井澤 英夫

OBJECTIVES: A new classification of heart failure based on the effects of medication has recently come into use. According to this classification, heart failure is divided into heart failure with normal ejection fraction (HFnEF; defined as an EF ≥55% for men and ≥60% for women) and non-HFnEF. However, the characteristics of patients with HFnEF are still unclear. Accordingly, in this study, we sought to identify the background characteristics, including non-cardiac factors, of patients with HFnEF. METHODS: We retrospectively divided 304 eligible patients who were hospitalized for worsening heart failure at our institution between December 2020 and December 2022 into an HFnEF group (n=37) and a non-HFnEF group (n=267) and compared their demographic and clinical characteristics. RESULTS: There were more elderly patients in the non-HFnEF group, along with fewer patients with coronary artery disease and low serum hemoglobin and NT-proBNP levels and a higher proportion of patients with a low skeletal muscle index (<7.0 kg/m2 for men and <5.7 kg/m2 for women). Multivariate analysis with addition of patient sex identified a low skeletal muscle index (odds ratio 2.96, p<0.01) to be an independent determinant of HFnEF along with older age and low NT-proBNP. CONCLUSIONS: A low skeletal muscle index was significantly more common in patients with HFnEF than in those with non-HFnEF. Intensive nutrition and exercise therapy to increase skeletal muscle mass may improve the prognosis in patients with HFnEF who respond poorly to standard pharmacological treatment.

Abstract Background Cardiac amyloidosis requires quantitative assessment using technetium-99m pyrophosphate (^99mTc-PYP) single-photon emission computed tomography (SPECT)/computed tomography (CT) for adequate discrimination and evaluation of disease extent. This study aimed to evaluate the utility of standardized uptake value (SUV) analysis using ^99mTc-PYP SPECT/CT in pathologically-confirmed transthyretin amyloid cardiomyopathy (ATTR-CM). The study also explored the relationship between local uptake heterogeneity and indicators of cardiac impairment. Methods Forty patients diagnosed via heart biopsy and genetic analysis (20 ATTR-CM; 4 light-chain amyloidosis, 16 non-amyloidosis) were enrolled. The mean SUVs of the heart and aorta were measured using SPECT images. Discrimination performance was evaluated by comparing each SUV, the heart-to-aorta ratio (rSUV_H/Ao), and the heart-to-contralateral-lung ratio with pathological findings serving as the gold standard. Polar maps were analyzed to assess local SUV distribution in patients with ATTR-CM. The coefficient of variation (COV) of myocardial uptake, difference score between the septum and lateral wall (%DS), base-to-apex variability, and total cardiac SUV were calculated and compared with echocardiographic parameters. Results All metrics were significantly different between the ATTR-CM and non-amyloidosis groups. The rSUV_H/Ao effectively differentiated patients with ATTR-CM from those with light-chain or non-amyloidosis. Local myocardial SUV distribution correlated with impaired cardiac function. Notably, COV showed significant correlations with e' (R = 0.782) and E/e' (R =  − 0.625), linking heterogeneity to myocardial stiffness and diastolic dysfunction. Larger %DS, which predominantly reflected the ATTR-CM pattern of high septal uptake, correlated significantly with thinner walls (average wall thickness, R =  − 0.655; relative wall thickness, R =  − 0.486). As the total cardiac SUV increased, the %DS decreased (reflecting more homogeneous distribution), and global longitudinal strain worsened (R = 0.614). These observations indicated that greater impairment was associated with a higher disease burden. Conclusions This study demonstrated that quantitative SPECT analysis provides a valuable tool for the diagnostic evaluation and differentiation of ATTR-CM. The rSUV_H/Ao offers high discriminatory performance. Local heterogeneity and total myocardial uptake are closely related to the disease burden and extent, as reflected by structural and functional abnormalities on echocardiography. These findings suggest potential relevance to the non-invasive assessment of these aspects of the disease at a single time point. Graphical abstract

OBJECTIVE: To directly compare coronary arterial stenosis evaluations by hybrid-type iterative reconstruction (IR), model-based IR (MBIR), deep learning reconstruction (DLR), and high-resolution deep learning reconstruction (HR-DLR) on coronary computed tomography angiography (CCTA) in both in vitro and in vivo studies. MATERIALS AND METHODS: For the in vitro study, a total of three-vessel tube phantoms with diameters of 3 mm, 4 mm, and 5 mm and with simulated non-calcified stepped stenosis plaques with degrees of 0%, 25%, 50%, and 75% stenosis were scanned with area-detector CT (ADCT) and ultra-high-resolution CT (UHR-CT). Then, ADCT data were reconstructed using all methods, although UHR-CT data were reconstructed with hybrid-type IR, MBIR, and DLR. For the in vivo study, patients who had undergone CCTA at ADCT were retrospectively selected, and each CCTA data set was reconstructed with all methods. To compare the image noise and measurement accuracy at each of the stenosis levels, image noise, and inner diameter were evaluated and statistically compared. To determine the effect of HR-DLR on CAD-RADS evaluation accuracy, the accuracy of CAD-RADS categorization of all CCTAs was compared by using McNemar's test. RESULTS: The image noise of HR-DLR was significantly lower than that of others on ADCT and UHR-CT (p < 0.0001). At a 50% and 75% stenosis level for each phantom, hybrid-type IR showed a significantly larger mean difference on ADCT than did others (p < 0.05). At in vivo study, 31 patients were included. Accuracy on HR-DLR was significantly higher than that on hybrid-type IR, MBIR, or DLR (p < 0.0001). CONCLUSION: HR-DLR is potentially superior for coronary arterial stenosis evaluations to hybrid-type IR, MBIR, or DLR shown on CCTA. KEY POINTS: Question How do coronary arterial stenosis evaluations by hybrid-type IR, MBIR, DLR, and HR-DLR compare to coronary CT angiography? Findings HR-DLR showed significantly lower image noise and more accurate coronary artery disease reporting and data system (CAD-RADS) evaluation than others. Clinical relevance HR-DLR is potentially superior to other reconstruction methods for coronary arterial stenosis evaluations, as demonstrated by coronary CT angiography results on ADCT and as shown in both in vitro and in vivo studies.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease that occasionally affects the heart and poses the risks of arrhythmias, heart failure, and sudden cardiac death. CASE SUMMARY: We report a rare case of cardiac sarcoidosis presenting as a large intracardiac mass in a 76-year-old woman that was incidentally detected during a health check-up. Transthoracic echocardiography revealed a 25× 33 mm mobile mass in the left atrium. Cardiac magnetic resonance and 18F-fluorodeoxyglucose positron emission tomography/computed tomography demonstrated heterogeneous enhancement and increased metabolic activity, respectively, raising the suspicion of cardiac sarcoidosis. Bronchoscopic biopsy confirmed the presence of epithelioid granulomas, supporting the diagnosis. Surgical resection was performed because of the size of the mass and the potential for mitral valve obstruction. Histopathology confirmed the presence of non-caseating granulomas consistent with sarcoidosis. Postoperatively, corticosteroid therapy with prednisolone (initially 30 mg/day, tapered to 5 mg/day) was initiated to treat the residual lesions identified on imaging. The residual mass showed regression, with resolution of inflammatory activity, through the use of steroid therapy during follow-up. DISCUSSION: This case report highlights the diagnostic and therapeutic challenges associated with cardiac sarcoidosis presenting as a large intracardiac mass. Our findings underscore the importance of a multidisciplinary approach that utilises advanced imaging techniques, histological confirmation, and tailored management strategies that combine surgical intervention and immunosuppressive therapy for diagnosis and treatment.

BACKGROUND: The efficacy of intravenous steroids (IS) for fulminant myocarditis (FMP) remains controversial. We aimed to compare outcomes in FMP patients who received IS [IS(+)] and those who did not [IS(-)]. METHODS AND RESULTS: Data from 344 patients with histologically confirmed FMP requiring catecholamines or mechanical support were extracted from the Japanese Registry of Fulminant Myocarditis. The primary outcome was a composite of 90-day mortality and heart transplantation. Among the patients (median age 54, 40 % female), 195 received IS, 98 died within 90 days, and 16 died or underwent transplantation after 90 days. The IS(+) group had lower left ventricular ejection fraction and lower ratio of lymphocytic myocarditis, higher use of intra-aortic balloon pumping, Venoarterial extracorporeal membrane oxygenation (VA-ECMO), and intravenous immunoglobulin. Crude analysis showed worse 90-day outcomes in the IS(+) group (36.3 % vs. 19.2 %, P = 0.0021); however, after propensity score matching (PSM), outcomes were similar (26.2 % vs. 24.2 %; P = 0.95). Unadjusted Cox regression indicated worse outcomes with IS (HR 1.95, 95 % CI 1.26-3.04; P = 0.0026), but this was not significant after PSM (HR 1.02, 95 % CI 0.56-1.87; P = 0.95). Among low-risk patients, the IS(-) group showed better outcomes than the IS(+) group post-PSM (P = 0.0031). In the patients with VA-ECMO or ventricular assist devices, early IS (within 2 days of admission) showed comparable prognosis to delayed/no IS, with a trend toward better outcomes post-PSM. CONCLUSIONS: IS effectiveness in FMP patients may vary, showing limited prognostic benefit overall. Careful consideration is warranted in its use for this population.

OBJECTIVES: This study aimed to measure right atrial (RA) strain in the reservoir, conduit, and contraction phases and examine its clinical utility in detecting pulmonary hypertension (PH). METHODS: One hundred and thirteen patients hospitalized in the intensive or coronary care units of our institution who underwent echocardiography and measurements of RA/right ventricular (RV) strain were retrospectively examined. RA strain was measured in the reservoir, conduit, and contraction phases of one cardiac cycle. PH was defined as peak tricuspid regurgitation velocity >2.8 m/s. Patients were grouped according to PH status (PH, no PH) and statistically compared. Logistic regression and receiver operating characteristic analyses were also performed. RESULTS: Mean age was 71.1±15.4 years and 72 were men (63.7%). The PH and no PH groups comprised 40 and 73 patients, respectively. Among the RA strain parameters, RA strain in the conduit phase was significantly lower in the PH group (-8.1±4.2% vs. -17.4±7.7%; p<0.001). In the receiver operating characteristic analysis for PH, RA strain in the conduit phase had the highest area under the curve among the RA/RV strain parameters (area under the curve, 0.88; sensitivity, 92.5%; specificity, 71.2%; p<0.001). CONCLUSIONS: RA strain is an echocardiographic parameter that can detect PH and should be considered when RV strain parameters are not measurable.

BACKGROUND: The effect of worsening renal function and baseline chronic kidney disease (CKD) on outcomes in patients with chronic coronary syndrome in the setting of optimal medical therapy remains unknown. METHODS AND RESULTS: The REAL-CAD (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease) study is a prospective, multicenter, randomized trial of high-dose (pitavastatin 4 mg/day) or low-dose (pitavastatin 1 mg/day) statin therapy in 12 118 patients with chronic coronary syndrome. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, or unstable angina requiring hospitalization (major adverse cardiac and cerebral events [MACCE]). CKD was defined as an estimated glomerular filtration rate [eGFR] <60 mL/min per 1.73 m2. WRF was defined as a decrease in eGFR ≥20% in the initial year; borderline renal function was an annual decrease of 0%<eGFR<20%, and stable renal function was no decrease. Of 12 118 patients, 4340 had baseline CKD and 7778 did not. The rate of MACCE at 5 years was significantly lower in those without (5.5%) versus with CKD (9.5%) (P<0.0001). After excluding 1247 patients who had MACCE, were censored, or missing eGFR within 1 year, 10 871 patients were included. Of these, 3885 were baseline CKD and the remaining 6986 did not have baseline CKD. Of the 10 871 patients, 577 patients had WRF, 6014 patients showed borderline renal function, and the remaining 4280 patients maintained stable renal function. In patients with CKD, WRF was an independent predictor for MACCE at 4 years as compared with stable renal function (hazard ratio [HR]: 1.67; [95% CI, 1.03-2.73; P=0.039]). In patients without CKD, borderline renal function was a significant predictor for MACCE at 4 years compared with stable renal function (HR: 1.40 [95% CI, 1.03-1.91; P=0.032]). CONCLUSIONS: Baseline CKD was an independent predictor for MACCE in patients with CCS. WRF was a significant predictor for MACCE in patients with CKD. Because borderline renal function was an independent predictor for MACCE even in patients without CKD, mild-to-moderate annual declines of eGFR should be carefully monitored (NCT01042730). REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT01042730.

Slow-flow or no-reflow phenomenon is a common procedural complication during percutaneous coronary intervention (PCI). Given the presence of fragile plaque or thrombotic materials, we hypothesized that long-time predilatation using a perfusion balloon in conjunction with intracoronary nicorandil administration reduces the risk of slow-flow or no-reflow in patients presenting with acute coronary syndrome (ACS). Subjects were patients presenting with ACS who underwent PCI between April 2020 and April 2022. We retrospectively investigated the incidence of slow-flow or no-reflow during the procedure as well as in-hospital outcomes in comparison between the cases undergoing 3-min predilatation using a perfusion balloon in conjunction with intracoronary nicorandil administration followed by DES implantation (PB group) and those with direct stenting (DS group). Among 439 ACS patients, 36 patients in the PB group and 51 patients in the DS group were examined. Mean age was 70 years and 78.2% was male. Distal protection devices were more frequently used in the DS group than in the PB group (31.3% vs. 11.1%, p = 0.02). The incidence rate of slow-flow or no-reflow was significantly lower in the PB group than in the DS group (2.8% vs. 23.5%; p < 0.01). Six cases (11.7%) in the DS group required intra-aortic balloon pumping (IABP), while none in the PB group required (p < 0.01). In-hospital clinical outcomes did not differ between the two groups. Prolonged perfusion balloon predilatation in conjunction with intracoronary nicorandil administration was safe and feasible. This novel strategy could be an attractive alternative to conventional direct stenting for ACS patients.

Preexisting cardiovascular disease (CVD) is a pivotal risk factor for severe coronavirus disease 2019 (COVID-19). We investigated the longitudinal (over 1 year and 9 months) humoral and cellular responses to primary series and booster doses of mRNA COVID-19 vaccines in patients with CVD. Twenty-six patients with CVD who received monovalent mRNA COVID-19 vaccines were enrolled in this study. Peripheral blood samples were serially drawn nine times from each patient. IgG against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) was measured using an enzyme-linked immunosorbent assay. The numbers of interferon-γ-releasing cells in response to SARS-CoV-2 peptides were measured using an enzyme-linked immunospot assay. The RBD-IgG titers increased 2 weeks after the primary series and booster vaccination and waned 6 months after vaccination. The S1-specific T cell responses in patients aged &lt; 75 years were favorable before and after booster doses; however, the Omicron BA.1-specific T cell responses were poor. These results suggest that regular vaccination is useful to maintain long-term antibody levels and has implications for booster dose strategies in patients with CVD. Additional booster doses, including Omicron variant-adapted mRNA vaccines, may be recommended for patients with CVD, regardless of age.

The CHA2DS2 -VASc score is a vital clinical tool for evaluating thromboembolic risk in patients with atrial fibrillation (AF). This study investigated the efficacy of the CHA2DS2 -VASc score in a cohort of 737 heterogeneous patients (mean age: 63 years) receiving care in cardiac intensive care units (CICUs), with a creatinine-based estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m2 upon admission and discharge. Incident chronic kidney disease (CKD) was defined as the emergence of a new-onset eGFR<60 mL/min/1.73 m2, accompanied by a decline of >5 mL/min/1.73 m2 compared to that at discharge. The primary endpoint was the incidence of CKD, and the secondary endpoints included all-cause mortality, cardiovascular events, and progression to end-stage kidney disease. In this cohort, 210 (28 %) patients developed CKD. Multivariate analyses revealed that CHA2DS2 -VASc score was a significant independent predictor of incident CKD, regardless of the presence of AF. Integration of CHA2DS2 -VASc scores with eGFR enhanced the predictive accuracy of incident CKD, as evidenced by the improved C-index, net reclassification improvement, and integrated discrimination improvement values (all p < 0.05). Over the 12-month follow-up period, a composite endpoint was observed in 61 patients (8.3 %), with elevated CHA2DS2 -VASc scores being independently associated with this endpoint. In conclusion, CHA2DS2-VASc scores have emerged as robust predictors of both CKD incidence and adverse outcomes. Their inclusion substantially refined the 12-month risk stratification of patients with preserved renal function hospitalized in the CICUs.

OBJECTIVES: Evaluation of in-stent restenosis (ISR), especially for small stents, remains challenging during computed tomography (CT) angiography. We used deep learning reconstruction to quantify stent strut thickness and lumen vessel diameter at the stent and compared it with values obtained using conventional reconstruction strategies. METHODS: We examined 166 stents in 85 consecutive patients who underwent CT and invasive coronary angiography (ICA) within 3 months of each other from 2019-2021 after percutaneous coronary intervention with coronary stent placement. The presence of ISR was defined as percent diameter stenosis ≥ 50% on ICA. We compared a super-resolution deep learning reconstruction, Precise IQ Engine (PIQE), and a model-based iterative reconstruction, Forward projected model-based Iterative Reconstruction SoluTion (FIRST). All images were reconstructed using PIQE and FIRST and assessed by two blinded cardiovascular radiographers. RESULTS: PIQE had a larger full width at half maximum of the lumen and smaller strut than FIRST. The image quality score in PIQE was higher than that in FIRST (4.2 ± 1.1 versus 2.7 ± 1.2, p < 0.05). In addition, the specificity and accuracy of ISR detection were better in PIQE than in FIRST (p < 0.05 for both), with particularly pronounced differences for stent diameters < 3.0 mm. CONCLUSION: PIQE provides superior image quality and diagnostic accuracy for ISR, even with stents measuring < 3.0 mm in diameter. CLINICAL RELEVANCE STATEMENT: With improvements in the diagnostic accuracy of in-stent stenosis, CT angiography could become a gatekeeper for ICA in post-stenting cases, obviating ICA in many patients after recent stenting with infrequent ISR and allowing non-invasive ISR detection in the late phase. KEY POINTS: • Despite CT technology advancements, evaluating in-stent stenosis severity, especially in small-diameter stents, remains challenging. • Compared with conventional methods, the Precise IQ Engine uses deep learning to improve spatial resolution. • Improved diagnostic accuracy of CT angiography helps avoid invasive coronary angiography after coronary artery stenting.

OBJECTIVE: To examine the clinical outcomes of optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) in patients presenting with ST-segment elevation myocardial infarction (STEMI). METHODS: We retrospectively investigated 533 consecutive patients who underwent primary PCI for STEMI between June 2016 and December 2020. The primary endpoint was a target lesion failure (TLF; defined as a composite of cardiac death, target vessel myocardial infarction, or target lesion revascularization). Propensity score (PS) matching was performed to allow direct comparison of OCT-guided and intravascular ultrasound (IVUS)-guided PCI. RESULTS: Patients in the OCT group (n=166) were younger than those in the IVUS group (n=367) and had a significantly higher left ventricular ejection fraction and estimated glomerular filtration rate. Killip class IV and left main stem disease were more common in the IVUS group. The median peak creatine kinase level was comparable between the two groups (1953 U/L vs 1603 U/L). A significantly larger amount of contrast was used in the OCT group (200 mL vs 165 mL; p<0.001). The cumulative incidence of TLF during a median follow-up of 2.2 years did not differ significantly between OCT and IVUS groups (9.6% vs 13.6%; p=0.221) but cardiac mortality was significantly higher in the IVUS group (8.7% vs 3.6%; p=0.047). After PS matching (n=161 in each group), there was no significant between-group difference in TLF or any other clinical outcome measures. CONCLUSIONS: OCT-guided PCI demonstrated clinical outcomes in patients with STEMI that were comparable to those of IVUS-guided PCI despite considerable differences in background characteristics.

The renal angina index (RAI) is a validated scoring tool for predicting acute kidney injury (AKI). We investigated the efficacy of the RAI in 2436 heterogeneous patients (mean age, 70 years) treated in cardiac intensive care units (CICUs). The RAI was calculated from creatinine and patient condition scores. AKI was diagnosed by the Kidney Disease: Improving Global Outcome criteria. The primary and secondary endpoints were the development of severe AKI and all-cause mortality, respectively. Four hundred thirty-three patients developed AKI, 87 of them severe. In multivariate analyses, the RAI was a significant independent predictor of severe AKI. During the 12-month follow-up period, 210 patients suffered all-cause death. Elevated RAI was independently associated with all-cause mortality, as was NT-proBNP (p < 0.001). The RAI is a potent predictor not only of severe AKI but also of adverse outcomes and substantially improved the 12-month risk stratification of patients hospitalized in CICUs.

OBJECTIVES: We aimed to identify which resting echocardiographic parameters can detect asymptomatic or mildly symptomatic patients with primary mitral regurgitation (MR) who require exercise stress echocardiography (ESE) to determine their suitability for surgery. METHODS: We examined 56 consecutive patients with primary moderate/severe MR who underwent ergometer-based ESE. Patients who met the surgical indications at rest were excluded. Eligible patients were divided into Group I (pulmonary artery systolic pressure [PASP] during exercise >60 mmHg; n=11) and Group II (PASP during exercise ≤60 mmHg; n=30). RESULTS: Forty-one patients were included. Group I was significantly older (65±12 vs. 54±14 years, P=0.042) and had significantly higher serum N-terminal pro-B-type natriuretic peptide concentrations than Group II (351±278 vs. 125±163 pg/mL, P=0.002). The univariate analysis demonstrated that peak E wave velocity (Group I vs. Group II: 125±45 vs. 101±24 cm/sec, P=0.050), left ventricular (LV) end-diastolic diameter index (32±4 vs. 30±3 mm/m2, P=0.035), and left atrial volume index (LAVI; 45±14 vs. 30±11 mL/m2, P=0.008) were predictors of increased PASP during exercise. In the multivariate analysis, resting LAVI best predicted exercise-induced pulmonary hypertension (hazard ratio 1.081 [95% confidence interval 1.009-1.158], P=0.028), with a cutoff value of 37 mL/m2. CONCLUSIONS: In asymptomatic or mildly symptomatic patients with primary moderate/severe MR, increased resting LAVI indicates the requirement for ESE, even without LV dilatation.

INTRODUCTION: Coronary computed tomography angiography (CCTA) is known to have a high negative predictive value (NPV) in identifying coronary artery disease (CAD). This study aimed to examine whether resting echocardiographic parameters could exclude significant CAD on CCTA. METHODS: We recruited 142 patients who had undergone both CCTA and echocardiography within a 3-month window. Based on the CCTA findings, patients were divided into two groups: Group A (non-significant CAD, defined as all coronary segments having <50% stenosis) and Group B (significant CAD). Resting echocardiographic parameters were compared between the two groups to identify predictors of non-significant CAD on CCTA. RESULTS: A total 92 patients (mean age, 68 ± 13 years; males, 62%) were eligible for this study; 50 in Group A and 42 in Group B. Among the various echo parameters, left atrial volume index (LAVI) and left ventricular (LV) global longitudinal strain (GLS) were significantly lower in Group A (23.5 ± 7.6 vs. 33.6 ± 7.4 mL/m2 , p < .001; -20.2 ± 1.8% vs. -16.8 ± 2.0%, p < .001, respectively). Analysis of the receiver operating characteristic curve revealed that the cutoff value to exclude significant CAD on CCTA was 29.0 mL/m2 for LAVI (NPV 80.8%) and -18.1% for GLS (NPV 80.7%). The NPV increased to 95.0% when these parameters were combined (LAVI < 29.0 mL/m2 and GLS < -18.1%). CONCLUSION: The combination of resting LAVI and GLS was clinically useful in excluding significant CAD via CCTA.

The purposes of the present study were: (1) to investigate the relationship between hospital-associated functional decline (HAFD) and non-lying time and (2) to clarify the optimal cut-off value for non-lying time associated with HAFD in older patients undergoing transcatheter aortic valve implantation (TAVI). From January 2021 to December 2022, patients admitted to a university hospital who underwent trans-femoral TAVI were consecutively recruited. We measured short physical performance battery (SPPB) pre and post-TAVI, and non-lying time from post-operative days 3-5. HAFD was defined as at least 1 point decrease in SPPB during pre and post-TAVI. Among 75 patients (47 female, mean age of 84.5 years) enrolled, 14 patients were classified as having HAFD. Non-lying time was significantly shorter in the HAFD group than in the non-HAFD group (371 min vs. 539 min, P < 0.001). Receiver-operating characteristic analysis determined an optimal cut-off value of 477 min for differentiating the patients more likely to experience HAFD (sensitivity, 75%; specificity, 92%; area under the curve, 0.798). The non-lying time could be one of the associated factors of HAFD in older patients with TAVI. Non-lying time of about 480 min (8 h) during hospitalization may be an initial target for preventing HAFD.

BACKGROUND: Coronary computed tomography angiography (CTA) followed by computed tomography angiography-derived fractional flow reserve (FFRCT) is now commonly used for the management of chronic coronary syndrome (CCS). CTA-verified high-risk plaque (HRP) characteristics have also been reported to be associated with a greater likelihood of adverse cardiac events but have not been used for management decisions. OBJECTIVES: The aim of this study was to evaluate clinical outcomes based on a combination of point-of-care computed tomography angiography-derived fractional flow reserve (POC-FFRCT) and the presence of HRP in CCS patients initially treated medically or with revascularization based on invasive coronary angiography findings. METHODS: CTA was performed as the initial test in 5,483 patients presenting with CCS between September 2015 and December 2020 followed by invasive coronary angiography and revascularization as necessary. POC-FFRCT assessment and HRP characterization were obtained subsequently in 745 consecutive patients. We investigated how HRP and POC-FFRCT, which were not available during the original clinical decision making, correlated with the endpoint defined as a composite of cardiac death, acute coronary syndrome, and a need for unplanned revascularization. RESULTS: Cardiac events occurred in 20 patients (2.7%) during a median follow-up of 744 days. The event rate was significantly higher in patients with POC-FFRCT <0.80 compared with POC-FFRCT ≥0.8 (5.4 vs 0.5 per 100 vessel years; log-rank P < 0.0001) and in patients with HRP compared to those without HRP (3.6 vs 0.8 per 100 vessel years; log-rank P = 0.0001). POC-FFRCT <0.80 and the presence of HRP were the independent predictors of cardiac events (HR: 16.67; 95% CI: 2.63-105.39; P = 0.002) compared with POC-FFRCT ≥0.8 and absent HRP. For the vessels with POC-FFRCT <0.80 and HRP, a significantly higher rate of adverse events was observed in patients who did not undergo revascularization compared with those revascularized (16.4 vs 1.4 per 100 vessel years; log-rank P = 0.006). CONCLUSIONS: POC-FFRCT <0.80 and the presence of HRP were the independent predictors of cardiac events, and revascularization of HRP lesions with abnormal POC-FFRCT was associated with a lower event rate.

OBJECTIVES: Malnutrition is associated with an increased risk of hospital readmission for heart failure in patients with acute decompensated heart failure (ADHF). Therefore, evaluation of the nutritional status in patients with ADHF may be important. The geriatric nutritional risk index (GNRI), the controlling nutritional status (CONUT) score, and the prognostic nutritional index (PNI) are widely used objective indexes for evaluation of the nutritional status. The present study was performed to determine the best nutritional index for predicting the prognosis in older adults with ADHF. METHODS: We retrospectively studied 167 older adults (>65 years of age) who were admitted with ADHF from January 2012 to December 2015 and discharged alive. The objective nutritional status was evaluated using the GNRI, CONUT score, and PNI at admission. The endpoint of this study was unplanned hospitalization for worsening heart failure (WHF) within 1 year after discharge. RESULTS: During the follow-up period, 58 patients were readmitted for WHF. In the multivariate Cox analysis, only the GNRI (p<0.0001) was independently associated with readmission for WHF among the three nutritional indexes. Kaplan-Meier analysis revealed that patients in the low-GNRI group (<90 as determined by receiver operating characteristic curve analysis) had a significantly greater risk of 1-year hospital readmission for WHF (p<0.0001; hazard ratio, 6.1; 95% confidence interval, 3.5-10.5). CONCLUSION: Among the objective nutritional indexes, the GNRI is the best predictor of readmission for WHF within 1 year after discharge in older adults with ADHF.

BACKGROUND Guideline-recommended therapies that improve prognosis remain underused in clinical practice. Physical frailty may lead to underprescription of life-saving therapy. We aimed to investigate the association between physical frailty and the use of evidence-based pharmacological therapy for heart failure with reduced ejection fraction and the impact of this on prognosis. METHODS AND RESULTS The FLAGSHIP (Multicentre Prospective Cohort Study to Develop Frailty-Based Prognostic Criteria for Heart Failure Patients) included patients hospitalized for acute heart failure, and data on physical frailty were collected prospectively. We analyzed 1041 patients with heart failure with reduced ejection fraction (aged 70 years; 73% male) and divided them by physical frailty categories using grip strength, walking speed, Self-Efficacy for Walking-7 score, and Performance Measures for Activities of Daily Living-8 score: categories I (n=371; least frail), II (n=275), III (n=224), and IV (n=171). Overall prescription rates of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and mineralocorticoid receptor antagonists were 69.7%, 87.8%, and 51.9%, respectively. The proportion of patients receiving all 3 drugs decreased as physical frailty increased (in category I patients, 40.2%; IV patients, 23.4%; P for trend<0.001). In adjusted analyses, the severity of physical frailty was an independent predictor for nonuse of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (odds ratio [OR], 1.23 [95% CI, 1.05-1.43] per 1 category increase) and β-blockers (OR, 1.32 [95% CI, 1.06-1.64]), but not mineralocorticoid receptor antagonists (OR, 0.97 [95% CI, 0.84-1.12]). Patients receiving 0 to 1 drug had a higher risk of the composite outcome of all-cause death or heart failure rehospitalization than those treated with 3 drugs in physical frailty categories I and II (hazard ratio [HR], 1.80 [95% CI, 1.08-2.98]) and III and IV (HR, 1.53 [95% CI, 1.01-2.32]) in the multivariate Cox proportional hazard model. CONCLUSIONS Prescription of guideline-recommended therapy decreased as severity of physical frailty increased in heart failure with reduced ejection fraction. Underprescription of guideline-recommended therapy may contribute to the poor prognosis associated with physical frailty.

UNLABELLED: We report a case of cardiac recovery from coronavirus disease 2019 (COVID-19)-associated fulminant myocarditis in a 48-year-old woman diagnosed with COVID-19 infection 4 days before, whose hemodynamic collapse were resuscitated first with venoarterial extracorporeal membranous oxygenation, followed by escalation to extracorporeal biventricular assist devices (ex-BiVAD) using two centrifugal pumps and an oxygenator. She was likely to be multisystem inflammatory syndrome in adults (MIS-A) negative. Cardiac contractility gradually recovered after the 9th day of ex-BiVAD support, and the patient was successfully weaned from ex-BiVAD on the 12th day of support. Due to postresuscitation encephalopathy, she was transferred to the referral hospital for rehabilitation with recovered cardiac function. The histopathology of the myocardial tissue showed smaller amounts of lymphocytes and more infiltration of macrophages. It is important to recognize two phenotypes of MIS-A+ or MIS-A-, with distinct manifestations and outcomes. It is also important to refer urgently such patients with COVID-19-associated fulminant myocarditis, showing different histopathology from usual viral myocarditis, with evolution toward refractory cardiogenic shock to a center with capability for advanced mechanical support to avoid a too-late cannulation. LEARNING OBJECTIVE: We should recognize the clinical course and histopathology of the multisystem inflammatory syndrome in adults phenotype of coronavirus disease 2019-associated fulminant myocarditis. We should urgently refer such patients with evolution toward refractory cardiogenic shock to a center with capability for advanced mechanical support, such as venoarterial extracorporeal membrane oxygenation, Impella (Abiomed, Danvers, MA, USA), and extracorporeal biventricular assist devices.

AIMS: This study aimed to determine the new cut-off value of serum angiotensin-converting enzyme (ACE) levels for detecting patients with sarcoidosis and to examine the change in ACE levels after the initiation of immunosuppressive therapy. METHODS AND RESULTS: We retrospectively examined patients in whom serum ACE levels were measured for suspected sarcoidosis between 2009 and 2020 in our institution. For patients diagnosed with sarcoidosis, changes in ACE levels were also observed. Of the 3781 patients (51.1% men, 60.1 ± 17.0 years old), 477 were excluded for taking ACE inhibitors and/or immunosuppression agents or those with any diseases affecting serum ACE levels. In 3304 patients including 215 with sarcoidosis, serum ACE levels were 19.6 IU/L [interquartile range, 15.1-31.5] in patients with sarcoidosis and 10.7 [8.4-16.5] in those without sarcoidosis (P < 0.01), and the best cut-off value was 14.7 IU/L with 0.865 of the area under the curves. Compared with the current ACE cut-off of 21.4, the sensitivity improved from 42.3 to 78.1 at the new cut-off, although specificity slightly decreased from 98.6 to 81.7. The ACE level significantly decreased more in those with immunosuppression therapy than in those without it (P for interaction <0.01), although it decreased in both groups (P < 0.01). CONCLUSIONS: Because the sensitivity for detecting sarcoidosis is comparatively low at the current standard value, further examinations are needed for patients suspected of sarcoidosis with relatively high ACE levels in the normal range. In patients with sarcoidosis, ACE levels decreased after the initiation of immunosuppression therapy.

BACKGROUND: Left ventricular (LV) global longitudinal strain (GLS) has emerged as a more sensitive index than LV ejection fraction (LVEF) for detecting subclinical LV dysfunction. We examined whether changes in GLS values are associated with the long-term prognosis of patients with a preserved LVEF and acute decompensated heart failure (HF). METHODS: We studied 100 consecutive patients (mean age: 71 years) who were hospitalized for HF with preserved ejection fraction (HFpEF) and had a preserved LVEF (≥ 50%) in both the acute and stable phases. We performed two-dimensional speckle-tracking echocardiography in the acute (GLS-acute) and stable (GLS-stable) phases at a median of 2 and 347 days after admission, respectively, and calculated the rate of change of the absolute value of GLS-stable with respect to that of GLS-acute. An improved GLS was defined as a rate of change in GLS ≥ 16%, and a non-improved GLS was a rate of change < 16%. The primary endpoint was the occurrence of major cardiovascular events (MACE). RESULTS: During a mean follow-up period of 1218 days, MACE occurred in 26 patients, including 8 all-cause deaths and 18 readmissions for HF. The rate of change in GLS for patients with MACE was lower than compared to those without MACE (10.6% vs 26.0%, p < 0.001). Multivariate Cox regression analyses indicated the rate of change in GLS was an independent predictor of MACE (p < 0.001). A non-improved GLS was correlated with a high risk of MACE. CONCLUSION: Changes in GLS values could be useful for the long-term risk stratification of patients hospitalized for HFpEF and persistently preserved LVEF.

BACKGROUND: This study compares the efficacy of coronary computed tomography angiography (CCTA) and near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) in patients with significant coronary stenosis for predicting periprocedural myocardial injury during percutaneous coronary intervention (PCI). METHODS: We prospectively enrolled 107 patients who underwent CCTA before PCI and performed NIRS-IVUS during PCI. Based on the maximal lipid core burden index for any 4-mm longitudinal segments (maxLCBI4mm) in the culprit lesion, we divided the patients into two groups: lipid-rich plaque (LRP) group (maxLCBI4mm ≥ 400; n = 48) and no-LRP group (maxLCBI4mm < 400; n = 59). Periprocedural myocardial injury was a postprocedural cardiac troponin T (cTnT) elevation of ≥5 times the upper limit of normal. RESULTS: The LRP group had a significantly higher cTnT (p = 0.026), lower CT density (p < 0.001), larger percentage atheroma volume (PAV) by NIRS-IVUS (p = 0.036), and larger remodeling index measured by both CCTA (p = 0.020) and NIRS-IVUS (p < 0.001). A significant negative linear correlation was found between maxLCBI4mm and CT density (rho = -0.552, p < 0.001). Multivariable logistic regression analysis identified maxLCBI4mm [odds ratio (OR): 1.006, p = 0.003] and PAV (OR: 1.125, p = 0.014) as independent predictors of periprocedural myocardial injury, while CT density was not an independent predictor (OR: 0.991, p = 0.22). CONCLUSION: CCTA and NIRS-IVUS correlated well to identify LRP in culprit lesions. However, NIRS-IVUS was more competent in predicting the risk of periprocedural myocardial injury.