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.

Indirect ultrasound evaluation of left ventricular outflow tract diameter implications for heart failure and aortic stenosis severity assessment.

BACKGROUND: Whereas dependency of left ventricular outflow tract diameter (LVOTD) from body surface area (BSA) has been established and a BSA-based LVOTD formula has been derived, the relationship between LVOTD and aortic root and LV dimensions has never been explored. This may have implications for evaluation of LV output in heart failure (HF) and aortic stenosis (AS) severity. METHODS: A cohort of 540 HF patients who underwent transthoracic echocardiography was divided in a derivation and validation subgroup. In the derivation subgroup (N = 340), independent determinants of LVOTD were analyzed to derive a regression equation, which was used for predicting LVOTD in the validation subgroup (N = 200) and compared with the BSA-derived formula. RESULTS: LVOTD determinants in the derivation subgroup were sinuses of Valsalva diameter (SVD, beta = 0.392, P < .001), BSA (beta = 0.229, P < .001), LV end-diastolic diameter (LVEDD, beta = 0.145, P = .001), and height (beta = 0.125, P = .037). The regression equation for predicting LVOTD with the aforementioned variables (LVOTD = 6.209 + [0.201 × SVD] + [1.802 × BSA] + [0.03 × LVEDD] + [0.025 × Height]) did not differ from (P = .937) and was highly correlated with measured LVOTD (R = 0.739, P < .001) in the validation group. Repeated analysis with LV end-diastolic volume instead of LVEDD and/or accounting for gender showed similar results, whereas BSA-derived LVOTD values were different from measured LVOTD (P < .001). CONCLUSION: Aortic root and LV dimensions affect LVOTD independently from anthropometric data and are included in a new comprehensive equation for predicting LVOTD. This should improve evaluation of LV output in HF and severity of AS when direct LVOTD measurement is difficult or impossible.

Echocardiographic evaluation of cardiac dyssynchrony: Does it still matter?

Cardiac resynchronization therapy (CRT) is an established treatment for patients with heart failure and left ventricular systolic dysfunction. For many years, cardiac mechanical dyssynchrony assessed by echocardiography has been considered as a key evaluation to characterize CRT candidates and predict CRT response. In current guidelines, however, CRT implant indications rely only on electrical dyssynchrony. The aim of this article was to clarify whether and how the evaluation of cardiac mechanical dyssynchrony should be performed today by echocardiography.

F13A1 Gene Variant (V34L) and Residual Circulating FXIIIA Levels Predict Short- and Long-Term Mortality in Acute Myocardial Infarction after Coronary Angioplasty.

Factor XIIIA (FXIIIA) levels are independent predictors of early prognosis after acute myocardial infarction (AMI) and the Valine-to-Leucine (V34L) single nucleotide polymorphism (SNP) seems associated with lower AMI risk. Since the long-term AMI prognosis merits deeper investigation, we performed an observational study evaluating relationships between FXIIIA residual levels, cardiovascular risk-factors, and inherited genetic predispositions. FXIIIA V34L was genotyped in 333 AMI patients and a five-year follow-up was performed. FXIIIA levels assessed at day-zero (d0) and four days after AMI (d4), and conventional risk factors were analyzed, focusing on the development of major adverse cardiovascular events (MACE). FXIIIA assessed at d0 and d4 was also an independent MACE predictor in the long-term follow-up (FXIIIAd0, Odds Ratio (OR) = 3.02, 1.79⁻5.1, p = 0.013; FXIIIAd4, OR = 4.46, 2.33⁻8.55, p = 0.0001). FXIIIAd4 showed the strongest MACE association, suggesting that the FXIIIA protective role is maximized when high levels are maintained for longer time. Conversely, FXIIIA levels stratified by V34L predicted MACE at a lesser extent among L34-carriers (Hazard Risk (HR)VV34 = 3.89, 2.19⁻6.87, p = 0.000003; HRL34-carriers = 2.78, 1.39⁻5.57, p = 0.0039), and V34L did not predict all MACE, only multiple-MACE occurrence (p = 0.0087). Finally, in survival analysis, heart failure and death differed significantly from stroke and recurrent ischemia (p = 0.0013), with FXIIIA levels appreciably lower in the former (p = 0.05). Overall, genetically-determined FXIIIA levels have a significant long-term prognostic role, suggesting that a pharmacogenetics approach might help to select those AMI patients at risk of poor prognosis in the need of dedicated treatments.

Temporal implementation of a regional referral pathway in transthyretin cardiac amyloidosis: Emilia-Romagna experience.

AIMS: Transthyretin cardiac amyloidosis (ATTR-CA) is a rare and progressive cardiomyopathy caused by amyloid fibril deposition in myocardial tissue. Diagnostic challenges have historically hampered timely detection. Recent advances in noninvasive diagnostic techniques have facilitated ATTR-CA diagnosis. We aimed to examine the development of a regional network for the diagnosis and management of ATTR-CA and describe a cohort of patients with ATTR-CA, investigate diagnostic pathways and assess clinical outcomes according to diagnosis periods. METHODS: We performed a survey study analyzing answers from 11 cardiology centers and we conducted a retrospective study including patients with ATTR-CA attending a referral center between 1 January 2012 and 31 December 2022, and categorized by the period of diagnosis (2012-2016 and 2017-2022). RESULTS: Over the years, a growing number of patients reached a diagnosis and were treated in the surveyed nonreferral centers of the region. The retrospective study showed a more significant diagnostic delay in the earlier period rather than the later one [13.4 (5-30.2) vs. 10.6 (5.0-17.9) months, P = 0.04]. Patients diagnosed after 2017 showed a greater survival rate than those diagnosed earlier ( P = 0.02). In the multivariate analysis, the year of diagnosis from 2017 remained independently associated with mortality [hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.28-0.79; P = 0.005]. CONCLUSION: This study emphasized the shift toward noninvasive diagnostic criteria. It revealed a positive impact on patient survival and disease management with the use of disease-modifying therapies and diagnostic developments in more recent years. The findings underscore the importance of disease awareness and networking to reduce diagnostic delays and enhance patient journeys for ATTR-CA.

Severe Impairment of Left Ventricular Regional Strain in STEMI Patients Is Associated with Post-Infarct Remodeling.

Background: Measures of global left ventricular (LV) systolic function have limitations for the prediction of post-infarct LV remodeling (LVR). Therefore, we tested the association between a new measure of regional LV systolic function­the percentage of severely altered strain (%SAS)- and LVR after acute ST-elevation myocardial infarction (STEMI). As a secondary objective, we also evaluated the association between %SAS and clinical events during follow-up. Methods: Of 177 patients undergoing echocardiography within 24 h from primary percutaneous coronary angioplasty, 172 were studied for 3 months, 167 for 12 months, and 10 died. The %SAS was calculated by dividing the number of LV myocardial segments with ≥−5% peak systolic longitudinal strain by the total number of segments. LVR was defined as the increase in end-diastolic volume >20% at its first occurrence compared to baseline. Results: LVR percentage was 10.2% and 15.8% at 3 and 12 months, respectively. Based on univariable analysis, a number of clinical, laboratory, electrocardiographic and echocardiographic variables were associated with LVR. Based on multivariable analysis, %SAS and TnI peak remained associated with LVR (for %SAS 5% increase, OR 1.226, 95% CI 1.098−1.369, p < 0.0005; for TnI peak, OR 1.025, 95% CI 1.004−1.047, p = 0.022). %SAS and LVR were also associated with occurrence of clinical events at a median follow-up of 43 months (HR 1.02, 95% CI 1.0−1.04, p = 0.0165). Conclusions: In patients treated for acute STEMI, acute %SAS is associated with post-infarct LVR. Therefore, we suggest performing such evaluations on a routine basis to identify, as early as possible, STEMI patients at higher risk.

New measures of right ventricle-pulmonary artery coupling in heart failure: An all-cause mortality echocardiographic study.

AIMS: Right ventricle-pulmonary artery coupling (RVPAC) has emerged from pathophysiology to clinical interest for prognostic implication in heart failure and is commonly measured as the ratio between tricuspid annular plane systolic excursion and systolic pulmonary artery pressure (TAPSE/SPAP). However, feasibility of SPAP is limited (down to 60% in trials, and maybe lower in clinical practice). We ought to assess the prognostic value of the TAPSE times pulmonary acceleration time (TAPSE x pACT) product and TAPSE to peak tricuspid regurgitation velocity (TAPSE/TRV) ratio as new alternative measures of RVPAC. METHODS AND RESULTS: Two-hundred patients hospitalized with heart failure were followed-up (median time of 2.7 years) and 82 died. Non survivors had significantly lower TAPSE/SPAP, TAPSE x pACT and TAPSE/TRV than survivors (0.31 vs 0.40 mm/mmHg, 130 vs 156 cm·ms, 5.0 vs 5.8 ms, respectively). Four multivariate models were performed, each one including TAPSE, TAPSE/SPAP, TAPSE x pACT or TAPSE/TRV. TAPSE/SPAP resulted the most powerful predictor of mortality (HR 0.74 per mm/mmHg increase, P < 0.001, C-Statistic 0.778), followed by TAPSE x pACT (HR 0.95 per 10 cm·ms increase, P = 0.013, C-Statistic 0.776), TAPSE/TRV (HR 0.76 per ms increase, P < 0.001, C-Statistic 0.774) and TAPSE (HR 0.91 per mm increase, P = 0.003, C-Statistic 0.769). Cutoff values of 140 cm·ms and 5.5 ms were respectively identified for TAPSE x pACT and TAPSE/TRV with receiving operating characteristic analysis for mortality. CONCLUSION: TAPSE x pACT product and TAPSE/TRV ratio are alternative measures of RVPAC for prognostic assessment in heart failure that can be applied if TAPSE/SPAP is not feasible.

Left ventricular output indices in hospitalized heart failure: when "simpler" may not mean "better".

Assessment of left ventricular (LV) output in hospitalized patients with heart failure (HF) is important to determine prognosis. Although echocardiographic LV ejection fraction (EF) is generally used to this purpose, its prognostic value is limited. In this investigation LV-EF was compared with other echocardiographic per-beat measures of LV output, including non-indexed stroke volume (SV), SV index (SVI), stroke distance (SD), ejection time (ET), and flow rate (FR), to determine the best predictor of all-cause mortality in patients hospitalized with HF. A final cohort of 350 consecutive patients hospitalized with HF who underwent echocardiography during hospitalization was studied. At a median follow-up of 2.7 years, 163 patients died. Non-survivors at follow-up had lower SD, SVI and SV, but not ET, FR and LV-EF than survivors. At multivariate analysis, only age, systolic blood pressure, chronic kidney disease, chronic obstructive pulmonary disease, use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and SVI remained significantly associated with outcome [HR for SVI 1.13 (1.04-1.22), P = 0.003]. In particular, for each 5 ml/m2 decrease in SVI, a 13% increase in risk of mortality for any cause was observed. SVI is a powerful prognosticator in HF patients, better than other per-beat measures, which may be simpler but partial or incomplete descriptors of LV output. SVI, therefore, should be considered for the routine echocardiographic evaluation of patients hospitalized with HF to predict prognosis.

Novel Echocardiographic Approach to Hemodynamic Phenotypes Predicts Outcome of Patients Hospitalized With Heart Failure.

BACKGROUND: Although in clinical practice heart failure (HF) patients are classified using left ventricular ejection fraction (LVEF), this categorization is insufficient for prognosis, especially when LVEF is preserved or there is a concomitant right ventricular (RV) dysfunction. We hypothesized that a combined noninvasive evaluation of LV forward flow, filling pressure, and RV function would be better than LVEF in predicting all-cause mortality of hospitalized patients with HF. METHODS: Transthoracic echocardiographic examinations of 603 patients hospitalized with HF were analyzed. In a subsample of 200 patients with HF, LV stroke volume index, LV filling pressure estimation, tricuspid annular plane systolic excursion, and systolic pulmonary artery pressure were combined to determine 4 hemodynamic profiles: normal flow-normal pressure, normal flow-high pressure, low flow without RV dysfunction, and low flow with RV dysfunction profile. This model was then applied in a validation cohort (n=403). RESULTS: Prognosis worsened from the normal flow-normal pressure profile to the low flow with right ventricular dysfunction profile. At the multivariate survival analysis, the model showed independent high risk-stratification capability (P<0.001), even in subgroups of patients with LVEF < or ≥50% (P=0.011 and P<0.001, respectively) and < or ≥40% (P=0.044 and P<0.001, respectively). LVEF and HF classification based on LVEF did not predict outcome. CONCLUSIONS: Echocardiographic-derived profiling of LV forward flow, filling pressure, and RV function allowed categorization of patients hospitalized with HF and predicted all-cause mortality independently of LVEF. This model is based on conventional echocardiography, is easy to apply, and is, therefore, suggested for clinical practice.

Echocardiographic Evaluation of Left Ventricular Output in Patients with Heart Failure: A Per-Beat or Per-Minute Approach?

BACKGROUND: Left ventricular (LV) output is a predictor of adverse outcome in patients with heart failure. It can be evaluated using a per-beat approach, measuring stroke volume index (SVI), or a per-minute approach, calculating cardiac index (CI). However, the prognostic value of these two approaches has never been compared. METHODS: A single-center retrospective observational study was conducted in 396 hospitalized patients who underwent echocardiography for suspected heart failure. In a group of 138 consecutive patients, SVI and CI cutoff values of 30 mL/m2 and 2.3 L/min/m2, respectively, were derived to separate normal from low LV forward flow conditions. Subsequently, the association of these values with all-cause mortality was compared in a group of 258 consecutive patients. Median follow-up duration was 2.6 years (interquartile range: 2-3.2 years). RESULTS: After adjustment for other outcome predictors, SVI <30 mL/m2 was independently associated with all-cause mortality with a hazard ratio of 2.67 (95% confidence interval, 1.74-4.1; P < .001), whereas CI was not. Additionally, three different subgroups of SVI (<30, 30-35, and >35 mL/m2) and CI (<1.8, 1.8-2.2, and ≥2.3 L/min/m2) were compared, and no incremental benefit of this risk stratification model was observed. CONCLUSIONS: Low LV output on the basis of a per-beat definition (SVI <30 mL/m2) is strongly associated with all-cause mortality in patients hospitalized with heart failure. A per-minute approach seems to add no further information to risk stratification. These findings may have implications for selecting the LV output index when evaluating prognosis in patients with heart failure.

Right Atrial Pressure Is Associated with Outcomes in Patients with Heart Failure and Indeterminate Left Ventricular Filling Pressure.

BACKGROUND: In a significant proportion of patients with left-sided heart failure (HF), left ventricular filling pressure (LVFP) may not be estimated using echocardiography, so filling pressure status may remain indeterminate. In these patients, mean right atrial pressure (mRAP) has been suggested as a surrogate of LVFP. The aim of this study was to determine whether high mRAP has prognostic value in patients with HF with indeterminate pressure (IP) and whether mRAP-based reclassification of patients with IP has an impact on outcomes. METHODS: A cohort of 465 patients hospitalized with HF was retrospectively studied and divided into groups with normal pressure (n = 102), high pressure (n = 265), and IP (n = 98). A composite end point of all-cause mortality and HF rehospitalization was evaluated after a median follow-up duration of 2.5 years. RESULTS: There were 282 events in the entire population (53 in the normal pressure group, 173 in the high pressure group, and 56 in the IP group; P = .047). High mRAP was independently associated with outcome only in patients with IP (hazard ratio, 2.72; 95% CI, 1.25-5.9; P = .012). Evaluation of LVFP after mRAP-based reclassification of patients with IP resulted in higher risk stratification capability than current recommendations alone (log-rank χ2 = 15.057 vs 8.148). CONCLUSIONS: In patients with inconclusive determination of LVFP, echocardiographic estimation of mRAP is associated with outcomes. This finding corroborates previous observation of mRAP as a surrogate marker of elevated LVFP in left-sided HF and suggests its use in clinical practice.

Paradoxical low-flow phenotype in hospitalized heart failure with preserved ejection fraction.

BACKGROUND: Low flow (LF) in heart failure with preserved ejection fraction (HFpEF) is a paradox but is associated with worse prognosis. Determinants of LF in HFpEF have not been clarified but their assessment could corroborate recognition and definition of such a paradoxical condition. METHODS: A cohort of 193 patients hospitalized with HFpEF was retrospectively studied and divided in a group with LF (N = 45), defined by a left ventricular (LV) stroke volume index (SVI) < 30 ml/m2, and a group with normal flow (N = 148). A small LV cavity was pre-defined as LV end diastolic diameter index (EDDI) below median values (<25 mm/m2 for males and <26 mm/m2 for females). Right ventricular dysfunction (RVD) was defined as the ratio between tricuspid annular plane systolic excursion and systolic pulmonary artery pressure < 0.36 mm/mmHg. An endpoint of all-cause mortality was evaluated after a median follow-up of 2.4 years. RESULTS: RVD (OR = 7.4; P < 0.001), atrial fibrillation (AF) during echocardiography (OR = 3.26; P = 0.008), and small LV cavity (OR = 3.81; P = 0.003) were independently associated with LF. After adjusting for age, body mass index, systolic blood pressure, renal function, chronic obstructed pulmonary disease, use of ACE inhibitors/angiotensin receptor blockers, moderate tricuspid regurgitation, RVD), LF was associated with mortality (HR = 3.69; P < 0.001) whereas the combination of the determinants of LF was not. CONCLUSION: Paradoxical LF in HFpEF is associated with small LV cavity, AF and RVD. None of the combination of different factors associated with LF could substitute direct assessment of LF status in predicting prognosis in this cohort.

[Treatment of secondary ischemic mitral regurgitation: controversial issues]. / Aspetti controversi nel trattamento dell'insufficienza mitralica secondaria ischemica.

The presence of secondary mitral regurgitation is an unfavorable prognostic factor in patients with chronic ischemic heart disease. This type of regurgitation can be treated with medical therapy, cardiac resynchronization therapy, surgically or percutaneously but each strategy has controversial aspects. The purpose of this review is to discuss the most debated issues relative to the various modalities available to treat ischemic secondary mitral regurgitation, highlighting also future perspectives.

Intracardiac Flow Analysis: Techniques and Potential Clinical Applications.

Analysis of intracardiac flows has gained increasing interest in the last years. This analysis has become possible due to the development of technologies for noninvasive cardiovascular imaging, which allow visualization and quantitation of intracardiac flow dynamics. Several studies have shown that abnormalities in cardiac function are related to changes in intracardiac vortical flows. Thus, analysis of cardiac vortex has been used for better understanding of the pathophysiology in many heart diseases and to test initial clinical hypotheses. The aims of this review are to introduce the reader to the topic of intracardiac flow dynamics, to briefly describe current cardiac imaging techniques for analysis of the intracardiac vortex, and to indicate potential clinical applications of a vortex-based approach to the study of cardiac function.

[Heart failure with mid-range ejection fraction. Looking for Middle Earth?] / Scompenso cardiaco con frazione di eiezione intermedia. Alla ricerca della Terra di Mezzo?

The latest guidelines of the European Society of Cardiology have proposed a classification of heart failure based on left ventricular ejection fraction. Three distinct groups have been identified: heart failure with ejection fraction ≥50%, between 40 and 49%, and <40%. This classification has the advantage to be simple but it has been criticized because it is not clear whether the mid-range ejection fraction group is an independent category or just a transition phase between the other two groups. The purpose of this article is to discuss the characteristics and prognosis of mid-range ejection fraction heart failure on the basis of current evidence.

[Echocardiography in ST-elevation myocardial infarction]. / L'ecocardiografia nell'infarto miocardico con sopraslivellamento del tratto ST.

Echocardiography is an imaging technique of paramount importance for the management of patients with ST-elevation myocardial infarction. In particular, this technique may be useful for diagnosis and is essential for prognosis and to guide drug therapy. The role in the recognition of mechanical complications and in the identification and management of other complications such as pericarditis and left ventricular thrombosis is also crucial. Finally, echocardiography offers important information for the prediction of the arrhythmic risk and the study of left ventricular remodeling. In recent years, speckle-tracking echocardiography has been added to conventional echocardiographic techniques, showing additional value for diagnostic and prognostic indications, but further confirmations are needed.