RESUMO
BACKGROUND: Polypharmacy in elderly patients with various comorbidities is associated with mortality and morbidity. However, the prognostic impact of polypharmacy in patients with severe aortic stenosis receiving trans-catheter aortic valve replacement remains unknown. METHODS: Patients with severe aortic stenosis who received trans-catheter aortic valve replacement between 2015 and 2022 and were followed up at our institute following index discharge were included in this retrospective study. The impact of polypharmacy, which was defined as medication numbers ≥10 at index discharge, upon 2-year all-cause death was investigated. RESULTS: A total of 345 patients (median age 85 [83, 89] years old, 99 (29%) men) were included. Median medication number was 9 (7, 10) at the index discharge and 88 (26%) were classified as receiving polypharmacy. Frailty index, including mini-mental state examination and CSHA score, were not significantly different between those with and without polypharmacy (p > 0.05 for both). Polypharmacy was associated with higher 2-year cumulative mortality with an adjusted hazard ratio of 21.4 (95% confidence interval, 6.06-74.8, p < 0.001). As a sub-analysis, the number of cardiovascular medications was not associated with 2-year mortality (hazard ratio 1.12, 95% confidence interval 0.86-1.48, p = 0.46), whereas a higher number of non-cardiovascular medications was associated with an incremental increase in 2-year mortality with a hazard ratio of 1.39 (95% confidence interval, 1.15-1.63, p < 0.001). CONCLUSIONS: In elderly patients with severe aortic stenosis, polypharmacy was associated with worse short-term survival following trans-catheter aortic valve replacement. Prognostic implication of aggressive intervention to decrease the amount of medication among those receiving TAVR requires further prospective studies.
RESUMO
Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors might improve renal anemia maintaining fewer cardiovascular complications. However, its safety and efficacy, as well as its impact on inflammatory biomarkers, in heart failure patients remain unknown. We initiated HIF-PH inhibitors in 13 patients with chronic heart failure and renal anemia (median age 77 years, median estimated glomerular filtration rate 24.9 mL/min/1.73m2) between September 2021 and February 2022. There were no drug-related complications, except for a patient who had a headache and hot flash, resulting in discontinuation of HIF-PH inhibitor at 3 months. Among 10 patients who continued HIF-PH inhibitors for over 3 months, hemoglobin levels increased significantly (median from 9.6 g/dL to 10.7 g/dL, p = 0.004) and hepcidin-25 levels tended to decrease (median from 11.5 ng/mL to 3.0 ng/mL, p = 0.294) at 3-month follow-up. In conclusion, HIF-PH inhibitors might be safe and effective for the treatment of renal anemia in patients with chronic heart failure.
Assuntos
Anemia , Insuficiência Cardíaca , Inibidores de Prolil-Hidrolase , Insuficiência Renal Crônica , Humanos , Idoso , Inibidores de Prolil-Hidrolase/uso terapêutico , Prolil Hidroxilases , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Prolina Dioxigenases do Fator Induzível por Hipóxia , Anemia/etiologia , Anemia/complicações , Doença Crônica , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Hipóxia/complicaçõesRESUMO
BACKGROUND: Mortality following transcatheter aortic valve replacement (TAVR) in patients with post-procedural left ventricular systolic dysfunction remains high. We investigated clinical variables associating with worse clinical outcomes following TAVR in patients with systolic dysfunction. METHODS: We retrospectively investigated 2588 patients with severe aortic stenosis who received TAVR and were enrolled in the optimized transcatheter valvular intervention (OCEAN-TAVI) multicenter registry (UMIN000020423). The association between the clinical variables following TAVR and 2-year cardiovascular mortality was investigated among those with post-TAVR left ventricular ejection fraction less than 50%. RESULTS: A total of 298 patients (median 85 years old, 131 men) were included. The presence of moderate or greater tricuspid regurgitation following TAVR was independently associated with 2-year mortality (adjusted hazard ratio 3.41, 95% confidence interval 1.15-10.1), and significantly discriminated 2-year cardiovascular mortality (30% vs. 12%, p = 0.001). No patients with any improvement in tricuspid regurgitation had cardiovascular death. CONCLUSION: Following TAVR, the existence of significant tricuspid regurgitation was associated with cardiovascular mortality in patients with heart failure with reduced ejection fraction.
Assuntos
Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Idoso de 80 Anos ou mais , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Humanos , Masculino , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Volume Sistólico , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
Heart rate reduction therapy using ivabradine has demonstrated its prognostic implication in patients with heart failure with reduced ejection fraction. However, the target heart rate with optimal clinical outcomes, particularly for those with systolic dysfunction following a transcatheter aortic valve replacement (TAVR), remains unknown. Consecutive patients with left ventricular ejection fraction (LVEF) < 50% and sinus rhythm following TAVR received transthoracic echocardiography at index discharge. The ideal heart rate was calculated using a formula: 93 - 0.13 × (deceleration time [ms]). Those whose actual heart rates at discharge were within 10 bpm of the calculated ideal heart rate were assigned to the optimal heart rate group, and their prognosis was compared with those without. Twenty-four patients (83 [78, 85] years old, LVEF 41% [35%, 44%], 16 males) were included. The median difference between actual heart rate and ideal heart rate was 12 (0, 16) bpm and 11 patients were assigned to the optimal heart rate group. One year later, the optimal heart rate group achieved more improvement in LVEF (24% [15%, 28%] vs. 7% [7%, 12%], p = .003) and had lower heart failure readmission rates (0.059 vs. 0.116 events/year; p = .49). In conclusion, an optimal heart rate might be associated with cardiac reverse remodeling and prevention of heart failure recurrences in patients with systolic dysfunction following TAVR. The implication of deceleration time-guided heart rate optimization therapy for such cohorts remains the next concern.
Assuntos
Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Idoso de 80 Anos ou mais , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Frequência Cardíaca , Humanos , Masculino , Volume Sistólico , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
A 76-year-old woman had received surgical mitral valve replacement with Magna Mitral Ease (Edwards Lifesciences, Irvine, CA, USA) 25 mm for functional severe mitral regurgitation 6 years previously. She presented recurrence of heart failure due to severe stenotic and moderate regurgitant degeneration of the implanted mitral bioprosthesis. Considering her comorbidities and left ventricular systolic dysfunction, our heart valve team eventually decided to perform percutaneous transseptal transcatheter mitral valve-in-valve replacement instead of surgical redo mitral valve replacement, using a 26 mm SAPIEN 3 valve (Edwards Lifesciences) via trans-femoral approach. Post-procedural course was uneventful and she was discharged on post-procedural day 2. This is, to the best of our knowledge, the first case of successful percutaneous transseptal transcatheter mitral valve-in-valve replacement in Japan. Further large-scale prospective studies are warranted to validate its long-term safety and efficacy, particularly by comparing with the redo surgery.
RESUMO
Low-voltage computed tomographic angiography (CTA) is a highly effective technique to reduce contrast media volume. We sought to examine the suitability of low tube voltage CTA with a reduced contrast media volume protocol using third-generation 192-slice dual-source CT in patients undergoing transcatheter aortic valve implantation (TAVI). CTA was performed to aid TAVI planning for 40 consecutive patients with severe aortic stenosis. For the first 10 patients (120/100 kV group), we used a conventional tube voltage combined CTA protocol (an ECG-gated helical scan; 120 kV, non-gated helical scan; 100 kV). For the subsequent 30 patients (70-kV group), we adopted a low tube voltage CTA protocol. We evaluated vascular attenuation, image noise, contrast-to-noise ratio (CNR), and renal function. The mean contrast media (CM) volume was 77.7 ± 17.7 mL in the 120/100-kV group and 30.9 ± 6.3 mL in the 70-kV group (P < 0.001). In the images of the aortic valve complex, the mean attenuation was not significant difference for both groups. In the images of the aorto-femoral arteries, mean attenuation was > 250 Hounsfield Units and CNR was > 10 in all vascular segments for both groups. There was no significant difference in the change of renal function in the 70-kV group, but renal function in the 120/100-kV group decreased within 1-3 months after CTA. Low tube voltage CTA using third-generation dual-source CT is suitable to assess procedural planning for TAVI. This approach maintains image quality and reduces the required CM volume.
Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Angiografia por Tomografia Computadorizada/métodos , Doses de Radiação , Exposição à Radiação/prevenção & controle , Substituição da Valva Aórtica Transcateter/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos de Coortes , Meios de Contraste , Feminino , Seguimentos , Hospitais Universitários , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do TratamentoRESUMO
Cardiac hypertrophy and fibrosis in heart failure with preserved ejection fraction are associated with a pro-inflammatory state and reduced NO bioavailability. Effects on myocardial structural and molecular alterations were compared between Waon therapy (WT; repeated dry sauna therapy) and statin in hypertensive rats. Seven-week-old Dahl salt-sensitive rats were assigned to 4 groups: low-salt (LS) diet, high-salt (HS) diet, HS diet with oral fluvastatin (FL; 10 mg/kg/day for 4 weeks) starting from the age of 9 weeks, and HS diet with WT treatment in a far-infrared dry sauna (39 °C for 15 min followed by 34 °C for 20 min once daily for 4 weeks). HS rats developed left ventricular (LV) hypertrophy with preserved LV systolic function. WT reduced LV wall thickness and myocyte cross-sectional area along with decreased levels of myocardial ANP and BNP mRNA expression compared with HS rats. Reduction in LV fibrosis and increase in capillary density in WT animals were accompanied by reductions in myocardial levels of TGF-ß1, MMP2, p22(phox) and gp91(phox) mRNA expression, and increases in myocardial levels of VEGF and HSP90 mRNA and phosphorylated eNOS protein. These effects were comparable between WT and FL animals. WT improves structural and molecular alterations in salt-induced hypertensive rats similarly to fluvastatin.
Assuntos
Ácidos Graxos Monoinsaturados/farmacologia , Temperatura Alta , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipertensão/terapia , Indóis/farmacologia , Miocárdio/patologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Capilares/efeitos dos fármacos , Modelos Animais de Doenças , Ecocardiografia , Fibrose , Fluvastatina , Proteínas de Choque Térmico HSP90/metabolismo , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertensão/induzido quimicamente , Óxido Nítrico Sintase Tipo III/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos Dahl , Sódio na Dieta , Fator A de Crescimento do Endotélio Vascular/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação VentricularRESUMO
Diabetic cardiomyopathy is associated with increased oxidative stress and vascular endothelial dysfunction, which lead to coronary microangiopathy. We tested whether statin-induced redox imbalance improvements could ameliorate diabetic cardiomyopathy and improve coronary microvasculature in streptozotocin-induced diabetes mellitus (DM). Fluvastatin (10 mg/kg/day) or vehicle was orally administered for 12 weeks to rats with or without DM. Myocardial oxidative stress was assessed by NADPH (nicotinamide adenine dinucleotide phosphate) oxidase subunit p22(phox) and gp91(phox) mRNA expression, and myocardial 8-iso-prostaglandin F(2α) (PGF(2α)) levels. Myocardial vascular densities were assessed using anti-CD31 and anti-α-smooth muscle actin (SMA) antibodies. Fluvastatin did not affect blood pressure or plasma cholesterol, but attenuated increased left ventricular (LV) minimum pressure and ameliorated LV systolic dysfunction in DM rats in comparison with vehicle (LV dP/dt, 8.9 ± 1.8 vs 5.4 ± 1.0 × 10(3) mmHg/s, P < 0.05). Myocardial oxidative stress increased in DM, but fluvastatin significantly reduced p22(phox) and gp91(phox) mRNA expression and myocardial PGF(2α) levels. Fluvastatin enhanced myocardial endothelial nitric oxide synthase (eNOS) protein levels and increased eNOS, vascular endothelial growth factor, and hypoxia-inducible factor-1α mRNA expression. CD31-positive cell densities were lower in DM rats than in non-DM rats (28.4 ± 13.2 vs 48.6 ± 4.3/field, P < 0.05) and fluvastatin restored the number (57.8 ± 18.3/field), although there were no significant differences in SMA-positive cell densities between groups. Fluvastatin did not affect cardiac function, oxidative stress, or vessel densities in non-DM rats. These results suggest that beneficial effects of fluvastatin on diabetic cardiomyopathy might result, at least in part, from improving coronary microvasculature through reduction in myocardial oxidative stress and upregulation of angiogenic factor.
Assuntos
Antioxidantes/farmacologia , Vasos Coronários/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Ácidos Graxos Monoinsaturados/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Indóis/farmacologia , Microvasos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Actinas/metabolismo , Animais , Vasos Coronários/metabolismo , Vasos Coronários/fisiopatologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/fisiopatologia , Dinoprostona/análogos & derivados , Dinoprostona/metabolismo , Fluvastatina , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Isoprostanos/metabolismo , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Microvasos/metabolismo , Microvasos/fisiopatologia , NADPH Oxidase 2 , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , RNA Mensageiro/metabolismo , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos , Pressão Ventricular/efeitos dos fármacosRESUMO
BACKGROUND: Repeated low-temperature sauna (Waon) therapy relieves ischemic symptoms in patients with peripheral arterial disease. We investigated whether Waon therapy could improve myocardial perfusion in patients with ischemia related to chronic total occlusion (CTO) of coronary arteries. METHODS: Twenty-four patients who had ischemia in the CTO-related area were examined. The severity of ischemia was quantified by thallium-201 myocardial perfusion scintigraphy with adenosine. The Waon group (n=16) was treated daily for three weeks with a 60 °C far infrared-ray dry sauna bath for 15 min and then kept in a bed covered with blankets for 30 min. The control group (n=8) underwent myocardial perfusion scintigraphy twice with a three-week interval. RESULTS: In the control group, neither summed stress score (SSS) nor summed difference score (SDS) of myocardial scintigraphy changed. However, Waon therapy improved both SSS (16 ± 7 to 9 ± 6, p<0.01) and SDS (7 ± 4 to 3 ± 2, p<0.01), and the improvement was greater in patients with higher SSS and SDS scores at the baseline. Waon therapy extended treadmill exercise time (430 ± 185 to 511 ± 192s, p<0.01) and improved flow-mediated dilation of the brachial artery (4.1 ± 1.3 to 5.9 ± 1.8%, p<0.05), but tended to decrease the number of circulating CD34-positive bone marrow-derived cells. CONCLUSIONS: Waon therapy improves CTO-related myocardial ischemia in association with improvement of vascular endothelial function. This therapy could be a complementary and alternative tool in patients with severe coronary lesions not suitable for coronary intervention.
Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Circulação Coronária/fisiologia , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/terapia , Banho a Vapor/métodos , Idoso , Idoso de 80 Anos ou mais , Velocidade do Fluxo Sanguíneo/fisiologia , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão do Miocárdio/métodos , Vasodilatação/fisiologiaRESUMO
Repeated sauna therapy (ST) increases endothelial nitric oxide synthase (eNOS) activity and improves cardiac function in heart failure as well as peripheral blood flow in ischemic limbs. The present study investigates whether ST can increase coronary vascularity and thus attenuate cardiac remodeling after myocardial infarction (MI). We induced MI by ligating the left coronary artery of Wistar rats. The rats were placed in a far-infrared dry sauna at 41°C for 15 min and then at 34°C for 20 min once daily for 4 wk. Cardiac hemodynamic, histopathological, and gene analyses were performed. Despite the similar sizes of MI between the ST and non-ST groups (51.4 ± 0.3 vs. 51.1 ± 0.2%), ST reduced left ventricular (LV) end-diastolic (9.7 ± 0.4 vs. 10.7 ± 0.5 mm, P < 0.01) and end-systolic (8.6 ± 0.5 vs. 9.6 ± 0.6 mm, P < 0.01) dimensions and attenuated MI-induced increases in LV end-diastolic pressure. Cross-sectional areas of cardiomyocytes were smaller in ST rats and associated with a significant reduction in myocardial atrial natriuretic peptide mRNA levels. Vascular density was reduced in the noninfarcted myocardium of non-ST rats, and the density of cells positive for CD31 and for α-smooth muscle actin was decreased. These decreases were attenuated in ST rats compared with non-ST rats and associated with increases in myocardial eNOS and vascular endothelial growth factor mRNA levels. In conclusion, ST attenuates cardiac remodeling after MI, at least in part, through improving coronary vascularity in the noninfarcted myocardium. Repeated ST might serve as a novel noninvasive therapy for patients with MI.