Log Brain Natriuretic Peptide Research Articles

Residual congestion in acute decompensated heart failure: A novel approach through microvascular imaging of renal circulation

Abstract Background In patients admitted for acute decompensated heart failure (ADHF), residual congestion at discharge is associated with adverse clinical outcomes. Traditionally, the extent of congestion has been inferred from central venous pressure, but it has also been highlighted that this is insufficient for a comprehensive evaluation of residual congestion. On the other hand, renal congestion is an important finding of organ congestion, and Superb Microvascular Imaging (SMI), a technique that reveals minute flow details, is promising for assessing renal circulation. We hypothesized that in patients with ADHF, assessment of renal circulation using SMI may be superior to conventional methods in assessing residual congestion. Methods In this prospective study, we enrolled 45 consecutive patients admitted with ADHF. We performed comprehensive evaluations including blood tests, echocardiography, and renal ultrasonography using SMI. The vascular index (VI), as measured by SMI, was calculated as the percentage of blood flow signal area in the region of interest. Subsequently, we calculated the intra-renal perfusion index (IRPI), representing cyclic variation in VI, as (maximum VI - minimum VI) within one cardiac cycle, divided by the maximum VI (Figure). Brain Natriuretic Peptide (BNP) levels were utilized to evaluate the state of decongestion. Results At discharge, the mean IRPI was 0.61±0.04, while the median BNP levels were 204.9 pg/ml (interquartile range: 102.7, 428.2). Patients exhibiting elevated log BNP levels at discharge (>2.31, based on median value) displayed significantly higher IRPI values [0.61(0.49, 0.86) vs 0.53(0.35, 0.59), p=0.02] and were older (80.8±8.5 vs 70.3±14.9 years, p=0.010). However, no significant differences were observed regarding laboratory parameters including hematocrit and creatinine levels, as well as echocardiographic parameters such as ejection fraction, E/e' ratio, and estimated right atrial pressure (RAP). Moreover, at discharge, creatinine levels (p=0.56) and estimated RAP (p=0.06) exhibited no significant correlation with IRPI. Conclusion Renal circulation evaluated by SMI may serve as a useful indicator of the extent of residual congestion at discharge compared to blood tests and echocardiographic estimates of right atrial pressure in patients admitted for ADHF.

Association of renal circulation at acute phase with decongestion level at discharge in patients admitted for acute decompensated heart failure

Abstract Background In patients admitted with acute decompensated heart failure (ADHF), renal hemodynamics may play an important role in the clinical course during hospitalization based on the close cardio-renal relationship. Superb Microvascular Imaging (SMI), distinguished by its advanced clutter suppression capabilities to reveal microflow details, holds promise for evaluating renal circulation. Consequently, our study aims to explore the association between renal circulation as assessed by SMI and the levels of brain natriuretic peptide (BNP) at discharge as an indicator of decongestion status. Methods In a prospective design, 45 ADHF patients were sequentially examined via renal ultrasound with SMI at discharge. The vascular index (VI) by SMI was calculated as the percentage of blood flow signal area in the region of interest. Then, the intra-renal perfusion index (IRPI) as an index of cyclic variation in VI, was calculated as the maximum VI minus the minimum VI within one cardiac cycle in the ROI divided by the Max.VI (Figure A). Results The values of IRPI were as follows: at 12h, 0.70±0.04; at 48h, 0.58±0.05; at 1W, 0.50±0.04; and at discharge, 0.61±0.04. The IRPI measured at 48h showed a stronger correlation with BNP at discharge (r = 0.57, p<0.001) than those at the other three points (Figure B). Patients with higher log BNP at discharge (> 2.31: determined by the median value) had significantly higher IRPI and age, and lower hemoglobin levels at 48h, however, there were no significant differences in estimated glomerular filtration rate, ejection fraction, or systolic pulmonary artery pressure at 48h. The area under the curve of IRPI at 48h for higher log BNP at discharge > 2.31 at discharge was 0.746 (sensitivity 100%, specificity 48%). Conclusion Early assessment of renal circulation by SMI around 48 hours after ADHF admission may predict congestion resolution at discharge. This underscores the potential utility of SMI in guiding more aggressive decongestive treatment strategies earlier in ADHF.

Ratio of pulmonary artery diameter to ascending aortic diameter and its association with right ventricular failure after left ventricular assist device implantation

BackgroundSeveral invasive hemodynamic parameters help predict right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation. However, prediction using non-invasive parameters alone has not been established. The ratio of the diameters of the pulmonary artery (PAD) to those of the ascending aorta (AoD) may indicate past hemodynamic load and cardiac dysfunction. We aimed to investigate a predictive model for RVF after LVAD implantation using non-invasive parameters including PAD/AoD ratio. MethodsWe studied 141 patients who underwent primary LVAD implantation and 117 healthy individuals with computed tomography (CT) data. RVF was defined as the need for a subsequent right ventricular assist device or intravenous inotrope administration for more than 30 days after LVAD implantation. The PAD/AoD ratio was measured at the level of the pulmonary artery bifurcation on the CT transaxial slices. ResultsRVF was observed in 29 patients. The correlation between PAD and AoD differed among healthy individuals, patients with and without RVF. Patients with RVF had higher total bilirubin and log brain natriuretic peptide (BNP) levels, a lower left ventricular end-diastolic diameter (LVDd) index, and a higher PAD/AoD ratio than those without RVF. Decision tree analysis indicated that the subgroup with a high PAD/AoD ratio (≥1.09) and a small LVDd index (<35.4 mm/m2) showed the highest probability of RVF (100 %), while the subgroup with a low PAD/AoD ratio (<1.09) and low log BNP (<2.79) showed the lowest probability of RVF (1 %). ConclusionCombining non-invasive parameters with the PAD/AoD ratio can predict RVF with high accuracy.

Usefulness of hypochloremia at the time of discharge to predict prognosis in patients with chronic heart failure after hospitalization

BackgroundHypochloremia has been suggested as a strong marker of mortality in hospitalized patients with heart failure (HF). This study aimed to clarify whether incorporating hypochloremia into pre-existing prognostic models improved the performance of the models. MethodsWe tested the prognostic value of hypochloremia (<97 mEq/L) measured at discharge in hospitalized patients with HF registered in the REALITY-AHF and NARA-HF studies. The primary outcome was 1-year mortality after discharge. ResultsAmong 2496 patients with HF, 316 (12.6 %) had hypochloremia at the time of discharge, and 387 (15.5 %) deaths were observed within 1 year of discharge. The presence of hypochloremia was strongly associated with higher 1-year mortality compared to those without hypochloremia (log-rank: p < 0.001), and this association remained even after adjustment for the Get With the Guideline–HF risk model (GWTG-HF), anemia, New York Heart Association (NYHA) classification, and log-brain natriuretic peptide (BNP) [hazard ratio (HR) 1.64; p < 0.001]. Furthermore, adding hypochloremia to the prediction model composed of GWTG-HF + anemia + NYHA class + log-BNP yielded a numerically larger area under the curve (0.740 vs 0.749; p = 0.059) and significant improvement in net reclassification (0.159, p = 0.010). ConclusionsIncorporating the presence of hypochloremia at discharge into pre-existing risk prediction models provides incremental prognostic information for hospitalized patients with HF.

Differences in Iron Kinetics during Cardiac Load between Patients with Atrial Fibrillation and Those with Sinus Rhythm.

The prevalence of atrial fibrillation (AF) increases with age. Although most AF cases are caused by irregular electrical impulses near the pulmonary vein, not all elderly individuals develop AF. Moreover, risk factors such as hypertension and diabetes do not always lead to AF, even in severe conditions such as pneumonia. We aimed to examine iron kinetics, including ferritin, in patients with AF and individuals in normal sinus rhythm (NSR) using peripheral blood samples. This case-control study included 178 patients who visited the outpatient clinic of a cardiovascular and arrhythmia specialist at the National Center for Geriatrics and Gerontology between August and October 2023. Patients with missing iron-related blood tests and those with pacemaker implantation were excluded. Iron parameters (ferritin, free iron, transferrin saturation) were compared between AF (n = 53) and NSR (n = 125) groups. The AF group had higher log brain natriuretic peptide (BNP) levels, indicating increased cardiac load (AF 2.18 vs. NSR 1.53). However, there were no significant differences in iron parameters between the AF and NSR groups. After matching for age, sex, and coronary artery disease, the AF group showed an increasing trend in ferritin and a decreasing trend in free iron with BNP elevation, suggesting chronic inflammation. In contrast, the NSR group showed no significant changes in iron parameters with BNP elevation. Patients with AF are more likely to have elevated ferritin levels and decreased free iron levels during cardiac overload. Thus, they are more likely to present with chronic inflammation associated with cardiac overload in AF. Future studies should investigate the mechanisms underlying this phenomenon and its implications for AF treatment.

#373 Risk factors for progressive cardiorenal syndrome in patients with chronic kidney disease: the CRIC study

Abstract Background and Aims Cardiorenal syndrome (CRS) is associated with poor outcomes. However, risk factors for progressive CRS are not well studied in patients with chronic kidney disease (CKD). We studied the incidence and risk factors for progressive CRS in a cohort of CKD patients. Method 3 557 participants with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study were included in this analysis after excluding those with heart failure (HF) at baseline visits. The mean follow-up time was 10.5 years. Progressive CRS was defined as development of both HF and renal failure (RF) (dialysis or transplant) within 12 months of each other. Cox proportional hazards models were used to examine the association of risk factors with progressive CRS. In a sensitivity analysis, risk factors for CRS type 2 (HF preceded RF during entire follow up) and CRS type 4 (RF preceded HF) were analyzed. Results The average baseline age was 59 years for those with progressive CRS and 57 years for those without. The age-adjusted incidence of progressive CRS was 4.5/1000 person-years and was 5.0/1000 person-years in Men and 5.9 in Black. The multivariable-adjusted hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for traditional risk factors are as follow: less than high school education (1.82, 1.2-2.73), history of cardiovascular disease (CVD) (1.48, 1.03-2.12), lower educational attainment (per 1 standard deviation [SD]) in eGFR (1.83, 1.40-2.39), and higher (per 1 SD) albumin-to-creatinine ratio (ACR) (2.26, 1.78-2.86). The multivariable-adjusted HRs with corresponding 95% CIs for a one-standard deviation increase in novel risk factors are as follows: hemoglobin (0.82, 0.68-0.99), hemoglobin A1C (1.31, 1.14-1.52), log alkaline phosphatase (1.18, 1.00-1.38), and log brain natriuretic peptide (1.32, 1.10-1.57), adjusting for age, sex, race, clinic sites, and all significant traditional risk factors (education, CVD, eGFR, and ACR). In sensitivity analysis, the risk factor associated with both CRS type 2 and 4 were kidney dysfunction, albuminuria, and mineral bone disorder (higher alkaline phosphatase and FGF23), inflammation (TNF-α), and fibrotic factor (GDF-15), while diabetes, CVD, systolic blood pressure, waist circumference, anemia, HbA1c, and volume overload were more strongly associated with CRS type 2 compared to CRS type 4. Conclusion This study indicates that education level, history of CVD, kidney dysfunction, albuminuria, mineral bone disorder, diabetes control, anemia, volume overload, inflammation, and fibrotic factors are associated with progressive CRS. Many of these risk factors are modifiable. Further studies are warranted to assess the benefits of specific interventions to improve CRS outcomes.

Association between left atrial strain and peri-operative stroke in catheter ablation for atrial fibrillation

Abstract Background It has been reported that left atrial (LA) phasic function, evaluated by LA strain, is associated with cardiogenic stroke in patients with atrial fibrillation (AF). There are no well-established echocardiographic findings to predict peri-operative stroke in AF ablation. Purpose The aim is to evaluate between LA strain and peri-operative stroke in AF ablation. Methods This study included 103 consecutive AF patients (90 paroxysmal and 13 non-paroxysmal AF cases) who underwent initial cryo-ablation without interruption of peri-operative anticoagulation from January 2019 to August 2022. Pre-operative echocardiography was used to measure the LA strain items: LA reservoir strain, contractile strain, and conduit strain in sinus rhythm. Twenty-three patients were excluded due to AF rhythm and atrial septal defect. Peri-operative stroke was detected by using magnetic resonance imaging on the day after ablation. Results Peri-operative stroke occurred in 9 patients (11.3%), and there was no symptomatic stroke. In univariate analysis, age (69.6 ± 4.8 years vs. 64.2 ± 10.9 years, p&amp;lt;0.05) and log brain natriuretic peptide (1.61 ± 0.26 vs. 1.32 ± 0.42 p&amp;lt;0.05) were significantly higher in the stroke group. On the other hand, LA reservoir strain (20.9 ± 5.6% vs. 29.8 ± 8.3%, p&amp;lt;0.01) and LA conduit strain (10.9 ± 2.3% vs. 15.9 ± 7.0%, p&amp;lt;0.01) in the stroke group was significantly lower compared with the non-stroke group. There were no significant differences in the rate of intra-operative electrical cardioversion and other clinical parameters between both groups. Receiver operating characteristic curve analysis revealed that LA reservoir strain cut-off value of 22.7% provided a c-statistic of 0.82 for predicting peri-operative stroke in AF ablation. Conclusions LA reservoir strain is closely associated with peri-operative stroke in AF ablation.ROC curve analysis

Abstract 13584: Prognostic Value of Combined Assessment of Cardiac Magnetic Resonance and Fluorodeoxyglucose Positron Emission Tomography in Patients With Cardiac Sarcoidosis

Background: Although the combined assessment of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) and 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) was useful for the detection of cardiac sarcoidosis (CS), its prognostic value remains unclear. Methods: We examined 90 consecutive CS patients diagnosed by both CMR and FDG-PET before prednisolone (PSL) therapy between September 2008 and April 2023 in our hospital. We calculated the overlap rate of FDG uptake area in the LGE-positive area to evaluate the association between concordance of FDG/LGE areas and adverse events. Patients were divided into two groups according to the median concordance ratio (overlap rate) between FDG and LGE areas (70 %). The primary outcome was a composite of sustained ventricular tachycardia/fibrillation (VT/VF), worsening heart failure, and sudden cardiac death. Results: Median interval between CMR and FDG-PET was 6.5 (IQR 3.0-24.0) days. There are no significant differences on age, sex, left ventricular ejection fraction (LVEF), brain natriuretic peptide (BNP) level, and extent of LGE between the groups. During a median follow-up period of 3.2 (IQR 1.0-6.2) years, the primary outcome occurred in 25 (28%) patients. Patients with lower concordance showed a higher incidence of the primary outcome (Figure A), and lower improvement in LVEF after PSL therapy (Figure B) compared to those with higher concordance. In multivariable Cox regressions, lower concordance was significantly associated with the primary outcome adjusted for history of VT/VF (HR 7.37, P = 0.001), LVEF (HR 7.75, P = 0.001), log BNP (HR 5.62, P = 0.006), and extent of LGE (HR 11.75, P = 0.017). Conclusions: Lower concordance ratio of FDG/LGE before PSL therapy was associated with higher incidence of adverse events and lower improvement of LVEF. Assessment of active inflammation in the extent of LGE might be useful for risk stratification and prediction of the response to PSL in patients with CS.

Circulating sLR11 levels predict severity of pulmonary hypertension due to left heart disease.

Heart failure is a severe condition often involving pulmonary hypertension (PH). Soluble low-density lipoprotein receptor with 11 ligand-binding repeats (sLR11) has been associated with pulmonary artery hypertension. We examined whether sLR11 correlates with PH in left heart disease and can be used as a predictive marker. We retrospectively analyzed patients with severe mitral regurgitation who underwent right heart catheterization before surgery for valve replacement or valvuloplasty from November 2005 to October 2012 at Juntendo University. We measured sLR11 levels before right heart catheterization and analyzed correlations with pulmonary hemodynamics. We compared prognoses between a group with normal sLR11 (≤9.4 ng/ml) and a group with high sLR11 (>9.4 ng/ml). Follow-up was continued for 5 years, with end points of hospitalization due to HF and death due to cardiovascular disease. Among 34 patients who met the inclusion criteria, sLR11 correlated with mean pulmonary artery pressure (r = 0.54, p<0.001), transpulmonary pressure gradient (r = 0.42, p = 0.012), pulmonary vascular resistance (r = 0.36, p<0.05), and log brain natriuretic peptide (BNP). However, logBNP did not correlate with pulmonary vascular resistance (p = 0.6). Levels of sLR11 were significantly higher in the 10 patients with PH (14.4±4.3 ng/ml) than in patients without PH (9.9±3.9 ng/ml; p = 0.002). At 5 years, the event rate was higher in the high-sLR11 group than in the normal-sLR11 group. The high-sLR11 group showed 5 hospitalizations due to HF (25.0%) and 2 deaths (10.0%), whereas the normal-sLR11 group showed no hospitalizations or deaths. Analyses using receiver operating characteristic curves showed a higher area under the concentration-time curve (AUC) for sLR11 level (AUC = 0.85; 95% confidence interval (CI) = 0.72-0.98) than for BNP (AUC = 0.80, 95%CI = 0.62-0.99) in the diagnosis of PH in left heart disease. Concentration of sLR11 is associated with severity of PH and offers a strong predictor of severe mitral regurgitation in patients after surgery.

Prognosis of patients with severe left ventricular dysfunction after transvenous lead extraction and the need for additional hemodynamic support in the perioperative period

Transvenous lead extraction (TLE) is necessary because of system infection, lead malfunction, or system upgrade. Patients with severe left ventricular dysfunction (SLVD) undergoing TLE may be at a higher risk because hemodynamic parameters may change unfavorably during or after TLE; however, this has not yet been clarified. The purpose of this study was to examine whether patients with SLVD undergoing TLE have higher mortality. All patients who underwent TLE were stratified as follows: patients with ejection fraction ≤ 35% (SLVD group) and those with ejection fraction > 35% (non-SLVD group). We assessed the data of 200 patients [SLVD group, 36 (18%); non-SLVD group, 164 (82%)]). Brain natriuretic peptide level and cardiac resynchronization therapy rate were higher in the SLVD group than in the non-SLVD group. There were no significant between-group differences in major complications and clinical success rates. Patients with SLVD were more likely to require additional hemodynamic support, such as catecholamine infusion, temporary atrium-ventricle sequential pacing, and temporary cardiac resynchronization therapy pacing (27.8% vs 1.2%; P < .001). The survival rate was not significantly different between the groups at 30 days and 1 year after TLE (SLVD vs non-SLVD: 30 days: 97.2% vs 99.4%; P = .215; 1 year: 80.6% vs 91.5%; P = .053). Multivariate Cox regression analysis revealed log brain natriuretic peptide and serum hemoglobin levels as predictors for 1-year mortality. The prognosis after TLE was comparable between patients with and without SLVD. However, additional hemodynamic support was often necessary for patients with SLVD.

Abstract 13454: Relationship Between Brain-type Natriuretic Peptide and Serum Growth Factors in Infants With Single Ventricle Heart Disease and Shunt- or Ductal-dependent Pulmonary Blood Flow

Introduction: For infants with shunt- or ductal-dependent single-ventricle heart disease (SD-SVHD), poor growth is common and associated with morbidity and impaired neurodevelopmental outcome. While attention has focused on nutrition to promote weight gain, little is known about the contribution of heart failure to diminished growth. Methods: A prospective observational pilot study was performed to assess the relationship between heart failure, assessed by brain natriuretic peptide (BNP), and growth factors [insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3)] at 4 visits: 1) prior to discharge from neonatal intervention, 2) immediately prior to stage 2 palliation, 3) prior to discharge after stage 2 palliation, and 4) 3-6 months after stage 2 discharge. IGF-1 Z-scores were generated by the analysis lab using reference data. The relationship between log-transformed BNP and growth factors was analyzed using pairwise correlations at each visit and modeled over time with a linear mixed-effects model. Correlations were considered statistically significant using a p-value &lt;0.10, given the exploratory nature of the study. Results: The study included 38 infants (66% male, 68% hypoplastic left heart syndrome). Median BNP was elevated at Visit 1 and decreased over time [287 pg/dL (IQR 147, 794), 85 pg/dL (52, 183), 90 pg/dL (70, 138), and 47 pg/dL (43, 135)]. Median IGF Z-score was &lt;0 at each visit but increased over time [-0.9 (IQR -1.1, 0.1), -0.7 (-1.2, 0.1), -0.5 (-1.2, 0), and -0.2 (-0.8, 0)]. Inverse correlations were noted between log BNP and IGF-1 Z-score at Visit 1 (r = -0.45, p=0.06) and Visit 3 (r = -0.50, p=0.02), and between log BNP and IFGBP-3 at Visit 1 (r = -0.44, p=0.06) and Visit 2 (r = -0.34, p=0.08). There was a small effect of log BNP on IGF-1 Z-score over all time periods (coefficient: -0.23, 95% CI: -0.49, 0.024, p=0.07). Conclusions: This pilot study demonstrates an inverse correlation between BNP and growth factors, suggesting that the heart failure state associated with this physiology may play a mechanistic role in impaired growth. Further work directed at therapies that target the underlying heart failure state might help to optimize the potential for growth in this vulnerable patient population.

Prognostic implications of late gadolinium enhancement for re-worsening left ventricular ejection fraction in patients with dilated cardiomyopathy: a longitudinal study of left ventricular function

Abstract Background Re-worsening left ventricular ejection fraction (LVEF) after initial recovery occurs in some patients with dilated cardiomyopathy (DCM). However, prevalence and predictors of re-worsening LVEF in longitudinal follow-up are unclear. Late gadolinium enhancement of cardiovascular magnetic resonance (LGE-CMR) can evaluate the damage of myocardial tissue. Purpose This study sought to evaluate the clinical parameters including LGE-CMR to predict re-worsening LVEF in patients with recent-onset DCM. Methods We included patients with recent-onset DCM who had an LVEF &amp;lt;45% and underwent LGE-CMR at diagnosis. We performed yearly echocardiographc follow-up [median 6 [4–8.3] years]. Initial LVEF recovery defined as patients increased in &amp;gt;5% LVEF from baseline and had an LVEF≥45% after medical therapy. Patients were divided into three groups: (1) Improved: defined as those with sustained LVEF ≥45% after initial LVEF recovery; (2) Re-worse: those with decreased &amp;gt;5% and had an LVEF &amp;lt;45% after initial LVEF recovery. and (3) Not-improved: those with no initial LVEF recovery during follow-up. To evaluate the prognostic factors for Re-worsening LVEF after initial LVEF recovery, multivariate logistic regression analysis performed between the Improved group and the Re-worse group. Cardiac events defined as hospitalization due to heart failure and sudden death. Results Of 138 patents, 82 patients (59%) were the Improved group, 42 patients (30%) were the Re-worse group, and 14 (10%) were the Not-improved group. Loess curves of long-term LVEF trajectories showed that LVEF in the Re-worse group increased first 2 years and declined slowly thereafter (Fig. 1A). Re-worsening LVEF occurred 4.5±2.2 years after initial LVEF recovery. Multivariate logistic regression analysis demonstrated that LGE area at baseline (Odds ratio: 1.09, 95% confidence interval (CI) 1.02–1.18, p=0.014) and Log brain natriuretic peptide (BNP) at initial LVEF recovery (Odds ratio: 1.53, 95% confidence interval (CI) 1.01–2.31, p=0.042) were independent predictors for Re-worsening LVEF. Kaplan Meier analysis demonstrated that the risk of cardiac events in the Re-worse group was significantly higher (hazard ratio: 3.93, 95% CI 1.49–10.36, p=0.006) than in the Improved group and lower risk than in the Not-improved group (hazard ratio: 0.28, 95% CI 0.12–0.62, p=0.002) (Fig. 1B). Conclusion Re-worsening LVEF occurred in 30% of patients in patients with recent-onset DCM. LGE area and BNP at initial LVEF recovery were independently associated with re-worsening LVEF after initial LVEF recovery. Figure 1 Funding Acknowledgement Type of funding source: None

Bisoprolol transdermal patch improves orthostatic hypotension in patients with chronic heart failure and hypertension

ABSTRACT β blockers (BBs) play an important role in heart failure (HF) treatment. However, orthostatic hypotension (OH) is sometimes caused by BBs. The bisoprolol transdermal patch works more slowly and is long acting compared with the bisoprolol fumarate tablet. The risk of OH may be reduced by using the bisoprolol transdermal patch. We evaluated 57 consecutive patients who were taking the bisoprolol fumarate tablet for chronic HF with hypertension from November 2016 to September 2017. We switched the patients to the bisoprolol transdermal patch. Because 12 of 57 subjects could not continue using the bisoprolol transdermal patch, we analyzed the remaining 45 patients. We investigated BP, blood tests, and changes in BP from supine to standing positions before and after 6 months of switching from tablet to patch. OH was diagnosed by observing a systolic/diastolic BP drop of at least 20/10 mmHg or an absolute systolic BP (sBP) of <90 mmHg from the standing position. No significant changes were observed in the BP and BPs from supine to standing positions, whereas log brain natriuretic peptide was significantly reduced after switching from patch to tablet (2.102 to 2.070pg/dl, P = .039). OH, which occurred in originally 17 patients, showed improvement and eventually appeared in 4 patients. In these patients, changes in BP from supine to standing positions were also significantly improved (changes in sBP, −11 to −6mmHg, P = .016). This study demonstrated that switching from the bisoprolol fumarate tablet to transdermal patch reduced the morbidity of OH in HF patients.

Significant Clinical Indexes of Exercise-Induced Pulmonary Hypertension in Patients With Connective Tissue Disease.

Background: Pulmonary hypertension (PH) is an important cause of morbidity in patients with connective tissue disease (CTD), and an early stage of PH could present as exercise-induced PH (EIPH). This study investigated the significant clinical indexes of EIPH in patients with CTD.Methods and Results: We enrolled 63 patients with CTD who did not have PH at rest. All patients underwent the 6-min walk test (6MWT), and systolic pulmonary artery pressure (SPAP) was evaluated on echocardiography before and after 6MWT. EIPH was defined as SPAP ≥40 mmHg after 6 WMT. Thirty-five patients had EIPH. On univariate logistic analysis, SPAP at rest, log brain natriuretic peptide (BNP), vital capacity (VC), and forced expiratory volume in 1 s (FEV1.0) were significantly correlated with EIPH. On multiple logistic analysis, SPAP at rest and VC were independent predictors of EIPH, whereas FEV1.0 and log BNP were not significantly associated with EIPH. The area under the receiver operating characteristics curve between EIPH and BNP, SPAP at rest, VC or FEV1.0 was 0.67, 0.76, 0.74, and 0.75, respectively.Conclusions: SPAP at rest and respiratory function, especially VC, could be independent predictors of EIPH in patients with CTD.

Circulating acetoacetate is associated with poor prognosis in heart failure patients

BackgroundAcetoacetate is used as an alternative energy source in the heart, and has the potential to improve cardiac function. However, the prognostic impact of acetoacetate has not been investigated in heart failure. MethodsThis study enrolled consecutive 615 hospitalized patients with heart failure. We investigated the associations between circulating acetoacetate and clinical characteristics or prognosis in HF patients. ResultsWe divided the patients into two groups based on circulating acetoacetate levels (high group: acetoacetate ≥35 µmoL/L, n = 313; and low group: acetoacetate <35 µmoL/L, n = 302). The high group had an older age (68 vs. 65 years, P = 0.003) and higher log brain natriuretic peptide levels (2.43 vs. 2.23, P < 0.001) compared with the low group. In contrast, there were no significant differences in the prevalence of co-morbidities, including diabetes mellitus, chronic kidney disease, and anemia, between the two groups. During the median follow-up period of 328 days, 66 all-cause deaths occurred. The high group had a worse prognosis compared with the low group (Log rank, P = 0.041). In the Cox proportional hazard analysis, circulating acetoacetate levels (per 10 µmoL/L increase) were associated with all-cause mortality (hazard ratio 1.020, 95% confidence interval 1.010–1.030, P < 0.001). ConclusionsCirculating acetoacetate is associated with all-cause mortality in patients with heart failure. These results provide new insights into the role of alternative cardiac metabolism in heart failure patients, and raise the possibility of acetoacetate as a novel biomarker to predict the prognosis of heart failure patients.

Progression of right ventricular dysfunction and predictors of mortality in patients with idiopathic interstitial pneumonias

BackgroundFew studies have examined the relationship between echocardiographic indices of right ventricular (RV) function and the severity of pulmonary disease, or their prognostic impact. We evaluated the RV function in patients with interstitial pneumonia and its prognostic impact at each stage of disease severity. MethodA total of 176 patients with idiopathic interstitial pneumonias (IIPs) were retrospectively enrolled and we evaluated RV function by transthoracic echocardiography. The severity of IIPs was graded according to the Goh score. The primary outcome was all-cause death. ResultsThere were 55 patients in mild group (31%), 66 in moderate group (38%), and 55 in severe group (31%). Regarding RV function, RV free wall longitudinal strain and tricuspid annular plane systolic excursion (TAPSE) deteriorated with increasing severity of IIPs, but fractional area change (FAC) decreased significantly only in severe group. There were 64 all-cause deaths during the follow-up period (median 908 days). In moderate group, TAPSE [hazard ratio (HR): 0.85, 95% confidence interval (CI): 0.74–0.97, p=0.017], FAC (HR: 0.89, 95% CI: 0.83–0.96, p=0.001), and mean pulmonary artery pressure (PAP)/cardiac output (HR: 1.50, 95% CI: 1.08–2.09, p=0.015) were independent predictors of all-cause death, even after adjusting for age and log brain natriuretic peptide (BNP). On the other hand, not RV function or PAP but male sex and BNP level were associated with mortality in severe group. ConclusionsAmong patients with IIPs, RV longitudinal function deteriorated with increasing severity of IIPs. Echocardiographic indices of RV function were independently associated with mortality in moderate-stage IIPs.

Predictors of Mortality in Light Chain Cardiac Amyloidosis with Heart Failure

Cardiac involvement in systemic amyloidosis (AL) occurs in ~50% of all AL patients. However once symptomatic heart failure develops, therapeutic options are limited thereby conferring a poor overall prognosis. The median survival is <6 months when AL patients are untreated for the underlying plasma cell dyscrasia. We thus sought to identify risk factors of increased mortality in treatment-naïve, AL cardiac amyloidosis with heart failure. Patients with biopsy-proven AL cardiac amyloid, who presented with heart failure and did not received prior AL treatment, were enrolled between 2004–2014, at the initial visit to the Amyloidosis Center at Boston University Medical Center. Routine laboratory tests, physical examination and echocardiography data were collected. There were 165 predominantly white (76.4%), and male (61%) patients, with a mean age of 61.6 ± 9.5 years. Median survival was 10.9 months (95% CI 6.2–14.7). By multivariate analysis increased relative wall thickness (RWT) [HR 6.70; 95% CI 2.45–18.30), older age (HR 1.04; 95% CI 1.01–1.06), higher New York Heart Association (NYHA) functional class (HR 1.50; 95% CI 1.02–2.2), log brain natriuretic peptide (BNP) levels (HR 1.45; 95% CI 1.15–1.81) and C-reactive protein (CRP) levels (HR 1.02; 95% CI 1.00–1.04) were significant predictors for increased mortality. In conclusion, in treatment-naïve, AL cardiac amyloidosis patients with heart failure symptoms who lack these high-risk features may have a better outcome. These findings might allow for better risk stratification although outcomes are still poor.

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

AimsThe 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 resultsOverall, 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).ConclusionsNutritional screening using the GNRI at discharge is helpful to predict the long‐term prognosis of elderly HFpEF patients.

Lower Hb at the initiation of dialysis does not adversely affect 1-year mortality rate

BackgroundThe management of renal anemia in the pre-dialysis period has been remarkably improved by long-acting erythropoiesis-stimulating agents (ESA). However, many incident dialysis patients cannot achieve target hemoglobin (Hb) levels (> 10 g/dL) and sometimes require blood transfusions. Anemia at the time of dialysis initiation is reportedly correlated with cardiomegaly and early cardiovascular events. Here, we investigated whether this V-shaped depression in Hb level at dialysis initiation adversely affects short-term prognosis.MethodsThe medical charts of 166 patients who underwent initial dialysis were retrospectively reviewed for Hb level, ESA treatment status, dry weight (DW), cardiothoracic rate (CTR), and brain natriuretic peptide (BNP) level at dialysis initiation and 1 year later. Patients were subdivided into three groups according to the tertile of Hb levels. The risk of mortality within 1 year after initiation was analyzed using multivariable-adjusted Cox proportional hazard model.ResultMean Hb level at initiation was 8.6 ± 1.3 g/dL despite the administration of sufficient ESA. After initiation, Hb levels rapidly increased and the Hb time course showed a V-shape with the bottom at initiation. Hb level, CTR, and log BNP showed a significant negative correlation. The Hb level and CTR 1 year after initiation did not correlate with Hb levels at initiation. Lower Hb levels at initiation as a V-shaped depression do not adversely affect 1-year mortality rate by multivariable-adjusted Cox proportional hazard model.ConclusionHb level around dialysis initiation showed a V-shaped depression despite ESA use. Our findings suggest that the V-shaped Hb depression at initiation does not affect short-term prognosis.

An improved algorithm calculated from intrathoracic impedance can precisely diagnose preclinical heart failure events: Sub-analysis of a multicenter MOMOTARO (Monitoring and Management of OptiVol Alert to Reduce Heart Failure Hospitalization) trial study

BackgroundAmbulatory measurement of intrathoracic impedance (ITI) with an implanted device has potential to assess fluid accumulation in patients with heart failure (HF), but it has failed to reduce HF-related hospitalization because of a high false-positive rate. ObjectiveWe aimed to examine whether a modified algorithm (OptiVol 2.0) could reduce false-positive HF events documented in our multicenter trial (MOMOTARO). MethodsThe MOMOTARO trial assessed the potential that fluid index could predict fluid accumulation and therefore HF. The MOMOTARO trial assessed whether HF events could be detected based on fluid accumulation as assessed by fluid index. We re-analyzed raw data of ITI trends of the threshold-crossing events with the modified algorithm. ResultsThe study consisted of 195 patients who had been implanted with a high-energy device. During a mean follow-up period of 658±165 days, there were 154 primary HF events detected by the previous algorithm (OptiVol 1.0). With the previous algorithm, there was no significant difference in log concentration of brain natriuretic peptide (BNP) between baseline and alert (p=0.21). Among 150 alerts of the previous algorithm, only 37 reached the threshold by the modified algorithm, and log BNP was significantly higher in these 37 events compared with the baseline value (2.40±0.46 vs. 2.27±0.52, p<0.01). ConclusionOur simulation study demonstrates that fluid index calculated with the modified algorithm reduces the number of false-positive threshold-crossing HF events and is promising for accurate diagnosis of fluid accumulation in patients.