Acute bilateral suppurative parotitis following treatment of acute decompensated heart failure with noninvasive positive-pressure ventilation.

We present a case of acute bilateral suppurative parotitis in an elderly patient with acute heart failure who was hospitalized and treated with noninvasive positive-pressure ventilation. In this case, sepsis due to infection occurred, leading to severe illness.

Pathophysiological role of right ventricular function and interventricular functional mismatch in the development of pulmonary edema in acute heart failure.

BACKGROUND: Parameters of cardiac function related to the development of pulmonary edema (PE) in acute heart failure (AHF), including right ventricular (RV) function and a mismatch of interventricular function, are not fully elucidated. The aim of this study was to verify the hypothesis that a relatively preserved RV function compared with left ventricular function may be associated with the development of PE by using two-dimensional speckle tracking echocardiography (2DSTE). METHODS: Hospitalized patients with AHF at 11 institutions were enrolled. PE was defined as lung congestion on chest X-ray with hypoxemia. Patients with systolic blood pressure ≥140 mmHg on admission were defined to have hypertensive AHF. Echocardiographic analyses, including 2DSTE, were performed prior to discharge. The index of mismatch between RV and left ventricular systolic function was assessed by interventricular longitudinal strain difference (IVLSD) which was defined as RV free wall longitudinal strain and left ventricular global longitudinal strain. RESULTS: Of 610 patients with AHF, 422 (69.2%) had PE. In patients with PE, IVLSD (p = 0.007) and RV fractional area change ratio (p<0.001) was significantly higher than those in patients without PE. In patients with non-hypertensive AHF, RV fractional area change ratio, age, ischemic etiology, and serum brain natriuretic peptide (BNP) levels were independent predictors of PE. In patients with hypertensive AHF, IVLSD, age, and serum BNP levels were independent predictors of PE. CONCLUSIONS: Preserved RV function might be one of the underlying mechanisms of the development of PE in AHF. Furthermore, interventricular functional mismatch might be related to the development of PE in hypertensive AHF.

Comparison of Soluble ST2, Pentraxin-3, Galectin-3, and High-Sensitivity Troponin T of Cardiovascular Outcomes in Patients With Acute Decompensated Heart Failure.

BACKGROUND: Data regarding a direct comparison of soluble suppression of tumorigenesis-2 (sST2), pentraxin 3 (PTX3), galectin-3 (Gal-3), and high-sensitivity troponin T of cardiovascular outcome in patients with heart failure (HF) are lacking. METHODS AND RESULTS: A total of 616 hospitalized patients with HF were evaluated prospectively. Biomarker data were obtained in the stable predischarge condition. sST2 levels were associated with age, sex, body mass index, inferior vena cava diameter, B-type natriuretic peptide (BNP), PTX3, C-reactive protein, and Gal-3 levels. During follow-up, 174 (28.4%) primary composite end points occurred, including 58 cardiovascular deaths and 116 HF rehospitalizations. sST2 predicted the end point after adjustment for 13 clinical variables (hazard ratio 1.422; 95% confidence interval [CI] 1.064 to 1.895, P = .018). The association between sST2 and the end point was no longer statistically significant after adjustment for BNP (P = .227), except in the subgroup of patients with preserved ejection fraction (hazard ratio 1.925, 95% CI 1.102-3.378, P = .021). Gal-3 and high-sensitivity troponin T predicted the risk for the end point after adjustment for age and sex, but were not significant after adjustment for clinical variables. The prognostic value of PTX3 was not observed (age and sex adjusted, P = .066). CONCLUSIONS: This study did not show significant additional value of biomarkers to BNP for risk stratification, except sST2 in patients with preserved ejection fraction.

Clinical impacts of changes of renal function during hospitalization depend on grades of renal dysfunction in acute decompensated heart failure.

Clinical impact of changes of renal function (RF) in heart failure (HF) hospitalization is controversial. This study aimed to clarify whether clinical impact of changes of RF during HF hospitalization depends on the intrinsic RF. In 786 hospitalized HF patients, RF were classified into 3 grades based on estimated glomerular filtration rate (eGFR, mL/min/1.73 m2) at discharge; ≥ 60 (n = 243), < 60 and ≥ 30 (n = 400), and < 30 (n = 143). Increase and decrease of serum creatinine over 0.3 mg/dL during HF hospitalization were defined as worsening renal function (WRF) and improved renal function (IRF), respectively, and remaining subjects were defined as stable RF. The primary endpoint was a composite of cardiovascular death and rehospitalization for HF. In all patients, WRF was not associated with clinical outcomes, although eGFR has a significant association with prognosis. Clinical outcomes did not differ between changes of RF patterns in both preserved and severely impaired RF groups. In contrast, IRF, not WRF, was an independent predictor of clinical outcomes in the moderately impaired RF group (HR 1.965, 95% CI 1.09-3.18, p = 0.01). Only in patients with moderately impaired RF, changes of RF were associated with clinical outcome, and IRF was an independent predictor of clinical outcomes.

Clinical utility of the 2016 ASE/EACVI recommendations for the evaluation of left ventricular diastolic function in the stratification of post-discharge prognosis in patients with acute heart failure.

AIMS: Left ventricular diastolic dysfunction (LVDD) has prognostic significance in heart failure (HF). We aimed to assess the impact of LVDD grade stratified by the updated 2016 echocardiographic algorithm (DD2016) on post-discharge outcomes in patients admitted for acute HF and compare with the previous 2009 algorithm (DD2009). METHODS AND RESULTS: The study included 481 patients hospitalized for acute decompensated HF. Comprehensive echocardiography and LVDD evaluation were performed just before hospital discharge. The primary endpoint was a composite of cardiovascular death and readmission for HF. The concordance between DD2016 and DD2009 was moderate (κ = 0.44, P < 0.001); the reclassification rate was 39%. During the follow-up (median: 15 months), 127 (26%) patients experienced the primary endpoint. In the Kaplan-Meier analysis, Grade III in DD2016 showed a lower event-free survival rate than Grades I and II (log rank, P < 0.001 and P = 0.048, respectively) and was independently associated with a higher incidence of the primary endpoint than Grade I [hazard ratio 1.89; 95% confidence interval (CI) 1.17-3.04; P = 0.009]. Grade II or III in DD2016, reflecting elevation of left ventricular (LV) filling pressure, added an incremental predictive value of the primary endpoint to clinical variables irrespective of LV ejection fraction. DD2016 was comparable to DD2009 in predicting the endpoint (net reclassification improvement = 11%; 95% CI -7% to 30%, P = 0.23). CONCLUSION: Despite simplification of the algorithm for LVDD evaluation, the prognostic value of DD2016 for post-discharge cardiovascular events in HF patients was maintained and not compromised in comparison with DD2009.

Geriatric nutritional risk index predicts all-cause deaths in heart failure with preserved ejection fraction.

AIMS: The objective of the study was to evaluate whether the geriatric nutritional risk index (GNRI) at discharge may be helpful in predicting the long-term prognosis of patients hospitalized with heart failure (HF) with preserved ejection fraction (HFpEF, left ventricular ejection fraction ≥50%), a common HF phenotype in the elderly. METHODS AND RESULTS: Overall, 110 elderly HFpEF patients (≥65 years) from the Ibaraki Cardiovascular Assessment Study-HF (n = 838) were enrolled. The mean age was 78.5 ± 7.2 years, and male patients accounted for 53.6% (n = 59). All-cause mortality was compared between the low GNRI (<92) with moderate or severe nutritional risk group and the high GNRI (≥92) with no or low nutritional risk group. Cox proportional hazard regression models were constructed to evaluate the influence of the GNRI on all-cause death with the following covariates using forward stepwise selection: age, sex, nutritional status based on the GNRI as a categorical variable, history of HF hospitalization, haemoglobin level, estimated glomerular filtration rate, log brain natriuretic peptide levels (logBNP), history of hypertension, log C-reactive protein levels, left ventricular ejection fraction, left ventricular mass index, and the New York Heart Association functional classification (I/II or III class). The prognostic value of the GNRI was compared with that of serum albumin using C-statistics. The GNRI was added to the logBNP, serum albumin or the body mass index was added to the logBNP, and the C-statistic was compared using DeLong's test. Cox regression analysis revealed that age and a low GNRI were independent predictors of all-cause death (P < 0.05, n = 103; hazard ratio = 1.095, 95% confidence interval = 1.031-1.163, for age, and hazard ratio = 3.075, 95% confidence interval = 1.244-7.600, for the GNRI). DeLong's test for the two correlated receiver operating characteristic curves [area under the receiver operating characteristic curve (AUROC) of serum albumin, 0.71; AUROC of the GNRI, 0.75] demonstrated significant differences between the groups (P = 0.038). Adding the GNRI to the logBNP increased the AUROC for all-cause death significantly (0.71 and 0.80, respectively; P = 0.040, n = 105). The addition of serum albumin or the body mass index to the logBNP did not significantly increase the AUROC for all-cause death (P = 0.082 and P = 0.29, respectively). CONCLUSIONS: Nutritional screening using the GNRI at discharge is helpful to predict the long-term prognosis of elderly HFpEF patients.

Different Impact of Changes in Left Ventricular Ejection Fraction Between Heart Failure Classifications in Patients With Acute Decompensated Heart Failure.

BACKGROUND: Left ventricular ejection fraction (LVEF) can dramatically change when the patient has acute decompensated heart failure (ADHF). We investigated the impact of LVEF and subsequent changes on prognosis in patients with ADHF through a prospective study.Methods and Results: A total of 516 hospitalized patients with ADHF were evaluated. Echocardiography was performed on admission, prior to discharge, and 1 year after discharge. The primary endpoint was a composite of cardiovascular death and hospitalization. In heart failure with reduced EF (HFrEF; LVEF <40%), LVEF did not significantly improve during hospitalization (P=0.348); however, it improved after discharge (P<0.001). In contrast, LVEF improved during hospitalization (P<0.001) in HF with preserved EF (HFpEF; LVEF ≥50%). In HF with mid-range EF (HFmrEF; LVEF 40-49%), LVEF consistently improved throughout the observation period (P<0.001). A multivariable Cox model showed that improved LVEF after discharge was associated with a better outcome in HFrEF (hazard ratio [HR]: 0.951; 95% confidence interval [CI]: 0.928-0.974; P<0.001), while improved LVEF during hospitalization was associated with a better outcome in HFpEF (HR: 0.969; 95% CI: 0.940-0.998; P=0.038). CONCLUSIONS: Improved LVEF after discharge in HFrEF and during hospitalization in HFpEF was associated with a better prognosis in patients with ADHF. Longitudinal improvements in LVEF had different prognostic impact, depending on the HF type by LVEF measurement.

Renoprotective effects of tolvaptan in hypertensive heart failure rats depend on renal decongestion.

The vasopressin type 2 receptor antagonist tolvaptan may have renoprotective effects in patients with heart failure (HF). This study aimed to reveal the renoprotective effect of tolvaptan from the viewpoint of hemodynamic combined with catheter and ultrasound examinations in a hypertensive HF model. Dahl salt-sensitive rats (n = 24) were fed an 8% high-salt diet after the age of 6 weeks and were treated with tolvaptan (n = 16) or vehicle (control group; n = 8). The tolvaptan-treated rats were divided into two groups: a low-dose group (0.01% tolvaptan diet; Low-Tol) and a high-dose group (0.05% tolvaptan diet; High-Tol). At 24 weeks, catheterizations to measure central venous pressure (CVP) and renal medullary pressure (RMP) were performed, followed by intrarenal Doppler (IRD) studies and contrast-enhanced ultrasonography (CEUS) to evaluate renal medullary perfusion. The tolvaptan diet reduced CVP (7.7 ± 1.5, 9.0 ± 1.1, and 12.2 ± 0.8 mmHg in the High-Tol, Low-Tol, and control groups, respectively; p < 0.001) and RMP (7.7 ± 0.8, 9.4 ± 1.3, and 13.7 ± 1.2 mmHg in the High-Tol, Low-Tol, and control groups, respectively; p < 0.001). Tolvaptan also reduced the venous impedance index (VII) in the IRD analysis (0.18 ± 0.03, 0.26 ± 0.04, and 0.40 ± 0.08 in the High-Tol, Low-Tol, and control groups, respectively; p < 0.001), and the time to peak intensity in CEUS (6.0 ± 0.5, 7.3 ± 1.3, 9.8 ± 1.8 s in the High-Tol, Low-Tol, and control groups, respectively; p < 0.001). Creatinine clearance (Ccr) was preserved in both the High-Tol and Low-Tol groups compared to the control group (4.80 ± 1.9, 4.24 ± 0.8, and 1.35 ± 0.3 mg/min, respectively; p = 0.001). Ccr was negatively correlated with RMP (R = -0.76, P < 0.001), the venous impedance index (R = -0.70, p < 0.001), time to peak intensity (R = -0.75, P < 0.001), and renal fibrosis (R = -0.70, p < 0.001). In contrast, Ccr had modest correlations with systolic blood pressure (R = -0.50, P = 0.02) and left ventricular ejection fraction (R = 0.48, P = 0.03). This study revealed that the renoprotective effects of tolvaptan in a hypertensive HF model depended on renal decongestion.

Soluble ST2 and brain natriuretic peptide predict different mode of death in patients with heart failure and preserved ejection fraction.

BACKGROUND: Soluble ST2 (sST2) is a marker of inflammation and fibrosis, which is a significant predictor of prognosis of heart failure (HF), independent of brain natriuretic peptide (BNP). This study aimed to clarify how sST2 associates with clinical outcome through investigations of clinical correlates and mode of death in patients with heart failure with preserved ejection fraction (HFpEF). METHODS: A total 191 patients with acute decompensated HF and EF ≥50% were prospectively enrolled. Echocardiographic and laboratory data including sST2 were obtained in pre-discharge stable condition. RESULTS: Serum sST2 level showed significant positive correlations with C-reactive protein and pentraxin3 levels, and negative correlations with body mass index, albumin, and hemoglobin. Serum sST2 level was significantly higher in patients with all-cause death and non-cardiovascular (CV) death compared to those without events, whereas there was no significant difference in sST2 level between patients with and without CV death. On the other hand, BNP level was significantly higher in patients with all-cause death and CV death compared to those without events. Cox regression analyses adjusted for age and sex revealed that sST2 was a significant predictor of non-CV death, whereas BNP was a significant predictor of CV death. CONCLUSIONS: Serum sST2 level was associated with non-CV death showing significant correlations with systemic factors including malnutrition and inflammation, while BNP was associated with CV death.

Comparison of effects of aldosterone receptor antagonists spironolactone and eplerenone on cardiovascular outcomes and safety in patients with acute decompensated heart failure.

Differences in the clinical impacts of the aldosterone receptor antagonists spironolactone and eplerenone in patients with heart failure (HF) are unclear. Among 838 prospectively enrolled patients hospitalized for HF, 90 treated with eplerenone were compared with 90 treated with spironolactone. The primary endpoint was a composite of cardiovascular death and hospitalization. A serial evaluation of the clinical parameters was performed 1 year after discharge. The mean dose of spironolactone was 27 ± 8 mg and of eplerenone was 34 ± 15 mg. During follow-up (mean 594 ± 317 days), primary endpoints occurred in 27 patients in the eplerenone group (30.0%) and 25 patients in the spironolactone group (27.8%). There were no significant intergroup differences in the primary endpoint (log-rank, p = 0.956). Serial changes in left ventricular ejection fraction, serum brain natriuretic peptide, systolic blood pressure, and estimated glomerular filtration rate did not differ significantly between groups. Although gynecomastia in men was common in the spironolactone group (p = 0.018), the discontinuation rates due to adverse events were similar in the two groups (p = 0.135). Subgroup analyses suggested that eplerenone was associated with a lower hazard rate of the primary endpoint in female patients (interaction, p = 0.076). Among patients with HF, eplerenone and spironolactone have similar impacts on cardiovascular outcomes and safety.

Incremental Prognostic Value of Right Ventricular Strain in Patients With Acute Decompensated Heart Failure.

BACKGROUND: Although 2-dimensional strain analyses based on speckle tracking echocardiography have been used to detect myocardial deformation, the prognostic impact of 2-dimensional strain is unclear in patients with acute decompensated heart failure (HF). We investigated whether left ventricular and right ventricular (RV) strain parameters assessed by speckle tracking echocardiography provide incremental prognostic information in hospitalized patients because of acute decompensated HF. METHODS AND RESULTS: Six hundred eighteen patients (age, 72±13 years; 38% women; ejection fraction, 46±16%) hospitalized for acute decompensated HF underwent clinical and echocardiographic evaluation just before discharge. We performed strain analyses of left ventricular global longitudinal strain and left ventricular global circumferential strain. We also analyzed RV longitudinal strain only from the free wall (RV-fwLS) and from all segments of the RV global longitudinal strain wall by using Tomtec software. The primary composite end point was cardiovascular death and readmission for HF. There were 34.8% cardiac events during a median follow-up of 427 days. In multivariate Cox models, among echocardiographic parameters, only impaired RV-fwLS (≥-13.1%; hazard ratio, 1.51; 95% CI, 1.12-2.04; P=0.01) was independently associated with cardiac events. Adding RV-fwLS to clinical risk evaluation (age, New York Heart Association class III/IV, blood urea nitrogen, and brain natriuretic peptide) markedly improved prognostic utility and consequently increased net reclassification improvement by 0.30 ( P=0.01). CONCLUSIONS: RV-fwLS is an independent predictor of cardiac events in acute decompensated HF and provides greater prognostic power than standard echocardiographic parameters.

Clinical implications of organ congestion in heart failure patients as assessed by ultrasonography.

In the management of heart failure (HF), decongestion is critical for improving clinical outcomes in addition to patients' symptoms. Although physicians accept this theory, there are no established markers for the achievement of optimal decongestion status. Organ congestion, in particular liver and kidney congestion, has recently attracted substantial attention. Ultrasound methods have been introduced for assessing organ congestion, although this is merely a preliminary step. Here, we review the clinical implications of the assessment of organ congestion by ultrasound.

Utility of Nutritional Screening in Predicting Short-Term Prognosis of Heart Failure Patients.

Controlling nutritional status (CONUT) uses 2 biochemical parameters (serum albumin and cholesterol level), and 1 immune parameter (total lymphocyte count) to assess nutritional status. This study examined if CONUT could predict the short-term prognosis of heart failure (HF) patients.A total of 482 (57.5%) HF patients from the Ibaraki Cardiovascular Assessment Study-HF (n = 838) were enrolled (298 men, 71.7 ± 13.6 years). Blood samples were collected at admission, and nutritional status was assessed using CONUT. CONUT scores were defined as follows: 0-1, normal; 2-4, light; 5-8, moderate; and 9-12, severe degree of undernutrition. Accordingly, 352 (73%) patients had light-to-severe nutritional disturbances. The logarithmically transformed plasma brain natriuretic peptide (log BNP) concentration was significantly higher in the moderate-severe nutritional disturbance group (2.92 ± 0.42) compared to the normal group (2.72 ± 0.45, P < 0.01). CONUT scores were significantly higher in the in-hospital death patients [4 (3-8), n = 14] compared with patients who were discharged following symptom alleviation [3 (1-5), n = 446, P < 0.05]. With the exception of transferred HF patients (n = 22), logistic regression analysis that incorporated the CONUT score and the log BNP, showed that a higher CONUT score (P = 0.019) and higher log BNP (P = 0.009) were predictors of in-hospital death, and the median duration of hospital stay was 20 days.Our results demonstrate the usefulness of CONUT scores as predictors of short-term prognosis in hospitalized HF patients.

Assessment of renal perfusion impairment in a rat model of acute renal congestion using contrast-enhanced ultrasonography.

Renal congestion is caused by elevated central venous pressure (CVP), and decreases glomerular filtration in patients with congestive heart failure. Since real-time contrast-enhanced ultrasonography (CEUS) using microbubble-based contrast agents can visualize the perfused microvascular bed, we sought to evaluate the impairment of renal perfusion during acute renal congestion with CEUS. In Wister rats, CEUS of kidney was performed with the direct monitoring of CVP and intra-renal pressure (IRP). When CVP was elevated to 10 and 15 mmHg after the bolus injection of normal saline via the femoral vein, peak intensity (PI, dB) and time to PI (TTP) in the renal cortex and medulla were compared with control rats. There was a strong correlation between IRP and CVP (r = 0.95, p < 0.0001). In the congestion model, more time was required for enhancement of the parenchyma, especially in the medulla compared to control; TTP of the medulla and cortex at 15 mmHg CVP (CVP15) was significantly prolonged compared with controls (medulla, 4351 ± 98 vs. 1415 ± 267 ms, p = 0.003; cortex, 3219 ± 106 vs. 1335 ± 264 ms, p = 0.005). In addition, medullary PI at CVP15 decreased, but not significantly, compared to those of controls and at 10 mmHg CVP (20.1 ± 0.9, 22.8 ± 1.6, 21.6 ± 0.2 dB). In contrast, cortical PIs at CVP15 were significantly lower than that of control (24.6 ± 1.0 vs. 31.4 ± 1.0 dB, p = 0.007). CEUS revealed that impaired renal parenchymal flow in an acute congestion model is accompanied with increased renal interstitial pressure.

Teneligliptin Prevents Cardiomyocyte Hypertrophy, Fibrosis, and Development of Hypertensive Heart Failure in Dahl Salt-Sensitive Rats.

BACKGROUND: We investigated the effects of the dipeptidyl peptidase 4 inhibitor teneligliptin on cardiac function and hemodynamics during heart failure in hypertensive model rats. METHODS AND RESULTS: Fifty-five male Dahl salt-sensitive rats were divided into 4 groups: control group (0.3% NaCl chow; n = 13), hypertension (HT) group (8% NaCl chow; n = 20), HT-early TNL group (8% NaCl chow and teneligliptin from 6 weeks; n = 10), and HT-late TNL group (8% NaCl chow and teneligliptin from 10 weeks; n = 12). Hemodynamic measurement and tissue analyses were performed at 18 weeks. In all of the HT groups, systolic blood pressures were similarly elevated (P = .66) and heart weights similarly increased (P = .36) with and without TNL administration. LV end-diastolic dimension was significantly enlarged only in the HT-early TNL group compared with the control group (P = .025). Histologic analysis showed less fibrosis (P = .008) and cardiomyocyte widths (P = .009) in the HT-early TNL group compared with the HT group. On hemodynamic analysis, only the HT group showed significant LV end-diastolic pressure elevation (P = .049) and lung congestion (P < .001) compared with the control group. CONCLUSIONS: These results suggest that teneligliptin prevents concentric LV hypertrophy, fibrosis, and development of congestive heart failure in Dahl salt-sensitive rats. Teneligliptin may inhibit pressure-overload hypertrophic adaption and result in LV eccentric hypertrophy with reduced LV ejection fraction.

Nutritional screening based on the controlling nutritional status (CONUT) score at the time of admission is useful for long-term prognostic prediction in patients with heart failure requiring hospitalization.

The objective of the study was to clarify whether controlling nutritional status (CONUT) is useful for predicting the long-term prognosis of patients hospitalized with heart failure (HF). A total of 482 (57.5%) HF patients from the Ibaraki Cardiovascular Assessment Study-HF (N = 838) were enrolled (298 men, 71.7 ± 13.6 years). At admission, blood samples were collected and nutritional status assessed using CONUT. CONUT scores were defined as follows: 0-1, normal; 2-4, light; 5-8, moderate; and 9-12, severe undernutrition. Accordingly, 352 (73%) patients had light-to-severe nutritional disturbances. In the follow-up period [median 541.5 (range 354-786) days], 109 deaths were observed. A Kaplan-Meier analysis revealed that all-cause deaths occurred more frequently in HF patients with nutritional disturbances [n = 93 (26.4%)] than in those with normal nutrition [n = 16 (12.3%); log-rank p < 0.001]. The Cox proportional hazard analyses revealed that a per point increase in the CONUT score was associated with an increased risk of all-cause death (hazard ratio 1.142; 95% confidence interval, 1.044-1.249) after controlling simultaneously for age, sex, previous history of HF hospitalization, log brain natriuretic peptide, and use of therapeutic agents at admission (tolvaptan and aldosterone antagonists). This study suggests that nutritional screening using CONUT scores is helpful in predicting the long-term prognosis of patients hospitalized with HF in a multicenter registry setting.

Effect of Dipeptidyl Peptidase-4 Inhibitors on Cardiovascular Outcome and Cardiac Function in Patients With Diabetes and Heart Failure　- Insights From the Ibaraki Cardiac Assessment Study-Heart Failure (ICAS-HF) Registry.

BACKGROUND: Although experimental animal studies report many pleiotropic effects of dipeptidyl peptidase-4 inhibitors (DPP-4i), their prognostic value has not been demonstrated in clinical trials.Methods and Results:Among 838 prospectively enrolled heart failure (HF) patients hospitalized for acute decompensated HF, 79 treated with DPP-4i were compared with 79 propensity score-matched non-DPP-4i diabetes mellitus (DM) patients. The primary endpoint was all-cause mortality; the secondary endpoint was a composite of cardiovascular death and hospitalization. During follow-up (423±260 days), 8 patients (10.1%) in the DPP-4i group and 13 (16.5%) in the non-DPP-4i group died (log-rank, P=0.283). The DPP-4i group did not have a significantly higher rate of all-cause mortality (log-rank, P=0.283), or cardiovascular death or hospitalization (log-rank, P=0.425). In a subgroup analysis of HF with preserved ejection fraction (HFpEF; n=75), the DPP-4i group had a significantly better prognosis than the non-DPP-4i group regarding the primary endpoint (log-rank, P=0.021) and a tendency to have better prognosis regarding the secondary endpoint (log-rank, P=0.119). In patients with HF with reduced EF (n=83), DPP-4i did not result in better prognosis. CONCLUSIONS: DPP-4i did not increase the risk of adverse clinical outcomes in patients with DM and HF. DPP-4i may be beneficial in HFpEF.

Clinical Implications of Intrarenal Hemodynamic Evaluation by Doppler Ultrasonography in Heart Failure.

OBJECTIVES: This study clarified the characteristics of intrarenal Doppler ultrasonography (IRD) profiles and their prognostic implications in heart failure (HF). BACKGROUND: IRD can assess intrarenal hemodynamics. METHODS: Initially, 224 patients with HF were prospectively enrolled; 151 inpatients were enrolled during hospitalization for HF, and 73 were outpatients in our institution. In IRD profiles of interlobar vessels, the arterial resistance index (RI), venous impedance index (VII), and intrarenal venous flow (IRVF) pattern were assessed. Patients were followed to evaluate the associations with 1-year prognosis. Primary endpoints included death from cardiovascular disease and unplanned hospitalization for HF. RESULTS: Finally, 217 patients with adequate IRD images were enrolled. IRD profiles were associated with conventional risk factors for HF. In particular, IRVF was associated with mean right atrial pressure (RAP); 3 IRVF patterns were stratified by RAP (in a continuous pattern: 5.4 ± 2.5; in a biphasic pattern: 9.5 ± 3.5; and in a monophasic pattern: 14.9 ± 4.3 mm Hg; p < 0.001). In addition, the monophasic IRVF pattern had a poorer prognosis than the other patterns (log rank p < 0.001), and prognosis was poorer for the biphasic pattern than for the continuous flow pattern (log rank p = 0.01). Multivariate Cox proportional hazard model analysis revealed that IRVF patterns were associated with the endpoints, independent of other HF risk factors. CONCLUSIONS: IRVF patterns, rather than RI, depended on RAP, suggesting a correlation with renal congestion. In addition, IRVF patterns strongly correlated with clinical outcomes independent of RAP and other risk factors and might provide additional information to stratify vulnerable HF patients.