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The clinical benefit of blood pressure (BP) reduction in individuals with diabetes has not been fully elucidated. We sought to identify the clinical impact of BP reduction on incident cardiovascular disease in people having diabetes and hypertension.We conducted a retrospective cohort study including 754,677 individuals (median age 47 years, 75.8 % men) with stage 1/stage 2 hypertension. Participants were categorized using fasting plasma glucose (FPG) at baseline as normal FPG (FPG100 mg/dL) (n = 517,372), prediabetes (FPG:100-125 mg/dL) (n = 197,836), or diabetes mellitus (FPG ≥126 mg/dL) (n = 39,469). The primary outcome was heart failure (HF), and the secondary outcomes included ischemic heart disease (IHD) including myocardial infarction and angina pectoris, and stroke.Over a mean follow-up of 1111 ± 909 days, 18,429 HFs, 17,058 IHDs, and 8,795 strokes were recorded. Reduction in BP of120/80 mmHg at 1year was associated with a lower risk of developing HF (HR:0.77, 95% CI:0.72-0.82), IHD (HR:0.84, 95% CI:0.79-0.89), and stroke (HR:0.75, 95% CI:0.69-0.82) in individuals with normal FPG, whereas it was not associated with a risk of developing HF (HR:0.98, 95% CI:0.81-1.17) and stroke (HR:0.82, 95% CI:0.62-1.09) in those with DM. Interaction analyses showed that the influence of BP reduction on incident HF was attenuated with people with prediabetes or DM. A multitude of sensitivity analyses confirmed our results.The association of BP reduction with the risk of developing HF was attenuated with deteriorating glucose tolerance. The optimal management strategy for hypertensive people with prediabetes or DM for the prevention of developing cardiovascular disease (particularly HF) is needed to be established.

Whether blood pressure (BP) classification using the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) BP guideline can identify patients at high risk for proteinuria remains unknown. We examined the association of BP classification using the 2017 ACC/AHA guideline with the subsequent risk for the development of proteinuria. This is an observational cohort study using the JMDC Claims Database. We analyzed 914,786 participants with negative proteinuria assessed using urine dipstick tests at the initial health check-ups, not taking BP-lowering medications, and who underwent repeated urine dipstick tests within 4 years. Based on the 2017 ACC/AHA guideline, each participant was categorized as having normal BP (n = 487,020), elevated BP (n = 134,798), stage 1 hypertension (n = 197,618), or stage 2 hypertension (n = 95,350). The primary outcome was incident proteinuria. We investigated the association of BP based on the 2017 ACC/AHA guideline category with incident proteinuria using multivariable analyses. We used restricted cubic spline functions to identify the relation between systolic BP (SBP) and the risk for proteinuria. The median age was 45 years, and 59.4% were men. Multivariable analysis demonstrated that stage 1 hypertension (relative risk 1.14, 95% confidence interval 1.11 to 1.17), and stage 2 hypertension (relative risk 1.48, 95% confidence interval 1.43 to 1.52) were associated with a higher incidence of proteinuria than normal BP. The restricted cubic spline demonstrated that the risk for proteinuria increased linearly with SBP after SBP exceeded 120 mm Hg. Not only stage 2 hypertension but also stage 1 hypertension was associated with a greater risk for proteinuria, suggesting the importance of establishing the management strategy for stage 1 hypertension.

BACKGROUND Aortic regurgitation (AR) is a common heart disease, with a relatively high prevalence of 4.9% in the Framingham Heart Study. Because the prevalence increases with advancing age, an upward shift in the age distribution may increase the burden of AR. To provide an effective screening method for AR, we developed a deep learning-based artificial intelligence algorithm for the diagnosis of significant AR using electrocardiography (ECG). METHODS Our dataset comprised 29,859 paired data of ECG and echocardiography, including 412 AR cases, from January 2015 to December 2019. This dataset was divided into training, validation, and test datasets. We developed a multi-input neural network model, which comprised a two-dimensional convolutional neural network (2D-CNN) using raw ECG data and a fully connected deep neural network (FC-DNN) using ECG features, and compared its performance with the performances of a 2D-CNN model and other machine learning models. In addition, we used gradient-weighted class activation mapping (Grad-CAM) to identify which parts of ECG waveforms had the most effect on algorithm decision making. RESULTS The area under the receiver operating characteristic curve of the multi-input model (0.802; 95% CI, 0.762-0.837) was significantly greater than that of the 2D-CNN model alone (0.734; 95% CI, 0.679-0.783; p

Background Extensive data support the clinical benefit of cardiac rehabilitation (CR) for patients with chronic heart failure (HF). However, whether CR could be beneficial for patients hospitalized for acute heart failure remains unclear. Methods We retrospectively analyzed data from the Diagnosis Procedure Combination database, a nationwide inpatient database. We included patients hospitalized for HF, who were aged ≥20 years and with New York Heart Association class ≥II, between January 2010 and March 2018. We excluded patients with length of hospital stay ≤2 days, those undergoing major procedures under general anesthesia, those requiring advanced mechanical supports within 2 days after admission, and those with disturbance of consciousness. Propensity score matching and instrumental variable analyses were conducted to compare clinical outcomes between the patients with and without acute-phase initiation of CR defined as initiation of CR within two days after hospital admission. Results Among 430,216 eligible patients, 63,470 patients (14.8%) received the acute-phase initiation of CR. Propensity score matching created 63,470 pairs and found that the acute-phase initiation of CR was associated with lower in-hospital mortality (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.73–0.80), shorter hospital stay and lower incidence of 30-day readmission due to HF. The instrumental variable analysis also showed patients with acute-phase initiation of CR was associated with lower in-hospital mortality than those without (OR, 0.73; 95% CI, 0.68–0.79). Conclusion Our analysis suggested a potential benefit of acute-phase initiation of CR for short-term clinical outcomes in hospitalized patients with acute HF.

Serum uric acid (SUA) was reported to be associated with incident cardiovascular disease (CVD). However, the relationship between SUA and CVD among young adults has not been clarified yet. In this study, we aimed to identify the association of medication naive SUA with incident CVD including myocardial infarction (MI), stroke, heart failure (HF) and atrial fibrillation (AF) using a nationwide epidemiological database. We analyzed 353,613 participants aged 20-49 years, who were not taking UA lowering medications, and had no prevalent history of cardiovascular disease (CVD) using a nationwide health claims database collected in the JMDC Claims Database between 2005 and 2018. Median [interquartile range] age was 40 [34-44] years, and 46.9% were men. Over a mean follow-up of 1,176±876 days, 391 (0.1%) incident MI, 1,308 (0.4%) incident stroke, 3,374 (1.0%) incident HF, and 684 (0.2%) incident AF events occurred. Kaplan-Meier curves and the log-rank test showed that there was a significant difference in incident MI, stroke, HF, and AF among the groups based on SUA tertile (all log-rank p< 0.001). Multivariable Cox regression analysis showed that the upper tertile of SUA (SUA ≥ 5.7 mg/dL) was associated with higher incidence of MI (HR 1.45, 95% CI 1.00-2.10), HF (HR 1.13, 95% CI 1.01-1.28), and AF (HR 1.35, 95% CI 1.02-1.78) compared with the first tertile of SUA (SUA < 4.4 mg/dL). SUA as continuous variable was independently associated with incident MI (HR 1.10, 95% CI 1.00-1.20), stroke (HR 1.06, 95% CI 1.00-1.11), HF (HR 1.07, 95% CI 1.03-1.10), and AF (HR 1.11, 95% CI 1.04-1.19). SUA ≥ 7.0 mg/dL was independently associated with incident HF (HR 1.24, 95% CI 1.12-1.38). In conclusion, higher SUA was associated with increased incidence of CVD events in individuals aged< 50 years, suggesting the potential significance of the optimal UA control for the primary CVD prevention even in young adults.

Extensive data on early nutrition support for patients requiring critical care are available. However, whether early initiation of feeding could be beneficial for patients hospitalized for acute heart failure (HF) remains unclear. We sought to compare outcomes of early and delayed initiation of feeding for hospitalized patients with acute HF using a nationwide inpatient database. We retrospectively analyzed data from the Diagnosis Procedure Combination database. We included patients hospitalized for HF between January 2010 and March 2018. We excluded patients with length of hospital stay ≤2 days, those patients who underwent major procedures under general anesthesia, and those requiring advanced mechanical supports within 2 days after admission including intubation, intra-aortic balloon pumping, and extracorporeal membrane oxygenation. Propensity score matching and instrumental variable analyses were conducted to compare in-hospital mortality, complications and length of stay between the early and delayed feeding groups. Among 432,620 eligible patients, 403,442 patients (93%) received early initiation of feeding (within 2 days after admission) and 29,178 patients (7%) received delayed initiation of feeding. Propensity score matching created 29,153 pairs and delayed initiation of feeding was associated with higher in-hospital mortality (odds ratio 1.32; 95% confidence interval 1.26 to 1.39), longer hospital stay and higher incidence of pneumonia and sepsis. The instrumental variable analysis also showed patients with delayed initiation of feeding had higher in-hospital mortality (odds ratio 1.34; 95% confidence interval 1.28 to 1.40). In conclusion, our analysis suggested a potential benefit of early initiation of feeding for in-hospital outcomes in hospitalized patients hospitalized for acute HF. Further investigations are required to confirm our results and to clarify the underlying mechanisms.

Epidemiological evidence on the relationship between eating behaviors, including breakfast skipping, late night dinner, and bedtime snacking, and cardiovascular disease (CVD) events among the general population is scarce. We sought to explore the association of eating behaviors with subsequent CVD using a nationwide epidemiological database.Medical records of 1,941,125 individuals without prior history of CVD were extracted from the Japan Medical Data Center contracting with more than 60 insurers from multiple regions in Japan, mainly including employed working-age individuals. Skipping breakfast3 times per week, late night dinner3 times per week, and bedtime snacking3 times per week were defined as optimal eating behaviors. Median age was 45 (interquartile range 39-53) years, and 1,138,676 were men. Median follow-up period was 978 (interquartile range 481-1790) days. Among them, 948,805 individuals (48.9%) had optimal eating behaviors, whereas 647,383 individuals (33.4%), 283,017 individuals (14.6%), and 61,920 individuals (3.2%) had single, double, and triple non-optimal eating behaviors, respectively. Individuals with non-optimal eating behaviors were younger and more likely to be men. Obesity and high waist circumference were more commonly observed in those with non-optimal eating behaviors. Multivariable Cox regression analysis showed that, compared with no non-optimal eating behavior, having non-optimal eating behaviors would have higher risk of myocardial infarction, angina pectoris, stroke, and heart failure. However, the dose-response relationship was not clear in the association between the number of non-optimal eating behaviors and incident CVD. Multivariable Cox regression analysis after multiple imputation for missing values also showed the association between non-optimal eating behaviors and incident CVD.Using a nationwide epidemiological database, we found a possible relationship between eating behaviors including skipping breakfast, late night dinner, and bedtime snacking, and subsequent cardiovascular events among the general population, suggesting the potential importance of maintaining optimal eating behaviors for the primordial and primary CVD prevention in the general population.

Epidemiological evidence on the relationship between lipid profile and cardiovascular disease (CVD) events in young adults remains insufficient. Thus, we sought to explore the association of lipid profile with subsequent CVD among young adults. Medical records of 1,451,997 young adults (20 to 49 years old) without prior history of CVD and not taking lipid lowering medications were extracted from the Japan Medical Data Center, a nationwide epidemiological database. We conducted multivariable Cox regression analyses to identify the association between lipid profile and the subsequent risk of CVD and used multiple imputation for missing data on body mass index, waist circumference, hypertension, diabetes mellitus, and cigarette smoking in our database. The mean age was 39.0 ± 7.4 years, and 58.5% were men. After a mean follow-up of 1,148 ± 893 days, myocardial infarction, angina pectoris, stroke, and heart failure developed in 1,638 (0.1%), 15,887 (1.1%), 5,593 (0.4%), and 14,351 (1.0%) subjects, respectively. Multivariable Cox regression analyses including covariates after multiple imputation for missing values demonstrated that LDL-C ≥ 140 mg/dL, HDL-C < 40 mg/dL, and triglycerides ≥ 150 mg/dL were independently associated with the incidence of myocardial infarction, angina pectoris, and heart failure. However, they were not associated with the incidence of stroke. Multivariable Cox regression analyses including the number of abnormal lipid profiles and covariates showed that the incidence of myocardial infarction, angina, and heart failure increased stepwise with the number of abnormal lipid profiles. However, the number of abnormal lipid profiles was not associated with the subsequent risk of stroke. In conclusion, the comprehensive analysis of a nationwide epidemiological database demonstrated a close relationship between lipid profile and subsequent CVD, suggesting the importance of maintaining an optimal lipid profile for the primary prevention of CVD in young generations.

Using a nationwide epidemiological database, we aimed to clarify the association of fasting plasma glucose (FPG) with subsequent cardiovascular disease (CVD) risk among young adults.Medical records of 1,180,062 young adults (20-49 years old) without a prior history of CVD and who were not taking antidiabetic medications were extracted from the Japan Medical Data Center. We categorized the study population into four groups: normal, FPG level100 mg/dL (1,007,747 individuals), normal-high, FPG level of 100-109 mg/dL (126,602 individuals), impaired fasting glucose (IFG), FPG level of 110-125 mg/dL (32,451 individuals), and diabetes mellitus (DM), FPG level ≥126 mg/dL (13,262 individuals). The mean age was 39.7 ± 6.9 years, and 57.0% of the study population were men. Mean follow-up period was 1201 ± 905 days on average. Multivariable Cox regression analysis showed that IFG (hazard ratio [HR]; 1.38) and DM (HR; 2.09) increased the risk of myocardial infarction. Normal-high (HR; 1.11), IFG (HR; 1.18), and DM (HR; 1.59) groups had an elevated angina pectoris risk. DM (HR; 1.31) increased the risk of stroke compared to normal FPG levels. Normal-high levels (HR; 1.10), IFG (HR; 1.22) and DM (HR; 1.58) elevated the risk of heart failure. DM (HR; 1.69) increased the risk of atrial fibrillation.Our analysis of a nationwide epidemiological database demonstrated a close association of the FPG category with subsequent CVD risk. Our results exemplify the importance of optimal FPG maintenance for the primary prevention of CVD in young adults.

Body weight (BW) gain in adulthood frequently leads to the development of obesity and is associated with subsequent cardiovascular disease (CVD). However, the pathological significance of BW gain in non-obese individuals is not fully understood.Using data from a nationwide epidemiological database, we studied 1,558,774 non-obese subjects aged ≥20 years and without prior history of CVD. The subjects' mean age was 44.7 ± 11.2 years, and 853,391 subjects (54.7%) were male. BW gain, which was defined as BW gain of ≥10 kg from the age of 20 years, was seen in 302,997 subjects (19.4%). Subjects with BW gain were older and more likely to be male than those without BW gain. Body mass index and waist circumference were higher in subjects with BW gain. The prevalence of classical CVD risk factors was higher in subjects with BW gain. Kaplan-Meier curves and log-rank tests showed that subjects with BW gain had higher incidences of composite endpoints, including myocardial infarction, angina pectoris, and stroke. Multivariable Cox regression analysis including other covariates presented that BW gain was independently associated with the incidence of composite endpoint (Hazard ratio 1.10, 95% confidence interval 1.07-1.13, p 0.001). Subgroup analyses showed that the association of BW gain with the development of CVD was observed regardless of age, sex, and body mass index.Subjects with BW gain of ≥10 kg from the age of 20 years had high incidence of cardiovascular events even if they did not yet develop obesity. The results suggest the significance of substantial BW gain in adulthood in the development of subsequent CVDs.

Patients with hypertrophic cardiomyopathy (HCM) are prohibited from engaging in intensive exercise, to avoid sudden death. Given that patients with HCM, even those without left-ventricular outflow tract obstruction at rest, potentially have exercise-induced obstruction, reasonable monitoring methods during exercise are required. We present the case of a woman with HCM with exercise-induced obstruction whose hemodynamics during stress echocardiography were under observation using noninvasive cardiac output monitoring. Stroke volume declined during exercise before the manifest elevation of the left-ventricular outflow tract pressure gradient. As shown here, a noninvasive monitoring method can be useful in monitoring hemodynamics during exercise in HCM patients.

Lymphedema is a debilitating progressive condition that severely restricts quality of life and is frequently observed after cancer surgery. The mechanism underlying lymphedema development remains poorly understood, and no effective pharmacological means to prevent or alleviate the ailment is currently available. Using a mouse model of lymphedema, we show here that excessive generation of immature lymphatic vessels is essential for initial edema development and that this early process is also important for later development of lymphedema pathology. We found that CD4 + T cells interact with macrophages to promote lymphangiogenesis, and that both lymphangiogenesis and edema were greatly reduced in macrophage-depleted mice, lymphocyte-deficient Rag2 −/− mice or CD4 + T-cell–deficient mice. Mechanistically, T helper type 1 and T helper type 17 cells activate lesional macrophages to produce vascular endothelial growth factor-C, which promotes lymphangiogenesis, and inhibition of this mechanism suppressed not only early lymphangiogenesis, but also later development of lymphedema. Finally, we show that atorvastatin suppresses excessive lymphangiogenesis and lymphedema by inhibiting T helper type 1 and T helper type 17 cell activation. These results demonstrate that the interaction between CD4 + T cells and macrophages is a potential therapeutic target for prevention of lymphedema after surgery.

Background Preoperative and intraoperative use of a contrast medium is unavoidable in catheter ablation for atrial fibrillation, which can become a particularly significant issue for patients suffering from renal impairment. Objective The purpose of this study is to investigate the feasibility and safety of a technique for atrial fibrillation ablation without a contrast medium via intra-cardiac ultrasound imaging only. Methods We prepared the geometry of the pulmonary vein and left atrium via a SOUNDSTAR catheter from inside the left atrium, without preoperative and intraoperative investigations using contrast mediums, for computed tomography or magnetic resonance imaging and pulmonary venography. This was followed by retrospective investigation of the success rate and complications observed in 200 successive paroxysmal and persistent atrial fibrillation cases that underwent catheter ablation from January 2011 to November 2012. The outcomes were assessed after the one-year follow-up. Results Inserting a SOUNDSTAR catheter into the left atrium was successful in all cases, wherein rendering of all pulmonary veins and the left atrium was possible, and extensive encircling pulmonary vein isolation was successful in all cases. The sinus rhythm maintenance rate one year after the procedure was 90.4% for paroxysmal atrial fibrillation and 76.0% for persistent atrial fibrillation. The major complication rate was 0.5% (cardiac tamponade), with no cases presenting aggravation of renal function. Conclusion Atrial fibrillation ablation using an intra-cardiac ultrasound from the left atrium without employing a contrast medium was safe, with no adverse effects on renal function.

BackgroundThe circadian autonomic fluctuation in chronic kidney disease (CKD) patients has not yet been fully elucidated. The aim of this study was to compare the autonomic fluctuation using heart rate variability between patients with and without CKD.MethodsThe study population consisted of consecutive 101 non-diabetic CKD patients (Stages 3–5, 54 males, 70±10years) and 129 age- and sex-matched controls without CKD (65 males, 68±10years) who underwent 24-hour Holter monitoring. The proportion of successive normal sinus NN intervals that differ >50ms (pNN50) and the high-frequency component (HF) were adopted as vagal parameters. The low- to high-frequency ratio (LF/HF ratio) was evaluated as a sympatho-vagal balance parameter. To evaluate the direct contribution of CKD and other comorbidities to the autonomic variation, the regression analysis was performed after we arbitrarily divided 24h into night-time (10PM–8AM) and day-time (8AM–10PM).ResultsThe CKD patients had higher prevalence of hypertension, hyperuricemia, and low hemoglobin as compared to controls (P0.05), but to low Hb (P

Key Teaching Points • In most patients, the His bundle pacing (HBP) lead is positioned on the atrial side of the His bundle; in others, it is positioned in the tricuspid valve or on the ventricular side of the His bundle. • Echocardiography showed no worsening of tricuspid regurgitation severity in any patient with a permanent HBP, even in those whose leads were located on or under the tricuspid valve. • The HBP lead tip can be positioned in a commissural position in the right ventricle without impinging on leaflet mobility.

YPERTROPHIC CARDIOMYOPATHY (HCM) often includes asymmetric (or nonphysiologic) massive left ventricular hypertrophy, which can be diagnosed by electrocardiography and echocardiography. In patients with HCM, hypertrophy is more common in the ventricular septum below the aortic valve, leading to left ventricular outflow tract (LVOT) obstruction. 1-3 There have been many reports of anesthetic management for noncardiac surgery of patients with ischemic heart disease. However, there have been only a few reports concerning the anesthetic management of patients with HCM undergoing noncardiac surgery. 4-7 Hreybe et al reported that the presence of HCM significantly increased the risk of death and myocardial infarction associated with noncardiac surgery. 8 Patients with HCM undergoing elective procedures may require more careful preoperative assessment and perioperative monitoring. However, it is not known exactly what factors associated with HCM have harmful effects on the perioperative condition of a patient. Left ventricular hypertrophy and LVOT, which induce left ventricular diastolic dysfunction and a pressure gradient, may be involved. In addition, better ways for decreasing the risks have not yet been established. Permanent dual-chamber pacing has been proposed as an adjunct treatment to lessen symptoms in markedly symptomatic patients with obstructive HCM refractory to drugs. 9 This approach is based on the concept that pre-excitation of the interventricular septum by right ventricular pacing would cause the septum to move away from the left ventricular wall during systole and artificially make dyssynchrony, resulting in an increase in LVOT dimensions and, hence, a decrease in LVOT blood velocities. This would, in turn, decrease the systolic anterior motion of the mitral valve, resulting in further relief of the LVOT obstruction and less severe mitral regurgitation. However, the application of this procedure in perioperative management has been rare. Here, the authors describe a case of noncardiac surgery with left ventricular hypertrophy and LVOT obstruction. The surgery included resection of a catecholamine-secreting endocrine tumor that was having a harmful effect on the patient’s hypertrophic heart. After assessing the effect with temporary pacing, the authors performed temporary dual-chamber pacing to decrease the perioperative risks. Noncardiac surgery then was performed successfully without any adverse cardiac events. The clinical course of left ventricular hypertrophy and LVOT obstruction complicated with a catecholamine-secreting tumor involves significant implications in clinical practice.