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Background: Diastolic dysfunction (DD) assessment in heart failure is still challenging. Peak atrial longitudinal strain (PALS) is strongly related to end-diastolic pressure and prognosis, but it is still not part of standard DD assessment. We tested the hypothesis that a machine learning approach would be useful to include PALS in DD classification and refine prognostic stratification. Methods: In a derivation cohort of 864 heart failure patients in sinus rhythm (age, 66.6±12 years; heart failure with reduced ejection fraction, n=541; heart failure with mildly reduced ejection fraction, n=129; heart failure with preserved ejection fraction, n=194), machine learning techniques were retrospectively applied to PALS and guideline-recommended diastolic variables. Outcome (death/heart failure rehospitalization) of the identified DD-clusters was compared with that by guidelines-based classification. To identify the best combination of variables able to classify patients in one of the identified DD-clusters, classification and regression tree analysis was applied (with DD-clusters as dependent variable and PALS plus guidelines-recommended diastolic variables as explanatory variables). The algorithm was subsequently validated in a prospective cohort of 189 heart failure outpatients (age, 65±13 years). Results: Three distinct echocardiographic DD-clusters were identified (cluster-1, n=212; cluster-2, n=376; cluster-3 DD, n=276), with modest agreement with guidelines-recommended classification (kappa=0.40; P P =0.033; net reclassification improvement 0.166 [95% CI, 0.035–0.276], P =0.013), without interaction with ejection fraction category. In the validation cohort (median follow-up: 18.5 months), cluster-based classification better predicted outcome than guideline-based classification (C-index 0.80 versus 0.78, P =0.093). Conclusions: Integrating PALS by machine learning algorithm in DD classification improves risk stratification over recommended current criteria, regardless of ejection fraction status. This proof of concept study needs further validation of the proposed algorithm to assess generalizability to other populations.

Sacubitril/valsartan reduces heart failure (HF)-related hospitalizations and cardiovascular mortality in PARADIGM-HF and has become a foundational treatment for HF with reduced ejection fraction (HFrEF). However, data of its routine real-world use are limited, and evidence from Italian settings is lacking. The REAL.IT study aimed to characterize the demographics, pharmacotherapy, clinical characteristics and outcomes of sacubitril/valsartan-treated Italian patients with HFrEF. Electronic medical records of patients initiating sacubitril/valsartan from October 2016 to June 2019 at nine specialized hospital outpatient HF centers across Italy were reviewed. Overall, 924 adults (mean age 64.5 years, 84.6% male) were included. At baseline, 38.7% had an ischemic HF etiology, 45.9% hypertension, 23.2% atrial fibrillation, 25.4% diabetes mellitus, 26.1% an implantable cardioverter-defibrillator and 31.9% coronary artery bypass grafting. There were no clear patterns of patient selection over time. During follow-up, NYHA class improved in 37.5% of patients after a mean of 5.3 ± 3.8 months; 36.1% and 16.7% of patients were in NYHA class III during characterization and after one year of follow-up, respectively. Left ventricular ejection fraction (LVEF) improved ≥5% in 56.3% of patients at one year; 39.7% had ≥30% reduction of N-terminal pro-B-type natriuretic peptide; 2.2% had hyperkalemia during characterization and 2.6% during follow-up; and 3.8% had hypotension during characterization and 12% during follow-up. A total of 50 (5.8%) of patients had device implantation (ICD/CRT) during follow-up. HF-related hospitalization was recorded in 19.6% of patients during follow-up; 3.8% of patients died, approximately 1.3% from cardiovascular causes. Our real-world data confirm the favorable effectiveness and tolerability of sacubitril/valsartan observed in pivotal randomized controlled trials.

International audience; Aims Pulmonary congestion during exercise assessed by lung ultrasound predicts negative outcome in patients with heart failure with preserved ejection fraction (HFpEF). We aimed at assessing predictors of exercise-induced pulmonary B-lines in HFpEF patients. Methods and results Eighty-one I-II NYHA class HFpEF patients (65.0 ± 8.2 y/o, 56.8% females) underwent standard and strain echocardiography, lung ultrasound, and natriuretic peptide assessment during supine exercise echocardiography (baseline and peak exercise). Peak values and their changes were compared in subgroups according to exercise lung congestion grading (peak B-lines >10 or ≤10). Exercise elicited significant changes for all echocardiographic parameters in both subgroups [39/81 (48.1%) with peak B-lines >10; 42/81 (51.9%) with B-lines ≤10]. Peak values and changes of E-wave (and its derived indices) were significantly higher in patients with >10 peak B-lines compared with those with ≤10 B-line (all P-values 10 (all P-values

Aims: Sacubitril/valsartan has changed the treatment of heart failure with reduced ejection fraction (HFrEF), due to the positive effects on morbidity and mortality, partly mediated by left ventricular (LV) reverse remodelling (LVRR). The aim of this multicenter study was to identify echocardiographic predictors of LVRR after sacubitril/valsartan administration. Methods and results: Patients with HFrEF requiring therapy with sacubitril/valsartan from 13 Italian centres were included. Echocardiographic parameters including LV global longitudinal strain (GLS) and global peak atrial longitudinal strain by speckle tracking echocardiography were measured to find the predictors of LVRR [=LV end-systolic volume reduction ≥10% and ejection fraction (LVEF) improvement ≥10% at follow-up] at 6month follow-up as the primary endpoint. Changes in symptoms [New York Heart Association (NYHA) class] and neurohormonal activations [N-terminal pro-brain natriuretic peptide (NT-proBNP)] were also evaluated as secondary endpoints; 341 patients (excluding patients with poor acoustic windows and missing data) were analysed (mean age: 65±10years; 18% female, median LVEF 30% [inter-quartile range: 25-34]). At 6month follow-up, 82 (24%) patients showed early complete response (LVRR and LVEF≥35%), 55 (16%) early incomplete response (LVRR and LVEF&nbsp

Aims: Heart failure (HF) and atrial fibrillation (AF) may coexist and influence each other. However, characteristics, anticoagulant treatment, and outcomes of contemporary AF patients with concurrent HF are ill-defined. This study analyses characteristics, treatment, and 2year outcomes in newly diagnosed Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) patients with vs. without HF. Methods and results: GARFIELD-AF is the world's largest observational AF patient study. At enrolment, 11758 of 52072 patients (22.6%) had HF; 76.3% were New York Heart Association class II–III. Patients with HF had comparable demographics, blood pressure, and heart rate but more likely had permanent (15.6% vs. 11.9%) or persistent AF (18.9% vs. 13.8%), acute coronary syndromes (16.7% vs. 8.9%), vascular disease (40.8% vs. 20.2%), and moderate-to-severe chronic kidney disease (14.6% vs. 9.0%) than those without. Anticoagulant prescription was similar between the two groups. At 2year follow-up, patients with HF showed a greater risk of all-cause mortality [hazard ratio (HR), 2.06; 95% confidence interval (CI), 1.91–2.21; P&nbsp

Sacubitril/valsartan improves outcome in patients with heart failure (HF) with reduced left ventricular (LV) ejection fraction (EF, HFrEF). However, little is known about possible mechanisms underlying this favourable effect.To assess changes in echocardiographically-derived hemodynamic profiles induced by sacubitril/valsartan and their impact on outcome.In this multicenter, open-label study, 727 HFrEF outpatients underwent comprehensive echocardiography at baseline (before starting sacubitril/valsartan) and after 12 months. Estimated LV filling pressure (E/e') and cardiac index (CI, l/min/mAt baseline, 29% had profile-A, 15% had profile-B, 32% profile-C, and 24% profile-D. After 12 months, the hemodynamic profile improved in 53% of patients (all profile-A achievers, or profile-D patients achieving either C or B profile), while it remained unchanged in 39% patients and worsened in 9%. Prevalence of improved profile progressively increased with increasing dose of sacubitril/valsartan (P 0.0001). After the second echocardiography, patients were followed up 12.6 ± 7.6 months: event-rate was lower in patients with improved profile (12.3%, 95%CI: 9.4-16.1) compared to patients in whom hemodynamic profile remained unchanged (29.9%, 24.0-37.3) or worsened (31.2%, 20.7-46.9, P 0.0001). Improved hemodynamic profile was associated with favourable outcome independent of LVEF and other covariates (HR 0.65, 95%CI: 0.45-0.95, P 0.05).In HFrEF patients, the beneficial prognostic effects of sacubitril/valsartan are associated with improvement in hemodynamic conditions.

Aims: In patients with heart failure with reduced ejection fraction (HFrEF), an association between left atrial (LA) dilatation and dysfunction is expected, but the degree of coexistence of the two abnormalities and their relative prognostic role is not known. Methods and results: A total of 626 HFrEF patients formed the study population. All of them underwent a comprehensive echocardiographic evaluation. LA maximal volume was indexed to body surface area (LAVi); LA function was assessed using strain analysis during the reservoir phase: peak atrial longitudinal strain (PALS) analysis. Study primary endpoint was overall mortality or hospitalization for worsening heart failure. Four groups of patients were included in this study according to LAVi (≤34 or >34 mL/m2 ) and PALS (≤23% or >23%); 61 (10%) patients had normal LA volume and function (Group 1), 58 (9%) had LA dilatation but normal function (Group 2), 100 (16%) had normal volume but abnormal function (Group 3), and 407 (65%) had enlarged left atrium and abnormal function (Group 4). PALS was associated with primary endpoint in patients with both normal-size [Groups 1 and 3: hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.88-0.96; P = 0.0006] and dilated left atria (Groups 2 and 4: HR 0.93, 95% CI 0.91-0.96; P < 0.0001). In contrast, LAVi was associated with the primary endpoint in patients with abnormal LA function (Groups 3 and 4: HR 1.018, 95% CI 1.011-1.024; P < 0.00001) but not in those with normal PALS (Groups 1 and 2: HR 1.023, 95% CI 0.99-1.057; P = 0.1). Conclusions: Left atrial dilatation and dysfunction frequently but not invariably coexist. PALS emerged as a significant prognostic parameter in HFrEF even in the absence of LA dilation.

Background: Patients with heart failure (HF) with preserved ejection fraction (HFpEF) typically develop dyspnea and pulmonary congestion upon exercise. Lung ultrasound is a simple diagnostic tool, providing semiquantitative assessment of extravascular lung water through B-lines. It has been shown that patients with HFpEF develop B-lines upon submaximal exercise stress echocardiography; however, whether exercise-induced pulmonary congestion carries prognostic implications is unknown. This study aimed at evaluating the prognostic value of B-line assessment during exercise in patients with HFpEF. Methods: Sixty-one New York Heart Association class I to II patients with HFpEF underwent standard echocardiography, lung ultrasound (28-scanning point method), and BNP (B-type natriuretic peptide) assessment during supine exercise echocardiography (baseline and peak exercise). The primary end point was a composite of cardiovascular death or HF hospitalization at 1 year. Results: B-lines, E/e′, and BNP significantly increased during exercise ( P P P =0.002) B-lines were retained as independent predictors of outcome (hazard ratios per 1 B-line increment), along with BNP and E/e′ ratio. Importantly, adding peak B-line on top of a clinical model significantly improved prognostic accuracy (C-index increase, 0.157 [0.056–0.258], P =0.002) and net reclassification (continuous net reclassification improvement, 0.51 [0.09–0.74], P =0.016), with similar results for B-line change. Conclusions: Detection of exercise-induced pulmonary congestion by lung ultrasound is an independent predictor of outcome in patients with HFpEF; its use may help refining the routine risk stratification of these patients on top of well-established clinical variables.

Background and aims Elevated serum uric acid (sUA) concentrations have been associated with worse prognosis in heart failure (HF) but little is known about elderly patients. We aimed to assess long-term additive prognostic value of sUA in elderly patients hospitalized for HF. Methods and results Clinical and echocardiographic characteristics of 310 consecutive elderly patients hospitalized for HF were collected. During index period, 206 had sUA concentrations available, which were obtained within 24 h prior to discharge; 10 patients were lost to follow-up, leaving 196 patients available. Patients had a median age of 77 (IQR 69–83) years, and were mostly male (64.5%). sUA ranges for tertiles I–III were: 1.5–6.1, 6.2–8.3, and 8.4–18.9 mg/dl, respectively. During a median follow-up of 27 months (IQR 10.5–39.5), 122 combined events occurred (87 deaths and 73 HF rehospitalizations). Four-year event-free survival for the combined endpoint was 46 ± 7% for tertile I, 34 ± 7% for tertile II, and 21 ± 5% for tertile III (P = 0.001). By multivariable Cox backward analysis, sUA was retained as a significant predictor. Compared with the lowest sUA tertile, tertile III showed a strong association with outcome, also after adjustment for other predictors (HR 1.84, 95% CI 1.16–2.93; P = 0.01). Importantly, addition of sUA to the other significant predictors of outcome resulted in improved risk classification (net reclassification improvement 0.19, P = 0.017). Conclusions High sUA at discharge is a strong predictor of adverse outcome in elderly hospitalized for HF, and it significantly improves risk classification. Measuring sUA can be a simple and useful tool to identify high-risk elderly hospitalized for HF.

Background: Current diagnosis of heart failure with preserved ejection fraction (HFpEF) is suboptimal. We tested the hypothesis that comprehensive machine learning (ML) of left ventricular function at rest and exercise objectively captures differences between HFpEF and healthy subjects. Methods and Results: One hundred fifty-six subjects aged >60 years (72 HFpEF+33 healthy for the initial analyses; 24 hypertensive+27 breathless for independent evaluation) underwent stress echocardiography, in the MEDIA study (Metabolic Road to Diastolic Heart Failure). Left ventricular long-axis myocardial velocity patterns were analyzed using an unsupervised ML algorithm that orders subjects according to their similarity, allowing exploration of the main trends in velocity patterns. ML identified a continuum from health to disease, including a transition zone associated to an uncertain diagnosis. Clinical validation was performed (1) to characterize the main trends in the patterns for each zone, which corresponded to known characteristics and new features of HFpEF; the ML-diagnostic zones differed for age, body mass index, 6-minute walk distance, B-type natriuretic peptide, and left ventricular mass index ( P Conclusions: The analysis of left ventricular long-axis function on exercise by interpretable ML may improve the diagnosis and understanding of HFpEF.

Background Chronic heart failure (HF) is a relevant and growing public health problem. Although the prognosis has recently improved, it remains a lethal disease, with a mortality that equals or exceeds that of many malignancies. Furthermore, chronic HF is costly, representing a large and growing drain on healthcare resources. Methods This narrative review is based on the material searched for and obtained via PubMed up to May 2017. The search terms we used were: “heart failure, echocardiography, natriuretic peptides” in combination with “treatment, biomarkers, guidelines”. Results Particularly, hospitalization contributes to the greatest proportion of expenditure. Recent studies have supported the value of natriuretic peptides (NPs) and Doppler echocardiographic biomarkers of increased left ventricular (LV) filling pressures or pulmonary congestion as tools to scrutinize patients with impending clinically overt HF. Therefore, combination of pulsed-wave tissue and blood-flow Doppler with NPs appears valuable in guiding HF management in the outpatient setting. In as much as both the echo and the plasma levels of NPs may reflect the presence of fluid overload and elevations of LV filling pressures, integrating NP and echocardiographic biomarkers with clinical findings may help the cardiologist to identify high-risk patients, i.e. to recognize whether a patient is stable or the condition is likely to evolve into decompensated HF, to optimize treatment, to improve the prognosis and to reduce re-hospitalization. Conclusion we discussed the rationale and the clinical significance of combining follow-up echo and NP assessment to guide management of ambulatory patients with chronic HF. This article is protected by copyright. All rights reserved.

Myocardial reflectivity, as assessed by calibrated integrated backscatter (cIB) analysis, is a non-invasive surrogate for the amount of left ventricular (LV) fibrosis. The aim of this study was to assess the myocardial reflectivity pattern in patients with heart failure and preserved ejection fraction (HFpEF), and to evaluate its relationship with longitudinal systolic deformation of LV by 2D-speckle tracking echocardiography, and degree of diastolic dysfunction. Transthoracic echocardiography, myocardial Doppler-derived systolic (Sm) and early diastolic velocity (E'), global longitudinal strain (GLS), and tissue characterization by cIB, were obtained in 86 subjects, 46 with HFpEF, and 40 controls. GLS was significantly impaired in HFpEF patients (-15.4 ± 3.5 % vs -21.5 ± 2.9 % in controls; P

Pulmonary congestion assessed at discharge by lung ultrasonography predicts poor prognosis in heart failure (HF) patients. We investigated the association of B-lines with indices of hemodynamic congestion [BNP, E/e’, pulmonary systolic arterial pressure (PAPs)] in HF patients, and their prognostic value overall and according to concomitant atrial fibrillation (AF), reduced (≤40%) ejection fraction (EF), and timing of quantification during hospitalisation for heart failure (HHF). In 110 HHF patients, B-lines were highly discriminative of BNP >400 pg/ml (AUC ≥ 0.80 for all), and moderately discriminative of PAPs >50 mmHg (AUC = 0.68, 0.56 to 0.80); conversely, B-lines poorly discriminated average E/e’ ≥ 15, except at discharge. B-line count significantly predicted mid-term recurrent HHF or death (overall and in subgroups), regardless of AF status, EF, and timing of quantification during HHF (all p for interaction >0.10). regardless, B-lines ≥30 at discharge were most predictive of outcome (HR = 7.11, 2.06–24.48; p = 0.002) while B-lines ≥45 early during HHF were most predictive of outcome (HR = 9.20, 1.82–46.61; p = 0.007). Lung ultrasound was able to identify patients with high BNP levels, but not with increased E/e’, also showing a prognostic role regardless of AF status, EF or timing of quantification; best B-line cut-off appears to vary according to the timing of quantification during hospitalization.

Myocardial performance index (MPI), or Tei index, is an indicator of systolic and diastolic myocardial function. MPI increases in case of cardiac dysfunction; however, whether reversal of left ventricular dysfunction is also reflected by concomitant improvement (i.e., decrease) of MPI is unknown.Fifty-two patients with chronic ischemic cardiomyopathy and viable myocardium by dobutamine stress echocardiography were studied by echocardiography before and more than 4 months after cardiac revascularization. Patients were in optimal medical therapy, which remained unchanged following revascularization.At baseline, ejection fraction (EF: 32 ± 6%) and wall motion score index (WMSI: 2.37 ± 0.32) were impaired, and MPI averaged 0.71 ± 0.19. Revascularization markedly improved EF (44 ± 10%, P0.0001) and WMSI (1.77 ± 0.44, P0.0001). MPI also improved (0.59 ± 0.26, P0.0001), and its decrease was significantly correlated with the improvement in EF (r =-0.68, P0.0001) and to the extent of viable myocardium (r =-0.45, P = 0.0007). Responders to revascularization (≥5% increase in EF at follow-up, n = 40% and 77%) achieved a significant improvement in MPI at follow-up in contrast with nonresponders (-23 ± 25% vs. 0.02 ± 0.18%, P = 0.001). Improvement in MPI was largely driven by a significant reduction in isovolumic contraction time (P0.001) with consequent prolongation of the ejection phase.In patients with chronic ischemic cardiomyopathy, MPI improves along with recovery of function, reflecting the intrinsic improvement of viable segments induced by revascularization.

Increased dispersion of the QT interval has been observed during pacing or exercise stress testing in patients with coronary artery disease (CAD). It has not been established whether this phenomenon is a consequence of ischemia. Therefore, we sought to evaluate whether dipyridamole-induced myocardial ischemia, as directly detected by echocardiographic monitoring of regional contractile function, would affect QT dispersion. Twenty-four patients with nonsignificant and 34 patients with significant CAD but no previous myocardial infarction underwent dipyridamole stress echocardiography while not taking medications. QT dispersion was measured on a 12-lead electrocardiogram at baseline and at various times after dipyridamole infusion. Dipyridamole infusion did not influence QT dispersion in patients without CAD. QT dispersion was similarly unaffected in patients with CAD in whom dipyridamole did not induce wall motion abnormalities. In contrast, in patients with positive dipyridamole stress test findings, QT dispersion increased from 60 +/- 17 ms at baseline to 94 +/- 25 ms during peak infusion (p0.0001), with a time course mirroring that of development of contractile abnormalities. QT dispersion returned to 63 +/- 25 ms upon relief of ischemia by administration of aminophylline. The increase in QT dispersion was significantly related to the extent of contractile dysfunction induced by dipyridamole. Although ST-segment depression occurred in only 40% of patients with positive dipyridamole stress test findings, 88% of such patients had an increase in QT dispersion. Analysis of the receiver-operating characteristic curve showed that a QT dispersion increase ofor =20 ms identified positive findings for dipyridamole stress echocardiography with 68% sensitivity and 91% specificity. Thus, QT dispersion is acutely affected by myocardial ischemia induced by the administration of dipyridamole. Measurement of QT dispersion may improve detection of stress-induced ischemia on surface electrocardiograms.

The prognostic impact of left ventricular (LV) geometry on cardiovascular risk for patients with a first, uncomplicated acute myocardial infarction (AMI), and echocardiographic ejection fractionor =50% has not been well described.Accordingly, 111 AMI consecutive patients (mean age 59.3+/-10 years) performed echocardiographic examination at predischarge. LV mass was calculated by means of Devereux's formula and subsequently indexed by body surface area. Fifty-three patients had LV hypertrophy and 58 patients had normal LV mass. The two groups were homogeneous for demographic, clinical and angiographic variables as well as for the incidence of residual ischemia on predischarge stress testing. During follow-up period there were 24 cardiac events (cardiac death, unstable angina and non-fatal reinfarction) in the 53 patients with LV hypertrophy and only four events in the remaining 58 patients without LV hypertrophy (RR=2.45; CI=1.76-3.41; P0.0001). The patients with concentric LV hypertrophy showed a higher incidence of events (64%) than patients with eccentric LV hypertrophy (32%, P0. 05) and patients with normal geometry and mass (6%, P0.0001). Multivariate Cox regression model identified concentric geometry as the most powerful predictor of combined end-points (chi(2)=32.7, P0. 0001).An increased LV mass and concentric geometry resulted important independent markers of an adverse outcome in patients with a first, uncomplicated myocardial infarction and good LV function.