A comparison between hospital follow‐up and collaborative follow‐up in patients with acute heart failure

AIMS: There are no previous studies focusing on collaborative follow-ups between hospitals and clinics for patients discharged after acute heart failure (AHF) in Japan. The purpose of this study was to determine the status of collaboration between hospitals and clinics for patients with AHF in Japan and to compare patient characteristics and clinical outcomes using a large Japanese observational database. METHODS AND RESULTS: Of 4056 consecutive patients hospitalized for AHF in the Kyoto Congestive Heart Failure registry, we analysed 2862 patients discharged to go home, who were divided into 1674 patients (58.5%) followed up at hospitals with index hospitalization (hospital follow-up group) and 1188 (41.5%) followed up in a collaborative fashion with clinics or other general hospitals (collaborative follow-up group). The primary outcome was a composite of all-cause death or heart failure (HF) hospitalization within 1 year after discharge. Previous hospitalization for HF and length of hospital stay longer than 15 days were associated with hospital follow-up. Conversely, ≥80 years of age, hypertension, and cognitive dysfunction were associated with collaborative follow-up. The cumulative 1-year incidence of the primary outcome, all cause death, and cardiovascular death were similar between the hospital and collaborative follow-up groups (31.6% vs. 29.6%, P = 0.51, 13.1% vs, 13.9%, P = 0.35, 8.4% vs. 8.2%, P = 0.96). Even after adjusting for confounders, the difference in risk for patients in the hospital follow-up group relative to those in the collaborative follow-up group remained insignificant for the primary outcome, all-cause death, and cardiovascular death (HR: 1.11, 95% CI: 0.97-1.27, P = 0.14, HR: 1.10, 95% CI: 0.91-1.33, P = 0.33, HR: 0.96, 95% CI: 0.87-1.05, P = 0.33). The cumulative 1-year incidence of HF hospitalization was higher in the hospital follow-up group than in the collaborative follow-up group (25.5% vs. 21.3%, P = 0.02). The risk of HF hospitalization was higher in the hospital follow-up group than in the collaborative follow-up group (HR: 1.19, 95% CI: 1.01-1.39, P = 0.04). CONCLUSIONS: In patients hospitalized for AHF, 41.5% received collaborative follow-up after discharge. The risk of HF hospitalization was higher in the hospital follow-up group than in the collaborative follow-up, although risk of the primary outcome, all-cause death, and cardiovascular death were similar between groups

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

AbstractBackgroundCurrent guidelines generally recommend watchful waiting until symptoms emerge for aortic valve replacement (AVR) in asymptomatic patients with severe aortic stenosis (AS).ObjectivesThe study sought to compare the long-term outcomes of initial AVR versus conservative strategies following the diagnosis of asymptomatic severe AS.MethodsWe 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 cm2) 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.ResultsBaseline 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).ConclusionsThe 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

A Risk Prediction Model in Asymptomatic Patients with Severe Aortic Stenosis under Conservative Management: CURRENT-AS risk score

Aims: 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. Methods and results: 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). Conclusion: 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

Long-Term Impact of Diabetes Mellitus on Initially Conservatively Managed Patients With Severe Aortic Stenosis

BACKGROUND: Although diabetes mellitus (DM) is a common comorbidity of aortic stenosis (AS), clinical evidence about the long-term effect of DM on patients with AS is insufficient.Methods and Results:Data were acquired from CURRENT AS, a large Japanese multicenter registry that enrolled 3, 815 patients with severe AS. Patients without initial valve replacement were defined as the conservative group; among them, 621 (23.4%) had DM, whereas 1997 did not. The DM group was further divided into 2 groups according to insulin treatment (insulin-treated DM, n=130; non-insulin treated DM, n=491). The primary outcome was a composite of aortic valve (AV)-related death and heart failure (HF) hospitalization. Secondary outcomes were AV-related death, HF hospitalization, all-cause death, cardiovascular death, sudden death, and surgical or transcatheter AV replacement during follow up. As a result, DM was associated with higher risk for the primary outcome (52.8% vs. 42.9%, P<0.001), with a statistically significant adjusted hazard ratio (HR 1.33, 95% confidence interval: 1.14-1.56, P<0.001). All secondary outcomes were not significantly different between DM and non-DM patients after adjusting for confounding factors, except for HF hospitalization. Insulin use was not associated with higher incidence of primary or secondary outcome. CONCLUSIONS: In initially conservatively managed patients with AS, DM was independently associated with higher risk for a composite of AV-related death or HF hospitalization; however, insulin use was not associated with poor outcomes

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

Background: There are limited data regarding the risk stratification based on peak aortic jet velocity (Vmax) in patients with severe aortic stenosis (AS). Methods and Results: Among 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). Conclusions: In 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

Transcatheter aortic valve implantation versus conservative management for severe aortic stenosis in real clinical practice

竹治, 泰明谷口, 智彦森本, 剛齋藤, 成達安藤, 献児白井, 伸一新井, 善雄坂口, 元一福, 康志川瀬, 裕一小宮, 達彦江原, 夏彦北井, 豪小山, 忠明渡邉, 真渡部, 宏俊塩見, 紘樹南野-牟田, 恵里松田, 真太郎夜久, 英憲芳川, 裕亮山﨑, 和裕川東, 正英坂本, 和久田村, 俊寛三宅, 誠阪口, 仁寿村田, 耕一郎中井, 真尚泉, 知里稲田, 司竹内, 泰代山根, 啓一郎田村, 崇豊福, 守石井, 充猪子, 森明池田, 智之石井, 克尚堀田, 幸造陣内, 俊和東谷, 暢也犬塚, 康孝湊谷, 謙司木村, 剛Background: Transcatheter aortic valve implantation (TAVI) is criticized by some as an expensive treatment in super-elder patients with limited life expectancy. However, there is a knowledge gap regarding the magnitude of clinical benefit provided by TAVI in comparison with conservative management in patients with severe aortic stenosis (AS) in real clinical practice, which would be important in the decision making for TAVI. Methods: We combined two independent registries, namely CURRENT AS and K-TAVI registries. CURRENT AS was a multicenter registry enrolling 3815 consecutive patients with severe AS irrespective to treatment modalities between January 2003 and December 2011. K-TAVI was a multicenter, prospective registry including 449 consecutive patients with severe AS, who underwent TAVI with SAPIEN XT balloon-expandable valves between October 2013 and June 2016. In these 2 registries, 449 patients received TAVI and 894 patients were managed with conservative strategy. We conducted propensity score matching and finally obtained a cohort of 556 patients (278 patients for each group) for the analysis. The primary outcome measures were all-cause death and heart failure (HF) hospitalization at 2-year. Results: The cumulative 2-year incidences of all-cause death and HF hospitalization were significantly lower in the TAVI group than in the conservative group (16.8% versus 36.6%, P<0.001, and 10.7% versus 37.2%, P<0.001). After adjusting the residual confounders, TAVI reduced the risks of all-cause death (HR, 0.46; 95%CI, 0.32–0.69; P = 0.0001) and HF hospitalizations (HR, 0.25; 95%CI, 0.16–0.40; P<0.0001) compared with conservative strategy. There was no difference in the cumulative incidence of non-cardiovascular death between the 2 groups. Conclusions: TAVI in the early Japanese experience was associated with striking risk reduction for all-cause death as well as HF hospitalization as compared with the historical cohort of patients with severe AS who were managed conservatively just before introduction of TAVI in Japan

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

Ryanodine receptor type 2 deficiency changes excitation–contraction coupling and membrane potential in urinary bladder smooth muscle

The possibility that the ryanodine receptor type 2 (RyR2) can function as the major Ca2+-induced Ca2+ release (CICR) channel in excitation–contraction (E-C) coupling was examined in smooth muscle cells (SMCs) isolated from urinary bladder (UB) of RyR2 heterozygous KO mice (RyR2+/−). RyR2 mRNA expression in UB from RyR2+/− was much lower than that in wild-type (RyR2plus;/plus;). In single UBSMCs from RyR2plus;/+, membrane depolarization under voltage clamp initially induced several local Ca2+ transients (hot spots) in peripheral areas of the cell. Then, Ca2+ waves spread from Ca2+ hot spots to other areas of the myocyte. The number of Ca2+ hot spots elicited by a short depolarization (< 20 ms) in UBSMCs of RyR2+/− was significantly smaller than in those of RyR2+/+. The force development induced either by direct electrical stimulation or by 10 μm acetylcholine in tissue segments of RyR2+/− was smaller than and comparable to those in RyR2+/+, respectively. The frequency of spontaneous transient outward currents in single myocytes and the membrane depolarization by 1 μm paxilline in tissue segments from RyR2+/− were significantly lower and smaller than those in RyR2+/+, respectively. The urination frequency and volume per voiding in RyR2+/− were significantly increased and reduced, respectively, compared with RyR2+/+. In conclusion, RyR2 plays a crucial role in the regulation of CICR during E-C coupling and also in the regulation of resting membrane potential, presumably via the modulation of Ca2+-dependent K+ channel activity in UBSMCs and, thereby, has a pivotal role in the control of bladder activity