Objective Myocardial energy metabolism is impaired in heart failure (HF), but the in vivo relationship between myocardial triglyceride (MTG) accumulation and fatty acid utilization remains unclear. Proton magnetic resonance spectroscopy ( 1 H-MRS) quantifies MTG, while iodine-123-β-methyl-p-iodophenyl-pentadecanoic acid ( 123 I-BMIPP) scintigraphy assesses myocardial fatty acid uptake and turnover (early heart-to-mediastinum ratio [H/M(e)] and washout rate [WR]). We investigated associations between MTG accumulation and 123 I-BMIPP-derived metabolic parameters in chronic HF patients. Methods Consecutive chronic HF patients (n = 33; mean age 62.8 ± 14.1 years) were prospectively enrolled between September 2020 and January 2024 during a stable phase. All patients underwent 123 I-BMIPP SPECT imaging (acquisition at 20 and 180 minutes post-injection) to calculate H/M(e) and WR, and cine cardiac MRI (1.5T) to measure left ventricular (LV) volumes, ejection fraction, and mass. MTG content was quantified by 1 H-MRS. Results WR did not correlate with any clinical or imaging parameters. In contrast, H/M(e) was significantly correlated with LV volume (r=-0.402, p = 0.020) and mass (r=-0.427, p = 0.013). MTG content was not related to 123 I-BMIPP-derived measures or LV function, but correlated significantly with immunoreactive insulin (IRI; r = 0.641, p = 0.0002) and HOMA-IR (r = 0.589, p = 0.001). No correlations were found among WR, H/M(e), and MTG. Conclusions Comprehensive assessment of myocardial fatty acid metabolism using 123 I-BMIPP scintigraphy and 1 H-MRS in patients with chronic heart failure suggested that WR, H/M(e), and MTG may reflect distinct metabolic stages. These parameters provide independent and complementary information and may contribute to a better understanding of heart failure pathophysiology, as well as to diagnostic support and prognostic assessment.

Background: Left ventricular ejection fraction (LVEF) is the most commonly clinically used imaging parameter for assessing cancer therapy-related cardiac dysfunction (CTRCD). However, LVEF declines may occur late, after substantial injury. This study sought to investigate cardiovascular magnetic resonance (CMR) imaging markers of subclinical cardiac injury in a miniature swine model. Methods: Female Yucatan miniature swine (n = 14) received doxorubicin (2 mg/kg) every 3 weeks for 4 cycles. CMR, including cine, tissue characterization via T-1 and T-2 mapping, and late gadolinium enhancement (LGE) were performed on the same day as doxorubicin administration and 3 weeks after the final chemotherapy cycle. In addition, magnetic resonance spectroscopy (MRS) was performed during the 3 weeks after the final chemotherapy in 7 pigs. A single CMR and MRS exam were also performed in 3 Yucatan miniature swine that were age- and weight-matched to the final imaging exam of the doxorubicin-treated swine to serve as controls. CTRCD was defined as histological early morphologic changes, including cytoplasmic vacuolization and myofibrillar loss of myocytes, based on post-mortem analysis of humanely euthanized pigs after the final CMR exam. Results: Of 13 swine completing 5 serial CMR scans, 10 (77%) had histological evidence of CTRCD. Three animals had neither histological evidence nor changes in LVEF from baseline. No absolute LVEF <40% or LGE was observed. Native T-1, extracellular volume (ECV), and T-2 at 12 weeks were significantly higher in swine with CTRCD than those without CTRCD (1178 ms vs. 1134 ms, p = 0.002, 27.4% vs. 24.5%, p = 0.03, and 38.1 ms vs. 36.4 ms, p = 0.02, respectively). There were no significant changes in strain parameters. The temporal trajectories in native T-1, ECV, and T-2 in swine with CTRCD showed similar and statistically significant increases. At the same time, there were no differences in their temporal changes between those with and without CTRCD. MRS myocardial triglyceride content substantially differed among controls, swine with and without CTRCD (0.89%, 0.30%, 0.54%, respectively, analysis of variance, p = 0.01), and associated with the severity of histological findings and incidence of vacuolated cardiomyocytes. Conclusion: Serial CMR imaging alone has a limited ability to detect histologic CTRCD beyond LVEF. Integrating MRS myocardial triglyceride content may be useful for detection of early potential CTRCD.

Summary Triglyceride deposit cardiomyovasculopathy (TGCV) is an intractable disease characterized by massive triglyceride (TG) accumulation in the myocardium and coronary arteries caused by genetic or acquired dysfunction of adipose TG lipase (ATGL). A phase IIa trial has been conducted involving patients with idiopathic TGCV using CNT-01 (tricaprin/trisdecanoin) by the Japan TGCV study group, which showed that CNT-01 improved myocardial lipolysis as demonstrated by iodine-123-beta-methyl iodophenyl-pentadecanoic acid (BMIPP) scintigraphy. We evaluated changes in myocardial TG content using proton magnetic resonance spectroscopy (1H-MRS) before/after CNT-01. This report describes a male patient with hypertension, diabetes, angina pectoris, repeated percutaneous coronary intervention, chest pain, and exertional dyspnea that persisted despite standard medications and nitroglycerin. Idiopathic TGCV was diagnosed based on a remarkably reduced washout rate (WR) for BMIPP scintigraphy, high myocardial TG content on 1H-MRS, and no ATGL mutation. After an 8-week, 1.5 g/day CNT-01 administration, the WR of BMIPP increased from 5.1 to 13.3% and the myocardial TG content decreased from 8.4 to 5.9%, with no adverse effects. CNT-01 corrected myocardial lipolysis and subsequently reduced TG content in idiopathic TGCV as evaluated using 1H-MRS, which may be a useful, noninvasive evaluation of therapeutic efficacy. Learning points Triglyceride deposit cardiomyovasculopathy (TGCV) is an intractable disease characterized by massive triglyceride accumulation in the myocardium and coronary arteries, caused by genetic or acquired dysfunction of adipose triglyceride lipase. Japan TGCV Study Group developed a specific treatment for idiopathic TGCV using CNT-01 (tricaprin/trisdecanoin), a type of medium-chain fatty acid. CNT-01 corrected myocardial lipolysis and reduced TG content in idiopathic TGCV using proton magnetic resonance spectroscopy, which may be a useful noninvasive evaluation of therapeutic efficacy.

Myocardial perfusion assessment using cardiac MRI allows non-invasive assessment of myocardial ischemia. In myocardial perfusion sequence, imaging is collected after a saturation pulse. An alternative approach based on steady-state imaging with radial sampling has been recently proposed. However, image reconstruction using compressed sensing in steady-state myocardial perfusion remains long and clinically not feasible. In this study, we sought to develop a deep learning-based image reconstruction platform for myocardial perfusion imaging.

An 81-year-old woman with a medical history of type 2 diabetes mellitus and diabetic nephropathy was admitted with a diagnosis of multiple cerebellar infarctions. Proteinuria and leg edema were observed on the day after admission and diagnosed as nephrotic syndrome. Furosemide and spironolactone were started but showed no diuretic effect, and the renal function deteriorated. These agents were then replaced with dapagli-flozin, which resulted in a positive diuretic effect and subsequent improvement of hypoalbuminemia and re-nal dysfunction. This case report demonstrates the utility of dapagliflozin for nephrotic syndrome to achieve a positive diuretic effect and improve hypoalbuminemia without deteriorating the renal function.

Although cardiac metastasis of malignant tumors has often been reported, undifferentiated uterine sarcoma (UUS) is a rare and aggressive uterine tumor. Thus, little is known of the UUS as a primary site of cardiac metastasis. We report a case of a 66-year-old woman, with a history of uterine myoma for 30 years, who was hospitalized with a large uterine tumor and cardiac masses. Although we investigated cardiac masses using imaging modalities, such as ultrasound, cardiac computer tomography, and magnetic resonance imaging, it was challenging to determine the masses as metastasis or thrombi. Cardiac masses were removed by surgery to assess the tissue characteristics and were later identified as tumors due to their appearance. Then, pathological findings revealed that UUS spreads to the right ventricle. We attempted chemotherapy after surgery; however, the disease progressed very quickly and the patient died on the 49th day of admission. In this report, we described the case of a patient with a difficult diagnosis and rapid disease progression of cardiac metastasis from UUS.

Background Exercise cardiovascular magnetic resonance (Ex-CMR) is a promising stress imaging test for coronary artery disease (CAD). However, Ex-CMR requires accelerated imaging techniques that result in significant aliasing artifacts. Our goal was to develop and evaluate a free-breathing and electrocardiogram (ECG)-free real-time cine with deep learning (DL)-based radial acceleration for Ex-CMR. Methods A 3D (2D + time) convolutional neural network was implemented to suppress artifacts from aliased radial cine images. The network was trained using synthetic real-time radial cine images simulated using breath-hold, ECG-gated segmented Cartesian k-space data acquired at 3 T from 503 patients at rest. A prototype real-time radial sequence with acceleration rate = 12 was used to collect images with inline DL reconstruction. Performance was evaluated in 8 healthy subjects in whom only rest images were collected. Subsequently, 14 subjects (6 healthy and 8 patients with suspected CAD) were prospectively recruited for an Ex-CMR to evaluate image quality. At rest ( n = 22), standard breath-hold ECG-gated Cartesian segmented cine and free-breathing ECG-free real-time radial cine images were acquired. During post-exercise stress ( n = 14), only real-time radial cine images were acquired. Three readers evaluated residual artifact level in all collected images on a 4-point Likert scale (1-non-diagnostic, 2-severe, 3-moderate, 4-minimal). Results The DL model substantially suppressed artifacts in real-time radial cine images acquired at rest and during post-exercise stress. In real-time images at rest, 89.4% of scores were moderate to minimal. The mean score was 3.3 ± 0.7, representing increased (P < 0.001) artifacts compared to standard cine (3.9 ± 0.3). In real-time images during post-exercise stress, 84.6% of scores were moderate to minimal, and the mean artifact level score was 3.1 ± 0.6. Comparison of left-ventricular (LV) measures derived from standard and real-time cine at rest showed differences in LV end-diastolic volume (3.0 mL [− 11.7, 17.8], P = 0.320) that were not significantly different from zero. Differences in measures of LV end-systolic volume (7.0 mL [− 1.3, 15.3], P < 0.001) and LV ejection fraction (− 5.0% [− 11.1, 1.0], P < 0.001) were significant. Total inline reconstruction time of real-time radial images was 16.6 ms per frame. Conclusions Our proof-of-concept study demonstrated the feasibility of inline real-time cine with DL-based radial acceleration for Ex-CMR.

Mid-aortic syndrome (MAS) is a rare vascular disorder that causes refractory hypertension. A 76-year-old woman was hospitalized for acute heart failure (HF) with drug-resistant hypertension; other comorbidities included epigastric artery rupture, old myocardial infarction, an intraventricular thrombus, and a cerebral artery aneurysm. Angiography revealed severe narrowing of the descending aorta, which led to the diagnosis of MAS. Although intensive medical treatment improved her HF, optimal blood pressure (BP) could not be achieved. Percutaneous coronary intervention and surgical bypass for diseased aorta was then performed in two stages, resulting in the achievement of optimal BP and alleviation of HF.

Abstract Asymmetric septal hypertrophy (ASH) is the most common phenotype of hypertrophic cardiomyopathy (HCM). However, the difference between myocardial metabolism and myocardial features such as myocardial fibrosis and myofiber disarray in HCM remains unclear. Cardiac magnetic resonance (CMR) and proton magnetic resonance spectroscopy (1H-MRS) were performed on 16 patients diagnosed as HCM with ASH to assess the differences in myocardial features and morphology. There were 7 patients who had LGE in ASH localized with the voxel of 1H-MRS. The LV ejection fraction was significantly lower in the LGE (+) group than in the LGE (−) group (64.8% ± 4.9% vs. 72.1% ± 3.8%, P = 0.004). LV end-systolic volume was significantly greater in the LGE (+) group than in the LGE (−) group (51 ± 11 ml vs. 33 ± 12 ml, P = 0.007). A significant difference in MTG content was observed between patients in the LGE (+) group and in the LGE (−) group (0.58% ± 0.22% vs 1.29% ± 0.73%, P = 0.03). MTG content was significantly associated with LV ejection fraction, LV end systolic volume, and LV mass. In multivariate analyses, LV ejection fraction had an independent association with MTG content (P = 0.01) Our data suggest that the metabolism of the septum in HCM with ASH may be different based on the absence or presence of LGE and that measurement of MTG content by 1H-MRS may be useful to evaluate the characteristics of myocardial metabolic changes caused by the LV remodeling process in HCM. (248 words)

The patient was a 73-year-old man with a history of hypertension, diabetes mellitus, dyslipidemia, rheumatoid arthritis, repeated percutaneous coronary intervention and percutaneous peripheral intervention procedures. He was frequently admitted to our hospital for congestive heart failure with orthopnea. The myocardial washout rate of iodine-123-β-methyl iodophenyl-pentadecanoic acid was defective on scintigraphy. He was diagnosed with triglyceride deposit cardiomyovasculopathy (TGCV). Proton magnetic resonance spectroscopy (1H-MRS) indicated the level of myocardial triglyceride (TG) content to be extremely high (4.92%). This is the first report to confirm a massive accumulation of TG in the myocardium of a patient with TGCV using 1H-MRS noninvasively.

Triglyceride deposit cardiomyovasculopathy (TGCV) is a phenotype primarily reported in patients carrying genetic mutations in PNPLA2 encoding adipose triglyceride lipase (ATGL) which releases long chain fatty acid (LCFA) as a major energy source by the intracellular TG hydrolysis. These patients suffered from intractable heart failure requiring cardiac transplantation. Moreover, we identified TGCV patients without PNPLA2 mutations based on pathological and clinical studies . We provided the diagnostic criteria, in which TGCV with and without PNPLA2 mutations were designated as primary TGCV (P-TGCV) and idiopathic TGCV (I-TGCV), respectively. We hereby report clinical profiles of TGCV patients. Between 2014 and 2018, 7 P-TGCV and 18 I-TGCV Japanese patients have been registered in the International Registry. Patients with I-TGCV, of which etiologies and causes are not known yet, suffered from adult-onset severe heart disease, including heart failure and coronary artery disease, associated with a marked reduction in ATGL activity and myocardial washout rate of LCFA tracer, as similar to those with P-TGCV. The present first registry-based study showed that TGCV is an intractable, at least at the moment, and heterogeneous cardiovascular disorder.

Introduction: Hypertrophic cardiomyopathy (HCM) is a diverse clinical and pathophysiologic entity that mainly involves the left ventricle (LV).It is caused by asymmetric or concentric hypertrophy of unknown cause.However, the difference in myocardial features associated with HCM depending on morphological disparity remains unclear. Purpose:The aim of this study is to assess differences in myocardial features in patients with HCM with asymmetric or without asymmetric hypertrophy.Method: Cardiac and proton magnetic resonance spectroscopy were performed to assess LV function, wall thickness, LV mass, extent of late gadolinium enhancement (LGE), and myocardial triglyceride (MTG) content in the septum of 32 patients diagnosed with HCM.Patients were divided into two groups: with or without asymmetric hypertrophy (ASH and non-ASH groups, respectively).Asymmetric hypertrophy was defined as asymmetric septal hypertrophy (ASH), which is measured as ≥1.3 of the echocardiographic interventricular septum to LV free wall thickness ratio.Result: Sixteen patients had ASH.LGE was detected in 20 patients with HCM, whereas LGE in the septum was detected in 12.Although no significant difference in MTG content was found between patients with (1.55% ± 1.03%) and without (1.03% ± 0.83%) septal LGE in the non-ASH group, a significant difference was observed in the MTG content between patients with (0.58% ± 0.22%) and without (1.29%± 0.73%) septal LGE in the ASH group (P = 0.03).In the non-ASH group, MTG content was not significantly associated with LV mass and diastolic parameters.Conversely, MTG content was significantly associated with LV mass (r = -0.49,P = 0.03) in the ASH group. Conclusion:The association between LGE and MTG was different in patients with HCM with or without ASH.Our data suggested that the MTG metabolism of the septum in HCM may be different based on the absence or presence of asymmetric hypertrophy.

Restless legs syndrome (RLS), characterized by leg restlessness and dysesthesia predominantly at night and at rest, disrupts sleep and quality of life. The reported prevalence of RLS is 2% to 5 %. Although a relation between RLS and coronary artery disease has been suggested, the prevalence and clinical significance of RLS in coronary artery disease patients remain unknown. We enrolled coronary artery disease patients who underwent percutaneous coronary intervention. Patients with RLS were identified according to international criteria. Subjective sleepiness, sleep quality, and health-related quality of life were assessed using the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, and Short Form-8, respectively. Among 326 patients with coronary artery disease, 26 (8.0%) had RLS. There were no significant differences in characteristics between patients with and without RLS. Sleep quality and quality of life were more disrupted in patients with RLS (Pittsburgh Sleep Quality Index score, 7.4 +/- 2.4 vs 5.6 +/- 2.5, p < 0.001; physical component summary and mental component summary scores of Short Form-8, 39.6 +/- 1.8 vs 43.5 +/- 0.5, p = 0.042 and 45.2 +/- 8.4 vs 48.4 +/- 7.4, p = 0.037, respectively), despite no significant difference in Epworth Sleepiness Scale score (8.2 +/- 5.1 vs 7.1 +/- 4.8, p = 0.293). In multiple linear regression analyses, RLS was independently associated with Pittsburgh Sleep Quality Index (beta = 0.174, p < 0.001), physical component summary (beta = -0.127, p = 0.029), and mental component summary (beta = -0.113, p = 0.042) scores. In conclusion, in patients with coronary artery disease, the prevalence of RLS was relatively high compared to that reported in the general population. The presence of RLS was associated with disrupted sleep quality and health-related quality of life in coronary artery disease patients. (C) 2019 Elsevier Inc. All rights reserved.

BACKGROUND:Restless legs syndrome (RLS) is a neurological disorder characterized by leg restlessness and dysesthesia. Although the relationship between RLS and heart failure (HF) has been reported, the prevalence and clinical significance of RLS in patients with HF remain to be elucidated. METHODS AND RESULTS:We enrolled consecutive patients with HF who were admitted to our institutions. RLS was diagnosed using the International Restless Legs Syndrome Study Group criteria. Subjective sleepiness, sleep quality, and quality of life (QoL) were assessed using the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and 8-item Short Form (SF-8), respectively. Among the 133 patients, 18 (13.6%) had RLS and were younger than those without RLS (62.4±13.4 vs 70.0±12.2, P = .017). The RLS group had significantly disrupted sleep quality and QoL, with greater PSQI score (8.0±3.2 vs 5.9±3.3, P = .015) and lower SF-8 physical component summary (PCS) score (35.6±6.5 vs 40.7±9.5, P = .031), despite similar ESS and SF-8 mental component summary scores. In the multivariable regression analysis, RLS was associated with greater PSQI (β=0.211; P = .014) and lower PCS score (β=-0.177; P = .045). CONCLUSION:In the patients with HF, RLS was prevalent, and sleep quality and QoL may be disrupted by RLS.

OBJECTIVES:Follistatin-like 1 (FSTL1) is a glycoprotein secreted by skeletal muscle cells and cardiac myocytes. Previous studies showed that serum FSTL1 concentrations were increased in acute coronary syndrome and chronic heart failure. The aim of this study was to assess the associations among plasma FSTL1 concentration, clinical parameters, and whether FSTL1 concentration could predict cardiovascular events in patients with elective percutaneous coronary intervention (PCI). METHODS AND RESULTS:A consecutive series of 410 patients who underwent elective PCI with drug-eluting stents (DES) were enrolled between August 2004 and December 2006 at Juntendo University hospital. We measured plasma FSTL1 levels prior to elective PCI and assessed the association among FSTL1 levels, clinical parameters, and occurrence of major adverse cardiac or cerebrovascular events (MACCE) defined as cardiac death, nonfatal myocardial infarction, unstable angina, stroke, and hospitalization for heart failure. FSTL1 concentration was positively correlated with high-sensitivity C-reactive protein (hsCRP), serum creatinine, and N-terminal pro b-type natriuretic peptide (all P < 0.01). After excluding patients with creatinine clearance < 60 mL/min and hsCRP ≥ 0.2 mg/dL, the remaining 214 were followed for a median of 5.1 years. Twenty (9.3%) patients experienced MACCE. Receiver operating characteristics curve analysis estimated an FSTL1 cutoff of 41.1 ng/mL to predict MACCE occurrence. Kaplan-Meier analysis found a higher MACCE rate in patients with high (≥ 41.1 ng/mL) than with low (< 41.1 ng/mL) FSTL1 (P < 0.01). Multivariate Cox hazard analysis found that high FSTL1 was an independent predictor of MACCE (hazard ratio 4.54, 95% confidence interval: 1.45-20.07, P < 0.01). CONCLUSION:High plasma FSTL1 may be a predictor of cardiovascular events in patients who underwent elective PCI with DES, especially with preserved renal function and low hsCRP.

A 40-year-old man who was diagnosed with bronchial asthma and eosinophilia was transferred to our hospital due to a worsening respiratory status. He was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA), and eosinophilic pneumoniae. Cardiac magnetic resonance (CMR) imaging indicated Löffler endocarditis. Treatment was initiated using intravenous methylprednisolone, cyclophosphamide, and heparin as anticoagulation therapy. Three months later, CMR showed the improvement of the LV myocardium. In this case, the early diagnosis of Löffler endocarditis by CMR could prevent systemic embolism and CMR was useful for assessing the curative effects of steroid and immunosuppressant therapy.

BACKGROUND:We examined the associations between visceral fat accumulation, presence of the components of metabolic syndrome (MetS), and exercise tolerance in non-obese subjects without diabetes.METHODS:Seventy-four non-obese, non-diabetic Japanese men were enrolled. The subjects were divided into the following two groups: non-obese subjects without any MetS risk factors (n = 38, Group A) and non-obese subjects with one or two MetS risk factors (n = 36, Group B). Anthropometric and metabolic parameters were measured. The response of heart rate (HR) and blood pressure (BP), and exercise tolerance were also evaluated with a cardiopulmonary exercise test using a bicycle ergometer.RESULTS:The body mass index, abdominal circumference, visceral fat area, and homeostasis model assessment-insulin resistance, were significantly higher, while levels of anaerobic threshold and maximal oxygen uptake were significantly lower in Group B than in Group A. The levels of resting HR, resting BP, and BP at maximal exercise were significantly higher in Group B than in Group A. There were no significant differences in the HR at maximal exercise as well as the HR and BP after exercise between the two groups. The visceral fat area was significantly and negatively correlated with exercise tolerance. Multivariate linear regression analyses demonstrated that visceral fat area, but not abdominal circumference, was significantly and independently associated with maximal oxygen uptake.CONCLUSIONS:These data suggest that the visceral fat area is a significant determinant for exercise tolerance even in non-obese subjects without diabetes.

Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare and intractable disease, first reported in Japanese patients with congestive heart failure (HF) requiring heart transplant. TGCV is characterized by the excessive accumulation of triglyceride (TG) in cardiomyocytes and vascular smooth muscle cells, which leads to coronary artery disease, HF, and arrhythmia. In TGCV, long-chain fatty acid (LCFA), a major energy source for the normal heart, accumulates as TG in cytoplasmic lipid droplets. In 2009, we launched the Japan TGCV study group to elucidate the pathophysiology of TGCV and have developed diagnostic procedures along with specific treatment. Single-photon emission computed tomography (SPECT) with iodine-123-β-methyl iodophenylpentadecanoic acid (BMIPP), a radioactive analogue for LCFA, is a useful diagnostic tool to detect impaired myocardial LCFA metabolism in TGCV. Since we posted the latest version of diagnostic criteria including the myocardial washout rate of BMIPP in SPECT in 2016, we have identified 138 patients with TGCV, 27 of whom have died. More recently, we developed a TGCV severity score consisting of specific questionnaires in order to assess symptoms and activities of daily living in patients with TGCV.