Sex-Specific Left Ventricular and Aorta Size Cut-Off Values for Hemodynamically Significant Chronic Aortic Regurgitation　- Implications for Treatment in Asian Populations.

BACKGROUND: There are no sex-specific guidelines for chronic aortic regurgitation (AR). This retrospective study examined sex-specific differences and propose treatment criteria from an Asian AR cohort.Methods and Results: Consecutive 1,305 patients with moderate-severe AR or greater at 3 tertiary centers in Taiwan and Japan (2008-2022) were identified. Study endpoints were aortic valve surgery (AVS), all-cause death (ACD), and cardiovascular death (CVD). The median follow up was 3.9 years (interquartile range 1.3-7.1 years). Compared with men (n=968), women (n=337) were older, had more advanced symptoms, more comorbidities, larger indexed aorta size (iAortamax) and indexed left ventricular (LV) end-systolic dimension (LVESDi; P<0.001 for all). Symptomatic status was poorly correlated with the degree of LV remodeling in women (P≥0.18). Women received fewer AVS (P≤0.001) and men had better overall 10-year survival (P<0.01). Ten-year post-AVS survival (P=0.9) and the progression of LV remodeling were similar between sexes (P≥0.16). Multivariable determinants of ACD and CVD were age, advanced symptoms, iAortamax, LV ejection fraction (LVEF), LVESDi, LV end-systolic volume index (LVESVi), and Taiwanese ethnicity (all P<0.05), but not female sex (P≥0.05). AVS was associated with better survival (P<0.01). Adjusted LVEF, LVESDi, LVESVi, and iAortamaxcut-off values for ACD were 53%, 24.8 mm/m2, 44 mL/m2, and 25.5 mm/m2, respectively, in women and 52%, 23.4 mm/m2, 52 mL/m2, and 23.2 mm/m2, respectively, in men. CONCLUSIONS: Early detection and intervention using sex-specific cut-off values may improve survival in women with AR.

Bicuspid aortic valve: long-term morbidity and mortality.

BACKGROUND AND AIMS: Bicuspid aortic valve (BAV) is the most common congenital heart anomaly. Lifetime morbidity and whether long-term survival varies according to BAV patient-sub-groups are unknown. This study aimed to assess lifetime morbidity and long-term survival in BAV patients in the community. METHODS: The authors retrospectively identified all Olmsted County (Minnesota) residents with an echocardiographic diagnosis of BAV from 1 January 1980 to 31 December 2009, including patients with typical valvulo-aortopathy (BAV without accelerated valvulo-aortopathy or associated disorders), and those with complex valvulo-aortopathy (BAV with accelerated valvulo-aortopathy or associated disorders). RESULTS: 652 consecutive diagnosed BAV patients [median (IQR) age 37 (22-53) years; 525 (81%) adult and 127 (19%) paediatric] were followed for a median (IQR) of 19.1 (12.9-25.8) years. The total cumulative lifetime morbidity burden (from birth to age 90) was 86% (95% CI 82.5-89.7); cumulative lifetime progression to ≥ moderate aortic stenosis or regurgitation, aortic valve surgery, aortic aneurysm ≥45 mm or z-score ≥3, aorta surgery, infective endocarditis and aortic dissection was 80.3%, 68.5%, 75.4%, 27%, 6% and 1.6%, respectively. Survival of patients with typical valvulo-aortopathy [562 (86%), age 40 (28-55) years, 86% adults] was similar to age-sex-matched Minnesota population (P = .12). Conversely, survival of patients with complex valvulo-aortopathy [90 (14%), age 14 (3-26) years, 57% paediatric] was lower than expected, with a relative excess mortality risk of 2.25 (95% CI 1.21-4.19) (P = .01). CONCLUSION: The BAV condition exhibits a high lifetime morbidity burden where valvulo-aortopathy is close to unavoidable by age 90. The lifetime incidence of infective endocarditis is higher than that of aortic dissection. The most common BAV clinical presentation is the typical valvulo-aortopathy with preserved expected long-term survival, while the complex valvulo-aortopathy presentation incurs higher mortality.

Analysis of Left Ventricular Indexes and Mortality Among Asian Adults With Hemodynamically Significant Chronic Aortic Regurgitation.

Importance: Chronic hemodynamically significant aortic regurgitation (AR) is associated with excess risk of death, yet data for Asian patients are lacking, and whether Asian patients can abide by Western guidelines as to when aortic valve surgery should be performed is unknown. Objective: To assess AR presentation and cutoffs of left ventricular ejection fraction (LVEF), LV end-systolic dimension index (LVESDi), and LV end-systolic volume index (LVESVi) that are associated with risk of death in Asian patients with AR. Design, Setting, and Participants: This retrospective cohort study included consecutive patients with chronic, moderately severe to severe AR from 3 tertiary referral centers (2 in Japan and 1 in Taiwan) from June 11, 2008, through November 19, 2020, with follow-up through November 11, 2021. Exposures: Aortic regurgitation severity, graded by a comprehensive integrated approach. Main Outcomes and Measures: The primary outcome was the association between volume-derived LVEF, LVESDi, and LVESVi and all-cause death (ACD). The secondary outcome was the association of these LV indexes with cardiovascular death (CVD). Clinical and echocardiographic data were analyzed retrospectively. A de novo disk-summation method was used to derive LV volumes and volume-derived LVEF. Results: Of 1259 patients (mean [SD] age, 64 [17] years; 934 [74%] male), 515 (41%) were Japanese and 744 (59%) were Taiwanese. The median follow-up was 4.1 years (IQR, 1.56-7.24 years). The mean (SD) body surface area was 1.67 (0.21) m2; LVEF, 55% (11%); LVESDi, 24.7 (5.7) mm/m2; LVESVi, 50.1 (28.0) mL/m2; and indexed mid-ascending aorta size, 24.7 (5.5) mm/m2. Aortic valve surgery occurred in 483 patients (38%); 240 patients (19%) died during follow-up. Overall mean (SD) 8-year survival was 74% (2%). Separate multivariate models adjusted for covariates demonstrated independent associations of LVEF, LVESDi, and LVESVi with ACD (LVEF: hazard ratio [HR] per 10%, 0.80; 95% CI, 0.70-0.92; P = .002; LVESDi: HR, 1.04; 95% CI, 1.01-1.06; P = .002; LVESVi: HR per 10 mL/m2, 1.11; 95% CI, 1.05-1.17; P < .001) and CVD (LVEF: HR per 10%, 0.69; 95% CI, 0.56-0.85; P < .001; LVESDi: HR, 1.05; 95% CI, 1.01-1.09; P = .01; LVESVi per 10 mL/m2: HR, 1.15; 95% CI, 1.06-1.24; P < .001). In the total cohort, spline curves showed that mortality started to increase for an LVEF of 53% or less, LVESDi of 22 mm/m2 or greater, and LVESVi of 46 mL/m2 or greater for both ACD and CVD. Early surgery was beneficial in 3 strata of LVESDi (<20, 20 to <25, and ≥25 mm/m2) and 2 strata of LVESVi (<46 and ≥46 mL/m2). Conclusions and Relevance: This multicenter cohort study of Asian patients with hemodynamically significant AR found cutoff values of LVEF, LVESDi, and LVESVi that were associated with increased risk of death. These findings suggest that Western guidelines seem applicable in Asian patients and, most importantly, that indexed LV parameters with a lower cutoff could be used in discriminating patients with excess mortality risk.

Comparison Between Bicuspid and Tricuspid Aortic Regurgitation: Presentation, Survival, and Aorta Complications.

Background: Although the Asian population is growing globally, data in Asian subjects regarding differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) in aortic regurgitation (AR) remain unexplored. Objectives: The aim of this study was to examine differences between Asian BAV-AR and TAV-AR in significant AR, including aorta complications. Methods: The study included 711 consecutive patients with chronic moderate to severe and severe AR from 2008 to 2020. Outcomes included all-cause death, aortic valve surgery (AVS), and incidence of aortic dissection (AD). Results: There were 149 BAV-AR (mean age: 48 ± 16 years) and 562 TAV-AR (mean age: 68 ± 15 years; P < 0.0001) patients; baseline indexed left ventricle and indexed aorta size were larger in TAV-AR. Total follow-up was 4.8 years (IQR: 2.0-8.4 years), 252 underwent AVS, and 185 died during follow-up; 18 cases (only 1 BAV) of AD occurred, with a mean maximal aorta size of 60 ± 9 mm. The 10-year AVS incidence was higher in TAV-AR (51% ± 4%) vs BAV-AR (40% ± 5%) even after adjustment for covariates (P < 0.0001). The 10-year survival was higher in BAV-AR (86% ± 4%) vs TAV-AR (57% ± 3%; P < 0.0001) and became insignificant after age adjustment (P = 0.33). Post-AVS 10-year survival was 93% ± 5% in BAV-AR and 78% ± 5% in TAV-AR, respectively (P = 0.08). The 10-year incidence of AD was higher in TAV-AR (4.8% ± 1.5%) than in BAV-AR (0.9% ± 0.9%) and was determined by aorta size ≥45 mm (P ≤ 0.015). Compared with an age- and sex-matched population in Taiwan, TAV-AR (HR: 3.1) had reduced survival (P < 0.0001). Conclusions: Our findings suggest that TAV-AR patients were at a later stage of AR course and had a high AD rate as opposed to BAV-AR patients in Taiwan, emphasizing the importance of early referral for timely management. Surgery on the aorta with a lower threshold in TAV-AR should be considered.

The Logistics of Medication and Patient Flow in Video-Based Virtual Clinics During a Sudden COVID-19 Outbreak in Taiwan: Observational Study.

BACKGROUND: The COVID-19 pandemic was well controlled in Taiwan until an outbreak in May 2021. Telemedicine was rapidly implemented to avoid further patient exposure and to unload the already burdened medical system. OBJECTIVE: To understand the effect of COVID-19 on the implementation of video-based virtual clinic visits during this outbreak, we analyzed the logistics of prescribing medications and patient flow for such virtual visits at a tertiary medical center. METHODS: We retrospectively collected information on video-based virtual clinic visits and face-to-face outpatient visits from May 1 to August 31, 2021, from the administrative database at National Taiwan University Hospital. The number of daily new confirmed COVID-19 cases in Taiwan was obtained from an open resource. RESULTS: There were 782 virtual clinic visits during these 3 months, mostly for the departments of internal medicine, neurology, and surgery. The 3 most common categories of medications prescribed were cardiovascular, diabetic, and gastrointestinal, of which cardiovascular medications comprised around one-third of all medications prescribed during virtual clinic visits. The number of virtual clinic visits was significantly correlated with the number of daily new confirmed COVID-19 cases, with approximately a 20-day delay (correlation coefficient 0.735; P<.001). The patient waiting time for video-based virtual clinic visits was significantly shorter compared with face-to-face clinic visits during the same period (median 3, IQR 2-6 min vs median 20, IQR 9-42 min; rank sum P<.001). Although the time saved was appreciated by the patients, online payment with direct delivery of medications without the need to visit a hospital was still their major concern. CONCLUSIONS: Our data showed that video-based virtual clinics can be implemented rapidly after a COVID-19 outbreak. The virtual clinics were efficient, as demonstrated by the significantly reduced waiting time. However, there are still some barriers to the large-scale implementation of video-based virtual clinics. Better preparation is required to improve performance in possible future large outbreaks.

Automated Global Longitudinal Strain Exhibits a Robust Association with Death in Asymptomatic Chronic Aortic Regurgitation.

BACKGROUND: Whether automated left ventricular global longitudinal strain (LVGLS) is associated with outcomes in patients with asymptomatic aortic regurgitation (AR) is unknown. The aim of this study was to explore the impact of automated LVGLS on survival and compare it with conventional left ventricular (LV) parameters in patients with chronic asymptomatic AR. METHODS: LVGLS (presented as an absolute value) was measured using fully automated two-dimensional strain software in consecutive patients with isolated chronic moderate to severe or greater AR between 2004 and 2020; the incremental value of LVGLS was assessed. Limited correction of endocardial border tracking was performed if needed. RESULTS: Of 550 asymptomatic patients (mean age, 60 ± 17 years; 86% men), average LVGLS was 17 ± 3% (first and second tertiles, 15.8% and 18.5%). In 16% of cases, tracking border was partially corrected; average time for analysis was 25 ± 5 sec. At a median of 4.8 years (interquartile range, 1.5-9.9 years), 87 patients had died (19 died after aortic valve surgery). Separate multivariable models adjusted for age, sex, Charlson index, AR severity, and time-dependent aortic valve surgery demonstrated that LV ejection fraction (hazard ratio [HR] per 10%, 0.9), LV end-systolic volume index (LVESVi; HR per 5 mL/m2, 1.08) and LVGLS (HR per unit, 0.87) were independently associated with death (P ≤ .018 for all); however, LVGLS remained statistically significant (HR: 0.86-0.9; P ≤ .007) when compared head-to-head with LV ejection fraction, LVESVi, and LV end-systolic dimension index. The association of LVGLS and mortality was consistent across all subgroups (P for interaction ≥ .08 for all). Spline curves showed that continuous risk for death rose at LVGLS < 15%. Those with LVGLS < 15% had a 2.6-fold risk for death (95% CI, 1.54-4.23) while those with LVGLS < 15% plus LVESVi ≥ 45 mL/m2 had 3.96-fold risk (95% CI, 1.94-8.03). CONCLUSIONS: In this large cohort of asymptomatic patients with moderate to severe or greater AR, automated LVGLS was feasible, efficient, and independently associated with death in head-to-head comparisons with conventional LV ejection fraction, LV end-systolic dimension index, and LVESVi. An automated LVGLS threshold of <15% alone or combined with LVESVi ≥ 45 mL/m2 was significantly associated with increased mortality risk and may be considered in early surgery decision-making.

The Mitral Annular Disjunction of Mitral Valve Prolapse: Presentation and Outcome.

OBJECTIVES: The aim of this study was to assess in patients with mitral valve prolapse (MVP) mitral annular disjunction (MAD) prevalence, phenotypic characteristics, and long-term outcomes (clinical arrhythmic events and excess mortality). BACKGROUND: Clinical knowledge regarding MAD of MVP remains limited and controversial, and its potential link with untoward outcomes is unsubstantiated. METHODS: A cohort of 595 (278 women, mean age 61 ± 16 years) consecutive patients with isolated MVP, with comprehensive clinical, rhythmic, Doppler echocardiographic, and consistent MAD assessment, were examined. MAD prevalence, associated MVP phenotypes, and outcomes (survival, clinical arrhythmic events) starting at diagnostic echocardiography were analyzed. To balance important baseline differences, propensity scoring matching was conducted among patients with and those without MAD. RESULTS: The presence of MAD was common (n = 186 [31%]) in patients with MVP, generally in younger patients, and was not random but was independently associated with severe myxomatous disease involving bileaflet MVP and marked leaflet redundancy (both P ≤ 0.0002). The presence of MAD was also independently associated with a larger left ventricle (P = 0.005). Age-matched cohort survival after MVP diagnosis was not worse with MAD (10-year survival 93% ± 2% for patients without MAD and 97% ± 1% for those with MAD; P = 0.40), even adjusted comprehensively for MVP characteristics (P = 0.80) and accounting for time-dependent mitral surgery (P = 0.60). During follow-up, 170 patients had clinical arrhythmic events (ventricular tachycardia, n = 159; arrhythmia ablation, n = 14; cardioverter-defibrillator implantation, n = 14; sudden cardiac death, n = 3). MAD was independently associated with higher risk for arrhythmic events (adjusted HR: 2.60; 95% CI: 1.87-3.62; P < 0.0001). The link between MAD and arrhythmic events persisted with time-dependent mitral surgery (adjusted HR: 2.54; 95% CI: 1.84-3.50; P < 0.0001), was strong under medical management (adjusted HR: 3.21; 95% CI: 2.03-5.06; P < 0.0001) but was weaker after mitral surgery (adjusted HR: 2.07; 95% CI: 1.24-3.43; P = 0.005). CONCLUSIONS: This large cohort with MVP comprehensively characterized shows that MAD is frequent at MVP diagnosis and is strongly linked to advanced myxomatous degeneration. The presence of MAD was independently associated with long-term excess incidence of clinical arrhythmic events. However, within the first 10 years post-diagnosis, MAD was not linked to excess mortality, and although reassurance should be provided from the survival point of view, careful monitoring for arrhythmias is in order for MAD.

Contemporary differences between bicuspid and tricuspid aortic valve in chronic aortic regurgitation.

OBJECTIVE: To comprehensively explore contemporary differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients with chronic haemodynamically significant aortic regurgitation (AR). METHODS: Consecutive patients with chronic ≥moderate-severe AR from a tertiary referral centre (2006-2017) were included. All-cause mortality, surgical indications and aortic valve surgery (AVS) were analysed. RESULTS: Of 798 patients (296 BAV-AR, age 46±14 years; 502 TAV-AR, age 67±14 years, p<0.0001) followed for 5.5 (IQR: 2.9-9.2) years, 403 underwent AVS (repair in 96) and 154 died during follow-up. The 8-year AVS incidence was 60%±3% versus 53%±3% for BAV-AR and TAV-AR, respectively (p=0.014). The unadjusted (real-life) 8-year total survival was 93%±7% versus 71%±2% for BAV-AR and TAV-AR, respectively (p<0.0001), and became statistically insignificant after sole adjustment for age (p=0.14). The within-group relative risk of death in BAV-AR patients demonstrated a large age-dependent increase (two fold at 50-55 years, up to 10-fold at 70 years). The presence of baseline symptoms was significantly associated with death for both BAV-AR (p=0.039) and TAV-AR (p<0.0001), but the strength of the association decreased with age adjustment for BAV-AR (age-adjusted HR 2.43 (0.92-6.39), p=0.07) and not for TAV-AR (age-adjusted HR, 2.3 (1.6-3.3), p<0.0001). As compared with general population, TAV-AR exhibited baseline excess risk which further increased at left ventricular ejection fraction (LVEF) <60% and left ventricular end-systolic dimension index (LVESDi) >20 mm/m2; similar thresholds were observed for BAV-AR patients. CONCLUSION: BAV-AR patients were two decades younger than TAV-AR and underwent AVS more frequently, resulting in a considerable real-life survival advantage for BAV-AR that was determined primarily by age and not valve anatomy. Pragmatically, regardless of valve anatomy, patients with haemodynamically significant AR and age >50-55 years require a low-threshold for surgical referral to prevent symptom development where LVEF <60% and LVESDi >20 mm/m2 seem appropriate referral thresholds.

Presentation and Outcome of Arrhythmic Mitral Valve Prolapse.

BACKGROUND: Mitral valve prolapse (MVP) is often considered benign but recent suggestion of an arrhythmic MVP (AMVP) form remains incompletely defined and uncertain. OBJECTIVES: This study determined ventricular arrhythmia prevalence, severity, phenotypical context, and independent impact on outcome in patients with MVP. METHODS: A cohort of 595 (age 65 ± 16 years; 278 women) consecutive patients with MVP and comprehensive clinical, arrhythmia (24-h Holter monitoring) and Doppler-echocardiographic characterization, was identified. Long-term outcomes were analyzed. RESULTS: Ventricular arrhythmia was frequent (43% with at least ventricular ectopy ≥5%), most often moderate (ventricular tachycardia [VT]; 120 to 179 beats/min) in 27%, and rarely severe (VT ≥180 beats/min) in 9%. Presence of ventricular arrhythmia was associated with male sex, bileaflet prolapse, marked leaflet redundancy, mitral annulus disjunction (MAD), a larger left atrium and left ventricular end-systolic diameter, and T-wave inversion/ST-segment depression (all p ≤ 0.001). Severe ventricular arrhythmia was independently associated with presence of MAD, leaflet redundancy, and T-wave inversion/ST-segment depression (all p < 0.0001) but not with mitral regurgitation severity or ejection fraction. Overall mortality after arrhythmia diagnosis (8 years; 13 ± 2%) was strongly associated with arrhythmia severity (8 years; 10 ± 2% for no/trivial, 15 ± 3% for mild and/or moderate, and 24 ± 7% for severe arrhythmia; p = 0.02). Excess mortality was substantial for severe arrhythmia (univariate hazard ratio [HR]: 2.70; 95% confidence interval [CI]: 1.27 to 5.77; p = 0.01 vs. no/trivial arrhythmia), even after it was comprehensively adjusted, including for MVP characteristics (adjusted HR: 2.94; 95% CI: 1.36 to 6.36; p = 0.006) and by time-dependent analysis (adjusted HR: 3.25; 95% CI: 1.56 to 6.78; p = 0.002). Severe arrhythmia was also associated with higher rates of mortality, defibrillator implantation, VT ablation (adjusted HR: 4.68; 95% CI: 2.45 to 8.92; p < 0.0001), particularly under medical management (adjusted HR: 5.80; 95% CI: 2.75 to 12.23; p < 0.0001), and weakly post-mitral surgery (adjusted HR: 3.69; 95% CI: 0.93 to 14.74; p = 0.06). CONCLUSIONS: In this large cohort of patients with MVP, ventricular arrhythmia by Holter monitoring was frequent but rarely severe. AMVP was independently associated with phenotype dominated by MAD, marked leaflet redundancy, and repolarization abnormalities. Long-term severe arrhythmia was independently associated with notable excess mortality and reduced event-free survival, particularly under medical management. Therefore, AMVP is a clinical entity strongly associated with outcome and warrants careful risk assessment and well-designed clinical trials.

Concomitant Mitral Regurgitation in Patients With Chronic Aortic Regurgitation.

BACKGROUND: Etiology, mechanisms, and survival of mitral regurgitation (MR) plus hemodynamically-significant chronic aortic regurgitation (AR) are mostly unknown. OBJECTIVES: The purpose of this study was to investigate the prevalence, mechanisms, etiologies, and survival impact of coexistent ≥ moderate MR in AR patients. METHODS: Consecutive patients with ≥ moderate-severe AR were retrospectively identified between 2004 and 2019. RESULTS: Of 1,239 eligible patients (61 ± 18 years, 80% men), 1,072 (86%) had pure AR, and 167 (14%) had AR + MR (9% functional mitral regurgitation [FMR] [84% nonischemic] and 5% organic mitral regurgitation [OMR] [62% degenerative]). At baseline transthoracic echocardiogram, pure AR versus AR + OMR versus AR + FMR exhibited differences in age (59 ± 18, 62 ± 16, and 73 ± 14 years, respectively), female sex (18%, 27%, and 39%, respectively), symptoms (36%, 41%, and 64%, respectively), atrial fibrillation (5%, 17%, and 36%, respectively), left ventricular (LV) ejection fraction (59%, 58%, and 46%, respectively), LV end-systolic dimension and volume index, ≥ moderate tricuspid regurgitation (TR) (7%, 35%, and 53%, respectively), and right ventricular systolic pressure (32 ± 11, 45 ± 15, and 50 ± 14 mm Hg, respectively), all p < 0.0001. After a median follow-up of 5.2 years (interquartile range: 2.2 to 10.0 years) and adjusting for demographics, New York Heart Association functional class, aortic valve surgery, LV ejection fraction, LV end-systolic dimension and volume index, presence of FMR was independently associated with all-cause mortality (p ≤ 0.004). Compared with pure AR, AR + MR + TR exhibited the highest adjusted risk of death (2.4-fold; p < 0.0001). When compared with expected population survival, excess mortality risks of pure AR, AR + OMR, and AR + FMR were 1.25-fold, 1.76-fold, and 2.34-fold, respectively (all p ≤ 0.02). CONCLUSIONS: In hemodynamically significant AR, coexistent MR is not uncommon (approximately 14%) and mostly comprises FMR and less commonly OMR. As compared with pure AR, AR + MR + TR exhibit the largest mortality risk. Both AR + OMR and AR + FMR carry a survival penalty compared with the general population, but AR + FMR is associated with the largest excess mortality and represents an advanced stage within the AR clinical spectrum.

Mitral Valve Prolapse Patients with Less than Moderate Mitral Regurgitation Exhibit Early Cardiac Chamber Remodeling.

BACKGROUND: Mild physiologic mitral regurgitation (MR) is common in normal individuals. Patients with primary MR due to mitral valve prolapse (MVP) may also exhibit less than moderate MR. We sought to determine whether MVP patients with less than moderate MR displayed early cardiac chamber remodeling or factors related to early remodeling and whether early remodeling predicted MR progression. METHODS: Consecutive MVP patients with less than moderate MR by proximal isovelocity surface area-derived effective regurgitant orifice < 20 mm2 and regurgitant volume < 30 mL, were matched for age and sex with non-MVP patients (controls) having less than moderate MR. Patients with moderate or greater dysfunctional left- or right-sided valves and left ventricular ejection fraction < 50% were excluded. We evaluated left ventricle (LV) and left atrium (LA) remodeling parameters (LV end-diastolic and end-systolic indexed diameters, LA volume-index, and LV mass-index) as well as determinants of remodeling. The last available transthoracic echocardiography was reviewed to identify progression to moderate-severe MR or more. RESULTS: A total of 253 MVP patients with less than moderate MR were matched to 344 controls (P for age and sex, ≥.18) with less than moderate MR. Patients with MVP (mean effective regurgitant orifice and regurgitant volume, 12 ± 4 mm2 and 18 ± 6 mL, respectively) had more premature ventricular contractions (PVCs), larger LV and LA remodeling parameters, and more mild-to-moderate MR (all P < .0001). Multivariate linear regression models showed that larger LV remodeling parameters were independently associated with MVP and female sex but not MR severity (all P < .0001). The LA volume index was independently associated with MVP, age, and E/e' (all P < .0001). The LV mass index was associated with MVP, age, and hypertension (all P ≤ .002). Presence of PVCs was associated with LV end-systolic diameter ≥ 40 mm and indexed ≥ 22 mm2 (P = .005). Among 323 (54%) patients having subsequent transthoracic echocardiography, 17 patients (all MVP) progressed to moderate-severe MR or more at a median of 4.3 (interquartile range, 1.7-6.4) years. Isolated posterior leaflet prolapse was the single factor associated with MR progression (adjusted hazard ratio, 2.70; 95% CI, 0.99-7.34; P = .048) after adjustment for MR severity. At a median of 5.9 (interquartile range, 4.6-7.2) years of follow-up, female sex and MVP (vs controls) were protective factors for mortality. CONCLUSIONS: Patients with less than moderate MR due to MVP exhibit early LV and LA remodeling, which does not predict MR progression or mortality. Left ventricle remodeling is associated with MVP, female sex, and presence of PVCs. Early chamber remodeling associated with MVP may be the phenotypical expression of a genetically mediated process and is at least partially related to PVCs.

Diastolic Blood Pressure and Heart Rate Are Independently Associated With Mortality in Chronic Aortic Regurgitation.

BACKGROUND: The prognostic significance of diastolic blood pressure (DBP) and resting heart rate (RHR) in patients with hemodynamically significant aortic regurgitation (AR) is unknown. OBJECTIVES: This study sought to investigate the association of DBP and RHR with all-cause mortality in patients with AR. METHODS: Consecutive patients with ≥ moderate to severe AR were retrospectively identified from 2006 to 2017. The association between all-cause mortality and routinely measured DBP and RHR was examined. RESULTS: Of 820 patients (age 59 ± 17 years; 82% men) followed for 5.5 ± 3.5 years, 104 died under medical management, and 400 underwent aortic valve surgery (AVS). Age, symptoms, left ventricular ejection fraction (LVEF), LV end-systolic diameter-index (LVESDi), DBP, and RHR were univariable predictors of all-cause mortality (all p ≤ 0.002). When adjusted for demographics, comorbidities, and surgical triggers (symptoms, LVEF, and LVESDi), baseline DBP (adjusted-hazard ratio [HR]: 0.79 [95% confidence interval: 0.66 to 0.94] per 10 mm Hg increase, p = 0.009) and baseline RHR (adjusted HR: 1.23 [95% confidence interval: 1.03 to 1.45] per 10 beat per min [bpm] increase, p = 0.01) were independently associated with all-cause mortality. These associations persisted after adjustment for presence of hypertension, medications, time-dependent AVS, and using average DBP and RHR (all p ≤ 0.02). Compared with the general population, patients with AR exhibited excess mortality (relative risk of death >1), which rose steeply in inverse proportion (p nonlinearity = 0.002) to DBP starting at 70 mm Hg and peaking at 55 mm Hg and in direct proportion to RHR starting at 60 bpm. CONCLUSIONS: In patients with chronic hemodynamically significant AR, routinely measured DBP and RHR demonstrate a robust association with all-cause death, independent of demographics, comorbidities, guideline-based surgical triggers, presence of hypertension, and use of medications. Therefore, DBP and RHR should be integrated into comprehensive clinical decision-making for these patients.

Predictors of Progression in Patients With Stage B Aortic Regurgitation.

BACKGROUND: The natural history of stage B aortic regurgitation (AR) is unknown. OBJECTIVES: This study sought to examine determinants, rate, and consequences of progression of AR. METHODS: Consecutive patients with ≤moderate chronic AR quantified by effective regurgitant orifice area (EROA) and regurgitant volume (RVol) from 2004 to 2017 who had ≥1 subsequent echocardiogram with quantitation were included. RESULTS: Of 1,077 patients (66 ± 15 years of age), baseline trivial/mild AR was noted in 196 (18%), mild-to-moderate AR in 465 (43%), and moderate AR in 416 (39%); 10-year incidence of progression to ≥moderate-severe AR (stage C/D; progressors) was 12%, 30%, and 53%, respectively. At 4.1-year follow-up (interquartile range: 2.1 to 7.2 years), there were 228 progressors (21%), whose annualized progression rates within 3 years before diagnosis of ≥moderate-severe AR were 4.2 mm2/year for EROA and 9.9 ml/year for RVol. Baseline AR severity and dimensions of sinotubular junction and annulus were associated with progression (all p ≤ 0.007); hypertension and systolic blood pressure were not. Progressors had faster chamber remodeling, functional class decline, and more aortic valve/aortic surgery. At medium-term follow-up, 242 patients (22%) died; poor survival was linked to age, comorbidities, functional class, resting heart rate, and left ventricular (LV) ejection fraction (p ≤ 0.003), not LV end-systolic dimension index. Survival after progression to stage C/D AR was associated with LV end-systolic dimension index (adjusted p = 0.02). CONCLUSIONS: Progression from stage B to stage C/D AR was observed in 21% patients. Repeat echocardiography for trivial/mild, mild-to-moderate, and moderate AR at every 5, 3, and 1 years, respectively, was reasonable. EROA, RVol, annulus, and sinotubular junction should be routinely measured to estimate progression rates and identify patients at high risk of progression, which was associated with adverse consequences.

Contemporary Etiologies, Mechanisms, and Surgical Approaches in Pure Native Aortic Regurgitation.

OBJECTIVE: To study contemporary etiologies, mechanisms, and corresponding surgical approaches in isolated aortic regurgitation (AR). PATIENTS AND METHODS: Consecutive patients undergoing surgery for moderately severe and severe AR were retrospectively identified from January 1, 2006, through October 20, 2017. Intraoperative echocardiograms, surgical reports, and pathology reports were reviewed. RESULTS: Of 382 patients (54±16 years, 82% men), there were 207 (54%) tricuspid (TAV), 167 (44%) bicuspid (BAV), 5 quadricuspid, and 3 unicuspid aortic valves. Isolated AR mechanisms (n=116, 30%) included cusp prolapse (n=44, 11%), restriction/retraction (n=33, 9%), aortic root dilatation (n=33, 9%), perforation (n=5, 1%), and fenestration (<1%); mixed mechanisms were present in 266 (70%). The most common mixed mechanism was root dilatation and prolapse (27% BAV vs 16% TAV, P=.01). Valve repair (AVr) was performed in 31% BAV and 23% TAV (P=.06). Aortic surgery was more common in BAV (37% vs 27%, P<.001). Overall, root dilatation was associated with AVr. In TAV, cusp prolapse and restriction/retraction were associated with replacement; in BAV, prolapse was associated with AVr. AR etiology was idiopathic in 43% TAV patients, 47% of whom had root dilatation. CONCLUSIONS: BAV accounted for 44% of surgical referrals for AR and, compared with TAV, was more often associated with prolapse, root dilatation, and mixed mechanisms of AR. Because mechanisms affected the choice of AVr differently in BAV and TAV, comprehensive mechanistic description of surgical AR is critical.

Outcomes in Chronic Hemodynamically Significant Aortic Regurgitation and Limitations of Current Guidelines.

BACKGROUND: Few data exist on the contemporary profiles and outcomes of patients with significant aortic regurgitation (AR). OBJECTIVES: This study sought to assess the benefits of aortic valve repair or replacement (AVR) and the prognostic value of left ventricular (LV) dimensions in significant AR. METHODS: From 2006 to 2017, consecutive patients with ≥moderate-severe chronic AR without prior heart surgery, myocardial infarction, or overt coronary artery disease were included. RESULTS: Of 748 participants (58 ± 17 years of age; 82% men), 387 (52%) were medically treated, and 361 (48%) had AVR. Of 361 patients having AVR, 334 (93%) met guideline criteria: Class I indications in 284 (79%) patients, which included symptoms in 236, and Class II indications in 50 (14%). The remaining 27 (7%) opted for surgery without Class I or II indications. At a median follow-up of 4.9 years (interquartile range: 2.3 to 8.3 years), 125 (17%) patients had died. Age, comorbidities, baseline symptoms, and higher LV end-systolic dimension index (LVESDi) were associated with all-cause mortality (all p ≤ 0.01). Compared with patients having LVESDi <20 mm/m2, those with LVESDi 20 to 25 mm/m2 (hazard ratio: 1.53; 95% confidence interval: 1.01 to 2.31) and ≥25 mm/m2 (HR: 2.23; 95% confidence interval: 1.32 to 3.77) had increased risks of death. AVR was associated with better survival (p < 0.0001). Patients with Class I indications for surgery had inferior post-operative survival (p < 0.003). CONCLUSIONS: Class I indications for surgery, mainly symptoms, are the most common triggers for AVR. Class II indications were associated with better post-operative outcome and thus merit more attention. LVESDi was the only LV parameter independently associated with all-cause mortality and the ideal cutoff seems to be lower than previously recommended.

Characteristics of Early and Late Adopting Hospitals Providing Percutaneous Coronary Intervention in Taiwan.

BACKGROUND: Studies in the United States suggested that the characteristics of hospitals providing percutaneous coronary intervention (PCI) differed from those not providing PCI. However, little is known on the differences between the characteristics of early-adopting hospitals and those of late-adopting hospitals, and on their potential impacts on PCI volume and access. METHODS AND RESULTS: We used inpatient claims data from 1997 to 2012 from the Taiwan National Health Insurance program to identify the hospitals offering PCI. Geographic information systems (GIS) were used to determine the population access to PCI hospital. As of 2012, 88 hospitals were capable of providing PCI. On the basis of the year that the hospitals started providing PCI, 32 hospitals were designated as early adopters (before 1998), 23 as early majority (1998-2002), 24 as late majority (2003-2007), and 16 as laggards (2008-2012). Hospitals that adopted PCI later were smaller in size and closer to an existing PCI hospital and had lower PCI volumes performed and less bypass surgery support. The median PCI volumes in 2012 were n=706, 330, 138, and 81 in early adopters, early majority, late majority, and laggards, respectively. Despite the low volume of PCI performed in laggard hospitals, the percentage with ST-elevation myocardial infarction and acute myocardial infarction as principal discharge diagnosis was higher than their early-adopting hospital counterparts. The percentage of the Taiwanese population living within 40 km of PCI hospitals (appropriate access defined in this study) was 95.7% in 1997 and 98.0% in 2002, and this has remained unchanged since 2002. CONCLUSIONS: The characteristics of early-adopting hospitals differed from those of late-adopting hospitals. Despite lower PCI volume performed in late-adopting hospitals, many of them are in remote areas and provide needed and timely services for patients with acute myocardial infarction.

Predictive value of left atrial deformation on prognosis in severe primary mitral regurgitation.

BACKGROUND: Impaired left atrial (LA) deformation is noted in patients with severe primary mitral regurgitation (MR), but its prognostic value is unknown. The aim of this study was to investigate the prognostic significance of LA deformation parameters in patients with chronic severe primary MR. METHODS: A total of 104 patients with asymptomatic chronic severe primary MR (Carpentier type II) and preserved left ventricular systolic function were prospectively recruited. Global peak positive strain of the left atrium (LASp) and strain rate in the LA filling phase (LASRr) as well as strain rate in the LA conduit phase were identified using two-dimensional speckle-tracking echocardiography. RESULTS: During a mean follow-up period of 13.2 ± 9.5 months, 22 patients reached a composite end point of death and mitral valve repair or replacement prompted by heart failure development. Among the clinical and echocardiographic parameters, LV end-systolic volume index (19.5 ± 9.5 vs 15.7 ± 6.3 mL/m(2), P = .028), LASp (22.7 ± 10.4% vs 27.2 ± 9.1%, P = .049), and LASRr (1.97 ± 0.6 vs 2.33 ± 0.6 1/sec, P = .013) varied between the two groups in terms of end points but not age, LA volume index, left ventricular ejection fraction, pulmonary artery systolic pressure, and presence of atrial fibrillation. After multivariate analysis, low LASp (odds ratio, 3.606; 95% CI, 1.294-10.052; P = .014) and low LASRr (odds ratio, 2.857; 95% CI, 1.078-7.572; P = .035) remained powerful outcome indicators. CONCLUSIONS: In patients with asymptomatic severe primary MR, reduced LASp and LASRr predicted a worse prognosis. These findings may offer additional information to guide early surgery.

Acute aortic regurgitation caused by spontaneous aortic valve rupture.

We report a rare case that manifested as severe aortic regurgitation (AR) resulting from spontaneous aortic valve (AV) rupture caused by valvular myxomatous transformation in a middle-aged woman. Before operation, 1 ruptured hole on the left coronary cusp (LLC) was clearly visualized with transesophageal echocardiography (TEE). There were no clinical findings of vegetations or sinus Valsalva aneurysms. The patient was treated successfully with mechanical AV replacement. Prompt imaging evaluation is mandatory in this rare critical situation for correct diagnosis and appropriate management.