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.

The MIDA-Q Mortality Risk Score: A Quantitative Prognostic Tool for the Mitral Valve Prolapse Spectrum.

BACKGROUND: Mitral valve prolapse (MVP) is responsible for a considerable disease burden but is widely heterogeneous. The lack of a comprehensive prognostic instrument covering the entire MVP spectrum, encompassing the quantified consequent degenerative mitral regurgitation (DMR), hinders clinical management and therapeutic trials. METHODS: The new Mitral Regurgitation International Database Quantitative (MIDA-Q) registry enrolled 8187 consecutive patients (ages 63±16 years, 47% women, follow-up 5.5±3.3 years) first diagnosed with isolated MVP, without or with DMR quantified prospectively (measuring effective regurgitant orifice [ERO] and regurgitant volume) in routine practice of 5 tertiary care centers from North America, Europe, and the Middle East. The MIDA-Q score ranges from 0 to 15 by accumulating guideline-based risk factors and DMR severity. Long-term survival under medical management was the primary outcome end point. RESULTS: MVP was associated with DMR absent/mild (ERO <20 mm2) in 50%, moderate (ERO 20-40 mm2) in 25%, and severe or higher (ERO ≥40 mm2) in 25%, with mean ERO 24±24 mm2, regurgitant volume 37±35 mL. Median MIDA-Q score was 4 with a wide distribution (10%-90% range, 0-9). MIDA-Q score was higher in patients with EuroScore II ≥1% versus <1% (median, 7 versus 3; P < 0.0001) but with wide overlap (10%-90% range, 4-11 versus 0-7) and mediocre correlation (R2 0.18). Five-year survival under medical management was strongly associated with MIDA-Q score, 97±1% with score 0, 95±1% with score 1 to 2, 82±1% with score 3 to 4, 67±1% with score 5 to 6, 60±1% with score 7 to 8, 44±1% with score 9 to 10, 35±1% with score 11 to 12, and 5±4% with MIDA-Q score ≥13, with hazard ratio 1.31 [1.29-1.33] per 1-point increment. Excess mortality with higher MIDA-Q scores persisted after adjustment for age, sex, and EuroScore II (adjusted hazard ratio, 1.13 [1.11-1.15] per 1-point increment). Subgroup analysis showed persistent association of MIDA-Q score with mortality in all possible subsets, in particular, with EuroScore II<1% (hazard ratio, 1.08 [1.02-1.14]) or ≥1% (hazard ratio, 1.11 [1.08-1.13]) and with no/mild DMR (hazard ratio, 1.14 [1.10-1.19]) or moderate/severe DMR (hazard ratio, 1.13 [1.10-1.16], all per 1-point increment with P<0.0001). Nested-model and bootstrapping analyses demonstrated incremental prognostic power of MIDA-Q score (all P<0.0001). CONCLUSIONS: This large, international cohort of isolated MVP, with prospective DMR quantification in routine practice, demonstrates the wide range of risk factor accumulation and considerable heterogeneity of outcomes after MVP diagnosis. The MIDA-Q score is strongly, independently, and incrementally associated with long-term survival after MVP diagnosis, irrespective of presentation, and is therefore a crucial prognostic instrument for risk stratification, clinical trials, and management of patients diagnosed with all forms of MVP.

Valvular heart disease: shifting the focus to the myocardium.

Adverse cardiac remodelling is the main determinant of patient prognosis in degenerative valvular heart disease (VHD). However, to give an indication for valvular intervention, current guidelines include parameters of cardiac chamber dilatation or function which are subject to variability, do not directly reflect myocardial structural changes, and, more importantly, seem to be not sensitive enough in depicting early signs of myocardial dysfunction before irreversible myocardial damage has occurred. To avoid irreversible myocardial dysfunction, novel biomarkers are advocated to help refining indications for intervention and risk stratification. Advanced echocardiographic modalities, including strain analysis, and magnetic resonance imaging have shown to be promising in providing new tools to depict the important switch from adaptive to maladaptive myocardial changes in response to severe VHD. This review, therefore, summarizes the current available evidence on the role of these new imaging biomarkers in degenerative VHD, aiming at shifting the clinical perspective from a valve-centred to a myocardium-focused approach for patient management and therapeutic decision-making.

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.

Improving accuracy in diagnosing aortic stenosis severity: An in-depth analysis of echocardiographic measurement error through literature review and simulation study.

AIMS: The present guidelines advise replacing the aortic valve for individuals with severe aortic stenosis (AS) based on various echocardiographic parameters. Accurate measurements are essential to avoid misclassification and unnecessary interventions. The objective of this study was to evaluate the influence of measurement error on the echocardiographic evaluation of the severity of AS. METHODS AND RESULTS: A systematic review was performed to examine whether measurement errors are reported in studies focusing on the prognostic value of peak aortic jet velocity (Vmax ), mean pressure gradient (MPG), and effective orifice area (EOA) in asymptomatic patients with AS. Out of the 37 studies reviewed, 17 (46%) acknowledged the existence of measurement errors, but none of them utilized methods to address them. Secondly, the magnitude of potential errors was collected from available literature for use in clinical simulations. Interobserver variability ranged between 0.9% and 8.3% for Vmax and MPG but was higher for EOA (range 7.7%-12.7%), indicating lower reliability. Assuming a circular left ventricular outflow tract area led to a median underestimation of EOA by 23% compared to planimetry by other modalities. A clinical simulation resulted in the reclassification of 42% of patients, shifting them from a diagnosis of severe AS to moderate AS. CONCLUSIONS: Measurement errors are underreported in studies on echocardiographic assessment of AS severity. These errors can lead to misclassification and misdiagnosis. Clinicians and scientists should be aware of the implications for accurate clinical decision-making and assuring research validity.

The year in cardiovascular medicine 2021: imaging.

This article reviews the most relevant literature published in 2021 on the role of cardiovascular imaging in cardiovascular medicine. Coronavirus disease 2019 (COVID-19) continued to impact the healthcare landscape, resulting in reduced access to hospital-based cardiovascular care including reduced routine diagnostic cardiovascular testing. However, imaging has also facilitated the understanding of the presence and extent of myocardial damage caused by the coronavirus infection. What has dominated the imaging literature beyond the pandemic are novel data on valvular heart disease, the increasing use of artificial intelligence (AI) applied to imaging, and the use of advanced imaging modalities in both ischaemic heart disease and cardiac amyloidosis.

New calcification model for intact murine aortic valves.

Calcific aortic valve disease (CAVD) is a common progressive disease of the aortic valves, for which no medical treatment exists and surgery represents currently the only therapeutic solution. The development of novel pharmacological treatments for CAVD has been hampered by the lack of suitable test-systems, which require the preservation of the complex valve structure in a mechanically and biochemical controllable system. Therefore, we aimed at establishing a model which allows the study of calcification in intact mouse aortic valves by using the Miniature Tissue Culture System (MTCS), an ex vivo flow model for whole mouse hearts. Aortic valves of wild-type mice were cultured in the MTCS and exposed to osteogenic medium (OSM, containing ascorbic acid, ß-glycerophosphate and dexamethasone) or inorganic phosphates (PI). Osteogenic calcification occurred in the aortic valve leaflets that were cultured ex vivo in the presence of PI, but not of OSM. In vitro cultured mouse and human valvular interstitial cells calcified in both OSM and PI conditions, revealing in vitro-ex vivo differences. Furthermore, endochondral differentiation occurred in the aortic root of ex vivo cultured mouse hearts near the hinge of the aortic valve in both PI and OSM conditions. Dexamethasone was found to induce endochondral differentiation in the aortic root, but to inhibit calcification and the expression of osteogenic markers in the aortic leaflet, partly explaining the absence of calcification in the aortic valve cultured with OSM. The osteogenic calcifications in the aortic leaflet and the endochondral differentiation in the aortic root resemble calcifications found in human CAVD. In conclusion, we have established an ex vivo calcification model for intact wild-type murine aortic valves in which the initiation and progression of aortic valve calcification can be studied. The in vitro-ex vivo differences found in our studies underline the importance of ex vivo models to facilitate pre-clinical translational studies.

Identification of known and unknown genes associated with mitral valve prolapse using an exome slice methodology.

PURPOSE: Although a familial distribution has been documented, the genetic aetiology of mitral valve prolapse (MVP) is largely unknown, with only four genes identified so far: FLNA, DCHS1, DZIP1 and PLD1. The aim of this study was to evaluate the genetic yield in known causative genes and to identify possible novel genes associated with MVP using a heart gene panel based on exome sequencing. METHODS: Patients with MVP were referred for genetic counselling when a positive family history for MVP was reported and/or Barlow's disease was diagnosed. In total, 101 probands were included to identify potentially pathogenic variants in a set of 522 genes associated with cardiac development and/or diseases. RESULTS: 97 (96%) probands were classified as Barlow's disease and 4 (4%) as fibroelastic deficiency. Only one patient (1%) had a likely pathogenic variant in the known causative genes (DCHS1). However, an interesting finding was that 10 probands (11%) had a variant that was classified as likely pathogenic in six different, mostly cardiomyopathy genes: DSP (1×), HCN4 (1×), MYH6 (1×), TMEM67 (1×), TRPS1 (1×) and TTN (5×). CONCLUSION: Exome slice sequencing analysis performed in MVP probands reveals a low genetic yield in known causative genes but may expand the cardiac phenotype of other genes. This study suggests for the first time that also genes related to cardiomyopathy may be associated with MVP. This highlights the importance to screen these patients and their family for the presence of arrhythmias and of 'disproportionate' LV remodelling as compared with the severity of mitral regurgitation, unravelling a possible coexistent cardiomyopathy.

Prognostic Implications of Right Ventricular Remodeling and Function in Patients With Significant Secondary Tricuspid Regurgitation.

BACKGROUND: In patients with significant (moderate and severe) tricuspid regurgitation (TR), the decision to intervene is influenced by right ventricular (RV) size and function. RV remodeling in significant secondary TR has been underexplored. The aim of this study was to characterize RV remodeling in patients with significant secondary TR and to investigate its prognostic implications. METHODS: RV remodeling was characterized by transthoracic echocardiography in 1292 patients with significant secondary TR (median age 71 [62-78]; 50% male). Four patterns of RV remodeling were defined according to the presence of RV dilation (tricuspid annulus≥40 mm) and RV systolic dysfunction (tricuspid annulus systolic excursion plane<17 mm): pattern 1, normal RV size and systolic function; pattern 2, dilated RV with preserved systolic function; pattern 3, normal RV size with systolic dysfunction; and pattern 4, dilated RV systolic dysfunction. The primary end point was all-cause mortality and the event rates were compared across the 4 patterns of RV remodeling. RESULTS: A total of 183 (14%) patients showed pattern 1 RV remodeling; 256 (20%) showed pattern 2; 304 (24%) presented with pattern 3; and 549 (43%) had pattern 4 RV remodeling. Patients with pattern 4 RV remodeling were more frequently male; more often had coronary artery disease, worse renal function, and impaired left ventricular ejection fraction; and were more often symptomatic. Only 98 (8%) patients underwent tricuspid valve annuloplasty during follow-up. During a median follow-up of 34 (interquartile range, 0-60) months, 510 (40%) patients died. The 5-year survival rate was significantly worse in patients presenting with patterns 3 and 4 RV remodeling in comparison with pattern 1 (52% and 49% versus 70%; P=0.002 and P<0.001, respectively), and were independently associated with poor outcome on multivariable analysis. CONCLUSIONS: In patients with significant secondary TR, patients with RV systolic dysfunction have worse clinical outcome regardless of the presence of RV dilation.

Procedural-related coronary atrial branch occlusion during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction and atrial arrhythmias at follow-up.

OBJECTIVES: To evaluate the frequency of procedural-related atrial branch occlusion in ST-segment elevation myocardial infarction (STEMI) patients and its association with atrial arrhythmias at 1-year follow-up. BACKGROUND: Atrial ischemia due to procedural-related coronary atrial branch occlusion in elective percutaneous coronary intervention (PCI) has been associated with atrial arrhythmias. Its role in a STEMI scenario is unknown. METHODS: STEMI patients treated with primary PCI were classified according to the loss or patency of an atrial branch at the end of the procedure. The occurrence of atrial arrhythmias was documented on 24-hr Holter-ECG at 3 and 6 months or on ECG during 1-year follow-up visits. RESULTS: Of 900 patients, 355 (age 61 ± 12 years, 79% male) underwent primary PCI involving the origin of an atrial branch. Procedural-related coronary atrial branch occlusion was observed in 18 (5%) individuals). During 1-year follow-up, 33% of patients with procedural-related atrial branch occlusion presented atrial arrhythmias, as compared with 55% in those with a patent atrial branch (p = .088). Age, no previous history of myocardial infarction, and a reduced flow in the culprit vessel were the only independent correlates of atrial arrhythmias. CONCLUSIONS: The frequency of procedural-related atrial branch occlusion during primary PCI is low (5%) and is not associated with increased frequency of atrial arrhythmias at 1-year follow-up.

Automated Cardiac Valve Tracking for Flow Quantification with Four-dimensional Flow MRI.

Purpose To compare four-dimensional flow MRI with automated valve tracking to manual valve tracking in patients with acquired or congenital heart disease and healthy volunteers. Materials and Methods In this retrospective study, data were collected from 114 patients and 46 volunteers who underwent four-dimensional flow MRI at 1.5 T or 3.0 T from 2006 through 2017. Among the 114 patients, 33 had acquired and 81 had congenital heart disease (median age, 17 years; interquartile range [IQR], 13-49 years), 51 (45%) were women, and 63 (55%) were men. Among the 46 volunteers (median age, 28 years; IQR, 22-36 years), there were 19 (41%) women and 27 (59%) men. Two orthogonal cine views of each valve were used for valve tracking. Wilcoxon signed-rank test was used to compare analysis times, net forward volumes (NFVs), and regurgitant fractions. Intra- and interobserver variability was tested by using intraclass correlation coefficients (ICCs). Results Analysis time was shorter for automated versus manual tracking (all patients, 14 minutes [IQR, 12-15 minutes] vs 25 minutes [IQR, 20-25 minutes]; P < .001). Although overall differences in NFV and regurgitant fraction were comparable between both methods, NFV variation over four valves was smaller for automated versus manual tracking (all patients, 4.9% [IQR, 3.3%-6.7%] vs 9.8% [IQR, 5.1%-14.7%], respectively; P < .001). Regurgitation severity was discordant for seven pulmonary valves, 22 mitral valves, and 21 tricuspid valves. Intra- and interobserver agreement for automated tracking was excellent for NFV assessment (intra- and interobserver, ICC ≥ 0.99) and strong to excellent for regurgitant fraction assessment (intraobserver, ICC ≥ 0.94; interobserver, ICC ≥ 0.89). Conclusion Automated valve tracking reduces analysis time and improves reliability of valvular flow quantification with four-dimensional flow MRI in patients with acquired or congenital heart disease and in healthy volunteers. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by François in this issue.

Left atrial function to identify patients with atrial fibrillation at high risk of stroke: new insights from a large registry.

Aims: Atrial fibrillation (AF) is an independent risk factor for ischaemic stroke. The CHA2DS2-VASc is the most widely used risk stratification model; however, echocardiographic refinement may be useful, particularly in low risk AF patients. The present study examined the association between advanced echocardiographic parameters and ischaemic stroke, independent of CHA2DS2-VASc score. Methods and results: One thousand, three hundred and sixty-one patients (mean age 65±12 years, 74% males) with first diagnosis of AF and baseline transthoracic echocardiogram were followed by chart review for the occurrence of stroke over a mean of 7.9 years. Left atrial (LA) volumes, LA reservoir strain, P-wave to A' duration on tissue Doppler imaging (PA-TDI, reflecting total atrial conduction time), and left ventricular (LV) global longitudinal strain (GLS) were evaluated in patients with and without stroke. The independent association of these echocardiographic parameters with the occurrence of ischaemic stroke was evaluated with Cox proportional hazard models. One-hundred patients (7%) developed an ischaemic stroke, representing an annualized stroke rate of 0.9%. The incident stroke rate in the year following the first diagnosis of AF was 2.6% in the entire population and higher than the remainder of the follow-up period. Left atrial reservoir (14.5% vs. 18.9%, P = 0.005) and conduit strains were reduced (10.5% vs. 13.5%, P = 0.013), and PA-TDI lengthened (166 ms vs. 141 ms, P < 0.001) in the stroke compared with non-stroke group, despite similar LV dimensions, LV ejection fraction, GLS, and LA volumes. Left atrial reservoir strain and PA-TDI were independently associated with risk of stroke in a model including CHA2DS2-VASc score, age, and anticoagulant use. Conclusion: The assessment of LA reservoir strain and PA-TDI on echocardiography after initial CHA2DS2-VASc scoring provides additional risk stratification for stroke and may be useful to guide decisions regarding anticoagulation for patients upon first diagnosis of AF.

Development of significant tricuspid regurgitation over time and prognostic implications: new insights into natural history.

Aims: To evaluate the risk factors influencing the development of significant (moderate and severe) tricuspid regurgitation (TR), and its impact on all-cause mortality in large registry of referral centre. Methods and results: In 1000 patients (mean age 68 ± 13 years; 50.9% male) with documented significant TR, clinical, and echocardiographic data were retrospectively analysed when the echocardiogram showed none/mild TR. Patients with congenital heart disease were excluded. The study population was divided into quartiles according to the time interval between the two echocardiograms: Group 1: ≤1.2 years, n = 251; Group 2: 1.3-4.7 years, n = 248, Group 3: 4.8-8.9 years, n = 251; Group 4: ≥9.0 years, n = 250. Baseline age [odds ratio (OR) 1.02], presence of pacemaker and defibrillator lead (OR 1.59), presence of mild (vs. none) TR (OR 8.96), reduced tricuspid annulus plane systolic excursion (OR 0.86), and tricuspid annulus dilation (OR 1.06) were independently associated with development of significant TR in a short period of time. Any valvular surgery (without concomitant tricuspid surgery) occurring between both echocardiograms was also associated with a higher risk of fast development of significant TR (OR 1.58). During a median follow-up of 2.9 years after the second echocardiogram (with significant TR), 42.1% patients died. Patients with fast development of significant TR showed worse survival than patients with slower significant TR development (log rank P = 0.001). Fast development of significant TR was independently associated with all-cause mortality (hazard ratio per preceding year of development: 0.92, confidence interval 0.90-0.94; P < 0.001). Conclusion: By identifying patients at increased risk of developing significant TR, close echocardiographic surveillance can be indicated permitting effective therapy at an earlier stage to improve survival.

Inter-ethnic differences in valve morphology, valvular dysfunction, and aortopathy between Asian and European patients with bicuspid aortic valve.

Background: Transcatheter aortic valve replacement (TAVR) has been shown safe and feasible in patients with bicuspid aortic valve (BAV) morphology. Evaluation of inter-ethnic differences in valve morphology and function and aortic root dimensions in patients with BAV is important for the worldwide spread of this therapy in this subgroup of patients. Comparisons between large European and Asian cohorts of patients with BAV have not been performed, and potential differences between populations may have important implications for TAVR. Aim: The present study evaluated the differences in valve morphology and function and aortic root dimensions between two large cohorts of European and Asian patients with BAV. Methods and results: Aortic valve morphology was defined on transthoracic echocardiography according to the number of commissures and raphe: type 0 = no raphe and two commissures, type 1 = one raphe and two commissures, type 2 = two raphes and one commissure. Aortic stenosis and regurgitation were graded according to current recommendations. For this study, aortic root dimensions were manually measured on transthoracic echocardiograms at the level of the aortic annulus, sinus of Valsalva (SOV), sinotubular junction (STJ), and ascending aorta (AA). Of 1427 patients with BAV (45.2 ± 18.1 years, 71.9% men), 794 (55.6%) were Europeans and 633 (44.4%) were Asians. The groups were comparable in age and proportion of male sex. Asians had higher prevalence of type 1 BAV with raphe between right and non-coronary cusps than Europeans (19.7% vs. 13.6%, respectively; P < 0.001), whereas the Europeans had higher prevalence of type 0 BAV (two commissures, no raphe) than Asians (14.5% vs. 6.8%, respectively; P < 0.001). The prevalence of moderate and severe aortic regurgitation was higher in Europeans than Asians (44.2% vs. 26.8%, respectively; P < 0.001) whereas there were no differences in BAV with normal function or aortic stenosis. After adjusting for demographics, comorbidities, and valve function, the dimensions of the aortic annulus [mean difference 1.17 mm/m2, 95% confidence interval (CI) 0.96-1.39], SOV (mean difference 1.86 mm/m2, 95% CI 1.47-2.24), STJ (mean difference 0.52 mm/m2, 95% CI 0.14-0.90) and AA (mean difference 1.05 mm/m2, 95% CI 0.57-1.52) were significantly larger among Asians compared with Europeans. Conclusions: This large multicentre registry reports for the first time that Asians with BAV showed more frequently type 1 BAV (with fusion between right and non-coronary cusp) and have larger aortic dimensions than Europeans. These findings have important implications for prosthesis type and size selection for TAVR.

Assessment of left ventricular dyssynchrony by three-dimensional echocardiography: Prognostic value in patients undergoing cardiac resynchronization therapy.

BACKGROUND: Systolic dyssynchrony index (SDI) using three-dimensional echocardiography (3DE) was shown to be a reliable measure of left ventricular (LV) dyssynchrony. However, the prognostic value of SDI on long-term outcomes after cardiac resynchronization therapy (CRT) remains unknown. METHODS AND RESULTS: A total of 414 patients (mean age 67 ± 10 years, 60% ischemic etiology) with 3DE evaluation before CRT implantation were included. SDI was evaluated as continuous value and in quartiles. The study endpoint was combined all-cause mortality, heart transplantation, and LV assist device implantation. At baseline, median SDI was 8.0% (IQR 5.6-11.3%). During a median follow-up of 45 months (IQR 25-59 months), the endpoint was observed in 94 (23%) patients. SDI was independently associated with the endpoint together with ischemic etiology, diabetes, and renal function (HR 0.914, P = 0.003) after adjustment for age, atrial fibrillation, hemoglobin level, NYHA functional class, and posterolateral LV lead position. Patients from the 1st, 2nd, and 3rd SDI quartiles showed similar survival and superior as compared to the 4th quartile with the lowest SDI values (≤5.5%; χ²: 30.4, log-rank P < 0.001). From receiver operating characteristic curve analysis, the optimal SDI cut-off value associated with the endpoint was >6.8% (area under the curve 0.634). Finally, a subgroup analysis (293 patients) demonstrated that a more pronounced reduction in SDI immediately after CRT (resynchronization) was independently associated with superior survival (HR 0.461, P = 0.011) after adjustment for prognostic relevant parameters. CONCLUSION: SDI is independently associated with long-term prognosis after CRT and might therefore be important to optimize risk-stratification in these patients.

Effects of Transcatheter Mitral Valve Repair With MitraClip on Left Ventricular and Atrial Hemodynamic Load and Myocardial Wall Stress.

AIMS: To evaluate the effects of MitraClip on left ventricular (LV) and left atrial (LA) myocardial wall stress as assessed with the use of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and strain imaging. METHODS AND RESULTS: Sixty-five patients with symptomatic moderate and severe mitral regurgitation (MR; age 75 ± 9 y, 57% male, 89% functional MR) treated with the use of MitraClip were evaluated. Patients were divided according to 6-month NT-proBNP tertiles. Changes in echocardiographic parameters over 6 months were assessed. Reductions in LV end-diastolic volumes (178 ± 77 mL to 170 ± 79 mL; P = .045) and LV end-systolic volumes (120 ± 70 mL to 111 ± 69 mL; P = .040) were observed in the overall population. Interestingly, low-NT-proBNP-tertile patients showed slight improvements in LV and LA longitudinal strain, whereas high-NT-proBNP-tertile patients showed impairment. CONCLUSIONS: Although MitraClip induces hemodynamic unloading in patients with predominantly functional MR, myocardial wall stress is not consistently improved. In patients with reduced NT-proBNP, improvements in LA volume index and LV and LA strains were observed. Patients who showed an increase in NT-proBNP exhibited impairment in LV and LA strain, suggesting an increase of myocardial wall stress.

To what extent do autoantibodies help to identify high-risk patients in systemic sclerosis?

OBJECTIVES: To evaluate the additive value of autoantibodies in identifying systemic sclerosis (SSc) patients with high complication risk. METHODS: Patients entering the Combined Care In SSc cohort, Leiden University Medical Centre between April 2009 and May 2016 were included. Subgroups of patients were determined using hierarchical clustering, performed on Principal Component Analysis scores, 1) using baseline data of demographic and clinical variables only and 2) with additional use of antibody status. Disease-risk within subgroups was assessed by evaluating 5-year mortality rates. Clinical and autoantibody characteristics of obtained subgroups were compared. RESULTS: In total 407 SSc patients were included, of which 91% (n=371) fulfilled ACR/EULAR 2013 criteria for SSc. Prevalences of autoantibodies were: anti-centromere 37%, anti-topoisomerase (ATA) 24%, anti-RNA polymerase III 5%, anti-fibrillarin 4% and anti-Pm/Scl 5%. Clinical cluster analysis identified 4 subgroups, with two subgroups showing higher than average mortality (resp. 17% and 7% vs. total group mortality of 4%). ATA-positivity ranged from 10 to 21% in low-risk groups and from 30 to 49% among high-risk groups. Adding autoantibody status to the cluster process resulted in 5 subgroups with 3 showing higher than average mortality. Still, 22% of ATA- positive patients were clustered into a low-risk subgroup, while the total number of patients stratified to a high-risk subgroup increased. CONCLUSIONS: Autoantibodies only partially contribute to risk-stratification and clinical subsetting in SSc. The current findings confirm that not all ATA-positive patients have worse prognosis and as such, additional biomarkers are needed to guide clinical follow-up in SSc.