Elevated arginine vasopressin levels surrogate acute lung injury in acute decompensated heart failure.

Activated arginine vasopressin (AVP) pathway worsens congestion in heart failure (HF), but its potential to relieve pulmonary congestion is also reported. The pathophysiological role and prognostic utility of AVP elevation in acute decompensated HF (ADHF) are poorly understood. We prospectively enrolled 52 hospitalized patients for ADHF to investigate the association between acute lung injury (ALI) in ADHF and AVP levels on admission. ALI was defined as respiratory failure leading to death, or requiring a respirator or a more than 12-h non-invasive intermittent positive pressure ventilation (NIPPV) support. In addition, we investigated the prognostic value of AVP levels on admission for cardiovascular death or recurrence of ADHF after discharge. ALI was documented in 7 patients (13.5%) during a median hospital stay of 14 days. And the patients with ALI demonstrated significantly higher AVP levels than those without (32.5 ± 21.6 vs. 6.4 ± 8.7 pg/ml, p = 0.018). Besides, the patients with ALI demonstrated significantly higher heart rates (HR) and lower E/e' on admission (HR: 127 ± 24 vs. 97 ± 28 bpm; E/e': 10.6 ± 3.7 vs. 17.4 ± 6.2, all p < 0.05, respectively). Of note, significant hemodilution assessed by hemoglobin and hematocrit values were observed in the patients with ALI 48 h after admission. A receiver operating characteristic curve analysis showed that higher than 7.2 pg/ml surrogate ALI in ADHF (AUC: 0.897, p = 0.001, Sensitivity: 85.7%, and Specificity: 77.8%). In contrast, increased AVP levels on admission could not predict cardiovascular events after discharge. Elevated AVP levels on admission are associated with ALI in ADHF but not cardiovascular events after discharge.

A Case of Myocardial Infarction with Non-obstructive Coronary Arteries Complicated by a Ventricular Septal Rupture: The Challenge of Achieving Hemodynamic Stability Using Impella Devices.

The prognosis of myocardial infarction with non-obstructive coronary arteries (MINOCA) is reported to be as worse as myocardial infarction with obstructive coronary arteries. However, its mechanical complications are still poorly understood. A 71-year-old woman developed MINOCA after ascending aortic replacement surgery. During treatment, the patient experienced cardiogenic shock due to a ventricular septal rupture (VSR). The introduction of Impella devices reduced the left-to-right shunt and improved the patient's hemodynamics. Finally, a scheduled surgical repair was performed under stable conditions. In this report, we focused on the pathophysiology of MINOCA-related VSR and discussed the effectiveness of Impella devices as a bridge to surgical repair and circulatory backup during the perioperative period.

Evaluation of renal circulation in heart failure using superb microvascular imaging, a microvascular flow imaging system.

PURPOSE: Renal circulation evaluation is essential in understanding the cardiorenal relationship in heart failure (HF), and there is a growing interest in imaging techniques that visualize renal circulation. This study aimed to assess the effectiveness of superb microvascular imaging (SMI) in evaluating renal circulation in HF patients. METHOD: The study included 71 HF patients undergoing cardiac catheterization. Prior to catheterization, renal ultrasound examinations were performed. A control group of 18 subjects without HF was also included. SMI was used to measure the vascular index (VI), which was calculated as the percentage of blood flow signal area in the region of interest. The intrarenal perfusion index (IRPI) was determined as a fluctuation index of VI, reflecting variations in the number of blood cells moving through renal tissue during the cardiac cycle. RESULTS: Using the upper 95% confidence interval of IRPI (0.6) from the control group, HF patients were classified into two groups. Patients with IRPI > 0.6 showed a more congestive profile. Right atrial pressure and biphasic or monophasic Doppler intrarenal flow pattern were independent determinants of IRPI > 0.6. In addition, IRPI remained a significant predictor of estimated glomerular filtration rate (eGFR). CONCLUSION: The parameter IRPI as variations in SMI signal during the cardiac cycle may be a useful evaluation method for renal perfusion impairment in HF.

Association Between Aortic Stiffness and Exercise Tolerance in Patients at the Risk Stage of Heart Failure.

BACKGROUND: The number of patients with heart failure (HF) has increased, and it is crucial to prevent the development of HF in patients at risk of HF. The present study aimed to risk stratify patients in Stage A and B HF based on associations between exercise-induced changes in aortic stiffness and exercise tolerance.Methods and Results: Patients in Stage A and B HF who performed a cardiopulmonary exercise test were enrolled in the study (n=106; median age 65.0 years [interquartile range 52.8-73.0 years]). Exercise tolerance was examined by the percentage of predicted peak oxygen consumption (%V̇O2peak). The ascending aortic pressure waveform was estimated non-invasively. Aortic stiffness was assessed using the augmentation index (AIx) and reflection magnitude (RM). Multivariable regression analysis showed that AIx measured both before and after exercise was significantly associated with %V̇O2peak (ß=-0.221 [P=0.049] and ß=-0.342 [P=0.003], respectively). When participants were divided into %V̇O2peak subgroups using a cut-off value of 60%, RM decreased immediately after exercise and remained lower 5 min after exercise in the group with preserved exercise tolerance, but recovered to baseline levels 5 min after exercise in the group with reduced exercise tolerance. CONCLUSIONS: Exercise-induced increases in aortic stiffness were associated with exercise tolerance in patients at risk of HF, suggesting that exercise-induced changes in aortic stiffness may be useful to stratify high-risk patients.

Malondialdehyde-Modified Low-Density Lipoprotein as a Predictor of Major Adverse Limb Events after Endovascular Therapy in Patients with Lower Extremity Arterial Disease.

AIM: Adverse limb events after endovascular therapy (EVT) are a major concern. This study aimed to investigate the relationship between serum malondialdehyde-modified low-density lipoprotein (MDA-LDL) level, a potentially potent indicator of atherosclerosis, and clinical outcomes after EVT in patients with lower extremity arterial disease (LEAD). METHODS: A total of 208 LEAD patients who underwent EVT and MDA-LDL measurements were retrospectively analyzed. Those with chronic limb-threatening ischemia (CLTI) were included in the CLTI subgroup (n=106). Patients were further categorized into the High or Low MDA-LDL groups according to the cut-off value calculated by receiver operating characteristic analysis. Major adverse limb events (MALE), a composite of cardiovascular death, limb-related death, major amputation, and target-limb revascularization, were evaluated. RESULTS: MALE occurred in 73 (35%) patients. The median follow-up interval was 17.4 months. The MDA-LDL cut-off values were 100.5 U/L (area under the curve [AUC] 0.651) in the overall population and 98.0 U/L (AUC 0.724) in the CLTI subgroup. Overall, the High MDA-LDL group showed significantly higher total cholesterol (189.7±37.5 mg/dL vs. 159.3±32.0 mg/dL, p＜0.01), low-density lipoprotein cholesterol (114.3±29.7 mg/dL vs. 87.3±25.3 mg/dL, p＜0.01), and triglyceride (166.9±91.1 mg/dL vs. 115.8±52.3 mg/dL, p＜0.01) than the Low MDA-LDL group. Multivariate Cox regression analyses revealed that MDA-LDL and C-reactive protein were independent predictors of MALE. In the CLTI subgroup, MDA-LDL was an independent predictor of MALE. The High MDA-LDL group showed worse MALE-free survival rates than the Low MDA-LDL group in overall (p＜0.01) and in the CLTI subgroup (p=0.01). CONCLUSIONS: Serum MDA-LDL level was associated with MALE after EVT.

Left Ventricular Hypertrophic Change Indicating Poor Prognosis in Patients With Normal-Flow, Low-Gradient Severe Aortic Stenosis With Preserved Left Ventricular Ejection Fraction.

Background: Risk stratification of normal-flow, low-gradient (NFLG) severe aortic stenosis (SAS) with preserved left ventricular (LV) ejection fraction (EF) remains unclear. Methods and Results: Of 289 consecutive patients diagnosed with SAS by aortic valve area <1.0 cm2, 66 with NFLG-SAS (stroke volume index >35 mL/m2, mean pressure gradient <40 mmHg, LVEF ≥50%) were enrolled in this study; patients with bicuspid aortic valve, acute coronary syndrome, hemodialysis, or a history of aortic valve replacement (AVR) were excluded. Adverse events (AEs) were defined as cardiovascular death, hospitalization for heart failure, and deteriorating condition requiring AVR. Factors associated with AEs were investigated using a Cox proportional hazards model. Over a median of 675 days of follow-up, 25 AEs were recorded: 4 cardiovascular deaths, 12 hospitalizations for heart failure, and 9 patients requiring AVR. In addition, there were 14 events of progression to high-gradient SAS. Multivariable analysis showed significant associations between AEs and the presence of symptoms (hazard ratio [HR] 10.276; 95% confidence interval [CI] 3.724-28.357; P<0.001), LV hypertrophy (LV mass index >115 and >95 mg/m2 for males and females, respectively; HR 3.257; 95% CI 1.172-9.050; P=0.024), and tricuspid regurgitation (TR) velocity (HR 2.761; 95% CI 1.246-6.118; P=0.012). Conclusions: The presence of symptoms, LV hypertrophy, and high TR velocity could be reliable prognostic indicators and may require watchful waiting for timely AVR in patients with NFLG-SAS.

Future bradyarrhythmia in patients with hypertrophic cardiomyopathy.

BACKGROUND: A few studies to evaluate an incidence of bradyarrhythmia in patients with hypertrophic cardiomyopathy (HCM) have been reported. METHODS: We enrolled 161 patients with HCM to evaluate their bradyarrhythmia risk, especially the risk of patients who were at risk for sudden cardiac death (SCD) and eligible for implantation of an implantable cardiac defibrillator (ICD). We defined symptomatic bradyarrhythmia requiring a pacing therapy as a bradyarrhythmia event and collected the data on an occurrence of the event after the time of diagnosis of HCM. The incidence of bradyarrhythmia events was compared between patients with ICD indications (ICD-candidate group) and those without (non-ICD-candidate group). Furthermore, we investigated the associated factors with bradyarrhythmia events using a Cox proportional-hazards model. RESULTS: During 5.5 ± 4.4 years follow-up, bradyarrhythmia events occurred in 8% (13 patients) of whole patients, and in 15% of the ICD-candidate group (n = 74). In contrast, only 2 events (2%) occurred in the non-ICD-candidate group. The incidence of bradyarrhythmia in the ICD-candidate group was significantly higher than that in the non-ICD-candidate group (log-rank p = 0.015). In the ICD-candidate group, a Cox proportional-hazards model demonstrated that lower heart rate at the time of diagnosis (HR: 1.072, 95%CI: 1.012 to 1.135, p = 0.018), and an eligibility of ICD implantation for secondary prevention of SCD (HR: 9.092, 95%CI: 2.644 to 31.258, p < 0.001) were significantly associated with future bradyarrhythmia. CONCLUSIONS: HCM patients with eligibility for ICD implantation, especially for secondary prevention of SCD, more frequently suffered from bradyarrhythmia events.

Left Ventricular End-Systolic Volume Is a Reliable Predictor of New-Onset Heart Failure with Preserved Left Ventricular Ejection Fraction.

BACKGROUND: Left ventricular (LV) ejection fraction (EF) and LV volumes were reported to have prognostic efficacy in cardiac diseases. In particular, the end-systolic volume index (LVESVI) has been featured as the most reliable prognostic indicator. However, such efficacy in patients with LVEF ≥ 50% has not been elucidated. METHODS: We screened the patients who received cardiac catheterization to evaluate coronary artery disease concomitantly with both left ventriculography and LV pressure recording using a catheter-tipped micromanometer and finally enrolled 355 patients with LVEF ≥ 50% and no history of heart failure (HF) after exclusion of the patients with severe coronary artery stenosis requiring early revascularization. Cardiovascular death or hospitalization for HF was defined as adverse events. The prognostic value of LVESVI was investigated using a Cox proportional hazards model. RESULTS: A univariable analysis demonstrated that age, log BNP level, tau, peak - dP/dt, LVEF, LV end-diastolic volume index (LVEDVI), and LVESVI were associated with adverse events. A correlation analysis revealed that LVESVI was significantly associated with log BNP level (r = 0.356, p < 0.001), +dP/dt (r = -0.324, p < 0.001), -dP/dt (r = 0.391, p < 0.001), and tau (r = 0.337, p < 0.001). Multivariable analysis with a stepwise procedure using the variables with statistical significance in the univariable analysis revealed that aging, an increase in BNP level, and enlargement of LVESVI were significant prognostic indicators (age: HR: 1.071, 95% CI: 1.009-1.137, p=0.024; log BNP : HR : 1.533, 95% CI: 1.090-2.156, p=0.014; LVESVI : HR : 1.051, 95% CI: 1.011-1.093, p=0.013, respectively). According to the receiver-operating characteristic curve analysis for adverse events, log BNP level of 3.23 pg/ml (BNP level: 25.3 pg/ml) and an LVESVI of 24.1 ml/m2 were optimal cutoff values (BNP : AUC : 0.753, p < 0.001, LVESVI : AUC : 0.729, p < 0.001, respectively). CONCLUSION: In patients with LVEF ≥ 50%, an increased LVESVI is related to the adverse events. LV contractile performance even in the range of preserved LVEF should be considered as a role of a prognostic indicator.

[Gastric Conduit Ulcer Pentration into the Right Middle Lobe after Esophageal Cancer Surgery;Report of a Case].

A 55-year-old man with esophageal cancer underwent esophagectomy along with lymph node dissection and reconstruction with gastric conduit through the sternal route. He developed a continuous cough with sputum production, 3 years postoperatively. Chest radiography revealed a right middle lung field infiltrate. Chest computed tomography revealed communication between the reconstructed esophagus and the gastric conduit( pull-up) and right middle lobe airways. Upper gastrointestinal examination revealed ulcerative lesions involving the gastric mucosa;however, biopsy of the ulcer showed no malignancy. Conservative therapy including fasting and proton-pump inhibitor administration did not improve symptoms caused by gastropleural fistula. Thoracotomy was performed through the anterolateral intercostal space under the right-up supine position, and the partial lung resection and direct closure of the stomach with muscle flap wrapping was performed.

Left ventricular contractile performance and heart failure in patients with left ventricular ejection fraction more than 40.

Heart failure (HF) with mid-range left ventricular ejection fraction (LVEF) (HFmrEF) is considered a new category of HF and LVEF < 50%, which is the upper threshold of LVEF for HFmrEF, is thought to represent a mild decrease in LV contractile performance. We aimed to consider an LVEF threshold value to be taken as a surrogate for impairment of LV contractile performance, resulting in new-onset HF. We enrolled 398 patients with LVEF ≥ 40% that underwent cardiac catheterization. Using the LV pressure recording with a catheter-tipped micromanometer, we calculated the inertia force of late systolic aortic flow (IFLSAF), which was sensitive to the slight impairment in LV contractile performance. We evaluated the utility of the IFLSAF for predicting future cardiovascular death or hospitalization for HF. We performed a receiver operating characteristic (ROC) curve analysis to determine the best LVEF threshold value for distinguishing whether the LV maintained the IFLSAF. A multivariate Cox proportional-hazards model revealed that the loss of IFLSAF was significantly associated with the future adverse events (HR: 7.798, 95%CI 2.174-27.969, p = 0.002). According to the ROC curve analysis, an LVEF ≥ 58% indicated that the LV could maintain the IFLSAF. We concluded that the loss of IFLSAF, which could reflect even slight impairment in LV contractile performance, was a reliable indicator for new-onset HF in patients with LVEF ≥ 40%. LVEF ≥ 58% could be taken as a surrogate for the IFLSAF maintenance; this threshold could be useful for risk stratification of new-onset HF in patients with preserved LVEF.

The impact of intraday glucose variability on coronary artery spasm in patients with dysglycemia.

Impaired glucose metabolism is associated with an increased risk of cardiovascular complications, and coronary artery spasm is thought to underlie the development of coronary artery disease. Intraday glucose variability (GV) accelerates oxidative stress and inflammatory cytokine release, but its impact on coronary artery spasm remains unclear. This study investigated the relationship between intraday GV and coronary artery spasm. The study included 50 patients with dysglycemia and suspected coronary spastic angina. GV was analyzed by 24-h monitoring of the blood glucose concentration using a flash glucose monitoring system. The mean amplitude of glycemic excursion (MAGE) was calculated as an index of GV. Coronary artery spasm was assessed using the intracoronary acetylcholine provocation test. Coronary spasm was defined as acetylcholine-induced total or subtotal coronary occlusion. Changes in vessel diameter in response to acetylcholine were evaluated with quantitative coronary angiography. Coronary artery spasms were observed in 21 patients (42%). MAGE was significantly higher in patients with spasms compared to those without spasms (127.5 ± 33.5 vs. 91.4 ± 37.6, p < 0.01). Regression analysis showed a positive correlation between MAGE levels and coronary diameter changes induced by acetylcholine (r = 0.47, p < 0.01). In multiple regression analysis, MAGE was independently associated with acetylcholine-induced coronary diameter change (ß = 0.47, p < 0.01). Intraday GV was associated with coronary artery spasm in patients with dysglycemia.

Delayed right ventricular perforation complicated by intracardiac thrombosis after implantable cardioverter-defibrillator implantation.

Cardiac perforation and intracardiac thrombosis are infrequent complications after implantable cardioverter-defibrillator (ICD) implantation, and a case of lead perforation complicated by thrombosis is extremely rare. We report the case of a 66-year-old man with delayed ICD lead perforation concomitant with intracardiac lead thrombosis successfully treated by anticoagulant therapy followed by transvenous lead management.

Mitotic phosphorylation of MPP8 by cyclin-dependent kinases regulates chromatin dissociation.

Repressive epigenetic modifications, DNA methylation at CpG sites and histone H3 lysine 9 (H3K9) methylation, are enriched in heterochromatin, which undergoes drastic changes in structure during mitosis. MPP8 (M phase phosphoprotein 8) has been proposed to regulate positive association between these two repressive modifications, but actual involvement of this protein in changes in the heterochromatin structure during mitosis remains elusive. We demonstrate here that MPP8 predominantly localized to, but dissociated from, chromatin during interphase and early mitosis, respectively. Chromatin dissociation from MPP8 appeared to correlate with the phosphorylation status of MPP8. Experiments using inhibitors of various mitotic kinases demonstrated that the chromatin dissociation of MPP8 during metaphase to anaphase was specifically regulated by cyclin B1-Cdk1. Indeed, cyclin B1-Cdk1 effectively phosphorylated MPP8 in vitro and on STA mutant of MPP8 (all possible sites phosphorylated by Cdk were substituted by alanine) failed to dissociate from chromatin during early mitosis. Taken together, our results indicate that the chromatin association of MPP8 is regulated by Cdk-dependent phosphorylation.