CURRENT Aortic Stenosis Registry Research Articles

Life Expectancy of Patients With Severe Aortic Stenosis in Relation to Age and Surgical Risk Score

BackgroundThere is a paucity of data regarding shorter life expectancy after aortic valve replacement (AVR) in patients with severe aortic stenosis (AS). MethodsAmong 3815 patients with severe AS enrolled in the CURRENT AS (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) registry, there were 1469 patients (initial AVR: n = 647; conservative strategy: n = 822) with low surgical risk, 1642 patients (initial AVR: n = 433; conservative strategy: n = 1209) with intermediate surgical risk, and 704 patients (initial AVR: n = 117; conservative strategy: n = 587) with high surgical risk. Among 1163 patients who actually underwent surgical AVR as the initial strategy, patients were divided into 4 groups according to age <65 years (n = 185), 65 to 74 (n = 394), 75 to 80 (n = 345), and >80 (n = 239). The expected survival of the general Japanese population was obtained from the Statistics Bureau of Japan. The surgical risk was estimated using The Society of Thoracic Surgery (STS) score. ResultsThe median follow-up was 3.7 years. The cumulative incidences of all-cause death were significantly lower in the initial AVR strategy than in the initial conservative strategy across the 3 STS groups. Shorter life expectancy after surgical AVR was seen especially in younger patients. The observed mortality in low-risk patients was comparable to the expected mortality across all the age-groups, while intermediate-risk patients aged <75 years, and high-risk patients across all age-groups had higher mortality compared with the expected mortality. ConclusionsThe risk stratification according to age and STS score might be useful to estimate shorter life expectancy after AVR, and these findings have implications for decision making in the choice of surgical or transcatheter AVR.

Atrial fibrillation in patients with severe aortic stenosis

BackgroundThere has been no previous report evaluating the long impact of atrial fibrillation (AF) on the clinical outcomes stratified by the initial management [conservative or aortic valve replacement (AVR)] strategies of severe aortic stenosis (AS). MethodsWe analyzed 3815 patients with severe AS enrolled in the CURRENT AS registry. Patients with AF were defined as those having a history of AF when severe AS was found on the index echocardiography. The primary outcome measure was a composite of aortic valve–related death or hospitalization for heart failure. ResultsThe cumulative 5-year incidence of the primary outcome measure was significantly higher in patients with AF than in those without AF (44.2 % versus 33.2 %, HR 1.54, 95 % CI 1.35–1.76). After adjusting for confounders, the risk of AF relative to no AF remained significant (HR 1.34, 95 % CI 1.16–1.56). The magnitude of excess adjusted risk of AF for the primary outcome measure was greater in the initial AVR stratum (N = 1197, HR 1.95, 95 % CI 1.36–2.78) than in the conservative stratum (N = 2618, HR 1.26, 95 % CI 1.08–1.47) with a significant interaction (p = 0.04). In patients with AF, there was a significant excess adjusted risk of paroxysmal AF (N = 254) relative to chronic AF (N = 528) for the primary outcome measure (HR 1.34, 95 % CI 1.01–1.78). ConclusionsIn patients with severe AS, concomitant AF was independently associated with worse clinical outcomes regardless of the initial management strategies. In those patients with conservative strategy, paroxysmal AF is stronger risk factor than chronic AF.

Concomitant Mitral Regurgitation in Severe Aortic Stenosis - A Report From the CURRENT AS Registry.

The clinical significance of concomitant mitral regurgitation (MR) has not been well addressed in patients with severe aortic stenosis (AS).Methods and Results:We analyzed 3,815 patients from a retrospective multicenter registry of severe AS in Japan (CURRENT AS registry). We compared the clinical outcomes between patients with moderate/severe MR and with none/mild MR according to the initial treatment strategy (initial aortic valve replacement [AVR] or conservative strategy). The primary outcome measure was a composite of aortic valve-related death or heart failure hospitalization. At baseline, moderate/severe MR was present in 227/1,197 (19%) patients with initial AVR strategy and in 536/2,618 (20%) patients with a conservative strategy. The crude cumulative 5-year incidence of the primary outcome measure was significantly higher in patients with moderate/severe MR than in those with none/mild MR, regardless of the initial treatment strategy (25.2% vs. 14.4%, P<0.001 in the initial AVR strategy, and 63.3% vs. 40.7%, P<0.001 in the conservative strategy). After adjusting confounders, moderate/severe MR was not independently associated with higher risk for the primary outcome measure in the initial AVR strategy (hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.67-1.83, P=0.69), and in the conservative strategy (HR 1.13, 95% CI 0.93-1.37, P=0.22). Concomitant moderate/severe MR was not independently associated with higher risk for the primary outcome measure regardless of the initial treatment strategy.

Abstract 9493: Differences in Prognostic Implications of Changes in Echocardiography in Asymptomatic Severe Aortic Stenosis Managed Conservatively

Background: No previous study has explored the association between the changes in echocardiographic parameters during follow-up and clinical outcomes in patients with asymptomatic severe aortic stenosis (AS) and who were managed conservatively. Objective: This study aimed to investigate the prognostic impact of the changes in echocardiographic parameter at 1-year follow-up in asymptomatic severe AS patients managed conservatively. Methods: Among 3815 patients with severe AS enrolled in the multicenter CURRENT AS registry in Japan, we analyzed conservatively managed 555 patients who underwent echocardiography at 1-year follow-up and remained asymptomatic. The primary outcome measure was a composite of AS-related deaths and hospitalization due to heart failure. A decline in left ventricular ejection fraction (LVEF), an increase in left ventricular end-diastolic dimension (LVEDD), and an increase in aortic valve pressure gradient (PG) were defined as above 10%, 5mm, and 30mmHg, respectively, based on the clinically relevant values. Results: There were 61 patients (11.0 %) with &gt;10% decline in LVEF and 494 patients (89.0%) without decline. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the decline in LVEF group than in no decline in LVEF group. After adjusting for confounders, the excess risk of the decline in LVEF relative to no decline in LVEF for the primary outcome measure remained significant (hazard ratio; 2.76, 95% confidence interval 1.66-4.45). The cumulative 3-year incidence of the primary outcome measure was significantly higher in the increase in LVEDD group than in no increase in LVEDD group. In contrast, there were no difference in cumulative 3-year incidence of the primary outcome measure between the increase in aortic valve PG and no increase group. Conclusions: Severe asymptomatic AS patients with a &gt;10% LVEF decline or &gt;5mm increase in LVEDD at 1-year after diagnosis had worse AS-related clinical outcome than those without under conservative management, whereas there were no differences in the outcomes stratified by changes in aortic valve PG. This indicated the importance in the LV morphology and function during follow-up in asymptomatic severe AS patients when managed conservatively.

Impact of concomitant mitral regurgitation in severe aortic stenosis in Japan – from the CURRENT AS registry

Abstract Background Clinical significance of concomitant mitral regurgitation (MR) in patients with severe aortic stenosis (AS) has not been well-studied. Purpose The purpose of this study is to investigate the prognostic impact of concomitant MR in patients with severe AS. Method We used the data of 3815 patients from the CURRENT AS registry, a retrospective multicenter registry of severe AS in Japan. We compared the clinical outcomes between patients with moderate/severe MR and with none/mild MR according to the initial treatment strategies (initial aortic valve replacement [AVR] or conservative strategy). The primary outcome measure was a composite of aortic valve-related death and heart failure hospitalisation. Results Among the study population, moderate/severe MR were observed in 227/1197 (19%) patients with initial AVR strategy and in 536/2618 (20%) patients with conservative strategy. Among survivors with the initial AVR strategy, moderate/severe MR improved in 61/62 (98%) patients with concomitant mitral procedures. The crude cumulative 5-year incidence of the primary outcome measure was significantly higher in patients with moderate/severe MR than in those with none/mild MR regardless of the treatment strategies (25.2% vs. 14.4%, P&amp;lt;0.001 in the initial AVR strategy; 63.3% vs 40.7%, P&amp;lt;0.001 in the conservative strategy). Multivariate analysis revealed moderate/severe MR at index echocardiography was independently associated with higher risk for the primary outcome measure in conservative strategy (adjusted HR 1.20, 95% CI 1.03–1.40, P=0.023), but not associated in the initial AVR strategy (adjusted HR 1.20, 95% CI 0.82–1.80, P=0.339). Conclusion Moderate/severe MR was independently associated with poorer outcome in patients with severe AS who were managed conservatively, but not in those with initial AVR strategy. Funding Acknowledgement Type of funding source: None

Clinical outcome after surgical aortic valve replacement in low-risk Japanese patients with severe aortic stenosis.

Two randomized control trials demonstrated that transcatheter aortic valve implantation was associated with 1-2year clinical outcomes comparable or even superior to surgical aortic valve replacement (SAVR) in low surgical risk patients with severe aortic stenosis (AS). However, no previous study has reported the clinical outcomes after SAVR in Japanese patients with low surgical risk. From 3815 consecutive patients enrolled in the CURRENT AS registry, we retrieved 220 patients who underwent SAVR in reference to the inclusion and exclusion criteria of the PARTNER 3 trial. Age and surgical risk score in the current study population were comparable to those in the PARTNER 3 trial (Age: 75years versus 74years, and STS-PROM score: 2.3 versus 1.9). The cumulative incidence of a composite all-cause death or stroke was comparable between the current study population and the SAVR patients in the PARTNER 3 trial both at 30-day (2.3% versus 3.3%), and at 1-year (4.1% versus 4.9%). The clinical outcomes of SAVR in low surgical risk patients with severe AS selected from a real world Japanese registry according to the inclusion and exclusion criteria of the PARTNER 3 trial was favorable and numerically comparable to those of SAVR patients in the PARTNER 3 trial.

Decline in Left Ventricular Ejection Fraction During Follow-Up in Patients With Severe Aortic Stenosis

ObjectivesThe aim of this study was to investigate the prognostic impact of the decline in left ventricular ejection fraction (LVEF) at 1-year follow-up in patients with severe aortic stenosis (AS) managed conservatively. BackgroundNo previous study has explored the association between LVEF decline during follow-up and clinical outcomes in patients with severe AS. MethodsAmong 3,815 patients with severe AS enrolled in the multicenter CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry in Japan, 839 conservatively managed patients who underwent echocardiography at 1-year follow-up were analyzed. The primary outcome measure was a composite of AS-related deaths and hospitalization for heart failure. ResultsThere were 91 patients (10.8%) with >10% declines in LVEF and 748 patients (89.2%) without declines. Left ventricular dimensions and the prevalence of valve regurgitation and atrial fibrillation or flutter significantly increased in the group with declines in LVEF. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the group with declines in LVEF than in the group with no decline (39.5% vs. 26.5%; p < 0.001). After adjusting for confounders, the excess risk of decline in LVEF over no decline for the primary outcome measure remained significant (hazard ratio: 1.98; 95% confidence interval: 1.29 to 3.06). When stratified by LVEF at index echocardiography (≥70%, 60% to 69%, and <60%), the risk of decline in LVEF on the primary outcome was consistently seen in all the subgroups, without any interaction (p = 0.77). ConclusionsPatients with severe AS with >10% declines in LVEF at 1 year after diagnosis had worse AS-related clinical outcomes than those without declines in LVEF under conservative management. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140)

Reasons for Choosing Conservative Management in Symptomatic Patients With Severe Aortic Stenosis - Observations From the CURRENT AS Registry.

There has not been a previous report on the long-term outcomes of those patients who refuse aortic valve replacement (AVR) despite physicians' recommendations.Methods and Results:Among 3,815 consecutive patients with severe aortic stenosis (AS) enrolled in the CURRENT AS registry, the study population comprised 2,005 symptomatic patients, who were subdivided into 3 groups by their treatment strategy and the reasons for conservative strategy (Initial AVR group: n=905; Patient rejection group: n=256; Physician judgment group, n=844). The primary outcome measure was a composite of aortic valve-related death and heart failure hospitalization. Patients in the patient rejection group as compared with those in the physician judgment group were younger, and had less comorbidities, and lower surgical risk scores. The cumulative 5-year incidence of the primary outcome measure in the patient rejection group was markedly higher than that in the initial AVR group, and was similar to that in the physician judgment group (60.7%, 19.0%, and 66.4%, respectively). Patient rejection was the reason for non-referral to AVR in nearly one-quarter of the symptomatic patients with severe AS who were managed conservatively. The dismal outcome in patients who refused AVR was similar to that in patients who were not referred to AVR based on physician judgment despite less comorbidities and lower surgical risk scores in the former than in the latter.

A risk prediction model in asymptomatic patients with severe aortic stenosis: CURRENT-AS risk score.

Early aortic valve replacement (AVR) might be beneficial in selected high-risk asymptomatic patients with severe aortic stenosis (AS), considering their poor prognosis when managed conservatively. This study aimed to develop and validate a clinical scoring system to predict AS-related events within 1 year after diagnosis in asymptomatic severe AS patients. We analysed 1274 asymptomatic severe AS patients derived from a retrospective multicentre registry enrolling consecutive patients with severe AS in Japan (CURRENT AS registry), who were managed conservatively and completed 1-year follow-up without AVR. From a randomly assigned derivation set (N = 849), we developed CURRENT AS risk score for the AS-related event (a composite of AS-related death and heart failure hospitalization) within 1 year using a multivariable logistic regression model. The risk score comprised independent risk predictors including left ventricular ejection fraction <60%, haemoglobin ≤11.0 g/dL, chronic lung disease (2 points), diabetes mellitus, haemodialysis, and any concomitant valve disease (1 point). The predictive accuracy of the model was good with the area under the curve of 0.79 and 0.77 in the derivation and validation sets (N = 425). In the validation set, the 1-year incidence of AS-related events was much higher in patients with score ≥2 than in patients with score ≤1 (Score 0: 2.2%, Score 1: 1.9%, Score 2: 13.4%, Score 3: 14.3%, and Score ≥4: 22.7%, P < 0.001). The CURRENT-AS risk score integrating clinical and echocardiographic factors well-predicted the risk of AS-related events at 1 year in asymptomatic patients with severe AS and was validated internally.

Anemia in Patients with Severe Aortic Stenosis

Prognostic impact of anemia complicating severe aortic stenosis (AS) remains unclear. We assessed the impact of anemia on cardiovascular and bleeding outcomes in 3403 patients enrolled in the CURRENT AS registry. 835 patients (25%) had mild (hemoglobin 11.0–12.9 g/dl for men/11.0–11.9 g/dl for women) and 1282 patients (38%) had moderate/severe anemia (Hb ≤ 10.9 g/dl) at diagnosis of severe AS. Mild and moderate/severe anemia were associated with significantly increased risks relative to no anemia (hemoglobin ≥13.0 g/dl for men/≥12.0 g/dl for women) for the primary outcome measure (aortic valve-related death or heart failure hospitalization) in the entire population [hazard ratio (HR): 1.30; 95% confidence interval (CI): 1.07–1.57 and HR: 1.56; 95%CI: 1.31–1.87, respectively] and in the conservative management stratum (HR: 1.73; 95%CI: 1.40–2.13 and HR: 2.05; 95%CI: 1.69–2.47, respectively). Even in the initial aortic valve replacement stratum, moderate/severe anemia was associated with significantly increased risk for the primary outcome measure (HR: 2.12; 95%CI: 1.44–3.11). Moreover, moderate/severe anemia was associated with significantly increased risk for major bleeding while under conservative management (HR: 1.93; 95%CI: 1.21–3.06). These results warrant further study to explore whether better management of anemia would lead to improvement of clinical outcomes.

Prognostic Impact of Aortic Valve Area in Conservatively Managed Patients With Asymptomatic Severe Aortic Stenosis With Preserved Ejection Fraction.

BackgroundData are scarce on the role of aortic valve area (AVA) to identify those patients with asymptomatic severe aortic stenosis (AS) who are at high risk of adverse events. We sought to explore the prognostic impact of AVA in asymptomatic patients with severe AS in a large observational database.Methods and ResultsAmong 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the present study included 1309 conservatively managed asymptomatic patients with left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on AVA (group 1: AVA >0.80 cm2, N=645; group 2: 0.8 cm2 ≥AVA >0.6 cm2, N=465; and group 3: AVA ≤0.6 cm2, N=199). The prevalence of very severe AS patients (peak aortic jet velocity ≥5 m/s or mean aortic pressure gradient ≥60 mm Hg) was 2.0%, 5.8%, and 26.1% in groups 1, 2, and 3, respectively. The cumulative 5‐year incidence of AVR was not different across the 3 groups (39.7%, 43.7%, and 39.9%; P=0.43). The cumulative 5‐year incidence of the primary outcome measure (a composite of aortic valve–related death or heart failure hospitalization) was incrementally higher with decreasing AVA (24.1%, 29.1%, and 48.1%; P<0.001). After adjusting for confounders, the excess risk of group 3 and group 2 relative to group 1 for the primary outcome measure remained significant (hazard ratio, 2.21, 95% CI, 1.56–3.11, P<0.001; and hazard ratio, 1.34, 95% CI, 1.01–1.78, P=0.04, respectively).ConclusionsAVA ≤0.6 cm2 would be a useful marker to identify those high‐risk patients with asymptomatic severe AS, who might benefit from early AVR.Clinical Trial RegistrationURL: www.umin.ac.jp. Unique identifier: UMIN000012140.

Asymptomatic versus Symptomatic Patients with Severe Aortic Stenosis

It is unknown how much different are the clinical outcomes between asymptomatic and symptomatic patients with severe aortic stenosis (AS). In the CURRENT AS registry enrolling 3,815 consecutive patients with severe AS, we compared the long-term outcomes between 1808 asymptomatic and 1215 symptomatic patients (exertional dyspnea: N = 813, syncope: N = 136, and angina: N = 266) without heart failure (HF) hospitalization. Symptomatic patients had greater AS severity, and more depressed left ventricular function than asymptomatic patients without much difference in other baseline characteristics. During a median follow-up of 3.2 years, aortic valve replacement (AVR) was performed in 62% of symptomatic patients, and 38% of asymptomatic patients. The cumulative 5-year incidences for the primary outcome measure (a composite of aortic valve-related death or HF hospitalization) was higher in symptomatic patients than in asymptomatic patients (32.3% versus 27.6%, P < 0.001). After adjusting for AVR and other variables, the greater risk of symptomatic relative to asymptomatic patients for the primary outcome measure was significant (hazard ratio 1.64, 95% confidence interval 1.41–1.96, P < 0.001). In conclusions, the excess risk of symptomatic relative to asymptomatic patients with severe AS for the aortic valve-related event was significant. However, the prevalence of AVR in symptomatic patients was not optimal.

Sudden Death in Patients With Severe Aortic Stenosis: Observations From the CURRENT AS Registry.

BackgroundThe annual incidence of sudden death has been reported to be low (<1%/year) in asymptomatic patients with severe aortic stenosis (AS), and there is a paucity of data on the risk factors of sudden death in patients with severe AS.Methods and ResultsWe evaluated the incidence and risk factors of sudden death during the median follow‐up period of 1334 days in the Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis (CURRENT AS) registry enrolling 3815 consecutive patients with severe AS between 2003 and 2011. The mean age was 78 years, and the prevalences of male sex and prior myocardial infarction were 38% and 8%, respectively. Sudden death occurred in 175 patients without aortic valve replacement. The cumulative 5‐year incidences of sudden death, censored at aortic valve replacement, which accounted for the competing risk, were 9.2% in symptomatic patients and 7.2% (1.4%/year) in asymptomatic patients (P<0.001). Among 82 asymptomatic patients experiencing sudden death, 54 patients (66%) died abruptly without any preceding symptoms, and 35 (65%) of these sudden deaths occurred within 3 months of the last clinical follow‐up visit. Independent risk factors for sudden death were hemodialysis (hazard ratio [HR] 3.63; 95% confidence interval [CI] 2.42‐5.43), prior myocardial infarction (HR 2.11; 95% CI 1.28‐3.50), body mass index <22 (HR 1.51; 95% CI 1.03‐2.21), peak aortic jet velocity ≥5 m/s (HR 1.76; 95% CI 1.12‐2.78), and left ventricular ejection fraction <60% (HR 1.52; 95% CI 1.08‐2.14).ConclusionsThe incidence of sudden death in asymptomatic patients with severe AS might be higher than that reported in previous reports. Several baseline clinical and echocardiographic characteristics were associated with increased risk of sudden death.Clinical Trial Registration URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000012140.

Malignant disease as a comorbidity in patients with severe aortic stenosis: clinical presentation, outcomes, and management.

To investigate the effect of malignancy on the outcomes of patients with severe aortic stenosis (AS) and the management strategy for AS with malignancy. Using data of 3815 patients with severe AS in a retrospective multicentre registry [CURRENT AS (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) registry], we compared 3-year clinical outcomes among three groups based on malignancy status: with malignancy currently under treatment including best supportive care (malignancy group), with a history of malignancy without any current treatment (past history group), or without history of malignancy (no malignancy group). Patients in the malignancy group (n = 124) were more often men and had higher prevalence of low body mass index, recurrence of malignancy, anaemia, and asymptomatic status, despite comparable surgical risks and echocardiographic parameters. The malignancy group or the past history group (n = 389) had significantly higher risk for all-cause death [hazard ratio (HR) 2.49, 95% CI (95% confidence interval) 1.98-3.14; HR 1.23, 95% CI 1.04-1.46] and for malignancy-related death (HR 16.2, 95% CI 10.64-24.54; HR 3.66, 95% CI 2.43-5.52) than that of the no malignancy group (n = 3302). The excess risk for aortic valve-related death was not observed in the malignancy group (HR 0.79, 95% CI 0.48-1.29) and was lower in the past history group (HR 0.72, 95% CI 0.53-0.96). In the malignancy group, the treatment strategy (surgery: n = 16, conservative management: n = 108) was determined based on the clinical status of AS or life expectancy. Malignancy had marked effect on all-cause death and malignancy-related death in patients with severe AS. History of malignancy also had a smaller but significant effect on mortality.

Prognostic Impact of Left Ventricular Ejection Fraction in Patients With Severe Aortic Stenosis

ObjectivesThe aim of this study was to evaluate the prognostic impact of left ventricular ejection fraction (LVEF) in patients with severe aortic stenosis (AS). BackgroundThe prognostic impact of LVEF in severe AS remains controversial. MethodsAmong 3,815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the present study population consisted of 3,794 patients after excluding 21 patients without LVEF data. Patients were divided into 4 groups according to LVEF at index echocardiography (<50%, 50% to 59%, 60% to 69%, and ≥70%; conservative strategy: n = 388, n = 390, n = 1,025, and n = 800; initial aortic valve replacement strategy: n = 206, n = 170, n = 375, and n = 440). Echocardiographic data were site reported, and there was no echocardiography core laboratory. ResultsIn the conservative group, the cumulative 5-year incidence of the primary outcome measure (a composite of aortic valve–related death or heart failure hospitalization) was significantly higher in patients with LVEFs <50% and 50% to 59% than in those with LVEFs 60% to 69% and ≥70% (72.3%, 58.4%, 38.7%, and 35.0%, respectively, p < 0.001), whereas in the initial aortic valve replacement group, the negative effect of low LVEF was markedly attenuated (20.2%, 20.3%, 17.7%, and 12.4%, respectively, p = 0.03). After adjusting for confounders, LVEF <50% (hazard ratio: 1.82; 95% confidence interval: 1.44 to 2.28; p < 0.001) and 50% to 59% (hazard ratio: 1.77; 95% confidence interval: 1.42 to 2.20; p < 0.001) but not 60% to 69% (hazard ratio: 1.14; 95% confidence interval: 0.94 to 1.39; p = 0.17) were independently associated with poorer outcomes compared with LVEF ≥70% (reference) in the conservative group. In the initial aortic valve replacement group, the adjusted risk for the primary outcome measure was not significantly different across the 4 LVEF groups. ConclusionsThis study demonstrates that survival in patients with severe AS is impaired when LVEF is <60%, and these findings have implications for decision making with regard to the timing of surgical intervention.

Causes of Death in Patients with Severe Aortic Stenosis: An Observational study

Whether patients with severe aortic stenosis (AS) die because of AS-related causes is an important issue for the management of these patients. We used data from CURRENT AS registry, a Japanese multicenter registry, to assess the causes of death in severe AS patients and to identify the factors associated with non-cardiac mortality. We enrolled 3815 consecutive patients with a median follow-up of 1176 days; the 1449 overall deaths comprised 802 (55.3%) from cardiac and 647 (44.7%) from non-cardiac causes. Heart failure (HF) (25.7%) and sudden death (13.0%) caused the most cardiac deaths, whereas infection (13.0%) and malignancy (11.1%) were the main non-cardiac causes. According to treatment strategies, infection was the most common cause of non-cardiac death, followed by malignancy, in both the initial aortic valve replacement (AVR) cohort (N = 1197), and the conservative management cohort (N = 2618). Both non-cardiac factors (age, male, body mass index <22, diabetes, prior history of stroke, dialysis, anemia, and malignancy) and cardiac factors (atrial fibrillation, ejection fraction <68%, and the initial AVR strategy) were associated with non-cardiac death. These findings highlight the importance of close monitoring of non-cardiac comorbidities, as well as HF and sudden death, to improve the mortality rate of severe AS patients.

Acute Heart Failure in Patients With Severe Aortic Stenosis - Insights From the CURRENT AS Registry.

Clinical profiles of acute heart failure (AHF) complicating severe aortic stenosis (AS) remain unclear.Methods and Results:From a Japanese multicenter registry enrolling consecutive patients with severe AS, 3,813 patients were categorized into the 3 groups according to the symptom of heart failure (HF); No HF (n=2,210), chronic HF (CHF) (n=813) and AHF defined as hospitalized HF at enrolment (n=790). Median follow-up was 1,123 days with 93% follow-up rate at 2 years. Risk factors for developing AHF included age, female sex, lower body mass index, untreated coronary artery stenosis, anemia, history of HF, left ventricular ejection fraction <50%, presence of any combined valvular disease, peak aortic jet velocity ≥5 m/s and tricuspid regurgitation pressure gradient ≥40 mmHg, and negative risk factors included dyslipidemia, history of percutaneous coronary intervention and hemodialysis. Respective cumulative 5-year incidences of all-cause death and HF hospitalization in No HF, CHF and AHF groups were 37.1%, 41.8% and 61.8% (P<0.001) and 20.7%, 33.8% and 52.3% (P<0.001). Even in the initial aortic valve replacement (AVR) stratum, AHF was associated with excess 5-year mortality risk relative to No HF and CHF (adjusted hazard ratio [HR] 1.64; 95% confidence interval [CI]: 1.14-2.36, P=0.008; adjusted HR 1.47; 95% CI: 1.03-2.11, P=0.03, respectively). AHF complicating severe AS was associated with an extremely dismal prognosis, which could not be fully resolved by AVR. Careful management to avoid the development of AHF is crucial.

Prognostic Impact of Peak Aortic Jet Velocity in Conservatively Managed Patients With Severe Aortic Stenosis: An Observation From the CURRENT AS Registry

BackgroundThere are limited data regarding the risk stratification based on peak aortic jet velocity (Vmax) in patients with severe aortic stenosis (AS).Methods and ResultsAmong 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the study population consisted of 1075 conservatively managed patients with Vmax ≥4.0 m/s and left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on Vmax (group 1, 4.0 ≤ Vmax <4.5 m/s, N=550; group 2, 4.5 ≤ Vmax <5 m/s, N=279; and group 3, Vmax ≥5 m/s, N=246). Cumulative 5‐year incidence of AS‐related events (aortic valve–related death or heart failure hospitalization) was incrementally higher with increasing Vmax (entire population; 38.0%, 49.4%, and 62.8%, P<0.001; symptomatic patients; 55.7%, 60.9%, and 72.2%, P=0.008; and asymptomatic patients; 29.4%, 38.9%, and 47.7%, P=0.005). After adjusting for confounders, the excess risk of group 2 and group 3 relative to group 1 for AS‐related events remained significant (hazard ratio, 1.39; 95% CI, 1.07–1.81; P=0.02, and hazard ratio, 1.53; 95% CI, 1.17–2.00; P=0.002, respectively). The effect size of group 3 relative to group 1 for AS‐related events in asymptomatic patients (N=479) was similar to that in symptomatic patients (N=596; hazard ratio, 1.59; 95% CI, 1.01–2.52; P=0.047, and hazard ratio, 1.67; 95% CI, 1.16–2.40, P=0.008, respectively), and there was no significant overall interaction between the symptomatic status and the effect of the Vmax categories on AS‐related events (interaction, P=0.88).ConclusionsIn conservatively managed severe AS patients with preserved left ventricular ejection fraction, increasing Vmax was associated with incrementally higher risk for AS‐related events. However, the cumulative 5‐year incidence of the AS‐related events remained very high even in asymptomatic patients with less greater Vmax.

Five-Year Clinical Outcome of Asymptomatic vs. Symptomatic Severe Aortic Stenosis After Aortic Valve Replacement

There is discordance regarding the effect of symptom status before aortic valve replacement (AVR) on long-term outcome after AVR in severe aortic stenosis (AS).Methods and Results:The CURRENT AS registry is a multicenter retrospective registry enrolling 3,815 consecutive patients with severe AS. Among 1,196 patients managed with the initial AVR strategy, long-term clinical outcomes were compared between the symptomatic patients (n=905), and asymptomatic patients (n=291). Median follow-up interval was 1337 days with a 91% follow-up rate at 2 years. AVR was performed in 886 patients (98%) in the symptomatic group and in 287 patients (99%) in the asymptomatic group. Symptomatic patients were older and more often had comorbidities than asymptomatic patients with similar echocardiographic AS severity. The cumulative 5-year incidences of all-cause death and heart failure (HF) hospitalization were significantly higher in symptomatic patients than in asymptomatic patients (25.6% vs. 15.4%, P=0.001, and 14.2% vs. 3.8%, P<0.001, respectively). On landmark analysis at 30 days after AVR, the differences in mortality and HF hospitalization between the 2 groups were mainly observed beyond 30 days. When managed with the initial AVR strategy, the long-term outcomes of symptomatic severe AS were worse than those of asymptomatic severe AS. Early AVR strategy might be recommended in some selected asymptomatic severe AS patients with reasonable operative risk.

Different clinical outcomes in patients with asymptomatic severe aortic stenosis according to the stage classification: Does the aortic valve area matter?

BackgroundThe ACC/AHA guidelines introduced a new classification of severe aortic stenosis (AS) mainly based on maximum jet velocity (Vmax) and mean pressure gradient (mPG), but not on aortic valve area (AVA). However, prognostic value of this new classification has not yet been fully evaluated. Methods and resultsWe studied 1512 patients with asymptomatic severe AS enrolled in the CURRENT AS registry in whom surgery was not initially planned. Patients were divided into 2 groups: Group 1 (N=122) comprised patients who met the recommendation for surgery; high-gradient (HG)-AS (Vmax≥4.0m/s or mPG≥40mmHg) with ejection fraction (EF)<50%, or very HG-AS (Vmax≥5.0m/s or mPG≥60mmHg), and Group 2 (N=1390) comprised patients who did not meet this recommendation. Group 2 was further subdivided into HG-AS with preserved EF (HGpEF-AS, N=498) and low-gradient (LG)-AS, but AVA<1.0cm2 (N=892). The excess risk of Group 1 relative to Group 2 for the primary outcome measure (a composite of aortic valve-related death or heart failure hospitalization) was significant (adjusted HR: 1.92, 95%CI: 1.37–2.68, P<0.001). The excess risk of HGpEF-AS relative to LG-AS for the primary outcome measure was also significant (adjusted HR: 1.45, 95%CI: 1.11–1.89, P=0.006). Among LG-AS patients, patients with reduced EF (<50%) (LGrEF-AS, N=103) had extremely high cumulative 5-year incidence of all-cause death (85.5%). ConclusionTrans-aortic valve gradient in combination with EF was a good prognostic marker in patients with asymptomatic AS. However, patients with LGrEF-AS had extremely poor prognosis when managed conservatively.