Impact of Advanced Extravascular Calcified Plaque on the Assessment of Coronary Stenosis Severity.

Coronary computed tomography angiography (CCTA) and CT-derived fractional flow reserve (FFRCT) provide high diagnostic accuracy for coronary artery disease (CAD), consistent with invasive coronary angiography (ICA), the gold standard diagnostic technique. The presence of calcified components, however, complicates the interpretation of coronary stenosis severity. We present a case where there was a discrepant assessment of coronary stenosis severity between CCTA/FFRCT (indicating significant obstructive CAD) and ICA (showing no apparent obstructive CAD). CCTA/FFRCT revealed that the stenotic lesion, located in the middle segment of the left circumflex artery, was surrounded by plaque components. The proximal and distal portions of the stenotic lesion consisted of 80.9% luminal volume, 0.2% low-attenuation plaque, 13.4% intermediate-attenuation plaque, and 5.5% calcified plaque. In contrast, the stenotic lesion itself contained 50.0% luminal volume, 0.3% low-attenuation plaque, 26.7% intermediate-attenuation plaque, and 22.9% calcified plaque. Invasive coronary angiography showed no apparent obstructive CAD, implying that the lesions appearing as significant obstructive CAD on CCTA/FFRCT were likely overestimated due to the effects of extravascular calcified plaque. Advanced extravascular calcified plaque surrounding the lesion may cause several artifacts (such as blooming and/or beam hardening artifacts) and/or vasodilator dysfunction (either organic and/or functional), potentially leading to an overestimation of the severity of coronary stenosis in CCTA/FFRCT assessments.

Supra-normal and mildly reduced ejection fraction in women -An overlooked vulnerable subpopulation in heart failure.

BACKGROUND: Recently, patients with supra-normal left ventricular ejection fraction (snEF) are reported to have high risk of adverse outcomes, especially in women. We sought to evaluate sex-related differences in the association between LVEF and long-term outcomes in heart failure (HF) patients. METHODS: The multicenter WET-HF Registry enrolled all patients hospitalized for acute decompensated HF (ADHF). We analyzed 3943 patients (age 77 years; 40.1% female) registered from 2006 to 2017. According to LVEF the patients were divided into the 3 groups: HF with reduced EF (HFrEF), mildly reduced EF (HFmrEF) and preserved EF. The primary endpoint was defined as the composite of cardiac death and ADHF rehospitalization after discharge. RESULTS: In HFmrEF, implementation of guideline-directed medical therapy (GDMT) such as the combination of renin-angiotensin-system inhibitor (RASi) and ß-blocker at discharge was significantly lower in women than men even after adjustment for covariates (p = 0.007). There were no such sex-related differences in HFrEF. Female sex was associated with higher incidence of the primary endpoint and ADHF rehospitalization after adjustment for covariates exclusively in HFmrEF. Restricted cubic spline analysis demonstrated a U-shaped relationship between LVEF and the hazard ratio of the primary endpoint showing higher event rate in HFmrEF and HFsnEF in women, but such relationship was not observed in men (p for interaction = 0.037). CONCLUSIONS: In women, mrEF and snEF were associated with worse long-term outcomes. Additionally, sex-related differences in the GDMT implementation for HFmrEF highlight the need for further exploration, which might lead to creation of sex-specific guidelines to optimize HF management.

Renin-angiotensin system inhibitors for patients with mild or moderate chronic kidney disease and heart failure with mildly reduced or preserved ejection fraction.

BACKGROUND: Renin-angiotensin system inhibitors (RASI) reduce adverse cardiovascular events in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤40% and mild or moderate chronic kidney disease (CKD). However, RASI administration rate and its association with long-term outcomes in patients with CKD complicated by HF with LVEF >40% remain unclear. METHODS: We analyzed 1923 consecutive patients with LVEF >40% registered within the multicenter database for hospitalized HF. We assessed RASI administration rate and its association with all-cause mortality among patients with mild or moderate CKD (estimated glomerular filtration rate [eGFR]: 30-60 mL/min/1.73 m2). Exploratory subgroups included patients grouped by age (<80, ≥80 years), sex, previous HF hospitalization, B-type natriuretic peptide (higher, lower than median), eGFR (30-44, 45-59 mL/min/1.73 m2), systolic blood pressure (<120, ≥120 mmHg), LVEF (41-49, ≥50%), and mineralocorticoid receptor antagonists (MRA) use. RESULTS: Among patients with LVEF >40%, 980 (51.0%) had mild or moderate CKD (age: 81 [74-86] years; male, 52.6%; hypertension, 69.7%; diabetes, 25.9%), and 370 (37.8%) did not receive RASI. RASI use was associated with hypertension, absence of atrial fibrillation, and MRA use. After multivariable adjustments, RASI use was independently associated with lower all-cause mortality over a 2-year median follow-up (hazard ratio: 0.58, 95% confidence interval: 0.43-0.79, P = 0.001), and the mortality rate difference was predominantly due to cardiac death, consistent in all subgroups. CONCLUSIONS: Approximately one-third of HF patients with mild or moderate CKD and LVEF >40% were discharged without RASI administration and demonstrated relatively guarded outcomes.

Discrepancy in Diagnosing Coronary Artery Occluded Lesion: CT-Derived Fractional Flow Reserve (FFRCT) Versus Invasive Coronary Angiography.

Coronary computed tomography angiography (CCTA) and CT-derived fractional flow reserve (FFRCT) findings demonstrate high diagnostic accuracy, aligning consistently with invasive coronary angiography (ICA), the gold standard diagnostic technique for coronary artery disease. The differential diagnosis of total versus subtotal coronary occlusion is crucial in determining the appropriate treatment strategy. Subtotal coronary occlusions composed of vulnerable tissue can sometimes present as total coronary occlusions on ICA. This presentation can be inconsistent with findings from CCTA and FFRCT. This case report presents discrepant findings between CCTA, which indicated subtotal coronary occlusion, and ICA, which suggested total coronary occlusion. The stenotic lesion, filled with vulnerable tissue (low-attenuation plaque volume: 20.3 mm3 and intermediate-attenuation plaque volume: 71.6 mm3), could be dilated with a vasodilator during maximal hyperemia. This dilation facilitated the acquisition of CCTA and FFRCT images. We were able to diagnose subtotal coronary occlusion and identify the overall anatomical structure of the vessels prior to percutaneous coronary intervention (PCI). This allowed us to perform a successful and uncomplicated PCI.

The Safety and Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors for Patients with Sarcopenia or Frailty: Double Edged Sword?

Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) show cardiovascular protective effects, regardless of the patient's history of diabetes mellitus (DM). SGLT2is suppressed cardiovascular adverse events in patients with type 2 DM, and furthermore, SGLT-2is reduced the risk of worsening heart failure (HF) events or cardiovascular death in patients with HF. Along with these research findings, SGLT-2is are recommended for patients with HF in the latest guidelines. Despite these benefits, the concern surrounding the increasing risk of body weight loss and other adverse events has not yet been resolved, especially for patients with sarcopenia or frailty. The DAPA-HF and DELIVER trials consistently showed the efficacy and safety of SGLT-2i for HF patients with frailty. However, the Rockwood frailty index that derived from a cumulative deficit model was employed for frailty assessment in these trials, which might not be suitable for the evaluation of physical frailty or sarcopenia alone. There is no fixed consensus on which evaluation tool to use or its cutoff value for the diagnosis and assessment of frailty in HF patients, or which patients can receive SGLT-2i safely. In this review, we summarize the methodology of frailty assessment and discuss the efficacy and safety of SGLT-2i for HF patients with sarcopenia or frailty.

Sex Differences in Cardiac and Clinical Phenotypes and Their Relation to Outcomes in Patients with Heart Failure.

Biological sex is one of the major factors characterizing the heart failure (HF) patient phenotype. Understanding sex-related differences in HF is crucial to implement personalized care for HF patients with various phenotypes. There are sex differences in left ventricular (LV) remodeling patterns in the HF setting, namely, more likely concentric remodeling and diastolic dysfunction in women and eccentric remodeling and systolic dysfunction in men. Recently supra-normal EF (snLVEF) has been recognized as a risk of worse outcome. This pathology might be more relevant in female patients. The possible mechanism may be through coronary microvascular dysfunction and sympathetic nerve overactivation from the findings of previous studies. Further, estrogen deficit might play a significant role in this pathophysiology. The sex difference in body composition may also be related to the difference in LV remodeling and outcome. Lower implementation in guideline-directed medical therapy (GDMT) in female HFrEF patients might also be one of the factors related to sex differences in relation to outcomes. In this review, we will discuss the sex differences in cardiac and clinical phenotypes and their relation to outcomes in HF patients and further discuss how to provide appropriate treatment strategies for female patients.

Rationale and protocol of the LAQUA-HF trial: a factorial randomised controlled trial evaluating the effects of neurohormonal and diuretic agents on health-status reported outcomes in heart failure patients.

INTRODUCTION: The current guidelines strongly recommend early initiation of multiple classes of cardioprotective drugs for patients with heart failure with reduced ejection fraction to improve prognosis and health status. However, evidence on the optimal sequencing of approved drugs is scarce, highlighting the importance of individualised treatment plans. Registry data indicate that only a portion of these patients can tolerate all four recommended classes, underscoring the need to establish the favoured sequence when using these drugs. Additionally, the choice between long-acting and short-acting loop diuretics in the present era remains uncertain. This is particularly relevant given the frequent use of angiotensin receptor-neprilysin inhibitor and sodium-glucose cotransporter 2 inhibitor, both of which potentiate natriuretic effects. METHODS AND ANALYSIS: In a prospective, randomised, open-label, blinded endpoint method, LAQUA-HF (Long-acting vs short-acting diuretics and neurohormonal Agents on patients' QUAlity-of-life in Heart Failure patients) will be a 2×2 factorial design, with a total of 240 patients randomised to sacubitril/valsartan versus dapagliflozin and torsemide versus furosemide in a 1:1 ratio. Most enrolment sites have participated in an ongoing observational registry for consecutive patients hospitalised for heart failure involved dedicated study coordinators, and used the same framework to enrol patients. The primary endpoint is the change in patients' health status over 6 months, defined by the Kansas City Cardiomyopathy Questionnaire. Additionally, clinical benefit at 6 months defined as a hierarchical composite endpoint will be assessed by the win ratio as the secondary endpoint. ETHICS AND DISSEMINATION: The medical ethics committee Keio University in Japan has approved this trial. All participants provide written informed consent prior to study entry. The results of this trial will be disseminated in one main paper and additional papers on secondary endpoints and subgroup analyses. TRIAL REGISTRATION NUMBER: UMIN000045229.

Impact of vessel morphology on CT-derived fractional-flow-reserve in non-obstructive coronary artery disease in right coronary artery.

OBJECTIVES: Computed tomography (CT)-derived fractional flow reserve (FFRCT) decreases continuously from proximal to distal segments of the vessel due to the influence of various factors even in non-obstructive coronary artery disease (NOCAD). It is known that FFRCT is dependent on vessel-length, but the relationship with other vessel morphologies remains to be explained. PURPOSE: To investigate morphological aspects of the vessels that influence FFRCT in NOCAD in the right coronary artery (RCA). METHODS: A total of 443 patients who underwent both FFRCT and invasive coronary angiography, with < 50% RCA stenosis, were evaluated. Enrolled RCA vessels were classified into two groups according to distal FFRCT: FFRCT ≤ 0.80 (n = 60) and FFRCT > 0.80 (n = 383). Vessel morphology (vessel length, lumen diameter, lumen volume, and plaque volume) and left-ventricular mass were assessed. The ratio of lumen volume and vessel length was defined as V/L ratio. RESULTS: Whereas vessel-length was almost the same between FFRCT ≤ 0.80 and > 0.80, lumen volume and V/L ratio were significantly lower in FFRCT ≤ 0.80. Distal FFRCT correlated with plaque-related parameters (low-attenuation plaque, intermediate-attenuation plaque, and calcified plaque) and vessel-related parameters (proximal and distal vessel diameter, vessel length, lumen volume, and V/L ratio). Among all vessel-related parameters, V/L ratio showed the highest correlation with distal FFRCT (r = 0.61, p < 0.0001). Multivariable analysis showed that calcified plaque volume was the strongest predictor of distal FFRCT, followed by V/L ratio (ß-coefficient = 0.48, p = 0.03). V/L ratio was the strongest predictor of a distal FFRCT ≤ 0.80 (cut-off 8.1 mm3/mm, AUC 0.88, sensitivity 90.0%, specificity 76.7%, 95% CI 0.84-0.93, p < 0.0001). CONCLUSIONS: Our study suggests that V/L ratio can be a measure to predict subclinical coronary perfusion disturbance. CLINICAL RELEVANCE STATEMENT: A novel marker of the ratio of lumen volume to vessel length (V/L ratio) is the strongest predictor of a distal CT-derived fractional flow reserve (FFRCT) and may have the potential to improve the diagnostic accuracy of FFRCT. KEY POINTS: • Physiological FFRCT decline depends not only on vessel length but also on the lumen volume in non-obstructive coronary artery disease in the right coronary artery. • FFRCT correlates with plaque-related parameters (low-attenuation plaque, intermediate-attenuation plaque, and calcified plaque) and vessel-related parameters (proximal and distal vessel diameter, vessel length, lumen volume, and V/L ratio). • Of vessel-related parameters, V/L ratio is the strongest predictor of a distal FFRCT and an optimal cut-off value of 8.1 mm3/mm.

Treatment patterns and trajectories in patients after acute heart failure hospitalization.

AIMS: The trajectories of systolic function after admission for acute heart failure (HF) and their effect on clinical outcomes have not been fully elucidated. We aimed to assess changes in left ventricular ejection fraction (LVEF) between the index and 1 year after discharge and to examine their prognostic implications. METHODS AND RESULTS: We extracted data from a prospective multicentre registry of patients hospitalized for acute HF and identified 1636 patients with LVEF data at admission and 1 year after discharge. We categorized them into five groups based on LVEF changes: HF with unchanged-preserved EF [HFunc-pEF (EF ≥ 50%); N = 527, 32.2%], unchanged-mildly reduced EF [HFunc-mrEF (EF 41-49%); N = 86, 5.3%], unchanged-reduced EF [HFunc-rEF (EF ≤ 40%); N = 377, 23.0%], worsened EF (HFworEF; N = 83, 5.1%), and improved EF (HFimpEF; N = 563, 34.4%). We then evaluated the subsequent composite outcome of cardiovascular death and HF readmission. During 1 year after discharge, 53% of patients with HF with reduced EF and 67% of those with HF with mildly reduced EF (HFmrEF) transitioned to other categories, whereas 92% of those with HF with preserved EF (HFpEF) remained within the same category. Patients with HFimpEF were more likely to be younger and had relatively preserved renal function, whereas those with HFworEF were the oldest and had more comorbidities among the five groups. After multivariable adjustment, patients with HFimpEF and HFunc-pEF had a lower risk for composite outcomes when referenced to patients with HFunc-rEF [hazard ratio (95% confidence interval), P-value: 0.28 (0.16-0.49), P < 0.001, and 0.40 (0.25-0.63), P < 0.001, respectively]. Conversely, patients with HFunc-mrEF and HFworEF had a comparable risk [0.44 (0.18-1.07), P = 0.07, and 0.63 (0.29-1.39), P = 0.26, respectively]. CONCLUSIONS: A substantial number of patients with HF experienced transitions to other categories after discharge. Notably, patients with decreased EF experienced a worse prognosis, even with slight decreases (e.g. HFpEF transitioning to HFmrEF). These findings emphasize the significance of longitudinal assessments of systolic function to better manage patients following acute decompensation.

Temporal Trends in Heart Failure Management and Outcomes: Insights From a Japanese Multicenter Registry of Tertiary Care Centers.

Background The management of heart failure (HF) has markedly changed, due to changes in demographics and the emergence of novel pharmacotherapies. However, detailed analyses on the temporal trends in characteristics and outcomes among patients with HF are scarcely available. This study aimed to assess the temporal trends over 11 years in clinical management and outcomes in patients with HF. Methods and Results We analyzed data from a multicenter registry of hospitalized patients with acute HF, including 6877 patients registered from 2011 to 2021. Age-adjusted mortality was calculated using standardized mortality ratios. During the study period, mean age increased from 75.2 years in 2011 to 2012 to 76.4 years in 2020 to 2021 (P for trend <0.001). The proportion of HF with reduced ejection fraction (HFrEF, left ventricular ejection fraction <40%) remained constant (from 43.4% to 42.7%, P for trend=0.38). The median duration of hospital stays (from 15 to 17 days, P for trend<0.001) had increased. As for the implementation of guideline-directed medical therapy, the use of mineralocorticoid receptor antagonist at discharge increased in patients with HFrEF (from 44.3% to 60.2%, P for trend<0.001). There was also an increase in the use of sodium-glucose cotransporter-2 inhibitors following their approval for use. The age-adjusted 1-year mortality decreased in patients with HFrEF (from 18.0% to 9.3%, P for trend<0.001) but not in patients with non-HFrEF (left ventricular ejection fraction ≥40%; from 9.2% to 9.5%, P for trend=0.79). Conclusions Hospitalized patients with HF have been aging over the past decade. Their long-term outcomes after discharge have improved predominantly because of decreased mortality in patients with HFrEF.

Initiation and Up-Titration of Guideline-Based Medications in Hospitalized Acute Heart Failure Patients　- A Report From the West Tokyo Heart Failure Registry.

BACKGROUND: Despite recommendations from clinical practice guidelines to initiate and titrate guideline-directed medical therapy (GDMT) during their hospitalization, patients with acute heart failure (AHF) are frequently undertreated. In this study we aimed to clarify GDMT implementation and titration rates, as well as the long-term outcomes, in hospitalized AHF patients.Methods and Results: Among 3,164 consecutive hospitalized AHF patients included in a Japanese multicenter registry, 1,400 (44.2%) with ejection fraction ≤40% were analyzed. We assessed GDMT dosage (ß-blockers, renin-angiotensin inhibitors, and mineralocorticoid-receptor antagonists) at admission and discharge, examined the contributing factors for up-titration, and evaluated associations between drug initiation/up-titration and 1-year post-discharge all-cause death and rehospitalization for HF via propensity score matching. The mean age of the patients was 71.5 years and 30.7% were female. Overall, 1,051 patients (75.0%) were deemed eligible for GDMT, based on their baseline vital signs, renal function, and electrolyte values. At discharge, only 180 patients (17.1%) received GDMT agents up-titrated to >50% of the maximum titrated dose. Up-titration was associated with a lower risk of 1-year clinical outcomes (adjusted hazard ratio: 0.58, 95% confidence interval: 0.35-0.96). Younger age and higher body mass index were significant predictors of drug up-titration. CONCLUSIONS: Significant evidence-practice gaps in the use and dose of GDMT remain. Considering the associated favorable outcomes, further efforts to improve its implementation seem crucial.

Variation of Computed Tomography-Derived Fractional Flow Reserve Related to Different Vessel Morphology.

A total of 1492 outpatients with suspected coronary artery disease and who underwent computed tomography-derived fractional flow reserve analysis were examined. To investigate the effects of vessel morphology such as lumen diameter or volume on computed tomography-derived fractional flow reserve, nearly the same or subthreshold values affecting computed tomography-derived fractional flow reserve hemodynamics vessels were compared. Case 1 and 2 present almost the same vessel length (case 1 vs. case 2; 135.0 mm vs. 133.6 mm), low-attenuation plaque volume (0 mm3 vs. 0 mm3), intermediate attenuation plaque volume (12.5 mm3 vs. 35.5 mm3), and calcified plaque volume (4.7 mm3 vs. 0 mm3) in the right coronary artery. However, lumen volume (877.8 mm3 vs. 2443.7 mm3) and distal computed tomography-derived fractional flow reserve (0.79 vs. 0.96) were markedly different between the 2 patients. Computed tomography-derived fractional flow reserve depends not only on vessel length or plaque characteristics but also on lumen volume or vessel morphology.

ß1 Adrenergic Receptor Autoantibodies and IgG Subclasses: Current Status and Unsolved Issues.

A wide range of anti-myocardial autoantibodies have been reported since the 1970s. Among them, autoantibodies against the ß1-adrenergic receptor (ß1AR-AAb) have been the most thoroughly investigated, especially in dilated cardiomyopathy (DCM). Β1AR-Aabs have agonist effects inducing desensitization of ß1AR, cardiomyocyte apoptosis, and sustained calcium influx which lead to cardiac dysfunction and arrhythmias. Β1AR-Aab has been reported to be detected in approximately 40% of patients with DCM, and the presence of the antibody has been associated with worse clinical outcomes. The removal of anti-myocardial autoantibodies including ß1AR-AAb by immunoadsorption is beneficial for the improvement of cardiac function for DCM patients. However, several studies have suggested that its efficacy depended on the removal of AAbs belonging to the IgG3 subclass, not total IgG. IgG subclasses differ in the structure of the Fc region, suggesting that the mechanism of action of ß1AR-AAb differs depending on the IgG subclasses. Our previous clinical research demonstrated that the patients with ß1AR-AAb better responded to ß-blocker therapy, but the following studies found that its response also differed among IgG subclasses. Further studies are needed to elucidate the possible pathogenic role of IgG subclasses of ß1AR-AAbs in DCM, and the broad spectrum of cardiovascular diseases including HF with preserved ejection fraction.

Association of pre-hospital precipitating factors with short- and long-term outcomes of acute heart failure patients: A report from the WET-HF2 registry.

BACKGROUND: Interest in clinical course preceding heart failure (HF) exacerbation has grown, with a greater emphasis placed on patients' clinical factors including precipitant factor (PF). Large-scale studies with precise PF documentation and temporal-outcome variation remain limited. METHODS: We reviewed prospectively collected 2412 consecutive patient-level records from a multicenter Japanese registry of hospitalized patients with HF (West Tokyo Heart Failure2 Registry: 2018-2020). Patients were categorized based on PFs: behavioral (i.e., poor adherence to physical activity, medicine, or diet regimen), treatment-required (i.e., anemia, arrhythmia, ischemia, infection, thyroid dysfunction or other conditions as suggested exacerbating factors), and no-PF. The composite outcomes of HF rehospitalization and death within 1 year after discharge and HF rehospitalization were individually assessed. RESULTS: Median patient age was 78 years (interquartile range: 68-85 years), and 1468 (61%) patients had documented PFs, of which 356 (15%) were considered behavioral. The behavioral PF group were younger, more male and had past HF hospitalization history compared to those in the other groups (all p < 0.05). Although risk of in-hospital death was lower in the behavioral PF group, their risk of composite outcome was not significantly different from the treatment-required group (hazard ratio [HR] 1.19 [95% confidence interval {CI} 0.93-1.51]) and the no-PF group (HR 1.28 [95%CI 1.00-1.64]). Furthermore, the risk of HF rehospitalization was higher in the behavioral PF group than in the other two groups (HR 1.40 [95%CI 1.07-1.83] and HR 1.39 [95%CI 1.06-1.83], respectively). CONCLUSION: Despite a better in-hospital prognosis, patients with behavioral PFs were at significantly higher risk of HF rehospitalization.

Impact of Plaque Components on Fractional Flow Reserve-Derived Computed Tomography in Severe Coronary Stenosis.

Fractional flow reserve derived from computed tomography decreases across severe coronary stenosis. The diagnostic accuracy of fractional flow reserve-derived computed tomography is high for severe coronary stenosis. In this report, we present a case of no significant fractional flow reserve-derived computed tomography changes even in severe coronary stenosis. A 75-year-old man showed severe stenosis (85% diameter stenosis) in the distal segment of the right coronary artery on both computed tomography angiography and invasive coronary angiography. However, fractional flow reserve-derived from computed tomography showed no significant changes from the proximal (0.97) to the distal (0.95) segments despite the presence of severe stenotic lesion. This patient had different features including the presence of a large acute marginal branch and significantly lower plaque components in the stenotic lesion compared with another patient who had coronary stenosis in the same segment. A large bifurcation branch and/or proportion of plaque components can affect fractional flow reserve-derived from computed tomography hemodynamics.

Sick sinus syndrome concomitant with myopathy associated with anti-mitochondrial antibodies: a case report.

Background: Anti-mitochondrial antibody (AMA)-associated myopathy is known to be concomitant with primary biliary cirrhosis and to cause both skeletal muscle disorders and arrhythmias, myocardium disorders, and respiratory muscle disorders. We report a case of AMA-associated myopathy in which the bradycardia-related symptoms preceded the skeletal muscle symptoms. Case summary: A 59-year-old woman visited the emergency room in our hospital following a syncopal event. The patient was bradycardiac (45 b.p.m.) with a junctional rhythm resulting from sick sinus syndrome (SSS) and was suffering from heart failure. Blood tests revealed elevated creatine kinase (CK) and hepatic enzymes. She underwent permanent pacemaker implantation. However, it proved difficult to detect the electrical potential in the right atrium. Although successful atrial pacing was achieved at the lower right atrial septum, the atrial threshold was markedly high and she depended on ventricular pacing. One year later, neurological examination and muscle biopsy confirmed the diagnosis of AMA-associated myopathy. Following this diagnosis, steroid pulse therapy was initiated. Steroid administration relieved her symptoms and lowered the CK levels but the atrial standstill persisted. The patient takes low-dose prednisolone and has had an uneventful course for 3 years. Discussion: To the best of our knowledge, this is the first case of AMA-associated myopathy diagnosed by the first symptom related to bradycardia due to SSS. Patients with AMA-associated myopathy can experience a variety of cardiac symptoms, including arrhythmias, and initially complain of cardiac symptoms without symptoms of skeletal myopathy. This disease should be considered when diagnosing patients with arrhythmia and elevated CK.

Coronary microvascular dysfunction in heart failure patients.

Coronary microcirculation has multiple layers of autoregulatory function to maintain resting flow and augment hyperemic flow in response to myocardial demands. Functional or structural alterations in the coronary microvascular function are frequently observed in patients with heart failure with preserved or reduced ejection fraction, which may lead to myocardial ischemic injury and resultant worsening of clinical outcomes. In this review, we describe our current understanding of coronary microvascular dysfunction in the pathogenesis of heart failure with preserved and reduced ejection fraction.

Reactive Oxygen Species in the Aorta and Perivascular Adipose Tissue Precedes Endothelial Dysfunction in the Aorta of Mice with a High-Fat High-Sucrose Diet and Additional Factors.

Metabolic syndrome (Mets) is the major contributor to the onset of metabolic complications, such as hypertension, type 2 diabetes mellitus (DM), dyslipidemia, and non-alcoholic fatty liver disease, resulting in cardiovascular diseases. C57BL/6 mice on a high-fat and high-sucrose diet (HFHSD) are a well-established model of Mets but have minor endothelial dysfunction in isolated aortas without perivascular adipose tissue (PVAT). The purpose of this study was to evaluate the effects of additional factors such as DM, dyslipidemia, and steatohepatitis on endothelial dysfunction in aortas without PVAT. Here, we employed eight-week-old male C57BL/6 mice fed with a normal diet (ND), HFHSD, steatohepatitis choline-deficient HFHSD (HFHSD-SH), and HFHSD containing 1% cholesterol and 0.1% deoxycholic acid (HFHSD-Chol) for 16 weeks. At week 20, some HFHSD-fed mice were treated with streptozocin to develop diabetes (HFHSD-DM). In PVAT-free aortas, the endothelial-dependent relaxation (EDR) did not differ between ND and HFHSD (p = 0.25), but in aortas with PVAT, the EDR of HFHSD-fed mice was impaired compared with ND-fed mice (p = 0.005). HFHSD-DM, HFHSD-SH, and HFHSD-Chol impaired the EDR in aortas without PVAT (p < 0.001, p = 0.019, and p = 0.009 vs. ND, respectively). Furthermore, tempol rescued the EDR in those models. In the Mets model, the EDR is compromised by PVAT, but with the addition of DM, dyslipidemia, and SH, the vessels themselves may result in impaired EDR.

Which congestion presentation pattern on the physical findings is associated with future adverse events? A cluster analysis in the multicenter acute heart failure registry.

BACKGROUND: Clinical congestion is the most frequent reason for hospital admission in patients with acute heart failure (AHF). However, few studies have investigated the patterns and prognostic implication of the physical congestion using unbiased and robust statistical methods. METHODS: A hierarchical agglomerative clustering analysis was performed in the multicenter Japanese AHF registry (N = 3151) with the distance calculated by Jaccard's distance for jugular vein distention (JVD), leg edema, S3, crackles, and orthopnea. The primary outcome was a composite of cardiac death and heart failure readmission within 1-year. RESULTS: At the time of admission, the median number of prevalent congestive signs was 2. We identified three phenogroups: 'no physical congestions' (N = 251); 'congestion without JVD' (N = 1415); and 'congestion with JVD' (N = 1495). Patients in 'no physical congestion' were the youngest (median 75 [62, 83] years) with the lowest systolic blood pressure (122 [106, 142] mmHg). Patients in 'congestion without JVD', and 'congestion with JVD' were similar in terms of age (77 [67, 84] vs. 78 [69, 84] years) and systolic blood pressure (138 [118, 160] vs. 137 [118, 158] mmHg). While 30-day mortality was similar (4.0%, 3.7%, and 4.3% in 'no physical congestion,' 'congestion without JVD,' and 'congestion with JVD', respectively), the patients in 'congestion with JVD' were at the highest risk for the primary outcome (adjusted hazard ratio 1.79, 95% CI 1.26-2.55 when 'no physical congestion' was a reference). CONCLUSIONS: Our clustering analysis demonstrated that congestion signs, particularly JVD, allowed identification of AHF phenogroups with distinct clinical characteristics and long-term outcomes.