Cardiovascular Magnetic Resonance Radiomics to Identify Components of the Extracellular Matrix in Dilated Cardiomyopathy.

BACKGROUND: Current cardiovascular magnetic resonance sequences cannot discriminate between different myocardial extracellular space (ECSs), including collagen, noncollagen, and inflammation. We sought to investigate whether cardiovascular magnetic resonance radiomics analysis can distinguish between noncollagen and inflammation from collagen in dilated cardiomyopathy. METHODS: We identified data from 132 patients with dilated cardiomyopathy scheduled for an invasive septal biopsy who underwent cardiovascular magnetic resonance at 3 T. Cardiovascular magnetic resonance imaging protocol included native and postcontrast T1 mapping and late gadolinium enhancement (LGE). Radiomic features were computed from the midseptal myocardium, near the biopsy region, on native T1, extracellular volume (ECV) map, and LGE images. Principal component analysis was used to reduce the number of radiomic features to 5 principal radiomics. Moreover, a correlation analysis was conducted to identify radiomic features exhibiting a strong correlation (r>0.9) with the 5 principal radiomics. Biopsy samples were used to quantify ECS, myocardial fibrosis, and inflammation. RESULTS: Four histopathological phenotypes were identified: low collagen (n=20), noncollagenous ECS expansion (n=49), mild to moderate collagenous ECS expansion (n=42), and severe collagenous ECS expansion (n=21). Noncollagenous expansion was associated with the highest risk of myocardial inflammation (65%). Although native T1 and ECV provided high diagnostic performance in differentiating severe fibrosis (C statistic, 0.90 and 0.90, respectively), their performance in differentiating between noncollagen and mild to moderate collagenous expansion decreased (C statistic: 0.59 and 0.55, respectively). Integration of ECV principal radiomics provided better discrimination and reclassification between noncollagen and mild to moderate collagen (C statistic, 0.79; net reclassification index, 0.83 [95% CI, 0.45-1.22]; P<0.001). There was a similar trend in the addition of native T1 principal radiomics (C statistic, 0.75; net reclassification index, 0.93 [95% CI, 0.56-1.29]; P<0.001) and LGE principal radiomics (C statistic, 0.74; net reclassification index, 0.59 [95% CI, 0.19-0.98]; P=0.004). Five radiomic features per sequence were identified with correlation analysis. They showed a similar improvement in performance for differentiating between noncollagen and mild to moderate collagen (native T1, ECV, LGE C statistic, 0.75, 0.77, and 0.71, respectively). These improvements remained significant when confined to a single radiomic feature (native T1, ECV, LGE C statistic, 0.71, 0.70, and 0.64, respectively). CONCLUSIONS: Radiomic features extracted from native T1, ECV, and LGE provide incremental information that improves our capability to discriminate noncollagenous expansion from mild to moderate collagen and could be useful for detecting subtle chronic inflammation in patients with dilated cardiomyopathy.

Peripartum Mid-Ventricular-Type Takotsubo Cardiomyopathy After Cesarean Delivery.

There are several causes of heart failure during pregnancy and the peripartum period, which include peripartum cardiomyopathy, Takotsubo cardiomyopathy or stress cardiomyopathy, exacerbation of a preexisting cardiomyopathy, and acute myocarditis. It is important to determine the cause of the heart failure as the medical treatment may be different based on the diagnosis. However, it has been sometimes challenging to diagnose the cause because of the limited diagnostic tools, especially in pregnant women. Cardiac MRI can characterize myocardial injury and can be used to track the changes in myocardial tissue. We herein report a 35-year-old woman diagnosed with peripartum mid-ventricular-type Takotsubo cardiomyopathy, who was referred to our hospital due to worsening dyspnea the day after cesarean delivery. On admission, electrocardiography showed sinus tachycardia and poor progression of R waves in the precordial leads. Bedside echocardiography revealed severe hypokinesis in the mid- and apical left ventricle (LV) with a LV ejection fraction of 20%. Cardiac catheterization showed normal coronary arteries, and myocardial biopsy revealed contraction band necrosis. On acute phase (Day 4), cardiac MRI showed prolonged native T1 and T2, and severe hypokinesis and decreased regional longitudinal peak strain in the mid-anterior LV wall. During the 1st week, precordial ST fluctuation was observed, and LV wall motion had gradually recovered. Repeat cardiac MRI revealed normalized LV wall motion and shortened values for global native T1 and T2. Thus, she was diagnosed with peripartum Takotsubo cardiomyopathy. Serial cardiac MRI may be able to differentiate Takotsubo cardiomyopathy during pregnancy and the peripartum period from other preexisting cardiomyopathies.

Apple polyphenols exhibits chondroprotective changes of synovium and prevents knee osteoarthritis.

Apple polyphenols (AP) have strong antioxidant and anti-inflammatory properties. We examined the effects of AP on the progression of osteoarthritis (OA) AP was administered to surgically-induced OA model rats for 4 or 8 weeks. This treatment suppressed inflammation and oxidative stress in the synovium, resulting in a decrease in the OA severity score, and the expression of tumor necrosis factor (TNF)-α and matrix metalloproteinase (MMP)-13 in the synovium. It was suggested that long-term administration of AP may be effective for the treatment of OA. In addition, superoxide dismutase (SOD) activity was enhanced in serum samples by AP. AP or its constituent procyanidin B2 (PC) were added to HIG-82 synoviocytes. The results showed that AP enhanced cell proliferation and hyaluronan production. This indicates that AP may improve synovial conditions in OA and suppress OA progression. These effects may be attributed to the antioxidant and anti-inflammatory properties of AP.

A novel partially covered metallic stent with a 20-mm long distal bare portion for EUS-guided hepaticogastrostomy.

Video 1EUS-guided hepaticogastrostomy with a novel partially covered self-expandable metallic stent for a patient with biliary obstruction owing to gallbladder cancer.

Trajectory of left ventricular geometry and diastolic dysfunction in hereditary transthyretin cardiac amyloidosis.

Amyloid transthyretin (ATTR) depositions cause left ventricular (LV) hypertrophy, diastolic dysfunction, and heart failure. The time course of changes in LV geometry and diastolic dysfunction has not been fully reported in patients with ATTR cardiomyopathy. A 79-year-old woman with previous myocardial infraction presented with shortness of breath on exertion, and progressive bilateral lower extremity weakness and polyneuropathy. She was diagnosed with Val30Met hereditary ATTR cardiomyopathy by cardiac biopsy and genetic testing. During the past 5 year period, significant LV concentric remodelling with small LV cavity occurred, resulting in an increased LV stiffness and prolonged LV relaxation. This case report highlights the time course of changes in LV geometry and diastolic function and the importance of early diagnosis of ATTR cardiomyopathy.

Coronary Microvascular Dysfunction Restored After Surgery in Inflammatory Bowel Disease: A Prospective Observational Study.

Background We aimed to investigate the presence and severity of coronary microvascular dysfunction (CMD) in inflammatory bowel disease (IBD) including Crohn disease and ulcerative colitis and to elucidate the influence of surgical resection of the diseased intestines on CMD by assessing coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography. Methods and Results Thirty-seven patients with IBD (aged 44±15 years; 22 patients with Crohn disease and 15 patients with ulcerative colitis) and 30 controls (aged 46±12 years) were enrolled. For CFVR measurement, coronary flow velocity was recorded at rest and during hyperemia by ADP infusion using transthoracic Doppler echocardiography, and CFVR <2.5 defined CMD. CFVR measurement was repeated before and within 1 year after surgery. CFVR was similarly and significantly lower in patients with Crohn disease and those with ulcerative colitis than controls (Crohn disease: 2.92±1.03 [P<0.05 versus controls], ulcerative colitis: 2.99±0.65 [P<0.05 versus controls], and controls: 3.84±0.75). Multiple linear regression analysis showed that the presence of IBD and baseline hs-CRP (high-sensitivity C-reactive protein) were independently associated with low CFVR among all study participants (ß=-0.403 [P=0.001] and -0.237 [P=0.037], respectively). Hyperemic coronary flow velocity significantly improved after surgery only in patients with IBD who had CMD. CFVR significantly improved in patients with IBD who had both CMD and non-CMD, and the extent of CFVR improvements were greater in patients with CMD than non-CMD. Multiple linear regression analysis showed that the reduction of hs-CRP was independently associated with improvement of hyperemic coronary flow velocity and CFVR among all patients with IBD (ß=-0.481 [P=0.003] and ß=-0.334 [P=0.043], respectively). Conclusions IBD is associated with CMD, which improved after surgical resection of diseased intestines.

Serial cardiac magnetic resonance imaging in wet beriberi.

A 69-year-old woman with previous pancreaticoduodenectomy was admitted for evaluation of chest discomfort on effort and leg edema for a few months. Oral flosemide before admission for 1 week failed to relieve her symptoms. Her blood pressure was 105/51 mmHg and heart rate was 76 beats/min. Chest X-ray revealed an enlarged heart and mild pulmonary congestion. Echocardiography demonstrated normal left ventricular ejection fraction and diastolic dysfunction with no left ventricular hypertrophy. Cardiac catheterization showed normal coronary arteries, high cardiac index, and elevated intracardial pressures. Myocardial biopsy from the right ventricular septum revealed nearly normal findings. Cardiac magnetic resonance imaging (CMRI) showed both ventricles enlarged and increased global extracellular volume fraction (ECV) of 37%, but normal native T1 and T2 values. As she had pancreaticoduodenectomy, beriberi was suspected. Vitamin B1 significantly increased urine output and lowered intracardiac pressures and cardiac index. After 3 months of vitamin B1, CMRI exhibited that the right ventricle had decreased in size and the global ECV value had been lowered. Our case highlights that chronic beriberi may be associated with little myocardial damage. The increased ECV suggests that the diffuse expansion of extracellular space unrelated to myocardial edema might have been reversed by vitamin B1treatment. Morphological changes in the ventricles and myocardial damage by wet beriberi can be demonstrated by CMRI. .

Myocardial Native T1 Predicts Load-Independent Left Ventricular Chamber Stiffness In Patients With HFpEF.

OBJECTIVES: This study sought to evaluate the potential of cardiac magnetic resonance T1 mapping to detect load-independent left ventricular (LV) chamber stiffness by histological confirmation. BACKGROUND: Accurate noninvasive diagnosis of LV diastolic dysfunction in heart failure with preserved ejection fraction (HFpEF) remains challenging. METHODS: Nineteen HFpEF patients (14 female, 65 ± 16 years of age) without primary cardiomyopathy were prospectively enrolled. Cine, late gadolinium enhancement cardiac magnetic resonance, and triple-slice T1 mapping using a modified Look-Locker inversion recovery sequence were performed at 3-T. Extracellular volume (ECV) was quantified from pre- and post-contrast T1 values of the blood and myocardium with hematocrit correction. LV stiffness constant (beta) was assessed by calculating the slope of the end-diastolic pressure-volume relationship curve during vena cava occlusion. Biopsy samples were used for quantification of collagen volume fraction (CVF) and myocardial cell size. RESULTS: Six patients showed focal scar on late gadolinium enhancement. There was no significant difference in histological CVF between patients with and without focal myocardial scarring (p = 0.2). Septal ECV rather than native T1 was a better surrogate marker for detecting histological CVF (r = 0.54; p = 0.02, and r = 0.44; p = 0.06, respectively). Global native T1 and ECV, but not native T1 and ECV in the septal myocardium, correlated well with the beta of passive LV stiffness, and had similar ability for predicting LV stiffness to histological CVF (r = 0.54, 0.50, 0.53, all p < 0.05, respectively). When the beta ≥0.054 was considered as moderately increased LV stiffness, global native T1 ≥1,362 ms provided 88% sensitivity and 64% specificity with the C-statistic of 0.81 (95% confidence interval: 0.56 to 0.95). CONCLUSIONS: Myocardial native T1 provides comparable ability in predicting LV stiffness to ECV and histological CVF and may be useful for monitoring patients with HFpEF who have renal dysfunction, allergy to gadolinium, or wheezing that can simulate asthma. Our feasibility study shows the potential of native T1 to allow for insight of heterogeneous pathophysiology and better risk stratification of HFpEF.

Mechanisms and prediction of short-term natriuretic effect of sodium-glucose cotransporter 2 inhibitor in heart failure patients coexisting type 2 diabetes mellitus.

The mechanisms of the diuretic effect of sodium-glucose cotransporter 2 (SGLT2) inhibitor and its predictors in heart failure (HF) patients with coexisting type 2 diabetes mellitus (T2DM) remain under investigation. A total of 40 hospitalized HF patients with T2DM (68 ± 13 years old, male gender 63%) were prospectively enrolled and received ipragliflozin at a dose of 50 mg once daily after breakfast for at least 4 consecutive days. They underwent first-morning blood and urine tests, and 24-h urine tests before and after short-term ipragliflozin therapy. Daily urine volume significantly increased from 1365 ± 511 mL/day on day 0 to 1698 ± 595 mL/day on day 3 (P < 0.001), which resulted in significant decreases in body weight and plasma brain natriuretic peptide level. Changes in 24-h urine volume were strongly and independently correlated with changes in 24-h urine sodium excretion (r = 0.80, P < 0.001), but was not significantly correlated with those in 24-h urine sugar excretion (r = 0.29, P = 0.07). Lower concentration of first-morning urine sodium and higher loop diuretic dosage before ipragliflozin therapy were associated with urine volume increment with ipragliflozin therapy, and former retained its independent predictor (Odds ratio 0.96, 95% CI 0.93-0.99, P = 0.02). First-morning urine sodium ≤ 53 mEq/L and baseline loop diuretics ≥ 20 mg/day predicted increased urine volume on day 3 with high diagnostic accuracy. Ipragliflozin has acute natriuretic activity, and first-morning urine sodium and baseline dosage of loop diuretics strongly predicted the diuretic effects. Ipragliflozin therapy may restore responsiveness to loop diuretics in symptomatic HF patients with T2DM.

Successful percutaneous treatment of recurrent post-infarction ventricular septal rupture using an Amplatzer duct occluder.

A 78-year-old woman was brought to our hospital for chest pain with shock status. An electrocardiogram showed ST elevation in the precordial leads. Echocardiography showed an anteroseptal wall motion abnormality with left-to-right shunt at the apex. Emergency coronary angiography revealed occlusion in the mid portion of the left anterior descending artery, and left ventriculography showed ventricular septal rupture (VSR). Despite successful emergency surgical VSR repair, the VSR recurred 10 days after surgery, and the patient required intra-aortic balloon pumping and mechanical ventilation. Although reoperation for VSR closure was attempted 33 days after admission, open heart surgery was not completed due to severe tissue adhesions from the prior cardiac surgery. The patient ultimately underwent transcatheter closure for VSR using an Amplatzer duct occluder 56 days after hospital admission, and her hemodynamics markedly improved. She was transferred to a regional hospital for rehabilitation without oxygen therapy or intravenous treatments 81 days after the percutaneous intervention. In conclusion, percutaneous device closure of post-infarction VSR may be an alternative treatment to surgical repair for inoperable cases. .

Enzymatic Cell-Surface Decoration with Proteins using Amphiphilic Lipid-Fused Peptide Substrates.

Lipid modification of proteins plays a significant role in the activation of cellular signals such as proliferation. Thus, the demand for lipidated proteins is rising. However, getting a high yield and purity of lipidated proteins has been challenging. We developed a strategy for modifying proteins with a wide variety of synthetic lipids using microbial transglutaminase (MTG), which catalyzes the cross-linking reaction between a specific glutamine (Q) in a protein and lysine (K) in the lipid-fused peptide. The synthesized lipid-G3 S-MRHKGS lipid (lipid: fatty acids, tocopherol, lithocholic acid, cholesterol) was successfully conjugated to a protein fused with LLQG (Q-tagged protein) by an MTG reaction, yielding >90 % conversion of the Q-tagged protein in a lipidated form. The purified lipid-protein conjugates were used for labeling the cell membrane in vitro, resulting in best-anchoring ability of cholesterol modification. Furthermore, in situ cell-surface decoration with the protein was established in a simple manner: subjection of cells to a mixture of cholesterol-fused peptides, Q-tagged proteins and MTG.

Predictors of confirmatory test results for the diagnosis of primary hyperaldosteronism in hypertensive patients with an aldosterone-to-renin ratio greater than 20. The SHRIMP study.

It remains unknown which surrogate markers can predict diagnostic test results for primary hyperaldosteronism (PA). The Secondary Hypertension Registry Investigation in Mie Prefecture (SHRIMP) study has sequentially and prospectively recruited 128 patients with hypertension with an aldosterone-to-renin ratio (ARR) greater than 20, evaluated the differences among essential hypertension (EHT), idiopathic hyperaldosteronism (IHA), and aldosterone-producing adenoma (APA), and analyzed the predictors for the confirmatory tests. The patients underwent saline-loading, captopril-challenge, and upright furosemide-loading tests. Carotid, renovascular, and cardiac echography, brachial ankle pulse wave velocity (baPWV), endothelial function, nocturnal blood pressure decline, and the apnea hypopnea index were evaluated. Multivariate regression analyses showed that the plasma aldosterone concentration (PAC) at screening was a strong predictor of the saline and captopril test results. The plasma renin activity (PRA) at screening, urine ß2-microglobulin, and left ventricular mass index (LVMI) were independent predictors for the captopril test. The estimated saline PAC and captopril 60 and 90 min ARRs predicted by the equations were highly correlated with the real values. The ROC curve analysis showed PAC at screening among each of predictors for the diagnostic tests and PAC after the saline-loading test had the highest diagnostic abilities of APA. Patients with IHA were older and had glucose intolerance and increased U-Alb/gCre and resistive indices. In patients with APA, the levels of U-Alb/gCre and urine ß2-microglobulin were increased, and levels of insulin and the HOMA-IR were decreased. In conclusion, our proposed equations may be useful for estimating saline PAC and captopril ARR. Diagnostic predictors may differ for each confirmatory test.

Native T1 Mapping and Extracellular Volume Mapping for the Assessment of Diffuse Myocardial Fibrosis in Dilated Cardiomyopathy.

OBJECTIVES: The purpose of this study was to examine the histological correlation of native myocardial T1 and extracellular volume fraction (ECV) measurement at 3-T for the assessment of diffuse pathological changes in the myocardial tissue, including myocardial fibrosis and extracellular space in dilated cardiomyopathy (DCM). BACKGROUND: Cardiac magnetic resonance T1 techniques allow the quantification of diffuse myocardial fibrosis. However, there are no definitive head-to-head studies of native T1 versus ECV for the detection, quantification, and characterization of pathological changes in the myocardial tissue in DCM by using histological samples for confirmation. METHODS: A total of 36 subjects with DCM (31 men, mean age 56 ± 16 years) underwent pre- and post-contrast T1 mapping as well as late gadolinium enhancement (LGE) cardiac magnetic resonance at 3-T. Biopsy samples were used for the quantification of collagen volume fraction using picrosirius red staining and an extracellular space component from hematoxylin and eosin-stained myocardium. RESULTS: Nonischemic LGE was observed in 14 of 36 patients. Although patients with LGE had significantly greater biopsy-proven collagen volume fraction than those without LGE (21 ± 12% vs. 11 ± 8%; p < 0.01), there was substantial overlap of collagen volume fraction values between patients with and without LGE. Both native T1 value and ECV were similarly and significantly associated with biopsy-proven collagen volume fraction (r = 0.77 and r = 0.66, respectively; p < 0.05). Furthermore, ECV had a strong correlation with the biopsy-proven extracellular space component (r = 0.86), whereas native T1 had only a moderate correlation (r = 0.55). Interobserver and intraobserver reproducibility for native T1 and ECV were 0.89, 0.95, 0.96, and 0.98, respectively. CONCLUSIONS: Native T1 exhibited comparable ability as ECV measurement in the detection and quantification of histological collagen volume fraction, with high reproducibility, and therefore diffuse myocardial fibrosis in DCM may be reliably assessed by native T1 mapping without the administration of gadolinium contrast agent. In addition, cardiac magnetic resonance-derived ECV showed excellent agreement with histological extracellular space.