Correlates of sleep-disordered breathing and Cheyne-Stokes respiration in patients with atrial fibrillation who have undergone pulmonary vein isolation.

Sleep disordered breathing (SDB) is a common comorbidity in patients with atrial fibrillation (AF). Patients undergoing pulmonary vein isolation (PVI) for AF have a high prevalence of SDB. In previous studies, some patients with AF had Cheyne-Stokes respiration (CSR). The aim of the present study was to assess the prevalence of SDB and the correlates of SDB severity and CSR in AF patients who have undergone PVI. The study was conducted using a single-center observational design. All participants underwent a home sleep apnea test (ApneaLink Air, ResMed, Australia), which could determine the severity of SDB as assessed by the apnea-hypopnea index (AHI) and the percentage of CSR (%CSR) pattern. 139 AF patients who underwent PVI were included in the study. Overall, 38 (27.3%) patients had no SDB (AHI < 5), 53 (38.1%) had mild SDB (5 ≤ AHI < 15), 33 (23.7%) had moderate SDB (15 ≤ AHI < 30), and 15 (10.8%) had severe SDB (AHI ≥ 30). Correlates of the increased AHI included male sex (ß = 0.23, p = 0.004), age (ß = 0.19, p = 0.020), high body mass index (ß = 0.31, p < 0.001), and ß blockers usage (ß = 0.18, p = 0.024). Conversely, correlates with the %CSR rate included male sex (ß = 0.18, p = 0.020), age (ß = 0.19, p = 0.015), non-paroxysmal AF (ß = 0.22, p = 0.008), and high glycohemoglobin A1c (ß = 0.36, p < 0.001) and N-terminal pro-brain natriuretic peptide (ß = 0.24, p = 0.005) levels. SDB is prevalent in patients with AF who have undergone PVI; predisposing factors for SDB include male sex, older age, and obesity. CSR occurs in patients with AF who have undergone PVI; predisposing factors for CSR include male sex, older age, high left ventricular filling pressure, and abnormal blood glucose level.

Clinical impact of cryoballoon posterior wall isolation using the cross-over technique in persistent atrial fibrillation.

BACKGROUND AND AIMS: Successful left atrial posterior wall isolation (LAPWI) using only the cryoballoon (CB) is technically challenging for the treatment of atrial fibrillation (AF). This study aimed to evaluate the efficacy of the cross-over technique, wherein an overlapped ablation is performed by placing the CB from both directions in contact with the LAPW. METHODS: This was a single-center, retrospective, observational study of 194 consecutive patients with persistent atrial fibrillation (PerAF) who underwent a first-time procedure of pulmonary vein isolation (PVI) + PWI (108 patients) or PVI-only (86 patients) using the CB. The cross-over technique was applied in all LAPWI. RESULTS: For ablation of the LA roof and bottom, respectively, a mean of 8.6 ± 1.0 (right to left [R→L] 4.3 ± 1.1 and left to right [L→R] 4.3 ± 1.1) and 9.1 ± 1.2 (R→L 4.6 ± 1.6 and L→R 4.5 ± 1.2) CB applications were delivered. LAPW was successfully isolated solely using the CB in 99.1% of patients. Although the PVI + PWI group had significantly longer procedure time, no severe adverse events were observed in either group. During a median follow-up of 19 months, freedom from recurrence of all atrial tachyarrhythmias was achieved in 93.5% of the PVI + PWI group and 72.9% of the PVI-only group (p = .011). CONCLUSIONS: LAPWI performed solely with the CB using the cross-over technique is feasibly, safe, and was independently associated with a significantly higher freedom from recurrence of atrial tachyarrhythmias compared with PVI alone in patients with PerAF.

Feasibility of self-measurement telemonitoring using a handheld heart sound recorder in patients with heart failure - SELPH multicenter pilot study.

BACKGROUND: Multi-parametric assessment, including heart sounds in addition to conventional parameters, may enhance the efficacy of noninvasive telemonitoring for heart failure (HF). We sought to assess the feasibility of self-telemonitoring with multiple devices including a handheld heart sound recorder and its association with clinical events in patients with HF. METHODS: Ambulatory HF patients recorded their own heart sounds, mono­lead electrocardiograms, oxygen saturation, body weight, and vital signs using multiple devices every morning for six months. RESULTS: In the 77 patients enrolled (63 ±â€¯13 years old, 84 % male), daily measurements were feasible with a self-measurement rate of >70 % of days in 75 % of patients. Younger age and higher Minnesota Living with Heart Failure Questionnaire scores were independently associated with lower adherence (p = 0.002 and 0.027, respectively). A usability questionnaire showed that 87 % of patients felt self-telemonitoring was helpful, and 96 % could use the devices without routine cohabitant support. Six patients experienced ten HF events of re-hospitalization and/or unplanned hospital visits due to HF. In patients who experienced HF events, a significant increase in heart rate and diastolic blood pressure and a decrease in the time interval from Q wave onset to the second heart sound were observed 7 days before the events compared with those without HF events. CONCLUSIONS: Self-telemonitoring with multiple devices including a handheld heart sound recorder was feasible even in elderly patients with HF. This intervention may confer a sense of relief to patients and enable monitoring of physiological parameters that could be valuable in detecting the deterioration of HF.

Impact of sleep-disordered breathing on overnight changes in arterial stiffness in patients with acute heart failure.

Overnight increases in arterial stiffness associated with sleep-disordered breathing may adversely affect patients with acute heart failure. Thus, we investigated overnight changes in arterial stiffness and their association with sleep-disordered breathing in patients hospitalized for acute heart failure. Consecutive patients with acute heart failure were enrolled. All participants underwent overnight full polysomnography following the initial improvement of acute signs and symptoms of acute heart failure. The arterial stiffness parameter, cardio-ankle vascular index (CAVI), was assessed before and after polysomnography. Overall, 60 patients (86.7% men) were analyzed. CAVI significantly increased overnight (from 8.4 ± 1.6 at night to 9.1 ± 1.7 in the morning, P < 0.001) in addition to systolic and diastolic blood pressure (from 114.1 mmHg to 121.6 mmHg, P < 0.001; and from 70.1 mmHg to 78.2 mmHg, P < 0.001, respectively). Overnight increase in CAVI (ΔCAVI ≥ 0) was observed in 42 patients (70%). The ΔCAVI ≥ 0 group was likely to have moderate-to-severe sleep-disordered breathing (i.e., apnea-hypopnea index ≥15, 55.6% vs 80.9%, P = 0.047) and greater obstructive respiratory events (29.4% vs 58.5%, P = 0.041). In multivariable analysis, moderate-to-severe sleep-disordered breathing and greater obstructive respiratory events were independently correlated with an overnight increase in CAVI (P = 0.033 and P = 0.042, respectively). In patients hospitalized for acute heart failure, arterial stiffness, as assessed by CAVI, significantly increased overnight. Moderate-to-severe sleep-disordered breathing and obstructive respiratory events may play an important role in the overnight increase in cardio-ankle vascular index.

Poor Nutritional Status during Recovery from Acute Myocardial Infarction in Patients without an Early Nutritional Intervention Predicts a Poor Prognosis: A Single-Center Retrospective Study.

Whether malnutrition during the early phase of recovery from acute myocardial infarction (AMI) could be a predictor of mortality or morbidity has not been ascertained. We examined 289 AMI patients. All-cause mortality and composite endpoints (all-cause mortality, nonfatal stroke, nonfatal acute coronary syndrome, and hospitalization for acute decompensated heart failure) during the follow-up duration (median 39 months) were evaluated. There were 108 (37.8%) malnourished patients with GNRIs of less than 98 on arrival; however, malnourished patients significantly decreased to 91 (31.4%) during the convalescence period (p < 0.01). The incidence rates of mortality and primary composite endpoints were significantly higher in the malnourished group than in the well-nourished group both on arrival and during the convalescence period (All p < 0.05). Nutrition guidance significantly improved GNRI in a group of patients who were undernourished (94.7 vs. 91.0, p < 0.01). Malnourished patients on admission who received nutritional guidance showed similar all-cause mortality with well-nourished patients, whereas malnourished patients without receiving nutritional guidance demonstrated significantly worse compared to the others (p = 0.03). The assessment of GNRI during the convalescence period is a useful risk predictor for patients with AMI. Nutritional guidance may improve the prognoses of patients with poor nutritional status.

Diurnal Variations in Serum Uric Acid, Xanthine, and Xanthine Oxidoreductase Activity in Male Patients with Coronary Artery Disease.

Hyperuricemia is influenced by diet and can cause gout. Whether it is a potential risk factor for cardiovascular disease (CVD) remains controversial, and the mechanism is unclear. Similar to CVDs, gout attacks occur more frequently in the morning and at night. A possible reason for this is the diurnal variation in uric acid (UA), However, scientific data regarding this variation in patients with CVD are not available. Thus, we aimed to investigate diurnal variations in serum levels of UA and plasma levels of xanthine, hypoxanthine, and xanthine oxidoreductase (XOR) activity, which were measured at 18:00, 6:00, and 12:00 in male patients with coronary artery disease. Thirty eligible patients participated in the study. UA and xanthine levels significantly increased from 18:00 to 6:00 but significantly decreased from 6:00 to 12:00. By contrast, XOR activity significantly increased both from 18:00 to 6:00 and 6:00 to 12:00. Furthermore, the rates of increase in UA and xanthine levels from night to morning were significantly and positively correlated. In conclusion, UA and xanthine showed similar diurnal variations, whereas XOR activity showed different diurnal variations. The morning UA surge could be due to UA production. The mechanism involved XOR activity, but other factors were also considered.

Usefulness of HANBAH Score in Japanese Patients With Acute Heart Failure.

The HANBAH score is a novel simple risk score consisting of hemoglobin level, age, sodium (N) level, blood urea nitrogen level, atrial fibrillation, and high-density lipoprotein. We aimed to validate this score in an external population. This retrospective study included 744 patients hospitalized for acute heart failure between 2015 and 2019. Each of the following criteria was scored as 1 point: hemoglobin level (<13.0 g/L for men and <12.0 g/L for women), atrial fibrillation, age (>70 years), serum blood urea nitrogen level (>26 mg/100 ml for men and >28 mg/100 ml for women), serum high-density lipoprotein level (<25 mg/100 ml), and serum sodium level (<135 mg/100 ml). HANBAH scores were available for 736 patients (age, 75 ± 13 years; 60% male; reduced [<40%] and preserved ejection fraction [≥50%]: 35% and 49%, respectively). All-cause death during follow-up, a composite of death and heart failure rehospitalization, and in-hospital death were observed in 173, 274, and 51 patients, respectively. The HANBAH score was significantly associated with these end points after adjustment for covariates (adjusted hazard ratio 1.38 [95% confidence interval 1.16 to 1.64], p <0.001; 1.27 [1.11 to 1.45], p <0.001; and 1.66 [1.18 to 2.33], p <0.001, respectively). Receiver operating characteristic and net reclassification improvement analyses showed that the HANBAH score performed significantly better than AHEAD (atrial fibrillation, hemoglobin [anemia], elderly, abnormal renal parameters, diabetes mellitus) and AHEAD-U (AHEAD with uric acid) scores and similar to the multi-domain ACUTE HF score for all end points. In conclusion, the HANBAH score showed powerful risk stratification in this external Japanese cohort. Despite its simplicity, it performed better than other simple risk scores and similar to a multidomain risk score.

Prognostic value of estimating appendicular muscle mass in heart failure using creatinine/cystatin C.

BACKGROUND AND AIMS: Heart failure with concomitant sarcopenia has a poor prognosis; therefore, simple methods for evaluating the appendicular skeletal muscle mass index (ASMI) are required. Recently, a model incorporating anthropometric data and the sarcopenia index (i.e., serum creatinine-to-cystatin C ratio [Cre/CysC]), was developed to estimate the ASMI. We hypothesized that this model was superior to the traditional model, which uses only anthropometric data to predict prognosis. This retrospective cohort study compared the prognostic value of low ASMI as defined by the biomarker and anthropometric models in patients with heart failure. METHODS AND RESULTS: Among 847 patients, we estimated ASMI using an anthropometric model (incorporating age, body weight, and height) in 791 patients and a biomarker model (incorporating age, body weight, hemoglobin, and Cre/CysC) in 562 patients. The primary outcome was all-cause mortality. Overall, 53.4% and 39.1% of patients were diagnosed with low ASMI (using the Asian Working Group for Sarcopenia cut-off) by the anthropometric and biomarker models, respectively. The two models showed a poor agreement in the diagnosis of low ASMI (kappa: 0.57, 95% confidence interval: 0.50-0.63). Kaplan-Meier curves showed that a low ASMI was significantly associated with all-cause death in both models. However, this association was retained after adjustment for other covariates in the biomarker model (hazard ratio: 2.32, p = 0.001) but not in the anthropometric model (hazard ratio: 0.79, p = 0.360). CONCLUSION: Among patients hospitalized with heart failure, a low ASMI estimated using the biomarker model, and not the anthropometric model, was significantly associated with all-cause mortality.

Overnight changes in uric acid, xanthine oxidoreductase and oxidative stress levels and their relationships with sleep-disordered breathing in patients with coronary artery disease.

Serum uric acid (UA) level is associated with the high cumulative incidence or prevalence of coronary artery disease (CAD), and hyperuricemia is considered as an independent risk marker for CAD. Sleep-disordered breathing (SDB) is also associated with an increased risk of CAD. Several studies have shown that SDB is associated with hyperuricemia, but the mechanisms are unclear. We measured serum levels of UA and xanthine oxidoreductase (XOR) activity and urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), all of which were assessed at 6 p.m. and the following 6 a.m. in males with CAD. In addition, nocturnal pulse oximetry was performed for the night. Overall 32 eligible patients with CAD were enrolled. Serum UA levels significantly increased overnight. (5.32 ± 0.98 mg/dl to 5.46 ± 1.02 mg/dl, p < 0.001) Moreover, XOR activity and urinary 8-OHdG levels significantly increased from 6 p.m. to 6 a.m. Furthermore, 3% Oxygen desaturation index (ODI) was correlated with the overnight changes in XOR activity (r = 0.36, P = 0.047) and urinary 8-OHdG levels (r = 0.41, P = 0.02). In addition, 3%ODI was independently correlated with the changes in XOR activity (correlation coefficient, 0.36; P = 0.047) and 8-OHdG (partial correlation coefficient, 0.63; P = 0.004) in multivariable analyses. SDB severity was associated with the overnight changes in XOR activity and urinary 8-OHdG, suggesting that SDB may be associated with oxidative stress via UA production. This trial is registered at University Hospital Medical Information Network (UMIN), number: UMIN000021624.

Clinical and prognostic implications of hyaluronic acid in hospitalized patients with heart failure.

We investigated the clinical and prognostic implications of hyaluronic acid, a liver fibrosis marker, in patients with heart failure. We measured hyaluronic acid levels on admission in 655 hospitalized patients with heart failure between January 2015 and December 2019. Patients were stratified into three groups according to hyaluronic acid level: low (< 84.3 ng/mL, n = 219), middle (84.3-188.2 ng/mL, n = 218), and high (≥ 188.2 ng/mL, n = 218). The primary endpoint was all-cause death. The high hyaluronic acid group had higher N-terminal pro-brain-type natriuretic peptide levels, larger inferior vena cava, and shorter tricuspid annular plane systolic excursion than the other two groups. During the follow-up period (median 485 days), 132 all-cause deaths were observed: 27 (12.3%) in the low, 37 (17.0%) in the middle, and 68 (31.2%) in the high hyaluronic acid (P < 0.001) groups. Cox proportional hazards analysis revealed that higher log-transformed hyaluronic acid levels were significantly associated with all-cause death (hazard ratio, 1.38; 95% confidence interval, 1.15-1.66; P < 0.001). No significant interaction was observed between hyaluronic acid level and reduced/preserved left ventricular ejection fraction on all-cause death (P = 0.409). Hyaluronic acid provided additional prognostic predictability to pre-existing prognostic factors, including the fibrosis-4 index (continuous net reclassification improvement, 0.232; 95% confidence interval, 0.022-0.441; P = 0.030). In hospitalized patients with heart failure, hyaluronic acid was associated with right ventricular dysfunction and congestion and was independently associated with prognosis regardless of left ventricular ejection fraction.

Prognostic Value of Cheyne-Stokes Respiration and Nutritional Status in Acute Decompensated Heart Failure.

Malnutrition frequently coexists with heart failure (HF), leading to series of negative consequences. Cheyne-Stokes respiration (CSR) is predominantly detected in patients with HF. However, the effect of CSR and malnutrition on the long-term prognosis of patients with acute decompensated HF (ADHF) remains unclear. We enrolled 162 patients with ADHF (median age, 62 years; 78.4% men). The presence of CSR was assessed using polysomnography and the controlling nutritional status score was assessed to evaluate the nutritional status. Patients were divided into four groups based on CSR and malnutrition. The primary outcome was all-cause mortality. In total, 44% of patients had CSR and 67% of patients had malnutrition. The all-cause mortality rate was 26 (16%) during the 35.9 months median follow-up period. CSR with malnutrition was associated with lower survival rates (log-rank p < 0.001). Age, hemoglobin, albumin, lymphocyte count, total cholesterol, triglyceride, low-density lipoprotein cholesterol, creatinine, estimated glomerular filtration rate, B-type natriuretic peptide, administration of loop diuretics, apnea-hypopnea index and central apnea-hypopnea index were significantly different among all groups (p < 0.05). CSR with malnutrition was independently associated with all-cause mortality. In conclusion, CSR with malnutrition is associated with a high risk of all-cause mortality in patients with ADHF.

External validation of the ACUTE HF score for risk stratification in acute heart failure.

BACKGROUND: The ACUTE HF score is a simple risk score that predicts the prognosis of patients with acute heart failure (HF) using clinical and echocardiographic parameters. As this score was developed for a small European population, we aimed to validate this score in an external population. METHODS AND RESULTS: This retrospective observational cohort analysis included patients hospitalized with acute HF during 2015-2019. Of 744 patients, 703 patients with available ACUTE HF scores were analyzed (75 ± 13 years; 61% male; left ventricular ejection fraction [LVEF] 49 ± 17%). Approximately one-third (34.4%) of the patients had reduced LVEF (<40%), and 51.4% exhibited preserved LVEF (≥50%). During a median follow-up of 452 days, primary and secondary outcomes were observed in 110 and 204 patients, respectively. The ACUTE HF score successfully stratified patients for primary (all-cause mortality) and secondary endpoints (a composite of all-cause mortality and heart failure rehospitalization) in Kaplan-Meier analyses (log-rank test, P < 0.001). Multivariable Cox proportional hazards models showed that the score was significantly independently associated with both primary and secondary endpoints after adjusted by covariates (P < 0.001). CONCLUSION: We validated the risk prediction ability of ACUTE HF score in an Asian population. This score may be applicable in clinical practice.

Usefulness of Dapagliflozin for Nephrotic Syndrome Secondary to Diabetic Kidney Disease.

An 81-year-old woman with a medical history of type 2 diabetes mellitus and diabetic nephropathy was admitted with a diagnosis of multiple cerebellar infarctions. Proteinuria and leg edema were observed on the day after admission and diagnosed as nephrotic syndrome. Furosemide and spironolactone were started but showed no diuretic effect, and the renal function deteriorated. These agents were then replaced with dapagliflozin, which resulted in a positive diuretic effect and subsequent improvement of hypoalbuminemia and renal dysfunction. This case report demonstrates the utility of dapagliflozin for nephrotic syndrome to achieve a positive diuretic effect and improve hypoalbuminemia without deteriorating the renal function.

Prevalence and Prognostic Relevance of Isolated Tubular Dysfunction in Patients With Acute Heart Failure.

BACKGROUND: Renal dysfunction includes glomerular dysfunction (GD) and tubular dysfunction (TD); however, there is limited information regarding the prevalence, coexistence, and prognostic relevance of TD and GD among patients with acute heart failure (AHF).Methods and Results:This study reviewed 489 patients with AHF who had undergone testing at the time of their admission to identify GD (estimated glomerular filtration rate <60 mL/min/1.73 m2) and TD (urinary ß-2-microglobulin ≥300 µg/gCr). Patients were grouped according to the presence/absence of GD and TD as having neither condition (n=116), isolated TD (n=101), isolated GD (n=83), or coexisting GD plus TD (n=189). During a median follow up of 466 days (interquartile range: 170-871 days), 107 deaths were observed. Kaplan-Meier curve analysis revealed that, relative to the absence of a GD and TD group, higher mortality rates were observed in the groups with isolated TD, isolated GD, and coexisting GD plus TD (log-rank P<0.001). Similarly, the adjusted Cox regression analyses revealed that significantly higher risks of mortality were associated with isolated TD, isolated GD, and coexisting GD plus TD. Moreover, isolated GD and isolated TD were both independently associated with increased risks of all-cause mortality. CONCLUSIONS: As a significant proportion of patients with AHF had isolated TD and an increased risk of mortality, patients with AHF should be screened for TD even if they do not have GD.

Urinary liver-type fatty acid-binding protein as a prognostic marker in patients with acute heart failure.

AIMS: Urinary liver-type fatty acid-binding protein (L-FABP) is expressed in proximal tubular epithelial cells and excreted into the urine during tubular injury. We hypothesized that high urinary L-FABP is associated with poor prognosis in patients with acute heart failure (AHF). METHODS AND RESULTS: We analysed 623 patients (74 ± 13 years old; 60.0% male patients) with AHF. Urinary L-FABP levels were measured at the time of admission and adjusted for the urinary creatinine concentration. The primary endpoint was all-cause mortality. The median value and interquartile range of urinary L-FABP levels were 6.66 and 3.37-21.1 µg/gCr, respectively. Urinary L-FABP levels were significantly correlated with both beta-2 microglobulin and cystatin C levels; the correlation with the former was higher than that with the latter. During the follow-up of 631 (interquartile range: 387-875) days, 142 deaths occurred. A high tertile of urinary L-FABP level was associated with high mortality; this association was retained after adjusting for other covariates (second tertile hazard ratio 1.40, P = 0.152 vs. first tertile; third tertile hazard ratio 1.94, P = 0.005 vs. first tertile). CONCLUSIONS: Urinary L-FABP is more closely associated with tubular dysfunction than with glomerular dysfunction. Tubular dysfunction, which was evaluated based on urinary L-FABP levels, in patients with AHF is associated with all-cause mortality and is independent of pre-existing risk factors. L-FABP should be considered for use in the prognosis of AHF.

Prognostic effect of sleep-disordered breathing on hospitalized patients following acute heart failure.

BACKGROUND: Identifying patients at risk for poor clinical outcomes following acute heart failure (AHF) is essential. However, data regarding the prognostic effect of sleep-disordered breathing (SDB) and treatment with positive airway pressure (PAP) on clinical outcomes of hospitalized patients following AHF is lacking. OBJECTIVES: This study investigated the prognostic effect of SDB, PAP treatment, and compliance with PAP treatment on patient clinical outcomes. Polysomnography was performed in hospitalized patients whose left ventricular ejection fraction was < 50%. Patients were divided into groups based on whether SDB was defined as an apnea-hypopnea index ≥ 15 and if they had received PAP treatment. Furthermore, patients with SDB and PAP were subdivided into more and less compliant groups. We assessed the incidences of deaths and rehospitalizations due to heart failure. RESULTS: Overall, 241 patients were enrolled; 73% had SDB and 29% were initiated on PAP treatment. At a median follow-up of 1.7 years, 74 clinical events (32 deaths, 42 rehospitalizations) occurred. In the multivariable analysis, compared with the non-SDB group, SDB without PAP treatment was associated with an increased risk of clinical outcomes (hazard ratio [HR] 1.79, P = 0.049), whereas SDB with PAP treatment was not (HR 0.78, P = 0.582). Among patients with PAP treatment, a more compliant group was also inversely associated with clinical events (HR 0.11, P = 0.012). CONCLUSIONS: In hospitalized patients with AHF, untreated SDB was associated with worse clinical outcomes that might be reversible by PAP treatment. However, this potential may be suppressed in less compliant patients.

Clinical and prognostic values of urinary alpha1-microglobulin as a tubular marker in acute heart failure.

BACKGROUND: Although urinary alpha-1-microglobulin has been used as a marker of tubular dysfunction, its clinical and prognostic values in patients with acute heart failure have not been validated. METHODS: We analyzed 623 patients (74 ± 13 years old, 60.0% male) with acute heart failure in whom urinary alpha-1-microglobulin (A1MG) levels were measured as tubular markers at the time of admission. The primary endpoint was all-cause mortality. RESULTS: The median levels of urinary alpha-1-microglobulin with and without correction for urinary creatinine concentration were 8.80 (interquartile range: 4.20-17.7) mg/dL and 12.9 (5.92-30.7) mg/gCr, respectively. Urinary A1MG levels were significantly correlated with all of beta-2-microglobulin (r = 0.77), N-acetyl-ß-D-glucosaminidase (r = 0.51), and estimated glomerular filtration rate (r = -0.42); however, alpha-1-microglobulin was most often predicted using beta-2-microglobulin or N-acetyl-ß-D-glucosaminidase. During the 488-day (interquartile range: 185-938 days) follow-up, 141 deaths occurred. Higher A1MG levels were associated with higher mortality even after adjustment for other covariates. Only A1MG, but not beta-2-microglobulin or N-acetyl-ß-D-glucosaminidase, yielded incremental prognostic information in addition to the preexisting prognostic factors (net-reclassification improvement: 0.254, P = 0.023; integrated discrimination improvement: 0.015, P = 0.028). CONCLUSIONS: In patients hospitalized due to acute heart failure, urinary alpha-1-microglobulin was a marker of tubular dysfunction. High alpha-1-microglobulin was associated with all-cause mortality independent of glomerular function and was a better predictor of mortality than urinary beta-2-microglobulin.

Prognostic effects of arterial carbon dioxide levels in patients hospitalized into the cardiac intensive care unit for acute heart failure.

AIMS: Although both hypercapnia and hypocapnia are common in acute heart failure (AHF) patients, routine assessment of arterial blood gas is not recommended. Additionally, no association between hypercapnia and increased mortality has been found, and the prognostic value of hypocapnia in AHF patients remains to be elucidated. In this observational study, we aimed to investigate the relationship between partial pressure of arterial carbon dioxide (PaCO2), especially low PaCO2, and long-term mortality in AHF patients. METHODS AND RESULTS: Acute heart failure patients hospitalized in the cardiac intensive care unit of our institution between 2007 and 2011 were screened. All eligible patients were divided into two groups based on the inflection point (i.e. 31.0 mmHg) of the 3-knot cubic spline curve of the hazard ratio (HR), with a PaCO2 of 40 mmHg as a reference. The association between PaCO2 levels and all-cause mortality was assessed using Cox proportional hazards regression models. Among 435 patients with a median follow-up of 1.8 years, 115 (26.4%) died. Adjusted analysis with relevant variables as confounders indicated that PaCO2 <31 mmHg was significantly associated with increased all-cause mortality [HR 1.71, 95% confidence interval (CI) 1.05-2.79; P = 0.032]. When PaCO2 was considered as a continuous variable, the lower was the log-transformed PaCO2, the greater was the increased risk of mortality (HR 0.71, 95% CI 0.52-0.96; P = 0.024). CONCLUSIONS: In AHF patients, lower PaCO2 at admission was associated with increased long-term mortality risk.

Utility of cyclic variation of heart rate score as a screening tool for sleep-disordered breathing in patients with heart failure.

STUDY OBJECTIVES: Patients with sleep-disordered breathing have cyclic variation of heart rate (CVHR) in response to respiratory events. However, limited data are available regarding the utility of CVHR as a screening tool for sleep-disordered breathing in patients with mixed heart failure (HF) and those without HF. METHODS: We enrolled consecutive patients with and without HF who underwent full polysomnographies with simultaneous Holter electrocardiogram monitoring. We determined the temporal position of the individual dips comprising the CVHR score using time-domain methods. RESULTS: The data of 101 patients, including 70 with and 31 without HF, were analyzed. The CVHR score was significantly correlated with the apnea-hypopnea index (r = .667, P < .001) and limits of agreement between the apnea-hypopnea index and CVHR score were -21.8 to 35.2. The receiver operating characteristic analysis demonstrated that the CVHR score (best cut-off of 23.5 events/h) identified severe sleep-disordered breathing with a sensitivity of 83.3%, specificity of 79.5%, and the area under the curve of 0.856. In addition, there was no interaction between the presence or absence of HF and the apnea-hypopnea index-CVHR score relationship (P = .323). CONCLUSIONS: The CVHR score, determined by Holter electrocardiogram monitoring, is a useful tool for evaluating sleep-disordered breathing even in patients with mixed HF and patients without HF. CITATION: Yatsu S, Kasai T, Naito R, et al. Utility of cyclic variation of heart rate score as a screening tool for sleep-disordered breathing in patients with heart failure. J Clin Sleep Med. 2021;17(11):2187-2196.

Changes in self-reported physical activity and health-related quality of life following 3-month astaxanthin supplementation in patients with heart failure: results from a pilot study.

BACKGROUND: Astaxanthin has a strong antioxidant effect. We recently demonstrated that following 3-month astaxanthin supplementation, cardiac contractility and exercise tolerance improved, possibly through the suppression of oxidative stress in a small pilot study involving patients with heart failure with left ventricular systolic dysfunction. This is a sub-study of our pilot study to investigate whether improvements of selfreported physical activity and health-related quality of life were observed following 3-month astaxanthin supplementation. METHODS: We investigated the changes in physical activity by the Specific Activity Scale score and healthrelated quality of life by physical and mental component summary scores in Short Form-8 at baseline and after 3-month astaxanthin supplementation. RESULTS: Data from 17 patients with heart failure were assessed. Following 3-month astaxanthin supplementation, the Specific Activity Scale score increased from the median of 4.5 (interquartile range, 2.0) to 6.5 (interquartile range, 1.1) metabolic equivalent (P=0.001), and the physical and mental component summary scores increased from 46.1±9.2 to 50.8±6.8 (P=0.015) and from 48.9±9.1 to 53.8±4.8 (P=0.022), respectively. There was a linear relationship of the baseline heart rate, or mental component summary score with the percent change in the Specific Activity Scale score (r=0.523, P=0.031 and r=-0.505, P=0.039, respectively). In addition, there was a direct relationship of ischemic etiology with the percent change in the physical component summary score (r=0.483, P=0.049, respectively). Finally, there was a linear relationship between the percent change in the Specific Activity Scale score and that in the mental component summary score (r=0.595, P=0.012). CONCLUSIONS: Following 3-month astaxanthin supplementation, improvements of the self-reported physical activity level and health-related quality of life in both mental and physical components were observed. In patients with heart failure, those with higher baseline heart rate, ischemic etiology, and poorer baseline health-related quality of life have potentials to have greater improvement of physical activity and/or health-related quality of life.