Periprocedural Thrombogenicity Change Is Associated With Subclinical Leaflet Thrombosis Progression in Patients Undergoing Transcatheter Aortic Valve Implantation.

Background: Subclinical leaflet thrombosis occasionally occurs after transcatheter aortic valve implantation (TAVI), but its exact etiology and relationship with thrombogenicity remain unknown. Methods and Results: This study enrolled 35 patients who underwent TAVI. Thrombogenicity was evaluated using a total thrombus-formation analysis system (T-TAS) to compute the thrombus-formation area under the curve (PL18-AUC10 and AR10-AUC30). Periprocedural thrombogenic parameters including T-TAS were investigated at pre-TAVI, 2 days, 7 days, and 3 months post-TAVI. Hypoattenuated leaflet thickening (HALT) and maximum leaflet thickness (MLT) were evaluated using contrast-enhanced computed tomography 7 days and 3 months post-TAVI. The associations between thrombogenicity and HALT or MLT were assessed. T-TAS parameters consistently decreased at 2 and 7 days post-TAVI, followed by improvement at 3 months. HALT was detected in 20% and 17% of patients at 7 days and 3 months, respectively, post-TAVI. The median MLT value was 1.60 mm at 7 days and 3 months post-TAVI. A significant positive correlation was observed between the decrease in the AR10-AUC30 and MLT at 7 days post-TAVI. Univariate linear regression analysis revealed a decrease in the AR10-AUC30 and an increase in the D-dimer level as a significant predictor of MLT deterioration. Conclusions: The findings suggested that a transient decrease in thrombogenicity following TAVI predicts leaflet thrombosis, implying that monitoring thrombogenicity may be useful for predicting progression of leaflet thrombosis.

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.

Time-dependent change of relative apical longitudinal strain index in patients with wild-type transthyretin amyloid cardiomyopathy.

Aim: This study was conducted to investigate the meaning of left ventricular (LV) apical sparing in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). Methods and results: 165 patients who were diagnosed with ATTRwt-CM at Kumamoto University Hospital from January 2002 to December 2020 and had sufficient data for two-dimensional speckle tracking echocardiography were enrolled. Of these, 86 patients (52 %) had LV apical sparing (relative apical longitudinal strain index (RapLSI) > 1.0). Multivariable logistic regression analysis revealed the following variables were significantly associated with LV apical sparing: interventricular septal thickness in diastole (odds ratio (OR), 1.19; 95 % confidence interval (CI), 1.01-1.41; p < 0.05); E/e' ratio (OR, 1.06; 95 % CI, 1.00-1.11; p < 0.05); and heart-to-contralateral ratio by 99mTc-labeled pyrophosphate scintigraphy (OR, 3.40; 95 % CI, 1.07-10.83; p < 0.05).Next, we compared RapLSI at the time of diagnosis with that during the follow-up period (396 days (346-458) after diagnosis) in 92 patients. RapLSI increased significantly during the follow-up period compared with RapLSI at diagnosis in the non-LV apical sparing group (0.89 ± 0.32 vs 0.74 ± 0.18, p < 0.01) but not in the LV apical sparing group (1.33 ± 0.53 vs 1.39 ± 0.45, p = 0.46). A total of 12 patients (29 %) in the non-LV apical sparing group developed LV apical sparing and 11 patients (22 %) in LV apical sparing group diminished LV apical sparing during the follow-up period. Conclusion: Approximately half of ATTRwt-CM patients did not have LV apical sparing at diagnosis. Because RapLSI in ATTRwt-CM significantly changed over time, repeated two-dimensional speckle tracking analysis is important for suspected ATTR-CM patients.

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.

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.

HFA-PEFF scores: prognostic value in heart failure with preserved left ventricular ejection fraction.

BACKGROUND/AIMS: The Heart Failure Association (HFA)-PEFF score is recognized as a simple method to diagnose heart failure (HF) with preserved ejection fraction (HFpEF). This study aimed to evaluate the relationship between HFA-PEFF scores and cardiovascular outcomes in HFpEF patients. METHODS: A total of 502 consecutive HFpEF patients were prospectively observed for up to 1,500 days. Cardiovascular outcomes were compared between two groups of patients, defined by their HFA-PEFF scores: those who scored 2-4 (the intermediate-score group) and those who scored 5-6 group (the high-score group). Overall, 236 cardiovascular events were observed during the follow-up period (median, 1,159 days). RESULTS: Kaplan-Meier analysis showed that there were significant differences in composite cardiovascular events and HF-related events between the intermediate-score group and the high-score group (p = 0.003 and p < 0.001, respectively). Multivariate Cox proportional hazards analysis showed that the HFA-PEFF scores significantly predicted future HF-related events (hazard ratio, 1.66; 95% confidence interval [CI], 1.11 to 2.50; p = 0.014); receiver operating characteristic analysis confirmed this relationship (area under the curve, 0.633; 95% CI, 0.574 to 0.692; p < 0.001). The cutoff HFA-PEFF score for the identification of HF-related events was 4.5. Decision curve analysis revealed that combining the HFA-PEFF score with conventional prognostic factors improved the prediction of HF-related events. CONCLUSION: HFA-PEFF scores may be useful for predicting HF-related events in HFpEF patients.

The usefulness of C-reactive protein to predict improving left ventricular function after aortic valve replacement in patients with aortic regurgitation.

Background: We aimed to clarify the predictive factors for left ventricular (LV) function after aortic valve replacement (AVR) in patients with aortic regurgitation (AR). Methods and results: Among 555 patients who underwent AVR at our institution from January 2015 to December 2020, we enrolled 44 patients for whom only AVR (or AVR + aortic replacement) was performed. We defined LV dysfunction under any of the following criteria: LV ejection fraction (LVEF) <50 %, LV diastolic dimension >65 mm, LV systolic dimension (LVDs) >50 mm, or LVDs/body surface area > 25 mm/m2. Multivariable logistic regression analysis revealed high natural logarithm (ln) C-reactive protein (CRP) and low LVEF in the pre-AVR period significantly associated with LV dysfunction after AVR (ln CRP: odds ratio [OR] 4.15, 95 % confidence interval [CI] 1.44-11.98, p < 0.01; LVEF: OR 0.79, 95%CI 0.65-0.97, p < 0.05). Receiver-operating characteristic analysis revealed an area under curve of CRP and LVEF in the pre-AVR period for LV dysfunction after AVR of 0.84 and 0.83, respectively. Upon dividing the patients into four groups according to cutoff values of CRP (0.13 mg/dL) and LVEF (50 %) in the pre-AVR period, no patients (0/19) had LV dysfunction in the low CRP (<0.13 mg/dL) and high LVEF (≥50 %) group, and all patients (5/5) in the high CRP (≥0.13 mg/dL) and low LVEF (<50 %) group had LV dysfunction after AVR. Conclusion: High CRP level was significantly and independently associated with LV dysfunction after AVR. Combination of CRP and LVEF values might be useful for predicting improvement in LV function after AVR.

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.

Prognostic significance of liver stiffness assessed by fibrosis-4 index in patients with heart failure.

BACKGROUND: Heart failure (HF)-related congestive hepatopathy is a well-recognized problem in management of HF. The fibrosis-4 (FIB4) index calculated by [age × aspartate aminotransferase (IU/L)/platelet count (109 /L) × square root of alanine aminotransferase (IU/L)] is useful for evaluating liver stiffness. We aimed to investigate the impact of the FIB4 index on prognosis in patients with HF. METHODS AND RESULTS: Consecutive HF patients referred for hospitalization at Kumamoto University Hospital, Japan, were registered between 2006 and 2015. We observed cardiovascular outcomes in each type of HF [HF with reduced left ventricular ejection fraction (LVEF) (HFrEF), HF with mid-range LVEF (HFmrEF) and with preserved LVEF (HFpEF)] according to their FIB4 index; Group 1 (FIB4 index <1.3), Group 2 (FIB4 index: 1.3-2.67), and Group 3 (FIB4 index >2.67). This study enrolled 83 HFrEF patients, 117 HFmrEF patients, and 504 HFpEF patients. In HFpEF patients, the Kaplan-Meier curve revealed that Group 3 had a significantly higher rate of total cardiovascular events compared with the other two groups. By contrast, the occurrences of total cardiovascular events were not different among three groups in HFrEF and HFmrEF patients. Multivariate Cox proportional hazard analysis with significant factors in univariate analysis identified that the FIB4 index as an independent and significant predictor for future total cardiovascular events in HFpEF patients (hazard ratio: 1.09, 95% confidence interval: 1.03-1.15, P = 0.001). CONCLUSIONS: The FIB4 index was a significant predictor for total cardiovascular events in HFpEF.

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.

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.

The controlling nutritional status score predicts outcomes of cardiovascular events in patients with heart failure with preserved ejection fraction.

BACKGROUNDS: The relationship between cardiovascular outcomes and the Controlling Nutritional Status (CONUT) score in heart failure (HF) with preserved ejection fraction (HFpEF) patients is unknown. This study aimed to evaluate the relationship between the score and cardiovascular outcomes in HFpEF patients. METHODS AND RESULTS: A total of 506 consecutive HFpEF patients were prospectively observed for up to 1500 days or until the occurrence of cardiovascular events. The mean age was 71.6 ± 9.4 years. Cardiovascular outcomes were compared between the CONUT score 0-1 group with a normal nutritional state (normal group), the CONUT score 2-4 group with a light degree of undernutrition (light group), and the CONUT score 5-8 group with a moderate degree of undernutrition (moderate group). In this study, there were no patients who scored 9-12, which was defined as a severe state of undernutrition. Overall, 238 cardiovascular events were observed during the follow-up period (median: 1159 days). Kaplan-Meier analysis showed that the moderate group was at higher risk of composite cardiovascular events than the normal group (P < 0.001) and the light group (P = 0.031). The analysis also showed that the light group was at higher risk of composite cardiovascular events than the normal group (P = 0.038). Multivariable Cox proportional hazards analysis with the significant factors from the univariate analysis showed that the CONUT score (hazard ratio: 1.12, 95% confidence interval: 1.03-1.21, P = 0.005) significantly predicted future cardiovascular events. CONCLUSION: Nutritional screening using the CONUT score may be useful for predicting cardiovascular events in HFpEF patients.