Systolic blood pressure and cardiac mortality related to serum total bilirubin levels at admission in patients with acute heart failure.

The impact of elevated total bilirubin (Tbil) levels on adverse clinical outcomes in patients with acute heart failure (HF) has not been fully established, although liver damage is common among these patients. We therefore examined the associations between Tbil levels at admission and systolic blood pressure (SBP) in patients with acute HF in an emergency setting and to evaluate clinical outcomes related to elevated Tbil, particularly in patients with SBP < 100 mmHg. Clinical data and outcomes in acute HF patients (n = 877) were compared according to Tbil quartiles. SBP values < 100 mmHg were more prevalent among patients in the highest quartile (Tbil ≥ 1.0 mg/dL) vs. others (15.4% vs. 3.1%, p < 0.001). Tbil levels were inversely and significantly correlated with SBP at admission (Spearman's ρ, - 0.243; p < 0.001). Kaplan-Meier estimate survival curves showed that event-free survival was worse among patients in the highest Tbil quartile vs. others (78.5% vs. 90.4%, p < 0.001). When comparing survival rates among patients in SBP < 100 mmHg (n = 50), the difference of survival rate became larger for the patients in the highest quartile (n = 29) vs. others (n = 21) (41.4% vs. 77.7%, p < 0.001). Multivariate Cox proportional hazard analysis showed that Tbil ≥ 1.3 mg/dL, not SBP or B-type natriuretic peptide, independently and significantly predicted cardiac death within 180 days in acute HF patients with SBP < 100 mmHg (hazard ratio 3.74; 95% confidence interval 1.39-10.05; p < 0.001). In conclusion, Tbil levels were inversely correlated with SBP at admission in patients with acute HF. Tbil levels independently predicted the risk of 180-day cardiac mortality, especially in acute HF patients with SBP < 100 mmHg.

Gastrointestinal bleeding increases the risk of subsequent cardiovascular events in patients with acute cardiovascular diseases requiring intensive care.

Gastrointestinal (GI) bleeding worsens the outcomes of critically ill patients in the intensive care unit (ICU). Owing to a lack of corresponding data, we aimed to investigate whether GI bleeding during cardiovascular-ICU (C-ICU) admission in acute cardiovascular (CV) disease patients is a risk factor for subsequent CV events. Totally, 492 consecutive C-ICU patients (40.9% acute coronary syndrome, 22.8% heart failure) were grouped into GI bleeding (n = 27; 12 upper GI and 15 lower GI) and non-GI bleeding (n = 465) groups. Thirty-nine patients died or developed CV events during hospitalization, and 453 were followed up from the date of C-ICU discharge to evaluate subsequent major adverse CV events. The GI bleeding group had a higher Acute Physiology and Chronic Health Evaluation II score (20.2 ± 8.2 vs. 15.1 ± 6.8, p < 0.001), higher frequency of mechanical ventilator use (29.6% vs. 13.1%, p = 0.039), and longer C-ICU admission duration (8 [5-16] days vs. 5 [3-8] days, p < 0.001) than the non-GI bleeding group. The in-hospital mortality rate did not differ between the groups. Of those who were followed-up, CV events after C-ICU discharge were identified in 34.6% and 14.3% of patients in the GI and non-GI bleeding groups, respectively, during a median follow-up period of 228 days (log rank, p < 0.001). GI bleeding was an independent risk factor for subsequent CV events (adjusted hazard ratio: 2.23, 95% confidence interval: 1.06-4.71; p = 0.035). GI bleeding during C-ICU admission was independently associated with subsequent CV events in such settings.

Are atherosclerotic risk factors associated with a poor prognosis in patients with hyperuricemic acute heart failure? The evaluation of the causal dependence of acute heart failure and hyperuricemia.

Atherosclerosis induces the elevation of uric acid (UA), and an elevated UA level is well known to lead to a poor prognosis in patients with acute heart failure (AHF). However, the prognostic value of atherosclerotic risk factors in hyperuricemic AHF patients remains to be elucidated. The data from 928 patients who were admitted to the intensive care unit (ICU) at Nippon Medical School Chiba Hokusoh Hospital between January 2001 and December 2014, and whose serum UA levels were measured were screened. A total of 394 AHF patients with hyperuricemia were enrolled in this study. The patients were assigned to a low-risk group (≤1 atherosclerosis risk factor) and a high-risk group (≥2 atherosclerosis risk factors) according to their number of risk factors. The patients in the low-risk group were more likely to have dilated cardiomyopathy, clinical scenario 3 than those in the high-risk group. The serum total bilirubin, blood urea nitrogen, C-reactive protein, and brain-type natriuretic peptide levels were significantly higher in the low-risk group than the high-risk group (p < 0.001, p = 0.005, p = 0.003, and p = 0.008, respectively). A multivariate Cox regression model revealed that the number of risk factors (number = 1, HR (hazard ratio) 0.243, 95 % CI 0.096-0.618, p = 0.003; number = 2, HR 0.253, 95 % CI 0.108-0.593, p = 0.002; number ≥3, HR 0.209, 95 % CI 0.093-0.472, p < 0.001), eGFR (per 1.0 mmol/l increase) (HR 0.977, 95 % CI 0.961-0.994, p = 0.007), and serum UA level (per 1 mg/dl increase) (HR 1.270, 95 % CI 1.123-1.435, p < 0.001) was an independent predictor of 1-year mortality. The prognosis, including all-cause death and HF events, was significantly poorer among the low-risk patients than among the high-risk patients. Atherosclerotic risk factors were not associated with a poor prognosis in patients with hyperuricemic AHF.

Matrix Metalloproteinase-9 as a Marker for Plaque Rupture and a Predictor of Adverse Clinical Outcome in Patients with Acute Coronary Syndrome: An Optical Coherence Tomography Study.

OBJECTIVES: The present study sought to clarify the relationship between matrix metalloproteinase-9 (MMP-9) levels and plaque morphology demonstrated by optical coherence tomography (OCT), and to examine their prognostic impacts in patients with acute coronary syndrome (ACS). METHODS: MMP-9 levels were measured for patients with ACS (n = 249). Among 249 patients, 120 with evaluable OCT images were categorized into patients with ruptured plaques (n = 65) and those with nonruptured plaques (n = 55) on the basis of culprit lesion plaque morphology demonstrated by OCT. RESULTS: MMP-9 levels on admission were significantly higher in the rupture group than in the nonrupture group (p = 0.029). Although creatine kinase-MB (CK-MB) on admission was comparable between the groups, peak CK-MB was higher in the rupture group than in the nonrupture group (p < 0.001). By receiver operating characteristic curve analysis, the optimal cut-off value of MMP-9 to detect ruptured plaques was 65.5 ng/ml (p = 0.029). There was a nonstatistically significant trend toward increased cardiac death at 2 years (5.9 vs. 1.0%, p = 0.059) in patients with high MMP-9 (≥65.5 ng/ml) compared to those with low MMP-9 (<65.5 ng/ml). CONCLUSIONS: MMP-9 can differentiate ACS with ruptured plaques from nonruptured plaques, and MMP-9 may be a valuable predictor of long-term cardiac mortality in patients with ACS reflecting plaque rupture.

Prognostic impact of plasma volume status during hospital admission in patients with acute decompensated heart failure.

AIMS: Plasma volume status (PVS), a measure of plasma volume, has been evaluated as a prognostic marker for chronic heart failure. Although the prognostic value of PVS has been reported, its significance in patients with acute decompensated heart failure (ADHF) admitted to the cardiovascular intensive care unit (CICU) remains unclear. In this study, we examined the relationship between PVS and long-term mortality in patients with ADHF admitted to the CICU. METHODS: Between January 2018 and December 2020, 363 consecutive patients with ADHF were admitted to the Nippon Medical School Hospital CICU. Of the 363 patients, 206 (mean age, 74.9 ± 12.9 years; men, 64.6%) were enrolled in this study. Patients who received red blood cell transfusions, underwent dialysis, were discharged from the CICU or died in the hospital were excluded from the study. We measured the PVS of the patients at admission, transfer to the general ward (GW) and discharge using the Kaplan-Hakim formula. The patients were assigned to four groups according to the quartiles of their PVS measured at each of the three abovementioned timepoints. We examined the association between PVS and all-cause mortality during the observation period (1134 days). The primary endpoint of this study was all-cause mortality. RESULTS: The Kaplan-Meier analysis showed that the high PVS group had a significantly higher mortality rate at admission, transfer to the GW and discharge than the other groups (log-rank test: P = 0.016, P = 0.005 and P < 0.001, respectively). Univariate Cox regression analysis showed that age, body mass index, history of heart failure, use of beta-blockers, albumin level, blood urea nitrogen level, N-terminal pro-brain natriuretic peptide level and left ventricular ejection fraction were significantly different among the PVS groups and thus were not significant prognostic factors for ADHF. Furthermore, the multivariate analysis revealed that PVS at discharge [hazard ratio (HR) = 1.06 (1.00-1.12), P = 0.048] was an independent poor prognostic factor for ADHF. CONCLUSIONS: This study highlights the effect of PVS measured at different timepoints on the prognoses of ADHF patients. Regular assessment of PVS, particularly at discharge, is crucial for optimising patient management and achieving favourable outcomes in cases of ADHF.

A rare mechanism of embolic stroke complicating coronary thrombus aspiration.

Aspiration thrombectomy is often performed in patients with acute myocardial infarction with high thrombus burden. Current guidelines, however, recommend against it because of stroke risk. We report a case of embolic stroke complicating coronary thrombus aspiration in a 62-year-old man. Aspiration thrombectomy during percutaneous coronary intervention migrated thrombus to the proximal right coronary artery (RCA), and the thrombus was subsequently released into the aorta by backflow of the contrast injection causing aspiration thrombectomy-associated stroke. This is an extremely rare mechanism by which complications arise from failed aspiration thrombectomy.

Angioscopic findings 1 year after percutaneous coronary intervention for chronic total occlusion.

BACKGROUND: Chronic total occlusion (CTO) is a high-risk factor for stent thrombosis, but little is known about the difference in neointimal healing between CTO and non-CTO lesions regarding implanted stents. We investigated factors affecting neointimal healing after stent implantation for CTO and non-CTO lesions using angioscopy. METHODS: We retrospectively evaluated 106 stents in 85 consecutive patients between March 2016 and July 2020. Their average age was 68 ±â€¯11 years, and participants (73 male and 12 female) underwent follow-up angiography and angioscopy 1 year after percutaneous coronary intervention (PCI). The stents (n = 106) were divided into three groups according to the lesion status at the previous PCI: CTO (n = 17), acute coronary syndrome (ACS) (n = 35), and stable coronary artery disease without CTO or non-CTO (n = 54). RESULTS: The neointimal stent coverage grade was significantly lower in the CTO and ACS groups than in the non-CTO group (0.4 ±â€¯0.5, 0.9 ±â€¯0.8, and 1.4 ±â€¯0.8, respectively, p < 0.001). Thrombi were significantly more frequent in CTO and ACS than in non-CTO (71 %, 51 %, and 15 %, respectively, p < 0.001). The yellow grade in CTO was comparable to that in ACS but significantly higher in CTO than in non-CTO (CTO vs. ACS vs. non-CTO 1.5 ±â€¯0.7, 1.4 ±â€¯0.6, and 0.9 ±â€¯0.7, respectively, p = 0.007). CONCLUSIONS: Delayed healing occurs in stents implanted for CTO lesions. Longer dual-antithrombotic therapy may be beneficial.

Hemodynamic Collapse Caused by Cardiac Dysfunction and Abdominal Compartment Syndrome in a Patient with Mitochondrial Disease.

We herein report a case of mitochondrial disease with heart and intestinal tract involvement resulting in hemodynamic collapse. A 66-year-old woman was transferred to our hospital because of cardiogenic shock. Vasopressors were administered, and a circulatory support device was deployed. However, her hemodynamics did not improve sufficiently, and we detected abdominal compartment syndrome caused by the aggravation of chronic intestinal pseudo-obstruction as a complication. Insertion of a colorectal tube immediately decreased the intra-abdominal pressure, improving the hemodynamics. Finally, we diagnosed her with mitochondrial disease, concluding that the resulting combination of acute heart failure and abdominal compartment syndrome had aggravated the hemodynamics.

Ethnic comparison in takotsubo syndrome: novel insights from the International Takotsubo Registry.

BACKGROUND: Ethnic disparities have been reported in cardiovascular disease. However, ethnic disparities in takotsubo syndrome (TTS) remain elusive. This study assessed differences in clinical characteristics between Japanese and European TTS patients and determined the impact of ethnicity on in-hospital outcomes. METHODS: TTS patients in Japan were enrolled from 10 hospitals and TTS patients in Europe were enrolled from 32 hospitals participating in the International Takotsubo Registry. Clinical characteristics and in-hospital outcomes were compared between Japanese and European patients. RESULTS: A total of 503 Japanese and 1670 European patients were included. Japanese patients were older (72.6 ± 11.4 years vs. 68.0 ± 12.0 years; p < 0.001) and more likely to be male (18.5 vs. 8.4%; p < 0.001) than European TTS patients. Physical triggering factors were more common (45.5 vs. 32.0%; p < 0.001), and emotional triggers less common (17.5 vs. 31.5%; p < 0.001), in Japanese patients than in European patients. Japanese patients were more likely to experience cardiogenic shock during the acute phase (15.5 vs. 9.0%; p < 0.001) and had a higher in-hospital mortality (8.2 vs. 3.2%; p < 0.001). However, ethnicity itself did not appear to have an impact on in-hospital mortality. Machine learning approach revealed that the presence of physical stressors was the most important prognostic factor in both Japanese and European TTS patients. CONCLUSION: Differences in clinical characteristics and in-hospital outcomes between Japanese and European TTS patients exist. Ethnicity does not impact the outcome in TTS patients. The worse in-hospital outcome in Japanese patients, is mainly driven by the higher prevalence of physical triggers. TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01947621.

Impact of the COVID-19 Pandemic on ST-elevation Myocardial Infarction from a Single-center Experience in Tokyo.

Objective The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on global healthcare systems. Some studies have reported the negative impact of COVID-19 on ST-elevation myocardial infarction (STEMI) patients; however, the impact in Japan remains unclear. This study investigated the impact of the COVID-19 pandemic on STEMI patients admitted to an academic tertiary-care center in Tokyo, Japan. Methods In this retrospective, observational, cohort study, we included 398 consecutive patients who were admitted to our institute from January 1, 2018, to March 10, 2021, and compared the incidence of hospitalization, clinical characteristics, time course, management, and outcomes before and after March 11, 2020, the date when the World Health Organization declared COVID-19 a pandemic. Results There was a 10.7% reduction in hospitalization of STEMI patients during the COVID-19 pandemic compared with that in the previous year (117 vs. 131 cases). During the COVID-19 pandemic, the incidence of late presentation was significantly higher (26.5% vs. 12.1%, p<0.001), and the onset-to-door [241 (IQR: 70-926) vs. 128 (IQR: 66-493) minutes, p=0.028] and door-to-balloon [72 (IQR: 61-128) vs. 60 (IQR: 43-90) min, p<0.001] times were significantly longer than in the previous year. Furthermore, the in-hospital mortality was higher, but the difference was not significant (9.4% vs. 5.0%, p=0.098). Conclusion The COVID-19 pandemic significantly impacted STEMI patients in Tokyo and resulted in a slight decrease in hospitalization, a significant increase in late presentation and treatment delays, and a slight but nonsignificant increase in mortality. In the COVID-19 era, the acute management system for STEMI in Japan must be reviewed.

Clinical Characteristics, Achievement of Secondary Prevention Goals, and Outcomes of Patients with Recurrent Acute Coronary Syndrome.

BACKGROUND: Because development of acute coronary syndrome (ACS) worsens the prognosis of patients with coronary artery disease, preventing recurrent ACS is crucial. However, the degree to which secondary prevention treatment goals are achieved in patients with recurrent ACS is unknown. METHODS: 214 consecutive ACS patients were classified as having First ACS (n=182) or Recurrent ACS (n=32), and the clinical characteristics of these groups were compared. Fifteen patients died or developed cardiovascular (CV) events during hospitalization, and the remaining 199 patients were followed from the date of hospital discharge to evaluate subsequent CV events. RESULTS: Patients in the Recurrent ACS group were older than those in the First ACS group (76.8±10.8 years vs 68.8±13.4 years, p=0.002) and had a higher rate of diabetes mellitus (DM) (65.6% vs 36.8%, p=0.003). The rate of achieving a low-density lipoprotein cholesterol (LDL-C) level of <70 mg/dL in the Recurrent ACS group was only 28.1%, even though 68.8% of these patients were taking statins. An HbA1c level of <7.0% was achieved in 66.7% of patients with recurrent ACS who had been diagnosed with DM. Overall, 12.5% of patients with recurrent ACS had received optimal treatment for secondary prevention. CV events after hospital discharge were noted in 37.9% of the Recurrent ACS group and 21.2% of the First ACS group (log-rank test: p=0.004). However, recurrent ACS was not an independent risk factor for CV events (adjusted hazard ratio: 2.09, 95% confidence interval: 0.95 to 4.63, p=0.068). CONCLUSION: Optimal treatment for secondary prevention was not achieved in some patients with recurrent ACS, and achievement of the guideline-recommended LDL-C goal for secondary prevention was especially low in this population.

The prognostic impact of uric acid in patients with severely decompensated acute heart failure.

BACKGROUND: The serum level of uric acid (UA) is a well-known prognostic factor for heart failure (HF) patients. However, the prognostic impact of hyperuricemia and the factors that induce hyperuricemia in acute HF (AHF) patients are not well understood. METHODS AND RESULTS: Eight hundred eighty-nine AHF patients were enrolled in this study. The patients were assigned into a low UA group (UA≤7.0mg/dl, n=495) or a high UA group (UA>7.0mg/dl, n=394) according to their UA level on admission. A Kaplan-Meier curve showed that the survival rate of the low UA group was significantly higher than that of the high UA group. A multivariate Cox regression model identified that a high UA level (HR: 1.192, 95%CI 1.112-1.277) was an independent predictor of 180-day mortality. A multivariate logistic regression model for a high serum UA level on admission indicated that chronic kidney disease (CKD) (OR: 2.030, 95%CI: 1.298-3.176, p=0.002) and the administration of loop diuretics before admission (OR: 1.556, 95%CI: 1.010-2.397, p=0.045) were independent factors. The prognosis, including all-cause death and HF events, was significantly poorer among patients who had a high UA level who had previously used loop diuretics and among CKD patients with a high UA level than among other patients. CONCLUSIONS: The serum UA level was an independent predictor in patients who were hospitalized during an emergent situation for AHF. An elevated serum UA level on admission was associated with the presence of CKD and the use of loop diuretics. These factors were also associated with adverse outcomes in hyperuricemic patients with AHF.

Impact of Brain Natriuretic Peptide, Calcium Channel Blockers, and Body Mass Index on Recovery Time from Left Ventricular Systolic Dysfunction in Patients With Takotsubo Cardiomyopathy.

Takotsubo cardiomyopathy (TC) is generally recognized to have a good prognosis, but it can be rarely aggravated. We sought to investigate the clinical characteristics of TC and to evaluate the effects of clinical parameters on predicting delayed recovery. We enrolled consecutive patients with TC admitted to our hospital from January 1991 to January 2014. We defined delayed recovery as sustained left ventricular (LV) systolic dysfunction requiring ≥10 days for LV contraction to normalize. We screened 9,630 patients suspected of having acute coronary syndrome, and 60 patients (0.6%; men/women: 20/38; mean age: 69.7 ± 11.9 years) were diagnosed as having TC. With the exception of 2 patients who died before LV systolic function improved, all patients recovered from LV systolic dysfunction within 6 months; the mean recovery period was 9.1 ± 11.5 days. Twenty-eight patients met the criteria for delayed recovery. Univariate logistic regression analyses showed that male gender, LV end-diastolic diameter, brain natriuretic peptide (BNP) level, body mass index (BMI), and nonuse of calcium channel blockers (CCBs) at baseline were associated with delayed recovery. Among these factors, multiple logistic regression analysis identified BNP ≥238 pg/ml (relative risk [RR] 11.6, p = 0.002) and nonuse of CCBs (RR 22.2, p = 0.0014) as independent risk factors for delayed recovery and leptosomic build (BMI <20 kg/m(2)) as an independent predictor of rapid recovery (RR 0.11, p = 0.02). In conclusion, BNP level, BMI, and use of CCBs are associated with recovery speed of LV systolic function in patients with TC.

Recovery of atrioventricular block following steroid therapy in patients with cardiac sarcoidosis.

BACKGROUND: Atrioventricular (AV) block is one of the main clinical manifestations in patients with cardiac sarcoidosis (CS). Although steroid therapy is considered to be effective for AV block, the efficacy has not been demonstrated in detail. METHODS AND RESULTS: Fifteen CS patients presenting with advanced or complete AV block were retrospectively investigated. All patients were treated with 30mg/day of prednisone after device implantation, which was tapered to a maintenance dosage of 5-10mg/day. During a mean follow-up of 7.1 years, AV block resolved to normal conduction or first-degree AV block in 7 patients (recovery group). The improvement was driven within the first week of steroid therapy in 4 patients, while 3 patients showed late recovery of AV conduction. The remaining 8 patients were classified as the non-recovery group. The recovery group showed a higher left ventricular ejection fraction (69.4±8.9% versus 44.1±19.3%, p=0.029) and higher prevalence of advanced AV block (87.5% versus 28.6%, p=0.040) compared with those of the non-recovery group. In patients with the recovery group, there was no late recurrence of AV block during the follow-up period. CONCLUSIONS: Early initiation of steroid therapy may be effective for AV block, and steroid therapy before device implantation is a possible therapeutic strategy for some selected patients.