Norio Kanamori

Initial Surgical Versus Conservative Strategies in Patients With Asymptomatic Severe Aortic Stenosis.

BACKGROUNDnCurrent guidelines generally recommend watchful waiting until symptoms emerge for aortic valve replacement (AVR) in asymptomatic patients with severe aortic stenosis (AS).nnnOBJECTIVESnThe study sought to compare the long-term outcomes of initial AVR versus conservative strategies following the diagnosis of asymptomatic severe AS.nnnMETHODSnWe used data from a large multicenter registry enrolling 3,815 consecutive patients with severe AS (peak aortic jet velocity >4.0 m/s, or mean aortic pressure gradient >40 mm Hg, or aortic valve area <1.0 cm(2)) between January 2003 and December 2011. Among 1,808 asymptomatic patients, the initial AVR and conservative strategies were chosen in 291 patients, and 1,517 patients, respectively. Median follow-up was 1,361 days with 90% follow-up rate at 2 years. The propensity score-matched cohort of 582 patients (n = 291 in each group) was developed as the main analysis set for the current report.nnnRESULTSnBaseline characteristics of the propensity score-matched cohort were largely comparable, except for the slightly younger age and the greater AS severity in the initial AVR group. In the conservative group, AVR was performed in 41% of patients during follow-up. The cumulative 5-year incidences of all-cause death and heart failure hospitalization were significantly lower in the initial AVR group than in the conservative group (15.4% vs. 26.4%, p = 0.009; 3.8% vs. 19.9%, p < 0.001, respectively).nnnCONCLUSIONSnThe long-term outcome of asymptomatic patients with severe AS was dismal when managed conservatively in this real-world analysis and might be substantially improved by an initial AVR strategy. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140).

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

BACKGROUNDnThere is discordance regarding the effect of symptom status before aortic valve replacement (AVR) on long-term outcome after AVR in severe aortic stenosis (AS).Methodsu2004andu2004Results: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.nnnCONCLUSIONSnWhen 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.

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 (Nu2009=u20091197), and the conservative management cohort (Nu2009=u20092618). 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.

High- Versus Low-Gradient Severe Aortic Stenosis: Demographics, Clinical Outcomes, and Effects of the Initial Aortic Valve Replacement Strategy on Long-Term Prognosis

Background— There is considerable debate on the management of patients with low-gradient severe aortic stenosis (LG-AS), defined as aortic valve area <1 cm2 with peak aortic jet velocity ⩽4.0 m/s, and mean aortic pressure gradient ⩽40 mm Hg. Methods and Results— In the CURRENT AS registry (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis), there were 2097 patients (initial aortic valve replacement [AVR] strategy: n=977, and conservative strategy: n=1120) with high-gradient severe aortic stenosis (HG-AS) and 1712 patients (initial AVR strategy: n=219, and conservative strategy: n=1493) with LG-AS. AVR was more frequently performed in HG-AS patients than in LG-AS patients (60% versus 28%) during the entire follow-up. In the comparison between the initial AVR and conservative groups, the propensity score–matched cohorts were developed in both HG-AS (n=887 for each group) and LG-AS (n=218 for each group) strata. The initial AVR strategy when compared with the conservative strategy was associated with markedly lower risk for a composite of aortic valve–related death or heart failure hospitalization in both HG-AS and LG-AS strata (hazard ratio, 0.30; 95% confidence interval, 0.25–0.37; P<0.001 and hazard ratio, 0.46; 95% confidence interval, 0.32–0.67; P<0.001, respectively). Among 1358 patients with LG-AS with preserved left ventricular ejection fraction, the initial AVR strategy was associated with a better outcome than the conservative strategy (adjusted hazard ratio, 0.37; 95% confidence interval, 0.23–0.59; P<0.001). Conclusions— The initial AVR strategy was associated with better outcomes than the conservative strategy in both HG-AS and LG-AS patients, although AVR was less frequently performed in LG-AS patients than in HG-AS patients. The favorable effect of initial AVR strategy was also seen in patients with LG-AS with preserved left ventricular ejection fraction. Clinical Trial Registration— URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000012140.

Sex Differences in Severe Aortic Stenosis ― Clinical Presentation and Mortality ―

BACKGROUNDnThere is a paucity of data on the sex differences in the prevalence, clinical presentation, and prognosis of aortic stenosis (AS).Methodsu2004andu2004Results:A total of 3,815 consecutive patients with severe AS were enrolled in the multicenter CURRENT AS registry between January 2003 and December 2011. The registry included 1,443 men (38%) and 2,372 women (62%). Women were much older than men (79±10 vs. 75±10 years, P<0.0001), and the ratio of women to men increased with age. The cumulative 5-year incidence of all-cause death was significantly higher in men than in women (47% vs. 41%, P=0.003), although women were more symptomatic and much older. The 5-year mortality was similar between men and women at age <65 years (16% vs. 15%, P=0.99), whereas it was significantly higher in men than in women at age ≥65 years (65-74 years, 38% vs. 19%, P<0.0001; 75-84 years, 55% vs. 34%, P<0.0001; ≥85 years: 82% vs. 72%, P=0.03).nnnCONCLUSIONSnA large Japanese multicenter registry of consecutive patients with severe AS included a much higher proportion of women than men, with the female:male sex ratio increasing with age. The 5-year mortality rate of women was lower than that of men. Lower 5-year mortality rates in women were consistently seen across all age groups >65 years.

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

BACKGROUNDnClinical profiles of acute heart failure (AHF) complicating severe aortic stenosis (AS) remain unclear.Methodsu2004andu2004Results: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).nnnCONCLUSIONSnAHF 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.

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

Background The 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 Results We 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). Conclusions The 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.

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: Nu2009=u2009813, syncope: Nu2009=u2009136, and angina: Nu2009=u2009266) 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%, Pu2009<u20090.001). 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, Pu2009<u20090.001). 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.

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

AimnTo investigate the effect of malignancy on the outcomes of patients with severe aortic stenosis (AS) and the management strategy for AS with malignancy.nnnMethods and resultsnUsing 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 (nu2009=u2009124) 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 (nu2009=u2009389) 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 (nu2009=u20093302). 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: nu2009=u200916, conservative management: nu2009=u2009108) was determined based on the clinical status of AS or life expectancy.nnnConclusionsnMalignancy 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.