Clinical and Histopathological Characteristics of Patients With Myocarditis After mRNA COVID-19 Vaccination.

BACKGROUND: The effects of myocarditis after mRNA COVID-19 vaccination (mCV) on myocardial tissue, and the association between cardiomyocyte injury and clinical presentation, are not fully understood. METHODS AND RESULTS: We retrospectively registered patients clinically diagnosed with myocarditis after the first or second mCV who underwent endomyocardial biopsy or autopsy from 42 participating centers in Japan. We investigated the histological features and their association with clinical presentation based on cardiomyocyte injury. Forty patients who underwent endomyocardial biopsy were included in the study. Of these, 19 (47.5%) showed mild lymphocytic infiltration and interstitial edema without cardiomyocyte injury. The remaining 21 (52.5%) patients showed cardiomyocyte injury accompanied by infiltrating inflammatory cells: 11 with lymphocytic infiltration, 7 with eosinophilic infiltration, and 3 with myocarditis with both lymphocyte and eosinophil infiltration. Compared with patients without cardiomyocyte injury, those with cardiomyocyte injury were clinically characterized by older age, a balanced sex distribution, less frequent chest pain, and a lower left ventricular ejection fraction. Fifteen of 21 (71.4%) patients with cardiomyocyte injury developed fulminant myocarditis, with 13 (86.7%) requiring mechanical circulatory support; in contrast, none of those without cardiomyocyte injury developed fulminant myocarditis (P<0.001). CONCLUSIONS: Our histological examination of patients with myocarditis after mCV revealed varying degrees of cardiomyocyte injury, ranging from pronounced to absent, along with various types of myocarditis. Cardiomyocyte injury was strongly associated with the severity of myocarditis.

Calcium-Phosphorus Product Is Associated with Adverse Prognosis in Hospitalized Patients with Heart Failure and Chronic Kidney Disease.

It has been reported that high levels of calcium-phosphorus (Ca-P) product are an indicator of coronary calcification and mortality risk in patients undergoing chronic hemodialysis. In the present study, we aimed to evaluate the significance of Ca-P product to predict the prognosis of patients with heart failure (HF) and chronic kidney disease (CKD). We conducted a prospective observational study of 793 patients with decompensated HF and CKD, and measured the value of Ca-P product. The cut-off value was obtained from the survival classification and regression tree (CART) analysis to predict post-discharge all-cause mortality and/or worsening HF, and the patients were divided into 2 groups: a high group (Ca-P product > 28, n = 594) and a low group (Ca-P product ≤ 28, n = 199). We compared the patient baseline characteristics and post-discharge prognosis between the 2 groups. The age as well as the prevalence of male sex, ischemic etiology, and anemia were significantly higher in the low group than in the high group. In contrast, there was no difference in echocardiographic parameters between the 2 groups. In the Kaplan-Meier analysis (mean follow-up 1089 days), all-cause mortality and/or worsening HF event rates were higher in the low group than in the high group (log-rank P = 0.001). In the multivariable Cox proportional hazard analysis, lower Ca-P product was found to be an independent predictor of all-cause mortality and/or worsening HF (hazard ratio 0.981, P = 0.031). Lower Ca-P product predicts adverse prognosis in patients with HF and CKD.

Predictive Value of Aortic Valve Calcium Volume Measured by Computed Tomography for Paravalvular Leakage After Transcatheter Aortic Valve Implantation.

Paravalvular leakage (PVL) is a complication of transcatheter aortic valve implantation (TAVI) for aortic stenosis, leading to an adverse prognosis. We investigated whether aortic valve calcium volume (Ca-Vol) measured by preoperative cardiac computed tomography had a predictive value for PVL after TAVI using a third-generation self-expandable valve.We retrospectively analyzed 59 consecutive patients who underwent TAVI using a third-generation self-expandable valve. We measured Ca-Vol in the aortic valve and each cusp (non-coronary cusp [NCC], right-coronary cusp [RCC], and left-coronary cusp [LCC]). We divided the patients into 2 groups: a PVL group (32.2%) and a non-PVL group (67.8%). Total Ca-Vol was significantly higher in the PVL group than in the non-PVL group (P < 0.001). Ca-Vol in each cusp was also significantly higher in the PVL group ([NCC] P < 0.001, [RCC] P = 0.001, [LCC] P < 0.001). Univariate logistic regression analysis for PVL indicated that the total and per-cusp Ca-Vols were predictors for PVL (total, odds ratio [OR] 4.0, P < 0.001; NCC, OR 12.5, P = 0.002; RCC, OR 16.0, P = 0.008; LCC, OR 44.5, P < 0.001).Receiver operating characteristic curve analysis of Ca-Vol for predicting PVL revealed the optimal cut-off values of Ca-Vol were 2.4 cm3 for the total, 0.74 cm3 for NCC, 0.73 cm3 for RCC, and 0.56 cm3 for LCC (area under the curve, 0.85, 0.79, 0.76, and 0.83, respectively).Preoperative total, NCC, RCC, and LCC calcium volumes were significant predictors for PVL after TAVI using third-generation self-expandable valves.

Prognostic Effects of Changes in Right Ventricular Fractional Area Change in Patients With Heart Failure.

BACKGROUND: It is still unclear whether changes in right ventricular function are associated with prognosis in heart failure (HF) patients. This study aimed to examine the prognostic effect of changes in right ventricular fractional area change (RVFAC).Methods and Results: This study enrolled 480 hospitalized patients with decompensated HF, and measured RVFAC with echocardiography at discharge (first examination) and post-discharge in the outpatient setting (second examination). RVFAC was divided into 3 categories: >35% in 314 patients, 25-35% in 108 patients, and <25% in 58 patients. Next, based on changes in RVFAC from the first to the second examination, the patients were further classed into 4 groups: (1) Preserved/Unchanged (preserved and unchanged RVFAC, n=235); (2) Reduced/Improved (improved RVFAC in at least 1 category, n=106); (3) Reduced/Unchanged (reduced and unchanged RVFAC, n=47); and (4) Preserved or Reduced/Worsened (deteriorated RVAFC in at least 1 category, n=92). Multivariate logistic regression analysis revealed that chronic kidney disease and anemia were the predictors of the preserved or reduced/worsened RVFAC. In the Kaplan-Meier analysis, changes in RVFAC were associated with the cardiac event rate and all-cause mortality. In the multivariable Cox proportional hazard analysis, the preserved or reduced/worsened RVFAC was an independent predictor of cardiac events and all-cause mortality. CONCLUSIONS: Changes in RVFAC were associated with post-discharge prognosis in hospitalized heart failure patients.

Simplified Academic Research Consortium for High Bleeding Risk (ARC-HBR) Definition Predicts Bleeding Events in Patients With Heart Failure.

BACKGROUND: It has recently been reported that the simplified Academic Research Consortium for High Bleeding Risk (ARC-HBR) definition, which excludes 6 rare criteria, is comparable to the original ARC-HBR definition in predicting major bleeding in patients with coronary artery disease (CAD) who undergo percutaneous coronary intervention. In this study, we investigated whether the simplified ARC-HBR definition could be applied to patients with heart failure (HF) to identify those at high bleeding risk (HBR).Methods and Results:In all, 2,437 patients hospitalized for HF were enrolled in this study. Patients were divided into 2 groups based on the simplified ARC-HBR definition: those at HBR (n=2,026; 83.1%) and those not (non-HBR group; n=411; 16.9%). The HBR group was older (72.0 vs. 61.0 years; P<0.001) and had a lower prevalence of CAD (31.1% vs. 36.5%; P=0.034) than the non-HBR group. Kaplan-Meier analysis showed that post-discharge bleeding events defined as hemorrhagic stroke or gastrointestinal bleeding were more frequent in the HBR than non-HBR group (log-rank P<0.001). The simplified ARC-HBR definition accurately predicted bleeding events (Fine-Gray model; hazard ratio 2.777, 95% confidence interval 1.464-5.270, P=0.001). CONCLUSIONS: The simplified ARC-HBR definition predicts a high risk of bleeding events in patients with HF.

Cardiac Troponin I Predicts Elevated B-type Natriuretic Peptide in Patients Treated with Anthracycline-Containing Chemotherapy.

BACKGROUND: Anthracycline is used to treat various types of cancer; however, cardiotoxicity negatively affects patient prognosis. OBJECTIVES: The aim of the present study was to investigate serial changes in levels of cardiac troponin I (TnI) and B-type natriuretic peptide (BNP) in patients treated with anthracycline-containing therapy. METHODS: 91 consecutive cancer patients planned for anthracycline treatment were enrolled and followed up for 12 months. All patients underwent echocardiography and blood sampling at baseline, 3, 6, and 12 months. RESULTS: The patients were divided into two groups based on their TnI level during the follow-up period: the elevated TnI group (TnI ≥0.03 ng/mL; n = 37) and the normal TnI group (n = 54). In the elevated TnI group, the TnI levels increased at 3 and 6 months, but they returned to within normal range at 12 months after anthracycline administration. Unlike TnI, the BNP levels began to increase after 6 months, and remained increased at 12 months. The occurrence of cancer therapeutics-related cardiac dysfunction was higher in the elevated TnI group than in the normal TnI group. When we set the cut-off value of TnI at 0.029 ng/mL, sensitivity and specificity to predict an elevated BNP level of more than 100 pg/mL were 90 and 63%, respectively. Multivariate logistic regression analysis revealed that elevated TnI was an independent predictor of elevated BNP levels. CONCLUSION: Elevated TnI was an independent predictor for the development of BNP increase. The different characteristics of TnI and BNP should be considered when managing patients treated with anthracycline-containing therapy.

Prognostic impact of moderate mitral regurgitation on hospitalized heart failure patients with preserved ejection fraction: A report from the JASPER registry.

A growing body of evidence suggests that mitral regurgitation (MR) is associated with higher mortality in heart failure patients with reduced ejection fraction. However, prognostic impact of MR on heart failure patients with preserved ejection fraction (HFpEF) has not been fully examined. The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, prospective registration of consecutive Japanese hospitalized HFpEF patients with LVEF ≥ 50%. Severe valvular heart disease was excluded from this cohort. We divided the consecutive 341 patients into two groups based on the severity of MR at discharge: no or mild MR group (n = 317) and moderate MR group (n = 24). Compared with no or mild MR group, moderate MR group showed larger left ventricular end-diastolic diameter (52 [48-59] vs. 46 [42-50] mm, P < 0.001), left ventricular systolic diameter (35 [30-37] vs. 29 [26-34] mm, P = 0.006), left atrial diameter (49 [46-56] vs. 45 [40-50] mm, P < 0.001), and higher tricuspid regurgitation peak gradient (33 [25-40] vs. 27 [21-33] mmHg, P = 0.012). In contrast, levels of plasma B-type natriuretic peptide and left ventricular ejection fraction were comparable between the two groups. In the follow-up period (median 738 days), there were 57 all-cause deaths. In the Kaplan-Meier analysis, all-cause mortality was higher in moderate MR group than in no or mild MR group (log-rank P = 0.023). In the Cox proportional hazard analysis, moderate MR at discharge was a predictor of all-cause mortality (hazard ratio 2.256, 95% confidence interval 1.035-4.917, P = 0.041). Moderate MR at discharge is associated with adverse prognosis in hospitalized patients with HFpEF.

Recovered Left Ventricular Ejection Fraction and Its Prognostic Impacts in Hospitalized Heart Failure Patients with Reduced Ejection Fraction.

It has been recently recognized that recovery of left ventricular ejection fraction (EF), termed "recovered EF", occurs in a proportion of heart failure patients with reduced EF (HFrEF), and is associated with better prognosis. However, the clinical characteristics of "recovered EF" have not been fully examined.Consecutive 567 patients hospitalized due to HFrEF (EF < 40% at 1st assessment at hospital discharge) were enrolled, and EF was re-assessed within half a year in an outpatient setting (2nd assessment). Among these HFrEF patients, 235 remained EF < 40% (reduced, rEF group), 82 changed to EF 40-49% (midrange, mrEF group), and 250 recovered to EF > 50% (preserved, pEF group "recovered EF" ) at the 2nd examination. Age was lower and body mass index and systolic blood pressure were higher in pEF than in rEF. The prevalence of atrial fibrillation (AF) and usage of an implantable cardiac defibrillator and cardiac resynchronization therapy were highest in pEF. Left ventricular end diastolic dimension (LVDd) was the smallest in the pEF group. Multivariable logistic regression analysis revealed that younger age, presence of AF, and lower levels of LVDd were predictors of "recovered EF". Kaplan-Meier analysis found that pEF presented the lowest cardiac event rate (P = 0.003) and all-cause mortality (P = 0.001). In multivariable Cox proportional hazard analyses, pEF (versus rEF) was an independent predictor of both cardiac event rate (HR = 0.668, 95%CI 0.450-0.994, P = 0.046) and all-cause mortality (HR = 0.655, 95%CI 0.459-0.934, P = 0.019).Hospitalized HFrEF patients with recovered EF are associated with younger age, higher presence of AF, and better prognosis.

Significance of Pulmonary Vascular Resistance and Diastolic Pressure Gradient on the New Definition of Combined Post-Capillary Pulmonary Hypertension.

Pulmonary hypertension (PH) caused by left-sided heart disease (LHD-PH) is classified into 2 types: isolated post-capillary PH (Ipc-PH) and combined pre- and post-capillary PH (Cpc-PH). However, the impact of pulmonary vascular resistance (PVR) or diastolic pressure gradient (DPG) on the prognosis of LHD-PH has varied among previous studies. Thus, we verified the significance of PVR or DPG on the prognosis of LHD-PH in our series.We analyzed 243 consecutive LHD-PH patients. The patients were divided into 3 groups: Group A, patients with PVR ≤ 3 Wood unit (WU) and DPG < 7 mmHg; Group B, patients with either PVR > 3 WU or DPG ≥ 7 mmHg; and Group C, patients with PVR > 3 WU and DPG ≥ 7 mmHg.The Kaplan-Meier curve demonstrated that Group B had lower cardiac death-free survival compared with Group A, whereas no significant differences were observed when compared with Group C. In the Cox hazard model, DPG was not associated with cardiac death in the LHD-PH patients. However, only in the ischemic heart disease group, patients with DPG ≥ 7 mmHg had worse prognosis compared with those with normal DPG.The cardiac death-free rate of patients with either increased PVR or DPG was close to that of patients with both increased PVR and DPG. It seems reasonable to define Cpc-PH only by PVR in the new criteria. However, the significance of DPG in LHD-PH might be dependent on the underlying cause of LHD-PH.

Prognostic Impact of Worsening Renal Function in Hospitalized Heart Failure Patients With Preserved Ejection Fraction: A Report From the JASPER Registry.

BACKGROUND: The characteristics and prognostic impact of persistent worsening renal function (WRF; defined as an increase in serum creatinine of >0.3 mg/dL during hospitalization) on heart failure with preserved ejection fraction have not yet been fully examined. METHODS AND RESULTS: This was a post hoc analysis of the Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry. We divided 523 patients with heart failure with preserved ejection fraction: the WRF group (n = 92 [17.6%]) and the non-WRF group (n = 431 [82.4%]). The WRF group showed a higher systolic blood pressure on admission and a higher prevalence of atherosclerotic diseases, respectively. Logistic regression analysis revealed that systolic blood pressure and loop diuretics were associated with WRF development (P < .05). The Kaplan-Meier analysis (median, 732 days) showed a higher all-cause death in the WRF group, as well as a higher composite end point of all-cause death or rehospitalization for HF (log-rank P < .001). The Cox proportional hazard analysis revealed WRF to be a predictor of both all-cause death (hazard ratio, 2.725; 95% confidence interval, 1.709-4.344; P < .001) and the composite end point (hazard ratio, 2.083; 95% confidence interval, 1.488-2.914; P < .001). CONCLUSIONS: Persistent WRF was associated with systolic blood pressure, atherosclerotic diseases, diuretics, and poor postdischarge prognosis in patients with heart failure with preserved ejection fraction.

Low T3 Syndrome Is Associated With High Mortality in Hospitalized Patients With Heart Failure.

BACKGROUND: We aimed to clarify the prognosis and pathophysiological parameters of low T3 syndrome in patients with heart failure (HF). METHODS AND RESULTS: Hospitalized patients with HF and euthyroidism (n = 911) were divided into 2 groups on the basis of free triiodothyronine (FT3) serum levels: the normal FT3 group (FT3 ≥2.3 pg/mL; n = 590; 64.8%) and the low FT3 group (FT3 <2.3 pg/mL; n = 321; 35.2%). We compared post-discharge cardiac and all-cause mortality by means of Kaplan-Meier analysis and Cox proportional hazard analysis, and the parameters of echocardiography and cardiopulmonary exercise testing by means of Student t test. In the follow-up period of median 991 (interquartile range 534-1659) days, there were 193 all-cause deaths, including 88 cardiac deaths. Cardiac and all-cause mortality were higher in the low FT3 group (log-rank P < .01). Low FT3 was a predictor of cardiac death (hazard ratio 1.926, 95% confidence interval [CI] 1.268-2.927; P = .002) and all-cause death (hazard ratio 2.304, 95% CI 1.736-3.058; P < .001). Although left ventricular ejection fraction was similar between the groups, the low FT3 group showed lower peak VO2 (13.6 ± 4.6 vs 16.6 ± 4.4 mL·kg-1·min,-oneP < .001) and higher VE/VCO2 slope (36.5 ± 8.2 vs 33.0 ± 7.5; P = .001). CONCLUSION: Low T3 syndrome in patients with HF is associated with higher cardiac and all cause-mortality.

Plasma levels of melatonin in dilated cardiomyopathy.

BACKGROUND: Melatonin is a multifunctional indolamine and has a cardioprotective role in a variety of cardiovascular processes via antioxidant, anti-inflammatory, antihypertensive, antithrombotic, and antilipemic effects. It has been reported that lower levels of circulating melatonin are significantly associated with a higher risk of acute myocardial infarction (AMI) and later cardiac remodeling. However, levels of melatonin in patients with dilated cardiomyopathy (DCM) and associations between melatonin levels and cardiac function remain unclear. METHODS AND RESULTS: We measured and compared plasma levels of melatonin in 61 control subjects, 81 AMI patients, and 77 DCM patients. Plasma levels of melatonin were progressively decreased from 71.9 pg/mL in the control group to 52.6 pg/mL in the DCM group and 21.9 pg/mL in the AMI group. Next, we examined associations of melatonin levels with parameters of laboratory data, echocardiography, and right-heart catheterization. In the DCM patients, circulating melatonin showed significant correlations with both high-sensitivity troponin T (R = -0.422, P < 0.001) and cardiac output (R = 0.431, P = 0.003), but not with B-type natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), pulmonary artery wedge pressure, or pulmonary artery pressure. CONCLUSION: Patients with not only AMI but also DCM had lower circulating melatonin levels. Circulating melatonin levels appear to correlate with myocardial injury and cardiac output in DCM patients.

Prior History and Incidence of Cancer Impacts on Cardiac Prognosis in Hospitalized Patients With Heart Failure.

BACKGROUND: Heart failure (HF) and cancer (CA) are becoming increasingly prevalent as the population ages. We aimed to evaluate prior history and occurrence of CA and its prognostic impact on HF.Methods and Results:Consecutive hospitalized HF patients (n=2,103) were divided into 2 groups according to prior history of CA: non-prior-CA group (n=1,828) and prior-CA group (n=275). Compared with the non-prior-CA group, the prior-CA group were older, and had higher prevalence of chronic kidney disease, anemia, and atrial fibrillation (P<0.05). In contrast, sex, other comorbidities, levels of natriuretic peptide and ejection fraction were comparable between groups. We focused on newly diagnosed CA after discharge for HF. In the follow-up period (median 623 days), 114 (6.2%) patients in the non-prior-CA and 17 (6.2%) patients in the prior-CA groups were newly diagnosed as having CA. Additionally, 83 (3.9%) CA-related patient deaths occurred (median 776 days). In the Kaplan-Meier analysis (median 1,037 days), not only all-cause death but also cardiac event rate was significantly higher in the prior-CA group than in the non-prior-CA group (log-rank P<0.01). In the Cox proportional hazard analysis, CA history was a predictor of cardiac event rate (HR 1.450, 95% CI 1.134-1.822), as well as all-cause death (HR 2.483, 95% CI 2.034-3.030). CONCLUSIONS: Prior-CA history was associated with high cardiac event and mortality rates. CA is notable comorbidity in HF patients.

PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction.

Cyclic nucleotide phosphodiesterase 1C (PDE1C) represents a major phosphodiesterase activity in human myocardium, but its function in the heart remains unknown. Using genetic and pharmacological approaches, we studied the expression, regulation, function, and underlying mechanisms of PDE1C in the pathogenesis of cardiac remodeling and dysfunction. PDE1C expression is up-regulated in mouse and human failing hearts and is highly expressed in cardiac myocytes but not in fibroblasts. In adult mouse cardiac myocytes, PDE1C deficiency or inhibition attenuated myocyte death and apoptosis, which was largely dependent on cyclic AMP/PKA and PI3K/AKT signaling. PDE1C deficiency also attenuated cardiac myocyte hypertrophy in a PKA-dependent manner. Conditioned medium taken from PDE1C-deficient cardiac myocytes attenuated TGF-ß-stimulated cardiac fibroblast activation through a mechanism involving the crosstalk between cardiac myocytes and fibroblasts. In vivo, cardiac remodeling and dysfunction induced by transverse aortic constriction, including myocardial hypertrophy, apoptosis, cardiac fibrosis, and loss of contractile function, were significantly attenuated in PDE1C-knockout mice relative to wild-type mice. These results indicate that PDE1C activation plays a causative role in pathological cardiac remodeling and dysfunction. Given the continued development of highly specific PDE1 inhibitors and the high expression level of PDE1C in the human heart, our findings could have considerable therapeutic significance.

Relation of Systolic Blood Pressure on the Following Day with Post-Discharge Mortality in Hospitalized Heart Failure Patients with Preserved Ejection Fraction.

The clinical scenario, which is based on systolic blood pressure (SBP) upon admission, is useful for classifying and determining initial treatment for acute heart failure (HF). However, the prognostic significance of SBP following the initial treatment is unclear.The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, and prospective registration of consecutive Japanese patients hospitalized with HF with preserved ejection fraction (HFpEF) and left ventricular ejection fraction ≥ 50%. We divided 525 patients into three groups based on their SBP on the day following hospitalization: high (SBP > 140 mmHg, n = 72, 13.7%); normal (100 ≤ SBP ≤ 140 mmHg, n = 379, 72.2%); and low (SBP < 100 mmHg, n = 74, 14.1%) groups. This analysis had two primary endpoints: (1) all-cause death and (2) all-cause death or rehospitalization for HF. In the Kaplan-Meier analysis, both of the endpoints were the highest in the low group (Log-Rank < 0.05, respectively). Compared to the normal and high groups, the low group demonstrated a higher prevalence of atrial fibrillation (67.1%, 63.9%, and 47.8%, P = 0.026) and the lowest left ventricular outflow tract velocity time integral determined by echocardiography (16.4 cm, 19.4 cm, and 23.3 cm, P = 0.001). In the multivariable Cox proportional hazard analysis, low SBP on the day following hospitalization was an independent predictor of all-cause death (hazard ratio 1.868, 95% confidence interval 1.024-3.407, P = 0.042) and the composite endpoint (hazard ratio 1.660, 95% confidence interval 1.103-2.500, P = 0.015).Classification based on SBP on the day following initial treatment predicts post-discharge prognosis in hospitalized patients with HFpEF.

Prognostic Impact of Restless Legs Syndrome on Patients with Heart Failure.

The restless legs syndrome (RLS) is a neurological disorder characterized by an irresistible urge to move the legs or arms for relief of uncomfortable or unpleasant sensations. Prevalence and prognostic impact of RLS on patients with heart failure (HF) remain unclear. We aimed to investigate the clinical characteristics and prognostic impact of RLS on HF patients.Consecutive 338 HF patients were evaluated for RLS and divided into two groups on the basis of presence of RLS: HF patients with RLS (RLS group, n = 29) and HF patients without RLS (non-RLS group, n = 309). We compared clinical characteristics, parameters of laboratory data and echocardiography, and rate of follow-up cardiac events including worsening HF and cardiac death between the two groups. Compared with the non-RLS group, the RLS group had higher prevalence of anemia (65.5% versus 40.8%, P = 0.010), higher usage of inotropic agents (31.0% versus 15.2%, P = 0.028), higher levels of B-type natriuretic peptide (570.8 versus 215.8 pg/mL, P = 0.018), and lower levels of left ventricular ejection fraction (40.4% versus 48.4%, P = 0.019). By contrast, age, gender, prevalence of other co-morbidities and medications were comparable between the groups. In the Kaplan-Meier analysis, the cardiac event rate was significantly higher in the RLS group than in the non-RLS group (log-rank P = 0.034). In the Cox proportional hazard analysis, RLS was a predictor for cardiac events in HF patients (hazard ratio: 1.783, 95% confidence interval: 1.038-3.063).RLS is associated with adverse prognosis in HF patients.

Utility of B-Type Natriuretic Peptide for Detecting Cardiac Involvement in Immunoglobulin Amyloidosis.

A useful biomarker for detecting cardiac amyloidosis (CA) has not been fully established. We aimed to investigate the utility of several biomarkers to detect CA in patients with amyloid light-chain (AL) amyloidosis.We examined the plasma levels of B-type natriuretic peptide (BNP), N-terminal fragment of the pro-brain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), serum amyloid A, and the difference between kappa and lambda free light chain (dFLC) between CA patients (n = 30, 47.6%) and non-CA patients (n = 33, 52.4%). Levels of BNP were significantly higher in the CA group compared to the non-CA group (1200.0 versus 224.0 pg/mL, P = 0.001). From the ROC analysis, the sensitivity and specificity of BNP for detecting CA (with a cut-off value of 412 pg/mL) were 83% and 70%, respectively, and the area under the receiver operating curve was 0.75 (95% CI 0.61-0.90, P < 0.001) in all AL amyloidosis patients (n = 63). In contrast, other markers such as NT-proBNP, hs-cTnT, serum amyloid A, and dFLC were not useful for detecting CA in AL amyloidosis patients. Additionally, in the Cox proportional hazard analysis, BNP was a predictor of all-cause mortality (hazard ratio 3.266, 95% confidence interval 1.498-7.119, P = 0.003).BNP is a useful biomarker for detecting cardiac involvement and predicting prognosis in AL amyloidosis patients.

The Fibrosis-4 Index Is Useful for Predicting Mortality in Patients with Pulmonary Hypertension due to Left Heart Disease.

Heart failure causes increased venous pressure, leading to liver dysfunction. The fibrosis-4 index is a simple index for liver fibrosis and has been reported to be useful for predicting prognosis in heart failure; however, its impact on patients with pulmonary hypertension due to left heart disease (PH-LHD) has not yet been fully elucidated.We enrolled consecutive 230 hospitalized patients who had been diagnosed as having PH-LHD. The fibrosis-4 index was calculated as follows: [aspartate transaminase (U/L) × age]/[alanine transaminase 1/2 (U/L) × platelet count (109/L) ]. We followed patients for all-cause mortality during the follow-up period (mean 1112 ± 822 days).The patients were divided into tertiles based on their fibrosis-4 index: the first tertile 0.335 to 1.381; the second tertile 1.391 to 2.311; and the third tertile 2.323 to 14.339. Compared with the first tertile, the third tertile had lower estimated glomerular filtration rates and hemoglobin levels. All-cause mortality was significantly higher in the third than in the first tertile. In a Cox proportional hazard model, the fibrosis-4 index was a predictor of all-cause mortality in PH-LHD patients (HR 1.212, 95% CI 1.099-1.337, P < 0.001).The fibrosis-4 index is associated with kidney function, anemia, and high mortality in PH-LHD patients.

Sporadic Cardiac Amyloidosis by Amyloidogenic Transthyretin V122I Variant.

Hereditary ATTR amyloid cardiomyopathy is defined as the intramyocardial deposition of amyloid fibrils derived from the mutation of transthyretin (TTR). A 51-year-old man was referred to our hospital for congestive heart failure. He and his family had no past history of heart diseases. Echocardiography showed remarkable left ventricular hypertrophy and reduced ejection fraction. Endomyocardial biopsy specimens presented positive staining of Congo-Red and transthyretin. A genetic test showed heterozygous V122I TTR gene mutation, which is very rare in Japan. We diagnosed him as with sporadic ATTR amyloidosis with mutation, and tafamidis was administered to stabilize TTR tetramer. Since the phenotype of ATTR amyloidosis varies depending on its penetration rate, it is crucial to always keep in mind the possibility of hereditary ATTR amyloidosis even in the case of amyloidosis with no clear family history.