Incremental Value of Biventricular Strain in Patients with Severe Aortic Stenosis.

(1) Background: Left ventricular global longitudinal (LVGLS) and right ventricular free wall strain (RVFWS) demonstrated separate prognostic values in patients with severe aortic stenosis (AS). However, studies evaluating the combined assessment of LVGLS and RVFWS have shown contradictory results. This study explored the prognostic value of combining LVGLS and RVFWS in a large group of severe AS patients referred for transcatheter aortic valve implantation. (2) Methods: Patients were classified into three groups: preserved (LVGLS ≥ 15% AND RVFWS > 20%), single-ventricle impaired (LVGLS < 15% OR RVFWS ≤ 20%), or biventricular-impaired strain group (LVGLS < 15% AND RVFWS ≤ 20%). The cut-off values were based on previously published data and spline analyses. The endpoint was all-cause mortality. (3) Results: Of the 712 patients included (age 80 ± 7 years, 53% men), 248 (35%) died. The single-ventricle impaired and biventricular-impaired (vs. preserved) strain groups showed significantly lower 5-year survival rates (68% and 55% vs. 77%, respectively, p < 0.001). Through multivariable analysis, single-ventricle impaired (HR 1.762; 95% CI: 1.114-2.788; p = 0.015) and biventricular-impaired strain groups (HR 1.920; 95% CI: 1.134-3.250; p = 0.015) were independently associated with all-cause mortality. These findings were confirmed with a sensitivity analysis in patients with preserved LV ejection fraction. (4) Conclusions: In patients with severe AS, biventricular strain allows better risk stratification, even if LV ejection fraction is preserved.

Association of right atrial strain and long-term outcome in severe secondary tricuspid regurgitation.

OBJECTIVE: Severe secondary tricuspid regurgitation (STR) causes significant right atrial (RA) volume overload, resulting in structural and functional RA-remodelling. This study evaluated whether patients with severe STR and reduced RA function, as assessed by RA-reservoir-strain (RASr), show lower long-term prognosis. METHODS: Consecutive patients, from a single centre, with first diagnosis of severe STR and RASr measure available, were included. Extensive echocardiographic analysis comprised measures of cardiac chamber size and function, assessed also by two-dimensional speckle-tracking strain analysis. Primary outcome was all-cause mortality, analysed from inclusion until death or last follow-up. The association of RASr with the outcome was evaluated by Cox regression analysis and Akaike information criterion. RESULTS: A total of 586 patients with severe STR (age 68±13 years; 52% male) were included. Patients presented with mild right ventricular (RV) dilatation (end-diastolic area 13.8±6.5 cm2/m2) and dysfunction (free-wall strain 16.2±7.2%), and with moderate-to-severe RA dilatation (max area 15.0±5.3 cm2/m2); the median value of RASr was 13%. In the overall population, 10-year overall survival was low (40%, 349 deaths), and was significantly lower in patients with lower RASr (defined by the median value): 36% (195 deaths) for RASr ≤13% compared with 45% (154 deaths) for RASr >13% (log-rank p=0.016). With a median follow-up of 6.6 years, RASr was independently associated with all-cause mortality (HR per 5% RASr increase:0.928; 95% CI 0.864 to 0.996; p=0.038), providing additional value over relevant clinical and echocardiographic covariates (including RA size and RV function/size). CONCLUSIONS: Patients with severe STR presented with significant RA remodelling, and lower RA function, as measured by RASr, was independently associated with all-cause mortality, potentially improving risk stratification in these patients.

Hemodynamic implications of mitral annular calcification in patients undergoing transcatheter aortic valve implantation for severe aortic stenosis.

PURPOSES: Predicting hemodynamic changes of stenotic mitral valve (MV) lesions with mitral annular calcification (MAC) following transcatheter aortic valve implantation (TAVI) may inform clinical decision-making. This study aimed to investigate the association between the MAC severity quantified by computed tomography (CT) and changes in mean transmitral gradient (mTMG), mitral valve area (MVA) and stroke volume index (SVi) following TAVI. METHODS AND RESULTS: A total of 708 patients (median age 81, 52% male) with severe aortic stenosis (AS) underwent pre-procedural CT and pre- and post-TAVI transthoracic echocardiography. According to the classification of MAC severity determined by CT, 299 (42.2%) patients had no MAC, 229 (32.3%) mild MAC, 102 (14.4%) moderate MAC, and 78 (11.0%) severe MAC. After adjusting for age and sex, there was no significant change in mTMG following TAVI (Δ mTMG = 0.07 mmHg, 95% CI -0.10 to 0.23, P = 0.92) for patients with no MAC. In contrast, patients with mild MAC (Δ mTMG = 0.21 mmHg, 95% CI 0.01 to 0.40, P = 0.018), moderate MAC (Δ mTMG = 0.31 mmHg, 95% CI 0.02 to 0.60, P = 0.019) and severe MAC (Δ mTMG = 0.43 mmHg, 95% CI 0.10 to 0.76, P = 0.0012) had significant increases in mTMG following TAVI, with greater changes associated with increasing MAC severity. In contrast, there was no significant change in MVA or SVi following TAVI. CONCLUSION: In patients with severe AS undergoing TAVI, MAC severity was associated with greater increases in post-procedural mTMG whereas MVA or SVi remained unchanged. MAC severity should be considered for potential subsequent MV interventions if TAVI does not improve symptoms.

Prognostic value of left ventricular myocardial work indices in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

AIMS: Left ventricular myocardial work (LVMW) is a novel echocardiographic-based method to assess left ventricular (LV) function using pressure-strain loops taking into account LV afterload. The aim of this study was to evaluate the prognostic value of LVMW indices in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: LV global work index (LV GWI), LV global constructive work (LV GCW), LV global wasted work (LV GWW), and LV global work efficiency (LV GWE) were calculated in 281 patients with severe AS [age 82, interquartile range (IQR) 78-85 years, 52% male] before the TAVR procedure. LV systolic pressure was derived non-invasively by adding the mean aortic gradient to the brachial systolic pressure to adjust for afterload and calculate LVMW indices. Overall, the average LV GWI was 1872 ± 753 mmHg%, GCW 2240 ± 797 mmHg%, GWW 200 (IQR 127-306) mmHg%, and GWE 89 (IQR 84-93)%. During a median follow-up of 52 (IQR 41-67) months, 64 patients died. While LV GWI was independently associated with all-cause mortality (Hazard ratio per-tertile-increase 0.639; 95%CI 0.463-0.883; P = 0.007), LV GCW, GWW, and GWE were not. When added to a basal model, LV GWI yielded a higher increase in predictivity compared to the left ventricular ejection fraction as well as LV global longitudinal strain and LV GCW, and also across the different haemodynamic categories (including low-flow low-gradient) of AS. CONCLUSION: LV GWI is independently associated with all-cause mortality in patients undergoing TAVR and has a higher prognostic value compared to both conventional and advanced parameters of LV systolic function.

Evolution and Prognostic Impact of Right Ventricular-Pulmonary Artery Coupling After Transcatheter Aortic Valve Replacement.

BACKGROUND: There is limited evidence regarding the association between right ventricular-to-pulmonary artery (RV-PA) coupling and outcomes after transcatheter aortic valve replacement (TAVR). OBJECTIVES: This study aimed to explore the evolution of RV-PA coupling in patients with severe aortic stenosis undergoing TAVR and its prognostic impact. METHODS: A total of 900 patients who underwent TAVR in 2 tertiary centers and with echocardiographic analysis performed within 3 months before and after the procedure were included. RV-PA coupling was measured as the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP). RV-PA uncoupling was defined by TAPSE/PASP <0.55, whereas a TAPSE/PASP <0.32 identified a severe uncoupling. The primary endpoint was all-cause mortality. RESULTS: A total of 520 patients (58%) showed RV-PA uncoupling before TAVR, whereas post-TAVR RV-PA uncoupling was observed in 407 patients (45%). During a median follow-up of 40 months, 250 deaths (28%) occurred. Post-TAVR RV-PA uncoupling was independently associated with an increased risk of mortality (adjusted HR: 1.474; 95% CI: 1.115-1.948; P = 0.006), whereas pre-TAVR uncoupling did not. Among patients with post-TAVR RV-PA uncoupling, the presence of severe uncoupling identified a subgroup with the worst survival (P = 0.008). Patients with RV-PA coupling recovery after TAVR showed similar outcomes as compared with patients with normal coupling. Conversely, the presence of either persistent or new-onset RV-PA uncoupling following TAVR was associated with an increased mortality risk. CONCLUSIONS: Post-TAVR RV-PA uncoupling is an independent predictor of long-term mortality, irrespective of coupling before intervention. Assessment of TAPSE/PASP response after TAVR may be helpful to improve risk stratification.

The Prognostic Value of Pulmonary Venous Flow Reversal in Patients with Significant Degenerative Mitral Regurgitation.

Background: The prognostic significance of pulmonary venous (PV) flow reversal in degenerative mitral regurgitation (dMR) is not well-established. Objective: We aimed to assess whether reversed PV flow is associated with adverse outcomes in patients with significant dMR. Methods: We retrospectively analyzed consecutive patients referred to a tertiary center for evaluation of dMR of greater than moderate degree, who had normal sinus rhythm, had a left ventricular ejection fraction of above 60%, and did not suffer from any other major valvular disorders. The primary outcome was the combined rate of all-cause mortality, mitral intervention, or new-onset atrial fibrillation (AF) at 5 years following index echocardiogram. Secondary outcomes included individual components of the primary outcome. Results: Overall, 135 patients (median age 68 (IQR, 58-74) years; 93 (68.9%) males; 89 (65.9%) with severe MR) met the inclusion criteria and were followed for 115.2 (IQR, 60.0-155.0) months. Patients with a reversed PV flow pattern (PVFP) (n = 34) more often presented with severe MR compared to those with a normal (n = 49) and non-reversed PVFP (n = 101) (RR = 2.03 and 1.59, respectively, all p < 0.001). At 5 years, they experienced the highest cumulative incidence of the primary outcome (80.2% vs. 59.2% and 67.3%, p = 0.008 and 0.018, respectively). Furthermore, a reversed PVFP was independently associated with a higher risk of the primary outcome compared to normal PVFP (HR 2.53, 95% CI 1.21-5.31, p = 0.011) and non-reversed PVFP (HR 2.14, 95% CI 1.12-4.10, p = 0.022). Conclusion: PV flow reversal is associated with a worse 5-year composite of mortality, mitral intervention, or AF in patients with significant dMR.

The impact of atrial fibrillation on prognosis in aortic stenosis.

BACKGROUND: Atrial fibrillation (AF) and aortic stenosis (AS) are both highly prevalent and often coexist. Various studies have focused on the prognostic value of AF in patients with AS, but rarely considered left ventricular (LV) diastolic function as a prognostic factor. OBJECTIVE: To evaluate the prognostic impact of AF in patients with AS while correcting for LV diastolic function. METHODS: Patients with first diagnosis of significant AS were selected and stratified according to history of AF. The endpoint was all-cause mortality. RESULTS: In total, 2849 patients with significant AS (mean age 72 ± 12 years, 54.8% men) were evaluated, and 686 (24.1%) had a history of AF. During a median follow-up of 60 (30-97) months, 1182 (41.5%) patients died. Ten-year mortality rate in patients with AF was 46.8% compared to 36.8% in patients with sinus rhythm (SR) (log-rank P < 0.001). On univariable (HR: 1.42; 95% CI: 1.25-1.62; P < 0.001) and multivariable Cox regression analysis (HR: 1.19; 95% CI: 1.02-1.38; P = 0.026), AF was independently associated with mortality. However, when correcting for indexed left atrial volume, E/e' or both, AF was no longer independently associated with all-cause mortality. CONCLUSION: Patients with significant AS and AF have a reduced survival as compared to patients with SR. Nonetheless, when correcting for markers of LV diastolic function, AF was not independently associated with outcomes in patients with significant AS.

Factors influencing post-surgical survival in degenerative mitral regurgitation.

AIMS: Indications for surgery in patients with degenerative mitral regurgitation (DMR) are increasingly liberal in all clinical guidelines but the role of secondary outcome determinants (left atrial volume index ≥60 mL/m2, atrial fibrillation, pulmonary artery systolic pressure ≥50 mmHg and moderate to severe tricuspid regurgitation) and their impact on post-operative outcome remain disputed. Whether these secondary outcome markers are just reflective of the DMR severity or intrinsically affect survival after DMR surgery is uncertain and may have critical importance in the management of patients with DMR. To address these gaps of knowledge the present study gathered a large cohort of patients with quantified DMR, accounted for the number of secondary outcome markers and examined their independent impact on survival after surgical correction of the DMR. METHODS AND RESULTS: The Mitral Regurgitation International DAtabase-Quantitative registry includes patients with isolated DMR from centres across North America, Europe, and the Middle East. Patient enrolment extended from January 2003 to January 2020. All patients undergoing mitral valve surgery within 1 year of registry enrolment were selected. A total of 2276 patients [65 (55-73) years, 32% male] across five centres met study eligibility criteria. Over a median follow-up of 5.6 (3.6 to 8.7) years, 278 patients (12.2%) died. In a comprehensive multivariable Cox regression model adjusted for age, EuroSCORE II, symptoms, left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LV ESD) and DMR severity, the number of secondary outcome determinants was independently associated with post-operative all-cause mortality, with adjusted hazard ratios of 1.56 [95% confidence interval (CI): 1.11-2.20, P = 0.011], 1.78 (95% CI: 1.23-2.58, P = 0.002) and 2.58 (95% CI: 1.73-3.83, P < 0.0001) for patients with one, two, and three or four secondary outcome determinants, respectively. A model incorporating the number of secondary outcome determinants demonstrated a higher C-index and was significantly more concordant with post-operative mortality than models incorporating traditional Class I indications alone [the presence of symptoms (P = 0.0003), or LVEF ≤60% (P = 0.006), or LV ESD ≥40 mm (P = 0.014)], while there was no significant difference in concordance observed compared with a model that incorporated the number of Class I indications for surgery combined (P = 0.71). CONCLUSION: In this large cohort of patients treated surgically for DMR, the presence and number of secondary outcome determinants was independently associated with post-surgical survival and demonstrated better outcome discrimination than traditional Class I indications for surgery. Randomised controlled trials are needed to determine if patients with severe DMR who demonstrate a cardiac phenotype with an increasing number of secondary outcome determinants would benefit from earlier surgery.

Incremental value of left ventricular global longitudinal strain in moderate aortic stenosis and reduced left ventricular ejection fraction.

BACKGROUND: Moderate aortic stenosis (AS) often coexists with left ventricular (LV) systolic dysfunction and may affect survival through afterload mismatch. Because outcomes are ultimately driven by the condition of the LV, accurate assessment of LV performance is crucial to improve risk stratification. This study investigated the prognostic value of LV global longitudinal strain (GLS) in patients with moderate AS and reduced LV systolic dysfunction. METHODS: Patients with moderate AS (aortic valve area 1.0-1.5 cm2) and reduced LV ejection fraction (EF) (<50%) were identified. LVGLS was evaluated with speckle-tracking echocardiography. Patients were divided into 2 groups according to an LVGLS value of 11%, based on spline curve analysis. The primary endpoint was all-cause mortality. RESULTS: A total of 166 patients (mean age 73 ± 11 years, 71% male) were included. The cumulative 1- and 5-year mortality rates were higher in patients with LVGLS <11% (25% and 60%) versus LVGLS ≥11% (10% and 27%) (p < 0.001). On multivariable analysis, LVGLS as a continuous variable (HR 0.753; 95% CI 0.673-0.843; p < 0.001) and as a categorical variable (<11%) (HR 3.028; 95% CI 1.623-5.648; p < 0.001) were independently associated with outcomes, whereas LVEF was not. LVGLS provided additional prognostic information in patients with/without coronary artery disease and with mildly versus severely reduced LVEF. In addition, LVGLS had incremental prognostic value over established risk factors, including LVEF. CONCLUSION: The combination of moderate AS and reduced LV systolic dysfunction is associated with a high mortality risk. LVGLS, but not LVEF, is independently associated with mortality and provides incremental prognostic value over established risk factors in patients with moderate AS and reduced LVEF.

Incorporating coronary artery calcium scoring in the prediction of obstructive coronary artery disease with myocardial ischemia: a study with sequential use of coronary computed tomography angiography and positron emission tomography imaging.

BACKGROUND: Additional strategies are needed to refine the referral for diagnostic testing of symptomatic patients with suspected coronary artery disease (CAD). We aimed to compare various models to predict hemodynamically obstructive CAD. METHODS AND RESULTS: Symptomatic patients with suspected CAD who underwent coronary artery calcium scoring (CACS) and sequential coronary computed tomography angiography (CCTA) and [15O]H2O positron emission tomography (PET) myocardial perfusion imaging were analyzed. Obstructive CAD was defined as a suspected coronary artery stenosis on CCTA with myocardial ischemia on PET (absolute stress myocardial perfusion ≤ 2.4 mL/g/min in ≥ 1 segment). Three models were developed to predict obstructive CAD-induced myocardial ischemia using logistic regression analysis: (1) basic model: including age, sex and cardiac symptoms, (2) risk factor model: adding number of risk factors to the basic model, and (3) CACS model: adding CACS to the risk factor model. Model performance was evaluated using discriminatory ability with area under the receiver-operating characteristic curves (AUC). A total of 647 patients (mean age 62 ± 9 years, 45% men) underwent CACS and sequential CCTA and PET myocardial perfusion imaging. Obstructive CAD with myocardial ischemia on PET was present in 151 (23%) patients. CACS was independently associated with myocardial ischemia (P < .001). AUC for the discrimination of ischemia for the CACS model was superior over the basic model and risk factor model (P < .001). CONCLUSIONS: Adding CACS to the model including age, sex, cardiac symptoms and number of risk factors increases the accuracy to predict obstructive CAD with myocardial ischemia on PET in symptomatic patients with suspected CAD.

Approach to optimal assessment of right ventricular remodelling in heart transplant recipients: insights from myocardial work index, T1 mapping, and endomyocardial biopsy.

AIMS: Right ventricular (RV) dysfunction is an important cause of graft failure after heart transplantation (HTx). We sought to investigate relative merits of echocardiographic tools and cardiac magnetic resonance (CMR) with T1 mapping for the assessment of functional adaptation and remodelling of the RV in HTx recipients. METHODS AND RESULTS: Sixty-one complete data set of echocardiography, CMR, right heart catheterization, and biopsy were obtained. Myocardial work index (MWI) was quantified by integrating longitudinal strain (LS) with invasively measured pulmonary artery pressure. CMR derived RV volumes, T1 time, and extracellular volume (ECV) were quantified. Endomyocardial biopsy findings were used as the reference standard for myocardial microstructural changes. In HTx recipients who never had a previous allograft rejection, longitudinal function parameters were lower than healthy organ donors, while ejection fraction (EF) (52.0 ± 8.7%) and MWI (403.2 ± 77.2 mmHg%) were preserved. Rejection was characterized by significantly reduced LS, MWI, longer T1 time, and increased ECV that improved after recovery, whereas RV volumes and EF did not change MWI was the strongest determinant of rejection related myocardial damage (area under curve: 0.812, P < 0.0001, 95% CI: 0.69-0.94) with good specificity (77%), albeit modest sensitivity. In contrast, T1 time and ECV were sensitive (84%, both) but not specific to detect subclinical RV damage. CONCLUSION: Subclinical adaptive RV remodelling is characterized by preserved RV EF despite longitudinal function abnormalities, except for MWI. While ultrastructural damage is reflected by MWI, ECV, and T1 time, only MWI has the capability to discriminate functional adaptation from transition to subclinical structural damage.

Prevalence and Prognostic Implications of Moderate or Severe Mitral Regurgitation in Patients with Bicuspid Aortic Valve.

BACKGROUND: Significant (moderate or greater) mitral regurgitation (MR) could augment the hemodynamic effects of aortic valvular disease in patients with bicuspid aortic valve (BAV), imposing a greater hemodynamic burden on the left ventricle and atrium, possibly culminating in a faster onset of left ventricular dilation and/or symptoms. The aim of this study was to determine the prevalence and prognostic implications of significant MR in patients with BAV. METHODS: In this large, multicenter, international registry, a total of 2,932 patients (mean age, 48 ± 18 years; 71% men) with BAV were identified. All patients were evaluated for the presence of significant primary or secondary MR by transthoracic echocardiography and were followed up for the end points of all-cause mortality and event-free survival. RESULTS: Overall, 147 patients (5.0%) had significant primary (1.5%) or secondary (3.5%) MR. Significant MR was associated with all-cause mortality (hazard ratio [HR], 2.80; 95% CI, 1.91-4.11; P < .001) and reduced event-free survival (HR, 1.97; 95% CI, 1.58-2.46; P < .001) on univariable analysis. MR was not associated with all-cause mortality (adjusted HR, 1.33; 95% CI, 0.85-2.07; P = .21) or event-free survival (adjusted HR, 1.10; 95% CI, 0.85-1.42; P = .49) after multivariable adjustment. However, sensitivity analyses demonstrated that significant MR not due to aortic valve disease retained an independent association with mortality (adjusted HR, 1.81; 95% CI, 1.04-3.15; P = .037). Subgroup analyses demonstrated an independent association between significant MR and all-cause mortality for individuals with significant aortic regurgitation (HR, 2.037; 95% CI, 1.025-4.049; P = .042), although this association was not observed for subgroups with significant aortic stenosis or without significant aortic valve dysfunction. CONCLUSIONS: Significant MR is uncommon in patients with BAV. Following adjustment for important confounding variables, significant MR was not associated with adverse prognosis in this large study of patients with BAV, except for the patient subgroup with moderate to severe aortic regurgitation. In addition, significant MR not due to aortic valve disease demonstrated an independent association with all-cause mortality.

Comparative analysis of right ventricular strain in Fabry cardiomyopathy and sarcomeric hypertrophic cardiomyopathy.

AIMS: To perform a comparative analysis of right ventricle (RV) myocardial mechanics, assessed by 2D speckle-tracking echocardiography (2D-STE), between patients with Fabry disease and patients with sarcomeric disease. METHODS AND RESULTS: Patients with Fabry cardiomyopathy (FC) (n = 28) were compared with patients with sarcomeric hypertrophic cardiomyopathy (HCM), matched for degree of left ventricle hypertrophy (LVH) and demographic characteristics (n = 112). In addition, patients with Fabry disease and no LVH [phenotype-negative carriers of pathogenic α-galactosidase gene mutations (GLA LVH-)] (n = 28) were compared with age and sex-matched carriers of sarcomeric gene mutations without LVH [Phenotype-negative carriers of pathogenic sarcomeric gene mutations (Sarc LVH-)] (n = 56). Standard echocardiography and 2D-STE were performed in all participants. Despite a subtle impairment of RV global longitudinal strain (RV-GLS) was common in both groups, patients with FC showed a more prominent reduction of RV free wall longitudinal strain (RV-FWS) and lower values of difference between RV-FWS and RV-GLS (ΔRV strain), in comparison to individuals with HCM (P < 0.001 and P = 0.002, respectively). RV-FWS and ΔRV strain demonstrated an independent and additive value in discriminating FC from HCM, over the presence of symmetric LVH, systolic anterior motion of the mitral valve and RV hypertrophy. Similar results were found in GLA LVH- patients: they had worse RV-FWS and lower values of ΔRV strain as compared to Sarc LVH- patients (both P < 0.001). CONCLUSION: Patients with FC show a specific pattern of RV myocardial mechanics, characterized by a larger impairment of RV-FWS and lower ΔRV strain in comparison to patients with HCM, which may be helpful in the differential diagnosis between these two diseases.

Evaluation of left cardiac chamber function with cardiac magnetic resonance and association with outcome in patients with systemic sclerosis.

OBJECTIVE: This study aimed to determine whether lower values of feature-tracking cardiovascular magnetic resonance (CMR)-derived left atrial reservoir strain (LARS) and impaired left ventricular (LV) global longitudinal strain (GLS) were associated with the presence of symptoms and long-term prognosis in patients with SSc. METHODS: A total of 100 patients {54 [interquartile range (IQR) 46-64] years, 42% male} with SSc who underwent CMR imaging at two tertiary referral centres were included. All patients underwent analysis of LARS and LV GLS using feature-tracking on CMR and were followed-up for the occurrence of all-cause mortality. RESULTS: The median LV GLS was -21.8% and the median LARS was 36%. On multivariable logistic regression, LARS [odds ratio (OR) 0.964 per %, 95% CI 0.929, 0.998, P = 0.049] was independently associated with New York Heart Association (NYHA) class II-IV heart failure symptoms. Over a median follow-up of 37 (21-62) months, a total of 24 (24%) patients died. Univariable Cox regression analysis demonstrated that LARS [hazard ratio (HR) 0.94 per 1%, 95% CI 0.91, 0.97, P < 0.0001) and LV GLS (HR 1.10 per %, 95% CI 1.03, 1.17, P = 0.005) were associated with all-cause mortality, while LV ejection fraction was not. Likelihood ratio tests demonstrated that LARS provided incremental value over prognostically important clinical and imaging parameters, including late gadolinium enhancement. CONCLUSION: In patients with SSc, LARS was independently associated with the presence of NYHA class II-IV heart failure symptoms. Although both LARS and LV GLS were associated with all-cause mortality, only LARS provided incremental value over all evaluated variables known to be prognostically important in patients with SSc.

Importance of plaque volume and composition for the prediction of myocardial ischaemia using sequential coronary computed tomography angiography/positron emission tomography imaging.

AIMS: Coronary atherosclerosis with a large necrotic core has been postulated to reduce the vasodilatory capacity of vascular tissue. In the present analysis, we explored whether total plaque volume and necrotic core volume on coronary computed tomography angiography (CCTA) are independently associated with myocardial ischaemia on positron emission tomography (PET). METHODS AND RESULTS: From a registry of symptomatic patients with suspected coronary artery disease and clinically indicated CCTA with sequential [15O]H2O PET myocardial perfusion imaging, we quantitatively measured diameter stenosis, total and compositional plaque volumes on CCTA. Primary endpoint was myocardial ischaemia on PET, defined as an absolute stress myocardial blood flow ≤2.4 mL/g/min in ≥1 segment. Multivariable prediction models for myocardial ischaemia were consecutively created using logistic regression analysis (stenosis model: diameter stenosis ≥50%; plaque volume model: +total plaque volume; plaque composition model: +necrotic core volume). A total of 493 patients (mean age 63 ± 8 years, 54% men) underwent sequential CCTA/PET imaging. In 153 (31%) patients, myocardial ischaemia was detected on PET. Diameter stenosis ≥50% (P < 0.001) and necrotic core volume (P = 0.029) were independently associated with myocardial ischaemia, while total plaque volume showed borderline significance (P = 0.052). The plaque composition model (χ2 = 169) provided incremental value for the prediction of ischaemia when compared with the stenosis model (χ2 = 138, P < 0.001) and plaque volume model (χ2 = 164, P = 0.021). CONCLUSION: The volume of necrotic core on CCTA independently and incrementally predicts myocardial ischaemia on PET, beyond diameter stenosis alone.

Prognostic value of left atrial volume index in degenerative mitral stenosis.

PURPOSE: Degenerative mitral stenosis (DMS) is associated with a poor prognosis. Although mean transmitral gradient (TMG) has shown a good correlation with outcome, little is known about the association between other echocardiographic parameters and prognosis in patients with DMS. The current study aimed to evaluate the prognostic value of left atrial volume index (LAVI) in patients with DMS. METHODS: A total of 155 patients with DMS (72[63-80] years, 67% female) were included. The population was divided according to LAVI: normal-sized LAVI (LAVI ≤ 34 ml/m2); and enlarged LAVI (> 34 ml/m2). RESULTS: Patients with enlarged LAVI had a higher left ventricular mass index (120[96-146] vs. 91[70-112] g/m2 p < 0.001), as well as a higher prevalence of significant mitral regurgitation and severe aortic stenosis (23% vs. 10% p = 0.046 and 38% vs. 15% p=0.001, respectively) compared to patients with normal-sized LAVI. During a median follow-up of 25 months, 56 (36%) patients died. Patients with enlarged LAVI had worse prognosis compared to patients with normal-sized LAVI (p = 0.026). In multivariable Cox regression model, an enlarged LAVI was independently associated with all-cause mortality (HR 2.009, 95% CI 1.040 to 3.880, P = 0.038). CONCLUSION: An enlarged LAVI (> 34 ml/m2) is significantly associated with excess mortality in patients with DMS. After adjusting for potential confounders, an enlarged LAVI was the only parameter that remained independently associated with prognosis.

Impact of Left Ventricular Ejection Fraction on Clinical Outcomes in Bicuspid Aortic Valve Disease.

BACKGROUND: The prognostic impact of left ventricular ejection fraction (LVEF) in patients with bicuspid aortic valve (BAV) disease has not been previously studied. OBJECTIVES: The purpose of this study was to determine the prognostic impact of LVEF in BAV patients according to the type of aortic valve dysfunction. METHODS: We retrospectively analyzed the data collected in 2,672 patients included in an international registry of patients with BAV. Patients were classified according to the type of aortic valve dysfunction: isolated aortic stenosis (AS) (n = 749), isolated aortic regurgitation (AR) (n = 554), mixed aortic valve disease (MAVD) (n = 190), or no significant aortic valve dysfunction (n = 1,179; excluded from this analysis). The study population was divided according to LVEF strata to investigate its impact on clinical outcomes. RESULTS: The risk of all-cause mortality and the composite endpoint of aortic valve replacement or repair (AVR) and all-cause mortality increased when LVEF was <60% in the whole cohort as well as in the AS and AR groups, and when LVEF was <55% in MAVD group. In multivariable analysis, LVEF strata were significantly associated with increased rate of mortality (LVEF 50%-59%: HR: 1.83 [95% CI: 1.09-3.07]; P = 0.022; LVEF 30%-49%: HR: 1.97 [95% CI: 1.13-3.41]; P = 0.016; LVEF <30%: HR: 4.20 [95% CI: 2.01-8.75]; P < 0.001; vs LVEF 60%-70%, reference group). CONCLUSIONS: In BAV patients, the risk of adverse clinical outcomes increases significantly when the LVEF is <60%. These findings suggest that LVEF cutoff values proposed in the guidelines to indicate intervention should be raised from 50% to 60% in AS or AR and 55% in MAVD.

Prevalence and Prognostic Implications of Discordant Grading and Flow-Gradient Patterns in Moderate Aortic Stenosis.

BACKGROUND: The prognostic implications of discordant grading in severe aortic stenosis (AS) are well known. However, the prevalence of different flow-gradient patterns and their prognostic implications in moderate AS are unknown. OBJECTIVES: The purpose of this study was to investigate the occurrence and prognostic implications of different flow-gradient patterns in patients with moderate AS. METHODS: Patients with moderate AS (aortic valve area >1.0 and ≤1.5 cm2) were identified and divided in 4 groups based on transvalvular mean gradient (MG), stroke volume index (SVi), and left ventricular ejection fraction (LVEF): concordant moderate AS (MG ≥20 mm Hg) and discordant moderate AS including 3 subgroups: normal-flow, low-gradient moderate AS (MG <20 mm Hg, SVi ≥35 mL/m2, and LVEF ≥50%); "paradoxical" low-flow, low-gradient moderate AS (MG <20 mm Hg, SVi <35 mL/m2, and LVEF ≥50%) and "classical" low-flow, low-gradient moderate AS (MG <20 mm Hg and LVEF <50%). The primary endpoint was all-cause mortality. RESULTS: Of 1,974 patients (age 73 ± 10 years, 51% men) with moderate AS, 788 (40%) had discordant grading, and these patients showed significantly higher mortality rates than patients with concordant moderate AS (P < 0.001). On multivariable analysis, "paradoxical" low-flow, low-gradient (HR: 1.458; 95% CI: 1.072-1.983; P = 0.014) and "classical" low-flow, low-gradient (HR: 1.710; 95% CI: 1.270-2.303; P < 0.001) patterns but not the normal-flow, low-gradient moderate AS pattern were independently associated with all-cause mortality. CONCLUSIONS: Discordant grading is frequently (40%) observed in patients with moderate AS. Low-flow, low-gradient patterns account for an important proportion of the discordant cases and are associated with increased mortality. These findings underline the need for better phenotyping patients with discordant moderate AS.

Left atrial dysfunction is an independent predictor of mortality in patients with cirrhosis treated by transjugular intrahepatic portosystemic shunt.

The present study aimed to investigate (1) the association between left ventricular diastolic dysfunction (LVDD), graded according to the algorithm proposed by the Cirrhotic Cardiomyopathy Consortium, and long-term survival in patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS) and (2) the additive prognostic value of left atrial (LA) function, as assessed by LA reservoir strain, using two-dimensional speckle-tracking echocardiography (2D-STE). A total of 129 TIPS candidates (mean ± SD, 61 ± 12 years; 61% men) underwent a comprehensive preprocedural echocardiography. LA dysfunction was defined by LA reservoir strain ≤35%, based on a previously suggested cut-off value. The outcome was all-cause mortality after TIPS. In the current cohort, 65 (50%) patients had normal diastolic function, 26 (20%) patients had grade 1 LVDD, 21 (16%) patients had grade 2 LVDD, and 17 (13%) patients had indeterminate diastolic function. Additionally, LA dysfunction (based on LA reservoir strain ≤35%) was noted in 67 (52%) patients. After a median follow-up of 36 months (range, 12-80), 65 (50%) patients died. All-cause mortality rates increased along worse grades of LVDD (log-rank p = 0.007) and with LA dysfunction (log-rank p = 0.001). On multivariable Cox regression analysis, Model for End-Stage Liver Disease score (hazard ratio [HR],1.06; p = 0.003), hemoglobin (HR, 0.74; p = 0.022), and LA strain, expressed as a continuous variable (HR, 0.96; p = 0.005) were independently associated with all-cause mortality. Notably, the addition of LA strain to the model provided incremental prognostic value over the established prognostic variables (delta χ2  = 8.27, p = 0.004). Conclusion: LA dysfunction assessed with 2D-STE is independently associated with all-cause mortality in patients with cirrhosis treated by TIPS.