A new staging system using right atrial strain in patients with immunoglobulin light-chain cardiac amyloidosis.

AIMS: There are minimal data on the prognostic impact of right atrial strain during the reservoir phase (RASr) in patients with immunoglobulin light-chain (AL) cardiac amyloidosis. METHODS AND RESULTS: Among 78 patients who were diagnosed with AL cardiac amyloidosis at Kumamoto University Hospital from 2007 to 2022, 72 patients with sufficient two-dimensional speckle tracking imaging data without chemotherapy before the diagnosis were retrospectively analysed. During a median follow-up of 403 days, 31 deaths occurred. Age and the rate of male sex were not significantly different between the all-cause death group and the survival group (age, 70.4 ± 8.8 years vs. 67.0 ± 10.0 years, P = 0.14, male sex, 65% vs. 66%, P = 0.91). The estimated glomerular filtration rate (eGFR) was significantly lower, and B-type natriuretic peptide (BNP) and high sensitivity cardiac troponin T (hs-cTnT) were significantly higher, in the all-cause death group versus the survival group (eGFR, 48.2 ± 21.0 mL/min/1.73 m2 vs. 59.4 ± 24.4 mL/min/1.73 m2, P < 0.05, BNP, 725 [360-1312] pg/mL vs. 123 [81-310] pg/mL, P < 0.01, hs-cTnT, 0.12 [0.07-0.18] ng/mL vs. 0.05 [0.03-0.08] ng/mL, P < 0.01). Left ventricular (LV) global longitudinal strain (GLS) (LV-GLS), left atrial strain during the reservoir phase (LASr), right ventricular GLS (RV-GLS), and RASr were significantly lower in the all-cause death group versus the survival group (LV-GLS, 8.5 ± 4.3% vs. 11.8 ± 3.8%, P < 0.01, LASr, 8.8 ± 7.1% vs. 14.3 ± 8.1%, P < 0.01, RV-GLS, 11.6 ± 5.1% vs. 16.4 ± 3.9%, P < 0.01, RASr, 10.2 ± 7.3% vs. 20.7 ± 9.5%, P < 0.01). RASr was significantly associated with all-cause death after adjusting for RV-GLS, LV-GLS and LASr (hazard ratio [HR]: 0.91, 95% confidence interval [95% CI]: 0.83-0.99, P < 0.05). RASr and log-transformed BNP were significantly associated with all-cause death after adjusting for log-transformed troponin T and eGFR (RASr, HR: 0.93, 95% CI: 0.87-1.00, P < 0.05; log-transformed BNP, HR: 2.10, 95% CI: 1.17-3.79, P < 0.05). The optimal cut-off values were RASr: 16.4% (sensitivity: 66%, specificity: 84%, area under curve [AUC]: 0.81) and BNP: 311.2 pg/mL (sensitivity: 83%, specificity: 78%, AUC: 0.82) to predict all-cause mortality using ROC analysis. Kaplan-Meier analysis revealed that patients with low RASr (<16.4%) or high BNP (>311.2 pg/mL) had a significantly high probability of all-cause death (both, P < 0.01). We devised a new staging score by adding 1 point if RASr decreased or BNP levels increased more than each cut-off value. The HR for all-cause death using score 0 as a reference was 5.95 (95% CI: 1.19-29.79; P < 0.05) for score 1 and 23.29 (95% CI: 5.37-100.98; P < 0.01) for score 2. CONCLUSIONS: The new staging system using RASr and BNP predicted prognosis in patients with AL cardiac amyloidosis.

Prognostic Significance of Soluble PD-L1 on Cardiovascular Outcomes in Patients with Coronary Artery Disease.

AIMS: Programmed cell death-1 (PD-1) and its ligand (PD-L1) regulate T cells, leading to immunotolerance. We previously demonstrated that patients with coronary artery disease (CAD) had increased circulating levels of soluble PD-L1 (sPD-L1). However, the prognostic significance of sPD-L1 on cardiovascular outcomes is unknown. In the present study, we evaluated the association between sPD-L1 and cardiovascular events in patients with CAD. METHODS: We prospectively measured sPD-L1 in patients with CAD admitted to Kumamoto University Hospital between December 2017 and January 2020 and observed their cardiovascular event rate. The primary outcome was a composite of death from non-cardiovascular causes, death from cardiovascular causes, non-fatal myocardial infarction, unstable angina pectoris, revascularization, hospitalization for heart failure, and ischemic stroke. RESULTS: Finally, 627 patients were enrolled, and 35 patients were lost to follow-up. The median follow-up duration was 522 days. In total, 124 events were recorded. The Kaplan-Meier curve showed that the event rate was higher in the higher sPD-L1 group (median ≥ 136 pg/dL) than in the lower sPD-L1 group (25.0% vs. 16.9%; p=0.028, log-rank test). Univariate Cox proportional hazards analysis showed that high-sensitivity C-reactive protein, an estimated glomerular filtration rate of ＜60 mL/min/1.73m2, B-type natriuretic peptide, left ventricular ejection fraction, and sPD-L1 were significantly associated with cardiovascular events. Multivariable Cox proportional hazards analysis of factors that were significant in univariate analysis identified that sPD-L1 was significantly and independently associated with cardiovascular events (hazard ratio: 1.364, 95% confidence interval: 1.018-1.828, p=0.038). CONCLUSIONS: Higher sPD-L1 levels were significantly associated with future cardiovascular events in patients with CAD.

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 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.

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.

Coronary Stent Evaluation by CTA: Image Quality Comparison Between Super-Resolution Deep Learning Reconstruction and Other Reconstruction Algorithms.

BACKGROUND. A super-resolution deep learning reconstruction (SR-DLR) algorithm may provide better image sharpness than earlier reconstruction algorithms and thereby improve coronary stent assessment on coronary CTA. OBJECTIVE. The purpose of our study was to compare SR-DLR and other reconstruction algorithms in terms of image quality measures related to coronary stent evaluation in patients undergoing coronary CTA. METHODS. This retrospective study included patients with at least one coronary artery stent who underwent coronary CTA between January 2020 and December 2020. Examinations were performed using a 320-row normal-resolution scanner and were reconstructed with hybrid iterative reconstruction (HIR), model-based iterative reconstruction (MBIR), normal-resolution deep learning reconstruction (NR-DLR), and SR-DLR algorithms. Quantitative image quality measures were determined. Two radiologists independently reviewed images to rank the four reconstructions (4-point scale: 1 = worst reconstruction, 4 = best reconstruction) for qualitative measures and to score diagnostic confidence (5-point scale: score ≥ 3 indicating an assessable stent). The assessability rate was calculated for stents with a diameter of 3.0 mm or less. RESULTS. The sample included 24 patients (18 men, six women; mean age, 72.5 ± 9.8 [SD] years), with 51 stents. SR-DLR, in comparison with the other reconstructions, yielded lower stent-related blooming artifacts (median, 40.3 vs 53.4-58.2), stent-induced attenuation increase ratio (0.17 vs 0.27-0.31), and quantitative image noise (18.1 vs 20.9-30.4 HU) and higher in-stent lumen diameter (2.4 vs 1.7-1.9 mm), stent strut sharpness (327 vs 147-210 ΔHU/mm), and CNR (30.0 vs 16.0-25.6) (all p < .001). For both observers, all ranked measures (image sharpness; image noise; noise texture; delineation of stent strut, in-stent lumen, coronary artery wall, and calcified plaque surrounding the stent) and diagnostic confidence showed a higher score for SR-DLR (median, 4.0 for all features) than for the other reconstructions (range, 1.0-3.0) (all p < .001). The assessability rate for stents with a diameter of 3.0 mm or less (n = 37) was higher for SR-DLR (86.5% for observer 1 and 89.2% for observer 2) than for HIR (35.1% and 43.2%), MBIR (59.5% and 62.2%), and NR-DLR (62.2% and 64.9%) (all p < .05). CONCLUSION. SR-DLR yielded improved delineation of the stent strut and in-stent lumen, with better image sharpness and less image noise and blooming artifacts, in comparison with HIR, MBIR, and NR-DLR. CLINICAL IMPACT. SR-DLR may facilitate coronary stent assessment on a 320-row normal-resolution scanner, particularly for small-diameter stents.

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.

Japanese high bleeding risk criteria status predicts low thrombogenicity and bleeding events in patients undergoing percutaneous coronary intervention.

Although the Japanese high bleeding risk criteria (J-HBR) were established to predict bleeding risk in patients undergoing percutaneous coronary intervention (PCI), the thrombogenicity in the J-HBR status remains unknown. Here, we examined the relationships among J-HBR status, thrombogenicity and bleeding events. This study was a retrospective analysis of 300 consecutive patients who underwent PCI. Blood samples obtained on the day of PCI were used in the total thrombus-formation analysis system (T-TAS) to investigate the thrombus-formation area under the curve (AUC; PL18-AUC10 for platelet chip; AR10-AUC30 for atheroma chip). The J-HBR score was calculated by adding 1 point for any major criterion and 0.5 point for any minor criterion. We assigned patients to three groups based on J-HBR status: a J-HBR-negative group (n = 80), a low score J-HBR-positive group (positive/low, n = 109), and a high score J-HBR-positive group (positive/high, n = 111). The primary end point was the 1-year incidence of bleeding events defined by the Bleeding Academic Research Consortium types 2, 3, or 5. Both PL18-AUC10 and AR10-AUC30 levels were lower in the J-HBR-positive/high group than the negative group. Kaplan-Meier analysis showed worse 1-year bleeding event-free survival in the J-HBR-positive/high group compared with the negative group. In addition, both T-TAS levels in J-HBR positivity were lower in those with bleeding events than in those without bleeding events. In multivariate Cox regression analyses, the J-HBR-positive/high status was significantly associated with 1-year bleeding events. In conclusion, the J-HBR-positive/high status could reflect low thrombogenicity as measured by T-TAS and high bleeding risk in patients undergoing PCI.

Differential effects of overweight/obesity depending on the severity of heart failure complicating acute myocardial infarction in Japan.

BACKGROUND: The existence of a paradoxical association between overweight/obesity and survival benefits, the so-called obesity paradox, in heart failure (HF) as well as coronary artery disease (CAD) remains contentious. Previously, we reported that a past history of CAD negated the obesity paradox in the general population with acute HF. Herein, we further focused on HF complicating acute myocardial infarction (AMI) and compared the prognostic effects of overweight/obesity with respect to the severity of HF. METHODS: We conducted a multicenter retrospective study of 7265 consecutive patients with AMI. The severity of HF was categorized according to the Killip classification. Overweight/obesity was defined as a body mass index (BMI) of ≥25 kg/m2. The interaction between overweight/obesity and the Killip classification for in-hospital mortality was tested in the entire cohort. Multivariable logistic regression analyses were performed to examine the effects of overweight/obesity on in-hospital mortality. RESULTS: Across the entire study cohort, 1931 patients had HF. Overweight/obesity had a significant association with reductions in in-hospital mortality in patients with mild HF (Killip class II; odds ratio [OR], 0.284; P = 0.019). Conversely, overweight/obesity was a significant risk factor for in-hospital mortality in patients with severe HF (Killip class IV; OR, 2.152; P = 0.001). The effects of overweight/obesity on in-hospital mortality in patients with moderate HF (Killip class III) were intermediate between those with mild HF and severe HF. CONCLUSION: Opposing effects of overweight/obesity on in-hospital mortality in patients with mild HF versus severe HF were demonstrated, suggesting a balance between beneficial and deleterious effects of overweight/obesity may be inclined toward the latter with the severity of HF complicating AMI.

Discordance between fractional flow reserve and instantaneous wave-free ratio in patients with severe aortic stenosis: A retrospective cohort study.

BACKGROUND: Discordance between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) occurs in approximately 20 % of cases. However, no studies have reported the discordance in patients with severe aortic stenosis (AS). We aimed to evaluate the diagnostic discordance between FFR and iFR in patients with severe AS. METHODS: We examined 140 consecutive patients with severe AS (164 intermediate coronary artery stenosis vessels). FFR and iFR were calculated in four quadrants based on threshold FFR and iFR values of ≤0.8 and ≤0.89, respectively (Group 1: iFR >0.89, FFR >0.80; Group 2: iFR ≤0.89, FFR >0.80; Group 3: iFR >0.89, FFR ≤0.80; and Group 4: iFR ≤0.89, FFR ≤0.80). Concordant groups were Groups 1 and 4, and discordant groups were Groups 2 and 3. Positive and negative discordant groups were Groups 3 and 2, respectively. RESULTS: The median (Q1, Q3) FFR and iFR were 0.84 (0.76, 0.88) and 0.85 (0.76, 0.91), respectively. Discordance was observed in 48 vessels (29.3 %). In the discordant group, negative discordance (Group 2: iFR ≤0.89 and FFR >0.80) was predominant (45 cases, 93.6 %). Multivariate analysis showed that the left anterior descending artery [odds ratio (OR), 3.88; 95 % confidence interval (CI): 1.54-9.79, p = 0.004] and peak velocity ≥5.0 m/s (OR, 3.21; 95%CI: 1.36-7.57, p = 0.008) were independently associated with negative discordance (FFR >0.8 and iFR ≤0.89). CONCLUSIONS: In patients with severe AS, discordance between FFR and iFR was predominantly negative and observed in 29.3 % of vessels. The left anterior descending artery and peak velocity ≥5.0 m/s were independently associated with negative discordance.

Effect of the ALDH2 Variant on the Prevalence of Atrial Fibrillation in Habitual Drinkers.

Background: Alcohol-a risk factor for atrial fibrillation (AF)-is metabolized by aldehyde dehydrogenase 2 (ALDH2). Dysfunctional alleles of ALDH2 (ALDH2-deficient variants) are prevalent among East Asians. Objectives: Because the prevalence of AF is estimated to be high in ALDH2-deficient variant carriers, we investigated the correlation between AF and ALDH2-deficient variant carriers, including the association with habitual alcohol consumption. Methods: A total of 656 consecutive patients were included in this investigation. ALDH2 genotypes were divided into ALDH2 homozygous wild-type (∗1/∗1), ALDH2 heterozygous-deficient allele (∗1/∗2), and ALDH2 homozygous-deficient allele (∗2/∗2). Multivariate analyses were applied to determine the correlation between ALDH2 genotype and AF. Results: ALDH2∗1/∗2 and ALDH2∗2/∗2 carriers who were ALDH2-deficient variant carriers comprised 199 (30.3%) and 27 (4.1%) patients, respectively. Among these patients, the proportions of habitual alcohol consumption were 26.1% and 0%, respectively. Multivariate analysis revealed that ALDH2∗1/∗2 itself was not a risk factor for AF (odds ratio [OR]: 1.28; P = 0.21). However, habitual alcohol consumption in ALDH2∗1/∗2 carriers was an independent risk factor of AF (OR: 4.13; P = 0.001). Contrary to expectations, ALDH2∗2/∗2 itself had a lower incidence of AF among other risk factors (OR: 0.37; P = 0.03). Conclusions: Although the ALDH2∗1/∗2 itself was not associated with AF, ALDH2∗1/∗2 carriers with habitual alcohol consumption could experience AF because of slow alcohol metabolism. In contrast, ALDH2∗2/∗2 itself had a lower incidence of AF. This might be related to the absence to habitual alcohol consumption in ALDH2∗2/∗2 carriers because of the negligible activity of ALDH2. Thus, abstaining from alcohol consumption might prevent the development of AF in patients who are ALDH2∗1/∗2 carriers.

Transcatheter Edge-to-Edge Repair for Atrial Secondary Mitral Regurgitation.

BACKGROUND: Atrial secondary mitral regurgitation (ASMR) is a subtype of SMR that has a poor prognosis, and thus far, evidence of the therapeutic options for the management of ASMR is limited. OBJECTIVES: This study aimed to investigate the effectiveness of transcatheter edge-to-edge repair (TEER) for ASMR. METHODS: The study retrospectively analyzed consecutive patients who underwent MitraClip at the Heart Center Bonn. ASMR was defined as cases that met all of the following criteria: 1) normal mitral leaflets without organic disorder; 2) left ventricular ejection fraction >50%; and 3) absence of LV enlargement and segmental abnormality. The primary outcome measure was MR reduction to ≤1+, and its predictors were explored in a logistic regression analysis. RESULTS: Among 415 patients with SMR, 118 patients met the criteria for ASMR (mean age 80 ± 8 years, 39.8% male). The technical success rate was 94.1%, and MR reduction to ≤1+ after TEER was achieved in 94 (79.7%) patients with ASMR. The in-hospital mortality rate was 2.5%. In multivariable logistic analysis, a large left atrial volume index and low leaflet-to-annulus index were associated with a lower incidence of MR reduction to ≤1+ after TEER for ASMR. In addition, the use of a newer generation of the MitraClip systems (NTR/XTR or G4 systems) was associated with a higher incidence of MR reduction to ≤1+. CONCLUSIONS: TEER is a safe and feasible therapeutic option for patients with ASMR. Assessments of left atrial volume index and leaflet-to-annulus index may assist with patient selection for TEER in patients with ASMR.

Longer leukocyte telomere length is associated with myeloid inflammation and increased mortality after transcatheter aortic valve replacement.

Aims: Inflammatory activation of leukocytes may limit prognosis of patients (pts) with severe aortic valve stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Leukocyte telomere length (LTL) is a marker of proliferative capacity and inflammatory responsiveness but the impact of LTL on the prognosis in AS remains elusive. The aim of this study was to analyse the association of LTL with inflammatory markers and prognosis of pts undergoing TAVR. Methods and results: LTL was analysed using quantitative real-time PCR in 285 consecutive pts (median age 82 years) undergoing TAVR and correlated with 18-month all-cause mortality. C-reactive protein was significantly elevated in pts with the longest LTL (P = 0.017), paralleled by increased procalcitonin (PCT) serum levels (P = 0.0006). This inflammatory reaction was accompanied by increased myeloid cells in the highest LTL tertile, mainly a rise in circulating neutrophils (P = 0.0025) and monocytes (P = 0.01). Multivariate analysis revealed LTL (HR 2.6, 95%CI 1.4-5.1, P= 0.004) and PCT levels (HR 4.3, 95%CI 1.7-11.0, P = 0.003) as independent predictors of mortality. Conclusions: Longer LTL is associated with increased mortality after TAVR. This might be explained by enhanced proliferative capacity of cells resulting in myeloid and systemic inflammation. Our findings suggest that targeting the specific inflammation pathways could present a novel strategy to augment survival in selected patients with degenerative aortic stenosis.

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.

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.

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.

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.

Recurrent Mitral Regurgitation After MitraClip: Predictive Factors, Morphology, and Clinical Implication.

BACKGROUND: Recurrent mitral regurgitation (MR) following MitraClip has not been thoroughly investigated. We aimed to examine the predictive factors, morphology, and long-term outcome of recurrent MR after MitraClip. METHODS: We assessed data from the Heart Failure Network Rhineland registry from August 2010 to October 2018. Competing risk analyses were performed using the Fine and Gray model to assess the risk of recurrent MR. RESULTS: Among 685 MitraClip patients with a reduction in MR to ≤2+, 61 patients developed recurrent MR within the first 12 months. Flail leaflet (hazard ratio, 3.68; P=0.002) and residual MR (MR grade 2+ versus ≤1+: hazard ratio, 2.56; P=0.03) were the predictors of recurrent MR in primary MR patients, while left atrial volume (per 10 mL increase: hazard ratio, 1.11; P<0.001) and residual MR (hazard ratio, 2.45; P=0.01) were independently associated with recurrent MR in secondary MR patients. In primary MR patients, loss of leaflet insertion or leaflet tear were the predominant morphologies with recurrent MR. In secondary MR patients, more than half of the patients with recurrent MR did not show any disorder of the clip or leaflets. Patients with recurrent MR were more likely to experience unplanned heart failure hospitalization or heart failure symptom with New York Heart Association scale III/IV (54.1% versus 37.8%; P=0.018) and undergo a repeat mitral valve intervention (9.8% versus 2.2%; P=0.005) during the follow-up. In the landmark survival analysis, patients with recurrent MR tended to have lower long-term survival (58.7% versus 83.9%; P=0.08) than patients without recurrent MR. CONCLUSIONS: Flail leaflet and residual MR were the predictors of recurrent MR in primary MR patients, while a larger left atrial volume and residual MR were associated with recurrent MR in secondary MR patients, which may be associated with long-term clinical outcomes of patients after MitraClip.

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.