Clinical outcomes of catheter ablation for atrial fibrillation, atrial flutter, and atrial tachycardia in wild-type transthyretin amyloid cardiomyopathy: a proposed treatment strategy for catheter ablation in each arrhythmia.

AIMS: Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is often accompanied by atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT), which are difficult to control because beta-blockers and antiarrhythmic drugs can worsen heart failure (HF). This study aimed to investigate the outcomes of catheter ablation (CA) for AF/AFL/AT in patients with ATTRwt-CM and propose a treatment strategy for CA. METHODS AND RESULTS: A cohort study was conducted on 233 patients diagnosed with ATTRwt-CM, including 54 who underwent CA for AF/AFL/AT. The background of each arrhythmia and the details of the CA and its outcomes were investigated. The recurrence-free rate of AF/AFL/AT overall in ATTRwt-CM patients with multiple CA was 70.1% at 1-year, 57.6% at 2-year, and 44.0% at 5-year follow-up, but CA significantly reduced all-cause mortality [hazard ratio (HR): 0.342, 95% confidence interval (CI): 0.133-0.876, P = 0.025], cardiovascular mortality (HR: 0.378, 95% CI: 0.146-0.981, P = 0.045), and HF hospitalization (HR: 0.488, 95% CI: 0.269-0.889, P = 0.019) compared with those without CA. There was no recurrence of the cavotricuspid isthmus (CTI)-dependent AFL, non-CTI-dependent simple AFL terminated by one linear ablation, and focal AT originating from the atrioventricular (AV) annulus or crista terminalis eventually. Twelve of 13 patients with paroxysmal AF and 27 of 29 patients with persistent AF did not have recurrence as AF. However, all three patients with non-CTI-dependent complex AFL not terminated by a single linear ablation and 10 of 13 cases with focal AT or multiple focal ATs originating beyond the AV annulus or crista terminalis recurred even after multiple CA. CONCLUSION: The outcomes of CA for ATTRwt-CM were acceptable, except for multiple focal AT and complex AFL. Catheter ablation may be aggressively considered as a treatment strategy with the expectation of improving mortality and hospitalization for HF.

Prevalence and clinical characteristics of diabetic cardiomyopathy in patients with acute heart failure.

BACKGROUND AND AIMS: Diabetic cardiomyopathy refers to cases of diabetes mellitus (DM) complicated by cardiac dysfunction in the absence of cardiovascular disease and hypertension. Its epidemiology remains unclear due to the high rate of coexistence between DM and hypertension. Therefore, this study aimed to examine the prevalence and clinical characteristics of diabetic cardiomyopathy among patients with acute heart failure (HF). METHODS AND RESULTS: This multicenter, retrospective study included 17,614 consecutive patients with acute HF. DM-related HF was defined as HF complicating DM without known manifestations of coronary artery disease, significant valvular heart disease, or congenital heart disease, while diabetic cardiomyopathy was defined as DM-related HF without hypertension. Univariable and multivariable logistic regression analyses were performed to identify factors associated with in-hospital mortality. Diabetic cardiomyopathy prevalence was 1.6 % in the entire cohort, 5.2 % in patients with acute HF complicating DM, and 10 % in patients with DM-related HF. Clinical characteristics, including the presence of comorbidities, laboratory data on admission, and factors associated with in-hospital mortality, significantly differed between the diabetic cardiomyopathy group and the DM-related HF with hypertension group. The in-hospital mortality rate was significantly higher in patients with diabetic cardiomyopathy than in patients with DM-related HF with hypertension (7.7 % vs. 2.8 %, respectively; P < 0.001). CONCLUSION: The prevalence of diabetic cardiomyopathy was 1.6 % in patients with acute HF, and patients with diabetic cardiomyopathy were at high risk for in-hospital mortality. The clinical characteristics of patients with diabetic cardiomyopathy were significantly different than those of patients with DM-related HF with hypertension.

Clinical, electrocardiographic, and echocardiographic parameters associated with the development of pacing and implantable cardioverter-defibrillator indication in patients with transthyretin amyloid cardiomyopathy.

AIMS: This study aimed to identify factors for attention leading to future pacing device implantation (PDI) and reveal the necessity of prophylactic PDI or implantable cardioverter-defibrillator (ICD) implantation in transthyretin amyloid cardiomyopathy (ATTR-CM) patients. METHODS AND RESULTS: This retrospective single-center observational study included consecutive 114 wild-type ATTR-CM (ATTRwt-CM) and 50 hereditary ATTR-CM (ATTRv-CM) patients, neither implanted with a pacing device nor fulfilling indications for PDI at diagnosis. As a study outcome, patient backgrounds were compared with and without future PDI, and the incidence of PDI in each conduction disturbance was examined. Furthermore, appropriate ICD therapies were investigated in all 19 patients with ICD implantation. PR-interval ≥220 msec, interventricular septum (IVS) thickness ≥16.9 mm, and bifascicular block were significantly associated with future PDI in ATTRwt-CM patients, and brain natriuretic peptide ≥35.7 pg/mL, IVS thickness ≥11.3 mm, and bifascicular block in ATTRv-CM patients. The incidence of subsequent PDI in patients with bifascicular block at diagnosis was significantly higher than that of normal atrioventricular (AV) conduction in both ATTRwt-CM [hazard ratio (HR): 13.70, P = 0.019] and ATTRv-CM (HR: 12.94, P = 0.002), whereas that of patients with first-degree AV block was neither (ATTRwt-CM: HR: 2.14, P = 0.511, ATTRv-CM: HR: 1.57, P = 0.701). Regarding ICD, only 2 of 16 ATTRwt-CM and 1 of 3 ATTRv-CM patients received appropriate anti-tachycardia pacing or shock therapy, under the number of intervals to detect for ventricular tachycardia of 16-32. CONCLUSIONS: According to our retrospective single-center observational study, prophylactic PDI did not require first-degree AV block in both ATTRwt-CM and ATTRv-CM patients, and prophylactic ICD implantation was also controversial in both ATTR-CM. Larger prospective, multi-center studies are necessary to confirm these results.

Prevalence of Cardiac Amyloidosis in Patients Undergoing Carpal Tunnel Release With Amyloid Deposition.

BACKGROUND: Carpal tunnel syndrome (CTS) is considered an early sign of cardiac amyloidosis (CA) because amyloid deposition is often confirmed in the tenosynovium removed during carpal tunnel release (CTR); however, the prevalence of concomitant CA is unclear.Methods and Results: We prospectively examined 700 patients who underwent CTR and evaluated amyloid deposition after tenosynovium removal. Amyloid deposition was observed in 261 (37%) patients, who were significantly older and predominantly male (P<0.05). Of them, 120 agreed to cardiac screening. We performed 99 mTc-labeled pyrophosphate (99 mTc-PYP) scintigraphy in 12 patients who met either of the following criteria: (1) interventricular septal diameter (IVSd) ≥14 mm or (2) 12 mm ≤ IVSd < 14 mm with above-normal limits in high-sensitivity cardiac troponin T (hs-cTnT). Six patients (50%) had positive findings on 99 mTc-PYP scintigraphy and were diagnosed with wild-type transthyretin CA. Concomitant CA was observed in 6/120 (5%) CTR patients with amyloid deposition and 50% (6/12) in patients with left ventricular hypertrophy (≥12 mm) with increased hs-cTnT levels. CONCLUSIONS: Amyloid deposition was frequently observed in the removed tenosynovium of elderly men with CTS. Cardiac screening may be useful for early diagnosis of CA in patients undergoing CTR with amyloid deposition.

Validation of the obesity paradox by body mass index and waist circumference in patients undergoing percutaneous coronary intervention.

BACKGROUND: The paradoxical association of obesity with mortality, named the "obesity paradox", has been inconsistent, possibly due to a difference between body mass index (BMI) and central obesity, estimated by waist circumference (WC) as patterns of adiposity. SUBJECTS/METHODS: We enrolled 8513 participants from the Kumamoto Intervention Conference Study, a multicenter registry that included consecutive patients undergoing percutaneous coronary intervention (PCI) at 18 centers between 2008 and 2017 in Japan. Patients were divided into quartiles in ascending order of the BMI or WC. The primary endpoints were all-cause mortality and cardiovascular death within a year. RESULTS: There were 186 deaths (case fatality rate, 22.1/1000 person-years) during the follow-up period. The lowest group (1st quartile) of BMI or WC had the worst prognosis among the quartiles (1st quartile, 4.2%; 2nd quartile, 1.9%; 3rd quartile, 1.5%; 4th quartile, 1.1%; P < 0.001 (χ2) and 1st quartile, 4.1%; 2nd quartile, 2.3%; 3rd quartile, 1.2%; 4th quartile, 1.5%; P < 0.001 (χ2), respectively). Similar results were obtained for cardiovascular death. In a multivariable analysis adjusted by nine conventional factors, the lowest group (1st quartile) of BMI (hazards ratio, 2.748; 95% confidence interval [CI], 1.712-4.411) and WC (hazards ratio, 2.340; 95% CI, 1.525-3.589) were independent prognostic factors for all-cause mortality. By dividing the participants into two groups according to either the BMI or WC based on the National Cholesterol Education Program Adult Treatment Panel III and World Health Organization classification, the highest mortality was observed in the lower group. However, the C-statistic after adding BMI (quartile) to conventional factors was found to be slightly higher than BMI (two categories) and WC (two categories) (0.735 vs. 0.734). CONCLUSIONS: The obesity paradox was observed in patients after PCI, and single-use of BMI (or WC) was sufficient to predict the prognosis of patients after PCI.

Increased thrombogenicity is associated with revascularization outcomes in patients with chronic limb-threatening ischemia.

OBJECTIVES: Clinically driven target lesion revascularization (CD-TLR) frequently occurs after endovascular therapy (EVT) in patients with chronic limb-threatening ischemia (CLTI). The total thrombus-formation analysis system (T-TAS) can quantitatively evaluate thrombogenicity. Therefore, we aimed to elucidate the association of the T-TAS parameters with CD-TLR. METHODS: We analyzed 34 patients with CLTI and 62 patients without CLTI who had undergone EVT. Blood samples collected on the day of EVT were used in the T-TAS to compute the thrombus formation area under the curve for the first 10 minutes for the platelet chip tested at a flow rate of 24 µL/min (PL24-AUC10) and area under the curve for the first 30 minutes for the atheroma chip tested at a flow rate of 10 µL/min (AR10-AUC30). After EVT, clinical follow-up was performed, and the presence of CD-TLR was assessed. RESULTS: During the follow-up period (median, 574 days), 10 patients (29%) in the CLTI group and 11 (18%) in the non-CLTI group had required CD-TLR. In the CLTI group, the patients with CD-TLR had had a higher AR10-AUC30 vs those without (median, 1694 [interquartile range, 1657-1799] vs median, 1561 [interquartile range, 1412-1697]; P = .01). In contrast, the PL24-AUC10 showed no significant differences when stratified by CD-TLR in either group. For the CLTI patients, multivariable Cox regression analysis using propensity score matching revealed that the AR10-AUC30 was an independent predictor of CD-TLR even after adjusting for baseline demographics, lesion characteristics, and anticoagulant use (hazard ratio, 2.04; 95% confidence interval, 1.18-3.88; P = .01; per 100-unit increase). In contrast, for those without CLTI, neither the AR10-AUC30 nor the PL24-AUC10 was significantly associated with CD-TLR. Receiver operating characteristics curve analysis identified an AR10-AUC30 level of 1646 as an optimal cutoff value to predict for CD-TLR (AUC, 0.85; sensitivity, 0.93; specificity, 0.56). CONCLUSIONS: For patients with CLTI, but not for those without CLTI, the AR10-AUC30 showed potential to predict for CD-TLR. This finding suggests that hypercoagulability might play a predominant role in the progression of CLTI and that anticoagulant therapy might be useful in preventing revascularization.

Extracardiac Biopsy Sensitivity in Transthyretin Amyloidosis Cardiomyopathy Patients With Positive 99 mTc-Labeled Pyrophosphate Scintigraphy Findings.

BACKGROUND: The accurate sensitivity of amyloid deposition in extracardiac tissue (subcutaneous tissue and gastrointestinal tract) has not been evaluated in transthyretin amyloidosis cardiomyopathy (ATTR-CM) patients. This study aimed to evaluate the sensitivity of amyloid deposition in obtained endomyocardial and extracardiac biopsies.Methods and Results: This study retrospectively evaluated 175 consecutive ATTR-CM patients (wild-type [ATTRwt]: 134, hereditary [ATTRv]: 41) who had positive findings on 99 mTc-labeled pyrophosphate (99 mTc-PYP) scintigraphy and underwent tissue biopsy of at least one organ (subcutaneous tissue, gastrointestinal tract, and endomyocardium). Amyloid deposition was observed in the subcutaneous tissue of 57/150 patients (38%), gastrointestinal tract of 80/131 patients (61%), and endomyocardium of 108/109 patients (99%). Compared to patients with ATTRv, ATTRwt had significantly lower sensitivity in subcutaneous tissue (73% vs. 25%, P<0.01) and tended to be lower in the gastrointestinal tract (74% vs. 57%, P=0.08) biopsies. Among 124 patients who underwent both subcutaneous tissue and gastrointestinal tract biopsies, amyloid was detected in at least 1 specimen in 91 (73%) patients. The sensitivity of the combination of extracardiac biopsies was 66% and 94% in ATTRwt-CM and ATTRv-CM, respectively. Multivariate analysis reveals that ATTRv was the only significant predictor of amyloid deposition in the subcutaneous tissue. CONCLUSIONS: Subcutaneous tissue and gastrointestinal tract biopsy sensitivity are inadequate, especially in patients with ATTRwt; however, the combination of these extracardiac biopsies contributes to increased sensitivity in patients with positive 99 mTc-PYP scintigraphy findings.

Malnutrition-associated high bleeding risk with low thrombogenicity in patients undergoing percutaneous coronary intervention.

BACKGROUND AND AIMS: Although antithrombotic treatments are established for coronary artery disease (CAD), they increase the bleeding risk, especially in malnourished patients. The total thrombus-formation analysis system (T-TAS) is useful for the assessment of thrombogenicity in CAD patients. Here, we examined the relationships among malnutrition, thrombogenicity and 1-year bleeding events in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: This was a retrospective analysis of 300 consecutive CAD patients undergoing PCI. Blood samples obtained on the day of PCI were used in the T-TAS to compute the thrombus formation area under the curve. We assigned patients to two groups based on the geriatric nutritional risk index (GNRI): 102 patients to the lower GNRI group (≤98), 198 patients to the higher GNRI group (98<). The primary endpoint was the incidence of 1-year bleeding events defined by Bleeding Academic Research Consortium criteria types 2, 3, or 5. The T-TAS levels were lower in the lower GNRI group than in the higher GNRI group. Kaplan-Meier analysis showed worse 1-year bleeding event-free survival in the lower GNRI group compared with the higher GNRI group. The combined model of the GNRI and the Academic Research Consortium for High Bleeding Risk (ARC-HBR) had good calibration and discrimination for bleeding risk prediction. In addition, having a lower GNRI and ARC-HBR positivity was associated with 1-year bleeding events. CONCLUSION: A lower GNRI could reflect low thrombogenicity evaluated by the T-TAS and determine bleeding risk in combination with ARC-HBR positivity.

Clinical impact of perioperative atrial fibrillation on long-term recurrence of malignancy.

Perioperative complications have been reported to be associated with a lower incidence of cancer-free survival. Perioperative atrial fibrillation (POAF) is one of occasionally observed complications in patients with malignancies who undergo noncardiac surgeries. However, the long-term clinical impact of POAF on those with malignancies have remained unknown. This was a prospective, single-center, observational study. Patients who underwent noncardiac surgeries for definitive malignancies between 2014 and 2017 were included. The primary and secondary endpoints were 3-year recurrence of malignancies and cancer death, respectively. The present study included consecutive 752 patients (mean age, 68 ± 11 years; males, 62%), and POAF was observed in 77 patients. The follow-up duration was 1037 (interquartile range, 699-1408) days. The 3-year recurrence of malignancies was observed in 239 (32%) patients (POAF, 32 [42%]; non-POAF, 207 [31%]) and 3-year mortality was 130 patients (17%). Cardiac, noncardiac, and cancer deaths were observed in 4 (0.5%), 126 (17%), and 111 (15%) patients, respectively. Multivariate Cox regression analysis demonstrated that POAF was associated with 3-year recurrence of malignancies (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.15-2.52). Landmark analysis demonstrated that POAF tended to be correlated with the incidence of 3-year cancer death (HR, 1.79; 95% CI, 0.96-3.31). In conclusion, POAF is associated with the subsequent recurrence of malignancies. The association of arrhythmia with cancer death may be revealed under longer follow-up durations.Clinical Trial Registration: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018270 . UMIN ID: UMIN000016146.

Impact of cerebrovascular comorbidity on prognosis in Japanese patients undergoing PCI: 1-year data from Japanese multicenter registry (KICS).

Cardiovascular and cerebrovascular diseases are considered the principal cause of morbidity and mortality worldwide; the effect of stroke-induced cardiac manifestations is well recognized; however, not enough clinical data have been found about the impact of stroke with underlying cardiac disease. This study's objective is to assess the impact of stroke on the prognosis of patients with underlying IHD, who underwent PCI treatment. This was a multicenter, 1-year observational study in patients undergoing PCI in one of the 17 participating centers across Japan. 18,495 patients were registered on the PCI list; 2481 patients had a prior stroke experience, whereas 15,979 were stroke-free. Our study revealed that stroke patients were significantly older (mean age 73.5 ± 9.6, 69.7(± 11.5), respectively), and suffered from more comorbidities (diabetes, hypertension, and chronic kidney disease, p < 0.0001). During the 1-year period, subjects with stroke showed higher incidence of clinical events compared to those without stroke; to illustrate, all-cause death accounted for 6.2% in patients with stroke, in contrast to only 2.8% in stroke-free patients (p < 0.0001), cardiac death amounted for 2.2 and 1.2%, respectively (p < 0.0001), recurrent stroke for 3.1% and 1.2% (p < 0.0001), non-cardiac death for 3.6 and 1.54% (p < 0.0001), and finally, hemorrhagic complications with 2.6 and 1.3% (p < 0.0001). Kaplan-Meier analysis revealed that stroke patients had a higher probability of all-cause mortality, cardiac death, and recurrent stroke (log-rank p < 0.0001). Cox hazard analysis also showed that the presence of stroke is a significant indicator in determining the outcome of cardiac death (HR = 1.457, 95% CI 1.036-2.051, p = 0.031); hence, proving it to be a crucial predictor on cardiac prognosis. History of prior stroke was common in PCI patients, and independently associated with a higher rate of subsequent cardiovascular and cerebrovascular events recurrence. Thus, highlighting an urgent need for comprehensive prevention of cardiac and cerebrovascular diseases.

A simple method of sarcopenia detection can predict adverse cardiovascular events in patients with abdominal obesity.

BACKGROUND: Although sarcopenic obesity is associated with a higher risk of cardiovascular events compared with obesity without sarcopenia, it is difficult to diagnose sarcopenia in daily clinical settings. Recently, a simple scoring system has been developed to identify sarcopenia patients based on three variables (age, hand grip strength, and calf circumference). However, the utility of this score for cardiovascular risk stratification in patients with abdominal obesity is unknown. METHODS: We calculated the sarcopenia score in 262 patients with abdominal obesity, defined as a waist circumference ≥90 cm in women or ≥85 cm in men. The composite endpoint of this study was cardiovascular mortality, nonfatal myocardial infarction, stroke, unstable angina, and heart failure hospitalization. RESULTS: Of the 262 patients, 108 had a high sarcopenia score based on previously established criteria (≥105 in men and ≥120 in women). The patients with a high sarcopenia score had a significantly higher plasma level of B-type natriuretic peptide compared with those with a low sarcopenia score (median 56.7, interquartile range [28.2-142.9] vs. 37.9 [13.8-76.1] pg/mL; p < 0.0001). Kaplan-Meier curves revealed a significantly lower event-free survival rate in those with a high compared with a low sarcopenia score (log-rank test p = 0.001), even after adjustment for confounding factors using propensity score matching (log-rank test p = 0.009). Multivariate Cox proportional hazard analysis identified a high sarcopenia score (hazard ratio: 2.46; 95% confidence interval: 1.31-4.64, p = 0.005) as an independent predictor of the primary endpoints. The combination of a high sarcopenia score and low body mass index (<25 kg/m2) predicted a significantly higher risk of future adverse events (p = 0.005). Furthermore, patients with a high sarcopenia score and high B-type natriuretic peptide level (≥200 pg/mL) had the poorest prognosis (p < 0.0001). CONCLUSIONS: This simple screening test for sarcopenia can predict future adverse cardiovascular events in patients with abdominal obesity.

Usefulness of Cardiac Computed Tomography in the Diagnosis of Anti-Cancer Therapy-Related Cardiac Dysfunction　- Consistency With Magnetic Resonance Imaging.

BACKGROUND: Cardiac magnetic resonance (CMR) imaging is the golden standard used for the diagnosis of cancer therapy-related cardiac dysfunction (CTRCD). The consistency of cardiac computed tomography (CCT) in CTRCD cases using CMR imaging is investigated in this study.Methods and Results:In 7 clinically confirmed CTRCD patients, focal late enhancement was confirmed on both CCT and CMR for 4 patients. Myocardial extracellular volume (ECV) values measured by CCT and CMR were elevated in all patients, suggesting the presence of diffuse myocardial damage. CONCLUSIONS: The study findings indicated that CCT could provide adequate information about late myocardial enhancement and ECV quantification, indicating the effective evaluation of CTRCD by CCT.

Usefulness of relative apical longitudinal strain index to predict positive 99m Tc-labeled pyrophosphate scintigraphy findings in advanced-age patients with suspected transthyretin amyloid cardiomyopathy.

BACKGROUND: We previously reported that a high score (2 or 3 points) according to the Kumamoto criteria, a combination of high-sensitivity cardiac troponin T (hs-cTnT) ≥0.308 ng/mL, the length of QRS ≥ 120 ms in electrocardiogram, and left ventricular (LV) posterior wall thickness ≥ 13.6 mm, increases the pretest probability of 99m Tc-labeled pyrophosphate (99m Tc-PYP) scintigraphy in patients with suspected transthyretin amyloid cardiomyopathy (ATTR-CM). However, some patients with a low score (0 or 1 point) show positive findings on 99m Tc-PYP scintigraphy. Therefore, we evaluated the usefulness of additional examinations, including echocardiographic assessment of myocardial strain, to raise the pretest probability of 99m Tc-PYP scintigraphy for these patients. METHODS AND RESULTS: We examined 109 consecutive patients aged ≥70 years with low scores according to the Kumamoto criteria who underwent 99m Tc-PYP scintigraphy. Nineteen patients (17%) had positive 99m Tc-PYP scintigraphy findings. The relative apical longitudinal strain (LS) index (apical LS/ basal LS + mid LS) (RapLSI) was significantly higher in patients with positive than negative 99m Tc-PYP scintigraphy findings (1.04 ± 0.37 vs 0.70 ± 0.28, P < .01). Multivariable logistic regression analysis revealed that a high RapLSI (≥1.04) was significantly associated with 99m Tc-PYP positivity (odds ratio, 14.14; 95% confidence interval, 3.36-59.47; P < .01). The sensitivity, specificity, and accuracy of the diagnostic model using the RapLSI for identification of 99m Tc-PYP positivity were 53%, 94%, and 87%, respectively. CONCLUSIONS: A high RapLSI can raise the pretest probability of 99m Tc-PYP scintigraphy in patients with a low score according to the Kumamoto criteria. The RapLSI can assist clinicians in determining strategies for these patients.

The study protocol for PREDICT AF RECURRENCE: a PRospEctive cohort stuDy of surveIllanCe for perioperaTive Atrial Fibrillation RECURRENCE in major non-cardiac surgery for malignancy.

BACKGROUND: A previous retrospective cohort study established the relationship between perioperative atrial fibrillation (POAF) and subsequent mortality and stroke. However, the details regarding the cause of death and etiology of stroke remain unclear. METHODS: The prospective cohort study of surveillance for perioperative atrial fibrillation recurrence in major non-cardiac surgery for malignancy (PREDICT AF RECURRENCE) registry is an ongoing prospective cohort study to elucidate the long-term recurrence rate and the clinical impact of new-onset POAF in the setting of head and neck, non-cardiac thoracic, and abdominal surgery for malignancy. In this study, cardiologists collaborate with a surgical team during the perioperative period, carefully observe the electrocardiogram (ECG) monitor, and treat arrhythmia as required. Furthermore, patients who develop new-onset POAF are followed up using a long-term Holter ECG monitor, SPIDER FLASH-t AFib®, to assess POAF recurrence. DISCUSSION: Even if patients with malignancy survive by overcoming the disease, they may die from any preventable cardiovascular diseases. In particular, those with POAF may develop cardiogenic stroke in the future. Because details of the natural history of patients with POAF remain unclear, investigating the need to continue anticoagulation therapy for such patients is necessary. This study will provide essential information on the recurrence rate of POAF and new insights into the prediction and treatment of POAF. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR): UMIN000016146 ; Data of Registration: January 7, 2015.

Effects of glycemic control on in-hospital mortality among acute heart failure patients with reduced, mid-range, and preserved ejection fraction.

The relationship between glycemic control and outcome in patients with heart failure (HF) remains contentious. A recent study showed that patients with HF with mid-range ejection fraction (HFmrEF) more frequently had comorbid diabetes relative to other patients. Herein, we examined the association between glycosylated hemoglobin (HbA1c) and in-hospital mortality in acute HF patients with reduced, mid-range, and preserved EF. A multicenter retrospective study was conducted on 5205 consecutive patients with acute HF. Potential risk factors for in-hospital mortality were selected by univariate analyses; then, multivariate Cox regression analysis with backward stepwise selection was performed to identify significant factors. Kaplan-Meier survival curves and log-rank testing were used to compare in-hospital mortality between groups. Across the study cohort, 44% (2288 patients) had reduced EF, 20% had mid-range EF, and 36% had preserved EF. The overall in-hospital mortality rate was 4.6%, with no significant differences among the HF patients with reduced, mid-range, and preserved EF groups. For patients with HFmrEF, higher HbA1c level was a significant risk factor for in-hospital mortality (hazard ratio 1.387; 95% confidence interval 1.014-1.899; P = 0.041). In contrast, HbA1c was not an independent risk factor for in-hospital mortality in HF patients with preserved or reduced EF. In conclusion, HbA1c is an independent risk factor for in-hospital mortality in acute HF patients with mid-range EF, but not in those with preserved or reduced EF. Elucidation of the pathophysiological mechanisms behind these findings could facilitate the development of more effective individualized therapies for acute HF.

Myocardial Injury Caused by Severe Blow: Importance of Carefulness in Accurate Diagnosis.

Blunt chest trauma may lead to cardiac involvement such as myocardial contusion, coronary artery dissection, cardiac rupture, or myocardial infarction. Early detection and treatment of complications such as these are essential. We describe a case status post collision with an iron ball and discuss how to detect myocardial infarction. We emphasize the importance of careful interview, physical examination, and electrocardiogram even in seemingly healthy patients. A severe blow, such as that described, can impair coronary artery flow and may potentially cause myocardial infarction.

Mesenchymal stem cells in obesity: insights for translational applications.

Obesity is now a major public health problem worldwide. Lifestyle modification to reduce the characteristic excess body adiposity is important in the treatment of obesity, but effective therapeutic intervention is still needed to control what has become an obesity epidemic. Unfortunately, many anti-obesity drugs have been withdrawn from market due to adverse side effects. Bariatric surgery therefore remains the most effective therapy for severe cases, although such surgery is invasive and researchers continue to seek new control strategies for obesity. Mesenchymal stem cells (MSCs) are a major source of adipocyte generation, and studies have been conducted into the potential roles of MSCs in treating obesity. However, despite significant progress in stem cell research and its potential applications for obesity, adipogenesis is a highly complex process and the molecular mechanisms governing MSC adipogenesis remain ill defined. In particular, successful clinical application of MSCs will require extensive identification and characterization of the transcriptional regulators controlling MSC adipogenesis. Since obesity is associated with the incidence of multiple important comorbidities, an in-depth understanding of the relationship between MSC adipogenesis and the comorbidities of obesity is also necessary to evaluate the potential of effective and safe MSC-based therapies for obesity. In addition, brown adipogenesis is an attractive topic from the viewpoint of therapeutic innovation and future research into MSC-based brown adipogenesis could lead to a novel breakthrough. Ongoing stem cell studies and emerging research fields such as epigenetics are expected to elucidate the complicated mechanisms at play in MSC adipogenesis and develop novel MSC-based therapeutic options for obesity. This review discusses the current understanding of MSCs in adipogenesis and their potential clinical applications for obesity.

Clinical impact of non-culprit lesions on 1-year mortality in very elderly patients with acute coronary syndrome.

Preventive percutaneous coronary intervention (PCI) for non-culprit lesions after primary PCI remains controversial in patients with acute coronary syndrome (ACS). We analyzed whether PCI for non-culprit lesions would be associated with a better long-term prognosis in very elderly (≥85 years) patients. This study included 91 consecutive patients with ACS (mean age, 88.2 ± 3.0, 52 % male). We investigated the association of residual lesions with 1-year mortality. Culprit lesions affected the left anterior descending artery (LAD) in 50 patients, the left circumflex artery (LCx) in 29, and the right coronary artery (RCA) in 31. Residual lesions affected LAD in 20 cases, LCx in 22, and RCA in 21 patients. Residual lesions in LAD were associated with a higher 1-year mortality (p = 0.013), whereas residual lesions in LCx or RCA were not (p = 0.547 and 0.473, respectively). A Cox regression model demonstrated that patients with residual lesions in LAD had an increased risk of 1-year mortality compared with those without residual lesions (hazard ratio, 2.39; 95 % confidence interval, 1.16-4.96; p = 0.019). Therefore, the option to not treat residual lesions in LAD of patients with PCI may be associated with a higher 1-year mortality. Further studies are needed to confirm these findings.

Considerations in cardio-oncology: Multiple mobile left-sided cardiac thrombi in chemotherapy-induced cardiomyopathy.

With advances in cancer chemotherapy, the importance of the new clinical discipline of cardio-oncology, which is concerned with the cardiac effects of chemotherapy, is increasing. Herein we describe the case of a 48-year-old woman with a history of breast cancer who presented with symptoms of heart failure due to chemotherapy-induced cardiomyopathy. Treatment for the patient's breast cancer had included surgery and chemotherapy with anthracyclines and trastuzumab. Echocardiography revealed multiple mobile thrombi in the left ventricle and atrium. In addition, brain magnetic resonance imaging revealed small acute cerebral infarctions due to embolization. Given the high risk of re-embolization, surgical thrombectomy was performed. Thus far, there are no standardized therapeutic guidelines for left-sided cardiac thrombi and the optimal treatment remains contentious. Although this patient was managed successfully with surgical thrombectomy, patients should be managed individually, taking into consideration embolization, bleeding, and surgical risks. With further improvements in cancer chemotherapy, there may be an increase in the incidence of complications such as multiple cardiac thrombi. From the cardio-oncology standpoint, we propose close interactions between cardiologists and oncologists for the optimal care of cancer patients.

Deletion of angiotensin II type 2 receptor accelerates adipogenesis in murine mesenchymal stem cells via Wnt10b/beta-catenin signaling.

Recent evidence suggests that the renin-angiotensin system (RAS) has a vital role in adipocyte biology and the pathophysiology of metabolic syndrome. Obesity is the main culprit of metabolic syndrome; and mesenchymal stem cells (MSCs) have been forwarded as a major source of adipocyte generation. Previously, we reported that MSCs have a local RAS and that pharmacological blockade of angiotensin II type 2 receptor (AT2R) promotes adipogenesis in human MSCs. However, the definitive roles of AT2R and how AT2R functions in adipogenesis remains unknown. To this end, we employed AT2R-null murine MSCs to characterize how AT2R affects the differentiation of MSCs into adipocytes. Murine MSCs were isolated from AT2R-null mice and wild-type littermates, grown to confluency, and then differentiated into adipocytes. Adipogenesis was quantitated by assessing the lipid droplet accumulation. Using the lipophilic fluorescent dye, the AT2R-null cells showed significantly increased total fluorescence (261.6±49.6% vs littermate) on day 7. Oil red O staining followed by extraction of the absorbed dye and measurement of the absorbance on day 14 also exhibited significantly increased lipid droplet accumulation in the AT2R-null cells (202.7±14.1% vs littermate). We also examined the expression of adipogenic marker genes by quantitative RT-PCR. The AT2R-null group exhibited significantly increased expression of PPAR-gamma, fatty acid synthase, and adiponectin (vs littermate). We further examined the role of Wnt10b/beta-catenin signaling, which reportedly has an important inhibitory role in adipogenesis. The AT2R-null group exhibited significantly decreased Wnt10b expression accompanied by decreased beta-catenin (vs littermate). Our results thus revealed that the AT2R inhibits adipogenic differentiation in murine MSCs. Moreover, this inhibitory effect is associated with Wnt10b/beta-catenin signaling. These results provide important insights into the pathophysiology of obesity and obesity-related consequences such as metabolic syndrome, hinting at possible future therapies.