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It is reported that immunostaining of Myoglobin (Mb) is useful for forensic diagnosis. In this study, we investigated the condition of fixation of striated muscle in 10 % neutral-buffered formalin to obtain appropriate stationarity of Mb in immunostaining. Firstly, criteria for staining intensity and definition of the stainability of examined were determined for sheep muscle tissue. Sheep myocardial tissue was fixed using 10 % neutral-buffered formalin under the 21 different conditions based on combinations of the following: three ratios of volume of formalin (mL) to weight of myocardium (g) (RFM) of 1, 4 or 9, 7 durations of fixation (DF) of 0.5, 3 or 6 h, and 1, 2, 5 or 7 days. Secondly, detection of Mb diffused form skeletal muscle from autopsy cases into formalin during fixation were confirmed by ELISA. Finally, the evaluation of stainability of Mb of striated muscle in routine autopsy examinations was confirmed using sheep staining intensity standards. From this experimental investigation, it has been demonstrated that the most suitable formalin fixation condition for using Mb staining in forensic diagnosis is RFM4 with a fixation time of at least DF 3 h up to 1 day. It was evident that staining intensity decreases with fixation durations exceeding 2 days, irrespective of the RFM. Thus, the fixation time was deemed the most influential factor affecting the staining properties of Mb staining in skeletal muscle tissue. When conducting Mb staining using striated muscle as an evaluation sample, particular attention should be paid to the fixation time.
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Malignant cardiac lymphoma is rare and commonly involves nodules on the right side of the heart. We herein report a case of malignant cardiac lymphoma with diffuse extension into the left ventricle. The patient was a woman in her 60s who complained of dyspnea and malaise. Echocardiography revealed left ventricular hypertrophy (LVH), and magnetic resonance imaging revealed diffuse contrast enhancement on delayed contrast. Cardiac catheterization and a myocardial biopsy suggested heart failure due to cardiac malignant lymphoma, and diastolic dysfunction was mild despite LVH. The patient underwent chemotherapy, and her cardiac function improved and was maintained.
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Myocardial calcification in myocarditis is rare and may be linked to poor outcomes. We herein report a case of fulminant myocarditis with massive myocardial calcification and its pathological outcomes at autopsy. A 49-year-old man experienced chest pain and was diagnosed with acute myocarditis. His cardiac function did not recover despite mechanical circulatory support in combination with V-A extracorporeal membrane oxygenation and IMPELLA CP®. He eventually developed sepsis and gastrointestinal bleeding and died on day 27. Diffuse myocardial calcification was observed on computed tomography at autopsy. The pathological autopsy depicted that calcification filled every myocardial cell in the left ventricle.
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Cardiomiopatias , Miocardite , Masculino , Humanos , Pessoa de Meia-Idade , Miocardite/patologia , Ventrículos do Coração , Miocárdio/patologia , AutopsiaRESUMO
This study examined the effects of pemafibrate, a selective peroxisome proliferator-activated receptor α agonist, on the serum biochemical parameters of male patients with coronary artery disease and metabolic syndrome (MetS). This was a post hoc analysis of a randomized, crossover study that treated hypertriglyceridemia with pemafibrate or bezafibrate for 24 weeks, followed by a crossover of another 24 weeks. Of the 60 patients enrolled in the study, 55 were male. Forty-one of 55 male patients were found to have MetS. In this sub-analysis, male patients with MetS (MetS group, n = 41) and those without MetS (non-MetS group, n = 14) were compared. The primary endpoint was a change in fasting serum triglyceride (TG) levels during pemafibrate therapy, and the secondary endpoints were changes in insulin resistance-related markers and liver function parameters. Serum TG levels significantly decreased (MetS group, from 266.6 to 148.0 mg/dL, p < 0.001; non-MetS group, from 203.9 to 97.6 mg/dL, p < 0.001); however, a percent change (%Change) was not significantly different between the groups (- 44.1% vs. - 51.6%, p = 0.084). Serum insulin levels and homeostasis model assessment of insulin resistance significantly decreased in the MetS group but not in the non-MetS group. %Change in liver enzyme levels was markedly decreased in the MetS group compared with that in the non-MetS group (alanine aminotransferase, - 25.1% vs. - 11.3%, p = 0.027; gamma-glutamyl transferase, - 45.8% vs. - 36.2%, p = 0.020). In conclusion, pemafibrate can effectively decrease TG levels in patients with MetS, and it may be a more efficient drug for improving insulin resistance and liver function in such patients.
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Benzoxazóis , Butiratos , Doença da Artéria Coronariana , Estudos Cross-Over , Hipertrigliceridemia , Resistência à Insulina , Síndrome Metabólica , Humanos , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Hipertrigliceridemia/sangue , Hipertrigliceridemia/tratamento farmacológico , Hipertrigliceridemia/complicações , Hipertrigliceridemia/diagnóstico , Pessoa de Meia-Idade , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/tratamento farmacológico , Benzoxazóis/uso terapêutico , Benzoxazóis/farmacologia , Butiratos/uso terapêutico , Butiratos/farmacologia , Resultado do Tratamento , Idoso , Triglicerídeos/sangue , Hipolipemiantes/uso terapêutico , Hipolipemiantes/farmacologia , Biomarcadores/sangue , PPAR alfa/agonistas , Bezafibrato/uso terapêutico , Bezafibrato/farmacologiaRESUMO
As more families are acquiring pets and the opportunities for wild animals to appear in human neighborhoods are increasing, the number of cases and accidents involving animals is increasing. Hence, the need to identify animal species from blood left over at accident sites is increasing. Human hemoglobin is used as a marker for human blood. Although tandem mass spectrometry is the dominant methodology used in proteomics research, peptide mass fingerprinting, given its instant applicability, may be useful for screening animal species, as the amino acid sequences of hemoglobin from various animals differ. In this study, solutions that were easily purifiedâusing hemoglobin reagents from humans, Japanese macaques, bears, cattle, goats, sheep, sika deer, pigs, wild boars, dogs, cats, and nutriasâwere digested by trypsin, and subjected to database searched using Mascot. No candidate proteins were found in the blood of goats, sheep, sika deer, wild boars, pigs, or nutrias. However, bloodstains from all animal species except nutria (which is not registered in the database) yielded candidates, which were identified as the hemoglobin of origin or its relatives. This difference may be attributed to more contaminants being included in blood. Further narrowing was possible using the average mass obtained via infusion electrospray ionization mass spectrometry measurement of the undigested solution in Mascot results. Saliva, urine, semen, and sweat collected from humans were also examined and searched for mascots, but no hits were obtained. In conclusion, this method may be useful for estimating animal species and identifying blood in forensic science.
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Massive methanol exposure can lead to severe and detrimental effects that can result in death or brain death. As organs from patients with brain death after methanol ingestion are less likely to be recovered, these patients have been considered marginal donors. We present a case of successful multiple organ transplantation (heart, lungs, and kidneys) from a methanol-poisoned patient. Our experience illustrates that donor death from methanol intoxication does not preclude organ transplantation.
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BACKGROUND: We examined the effect of switching from angiotensin receptor-neprilysin inhibitor (ARNI) to angiotensin-receptor blocker (ARB) on plasma levels of natriuretic peptides and myocardial remodeling. METHODS: This is a prospective study that included 11 patients with heart failure (HF) treated with ARNI. The patients were divided into two groups: 5 patients who continued treatment with sacubitril/valsartan 194/206 mg/day (ARNI-continue group) and 6 patients who were switched to valsartan 160 mg/day (ARB-switch group). The primary endpoint was percent change (%Change) in plasma A-, B-, and N-terminal pro-B-type natriuretic peptide (ANP, BNP, and NT-proBNP) levels from the baseline to week 24. The secondary endpoint was the change in echocardiographic parameters related to myocardial remodeling from the baseline to week 24. RESULTS: ANP levels in the ARB-switch group significantly decreased (from 1155.7 ± 592.6 pg/mL to 231.6 ± 233.8 pg/mL, p = 0.035), whereas those in the ARNI-continue group were not significant (p = 0.180). The %Change of decrease in ANP levels was significantly greater in the ARB-switch group than the ARNI-continue group (- 76.9% vs. -9.1%, p = 0.009). BNP levels were not significantly different between the baseline and week 24 in both groups. NT-proBNP levels in the ARB-switch group increased from 1185.3 ± 835.6 pg/mL to 1515.2 ± 1213.5 pg/mL, although the changes were not statistically significant (p = 0.345). The %Change of increase in NT-proBNP levels was significantly greater in the ARB-switch group than the ARNI-continue group (57.9% vs. 17.3%, p = 0.016). In the ARB-switch group, there was a significant increase in left ventricular (LV) end-systolic volume (from 41.3 ± 24.1 mL/m2 to 71.4 ± 8.8 mL/m2, p = 0.043) and LV peak-systolic wall stress (from 187.0 ± 42.7 × 103 dynes/cm2 to 279.7 ± 34.1 × 103 dynes/cm2, p = 0.012) from the baseline to week 24 and a trend toward a decrease in LV ejection fraction (p = 0.080). In the ARNI-continue group, no differences in echocardiographic parameters were observed from the baseline to week 24. CONCLUSION: Switching from ARNI to ARB may worsen HF due to returning to myocardial remodeling induced by a sustained decline in ANP levels.
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Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Humanos , Antagonistas de Receptores de Angiotensina/efeitos adversos , Volume Sistólico , Estudos Prospectivos , Tetrazóis/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina , Resultado do Tratamento , Valsartana , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/tratamento farmacológico , Disfunção Ventricular Esquerda/induzido quimicamente , Anti-Hipertensivos/farmacologiaRESUMO
AIM: Pemafibrate is a highly selective agonist for peroxisome proliferator-activated receptor (PPAR)-α, a key regulator of lipid and glucose metabolism. We compared the efficacy and safety of pemafibrate with those of bezafibrate, a nonselective PPAR-α agonist. METHODS: In this randomized crossover study, 60 patients with hypertriglyceridemia (fasting triglyceride [TG] ≥ 150 mg/dL) were treated with pemafibrate of 0.2 mg/day or bezafibrate of 400 mg/day for 24 weeks. The primary endpoint was percent change (%Change) from baseline in TG levels, while the secondary endpoints were %Change in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (Apo A-I) levels. RESULTS: The %Change in TG and Apo A-I levels was significantly greater with pemafibrate than with bezafibrate (-46.1% vs. -34.7%, pï¼0.001; 9.2% vs. 5.7%, p =0.018, respectively). %Change in HDL-C levels was not significantly different between the two treatments. %Change in liver enzyme levels was markedly decreased with pemafibrate than with bezafibrate. Creatinine levels significantly increased in both treatments; however, its %Change was significantly lower with pemafibrate than with bezafibrate (5.72% vs. 15.5%, pï¼0.001). The incidence of adverse events (AEs) or serious AEs did not differ between the two treatments; however, the number of patients with elevated creatinine levels (≥ 0.5 mg/dL and/or 25% from baseline) was significantly higher in the bezafibrate group than in the pemafibrate group (14/60 vs. 3/60, p =0.004) [corrected]. CONCLUSION: Compared with bezafibrate, pemafibrate is more effective in decreasing TG levels and increasing Apo A-I levels and is safer regarding liver and renal function.
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Apolipoproteína A-I , Bezafibrato , HDL-Colesterol , Hipertrigliceridemia , Humanos , Hipertrigliceridemia/tratamento farmacológico , Bezafibrato/uso terapêutico , Butiratos/uso terapêutico , Benzoxazóis/uso terapêutico , Estudos Cross-Over , Apolipoproteína A-I/sangue , Apolipoproteína A-I/efeitos dos fármacos , HDL-Colesterol/sangue , HDL-Colesterol/efeitos dos fármacos , Resultado do Tratamento , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Triglicerídeos/metabolismo , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
Background: Guidelines for the prevention and management of cardiovascular disease (CVD) highly recommend cardiac rehabilitation (CR) on the basis of abundant evidence of its effectiveness. However, the current understanding and dissemination of CR in Japan are far from sufficient. MethodsâandâResults: The Japanese Association of Cardiac Rehabilitation Registry (J-CARRY) is an academic society-led prospective multicenter observational registry conducted by the Registration and Facility Accreditation System Committee of the Japanese Association of Cardiac Rehabilitation. Data are collected prospectively using an electronic data capture system. Items related to patients' clinical background and CR, as well as mortality and major adverse cardiac and cerebrovascular events, will be collected in all cases. This Registry started in May 2014, and the number of participating medical institutions is expected to increase to >30; the targeted number of cases exceeded 3,000 per year as of April 30, 2022. Focusing on late Phase II data collection is a novel and significantly different approach compared with previous studies. The results of this study are currently under investigation. Conclusions: J-CARRY will provide real-world data regarding the current status and prognosis of CVD in patients who undergo Phase II CR in Japan.
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AIMS: Prognostic impacts of serum uric acid (UA) levels in patients with chronic heart failure (CHF) remain inconclusive, especially for the whole range of serum UA levels. METHODS AND RESULTS: In the Chronic Heart Failure Registry and Analysis in the Tohoku District-2 (CHART-2) study, we enrolled 4652 consecutive patients with CHF and classified them into four groups based on baseline serum UA levels by the Classification and Regression Tree: G1 (<3.8 mg/dL, N = 313), G2 (3.8-7.1 mg/dL, N = 3070), G3 (7.2-9.2 mg/dL, N = 1018), and G4 (>9.2 mg/dL, N = 251). Mean age was 71 ± 12, 69 ± 12, 68 ± 13, and 69 ± 15 years in G1, G2, G3, and G4, respectively (P < 0.001). During the median follow-up of 6.3 years, in G1, G2, G3, and G4, 111 (35%), 905 (29%), 370 (36%), and 139 (55%) patients died and 79 (25%), 729 (24%), 300 (29%), and 115 (46%) experienced heart failure hospitalization, respectively (both P < 0.001). G1 was characterized by a significantly high prevalence of women as compared with G2, G3, and G4 (59%, 32%, 24%, and 23%, respectively). Serum creatinine levels (0.8 ± 0.4, 0.9 ± 0.4, 1.2 ± 0.6, and 1.4 ± 0.8 mg/dL, respectively), prevalence of atrial fibrillation (34%, 39%, 45%, and 50%, respectively), and diuretics use (36%, 45%, 67%, and 89%, respectively) increased from G1, G2, G3 to G4 (all P < 0.001), while left ventricular ejection fraction decreased from G1, G2, G3 to G4 (59 ± 15, 58 ± 15, 54 ± 15, and 52 ± 17%, respectively, P < 0.001). Multivariable Cox proportional hazards models showed that, as compared with G2, both G1 and G4 had increased incidence of all-cause death [adjusted hazard ratio (aHR) 1.34, 95% confidence interval (CI) 1.08-1.67, P = 0.009; aHR 1.28, 95% CI 1.02-1.61, P = 0.037, respectively] and heart failure admission (aHR 1.39, 95% CI 1.09-1.78, P = 0.008 and aHR 1.35, 95% CI, 1.06-1.71, P = 0.014, respectively). This U-shaped relationship was evident in the elderly patients. Furthermore, abnormal transitions to either higher or lower levels of serum UA from G2 were associated with increased mortality (aHR 1.29, 95% CI 1.06-1.57, P = 0.012; aHR 1.57, 95% CI 1.12-2.20, P = 0.009). CONCLUSIONS: These results demonstrate that serum UA levels have the U-shaped prognostic effects and abnormal transitions to either higher or lower levels are associated with poor prognosis in the elderly patients with CHF.
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Insuficiência Cardíaca , Ácido Úrico , Idoso , Idoso de 80 Anos ou mais , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Pessoa de Meia-Idade , Prognóstico , Volume Sistólico , Função Ventricular EsquerdaRESUMO
BACKGROUND: Although balloon pulmonary angioplasty (BPA) improves symptoms and pulmonary hemodynamics in patients with chronic thromboembolic pulmonary hypertension (CTEPH), the effects of riociguat on hemodynamics and exercise capacity in patients after BPA remain to be elucidated. METHODS AND RESULTS: This study was a single-center, prospective, randomized, open-label trial. From November 2015 to November 2018, we prospectively examined 21 patients with CTEPH (65 ± 9 years old, M/F 2/19) who showed hemodynamic improvement with mean pulmonary arterial pressure (mPAP) < 30 mmHg after BPA without any vasodilators. We performed hemodynamic evaluation and expired gas analysis both at rest and during exercise in supine position using cycle ergometer. After right heart catheterization during exercise, they were randomly assigned to 2 groups with minimized method, using age, sex, and resting mPAP; riociguat (N = 10) and control (N = 11) groups. After 6 months, exercise capacity evaluated by 6-min walk distance and cardiopulmonary exercise testing, and resting hemodynamic parameters were comparable in both groups. However, cardiac output (CO) (6.0 ± 1.7-7.4 ± 1.6, P < 0.01) and pulmonary vascular resistance (4.8 ± 1.8-3.2 ± 0.7 Wood units, P = 0.02) at peak workload were significantly improved in the riociguat group as compared with the control group. The slope of linearized mPAP-CO relationship was significantly decreased in the riociguat group [14.5 (7.8, 14.7) to 6.41 (5.1, 11.4), P < 0.01] but not in the control group. CONCLUSIONS: These results indicate that riociguat exerts beneficial effects on hemodynamic response to exercise in CTEPH patients even after hemodynamic improvement by BPA.
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AIMS: We aimed to examine temporal changes in left ventricular (LV) structures and their prognostic impacts in patients with heart failure (HF) and preserved ejection fraction (HFpEF). METHODS AND RESULTS: In the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) study (n = 10 219), we divided 2698 consecutive HFpEF patients (68.9 ± 12.2 years, 32.1% female) into three groups by LV hypertrophy (LVH) and enlargement (LVE) at baseline: (-)LVH/(-)LVE (n = 989), (+)LVH/(-)LVE (n = 1448), and (+)LVH/(+)LVE (n = 261). We examined temporal changes in LV structures and their prognostic impacts during a median 8.7-year follow-up. From (-)LVH/(-)LVE, (+)LVH/(-)LVE to (+)LVH/(+)LVE at baseline, the incidence of the primary outcome, a composite of cardiovascular death or HF admission, significantly increased. Among 1808 patients who underwent echocardiography at both baseline and 1 year, we noted substantial group transitions from baseline to 1 year; the transition rates from (-)LVH/(-)LVE to (+)LVH/(-)LVE, from (+)LVH/(-)LVE to (-)LVH/(-)LVE, from (+)LVH/(-)LVE to (+)LVH/(+)LVE, and from (+)LVH/(+)LVE to (+)LVH/(-)LVE were 27% (182/671), 22% (213/967), 6% (59/967), and 26% (44/170), respectively. In the univariable Cox proportional hazard model, patients who transitioned from (+)LVH/(-)LVE to (+)LVH/(+)LVE or remained in (+)LVH/(+)LVE had the worst subsequent prognosis [hazard ratio (HR) 4.65, 95% confidence interval (CI) 3.09-6.99, P < 0.001; HR 4.01, 95% CI 2.85-5.65, P < 0.001, respectively], as compared with those who remained in (-)LVH/(-)LVE. These results were unchanged after adjustment for the covariates including baseline LV ejection fraction (LVEF) and 1-year LVEF change. CONCLUSION: In HFpEF patients, LV structures dynamically change over time with significant prognostic impacts, where patients who develop LVE with LVH have the worst prognosis.
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Cardiomegalia , Insuficiência Cardíaca , Ventrículos do Coração , Idoso , Idoso de 80 Anos ou mais , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/mortalidade , Cardiomegalia/fisiopatologia , Doença Crônica , Progressão da Doença , Ecocardiografia , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sistema de Registros , Volume Sistólico/fisiologia , Fatores de TempoRESUMO
BACKGROUND: Since most of the randomized clinical trials for heart failure (HF) were designed to exclude elderly patients, limited data are available on their clinical characteristics, prognosis, and prognostic factors. METHODS: We compared clinical characteristics, prognosis, and prognostic factors among Stage C/D HF patients in our CHART-2 Study (N = 4876, mean 69 years, women 32%, 6.3-year follow-up) by age (G1, ≤64 years, N = 1521; G2, 65-74 years, N = 1510; and G3, ≥75 years, N = 1845). RESULTS: From G1 to G3, the prevalence of women, left ventricular ejection fraction (LVEF) and plasma levels of B-type natriuretic peptide (BNP) increased (all P < 0.001). Similarly, 5-year mortality increased (9.9, 17.3 to 39.9%, P < 0.001) along with a decrease in proportion of cardiovascular death and an increase in non-cardiovascular death in both sexes. While all-cause and cardiovascular mortality was comparable between the sexes, women had significantly lower incidence of non-cardiovascular death than men in G2 and G3, which was attributable to the higher incidence of cancer death and pneumonia death in men than in women. Although NYHA functional class III-IV, chronic kidney disease, cancer, LVEF, and BNP had significant impacts on all-cause death in all groups, their impacts were less evident in G3 as compared with G1. CONCLUSIONS: The elderly HF patients, as compared with younger HF patients, were characterized by more severe clinical background, increased proportion of non-cardiovascular death and worse prognosis with different impacts of prognostic factors across the age groups.
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BACKGROUND: We have recently demonstrated that left ventricular ejection fraction (LVEF) dynamically changes over time with prognostic impacts in Stage C/D patients, namely, those who have a current or past history of heart failure (HF). However, it is unknown whether this is also the case in asymptomatic Stage B patients, namely, those who have a risk of HF, but do not have a history of HF. METHODS: In our CHART-2 Study (N = 10,219), we enrolled 4005 Stage B patients and divided them into 3 groups by LVEF; preserved EF (pEF, LVEF ≥50%, N = 3526), mid-range EF (mrEF, LVEF 41-49%, N = 302), and reduced EF (rEF, LVEF ≤40%, N = 177). We examined the prognostic impacts of LVEF transitions among the 3 groups in comparison with 4477 patients with Stage C/D HF. RESULTS: Stage B were characterized by less severe clinical status and better prognosis compared with Stage C/D. Stage B in mrEF and rEF at baseline dynamically transitioned to other groups at 1-year, whereas those in pEF unchanged; at 1-year, mrEF transitioned to pEF/rEF by 50/16%, and rEF transitioned to pEF/mrEF by 25/31%, respectively, whereas pEF transitioned to mrEF/rEF by only 3.6/0.7%, respectively, which were consistent with findings in findings with Stage C/D. Although LVEF decrease was directly associated with all-cause mortality in both the Stage B and Stage C/D with pEF, factors related to LVEF changes were different between the 2 groups. CONCLUSIONS: In Stage B, LVEF dynamically changes with prognostic impacts as in Stage C/D, whereas different determination factors may be involved in the 2 stages. CLINICAL TRIAL REGISTRATION: Chronic Heart Failure Analysis and Registry in the Tohoku District (CHART)-2 (NCT00418041).
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Insuficiência Cardíaca , Função Ventricular Esquerda , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Prognóstico , Sistema de Registros , Volume SistólicoRESUMO
AIMS: Asymptomatic patients with structural heart diseases are classified as a population at high risk for heart failure (HF) in Stage B. However, limited data are available regarding incidence and related factors of de-novo HF (DNHF) considering competing risk in this population. METHODS AND RESULTS: In 3362 Stage B patients (mean age 68 yrs, male 76%) from the CHART-2 Study (N = 10,219), we examined incidence of death and DNHF, defined as the first episode of either HF hospitalization or HF death, and factors related to DNHF. RESULTS: During the median 6.0-year follow-up, 627 deaths (31/1000 person-years) and 293 DNHF (15/1000 person-years) occurred. Among the 627 deaths, 212 (34%) and 325 (52%) were specified as cardiovascular and non-cardiovascular deaths, respectively. During the follow-up of 271 DNHF hospitalizations, we observed 124 deaths, including 65 (52%) cardiovascular and 47 (40%) non-cardiovascular deaths. The competing risk model showed that age, diabetes mellitus, stroke, atrial fibrillation, diastolic blood pressure, hemoglobin levels, estimated glomerular filtration ratio and left ventricular ejection fraction was significantly associated with DNHF. Bayesian structural equation modeling showed that many of these cardiac and non-cardiac variables contribute to DNHF by affecting each other, while diabetes mellitus was independently associated with DNHF. CONCLUSIONS: Stage B patients had a high incidence of DNHF as well as that of death due to both cardiovascular and non-cardiovascular causes. Thus, management of Stage B patients should include multidisciplinary approaches considering both cardiac and non-cardiac factors, in order to prevent DNHF as well as non-HF death as a competing risk. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00418041.
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Insuficiência Cardíaca , Função Ventricular Esquerda , Idoso , Teorema de Bayes , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Hospitalização , Humanos , Masculino , Fatores de Risco , Volume SistólicoRESUMO
Physical activity (PA) in the daily life is strongly related to prognosis in patients with or at high risk of heart failure (HF). However, factors limiting habitual exercise and their prognostic impacts remain unknown in HF patients. We sent questionnaires asking factors limiting habitual exercise in the daily life to 8370 patients with Stage A/B/C/D HF in our nationwide registry and received valid responses from 4935 patients (mean age 71.8 years, 71.0% male). Among the 5 components consisting of "busyness", "weak will", "dislike, "socioeconomic reasons" and "diseases" in the questionnaires, "busyness" (34.5%) and "diseases" (34.7%) were the most frequently reported factors limiting habitual exercise, while "socioeconomic reasons" were the least (15.3%). Multiple Cox proportional hazard models indicated that "busyness"and "diseases" were associated with better (hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.39-0.72, P < 0.001) and worse prognosis (HR 1.57, 95% CI 1.21-1.98, P < 0.001), respectively, while other components were not. Furthermore, it was noted that, while prognostic relevance of "busyness" limiting exercise did not differ by age or sex, negative impact of "diseases" was particularly evident in patients with age < 75 years (P for interaction < 0.01). Factors limiting habitual exercise were associated with "busyness" and "diseases", but not with "weak will", "dislike, or "socioeconomic reasons". While "busyness" was associated with better prognosis regardless of age and sex, "diseases" was associated with worse prognosis in younger populations. Thus, physicians may pay more attentions to the reasons that limit exercise in the daily lives of HF patients rather than the low amount of exercise itself.
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Tolerância ao Exercício , Exercício Físico , Hábitos , Conhecimentos, Atitudes e Prática em Saúde , Insuficiência Cardíaca/fisiopatologia , Motivação , Idoso , Idoso de 80 Anos ou mais , Feminino , Nível de Saúde , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/psicologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Although cardiac troponin and natriuretic peptide have been shown to decrease after balloon pulmonary angioplasty (BPA) with improved right ventricular afterload in chronic thromboembolic pulmonary hypertension (CTEPH), biomarkers to evaluate the effects of BPA independently of heart failure status remain to be developed. METHODS: In 39 consecutive CTEPH patients including 31 who underwent BPA, we measured plasma levels of cyclophilin A (CyPA), which we demonstrated is secreted from pulmonary vascular smooth muscle cells in response to mechanical stretch and hypoxia. RESULTS: CyPA levels were elevated in CTEPH patients (12.7, IQR: 7.6-16.0) compared with 8 thromboembolic controls with a history of venous thromboembolism (4.9, IQR: 2.4-11.2) or 18 healthy controls (4.1, IQR: 2.4-6.8) (both p< 0.05) and were linearly correlated with mean pulmonary arterial pressure (r=0.50, p = 0.0003) and pulmonary vascular resistance (r=0.32, p= 0.026). BPA reduced CyPA levels and tended to lower brain-type natriuretic peptide (BNP) levels (p< 0.01 and p = 0.07). When comparing the changes in CyPA before and after BPA in the two subgroups with higher (≥35pg/mL) and normal (<35pg/mL) BNP at baseline, CyPA decreased both in patients with higher BNP and those with normal BNP (both p< 0.05). In contrast, BNP decreased only in patients with higher BNP (p< 0.05). Also, CyPA decreased both in patients with lower (<25 kg/m2) and higher (≥25kg/m2) body mass index (BMI) at baseline (both p<0.05), whereas BPA tended to reduce BNP in patients with lower BMI (p = 0.12) but not in those with higher BMI (p = 0.55). CONCLUSIONS: CyPA could be a useful biomarker to evaluate the effects of BPA even in patients with normal BNP or high BMI.
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Angioplastia com Balão , Ciclofilina A/sangue , Hipertensão Pulmonar/cirurgia , Tromboembolia Venosa/cirurgia , Idoso , Biomarcadores/sangue , Doença Crônica , Feminino , Humanos , Hipertensão Pulmonar/sangue , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Tromboembolia Venosa/sangueRESUMO
BACKGROUND: The benefits of antithrombotic therapy (ATT) for atrial fibrillation (AF) are occasionally offset by major bleeding complications. However, the clinical benefits and risks of ATT in AF patients, with special references to comorbidities, such as heart failure (HF), coronary artery disease (CAD), and the patterns of AF, remain to be fully elucidated. METHODS: A total of 3221 consecutive AF patients from our Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study (Nâ¯=â¯10,219) were divided into 4 groups based on ATT at enrollment; no-ATT, anticoagulant alone, antiplatelet alone, and both of them (AC&AP). Then, efficacy and safety outcomes including thromboembolic events, major bleeding, and mortality were evaluated among the 4 groups. RESULTS: Anticoagulant monotherapy was associated with reduced risk of ischemic stroke in patients with but not in those without HF, CAD, or non-paroxysmal AF. Although there was no significant difference in major bleeding among the 4 groups, a composite of thromboembolism and major bleeding occurred more frequently in the AC&AP group, even in combination with anticoagulants and single antiplatelet therapy, indicating that the combination therapy is more harmful than anticoagulant monotherapy for AF patients, especially for those with HF or CAD. Lastly, no-ATT group was associated with worse prognosis compared with other 3 groups. CONCLUSIONS: These results indicate that ATT is beneficial for AF patients particularly for those with HF, CAD, or non-paroxysmal AF and that among ATT, anticoagulant monotherapy may be most profitable for both clinical benefits and risks for AF patients.
Assuntos
Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Fibrinolíticos/uso terapêutico , Relatório de Pesquisa , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/diagnóstico , Comorbidade , Feminino , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Tromboembolia/induzido quimicamente , Resultado do TratamentoRESUMO
Patients with adult congenital heart disease (ACHD) are at increased risk of developing late cardiovascular complication. However, little is known about the predictive factors for long-term outcome. The Model for End-Stage Liver Disease eXcluding INR (MELD-XI) score was originally developed to assess cirrhotic patients and has the prognostic value for heart failure (HF) patients. In the present study, we examined whether the score also has the prognostic value in this population. We retrospectively examined 637 ACHD patients (mean age 31.0 years) who visited our Tohoku University hospital from 1995 to 2015. MELD-XI score was calculated as follows; 11.76 x ln(serum creatinine) + 5.11 x ln(serum total bilirubin) + 9.44. We compared the long-term outcomes between the high (≥10.4) and the low (<10.4) score groups. The cutoff value of MELD-XI score was determined based on the survival classification and regression tree (CART) analysis. The major adverse cardiac event (MACE) was defined as a composite of cardiac death, HF hospitalization, and lethal ventricular arrhythmias. During a mean follow-up period of 8.6 years (interquartile range 4.4-11.4 years), MACE was noted in 51 patients, including HF hospitalization in 37, cardiac death in 8, and lethal ventricular arrhythmias in 6. In Kaplan-Meier analysis, the high score group had significantly worse MACE-free survival compared with the low score group (log-rank, P<0.001). Multivariable Cox regression analysis showed that the MELD-XI score remained a significant predictor of MACE (hazard ratio 1.36, confidence interval 1.17-1.58, P<0.001) even after adjusting for patient characteristics, such as sex, functional status, estimated glomerular filtration rate, and cardiac function. Furthermore, CART analysis revealed that the MELD-XI score was the most important variable for predicting MACE. These results demonstrate that the MELD-XI score can effectively predict MACE in ACHD patients, indicating that ACHD patients with high MELD-XI score need to be closely followed.