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1.
Hum Mol Genet ; 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33949662

RESUMO

Desmoglein-2, encoded by DSG2, is one of the desmosome proteins that maintains the structural integrity of tissues, including heart. Genetic mutations in DSG2 cause arrhythmogenic cardiomyopathy, mainly in an autosomal dominant manner. Here, we identified a homozygous stop-gain mutations in DSG2 (c.C355T, p.R119X) that led to complete desmoglein-2 deficiency in a patient with severe biventricular heart failure. Histological analysis revealed abnormal deposition of desmosome proteins, disrupted intercalated disc structures in the myocardium. Induced pluripotent stem cells were generated from the patient (R119X-iPSC), and the mutated DSG2 gene locus was heterozygously corrected to a normal allele via homology-directed repair (HDR-iPSC). Both isogenic iPSCs were differentiated into cardiomyocytes (iPSC-CMs). Multielectrode array analysis detected abnormal excitation in R119X-iPSC-CMs but not HDR-iPSC-CMs. Micro force testing of 3-dimensional self-organized tissue rings (SOTRs) revealed tissue fragility and a weak maximum force in SOTRs from R119X-iPSC-CMs. Notably, these phenotypes were significantly recovered in HDR-iPSC-CMs. Myocardial fiber structures in R119X-iPSC-CMs were severely aberrant, and electron microscopic analysis confirmed that desmosomes were disrupted in these cells. Unexpectedly, the absence of desmoglein-2 in R119X-iPSC-CMs led to decreased expression of desmocollin-2 but no other desmosome proteins. Adeno-associated virus-mediated replacement of DSG2 significantly recovered the contraction force in SOTRs generated from R119X-iPSC-CMs. Our findings confirm the presence of a desmoglein-2-deficient cardiomyopathy among clinically diagnosed dilated cardiomyopathies. Recapitulation and correction of the disease phenotype using iPSC-CMs provides evidence to support the development of precision medicine and the proof of concept for gene replacement therapy for this cardiomyopathy.

2.
Circ J ; 2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33967107

RESUMO

BACKGROUND: It is unclear whether balloon size can influence lesion formation. The aim of this study was to evaluate the impact of balloon size on lesion formation during laser balloon procedures in an in vitro model.Methods and Results:Laser energy was applied to chicken muscle using a first generation laser balloon. Laser ablation was performed with 2 different balloon sizes (18 mm and 32 mm) using 2 different power settings (12 W/20 s and 8.5 W/20 s) on the chicken muscle. The lesion characteristics, including maximum lesion depth, maximum lesion diameter, surface diameter and depth at maximum diameter, were compared between the 18-mm and 32-mm balloon groups at 12 W/20 s and 8.5 W/20 s, respectively. We created 40 lesions using laser energy at 12 W/20 s and 80 lesions at 8.5 W/20 s. At both power settings, the maximum lesion depth and the depth at the maximum diameter were larger in the 18-mm than in the 32-mm balloon group. At both power settings, the maximum lesion diameter and the surface diameter were smaller in the 18-mm than in the 32-mm balloon group. CONCLUSIONS: The balloon size could affect the lesion formation during laser balloon ablation. The lesion with the larger balloon size was wider and shallower than the lesion with the smaller balloon size.

3.
ESC Heart Fail ; 2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-33934563

RESUMO

AIMS: The impacts of high density lipoprotein cholesterol (HDL-C) as an anti-inflammatory and C reactive protein (CRP) as inflammatory properties on the pathogenesis of heart failure were reported. At present, the clinical significance of the HDL-C/CRP ratio in heart failure with preserved ejection fraction (HFpEF) patients remains unknown. METHODS AND RESULTS: We examined the data on 796 consecutive HFpEF (left ventricular ejection fraction ≥50%) patients hospitalized due to acute decompensated heart failure from the PURSUIT-HFpEF registry, a prospective, multicentre observational study. We calculated the HDL/CRP ratios and evaluated the relationship between the values and clinical outcomes, including degree of cardiac function. The mean follow-up duration was 420 ± 346 days. All-cause death occurred in 118 patients, of which 51 were cardiac deaths. HDL/CRP ≤ 4.05 was independently and significantly associated with all-cause death (odds ratio = 1.84, 95% CI: 1.06-3.20, P = 0.023), and HDL/CRP ≤ 3.14 was associated with cardiac death by multivariate Cox proportional hazard analysis (odds ratio = 2.86, 95% CI: 1.36-6.01, P = 0.003). HDL-C/CRP ratio significantly correlated with the product of the left atrial volume and left ventricular mass index as well as the tricuspid annular plane systolic excursion by multiple regression analysis (standardized beta-coefficient = -0.085, P = 0.034 and standardized beta-coefficient = 0.081, P = 0.044, respectively). CONCLUSIONS: HDL-C/CRP ratio was a useful marker for predicting all-cause death and cardiac death and correlated with left ventricular diastolic function and right ventricular systolic function in HFpEF patients.

4.
J Cardiothorac Surg ; 16(1): 99, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879203

RESUMO

BACKGROUND: In this study, we evaluated the prevalence of tricuspid regurgitation (TR) worsening in patients with left ventricular assist devices (LVADs) and its impact on late right ventricular (RV) failure. METHODS: We enrolled 147 patients of the 184 patients who underwent continuous-flow LVAD implantations from 2005 to March 2018. The prevalence of postoperative TR worsening and late RV failure were retrospectively evaluated. RESULTS: Concomitant tricuspid annuloplasty (TAP) was performed in 28 of 41 patients (68%) with preoperative TR greater than or equal to moderate (TR group) and in 23 of 106 patients (22%) with preoperative TR less than or equal to mild (non-TR group). Regarding the TR-free rates, despite receiving or not receiving concomitant TAP, there was no significant difference between the 2 groups (TR group: p = 0.37; non-TR group: p = 0.42). Of the 9 patients with postoperative TR greater than or equal to moderate, late RV failure developed in 3 patients, with TR worsening after RV failure in each case. During follow-up, 16 patients (11%) had late RV failure. As for the late RV failure-free rates, despite receiving or not receiving concomitant TAP, there was no significant difference between the 2 groups (TR group: p = 0.37; non-TR group: p = 0.96). CONCLUSIONS: TR prognosis was preferable regardless of a patient receiving concomitant TAP; however, the presence of postoperative TR seemed to unrelated to late RV failure. Prophylactic TAP might not be necessary to prevent late RV failure.

6.
Proc Natl Acad Sci U S A ; 118(11)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33836606

RESUMO

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by arteriopathy in the small to medium-sized distal pulmonary arteries, often accompanied by infiltration of inflammatory cells. Aryl hydrocarbon receptor (AHR), a nuclear receptor/transcription factor, detoxifies xenobiotics and regulates the differentiation and function of various immune cells. However, the role of AHR in the pathogenesis of PAH is largely unknown. Here, we explore the role of AHR in the pathogenesis of PAH. AHR agonistic activity in serum was significantly higher in PAH patients than in healthy volunteers and was associated with poor prognosis of PAH. Sprague-Dawley rats treated with the potent endogenous AHR agonist, 6-formylindolo[3,2-b]carbazole, in combination with hypoxia develop severe pulmonary hypertension (PH) with plexiform-like lesions, whereas Sprague-Dawley rats treated with the potent vascular endothelial growth factor receptor 2 inhibitors did not. Ahr-knockout (Ahr -/- ) rats generated using the CRISPR/Cas9 system did not develop PH in the SU5416/hypoxia model. A diet containing Qing-Dai, a Chinese herbal drug, in combination with hypoxia led to development of PH in Ahr +/+ rats, but not in Ahr -/- rats. RNA-seq analysis, chromatin immunoprecipitation (ChIP)-seq analysis, immunohistochemical analysis, and bone marrow transplantation experiments show that activation of several inflammatory signaling pathways was up-regulated in endothelial cells and peripheral blood mononuclear cells, which led to infiltration of CD4+ IL-21+ T cells and MRC1+ macrophages into vascular lesions in an AHR-dependent manner. Taken together, AHR plays crucial roles in the development and progression of PAH, and the AHR-signaling pathway represents a promising therapeutic target for PAH.

7.
ESC Heart Fail ; 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33760383

RESUMO

AIMS: The HFA-PEFF score is a part of the stepwise diagnostic algorithm of heart failure with preserved ejection fraction (HFpEF). We aimed to evaluate the prognostic significance of the HFA-PEFF score on the clinical outcomes in patients with HFpEF. METHODS AND RESULTS: The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with preserved Ejection Fraction (PURSUIT-HFpEF) study is a prospective, multicentre, observational study in which collaborating hospitals in Osaka record clinical, echocardiographic, and outcome data of patients with acute decompensated heart failure with preserved left ventricular ejection fraction (≥50%) [UMIN-CTR ID: UMIN000021831]. Acute decompensated heart failure was diagnosed on the basis of the following criteria: (i) clinical symptoms and signs according to the Framingham Heart Study criteria; and (ii) serum N-terminal pro-B-type natriuretic peptide level of ≥400 pg/mL or brain natriuretic peptide level of ≥100 pg/mL. The HFA-PEFF score has functional, morphological, and biomarker domains. We evaluated the prognostic significance of the HFA-PEFF score (calculated based on the data at hospital discharge) on post-discharge clinical outcomes in this cohort. The primary endpoint of the present study was a composite of all-cause death and heart failure readmission. Between June 2016 and December 2019, 871 patients were enrolled from 26 hospitals (mean follow-up duration 399 ± 349 days). A total of 804 patients were finally analysed after excluding patients with scores of 0 (N = 5) and 1 (N = 15) from 824 patients with available HFA-PEFF score based on the echocardiographic and laboratory data at discharge. According to the laboratory and echocardiographic data at the time of discharge, 487 patients (59.1%) were diagnosed as HFpEF (HFA-PEFF score ≥ 5) while 317 patients (38.5%) had intermediate score. Kaplan-Meier analysis divided by the HFA-PEFF score [low, score 2-5 (N = 494) vs. high, score 6 (N = 310)] indicated that the HFA-PEFF score successfully stratified the patients for the primary endpoint (log-rank test P < 0.001). Cox proportional hazard model showed that the HFA-PEFF score was significantly associated with the primary endpoint (high score with reference to low score, adjusted hazard ratio 1.446, 95% confidence interval [1.099-1.902], P = 0.008). CONCLUSION: The HFA-PEFF score at discharge was significantly associated with the post-discharge clinical outcomes in acute decompensated heart failure patients with preserved ejection fraction. This study suggested clinical usefulness of the HFA-PEFF score not only as a diagnostic tool but also a practical prognostic tool.

8.
ESC Heart Fail ; 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33689231

RESUMO

AIMS: Heart failure (HF) readmissions with preserved ejection fraction (HFpEF) are increasing in the elderly, which is a major socioeconomic problem. We investigated the clinical impact of HF readmissions (HFR) on octogenarians with HFpEF. METHODS AND RESULTS: We enrolled consecutive octogenarians (≥80 years old) from June 2016 to February 2020 in PURSUIT-HFpEF registry. We divided them into HFR group readmitted for HF during the follow-up period and non-HF readmission (non-HFR) group. We evaluated the impact of HFR on all-cause mortality, cardiac death, and quality of life (QOL). Additionally, we evaluated the factors at discharge correlated with HFR. HFR group comprised 116 patients (21.4%). Among all-cause deaths, 40 patients suffered cardiac deaths (48.2%). The Kaplan-Meier analysis revealed a similar prognosis between HFR and non-HFR groups as well as similar incidences of HF deaths. The QOL scores had significantly deteriorated by 1 year later in the HFR group (0.71 ± 0.19 vs. 0.59 ± 0.21, P < 0.001), while it was similar at 1 year in the non-HFR group. In the multivariate analysis, diabetes mellitus (DM) (P = 0.019), N-terminal pro-B-type natriuretic peptide (NT-pro BNP) levels ≥ 1611 pg/mL (P < 0.001), and serum albumin level ≤ 3.7 g/dL (P = 0.011) were useful markers for HFR in octogenarians. CONCLUSIONS: In octogenarians with HFpEF, HF readmission was not directly correlated with the prognosis but was well correlated with the QOL. Close follow-up is essential to decrease HFR of octogenarians with HFpEF with DM, high NT-pro BNP (≥1611 pg/mL) and low albumin (≤3.7 g/dL) levels at discharge.

9.
FASEB J ; 35(4): e21495, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33689182

RESUMO

Enhancers regulate gene expressions in a tissue- and pathology-specific manner by altering its activities. Plasma levels of atrial and brain natriuretic peptides, encoded by the Nppa and Nppb, respectively, and synthesized predominantly in cardiomyocytes, vary depending on the severity of heart failure. We previously identified the noncoding conserved region 9 (CR9) element as a putative Nppb enhancer at 22-kb upstream from the Nppb gene. However, its regulatory mechanism remains unknown. Here, we therefore investigated the mechanism of CR9 activation in cardiomyocytes using different kinds of drugs that induce either cardiac hypertrophy or cardiac failure accompanied by natriuretic peptides upregulation. Chronic treatment of mice with either catecholamines or doxorubicin increased CR9 activity during the progression of cardiac hypertrophy to failure, which is accompanied by proportional increases in Nppb expression. Conversely, for cultured cardiomyocytes, doxorubicin decreased CR9 activity and Nppb expression, while catecholamines increased both. However, exposing cultured cardiomyocytes to mechanical loads, such as mechanical stretch or hydrostatic pressure, upregulate CR9 activity and Nppb expression even in the presence of doxorubicin. Furthermore, the enhancement of CR9 activity and Nppa and Nppb expressions by either catecholamines or mechanical loads can be blunted by suppressing mechanosensing and mechanotransduction pathways, such as muscle LIM protein (MLP) or myosin tension. Finally, the CR9 element showed a more robust and cell-specific response to mechanical loads than the -520-bp BNP promoter. We concluded that the CR9 element is a novel enhancer that responds to mechanical loads by upregulating natriuretic peptides expression in cardiomyocytes.

10.
Heart Vessels ; 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33744995

RESUMO

Although several studies have suggested that catheter ablation (CA) of atrial fibrillation (AF) can improve left ventricular ejection fraction (LVEF) in patients with heart failure with reduced ejection fraction (HFrEF), the predictor of improvement of LVEF is unclear. A total of 401 patients with persistent AF underwent an initial CA between September 2014 and October 2019 in our hospital. Among them, we analyzed consecutive patients with moderately or severely reduced LVEF (< 50%) measured by transthoracic echocardiography (TTE) within 2 months before CA and underwent follow-up TTE during sinus rhythm at 6 months or more after CA. These patients were categorized into two groups: improve group (I group) with the absolute improvement of LVEF ≥ 10% at follow-up TTE, and non- improve group (NI group) with the absolute improvement of LVEF < 10% at follow-up TTE. We compared patient characteristics, ablation procedures, and clinical outcomes between the two groups. 81 patients were analyzed, and I group consisted of 48 patients (59%). In the univariate analysis, absence of ischemic cardiomyopathy, left ventricular end-diastolic diameter (LVEDD), and absence of recurrence of AF between 3 and 6 months after CA were associated with improvement of LVEF. A receiver operating characteristics analysis determined the suitable cut-off value for LVEDD was 53 mm (sensitivity: 62.2%, specificity: 86.2%, area under curve: 0.762). A multivariate analysis showed that LVEDD < 53 mm was independently associated with improvement of LVEF (odds ratio 2.58, 95% confidence interval 1.29-6.12; P = 0.021). In conclusion, LVEDD < 53 mm might be an independent predictor of improvement of LVEF after CA of persistent AF in HFrEF patients.

11.
Circ J ; 85(5): 584-594, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33731544

RESUMO

BACKGROUND: In the Prospective Comparison of angiotensin receptor neprilysin inhibitor (ARNI) With ACEi to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) study, treatment with sacubitril/valsartan reduced the primary outcome of cardiovascular (CV) death and heart failure (HF) hospitalization compared with enalapril in patients with chronic HF and reduced ejection fraction (HFrEF). A prospective randomized trial was conducted to assess the efficacy and safety of sacubitril/valsartan in Japanese HFrEF patients.Methods and Results:In the Prospective comparison of ARNI with ACEi to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients (PARALLEL-HF) study, 225 Japanese HFrEF patients (New York Heart Association [NYHA] class II-IV, left ventricular ejection fraction [LVEF] ≤35%) were randomized (1 : 1) to receive sacubitril/valsartan 200 mg bid or enalapril 10 mg bid. Over a median follow up of 33.9 months, no significant between-group difference was observed for the primary composite outcome of CV death and HF hospitalization (HR 1.09; 95% CI 0.65-1.82; P=0.6260). Early and sustained reductions in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline were observed with sacubitril/valsartan compared with enalapril (between-group difference: Week 2: 25.7%, P<0.01; Month 6: 18.9%, P=0.01, favoring sacubitril/valsartan). There was no significant difference in the changes in NYHA class and Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score at Week 8 and Month 6. Sacubitril/valsartan was well tolerated with fewer study drug discontinuations due to adverse events, although the sacubitril/valsartan group had a higher proportion of patients with hypotension. CONCLUSIONS: In Japanese patients with HFrEF, there was no difference in reduction in the risk of CV death or HF hospitalization between sacubitril/valsartan and enalapril, and sacubitril/valsartan was safe and well tolerated.

13.
Int Heart J ; 62(2): 238-245, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33731519

RESUMO

The effect of a history of cancer on the prognosis of patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) is poorly understood.From the Osaka Acute Coronary Insufficiency Study (OACIS) registry in Osaka, Japan, we enrolled the case data of a total of 3499 patients with AMI treated with PCI between 1998 and 2014, of whom 462 had a cancer history (cancer group, 13.2%) and 3037 did not (non-cancer group, 86.8%). All of the cases were followed for up to five years from discharge.The Kaplan-Meier curve and multivariate analysis using Cox proportional hazards models revealed that all-cause mortality was significantly higher in the cancer group than in the non-cancer group (adjusted hazard ratio [HR], 2.43; P < 0.001). Deaths from cardiac, cancer, and other causes were treated as competing events, and competing analysis using the cumulative incidence function (CIF) and Fine-Gray model revealed that mortality due to cancer was higher in the cancer group than in the non-cancer group, whereas cardiac mortality was similar between the two groups. The incidences of cardiovascular events, including stroke, recurrent infarction, and heart failure requiring readmission, were also similar between the two groups, although the Kaplan-Meier analysis and univariate Cox proportional hazards model revealed that the incidence of stroke was higher in the cancer group than in the non-cancer group.A history of cancer increased all-cause and cancer mortality among patients with AMI treated with PCI, although it was not associated with cardiovascular events.


Assuntos
Infarto do Miocárdio/complicações , Neoplasias/epidemiologia , Intervenção Coronária Percutânea , Sistema de Registros , Medição de Risco/métodos , Idoso , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/cirurgia , Neoplasias/etiologia , Período Pós-Operatório , Prognóstico , Estudos Prospectivos , Fatores de Risco
14.
Artigo em Inglês | MEDLINE | ID: mdl-33715034

RESUMO

BACKGROUND: The relationship between general obesity or abdominal obesity (abdominal circumference of ≥85 cm in men and ≥ 90 cm in women) and the heart-to-mediastinum ratio (HMR), a measure of cardiac sympathetic innervation, on cardiac iodine-123-metaiodobenzylguanidine scintigraphy (MIBG) in patients with heart failure with preserved ejection fraction (HFpEF) has not been clarified. METHODS: A total of 239 HFpEF patients with both MIBG and abdominal circumference data were examined. We divided these patients into those with abdominal obesity and those without it. In the cardiac MIBG study, early phase image was acquired 15-20 min after injection, and late phase image was acquired 3 h after the early phase. A HMR obtained from a low-energy type collimator was converted to that obtained by a medium-energy type collimator. RESULTS: Early and late HMRs were significantly lower in those with abdominal obesity, although washout rates were not significantly different. The incidence of patients with early and late HMRs <2.2 was significantly higher in those with abdominal obesity. Multivariate linear regression analysis revealed that abdominal obesity was independently associated with early HMR (standardized ß = -0.253, P = 0.003) and late HMR (standardized ß = -0.222, P = 0.010). Multivariate logistic regression analysis revealed that abdominal obesity was independently associated with early (odds ratio [OR] [95% confidence interval {CI}] = 4.25 [2.13, 8.47], P < 0.001) and late HMR < 2.2 (OR [95% CI] = 2.06 [1.11, 3.83], P = 0.022). Elevated BMI was not significantly associated with low early and late HMR. The presence of abdominal obesity was significantly associated with low early and late HMR even in patients without elevated BMI values. CONCLUSION: Abdominal obesity, but not general obesity, in HFpEF patients was independently associated with low HMR, suggesting that visceral fat may contribute to decreased cardiac sympathetic activity in patients with HFpEF. TRIAL REGISTRATION: UMIN000021831.

15.
Heart Vessels ; 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33743047

RESUMO

BACKGROUND: The Japanese high-bleeding-risk criteria (Japanese-HBR), modified criteria of the Academic Research Consortium (ARC) HBR, has been recently proposed. We aimed to investigate the prevalence of the ARC-HBR and the Japanese-HBR, and to assess their prognostic significance in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: We applied the ARC-HBR and the Japanese-HBR criteria to the OACIS prospective multicenter acute myocardial infarction registry (12,093 patients, 66 ± 12 years, 9,096 males). The primary endpoint was fatal bleeding (BARC-5). Median follow-up duration was 4.84 [inter-quartile range 1.35, 5.01] years. Prevalence of the ARC-HBR was 43.8%, while that of the Japanese-HBR was 61.8%. Cumulative incidence of fatal bleeding was higher in the ARC-HBR group than in the no ARC-HBR group at 1 year (1.3 vs. 0.6%) and at 5 years (2.0 vs. 0.7%). The Kaplan-Meier curves stratified by the Japanese-HBR criteria more prominently diverged (1.3 vs. 0.2% at 1 year; and 1.9 vs. 0.3% at 5 years). The Japanese-HBR criteria showed superior discriminative performance over the ARC-HBR criteria (C-statistics: 0.677 vs. 0.598, P < 0.001). CONCLUSIONS: In the real-world Japanese AMI registry, nearly half of the patients fulfilled the criteria of ARC-HBR, and two-thirds met the Japanese-HBR. Our findings support the validity of both ARC- and Japanese-HBR criteria in AMI patients but encourage the future application of the Japanese-HBR criteria to the Japanese AMI cohort. TRIAL REGISTRATION NUMBER: UMIN000004575.

16.
Circ J ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33775981

RESUMO

BACKGROUND: Extensive ablation in addition to pulmonary vein isolation (PVI) would be effective for modification of non-pulmonary vein (non-PV) substrates, whereas PVI might be sufficient for elimination of PV triggers. This study aimed to test the hypothesis that in patients with reproducible atrial fibrillation (AF) triggered by premature atrial contractions originating only from PVs, PVI alone can be sufficient to maintain sinus rhythm.Methods and Results:This study is a prespecified subanalysis of the EARNEST-PVI randomized controlled trial. This study investigated the efficacy of the PVI-alone strategy (PVI-alone) in comparison with the extensive strategy (PVI-plus) for persistent AF with a trigger-based mechanism vs. a substrate-based mechanism. Patients were stratified into 3 groups based on AF mechanisms: (1) Substrate group (N=236); (2) PV trigger group (N=236); and (3) non-PV trigger group (N=24). The hazard ratios for AF recurrence of the PVI-alone strategy with reference to the PVI-plus strategy were 1.456 (95% confidence interval [CI] [0.864-2.452]) in the substrate group, 1.648 (95% CI 0.969-2.801) in the PV trigger group, and 0.937 (95% CI 0.252-3.488) in the non-PV trigger group. No significant interaction between ablation strategy and AF mechanism was observed (P for interaction=0.748). CONCLUSIONS: This study indicated that the efficacies of the PVI-alone strategy compared with the PVI-plus strategy were consistent across persistent AF with trigger-based and substrate-based mechanisms.

17.
J Card Fail ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33663906

RESUMO

In this document, we propose a universal definition of heart failure (HF) as the following: HF is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and or objective evidence of pulmonary or systemic congestion. We propose revised stages of HF as follows. At-risk for HF (Stage A), for patients at risk for HF but without current or prior symptoms or signs of HF and without structural or biomarkers evidence of heart disease. Pre-HF (stage B), for patients without current or prior symptoms or signs of HF, but evidence of structural heart disease or abnormal cardiac function, or elevated natriuretic peptide levels. HF (Stage C), for patients with current or prior symptoms and/or signs of HF caused by a structural and/or functional cardiac abnormality. Advanced HF (Stage D), for patients with severe symptoms and/or signs of HF at rest, recurrent hospitalizations despite guideline-directed management and therapy (GDMT), refractory or intolerant to GDMT, requiring advanced therapies such as consideration for transplant, mechanical circulatory support, or palliative care. Finally, we propose a new and revised classification of HF according to left ventricular ejection fraction (LVEF). The classification includes HF with reduced EF (HFrEF): HF with an LVEF of ≤40%; HF with mildly reduced EF (HFmrEF): HF with an LVEF of 41% to 49%; HF with preserved EF (HFpEF): HF with an LVEF of ≥50%; and HF with improved EF (HFimpEF): HF with a baseline LVEF of ≤40%, a ≥10-point increase from baseline LVEF, and a second measurement of LVEF of >40%.

18.
Eur J Heart Fail ; 23(3): 352-380, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33605000

RESUMO

In this document, we propose a universal definition of heart failure (HF) as a clinical syndrome with symptoms and/or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion. We also propose revised stages of HF as: At risk for HF (Stage A), Pre-HF (Stage B), Symptomatic HF (Stage C) and Advanced HF (Stage D). Finally, we propose a new and revised classification of HF according to left ventricular ejection fraction (LVEF). This includes HF with reduced ejection fraction (HFrEF): symptomatic HF with LVEF ≤40%; HF with mildly reduced ejection fraction (HFmrEF): symptomatic HF with LVEF 41-49%; HF with preserved ejection fraction (HFpEF): symptomatic HF with LVEF ≥50%; and HF with improved ejection fraction (HFimpEF): symptomatic HF with a baseline LVEF ≤40%, a ≥10 point increase from baseline LVEF, and a second measurement of LVEF > 40%.

19.
Eur J Heart Fail ; 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33620131

RESUMO

AIMS: Nitroxyl provokes vasodilatation and inotropic and lusitropic effects in animals via post-translational modification of thiols. We aimed to compare effects of the nitroxyl donor cimlanod (BMS-986231) with those of nitroglycerin (NTG) or placebo on cardiac function in patients with chronic heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: In a randomized, multicentre, double-blind, crossover trial, 45 patients with stable HFrEF were given a 5 h intravenous infusion of cimlanod, NTG, or placebo on separate days. Echocardiograms were done at the start and end of each infusion period and read in a core laboratory. The primary endpoint was stroke volume index derived from the left ventricular outflow tract at the end of each infusion period. Stroke volume index with placebo was 30 ± 7 mL/m2 and was lower with cimlanod (29 ± 9 mL/m2 ; P = 0.03) and NTG (28 ± 8 mL/m2 ; P = 0.02). Transmitral E-wave Doppler velocity on cimlanod or NTG was lower than on placebo and, consequently, E/e' (P = 0.006) and E/A ratio (P = 0.003) were also lower. NTG had similar effects to cimlanod on these measurements. Blood pressure reduction was similar with cimlanod and NTG and greater than with placebo. CONCLUSION: In patients with chronic HFrEF, the haemodynamic effects of cimlanod and NTG are similar. The effects of cimlanod may be explained by venodilatation and preload reduction without additional inotropic or lusitropic effects. Ongoing trials of cimlanod will further define its potential role in the treatment of heart failure.

20.
J Cardiol ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33579602

RESUMO

BACKGROUND: Cardiac rehabilitation (CR) is a widely recommended evidence-based intervention for patients with cardiovascular disease. However, the participation rate in CR has been reported to be low globally, mainly due to barriers in access to the CR center. We evaluated the feasibility and safety of a new remote real-time monitoring system for supervising home-based CR among elderly patients with heart failure (HF). METHODS: Hospitalized patients or outpatients followed for HF were enrolled. Patients received 12-week home-based CR under remote supervision using an integrated platform for telerehabilitation. Feasibility was evaluated by the participation and completion rates of the home-based CR sessions. Safety was assessed by adverse events during the sessions. All patients underwent baseline and 12-week assessment of exercise tolerance and lower extremity muscle strength. RESULTS: All 10 patients (mean age 76 ± 7 years; 60% male) who participated in the study completed the program without withdrawal during the study period. Median participation rate in the exercise sessions was 94.4% (interquartile range: 88.9-97.9%). While fatigue, common cold, and palpitation were observed, no serious cardiovascular events were reported. Six-minute walk distance significantly improved from 383 ± 94 m to 432 ± 83 m (p=0.003). CONCLUSIONS: Home-based CR under real-time supervision was feasible and safe among elderly HF patients. Our study suggests that home-based CR using an integrated telerehabilitation platform may be a potential option for patients who are unable to participate in center-based CR due to geographic or social accessibility and physical barrier issues.

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