Very short-term blood pressure variability by pulse transit time-based measurements during night-time predicts future cardiovascular events in patients with ischemic heart disease.

Blood pressure (BP) variability (BPV) is associated with an increased risk of cardiovascular events, independent of absolute BP values. However, the predictive significance of very short-term BPV, occurring within seconds or minutes, in patients with ischemic heart disease (IHD) has yet to be established. This prospective study involved 206 consecutive hospitalized patients with IHD (mean age 67.6 years, 78.2% male) who underwent pulse transit time (PTT)-based continuous BP recording during the night-time. Very short-term BPV was assessed by standard deviation (SD), coefficient of variation (CV), and variation independent of mean (VIM) of PTT-BP. Clinical outcome data were collected. When the patients were categorized into two groups according to the median value of very short-term BPV, Kaplan-Meier analysis revealed that patients with elevated SD, CV, and VIM of systolic and diastolic PTT-BP were associated with lower event-free survival rates from the composite cardiovascular events including cardiac deaths, worsening heart failure cases, nonfatal myocardial infarctions, unplanned revascularizations, and strokes over a median follow-up of 797 days. In a multivariate Cox proportional hazards analysis adjusting for confounding variables, each parameter as a continuous variable was independently associated with adverse events. Incorporating very short-term BPV into basic models had a significant impact on risk reclassification and integrated discrimination for cardiovascular outcomes. In conclusion, the identification of patients with elevated very short-term BPV during the night-time through a PTT-driven approach helps stratify the future risk in IHD patients.

Impact of Cardio-Ankle Vascular Index on Future Cancer in Patients With Coronary Artery Disease.

Background: Cardiovascular risk factors are associated with increased risk of future cancer. However, the relationship between quantitative parameters of atherosclerosis and future cancer risk is unclear. Methods and Results: A total of 1,057 consecutive patients with coronary artery disease was divided into 2 groups according to the cutoff value of the cardio-ankle vascular index (CAVI) derived by receiver operating characteristic curve analysis: low CAVI group (CAVI <8.82; n=487), and high CAVI group (CAVI ≥8.82; n=570). Patients in the high CAVI group were older and had a higher prevalence of diabetes, chronic kidney disease, anemia and history of stroke compared with patients in the low CAVI group. There were 141 new cancers during the follow-up period. The cumulative incidence of new cancer was significantly higher in the high CAVI group than in the low CAVI group (P=0.001). In a multivariate Cox proportional hazard analysis, high CAVI was found to be an independent predictor of new cancer diagnosis (hazard ratio 1.62; 95% confidence interval 1.11-2.36; P=0.012). In the analysis of individual cancer types, high CAVI was associated with lung cancer (hazard ratio 2.85; 95% confidence interval 1.01-8.07; P=0.049). Conclusions: High CAVI was associated with the risk of future cancer in patients with coronary artery disease.

Reduced Fetuin-A Levels Are Associated With Exercise Intolerance and Predict the Risk of Adverse Outcomes in Patients With Heart Failure: The Role of Cardiac-Hepatic-Peripheral Interaction.

BACKGROUND: Exercise intolerance in heart failure arises from multifactorial pathophysiological mechanisms. Hepatokines, liver-synthesized molecules, regulate systemic metabolisms in peripheral tissues. We previously identified the hepatokine fetuin-A as being linked to liver hypoperfusion in heart failure. Here, we investigated the role of fetuin-A in connecting cardiac-hepatic-peripheral interaction. METHODS AND RESULTS: We conducted a prospective study involving 202 consecutive hospitalized patients (mean age, 56.8 years; 76.2% men) with heart failure who underwent cardiopulmonary exercise testing. We measured the serum concentration of fetuin-A by ELISA. Correlation analysis revealed a negative association between fetuin-A levels and the ratio of minimum minute ventilation to carbon dioxide production, its slope, and a tendency toward a positive correlation with peak oxygen uptake. Patients with impaired exercise tolerance exhibited lower fetuin-A levels. During a median follow-up of 1045 days, 18.3% experienced cardiac events, including 4 cardiac deaths and 33 cases of worsening heart failure. Classification and regression tree analysis identified a high-risk subgroup with lower fetuin-A (<24.3 mg/L) and impaired exercise tolerance (peak oxygen uptake<14.2 mL/kg per min). Kaplan-Meier analysis revealed that this subgroup had the highest risk of cardiac events. In a multivariable Cox proportional hazard model, the combination of lower fetuin-A and exercise intolerance was independently associated with increased risks of cardiac events. CONCLUSIONS: Reduced circulating fetuin-A levels were associated with exercise intolerance in heart failure patients. Fetuin-A could emerge as a target implicated in exercise capacity connecting cardiac-hepatic-peripheral interaction and as a valuable biomarker for predicting prognosis when combined with peak oxygen uptake.

Malnutrition stratified by marasmus and kwashiorkor in adult patients with heart failure.

Malnutrition is classified into marasmus and kwashiorkor in children. However, the clinical significance of these aspects is unclear in adult patients with heart failure (HF). We divided 2308 adult patients with HF into four groups according to marasmus type (body mass index < 18.5 kg/m2) and kwashiorkor type (serum albumin < 3.4 g/dL) malnutrition: Group C (no malnutrition, n = 1511, 65.5%), Group M (marasmus type malnutrition, n = 133, 5.8%), Group K (kwashiorkor type malnutrition, n = 554, 24.0%) and Group MK (marasmic-kwashiorkor type malnutrition, n = 110, 4.8%). Group M showed the lowest blood pressure. Groups K and MK showed higher levels of B-type natriuretic peptide. Right atrial pressure was lowest in Groups M and MK. Kaplan-Meir analysis demonstrated that Group MK had the lowest event-free rate of all-cause death and cardiac death. In the multivariable Cox proportional hazard analysis, Groups M, K, and MK were associated with all-cause death (hazard ratio 1.790, 1.657 and 2.313, respectively) and cardiac death (hazard ratio 2.053, 1.855 and 3.001, respectively) compared to Group C as a reference. Marasmus type and kwashiorkor type malnutrition are associated with distinct profiles and high mortality, and marasmic-kwashiorkor type malnutrition has the poorest prognosis.

Elevated blood bicarbonate levels and long-term adverse outcomes in patients with chronic heart failure.

AIMS: The bicarbonate (HCO3 -) buffer system is crucial for maintaining acid-base homeostasis and blood pH. Recent studies showed that elevated serum HCO3 - levels serve as an indicator of the beneficial effects of acetazolamide in improving decongestion in acute heart failure. In this study, we sought to clarify the clinical relevance and prognostic impact of HCO3 - in chronic heart failure (CHF). METHODS: This cohort study enrolled 694 hospitalized patients with CHF (mean age 68.6 ± 14.6, 62% male) who underwent arterial blood sampling and exhibited neutral pH ranging from 7.35 to 7.45. We characterized the patients based on HCO3 - levels and followed them to register cardiac events. RESULTS: Among the patients, 17.3% (120 patients) had HCO3 - levels exceeding 26 mmol/L. Patients presenting HCO3 - > 26 mmol/L were more likely to use loop diuretics and had higher serum sodium and lower potassium levels, but left ventricular ejection fraction did not differ compared with those with HCO3 - between 22 and 26 (379 patients) or those with HCO3 - < 22 mmol/L (195 patients). During a median follow-up period of 1950 days, Kaplan-Meier analysis revealed that patients with HCO3 - > 26 mmol/L had the lowest event-free survival rate from either cardiac deaths or heart failure-related rehospitalization (P < 0.01 and 0.03, respectively). In the multivariable Cox model, the presence of HCO3 - > 26 mmol/L independently predicted increased risks of each cardiac event with a hazard ratio of 2.31 and 1.69 (P < 0.01 and 0.02, respectively), while HCO3 - < 22 mmol/L was not associated with these events (hazard ratios, 0.99 and 1.19; P = 0.98 and 0.43, respectively). CONCLUSIONS: Elevated blood HCO3 - levels may signify enhanced proximal nephron activation and loop diuretic resistance, leading to long-term adverse outcomes in patients with CHF, even within a normal pH range.

Organ injury and its management in heart failure: Liver, kidney, and thyroid gland dysfunction.

Heart failure is hemodynamically characterized as congestion and/or end-organ hypoperfusion, and is associated with increased morbidity and mortality. Underlying pathophysiology, such as neuro-hormonal activation, exacerbates heart failure and leads to functional deterioration of other organs. We have been conducting clinical research to study the pathophysiology of heart failure and discover prognostic factors. In this review article, we report the results and implications of our clinical research on heart failure.

Neutrophil Extracellular Traps in Myocardial Tissue Drive Cardiac Dysfunction and Adverse Outcomes in Patients With Heart Failure With Dilated Cardiomyopathy.

BACKGROUND: The immune systems and chronic inflammation are implicated in the pathogenesis of dilated cardiomyopathy (DCM) and heart failure. However, the significance of neutrophil extracellular traps (NETs) in heart failure remains to be elucidated. METHODS: We enrolled consecutive 62 patients with heart failure with idiopathic DCM who underwent endomyocardial biopsy. Biopsy specimens were subjected to fluorescent immunostaining to detect NETs, and clinical and outcome data were collected. Ex vivo and in vivo experiments were conducted. RESULTS: The numbers of NETs per myocardial tissue area and the proportion of NETs per neutrophil were significantly higher in patients with DCM compared with non-DCM control subjects without heart failure, and the numbers of NETs were negatively correlated with left ventricular ejection fraction. Patients with DCM with NETs (n=32) showed lower left ventricular ejection fraction and higher BNP (B-type natriuretic peptide) than those without NETs (n=30). In a multivariable Cox proportional hazard model, the presence of NETs was independently associated with an increased risk of adverse cardiac events in patients with DCM. To understand specific underlying mechanisms, extracellular flux analysis in ex vivo revealed that NETs-containing conditioned medium from wild-type neutrophils or purified NET components led to impaired mitochondrial oxygen consumption of cardiomyocytes, while these effects were abolished when PAD4 (peptidyl arginine deiminase 4) in neutrophils was genetically ablated. In a murine model of pressure overload, NETs in myocardial tissue were predominantly detected in the acute phase and persisted throughout the ongoing stress. Four weeks after transverse aortic constriction, left ventricular ejection fraction was reduced in wild-type mice, whereas PAD4-deficient mice displayed preserved left ventricular ejection fraction without inducing NET formation. CONCLUSIONS: NETs in myocardial tissue contribute to cardiac dysfunction and adverse outcomes in patients with heart failure with DCM, potentially through mitochondrial dysfunction of cardiomyocytes.

Collagen Triple Helix Repeat-Containing Protein 1 Is a Novel Biomarker of Right Ventricular Involvement in Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension leads to right ventricular failure, which is a major determinant of prognosis. Circulating biomarkers for right ventricular function are poorly explored in pulmonary hypertension. This study aimed to clarify the significance of collagen triple helix repeat-containing protein 1 (CTHRC1) as a biomarker of right ventricular failure in pulmonary hypertension. METHODS: A monocrotaline-induced pulmonary hypertension rat model was used to evaluate right ventricular CTHRC1 expression and its relationship with fibrosis. Next, human plasma CTHRC1 levels were measured in controls (n = 20), pulmonary arterial hypertension (n = 46), and patients with chronic thromboembolic pulmonary hypertension (CTEPH) (n = 64) before the first and after the final balloon pulmonary angioplasty. RESULTS: CTHRC1 expression was higher in the right ventricles of rats with monocrotaline-induced pulmonary hypertension than in those of controls. CTHRC1 was colocalized with vimentin and associated with fibrosis in the right ventricles. Plasma CTHRC1 levels were higher in human patients with pulmonary arterial hypertension (P = 0.006) and CTEPH (P = 0.011) than in controls. Plasma CTHRC levels were correlated with B-type natriuretic peptide (R = 0.355, P < 0.001), tricuspid lateral annular peak systolic velocity (R = -0.213, P = 0.029), and right ventricular fractional area change (R = -0.225, P = 0.017). Finally, plasma CTHRC1 levels were decreased after the final balloon pulmonary angioplasty (P < 0.001) in CTEPH. CONCLUSIONS: CTHRC1 can be a circulating biomarker associated with right ventricular function and fibrosis in pulmonary hypertension and might reflect the therapeutic efficacy of balloon pulmonary angioplasty in CTEPH.

Prognostic significance of left atrial strain combined with left ventricular strain using cardiac magnetic resonance feature tracking in patients with heart failure with preserved ejection fraction.

We aimed to evaluate the prognostic value of left ventricular global longitudinal strain (LVGLS) and left atrial strain (LAS) obtained from magnetic resonance imaging (MRI) feature tracking in patients with heart failure with preserved ejection fraction (HFpEF). We retrospectively enrolled consecutive patients with HFpEF admitted to our hospital who underwent cardiac MRI. LVGLS and LAS were obtained from cine MRI by feature tracking. The end point was defined as a composite of all-cause death, myocardial infarction, and hospitalization due to decompensated HF. One-hundred patients with HFpEF were enrolled. Mean LVGLS and LAS were - 13.7 ± 3.7% and 22.5 ± 11.6%, respectively. During follow-up of 4.4 ± 1.9 years, 24 events occurred. Multivariate Cox proportional hazards model analysis demonstrated LAS was independently associated with adverse cardiac events. Kaplan-Meier curve analysis revealed that the patients with both LVGLS and LAS worse than the median (LVGLS ≥ - 12.2% and LAS ≤ 13.8%) had a significantly lower event-free rate compared to those with preserved strain (Log-rank P < 0.001). Simultaneous assessment of LVGLS and LAS using MRI was useful for risk stratification in the patients with HFpEF.

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.

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.

Geriatric Nutritional Risk Index predicts bleeding event in patients with heart failure.

AIMS: We aimed to elucidate the association between malnutrition and the occurrence of bleeding events in patients with heart failure. METHODS AND RESULTS: We evaluated the nutritional status of patients with heart failure [n = 2044, median (inter-quartile range) age 69.0 (59.0-78.0) years, 1209 (59.1%) males] using the Geriatric Nutritional Risk Index (GNRI). The primary endpoint was a composite of bleeding events such as haemorrhagic stroke or gastrointestinal bleeding. According to the survival classification and regression tree analysis, the accurate cut-off point of GNRI for predicting the primary endpoint was 106.2. We divided the patients into two groups based on GNRI levels: high GNRI group (GNRI ≥ 106.2, n = 606, 29.6%) and low GNRI group (GNRI < 106.2, n = 1438, 70.4%). We compared the patients' characteristics and prognosis between the two groups. The low GNRI group was older [72.0 (63.0-79.0) vs. 63.0 (53.0-73.0) years, P < 0.001] and had a lower prevalence of male sex (56.9% vs. 64.5%, P = 0.001). There were no differences in the use of antiplatelet agents and anticoagulants between the two groups. Levels of B-type natriuretic peptide were higher [321.1 (123.3-667.4) vs. 111.6 (42.6-235.4) pg/mL, P < 0.001] and levels of haemoglobin were lower [12.4 (10.8-13.7) vs. 14.2 (12.9-15.4) g/dL, P < 0.001] in the low GNRI group. The Kaplan-Meier analysis demonstrated that bleeding event rates were higher in the low GNRI group (log-rank P < 0.001). The multivariable Cox proportional hazard analysis revealed that low GNRI (hazard ratio 1.952, 95% confidence interval 1.002-3.805, P = 0.049) was associated with bleeding events. CONCLUSIONS: Heart failure patients with poor nutritional status, determined by GNRI under 106.2, experienced high bleeding event rates. Comprehensive management is required to avoid bleeding event in those populations.

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.

Hepatic Venous Stasis Index Reflects Hepatic Congestion and Predicts Adverse Outcomes in Patients With Heart Failure.

Background It has been reported that the hepatic vein waveforms determined by abdominal ultrasonography can assess hepatic congestion in patients with heart failure (HF). However, the parameter that quantifies hepatic vein waveforms has not been established. We suggest the hepatic venous stasis index (HVSI) as the novel indicator to evaluate hepatic congestion quantitatively. To examine the clinical significance of HVSI in patients with HF, we aimed to clarify the associations of HVSI with the parameters of cardiac function and right heart catheterization, as well as that with prognosis, in patients with HF. Methods and Results We performed abdominal ultrasonography, echocardiography, and right heart catheterization in patients with HF (n=513). The patients were divided into 3 groups based on HVSI as follows: HVSI 0 (HVSI=0, n=253), low HVSI (HVSI 0.01-0.20, n=132), and high HVSI (HVSI>0.20, n=128). We examined the associations of HVSI with parameters of cardiac function and right heart catheterization and followed up for cardiac events defined as cardiac death or worsening HF. There was a significant increase in level of B-type natriuretic peptide, inferior vena cava diameter, and mean right atrial pressure with increasing HVSI. During the follow-up period, cardiac events occurred in 87 patients. In the Kaplan-Meier analysis, cardiac event rate increased across increasing HVSI (log-rank, P=0.002). Conclusions HVSI assessed by abdominal ultrasonography reflects hepatic congestion and right-sided HF and is associated with adverse prognosis in patients with HF.

Prognostic Role of Circulating LTBP-2 in Patients With Dilated Cardiomyopathy: A Novel Biomarker Reflecting Extracellular Matrix LTBP-2 Accumulation.

BACKGROUND: Dilated cardiomyopathy (DCM) is a life-threatening disease related to heart failure. Extracellular matrix proteins have an important role in the pathogenesis of DCM. Latent transforming growth factor beta-binding protein 2 (LTBP-2), a type of extracellular matrix protein, has not been investigated in DCM. METHODS: First, we compared plasma LTBP-2 levels in 131 patients with DCM who underwent endomyocardial biopsy and 44 controls who were matched for age and sex and had no cardiac abnormalities. Next, we performed immunohistochemistry for LTBP-2 on endomyocardial biopsy specimens and followed the DCM patients for ventricular assist device (VAD) implantation, cardiac death, and all-cause death. RESULTS: Patients with DCM had elevated plasma LTBP-2 levels compared with controls (P < 0.001). Plasma LTBP-2 levels were positively correlated with LTBP-2-positive fraction in the myocardium from the biopsy specimen. When patients with DCM were divided into 2 groups according to LTBP-2 levels, Kaplan-Meier analysis demonstrated that patients with high plasma LTBP-2 were associated with increased incidences of cardiac death/VAD and all-cause death/VAD. In addition, patients with high myocardial LTBP-2-positive fractions were associated with increased incidences of these adverse outcomes. Multivariable Cox proportional hazard analysis showed that plasma LTBP-2 and myocardial LTBP-2-positive fraction were independently associated with adverse outcomes. CONCLUSIONS: Circulating LTBP-2 can serve as a biomarker to predict adverse outcomes, reflecting extracellular matrix LTBP-2 accumulation in the myocardium in DCM.

Impact of bleeding event for new cancer diagnosis in patients with antiplatelet therapy after percutaneous coronary intervention.

BACKGROUND: Bleeding is a frequent event in coronary artery disease (CAD) patients treated with antiplatelet therapy after percutaneous coronary intervention (PCI). The impact of bleeding in CAD patients with antiplatelet therapy for cancer diagnosis remains unclear. METHODS AND RESULTS: Consecutive 1565 CAD patients treated with antiplatelet therapy after PCI, without anticoagulation therapy, were enrolled. We aimed to investigate the relationships between bleeding events and the incidence of new cancer diagnosis. Among 1565 patients, 178 (11.3 %) experienced any bleeding events defined as Bleeding Academic Research Consortium (BARC) type 1, 2, 3, or 5 bleeding and 75 (4.7 %) experienced minor bleeding events defined as BARC 1 or 2 bleeding, and 116 (7.4 %) were diagnosed with new cancer during a mean follow-up period of 1528 days. Among 178 patients with any bleeding and 75 patients with minor bleeding events, 20 (11.2 %) and 13 (17.3 %) were subsequently diagnosed with new cancer, respectively. The proportion of new cancer diagnosis was higher in patients with any bleeding and minor bleeding events than in those without bleeding events (3.3 versus 1.6 per 100 person-years, p < 0.001 and 6.2 versus 1.6 per 100 person-years, p < 0.001, respectively). Multivariate Cox proportional hazard analysis revealed that any bleeding and minor bleeding events were associated with higher rate of new cancer diagnosis [hazard ratio (HR) 2.27, p = 0.003 and HR 3.93, p < 0.001, respectively]. Additionally, any gastrointestinal bleeding and minor gastrointestinal bleeding events were associated with higher rate of new gastrointestinal cancer diagnosis (HR 8.67, p < 0.001 and HR 12.74, p < 0.001, respectively). CONCLUSIONS: In CAD patients with antiplatelet therapy after PCI, any bleeding and minor bleeding events were associated with subsequent new cancer diagnosis. Even minor bleeding events may be the first manifestation of underlying cancer during antiplatelet therapy after PCI.

Regional Variation in the Clinical Practice and Prognosis in Patients With Heart Failure With Reduced Ejection Fraction in Japan　- A Report From the Japanese Registry of Acute Decompensated Heart Failure (JROADHF).

BACKGROUND: The present study aimed to clarify the regional variations in clinical practice and the prognosis of patients with heart failure with reduced ejection fraction (HFrEF) in Japan using the Japanese Registry of Acute Decompensated Heart Failure (JROADHF).Methods and Results: We recruited data of hospitalized patients with HFrEF (n=4,329) from the JROADHF. The patients were divided into 6 groups based on the region of Japan where they were hospitalized: Hokkaido-Tohoku (n=504), Kanto (n=958), Chubu (n=779), Kinki (n=902), Chugoku-Shikoku (n=446), and Kyushu (n=740). We compared the patients' characteristics, including etiology of HF and prognosis after discharge. The age of the patients was lowest in the Kanto and Kinki regions. In contrast, there were no differences in the prevalence of comorbidities, levels of B-type natriuretic peptide, or left ventricular EF among the 6 groups. Post-discharge cardiospecific prognosis, specifically, the composite of cardiac death or HF hospitalization, cardiac death, and HF hospitalization, was comparable among the 6 regions. CONCLUSIONS: There were no differences in cardiospecific prognosis in patients with HFrEF among the 6 regions in Japan.

Prognostic significance of spleen shear wave elastography and dispersion in patients with heart failure: the crucial role of cardio-splenic axis.

INTRODUCTION: The interaction between the heart and spleen plays a crucial role among cardiac and multiple organ networks, particularly in heart failure (HF). Ultrasound shear wave imaging is a non-invasive technology capable of quantifying tissue quality, but its significance in the spleen in patients with HF is poorly understood. METHODS AND RESULTS: This prospective observational study enrolled hospitalized 232 patients with HF undergoing abdominal ultrasonography. We used shear wave elastography (SWE) to assess spleen tissue elasticity and shear wave dispersion (SWD) to assess spleen tissue viscosity. Clinical, echocardiography, right heart catheterization, and outcome data were collected. Spleen SWE was negatively correlated with right ventricular fractional area change (R = - 0.180, P = 0.039), but not with right-sided pressure or congestion indices. When patients were divided into three groups based on tertile values of splenic parameters, Kaplan-Meier analysis demonstrated that patients with the highest spleen SWE and SWD had lower event-free survival rates from cardiac deaths and decompensated HF over a median 494-days follow-up period (P < 0.0001 and P < 0.0001, respectively). In a multivariable Cox proportional hazard model, both spleen SWE and SWD were independently associated with increased risks of adverse cardiac events (hazard ratio, 4.974 and 1.384; P = 0.003 and P < 0.0001). Mechanistically, we evaluated mRNA expressions of CD36, a monocyte/macrophage-associated molecule, in peripheral leukocytes, and found that enhanced spleen stiffness was associated with the upregulation of CD36 expressions. CONCLUSION: Share wave imaging of the spleen is useful for stratifying the prognosis of HF patients and may suggest a role of the cardio-splenic axis in HF pathogenies.

Effects of continuous positive airway pressure on very short-term blood pressure variability associated with sleep-disordered breathing by pulse transit time-based blood pressure measurements.

BACKGROUND: Blood pressure (BP) variability (BPV) is a predictor of cardiovascular outcomes independently of BP absolute values. We previously reported that pulse transit time (PTT) enables monitoring beat-to-beat BP, identifying a strong relationship between the extent of very short-term BPV and the severity of sleep-disordered breathing (SDB). Here, we investigated the effects of continuous positive airway pressure (CPAP) on very short-term BPV. METHODS: We studied 66 patients (mean age 62 years old, 73% male) with newly diagnosed SDB who underwent full polysomnography on two consecutive days for diagnosis (baseline) and CPAP, together with PTT-driven BP continuous recording. PTT index was defined as the average number of acute transient rises in BP (≥12 mmHg) within 30 s/h. RESULTS: CPAP treatment effectively improved SDB parameters, and attenuated PTT-based BP absolute values during the night-time. Very short-term BPV that includes PTT index and standard deviation (SD) of systolic PTT-BP was significantly reduced by CPAP therapy. The changes in PTT index from baseline to CPAP were positively correlated with the changes in apnea-hypopnea index, obstructive apnea index (OAI), oxygen desaturation index, minimal SpO 2 , and mean SpO 2 . Multivariate regression analysis revealed that changes in OAI and minimal SpO 2 , as well as heart failure, were the independent factors in determining the reduction of PTT index following CPAP. CONCLUSION: PTT-driven BP monitoring discovered the favorable effects of CPAP on very short-term BPV associated with SDB events. Targeting very short-term BPV may be a novel approach to identifying individuals who experience greater benefits from CPAP.