Pulmonary Vein Systolic Flow Reversal and Outcomes in Patients From the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) Trial.

Background: The implications of pulmonary vein (PV) flow patterns in patients with heart failure (HF) and mitral regurgitation (MR) are uncertain. We examined PV flow patterns in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) trial (NCT01626079), in which patients with HF and moderate-to-severe or severe functional MR were randomized to transcatheter edge-to-edge repair (TEER) with the MitraClip device plus guideline-directed medical therapy (GDMT) vs. GDMT alone. We sought to evaluate the prognostic utility of baseline PV systolic flow reversal (PVSFR) in HF patients with severe MR and to determine whether the presence of PVSFR can discriminate patients most likely to benefit from TEER in COAPT trial patients. Methods: Patients were categorized by the echocardiographic core laboratory-assessed baseline presence of PVSFR. Two-year outcomes were examined according to PVSFR and treatment. Results: Baseline PV flow patterns were evaluable in 526/614(85.7%) patients, 48.9% of whom had PVSFR. Patients with PVSFR had more severe MR, reduced stroke volume and cardiac output, greater right ventricular dysfunction, and worse hemodynamics. By multivariable analysis, PVSFR was not an independent predictor of 2-year all-cause death, or heart failure hospitalization (HFH). The reductions in the 2-year rates of all-cause death and HFH with TEER compared with GDMT alone were similar in patients with and without PVSFR (Pinteraction = 0.40 and 0.12, respectively). The effect of TEER on improving Kansas City Cardiomyopathy Questionnaire scores and 6-minute walk distance were also independent of PVSFR. Conclusions: In the COAPT trial, PVSFR identified HF patients with severe MR and more advanced heart disease. Patients with and without PVSFR had consistent reductions in mortality, HFH, and improved quality-of-life and functional capacity after TEER. Clinical Trial Registration: ClinicalTrial.gov IdentifierNCT01626079.

Lesion delivery and scar formation in catheter ablation for atrial fibrillation: The DECAAF II trial.

BACKGROUND: The Efficacy of Delayed Enhancement MRI-Guided Fibrosis Ablation vs Conventional Catheter Ablation of Atrial Fibrillation randomized trial showed no difference in atrial fibrillation (AF) recurrence with additional delayed enhancement magnetic resonance imaging (DE-MRI) fibrosis-targeted ablation to pulmonary vein isolation (PVI) in persistent AF. OBJECTIVE: We evaluated the effect of lesion delivery on ablation-induced scarring and AF recurrence. METHODS: Lesions delivered, targeting fibrotic and nonfibrotic areas identified from preablation DE-MRI, were studied in relation to ablation-induced scarring on 3-month DE-MRI, including their association with arrhythmia recurrence. RESULTS: A total of 593 patients treated with radiofrequency were analyzed: 293 (49.4%) underwent PVI and 300 (50.6%) underwent additional fibrosis-guided ablation. Lesion analysis showed that 80.9% in the MRI fibrosis-guided group vs 16.5% in the PVI group (P < .001) had ≥40% of baseline fibrosis targeted. MRI assessment of ablation-induced scar showed that 44.8% of fibrosis-guided ablation and 15.5% of PVI had ≥40% of their fibrosis covered by scar (P < .001), demonstrating significant attenuation from lesions delivered to scar formed. In the overall population, fibrosis coverage with scar was not associated with recurrence (hazard ratio [HR] 0.90; 95% confidence interval [CI] 0.80-1.01; P = .08 per 20% increase). In patients with baseline fibrosis < 20%, fibrosis coverage with scar was associated with lower recurrence than PVI (HR 0.85; 95% CI 0.73-0.97; P = .03), whereas the association was not significant when baseline fibrosis ≥ 20% (HR 0.97; 95% CI 0.80-1.17; P = .77). Significant center variation was observed in fibrosis targeting and coverage with scarring. CONCLUSION: Radiofrequency ablation lesions do not uniformly result in scar formation. A post hoc analysis suggests reduced arrhythmia recurrence when ablation-induced scarring covers fibrotic regions in patients with low baseline fibrosis.

Interatrial Shunt Treatment for Heart Failure: The Randomized RELIEVE-HF Trial.

BACKGROUND: An interatrial shunt may provide an autoregulatory mechanism to decrease left atrial pressure and improve heart failure (HF) symptoms and prognosis. METHODS: Patients with symptomatic HF with any left ventricular ejection fraction (LVEF) were randomized 1:1 to transcatheter shunt implantation versus a placebo procedure, stratified by reduced (≤40%) versus preserved (>40%) LVEF. The primary safety outcome was a composite of device-related or procedure-related major adverse cardiovascular or neurological events at 30 days compared with a prespecified performance goal of 11%. The primary effectiveness outcome was the hierarchical composite ranking of all-cause death, cardiac transplantation or left ventricular assist device implantation, HF hospitalization, outpatient worsening HF events, and change in quality of life from baseline measured by the Kansas City Cardiomyopathy Questionnaire overall summary score through maximum 2-year follow-up, assessed when the last enrolled patient reached 1-year follow-up, expressed as the win ratio. Prespecified hypothesis-generating analyses were performed on patients with reduced and preserved LVEF. RESULTS: Between October 24, 2018, and October 19, 2022, 508 patients were randomized at 94 sites in 11 countries to interatrial shunt treatment (n=250) or a placebo procedure (n=258). Median (25th and 75th percentiles) age was 73.0 years (66.0, 79.0), and 189 patients (37.2%) were women. Median LVEF was reduced (≤40%) in 206 patients (40.6%) and preserved (>40%) in 302 patients (59.4%). No primary safety events occurred after shunt implantation (upper 97.5% confidence limit, 1.5%; P<0.0001). There was no difference in the 2-year primary effectiveness outcome between the shunt and placebo procedure groups (win ratio, 0.86 [95% CI, 0.61-1.22]; P=0.20). However, patients with reduced LVEF had fewer adverse cardiovascular events with shunt treatment versus placebo (annualized rate 49.0% versus 88.6%; relative risk, 0.55 [95% CI, 0.42-0.73]; P<0.0001), whereas patients with preserved LVEF had more cardiovascular events with shunt treatment (annualized rate 60.2% versus 35.9%; relative risk, 1.68 [95% CI, 1.29-2.19]; P=0.0001; Pinteraction<0.0001). There were no between-group differences in change in Kansas City Cardiomyopathy Questionnaire overall summary score during follow-up in all patients or in those with reduced or preserved LVEF. CONCLUSIONS: Transcatheter interatrial shunt implantation was safe but did not improve outcomes in patients with HF. However, the results from a prespecified exploratory analysis in stratified randomized groups suggest that shunt implantation is beneficial in patients with reduced LVEF and harmful in patients with preserved LVEF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03499236.

Pericoronary adipose tissue for predicting long-term outcomes.

AIMS: Pericoronary adipose tissue (PCAT) attenuation obtained by coronary computed tomography angiography (CCTA) has been associated with coronary inflammation and outcomes. Whether PCAT attenuation is predictive of major adverse cardiac events (MACE) during long-term follow-up is unknown. METHODS AND RESULTS: Symptomatic patients with coronary artery disease (CAD) who underwent CCTA were included, and clinical outcomes were evaluated. PCAT was measured at all lesions for all three major coronary arteries using semi-automated software. A comparison between patients with and without MACE was made on both a per-lesion and a per-patient level. The predictive value of PCAT attenuation for MACE was assessed in Cox regression models. In 483 patients (63.3 ± 8.5 years, 54.9% men), 1561 lesions were analysed over a median follow-up duration of 9.5 years. The mean PCAT attenuation was not significantly different between patients with and without MACE. At a per-patient level, the adjusted hazard ratio (HR) and 95% confidence interval (CI) for MACE were 0.970 (95% CI: 0.933-1.008, P = 0.121) when the average of all lesions per patient was analysed, 0.992 (95% CI: 0.961-1.024, P = 0.622) when only the most obstructive lesion was evaluated, and 0.981 (95% CI: 0.946-1.016, P = 0.285) when only the lesion with the highest PCAT attenuation per individual was evaluated. Adjusted HRs for vessel-specific PCAT attenuation in the right coronary artery, left anterior descending artery, and left circumflex artery were 0.957 (95% CI: 0.830-1.104, P = 0.548), 0.989 (95% CI: 0.954-1.025, P = 0.550), and 0.739 (95% CI: 0.293-1.865, P = 0.522), respectively, in predicting long-term MACE. CONCLUSION: In patients referred to CCTA for clinically suspected CAD, PCAT attenuation did not predict MACE during long-term follow-up.

Heart failure risk assessment in patients with hypertrophic cardiomyopathy based on the H2FPEF score.

AIMS: The aim of this study was to investigate whether the H2FPEF score, which was developed to improve the diagnosis of heart failure (HF) with preserved ejection fraction, is associated with HF outcomes in patients with hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Patients with HCM and preserved left ventricular ejection fraction (LVEF ≥50%) were included from a multicentre registry and the H2FPEF score was calculated. Patients were divided into three groups: low (0-1), intermediate (2-5) and high (6-9) H2FPEF score. The primary combined endpoint was a composite of all-cause death and HF admissions, while the secondary endpoints were all-cause death and HF admissions separately. A total of 955 patients were included (age 51 ± 17 years, 310 [32.5%] female). Patients with a high H2FPEF score (n = 105) were more often female, and presented with more symptoms and comorbidities. On echocardiography, patients with a high H2FPEF score had lower LVEF, more impaired diastolic function and more frequently left ventricular outflow tract obstruction. During follow-up (median 90 months [interquartile range 49-176]), 103 (11%) patients died and 57 (6%) patients had a first HF hospitalization. Event-free survival rate for the primary combined and secondary endpoints was lower for patients with an intermediate and high H2FPEF score. On multivariate Cox regression analysis, female sex (hazard ratio [HR] 1.670, 95% confidence interval [CI] 1.157-2.410; p = 0.006), Asian ethnicity (HR 6.711, 95% CI 4.076-11.048; p < 0.001), ischaemic heart disease (HR 1.732, 95% CI 1.133-2.650; p = 0.011), left atrial diameter (HR 1.028, 95% CI 1.005-1.051; p = 0.016) and intermediate (HR 2.757, 95% CI 1.612-4.713; p < 0.001) or high H2FPEF score (HR 3.689, 95% CI 1.908-7.134; p < 0.001) were independently associated with the primary combined endpoint. CONCLUSION: The H2FPEF score is independently associated with HF outcome in patients with HCM and may be considered for risk stratification.

Rapid Plaque Progression Is Independently Associated With Hyperglycemia and Low HDL Cholesterol in Patients With Stable Coronary Artery Disease: A PARADIGM Study.

BACKGROUND: We assessed whether combinations of cardiometabolic risk factors independently predict coronary plaque progression (PP) and major adverse cardiovascular events in patients with stable coronary artery disease. METHODS: Patients with known or suspected stable coronary artery disease (60.9±9.3 years, 55.4% male) undergoing serial coronary computed tomography angiographies (≥2 years apart), with clinical characterization and follow-up (N=1200), were analyzed from the PARADIGM study (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging). Plaque volumes measured in coronary segments (≥2 mm in diameter) were summed to provide whole heart plaque volume (mm3) and percent atheroma volume (plaque volume/vessel volume×100; %) per patient at baseline and follow-up. Rapid PP was defined as a percent atheroma volume increase of ≥1.0%/y. Major adverse cardiovascular events included nonfatal myocardial infarction, death, and unplanned coronary revascularization. RESULTS: In an interscan period of 3.2 years (interquartile range, 1.9), rapid PP occurred in 341 patients (28%). At multivariable analysis, the combination of cardiometabolic risk factors defined as metabolic syndrome predicted rapid PP (odds ratio, 1.51 [95% CI, 1.12-2.03]; P=0.007) together with older age, smoking habits, and baseline percent atheroma volume. Among single cardiometabolic variables, high fasting plasma glucose (diabetes or fasting plasma glucose >100 mg/dL) and low HDL-C (high-density lipoprotein cholesterol; <40 mg/dL in males and <50 mg/dL in females) were independently associated with rapid PP, in particular when combined (odds ratio, 2.37 [95% CI, 1.56-3.61]; P<0.001). In a follow-up of 8.23 years (interquartile range, 5.92-9.53), major adverse cardiovascular events occurred in 201 patients (17%). At multivariable Cox analysis, the combination of high fasting plasma glucose with high systemic blood pressure (treated hypertension or systemic blood pressure >130/85 mm Hg) was an independent predictor of events (hazard ratio, 1.79 [95% CI, 1.10-2.90]; P=0.018) together with family history, baseline percent atheroma volume, and rapid PP. CONCLUSIONS: In patients with stable coronary artery disease, the combination of hyperglycemia with low HDL-C is associated with rapid PP independently of other risk factors, baseline plaque burden, and treatment. The combination of hyperglycemia with high systemic blood pressure independently predicts the worse outcome beyond PP. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02803411.

Right ventricular-pulmonary arterial coupling in patients with first acute myocardial infarction: an emerging post-revascularization triage tool.

BACKGROUND: The tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio is a non-invasive surrogate for right ventricular-pulmonary arterial (RV-PA) coupling, studied in chronic RV pressure overload syndromes. However, its prognostic utility in patients with acute myocardial infarction (AMI), which may cause acute RV pressure overload, remains unexplored. OBJECTIVE: This study aimed to determine predictors of RV-PA uncoupling in patients with first AMI and examine whether it could improve risk stratification for cardiovascular in-hospital mortality after revascularization. METHODS: Three-hundred consecutive patients with first AMI were prospectively studied (age 61.2 ± 11.8, 24% females). Echocardiography was performed 24 h after successful revascularization, and TAPSE/PASP was evaluated. Cardiovascular in-hospital mortality was recorded. RESULTS: The optimal cutoff value of TAPSE/PASP to determine cardiovascular in-hospital mortality was 0.49 mm/mmHg. RV-PA uncoupling was considered for patients with TAPSE/PASP ≤0.49 mm/mmHg. Left ventricular ejection fraction (LVEF) was independently associated with RV-PA uncoupling. A total of 23 (7.7%) patients died in hospital despite successful revascularization. TAPSE/PASP was independently associated with in-hospital mortality after adjustment for Global Registry of Acute Coronary Events (GRACE) risk score and LVEF (odds ratio 0.14 [95% confidence interval 0.03-0.56], P = 0.007). The prognostic value of a baseline model including the GRACE risk score and NT-pro-BNP (χ2 26.55) was significantly improved by adding LVEF ≤40% (χ2 44.71, P < 0.001), TAPSE ≤ 17 mm (χ2 75.42, P < 0.001) and TAPSE/PASP ≤ 0.49 mm/mmHg (χ2 101.74, P < 0.001) for predicting cardiovascular in-hospital mortality. CONCLUSION: RV-PA uncoupling, assessed by echocardiographic TAPSE/PASP ≤ 0.49 mm/mmHg 24 h after revascularization, may improve risk stratification for cardiovascular in-hospital mortality after first AMI.

Echocardiographic assessment of patient hemodynamics in heart failure.

Heart failure (HF) is a clinical syndrome which is due to cardiac structural and/or functional abnormalities that result in elevated intra-cardiac pressures and/or inadequate cardiac output. Hemodynamic assessment in HF allows the identification and characterization of cardiac dysfunction, systemic and/or pulmonary congestion and the eventual impairment of systemic perfusion which are fundamental to phenotype HF, risk stratify HF patients and to guide their treatment. Patient hemodynamics can be characterized invasively with right heart catheterization but also non-invasively with the use of echocardiography and other non-invasive ultrasound tools. The aim of the present review is to summarize the main echocardiographic and ultrasound parameters to characterize the hemodynamics of patients with HF and help clinicians to make the most of these non-invasive tools to guide HF patient management.

Changes in Global Longitudinal Strain after TAVI: Additional Prognostic Value over Cardiac Damage in Patients with Severe Aortic Stenosis.

Background: Previous studies demonstrated the prognostic value of baseline cardiac damage staging as well as left ventricular global longitudinal strain (LVGLS) in patients undergoing transcatheter aortic valve implantation (TAVI). The aim of the present study was to evaluate the changes in cardiac damage stage and LVGLS after TAVI and to investigate their prognostic values when integrated into the follow-up assessment. Methods: Patients with severe aortic stenosis undergoing TAVI were hierarchically classified into cardiac damage stages based on echocardiographic criteria before TAVI and at a 6-month follow-up. At the same time, LVGLS was measured. The staging system included stage 0 = no signs of cardiac damage; stage 1 = LV damage; stage 2 = mitral or left atrial damage; stage 3 = pulmonary vasculature or tricuspid damage; and stage 4 = right ventricular damage. The primary endpoint was all-cause mortality. Results: A total of 620 patients were included. At follow-up, LVGLS significantly improved, and the improvement was similar among each baseline cardiac damage stage. Follow-up LVGLS values were divided into quintiles, and each quintile was integrated into the cardiac damage staging, leading to a reclassification of 308 (50%) patients. At the time of a median follow-up at 48 (IQR 31-71) months starting from the 6-month follow-up after TAVI, 262 (38%) patients had died. A multivariable Cox regression model showed that LVGLS-integrated cardiac damage staging at follow-up had an incremental prognostic value over the baseline assessment (HR per 1-stage increase 1.384; 95% CI 1.152-1.663; p < 0.001). Conclusions: The integration of LVGLS with conventional echocardiographic parameters of cardiac damage at a 6-month follow-up after TAVI can improve patient risk-stratification.

Prognostic Implications and Alterations in Left Atrial Deformation Following Transcatheter Aortic Valve Implantation.

AIMS: To evaluate the prognostic implications of left atrial reservoir strain-defined diastolic dysfunction (LARS-DD) grade in patients undergoing TAVI for severe aortic stenosis (AS) and to determine if post-TAVI LARS was more closely associated with new-onset atrial fibrillation than pre-TAVI LARS. METHODS AND RESULTS: Pre-TAVI LARS-DD was evaluated by speckle-tracking echocardiography and was assigned as grade 0 to 1 (LARS≥24%), grade 2 (LARS≥19 to <24%) and grade 3 (LARS<19%). Patients were followed-up for the primary endpoint of all-cause mortality from the date of TAVI. For the secondary endpoint, patients with pre- and post-TAVI LARS measurements and no history of atrial fibrillation were evaluated for the occurrence of new-onset atrial fibrillation. A total of 601 patients (median age 81 [76-85] years, 53% male) were included. Overall, 169 patients (28%) were LARS-DD grade 0/1, 96 patients (16%) were LARS-DD grade 2 and 336 (56%) were LARS-DD grade 3. Over a median follow-up of 40 (IQR 26-58) months, a total of 258 (43%) patients died. In a comprehensive multivariable Cox regression model, LARS-DD grade was independently associated with all-cause mortality (adjusted HR 1.28 per one-grade increase, 95%CI 1.07-1.53, P=0.007). For the secondary endpoint of new-onset atrial fibrillation, a total of 285 patients were evaluated. Post-TAVI LARS (SDHR 1.14 per 1%<20%, 95%CI 1.05-1.23, P=0.0009), but not pre-TAVI LARS (P=0.93) was independently associated with new-onset atrial fibrillation. CONCLUSIONS: Increasing LARS-DD grade was independently associated with long-term post-TAVI survival in patients with severe AS. Post-TAVI LARS was closely related to the occurrence of new-onset atrial fibrillation.

Association between echocardiography-derived haemodynamic force parameters and left ventricular reverse remodelling after cardiac resynchronization therapy.

AIMS: Cardiac resynchronization therapy (CRT) may induce left ventricular (LV) reverse remodelling (=LV response) in patients with heart failure. Intraventricular pressure gradients can be quantified using echocardiography-derived haemodynamic forces (HDF). The aim was to evaluate the association between baseline HDF and LV response and to compare the change of HDF after CRT between LV responders and LV non-responders. METHODS AND RESULTS: The following HDF parameters were assessed: 1)apical-basal (AB) strength, 2)lateral-septal strength, 3)force vector angle, 4)systolic AB impulse, 5)systolic force vector angle. LV response was defined as a reduction of LV end-systolic volume ≥15% at six months. One hundred ninety-six patients were included (64±11 years, 122(62%) men), 136(69%) showed LV response. On multivariable logistic regression analysis, the force vector angle in the complete heart cycle (OR 1.083 (95%CI 1.018, 1.153), p=0.012) and the systolic force vector angle (OR 1.089 (95%CI 1.021, 1.161), p=0.009), both included in separate models, were independently associated with LV response. Six months after CRT, LV responders had greater AB strength, AB impulse and higher force vector angles, while LV non-responders only showed improvement in the force vector angle in the complete heart cycle. CONCLUSION: The orientation of HDF at baseline is associated with LV response to CRT. Six months after CRT, the orientation of HDF improves in LV responders and LV non-responders, while the magnitude of AB HDF only improves in LV responders.

Reappraisal of the Concept and Implications of Pulmonary Hypertension in Degenerative Mitral Regurgitation.

BACKGROUND: European and U.S. clinical guidelines diverge regarding pulmonary hypertension (PHTN) in degenerative mitral regurgitation (DMR). Gaps in knowledge underpinning these divergences affect risk assessment and management recommendations attached to systolic pulmonary pressure (SPAP) in DMR. OBJECTIVES: This study sought to define PHTN links to DMR severity, prognostic thresholds, and independent outcome impact in a large quantitative DMR registry. METHODS: This study gathered a large multicentric registry of consecutive patients with isolated moderate-to-severe DMR, with DMR and SPAP quantified prospectively at diagnosis. RESULTS: In 3,712 patients (age 67 ± 15 years, 36% women) with ≥ moderate-to-severe DMR, effective regurgitant orifice (ERO) was 0.42 ± 0.19 cm2, regurgitant volume 66 ± 327 mL/beat and SPAP 41 ± 16 mm Hg. Spline-curve analysis showed excess mortality under medical management emerging around SPAP 35 mm Hg and doubling around SPAP 50 mm Hg. Accordingly, severe pulmonary hypertension (sPHTN) (SPAP ≥50 mm Hg) was detected in 916 patients, moderate pulmonary hypertension (mPHTN) (SPAP 35-49 mm Hg) in 1,128, and no-PHTN (SPAP <35 mm Hg) in 1,668. Whereas SPAP was strongly associated with DMR-ERO, nevertheless excess mortality with sPHTN (adjusted HR: 1.65; 95% CI: 1.24-2.20) and mPHTN (adjusted HR: 1.44; 95% CI: 1.11-1.85; both P ≤ 0.005) was observed independently of ERO and all baseline characteristics and in all patient subsets. Nested models demonstrated incremental prognostic value of mPHTN and sPHTN (all P < 0.0001). Despite higher operative risk with mPHTN and sPHTN, DMR surgical correction was followed by higher survival in all PHTN ranges with strong survival benefit of early surgery (<3 months). Postoperatively, excess mortality was abolished (P ≥ 0.30) in mPHTN, but only abated in sPHTN. CONCLUSIONS: This large international registry, with prospectively quantified DMR and SPAP, demonstrates a Doppler-defined PHTN impact on mortality, independent of DMR severity. Crucially, it defines objectively the new and frequent mPHTN range, independently linked to excess mortality under medical management, which is abolished by DMR correction. Thus, at DMR diagnosis, Doppler-SPAP measurement defining these new PHTN ranges, is crucial to guiding DMR management.

Cardiac Damage Staging Predicts Outcomes in Aortic Valve Stenosis After Aortic Valve Replacement: Meta-Analysis.

Background: The prognostic value of cardiac damage staging classification based on the extent of extravalvular damage has been proposed in moderate/severe aortic stenosis (AS). Objectives: The purpose of this study was to assess the association of cardiac damage staging with mortality across the spectrum of patients with AS following aortic surgical or transcatheter aortic valve replacement (AVR). Methods: We conducted a pooled meta-analysis of Kaplan-Meier-derived reconstructed time-to-event data from studies published through February 2023. Results: In total, 16 studies (n = 14,499) met our eligibility criteria and included 12,282 patients with symptomatic severe AS and 2,217 patients with asymptomatic severe/moderate AS. For patients with symptomatic severe AS, all-cause mortality was 24.0%, 27.7%, 38.0%, 56.3%, and 57.3% at 5 years in patients with cardiac damage stage 0, 1, 2, 3, and 4, respectively (stage 0 as reference; HR in stage 1: 1.30 [95% CI: 1.03-1.64]; P = 0.029; stage 2: 1.74 [95% CI: 1.41-2.16]; P < 0.001; stage 3: 2.92 [95% CI: 2.35-3.64]; P < 0.001, and stage 4: 3.51 [95% CI: 2.79-4.41]; P < 0.001). For patients with asymptomatic moderate/severe AS, all-cause mortality was 19.3%, 36.9%, 51.7%, and 67.8% at 8 years in patients with cardiac damage stage 0, 1, 2, and 3 to 4, respectively (HR in stage 1: 1.70 [95% CI: 1.21-2.38]; P = 0.002; stage 2: 2.20 [95% CI: 1.60-3.02]; P < 0.001; and stage 3 to 4: 3.90 [95% CI: 2.79-5.47]; P < 0.001). Conclusions: In patients undergoing AVR across the symptomatic and severity spectrum of AS, cardiac damage staging at baseline has important prognostic implications. This pooled meta-analysis in patients undergoing AVR suggests that staging of baseline cardiac damage could be considered for timing and selection of therapy in patients with moderate or severe AS to determine the need for earlier AVR or adjunctive pharmacotherapy to prevent irreversible cardiac damage and improve the long-term prognosis.

Resumen: Consenso internacional para la nomenclatura y clasificación de la válvula aórtica bicúspide congénita y su aortopatía, con fines clínicos, quirúrgicos, intervencionistas y de investigación / Summary: International consensus statement on nomenclature and classification of the congenital bicuspid aortic valve and its aortopathy, for clinical, surgical, interventional and research purposes

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Abstract This consensus of nomenclature and classification for congenital bicuspid aortic valve and its aortopathy is evidence-based and intended for universal use by physicians (both pediatricians and adults), echocardiographers, advanced cardiovascular imaging specialists, interventional cardiologists, cardiovascular surgeons, pathologists, geneticists, and researchers spanning these areas of clinical and basic research. In addition, as long as new key and reference research is available, this international consensus may be subject to change based on evidence-based data1.

Cardiac amyloidosis is not a single disease: a multiparametric comparison between the light chain and transthyretin forms.

AIMS: Systemic amyloidosis represents a heterogeneous group of diseases resulting from amyloid fibre deposition. The purpose of this study is to establish a differential diagnosis algorithm targeted towards the two most frequent subtypes of CA. METHODS AND RESULTS: We prospectively included all consecutive patients with ATTR and AL evaluated between 2018 and 2022 in two centres in a score derivation cohort and a different validation sample. All patients had a complete clinical, biomarker, electrocardiographic, and imaging evaluation. Confirmation of the final diagnosis with amyloid typing was performed according to the current international recommendations. The study population included 81 patients divided into two groups: ATTR (group 1, n = 32: 28 variant and 4 wild type) and AL (group 2, n = 49). ATTR patients were younger (50.7 ± 13.9 vs. 60.2 ± 7.3 years, P = 0.0001), and significantly different in terms of NT-proBNP [ATTR: 1472.5 ng/L (97-4218.5) vs. AL 8024 ng/L (3058-14 069) P = 0.001], hs-cTn I [ATTR: 10 ng/L (4-20) vs. AL 78 ng/L (32-240), P = 0.0002], GFR [ATTR 95.4 mL/min (73.8-105.3) vs. AL: 68.4 mL/min (47.8-87.4) P = 0.003]. At similar left ventricular (LV) wall thickness and ejection fraction, the ATTR group had less frequently pericardial effusion (ATTR: 15% vs. AL: 33% P = 0.0027), better LV global longitudinal strain (ATTR: -13.1% ± 3.5 vs. AL: -9.1% ± 4.3 P = 0.04), RV strain (ATTR: -21.9% ± 6.2 vs. AL: -16.8% ± 6 P = 0.03) and better reservoir function of the LA strain (ATTR: 22% ± 12 vs. AL: 13.6% ± 7.8 P = 0.02). Cut-off points were calculated based on the Youden method. We attributed to 2 points for parameters having an AUC > 0.75 (NT-proBNP AUC 0.799; hs-cTnI AUC 0.87) and 1 point for GFR (AUC 0.749) and TTE parameters (GLS AUC 0.666; RV FWS AUC 0.649, LASr AUC 0.643). A score of equal or more than 4 points has been able to differentiate between AL and ATTR (sensitivity 80%, specificity 62%, AUC = 0.798). The differential diagnosis score system was applied to the validation cohort of 52 CA patients showing a sensitivity of 81% with specificity of 77%. CONCLUSIONS: CA is a complex entity and requires extensive testing for a positive diagnosis. This study highlights a series of non-invasive checkpoints, which can be useful in guiding the decision-making process towards a more accurate and rapid differential diagnosis.

In vivo fluid dynamics of the Ventura interatrial shunt device in patients with heart failure.

AIMS: Interatrial shunts are under evaluation as a treatment for heart failure (HF); however, their in vivo flow performance has not been quantitatively studied. We aimed to investigate the fluid dynamics properties of the 0.51 cm orifice diameter Ventura shunt and assess its lumen integrity with serial transesophageal echocardiography (TEE). METHODS AND RESULTS: Computational fluid dynamics (CFD) and bench flow tests were used to establish the flow-pressure relationship of the shunt. Open-label patients from the RELIEVE-HF trial underwent TEE at shunt implant and at 6 and 12 month follow-up. Shunt effective diameter (Deff) was derived from the vena contracta, and flow was determined by the continuity equation. CFD and bench studies independently validated that the shunt's discharge coefficient was 0.88 to 0.89. The device was successfully implanted in all 97 enrolled patients; mean age was 70 ± 11 years, 97% were NYHA class III, and 51% had LVEF ≤40%. Patency was confirmed in all instances, except for one stenotic shunt at 6 months. Deff remained unchanged from baseline at 12 months (0.47 ± 0.01 cm, P = 0.376), as did the trans-shunt mean pressure gradient (5.1 ± 3.9 mmHg, P = 0.316) and flow (1137 ± 463 mL/min, P = 0.384). TEE measured flow versus pressure closely correlated (R2 ≥ 0.98) with a fluid dynamics model. At 12 months, the pulmonary/systemic flow Qp/Qs ratio was 1.22 ± 0.12. CONCLUSIONS: When implanted in patients with advanced HF, this small interatrial shunt demonstrated predictable and durable patency and performance.

Left Atrial Improvement in Patients With Secondary Mitral Regurgitation and Heart Failure: The COAPT Trial.

BACKGROUND: Functional mitral regurgitation induces adverse effects on the left ventricle and the left atrium. Left atrial (LA) dilatation and reduced LA strain are associated with poor outcomes in heart failure (HF). Transcatheter edge-to-edge repair (TEER) of the mitral valve reduces heart failure hospitalization (HFH) and all-cause death in selected HF patients. OBJECTIVES: The aim of this study was to evaluate the impact of LA strain improvement 6 months after TEER on the outcomes of patients enrolled in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial. METHODS: The difference in LA strain between baseline and the 6-month follow-up was calculated. Patients with at least a 15% improvement in LA strain were labeled as "LA strain improvers." All-cause death and HFH were assessed between the 6- and 24-month follow-up. RESULTS: Among 347 patients (mean age 71 ± 12 years, 63% male), 106 (30.5%) showed improvement of LA strain at the 6-month follow-up (64 [60.4%] from the TEER + guideline-directed medical therapy [GDMT] group and 42 [39.6%] from the GDMT alone group). An improvement in LA strain was significantly associated with a reduction in the composite of death or HFH between the 6-month and 24-month follow-up, with a similar risk reduction in both treatment arms (Pinteraction = 0.27). In multivariable analyses, LA strain improvement remained independently associated with a lower risk of the primary composite endpoint both as a continuous variable (adjusted HR: 0.94 [95% CI: 0.89-1.00]; P = 0.03) and as a dichotomous variable (adjusted HR: 0.49 [95% CI: 0.27-0.89]; P = 0.02). The best outcomes were observed in patients treated with TEER in whom LA strain improved. CONCLUSIONS: In symptomatic HF patients with severe mitral regurgitation, improved LA strain at the 6-month follow-up is associated with subsequently lower rates of the composite endpoint of all-cause mortality or HFH, both after TEER and GDMT alone. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [COAPT]; NCT01626079).

Diagnostic Value of Aortic Valve Calcification Levels in the Assessment of Low-Gradient Aortic Stenosis.

BACKGROUND: In patients with low-gradient aortic stenosis (AS) and low transvalvular flow, dobutamine stress echocardiography (DSE) is recommended to determine AS severity, whereas the degree of aortic valve calcification (AVC) supposedly correlates with AS severity according to current European and American guidelines. OBJECTIVES: The purpose of this study was to assess the relationship between AVC and AS severity as determined using echocardiography and DSE in patients with aortic valve area <1 cm2 and peak aortic valve velocity <4.0 m/s. METHODS: All patients underwent DSE to determine AS severity and multislice computed tomography to quantify AVC. Receiver-operating characteristics curve analysis was used to assess the diagnostic value of AVC for AS severity grading as determined using echocardiography and DSE in men and women. RESULTS: A total of 214 patients were included. Median age was 78 years (25th-75th percentile: 71-84 years) and 25% were women. Left ventricular ejection fraction was reduced (<50%) in 197 (92.1%) patients. Severe AS was diagnosed in 106 patients (49.5%). Moderate AS was diagnosed in 108 patients (50.5%; in 77 based on resting transthoracic echocardiography, in 31 confirmed using DSE). AVC score was high (≥2,000 for men or ≥1,200 for women) in 47 (44.3%) patients with severe AS and in 47 (43.5%) patients with moderate AS. AVC sensitivity was 44.3%, specificity was 56.5%, and positive and negative predictive values for severe AS were 50.0% and 50.8%, respectively. Area under the receiver-operating characteristics curve was 0.508 for men and 0.524 for women. CONCLUSIONS: Multi-slice computed tomography-derived AVC scores showed poor discrimination between grades of AS severity using DSE and cannot replace DSE in the diagnostic work-up of low-gradient severe AS.