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.

Comparing Anticoagulation Strategies for Venous Thromboembolism Associated With Active Cancer: A Systematic Review and Meta-Analysis.

Background: Current guidelines recommend several direct oral anticoagulant agents (DOACs) equally for managing cancer-associated venous thromboembolism (VTE). Objectives: The aim of this study was to assess the efficacy and safety of DOACs in patients with active cancer. Methods: Literature searches were conducted in PubMed, Embase, and Cochrane Central in November 2022. Randomized controlled trials investigating anticoagulation strategies (vitamin K antagonists, parenteral anticoagulation [eg, low-molecular weight heparin], and DOACs) for VTE in patients with active cancer were identified for network meta-analysis. The outcomes included recurrent VTE, recurrent pulmonary embolism, recurrent deep venous thrombosis, major bleeding, clinically relevant nonmajor bleeding (CRNMB), and a composite outcome of major bleeding or CRNMB. Pooled HRs and 95% CIs were estimated using either the HR or relative risk provided from each study. Random-effects models were used for all the analyses. Results: Seventeen randomized controlled trials involving 6,623 patients with active cancer were included. No significant differences were found among the DOACs for efficacy outcomes (recurrent VTE, pulmonary embolism, and deep venous thrombosis). In terms of major bleeding, apixaban was similarly safe compared with dabigatran and rivaroxaban but was associated with a decreased risk compared with edoxaban (HR: 0.38; 95% CI: 0.15-0.93). Regarding CRNMB, edoxaban was similarly safe compared with apixaban but was associated with a decreased risk compared with rivaroxaban (HR: 0.31; 95% CI: 0.10-0.91). Compared with parenteral anticoagulation, apixaban was associated with a reduced risk for recurrent VTE (HR: 0.60; 95% CI: 0.38-0.93) without increasing bleeding, edoxaban was associated with an increased risk for major bleeding or CRNMB (HR: 1.35; 95% CI: 1.02-1.79), and rivaroxaban was associated with an increased risk for CRNMB (HR: 3.76; 95% CI: 1.43-9.88). Conclusions: DOACs demonstrate comparable efficacy but exhibit different safety profiles. Apixaban may confer an antithrombotic benefit without an increased risk for bleeding, distinguishing it from other contemporary anticoagulation strategies in patients with active cancer and VTE.

Prognostic impact of diabetes mellitus on in-hospital mortality in patients with acute myocardial infarction complicating renal dysfunction according to age and sex.

BACKGROUND: Patients with acute myocardial infarction (AMI) complicating renal dysfunction (RD) are recognized as being at high risk. Although diabetes mellitus (DM) is a major cause of RD, the prognostic impact of coexisting DM on mortality in patients with AMI complicating RD is ill-defined. This study compared the prognostic impact of coexisting DM in patients with AMI complicating RD according to both age and sex. METHODS: A multicenter retrospective study was conducted on 2988 consecutive patients with AMI complicating RD (estimated glomerular filtration rate <60 mL/min per 1.73 m2). Multivariable Cox regression analysis was performed to investigate the effects of DM on in-hospital mortality. RESULTS: Statistically significant interactions between age and DM and between sex and DM for in-hospital mortality were revealed in the entire cohort. Coexisting DM was identified as an independent risk factor for in-hospital mortality (hazard ratio [HR], 2.543) in young (aged <65 years), but not old (aged ≥65 years), patients. DM was identified as an independent risk factor (HR, 1.469) in male, but not female, patients. Kaplan-Meier survival curves showed that DM correlated with significantly low survival rates in patients that were young or male as compared to those who were old or female. CONCLUSIONS: There were significant differences in the prognostic impact of DM on in-hospital mortality between young and old as well as male and female patients with AMI complicating RD. These results have implications for future research and the management of patients with DM, RD, and AMI comorbidities.

Prognostic value of right ventricular global longitudinal strain in patients with immunoglobulin light-chain cardiac amyloidosis.

Aims: Left ventricular (LV) global longitudinal strain (GLS) (LV-GLS) is a strong and independent predictor of outcomes in patients with immunoglobulin light-chain (AL) cardiac amyloidosis. This study was performed to investigate whether right ventricular (RV) GLS (RV-GLS) provides prognostic information in patients with AL amyloidosis. Methods and results: Among 74 patients who were diagnosed with AL cardiac amyloidosis at Kumamoto University Hospital from December 2005 to December 2022, 65 patients who had enough information for two-dimensional speckle tracking imaging and did not receive chemotherapy before the diagnosis of cardiac amyloidosis were retrospectively analysed. During a median follow-up of 359 days, 29 deaths occurred. In two-dimensional echocardiographic findings, LV-GLS, left atrium reservoir strain (LASr), and RV-GLS were significantly lower in the all-cause death group than in the survival group (LV-GLS: 8.9 ± 4.2 vs. 11.7 ± 3.9, P < 0.01; LASr: 9.06 ± 7.28 vs. 14.09 ± 8.32, P < 0.05; RV-GLS: 12.0 ± 5.1 vs. 16.8 ± 4.0, P < 0.01). Multivariable Cox proportional hazard analysis showed RV-GLS was significantly and independently associated with all-cause death in patients with AL cardiac amyloidosis (hazard ratio 0.85; 95% confidence interval, 0.77-0.94; P < 0.01). Receiver operating characteristic analysis showed that the area under the curve of RV-GLS for all-cause death was 0.774 and that the best cut-off value of RV-GLS was 14.5% (sensitivity, 75%; specificity, 72%). In the Kaplan-Meier analysis, patients with AL cardiac amyloidosis who had low RV-GLS (<14.5%) had a significantly higher probability of all-cause death (P < 0.01). Conclusion: RV-GLS has prognostic value in patients with AL cardiac amyloidosis and provides greater prognostic power than LV-GLS and LASr.

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.

Prognostic value of right ventricular global longitudinal strain in transthyretin amyloid cardiomyopathy.

BACKGROUND: This study was performed to investigate whether right ventricular global longitudinal strain (RV-GLS) provides prognostic information in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). METHODS AND RESULTS: Among 129 patients who were diagnosed with ATTRwt-CM at Kumamoto University Hospital from December 2002 to December 2019, 111 patients who had enough information for two-dimensional speckle tracking imaging were retrospectively analyzed. During a median follow-up of 615 days, 26 cardiovascular deaths occurred. Compared with patients in the non-event group, those in the cardiovascular death group were significantly older (81.1 ±â€¯7.4 years vs. 78.2 ±â€¯6.2 years, p = 0.009) and had significantly higher interventricular septal thickness in diastole (16.6 ±â€¯3.1 mm vs. 15.3 ±â€¯2.4 mm, p = 0.048), lower RV-GLS (10.9 ±â€¯2.7% vs. 12.8 ±â€¯3.5%, p = 0.010), and lower right ventricular free wall longitudinal strain (RVFWLS) (13.1 ±â€¯3.3% vs. 15.5 ±â€¯3.8%, p = 0.004). In the univariate Cox proportional hazard analysis, age, left atrial volume index (LAVI), RV-GLS, and RVFWLS were significantly associated with cardiovascular death [age, hazard ratio (HR), 1.10; 95% confidence interval (CI), 1.02-1.19, p = 0.010; LAVI, HR, 1.02; 95% CI, 1.00-1.03, p = 0.009; RV-GLS, HR, 0.86; 95% CI, 0.75-0.97, p = 0.017; RVFWLS, HR 0.89; 95% CI, 0.79-1.00; p = 0.041]. Multivariable Cox proportional hazard analysis showed RV-GLS was significantly and independently associated with cardiovascular death in patients with ATTRwt-CM (HR, 0.86; 95% CI, 0.74-0.99; p = 0.038). Receiver operating characteristic analysis showed that the area under the curve of RV-GLS for cardiovascular death was 0.668 and that the best cut-off value of RV-GLS was 11.59% (sensitivity, 69.2%; specificity, 63.5%). In the Kaplan-Meier analysis, patients with ATTRwt-CM who had low RV-GLS (<11.59%) had a significantly higher probability of total cardiovascular death (p = 0.004) and heart failure-related hospitalization (p = 0.013). CONCLUSION: RV-GLS has significant prognostic value in patients with ATTRwt-CM and provides greater prognostic power than conventional echocardiographic findings.

Cardiac computed tomography-derived myocardial tissue characterization after anthracycline treatment.

AIMS: Understanding cardiac function after anthracycline administration is very important from the perspective of preventing the onset of heart failure. Although cardiac magnetic resonance and echocardiography are recognized as the 'gold standard' for detecting cardiotoxicity, they have many shortcomings. We aimed to investigate whether cardiac computed tomography (CCT) could replace these techniques, assessing serial changes in cardiac tissue characteristics as determined by CCT after anthracycline administration. METHODS AND RESULTS: We prospectively investigated 15 consecutive breast cancer patients who were scheduled to receive anthracycline therapy. We performed echocardiography and CCT before and 3, 6, and 12 months after anthracycline treatment. The mean cumulative administered anthracycline dose was 269.9 ± 14.6 mg/m2 (doxorubicin-converted dose). Of the 15 enrolled patients who received anthracycline treatment for breast cancer, none met the definition of cardiotoxicity. The CCT-derived extracellular volume fraction tended to continue to increase after anthracycline treatment and had relatively similar dynamics to the left ventricular ejection fraction and global longitudinal strain as determined by echocardiography. CONCLUSIONS: Our findings indicated that CCT could provide adequate information about the characteristics of myocardial tissue after anthracycline administration. CCT may improve the understanding of cardiotoxicity by compensating for the weaknesses of echocardiography. This technique could be useful for understanding cardiac tissue characterization as a 'one-stop shop' evaluation, providing new insight into cardiooncology.

Utility of left atrial and ventricular strain for diagnosis of transthyretin amyloid cardiomyopathy in aortic stenosis.

AIMS: To clarify the usefulness of left atrial (LA) function and left ventricular (LV) function obtained by two-dimensional (2D) speckle tracking echocardiography to diagnose concomitant transthyretin amyloid cardiomyopathy (ATTR-CM) in patients with aortic stenosis (AS). METHODS AND RESULTS: We analysed 72 consecutive patients with moderate to severe AS who underwent 99m Tc-pyrophosphate (PYP) scintigraphy at Kumamoto University Hospital from January 2012 to September 2020. We divided these 72 patients into 2 groups based on their 99m Tc-PYP scintigraphy positivity or negativity. Among 72 patients, 16 patients (22%) were positive, and 56 patients (78%) were negative for 99m Tc-PYP scintigraphy. In clinical baseline characteristics, natural logarithm troponin T was significantly higher in the 99m Tc-PYP scintigraphy-positive than scintigraphy-negative group (-2.9 ± 0.5 vs. -3.5 ± 0.8 ng/mL, P < 0.05). In conventional echocardiography, the severity of AS was not significantly different between these two groups. In 2D speckle tracking echocardiography, the relative apical longitudinal strain (LS) index (RapLSI) [apical LS/ (basal LS + mid LS)] was significantly higher (1.09 ± 0.49 vs. 0.78 ± 0.23, P < 0.05) and the peak longitudinal strain rate (LSR) in LA was significantly lower in the 99m Tc-PYP scintigraphy-positive than scintigraphy-negative group (0.36 ± 0.14 vs. 0.55 ± 0.20 s-1 , P < 0.05). Multivariable logistic analysis revealed the peak LSR in LA and RapLSI were significantly associated with 99m Tc-PYP scintigraphy positivity. Receiver operating characteristic analysis showed that the area under the curve (AUC) of the peak LSR in LA for 99m Tc-PYP scintigraphy positivity was 0.79 and that the best cut-off value of the peak LSR in LA was 0.47 s-1 (sensitivity: 78.6% and specificity: 72.3%). The AUC of RapLSI for 99m Tc-PYP scintigraphy positivity was 0.69, and the cut-off value of RapLSI was decided as 1.00 (sensitivity: 43.8% and specificity: 87.5%) according to the previous report. The 99m Tc-PYP scintigraphy positivity in patients with RapLSI ≥ 1.0 and the peak LSR in LA ≤ 0.47 s-1 was 83.3% (5/6), and the 99m Tc-PYP scintigraphy negativity in patients with RapLSI < 1.0 and the peak LSR in LA > 0.47 s-1 was 96.6% (28/29). CONCLUSIONS: Left atrial and LV strain analysis were significantly associated with 99m Tc-PYP scintigraphy positivity in ATTR-CM patients with moderate to severe AS. The combination of the peak LSR in LA and RapLSI might be a useful predictor of the presence of ATTR-CM in patients with moderate to severe AS.

A simple staging system using biomarkers for wild-type transthyretin amyloid cardiomyopathy in Japan.

AIMS: It has been reported that a staging system combining N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T (hs-cTnT) or estimated glomerular filtration rate (eGFR) is useful in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). However, these studies were mainly conducted in Western countries, and their usefulness for the Japanese population is unclear. We examined and validated the staging system using hs-cTnT, eGFR, and B-type natriuretic peptide (BNP) in Japanese patients with ATTRwt-CM. METHODS AND RESULTS: We retrospectively evaluated 176 patients with ATTRwt-CM. The cut-off values of hs-cTnT and eGFR were selected as 0.05 ng/mL and 45 mL/min/1.73 m2 , respectively, based on a previous report. The optimal cut-off value of BNP was 255.6 pg/mL to predict all-cause mortality (sensitivity, 75%; specificity, 58%; area under the curve, 0.69; 95% confidence interval [CI], 0.61-0.78; P < 0.001) based on a receiver operating characteristic curve. We defined the cut-off value of BNP as 250 pg/mL. Increased hs-cTnT (>0.05 ng/mL) and BNP (>250 pg/mL) and decreased eGFR (<45 mL/min/1.73 m2 ) were significant predictors of poor prognosis (P < 0.05). We calculated the score by adding 1 point if hs-cTnT and BNP levels increased or eGFR decreased by more than the cut-off value. The hazard ratio of all-cause death adjusted by age and sex, using score 0 as a reference, was 0.44 (95% CI 0.08-2.49, P = 0.44) for score 1, 3.69 (95% CI 1.21-11.21, P = 0.02) for score 2, and 5.40 (95% CI 1.57-18.54, P = 0.007) for score 3. We divided patients into a low score group (0-1 point) and high score group (2-3 points). Kaplan-Meier analyses revealed significant differences in all-cause death and rehospitalization for heart failure (log rank test; P < 0.001), and after adjusting for sex and age, the hazard ratio of all-cause death was 6.96 (95% Cl 2.88-16.83, P < 0.001) and that for rehospitalization for heart failure was 4.27 (95% Cl 2.26-8.07, P < 0.001) in the high-risk group, compared with those in the low-risk group. The median survival period was 32.0 months in the high-risk group. CONCLUSIONS: This simple staging system, which combines hs-cTnT, BNP, and eGFR, was useful for predicting prognosis in Japanese patients with ATTRwt-CM. This system can objectively evaluate the disease progression of ATTRwt-CM and may be useful for patient selection for disease-modifying therapy.

Increased soluble programed cell death-ligand 1 is associated with acute coronary syndrome.

BACKGROUND: Programmed cell death (PD)-1 and its ligand (PD-L1) plays crucial roles in T-cell tolerance as immune checkpoint. Previous studies reported that increased serum levels of soluble PD-L1 (sPD-L1) reflect myocardial and vascular inflammation. However, little is known about the clinical relationship between sPD-L1 and acute coronary syndrome (ACS). We investigated the relation of sPD-L1 and ACS. METHODS: We prospectively measured serum levels of sPD-L1 using a commercially available enzyme-linked immunosorbent assay kit in patients with coronary artery disease (CAD) and continuous non-CAD admitted to Kumamoto University Hospital between December 2017 and June 2019. All malignant diseases, patients who underwent hemodialysis, active collagen diseases, and severe infectious diseases were excluded. RESULTS: Totally, 446 CAD patients [ACS, n = 124; chronic coronary syndrome (CCS), n = 322] and 24 non-CAD patients were analyzed. The levels of sPD-L1 were significantly higher in patients with ACS than those both with non-CAD and CCS {ACS, 188.7 (111.0-260.8) pg/mL, p < 0.001 vs. non-CAD [83.5 (70.8-130.4) pg/mL]; and p = 0.009 vs. CCS [144.2 (94.8-215.5) pg/mL], respectively}. Univariate logistic regression analysis identified that sPD-L1 was significantly associated with ACS [odds ratio (OR): 1.459, 95% confidence interval (CI): 1.198-1.778, p < 0.001]. Multivariable logistic regression analysis with nine significant factors identified from the univariate analysis revealed that sPD-L1 was significantly and independently associated with ACS (OR: 1.561, 95% CI: 1.215-2.006, p < 0.001). CONCLUSIONS: This is the first clinical study to demonstrate the increased level of sPD-L1 in patients with CAD, and the significant association with ACS.

Associations of cardiovascular risk factors with survival outcomes in a cancer registration: Findings from the KUMAMON registry.

ABSTRACT: Although the relationship between cardiovascular diseases and malignant diseases has recently attracted attention, the associations of cardiovascular risk factors and clinical outcomes in cancer patients remain to be elucidated. We performed a retrospective, observational study that explored the clinical outcomes of patients with cancer or with a history of cancer.We enrolled 30,706 consecutive adult cancer patients from Kumamoto University Hospital. We investigated mortality and morbidity, including cardiovascular conditions (dyslipidemia [DL]/diabetes mellitus [DM]/hypertension [HT]). The primary endpoint was all-cause mortality.Of the enrolled patients, 9032 patients (29.4%) died within the follow-up period. The Kaplan-Meier analysis demonstrated that in the groups classified according to the number of DL/DM/HT (LDH) factors, the LDH1 and LDH2 groups had a significantly higher probability of the primary endpoint than the LDH0 group (P < .001 and P < .001, respectively), whereas there were no significant differences between the LDH0 group and LDH3 group (P = .963). Univariate Cox proportional hazards regression analyses of mortality complemented by the multiple imputation method including various factors demonstrated that the presence of DL in cancer patients was a significant negative predictor of mortality (hazard ratio = 0.79, P < .01).The all-cause mortality rate did not always increase as the number of LDH factors increased. The present study revealed that the presence of DL is a negative risk factor for all-cause mortality in cancer patients.

Prognostic value of left atrial strain in patients with wild-type transthyretin amyloid cardiomyopathy.

AIMS: This study was performed to investigate whether left atrial (LA) strain by echocardiography provides prognostic information in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). METHODS AND RESULTS: Among 129 patients who were diagnosed with ATTRwt-CM at Kumamoto University Hospital from December 2002 to December 2019, 113 patients who had enough information for two-dimensional speckle tracking echocardiography were enrolled in this study. During a median follow-up of 668 days, 28 cardiovascular deaths occurred. Compared with patients in the non-event group, those in the cardiovascular death group were significantly older (81.5 ± 7.4 vs. 78.1 ± 6.1 years, P < 0.01), had a lower incidence of carpal tunnel syndrome (21% vs. 47%, P < 0.05), and had a higher high-sensitivity cardiac troponin T [0.085 (0.063-0.105) vs. 0.049 (0.036-0.079) ng/mL, P < 0.01] and B-type natriuretic peptide concentrations [419 (239-541) vs. 271 (155-462) pg/mL, P < 0.01] and lower estimated glomerular filtration rate (41.8 ± 15.4 vs. 53.4 ± 14.6 mL/min/1.73 m2 , P < 0.01). Electrocardiography showed higher rate of a V1-V3 QS pattern (52% vs. 24%, P < 0.01) and complete left bundle branch block (27% vs. 6%, P < 0.01), and echocardiography showed a significantly lower peak LA strain rate during the contraction phase (0.16 ± 0.13 vs. 0.28 ± 0.27 S-1 , P < 0.05), LA strain during the reservoir phase (LASr) (5.84 ± 2.41 vs. 8.22 ± 4.05%, P < 0.01), and peak LA strain rate during the reservoir phase (0.26 ± 0.09 vs. 0.33 ± 0.15 S-1 , P < 0.05) in the cardiovascular death group than in non-event group. By contrast, conventional echocardiographic findings were not significantly different between these two groups. After adjusting for conventional predictive factors of ATTRwt-CM (age, high-sensitivity cardiac troponin T and B-type natriuretic peptide concentrations, and estimated glomerular filtration rate), multivariable Cox proportional hazard analyses showed that LASr was significantly and independently associated with cardiovascular death in patients with ATTRwt-CM (odds ratio, 0.84; 95% confidence interval, 0.72-0.98; P < 0.05). After adjusting for age and echocardiographic findings associated with cardiovascular death (LA volume index and peak LA strain rate during the contraction phase), LASr was significantly and independently associated with cardiovascular death in patients with ATTRwt-CM (odds ratio, 0.83; 95% confidence interval, 0.70-0.98; P < 0.05). Receiver operating characteristic curve analysis showed that the area under the curve of LASr for cardiovascular death was 0.686 and that the best cut-off value of LASr was 6.69% (sensitivity, 62.4%; specificity, 64.3%). In the Kaplan-Meier analysis, patients with low LASr (<6.69%) had a significantly higher probability of total cardiovascular death (P < 0.05) and heart failure-related hospitalization (P < 0.05). CONCLUSIONS: Left atrial strain during the reservoir phase provides significant prognostic value in patients with ATTRwt-CM even after adjusting for conventional predictive factors.

Cardiac computed tomography-derived extracellular volume fraction in late anthracycline-induced cardiotoxicity.

Cardiotoxicity in the late phase after anthracycline drugs administration remains to be defined. Of the 44 patients who received anthracycline treatment, 7 were found to have cancer therapeutics-related cardiac dysfunction (CTRCD). The global longitudinal strain determined by echocardiography and myocardial extracellular volume fraction (ECV) determined by cardiac computed tomography (CCT) of the CTRCD(+) group were significantly higher than those of the control group and CTRCD(-) group, whereas there were no significant differences between the control and CTRCD(-) groups. Our findings indicated that CCT may be a tool comparable to echocardiography, indicating the effective evaluation of CTRCD by CCT.

Hemodialysis-related low thrombogenicity measured by total thrombus-formation analysis system in patients undergoing percutaneous coronary intervention.

BACKGROUND: Established antithrombotic therapies can increase bleeding risk, especially in hemodialysis (HD) patients. The Total Thrombus-formation Analysis System (T-TAS) is useful for evaluating thrombogenicity. The aim of this study was to examine the relationship between HD and thrombogenicity, or bleeding events in patients undergoing percutaneous coronary intervention (PCI). METHODS: In this retrospective cohort study, 300 patients undergoing elective PCI were enrolled between April 2017 and March 2019. Blood samples obtained on the day of PCI were analyzed with T-TAS to compute the thrombus formation area under the curve (AUC; PL18-AUC10 for platelet chip; AR10-AUC30 for atheroma chip). The patients were divided into three groups according to estimated glomerular filtration rate (eGFR): 33 HD patients, 124 non-HD patients with eGFR <60 mL/min/1.73m2, and 143 non-HD patients with eGFR ≥60. We examined the thrombogenicity and spontaneous bleeding events within 1-year post-PCI. RESULTS: HD was significantly associated with both low PL18-AUC10 and AR10-AUC30 levels determined by T-TAS. Bleeding events defined by the Bleeding Academic Research Consortium criteria types 2, 3, or 5 occurred during follow-up in 27 patients (9.0%): 7 in HD, 10 in non-HD with eGFR <60, and 10 in non-HD with eGFR ≥60. Both T-TAS parameters in the patients with bleeding were lower compared with those in the patients without bleeding, and HD was significantly associated with 1-year bleeding events. CONCLUSIONS: The results suggested that HD patients undergoing PCI might be a predictor for low thrombogenicity measured by T-TAS and 1-year bleeding risk.

Validation of the Khorana Venous Thromboembolism Risk Score in Japanese Cancer Patients.

Background: Although the Khorana venous thromboembolism (VTE) risk score (KRS) is well recognized as a simple VTE risk assessment method in patients with cancer, whether it is suitable for Asian populations is unclear. Objectives: This study validated KRS for the prediction of VTE and investigated the value of the KRS in predicting mortality in Japanese patients with cancer. Methods: A body mass index value of 25 kg/m2 or more was defined as obesity according to World Health Organization consensus. A total of 27,687 patients with cancer were subdivided into low- (0), intermediate- (1-2), and high-score (3) groups by the KRS. The primary and secondary endpoints were VTE and all-cause mortality, respectively. Results: The prevalence of VTE was 1.7%, 7.3%, and 11.0% for low-, intermediate-, and high-score patients, respectively. Receiver operating characteristic (ROC) analysis showed that the KRS significantly predicted VTE (area under the curve, 0.679; 95% confidence interval [CI] 0.666-0.692; P < 0.001). The cutoff value for the KRS was 1.0. Logistic regression analysis demonstrated that the KRS was an independent predictor of VTE (odds ratio 1.766; 95% CI 1.673-1.865; P < 0.01). The cutoff value of the KRS for all-cause mortality determined by ROC analysis was 2.0. Kaplan-Meier analysis demonstrated a significantly higher incidence of mortality in the KRS ≥2 group than in the KRS 0-1 group (log-rank: P < 0.01). Conclusions: The KRS was useful in Japanese patients with cancer and might be a potentially useful marker for the prediction of mortality. Establishing optimal scores for Japanese subjects is mandatory because of its low diagnostic ability. (KUMAMON Cancer registry; UMIN000047554).

Imaging-guided PCI for event suppression in Japanese acute coronary syndrome patients: community-based observational cohort registry.

Although there is accumulating evidence for the usefulness of imaging-guided percutaneous coronary intervention (PCI), there are few studies for acute coronary syndrome (ACS), and the impact of the frequency of use has not been well addressed. From the Kumamoto Intervention Conference Study; a Japanese registry comprising 17 institutions, consecutive patients undergoing successful PCI from April 2008 through March 2014 were enrolled. Subjects were divided into two groups: imaging-guided PCI and angiography-guided PCI. Clinical outcome was a composite of cardiac death, non-fatal myocardial infarction, and stent thrombosis within 1 year. A total of 6025 ACS patients were enrolled: 3613 and 2412 patients with imaging- and angiography-guided PCI, respectively. Adverse cardiac events were significantly lower in the imaging-guided PCI group (long-rank P < 0.001). Even after propensity-score matching, the event rates still showed significant differences between the two groups (log-rank P = 0.004). To assess the effects of frequency of imaging usage, we divided the 17 institutions into six low-, six moderate-, and five high-frequency groups. The event rates decreased depending on the frequency, seemingly driven by stepwise event suppression in angiography-guided PCI. In Japanese ACS patients, the incidence of adverse clinical events in patients treated with imaging-guided PCI were significantly lower than that in patients with angiography-guided PCI. Better clinical result was found in the institutions using intravascular imaging more frequently. University Hospital Medical Information Network (UMIN)-CTR ( http://www.umin.ac.jp/ctr/ ). Identifier: KICS (UMIN000015397).

Elevated C-reactive protein is significantly associated with left ventricular dysfunction in patients with aortic regurgitation and concomitant collagen disease.

BACKGROUND: Collagen disease is an important cause of aortic regurgitation (AR). Although aortic valve surgery is recommended for patients with AR and depressed left ventricular (LV) function, there have been few reports about risk factors for LV dysfunction in patients with AR concomitant with collagen disease. METHODS AND RESULTS: We conducted this study at Kumamoto University Hospital in Japan. A total of 41 patients who had moderate to severe AR and concomitant collagen disease between January 2014 and December 2019 were enrolled. With regard to baseline characteristics, there were no significant differences in the type of collagen disease or El Khoury class between patients with preserved LV function and those with reduced LV function. B-type natriuretic peptide (375.2 [257.9-3852.6]pg/ml vs. 64.0 [33.3-133.6]pg/ml, p < 0.01), C-reactive protein (CRP) levels (2.00 [1.24-9.14]mg/dl vs. 0.19 [0.06-0.52]mg/dl, p < 0.01) and neutrophil-to-lymphocyte ratio (7.94 [3.30-9.98] vs. 3.94 [1.83-5.58], p < 0.05) were significantly higher, and hemoglobin level (10.7 ± 1.6 g/dl vs. 12.2 ± 1.8 g/dl, p < 0.05) was significantly lower in patients with reduced LV function than in those with preserved LV function. There were no significant differences in any variables associated with severity and features of AR. Multivariable logistic regression analysis showed that high CRP levels (≥1.0 mg/dl) were independently and significantly associated with LV dysfunction in patients with AR and collagen disease, even after adjusting for the severity of AR (odds ratio: 95.7; 95% confidence interval: 4.6-1990.4, p < 0.01). CONCLUSIONS: Uncontrolled inflammation, represented as high CRP levels, is an important marker for LV dysfunction in patients with AR and collagen disease.

Clinical characteristics and natural history of wild-type transthyretin amyloid cardiomyopathy in Japan.

AIMS: The focus on wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is increasing because of novel treatment options. There is currently no report on a large number of Japanese patients with ATTRwt-CM. The study aimed to examine the characteristics and prognosis of ATTRwt-CM in Japan. METHODS AND RESULTS: Consecutive patients (78.5 ± 6.4 years old at diagnosis) with ATTRwt-CM diagnosed at Kumamoto University Hospital between December 2002 and December 2019 were retrospectively reviewed. Data, including demographic characteristics, co-morbidities, clinical manifestations at diagnosis, laboratory results, electrocardiographic and echocardiographic data, imaging and pathological findings, and treatment were obtained. Of 129 patients included in this study, 110 patients (85%) were male. The median period from initial symptom onset to diagnosis was 15.5 (2-75) months. Heart failure was the most common clinical manifestation leading to diagnosis (61%) and initial manifestations (49%). Of 106 patients, carpal tunnel syndrome was observed in 57 patients (54%), and the median period from initial symptom onset to diagnosis was 96 (48-120) months. Histopathological confirmation of transthyretin amyloid was achieved in 94 patients (73%), including 66 (51%) and 28 cases (22%) with endomyocardial and extracardiac biopsies. During the observation period (median 15.0 [inter-quartile range, 5.4-33.2] months after diagnosis), 34 patients (26%) died. Of these, 27 patients (79%) had cardiovascular deaths (heart failure, 25; sudden death, two). The median survival duration was 58.9 months and the 5 years' survival rate was 48%. According to a multivariate Cox hazard analysis, age [hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.05-1.23, P = 0.002] and low serum sodium levels (HR, 0.89; 95% CI, 0.79-0.996; P = 0.04) contributed to all-cause mortality, and low serum sodium levels contributed to hospitalization for heart failure (HR, 0.86; 95% CI, 0.77-0.96; P = 0.005). CONCLUSIONS: Clinical characteristics and prognosis of ATTRwt-CM patients in Japan were examined. Carpal tunnel syndrome can be considered an indication for diagnosis of ATTRwt-CM. Age and low serum sodium level were significant predictive factors of all survival outcomes. The clinical features of ATTRwt-CM should be recognized to provide appropriate treatment.

Impact of hydrostatic pressure on fractional flow reserve: in vivo experimental study of anatomical height difference of coronary arteries.

BACKGROUND: Although pressure equalization of the sensor-tipped guidewire and systemic pressure is mandatory in measuring fractional flow reserve (FFR), pressure in the distal artery (Pd) with wire advancement can be influenced by hydrostatic pressure related to the height difference between the catheter tip and the distal pressure sensor. We therefore analyzed the impact of hydrostatic pressure on FFR in vivo by modification of the height difference. METHODS: To reveal the anatomical height difference in human coronary arteries, measurement was performed during computed tomography angiography (CTA) of five consecutive patients. Utilizing the healthy coronary arteries of female swine, height difference diversity was reproduced by body rotation and vertical inclination. FFR measurements were performed during maximum hyperemia with adenosine. The height difference was calculated fluoroscopically with a contrast medium-filled balloon for reference. RESULTS: In human coronary CTA, height averages from the ostium in the left anterior descending artery (34.6 mm) were significantly higher than in the left circumflex (-15.5 mm, p = 0.008) and right coronary arteries (-2.3 mm, p = 0.008). In our swine model, reproduced height variation ranged from -7.2 cm to +6.5 cm. Mean FFR was significantly lower in positive sensor height and higher in negative sensor height compared to the reference height. Linear regression analyses revealed significant correlations between height difference and FFR, observed among all coronary arteries, as well as between the height difference and Pd-aortic pressure mismatch. Subtracting 0.622 mmHg/cm height difference from Pd could correct the expected hydrostatic pressure influence. CONCLUSION: Hydrostatic pressure variation resulting from sensor height influenced FFR values might affect interpretation during FFR assessment.

Temporal Change in Longitudinal Strain After Domino Liver Transplantation With Liver Grafts Explanted From Patients With Hereditary Amyloidogenic Transthyretin Amyloidosis.

Background: Using transthoracic echocardiography, including 2D speckle tracking imaging (STI), this study examined cardiac function after domino liver transplantation (DLT) with liver grafts explanted from patients with hereditary amyloidogenic transthyretin amyloidosis. Methods and Results: In all, 14 patients who underwent DLT at Kumamoto University Hospital and for whom 2D STI information was available were enrolled in the study; time-dependent echocardiographic changes were evaluated in 7. Although left ventricular (LV) systolic and diastolic function did not differ between the pre- and post-DLT periods (mean [±SD] 5.4±1.0 years after DLT), there were significant (P<0.05 for all) increases in the post- vs. pre-DLT period in basal longitudinal strain (LS; -13.4±2.3 vs. -19.3±4.4), relative apical LS index (=apical LS/[basal LS+mid LS]; 0.75±0.20 vs. 0.58±0.08), and LV ejection fraction/global LS (3.91±0.58 vs. 3.06±0.44). Age at the time of DLT was significantly higher in the group with impaired (>-14%) than preserved basal LS (57.2±3.5 vs. 39.6±16.0 years; P<0.05). When control subjects (n=14) were added to the enrolled DLT recipients, multivariable logistic regression analysis revealed that a history of DLT was significantly associated with impaired basal LS (>-14%; odds ratio 28.39, 95% confidence interval 1.89-427.45, P<0.05). Conclusions: LV systolic and diastolic function was preserved in the long term after DLT. However, 2D STI revealed subtle cardiac dysfunction in DLT recipients, which may be an early manifestation of cardiac amyloidosis.