Characteristics of Patients with an Abnormally Decreased Plasma Xanthine Oxidoreductase Activity in Acute Heart Failure Who Visited the Emergency Department.

BACKGROUND: The factors associated with a low plasma xanthine oxidoreductase (XOR) activity were not elucidated in patients with acute heart failure (AHF). METHODS: Two-hundred and twenty-nine AHF patients who visited the emergency department were prospectively analyzed. AHF patients were divided into 3 groups according to the plasma XOR quartiles (Q1 = low-XOR group [n = 57], Q2/Q3 = middle-XOR group [n = 115], and Q4 = high-XOR group [n = 57]). The prognostic nutritional index (PNI) and the controlling nutritional status (CONUT) score were evaluated. RESULTS: The multivariate logistic regression model showed that the nutritional status (PNI: OR 1.044, 95% CI 1.000-1.088; CONUT: OR 3.805, 95% CI 1.158-12.498), age, and serum creatinine level were independently associated with a low plasma XOR activity. The Kaplan-Meier curve showed a significantly lower incidence of heart failure events in the low-XOR group than in the middle + high-XOR group (hazard ratio, HR 1.648, 95% CI 1.061-2.559). In particular, a low XOR activity with an increased serum creatinine level (>1.21 mg/dL) was independently associated with heart failure events (HR 1.937, 95% CI 1.199-3.130). CONCLUSION: A low plasma XOR activity was associated with malnutrition, renal dysfunction, and aging in AHF. A low XOR activity complicated with renal dysfunction leads to adverse long-term outcomes.

Plasma xanthine oxidoreductase (XOR) activity in patients who require cardiovascular intensive care.

Hyperuricemia is known to be associated with adverse outcomes in cardiovascular intensive care patients, but its mechanisms are unknown. A total of 569 emergency department patients were prospectively analyzed and assigned to intensive care (ICU group, n = 431) or other departments (n = 138). Uric acid (UA) levels were significantly higher in the intensive care patients (6.3 [5.1-7.6] mg/dl vs. 5.8 [4.6-6.8] mg/dL). The plasma xanthine oxidoreductase (XOR) activity in the ICU group (68.3 [21.2-359.5] pmol/h/mL) was also significantly higher than that in other departments (37.2 [15.1-93.6] pmol/h/mL). Intensive care patients were divided into three groups according to plasma XOR quartiles (Q1, low-XOR, Q2/Q3, normal-XOR, and Q4, high-XOR group). A multivariate logistic regression model showed that lactate (per 1.0 mmol/L increase, OR 1.326; 95%, CI 1.166-1.508, p < 0.001) and the Acute Physiology and Chronic Health Evaluation II score (per 1.0 point increase, OR 1.095, 95% CI 1.034-1.160, p = 0.002) were independently associated with the high-XOR group. In-hospital mortality was significantly higher in the high-XOR group (n = 28, 26.2%) than in the normal- (n = 11, 5.1%) and low- (n = 9, 8.3%) XOR groups. The high-XOR group (vs. normal-XOR group) was independently associated with the in-hospital mortality (OR 2.934; 95% CI 1.170-7.358; p = 0.022). Serum UA levels and plasma XOR activity were high in patients admitted to intensive care. The enhanced XOR activity may be one of the mechanisms under which hyperuricemia was associated with adverse outcomes in patients requiring cardiovascular intensive care.

Mechanisms of Urgently Presenting Acute Heart Failure.

The mechanisms of urgently presenting acute heart failure (AHF) are not clear. We evaluated the serum catecholamine values of AHF patients immediately after admission. A total of 1,475 AHF patients were screened, and 484 who were admitted from their homes and in whom serum catecholamine could be evaluated immediately after admission were analyzed. The patients were divided into three groups according to the time interval from the onset of symptoms to admission (OA): < 3 hours (early-OA group; n = 283), 3-24 hours (middle-OA group; n = 142), and ≥24 hours (late-OA group; n = 59). In the early-OA group, the systolic blood pressure (SBP) was significantly higher, orthopnea was more frequent, the pH value was significantly decreased, and the use of noninvasive positive-pressure ventilation was required significantly more often than in the other groups. The serum noradrenaline level was significantly increased in the early-OA group (1.96 [1.02-3.60] ng/mL) than in the middle-OA (1.49 [0.73-3.41] ng/mL) and late-OA (1.40 [0.91-2.42] ng/mL) groups, and the adrenaline level was significantly increased in the early-OA group (0.36 [0.13-1.17] ng/mL) than in the late-OA (0.22 [0.09-0.52] ng/mL) group. A multivariate logistic regression model indicated the early-OA group was independently associated with the SBP > 140 mmHg (odds ratio [OR]: 2.219, 95% CI: 1.375-3.581), midnight/early morning admission (OR: 3.158, 95% CI: 2.048-4.868), and high serum catecholamine value (adrenaline > 0.96 ng/mL, noradrenaline > 3.39 ng/mL, and dopamine > 0.21 ng/mL) (OR 2.091, 95% CI: 1.161-3.767). In conclusion, urgently presented AHF might be induced by an endogenous catecholamine surge, which causes an excessive rise in blood pressure leading to increased after-overload and volume-shift lung congestion.

Impact of Accumulated Serum Uric Acid on Coronary Culprit Lesion Morphology Determined by Optical Coherence Tomography and Cardiac Outcomes in Patients with Acute Coronary Syndrome.

OBJECTIVES: We aimed to examine the relations of very high levels of serum uric acid (sUA) with features of culprit lesion plaque morphology determined by optical coherence tomography (OCT) and adverse clinical outcomes in patients with acute coronary syndrome (ACS). METHODS: We retrospectively compared ACS patients according to sUA levels of > 8.0 mg/dL (n = 169), 7.1-8.0 mg/dL (n = 163), 6.1-7.0 mg/dL (n = 259), and ≤6.0 mg/dL (n = 717). Angiography and OCT findings were analyzed in patients with preintervention OCT and the 4 sUA groups (> 8.0 mg/dL, n = 61; 7.1-8.0 mg/dL, n = 72; 6.1-7.0 mg/dL, n = 131; and ≤6.0 mg/dL, n = 348) were compared. RESULTS: Cardiogenic shock was more prevalent in ACS patients with sUA > 8.0 mg/dL (22% vs. 19% vs. 10% vs. 6%, p < 0.001). Plaque rupture was observed more prevalently by OCT in patients with sUA > 8.0 mg/dL (67% vs. 47% vs. 56% vs. 45%, p = 0.027). At the 2-year follow-up, Kaplan-Meier estimates showed higher cardiac mortality in patients with sUA > 8.0 mg/dL (25% vs. 12% vs. 5% vs. 5%, p < 0.001). After adjusting for traditional cardiovascular risk factors and creatinine levels, patients with sUA > 8.0 mg/dL showed a 4.5-fold increased risk in 2-year cardiac death by multivariate Cox proportional hazard analysis (hazard ratio 4.54, 95% confidence interval 2.98-6.91; p < 0.001). CONCLUSIONS: Very high sUA levels like > 8.0 mg/dL are the primary predictor of 2-year cardiac mortality and could partly be caused by adverse effects of accumulated sUA on plaque morphology in patients with ACS.

Clinical Approach to Shortening Length of Hospital Stay in Elderly Patients With Acute Heart Failure Requiring Intensive Care.

Background: The length of hospital stay (LOHS) after acute heart failure (AHF) is too long in Japan. The clinical approach to shortening LOHS is an urgent issue in the aging Japanese society. Methods and Results: Of 1,473 AHF patients screened, 596 patients >75 years old were enrolled. They were divided by LOHS: <28 days (<28-day group, n=316) and ≥28 days (≥28-day group, n=280). Systolic blood pressure and serum hemoglobin were significantly higher and serum blood urea nitrogen and creatinine significantly lower in the <28-day group than in the ≥28-day group. Non-invasive positive pressure ventilation (NPPV) use was significantly more frequent in the <28-day group than in the ≥28-day group. Furthermore, newly initiated tolvaptan in <12 h was significantly more frequent in the <28-day group than in the ≥28-day group (P=0.004). On multivariate logistic regression analysis, newly initiated tolvaptan in <12 h (OR, 2.574; 95% CI: 1.146-5.780, P=0.022) and NPPV use (OR, 1.817; 95% CI: 1.254-2.634, P=0.002) were independently associated with the <28-day group. The same result was found after propensity score matching for LOHS. Conclusions: LOHS was prolonged in patients with severe HF but could be shortened by early tolvaptan treatment.

Relation of Low Triiodothyronine Syndrome Associated With Aging and Malnutrition to Adverse Outcome in Patients With Acute Heart Failure.

Low triiodothyronine (T3) syndrome has recently been evaluated as a prognostic marker of acute heart failure (AHF). However, in which cases low T3 syndrome typically leads to adverse outcomes remain unclear. Of 1,432 AHF patients screened, 1,190 were enrolled. Euthyroidism was present in 956 patients (80.3%), who were divided into 2 groups: the normal group (n = 445, FT3 ≥1.88 µIU/L) and low-FT3 group (n = 511, FT3 <1.88 µIU/L). The survival rates and event-free rates within 365 days were significantly lower in the low-FT3 group than in the normal group. A multivariate Cox regression model showed that the low-FT3 group was an independent predictor of 365-day mortality (hazard ratio [HR] 1.429, 95% confidence interval [CI] 1.013 to 2.015) and HF events (HR 1.349, 95% CI 1.047 to 1.739). The multivariate logistic regression analysis revealed that age (per 10-year old increase, odds ratio [OR]: 1.186, 95% CI: 1.046 to 1.345) and prognostic nutritional index (PNI; per 1-point increase, OR: 1.067, 95% CI: 1.046 to 1.089) were independently associated with the low-FT3 group. The prognosis in patients with a low PNI and over 75 years old, including all-cause death within 365 days, was significantly poorer in the low-FT3 group than in the normal group. In conclusion, adverse outcomes were predicted by the presence of low T3. AHF patients with low T3 syndrome are strongly associated with aging and malnutrition. Low T3 syndrome complicated with older age and malnutrition is likely to lead to adverse outcomes in patients with AHF.

Prognostic impact of new-onset atrial fibrillation associated with worsening heart failure in aging patients with severely decompensated acute heart failure.

BACKGROUNDS: The prevalence of atrial fibrillation (AF) has been increasing in aging societies. The prognostic impact of AF associated with worsening heart failure (HF) remains obscure. METHODS AND RESULTS: We analyzed 1170 acute heart failure (AHF) patients who required intensive care. Patients were assigned to two groups according to the prevalence of AF: no episode of AF (n = 940) and pre-existing AF (Group-1, n = 230). Patients with no episode of AF (n = 940) were further divided into two groups according to presence of new-onset of AF after admission (Group-2a, n = 258) or not (Group-2b, n = 682). Kaplan-Meier curve analysis showed that prognosis, including all-cause mortality and HF-events within 1000 days, was significantly poorer in the Group-1 compared to the Group-2b. However, a multivariate Cox regression model showed that the Group-1 was not an independent predictor of 1000-day mortality and HF-events. Furthermore, Kaplan-Meier curve analysis showed that prognosis, including all-cause mortality and HF-events within 1000 days, was significantly poorer in the Group-2a than in the Group-2b. A multivariate Cox regression model revealed that the Group-2a was an independent predictor of 1000-day mortality (HR: 1.403, 95% CI: 1.018-1.934) and HF-events (HR: 1.352, 95% CI: 1.071-1.708). A multivariate logistic regression model showed that only age (≥75 years old) was independently associated with new-onset of AF after admission (odds ratio: 1.556, 95% CI: 1.130-2.143). CONCLUSIONS: New-onset AF associated with worsening HF increases with age and is independently-associated with adverse outcome in patients with AHF.

Plasma Xanthine Oxidoreductase (XOR) Activity in Cardiovascular Disease Outpatients.

Background: The mechanisms of the increased plasma xanthine oxidoreductase (XOR) activity in outpatients with cardiovascular disease were unclear. Methods and Results: A total of 372 outpatients were screened, and 301 outpatients with cardiovascular disease were prospectively analyzed. Blood samples were collected from patients who visited a daily cardiovascular outpatient clinic. Patients with diabetes mellitus (DM) were significantly more likely to be classified into the high-XOR group (≥100 pg/h/mL; 50%) than the low-XOR group (<100 pmol/h/mL; 28.7%). On multivariate logistic regression analysis, DM (OR, 2.683; 95% CI: 1.441-4.996) was independently associated with high plasma XOR activity in all cohorts. In the diabetic cardiovascular disease patients (n=100), median body mass index (BMI) in the high-XOR group (28.0 kg/m2; IQR, 25.2-29.4 kg/m2, n=32) was significantly higher than in the low-XOR group (23.6 kg/m2; IQR, 21.2-25.7 kg/m2, n=68), and BMI was independently associated with high plasma XOR activity (OR, 1.340; 95% CI: 1.149-1.540). Plasma hydrogen peroxide was significantly higher in DM patients with high plasma XOR activity and obesity (>22 kg/m2) than in other patients. Conclusions: DM with obesity is one of the mechanisms of XOR enhancement in cardiovascular disease. The increase of XOR is a possible pathway for the production of reactive oxygen species in obese cardiovascular disease patients with DM.

Clinical Features of Acute Heart Failure During Sleep　- Prognostic Impact of a Prodrome in Patients With Severely Decompensated Acute Heart Failure Admitted at Midnight or Early Morning.

Background: The features of sleep-associated acute heart failure (AHF) patients admitted at midnight or early morning (M/E) are unclear. Methods and Results: Of 1,268 AHF patients screened, 932 were analyzed, and divided into 2 groups by admission time (M/E group, 23:00-06:59, n=399; daytime group, 07:00-22:59, n=533). Those in the M/E group were further divided by the presence of a prodrome: with (n=176; prodrome group) or without (n=223; sudden onset group). The median time from symptom onset to hospitalization was significantly shorter in the M/E group (98 min; range, 65-170 min) than in the daytime group (123 min; range, 68-246 min). The 365-day HF event rate in the M/E group was significantly lower than that of the daytime group. On multivariate logistic regression modeling the M/E group was independently associated with a better outcome than the daytime group (OR, 0.673; 95% CI: 0.500-0.905). In the M/E group, the 365-day HF event rate was significantly lower in the prodrome group than in the sudden onset group. On multivariate logistic regression modeling, inclusion in the prodrome group was independently associated with a better outcome (OR, 0.544; 95% CI: 0.338-0.877). Conclusions: AHF patients admitted during sleeping hours were not sicker than those admitted during the daytime. The absence of a prodrome, however, might be associated with future repeated HF events.

Hyperuricemia complicated with acute kidney injury is associated with adverse outcomes in patients with severely decompensated acute heart failure.

BACKGROUND: The relationship between the serum level of uric acid (UA) and the acute kidney injury on admission in patients with acute heart failure (AHF) remain unclear. METHODS AND RESULTS: A total of 1326 AHF patients were screened, and data for 1047 patients who were admitted to the intensive-care unit were analyzed. The patients were assigned to a low-UA group (UA ≤ 7.0 mg/dl, n = 569) or a high-UA group (UA > 7.0 mg/dl, n = 478) according to their UA level at admission. Acute kidney injury (AKI) at admission was defined based on the ratio of the serum creatinine value recorded on admission to the baseline creatinine value: no-AKI (n = 736) or AKI (n = 311). The patients were therefore assigned to four groups: low-UA/no-AKI (n = 428), high-UA/no-AKI (n = 308), low-UA/AKI (n = 141) and high-UA/AKI (n = 170). The high-UA patients were significantly more frequent in the AKI group than in the non-AKI group among all patients and the non-chronic kidney injury (CKD) cohort. A Kaplan-Meier curve showed a significantly lower 365-day survival rate in the high-UA/AKI group than in the other groups. The multivariate Cox regression model identified only high-UA/AKI as an independent predictor of 365-day mortality (hazard ratio [HR]: 2.511, 95% confidence interval [CI] 1.671-3.772 in all AHF patients, HR: 1.884, 95% CI 1.022-3.473 in non-CKD patients and HR: 3.546, 95% CI 2.136-5.884 in CKD patients). CONCLUSION: An elevated serum UA level complicated with AKI was an independent predictor of mortality in patients with severely decompensated AHF.

Trends in the Management of Acute Heart Failure Requiring Intensive Care.

The aim of the present study was to elucidate trends in managing acute heart failure (AHF) patients who require intensive care over a 19-year period. We evaluated a total of 1,475 AHF patients, comparing patient backgrounds, in-hospital management, and prognosis according to the year of admission (2000s group, n = 608 and 2010s group, n = 867). A multivariate logistic regression analysis revealed that age (≥75 years; odds ratio [OR] 1.334, 95% confidence interval [CI] 1.048 to 1.700), systolic blood pressure (<100 mm Hg; OR 1.934, 95% CI 1.170 to 3.198), left ventricular ejection fraction (>40%; OR 1.441, 95% CI 1.125 to 1.847), and prognostic nutritional index (severe; OR 1.865, 95% CI 1.224 to 2.841) were independently associated with admission in the 2010s group. The use of intra-aortic balloon pumping and noninvasive positive pressure ventilation increased significantly, whereas the need for endotracheal intubation and administration of furosemide and carperitide in the 2010s group decreased significantly compared with the 2000s group. Tolvaptan therapy was introduced from 2010. The duration of intensive care unit admission and total hospitalization in the 2010s group (4 [3 to 6] and 23 [15 to 40] days, respectively) were significantly shorter than in the 2000s group (5 [4 to 8] and 30 [20 to 54] days, respectively). A Kaplan-Meier survival curve analysis showed the survival rate of the 2010s group was significantly poorer compared with the 2000s group (hazards ratio 1.435, 95% CI 1.113 to 1.851). After propensity score matching, the 365-day mortality rates of the 2 groups did not significantly differ. In conclusion, the condition of AHF patients became more critical year by year, leading to poorer long-term prognosis despite improved treatment strategy. These findings will be useful for managing AHF in the next pandemic era.

Comparison of Coronary Culprit Lesion Morphology Determined by Optical Coherence Tomography and Relation to Outcomes in Patients Diagnosed with Acute Coronary Syndrome During Winter -vs- Other Seasons.

Patients diagnosed with acute coronary syndrome (ACS) during winter have worse outcomes; however, mechanisms driving this trend are unclear. We examined coronary culprit lesion morphologies using optical coherence tomography (OCT). Features and outcomes were retrospectively compared between patients admitted with ACS in winter (W-ACS; n = 390) and in other seasons (O-ACS; n = 1,027). Angiography and OCT results were analyzed in patients who underwent OCT examination (173 patients in W-ACS and 450 in O-ACS). On initial angiography, minimum lumen diameter was smaller (median; 0.12 mm vs 0.25 mm, p = 0.021) and Thrombolysis in myocardial infarction flow grade was worse (Thrombolysis in myocardial infarction 0/1; 57% vs 44%, p = 0.005) in W-ACS. OCT performed before coronary interventions or just after intracoronary thrombectomy showed that plaque rupture (56% vs 46%) and calcified nodules (8% vs 5%) were more prevalent, and plaque erosion (37% vs 49%) was less prevalent in W-ACS (p = 0.039 for all 3 variables). At 2-year follow-up for all admitted ACS patients, Kaplan-Meier estimates showed higher cardiac mortality in W-ACS (11.8% vs 8.3%, p = 0.043). Multivariate Cox proportional hazard analysis showed that patients in W-ACS group had a 1.5-fold increased risk of cardiac death within 2 years after adjusting for traditional cardiovascular risk factors (hazard ratio, 1.54 [95% confidence interval, 1.06 to 2.23]; p = 0.024). In conclusion, patients diagnosed with ACS during winter had worse angiographic results and OCT revealed less plaque erosion (more plaque rupture or calcified nodules) at the culprit lesions, which may be partly associated with worse cardiac mortality within 2 years.

Prognostic Value of Both Plasma Volume Status and Nutritional Status in Patients With Severely Decompensated Acute Heart Failure.

BACKGROUND: Plasma volume status (PVS) has been evaluated recently as a prognostic marker of acute heart failure (AHF). However, whether evaluating PVS alone is sufficient remains unclear. METHODS: Of 675 patients with AHF screened, 601 were enrolled. The PVS, prognostic nutritional index (PNI) (lower = worse), and Controlling Nutritional Status (CONUT) score (higher = worse) were evaluated. Patients were divided into 2 groups according to PVS value (low- or high-PVS group) and were further subdivided into 4 groups (low- or high-PVS/CONUT group and low- or high-PVS/PNI group). RESULTS: A Kaplan-Meier curve showed a significantly lower survival rate in the high-PVS group than in the low-PVS group, the high-PVS/high-CONUT group than in the high-PVS/low-CONUT group, and the high-PVS/low-PNI group than in the high-PVS/high-PNI group. A multivariate Cox regression model showed that high PVS (hazard ratio [HR], 1.642; 95% confidence interval [CI], 1.049-2.570) and high PVS/high CONUT (HR, 2.076; 95% CI, 1.147-3.757) and high PVS/low PNI (HR, 2.094; 95% CI, 1.166-3.761) were independent predictors of 365-day mortality. CONCLUSIONS: An adverse outcome was predicted by the evaluation of PVS; furthermore, a malnutrition status with a high PVS leads to an adverse outcome. The simultaneous evaluation of nutrition status and PVS is essential to predict an AHF outcome.

CONTEXTE: La valeur pronostique du volume plasmatique (VP) dans l'insuffisance cardiaque aiguë (ICA) a récemment été évaluée. On ne sait toutefois pas si le volume plasmatique à lui seul peut suffire. MÉTHODOLOGIE: Sur les 675 patients présentant une ICA diagnostiquée, 601 ont été retenus. Le VP, l'indice nutritionnel pronostique (PNI; plus l'indice est faible, plus l'état nutritionnel est mauvais) et le score CONUT (Controlling Nutritional Status, contrôle de l'état nutritionnel; plus le score est élevé, plus l'état nutritionnel est mauvais) ont été évalués. Les patients ont été répartis en deux groupes en fonction du VP (VP faible et VP élevé), puis de nouveau en quatre sous-groupes (VP/CONUT faible ou élevé et VP/PNI faible ou élevé). RÉSULTATS: La courbe de Kaplan-Meier montre que le taux de survie est significativement inférieur dans le groupe VP élevé par rapport au groupe VP faible, dans le groupe VP élevé/score CONUT élevé par rapport au groupe VP élevé/score CONUT faible, et dans le groupe VP élevé/PNI faible par rapport au groupe VP élevé/PNI élevé. L'analyse au moyen d'un modèle de régression de Cox multivarié a révélé qu'un VP élevé (rapport des risques instantanés [RRI] de 1,642; intervalle de confiance [IC] à 95 % : de 1,049 à 2,570), un VP élevé assorti d'un score CONUT élevé (RRI de 2,076; IC à 95 % : de 1,147 à 3,757) et un VP élevé assorti d'un PNI faible (RRI de 2,094; IC à 95 % : de 1,166 à 3,761) étaient des facteurs prédictifs indépendants de la mortalité à 365 jours. CONCLUSIONS: L'évaluation du VP a permis de prédire une issue défavorable; en outre, les données montrent qu'un état de malnutrition conjugué à un VP élevé est un facteur de mauvais pronostic. Il est essentiel d'évaluer simultanément l'état nutritionnel et le VP pour prédire l'ICA.

Gender Differences in the Social Determinants of the Long-term Prognosis for Severely Decompensated Acute Heart Failure in Patients over 75 Years of Age.

Objective The aim of present study was to elucidate the gender differences in social determinants among patients with acute heart failure (AHF). Methods A total of 1,048 AHF patients were enrolled, and the 508 AHF patients who were ≥75 years old and the 540 patients who were <75 years old were evaluated as the elderly and non-elderly cohorts, respectively. Participants who met one of the three marital status-, offspring-, and living status-related criteria were considered socially vulnerable, and subjects were thus classified into socially vulnerable and non-socially vulnerable groups by gender in both the non-elderly and elderly cohorts. Social vulnerability was significantly more common in the elderly cohort (n=246, 48.4%) than in the non-elderly cohort (n=197, 36.5%) and significantly more common in the elderly women (n=157, 69.4%) than in the elderly men (n=89, 31.5%). Kaplan-Meier curves showed that the survival rate of the socially vulnerable group was significantly poorer than that of the non-socially vulnerable group in the elderly male cohort (p=0.010). Social vulnerability was an independent predictor of the 1,000-day mortality in the elderly male cohort (hazard ratio: 1.942, 95% confidence interval: 1.102-3.422) but not in the elderly female cohort according to a multivariate analysis. Conclusion Social vulnerability was shown to be more common in elderly female AHF patients than in elderly men, although it was associated with a poor prognosis in elderly men. Reinforcing the social structure of elderly male AHF patients might help improve their prognosis.