Clinical and echocardiographic parameters associated with outcomes in patients with moderate secondary mitral regurgitation.

BACKGROUND: Significant secondary mitral regurgitation (SMR) is known to be associated with worse prognosis. However, data focusing specifically on moderate SMR and associated risk factors are lacking. In the present study, clinical and echocardiographic parameters associated with outcomes were evaluated in a large cohort of patients with moderate SMR. METHODS: Patients with moderate SMR were retrospectively included and stratified by New York Heart Association (NYHA) class and specific aetiology (atrial SMR (aSMR) or ventricular SMR (vSMR)) with a further classification of vSMR based on left ventricular ejection fraction (LVEF) ≥40% or <40%. The primary endpoint was all-cause mortality and the secondary endpoint was the composite of all-cause mortality and heart failure (HF) events. RESULTS: Of the total 1061 patients with moderate SMR (age 69±11 years, 59% male) included, 854 (80%) were in NYHA class I-II and 207 (20%) were in NYHA class III-IV. Regarding the aetiology, 352 (33%) had aSMR and 709 (67%) had vSMR, of which 329 (46%) had LVEF ≥40% and 380 (54%) had LVEF <40%. During a median follow-up of 82 (IQR 55-115) months, 397 (37%) died and 539 (51%) patients had HF events or died. On multivariable analysis, NYHA class III-IV (HR 1.578; 95% CI 1.244 to 2.002, p<0.001) and SMR aetiology were independently associated with both endpoints. Specifically, compared to aSMR, vSMR with LVEF ≥40% had a HR of 1.528 (95% CI 1.108 to 2.106, p=0.010) and vSMR with LVEF <40% had a HR of 1.960 (95% CI 1.434 to 2.679, p<0.001). To further support these findings, patients were matched for (1) NYHA class and (2) SMR aetiology by propensity scores including age, sex, diabetes, chronic obstructive pulmonary disease, renal function, left atrial volume index, NYHA class (only for SMR aetiology matching), LVEF, SMR aetiology (only for NYHA class matching), tricuspid regurgitation severity and right ventricular pulmonary artery coupling index. After matching, NYHA class and SMR aetiology remained associated with both outcomes (for both: log rank p<0.050). CONCLUSION: In patients with moderate SMR, distinction in SMR aetiology and assessment of symptoms are important independent determinants of outcome.

Association between Left Atrial Function and Survival in Systemic Sclerosis.

Systemic sclerosis (SSc) is a multisystemic autoimmune disorder in which cardiac involvement is frequent and portends negative prognosis. Left ventricular (LV) diastolic dysfunction is one of the most common cardiac alterations in these patients, and left atrial (LA) reservoir strain (ƐR) measurement using speckle tracking echocardiography has been proposed as a novel parameter for a better assessment of LV diastolic function. Therefore, the aim of this study was to test the prognostic value of ƐR in a large multicenter cohort of SSc patients. In total, 311 SSc patients (54 ± 14 years, 85% female) were included from two different centers. Echocardiography was performed at the time of first visit, including ƐR measurement. Over a median follow-up of 132 (interquartile range: 110 to 157) months, 67 (21.5%) patients experienced the outcome of all-cause mortality. Spline curve analysis identified an optimal cut-off value of 30% for ƐR, and patients with ƐR ≤ 30% showed a 10-year cumulative survival rate of 71% as compared to 88% for patients with ƐR > 30% (log-rank p < 0.001). At the multivariable Cox regression analysis, ƐR was independently associated with the endpoint (HR 1.830; 95% confidence interval (CI) 1.031-3.246; p = 0.039) together with age (HR 1.071, 95% CI 1.043 to 1.099; p < 0.001), sex (female) (HR 0.444, 95% CI 0.229 to 0.861; p = 0.016), and diffusing lung capacity for carbon monoxide (HR 0.969 95% CI 0.956 to 0.982; p < 0.001). ƐR is of independent prognostic value in SSc and might help optimizing risk stratification in these patients.

Evolution and Prognostic Impact of Left Ventricular Myocardial Work Indices After Transcatheter Aortic Valve Replacement in Patients With Severe Aortic Stenosis.

PURPOSE: Left ventricular myocardial work (LVMW) has been shown to better characterize LV function in patients with severe aortic stenosis by correcting LV afterload. The aim of this study was to evaluate the evolution in LVMW indices after transcatheter aortic valve replacement (TAVR) and their prognostic value. METHODS: The following LVMW indices were calculated before and immediately after TAVR in 255 patients (median age 82 years, 51% male): global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE). The study endpoint was all-cause mortality. RESULTS: After TAVR, LV ejection fraction and LV global longitudinal strain (GLS) did not change significantly (from 56% to 55%, p = 0.470 and from 13.6% to 13.2%, p = 0.068). Concerning LVMW indices, while LV GWW remained unchanged after TAVR (from 247 to 258 mmHg%, p = 0.080), LV GWI, LV GCW, and LV GWE significantly decreased (from 1882 to 1291 mmHg%, p < 0.001, from 2248 to 1671 mmHg%, p < 0.001, and from 89% to 85%, p < 0.001, respectively). During a median follow-up of 59 [40-72] months, 129 patients died. After correcting for potential confounders (sex, diabetes, renal function, atrial fibrillation, Charlson comorbidity index, and pacemaker implantation post-TAVR), post-TAVR LV GLS, GWI, and GCW remained independently associated with all-cause mortality. However, post-TAVR LV GWI demonstrated the highest increase in model predictivity. CONCLUSION: In patients undergoing TAVR, LVMW parameters significantly change after intervention. LV GWI after TAVR showed the strongest association with all-cause mortality among both conventional and advanced parameters of LV systolic function both pre- and post-TAVR and might enable better risk stratification of these patients after intervention.

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.

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.

Cardiovascular toxicities of immune therapies for cancer - a scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Council of Cardio-Oncology.

The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors (ICIs). The second class are cell-based immune therapies including chimeric antigen receptor T lymphocyte (CAR-T) cell therapies, natural killer (NK) cell therapies, and tumour infiltrating lymphocyte (TIL) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune-related adverse events (irAEs), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune-related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI-related myocarditis with cardiogenic shock to more common complications including less severe ICI-related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non-inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI, CAR-T, NK, and TIL therapies. We also highlight gaps in the literature and where future research should focus.

The prognostic value of changes in pulmonary vein flow patterns after surgical repair for primary mitral regurgitation.

BACKGROUND: The pulmonary vein (PV) flow pattern is influenced by the presence of mitral regurgitation (MR). After a successful reduction in MR severity, the pattern is expected to be changed. We aimed to evaluate the prognostic value of a change in the PV flow pattern in patients with primary MR undergoing mitral valve repair (MVR). METHODS: The PV flow pattern was assessed with transthoracic echocardiography in 216 patients (age 65 [IQR 56-72] years, 70% male) with primary MR before and after surgical MVR. The population was divided according to a change in the PV flow pattern following MVR into 'improvers' and 'non-improvers'. RESULTS: Non-improvers (15%) had a higher prevalence of paroxysmal AF at baseline (46% vs. 22%, p = 0.004), left ventricular dysfunction (LVEF ≤60%) (39% vs. 21%, p = 0.020), and had lower systolic pulmonary artery pressure (28[IQR 25-38] vs. 35[IQR 26-48] mmHg, p = 0.018) compared to improvers (85%). After a median follow-up of 83[IQR 43-140] months, 26(12%) patients died. Non-improvers had higher mortality rates than improvers (p = 0.009). On multivariable Cox regression analysis, a lack of improvement in the PV flow pattern remained independently associated with all-cause mortality (HR 2.322, 95% CI 1.140 to 4.729, P = 0.020). CONCLUSION: A lack of improvement in the PV flow pattern is independently associated with worse long-term survival in patients with primary MR undergoing MVR.

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.

Sex-related differences in severe native valvular heart disease: the ESC-EORP Valvular Heart Disease II survey.

BACKGROUND AND AIMS: To assess sex differences in disease characteristics and treatment of patients with severe native valvular heart disease (VHD) included in the VHD II EURObservational Research Programme. METHODS: A total of 5219 patients were enrolled in 208 European and North African centres and followed for 6 months [41.2% aortic stenosis (AS), 5.3% aortic regurgitation (AR), 4.5% mitral stenosis (MS), 21.3% mitral regurgitation (MR), 2.7% isolated right-sided VHD, 24.9% multiple left-sided VHD]. Indications for intervention were considered concordant if corresponding to class I recommendations specified in the 2012 ESC or 2014 AHA/ACC VHD guidelines. RESULTS: Overall, women were older, more symptomatic, and presented with a higher EuroSCORE II. Bicuspid aortic valve and AR were more prevalent among men while mitral disease, concomitant tricuspid regurgitation (TR), and AS above age 65 were more prevalent among women. On multivariable regression analysis, concordance with recommended treatment was significantly poorer in women with MS and primary MR (both P < .001). Age, patient refusal, and decline of symptoms after conservative treatment were reported significantly more often as reasons to withhold the intervention in females. Concomitant tricuspid intervention was performed at a similar rate in both sexes although prevalence of significant TR was significantly higher in women. In-hospital and 6-month survival did not differ between sexes. CONCLUSIONS: (i) Valvular heart disease subtype varied between sexes; (ii) concordance with recommended intervention for MS and primary MR was significantly lower for women; and (iii) survival of men and women was similar at 6 months.

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.

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.

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.

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.

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.

Left Atrioventricular Coupling Index: A Novel Diastolic Parameter to Refine Prognosis in Heart Failure.

BACKGROUND: Left atrioventricular coupling index (LACI), an index coupling left atrial to left ventricular (LV) volume at end-diastole, has been shown to be associated with prognosis in different clinical settings. However, the relation between LACI and LV diastolic dysfunction (DD) remains to be established. The aims of the present study were to investigate the association between LACI and LV DD and to assess its prognostic value in patients with heart failure (HF). METHODS: A total of 1,158 patients with HF in stable condition, on optimal medical therapy, were retrospectively analyzed (derivation cohort). Clinical and echocardiographic features were characterized across LACI tertiles. The independent prognostic value of LACI (end point: all-cause death or HF hospitalization) was assessed using Cox regression. Results were validated in an external cohort of 242 patients with HF. RESULTS: In the derivation cohort, the median LACI value was 0.29 (interquartile range, 0.19-0.42). Patients in the third tertile (LACI > 0.36) were older and presented with more advanced HF symptoms. Although the prevalence of grade 1 DD (American Society of Echocardiography/European Association of Cardiovascular Imaging classification) progressively decreased across LACI tertiles, the prevalence of grade 3 DD significantly increased (8%, 23%, and 46%, respectively; P < .0001). A cutoff value of ≥0.26 identified moderate to severe DD with an area under the curve of 0.75. During follow-up (median, 28 months; interquartile range, 11-53 months), 407 patients (35%) reached the end point. On multivariable analysis, LACI was independently associated with outcomes (hazard ratio for a 1-SD increase, 1.16; 95% CI, 1.06-1.28; P = .002), showing incremental predictive value over the DD grading system (net reclassification improvement = 0.150, P < .0001). The prognostic value of LACI was consistent in the external validation cohort. CONCLUSIONS: LACI is associated with DD severity and is an independent predictor of outcomes in patients with HF.

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.