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Background: Preplanning of care is necessary for patients with endstage heart failure (HF), but advance care planning (ACP) before the loss of a patient's comprehensive capacity is not yet routine for the public or the medical community. The challenge in accurately predicting a patient's prognosis is a strong barrier to implementing ACP. To address this problem, several models for risk stratification have been proposed and are available in clinical settings. MethodsâandâResults: We randomized the procedure to provide estimated patient survival information to attending physicians and then assessed whether there was a change in (1) the frequency of ACP initiation occurred (physician-side evaluation), and/or (2) the patients' quality of life, including mental state (patient-side evaluation). Conclusions: This multicenter, open-label, single-blinded randomized clinical trial aims to assess the hypothesis that providing information on the estimated survival of a patient to the attending physicians will improve the frequency of ACP initiation and quality of life in patients with HF.
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AIMS: The ALIMENT-HF trial aims to determine whether high-calorie and high-protein oral nutritional supplements (ONS) are safe and beneficial for older adult outpatients with heart failure (HF). METHODS AND RESULTS: This multicentre, single-arm, interventional pilot trial is designed to evaluate the tolerance, efficacy, and safety of ONS in older adult outpatients with chronic HF, malnutrition, and anorexia. In total, 80 outpatients with HF regardless of their left ventricular ejection fraction will be treated with ONS, including high-energy (900 kcal/day) and high protein (36 g/day) supplementation, at eight sites in Japan. Inclusion criteria are as follows: age, ≥65 years; outpatients receiving maximally tolerated guideline-directed medical therapy for HF and without change in their diuretic dosage during the last 3 months; outpatients at risk of malnutrition, defined as a Malnutrition Universal Screening Tool score ≥1 point, and anorexia, defined using a Simplified Nutritional Appetite Questionnaire for the Japanese Elderly (SNAQ-JE) score of ≤14 points. Nutritional intervention will continue for up to 120 days, with an observational period lasting for a further 60 days. The primary outcome is a change in body weight between baseline and day 120. CONCLUSIONS: The ALIMENT-HF trial will evaluate the tolerance, efficacy, and safety of high-calorie and high-protein-rich ONS in older outpatients with HF co-morbid with malnutrition and anorexia and will provide insightful information for future randomized controlled trials.
Subject(s)
Dietary Supplements , Heart Failure , Outpatients , Humans , Heart Failure/complications , Heart Failure/physiopathology , Aged , Male , Female , Pilot Projects , Administration, Oral , Malnutrition/prevention & control , Japan/epidemiology , Nutritional Status , Follow-Up Studies , Treatment Outcome , Stroke Volume/physiologyABSTRACT
AIMS: Interleukin-16 (IL-16) has been reported to mediate left ventricular myocardial fibrosis and stiffening in patients with heart failure with preserved ejection fraction (HFpEF). We sought to elucidate whether IL-16 has a distinct impact on pathophysiology and prognosis across different subphenotypes of acute HFpEF. METHODS AND RESULTS: We analysed 211 patients enrolled in a prospective multicentre registry of acute decompensated HFpEF for whom serum IL-16 levels after stabilization were available (53% female, median age 81 [interquartile range 75-85] years). We divided this sub-cohort into four phenogroups using our established clustering algorithm. The study endpoint was all-cause death. Patients were subclassified into phenogroup 1 ('rhythm trouble' [n = 69]), phenogroup 2 ('ventricular-arterial uncoupling' [n = 49]), phenogroup 3 ('low output and systemic congestion' [n = 41]), and phenogroup 4 ('systemic failure' [n = 52]). After a median follow-up of 640 days, 38 patients had died. Among the four phenogroups, phenogroup 2 had the highest IL-16 level. The IL-16 level showed significant associations with indices of cardiac hypertrophy, diastolic dysfunction, and congestion only in phenogroup 2. Furthermore, the IL-16 level had a significant predictive value for all-cause death only in phenogroup 2 (C-statistic 0.750, 95% confidence interval 0.606-0.863, P = 0.017), while there was no association between the IL-16 level and the endpoint in the other phenogroups. CONCLUSIONS: Our results indicated that the serum IL-16 level had a significant association with indices that reflect the pathophysiology and prognosis of HFpEF in a specific phenogroup in acute HFpEF.
Subject(s)
Biomarkers , Heart Failure , Interleukin-16 , Stroke Volume , Humans , Female , Male , Heart Failure/physiopathology , Heart Failure/blood , Stroke Volume/physiology , Aged , Acute Disease , Aged, 80 and over , Prospective Studies , Prognosis , Interleukin-16/blood , Interleukin-16/genetics , Biomarkers/blood , Follow-Up Studies , Ventricular Function, Left/physiology , Registries , Cause of Death/trendsABSTRACT
INTRODUCTION: Heterogeneous distribution in myocardial perfusion images (MPI) obtained by scintigraphy is often observed in cardiac diseases with normal myocardial perfusion. However, quantitative assessments of such heterogeneity have not been established. We hypothesized that the heterogeneity in MPI can be quantitatively evaluated through histogram analysis, calculating the standard deviation (SD), the 95% bandwidth (BW95%), and entropy. METHODS: We examined resting 99mTc-MIBI images in 20 healthy subjects and 29 patients with cardiac disease who had none or very-mild reduced myocardial perfusion evaluated as a low summed rest score (0 to 4, the range of the studied healthy subjects). Two nuclear medicine specialists blindly divided them into two groups: non-heterogeneity or heterogeneity group, based solely on their visual assessments of heterogeneity on splash and polar maps generated from single-photon emission computed tomography (SPECT) images. The %uptake was determined by dividing the tracer count of each pixel by the tracer count of the pixel with the highest value in the LV myocardium. SD, BW95%, and entropy from histogram patterns were analyzed from the polar map data array of each %uptake. We investigated whether heterogeneity could be assessed using SD, BW95, and entropy in two groups classified by visual assessments. Additionally, we evaluated the area under the curve (AUC) to identify heterogeneity in the receiver operating characteristic curve analysis. RESULTS: Based solely on visual assessments, 11 (22%) and 38 (78%) cases were classified into the non-heterogeneity and heterogeneity groups, respectively. The non-heterogeneity group consisted of only healthy subjects, and all patients with cardiac disease were classified into the heterogeneity group. The cases in the heterogeneity group had significantly higher values of heterogeneity indices (SD, BW95%, and entropy) in %uptake than those in the non-heterogeneity group (p < 0.05 for all). The AUCs of the heterogeneity indices were sufficiently high (AUCs > 0.90 for all) in distinguishing cases with visually heterogeneous distribution or patients with cardiac disease. CONCLUSIONS: Heterogeneity in MPI can be evaluated using SD, BW95%, and entropy through histogram analysis. These novel indices may help identify patients with subtle myocardial changes, even in images that show preserved perfusion (345/350).
Subject(s)
Myocardial Perfusion Imaging , Technetium Tc 99m Sestamibi , Humans , Myocardial Perfusion Imaging/methods , Male , Female , Middle Aged , Aged , Tomography, Emission-Computed, Single-Photon , Adult , Image Processing, Computer-Assisted/methods , ROC Curve , Heart Diseases/diagnostic imagingABSTRACT
BACKGROUND: Dilated cardiomyopathy (DCM) presents with diverse clinical courses, hardly predictable solely by the left ventricular (LV) ejection fraction (EF). Longitudinal strain (LS) offers distinct information from LVEF and exhibits various distribution patterns. This study aimed to evaluate the clinical significance of LS distribution patterns in DCM. METHODS: We studied 139 patients with DCM (LVEF ≤ 35%) who were admitted for heart failure (HF). LS distribution was assessed using a bull's eye map and the relative apical LS index (RapLSI), calculated by dividing apical LS by the sum of basal and mid-LS values. We evaluated the associations of LS distribution with cardiac events (cardiac death, LV assist device implantation, or HF hospitalization) and LV reverse remodeling (LVRR), as indicated by subsequent LVEF changes. RESULTS: Twenty six (19%) and 29 (21%) patients exhibited a pattern of relatively apical impaired or preserved LS (defined by RapLSI < 0.25 or > 0.75, signifying a 50% decrease or increase in apical LS compared to other segments), and the remaining patients exhibited a scattered/homogeneously impaired LS pattern. The proportion of new-onset heart failure and LVEF differed between the three groups. During the median 595-day follow-up, patients with relatively-impaired apical LS had a higher rate of cardiac events (both log-rank p < 0.05) and a lower incidence of LVRR (both p < 0.01) compared to patients with other patterns. RapLSI was significantly associated with cardiac event rates after adjusting for age, sex, and new-onset HF or global LS. CONCLUSION: DCM patients with reduced EF and distinct distribution patterns of impaired LS experienced different outcomes.
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The Japanese national guidelines recommend significantly lower doses of carvedilol for heart failure with reduced ejection fraction (HFrEF) management than the US guidelines. Using real-world data, we determined whether initial and target doses of carvedilol in Japanese patients (JPNs) differ from those in US patients (USPs), especially in Asian Americans (ASA) and Caucasians (CA), and investigated differences in outcomes. We collected data from the electronic medical records, including demographics, carvedilol dosing, tolerability, cardiac functional indicators like EF, cardiovascular events including all-cause deaths, and laboratory values from the University of California, San Diego Health and Osaka University. JPNs had significantly lower doses (mg/day) of carvedilol initiation (66 USPs composed of 38 CAs and 28 ASAs, 17.1±16.2; 93 JPNs, 4.3±4.2, p<0.001) and one year after initiation (33.0±21.8; 11.2±6.5, p<0.001), and a significantly lower relative rate (RR) of dose discontinuation and reduction than USPs (RR: 0.406, 95% confidence interval (CI): 0.181-0.911, p<0.05). CAs showed the highest reduction rate (0.184), and ASAs had the highest discontinuation rate (0.107). A slight mean difference with narrow 95% CI ranges straddling zero was observed between the two regions in the change from the baseline of each cardiac functional indicator (LVEF, -0.68 [-5.49-4.12]; LVDd, -0.55 [-3.24-2.15]; LVDd index, -0.25 [-1.92-1.43]; LVDs, -0.03 [-3.84-3.90]; LVDs index, -0.04 [-2.38-2.30]; heart rate, 1.62 [-3.07-6.32]). The event-free survival showed no difference (p = 0.172) among the races. Conclusively, despite JPNs exhibiting markedly lower carvedilol doses, their dose effectiveness has the potential to be non-inferior to that in USPs. Dose de-escalation, not discontinuation, could be an option in some Asian and ASA HFrEF patients intolerable to high doses of carvedilol.
Subject(s)
Carvedilol , Heart Failure , Ventricular Dysfunction, Left , Humans , Adrenergic beta-Antagonists , Carvedilol/therapeutic use , Heart Failure/drug therapy , Japan , Stroke Volume , Treatment Outcome , Ventricular Dysfunction, Left/drug therapyABSTRACT
OBJECTIVE: The heterogeneous pathophysiology of the diverse heart failure with preserved ejection fraction (HFpEF) phenotypes needs to be examined. We aim to assess differences in the biomarkers among the phenotypes of HFpEF and investigate its multifactorial pathophysiology. METHODS: This study is a retrospective analysis of the PURSUIT-HFpEF Study (N=1231), an ongoing, prospective, multicentre observational study of acute decompensated HFpEF. In this registry, there is a predefined subcohort in which we perform multibiomarker tests (N=212). We applied the previously established machine learning-based clustering model to the subcohort with biomarker measurements to classify them into four phenotypes: phenotype 1 (n=69), phenotype 2 (n=49), phenotype 3 (n=41) and phenotype 4 (n=53). Biomarker characteristics in each phenotype were evaluated. RESULTS: Phenotype 1 presented the lowest value of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive C reactive protein, tumour necrosis factor-α, growth differentiation factor (GDF)-15, troponin T and cystatin C, whereas phenotype 2, which is characterised by hypertension and cardiac hypertrophy, showed the highest value of these markers. Phenotype 3 showed the second highest value of GDF-15 and cystatin C. Phenotype 4 presented a low NT-proBNP value and a relatively high GDF-15. CONCLUSIONS: Distinctive characteristics of biomarkers in HFpEF phenotypes would indicate differential underlying mechanisms to be elucidated. The contribution of inflammation to the pathogenesis varied considerably among different HFpEF phenotypes. Systemic inflammation substantially contributes to the pathophysiology of the classic HFpEF phenotype with cardiac hypertrophy. TRIAL REGISTRATION NUMBER: UMIN-CTR ID: UMIN000021831.
Subject(s)
Heart Failure , Humans , Heart Failure/diagnosis , Growth Differentiation Factor 15 , Cystatin C , Stroke Volume/physiology , Retrospective Studies , Prospective Studies , Biomarkers , Natriuretic Peptide, Brain , Inflammation , Peptide Fragments , Cardiomegaly , PrognosisABSTRACT
Electromagnetic interference (EMI) between implantable left ventricular assist devices and cardiac implantable electronic devices has been observed. We demonstrated the first case of EMI between a percutaneous ventricular assist device and an implantable cardioverter-defibrillator, validated by an extra vivo simulation test. EMI might depend on the distance between devices. (Level of Difficulty: Advanced.).
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OBJECTIVE: Our previously established machine learning-based clustering model classified heart failure with preserved ejection fraction (HFpEF) into four distinct phenotypes. Given the heterogeneous pathophysiology of HFpEF, specific medications may have favourable effects in specific phenotypes of HFpEF. We aimed to assess effectiveness of medications on clinical outcomes of the four phenotypes using a real-world HFpEF registry dataset. METHODS: This study is a posthoc analysis of the PURSUIT-HFpEF registry, a prospective, multicentre, observational study. We evaluated the clinical effectiveness of the following four types of postdischarge medication in the four different phenotypes: angiotensin-converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARB), beta blockers, mineralocorticoid-receptor antagonists (MRA) and statins. The primary endpoint of this study was a composite of all-cause death and heart failure hospitalisation. RESULTS: Of 1231 patients, 1100 (83 (IQR 77, 87) years, 604 females) were eligible for analysis. Median follow-up duration was 734 (398, 1108) days. The primary endpoint occurred in 528 patients (48.0%). Cox proportional hazard models with inverse-probability-of-treatment weighting showed the following significant effectiveness of medication on the primary endpoint: MRA for phenotype 2 (weighted HR (wHR) 0.40, 95% CI 0.21 to 0.75, p=0.005); ACEi or ARB for phenotype 3 (wHR 0.66 0.48 to 0.92, p=0.014) and statin therapy for phenotype 3 (wHR 0.43 (0.21 to 0.88), p=0.020). No other medications had significant treatment effects in the four phenotypes. CONCLUSIONS: Machine learning-based clustering may have the potential to identify populations in which specific medications may be effective. This study suggests the effectiveness of MRA, ACEi or ARB and statin for specific phenotypes of HFpEF. TRIAL REGISTRATION NUMBER: UMIN000021831.
Subject(s)
Heart Failure , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Female , Heart Failure/diagnosis , Heart Failure/drug therapy , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Stroke Volume/physiology , Prospective Studies , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin Receptor Antagonists/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Aftercare , Patient Discharge , Cluster Analysis , PhenotypeABSTRACT
OBJECTIVES: Heart failure with preserved ejection fraction (HFpEF) is often complicated by pulmonary hypertension (PH), which is mainly characterised by postcapillary PH and occasionally accompanied by a precapillary component of PH. Haemodynamic changes in worsening heart failure (HF) can modify the characteristics of PH. However, the clinical features of PH after HF treatment in HFpEF remain unclear. We investigated the prevalence and clinical significance of the precapillary component of PH after HF treatment in HFpEF, using data from the Prospective Multicentre Observational Study of Patients with HFpEF (PURSUIT-HFpEF). METHODS: From the PURSUIT-HFpEF registry, 219 patients hospitalised with acute HF who underwent right heart catheterisation after initial HF treatment were divided into four groups according to the 2015 and 2018 PH definitions: non-PH, isolated postcapillary pulmonary hypertension (Ipc-PH), precapillary PH and combined postcapillary and precapillary pulmonary hypertension (Cpc-PH). The latter two were combined as PH with the precapillary component. RESULTS: Using the 2015 definition, we found that the prevalence of PH after HF treatment was 27% (Ipc-PH: 20%, precapillary PH: 3%, Cpc-PH: 4%). Applying the 2018 definition resulted in a doubled frequency of precapillary PH (6%). PH with a precapillary component according to the 2015 definition was associated with poor clinical outcomes and characterised by small left ventricular dimension and high early diastolic mitral inflow velocity/early diastolic mitral annular tissue velocity. CONCLUSION: After initial HF treatment, 7% of hospitalised patients with HFpEF had precapillary component of PH according to the 2015 definition. Echocardiographic parameters of the left ventricle can contribute to the risk stratification of patients with HFpEF with a precapillary component of PH.
Subject(s)
Heart Failure , Hypertension, Pulmonary , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/epidemiology , Hypertension, Pulmonary/complications , Heart Failure/complications , Heart Failure/diagnosis , Heart Failure/epidemiology , Stroke Volume , Prospective Studies , Echocardiography/methodsABSTRACT
BACKGROUND: Although B-type natriuretic peptide (BNP) and N-terminal (NT)-proBNP are commonly used markers of heart failure, a simple conversion formula between these peptides has not yet been developed for clinical use.MethodsâandâResults: A total of 9,394 samples were obtained from Nara Medical University, Jichi Medical University, and Osaka University. We randomly selected 70% for a derivation set to investigate a conversion formula from BNP to NT-proBNP using estimated glomerular filtration rate (eGFR) and body mass index (BMI); the remaining 30% was used as the internal validation set and we used a cohort study from Nara Medical University as an external validation set. Multivariate linear regression analysis revealed a new conversion formula: log NT-proBNP = 1.21 + 1.03 × log BNP - 0.009 × BMI - 0.007 × eGFR (r2=0.900, P<0.0001). The correlation coefficients between the actual and converted values of log NT-proBNP in the internal and external validation sets were 0.942 (P<0.0001) and 0.891 (P<0.0001), respectively. We applied this formula to samples obtained from patients administered with sacubitril/valsartan. After treatment initiation, NT-proBNP levels decreased and actual BNP levels increased. However, the calculated BNP levels decreased roughly parallel to the NT-proBNP levels. CONCLUSIONS: This new and simple conversion formula of BNP and NT-proBNP with eGFR and BMI is potentially useful in clinical practice.
Subject(s)
Heart Failure , Natriuretic Peptide, Brain , Humans , Cohort Studies , Peptide Fragments , Heart Failure/diagnosis , Heart Failure/drug therapy , BiomarkersABSTRACT
BACKGROUND: Detailed morphological characteristics of de novo and donor-transmitted plaques and the association of serum T-lymphocyte cytokine levels with plaque progression of coronary allograft vasculopathy within 1 year after heart transplantation are unknown. METHODS: In this retrospective analysis of data in a prospectively maintained database, 40 heart transplant recipients were included. We performed serial 3 vessel optical coherence tomography and intravascular ultrasound analyses, at the 8 week (baseline) and 12 month post-transplantation follow-ups, and serum cytokine measurements (n = 23). The correlation between serum cytokines and Δplaque burden (between baseline and follow-up) was evaluated depending on plaque morphology. RESULTS: Thirteen de novo plaques (maximum intimal thickness ≥0.5 mm at the 12 month follow-up without plaques at baseline) were identified in 8 recipients, and 31 donor-transmitted plaques (maximum intimal thickness ≥0.5 mm at baseline) were detected in 17 recipients. Compared with donor-transmitted plaques, the Δplaque burden in the de novo plaques, with mainly fibrous morphology, was high (38.8% [29.6%-41.2%] vs 8.7% [1.33%-13.6%], p < 0.001). Stratification of the morphology of donor-transmitted plaques revealed that the Δplaque burden in fibrous plaques (10.6% [7.0%-18.0%]) was similar to that in fibroatheroma (10.3% [8.7%-23.8%]). Serum interleukin-31 levels at baseline correlated with fibrous plaque proliferation (r = 0.73, p = 0.007) even under immunosuppressive conditions, whereas other cytokines (interleukin-1ß, interleukin-17, and interferon-gamma) were mostly undetectable. CONCLUSIONS: Intimal fibrous proliferation contributed to the progression of donor-transmitted and de novo plaques. Serum interleukin-31 levels at baseline may contribute to intimal fibrous proliferation within 1 year after heart transplantation.