Device Closure or Antithrombotic Therapy After Cryptogenic Stroke in Elderly Patients With a High-Risk Patent Foramen Ovale.

BACKGROUND AND PURPOSE: In young patients (aged 18-60 years) with patent foramen ovale (PFO)-associated stroke, percutaneous closure has been found to be useful for preventing recurrent ischemic stroke or transient ischemic attack (TIA). However, it remains unknown whether PFO closure is also beneficial in older patients. METHODS: Patients aged ≥60 years who had a cryptogenic stroke and PFO from ten hospitals in South Korea were included. The effect of PFO closure plus medical therapy over medical therapy alone was assessed by a propensity-score matching method in the overall cohort and in those with a high-risk PFO, characterized by the presence of an atrial septal aneurysm or a large shunt. RESULTS: Out of the 437 patients (mean age, 68.1), 303 (69%) had a high-risk PFO and 161 (37%) patients underwent PFO closure. Over a median follow-up of 3.9 years, recurrent ischemic stroke or TIA developed in 64 (14.6%) patients. In the propensity score-matched cohort of the overall patients (130 pairs), PFO closure was associated with a significantly lower risk of a composite of ischemic stroke or TIA (hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.24-0.84; P=0.012), but not for ischemic stroke. In a subgroup analysis of confined to the high-risk PFO patients (116 pairs), PFO closure was associated with significantly lower risks of both the composite of ischemic stroke or TIA (HR: 0.40; 95% CI: 0.21-0.77; P=0.006) and ischemic stroke (HR: 0.47; 95% CI: 0.23-0.95; P=0.035). CONCLUSION: Elderly patients with cryptogenic stroke and PFO have a high recurrence rate of ischemic stroke or TIA, which may be significantly reduced by device closure.

Patent Foramen Ovale Closure in Older Patients With Stroke: Patient Selection for Trial Feasibility.

BACKGROUND AND OBJECTIVES: Whether patent foramen ovale (PFO) closure benefits older patients with PFO and cryptogenic stroke is unknown because randomized controlled trials (RCTs) have predominantly enrolled patients younger than 60 years of age. Our objective was to estimate anticipated effects of PFO closure in older patients to predict the numbers needed to plan an RCT. METHODS: Effectiveness estimates are derived from major observational studies (Risk of Paradoxical Embolism [RoPE] Study and Oxford Vascular Study, together referred to as the "RoPE-Ox" database) and all 6 major RCTs (Systematic, Collaborative, PFO Closure Evaluation [SCOPE] Consortium). To estimate stroke recurrence risk, observed outcomes were calculated for patients older than 60 years in the age-inclusive observational databases (n = 549). To estimate the reduction in the rate of recurrent stroke associated with PFO closure vs medical therapy based on the RoPE score and the presence of high-risk PFO features, a Cox proportional hazards regression model was developed on the RCT data in the SCOPE database (n = 3,740). These estimates were used to calculate sample sizes required for a future RCT. RESULTS: Five-year risk of stroke recurrence using Kaplan-Meier estimates was 13.7 (95% CI 10.5-17.9) overall, 14.9% (95% CI 10.2-21.6) in those with high-risk PFO features. Predicted relative reduction in the event rate with PFO closure was 12.9% overall, 48.8% in those with a high-risk PFO feature. Using these estimates, enrolling all older patients with cryptogenic stroke and PFO would require much larger samples than those used for prior PFO closure trials, but selectively enrolling patients with high-risk PFO features would require totals of 630 patients for 90% power and 471 patients for 80% power, with an average of 5 years of follow-up. DISCUSSION: Based on our projections, anticipated effect sizes in older patients with high-risk features make a trial in these subjects feasible. With lengthening life expectancy in almost all regions of the world, the utility of PFO closure in older adults is increasingly important to explore.

Predictors of Late Adverse Events in Patients with Surgically Treated Type I Aortic Dissection.

OBJECTIVE: Residual aortic dissection (AD) following DeBakey type I AD repair is associated with a high rate of adverse events that need additional intervention or surgery. This study aimed to identify clinical and early post-operative computed tomography (CT) imaging factors associated with adverse events in patients with type I AD after ascending aorta replacement. METHODS: This single centre, retrospective cohort study included consecutive patients with type I AD who underwent ascending aorta replacement from January 2011 to December 2017 and post-operative CT within three months. The primary outcome was AD related adverse events, defined as AD related death and re-operation due to aortic aneurysm or impending rupture. The location and size of the primary intimal tears, aortic diameter, and false lumen status were evaluated. Regression analyses were performed to identify factors associated with AD related adverse events. A decision tree model was used to classify patients as high or low risk. RESULTS: Of 103 participants (55.43 ± 13.94 years; 49.5% male), 24 (23.3%) experienced AD related adverse events. In multivariable Cox regression analysis, connective tissue disease (hazard ratio [HR] 15.33; p < .001), maximum aortic diameter ≥ 40 mm (HR 4.90; p < .001), and multiple (three or more) intimal tears (HR 7.12; p < .001) were associated with AD related adverse events. The three year cumulative survival free from AD related events was lower in the high risk group with aortic diameter ≥ 40 mm and multiple intimal tears (41.7% vs. 90.9%; p < .001). CONCLUSION: Early post-operative CT findings indicating a maximum aortic diameter ≥ 40 mm and multiple intimal tears may predict a higher risk of adverse events. These findings suggest the need for careful monitoring and more vigilant management approaches in these cases.

Autotaxin inhibition attenuates the aortic valve calcification by suppressing inflammation-driven fibro-calcific remodeling of valvular interstitial cells.

BACKGROUND: Patients with fibro-calcific aortic valve disease (FCAVD) have lipid depositions in their aortic valve that engender a proinflammatory impetus toward fibrosis and calcification and ultimately valve leaflet stenosis. Although the lipoprotein(a)-autotaxin (ATX)-lysophosphatidic acid axis has been suggested as a potential therapeutic target to prevent the development of FCAVD, supportive evidence using ATX inhibitors is lacking. We here evaluated the therapeutic potency of an ATX inhibitor to attenuate valvular calcification in the FCAVD animal models. METHODS: ATX level and activity in healthy participants and patients with FCAVD were analyzed using a bioinformatics approach using the Gene Expression Omnibus datasets, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and western blotting. To evaluate the efficacy of ATX inhibitor, interleukin-1 receptor antagonist-deficient (Il1rn-/-) mice and cholesterol-enriched diet-induced rabbits were used as the FCAVD models, and primary human valvular interstitial cells (VICs) from patients with calcification were employed. RESULTS: The global gene expression profiles of the aortic valve tissue of patients with severe FCAVD demonstrated that ATX gene expression was significantly upregulated and correlated with lipid retention (r = 0.96) or fibro-calcific remodeling-related genes (r = 0.77) in comparison to age-matched non-FCAVD controls. Orally available ATX inhibitor, BBT-877, markedly ameliorated the osteogenic differentiation and further mineralization of primary human VICs in vitro. Additionally, ATX inhibition significantly attenuated fibrosis-related factors' production, with a detectable reduction of osteogenesis-related factors, in human VICs. Mechanistically, ATX inhibitor prohibited fibrotic changes in human VICs via both canonical and non-canonical TGF-ß signaling, and subsequent induction of CTGF, a key factor in tissue fibrosis. In the in vivo FCAVD model system, ATX inhibitor exposure markedly reduced calcific lesion formation in interleukin-1 receptor antagonist-deficient mice (Il1rn-/-, P = 0.0210). This inhibition ameliorated the rate of change in the aortic valve area (P = 0.0287) and mean pressure gradient (P = 0.0249) in the FCAVD rabbit model. Moreover, transaortic maximal velocity (Vmax) was diminished with ATX inhibitor administration (mean Vmax = 1.082) compared to vehicle control (mean Vmax = 1.508, P = 0.0221). Importantly, ATX inhibitor administration suppressed the effects of a high-cholesterol diet and vitamin D2-driven fibrosis, in association with a reduction in macrophage infiltration and calcific deposition, in the aortic valves of this rabbit model. CONCLUSIONS: ATX inhibition attenuates the development of FCAVD while protecting against fibrosis and calcification in VICs, suggesting the potential of using ATX inhibitors to treat FCAVD.

Incidence and predictors of left atrial thrombus in patients with atrial fibrillation under anticoagulation therapy.

BACKGROUND: Left atrial thrombus (LAT) formation is associated with thromboembolic events. OBJECTIVE: To investigate the incidence and associated factors of LAT in patients with atrial fibrillation (AF) who had been receiving anticoagulation therapy for more than 4 weeks, and to develop a prediction model using clinical and echocardiographic features. METHODS: Medical records of 1,122 patients with AF (mean age, 59.4 ± 11.0 years, 58.3% male) who were on anticoagulation more than 4 weeks and underwent transesophageal echocardiography (TEE) were evaluated. The main outcome was the presence of LAT on TEE. RESULTS: Warfarin and non-vitamin K oral anticoagulants were used in 74.4% and 25.6% of the patients at the time of examination, respectively. LAT was present in 60 patients (5.3%). Presence of LAT on TEE was associated with age ≥ 75 years (odds ratio [OR] 2.13 [95% confidence interval, 0.94-4.58]), persistent/permanent AF (OR 2.61 [1.42-4.93]), CHA2DS2-VASc score ≥ 3 points (OR 1.91 [1.05-3.48]), left ventricular ejection fraction < 40% (OR 2.35 [1.07-4.81]), and severe left atrial enlargement (OR 3.52 [1.89-6.79]). The presence of moderate-to-severe mitral regurgitation was associated with a lower risk of LAT (OR 0.13 [0.04-0.34]). A scoring system composed of the aforementioned predictors showed excellent discrimination performance (area under the curve 0.791 [95% CI, 0.727-0.854]). CONCLUSIONS: LAT was present in a considerable number of patients who were already receiving anticoagulation therapy. A prediction model that combines clinical and echocardiographic predictors could be useful in distinguishing patients who require imaging evaluations before left atrial intervention.

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

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

Este consenso de nomenclatura y clasificación para la válvula aórtica bicúspide congénita y su aortopatía está basado en la evidencia y destinado a ser utilizado universalmente por médicos (tanto pediatras como de adultos), médicos ecocardiografistas, especialistas en imágenes avanzadas cardiovasculares, cardiólogos intervencionistas, cirujanos cardiovasculares, patólogos, genetistas e investigadores que abarcan estas áreas de investigación clínica y básica. Siempre y cuando se disponga de nueva investigación clave y de referencia, este consenso internacional puede estar sujeto a cambios de acuerdo con datos basados en la evidencia1.

Path analysis of illness uncertainty and psychosocial adaptation of patients with Marfan syndrome.

AIMS: Marfan syndrome (MFS) is a genetic disorder that causes sudden or chronic cardiovascular problems, which can be fatal. Since MFS patients require regular close medical observation, it is important to understand the factors and pathways associated with psychosocial adaptation to the disease. This study aimed to identify the relationships among illness uncertainty, uncertainty appraisal, and psychosocial adaptation in MFS patients using path analysis. METHOD AND RESULTS: This descriptive cross-sectional survey study was conducted from October 2020 to March 2021, in compliance with STROBE guidelines. Using data from 179 participants aged older than 18 years, we constructed a hypothetical path model to identify determinants of illness uncertainty, uncertainty appraisal, and psychosocial adaptation. In the path analysis, disease severity, illness uncertainty, anxiety, and social support were significant factors influencing MFS patients' psychosocial adaptation. Disease severity and illness uncertainty exerted direct effects, while anxiety and social support exerted both direct and indirect (through illness uncertainty) effects. Finally, anxiety showed the greatest total effect. CONCLUSION: These findings are useful for enhancing MFS patients' psychosocial adaptation. Medical professionals should focus on managing disease severity, decreasing anxiety, and increasing social support.

Risk of recurrent ischemic stroke in patients with patent foramen ovale: The role of D-dimer.

BACKGROUND: Paradoxical embolism under elevated thromboembolic conditions is known to be the primary mechanism of patent foramen ovale (PFO)-related stroke. We hypothesized that higher levels of D-dimer, a marker of thromboembolism, could increase the risk of stroke recurrence in patients with PFO. METHODS: We conducted a retrospective analysis of data from 1226 consecutive patients with acute ischemic cryptogenic stroke (CS) who underwent transesophageal echocardiography (TEE). D-dimer was assessed during admission. We used a multivariate Cox proportional hazards model to evaluate the association of long-term outcomes between the presence of PFO and levels of D-dimer. RESULTS: Of the 1226 patients, the study included 461 who underwent TEE. Among them, 242 (52.5%) had PFOs. Among PFO patients, those with a D-dimer level >1.0 mg/L had a significantly higher risk of stroke recurrence compared to those with <0.5mg/L (adjusted hazard ratio (aHR) 4.04, 95% confidence interval [CI] 1.63-10.02). A pattern of increased risk of event with increasing D-dimer levels was observed (Ptrend=0.008). However, there was no significant difference in the risk of stroke recurrence at any D-dimer level compared to D-dimer level <0.5 mg/L among patients without PFO. In these patients, there was little evidence of increased risk with increasing D-dimer levels (Ptrend=0.570). CONCLUSIONS: This study demonstrated that the elevated D-dimer level increased the recurrence of stroke in CS patients with PFO, particularly showing a dose-dependent relationship between D-dimer levels and recurrence. However, no such effect was observed in patients without PFO. These findings provide valuable insights into the potential benefits of anticoagulation for strokes related to PFO.

Impact of routine brain imaging on the prognosis of patients with left-sided valve infective endocarditis without neurological manifestations.

BACKGROUND: There are limited data on the impact of routine use of brain magnetic resonance imaging (MRI) on the prognosis of neurologically asymptomatic patients with left-sided infective endocarditis (IE). METHODS: Among patients diagnosed with possible or definite IE in two tertiary referral centers between January 2005 and March 2019, we identified 527 left-sided IE patients without neurological symptoms or signs at the time of diagnosis. Patients who underwent brain MRI within 1 week after the IE diagnosis were classified as the routine brain imaging group (n = 216), and the rest were categorized as the control group (n = 311). All-cause mortality at 3 months, attributable mortality (defined as death directly related to IE), and fatal neurological events compared after adjustment using inverse probability of treatment weighting (IPTW). RESULTS: During a median follow-up of 57 months, the routine brain imaging group had a similar risk of 3-month all-cause mortality to the control group in the multivariate analysis (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.24-1.14) and IPTW-adjusted cohort (HR, 0.59; 95% CI, 0.25-1.42). The risks of attributable mortality and fatal neurological events were also similar between the two groups in the multivariable analysis and IPTW-adjusted cohort. In the subgroup analysis, the routine brain imaging group showed more favorable outcomes in cases of large vegetation (> 10 mm) or acute-onset microorganisms. CONCLUSIONS: Routine use of brain MRI in left-sided IE patients without neurological manifestations is not associated with improved clinical outcomes. However, routine brain imaging in appropriate clinical settings could improve clinical outcomes.

Association of citrullination with the progression of aortic stenosis.

Despite its clinical importance, biomarkers of disease activity in aortic stenosis (AS) are lacking. We investigated the association between anti-cyclic citrullinated peptide (CCP) antibodies and AS. All 678 patients who underwent echocardiography and anti-CCP antibody testing were analysed. Anti-CCP antibody status was categorized as negative, low-positive, and high-positive. In addition, aortic valve (AV) tissues were obtained from the patients with and without AS to analyze the presence of citrullinated proteins. At baseline, 241 (35.5%) subjects with AV degeneration had a higher rate of anti-CCP antibody positivity (42.7% versus 34.6%, p = 0.035) than those without AV degeneration. Out of the 331 (48.8%) subjects who underwent echocardiographic follow-up, progression of AS was observed in 34 (10.3%) patients, with a higher incidence in the high-positive group compared to the low-positive or negative group (19.0% vs. 11.3% vs. 8.4%, respectively; p = 0.041). On multivariable analysis, high anti-CCP antibody positivity was independently associated with progression to AS (odds ratio: 2.312; 95% confidence interval: 1.006-5.310; p = 0.048). Furthermore, immunohistochemistry and Western blotting revealed increased citrullination in diseased AV compared to normal AV tissue. This study demonstrated that a high positive anti-CCP antibody result is associated with AV degeneration and may be an independent factor for AS progression.

Pearls and Pitfalls in the Transesophageal Echocardiographic Diagnosis of Patent Foramen Ovale.

Large randomized controlled trials have shown the benefits of percutaneous closure of patent foramen ovale (PFO) in patients with cryptogenic stroke and PFO. Recent studies have highlighted the clinical significance and prognostic implication of various anatomical features of PFO and the adjacent atrial septum, such as atrial septal aneurysm (ASA), PFO size, large shunt, and hypermobility. Transthoracic echocardiography with contrast study is used for the indirect diagnosis of PFO, as it reveals the passage of the contrast into the left atrium. In contrast, transesophageal echocardiography (TEE) offers a direct demonstration of PFO by measuring its size using the maximum separation distance between the septum primum and septum secundum. Furthermore, TEE enables the acquisition of detailed anatomical features of the adjacent atrial septum including ASA, hypermobility, and PFO tunnel length, which carry significant prognostic implications. Transesophageal echocardiography also facilitates the diagnosis of pulmonary arteriovenous malformation, a relatively rare cause of paradoxical embolism. This review provides evidence for supporting TEE as a useful screening test for patients with cryptogenic stroke to identify suitable candidates for percutaneous device closure of PFO. Additionally, cardiac imaging specialists with proficiency in comprehensive TEE examination should be part of the heart-brain team for proper evaluation of and decision-making in patients with cryptogenic stroke.

Effect of race on pressure recovery adjustment for prevention of aortic stenosis grading discordance.

OBJECTIVE: We sought to evaluate the potential impact of racial difference (Asians vs Caucasians) on the clinical usefulness of pressure recovery (PR) adjustment for preventing discordant aortic stenosis (AS) grading in patients with severe AS. METHODS: Data from 1450 patients (mean age, 70.2±10.6 years; 290 (20%) Caucasians; aortic valve area (AVA), 0.77±0.26 cm2) were retrospectively analysed. PR-adjusted AVA was calculated using a validated equation. Discordant grading of severe AS was defined as AVA of <1.0 cm2 and mean gradient of <40 mm Hg. The frequency of discordant grading was assessed in the overall cohort and the propensity score-matched cohort. RESULTS: Before PR adjustment, 1186 patients showed AVA values of <1.0 cm2; after PR adjustment, 170 (14.3%) were reclassified as having moderate AS. PR adjustment decreased the frequency of discordant grading from 31.4% to 14.1% in Caucasians and from 13.8% to 7.9% in Asians. Patients with reclassification to moderate AS after PR adjustment had a significantly lower risk of a composite of aortic valve replacement or all-cause death than did those with severe AS after PR adjustment (HR 0.38; 95% CI 0.31-0.46; p<0.001). In propensity score-matched cohorts (173 pairs), the frequency of discordant grading before PR adjustment was 42.2% and 43.9% in the Caucasian and Asian patients, respectively, which decreased to 21.4% and 20.2%, respectively, after PR adjustment. CONCLUSIONS: Clinically relevant PR occurred, regardless of race in patients with moderate to severe AS. Routine PR adjustment may be useful for reconciling discordant AS grading.

Differences in aortic valve area measured on cardiac CT and echocardiography in patients with aortic stenosis.

BACKGROUND: A certain proportion of patients with severe aortic stenosis (AS) present with discordant grading between different diagnostic modalities, which raises uncertainty about the true severity of AS. The aim of this study was to compare the aortic valve area (AVA) measured on CT and echocardiography and demonstrate the factors affecting AVA discrepancies. METHODS: Between June 2011 and March 2016, 535 consecutive patients (66.83±8.80 years, 297 men) with AS who underwent pre-operative cardiac CT and echocardiography for aortic valve replacement were retrospectively included. AVA was obtained by AVA on echocardiography (AVAecho) and CT (AVACT) using a measurement of the left ventricular outflow tract on each modality and correlations between those measures were evaluated. Logistic regression analysis was performed to identify factors affecting the discordance for grading severe AS. RESULTS: The AVACT and AVAecho showed a high correlation (r: 0.79, P <0.001) but AVACT was larger than the AVAecho (difference 0.26 cm2, P <0.001). By using the cut-off values of AVACT (<1.2 cm2) and AVAecho (<1.0 cm2) for diagnosing severe AS, the BSA (odds ratio [OR]: 68.03, 95% confidence interval [CI]: 5.45-849.99; P = 0.001), AVAecho (OR: 1.19, 95%CI: 1.14-1.24; P <0.001), tricuspid valve morphology (OR: 2.83, 95%CI: 1.23-6.50; P = 0.01), and normalized annulus area (OR: 1.02; 95%CI:1.02-1.03; P <0.001) were significant factors associated with the discordance between the AVAecho and AVACT. CONCLUSION: Patients with larger BSA, AVAecho, and annulus, and tricuspid valve morphology were associated with the AVA discordance between the echocardiography and CT. Complementary use of CT with echocardiography for grading severe AS could be helpful in such conditions.

Association of Atrial Septal Aneurysm and Shunt Size With Stroke Recurrence and Benefit From Patent Foramen Ovale Closure.

Importance: The Patent Foramen Ovale (PFO)-Associated Stroke Causal Likelihood classification system combines information regarding noncardiac patient features (vascular risk factors, infarct topography) and PFO features (shunt size and presence of atrial septal aneurysm [ASA]) to classify patients into 3 validated categories of responsiveness to treatment with PFO closure. However, the distinctive associations of shunt size and ASA, alone and in combination, have not been completely delineated. Objective: To evaluate the association of PFO closure with stroke recurrence according to shunt size and/or the presence of an ASA. Design, Setting, and Participants: Pooled individual patient data from 6 randomized clinical trials conducted from February 2000 to October 2017 that compared PFO closure with medical therapy. Patients in North America, Europe, Australia, Brazil, and South Korea with PFO-associated stroke were included. Analysis was completed in January 2022. Exposures: Transcatheter PFO closure plus antithrombotic therapy vs antithrombotic therapy alone, stratified into 4 groups based on the combination of 2 features: small vs large PFO shunt size and the presence or absence of an ASA. Main Outcomes and Measures: Recurrent ischemic stroke. Results: A total of 121 recurrent ischemic strokes occurred in the pooled 3740 patients (mean [SD] age, 45 [10] years; 1682 [45%] female) during a median (IQR) follow-up of 57 (23.7-63.8) months. Treatment with PFO closure was associated with reduced risk for recurrent ischemic stroke (adjusted hazard ratio [aHR], 0.41 [95% CI, 0.28-0.60]; P < .001). The reduction in hazard for recurrent stroke was greater for patients with both a large shunt and an ASA (aHR, 0.15 [95% CI, 0.06-0.35]) than for large shunt without ASA (aHR, 0.27 [95% CI, 0.14-0.56]), small shunt with ASA (aHR, 0.36 [95% CI, 0.17-0.78]), and small shunt without ASA (aHR, 0.68 [95% CI, 0.41-1.13]) (interaction P = .02). At 2 years, the absolute risk reduction of recurrent stroke was greater (5.5% [95% CI, 2.7-8.3]) in patients with large shunt and ASA than for patients in the other 3 categories (1.0% for all). Conclusions and Relevance: Patients with both a large shunt and an ASA showed a substantially greater beneficial association with PFO closure than patients with large shunt alone, patients with small shunt and ASA, and patients with neither large shunt nor ASA. These findings, combined with other patient features, may inform shared patient-clinician decision-making.

Transcatheter versus surgical closure of atrial septal defect in adult patients with tricuspid regurgitation.

OBJECTIVES: Transcatheter closure using a device has been established as an effective atrial septal defect (ASD) treatment, but its value in treating patients with concomitant functional tricuspid regurgitation (TR) is relatively unknown. We sought to evaluate outcomes of patients with ASD and significant TR after transcatheter ASD closure or surgical treatment. METHODS: A total of 252 consecutive adult patients (53.8±13.8 years, 180 females) who had a significant functional TR before ASD closure were retrospectively analysed. The primary end point was a composite of all-cause death, stroke and heart failure. The secondary end point was significant residual TR early and at 1 year after ASD closure. RESULTS: Transcatheter ASD closure alone and surgical ASD closure along with tricuspid annuloplasty (TAP) were performed in 68 and 184 patients, respectively. Significant TR remained in 32% (81/252) early after ASD closure and in 29% (52/182) after 1 year. The severity of TR was significantly decreased after transcatheter ASD closure (p<0.001). In multivariable analysis, TAP (OR 0.07; p<0.001) and ASD diameter (OR 0.90; p=0.040) were independent predictors of the significant residual TR early after treatment, while only TAP (OR 0.08; p<0.001) was a significant predictor at 1 year after treatment. After propensity score matching in patients with moderate or severe TR, there were no significant differences between the transcatheter ASD closure group and surgical ASD closure plus TAP group in terms of the event rates at 5 years (10.3% vs 5.5%, p=0.963). CONCLUSIONS: While TAP was effective for the treatment of significant TR, transcatheter ASD closure also significantly reduced TR as well. Transcatheter ASD closure may be considered an alternative treatment option in patients with moderate or severe TR.

Network Analysis of Cardiac Remodeling by Primary Mitral Regurgitation Emphasizes the Role of Diastolic Function.

BACKGROUND: Topological data analysis (TDA) can generate patient-patient similarity networks by analyzing large, complex data and derive new insights that may not be possible with standard statistics. OBJECTIVES: The purpose of this paper was to discover novel phenotypes of chronic primary mitral regurgitation (MR) patients and to analyze their clinical implications using network analysis of echocardiographic data. METHODS: Patients with chronic moderate to severe primary MR were prospectively enrolled from 11 Asian tertiary hospitals (n = 850; mean age 56.9 ± 14.2 years, 57.9% men). We performed TDA to generate network models using 14 demographic and echocardiographic variables. The patients were grouped by phenotypes in the network, and the prognosis was compared by groups. RESULTS: The network model by TDA revealed 3 distinct phenogroups. Group A was the youngest with fewer comorbidities but increased left ventricular (LV) end-systolic volume, representing compensatory LV dilation commonly seen in chronic primary MR. Group B was the oldest with high blood pressure and a predominant diastolic dysfunction but relatively preserved LV size, an unnoticed phenotype in chronic primary MR. Group C showed advanced LV remodeling with impaired systolic, diastolic function, and LV dilation, indicating advanced chronic primary MR. During follow-up (median 3.5 years), 60 patients received surgery for symptomatic MR or died of cardiovascular causes. Kaplan-Meier curves demonstrated that although group C had the worst clinical outcome (P < 0.001), group B, characterized by diastolic dysfunction, had an event-free survival comparable to group A despite preserved LV chamber size. The grouping information by the network model was an independent predictor for the composite of MR surgery or cardiovascular death (adjusted HR: 1.918; 95% CI: 1.257-2.927; P = 0.003). CONCLUSIONS: The patient-patient similarity network by TDA visualized diverse remodeling patterns in chronic primary MR and revealed distinct phenotypes not emphasized currently. Importantly, diastolic dysfunction deserves equal attention when understanding the clinical presentation of chronic primary MR.

Classification of severe aortic stenosis and outcomes after aortic valve replacement.

Aortic valve calcium scoring by cardiac computed tomographic (CT) has been recommended as an alternative to classify the AS (aortic stenosis) severity, but it is unclear that whether CT findings would have additional value to discriminate significant AS subtypes including high gradient severe AS, classic low-flow, low gradient (LF-LG) AS, paradoxical LF-LG AS, and moderate AS. In this study, we examined the preoperative clinical and cardiac CT findings of different subtypes of AS in patients with surgical aortic valve replacement (AVR) and evaluated the subtype classification as a factor affecting post-surgical outcomes. This study included 511 (66.9 ± 8.8 years, 55% men) consecutive patients with severe AS who underwent surgical AVR. Aortic valve area (AVA) was obtained by echocardiography (AVAecho) and by CT (AVACT) using each modalities measurement of the left ventricular outflow tract. Patients with AS were classified as (1) high-gradient severe (n = 438), (2) classic LF-LG (n = 18), and (3) paradoxical LF-LG (n = 55) based on echocardiography. In all patients, 455 (89.0%) patients were categorized as severe AS according to the AVACT. However, 56 patients were re-classified as moderate AS (43 [9.8%] high-gradient severe AS, 5 [27.8%] classic LF-LG AS, and 8 [14.5%] paradoxical LF-LG AS) by AVACT. The classic LF-LG AS group presented larger AVACT and aortic annulus than those in high-gradient severe AS group and one third of them had AVACT ≥ 1.2 cm2. After multivariable adjustment, old age (hazard ratio [HR], 1.04, P = 0.049), high B-type natriuretic peptide (BNP) (HR, 1.005; P < 0.001), preoperative atrial fibrillation (HR, 2.75; P = 0.003), classic LF-LG AS (HR, 5.53, P = 0.004), and small aortic annulus on CT (HR, 0.57; P = 0.002) were independently associated with major adverse cardiac and cerebrovascular events (MACCE) after surgical AVR.

Incremental Prognostic Value of Left Ventricular Global Longitudinal Strain in Patients with Preserved Ejection Fraction Undergoing Transcatheter Aortic Valve Implantation.

BACKGROUND: Evaluation of left ventricular global longitudinal strain (LVGLS) has allowed better characterization than left ventricular ejection fraction (LVEF) of subtle differences in left ventricular performance. The aim of this study was to determine whether LVGLS has prognostic value in patients with severe aortic stenosis and preserved LVEF undergoing transcatheter aortic valve implantation (TAVI). METHODS: Among 412 consecutive patients who underwent TAVI, 344 patients (mean age, 78.9 ± 5.0 years; 161 men) with preserved LVEF (≥50%) at baseline were analyzed. Patients with low LVEF (<50%) were used as a comparison group in the survival analysis. The primary and secondary end points were all-cause death and a composite of cardiovascular death and heart failure hospitalization, respectively. RESULTS: The mean LVGLS and LVEF were -17.1 ± 2.7% and 63 ± 5%, respectively. Impaired LVGLS was defined as >-16%, which was the first LVGLS quartile (cutoff value, -16%). The estimated actuarial 5-year survival rate was 81.7 ± 4.2% in the normal LVGLS group and 66.8 ± 7.5% in the impaired LVGLS group (P = .005). In the multivariable analysis, impaired LVGLS was an independent predictor of all-cause death (adjusted hazard ratio, 2.26; 95% CI, 1.11-4.60) and the composite outcome (adjusted hazard ratio, 3.03; 95% CI, 1.45-6.33). Moreover, the impaired LVGLS group had a poor prognosis, similar to the impaired LVEF group (<50%). The addition of the absolute value of LVGLS to the clinical parameters and LVEF led to significant improvement in the prediction of all-cause mortality. CONCLUSIONS: In patients with severe aortic stenosis and preserved LVEF undergoing TAVI, subclinical LV dysfunction defined by impaired LVGLS is independently associated with poor clinical outcomes. LVGLS measurement provides incremental prognostic value above the established clinical and echocardiographic parameters.