Keiichiro Yamane

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

BACKGROUND Current guidelines generally recommend watchful waiting until symptoms emerge for aortic valve replacement (AVR) in asymptomatic patients with severe aortic stenosis (AS). OBJECTIVES The study sought to compare the long-term outcomes of initial AVR versus conservative strategies following the diagnosis of asymptomatic severe AS. METHODS We 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. RESULTS Baseline 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). CONCLUSIONS The 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).

In patients with heart failure and non-ischemic heart disease, cardiac troponin T is a reliable predictor of long-term echocardiographic changes and adverse cardiac events

BACKGROUND The relationships between (1) serum concentration of cardiac troponin T (cTnT) and clinical hemodynamic profiles, (2) cTnT versus B-type natriuretic peptide (BNP) and long-term echocardiographic changes, and (3) cTnT versus BNP and echocardiographic changes, and rates of adverse cardiac events, have not been well elucidated. METHODS Retrospective analysis of 100 consecutive patients with heart failure, left ventricular ejection fraction < 50%, and non-ischemic heart disease was performed. RESULTS Baseline cTnT was > or = 0.01 ng/ml in 30 patients. By multiple variable logistic regression analysis, diabetes mellitus [DM; odds ratio (OR) 7.5; p=0.014], serum creatinine (OR 25.9; p=0.0157), and pulmonary capillary wedge pressure (PCWP; OR 1.12; p=0.0214) were independent predictors of baseline elevation of cTnT. At a follow-up of 40.6+/-20.6 months, echocardiograms and cTnT and BNP measurements were available in 93 patients, of whom 23 experienced an adverse cardiac event. By multiple variable analyses, elevated cTnT at follow-up was negatively correlated with echocardiographic improvements in cardiac function (OR 0.10; p=0.019), and was a significant predictor of adverse cardiac events after adjustment for covariables, including follow-up BNP and echocardiographic changes (hazard ratio 5.6; p=0.0046). CONCLUSIONS DM, serum creatinine, and PCWP were correlated with elevated baseline serum cTnT concentrations. cTnT concentration during follow-up might be a surrogate marker of heart failure.

The clinical and hemodynamic factors that influence the concentrations of biomarkers of myocyte injury measured by high sensitive assay PATHFAST

BACKGROUND Subclinical myocyte injury plays an important role in the progression of congestive heart failure. However, the clinical and hemodynamic factors that influence the concentrations of biomarkers of myocyte injury have not been clarified. METHODS Blood was sampled during diagnostic cardiac catheterization from 108 consecutive patients without acute coronary syndrome and acute cardiac decompensation. The serum concentrations of B-type natriuretic peptide (BNP), cardiac troponin I (cTnI), creatine kinase (CK)-MB, and myoglobin were measured simultaneously by high sensitive PATHFAST assay. Single and multiple variable regression analyses were carried out in search of correlations between clinical and hemodynamic variables and concentrations of biomarkers. RESULTS By multiple variable analysis, hemoglobin concentration, pulmonary capillary wedge pressure (PCWP), left ventricular (LV) ejection fraction, and estimated glomerular filtration rate (GFR) were independently correlated with a BNP concentration ≥ median 72.1 pg/ml. The only factors independently correlated with a concentration of cTnI ≥ median 0.01 ng/ml were PCWP and estimated GFR. Cardiac index emerged as a single, powerful, independent correlate of CK-MB concentration ≥ median 0.66 ng/ml, and estimated GFR emerged as a single independent correlate of myoglobin concentration ≥ median 40.1 ng/ml. CONCLUSIONS Clinical and hemodynamic factors influence the concentrations of BNP, cTnI, CK-MB, and myoglobin. These factors should be considered when interpreting the concentrations of these biochemical markers.

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.

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 ―

BACKGROUND There is a paucity of data on the sex differences in the prevalence, clinical presentation, and prognosis of aortic stenosis (AS).Methods and Results: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). CONCLUSIONS A 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 ―

BACKGROUND 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). CONCLUSIONS 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.

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.

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

Aim To investigate the effect of malignancy on the outcomes of patients with severe aortic stenosis (AS) and the management strategy for AS with malignancy. Methods and results 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. Conclusions 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.