Abstract Background/Objectives Reduced coronary flow reserve (CFR) was described in dilated cardiomyopathy (DCM). To match increased metabolic demand from the myocardium, resting coronary flow (rCF) increases with CFR consumption. Whether an increased rCF causing a reduction of CFR is associated with worse clinical outcomes in DCM remains debated. RCF is inversely correlated to the resting mean transit time (mtt) required for blood to pass through the coronary artery (rCF=1/mtt). A reliable surrogate of mtt is the ratio n frames/frame rate where n frames are the number of frames required for the dye to reach standard distal landmarks of coronary arteries during invasive coronary angiography (ICA) and frame rate is the frame rate acquisition. We aim to assess the prognostic role of rCF evaluated at the ICA performed as standard clinical practice at the time of diagnosis at long–term follow–up in DCM. Methods This is a retrospective analysis of a prospective cohort of patients with idiopathic DCM under medical management enrolled in the Verona Heart Failure registry between 01/2012 and 12/2022. RCF was evaluated at the ICA performed at the time of diagnosis as 1/(n frames/frame rate). The primary endpoint was a composite of cardiovascular death, rehospitalization for heart failure, resuscitated cardiac arrest, hemodynamically unstable ventricular arrhythmias, implanted cardiac defibrillator intervention and cardiac transplantation due to advanced heart failure. Results 110 patients were enrolled in the final cohort. 15 patients (13.6%) suffered the primary endpoint at a median follow–up time of 42 months (IQR 18–71). At the ROC curve analysis rCF predicts the primary endpoint at a cut–off of 2.32 with an AUC of 0.728 (0.599–0.858, p=0.005) with sensitivity, specificity, negative and positive predictive value of 73.3%, 69.5%, 94.3% and 27.5% respectively. Patients suffering the primary endpoint tended to be older (66 years [60–74] vs 59 years [51–69], p=0.060) and were characterized by an increased rCF (3 [1.87–3.75] vs 1.87 [1.36–2.5]). Patients with rCF<2.32 suffered the primary endpoint more frequently when compared to those with rCF≥2.32 (27.5% vs 5.7%, log rank test p=0.007). Conclusions Increased rCF leading to a consumption of CFR is associated with worse clinical outcomes at long term follow–up in idiopathic DCM. Whether coronary microvascular dysfunction can play a prognostic role in this setting remains to be explored by proper prospective studies.

Aims:Speckle tracking echocardiography increasingly supports left atrial (LA) strain (LAS) analysis for diagnosis and prognosis of various clinical conditions. Prior limitations, such as the absence of dedicated software, have been overcome by validated ventricular-based software. A newly automated real-time and offline LA-specific software have now become available on echocardiographs and dedicated workstations. This study aimed at comparing LA strain measures obtained from new fully automated software vs. traditional semi-automated ventricular-based methods in different groups of patients. Methods and results:Two operators acquired LA images in a mixed population of healthy individuals and patients with pressure overload (hypertension and aortic stenosis) or pressure-volume overload (mitral regurgitation and heart failure). Subjects with prosthetic valves, heart transplant, or atrial fibrillation were excluded. Strain analysis was performed twice by old semi-automated software and new LA dedicated. LAS was then measured online on the scanning echocardiograph. Overall, 100 patients were analysed (41 healthy subjects, 28 pressure overload, 31 volume overload). LAS proved to be highly reproducible with both software. The dedicated method exhibited slightly superior inter- and intra-operator reproducibility. The online software results showed a nearly perfect reproducibility with offline software [intraclass correlation coefficient = 0.99 [0.99; 1.00]] in addition to being able to save an average of ∼30 s. Conclusion:The recently developed fully automated software for dedicated LAS analysis demonstrates excellent inter- and intra-operator reproducibility, making it a reliable and efficient strain calculation method in routine clinical practice. Another advantage of online LAS calculation is time efficiency.

Abstract Funding Acknowledgements Type of funding sources: None. Background Severe aortic-stenosis (AS) is the guideline-based indication for aortic-valve-replacement (AVR) performance, which has markedly increased with transcatheter approaches, suggesting possible increasing AS incidence. However, reported secular trends of AS incidence remain contradictory, uncertain and lacking quantitative Doppler-Echocardiographic ascertainment. Thus, population-based trends in presentation, treatment and outcome are unknown. Methods All adults residents our County (MN,USA) diagnosed with incident (first-diagnosis) severe AS based on quantitative Doppler-Echocardiography (aortic-valve-area≤1cm2, aortic-valve-area-index≤0.6cm2/m2, mean-gradient≥40mmHg, peak-velocity≥4m/s, Doppler-velocity-index≤0.25) between 1997–2016, were accounted for and trends for incidence, presentation, treatment and outcome analysed. Results Incident severe-AS was diagnosed in 1069 community-residents over 20-years. Incidence-rate was 52.5[49.4–55.8] per 100.000 patient/year, slightly higher in male vs. female and was almost unchanged after age and sex adjustment for the US population 53.8[50.6–57.0] per-100000 residents/year. Over 20-years severe AS-incidence remained stable (p = 0.20) but absolute-burden of incident-cases markedly increased (p = 0.0004) due to population growth. Incidence-trend differed by sex, stable in men (incidence-rate-ratio 0.99, p = 0.72) but declining in women: (incidence-rate-ratio 0.93, p = 0.024). AS clinical-presentation, age, symptoms, comorbidity, ventricular size/function, valve-area-index, low-flow or low-ejection-fraction AS, remained stable. Over the study 20 years, AVR performance grew (1997–2001 to 2012–2016, at 3-month:14% to 21%, p = 0.02; at 1-year 19% to 33%,p<0.0001), and was more prompt (from 1.3[0.11–3.3]years in 1997–2001 to 0.48[0.15–2.11]years in 2013–2016, p = 0.001) but severe AS undertreatment remained prominent (>40%). Early-AVR (within 3-months) was associated with survival benefit (adjusted-hazard-ratio 0.55[0.42–0.71], p<0.0001) stable throughout the 20-years. Despite these improvements, overall mortality, 8.3% within 3-months, 17.8% within 1-year, 36% within 3-years, was swift, considerable and unabated (all p≥0.44) throughout the 20-year study. Conclusion Over 20 years, the population incidence of severe-AS remained stable with increased absolute case-burden purely related to population growth. Despite stable severe-AS presentation, AVR performance grew notably, but while declining, undertreatment remained substantial and disease-lethality did not decline. These findings have important population-health management implications.

Abstract Funding Acknowledgements Type of funding sources: None. Background left atrial (LA) strain by speckle tracking echocardiography (STE) is gaining increasing evidence as diagnostic and prognostic tool in several clinical settings. However, the lack of a dedicated software was considered one of its main limitations, although many studies proved a good feasibility and reproducibility of a ventricular-based software. Brand-new fully automated software tools dedicated to the LA have been developed, both for on-line use on the echocardiographic machine and for off-line use on the workstation. Purpose The purpose of our study was to compare LA strain measures acquired by the new fully automated dedicated software with the "traditional" semi-automated ventricular based one in healthy, pressure-overloaded, and volume-overloaded patients. Methods Grey scale apical 4-chamber view echocardiographic images acquired by an experienced operator (GE, Vivid E9, Orthern, Norway) in healthy patients, patients with pressure overload (arterial hypertension, aortic stenosis) and pressure-volume overload (mitral regurgitation, heart failure) were analyzed. STE was performed offline by two independent experienced operators, using both the semi-automated and the fully automated Echopac (Milwaukee,Wisconsin) software, which was then compared using matched-pairs analysis. Both operators were blinded to the other measures and repeated the same measurement on the same images after 10 days. Measurement of LA strain was performed on-line on the echocardiographic machine in a selected group of 20 patients by one of the two operators. Patients with prosthetic valves, heart transplantation, atrial fibrillation were excluded. Results Overall, 100 patients were analyzed (41 healthy patients, 28 with pressure overload, 31 with pressure-volume overload). Peak atrial longitudinal strain (PALS) showed a high reproducibility with both methods. However, the dedicated method had a slightly higher inter-operator reproducibility (intraclass correlation coefficient(ICC)=0.97; 95% CI=[0.87;0.99] vs. ICC=0.96 [9.87;0.99] ) (Fig.1) and intra-operator reproducibility (ICC=0.99 [0.99;0.99] vs. 0.98 [0.98;0.99] (Fig.2); correlation=0.85, p<0.001in operator 1 and 0.97 [0.95;0.98] vs. 0.95 [0.92;0.96]; correlation=0.83, p<0.001 in operator 2) with a slightly lower time consumption (90 s vs. 105 s) than the traditional ventricular-based one. On-line software showed a nearly perfect reproducibility with offline software [ICC=0.99 [0.99;1]] with a further time saving (60 vs. 90 s). Conclusions the new fully automated software for the analysis of LA strain has a high inter-operator and intra-operator reproducibility. Both the automated and the traditionally used semi-automated software calculation provided optimal reproducibility and time-consumption, for different categories of subjects, and could be equally chosen for strain calculation in daily clinical practice. On-line LA strain calculation allows a reliable and time-saving measurement.

Abstract Funding Acknowledgements Type of funding sources: None. Background Multicenter longitudinal data are lacking regarding the incidence and the time needed for total left ventricular thrombus (LVT) regression obtained with contemporary antithrombotic regimens diagnosed with modern echocardiographic technology. Purpose To quantify the effect of antithrombotic therapy on LVT evolution using sequential up-to-date echocardiography in a large cohort of patients with LVT. Methods Ten centers were involved in this observational prospective multicenter study. LVT was defined as an echo-dense mass adjacent to a hypokinetic or akinetic myocardial segment. To be distinguishable from the underlying myocardium, a clear thrombus–blood interface was required and the LVT had to be visible on at least 2 views during the cardiac cycle. Initial follow-up echocardiograph was scheduled at 14±7 days (T0) and 42±7 days (T1). The early resolution was defined when LVT was no longer detected at T1. The use of different anticoagulant regimens and ultrasound contrast was left at the discretion of attending physicians, according to good clinical practice. Results From October 2020 to November 2022, 99 patients with LVT (mean age 66 ± 11 years, 80% men) were identified with echocardiography, in 53% ultrasound contrast was used. Early resolution of LVT was observed in 42%. Echocardiographic characteristics by early resolution of LVT are shown in Table. The independent correlates of early LVT regression were smaller baseline LVT area, higher LVEF, and mobile LVT (p<0.05). Conclusions In this large and well-characterized present-day cohort of patients with LVT, early regression by echocardiography was achieved in less than half of the patients and was mostly related to the size of the LVT and heart function rather than treatment despite a high proportion of antithrombotic therapy. The next step will be to assess the impact of LVT persistence on subsequent clinical outcomes.

Abstract Background Trastuzumab (TZ) is widely used for his key role in HER2 positive breast cancer. However, the most concerning cardiovascular complication is cardiotoxicity. Many studies have highlighted the importance of screening for subclinical myocardial dysfunction using left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). However, there are only few studies investigating a possible atrial damage. Purpose Aim of this study is to analyze the modification of GLS and peak atrial systolic longitudinal strain (PALS) in patients undergoing therapy with TZ in a follow-up period of 12 months. The eventual fluctuation of left atrial function under chemotherapy was evaluated and the correlation between subclinical atrial disfunction and early left ventricular impairment was investigated. Methods 105 women affected by breast cancer treated with TZ were enrolled. Each patient underwent a complete echocardiography at baseline and every 3 months. 37 patients (35%) were excluded from the left atrial function analysis while LV function evaluation was performed in 83 patients (21%). Exclusion criteria were poor quality imaging and lack of a complete follow up with consequent missing data. 2D-Speckle tracking analysis was performed at baseline and at each examination using Tomtec software in order to analyze both atrial and left ventricular function. Subclinical LV disfunction was defined as a GLS reduction of ≥15% compared to the baseline value. Left atrial impairment was arbitrary defined as a PALS reduction of ≥25% compared to the initial value. Finally, trends of GLS and PALS during 12 months-follow up periods were analyzed. Additionally, we explored if diabetes and renal impairment were associated with more prevalent atrial subclinical disfunction as demonstrated in previous studies. Results A total of 49% patients developed subclinical LV dysfunction. Similarly, 48% patients showed a left atrial impairment. Interestingly a significant (p=0.0001) reduction in GLS was observed during the follow-up, particularly in the first six months of treatment. PALS showed a similar trend with a significant decrease during the whole 12 months-follow up (p=0.0001) and mostly in the first 6 months. 6 patients presented a diagnosis of diabetes at baseline, and presented lower PALS compared to the non-diabetic counterpart (37.6±9.9% vs 48.7±12.2%, p=0.03). 2 patients presented a significant renal impairment (eGFR ≤30 ml/min). Similarly, these patients presented a lower PALS at baseline (32±7 and 48±7; p=0.05). Conclusions In patients treated with Trastuzumab development of left atrial impairment is frequent and PALS modifications follow a similar pattern to GLS variations during the treatment, suggesting a possible cardiotoxic effect of such therapy on both atrial and left ventricular myocardium and physiology. Funding Acknowledgement Type of funding sources: None.

Abstract Funding Acknowledgements Type of funding sources: None. Background Pulmonary hypertension is a frequent complication of severe degenerative mitral regurgitation (DMR) associated with major outcome implications. However, whether pulmonary hypertension is linked with worse outcome in less that severe MR is uncertain and even more unsubstantiated is the link of elevated systolic pulmonary artery pressure (sPAP) < 50mmHg with clinical presentation and outcome. Purpose To assess the outcome implication of sPAP elevation, even moderate, among mitral regurgitation severity subgroups. Methods The MIDA-Quantitative (MIDA-Q) unprecedented registries included 7373 consecutive patients (age 64 ± 17 years, 45% women, follow-up 5.5 ± 3.4 years) with isolated DMR diagnosed at tertiary (European/North-American/Middle East) centers in which systolic pulmonary artery pressure (sPAP) was measured prospectively at baseline. Long-term survival overall, under medical management and post-mitral surgery was analyzed. Results Elevated pulmonary pressure (sPAP >50mmHg) was observed in 1371 patients (19%, mean 63 ± 13mmHg) and moderate increase in pulmonary pressure (35< sPAP < 50mmHg) in 1874 patients (25%, mean 41 ± 14mmHg), with no/mild MR in 4067 (50%), moderate in 2073 (25%), and severe or above in 2047 (25%), mean ERO 0.24 ± 24cm2, RVol 37 ± 35mL and posterior leaflet prolapse in 34%. sPAP severe but also moderate both strongly and independently linked to more severe clinical presentation, with more dyspnea, more AFib, and impaired renal function (P ≤ 0.0001). By sPAP categories, 35 < sPAP< 50mmHg (vs. 35mmHg) was independently associated with worse outcome under medical management adjusted-HR 1.62[1.40-1/87], with considerable excess-mortality for sPAP > 50mmHg (vs. <35mmHg) adjusted-HR 2.54[2.17-2.96], all P < 0.0001. As continuous variable, sPAP was associated with worse outcome adjusted-HR 1.25[1.21-1.29], P < 0.0001 per 10mmHg-increase. Mitral valve surgery (performed in 2378 patients, 32%) improved outcome without alleviating completely higher mortality associated with sPAP > 50mmHg (P < 0.0001). Conclusion In this very large international cohort of patients with DMR of all range and prospective sPAP grading, higher sPAP is associated at diagnosis with more severe clinical presentation. Long term, sPAP > 50mmHg but also 35-50mmHg is independently of all confounders, associated with worse mortality. Thus careful assessment and consideration for mitral surgery/transcatheter therapy is warranted even in patients with sPAP <50mmHg. Abstract Figure. Survival stratified by sPAP Categories Abstract Figure. Postop survival by sPAP Categories

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND The debate about the independent prognostic responsibility of functional mitral regurgitation (FMR) is still in turmoil. Growing findings about the predictive role of left atrial (LA) function are emerging in several scenarios. PURPOSE This study aims to define FMR linkage to cardiovascular (CV) outcomes and the interplay with LA function in a prospective cohort of consecutive heart failure patients with reduced ejection fraction (HFrEF). METHODS 286 consecutive outpatients with chronic HFrEF were enrolled. FMR was quantified by effective regurgitant orifice area (EROA). Global peak atrial longitudinal strain (PALS) was measured by speckle tracking echocardiography (STE). The primary endpoint was defined as a composite of congestive HF hospitalization and CV death. RESULTS The majority (81%) of patients were men (mean age: 67 ± 11 years, mean LVEF: 32 ± 6%). The median global PALS was 17.7% ranging from 2.7% to 49.2%. FMR was quantifiable in 240 (84%) patients. During a median follow-up period of 6.4 (IQR 3.9-7.7) years, the primary endpoint occurred in 88 (31%) patients (35 HF admissions, and 53 deaths). EROA showed independent prediction for the primary endpoint (HR 1.30 [1.05-1.57], P = 0.01). The spline modeling of the risk by EROA values showed an excess event risk starting at about the EROA value of 0.1 cm2 (Figure 1). There was a remarkable graded association between the EROA strata, even if tested per 0.1 cm2 increase, and the risk of congestive HF hospitalization and CV death (P = 0.0004). Any FMR grade presenting with reduced LA function (PALS < 14%) was associated with dismal outcome (event rate of 63 ± 10% for EROA exceeding 0.3 cm2 and 49 ± 6% for EROA ≥0.1 cm2 at 5 years). Conversely, the presence of EROA ≥0.1 in the context of preserved global PALS showed a better outcome (Figure 2). CONCLUSIONS Our results refine the independent association between FMR and CV outcome among HFrEF outpatients. The risk of CV events starts at a low EROA value, reaching a severe level above the threshold of 0.3 cm2. Within a moderate EROA range, the LA function mitigates the clinical consequences of the mitral regurgitation, providing measurable proof of the interplay between the regurgitation and the LA compliance. Abstract Figure 1 Abstract Figure 2

Abstract Background Little is known about coronary microvascular function of patients with low-flow low-gradient aortic stenosis (LFLGAS). We hypothesized that LFLGAS is associated with more severe coronary microvascular dysfunction (CMD) compared with normal-flow high-gradient aortic stenosis (NFHGAS) and that CMD is related to reduced cardiac efficiency. Purpose To perform a prospective invasive assessment of CMD in patients with LFLGAS undergoing TAVI and to compare it with patients with NFHGAS. Moreover, we aimed to assess the possible acute impact of TAVI on coronary microvascular function and the interactions between CMD and of cardiac performance at speckle tracking echocardiography (STE). Methods Invasive thermodilution-based assessment was systematically performed in 41 consecutive patients with isolated severe AS with angiographic unobstructed coronary arteries undergoing TAVI. The index of microcirculatory resistance (IMR), resistive reserve ratio (RRR) and coronary flow reserve (CFR) were derived to assess coronary microcirculatory function before and after TAVI. Advanced echocardiographic imaging, including STE, was performed to assess cardiac function. Results IMR was significantly higher in patients with LFLGAS compared with patients with NFHGAS (24.1 [14.6–39.1] vs 12.8 [8.6–19.2] p=0.002). Similarly, RRR was significantly lower in LFLGAS compared with NFHGAS (1.4 [1.1–2.1] vs 2.6 [1.5–3.3] p=0.020). No significant differences were observed in CFR between the two groups. High IMR was associated with low stroke volume index (rho=−0.427, p=0.005), low cardiac output (rho=−0.517, p=0.001), reduced peak atrial longitudinal strain (PALS) (rho=−0.610, p≤0.001) and presence of atrial fibrillation (54.6% vs 21.1%, p=0.036). Conversely, IMR was only modestly associated with the mean pressure aortic valve gradient (rho=−0.304, p=0.054). Notably, the mean gradient was significantly associated with IMR in the NFHGAS group (rho=0.632, p=0.003) but not in the LFLGAS (rho=−0.222, p=0.333). Similarly, high IMR was associated with the AVA in the NFHGAS group (rho=−0.50, p=0.025) but not in patients with LFLGAS (rho=0.157, p=0.497). Paradoxical LFLGAS emerged as a phenotype associated with CMD, poor left ventricular longitudinal systolic function and left atrial dysfunction. TAVI determined no significant variation in microvascular function (IMR: 16.0 [10.4–26.1] vs 16.6 [10.2–25.6], p=0.403) and in PALS (15.9 [9.9–26.5] vs 20.1 [12.3–26.7], p=0.222). Conversely, left ventricular global longitudinal strain increased overall after TAVI (−13.2 [8.4–16.6] vs −15.1 [9.4–17.8], p=0.047). Conclusions LFLGAS is associated with impaired coronary microvascular function compared with NFHGAS. Combined invasive assessment of microvascular function and advanced non-invasive imaging contributed to define different AS phenotypes. CMD was associated with low-flow state, left atrial dysfunction and reduced cardiac efficiency in patients with AS. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Abbott Vascular

Abstract Funding Acknowledgements Type of funding sources: None. Background Trastuzumab (TZ) is a key therapy for HER-2 positive breast cancer that may have different side effects on the cardiovascular system. One of the most concerning complications is cancer therapy-related cardiac dysfunction (CTRCD). In literature there are conflicting data about the efficacy of heart failure drugs like ACE-inhibitors, ARBs and beta-blockers to prevent such an event. Purpose Aim of this study is to describe our experience on cardioprotective drugs in preventing TZ-related CTRCD. Methods 105 consecutive women affected by HER-2 positive breast cancer treated with TZ referring to our echo-lab were enrolled in our single center prospective study. 3 patients were excluded due to an early TZ suspension not related to cardiovascular complications. Thus 102 patients (97,1%) were eligible for analyses. 86 of these (84,3%) were also treated with Anthracyclines. All patients underwent consecutive transthoracic echocardiography (TTE) before starting TZ and then every 3 months up to 12 months. 2D-Speckle tracking analysis was performed at baseline and at each examination using Tomtec software. A complete clinical evaluation was also performed at each follow up. LV systolic dysfunction was defined as an absolute reduction of LVEF >10% from baseline to LVEF < 53% or a relative reduction of GLS >15% from baseline and a reduction of LVEF >10% from baseline. Results Overall, before starting TZ, 12 patients were taking ACE-inhibitors or ARBs (11,8%) and 5 patients beta-blockers (4,9%). CTRCD occurred in 11 patients (10,8%), among these 9 (81,8%) weren’t taking any heart failure drugs and 5 (45,5%) didn’t present any cardiovascular risk factor. We observed no significant association among cardiovascular risk factors. Use of potential cardioprotective drugs before TZ administration seems to reduce the risk of development of myocardial dysfunction (relative risk 1,67; 95% confidence interval [CI], 0,41 to 6,82; P > 0.05). No clear association was found between any cardiovascular risk factors and CTRCD (relative risk 0,81; 95% confidence interval [CI], 0,26 to 2,47; P > 0.05). Conclusions In HER-2 positive breast cancer patients treated with TZ an early treatment with ACE-inhibitors or ARBs and/or beta-blockers is associated to the prevention of CTRCD. CTRCD seems not to be related to the presence of cardiovascular risk factors. Abstract Figure. Baseline patient characteristics

Abstract Funding Acknowledgements Type of funding sources: None. OnBehalf MASCOT investigators Background Few studies analyzed left atrial (LA) peak atrial longitudinal strain (PALS) determinants, particularly across heart failure (HF) stages. We aimed to analyze the pathophysiological and clinical PALS correlates in a large international prospective registry. Methods This is a multicenter prospective observational study enrolling 745 patients with HF stages 0-C from July to October 2018. Data included PALS and left ventricular global longitudinal strain (LV-GLS). Exclusion criteria were: valvular prosthesis; atrial fibrillation; cardiac transplantation; poor acoustic window. Results Median global PALS was 17% [24-32]. 29% of patients were in HF-stage 0/A, 35% in stage-B, and 36% in stage-C. Together with age, the echocardiographic determinants of PALS were LA volume and LV-GLS (overall model R²=0.50, p < 0.0001). LV-GLS had the strongest association with PALS at multivariable analysis (beta:-3.60 ± 0.20, p < 0.0001). Among HF-stages (Figure 1), LV-GLS remained the most important PALS predictor (p < 0.0001) whereas age was only associated with PALS in lower HF-stage 0/A or B (R=-0.26 p < 0.0001, R=-0.23 p = 0.0001). LA volume increased its association to PALS moving from stage 0-A (R=-0.11; P = 0.1) to C (R=-0.42; P < 0.0001). PALS was the single most potent echocardiographic parameter in predicting HF stage (AUC for B vs. 0/A 0.81, and AUC vs. 0/A for C 0.76). PALS remained independently associated with HF stages after adjusting for ejection fraction, E/e’ ratio and mitral regurgitation grade (p < 0.0001). Conclusion Although influenced by LV-GLS and LA size across HF-stages, PALS is incrementally and independently associated with clinical status. LA function may reflect a substantial part of the hemodynamic consequences of ventricular dysfunction. Abstract Figure 1

Abstract Background It is well known that left atrial (LA) function and size can provide significant information regarding the risk of atrial fibrillation (AF) and heart failure (HF). The ratio of LA volume index and tissue doppler imaging a' (peak myocardial velocity of the left ventricle in late diastole exposing the atrial contraction) provides the LA volumetric/mechanical coupling index (LACi). LACI is a novel echocardiographic measurement which combines information of LA size and function in one measure with limited previous investigation. Purpose The aim of the present study was to investigate the prognostic value of LACi in relation to incident HF and AF in the general population. Methods The present study included 4,003 participants from a prospective general population. All participants were examined with echocardiography. Incident HF and AF were investigated as separate outcomes. Exclusion criteria were AF and/or HF at baseline. LACi was calculated as the index of LAVI (left atrial volume index) and peak tissue velocity at late diastole measured with pulsed wave Doppler at the septal base of the left ventricle. Results Mean age was 56±17 years, 57% were female, and median LACi was 2.3 [IQR: 1.8, 3.0]. The median follow-up time was 5.4 [IQR: 4.5, 6.3] years. A total of 82 and 164 developed HF and AF during follow-up, respectively. Median LACi was significantly higher among participants developing HF (2.6 [IQR: 2.1, 3.8], P<0.001) and AF (2.8 [IQR: 2.1, 4.1], P<0.001) compared to those who remained event free (2.3 [IQR: 1.8, 3.0]). Multivariable Cox proportional hazard regression models were constructed and adjusted for gender, age, smoking status, hypercholesterolemia, diabetes mellitus, ischaemic heart disease at baseline, hypertension, left ventricular ejection fraction and left ventricular diastolic function (E/e'). LACi was an independent predictor of incident HF and of AF in both univariable and multivariable Cox regression models (Figure 1). LACi remained a significant predictor of both HF and AF in a sensitivity analysis with subgroups in which LAVI was normal and enlarged, respectively (Figure 1). Conclusion LACi is an independent predictor of HF and AF in the general population. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): The Danish Heart Foundation and The Metropolitan Region of Denmark.

Abstract Background Multimodality imaging approach is becoming more and more common in evaluating the severity and outcome of aortic stenosis (AS). Aim To assess the outcome of asymptomatic AS and the usefulness of aortic calcium score (CS) by computed tomography (CT) for solving the dilemma of low flow, low gradients (LFLG) severe AS. Methods 70 (81.4±8.4 years) prospective asymptomatic patients with AS were followed for 2.77±2.01 years with a trans-thoracic echo (TTE) every 6 months. End-points were all cause mortality, aortic valve replacement (AVR or TAVR), aortic velocity and gradients progression and symptoms occurrence. Prevalence of LFLG-AS was investigated and these patients underwent CT for CS calculation at the end of follow-up (FU), Figure 1. Results Baseline TTE results from the 70 pts were: peak velocity 3.1±0.8m/sec; peak gradient 44±21mmHg; mean gradient 26±14 mmHg; AVA 1±0.3 cm2; DVI 0.31±0.1; Svi 33.8±18 ml/m2; EF: 55±9% with an AS being mild in 32.9%, moderate in 28.4%, severe in 27.1%; 36.8% of severe AS were LFLG. During FU, 23 (32.8%) pts died (5.7% LFLG) and 13 (18.5%) underwent AVR/TAVR. Predictors of mortality were aortic gradients (p=0.03), AVA (p=0.008), DVI (p<0.001), pulse pressure (p=0.005) and dilated ascending aorta (p<0001). Predictors of AVR/TAVR were: gradients (p=0.003), peak aortic velocity (p=0.02) and dilated ascendent aorta (p=0.01). The best cut-off to predict survival was AVA = 1 cm2 (100% sensitivity and 80% specificity). In 34 pts ending FU we found an overall progression of AS severity (peak velocity 3.6±0.9m/sec; peak gradient 50±24 mmHg; mean gradient 33±15 mmHg; AVA 0.7±0.3 cm2; DVI 0.25±0.08; Svi 36±10 ml/m2; EF 54±10%; p<0.05 for all vs baseline) with 24 (70.5%) pts with severe AS and 10 (29.5%) with not severe AS. 18 (75%) of progressive severe AS were LFLG, 12 asymptomatic and 6 symptomatic and all underwent CS revealing that AS was not severe in 6 (1233±1123 AU; 622±55 AU/m2) and true severe in 12 (3388±1188 AU; 1858±795 AU/m2; p=0.005 and p=0.002, respectively). Symptomatic severe LFLG AS were all true severe according to CS (Figure 1). Table 1 shows the main CS correlations. Conclusions Asymptomatic AS in elderly people is associated with high mortality risk and rapid progression. AVA remains the best predictor of outcome. In severe LFLG AS, calcium score correlates with symptoms occurrence, progression of valve disease, LV hypertrophy and function and also with RV function. Funding Acknowledgement Type of funding sources: None.

Abstract Funding Acknowledgements Type of funding sources: None. Background Radiofrequency catheter ablation of pulmonary veins has become a common procedure for treatment of atrial fibrillation (AF). Nevertheless, the procedure is characterized by an extremely variable success rate, which reflects a great heterogeneity of factors implicated in AF recurrence and AF burden. Purpose We focused on the role of left atrium (LA) in patients with paroxysmal and persistent AF who underwent catheter pulmonary veins ablation procedure. In particular we paid attention to three factors: echocardiographic evaluation of LA function, LA scar evaluated by electroanatomic mapping and LA pressures (LAP) during ablation procedure. The aim of the study was to investigate the correlation between echocardiographic parameters indicating atrial dysfunction (LA volume indexed, E/E’, LAA contraction velocity, LA stiffness and LA longitudinal strain during reservoir phase (LASr)) and intraprocedural parameters (such as LAPpeak and the amount of fibrosis). Methods The study included 25 patients; mean age was 63 ± 8 years; nineteen patients (76%) had paroxysmal AF, eighteen patients (72%) were in sinus rhythm at the time of ablation. The population was divided into two subgroups according to the amount of fibrosis evaluated by electroanatomic mapping: patients with fibrosis ≥ 5% of the total LA volume were considered as having an atrial scar. All patients underwent a comprehensive transthoracic echocardiography and a transesophageal echocardiography before the ablation procedure. Intraprocedural data regarding LAPpeak and electroanatomic mapping were collected. Measurements were acquired during both sinus rhythm (SR) and AF. Results Patients with atrial scar had similar LA volume compared to patients without scar (44 ml vs 37.4 ml, p = 0.108) , but presented a trend towards higher LAPpeak (24.3 mmHg vs 15.9 mmHg, p = 0.053) and had higher E/E’ (11 vs 7, p = 0.037) and consequently increased LA stiffness (0.72 vs 0.23, p= 0.006). Still, they had lower LASr (16.6% vs 33.2%, p = 0.013) and tended to have reduced LAA contraction velocity (0.4 m/sec vs 0.7 m/sec, p= 0.005). Conclusions The present findings suggest that functional remodeling of the LA, more than morphological changes, are correlated with the presence of atrial fibrosis and elevated atrial pressure detected during ablation procedures. These parameters may represent potential criteria to guide patients’ selection for ablation procedure and deserve dedicated studies to be confirmed. Abstract Figure.

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Copenhagen City Heart Study was funded by the Danish Heart Foundation, and the echocardiographic substudy was further funded by the Lundbeck Foundation. Background Atrial fibrillation (AF) represent a global health burden. Identifying people at risk based on echocardiography has always been challenging. Hence, we aimed to assess the distribution of left atrial volumetric/mechanical coupling index (LACI) in the general population and test its potential to predict incident AF. Methods In a large community-based population study, LACI was calculated by dividing the left atrial (LA) maximal volume by the a’ peak velocity obtained by color Tissue-Doppler Imaging. Clinical endpoint was incident AF. The exclusion criteria were history of AF or previous heart failure. Results A total of 1021 patients formed the study cohort (mean age 52.8 ± 13.3, 45% (n = 459) were male); Median LACI was 2.84 [IQR: 2.14-3.82], rarely exceeding the value of 6. During a follow-up period of 16.1 years (IQR15.6-16.3), 8.9 % (n = 91) of patients developed AF. LACI independently predicted AF (HR 1.11 [1.04-1.17], p = 0.001 unadjusted and HR 1.20 (1.06-1.35), p = 0.003 after a comprehensive multivariable adjustment (including clinical, biochemical, and echocardiographic variables). The Figure illustrates the strong relationship between LACI and the incidence of AF, almost linear, with no plateau effect. In a sensitivity analysis, the association between LACI and incident AF persisted in both hypertensive (HR 1.12 (1.05-1.19) p = 0.001) and non-hypertensive participants (HR 1.18 (1.03-1.35) p = 0.02). Conclusion LACI is a measure of LA function which is routinely available and presents a skewed distribution towards low values in the general population. LACI independently predicts incident AF, irrespective the presence of systemic arterial hypertension. Abstract Figure

Abstract Introduction Left atrial (LA) function has been associated to right chambers hemodynamics in the context of mitral valve regurgitation (MR). However, this physiological interplay between left atrial function, mitral regurgitation and right ventricular (RV) parameters has not yet been clarified in patients with aortic valve stenosis (AS). Aim of the study To assess the combination of LA function and different MR grades with right chambers performance and pulmonary non-invasive hemodynamics status in patients with severe AS using an advanced automated echocardiographic approach. Methods Consecutive patients with severe AS referred to our institution were analyzed. Mitral regurgitation was classified according to integrative guideline-based criteria. 2D advanced speckle tracking echocardiography analysis was conducted to measure the LA peak atrial longitudinal strain (PALS) and right ventricular free wall strain, (RVFWS) using Tomtec Arena, version TTA2 41.00, with dedicated LV/LA/RV analysis option (Tomtec, Unterschlei heim, Germany). All conventional right chambers performance indexes were also measured: TAPSE, S'- TDI, fractional area change, systolic pulmonary artery pressure (sPAP). We featured 3 patients groups based on MR grade and LA function: (a) no/mild MR and preserved PALS (above the median); (c) >mild MR and reduced PALS; (b) the remaining patients with >mild MR and low PALS or >mild MR and high PALS. Results A total of 102 patients with severe aortic stenosis formed the study cohort: age was 82±9, 47% were female, mean left-ventricular-ejection-fraction 56%±12, more than mild MR was present in 24% of patients, mean PALS was 19±10%, sPAP 38±12 mmHg, RVFW strain 21±6%, and RVFW/sPAP 0.62±0.25. The 3 subgroups presented similar age and sex distribution. Right ventricular function significantly worsened moving from group (a) to (c); RVFW strain decreased from 25±5 (a) to 19±7 (b) and 17±5% (c), p<0.001; sPAP increased from 34±9 (a) to 39±12 (b) and 47±13 mmhg (c), p<0.001; and RVFW/sPAP decreased from 0.76±0.21 (a) to 0.54±0.23 (b) and 0.39±0.11 (c), p<0.001. Patients in the group (c) were more symptomatic (NYHA class III/IV increase from 40% in group a and 63% in group (b) to 80% in group c, p=0.006). When added to MR grade, in a logistic regression analysis, PALS provided incremental prediction of all right ventricular parameters (p<0.01). Conclusion This study highlights that the combination of MR and reduced LA function is associated with symptoms and RV impairment in patients with severe AS. These preliminary results suggest that preserved LA function may modulate the adverse effects of the AS-MR combination by preventing/delaying the development of pulmonary hypertension and right ventricular dysfunction. Funding Acknowledgement Type of funding sources: None.

Right ventricular failure (RVF) after left ventricular assist device (LVAD) implant is associated with increasing morbidity and mortality. The aim of this study was to identify the best predictors of RVF post LVAD-implant among biochemical, haemodynamic and echocardiographic parameters. From 2009 to 2019, 38 patients who underwent LVAD implantation at our centre were prospectively enrolled. Preoperative clinical, laboratory, echocardiographic and haemodynamic parameters were reported. Overall, eight patients (21%) developed RVF over time, which revealed to be strongly related to overall mortality. Pulmonary artery pulsatility index (PAPi) resulted to be the most significant right heart catheterization index in discriminating RVF vs no RVF patients [(1.32 ± 0.26 vs. 3.95 ± 3.39 respectively) p = 0.0036]. Regarding transthoracic echocardiography, RVF was associated with reduced free wall right ventricular longitudinal strain (fw-RVLS) (− 7.9 ± 1.29 vs. − 16.14 ± 5.83) (p < 0.009), which was superior to other echocardiographic determinants of RVF. Among laboratory values, N-terminal pro-brain natriuretic peptide (NT-proBNP) was strongly increased in RVF patients [(10,496.13 pg/ml ± 5272.96 pg/ml vs. 2865, 5 pg/ml ± 2595.61 pg/ml) p = 0.006]. PAPi, NT-proBNP and fwRVLS were the best pre-operative predictors of RVF, a post-LVAD implant complication which was confirmed to have a great impact on survival. In particular, fwRVLS has been proven to be the strongest independent predictor.

Right ventricular (RV) involvement is frequently detected in patients presenting with acute left ventricular myocardial infarction. The ischemic right ventricle carries a dismal outcome by predisposing the heart to arrhythmic events and mechanical or hemodynamic complications. A comprehensive RV evaluation by multimodality imaging could guide clinical practice but has always been a conundrum for the imagers. Two-dimensional echocardiography is the best first-line tool due to its availability of bedside capabilities. More advanced imaging techniques provide a more comprehensive evaluation of the complex RV geometry but are mostly reserved for the post-acute setting. Three-dimensional echocardiography has improved the evaluation of RV volumes and function. The recent application of speckle-tracking echocardiography to the right ventricle appears promising, allowing the earlier detection of subtle RV dysfunction. Cardiac magnetic resonance imaging is considered the gold standard for the RV assessment. Cardiac multidetector computed tomography could be a reliable alternative. The aim of this review is to focus on the growing importance of multimodality imaging of the ischemic right ventricle and to propose a diagnostic algorithm, in order to reach a comprehensive assessment of this too frequently neglected chamber.

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Mayo Clinic Foundation Background Left atrial (LA) volume is linked to outcome in degenerative mitral regurgitation (DMR) but does not encompass LA function assessment. Thus, we ought to determine the prognostic role of left atrial coupling-index (LACI), as left atrial volume-index (LAVI) by Tissue-Doppler-Imaging a’ (TDI-a’), in a large cohort of DMR. Methods All consecutive 4792 patients (61 ± 16 years, 48% women) with isolated degenerative mitral valve disease diagnosed at Mayo Clinic 2003-2011, comprehensively characterized, in whom LAVI and TDI-a’ in sinus rhythm was prospectively measured in routine practice, was enrolled and their long-term survival analyzed. Results LACI (5.8 ± 3.7–T1 < 3.8; T2 3.8-6.3; T3 > 6.3) was significantly higher through different DMR grades (no, mild, moderate, severe DMR: 3.77 ± 2.26, 5.08 ± 2.95, 6.54 ± 3.74 and 7.84 ±4.29 respectively; p < 0.0001). Independent determinants of LA dysfunction assessed by LACI were age, E/e’, left-ventricle (LV) end-systolic-diameter, mitral-regurgitation (MR) grade, and LV ejection-fraction (all P ≤ 0.0001). LACI > 6 was independently associated with dyspnea, edema, more severe functional tricuspid-regurgitation and elevated pulmonary artery pressure, irrespective of age, sex, Charlson-comorbidity-index, ventricular function and MR severity. Total follow-up was 7.03 ± 3.0 years, during which 1146 (24%) underwent mitral-valve surgery (94% repair-6% replacement) and 880 (18%) died, 780 under medical treatment and 100 after surgery. Overall survival throughout follow-up (10-year 76 ± 1%) was strongly associated with LACI (88 ± 1% vs. 78 ± 1% and 62 ± 2% for LACI <3.8, 3.8-6.3 and ≥6.3, P < 0.0001) even adjusting comprehensively, including for DMR severity (adjusted-hazard-ratio 1.23[1.07-1.43] for LACI > 5.79, P = 0.005). Mortality under medical management was profoundly affected by LACI (adjusted-hazard-ratio 1.11[1.05-1.18] per 3 unit increment; 1.35[1.15-1.58] for LACI > 5.79 vs. ≤5.79, both P = 0.0002). Survival improved after mitral surgery (time-dependent adjusted-hazard-ratio 0.40[0.28-0.65], P < 0.0001) but remained humbly linked to LACI (10-year 93 ± 3% vs. 90 ± 2% and 80 ± 3% for LACI tertiles, P = 0.0008). Most importantly, LACI provided incremental prognostic information over LAVI and other conventional determinants of survival (P < 0.0001) with Net-reclassification-improvement vs. LAVI of 0.21 ± 0.02, P < 0.0001. Conclusion LA function assessed by LACI in routine practice, by conventional echocardiographic measurements, displays incremental and independent link to excess-mortality, considerable under medical management and partially alleviated by mitral surgery. Thus, LACI is a simple tool of crucial interest in DMR risk-stratification. Abstract Figure. LACI in DMR