RESUMO
INTRODUCTION: The aim of the current study was to elucidated the reliable atrial fibrillation (AF) drivers identified by CARTOFINDER using OctaRay catheter. METHODS AND RESULTS: The reliability of focal and rotational activations identified by CARTOFINDER using OctaRay catheter was assessed by the sequential recordings in each site of both atrium before and after pulmonary vein isolation (PVI) in 10 persistent AF patients. The outcome measures were the reproducibility rate during the sequential recordings and the stability rate between pre- and post-PVI as reliable focal and rotational activations. The study results were compared with those under use of PentaRay catheter (N = 18). Total 68928 points of 360 sites in OctaRay group and 24 177 points of 311 sites in PentaRay were assessed. More focal activation sites were identified in OctaRay group than PentaRay group (7.9% vs. 5.7%, p < .001), although the reproducibility rate and the stability rate were significantly lower in OctaRay group (45.3% vs. 58.9%, p < .001; 11.2% vs. 28.4%, p < .001). Meanwhile, the prevalence of reproducible focal activation sites among overall points was comparable (3.6% vs. 3.3%, p = .08). Regarding rotational activation, more rotational activation sites were identified in OctaRay group (5.1% vs. 0.2%, p < .001), and the reproducibility rate and the stability rate were significantly higher in OctaRay group (45.2% and 12.5% vs. 0.0%, p < .001). Both reliable focal and rotational activation sites were characterized by significantly shorter AF-cycle length (CL) and higher repetition of focal and rotational activations during the recordings compared with the sites of non or unreliable focal and rotational activations. CONCLUSION: In CARTOFINDER, OctaRay catheter could identify reliable focal activation with high resolution and reliable rotational activation compared with PentaRay catheter. The repetitive focal and rotational activations with short AF-CL could be the potential target during ablation.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Frequência Cardíaca , Reprodutibilidade dos Testes , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Técnicas Eletrofisiológicas Cardíacas/métodos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/etiologia , Catéteres , Veias Pulmonares/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: The clinical significance of concomitant mitral regurgitation (MR) has not been well addressed in patients with severe aortic stenosis (AS).MethodsâandâResults: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). CONCLUSIONS: Concomitant moderate/severe MR was not independently associated with higher risk for the primary outcome measure regardless of the initial treatment strategy.
Assuntos
Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/epidemiologia , Sistema de Registros , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Cardiac sympathetic innervation is critically involved in the regulation of circulatory dynamics. However, the molecular mechanism for the innervation patterning has remained elusive. Here, we demonstrate that nardilysin (NRDC, Nrdc), an enhancer of ectodomain shedding, regulates cardiac sympathetic innervation. Nardilysin-deficient (Nrdc-/- ) mice show hypoplastic hearts, hypotension, bradycardia, and abnormal sympathetic innervation patterning. While the innervation of left ventricle (LV) of wild-type mice is denser in the subepicardium than in the subendocardium, Nrdc-/- LV lacks such a polarity and is uniformly and more abundantly innervated. At the molecular level, the full-length form of p75 neurotrophin receptor (p75NTR , Ngfr) is increased in Nrdc-/- LV due to the reduced ectodomain shedding of p75NTR . Importantly, the reduction of p75NTR rescued the abnormal innervation phenotype of Nrdc-/- mice. Moreover, sympathetic neuron-specific, but not cardiomyocyte-specific deletion of Nrdc recapitulated the abnormal innervation patterning of Nrdc-/- mice. In conclusion, neuronal nardilysin critically regulates cardiac sympathetic innervation and circulatory dynamics via modulation of p75NTR .
Assuntos
Coração/inervação , Metaloendopeptidases/genética , Receptor de Fator de Crescimento Neural/genética , Sistema Nervoso Simpático/metabolismo , Animais , Pressão Sanguínea/genética , Pressão Sanguínea/fisiologia , Bradicardia/genética , Bradicardia/fisiopatologia , Células Cultivadas , Ecocardiografia , Coração/fisiopatologia , Frequência Cardíaca/genética , Frequência Cardíaca/fisiologia , Metaloendopeptidases/deficiência , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/metabolismo , Células PC12 , Ratos , Receptor de Fator de Crescimento Neural/deficiência , Sistema Nervoso Simpático/citologia , Sistema Nervoso Simpático/fisiopatologiaRESUMO
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.MethodsâandâResults: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.
Assuntos
Estenose da Valva Aórtica , Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Insulinas , Substituição da Valva Aórtica Transcateter , Estenose da Valva Aórtica/cirurgia , Diabetes Mellitus/epidemiologia , Humanos , Sistema de Registros , Fatores de Risco , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: This study aimed to evaluate the effect of the initial aortic valve replacement (AVR) strategy relative to a conservative strategy on long-term outcomes stratified by age among asymptomatic patients with severe aortic stenosis (AS).MethodsâandâResults:Among 1,808 asymptomatic severe AS patients in the CURRENT AS registry, there were 1,166 patients aged ≥75 years (initial AVR: n=124, and conservative: n=1,042), and 642 patients with age <75 years (initial AVR: n=167, and conservative: n=475). Median follow-up interval was 1,280 (interquartile range [IQR]: 1,012-1,611) days, and 1461 (IQR: 1,132-1,886) days in patients aged ≥ and <75 years, respectively. The favorable effect of the initial AVR strategy relative to conservative strategy for heart failure (HF) hospitalization was seen regardless of the age stratum (≥75 years: adjusted hazard ratio [HR] 0.13, 95% confidence interval [CI] 0.05-0.34, and <75 years: HR 0.37, 95% CI 0.14-0.99, interaction P=0.35). However, the lower mortality risk of the initial AVR strategy relative to conservative strategy was significant in patients aged ≥75 years, but not in patients <75 years, with significant interaction (HR 0.35, 95% CI 0.20-0.61, and HR 0.69, 95% CI 0.41-1.16, interaction P=0.016). CONCLUSIONS: The benefit of initial AVR in reducing HF hospitalization in asymptomatic patients with severe AS was consistently seen regardless of age. The magnitude of mortality benefit of initial AVR was greater in super-elder patients than in non-super-elder patients.
Assuntos
Estenose da Valva Aórtica/terapia , Tratamento Conservador , Implante de Prótese de Valva Cardíaca , Hemodinâmica , Tempo para o Tratamento , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/fisiopatologia , Doenças Assintomáticas , Tratamento Conservador/efeitos adversos , Tratamento Conservador/mortalidade , Feminino , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/instrumentação , Implante de Prótese de Valva Cardíaca/mortalidade , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: There are no data comparing transcatheter aortic valve implantation (TAVI) with surgical aortic valve replacement (SAVR) outcomes in real clinical practice in Japan. METHODSâANDâRESULTS: We combined 2 independent registries, the K-TAVI Registry (a 6-center prospective registry of consecutive patients who underwent TAVI) and the CURRENT AS Registry (a large, 27-center registry of 3,815 consecutive patients with severe aortic stenosis [AS]). In the K-TAVI Registry, 338 patients underwent TAVI with SAPIEN XT balloon-expandable valves from October 2013 to January 2016, whereas in the CURRENT AS Registry 237 patients with severe AS underwent SAVR from January 2003 to December 2011. Propensity score matching was conducted, with final cohort comprising 306 patients. The cumulative 2-year incidence of all-cause death and heart failure (HF) hospitalization did not differ significantly between the TAVI and SAVR groups (13.7% vs. 12.4% [P=0.81] and 7.9% vs 3.9% [P=0.13], respectively). After adjusting for residual confounders, there were no significant differences between the TAVI and SAVR groups in the risk for all-cause death (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.35-1.58; P=0.43) or HF hospitalization (HR 1.27; 95% CI 0.40-4.59; P=0.69). CONCLUSIONS: These findings from 2 independent Japanese registries suggest that the 2-year risk of all-cause mortality and HF does not differ significantly between TAVI and SAVR groups in real-world practice in Japan.
Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca , Substituição da Valva Aórtica Transcateter , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/fisiopatologia , Feminino , Insuficiência Cardíaca/etiologia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/mortalidade , Humanos , Japão , Masculino , Recuperação de Função Fisiológica , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/mortalidade , Resultado do TratamentoRESUMO
BACKGROUND: There has not been a previous report on the long-term outcomes of those patients who refuse aortic valve replacement (AVR) despite physicians' recommendations.MethodsâandâResults: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). CONCLUSIONS: 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.
Assuntos
Estenose da Valva Aórtica/terapia , Tomada de Decisão Clínica , Tratamento Conservador , Seleção de Pacientes , Padrões de Prática Médica , Recusa do Paciente ao Tratamento , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/fisiopatologia , Feminino , Nível de Saúde , Implante de Prótese de Valva Cardíaca , Humanos , Japão , Masculino , Prognóstico , Encaminhamento e Consulta , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de TempoRESUMO
BACKGROUND: Clinical profiles of acute heart failure (AHF) complicating severe aortic stenosis (AS) remain unclear.MethodsâandâResults: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.
Assuntos
Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/etiologia , Insuficiência Cardíaca/etiologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/terapia , Feminino , Próteses Valvulares Cardíacas , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Fatores de RiscoRESUMO
BACKGROUND: There is a paucity of data on the sex differences in the prevalence, clinical presentation, and prognosis of aortic stenosis (AS).MethodsâandâResults: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.
Assuntos
Estenose da Valva Aórtica/mortalidade , Sistema de Registros , Caracteres Sexuais , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores SexuaisRESUMO
OBJECTIVE: The frozen lesion formation created by cryoballoon ablation, especially with non-occluded applications, has not been fully evaluated. This study aimed to validate the lesion size under different cryoballoon ablation settings: application duration, push-up technique, and laminar flow. METHODS: The frozen lesion size was evaluated immediately after ending the freezing with three different application durations (120, 150, and 180 seconds) in porcine hearts (N = 24). During the application, the push-up technique was applied at 10, 20, and 30 seconds after starting the freezing with or without laminar flow. RESULTS: The lesion size was significantly correlated with the nadir balloon temperature (P<0.001). The lesion volume became significantly larger after 150 seconds than 120 seconds (1272mm3 versus 1709mm3, P = 0.004), but not after 150 seconds (versus 1876mm3 at 180 seconds, P = 0.29) with a comparable nadir balloon temperature. Furthermore, the lesion volume became significantly larger with the push-up technique with the largest lesion size with a 20-second push-up after the freezing (1193mm3 without the push-up technique versus 1585mm3 with a push-up at 10 seconds versus 1808mm3 with a push-up at 20 seconds versus 1714mm3 with a push-up at 30 seconds, P = 0.04). Further, the absence of laminar flow was not associated with larger lesion size despite a significantly lower nadir balloon temperature. CONCLUSION: The frozen lesion size created by cryoballoon ablation became larger with longer applications at least 150 seconds and with a push-up technique especially at 20 seconds after the freezing.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Criocirurgia , Veias Pulmonares , Animais , Suínos , Congelamento , Ablação por Cateter/métodos , Veias Pulmonares/cirurgia , Criocirurgia/métodos , Temperatura , Fibrilação Atrial/cirurgia , Resultado do TratamentoRESUMO
AIMS: Intracardiac dynamics during atrial fibrillation(AF) complicated by heart failure(HF) are not fully understood. The aim of this study was to evaluate the impact of intracardiac dynamics assessed by echo-vector flow mapping on AF complicated by HF. METHODS AND RESULTS: We enrolled 76 AF patients receiving sinus restoration therapy and assessed energy loss(EL) by echo-vector flow mapping during both AF rhythm and sinus rhythm. Patients were divided into 2 groups according to serum NT-proBNP level: high NT-proBNP group(≥1800 pg/ml during AF rhythm: N = 19), and low NT-proBNP group(N = 57). Outcome measures were average ELs/stroke volume(SV) in left ventricle(LV) and left atrium(LA). Average EL/SVs during AF rhythm in the LV and LA were significantly larger in the high NT-proBNP group than the low NT-proBNP group(54.2 mE/m·L versus 41.2 mE/m·L, P = 0.02; 3.2 mE/m·L versus 1.9 mE/m·L, P = 0.01). The significantly larger EL/SV in the high NT-proBNP group was recorded for maximum EL/SVs. In patients with high NT-proBNP, large vortex formation with extreme EL was detected in the LV and LA during the diastolic phase. After sinus restoration, the average decrease of EL/SV in the LV and LA was larger in the high NT-proBNP group(-21.4 mE/m·L versus +2.6 mE/m·L, P = 0.04; -1.6 mE/m·L versus -0.3 mE/m·L, P = 0.02). Average EL/SV during sinus rhythm did not significantly differ between the high and low NT-proBNP groups in the LV and LA. CONCLUSIONS: High EL during AF rhythm as intracardiac energy inefficiency was associated with high serum NT-proBNP levels and improved after sinus restoration.
Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Humanos , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/complicações , Mercaptoetanol , Biomarcadores , Insuficiência Cardíaca/diagnóstico por imagem , Peptídeo Natriurético Encefálico , Átrios do Coração , Fragmentos de PeptídeosRESUMO
BACKGROUND: There 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). METHODS: We 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. RESULTS: The cumulative 5-year incidence of the primary outcome measure was significantly higher in patients with AF than in those without AF (44.2â¯% versus 33.2â¯%, HR 1.54, 95â¯% CI 1.35-1.76). After adjusting for confounders, the risk of AF relative to no AF remained significant (HR 1.34, 95â¯% 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 (Nâ¯=â¯1197, HR 1.95, 95â¯% CI 1.36-2.78) than in the conservative stratum (Nâ¯=â¯2618, HR 1.26, 95â¯% CI 1.08-1.47) with a significant interaction (pâ¯=â¯0.04). In patients with AF, there was a significant excess adjusted risk of paroxysmal AF (Nâ¯=â¯254) relative to chronic AF (Nâ¯=â¯528) for the primary outcome measure (HR 1.34, 95â¯% CI 1.01-1.78). CONCLUSIONS: In 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.
Assuntos
Estenose da Valva Aórtica , Fibrilação Atrial , Implante de Prótese de Valva Cardíaca , Substituição da Valva Aórtica Transcateter , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/epidemiologia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Resultado do Tratamento , Valva Aórtica/cirurgia , Fatores de Risco , Substituição da Valva Aórtica Transcateter/efeitos adversosRESUMO
Brown adipose tissue (BAT) dissipates chemical energy as heat through uncoupling protein 1 (UCP1). The induction of mitochondrial reactive oxygen species (ROS) in BAT was recently identified as a mechanism that supports UCP1-dependent thermogenesis. We previously demonstrated that nardilysin (NRDC) plays critical roles in body temperature homeostasis. Global NRDC-deficient (Nrdc-/-) mice show hypothermia due to a lower set point for body temperature, whereas BAT thermogenesis at room temperature (RT) is enhanced mainly to compensate for poor thermal insulation. To examine the primary role of NRDC in BAT thermogenesis, we generated adipocyte-specific NRDC-deficient (Adipo-KO) mice by mating Nrdc floxed (Nrdcflox/flox) mice with adiponectin-Cre mice. Adipo-KO mice showed hyperthermia at both RT and thermoneutrality. They were also more cold-tolerant than Nrdcflox/flox mice. However, UCP1 mRNA levels were significantly lower in Adipo-KO BAT at RT, thermoneutrality, and 4 °C, whereas no significant differences were observed in UCP1 protein levels at RT and 4 °C. We examined the protein stability of UCP1 using the cycloheximide chase assay and found that NRDC negatively regulated its stability via the ubiquitin-proteasome pathway. NRDC may be also involved in ROS-mediated in vivo thermogenesis because the inhibitory effects of N-acetyl cysteine, an ROS scavenger, on ß3 agonist-induced thermogenesis were stronger in Adipo-KO mice. Collectively, the present results demonstrate that NRDC in BAT controls adaptive thermogenesis and body temperature homeostasis possibly via the regulation of UCP1 protein stability and ROS levels.
Assuntos
Regulação da Temperatura Corporal , Metaloendopeptidases , Termogênese , Proteína Desacopladora 1 , Adipócitos/metabolismo , Tecido Adiposo Marrom/metabolismo , Animais , Temperatura Corporal , Regulação da Temperatura Corporal/fisiologia , Metaloendopeptidases/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Espécies Reativas de Oxigênio/metabolismo , Termogênese/genética , Proteína Desacopladora 1/biossíntese , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismoRESUMO
Two randomized control trials demonstrated that transcatheter aortic valve implantation was associated with 1-2 year 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: 75 years versus 74 years, 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.
Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Próteses Valvulares Cardíacas , Sistema de Registros , Substituição da Valva Aórtica Transcateter/métodos , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/epidemiologia , Causas de Morte/tendências , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
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.
Assuntos
Estenose da Valva Aórtica/diagnóstico , Valva Aórtica/cirurgia , Doenças Assintomáticas , Implante de Prótese de Valva Cardíaca/métodos , Próteses Valvulares Cardíacas , Sistema de Registros , Função Ventricular Esquerda/fisiologia , Idoso , Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/cirurgia , Ecocardiografia , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores de TempoAssuntos
Algoritmos , Ablação por Cateter , Taquicardia por Reentrada no Nó Atrioventricular , Humanos , Taquicardia por Reentrada no Nó Atrioventricular/cirurgia , Taquicardia por Reentrada no Nó Atrioventricular/fisiopatologia , Taquicardia por Reentrada no Nó Atrioventricular/diagnóstico , Ablação por Cateter/métodos , Eletrocardiografia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Nó Atrioventricular/fisiopatologia , Nó Atrioventricular/cirurgia , Sistema de Condução Cardíaco/fisiopatologiaRESUMO
OBJECTIVES: The 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. BACKGROUND: No previous study has explored the association between LVEF decline during follow-up and clinical outcomes in patients with severe AS. METHODS: Among 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. RESULTS: There 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). CONCLUSIONS: Patients 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).
Assuntos
Estenose da Valva Aórtica/terapia , Tratamento Conservador , Volume Sistólico , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Idoso , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/fisiopatologia , Progressão da Doença , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/epidemiologiaRESUMO
OBJECTIVES: We sought to evaluate the prognostic impact of the B-type natriuretic peptide (BNP) levels in patients with asymptomatic severe aortic stenosis (AS), who were not referred for aortic valve replacement (AVR). METHODS: We used data from a Japanese multicentre registry, the Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis Registry, which enrolled 3815 consecutive patients with severe AS. Of those, 387 asymptomatic patients who were not referred for AVR without left ventricular dysfunction and very severe AS were subdivided into four groups based on their BNP levels (BNP<100 pg/mL, n=201; 100≤BNP<200 pg/mL, n=94; 200≤BNP<300 pg/mL, n=42 and BNP>300 pg/mL, n=50). RESULTS: The cumulative 5-year incidence of AS-related events (aortic valve-related death or heart failure hospitalisation) was incrementally higher with increasing BNP level (14.2%, 29.6%, 46.3% and 47.0%, p<0.001). After adjusting for confounders, the risk for AS-related events was incrementally greater with increasing BNP levels (HR: 1.97, 95% CI: 0.97 to 3.98, p=0.06; HR: 3.59, 95% CI: 1.55 to 8.32, p=0.03 and HR: 7.38, 95% CI: 3.21 to 16.9, p<0.001, respectively). Notably, asymptomatic patients with BNPlevels of <100 pg/mL had an event rate of only 2.1% at 1 year. CONCLUSIONS: Increased BNP level was associated with a higher risk for AS-related adverse events in patients with asymptomatic severe AS with normal left ventricular ejection fraction who were not referred for AVR. Asymptomatic patients with BNP levels of <100 pg/mL had relatively low event rate, who might be safely followed with watchful waiting strategy. TRAIL REGISTRATION NUMBER: UMIN000012140.
Assuntos
Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Medição de Risco/métodos , Idoso , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/mortalidade , Doenças Assintomáticas , Biomarcadores/sangue , Causas de Morte , Ecocardiografia/métodos , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Hospitalização/estatística & dados numéricos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros/estatística & dados numéricos , Índice de Gravidade de DoençaRESUMO
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.
Assuntos
Anemia/mortalidade , Estenose da Valva Aórtica/mortalidade , Anemia/sangue , Anemia/etiologia , Anemia/cirurgia , Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/cirurgia , Estudos Transversais , Seguimentos , Sistema de Registros , Índice de Gravidade de Doença , Taxa de SobrevidaRESUMO
Background Data 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 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 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). Conclusions AVA ≤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 Registration URL: www.umin.ac.jp . Unique identifier: UMIN000012140.