standing persistent AF and SR, follow-up LAS increased to values observed in the redo-CA group. Conclusion LA performance following CA is strongly affected by complex interplay between extent of atrial electro-structural remodeling and CA procedure. Repeated wide CA might affects negatively LA compliance and contractility despite SR restoration. Figure 1. Reservoir and contractile LAS at Baseline and 12-month follow-up in the First-CA (1A), the Redo-CA (1B) and the long-standing persistent AF (1C) groups in patients who maintained SR versus patients who had AF recurrence. *p value Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): International PhD programme in Cardiovascular Pathophysiology and Therapeutics (CardioPaTh).

Background Diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with dyspnea and paroxysmal atrial fibrillation (AF) is challenging. Speckle tracking-derived left atrial strain (LAS) provides an accurate estimate of left ventricular filling pressures and left atrial phasic function. However, data on clinical utility of LAS in patients with dyspnea and AF are scarce. Objective To assess relationship between LAS and probability of HFpEF in patients with dyspnea and paroxysmal AF. Methods The study included 205 consecutive patients (62±10 years, 58% males) with limiting dyspnea (NYHA ≥ II), paroxysmal AF and preserved LVEF (≥50%), who underwent speckle tracking echocardiography and natriuretic peptide (NT-proBNP) assessment during sinus rhythm. Patients with manifest ischemic heart or valve disease, and cardiomyopathy were excluded. Probability of HFpEF was estimated using H2FPEF and HFA-PEFF scores, which combine clinical characteristics, echocardiographic parameters and natriuretic peptides. Results A total of 61 (30%), 115 (56%) and 29 (14%) had respectively high, intermediate and low probability of HFpEF. Patients with high probability of HFpEF were significantly older, had higher body mass index, NT-proBNP, E/e', pulmonary artery pressure and larger LA volume index than patients in low-to-intermediate probability groups (all p Conclusions Reservoir LAS shows a strong independent association with probability of HFpEF in patients with dyspnea and paroxysmal AF. This advocates for more liberal use of LAS assessment to distinguish cardiac from non-cardiac dyspnea in patients with history of AF. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): International PhD programme in Cardiovascular Pathophysiology and Therapeutics (CardioPaTh).

Background Radio-frequency catheter isolation of pulmonary veins (RF-PVI) is associated with changes of left atrial (LA) structure and function. However, there is limited knowledge regarding the long-term impact of successful RF-PVI on the LA mechanics. The aim of the current study was to assess the time course of LA performance in patients with paroxysmal atrial fibrillation (pAF) undergoing RF-PVI. Methods The study population included 24 consecutive patients (age:62 ± 21 years; 66% male) with symptomatic pAF and preserved left ventricular ejection fraction (≥50%) undergoing the first RF-PVI and 23 healthy controls. A comprehensive echocardiographic examination was performed one day before and 1 day, 3- and 12- months after RF-PVI. The reservoir, conduit and contractile LA strain (LAS), strain rate (LASR) and mechanical dispersion (LAMD) were assessed using two-dimensional speckle tracking echocardiography in apical views. Results At baseline, patients with pAF showed a significant reduction of all three components of LAS and LASR compared with controls (all p Conclusion Successful RF-PVI is associated with acute decrease in LAS, followed by recovery to baseline values within 3 months and further improvement during one year. Reservoir and contractile LAS appears to be the most clinically useful indices to monitor LA performance in patients with pAF undergoing RF-PVI. Figure Time course of LA reservoir and contractile strain, LA max and min volume index, and LA mechanical dispersion (Baseline, 1-day FUP, 3- and 12-month FUP). Abstract 1039 Figure.

Background Atrial mechanical dispersion (MD) might increase the risk of atrial fibrillation (AF). However, the data on atrial mechanical dispersion in patients with AF undergoing catheter ablation (CA) are scarce. Purpose To describe effects of CA on inter- and left intra-atrial MD in patients with different sub-types of AF undergoing CA. Methods We prospectively enrolled 138 symptomatic patients (age: 63 ± 21 years, 32% females) with paroxysmal AF undergoing first (81%) or redo (19%) CA during sinus rhythm, and 20 individuals (age: 66 ± 23 years, 20% females) with long-standing persistent AF undergoing first CA during AF. All patients had normal (≥50%) left ventricular ejection fraction. Control group consisted of 23 healthy controls. The atrial strain and strain rate (SR) were assessed using the two-dimensional speckle tracking echocardiography as average of segmental values in all apical views for LA and in four chamber (4CH) apical view for RA. We quantified inter-atrial MD as the standard deviation of time from the onset of the P wave to peak negative strain curves (Figure 1), and left intra-atrial MD as the standard deviation of time from the onset of QRS wave to peak positive strain curves (Figure 2) of all LA segmental components in 4CH apical view after setting adjusting the reference frame to coincide with the onset of the QRS. Results Figure 3 shows a time course of reservoir LA strain and left intra-atrial MD in patients with paroxysmal AF undergoing the First-CA (3A) versus the Redo-CA (3B), and in patients with long-standing persistent AF (3C). At 1-day pre-ablation, patients with long-standing persistent AF showed significantly lower reservoir strain of both atria and higher left intra-atrial MD as compared with both paroxysmal AF groups and controls (all p Conclusion Atrial strain and MD shows distinct behavior in patients with different sub-types of AF post CA. Atrial MD may provide a complimentary information to strain when assessing LA function. Abstract 554 Figure.

There is little information on left ventricular (LV) hypertrophy (LVH) development during antihypertensive treatment. We evaluate incident LVH in a treated hypertensive cohort, the Campania Salute Network registry. We analyzed prospectively 4290 hypertensives (aged 50.3±11.1 years, 40% women) with at least 1-year follow-up, without LVH at baseline. Incident LVH was defined as the first detection of echocardiographic LV mass index ≥47 in women or ≥50 g/m 2.7 in men. During a median 48-month follow-up, 915 patients (21.3%) developed LVH. They were older, more frequently women, and obese ( P P ++ -channel blockers and diuretics (both P P P =0.019; and obese versus nonobese women: hazard ratio, 1.34; confidence interval, 1.08–1.66; P =0.007). Despite more aggressive antihypertensive therapy, 21% of hypertensive patients develop clear-cut LVH. After adjusting for confounders, risk of incident LVH is particular relevant among women and is further increased by the presence of obesity. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02211365.

Background Duration of Dual Antiplatelet Therapy (DAPT) following Acute Coronary Syndromes (ACS) or Stable Coronary Artery Disease (SCAD) treated with coronary stenting is still debated. Although current guidelines consider several “clinical” criteria to decide for short DAPT (12 months), the relationship between DAPT duration, treatment of bifurcations and its impact on clinical outcome has been poorly investigated in real world registries. Purpose We evaluated the impact of DAPT duration on clinical outcomes in consecutive all-comers patients treated with stenting of coronary artery bifurcation lesions included in the Euro Bifurcation Club -P2BiTO - registry. Methods Data on 5036 consecutive patients who underwent PCI on coronary bifurcation at 17 major coronary intervention centres between January 2012 and December 2014 were collected. The primary endpoint of the study was the cumulative occurrence of Major Adverse Cardiac Events (MACCE), defined as a composite of overall-death death, non-fatal myocardial infarction (MI), target vessel revascularization (TVR) and stroke during the follow-up; the secondary endpoints were the single occurrence of any of the above mentioned events. Results Data on DAPT duration was available for 3992 patients (79%). Patients were divided into 3 groups: Group 1) DAPT 6-months but 12-months (n=1670). Follow up was completed in 3935 (98%) patients with a median of 20 months (C.I.=12–28). At 24 months after the index procedure, MACCE occurred more frequently in the DAPT Figure 1. Kaplan-Meier curves Conclusions In the P2BiTO registry, short DAPT duration of less than 6 months was associated with a significantly higher risk of MACCE compared to longer DAPT in a real-world registry of patients treated for coronary artery bifurcation stenosis.

Background Both atrial fibrillation (AF) and catheter ablation (CA) may be associated with changes in left atrial (LA) structure and function. However, the data describing acute and short-term effects of CA on LA contractile function in different sub-types of AF are scarce. Purpose First, to describe patterns of LA structural and functional remodeling in patients with paroxysmal AF (PAF) or long-standing persistent AF (LSPAF) undergoing first or redo CA. Second, to assess clinical feasibility of LA strain and strain rate (SR) to monitor effect of AF and CA on LA contractile function. Methods We prospectively enrolled 138 consecutive patients (age: 63±21 years, 32% females) with PAF undergoing first (81%) or redo (19%) CA during sinus rhythm, and 20 individuals (age: 66±23 years, 20% females) with LSPAF undergoing first CA during AF. All patients were symptomatic and preserved (≥50%) left ventricular ejection fraction. Control group consisted of 23 healthy controls. All patients underwent comprehensive echocardiography one day pre-CA and post-CA, and at 3 month follow-up. The LA reservoir, conduit and contractile longitudinal strain (LAS) and LASR were assessed using 2D speckle tracking echocardiography as average of segmental values in apical views. Results A total of 14 (9%) patients had insufficient image quality for LA assessment and were excluded (feasibility: 91%). Pre-CA, patients with LSPAF showed the largest left atrial volume index (LAVI) (45±14 ml/m2), followed by PAF (35±8 ml/m2) and controls (24±10 ml/m2) (p Conclusion Different sub-types of AF show different patterns of LA structural and functional remodeling after CA. Both reservoir and contractile LAS appear highly feasible and reproducible to monitor LA contractile function in this clinical setting.

Background The optimal PCI technique for bifurcation lesions remains a matter of debate. Several RCT have compared different bifurcation PCI techniques. Provisional stenting has been recommended as the default technique for most bifurcation lesions. However, emerging data suggests that double-kissing crush technique can be considered in true left main bifurcation lesions and has been endorsed by the European Society of Cardiology Guidelines. Purpose To compare the clinical outcome between different bifurcation PCI techniques. Methods We searched MEDLINE for randomized clinical trials (RCT) comparing PCI bifurcation techniques for coronary bifurcation lesions. Outcomes of interest were major adverse cardiovascular events (MACE) defined as the composite of cardiac death, myocardial infarction (MI) and target vessel or lesion revascularization (TVR/TLR), and the individual components of MACE. Stent thrombosis was assessed as defined by the ARC. Stratification based on left-main or distal bifurcations was performed. We evaluated the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. We estimated summary odds ratios (ORs) using pairwise and Bayesian network meta-analysis. Results We identified 263 studies and of these included 19 RCT including 5572 patients treated with 5 bifurcation PCI techniques namely provisional stenting, systematic T-stenting, crush, culotte and double-kissing crush. Median follow-up was 12 months (IQR 8 to 36). When all bifurcation lesions were combined, double-kissing crush technique reduced the occurrence of MACE (OR 0.42; CrI 0.28 to 0.61) compared to provisional stenting. This difference was driven by a reduction in TVR/TLR (OR 0.39; CrI 0.25 to 0.65). No differences were found in cardiac death, MI or stent thrombosis among analyzed PCI techniques. No differences in MACE were observed between provisional stenting, systematic T-stenting, crush. In distal bifurcations (n=17 studies, 4634 patients), double-kissing crush also showed to reduce MACE (OR 0.48; CrI 0.29 to 0.67 vs. Provisional). In left-main bifurcations (n=3 studies, 938 patients) no differences in MACE were found between PCI techniques. Conclusions In this network meta-analysis, PCI bifurcation techniques were similar with respect to the occurrence of cardiac death, myocardial infarction and stent thrombosis. When all coronary bifurcations were combined, an advantage of double-kissing crush was observed in terms of MACE driven by lower rate of repeated revascularization. Further studies are required to define the best PCI bifurcation technique for left main coronary artery disease.

Background: Catheter ablation is the recommended treatment in patients with paroxysmal atrial fibrillation (AF). However, the data on acute effects of catheter ablation on left atrial (LA) contractile function are scarce. Therefore, the purpose of the study was twofold:Purpose: Firstly, to describe acute effects of catheter ablation on LA contractile function in patients with paroxysmal AF and in sinus rhythm at the time of ablation. Secondly, to assess potential value of different indices of LA morphology and function. Background: Catheter ablation is the recommended treatment in patients with paroxysmal atrial fibrillation (AF). However, the data on acute effects of catheter ablation on left atrial (LA) contractile function are scarce. Therefore, the purpose of the study was twofold:Purpose: Firstly, to describe acute effects of catheter ablation on LA contractile function in patients with paroxysmal AF and in sinus rhythm at the time of ablation. Secondly, to assess potential value of different indices of LA morphology and function. ispartof: Eur Heart J vol:39 issue:suppl_1 status: Published online

Fractional flow reserve (FFR) is the invasive standard of reference in identifying haemodynamically significant stenoses, those that are able to induce reversible myocardial ischaemia. Although defined as the ratio of maximum blood flow in a stenotic coronary to maximum blood flow if the same coronary would be normal, FFR is expressed as the ratio of two pressures: the distal coronary pressure measured by an intracoronary pressure guidewire and the proximal coronary or aortic pressure measured at the tip of the guiding catheter during maximal coronary hyperaemia. A threshold value of FFR less than or equal to 0.80 is currently recommended to indicate or defer coronary revascularization. In fact, a FFR-guided revascularization strategy has been shown to be safe and effective in reducing adverse events in a number of anatomical lesion subsets, including intermediate coronary stenoses, left main stenoses, multivessel disease, bifurcation lesions, sequential stenoses, stented vessels, and bypass grafts. There is growing interest in the use of FFR also in the setting of acute coronary syndrome. In patients with acute ST-elevation myocardial infarction, FFR has been adopted to assess intermediate stenoses incidentally found in non-culprit coronaries, and may be useful to guide the completeness of revascularization in the presence of multivessel disease. Finally, FFR is emerging as a novel potential area for invasive functional assessment of coronary atherosclerotic disease in patients with aortic stenosis, due to the increasing indications to transcatheter aortic valve implantation.

The JT-60SA tokamak, being built under the Broader Approach agreement jointly by Europe and Japan, is due to start operation in 2020 and is expected to give substantial contributions to both ITER and DEMO scenario optimisation. A broad set of preparation activities for an efficient start of the experiments on JT-60SA is being carried out, involving elaboration of the Research Plan, advanced modelling in various domains, feasibility and conception studies of diagnostics and other sub-systems in connection with the priorities of the scientific programme, development and validation of operation tools. The logic and coherence of this approach, as well as the most significant results of the main activities undertaken are presented and summarised. EURATOM 633053

Aim The aim of this study was to evaluate the hemodynamic effect of physiological exercise during coronary angiogram with Pd/Pa, end diastolic Pd/Pa and FFR measurements in symptomatic patients with myocardial bridge (MB). Material and methods We included all consecutive patients with symptomatic MB without significant coronary artery disease between 2014 and 2015. Coronary angiogram was performed with radial approach and supine bicycle set on the table. A pressure wire was placed downstream the MB. Systolic compression was assessed with quantitative coronary angiography. The exercise protocol started at 50 watts and increased by steps of 15 watts every 2 minutes. After exercise, intracoronary nitrates was used and finally intracoronary adenosine administration for FFR measurement. Results 9 symptomatic patients with an isolated LAD MB were included. Patients reached 73% ± 10% of maximum heart rate. No complication occurs during this protocol. FFR was significantly lower compared to rest, peak exercise and after nitrates (P 0.05 for all) ( Fig. 1 ). Conclusion We reported invasive hemodynamic assessment of MB during physiological exercise conditions with supine bicycle. MB increase systolic compression during exercise with a preserved hemodynamic indices.

Recent experiments on lower hybrid (LH) penetration at reactor-relevant densities, together with the recent demonstration of the technological viability of the passive-active multijunction launcher...

A prototype detection unit of the KM3NeT deep-sea neutrino telescope has been installed at 3500m depth 80 km offshore the Italian coast. KM3NeT in its final configuration will contain several hundreds of detection units. Each detection unit is a mechanical structure anchored to the sea floor, held vertical by a submerged buoy and supporting optical modules for the detection of Cherenkov light emitted by charged secondary particles emerging from neutrino interactions. This prototype string implements three optical modules with 31 photomultiplier tubes each. These optical modules were developed by the KM3NeT Collaboration to enhance the detection capability of neutrino interactions. The prototype detection unit was operated since its deployment in May 2014 until its decommissioning in July 2015. Reconstruction of the particle trajectories from the data requires a nanosecond accuracy in the time calibration. A procedure for relative time calibration of the photomultiplier tubes contained in each optical module is described. This procedure is based on the measured coincidences produced in the sea by the $$^{40}$$40K background light and can easily be expanded to a detector with several thousands of optical modules. The time offsets between the different optical modules are obtained using LED nanobeacons mounted inside them. A set of data corresponding to 600 h of livetime was analysed. The results show good agreement with Monte Carlo simulations of the expected optical background and the signal from atmospheric muons. An almost background-free sample of muons was selected by filtering the time correlated signals on all the three optical modules. The zenith angle of the selected muons was reconstructed with a precision of about 3$$^\circ $$∘. © 2016, The Author(s).

The JT-60SA tokamak, being built under the Broader Approach agreement jointly by Europe and Japan, is due to start operation in 2019 and is expected to give substantial contributions to both ITER and DEMO scenario optimization. A broad set of preparation activities for an efficient start of the experiments on JT-60SA is being carried out, involving the elaboration of the Research Plan, advanced modelling in various domains, feasibility and conception studies of diagnostics and other sub-systems in connection with the priorities of the scientific programme, development and validation of operation tools. The logic and coherence of this approach, as well as the main activities undertaken are presented and summarized.