Human epididymis protein 4 is a useful predictor of post-operative prognosis in patients with severe aortic stenosis.

AIMS: The human epididymis protein 4 (HE4), a novel fibrosis marker, is expressed only in activated fibroblasts and is thought to reflect ongoing left ventricular (LV) fibrosis. LV fibrosis is a feature of severe aortic stenosis (AS) and is related to the post-operative outcome of patients with AS. We investigated the relationship between serum levels of HE4 and the post-operative prognosis of patients with severe AS. METHODS AND RESULTS: We measured the serum HE4 levels of 55 participants (80.8 ± 8.0 years old, male n = 26, 46%) with severe AS prior to surgical aortic valve replacement (n = 31, 56%) or transcatheter aortic valve implantation (n = 24, 44%) at Kumamoto University Hospital in 2018. We followed them for cardiovascular (CV) death or hospitalization for heart failure (HF) for 3 years. Serum HE4 levels were positively correlated with computed tomography-extracellular volume (CT-ECV) values (r = 0.53, P = 0.004). Kaplan-Meier curves demonstrated a significantly higher probability of hospitalization for HF or CV-related death in the patients with high HE4 (greater than the median HE4 value) compared with the patients with low HE4 (lower than the median HE4 value) (log-rank P = 0.003). Multivariate analysis showed HE4 (log(HE4)) to be an independent prognostic factor [hazard ratio (HR): 7.50; 95% confidence interval (CI): 1.81-31.1; P = 0.005]. Receiver operating characteristic (ROC) curve analysis suggested that HE4 is a marker of increased risk of CV-related death or hospitalization for HF at 3 years after surgery, with an area under the curve (AUC) of 0.76 (95% CI: 0.62-0.90; P = 0.003). CONCLUSIONS: We found that HE4 is a potentially useful biomarker for predicting future CV events in patients scheduled for AS surgery. Measuring serum HE4 values could help consider AS surgery.

Incidence Rate of Hospitalization for Heart Failure in a Japanese City　- An Updated Reference for Japan's Aging Society.

Background: The prevalence of heart failure (HF) is increasing in aging societies, such as Japan. The current incidence rate (IR) of HF hospitalization in Japan is unknown. Methods and Results: We conducted a regional population-based study assessing the IR of HF hospitalization in Nobeoka City. Data were collected over a period of 3 years from all patients with HF admitted for the first time to hospitals and clinics. 406 HF hospitalizations were registered (54% female; mean age 82 years). The IR of HF hospitalization was 129/100,000 person-years. The difference in the IR between women and men was not significant (131 vs. 127/100,000 person-years, respectively; P=0.767). The age-adjusted IR in the 2015 Japanese population was 105/100,000 person-years. According to 5-year age bands, the IR of HF hospitalization gradually increased up to 60-70 years of age, then increased rapidly in those aged ≥95 years for both sexes. The IR ratio compared with age <65 years was higher in women than men in each older age group. Conclusions: In this population-based study, the current IR of HF hospitalization in a region of Japan was higher than the IR from another study conducted in a different region in early 2000. By presenting detailed age-related data, the research findings will contribute to estimating the number of HF hospitalizations in other areas of Japan.

Relationship Between Heart Failure Hospitalization Costs and Left Ventricular Ejection Fraction in an Advanced Aging Society.

Background: Left ventricular ejection fraction (LVEF) is a basic clinical index that determines the heart failure (HF) treatment strategy. We aimed to evaluate the association between hospitalization costs for HF patient and LVEF in an advanced aging society in a region in Japan. Methods and Results: Consecutive HF patients admitted to Miyazaki Prefectural Nobeoka Hospital between January 2015 and March 2018 were included in the study. The 346 HF patients (mean age 78 years) were divided into 2 groups: HF with reduced ejection fraction (HFrEF; LVEF <40%; n=129) and HF with preserved ejection fraction (HFpEF; LVEF ≥40%; n=217). Median hospitalization costs (in 2017 US dollars) were higher in the HFrEF than HFpEF group, but the difference was not statistically significant ($7,128 vs. $6,580; P=0.189). However, in older adults (age ≥75 years; n=252), median hospitalization costs were significantly higher in the HFrEF than HFpEF group ($7,240 vs. $6,471; P=0.014), and LVEF was an independent factor of hospitalization costs (ß=-0.0301, P=0.006). Median hospitalization costs were significantly lower in the older than younger HFpEF group ($6,471 vs. $7,250; P=0.011), but there was no significant difference in costs between the older and younger HFrEF groups ($7,240 vs. $6,760; P=0.351). Conclusions: The relationship between LVEF and hospitalization costs became more pronounced with age, and LVEF was a negative independent factor for hospitalization costs in the older population.

Primary cardiac angiosarcoma directly invading the right lung: An autopsy report.

We presented a difficult-to-diagnose case of cardiac angiosarcoma. The patient presented pericardial effusion, but cytology of the effusion was negative. Because cytological detection of angiosarcoma cells is difficult, a possibility of malignancy should not be excluded with negative cytological examination. Biopsy of cardiac mass is the best way for diagnosis.

Association of early administration of furosemide with improved oxygenation in patients with acute heart failure.

AIMS: Optimal pharmacological treatment for chronic heart failure has been established. However, treatments that can improve the prognosis of acute heart failure (AHF) are controversial. Although intravenous diuretics may be one optimal treatment option, little evidence has shown the effect of early administration of diuretics on clinical outcomes in patients with AHF. The aim of this study was to evaluate the association between door-to-furosemide (D2F) time, improved oxygenation, and in-hospital mortality in patients hospitalized for AHF. METHODS AND RESULTS: We screened 494 patients hospitalized for AHF in Miyazaki Prefectural Nobeoka Hospital. AHF patients who were treated with intravenous furosemide within 24 h of arrival at the hospital were included in this study. D2F time was defined as the time from patient arrival at the hospital to the first intravenous dose of furosemide. The early administration group was defined as those with D2F time ≤60 min, whereas the non-early group was defined as those with D2F time >60 min. The primary outcome was the rate of improved oxygenation at Day 1. The secondary outcomes were in-hospital mortality and cardiac death. There were 219 patients treated with the first intravenous dose of furosemide within 24 h analysed after the exclusion of 275 patients. The median D2F time was 55 min (interquartile range: 30-120 min) in the final cohort. The early administration group included 121 patients (55.3%). The rate of improved oxygenation was higher in the early group than the non-early group [median 16.7% (interquartile range: 0.0-40.0) vs. 0.0% (0.0-20.6), respectively, P < 0.001]. During the study period, there were six patients (5.0%) with in-hospital mortality in the early group and nine patients (9.2%) in the non-early group (P = 0.218). Cardiac death was observed less frequently in the early group than in the non-early group, but without statistical significance (3.3% and 9.2%, respectively) (P = 0.067). The univariable logistic regression analyses showed that early administration of furosemide was associated with improved oxygenation [odds ratio (OR): 2.26; 95% confidence interval (CI): 1.31-3.91; P = 0.004], but not with in-hospital mortality (OR: 0.52; 95% CI: 0.18-1.50; P = 0.225) or cardiac death (OR: 0.34; 95% CI: 0.10-1.13; P = 0.079). In multivariable analyses adjusted for risk score or relevant variables, early administration of furosemide was consistently associated with improvement of oxygenation. CONCLUSIONS: The present study showed that in AHF patients, the early administration of furosemide was associated with improved oxygenation.

Incidence Rate of Acute Coronary Syndrome Including Acute Myocardial Infarction, Unstable Angina, and Sudden Cardiac Death in Nobeoka City for the Super-Aged Society of Japan.

BACKGROUND: This study aimed to calculate incidence rates (IR) of acute coronary syndrome (ACS) including acute myocardial infarction (AMI), unstable angina (UAP), and sudden cardiac death (SCD) in Nobeoka city, Japan.Methods and Results:This was an observational study based on a city-wide comprehensive registration between 2015 and 2017 in Nobeoka city, Japan, using 2 databases: all patients with cardiogenic out-of-hospital cardiac arrest in Nobeoka city and hospitalized ACS patients from Miyazaki Prefectural Nobeoka Hospital in which all ACS patients in Nobeoka city were hospitalized except for possible rare cases of patients highly unlikely to be hospitalized elsewhere. The IRs of ACS based on the population size of Nobeoka city (125,000 persons), and their age-adjusted IRs by using the direct method and the 2015 model population of Japan were calculated. There were 260 eligible patients hospitalized with first-onset ACS (age [SD]=71.1 [12.4], 34.2% women) and 107 eligible SCD patients. Crude IRs of hospitalized ACS and SCD patients, and hospitalized AMI and SCD patients, respectively, were 130.2 (183.3 for men, 85.6 for women) and 107.5 (148.4 for men, 73.2 for women) per 100,000. Crude IRs of hospitalized ACS, AMI, and UAP patients, respectively, were 92.3 (132.8 for men, 58.1 for women), 69.6 (97.9 for men, 45.7 for women), and 22.7 (35.0 for men, 12.4 for women) per 100,000. CONCLUSIONS: The calculated IRs can be useful in building a health strategy for treating ACS.

Risk Prediction Score for Cancer Development in Patients With Acute Coronary Syndrome.

BACKGROUND: Cancer is a known prognostic factor in patients with acute coronary syndrome (ACS), but few risk assessments of cancer development after ACS have been established.Methods and Results:Of the 573 consecutive ACS admissions between January 2015 and March 2018 in Nobeoka City, Japan, 552 were analyzed. Prevalent cancer was defined as a treatment history of cancer, and incident cancer as post-discharge cancer incidence. The primary endpoint was post-discharge cancer incidence, and the secondary endpoint was all-cause death during follow-up. All-cause death occurred in 9 (23.1%) patients with prevalent cancer, and in 17 (3.5%) without cancer. In the multivariable analysis, prevalent cancer was associated with all-cause death. To develop the prediction model for cancer incidence, 21 patients with incident cancer and 492 without cancer were analyzed. We compared the performance of D-dimer with that of the prediction model, which added age (≥65 years), smoking history, and high red blood cell distribution width to albumin ratio (RAR) to D-dimer. The areas under the receiver-operating characteristics curves of D-dimer and the prediction model were 0.619 (95% confidence interval: 0.512-0.725) and 0.774 (0.676-0.873), respectively. Decision curve analysis showed superior net benefits of the prediction model. CONCLUSIONS: By adding elderly, smoking, and high RAR to D-dimer to the prediction model it became clinically useful for predicting cancer incidence after ACS.

Optical Coherence Tomography-Guided Percutaneous Coronary Intervention With Low-Molecular-Weight Dextran　- Effect on Renal Function.

BACKGROUND: The excessive volume of contrast needed is a significant limitation of optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI). Low-molecular-weight dextran (LMWD) has been used for OCT image acquisition instead of contrast media. This study compared the effects of OCT-guided PCI using LMWD on renal function and clinical outcomes to those of intravascular ultrasound (IVUS)-guided PCI.Methods and Results:In all, 1,183 consecutive patients who underwent intracoronary imaging-guided PCI were enrolled in this single-center, retrospective, observational study. After propensity score matching, 133 pairs of patients were assigned to undergo either OCT-guided PCI using LMWD or IVUS-guided PCI. There was no significant change from baseline in the primary endpoint, serum creatinine concentrations, after the procedure in either group. There were no significant differences between the OCT and IVUS groups in the volume of contrast medium, the incidence of contrast-induced nephropathy (1.5% vs. 2.3%; P=0.65), and major adverse cardiovascular events (MACE) at 30 days (2.3% vs. 6.0%; P=0.12) and 12 months (2.3% vs. 3.0%; P=0.70) after the procedure. Kaplan-Meier analysis at the 12-month follow-up revealed no significant difference in the incidence of MACE between the 2 groups (P=0.75). CONCLUSIONS: OCT-guided PCI using LMWD did not negatively affect renal function and achieved similar short- and long-term clinical outcomes to IVUS-guided PCI.

Prognostic impact of the presence of on-duty cardiologist on patients with acute myocardial infarction admitted during off-hours.

BACKGROUND: Owing to reduced staffing, patients hospitalized for acute myocardial infarction (AMI) during off-hours (nights, weekends, and holidays) have poorer outcomes than those admitted during regular hours. Whether the presence of an on-duty cardiologist in a hospital during off-hours is related to better outcomes for patients with AMI remains unclear. The Miyazaki Prefectural Nobeoka Hospital had a unique medical care system in that cardiologists were on call for half of the week and on duty for the other half during off-hours, thus providing an opportunity to assess the relationship between the presence of an on-duty cardiologist and patient outcomes. We examined clinical outcomes of patients admitted for AMI during off-hours according to the presence of an on-duty cardiologist. METHODS: We recruited 225 consecutive patients with AMI hospitalized during off-hours, who underwent stent implantation at Miyazaki Prefecture Nobeoka Hospital from 2013 to 2017. The endpoints were in-hospital death or long-term major adverse cardiac events (MACE) including cardiovascular death, non-fatal MI, non-fatal stroke, stent thrombosis, ischemia-driven target-lesion revascularization, admission owing to unstable angina, or admission owing to heart failure. RESULTS: Based on the presence of an on-call cardiologist at admission, we divided patients into the cardiologist on-call group (n = 112) or cardiologist on-duty group (n = 113). The presence of an on-duty cardiologist did not affect door-to-reperfusion time (p = 0.776), level of peak creatine kinase (p = 0.971), or in-hospital death (p = 0.776). The Kaplan-Meier curve analysis showed similar prognosis for the cardiologist on-duty and cardiologist on-call groups (p = 0.843), and multivariable Cox regression analysis showed that the presence of an on-duty cardiologist was not associated with MACE. CONCLUSIONS: The presence of an on-duty cardiologist is not a prognostic factor for patients hospitalized for AMI during off-hours in our medical system. Further prospective multicenter studies should confirm our results.

Persistent Renal Dysfunction in Patients Undergoing Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction.

Background The long-term prognosis of patients with acute myocardial infarction who develop persistent renal dysfunction (RD) remains unclear. We investigated risk factors and prognostic implications of persistent RD after contrast-induced nephropathy (CIN) in patients with acute myocardial infarction after primary percutaneous coronary intervention. Methods and Results We enrolled 952 consecutive patients who underwent primary percutaneous coronary intervention for acute myocardial infarction. CIN was defined as an increase in serum creatinine levels ≥0.5 mg/dL or ≥25% from baseline within 72 hours after percutaneous coronary intervention. Persistent RD was defined as residual impairment of renal function over 2 weeks, and transient RD was defined as recovery of renal function within 2 weeks, after CIN. The overall incidence of CIN was 8.8% and that of persistent CIN was 3.1%. A receiver-operator characteristic curve showed that the optimal cutoff value of the contrast volume/baseline estimated glomerular filtration rate ratio for persistent CIN was 3.45. In multivariable logistic analysis, a contrast volume/baseline estimated glomerular filtration rate >3.45 was an independent correlate of persistent RD. At 3 years, the incidence of death was significantly higher in patients with persistent RD than in those with transient RD (P=0.001) and in those without CIN (P<0.001). Cox regression analysis showed that persistent RD (hazard ratio, 4.99; 95% CI, 2.30-10.8; P<0.001) was a significant risk factor for mortality. A similar trend was observed for the combined end points, which included mortality, hemodialysis, stroke, and acute myocardial infarction. Conclusions Persistent RD, but not transient RD, is independently associated with long-term mortality. A contrast volume/baseline estimated glomerular filtration rate >3.45 is an independent predictor of persistent RD.

Successful removal of side branch-jailed stent struts by reused balloon.

N/A.

Empagliflozin lessened cardiac injury and reduced visceral adipocyte hypertrophy in prediabetic rats with metabolic syndrome.

BACKGROUND: The potential benefit of SGLT2 inhibitors in metabolic syndrome is with prediabetic stage unclear. This work was undertaken to investigate the non-glycemic effect of empagliflozin on metabolic syndrome rats with prediabetes. METHODS: SHR/NDmcr-cp(+/+) rats (SHRcp), a model of metabolic syndrome with prediabetes, were given empagliflozin for 10 weeks to examine the effects on urinary sodium and water balance, visceral and subcutaneous adipocyte, and cardiac injury. Further, the effect of empagliflozin on blood pressure and autonomic nervous system was continuously investigated by using radiotelemetry system. RESULTS: Empagliflozin significantly reduced urinary sodium and water balance of SHRcp only within 1 week of the treatment, but later than 1 week did not alter them throughout the treatment. Empagliflozin significantly reduced body weight of SHRcp, which was mainly attributed to the significant reduction of subcutaneous fat mass. Empagliflozin significantly reduced the size of visceral adipocytes and increased the number of smaller size of adipocytes, which was associated with the attenuation of oxidative stress. Empagliflozin ameliorated cardiac hypertrophy and fibrosis of SHRcp, in association with the attenuation of cardiac oxidative stress and inflammation. However, empagliflozin did not significantly change blood pressure, heart rate, sympathetic activity, or baroreceptor function, as evidenced by radiotelemetry analysis. CONCLUSIONS: Our present work provided the evidence that SGLT2 inhibition reduced visceral adipocytes hypertrophy and ameliorated cardiac injury in prediabetic metabolic syndrome rat, independently of diuretic effect or blood pressure lowering effect. Thus, SGLT2 inhibition seems to be a promising therapeutic strategy for prediabetic metabolic syndrome.

The clinical significance of plasma neopterin in heart failure with preserved left ventricular ejection fraction.

AIMS: Although inflammation plays an important role in the pathogenesis of heart failure (HF), the precise pathophysiological role of inflammation in HF with preserved left ventricular ejection fraction (HFpEF) still remains unclear. Hence, we examined the clinical significance of plasma neopterin, an inflammatory biomarker, in HFpEF patients. METHODS AND RESULTS: In the present study, we recruited consecutive HFpEF patients hospitalized in Kumamoto University Hospital, and further measured plasma neopterin by high-performance liquid chromatography and serum derivatives of reactive oxidative metabolites (DROM), a new biomarker of reactive oxygen species. Compared with risk factors (number of patients, age, sex, and equal incidence of diabetes mellitus, hypertension, and dyslipidemia) -matched non-HF patients (n = 68), plasma neopterin levels, but not serum high-sensitivity C-reactive protein levels, were significantly increased in patients with HFpEF (n = 68) (P < 0.001 and P = 0.15, respectively), accompanied by an elevation in serum DROM levels (P < 0.001). Plasma neopterin levels in New York Heart Association (NYHA) class III/IV HFpEF patients were significantly higher than in NYHA class II patients (P < 0.004). Furthermore, plasma ln-neopterin levels had significant and positive correlation with ln-DROM values (r = 0.57) and parameters of cardiac diastolic dysfunction [the ratio of early transmitral flow velocity to tissue Doppler early diastolic mitral annular velocity (r = 0.34), left atrial volume index (r = 0.17), and B-type natriuretic peptide (r = 0.38)]. Kaplan-Meier analysis showed that the high-neopterin group (>51.5 nM: median value of neopterin in HFpEF patients) had a higher probability of cardiovascular events than the low-neopterin group (log-rank test, P = 0.003). CONCLUSIONS: Plasma neopterin levels significantly increased in HFpEF and correlated with the severity of HF. Furthermore, high neopterin were significantly correlated with future cardiovascular events, indicating that measurement of plasma neopterin might provide clinical benefits for risk stratification of HFpEF patients. © 2015 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Clinical significance of pulse pressure in patients with heart failure with preserved left ventricular ejection fraction.

AIMS: Although pulse pressure (PP) is a recognized risk factor for various cardiovascular diseases, its association with cardiovascular outcomes in patients with heart failure with preserved ejection fraction (HFpEF) is uncertain. METHODS AND RESULTS: We enrolled 512 of 951 consecutive HFpEF patients admitted to the Kumamoto University Hospital between 2007 and 2013 and divided them into five groups according to PP quintiles. Blood pressure and pulse wave velocity (PWV) were measured by an ankle-brachial index device. The PP values in HFpEF were significantly and positively correlated with PWV and LV stroke volume index, and were negatively correlated with estimated glomerular filtration rate and haemoglobin levels. Furthermore, plasma B-type natriuretic peptide levels in HFpEF patients with the lowest (<45 mmHg) and highest PP (≥75 mmHg) were significantly higher than those with other PP (45-74 mmHg). The percentage of total cardiovascular and heart failure (HF)-related events by PP category resulted in U- and J-shaped curves. The higher frequency of coronary-related events was nearly linear. In the Kaplan-Meier analysis, HFpEF patients with the lowest and highest PP quintiles had a significantly higher risk of cardiovascular and HF-related events than those with other PPs (45-74 mmHg) (log-rank test, both P < 0.01). Conversely, the frequency of coronary-related events in the highest PP group, but not in the lowest PP group, was significantly higher than in other PP groups. CONCLUSION: Pulse pressure lower than 45 mmHg and higher than 75 mmHg was closely associated with HFpEF prognosis, indicating the clinical significance of PP for risk stratification of HFpEF.

Low-Normal Serum Sodium and Heart Failure-Related Events in Patients With Heart Failure With Preserved Left Ventricular Ejection Fraction.

BACKGROUND: Hyponatremia has been shown to be a prognostic factor in heart failure (HF) with preserved ejection fraction (HFpEF). Serum sodium (sNa) cut-off, however, is not defined in HFpEF. Therefore, we investigated the relationship between sNa and HF-related events (cardiovascular death and hospitalization for HF decompensation) in HFpEF patients. METHODS AND RESULTS: We assessed cardiac function using echocardiography and measured sNa in HFpEF patients with New York Heart Association class II (n=321) or III (n=84) in a compensated condition after implementing medical therapy for HF. During a mean follow-up of 27 months, 73 patients developed HF-related events. On multivariate Cox hazard analysis including established predictors in HF, sNa level as a continuous variable was identified as an independent predictor for HF-related events in HFpEF (per 1.0 mmol/L: HR, 0.93; 95% CI: 0.87-0.98; P<0.01). Kaplan-Meier analysis demonstrated significantly higher probability of HF-related events in the lower sNa group (sNa <140 mmol/L) than in the higher sNa group (sNa ≥140 mmol/L; P<0.001, log-rank test). Further, the low-normal sNa group (135 mmol/L

Therapy with the Combination of Amlodipine and Irbesartan Has Persistent Preventative Effects on Stroke Onset Associated with BDNF Preservation on Cerebral Vessels in Hypertensive Rats.

Although calcium channel blockers, angiotensin II receptor blockers, and combination therapy are effective for hypertensive patients, the significant differences among them against stroke onset are undetermined. In this study, we investigated the significant beneficial effects of the combination therapy using amlodipine and irbesartan against stroke onset in hypertensive rats. The animals were fed an 8% sodium diet and assigned to (1) vehicle, (2) amlodipine (2 mg/kg/day), (3) irbesartan (20 mg/kg/day), and (4) amlodipine + irbesartan groups. The drugs were given orally until 35 days, and incidences of stroke-related signs and mortality and blood pressure (BP) were monitored. Cerebral blood flow (CBF), brain water content, weight of the brain and left ventricle, and histological evaluations were conducted for the treated groups at 42 days after the start of the high-salt diet. Amlodipine and the combination therapy significantly reduced BP compared with the vehicle. Although the rates of stroke-related signs and mortality were high in the vehicle group, the rats in the treatment groups were mostly healthy until 35 days. After all drugs were discontinued, stroke onset was frequently seen in the monotherapy groups until 42 days, but no signs were observed in the combination therapy group. Although there were no significant differences in CBF or brain edema, the combination therapy reduced blood-brain barrier disruption, white matter injury, and reactive astrocytes compared with irbesartan, and the combination also inhibited left ventricular hypertrophy and preserved brain-derived neurotrophic factor (BDNF) expression on cerebral vessels compared to the monotherapies. These data suggest that the combination therapy had a persistent preventive effect on stroke onset in hypertensive rats, and the effects might be associated with BDNF preservation on cerebral vessels.

High serum levels of thrombospondin-2 correlate with poor prognosis of patients with heart failure with preserved ejection fraction.

Thrombospondin-2 (TSP-2) is highly expressed in hypertensive heart. Interstitial fibrosis is frequently observed in hypertensive heart, and it is a characteristic feature of heart failure with preserved ejection fraction (HFpEF). We tested here the hypothesis that high TSP-2 serum levels reflect disease severity and can predict poor prognosis of patients with HFpEF. Serum TSP-2 levels were measured by ELISA in 150 patients with HFpEF. HFpEF was defined as left ventricular ejection fraction ≥ 50%, B-type natriuretic peptide (BNP) ≥ 100 pg/ml or E/e' ≥ 15. The endpoints were mortality rate, HF-related hospitalization, stroke and non-fatal myocardial infarction. The median serum TSP-2 level was 19.2 (14.4-26.0) ng/ml. Serum TSP-2 levels were associated with the New York Heart Association (NYHA) functional class. Circulating levels of BNP and high-sensitivity troponin T were positively correlated with serum TSP-2 levels. Kaplan-Meier survival curve showed high risk of adverse cardiovascular events in the high TSP-2 group (>median value), and that the combination of high TSP-2 and high BNP (≥ 100 pg/ml) was associated with the worst event-free survival rate. Multivariate Cox proportional hazard analysis identified TSP-2 as independent predictor of risk of death and cardiovascular events. Circulating TSP-2 correlates with disease severity in patients with HFpEF. TSP-2 is a potentially useful predictor of future adverse cardiovascular events in patients with HFpEF.

Prognostic Significance of Peripheral Microvascular Endothelial Dysfunction in Heart Failure With Reduced Left Ventricular Ejection Fraction.

BACKGROUND: Endothelial dysfunction plays a crucial role in heart failure (HF), but the association between peripheral microvascular endothelial function assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT) and prognosis remains unknown in HF with reduced left ventricular (LV) ejection fraction (HFREF). We prospectively investigated the association between peripheral microvascular endothelial function and HF-related near-future cardiovascular outcomes in HFREF patients. METHODS AND RESULTS: The 362 HFREF patients (LVEF <50%) were followed for HF-related events (composite of cardiovascular death and HF hospitalization) up to 3 years. A natural logarithmic-scaled RH-PAT index (Ln-RHI) was obtained for each patient. A total of 82 HF-related events were recorded. The lower-RHI group (Ln-RHI ≤0.49, median) experienced a higher rate of HF-related events compared with the higher-RHI group by Kaplan-Meier analysis (30.9% vs. 14.4%, log-rank test: P<0.001). Multivariable Cox hazard analysis identified Ln-RHI as an independent predictor for HF-related events (per 0.1, hazard ratio: 0.84, 95% confidence interval: 0.75-0.95, P=0.005). Adding Ln-RHI to the Meta-analysis Global Group in Chronic HF risk score (MAGGICs) and Seattle Heart Failure Model (SHFM), powerful prognostic predictors of HF, significantly improved the net reclassification index (MAGGICs: 20.11%, P=0.02, SHFM: 24.88%, P<0.001), and increased the C-statistics for prediction of HF-related events (MAGGICs+Ln-RHI: from 0.612 to 0.670, SHFM+Ln-RHI: from 0.662 to 0.695). CONCLUSIONS: Peripheral microvascular endothelial dysfunction assessed by RH-PAT was associated with future HF-related events in HFREF.