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.

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.

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.

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.

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.

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.

Dislodged and mechanically distorted stent stuck within a previously implanted drug-eluting stent.

Coronary stent loss during percutaneous coronary intervention is rare and is often associated with significant morbidity. Several retrieval techniques, overlying stent deployment and crushing, and surgical removal can be used to deal with a stent lost in the coronary system. We successfully treated a dislodged and mechanically distorted coil stent stuck within a previously implanted drug-eluting stent (DES) by stent-crush technique. This case might provide insight into the mechanisms responsible for the longitudinal fragility of cobalt alloy and coil-structure stents and stent fracture of DES. In the DES era, careful attention should be paid to such complications when attempting to deliver a stent to a distal vessel through a pre-existing DES.

Effect of hospital case volume on treatment and in-hospital outcomes in patients undergoing percutaneous coronary intervention for acute myocardial infarction. Results from the Ibaraki Coronary Artery Disease Study (ICAS) Registry.

The volume of percutaneous coronary interventions (PCI) performed in a hospital has been suggested to correlate with favorable outcomes in patients undergoing primary PCI for acute myocardial infarction (AMI). However, studies that use current data and compare treatment and outcomes for AMI among hospitals with different volumes are still limited in Japan. Between January 2004 and March 2006, 401 AMI patients underwent primary PCI in the 11 hospitals participating in the Ibaraki Coronary Artery Disease Study (ICAS). Clinical characteristics, treatment, and in-hospital outcomes were retrospectively compared between 254 patients admitted to high-volume PCI hospitals and 147 patients admitted to low-volume hospitals. Low-volume hospitals had a higher prevalence of multivessel disease patients. High-volume hospitals had longer onset-to-door times, which were offset by faster door-to-balloon times. Rates of coronary stent use and successful PCI were comparable between the groups. Low-volume hospitals more frequently performed intra-aortic balloon pumping. Length of stay was longer in low-volume hospitals, whereas in-hospital mortality, bypass surgery, and repeat PCI rates did not differ between groups. Although the present study assessed limited data based on small sample size, we observed that contemporary standard treatments including stent implantation were performed for AMI patients undergoing primary PCI in hospitals with both high and low case volumes. We did not find an obvious relationship between hospital PCI volume and in-hospital outcomes in our data. However, further prospective surveys should be attempted to confirm these results.

The wake of a large vortex is associated with intraventricular filling delay in impaired left ventricles with a pseudonormalized transmitral flow pattern.

UNLABELLED: Although an intraventricular filling delay has been observed in patients with a psuedonormalized transmitral flow pattern, little is known about the underlying hydrodynamic nature of this phenomenon. METHODS: To examine those hydrodynamics, we studied every echocardiographic frame showing ventricular inflow (80 Hz) in the apical long-axis view and M-mode image using contrast echocardiography in 29 patients with a psuedonormalized pattern and in 26 normal controls. The velocity of the filling flow front (Vp), the ratio of Vp to E, and the mean radius of the vortices associated with the filling flow were measured. RESULTS: In both groups, vortices were observed at the ridge of the mitral valve during acceleration of the E-wave. The mean radius of the vortices was greater in the pseudonormalized filling group than that in the control group (8 +/- 2 vs 3 +/- 1 mm, P < 0.0001). Vp was smaller in the pseudonormalized group than in the control group (36 +/- 6 vs 47 +/- 6 cm/sec, P = 0.0008). Vp/E was < 1 and smaller in the pseudonormalized group than that in the control group (0.46 +/- 0.13 vs 0.59 +/- 0.07, P = 0.014) and negatively correlated with the mean radius of the vortices (r = 0.54, P < 0.0001). CONCLUSIONS: Contrast echocardiography identified uniform flow characteristics with blood in the filling flow front moving in well-developed vortices and resulting in a left ventricular filling delay in the impaired left ventricle in spite of an increased early transmitral flow velocity.

Assessment of propagation velocity by contrast echocardiography for standardization of color Doppler propagation velocity measurements.

BACKGROUND: Color Doppler propagation velocity (Vp) (color-Vp) has not yet been standardized, although it should be able to specifically reflect the intraventricular movements of left ventricular (LV) inflow. Because contrast echocardiography can depict a specified flow, we used this modality to standardize measurements of color-Vp of LV inflow. METHODS: We performed contrast echocardiographic examinations in 100 patients (70 men, 30 women; age 53 +/- 12 years). Four types of color-Vp were measured: by the flow wave front method and by aliasing method using 3 aliasing velocity levels based on the peak velocity of early diastolic flow of transmitral flow. We also determined contrast echocardiographic Vp by M-mode imaging of LV inflow (contrast-Vp). RESULTS: Contrast-Vp and all 4 types of color-Vp could be compared in 86 patients. Contrast-Vp was significantly lower than color-Vp ( P < .01), except for color-Vp measured at the aliasing level 50% > peak velocity of early diastolic flow >/= 40% (color-Vp 40). A close relationship was observed between contrast-Vp and color-Vp 40 ( r = 0.801, P < .0001). Contrast-Vp and color-Vp 40 showed high ability to detect abnormal transmitral flow patterns according to receiver operating characteristics curves (area under curve for contrast-Vp, 0.94; for color-Vp 40, 0.90). CONCLUSIONS: Our results should be useful in standardization of color-Vp measurement to specifically reflect propagation of the fluid elements derived from LV inflow, with ability to distinguish LV filling abnormalities.

Effect of age on carotid arterial intima-media thickness in childhood.

To investigate relationships between carotid arterial intima-media thickness (IMT) and age in childhood, we performed high-resolution carotid arterial ultrasonography in 60 healthy children (27 boys, 33 girls; age range, 5-14 years) determined by screening to have no dyslipidemia or hypertension. No plaque formation was found, and irregularity of IMT (root mean square roughness of IMT) did not correlate with age. Mean IMT increased in a linear manner with age [IMT in millimeters = (0.009 x age in years) + 0.35] ( r = 0.39, P = 0.002). This correlation remained significant after adjustment for gender, parental smoking, systolic and diastolic blood pressure, body mass index, and serum concentrations of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. None of these known cardiovascular disease risk factors in adults had a significant relationship with age-adjusted IMT in children. While circumferential wall stress and diastolic blood pressure were not correlated with age, mean IMT and lumen diameter showed significant positive relationships with circulating blood volume, which was calculated as the function of height and weight. These data suggested that age-dependent physiologic thickening of arterial walls begins in childhood.

Preload-dependent variation of the propagation velocity in patients with congestive heart failure.

BACKGROUND: Although color Doppler M-mode propagation velocity (Vp) is preload-independent, the variation in Vp with the temporal variation of preload in the clinical setting has not been evaluated. Because left ventricular filling pressure changes dramatically with treatment of congestive heart failure (CHF), we hypothesized that preload-dependent variations in Vp occur with treatment of CHF. METHODS: We performed Doppler echocardiographic and hemodynamic evaluation in 24 patients with CHF (15 men, 62 +/- 10 years) at initial presentation (baseline study) and after CHF had improved with therapy (second study). RESULTS: The interval between the baseline and the second study was 48.6 +/- 21.5 hours. Vp decreased between the baseline study (41 +/- 5 cm/s) and the second study (28 +/- 5 cm/s, P <.0001). Only the change in pulmonary capillary wedge pressure (-8.3 +/- 3.3 mm Hg) between the baseline and second study was an independent predictor of the change in Vp (-12.5 +/- 5.9 cm/s) by stepwise linear regression (r = 0.68, P =.0002). CONCLUSIONS: Vp decreases significantly with decreases in pulmonary capillary wedge pressure with the treatment of CHF. The preload-dependent variation should be taken into account in the assessment of Vp in patients with CHF.

The correlation of irregularities in carotid arterial intima-media thickness with coronary artery disease.

Noninvasive ultrasonographic assessment of carotid artery intima-media thickness (IMT) can improve risk stratification for coronary artery disease (CAD) in certain patients. Several measurements have been used to evaluate carotid atherosclerosis by ultrasonography. Although it has been reported that angiographic arterial irregularities correlate with pathologic changes of atherosclerosis and the occurrence of cardiovascular events, only a few studies have assessed carotid arterial wall irregularity by ultrasonography. The purpose of this study was to evaluate the irregularity of IMT quantitatively, and its association with the presence or absence of CAD. The correlation of maximum and mean IMT values, and IMT irregularity with the presence or absence of CAD, was investigated in 90 patients who had undergone coronary angiography. IMT was measured by manual tracking of the far wall of the common carotid arteries, carotid bulbs, and internal carotid arteries. The IMT irregularity was defined as the root mean square (RMS) difference between each IMT and averaged IMT. Multiple logistic regression analysis, after adjustment for coronary risk factors, indicated that the RMS difference was a more accurate predictor of CAD than were the mean or maximum IMT values. These results indicate that the evaluation of IMT irregularity by ultrasonography is a useful predictor for the presence of coronary atherosclerosis.