How to Conduct Clinical Research in Cardiovascular Imaging: A Primer for Clinical Cardiologists and Researchers. A Statement of the European Association of Cardiovascular Imaging (EACVI) of the ESC.

This statement from the European Association of Cardiovascular Imaging (EACVI) of the ESC aims to address the fundamental principles that guide clinical research in the field of cardiovascular imaging. It provides clinical researchers, cardiology fellows, and Ph.D. students with a condensed, updated, and practical reference document to support them in designing, implementing, and conducting imaging protocols for clinical trials. Although the present article cannot replace formal research training and mentoring, it is recommended reading for any professional interested in becoming acquainted with or participating in clinical trials involving cardiovascular imaging.

Right Ventricular Free Wall Strain Predicts ATTR Prognosis as Well as Biomarker- Based Staging Systems.

AIMS: The diagnosis of transthyretin amyloidosis (ATTR) significantly impacts the management and prognosis of patients initially presenting with heart failure (HF). Despite recent advances in treatment, prognosticating ATTR remains challenging. We aimed to assess echocardiographic parameters associated with mid-term prognosis in patients with wild-type ATTR using a biomarker staging system as a reference point. METHODS AND RESULTS: We studied 182 consecutive patients with wild-type ATTR (91% male, median age 82 years) who were referred to our center between 2016 and 2022. Using NT- proBNP and eGFR cutoffs, we divided patients into stage I (101 patients, 55.5%), stage II (53, 29.0%), and stage III disease (28, 15.5%). We then compared traditional echocardiographic indices and markers of subclinical ventricular dysfunction (LV global longitudinal strain, RV free wall strain, and LA strain) among groups. Over a fixed follow-up of 18 months, which included treatment with tafamidis 61 mg daily, 48 patients (26.4%) experienced the composite outcome of death or HF hospitalization. When compared with stage I ATTR, the hazard ratio for death or hospitalization was 1.55 (95% CI 0.62-3.86) for stage II ATTR and 4.53 (95% CI 1.66-12.4, p = 0.0116) for stage III ATTR. Among echocardiographic parameters, reduced RV FWS was independently associated with all-cause mortality or HF hospitalization after adjustment for the staging system (HR 2.03, 95% CI 1.07-3.85, p < 0.05). CONCLUSION: RV FWS should be routinely assessed for all patients with ATTR. It is an independent predictor of poor prognosis and provides additional value beyond biomarker staging systems.

Imaging in acute percutaneous mechanical circulatory support in adults. A clinical consensus statement of the Association for Acute CardioVascular Care (ACVC) of the ESC, the European Association of Cardiovascular Imaging (EACVI) of the ESC and the European branch of the Extracorporeal Life Support Organization (EuroELSO).

The use of temporary mechanical circulatory support (tMCS) in cardiogenic shock patients has increased during the last decades with most management strategies relying on observational studies and expert opinion, including hemodynamic monitoring, device selection and timing of support institution/duration. In this context, imaging has a pivotal role throughout the patient pathway, from identification to initiation, monitoring and weaning. This manuscript summarizes the consensus of an expert panel from the European Society of Cardiology Association for Acute CardioVascular Care, the European Association of CardioVascular Imaging and the European Extracorporeal Life Support Organization, providing the rationale for and practical guidance of imaging to tMCS based on existing evidence and consensus on best current practice.

Randomised study for the Optimal Treatment of symptomatic patients with low-gradient severe Aortic valve Stenosis and preserved left ventricular ejection fraction (ROTAS trial).

BACKGROUND: The best management of symptomatic patients with low-gradient (LG) severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF) has not been established. The Randomised study for the Optimal Treatment of symptomatic patients with low-gradient severe Aortic valve Stenosis (ROTAS) trial aimed to assess the superiority of aortic valve replacement (AVR) versus medical treatment (MT) in this specific group of AS patients. METHODS: Patients with symptomatic LG severe AS and preserved LVEF (>50%) underwent dobutamine stress echocardiography and/or CT-aortic calcium score to confirm AS severity and were then randomised 1:1 to AVR or MT. The primary endpoint was a composite of overall death and/or cardiovascular hospitalisation. RESULTS: The ROTAS study was stopped early because of insufficient recruitment. In the end, only 52 patients (age 79±7 years; women 54%; NYHA III-IV 27%; median STS score 3.3%) were included in the study. During follow-up (mean: 14±7 months), the primary endpoint occurred in 12 (23%) patients. Compared with MT, AVR was not associated with a significant prognostic benefit (events: 5/26 (19%) vs 7/26 (27%) (HR 0.76, 95% CI 0.24 to 2.39, p=0.63). During follow-up, 11 (42%) patients in the MT group developed class I criteria for AVR or severe symptoms justifying a cross-over to the AVR group. CONCLUSIONS: Because of the small number of included patients and short follow-up the ROTAS trial was underpowered and unable to demonstrate a difference in the study endpoint between treatment arms. In patients in the MT arm, a regular echocardiographic and clinical assessment might be useful to disclose those developing class I indications of AVR or severe AS-related symptoms. TRIAL REGISTRATION NUMBER: NCT01835028.

Benefit of isolated surgical valve repair or replacement for functional tricuspid regurgitation and long-term outcomes stratified by the TRI-SCORE.

BACKGROUND AND AIMS: Severe tricuspid regurgitation (TR) is associated with increased mortality rates, but benefit of its correction and ideal timing are not clearly determined. This study aimed to identify patient subsets who might benefit from surgery. METHODS: In TRIGISTRY, an international cohort study of consecutive patients with severe isolated functional TR (33 centers, 10 countries), survival rates up to 10 years were compared between patients who underwent isolated tricuspid valve (TV) surgery (repair or replacement) and those conservatively managed, overall and according to TRI-SCORE category (low: ≤3, intermediate: 4-5, high: ≥6). RESULTS: 1,217 were managed conservatively, and 551 underwent isolated TV surgery (200 repairs, 351 replacements). TRI-SCORE distribution was 33% low, 32% intermediate, and 35% high. At 10 years, survival rates were similar between surgical and conservative management (41% vs. 36%; hazard ratio [HR] 0.97; 95% confidence interval [CI] 0.88-1.08, P=0.57). Surgery improved survival compared to conservative management in the low TRI-SCORE category (72% vs. 44%; HR 0.27; 95% CI 0.20-0.37, P<0.0001), but not in the intermediate (36% vs. 37%, HR 1.17; 95%CI 0.98-1.40, P=0.09) or high categories (20% vs. 24%; HR 1.06; 95% CI 0.91-1.25, P=0.45). Both repair and replacement improved survival in the low TRI-SCORE category (84% and 61% vs. 44%; HR 0.11; 95% CI 0.06-0.19, P<0.0001, and HR 0.65; 95% CI 0.47-0.90, P=0.009). Repair showed benefit in the intermediate category (59% vs. 37%; HR 0.49; 95% CI 0.35-0.68, P<0.0001) while replacement was possibly harmful (25% vs. 37%; HR 1.43; 95% CI 1.18-1.72, P=0.0002). CONCLUSIONS: Higher survival rates were observed with repair than replacement and benefit of intervention declined as TRI-SCORE increased with no benefit of any type of surgery in the high TRI-SCORE category. These results emphasize the importance of timely intervention and patient selection to achieve the best outcomes and the need for randomized controlled trials. TRIAL REGISTRATION: TRIGISTRY: ClinicalTrials.gov, NCT05825898.

Transjugular Transcatheter Tricuspid Valve Replacement: Early Compassionate Use Outcomes.

BACKGROUND: Data on procedural and early outcomes after transjugular transcatheter tricuspid valve replacement (TTVR) are limited. OBJECTIVES: This study sought to evaluate first-in-man procedural and clinical outcomes after transjugular TTVR with a special focus on patients who received large device sizes in whom TTVR outcomes have been questioned. METHODS: The retrospective registry included patients who underwent TTVR using the LuX-Valve Plus system (Jenscare Biotechnology Co Ltd) for symptomatic tricuspid regurgitation (TR) from January 2022 until February 2024 at 15 international centers in a compassionate use setting. The endpoints were procedural TR reduction, in-hospital death, adverse events, and 1-month survival. We further stratified results according to the size of the implanted device (<55 vs ≥55 mm). RESULTS: The registry included a total of 76 patients at a median age of 78 years (Q1-Q3: 72-83 years, 47.4% women). TR was reduced to ≤2+ and ≤1+ in 94.7% and 90.8% of patients (75.0% of patients received TTVR devices ≥55 mm) with well-sustained results at 1-month follow-up (TR ≤2+ in 95.0% and ≤1+ 86.8%). Residual TR was paravalvular in all cases. In-hospital death occurred in 4 patients (5.3%). Four patients (5.3%) underwent cardiac surgery during index hospitalization. Major in-hospital bleeding events occurred in 5 patients (6.6%). New in-hospital pacemaker implantation was required in 3.9% of patients in the overall cohort (5.7% in "pacemaker-naive" individuals). No cases of valve thrombosis, stroke, myocardial infarction, or pulmonary embolism were observed. At 1-month follow-up, survival was 94.4%, and NYHA functional class significantly improved. One further patient received a pacemaker, 1 further bleeding event occurred, and 2 patients underwent reintervention or surgery within the first 30 days after TTVR. No differences in procedural outcomes or adverse events were observed after stratification for valve size. CONCLUSIONS: Transjugular TTVR appears to be a safe and effective treatment option for patients with severe TR with comparable outcomes in very large tricuspid anatomies.

Characterization of cardiac resynchronization therapy response through machine learning and personalized models.

INTRODUCTION: The characterization and selection of heart failure (HF) patients for cardiac resynchronization therapy (CRT) remain challenging, with around 30% non-responder rate despite following current guidelines. This study aims to propose a novel hybrid approach, integrating machine-learning and personalized models, to identify explainable phenogroups of HF patients and predict their CRT response. METHODS: The paper proposes the creation of a complete personalized model population based on preoperative CRT patient strain curves. Based on the parameters and features extracted from these personalized models, phenotypes of patients are identified thanks to a clustering algorithm and a random forest classification is provided. RESULTS: A close match was observed between the 162 experimental and simulated myocardial strain curves, with a mean RMSE of 4.48% (±1.08) for the 162 patients. Five phenogroups of personalized models were identified from the clustering, with response rates ranging from 52% to 94%. The classification results show a mean area under the curves (AUC) of 0.86 ± 0.06 and provided a feature importance analysis with 22 features selected. Results show both regional myocardial contractility (from 22.5% to 33.0%), tissue viability and electrical activation delays importance on CRT response for each HF patient (from 55.8 ms to 88.4 ms). DISCUSSION: The patient-specific model parameters' analysis provides an explainable interpretation of HF patient phenogroups in relation to physiological mechanisms that seem predictive of the CRT response. These novel combined approaches appear as promising tools to improve understanding of LV mechanical dyssynchrony for HF patient characterization and CRT selection.

Mechanical dyssynchrony as a selection criterion for cardiac resynchronization therapy: Design of the AMEND-CRT trial.

AIMS: One third of patients do not improve after cardiac resynchronization therapy (CRT). Septal flash (SF) and apical rocking (ApRock) are deformation patterns observed on echocardiography in most patients eligible for CRT. These markers of mechanical dyssynchrony have been associated to improved outcome after CRT in observational studies and may be useful to better select patients. The aim of this trial is to investigate whether the current guideline criteria for selecting patients for CRT should be modified and include SF and ApRock to improve therapy success rate, reduce excessive costs and prevent exposure to device-related complications in patients who would not benefit from CRT. METHODS: The AMEND-CRT trial is a multicentre, randomized, parallel-group, double-blind, sham-controlled trial with a non-inferiority design. The trial will include 578 patients scheduled for CRT according to the 2021 ESC guidelines who satisfy all inclusion criteria. The randomization is performed 1:1 to an active control arm ('guideline arm') or an experimental arm ('echo arm'). All participants receive a device, but in the echo arm, CRT is activated only when SF or ApRock or both are present. The outcome of both arms will be compared after 1 year. The primary outcome measures are the average change in left ventricular end-systolic volume and patient outcome assessed using a modified Packer Clinical Composite Score. CONCLUSIONS: The findings of this trial will redefine the role of echocardiography in CRT and potentially determine which patients with heart failure and a prolonged QRS duration should receive CRT, especially in patients who currently have a class IIa or class IIb recommendation.

How to diagnose heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a major healthcare problem that is raising in prevalence. There has been a shift in HpEF management towards early diagnosis and phenotype-specific targeted treatment. However, the diagnosis of HFpEF remains a challenge due to the lack of universal criteria and patient heterogeneity. This review aims to provide a comprehensive assessment of the diagnostic workup of HFpEF, highlighting the role of echocardiography in HFpEF phenotyping.

Right atrial and right ventricular strain: prognostic value depends on the severity of tricuspid regurgitation.

AIMS: Assessing right heart function is challenging, particularly when significant tricuspid regurgitation (TR) is present. Among available echocardiographic techniques for assessment, literatures suggests that strain imaging may be more reliable and less susceptible to loading conditions. Thus, we aimed to assess the validity of RA and RV strain relative to conventional metrics as well as their utility in predicting patient outcomes in TR. METHODS: We studied 262 consecutive patients (mean age 74 ± 11.2 years, 53% male) who underwent same-day echocardiography and right heart catheterization between 2018 and 2023. We compared right heart strain to traditional metrics of RV function and subsequently correlated RA and RV strain to heart failure (HF)-related death or hospitalization, whichever came first. RESULTS: Over a mean follow-up of 34 ± 15 months, there were 103 deaths and HF hospitalizations. Both RA and RV strain were correlated with echocardiographic and invasive measures of right heart function. Across all patients, preserved RA strain was associated with lower risk of adverse outcomes (HR 0.763, 95% CI 0.618-0.943). Similarly, preserved RV strain was correlated with better outcomes, though this was only statistically significant in patients without severe TR or pulmonary hypertension (HR 2.450, 95% CI 1.244-4.825). Moreover, abnormal ratios of RV strain to pulmonary pressures and RV size were significantly correlated with adverse outcomes (p < 0.05 each). CONCLUSION: RA and RV strain are independently correlated with echocardiographic and invasive measures of cardiac function. Moreover, preserved RA and RV strain are likely associated with better clinical outcomes.

Impact of Intraprocedural Mitral Regurgitation and Gradient Following Transcatheter Edge-to-Edge Repair for Primary Mitral Regurgitation.

BACKGROUND: The impact of intraprocedural results following transcatheter edge-to-edge repair (TEER) in primary mitral regurgitation (MR) is controversial. OBJECTIVES: This study sought to investigate the prognostic impact of intraprocedural residual mitral regurgitation (rMR) and mean mitral valve gradient (MPG) in patients with primary MR undergoing TEER. METHODS: The PRIME-MR (Outcomes of Patients Treated With Mitral Transcatheter Edge-to-Edge Repair for Primary Mitral Regurgitation) registry included consecutive patients with primary MR undergoing TEER from 2008 to 2022 at 27 international sites. Clinical outcomes were assessed according to intraprocedural rMR and mean MPG. Patients were categorized according to rMR (optimal result: ≤1+, suboptimal result: ≥2+) and MPG (low gradient: ≤5 mm Hg, high gradient: > 5 mm Hg). The prognostic impact of rMR and MPG was evaluated in a Cox regression analysis. The primary endpoint was 2-year all-cause mortality or heart failure hospitalization. RESULTS: Intraprocedural rMR and mean MPG were available in 1,509 patients (median age = 82 years [Q1-Q3: 76.0-86.0 years], 55.1% male). Kaplan-Meier analysis according to rMR severity showed significant differences for the primary endpoint between rMR ≤1+ (29.1%), 2+ (41.7%), and ≥3+ (58.0%; P < 0.001), whereas there was no difference between patients with a low (32.4%) and high gradient (42.1%; P = 0.12). An optimal result/low gradient was achieved in most patients (n = 1,039). The worst outcomes were observed in patients with a suboptimal result/high gradient. After adjustment, rMR ≥2+ was independently linked to the primary endpoint (HR: 1.87; 95% CI: 1.32-2.65; P < 0.001), whereas MPG >5 mm Hg was not (HR: 0.78; 95% CI: 0.47-1.31; P = 0.35). CONCLUSIONS: Intraprocedural rMR but not MPG independently predicted clinical outcomes following TEER for primary MR. When performing TEER in primary MR, optimal MR reduction seems to outweigh the impact of high transvalvular gradients.

Rates and predictors of cardiovascular and non-cardiovascular outcomes in heart failure with preserved ejection fraction.

AIMS: The detailed sub-categories of death and hospitalization, and the impact of comorbidities on cause-specific outcomes, remain poorly understood in heart failure (HF) with preserved ejection fraction (HFpEF). We sought to evaluate rates and predictors of cardiovascular (CV) and non-CV outcomes in HFpEF. METHODS: The Karolinska-Rennes study was a bi-national prospective observational study designed to characterize HFpEF (ejection fraction ≥45%). Patients were followed for cause-specific death and hospitalization. Baseline characteristics were pre-selected based on clinical relevance and potential eligibility criteria for HFpEF trials. The associations between characteristics and cause-specific outcomes were assessed with univariable and multivariable Cox regressions. RESULTS: Five hundred thirty-nine patients [56% females; median (inter-quartile range) age 79 (72-84) years; NT-proBNP/BNP 2448 (1290-4790)/429 (229-805) ng/L] were included. Over 1196 patient-years follow-up [median (min, max) 744 days (13-1959)], there were 159 (29%) deaths (13 per 100 patient-years: CV 5.1 per 100, dominated by HF 3.9 per 100; and non-CV 5.8 per 100, dominated by cancer, 2.3 per 100). There were 723 hospitalizations in 338 patients (63%; 60 per 100 patient-years: CV 33 per 100, dominated by HF 17 per 100; and non-CV 27 per 100, dominated by lung disease 5 per 100). Higher age and natriuretic peptides, lower serum natraemia and NYHA class III-IV were independent predictors of CV death; lower serum natraemia, anaemia and stroke of non-CV death; and anaemia and lower serum natraemia of non-CV death or hospitalizations. There were no apparent predictors of CV death or hospitalization. CONCLUSIONS: In a clinical cohort hospitalized and diagnosed with HFpEF, death and hospitalization rates were roughly similar for CV and non-CV causes. CV deaths were predicted primarily by severity of HF; non-CV deaths primarily by anaemia and prior stroke. Lower serum sodium predicted both. Hospitalizations were difficult to predict.

Multimodality imaging for the evaluation and management of patients with long-term (durable) left ventricular assist devices A Clinical Consensus Statement of the European Association of Cardiovascular Imaging (EACVI) of the ESC.

Left ventricular assist devices (LVADs) are gaining increasing importance as therapeutic strategy in advanced heart failure (HF), not only as bridge to recovery or to transplant, but also as destination therapy. Even though long-term LVADs are considered a precious resource to expand the treatment options and improve clinical outcome these patients, these are limited by peri-operative and post-operative complications, such as device-related infections, haemocompatibility-related events, device mispositioning and right ventricular failure. For this reason, a precise pre-operative, peri-operative and post-operative evaluation of these patients is crucial for the selection of LVADs candidates and the management LVADs recipients. The use of different imaging modalities offers important information to complete the study of patients with LVADs in each phase of their assessment, with peculiar advantages/disadvantages, ideal application and reference parameters for each modality. This clinical consensus statement sought to guide the use of multimodality imaging for the evaluation of patients with advanced HF undergoing LVADs implantation.

Evaluation of left ventricular filling pressure by echocardiography in patients with atrial fibrillation.

BACKGROUND: Echocardiography is widely used to evaluate left ventricular (LV) diastolic function in patients suspected of heart failure. For patients in sinus rhythm, a combination of several echocardiographic parameters can differentiate between normal and elevated LV filling pressure with good accuracy. However, there is no established echocardiographic approach for the evaluation of LV filling pressure in patients with atrial fibrillation. The objective of the present study was to determine if a combination of several echocardiographic and clinical parameters may be used to evaluate LV filling pressure in patients with atrial fibrillation. RESULTS: In a multicentre study of 148 atrial fibrillation patients, several echocardiographic parameters were tested against invasively measured LV filling pressure as the reference method. No single parameter had sufficiently strong association with LV filling pressure to be recommended for clinical use. Based on univariate regression analysis in the present study, and evidence from existing literature, we developed a two-step algorithm for differentiation between normal and elevated LV filling pressure, defining values ≥ 15 mmHg as elevated. The parameters in the first step included the ratio between mitral early flow velocity and septal mitral annular velocity (septal E/e'), mitral E velocity, deceleration time of E, and peak tricuspid regurgitation velocity. Patients who could not be classified in the first step were tested in a second step by applying supplementary parameters, which included left atrial reservoir strain, pulmonary venous systolic/diastolic velocity ratio, and body mass index. This two-step algorithm classified patients as having either normal or elevated LV filling pressure with 75% accuracy and with 85% feasibility. Accuracy in EF ≥ 50% and EF < 50% was similar (75% and 76%). CONCLUSIONS: In patients with atrial fibrillation, no single echocardiographic parameter was sufficiently reliable to be used clinically to identify elevated LV filling pressure. An algorithm that combined several echocardiographic parameters and body mass index, however, was able to classify patients as having normal or elevated LV filling pressure with moderate accuracy and high feasibility.

Recurrent ventricular tachycardia in a patient with A19D mutation-associated hereditary transthyretin amyloidosis: a case report.

Background: Previous literature suggests that patients with transthyretin amyloidosis (ATTR) experience a high burden of ventricular arrhythmias. Despite this evidence, optimal strategies for arrhythmia prevention and treatment remain subject to debate. Case summary: We report the case of a patient with hereditary ATTR cardiomyopathy who developed recurrent ventricular tachycardia prior to a decline in his left ventricular ejection fraction (LVEF). Although he ultimately received an intracardiac device (ICD) for secondary prevention of ventricular tachycardia, his clinical course begets the question of whether more aggressive arrhythmia prevention upfront could have prevented his global functional decline. Discussion: Given the advent of new disease-modifying therapies for ATTR, it is imperative to reconsider antiarrhythmic strategies in these patients. New decision tools are needed to decide what additional parameters (beyond LVEF ≤ 35%) may warrant ICD placement for primary prevention of ventricular arrhythmias in these patients.

Heterogeneity of right ventricular echocardiographic parameters in systemic lupus erythematosus among four clinical subgroups, as stratified by clinical organ involvement in observational cohort.

BACKGROUND: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Cardiac involvement in SLE is rare but plays an important prognostic role. The degree of cardiac involvement according to SLE subsets defined by non-cardiac manifestations is unknown. The objective of this study was to identify differences in transthoracic echocardiography (TTE) parameters associated with different SLE subgroups. METHODS: One hundred eighty-one patients who fulfilled the 2019 American College of Rheumatology/EULAR classification criteria for SLE and underwent baseline TTE were included in this cross-sectional study. We defined four subsets of SLE based on the predominant clinical manifestations. A multivariate multinomial regression analysis was performed to determine whether TTE parameters differed between groups. RESULTS: Four clinical subsets were defined according to non-cardiac clinical manifestations: group A (n=37 patients) showed features of mixed connective tissue disease, group B (n=76 patients) had primarily cutaneous involvement, group C (n=18) exhibited prominent serositis and group D (n=50) had severe, multi-organ involvement, including notable renal disease. Forty TTE parameters were assessed between groups. Per multivariate multinomial regression analysis, there were statistically significant differences in early diastolic tricuspid annular velocity (RV-Ea, p<0.0001), RV S' wave (p=0.0031) and RV end-diastolic diameter (p=0.0419) between the groups. Group B (primarily cutaneous involvement) had the lowest degree of RV dysfunction. CONCLUSION: When defining clinical phenotypes of SLE based on organ involvement, we found four distinct subgroups which showed notable differences in RV function on TTE. Risk-stratifying patients by clinical phenotype could help better tailor cardiac follow-up in this population.