Ionizing radiation promotes, whereas calorie restriction suppresses, NASH and hepatocellular carcinoma in mice.

The pathological conditions of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH) are the major risk factors for hepatocellular carcinoma (HCC). Exposure to DNA-damaging agents such as ionizing radiation is another risk factor for HCC; calorie restriction (CR), however, effectively delays the onset of radiation-induced HCC. We investigated whether NASH is relevant to radiation-induced HCC and the cancer-preventing effect of CR. Eight-day-old male B6C3F1 mice were irradiated with 3.8 Gy of X-rays and then fed a standard diet or 30% CR diet from 49 days of age until necropsy, which was performed from 56 to 600 days with ~100-day intervals to assess both pathological changes and gene expression levels. We found that early-life exposure to radiation accelerated lipid accumulation and NASH-like histopathological changes in the liver, accompanied by accelerated development of HCC. CR ameliorated the changes in lipid metabolism in the liver and reversed the NASH-like pathology, which effectively delayed HCC development. Gene-expression profiling revealed the radiation-related activation and CR-related suppression of the peroxisome proliferator-activated receptor gamma/Cd36 pathway of transmembrane fatty-acid translocation before development of the NASH-like state. Thus, early-life exposure to radiation affects lipid metabolism and induces a steatoinflammatory microenvironment that favors HCC development. Therefore, targeting this pathway by CR (or measures that mimic CR) may be a promising strategy for preventing HCC caused by either radiation or other DNA-damaging agents.

Myocardial T-Lymphocytes as a Prognostic Risk-Stratifying Marker of Dilated Cardiomyopathy　- Results of the Multicenter Registry to Investigate Inflammatory Cell Infiltration in Dilated Cardiomyopathy in Tissues of Endomyocardial Biopsy (INDICATE Study).

BACKGROUND: Dilated cardiomyopathy (DCM) associated with inflammation is diagnosed by endomyocardial biopsy; patients with this have a poorer prognosis than patients without inflammation. To date, standard diagnostic criteria have not been established.Methods and Results: This study analyzed clinical records and endomyocardial biopsy samples of 261 patients with DCM (201 males, median left ventricular ejection fraction; 28%) from 8 institutions in a multicenter retrospective study. Based on the European Society of Cardiology criteria and CD3 (T-lymphocytes) and CD68 (macrophages) immunohistochemistry, 48% of patients were categorized as having inflammatory DCM. For risk-stratification, we divided patients into 3 groups using Akaike Information Criterion/log-rank tests, which can determine multiple cut-off points: CD3+-Low, <13/mm2(n=178, 68%); CD3+-Moderate, 13-24/mm2(n=58, 22%); and CD3+-High, ≥24/mm2(n=25, 10%). The survival curves for cardiac death or left ventricular assist device implantation differed significantly among the 3 groups (10-year survival rates: CD3+-Low: 83.4%; CD3+-Moderate: 68.4%; CD3+-High: 21.1%; Log-rank P<0.001). Multivariate Cox analysis revealed CD3+count as a potent independent predictive factor for survival (fully adjusted hazard ratio: CD3+-High: 5.70, P<0.001; CD3+-Moderate: 2.64, P<0.01). CD3+-High was also associated with poor left ventricular functional and morphological recovery at short-term follow up. CONCLUSIONS: Myocardial CD3+T-lymphocyte infiltration has a significant prognostic impact in DCM and a 3-tiered risk-stratification model could be helpful to refine patient categorization.

Impact of an angulated aorto-septal relationship on cardio-cerebrovascular outcomes in patients undergoing hemodialysis.

Aortic and valvular calcification are well-known risk factors for cardio-cerebrovascular events in patients undergoing hemodialysis. We investigated the clinical impact of an angulated aorto-septal angle as a result of aortic elongation due to aortic calcification on cardio-cerebrovascular outcomes in patients undergoing hemodialysis. We investigated 306 patients (mean age 65.4 years, 68% male) who underwent pre-scheduled routine echocardiography between April and September 2018. The angle between the anterior wall of the aorta and the ventricular septal surface (ASA) was quantified. We determined aortic and mitral valve calcification scores based on calcified cardiac changes; the aortic and mitral valve scores ranged between 0-9 and 0-6, respectively. The primary endpoint was a composite including cardio-cerebrovascular events and cardio-cerebrovascular death. The mean duration of dialysis among the patients in this analysis was 9.6 years. The primary endpoint was observed in 54 patients during the observational period (median 1095 days). Multivariable Cox proportional hazards analyses identified left ventricular ejection fraction (per 10% increase: hazard ratio [HR] 0.67; 95% confidential interval [CI] 0.53-0.84, P = 0.001), left ventricular mass index (per 10 g/m2 increase: HR 1.14; 95% CI 1.05-1.24, P = 0.001), ASA (per 10 degree increase: HR 0.69; 95% CI 0.54-0.88; P = 0.003), and aortic valve calcification score (HR 1.15; 95% CI 1.04-1.26, P = 0.005) as independent determinants of the primary endpoint. Kaplan-Meier analysis showed a higher incidence of the primary endpoint in patients with ASA <119.4 degrees than those with ASA ≥119.4 degrees (Log-rank P < 0.001). An angulated aorto-septal angle is an independent risk factor for cardio-cerebrovascular events and cardio-cerebrovascular death in patients undergoing hemodialysis.

Fresh human amniotic membrane wrapping promotes peripheral nerve regeneration in PGA-collagen tubes.

BACKGROUND: An artificial nerve conduit can interpose the peripheral nerve defect without donor site morbidity. However, treatment outcomes are often unsatisfactory. Human amniotic membrane (HAM) wrapping has been reported to promote peripheral nerve regeneration. We evaluated the effects of a combined application of fresh HAM wrapping and a polyglycolic acid tube filled with collagen (PGA-c) in a rat sciatic nerve 8-mm defect model. METHODS: The rats were divided into three groups: (1) the PGA-c group (n = 5), in which the gap was interposed with the PGA-c; (2) the PGA-c/HAM group (n = 5), in which the gap was interposed with the PGA-c bridge, then HAM (14 × 7 mm) was wrapped around it; and (3) the Sham group (n = 5). Walking-Track recovery, electromyographic recovery, and histological recovery of the regenerated nerve were evaluated at 12 weeks postoperatively. RESULTS: Compared to the PGA-c group, the PGA-c/HAM group showed significantly better recovery in terminal latency (3.4 ± 0.31 ms vs. 6.6 ± 0.72 ms, p < 0.001), compound muscle action potential (0.19 ± 0.025 mV vs. 0.072 ± 0.027 mV, p < 0.01), myelinated axon perimeter (15 ± 1.3 µm vs. 8.7 ± 0.63 µm, p < 0.01), and g-ratio (0.69 ± 0.0089 vs. 0.78 ± 0.014, p < 0.001). CONCLUSION: This combined application highly promotes peripheral nerve regeneration and may be more useful than PGA-c alone.

Risk factors associated with overall survival in patients with multiple myeloma following carfilzomib treatment: A retrospective study from a large claims database in Japan.

BACKGROUND: Carfilzomib is a selective proteasome inhibitor approved for treating relapsed or refractory multiple myeloma (RRMM). Carfilzomib improves overall survival (OS) and progression-free survival (PFS); however, treatment with carfilzomib results in a higher incidence of cardiovascular and renal toxicity. More than 70% of patients with RRMM in clinical practice do not meet the eligibility criteria for randomized clinical trials (RCT). OS and PFS are negatively influenced by complications, concomitant medications and prior treatments. Therefore, we assessed the risk factors influencing the OS and time to next treatment (TTNT) in the real world. TTNT has emerged as a relevant alternative clinical endpoint to PFS. METHODS: A retrospective analysis of a large claims database prepared during the post-marketing stages in Japan was performed. The patients treated with carfilzomib for the first time were identified. Multivariable Cox proportional hazards regression analysis was performed to evaluate the risk factors influencing OS and TTNT following carfilzomib treatment. RESULTS: A total of 732 patients with RRMM who received carfilzomib-containing chemotherapy between April 2014 and September 2021 were identified. Multivariable Cox regression analysis for OS and TTNT showed a significantly higher hazard ratio (HR) of 1.48 (95% confidence interval [Cl]: 1.10-2.00; p = 0.010) and 1.38 (95% Cl: 1.15-1.65; p < 0.001), respectively, for patients with renal impairment compared to those without renal impairment. Multivariable Cox regression analysis for OS and TTNT showed a significantly higher HR of 1.80 (95% Cl: 1.27-2.55; p = 0.0010) and 1.38 (95% Cl: 1.14-1.66; p < 0.001), respectively, for patients with prior lenalidomide treatment compared to those without prior lenalidomide treatment. CONCLUSION: Complication of renal impairment and prior lenalidomide treatment could be risk factors influencing OS and TTNT during carfilzomib treatment.

Calorie restriction alters the mechanisms of radiation-induced mouse thymic lymphomagenesis.

Calorie restriction (CR) suppresses not only spontaneous but also chemical- and radiation-induced carcinogenesis. Our previous study revealed that the cancer-preventive effect of CR is tissue dependent and that CR does not effectively prevent the development of thymic lymphoma (TL). We investigated the association between CR and the genomic alterations of resulting TLs to clarify the underlying resistance mechanism. TLs were obtained from previous and new experiments, in which B6C3F1 mice were exposed to radiation at 1 week of age and fed with a CR or standard (non-CR) diet from 7 weeks throughout their lifetimes. All available TLs were used for analysis of genomic DNA. In contrast to the TLs of the non-CR group, those of the CR group displayed suppression of copy-neutral loss of heterozygosity (LOH) involving relevant tumor suppressor genes (Cdkn2a, Ikzf1, Trp53, Pten), an event regarded as cell division-associated. However, CR did not affect interstitial deletions of those genes, which were observed in both groups. In addition, CR affected the mechanism of Ikzf1 inactivation in TLs: the non-CR group exhibited copy-neutral LOH with duplicated inactive alleles, whereas the CR group showed expression of dominant-negative isoforms accompanying a point mutation or an intragenic deletion. These results suggest that, even though CR reduces cell division-related genomic rearrangements by suppressing cell proliferation, tumors arise via diverse carcinogenic pathways including inactivation of tumor suppressors via interstitial deletions and other mutations. These findings provide a molecular basis for improved prevention strategies that overcome the CR resistance of lymphomagenesis.

Hemodialysis-induced Myocardial Stunning with No Obstructive Coronary Artery Disease: Pathophysiological Significance of Coronary Microvascular Dysfunction.

Hemodialysis (HD)-induced myocardial stunning, characterized by transient left ventricular systolic dysfunction during HD, has been reported to be common and associated with a poor prognosis. However, the pathophysiology is not fully understood. We herein report a case of HD-induced myocardial stunning without obstructive coronary artery disease complicated by coronary microvascular dysfunction (CMD), suggesting that CMD plays a crucial role in the pathophysiology of this disease.

Non-A Blood Type Is a Risk Factor for Poor Cardio-Cerebrovascular Outcomes in Patients Undergoing Dialysis.

The clinical impact of ABO blood type on cardio-cerebrovascular outcomes in patients undergoing dialysis has not been clarified. A total of 365 hemodialysis patients participated in the current study. The primary endpoint was defined as a composite including cardio-cerebrovascular events and cardio-cerebrovascular death. The primary endpoint was observed in 73 patients during a median follow-up period of 1182 days, including 16/149 (11%) with blood type A, 22/81 (27%) with blood type B, 26/99 (26%) with blood type O, and 9/36 (25%) with blood type AB. At baseline, no difference was found in the echocardiographic parameters. Multivariable Cox regression analyses revealed that blood type (type A vs. non-A type; hazard ratio (HR): 0.46, 95% confidence interval (95% CI): 0.26-0.81, p = 0.007), age (per 10-year increase; HR: 1.47, 95% CI: 1.18-1.84), antiplatelet or anticoagulation therapy (HR: 1.91, 95% CI: 1.07-3.41), LVEF (per 10% increase; HR: 0.78, 95% CI: 0.63-0.96), and LV mass index (per 10 g/m2 increase; HR: 1.07, 95% CI: 1.01-1.13) were the independent determinants of the primary endpoint. Kaplan-Meier curves also showed a higher incidence of the primary endpoint in the non-A type than type A (Log-rank p = 0.001). Dialysis patients with blood type A developed cardio-cerebrovascular events more frequently than non-A type patients.

Efficacy of azilsartan on left ventricular diastolic dysfunction compared with candesartan: J-TASTE randomized controlled trial.

Characterized by ventricular and vascular stiffness, heart failure with preserved ejection fraction (HFpEF) has led to high morbidity and mortality. As azilsartan is an angiotensin receptor blocker with the highest myocardial and vascular affinities, azilsartan may improve the left ventricular (LV) diastolic function in patients with hypertension and either HFpEF or HF with mildly reduced ejection fraction (HFmrEF) more than candesartan. In this randomized, open-label trial, we randomly assigned 193 hypertensive patients with HF and LV ejection fraction ≥ 45% to 20 mg of azilsartan (n = 95) or 8 mg of candesartan (n = 98), once daily for 48 weeks. After the initiation of treatment, changes in the doses of the study drugs were permitted based on the patient's conditions, including blood pressure (median dose at 48 weeks: azilsartan 20.0 mg/day, candesartan 8.0 mg/day). The primary endpoint was the baseline-adjusted change in the ratio of peak early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (e') (E/e'). Adjusted least-squares mean (LSM) change in E/e' was - 0.8 (95% confidence interval [CI] - 1.49 to - 0.04) in the azilsartan group and 0.2 (95% CI - 0.49 to 0.94) in the candesartan group, providing the LSM differences of - 1.0 (95% CI - 2.01 to 0.03, P = 0.057). The median change in left atrial volume index was - 2.7 mL/m2 with azilsartan vs 1.4 mL/m2 with candesartan (P = 0.091). The frequency of adverse events related to hypotension and hyperkalemia did not differ between the groups. The current study did not provide strong evidence that azilsartan improves LV diastolic dysfunction, and further confirmatory study is required.

Effects of hemodialysis and reduced estimated glomerular filtration rate in nonhemodialysis on clinical outcomes after fractional flow reserve-guided deferral of revascularization.

ABSTRACT: The effect of renal dysfunction on clinical outcomes following fractional flow reserve (FFR)-guided deferral of revascularization remains unelucidated.We retrospectively analyzed 224 patients with atherosclerotic coronary lesions who underwent deferred revascularization based on an FFR of >0.80. The median follow-up interval was 28.1 months. Patients were divided into 2 groups: the hemodialysis (HD) and the non-HD group. The non-HD group was further classified into 2 subgroups according to their estimated glomerular filtration rate (eGFR) level: eGFR <45, equivalent to chronic kidney disease stage 3b-5 and eGFR ≥45. We evaluated major adverse cardiac events (MACE), defined as a composite of cardiac death, myocardial infarction, and any revascularization.MACE occurred in 36 patients (16.1%). The rate of HD was significantly higher in the MACE group (19% vs 6%, P < .01). In non-HD patients, the eGFR was significantly lower in the MACE group (51.2 vs 63.2 mL/min/1.73 m2, P < .01). Overall, univariate Cox regression analysis revealed a significant relationship between HD and MACE (HR 2.91, P = .01), as did the multivariate model (HR 2.90, P = .01). Of the MACE, more deaths occurred in HD patients (15.8% vs 2.9%, P = .03). Among non-HD patients, eGFR <45 (HR 2.70, P = .02), FFR (per 0.01, HR 0.87, P < .01), and low-density lipoprotein cholesterol (per 10 mg/dL, HR 1.17, P = .02) were independent predictors of MACE. Any revascularization was more common in patients with eGFR<45 than in those with eGFR ≥45 (21.4% vs 7.3%, P = .02). Kaplan-Meier estimates revealed that the HD group showed a significantly lower MACE-free survival rate than the nonHD group (log-rank P < .01). In non-HD patients, the eGFR<45 group showed a lower MACE-free survival rate than the eGFR ≥45 group (log-rank P = .01).HD and reduced eGFR in non-HD patients were associated with adverse cardiac events after FFR-guided deferral of revascularization.

Impact of glucose variability on coronary plaque vulnerability in patients with dysglycemia: A whole coronary analysis with multislice computed tomography.

BACKGROUND: Dysglycemia is associated with an increased risk of acute coronary syndrome caused by the disruption of vulnerable plaques. The relationship between glycemic variability (GV), which is a component of impaired glucose metabolism, and coronary plaque vulnerability has not been fully elucidated. This study investigated the impact of GV on whole coronary plaque vulnerability using multislice computed tomography (MSCT). METHODS: We analyzed 88 patients with dysglycemia who underwent 24 h blood glucose monitoring and MSCT. The mean amplitude of glycemic excursion (MAGE) was calculated as an index of the GV. We defined a CT-derived vulnerable plaque as a plaque with a remodeling index > 1.10 and a mean CT density < 30 HU. We calculated the percentage of low-attenuation plaque (% LAP) as the ratio of the low-attenuation component (CT density < 30HU) volume to the total vessel volume. RESULTS: Vulnerable plaques were detected in 27 patients (31%). Patients with vulnerable plaques had higher MAGE (110.0 ± 40.7 vs. 71.7 ± 21.7, p < 0.01) than patients without vulnerable plaques. A univariate logistic regression analysis showed that vulnerable plaques were associated with the MAGE [odds ratio (OR) 1.04, 95% confidence interval (CI), 1.02-1.07, p < 0.01]. In a multivariate model, the MAGE (OR 1.05, 95% CI 1.02-1.07) remained a significant predictor of vulnerable plaque presence. Patients with multivessel-vulnerable plaques had higher MAGE values than those with single-vessel involvement or no vulnerable plaques (132.3 ± 39.4 vs. 102.2 ± 39.7, vs. 71.7 ± 21.7, p < 0.01). The regression analysis showed a positive correlation between MAGE levels and the % LAP (r = 0.55, p < 0.01). In a multiple linear regression analysis, the MAGE was independently associated with the % LAP (ß = 0.42, p < 0.01). CONCLUSIONS: Increased GV is associated with the presence and extent of vulnerable plaques.

Clinical impact of the pathological quantification of myocardial fibrosis and infiltrating T lymphocytes using an endomyocardial biopsy in patients with hypertrophic cardiomyopathy.

BACKGROUND: The impact of quantitative pathological findings derived from endomyocardial biopsies (EMB) on clinical prognosis in patients with hypertrophic cardiomyopathy (HCM) remains unclear. METHODS: We retrospectively studied 55 consecutive HCM patients who underwent EMB. We quantified the collagen area fraction (CAF), the cardiomyocyte diameter, the nuclear area and circularity, and the number of myocardial infiltrating CD3+ cells using EMB samples by image analyzing software. The primary clinical endpoint was defined as a composite including cardiovascular death, admission due to heart failure and ventricular arrhythmia. RESULTS: During the median follow-up of 37.2 months, the primary endpoint was found in 12 patients. No significant difference in the risk score of 5-year sudden cardiac death was observed between the event-occurrence group and the event-free group. In the multivariable Cox proportional-hazard analysis, CAF [hazard ratio (HR) per 10% increase: 1.555, 95% CI: 1.014-2.367, p = 0.044] and the number of infiltrating CD3+ cells (HR per 10% increase: 1.231, 95% CI: 1.011-1.453, p = 0.041) were the independent predictors of the primary endpoint, while the myocardial diameter and the nuclear irregularity had no significant prognostic impact. Kaplan-Meier survival curves demonstrated that patients with both higher CAF and higher number of CD3+ cells had the worst prognosis (log-rank, P < 0.001). CONCLUSIONS: The higher CAF and the higher number of infiltrating CD3+ cells quantified using EMB samples were the independent predictors of poor clinical outcomes in patients with HCM. Cardiomyocyte diameter and nuclear irregularity did not significantly impact the clinical prognosis.

Reclassification of Heart Failure with Preserved Ejection Fraction Following Cardiac Sympathetic Nervous System Activation: A New Cutoff Value of 58.

Heart failure (HF) with preserved left ventricular ejection fraction (LVEF) is a heterogeneous syndrome. An LVEF of 50% is widely used to categorize patients with HF; however, this is controversial. Previously, we have reported that patients with an LVEF of ≥ 58% have good prognoses. Further, cardiac sympathetic nervous system (SNS) activation is a feature of HF. In this retrospective, observational study, the cardiac SNS activity of HF patients (n = 63, age: 78.4 ± 9.6 years; male 49.2%) with LVEF ≥ 58% (n = 15) and LVEF < 58% (n = 48) were compared using 123I-metaiodobenzylguanidine scintigraphy. During the follow-up period (median, 3.0 years), 18 all-cause deaths occurred. The delayed heart/mediastinum (H/M) ratio was significantly higher in the LVEF ≥ 58% group than in the LVEF < 58% group (2.1 ± 0.3 vs. 1.7 ± 0.4, p = 0.004), and all-cause mortality was significantly lower in patients in the former than those in the latter group (log-rank, p = 0.04). However, when these patients were divided into LVEF ≥ 50% (n = 22) and LVEF < 50% (n = 41) groups, no significant differences were found in the delayed H/M ratio, and the all-cause mortality did not differ between the groups (log-rank, p = 0.09). In conclusion, an LVEF of 58% is suitable for reclassifying patients with HF according to cardiac SNS activity.

Multimorbidity, polypharmacy, and mortality in older patients with pacemakers.

BACKGROUND: The prevalence of multimorbidity and polypharmacy and its association with all-cause mortality in older patients with pacemakers are largely unknown. We aimed to clarify the prevalence of multimorbidity and polypharmacy, and its association with all-cause mortality in patients ≥75 years of age with pacemakers. METHODS: We retrospectively investigated 256 patients aged ≥75 years (mean age 84.0 ± 5.3 years; 45.7% male) with newly implanted pacemakers. The study endpoint was all-cause mortality ("with events"). Multimorbidity was defined as a Charlson Comorbidity Index ≥3. Polypharmacy was defined as the use of ≥5 medications. RESULTS: During the follow-up period (median, 3.1 years), 60 all-cause deaths were reported. The Charlson Comorbidity Index (2.9 ± 1.9 vs. 1.7 ± 1.7, p < .001) and prevalence of multimorbidity (56.7% vs. 26.0%, p < .001) were significantly higher in deceased patients than in survivors. The number of drugs (6.9 ± 3.0 vs. 5.9 ± 3.3, p = .03) and the prevalence of polypharmacy (78.3% vs. 63.8%, p = .04) were significantly higher in patients with events than in those without events. The event-free survival rate was significantly higher among patients without multimorbidity than in those with multimorbidity (log-rank, p < .001), and was also significantly higher among patients without polypharmacy than in those with polypharmacy (log-rank, p < .001). Multimorbidity (hazard ratio [HR]: 3.21; 95% confidence interval [CI]: 1.85-5.58; p < .001) and polypharmacy (HR: 1.97; 95% CI: 1.03-3.77; p = .04) were independent predictors of all-cause mortality. CONCLUSIONS: Multimorbidity and its associated polypharmacy, which are common in the older population, are prevalent in patients with pacemakers and are independent predictors of poor prognosis.

Impact of left ventricular hypertrophy on clinical outcomes in patients with dialysis: a single-center study in Japan.

PURPOSE: Left ventricular hypertrophy (LVH) is a well-known risk factor for poor clinical outcomes in patients undergoing dialysis. However, little evidence supports the above notion in Japan, and the influence of subtypes of LVH on prognosis. METHODS: We investigated 367 patients undergoing dialysis who underwent routine echocardiographic examinations between April and September 2018. LVH was defined as any LV mass ≥ 115 g/m2 in men and ≥ 95 g/m2 in women obtained by echocardiography. The primary endpoint was a composite outcome including all-cause death, admission due to heart failure, and ischemic heart event or stroke. LVH was divided into subtype-groups according to eccentric hypertrophy or concentric hypertrophy, and with and without hypertension. RESULTS: LVH was observed in 171 (47%) patients. The primary endpoint was observed in 58 patients (16%) during the median follow-up period of 500 days. Multivariable Cox regression analyses identified four independent risk factors for the primary endpoint: age, pulse rate, serum albumin level, and LV mass index (per 10-g/m2 increase; hazard ratio: 1.12, 95% confidence interval: 1.06-1.18, P < 0.001). Kaplan-Meier analyses demonstrated that patients with LVH had a worse prognosis than those without LVH in terms of the primary endpoint (log-rank P < 0.001). The incidence of the primary outcome was not significantly different between patients with eccentric or concentric hypertrophy, and between LVH patients with and without hypertension. CONCLUSION: Japanese patients with LVH undergoing dialysis had a worse prognosis than those without LVH in terms of the composite clinical endpoint.

Ventricular Sigmoid Septum as a Risk Factor for Anthracycline-Induced Cancer Therapeutics-Related Cardiac Dysfunction in Patients With Malignant Lymphoma.

Background: Identifying risk factors for cancer therapeutics-related cardiac dysfunction (CTRCD) is essential for the early detection and prompt initiation of medial therapy for CTRCD. No study has investigated whether the sigmoid septum is a risk factor for anthracycline-induced CTRCD. Methods and Results: We enrolled 167 patients with malignant lymphoma who received a CHOP-like regimen from January 2008 to December 2017 and underwent both baseline and follow-up echocardiography. Patients with left ventricular ejection fraction (LVEF) ≤50% were excluded. CTRCD was defined as a ≥10% decline in LVEF and LVEF <50% after chemotherapy. The angle between the anterior wall of the aorta and the ventricular septal surface (ASA) was measured to quantify the sigmoid septum. CTRCD was observed in 36 patients (22%). Mean LVEF and global longitudinal strain (GLS) were lower, left ventricular mass index was higher, and ASA was smaller in patients with CTRCD. In a multivariable Cox proportional hazard analysis, GLS (hazard ratio [HR] per 1% decrease 1.20; 95% confidence interval [CI] 1.07-1.35) and ASA (HR per 1° increase 0.97; 95% CI 0.95-0.99) were identified as independent determinants of CTRCD. An integrated discrimination improvement evaluation confirmed the significant incremental value of ASA for developing CTRCD. Conclusions: Smaller ASA was an independent risk factor and had significant incremental value for CTRCD in patients with malignant lymphoma who received the CHOP-like regimen.

Cardiac ß-Adrenergic Receptor Downregulation, Evaluated by Cardiac PET, in Chronotropic Incompetence.

The mechanism of chronotropic incompetence (CTI), which has been associated with autonomic dysfunction, has not been elucidated in patients without heart failure (HF). Methods: Cardiac PET using 11C-CGP12177 was performed to investigate the cardiac ß-adrenergic receptor density (ß-ARD) in 13 patients with CTI without HF and 6 healthy controls. The maximum number of available specific 11C-CGP12177 binding sites per gram of tissue was calculated in regions of interest using an established graphical method. Results: Peak heart rate was significantly lower in CTI patients than in controls (116.9 ± 11.0 vs. 154.8 ± 14.4 beats/min, P < 0.001). ß-ARD of the total myocardium was significantly lower in CTI patients than in controls (4.3 ± 1.7 vs. 7.0 ± 1.7 pmol/mL, P = 0.005). Conclusion: ß-adrenergic receptor downregulation was demonstrated in patients with CTI without HF. Decreased ß-ARD is a common feature in patients with CTI, with or without HF.

Unusual interventional treatment of spontaneous coronary artery dissection without stent implantation: a case series.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a unique cause of myocardial infarction, and optimal treatment should be selected according to the ischaemic condition. Patients with ongoing ischaemia or haemodynamic instability may require revascularization. Cutting balloon (CB) angioplasty has been acknowledged as an option for revascularization. However, few observations of the coronary artery conditions after CB angioplasty in SCAD patients have been reported. Here, we demonstrate two cases in which we evaluated the angiographic morphology of targeted coronary arteries in the chronic phase after CB angioplasty. CASE SUMMARY: Patient 1 was a 46-year-old woman who presented at our hospital with chest pain. Electrocardiography suggested acute coronary syndrome and coronary angiography was performed. The coronary angiography and intravascular ultrasound (IVUS) examinations revealed SCAD in the left anterior descending artery (LAD). Revascularization with CB angioplasty was successful. Follow-up coronary angiography 15 months after the angioplasty showed no visible stenosis in the LAD. Accordingly, the patient no longer needed to antiplatelet therapy. Patient 2 was a 50-year-old woman who was transported to our hospital for ventricular tachycardia. Coronary angiography and IVUS revealed SCAD in the right coronary artery. Coronary flow was restored by CB angioplasty. Follow-up contrast-enhanced computed tomography angiography 36 months after angioplasty showed a healed appearance. Thus, she was able to discontinue antiplatelet therapy. DISCUSSION: Cutting balloon angioplasty may be a possible method to treat SCAD.

Thyroid dose estimates for the genome-wide association study of thyroid cancer in persons exposed in Belarus to 131I after the Chernobyl accident.

The Chernobyl accident on 26 April 1986 led to a sharp increase in thyroid cancer (TC) incidence in the individuals exposed to radiation in childhood. The major risk factor for TC was exposure to Iodine-131 (131I). Here, we estimated the thyroid doses due to 131I intake for 2041 participants of the genome-wide association study of TC in Belarusian people exposed to radioactive fallout from the Chernobyl accident. The following parameter-values specially developed in this study were used to estimate individual thyroid doses: (i) scaling factors for adjustment of the model-based doses, (ii) age and gender diet to characterize 131I intake, and (iii) area-, age- and gender-specific S-values for the thyroid gland per 131I decay in the thyroid. The most reliable doses were calculated for 103 people with measured 131I thyroid activity (the arithmetic mean of 1.2 Gy, median 0.52 Gy), and 275 individuals with detailed residential history and dietary data (the arithmetic mean of 0.41 Gy, median 0.24 Gy). The arithmetic mean of thyroid doses among all study participants was 0.23 Gy (median 0.082 Gy); the highest individual dose was 9.0 Gy. Special attention was paid to the reliability and validity of the obtained estimates, in particular for the individuals without 131I thyroid activity measurements and individual data on residential history and diet, by comparing those with the doses from other post-Chernobyl epidemiological studies. Overall, the doses estimated in the current study were in reasonable agreement with previously reported thyroid doses. These doses will be used in the genome-wide association study of TC in people exposed in Belarus to 131I after the Chernobyl accident.

Transmission Rate of Remote Monitoring and Mortality in Patients With Pacemaker.

Background: Remote monitoring of cardiac implantable electronic devices improves clinical outcomes, but data on the association between the transmission rate (TR) of the remote monitoring, calculated in percentage as the ratio between days of transmission and days of follow-up after remote monitoring introduction, and death in patients with a pacemaker are limited. Methods and Results: In this single-center retrospective observational study, we investigated 180 patients with a newly implanted pacemaker capable of using a specific remote monitoring system with daily transmission (79.5±8.8 years, men 50.6%). The study endpoint was all-cause death. During the follow-up period (median 2.7 years), 33 all-cause deaths were reported, and the TR was significantly lower in the deceased patients than in the survivors (89.6±9.6% vs. 95.4±7.0%, P<0.001). The area under the receiver-operating characteristic curve for TR to predict all-cause death was 0.72 (95% confidence interval [CI] 0.62-0.81, P<0.001). A TR of 95% had sensitivity of 74.1% and specificity of 63.6% for predicting all-cause death. In the multivariate Cox regression analysis, TR <95% was selected as a predictor of all-cause death (hazard ratio 3.43, 95% CI 1.61-7.27, P=0.001). Conclusions: Low TR is a predictor of all-cause death in patients with a pacemaker. Patients with TR ≥95% may experience a lower incidence of death, and should have a good prognosis.