Impact of Aromatase Inhibitors Treatment Duration on Coronary Artery Calcification in Postoperative Patients With Breast Cancer.

BACKGROUND: Aromatase inhibitors (AIs) are the standard therapeutic approach for hormone receptor-positive postmenopausal breast cancer. However, there are concerns about increased cardiovascular risk due to their antioestrogenic effects. This study aimed to investigate the potential association between duration of AI treatment and the severity of coronary artery calcification (CAC). METHODS: The study included outpatients who initiated adjuvant endocrine therapy with AIs for breast cancer from August 2010 to October 2022. CAC was quantified according to a visual ordinal scoring system. Patient characteristics were assessed based on the presence of CAC. Independent risk factors for elevated CAC scores were identified through a multivariable logistic regression model. RESULTS: Among 357 patients, 44.8% exhibited CAC. No significant difference in AI treatment duration was observed between groups (1268 d [interquartile range (IQR) 725-1743 d] vs 1104 d [IQR 685-1683.25 d]; P = 0.236). Patients with CAC were characterised by higher age (63.06 y [56.81-68.78 y] vs 74.39 y [68.98-80.03 y]; P < 0.001), lower hemoglobin levels (g/dL: 13.20L [IQR 12.60-13.70L] vs 12.60 [IQR 11.60-13.43]; P < 0.001), and reduced estimated glomerular filtration rate (mL/min/1.73 m2: 72.00 [IQR 61.80-81.50] vs 62.80 [IQR 51.27-71.90]; P < 0.001) compared with those without CAC. The prevalences of hypertension, diabetes mellitus, and dyslipidemia were significantly higher in patients with CAC. No correlation was found between the duration of AI treatment and CAC score (R = -0.02; P = 0.78). Independent risk factors for CAC included higher age, lower hemoglobin levels, and the presence of hypertension and diabetes mellitus in postoperative patients with breast cancer. CONCLUSIONS: The duration of AI treatment does not exert a significant influence on CAC in postoperative patients with breast cancer.

Cardiohistological Findings in Refeeding Syndrome.

Severe eating disorders may develop refeeding syndrome, which sometimes resembles severe cardiac dysfunction. A woman in her thirties was admitted to our hospital because of cardiogenic shock. Transthoracic echocardiography showed reduced left ventricular systolic function. In her medical history, she had been diagnosed with refeeding syndrome. A ventricular endocardial biopsy was performed to exclude other cardiac diseases. A histological examination showed conspicuously atrophied cardiomyocytes with nuclear swelling and irregularities; the myocardial sequence was disturbed with fibrosis. Immunostaining revealed that lipid droplet markers, adipose triglyceride lipase, and perilipin 2 were poorly observed in the cardiomyocytes, while expression of both proteins was attenuated in fibroblasts within the myocardial layer. The abnormal metabolism of fatty acids was the presumed cause of cardiac dysfunction.

Prognostic value of right atrial function in patients with significant tricuspid regurgitation.

AIMS: Although right ventricular (RV) dysfunction is associated with adverse outcomes in tricuspid regurgitation (TR), the potential role of right atrial (RA) function is unknown. We aimed to investigate the relationship between RA function and clinical outcomes in patients with significant TR. METHODS: This retrospective study included 169 outpatients with moderate or severe TR due to left-sided heart diseases who underwent transthoracic echocardiography between June 2020 and April 2023 (average age, 75 ± 10 years; male, 40%). Patients with atrial fibrillation were excluded from this study due to the inaccuracy of the evaluation using 2D speckle-tracking echocardiography. RA function was compared between patients with and without events, which were defined as all-cause mortality or hospitalization due to heart failure. RA function was calculated as RA global longitudinal strain (RAGLS) with the 2D speckle-tracking echocardiography. RESULTS: During a median follow-up of 13 months, 19 patients had events (all-cause mortality: 14 cases, hospitalization due to heart failure: 5 cases). RAGLS was lower in patients with events than in those without events (13% ± 10% vs. 18% ± 9%, P = 0.02). When the patients were categorized into two groups [low RAGLS ≤ 16.2% vs. high RAGLS > 16.2%, high RA volume index (RAVI) ≥ 50 mL/m2 vs. low RAVI < 50 mL/m2], Kaplan-Meier curves showed that patients with low RAGLS had higher event rates than those with high RAGLS (log-rank test, P = 0.003). Patients with high RAVI had higher event rates than those with low RAVI (log-rank test, P < 0.001). In the multivariate Cox regression analysis, low RAGLS (≤16.2%) was significantly associated with events in a model that included RV dysfunction (RV fractional area change ≤ 35%) or high RAVI (≥50 mL/m2) (hazard ratio: 4.55, 95% confidence interval: 1.51-13.71, P < 0.01; hazard ratio: 4.57, 95% confidence interval: 1.52-13.79, P < 0.01, respectively). CONCLUSIONS: RAGLS is associated with all-cause mortality and hospitalization due to heart failure in patients with significant TR. Our results suggest that RA function is a sensitive marker for identifying the risk stratification of significant TR.

Impact of Serum Indoxyl Sulfate on One-Year Adverse Events in Chronic Kidney Disease Patients with Heart Failure.

Background/Objectives: Indoxyl sulfate, a uremic toxin, is associated with mortality and cardiovascular events in patients with chronic kidney disease (CKD). This study aimed to evaluate the prognostic implications of serum indoxyl sulfate levels in patients with heart failure and CKD. Methods and Results: This was a prospective multicenter observational study. Overall, 300 patients with chronic heart failure with a previous history of hospitalization and an estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73 m2 or less (CKD stage G3b to G5) without dialysis were analyzed. The primary outcome assessed in a time-to-event analysis from the measurement of indoxyl sulfate was a composite of all-cause death, hospitalization for heart failure, nonfatal myocardial infarction, and nonfatal stroke. Clinical events were followed-up to one year after indoxyl sulfate measurement. The median patient age was 75 years, and 57% of the patients were men. We divided the cohort into low and high indoxyl sulfate categories according to a median value of 9.63 mg/mL. The primary outcome occurred in 27 of 150 patients (18.0%) in the low indoxyl sulfate group and 27 of 150 patients (18.0%) in the high indoxyl sulfate group (hazard ratio, 1.00; 95% confidence interval, 0.58 to 1.70, p = 0.99). In the post hoc exploratory analyses, the results were consistent across age, sex, body mass index, left ventricular ejection fraction, eGFR, and N-terminal pro b-type natriuretic peptide. Conclusions: Among heart failure patients with CKD stages G3b to 5G, serum indoxyl sulfate concentrations were not significantly associated with the subsequent occurrence of cardiovascular events.

Utility of Adjunctive Impella Support to Venoarterial Extracorporeal Membrane Oxygenation for a Refractory Electrical Storm.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) stabilizes hemodynamics in an electrical storm leading to cardiogenic shock. However, adverse effects of VA-ECMO are increased left ventricular (LV) afterload and LV end-diastolic pressure due to retrograde blood return. These adverse effects could be ameliorated by LV unloading with Impella insertion. This case illustrates the possible efficacy of adjunctive Impella insertion for a refractory electrical storm that is resistant to defibrillation under mechanical support with VA-ECMO for cardiogenic shock.

Impact of extracardiac sarcoidosis on clinical outcomes in patients with cardiac sarcoidosis: Importance of continued screening for cardiac involvement.

BACKGROUND: The prognostic impact of extracardiac sarcoidosis remains unknown in cardiac sarcoidosis (CS). We aimed to evaluate the influence of extracardiac sarcoidosis on clinical outcomes and the effect of continued outpatient visits for screening of cardiac involvement. METHODS: Ninety-nine patients with CS were divided into two groups: patients with systemic CS who had prior extracardiac sarcoidosis, patients with isolated CS who had no prior extracardiac sarcoidosis. Patients with systemic CS were divided according to the continuation of outpatient visits. The endpoint was cardiac death, fatal ventricular arrhythmia, or hospitalization for heart failure. RESULTS: At the time of diagnosing CS, patients with isolated CS had a higher prevalence of high-grade atrioventricular block or fatal ventricular arrhythmia, and left ventricular contractile dysfunction than those with systemic CS. Over a median follow-up of 42 months, cardiac events occurred in 19 (37%) of 52 patients with systemic CS and in 27 (57%) of 47 patients with isolated CS. The event-free survival rate was worse in patients with isolated CS than in those with systemic CS. Cox proportional hazard analysis showed that the absence of prior extracardiac sarcoidosis was an independent predictor of adverse outcomes. Patients with systemic CS who ceased outpatient visits had a lower left ventricular ejection fraction with severe heart failure symptoms and a worse event-free survival rate than those who continued outpatient visits. CONCLUSIONS: The presence of extracardiac sarcoidosis is associated with clinical outcomes. The cessation of screening for cardiac involvement after diagnosing extracardiac sarcoidosis is associated with adverse outcomes.

Remote dielectric sensing predicts elevated left atrial pressure in patients with atrial fibrillation.

Background: There are currently no established non-invasive indices of echocardiography for elevated left atrial pressure (LAP) especially in patients with atrial fibrillation (AF). Remote dielectric sensing (ReDS) is a novel non-invasive electromagnetic energy-based technology that quantifies total lung fluid, enabling the monitoring of volume status in patients with heart failure. The utility of ReDS for estimating LAP in patients with AF remains unknown. Methods: We prospectively investigated patients with AF in whom LAP was directly measured during catheter ablation for AF, and ReDS measurements were conducted the day before ablation. Elevated LAP was defined as LAP ≥ 15 mmHg. Results: A total of 61 patients were included (median age 66 years, 38 % female). Among them, 26 patients had elevated LAP. There was a positive correlation between ReDS and LAP (r = 0.363, P = 0.004). Receiver operating characteristic curve analysis for the prediction of elevated LAP demonstrated that the best cut-off value of ReDS was 30 %, with a sensitivity of 65 %, specificity of 69 %, and an area under the curve of 0.703 (95 % confidence interval 0.568-0.837). Multivariate logistic regression analysis revealed that ReDS was an independent predictor of elevated LAP, among covariates including left ventricular ejection fraction, the ratio of early transmitral flow velocity to septal mitral annular early diastolic velocity, and left atrial volume index. Conclusions: Our results suggest ReDS could be a valuable marker of elevated LAP even in patients with AF. Further studies are needed to elucidate the effectiveness of a ReDS-guided decongestive strategy in patients with heart failure.

Prognostic Implications of Insulin Resistance in Heart Failure in Japan.

Diabetes mellitus (DM) is a major risk and prognostic factor for heart failure (HF). Insulin resistance (IR) is an important component of DM, but the relationship between IR and HF prognosis has not yet been established across a wide variety of HF populations. We retrospectively evaluated the relationship between IR and clinical outcomes of HF patients at our hospital between 2017 and 2021. IR was defined as a homeostatic model assessment of IR (HOMA-IR) index ≥ 2.5, calculated from fasting blood glucose and insulin concentrations. The primary outcome was a composite of all-cause death and hospitalisation for HF (HHF). Among 682 patients included in the analyses, 337 (49.4%) had IR. The median age was 70 [interquartile range (IQR): 59-77] years old, and 66% of the patients were men. Among the patients, 41% had a left ventricular ejection fraction below 40%, and 32% had DM. The median follow-up period was 16.5 [IQR: 4.4-37.3] months. IR was independently associated with the primary outcome (HR: 1.91, 95% CI: 1.39-2.62, p < 0.0001), death (hazard ratio [HR]: 1.86, 95% confidence interval [CI]: 1.28-2.83, p < 0.01), and HHF (HR: 1.91, 95% CI: 1.28-2.83, p < 0.01). HOMA-IR is an independent prognostic factor of HF in a wide variety of HF populations.

The binding of LARP6 and DNAAF6 in biomolecular condensates influences ciliogenesis of multiciliated cells.

Motile cilia on the cell surface produce fluid flows in the body and abnormalities in motile cilia cause primary ciliary dyskinesia. Dynein axonemal assembly factor 6 (DNAAF6), a causative gene of primary ciliary dyskinesia, was isolated as an interacting protein with La ribonucleoprotein 6 (LARP6) that regulates ciliogenesis in multiciliated cells (MCCs). In MCCs of Xenopus embryos, LARP6 and DNAAF6 were colocalized in biomolecular condensates termed dynein axonemal particles and synergized to control ciliogenesis. Moreover, tubulin alpha 1c-like mRNA encoding α-tubulin protein, that is a major component of ciliary axoneme, was identified as a target mRNA regulated by binding LARP6. While DNAAF6 was necessary for high α-tubulin protein expression near the apical side of Xenopus MCCs during ciliogenesis, its mutant, which abolishes binding with LARP6, was unable to restore the expression of α-tubulin protein near the apical side of MCCs in Xenopus DNAAF6 morphant. These results indicated that the binding of LARP6 and DNAAF6 in dynein axonemal particles regulates highly expressed α-tubulin protein near the apical side of Xenopus MCCs during ciliogenesis.

Prognostic value of metabolic dysfunction-associated steatotic liver disease over coronary computed tomography angiography findings: comparison with no-alcoholic fatty liver disease.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the proposed name change for non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the association of cardiovascular disease risk with MASLD and NAFLD in patients who underwent clinically indicated coronary computed tomography angiography (CCTA). METHODS: This retrospective study included 2289 patients (60% men; mean age: 68 years) with no history of coronary artery disease who underwent CCTA. The steatotic liver was defined as a hepatic-to-spleen attenuation ratio of < 1.0 on CT just before CCTA. MASLD is defined as the presence of hepatic steatosis along with at least one of the five cardiometabolic risk factors. Adverse CCTA findings were defined as obstructive and/or high-risk plaques. Major adverse cardiac events (MACE) encompassed composite coronary events, including cardiovascular death, acute coronary syndrome, and late coronary revascularization. RESULTS: MASLD and NAFLD were identified in 415 (18%) and 368 (16%) patients, respectively. Adverse CCTA findings were observed in 40% and 38% of the patients with MASLD and with NAFLD, respectively. Adverse CCTA findings were significantly associated with MASLD (p = 0.007) but not NAFLD (p = 0.253). During a median follow-up of 4.4 years, 102 (4.4%) MACE were observed. MASLD was significantly associated with MACE (hazard ratio 1.82, 95% CI 1.18-2.83, p = 0.007), while its association with NAFLD was not significant (p = 0.070). By incorporating MASLD into a prediction model of MACE, including the risk score and adverse CCTA findings, global chi-squared values significantly increased from 87.0 to 94.1 (p = 0.008). CONCLUSIONS: Patients with MASLD are likely to have a higher risk of cardiovascular disease than those with NAFLD. Concurrent assessment of MASLD during CCTA improves the identification of patients at a higher risk of cardiovascular disease among those with clinically indicated CCTA.

Diagnostic improvements of calcium-removal image reconstruction algorithm using photon-counting detector CT for calcified coronary lesions.

OBJECTIVE: To investigate the diagnostic performance of a calcium-removal image reconstruction algorithm with photon-counting detector-computed tomography (PCD-CT), a technology that hides only the calcified plaque from the spectral data in coronary calcified lesions. METHODS: This retrospective study included 17 patients who underwent PCD-coronary CT angiography (CCTA) with at least one significant coronary stenosis (≥50 %) with calcified plaque by CCTA and invasive coronary angiography (ICA) performed within 60 days of CCTA. A total of 162 segments with calcified plaque were evaluated for subjective image quality using a 4-point scale. Their calcium-removal images were reconstructed from conventional images, and both images were compared with ICA images as the reference standard. The contrast-to noise ratios for both images were calculated. RESULTS: Conventional and calcium-removal images had a subjective image quality of 2.7 ± 0.5 and 3.2 ± 0.9, respectively (p < 0.001). The percentage of segments with a non-diagnostic image quality was 32.7 % for conventional images and 28.3 % for calcium-removal images (p < 0.001). The segment-based diagnostic accuracy revealed an area under the receiver operating characteristic curve of 0.87 for calcium-removal images and 0.79 for conventional images (p = 0.006). Regarding accuracy, the specificity and positive predictive value of calcium-removal images were significantly improved compared with those of conventional images (80.5 % vs. 69.5 %, p = 0.002 and 64.1 % vs. 52.0 %, p < 0.001, respectively). The objective image quality of the mean contrast-to-noise ratio did not differ between the images (13.9 ± 3.6 vs 13.3 ± 3.4, p = 0.356) CONCLUSIONS: Calcium-removal images with PCD-CT can potentially be used to evaluate diagnostic performance for calcified coronary artery lesions.

Association between Non-Lipid Residual Risk Factors and Cardiovascular Events in Patients with Stable Coronary Artery Disease Treated with Pitavastatin: An Observation from the REAL-CAD Study.

AIMS: We aimed to investigate the association between non-lipid residual risk factors and cardiovascular events in patients with stable coronary artery disease (CAD) who achieved low-density lipoprotein cholesterol (LDL-C) ＜100 mg/dL from the Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study. METHODS: The REAL-CAD study was a prospective, multicenter, open-label trial. As a sub-study, we examined the prognostic impact of non-lipid residual risk factors, including blood pressure, glucose level, and renal function, in patients who achieved LDL-C ＜100 mg/dL at 6 months after pitavastatin therapy. Each risk factor was classified according to severity. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, and unstable angina requiring emergency hospitalization. RESULTS: Among 8,743 patients, the mean age was 68±8.2 years, and the mean LDL-C level was 84.4±18 mg/dL. After adjusting for the effects of confounders, an estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2 showed the highest risk of the primary outcome (hazard ratio [HR] 1.92; 95% confidence interval [CI] 1.45-2.53). The combination of eGFR ≤ 60 and hemoglobin A1c (HbA1c) ≥ 6.0% also showed the highest risk of all-cause death (HR, 2.42; 95% CI, 1.72-3.41). CONCLUSIONS: In patients with stable CAD treated with pitavastatin and who achieved guidelines-directed levels of LDL-C, eGFR and HbA1c were independently associated with adverse events, suggesting that renal function and glycemic control could be residual non-lipid therapeutic targets after statin therapy.