New perspectives in the echocardiographic hemodynamics multiparametric assessment of patients with heart failure.

International Guidelines consider left ventricular ejection fraction (LVEF) as an important parameter to categorize patients with heart failure (HF) and to define recommended treatments in clinical practice. However, LVEF has some technical and clinical limitations, being derived from geometric assumptions and is unable to evaluate intrinsic myocardial function and LV filling pressure (LVFP). Moreover, it has been shown to fail to predict clinical outcome in patients with end-stage HF. The analysis of LV antegrade flow derived from pulsed-wave Doppler (stroke volume index, stroke distance, cardiac output, and cardiac index) and non-invasive evaluation of LVFP have demonstrated some advantages and prognostic implications in HF patients. Speckle tracking echocardiography (STE) is able to unmask intrinsic myocardial systolic dysfunction in HF patients, particularly in those with LV preserved EF, hence allowing analysis of LV, right ventricular and left atrial (LA) intrinsic myocardial function (global peak atrial LS, (PALS)). Global PALS has been proven a reliable index of LVFP which could fill the gaps "gray zone" in the previous Guidelines algorithm for the assessment of LV diastolic dysfunction and LVFP, being added to the latest European Association of Cardiovascular Imaging Consensus document for the use of multimodality imaging in evaluating HFpEF. The aim of this review is to highlight the importance of the hemodynamics multiparametric approach of assessing myocardial function (from LVFP to stroke volume) in patients with HF, thus overcoming the limitations of LVEF.

Role of speckle tracking echocardiography beyond current guidelines in cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is a device-based treatment applied to patients with a specific profile of heart failure. According to current guidelines, indication for CRT is given on the basis of QRS morphology and duration, and traditional transthoracic echocardiography is mainly used to estimate left ventricular (LV) ejection fraction. However, the identification of patients who may benefit from CRT remains challenging, since the application of the above-mentioned guidelines is still associated with a high rate of non-responders. The assessment of various aspects of LV mechanics (including contractile synchrony, coordination and propagation, and myocardial work) performed by conventional and novel ultrasound technologies, first of all speckle tracking echocardiography (STE), may provide additional, useful information for CRT patients' selection, in particular among non-LBBB patients, who generally respond less to CRT. A multiparametric approach, based on the combination of ECG criteria and echocardiographic indices of LV dyssynchrony/discoordination would be desirable to improve the prediction of CRT response.

Arrhythmic mitral valve prolapse: a practical approach for asymptomatic patients.

Mitral valve prolapse (MVP) is usually regarded as a benign condition though the proportion of patients with a life-threatening arrhythmic MVP form remains undefined. Recently, an experts' consensus statement on arrhythmic MVP has proposed approaches for risk stratification across the spectrum of clinical manifestation. However, sudden cardiac death may be the first presentation, making clinicians focused to early unmasking this subset of asymptomatic patients. Growing evidence on the role of cardiac imaging in the in-deep stratification pathway has emerged in the last decade. Pathology findings have suggested the fibrosis of papillary muscles and inferobasal left ventricular wall as the malignant hallmark. Cardiac magnetic resonance, while of limited availability, allows the identification of this arrhythmogenic substrate. Therefore, speckle-tracking echocardiography may be a gateway to prompt referring patients to further advanced imaging investigation. Our review aims to summarize the phenotypic features linked to the arrhythmic risk and to propose an image-based algorithm intended to help stratifying asymptomatic MVP patients.

Exercise Stress Echocardiography in Athletes: Applications, Methodology, and Challenges.

This comprehensive review explores the role of exercise stress echocardiography (ESE) in assessing cardiovascular health in athletes. Athletes often exhibit cardiovascular adaptations because of rigorous physical training, making the differentiation between physiological changes and potential pathological conditions challenging. ESE is a crucial diagnostic tool, offering detailed insights into an athlete's cardiac function, reserve, and possible arrhythmias. This review highlights the methodology of ESE, emphasizing its significance in detecting exercise-induced anomalies and its application in distinguishing between athlete's heart and other cardiovascular diseases. Recent advancements, such as LV global longitudinal strain (GLS) and myocardial work (MW), are introduced as innovative tools for the early detection of latent cardiac dysfunctions. However, the use of ESE also subsumes limitations and possible pitfalls, particularly in interpretation and potential false results, as explained in this article.

Speckle tracking echocardiography in early disease stages: a therapy modifier?

Echocardiography has been included as a first-line tool in several international guidelines for the management of patients with various cardiac diseases. Beyond diagnosis, echocardiographic examination helps in characterizing the severity of the condition since the very first stages. In particular, the application of second-level techniques, speckle tracking echocardiography in particular, can also reveal a subclinical dysfunction, while the standard parameters are in the normality range. The present review describes the potentialities of advanced echocardiography in different settings, including arterial hypertension, atrial fibrillation, diastolic dysfunction, and oncological patients, thus opening up potential starting points for its application as a clinical routine changer.

Deformation Imaging by Strain in Chronic Heart Failure Over Sacubitril-Valsartan: A Multicenter Echocardiographic Registry.

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 6 month 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 ± 10 years; 18% female, median LVEF 30% [inter-quartile range: 25-34]). At 6 month follow-up, 82 (24%) patients showed early complete response (LVRR and LVEF ≥ 35%), 55 (16%) early incomplete response (LVRR and LVEF < 35%), and 204 (60%) no response (no LVRR and LVEF < 35%). Non-ischaemic aetiology, a lower left atrial volume index, and a higher GLS were all independent predictors of LVRR at multivariable logistic analysis (all P < 0.01). A baseline GLS < -9.3% was significantly associated with early response (area under the curve 0.75, P < 0.0001). Left atrial strain was the best predictor of positive changes in NYHA class and NT-proBNP (all P < 0.05). CONCLUSIONS: Speckle tracking echocardiography parameters at baseline could be useful to predict LVRR and clinical response to sacubitril-valsartan and could be used as a guide for treatment in patients with HFrEF.

Role of comorbidities on the mortality in patients with SARS-CoV-2 infection: an Italian cohort study.

BACKGROUND: Cardiovascular comorbidities are a common cause of death in COVID-19 and the aim of this study is to evaluate the effect of comorbidities on mortality in COVID-19 patients. METHODS: In this retrospective observational study we enrolled 1049 patients hospitalized with confirmed SARS-CoV-2 infection in a single Italian Center from 21 February to 20 March 2020 Evaluated risk factors (RFs) were: advanced age, gender, hypertension, diabetes, atrial fibrillation, hyperlipidemia, chronic kidney disease, thyroid disease, chronic obstructive pulmonary disease, malignancy, stroke, cardiovascular disease, and peripheral vascular disease. Endpoint of the study was death from any cause. A multivariate logistic regression model was built using covariates that showed as statistically significant at univariate regression analysis. RESULTS: Median age at presentation was 71.1 years (IQR: 59.1-80.5); 244 (72.2%) were males. Primary outcome occurred in 338 patients (32.2%). In decedents, median survival from Hospitalization was 6 (IQR: 3-10) days. 264 decedents had 1 RF, 120 had 2 RFs and 39 had ≥3 RFs. At multivariate logistic regression model, variables associated with primary outcome were: age class (64-69 years) (OR 3.03, CI: 1.75-5.31, P<0.001), age class (70-88 years) (OR 10.08, CI: 6.67-15.72, P<0.001), age class (≥88 years) (OR 23.99, CI: 13.21-44.82, P<0.001), male gender (OR 1.88, CI: 1.36-2.62, P<0.001), diabetes (OR 1.56, CI: 1.07-2.26, P=0.02), stroke (OR 3.41, CI: 1.33-9.91, P=0.015). CONCLUSIONS: Age, male gender, presence of diabetes and stroke appeared as independent predictors of mortality in COVID-19 patients. A table for risk of 30 days-mortality in SARS-CoV-2 infection was built, based on odds ratios derived from multivariate regression analysis.

Left atrial strain determinants and clinical features according to the heart failure stages. New insight from EACVI MASCOT registry.

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 multicentric prospective study. This is a multicenter prospective observational study enrolling 745 patients with HF stages. Data included PALS and left ventricular global longitudinal strain (LV-GLS). Exclusion criteria were: valvular prosthesis; atrial fibrillation; cardiac transplantation; poor acoustic window. 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, 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 the 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). 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.

Sacubitril/valsartan reduces indications for arrhythmic primary prevention in heart failure with reduced ejection fraction: insights from DISCOVER-ARNI, a multicenter Italian register.

Aims: This sub-study deriving from a multicentre Italian register [Deformation Imaging by Strain in Chronic Heart Failure Over Sacubitril-Valsartan: A Multicenter Echocardiographic Registry (DISCOVER)-ARNI] investigated whether sacubitril/valsartan in addition to optimal medical therapy (OMT) could reduce the rate of implantable cardioverter-defibrillator (ICD) indications for primary prevention in heart failure with reduced ejection fraction (HFrEF) according to European guidelines indications, and its potential predictors. Methods and results: In this observational study, consecutive patients with HFrEF eligible for sacubitril/valsartan from 13 Italian centres were included. Lack of follow-up or speckle tracking data represented exclusion criteria. Demographic, clinical, biochemical, and echocardiographic data were collected at baseline and after 6 months from sacubitril/valsartan initiation. Of 351 patients, 225 (64%) were ICD carriers and 126 (36%) were not ICD carriers (of whom 13 had no indication) at baseline. After 6 months of sacubitril/valsartan, among 113 non-ICD carriers despite having baseline left ventricular (LV) ejection fraction (EF) ≤ 35% and New York Heart Association (NYHA) class = II-III, 69 (60%) did not show ICD indications; 44 (40%) still fulfilled ICD criteria. Age, atrial fibrillation, mitral regurgitation > moderate, left atrial volume index (LAVi), and LV global longitudinal strain (GLS) significantly varied between the groups. With receiver operating characteristic curves, age ≥ 75 years, LAVi ≥ 42 mL/m2 and LV GLS ≥-8.3% were associated with ICD indications persistence (area under the curve = 0.65, 0.68, 0.68, respectively). With univariate and multivariate analysis, only LV GLS emerged as significant predictor of ICD indications at follow-up in different predictive models. Conclusions: Sacubitril/valsartan may provide early improvement of NYHA class and LVEF, reducing the possible number of implanted ICD for primary prevention in HFrEF. Baseline reduced LV GLS was a strong marker of ICD indication despite OMT. Early therapy with sacubitril/valsartan may save infective/haemorrhagic risks and unnecessary costs deriving from ICDs.

Sustained right ventricular dysfunction in severe COVID-19: The role of disseminated intravascular coagulation.

BACKGROUND: Acute right ventricular (RV) failure is common in patients hospitalized with COVID-19. Compared to the conventional echocardiographic parameters, right ventricular longitudinal strain (RVLS) is more sensitive and accurate for the diagnosis of RV systolic dysfunction. OBJECTIVE: Our purpose was to investigate the sustained RV dysfunction echo-quantified by RVLS in patients recovered from severe COVID-19. Furthermore, we aimed to assess whether disseminated intravascular coagulation (DIC) has a key role to predict the impaired RV strain. METHODS: Of 198 consecutive COVID-19 patients hospitalized from March 1, 2020, to April 15, 2020, 45 selected patients who survived from severe COVID-19 were enrolled in the study and referred to our echo-lab for transthoracic echocardiography 6-months after discharge. RVLS was calculated as the mean of the strain values of RV free wall. DIC was defined with a validated scoring system: DIC score equal to or more than 5 is compatible with overt-DIC. Categories of acute respiratory distress syndrome (ARDS) were defined based on PaO2 /FiO2 ratio. RESULTS: A total 26 of 45 patients showed impaired RVLS at 6-months' follow-up. DIC score was significantly higher in patients with worse RVLS than in those with better RVLS (4.8 ± .5 vs. 3.6 ± .6, p =.03). Stages of ARDS did not modulate this relationship. Finally, overt-DIC results the only independent predictor of sustained RV dysfunction (OR 1.233, 95% CI 1.041-1.934, p =.043). CONCLUSIONS: Sustained RV impairment frequently occurs in patients recovered from severe COVID-19. DIC plays a key role, resulting in an independent predictor of sustained RV dysfunction.

Quantified mitral regurgitation and left atrial function in heart failure with reduced ejection fraction: interplay and outcome implications.

AIMS: The clinical and prognostic importance of functional mitral regurgitation (FMR) in heart failure patients with reduced ejection fraction (HFrEF) has been highly debated. This study aims to define FMR linkage to cardiovascular (CV) outcomes and the interplay with left atrial (LA) function in a prospective cohort of consecutive HFrEF outpatients. METHODS AND RESULTS: Overall, 286 consecutive outpatients with chronic HFrEF were prospectively enrolled. FMR was quantified by effective regurgitant orifice area (EROA). Global peak atrial longitudinal strain (PALS) was measured by speckle tracking echocardiography. The primary endpoint was a composite of congestive heart failure hospitalization or CV death. During a mean follow-up of 4.1 ± 1.5 years, the primary endpoint occurred in 99 patients (35%). The spline modelling of the risk by FMR severity showed an excess event risk starting at about the EROA value of 0.1 cm2 . There was a remarkable graded association between the EROA strata, even if tested per 0.1 cm2 increase, and the risk of CV events (hazard ratio [HR] EROA per 0.10 cm2 increase: 1.42, 95% confidence interval [CI] 1.19-1.68; p < 0.0001). EROA ≥0.30 cm2 was associated with CV events regardless of LA function (HR 2.34, 95% CI 1.29-4.19; p = 0.005). Less severe FMR (EROA ≥0.10 cm2 ) was associated with a dismal outcome only in patients with reduced LA function (PALS <14%) (5-year CV event rate 51 ± 4%); conversely, the risk of events was relative reduced when preserved global PALS and FMR coexisted (5-year CV event rate 38 ± 6%). CONCLUSIONS: Our results refine the independent association between FMR and CV outcome among HFrEF outpatients. Within a moderate EROA range, LA function mitigates the clinical consequences of mitral regurgitation, providing measurable proof of the interplay between regurgitation and LA compliance.

Biomarkers Predict In-Hospital Major Adverse Cardiac Events in COVID-19 Patients: A Multicenter International Study.

BACKGROUND: The COVID-19 pandemic carries a high burden of morbidity and mortality worldwide. We aimed to identify possible predictors of in-hospital major cardiovascular (CV) events in COVID-19. METHODS: We retrospectively included patients hospitalized for COVID-19 from 10 centers. Clinical, biochemical, electrocardiographic, and imaging data at admission and medications were collected. Primary endpoint was a composite of in-hospital CV death, acute heart failure (AHF), acute myocarditis, arrhythmias, acute coronary syndromes (ACS), cardiocirculatory arrest, and pulmonary embolism (PE). RESULTS: Of the 748 patients included, 141(19%) reached the set endpoint: 49 (7%) CV death, 15 (2%) acute myocarditis, 32 (4%) sustained-supraventricular or ventricular arrhythmias, 14 (2%) cardiocirculatory arrest, 8 (1%) ACS, 41 (5%) AHF, and 39 (5%) PE. Patients with CV events had higher age, body temperature, creatinine, high-sensitivity troponin, white blood cells, and platelet counts at admission and were more likely to have systemic hypertension, renal failure (creatinine ≥ 1.25 mg/dL), chronic obstructive pulmonary disease, atrial fibrillation, and cardiomyopathy. On univariate and multivariate analysis, troponin and renal failure were associated with the composite endpoint. Kaplan-Meier analysis showed a clear divergence of in-hospital composite event-free survival stratified according to median troponin value and the presence of renal failure (Log rank p < 0.001). CONCLUSIONS: Our findings, derived from a multicenter data collection study, suggest the routine use of biomarkers, such as cardiac troponin and serum creatinine, for in-hospital prediction of CV events in patients with COVID-19.

Pre-admission acetylsalicylic acid therapy and impact on in-hospital outcome in COVID-19 patients: The ASA-CARE study.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) exhibit high thrombotic risk. The evidence on a potential independent prognostic role of antiplatelet treatment in those patients is limited. The aim of the study was to evaluate the prognostic impact of pre-admission low-dose acetylsalicylic acid (ASA) in a wide series of hospitalized patients with COVID-19. METHODS: This cohort study included 984 COVID-19 patients stratified according to ASA intake before hospitalization: ASA+ (n = 253) and ASA- (n = 731). Patients were included in ASA+ group if they received it daily in the 7 days before admission. 213 (83%) were on ASA 100 mg daily. Primary endpoint was a composite of in-hospital death and/or need for respiratory support upgrade, secondary endpoints were in-hospital death and need for respiratory support upgrade. RESULTS: Mean age was 72 [62; 81] with 69% of male patients. ASA+ patients were significantly older, with higher prevalence of comorbidities. No significant differences regarding the degree of respiratory dysfunction were observed. At 30-day Kaplan-Meier analysis, ASA+ patients had higher survival free from the primary endpoint and need for respiratory support upgrade, conversely in-hospital death did not significantly differ between groups. At multivariate analysis ASA intake was independently associated with a lower probability of reaching primary endpoint (HR 0.697, 95% C.I. 0.525-0.924; p = 0.012). CONCLUSIONS: In COVID-19 patients undergoing hospitalization, pre-admission treatment with ASA is associated with better in-hospital outcome, mainly driven by less respiratory support upgrade.

Myocardial Work by Echocardiography: Principles and Applications in Clinical Practice.

Left ventricular (LV) global longitudinal strain (GLS) has established itself in the last decade as a reliable, more objective method for the evaluation of LV systolic function, able to detect subtle abnormalities in LV contraction even in the presence of preserved ejection fraction (EF). However, recent studies have demonstrated that GLS, similar to LV EF, has important load dependency. Non-invasive myocardial work (MW) quantification has emerged in the last years as an alternative tool for myocardial function assessment. This new method, incorporating measurement of strain and LV pressure, has shown to overcome GLS and LV EF limitations and provide a loading-independent evaluation of myocardial performance. The presence of a commercially available echocardiographic software for the non-invasive MW calculation has allowed the application of this new method in different settings. This review sought to provide an overview on the current knowledge of non-invasive MW estimation, showing its potential applications and possible added value in clinical practice.

Impaired myocardial work efficiency in heart failure with preserved ejection fraction.

AIMS: Heart failure with preserved ejection fraction (HFpEF) is a growing public health problem. Impairment in left ventricular (LV) diastolic function has been proposed as a key pathophysiologic determinant. However, the role of concomitant systolic dysfunction despite preserved LV ejection fraction (LVEF) has not been well characterized. To analyse LV myocardial deformation, diastolic function, and contractile reserve (CR) in patients with HFpEF at rest and while during exercise, as well as their correlation with functional capacity. METHODS AND RESULTS: Standard echo, lung ultrasound, LV 2D speckle-tracking strain, and myocardial work efficiency (MWE) were performed at rest and during exercise in 230 patients with HFpEF (female sex 61.2%; 71.3 ± 5.3 years) in 150 age- and sex-comparable healthy controls. LV mass index and LAVI were significantly increased in HFpEF. Conversely, global longitudinal strain (GLS) and MWE were consequently reduced in HFpEF patients. During effort, HFpEF showed reduced exercise time, capacity, and VO2 peak. Increase in LVEF and LV GLS was significantly lower in HFpEF patients, while LV E/e' ratio, pulmonary pressures, and B-lines by lung ultrasound rose. A multivariable analysis outlined that LV MWE at rest was closely related to maximal Watts reached (beta coefficient: 0.43; P < 0.001), peak VO2 (beta: 0.50; P < 0.001), LV E/e' (beta: 0.52, P < 0.001), and number of B-lines during effort (beta: -0.36; P < 0.01). CONCLUSIONS: The lower resting values of LV GLS and MWE in HFpEF patients suggest an early subclinical myocardial damage, which seems to be closely associated with lower exercise capacity, greater pulmonary congestion, and blunted LV contractile reserve during effort.

Imaging Quality Control, Methodology Harmonization and Clinical Data Management in Stress Echo 2030.

Stress echo (SE) 2030 study is an international, prospective, multicenter cohort study that will include >10,000 patients from ≥20 centers from ≥10 countries. It represents the logical and chronological continuation of the SE 2020 study, which developed, validated, and disseminated the "ABCDE protocol" of SE, more suitable than conventional SE to describe the complex vulnerabilities of the contemporary patient within and beyond coronary artery disease. SE2030 was started with a recruitment plan from 2021 to 2025 (and follow-up to 2030) with 12 subprojects (ranging from coronary artery disease to valvular and post-COVID-19 patients). With these features, the study poses particular challenges on quality control assurance, methodological harmonization, and data management. One of the significant upgrades of SE2030 compared to SE2020 was developing and implementing a Research Electronic Data Capture (REDCap)-based infrastructure for interactive and entirely web-based data management to integrate and optimize reproducible clinical research data. The purposes of our paper were: first, to describe the methodology used for quality control of imaging data, and second, to present the informatic infrastructure developed on RedCap platform for data entry, storage, and management in a large-scale multicenter study.

Cardiac Imaging in Anderson-Fabry Disease: Past, Present and Future.

Anderson-Fabrydisease is an X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme α-galactosidase A. This results in pathological accumulation of glycosphingolipids in several tissues and multi-organ progressive dysfunction. The typical clinical phenotype of Anderson-Fabry cardiomyopathy is progressive hypertrophic cardiomyopathy associated with rhythm and conduction disturbances. Cardiac imaging plays a key role in the evaluation and management of Anderson-Fabry disease patients. The present review highlights the value and perspectives of standard and advanced cardiovascular imaging in Anderson-Fabry disease.

Echocardiographic assessment of coronary microvascular dysfunction: Basic concepts, technical aspects, and clinical settings.

Coronary flow reserve is the capacity of the coronary circulation to augment the blood flow in response an increase in myocardial metabolic demands and has a powerful prognostic significance in different clinical situations. It might assess with invasive and noninvasive technique. Transthoracic echocardiography Doppler is an emerging diagnostic technique, noninvasive, highly feasible, safe for patient and physician, without radiation, and able to detect macrovascular and microvascular anomalies in the coronary circulation. This review aims to describe the benefit and limits of echocardiographic assessment of coronary flow reserve.