Chemical Shift-Encoded MRI of the Lumbar Vertebral Bone Marrow for Detecting Osteoporosis With Low Trabecular Bone Quality in Patients With Breast Cancer Receiving Aromatase Inhibitors.

BACKGROUND: Osteoporosis with low trabecular bone quality (OLB) in patients with breast cancer receiving aromatase inhibitor (AI) therapy is associated with an increased risk of vertebral fractures. The capability of chemical shift-encoded MRI (CSE-MRI) in detecting OLB needs to be investigated. PURPOSE: To assess the diagnostic performance of proton density fat fraction (PDFF) and R2* measurements from CSE-MRI for detecting OLB in postmenopausal women with breast cancer undergoing AI therapy. STUDY TYPE: Prospective. POPULATION: 126 postmenopausal females (mean age: 69.5 ± 8.8 years) receiving AIs (average period: 41.6 ± 26.5 months) after breast cancer surgery. FIELD STRENGTH/SEQUENCE: 1.5-T, three-dimensional CSE-MRI (six echoes), T1-weighted Dixon, short tau inversion recovery, and diffusion-weighted images. ASSESSMENT: Both CSE-MRI and dual-energy x-ray absorptiometry were performed on the same day. Measurements included averaged PDFF, R2*, bone mineral density (BMD), and trabecular bone score (TBS) from L1 to L4 vertebrae. A T-score ≤ -2.5 from BMD measurements indicated osteoporosis, whereas T-scores of ≤ - 2.5 plus TBS ≤-3.7 indicated OLB. The diagnostic performance of PDFF, R2*, and the combination of PDFF and R2* for identifying osteoporosis or OLB was assessed. STATISTICAL TESTS: Student's t-test; Mann-Whitney U test; χ2 or Fisher exact tests; Pearson correlation; multivariate analysis; Receiver operating characteristic (ROC) analysis with the area under the curve (AUC); logistic regression model; intraclass correlation coefficient. A P-value <0.05 was considered statistically significant. RESULTS: For detecting osteoporosis, AUC values were 0.59 (PDFF), 0.66 (R2*), and 0.65 (combined PDFF and R2*). Significant mean differences were noted between patients with and without OLB for PDFF (66.11 ± 5.36 vs. 57.49 ± 6.43) and R2* (46.62 ± 9.24 vs. 63.36 ± 12.44). AUC values for detecting OLB were 0.75 (PDFF), 0.82 (R2*), and 0.84 (combined PDFF and R2*). DATA CONCLUSION: R2* may perform better than PDFF for identifying OLB in patients with breast cancer receiving AIs. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 4.

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.

The Prognostic Implications of Living Alone on Long-Term Mortality in Patients with Chronic Coronary Syndrome after Percutaneous Coronary Intervention.

Living alone is associated with increased cardiac events and mortality in patients with acute myocardial infarction. However, the prognostic impact of living alone with chronic coronary syndrome (CCS) still remains unclear. In the present study, we examined the relationship between living alone and long-term mortality in patients with CCS who underwent percutaneous coronary intervention (PCI).Consecutive 830 patients with CCS who underwent PCI were enrolled and divided into 2 groups according to whether or not they were living alone at the time of admission (living alone group and non-living alone group). We compared the clinical characteristics between the 2 groups and followed up cardiac mortality. The living alone group was younger compared with the non-living alone group (67.5 versus 70.7 years old, P = 0.017). The prevalence of comorbidities, including coronary risk factors, atrial fibrillation, heart failure, stroke, peripheral artery disease, coronary lesion characteristics, laboratory data, and left ventricular ejection fraction, were comparable between the 2 groups. During the follow-up period (median 1,622 days), 52 cardiac deaths occurred. In the Kaplan-Meier analysis, cardiac mortality was significantly higher in the living alone group than in the non-living alone group (24% versus 11%, P = 0.008). In the multivariable Cox proportional hazard analyses after adjusting for possible confounding factors, living alone was an independent predictor of cardiac mortality (hazard ratio, 2.426, 95% confidence interval 1.225-4.804, P = 0.011).Among CCS patients who underwent PCI, living alone was associated with high long-term cardiac mortality.

Acute myocardial infarction caused by Kawasaki disease requires more intensive therapy: Insights from the Japanese registry of All Cardiac and Vascular Diseases-Diagnosis Procedure combination.

BACKGROUND: Kawasaki disease (KD) induces coronary arteritis, which causes subsequent coronary aneurysms, and contributes to acute myocardial infarction (AMI). However, the differences regarding real-world treatment selection and mortality between AMI-complicated KD and AMI due to typical atherosclerosis (AMI-non KD) are unknown. AIM: The aim of the present study was to examine the current treatment strategy and prognosis of AMI-complicated KD compared with AMI due to typical atherosclerosis. METHOD: We used data from 2012 to 2019 from a nationwide claim database, the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination. RESULTS: Compared to the AMI-non KD patients (n = 70,227), the AMI-complicated KD patients (n = 73): (1) underwent percutaneous coronary intervention (PCI) less often and more coronary artery bypass grafting, intracoronary thrombolysis or intravenous coronary thrombolysis more often; (2) underwent stentless PCI using old balloon angioplasty or rotablator, when they underwent PCI; and (3) needed in-hospital cardiopulmonary resuscitation and intensive mechanical therapy such as intra-aortic balloon pump, percutaneous cardiopulmonary support or a respirator. Both the AMI-non KD and AMI-complicated KD patients had similar in-hospital mortality rates. CONCLUSIONS: Compared with AMI-non KD patients, AMI-complicated KD patients underwent non-PCI strategies such as bypass surgery or thrombolysis, and required intensive therapy with mechanical supports more often, but presented similar in-hospital mortality. When the AMI-complicated KD patients underwent PCI, stentless PCI using balloon angioplasty or rotablator was performed more often compared with the AMI-non KD patients.

Temporal Trends in the Practice Pattern for Sleep-Disordered Breathing in Patients With Cardiovascular Diseases in Japan　- Insights From the Japanese Registry of All Cardiac and Vascular Diseases - Diagnosis Procedure Combination.

BACKGROUND: After the publication of the Japanese Circulation Society guideline of sleep-disordered breathing (SDB) in 2010, with new evidence and changes to the health insurance system, trends in the practice pattern for SDB in patients with cardiovascular disease (CVD) might have changed.Methods and Results: This study evaluated the temporal changes in the practice pattern for SDB by using a nationwide claim database, the Japanese Registry of All Cardiac and Vascular Diseases - Diagnosis Procedure Combination (JROAD-DPC), from 2012 to 2019. The main findings were: (1) the number of CVD patients diagnosed with SDB increased (especially those with atrial fibrillation [AF] and heart failure [HF]); (2) the number of diagnostic tests for SDB performed during hospitalization increased for AF patients (from 1.3% in 2012 to 1.8% in 2019), whereas it decreased for other CVD patients; (3) the number of patients diagnosed with SDB increased in each type of CVD, except for patients with acute myocardial infarction (AMI); (4) continuous positive airway pressure (CPAP) treatment increased for AF patients (from 15.2% to 17.5%); (5) CPAP treatment decreased for patients with angina pectoris (AP) and AMI, and any treatment decreased for HF patients (from 46.1% to 39.7%); and (6) SDB was treated more often in HF patients than in AF, AP, and AMI patients (41.7% vs. 17.2%, 19.1% and 20.4%, respectively). CONCLUSIONS: The practice pattern for SDB in CVD patients has changed from 2012 to 2019.

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.

Prognostic Value of Simultaneous Analysis with Myocardial Flow Reserve and Right Ventricular Strain by Hybrid 13N-Ammonia Positron Emission Tomography/Magnetic Resonance Imaging in Coronary Artery Disease.

Myocardial flow reserve (MFR) derived from 13N-ammonia positron emission tomography (PET) is used to predict adverse cardiac events in patients with coronary artery disease (CAD). Right ventricular global longitudinal strain (RVGLS) measured by magnetic resonance imaging (MRI) is used to evaluate RV function and predict cardiac events. This study aimed to evaluate the prognostic value of MFR and RVGLS measured by hybrid 13N-ammonia PET/MRI in patients with CAD.Sixty-one patients who underwent 13N-ammonia PET/MRI were analyzed. The end points were defined as a composite of all-cause death, myocardial infarction, sustained ventricular arrhythmia, hospitalization due to decompensated heart failure, and revascularization. At a follow-up of 2.8 ± 1.9 years, 21 events had occurred. Kaplan-Meier analysis showed that the event-free rate was significantly lower in the group with MFR < 1.80 than in that with MFR ≥ 1.80 (P < 0.001). Additionally, the event-free rate was significantly lower in the group with RVGLS > -18.22% than in that with RVGLS ≤ -18.22% (P = 0.025). After dividing the patients into 4 groups by the median MFR and the median RVGLS, the event-free rate was lowest in the combined group of MFR < 1.80 and RVGLS > -18.22% than any other groups (P < 0.001). In a Cox proportional hazard analysis, MFR and RVGLS were independent predictors of cardiac adverse events in the patients with CAD.The simultaneous assessment of MFR and RVGLS by 13N-ammonia PET/MRI revealed the feasibility of precise risk stratification for cardiac events in patients with CAD.

The Prognostic Impact of D-Dimer on Long-Term Mortality in Patients with Coronary Artery Disease after Percutaneous Coronary Intervention.

D-dimer is a common measurable coagulation marker that is associated with the risk of thrombotic events in vascular diseases. However, the impact of D-dimer on long-term mortality in coronary artery disease (CAD) patients remains unclear. This study investigated the association between D-dimer and long-term all-cause, cardiac and cancer mortality in CAD patients. Continuous 1,440 patients with CAD who underwent percutaneous coronary intervention (PCI) and survived to discharge were enrolled. These patients were divided into 3 groups based on plasma D-dimer levels at admission. Baseline D-dimer levels were grouped by tertiles: first (D-dimer < 0.7 µg/mL, n = 455), second (0.7 ≤ D-dimer < 1.2, n = 453), and third (1.2 ≤ D-dimer, n = 532). In a Kaplan-Meier analysis (mean follow-up periods 1,572 days), all-cause, cardiac and cancer mortalities were significantly higher in the third tertile than others (P < 0.001, P < 0.001 and P < 0.001, respectively). In multivariable Cox proportional hazard analyses after adjusting for confounding factors, a high D-dimer level was an independent predictor of all-cause, cardiac, non-cardiac and cancer mortalities (HR 3.23, P < 0.001; HR 3.06, P = 0.008; HR 3.11, P = 0.026). In a subgroup analysis, there were no interactions except for the gender subgroup in cancer mortality. In patients with CAD after PCI, high D-dimer levels were associated with long-term all-cause, cardiac and cancer mortality.

Amyloid precursor protein 770 is specifically expressed and released from platelets.

Platelets not only play an essential role in hemostasis after vascular injury but are also involved in the development of coronary artery disease (CAD) and cerebrovascular lesions. Patients with CAD and cerebral ischemia are recommended to undergo antiplatelet therapy, but they have an increased incidence of major bleeding complications. Both assessment of the platelet activation status and response to antiplatelet therapy in each patient are highly desired. ß-Amyloid precursor protein (APP) 770 is expressed in vascular endothelial cells, and its extracellular region, a soluble form of APP770 (sAPP770, also called nexin-2), is proteolytically cleaved for shedding. Abundant sAPP770 is also released from activated platelets. In this study, we used peripheral blood samples from patients with CAD and control subjects and evaluated sAPP770 as a specific biomarker for platelet activation. First, the plasma levels of sAPP770 correlated well with those of the soluble form CD40 ligand (CD40L), an established biomarker for platelet activation. Additionally, flow cytometry analysis using peripheral blood cells showed that CD40L expression is up-regulated in activated T cells, whereas APP770 expression is negligible in all blood cell types except platelets. Following stimulation with collagen or ADP, aggregating platelets immediately released sAPP770. Finally, patients with dual antiplatelet therapy showed significantly lower levels of plasma sAPP770 than those with no therapy. Taken together, our data show that plasma sAPP770 could be a promising biomarker for platelet activation.

Crucial role of hematopoietic JAK2 V617F in the development of aortic aneurysms.

JAK2V617F is the most frequent driver mutation in myeloproliferative neoplasms (MPNs) and is associated with vascular complications. However, the impact of hematopoietic JAK2V617F on the aortic aneurysms (AAs) remains unknown. Our cross-sectional study indicated that 9 (23%) out of 39 MPN patients with JAK2V617F exhibited the presence of AAs. Next, to clarify whether the hematopoietic JAK2V617F contributes to the AAs, we applied a bone marrow transplantation (BMT) with the donor cells from Jak2V617F transgenic (JAK2V617F) mice or control wild-type (WT) mice into lethally irradiated apolipoprotein E-deficient mice. Five weeks after BMT, the JAK2V617F-BMT mice and WT-BMT mice were subjected to continuous angiotensin II infusion to induce AA formation. Four weeks after angiotensin II infusion, the abdominal aorta diameter in JAK2V617F-BMT mice was significantly enlarged compared to that in the WT-BMT mice. Additionally, the abdominal AA-free survival rate was significantly lower in the JAK2V617F-BMT mice. Hematopoietic JAK2V617F accelerated aortic elastic lamina degradation as well as activation of matrix metalloproteinase (MMP)-2 and MMP-9 in the abdominal aorta. The numbers of infiltrated macrophages were significantly upregulated in the abdominal aorta of the JAK2V617F-BMT mice accompanied by STAT3 phosphorylation. The accumulation of BM-derived hematopoietic cells carrying JAK2V617F in the abdominal aorta was confirmed by use of reporter GFP-transgene. BM-derived macrophages carrying JAK2V617F showed increases in mRNA expression levels of Mmp2, Mmp9, and Mmp13. Ruxolitinib decreased the abdominal aorta diameter and the incidence of abdominal AA in the JAK2V617F-BMT mice. Our findings provide a novel feature of vascular complications of AAs in MPNs with JAK2V617F.

Myocardial viability with chronic total occlusion assessed by hybrid positron emission tomography/magnetic resonance imaging.

BACKGROUND: The present study was performed to compare the relationship of 18F-fluorodeoxyglucose (FDG) uptake and late gadolinium enhancement (LGE) transmurality with the improvement of left ventricular function in patients with coronary chronic total occlusion (CTO) assessed by hybrid FDG positron emission tomography (PET)/magnetic resonance imaging (MRI). METHODS: Thirty-eight consecutive patients with CTO underwent FDG PET/MRI. Twenty-three patients then underwent percutaneous coronary intervention (PCI), and the final study population comprised 15 patients who underwent both initial and follow-up MRI. The degree of wall motion abnormality in each of the 17 myocardial segments was evaluated based on the extent of wall thickening on cine MRI using a 5-point scale. RESULTS: Among all 646 myocardial segments at baseline, FDG uptake significantly decreased as the transmurality of LGE is advanced. Of the 15 patients who underwent PCI, 152 segments showed wall motion abnormalities at baseline. The functional recovery of the wall motion abnormality of the PET-viable/MRI-viable segments was highest, and that of the PET-nonviable/MRI-nonviable segments was lowest. There were no differences in functional recovery between the PET-viable/MRI-nonviable and PET-nonviable/MRI-viable segments. CONCLUSION: Simultaneous assessment of FDG and LGE using a hybrid PET/MRI system can help to predict functional recovery after PCI in patients with CTO.

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.

High-fat diet attenuates the improvement of hypoxia-induced pulmonary hypertension in mice during reoxygenation.

BACKGROUND: It is widely recognized that metabolic disorder is associated with pulmonary hypertension (PH). It is known that hypoxia-induced elevated pulmonary artery pressure in mice returns to normal pressure during reoxygenation. However, it is still unclear how metabolic disorder affects the reverse remodeling of pulmonary arteries. In this study, we investigated the effects of high-fat diet (HFD) on the decrease in pulmonary artery pressure and reverse remodeling of pulmonary arteries in mice with hypoxia-induced PH. METHODS: We used female C57BL/6 mice aged 8 weeks. After being exposed to hypoxia (10% oxygen for four weeks) to induce PH, the mice were returned to normoxic conditions and randomized into a normal diet (ND) group and HFD group. Both groups were fed with their respective diets for 12 weeks. RESULTS: The Fulton index and right ventricular systolic pressure measured by a micro-manometer catheter were significantly higher in the HFD group than in the ND group at 12 weeks after reoxygenation. The medial smooth muscle area was larger in the HFD group. Caspase-3 activity in the lung tissue of the HFD group was decreased, and the apoptosis of pulmonary smooth muscle cells was suppressed after reoxygenation. Moreover, the expression levels of peroxisome proliferator-activated receptor-γ and apelin were lower in the HFD group than in the ND group. CONCLUSIONS: The results suggest that metabolic disorder may suppress pulmonary artery reverse remodeling in mice with hypoxia-induced PH during reoxygenation.

Clinical impact of long PR-interval and presence of late gadolinium enhancement on hospitalized patients with non-ischemic heart failure.

BACKGROUND: The combination of electrical and structural remodeling may have a strong effect on the prognosis of non-ischemic heart failure (HF). We aimed to clarify whether prolonged PR-interval and the presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) influence the outcomes of patients with non-ischemic HF. METHODS: We studied 262 consecutive hospitalized patients with non-ischemic HF. In a clinically stable condition, a 12-lead electrocardiogram and CMR were performed, and the clinical characteristics and outcomes were investigated. RESULTS: During the follow-up of 967.7 ± 851.8 days, there were 68 (25.9%) cardiac events (HF or sudden death, re-hospitalization due to HF, or ventricular tachyarrhythmias). In a multivariable analysis, a median rate-adjusted PR (PRa)-interval of ≥173.5 ms and the presence of LGE were associated with cardiac events with a hazard ratio of 1.690 and 2.045 (p = .044 and p = .006, respectively). Study subjects were then divided into four groups based on long (≥173.5 ms) or short (<173.5 ms) PRa-interval and LGE status: short PRa/non-LGE (n = 80), long PRa/non-LGE (n = 72), short PRa/LGE (n = 51), and long PRa/LGE (n = 59). Cardiac events were 16.2% in short PRa/non-LGE, 25.0% in long PRa/non-LGE, 27.4% in short PRa/LGE, and 38.9% in long PRa/LGE (p = .026), respectively. The multivariable Cox proportional hazard analysis showed that long PRa/LGE was an independent predictor for cardiac events compared to short PRa/non-LGE (hazard ratio, 3.378, p = .001). CONCLUSIONS: The combination of a long PRa-interval and the presence of LGE provide a better predictive value of cardiac events in non-ischemic 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.

Autonomic dysfunction in cardiac amyloidosis assessed by heart rate variability and heart rate turbulence.

BACKGROUND: Cardiac amyloidosis (CA) is characterized by left ventricular hypertrophy (LVH) and autonomic nervous imbalance due to amyloid infiltration. However, autonomic dysfunction is often seen in heart failure (HF) with LVH from other etiologies. We aimed to characterize autonomic dysfunction in CA from other etiologies of LVH. METHODS: Fifty-five HF patients with LVH (35 males, mean age 65 ± 16 years) were enrolled. LVH was defined as left ventricular mass index measured by echocardiography >95 g/m2 in women and 115 g/m2 in men. The etiology was as follows: amyloid light chain (AL)-CA, n = 14; hypertrophic cardiomyopathy, n = 21; and aortic stenosis (AS), n = 20. With the patient in a clinically stable condition, heart rate variability (HRV) and heart rate turbulence (HRT), which reflect autonomic dysfunction, were measured using Holter monitoring and compared among the three groups. RESULTS: Brain natriuretic peptide levels, LVH severity, left ventricular ejection fraction, and tissue Doppler index E/e' did not differ among the three groups. However, severe abnormalities of HRV and HRT were obtained in AL-CA. In the ROC analysis to identify AL-CA in HF with LVH, the best cutoff value for standard deviation of all R-R intervals, standard deviation of the 5-min mean R-R intervals, turbulence onset, and turbulence slope were 68.5 ms (AUC: 0.865), 58.5 ms (AUC: 0.834), 0.25% (AUC: 0.813), and 1.00 ms/RR (AUC 0.736), respectively. CONCLUSION: Autonomic dysfunction is a hallmark of AL-CA, and its noninvasive assessment by Holter monitoring may be a useful tool for differential diagnosis of HF with LVH.

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.

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.

Ablation of Toll-like receptor 9 attenuates myocardial ischemia/reperfusion injury in mice.

In myocardial ischemia/reperfusion injury, the innate immune and subsequent inflammatory responses play a crucial role in the extension of myocardial damage. Toll-like receptor 9 (TLR9) is a critical receptor for recognizing unmethylated CpG motifs that mitochondria contain in their DNA, and induces inflammatory responses. The aim of this study was to elucidate the role of TLR9 in myocardial ischemia/reperfusion injury. Isolated hearts from TLR9-deficient and control wild-type mice were subjected to 35 min of global ischemia, followed by 60 min of reperfusion with Langendorff apparatus. Furthermore, wild-type mouse hearts were infused with DNase I and subjected to ischemia/reperfusion. Ablation of TLR9-mediated signaling pathway attenuates myocardial ischemia/reperfusion injury and inflammatory responses, and digestion of extracellular mitochondrial DNA released from the infarct heart partially improved myocardial ischemia/reperfusion injury with no effect on inflammatory responses. TLR9 could be a therapeutic target to reduce myocardial ischemia/reperfusion injury.