Deep Learning for Echocardiography

Objectives: The aim of this study was to evaluate whether a deep convolutional neural network (DCNN) could detect regional wall motion abnormalities (RWMAs) and differentiate groups of coronary infarction territories from conventional 2-dimensional echocardiographic images compared with cardiologist/sonographer or resident readers. Background: An effective intervention for reduction of misreading of RWMAs is needed. We hypothesized that a DCNN trained with echocardiographic images may provide improved detection of RWMAs in the clinical setting. Methods: A total of 300 patients with history of myocardial infarction were enrolled. In this cohort, 100 each had infarctions of the left anterior descending branch (LAD), left circumflex branch (LCX), and right coronary artery (RCA). The age-matched 100 control patients with normal wall motion were selected from our database. Each case contained cardiac ultrasound images from short axis views at end-diastolic, mid-systolic and end-systolic phases. After 100 steps of training, diagnostic accuracies were calculated on the test set. We independently trained 10 versions of the same model, and performed ensemble predictions with them. Results: For detection of the presence of wall motion abnormality, the area under the receiver-operating characteristic curve (AUC) by deep learning algorithm was similar to that by cardiologist/sonographer readers (0.99 vs. 0.98, p =0.15), and significantly higher than the AUC by resident readers (0.99 vs. 0.90, p =0.002). For detection of territories of wall motion abnormality, the AUC by the deep learning algorithm was similar to the AUC by cardiologist/sonographer readers (0.97 vs. 0.95, p =0.61) and significantly higher than the AUC by resident readers (0.97 vs. 0.83, p =0.003). In a validation group from an independent site (n=40), the AUC by the DL algorithm was 0.90. Conclusions: Our results support the possibility of DCNN use for automated diagnosis of RWMAs in the field of echocardiography

Imaging of Cardiomyopathy

Background: In cardiomyopathy, 99mTc-MIBI washout can reflect mitochondrial dysfunction and late gadolinium enhancement (LGE) on cardiac magnetic imaging (MRI) is associated with tissue fibrosis. We sought to determine the relationship between 99mTc-MIBI uptake, 99mTc-MIBI washout, and LGE on MRI in patients with cardiomyopathy. Methods: Twenty-one patients underwent rest myocardial perfusion scintigraphy at 45 minutes (early) and 4 hours (delayed) after intravenous 99mTc-MIBI administration and cardiac MRI. We assessed myocardial perfusion, 99mTc-MIBI washout, and LGE. We divided the left ventricle (LV) wall into 16 segments using a polar map. Then, we classified each segment into 5 groups according to 99mTc-MIBI uptake in early-rest images and washout. Additionally, we created a contingency table based on LGE presence/absence in the groups. Results: We evaluated 336 segments in 21 patients. 99mTc-MIBI uptake was decreased in 168 segments in the early-rest 99mTc-MIBI images. 99mTc-MIBI washout was observed in 108 segments with either normal perfusion or reduced perfusion in the early-rest 99mTc-MIBI images. LGE was positive in 104 segments. A contingency table analysis with Fisher’s exact test showed that LGE was observed significantly more frequently in the segments with decreased 99mTc-MIBI uptake (p < 0.001). In segments without a decreased 99mTc-MIBI uptake, there was a significant correlation between increased 99mTc-MIBI washout and the presence of LGE (p = 0.033). Conclusions: In cardiomyopathy, the mitochondrial dysfunction in the early stage is shown as 99mTc-MIBI washout, and fibrotic changes in the myocardium in advanced stages are shown as LGE on cardiac MRI. The severity of myocardial damage and the clinical stage of cardiomyopathy can be evaluated using multimodal imaging

Effects of canagliflozin in patients with type 2 diabetes and chronic heart failure : a randomized trial (CANDLE)

Aims Little is known about the impact of sodium glucose co‐transporter 2 (SGLT2) inhibitors on cardiac biomarkers, such as natriuretic peptides, in type 2 diabetes (T2D) patients with concomitant chronic heart failure (CHF). We compared the effect of canagliflozin with glimepiride, based on changes in N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), in that patient population. Methods and results Patients with T2D and stable CHF, randomized to receive canagliflozin 100 mg or glimepiride (starting‐dose: 0.5 mg), were examined using the primary endpoint of non‐inferiority of canagliflozin vs. glimepiride, defined as a margin of 1.1 in the upper limit of the two‐sided 95% confidence interval (CI) for the group ratio of percentage change in NT‐proBNP at 24 weeks. Data analysis of 233 patients showed mean left ventricular ejection fraction (LVEF) at randomization was 57.6 ± 14.6%, with 71% of patients having a preserved LVEF (≥50%). Ratio of NT‐proBNP percentage change was 0.48 (95% CI, −0.13 to 1.59, P = 0.226) and therefore did not meet the prespecified non‐inferiority margin. However, NT‐proBNP levels did show a non‐significant trend lower in the canagliflozin group [adjusted group difference; −74.7 pg/mL (95% CI, −159.3 to 10.9), P = 0.087] and also in the subgroup with preserved LVEF [−58.3 (95% CI, −127.6 to 11.0, P = 0.098]). Conclusions This study did not meet the predefined primary endpoint of changes in NT‐proBNP levels, with 24 weeks of treatment with canagliflozin vs. glimepiride. Further research is warranted to determine whether patients with heart failure with preserved ejection fraction, regardless of diabetes status, could potentially benefit from treatment with SGLT2 inhibitors

Effect of ipragliflozin on carotid intima-media thickness in type 2 diabetes patients

Aims To examine the effects of a 24-month treatment with ipragliflozin on carotid intima-media thickness (IMT) in type 2 diabetes patients. Methods and results In this multicenter, prospective, randomized, open-label, and blinded-endpoint investigator-initiated clinical trial, adults with type 2 diabetes and haemoglobin A1C (HbA1c) of 6.0–10.0% (42–86 mmol/mol) were randomized equally to ipragliflozin (50 mg daily) and non-sodium-glucose cotransporter-2 (SGLT2) inhibitor use of standard-care (control group) for type 2 diabetes and were followed-up to 24 months. The primary endpoint was the change in mean common carotid artery IMT (CCA-IMT) from baseline to 24 months. A total of 482 patients were equally allocated to the ipragliflozin (N = 241) and control (N = 241) groups, and 464 patients (median age 68 years, female 31.7%, median type 2 diabetes duration 8 years, median HbA1c 7.3%) were included in the analyses. For the primary endpoint, the changes in the mean CCA-IMT from baseline to 24 months were 0.0013 [95% confidence interval (CI), −0.0155–0.0182] mm and 0.0015 (95% CI, −0.0155–0.0184) mm in the ipragliflozin and control groups, respectively, with an estimated group difference (ipragliflozin-control) of −0.0001 mm (95% CI, −0.0191–0.0189; P = 0.989). A group difference in HbA1c change at 24 months was also non-significant between the treatment groups [−0.1% (95% CI, −0.2–0.1); P = 0.359]. Conclusion Twenty-four months of ipragliflozin treatment did not affect carotid IMT status in patients with type 2 diabetes recruited in the PROTECT study, relative to the non-SGLT2 inhibitor-use standard care for type 2 diabetes

The physiological uptake pattern of 18F-FDG in the left ventricular myocardium of patients without heart disease

Purpose : The purpose of this study was to evaluate the physiological uptake pattern of 18F-FDG in the left ventricular myocardium of patients under preparation for tumor FDG-PET. Patients and Methods : We enrolled 188 patients without cardiac disease. The accumulation patterns were classified as either ‘none’, ‘diffuse’, ‘focal’ or ‘focal on diffuse’. When a focal uptake was only observed on the basal wall, then the patterns were classified as having either a ‘ring’, ‘over half’ or ‘spot’ uptake. Results : The frequencies of the myocardial FDG uptake patterns were as follows : none, n=52 (27.7%) ; diffuse, n= 63 (33.5%) ; focal on diffuse, n=40 (21.3%) and focal, n=33 (17.6%). The age, blood glucose level, weight and dose of FDG did not differ significantly for each pattern. The focal and focal on diffuse patterns were seen in 73 patients, and 65 patients had a focal uptake only on the basal wall ; ring uptake in 29 patients, over half in 20 and spot uptake in 16 patients. Conclusions : The physiological myocardial uptake showed several patterns. Focal uptake was often seen in patients with cardiac disease, but it did not always indicate an abnormal finding when the accumulation was only on the basal wall

左前下行枝冠動脈周囲の局所心外膜脂肪厚は簡便な冠動脈疾患の予測因子である : フラミンガムリスクスコアと組み合わせた新しい予測モデル

Background: Compared with global cardiac adiposity, the local accumulation of fat surrounding coronary arteries might have a more direct impact on coronary artery disease (CAD). Here, we compared the local epicardial adipose tissue (EAT) thickness and global cardiac adiposity volumes for predicting CAD. Methods and Results: A total of 197 consecutive subjects underwent 320-slice multi-detector computed tomography coronary angiography and were segregated into CAD (≥1 coronary artery branch stenosis ≥50%) and non-CAD groups. EAT thickness was measured at the right coronary artery (EATRCA), the left anterior descending artery (EATLAD), and the left circumflex artery (EATLCX). Although EATRCA and EATLCX were similar between the 2 groups, EATLAD was larger in the CAD group than in the non-CAD group (5.45±2.16 mm vs. 6.86±2.19 mm, P<0.001). EATLAD, after correcting for confounding factors, was strongly associated with CAD (r=0.276, P<0.001) and Gensini score (r=0.239, P<0.001). On multiple regression analysis, Framingham risk score combined with EATLAD was a strong predictor of CAD (adjusted R2=0.121; P<0.001). Conclusions: The local fat thickness surrounding the LAD is a simple and useful surrogate marker for estimating the presence, severity, and extent of CAD, independent of classical cardiovascular risk factors

Rationale and design of a randomized trial to test the safety and non‑inferiority of canagliflozin in patients with diabetes with chronic heart failure : the CANDLE trial

Background: Because type 2 diabetes mellitus is associated strongly with an increased risk of cardiovascular diseases, the number of patients with diabetes with chronic heart failure is increasing steadily. However, clinical evidence of therapeutic strategies in such patients is still lacking. A recent randomized, placebo-controlled trial in patients with type 2 diabetes with high cardiovascular risk demonstrated that the SGLT2 inhibitor, empagliflozin, reduced the incidence of hospitalization for heart failure. Because SGLT2 inhibitors cause a reduction in body weight and blood pressure in addition to improving glycemic control, they have the potential to exert beneficial effects on the clinical pathophysiology of heart failure. The aim of the ongoing CANDLE trial is to test the safety and non-inferiority of canagliflozin, another SGLT2 inhibitor, compared with glimepiride, a sulfonylurea agent, in patients with type 2 diabetes mellitus and chronic heart failure. Methods: A total of 250 patients with type 2 diabetes who are drug-naïve or taking any anti-diabetic agents and suffering from chronic heart failure with a New York Heart Association classification I to III will be randomized centrally into either canagliflozin or glimepiride groups (1: 1) using the dynamic allocation method stratified by age (<65, ≥65 year), HbA1c level (<6.5, ≥6.5 %), and left ventricular ejection fraction (<40, ≥40 %). After randomization, all the participants will be given the add-on study drug for 24 weeks in addition to their background therapy. The primary endpoint is the percentage change from baseline in NT-proBNP after 24 weeks of treatment. The key secondary endpoints after 24 weeks of treatment are the change from baseline in glycemic control, blood pressure, body weight, lipid profile, quality of life score related to heart failure, and cardiac and renal function. Discussion: The CANDLE trial is the first to assess the safety and non-inferiority of canagliflozin in comparison with glimepiride in patients with type 2 diabetes with chronic heart failure. This trial has the potential to evaluate the clinical safety and efficacy of canagliflozin on heart failure

Rationale and design of a multicenter randomized controlled study to evaluate the preventive effect of ipragliflozin on carotid atherosclerosis : the PROTECT study

Background: Type 2 diabetes mellitus is associated strongly with an increased risk of micro- and macro-vascular complications, leading to impaired quality of life and shortened life expectancy. In addition to appropriate glycemic control, multi-factorial intervention for a wide range of risk factors, such as hypertension and dyslipidemia, is crucial for management of diabetes. A recent cardiovascular outcome trial in diabetes patients with higher cardiovascular risk demonstrated that a SGLT2 inhibitor markedly reduced mortality, but not macro-vascular events. However, to date there is no clinical evidence regarding the therapeutic effects of SGLT2 inhibitors on arteriosclerosis. The ongoing PROTECT trial was designed to assess whether the SGLT2 inhibitors, ipragliflozin, prevented progression of carotid intima-media thickness in Japanese patients with type 2 diabetes mellitus. Methods: A total of 480 participants with type 2 diabetes mellitus with a HbA1c between 6 and 10 % despite receiving diet/exercise therapy and/or standard anti-diabetic agents for at least 3 months, will be randomized systematically (1:1) into either ipragliflozin or control (continuation of conventional therapy) groups. After randomization, ipragliflozin (50–100 mg once daily) will be added on to the background therapy in participants assigned to the ipragliflozin group. The primary endpoint of the study is the change in mean intima-media thickness of the common carotid artery from baseline to 24 months. Images of carotid intima-media thickness will be analyzed at a central core laboratory in a blinded manner. The key secondary endpoints include the change from baseline in other parameters of carotid intima-media thickness, various metabolic parameters, and renal function. Other cardiovascular functional tests are also planned for several sub-studies. Discussion: The PROTECT study is the first to assess the preventive effect of ipragliflozin on progression of carotid atherosclerosis using carotid intima-media thickness as a surrogate marker. The study has potential to clarify the protective effects of ipragliflozin on atherosclerosis

Sitagliptin and Carotid Atherosclerosis in Type 2 Diabetes

Background Experimental studies have suggested that dipeptidyl peptidase-4 (DPP-4) inhibitors provide cardiovascular protective effects. We performed a randomized study to evaluate the effects of sitagliptin added on to the conventional therapy compared with conventional therapy alone (diet, exercise, and/or drugs, except for incretin-related agents) on the intima-media thickness (IMT) of the carotid artery, a surrogate marker for the evaluation of atherosclerotic cardiovascular disease, in people with type 2 diabetes mellitus (T2DM). Methods and Findings We used a multicenter PROBE (prospective, randomized, open label, blinded endpoint) design. Individuals aged ≥30 y with T2DM (6.2% ≤ HbA1c < 9.4%) were randomly allocated to receive either sitagliptin (25 to 100 mg/d) or conventional therapy. Carotid ultrasound was performed at participating medical centers, and all parameters were measured in a core laboratory. Of the 463 enrolled participants with T2DM, 442 were included in the primary analysis (sitagliptin group, 222; conventional therapy group, 220). Estimated mean (± standard error) common carotid artery IMT at 24 mo of follow-up in the sitagliptin and conventional therapy groups was 0.827 ± 0.007 mm and 0.837 ± 0.007 mm, respectively, with a mean difference of −0.009 mm (97.2% CI −0.028 to 0.011, p = 0.309). HbA1c level at 24 mo was significantly lower with sitagliptin than with conventional therapy (6.56% ± 0.05% versus 6.72%± 0.05%, p = 0.008; group mean difference −0.159, 95% CI −0.278 to −0.041). Episodes of serious hypoglycemia were recorded only in the conventional therapy group, and the rate of other adverse events was not different between the two groups. As it was not a placebo-controlled trial and carotid IMT was measured as a surrogate marker of atherosclerosis, there were some limitations of interpretation. Conclusions In the PROLOGUE study, there was no evidence that treatment with sitagliptin had an additional effect on the progression of carotid IMT in participants with T2DM beyond that achieved with conventional treatment