Forecasting the Acute Heart Failure Admissions: Development of Deep Learning Prediction Model Incorporating the Climate Information.

BACKGROUND: Climate is known to influence the incidence of cardiovascular events. However, their prediction with traditional statistical models remains imprecise. METHODS AND RESULTS: We analyzed 27,799 acute heart failure (AHF) admissions within the Tokyo CCU Network Database from January 2014 to December 2019. High-risk AHF (HR-AHF) day was defined as a day with the upper 10th percentile of AHF admission volume. Deep neural network (DNN) and traditional regression models were developed using the admissions in 2014-2018 and tested in 2019. Explanatory variables included 17 meteorological parameters. Shapley additive explanations were used to evaluate their importance. The median number of incidences of AHF was 12 (9-16) per day in 2014-2018 and 11 (9-15) per day in 2019. The predicted AHF admissions correlated well with the observed numbers (DNN: R2 = 0.413, linear regression: R2 = 0.387). The DNN model was superior in predicting HR-AHF days compared with the logistic regression model [c-statistics: 0.888 (95% CI: 0.818-0.958) vs 0.827 (95% CI: 0.745-0.910): P = .0013]. Notably, the strongest predictive variable was the 7-day moving average of the lowest ambient temperatures. CONCLUSIONS: The DNN model had good prediction ability for incident AHF using climate information. Forecasting AHF admissions could be useful for the effective management of AHF.

Effect of Hinge Motion on Stent Edge-Related Restenosis After Right Coronary Artery Treatment in the Current Drug-Eluting Stent Era.

BACKGROUND: Stent edge-related restenosis (SER) remains a potential limitation of drug-eluting stent (DES). Hinge motion at the stent edge could lead to mechanical stress and contribute to incidents of SER. We investigated the effect of hinge motion on SER after implantation of current-generation DES in the right coronary artery (RCA), where excessive vessel movement is commonly observed.Methods and Results:Of 647 consecutive lesions in the RCA treated with second-generation or later DESs, 426 with follow-up angiography were included in this study. Intravascular imaging analysis was performed for 584 stent edges and reference segments. Binary restenosis occurred in 42 lesions (9.9%), and 55% were SERs. The hinge angle was significantly larger in the SER group than in the other restenosis or the no-restenosis group (17.9° vs. 11.6° and 10.6°, respectively; P<0.001). Lesions with an excessive hinge angle (>11.5°) had an increased rate of target lesion revascularization (19.1% vs. 7.2%; P<0.001) during the median follow-up period of 1,578 days. In per-edge analysis, hinge angle and residual plaque burden were independent predictors of SER. The coexistence of excessive hinge motion and residual plaque burden had a synergistic effect on stenotic progression in quantitative angiographic analysis (Pinteraction<0.001) at follow-up angiography. CONCLUSIONS: Substantial stress determined by angulation at a stent edge and its interaction with residual plaque can be considered as one plausible mechanism for SER.

Empagliflozin attenuates neointimal hyperplasia after drug-eluting-stent implantation in patients with type 2 diabetes.

The effects of empagliflozin, a sodium-glucose co-transporter 2 inhibitor, on neointimal response after drug-eluting-stent (DES) implantation remains unknown. Insufficiently controlled diabetes patients with coronary artery disease planned for DES stenting were consecutively enrolled. The patients were assigned to receive empagliflozin in addition to standard therapy or intensive therapy using other glucose-lowering drugs (oGLD). The primary endpoint was thickness of neointimal hyperplasia (NIH) 12 months after stenting assessed by optical coherence tomography (OCT). A total of 28 patients were analyzed (n = 15 in the empagliflozin group, n = 13 in the oGLD group). The levels of glucose profile were not significantly different between both groups at follow-up [HbA1c; 7.2 ± 0.8 vs 7.3 ± 0.9%, p = 0.46]. In OCT analysis, neointima was significantly less in the empagliflozin group than the oGLD group [mean NIH thickness: 137 ± 32 vs 168 ± 39 µm, p = 0.02]. Changes of systolic and diastolic blood pressure (BP), changes of body mass index, and changes of hematocrit after additional treatment were significantly associated with NIH attenuation, whereas no correlation was observed in changes in blood glucose parameters. Multivariate logistic regression analysis revealed that changes in systolic BP was the strongest predictor for NIH attenuation, followed by changes in diastolic BP. In patients with type 2 diabetes, standard plus empagliflozin attenuated neointimal progression as compared with intensive standard therapy after DES implantation. Our data possibly support a beneficial effect of empagliflozin in type 2 diabetes required for coronary revascularization therapy.

Case report of belt electrode-skeletal muscle electrical stimulation for acute heart failure with severe obesity: a novel therapeutic option for acute phase rehabilitation.

Background: Belt electrode skeletal muscle electrical stimulation (B-SES) is an emerging therapy anticipated to yield more favorable outcomes than conventional neuromuscular electrical stimulation (NMES), owing to its larger stimulation area. However, information on its efficacy and safety in patients with heart failure remains limited. Case presentation: A 43-year-old man with a body mass index of 41 kg/m2 was admitted to our hospital for acute heart failure due to dilated cardiomyopathy. The patient required prolonged catecholamine support owing to poor cardiac function, and heart transplantation was considered. We initiated a mobilization program, but the patient's mobility was highly limited due to severe obesity and symptomatic orthostatic hypotension. B-SES was introduced to accomplish weight loss and early ambulation. We applied an intensive monitoring program for safe use and modulated the intensity of B-SES according to physical function. During the B-SES program, the patient's body weight decreased from 89.6 kg to 78.6 kg. Sequential evaluations of body composition and skeletal muscle ultrasonography revealed improved muscle mass, quality, and physical function. Furthermore, we explored the workload of B-SES using expiratory gas analysis. No adverse events were observed during B-SES. Discussion: We successfully used B-SES to improve muscle function and morbidity in the treatment of acute heart failure. B-SES could be an option for patients with heart failure who have limited mobility and obesity.

A case of progressive right ventricular failure with ventricular arrhythmia and aortic insufficiency after implantable left ventricular assist device implantation.

Right ventricular failure (RVF) is a serious complication after left ventricular assist device (LVAD) implantation. In this report, a case of RVF that developed over two years after LVAD implantation is presented. The patient was a 12-year-old male with dilated phase of hypertrophic cardiomyopathy. He had no risk factors for early or late-onset RVF. However, his right ventricular function worsened after he developed ventricular arrhythmia (VA), and right ventricular dysfunction became exacerbated with an increasing frequency of VAs. He also developed moderate aortic insufficiency (AI), which became severe. Two years after implantation, he was admitted for treatment of recurrent ventricular tachycardia and became inotropic-dependent during hospitalization. Finally, he underwent successful heart transplantation 2 years and 9 months after LVAD implantation. This case suggests that vicious cycle of RV dysfunction, recurrent VAs and severe AI could lead to RVF in patients without known risk factors for RVF, even long after LVAD implantation. Learning objective: This report shows a progressive right ventricular failure (RVF) two years after left ventricular assist device (LVAD) implantation. Although the patient had no known risk factor, vicious circle of RV dysfunction, ventricular arrhythmias (VAs) and aortic insufficiency (AI) lead to RVF. Patients with LVAD as destination therapy will increase and require long-term LVAD management. We should recognize that these patients could develop RVF even years after LVAD implantation in association with VAs and AI.

Efficacy and safety of remote cardiac rehabilitation in the recovery phase of cardiovascular diseases (RecRCR study): A multicenter, nonrandomized, and interventional trial in Japan.

Backgrounds: Remote cardiac rehabilitation has proven useful in patients with cardiovascular disease; however, the methodology had not been fully validated. This study aimed to investigate the efficacy and safety of remote cardiac rehabilitation (RCR) with real-time monitoring and an ergometer using a bidirectional communication tool during the recovery phase of cardiovascular diseases. Methods: This multicenter, nonrandomized, interventional study was conducted at 29 institutions across Japan and enrolled patients with cardiovascular diseases who met indications for cardiac rehabilitation (CR) after receiving in-hospital treatment. The RCR group exercised at home using an ergometer and was monitored in real-time using interactive video and monitoring tools for 2-3 months. Educational instructions were provided concurrently through e-learning approaches. The safety of the RCR protocol and the improvement in peak oxygen consumption (VO2) were compared with those of the historical control group that participated in center-based CR. Results: Fifty-three patients from the RCR group were compared with 103 historical controls having similar background characteristics. No patients in RCR experienced significant cardiovascular complications while engaging in exercise sessions. After 2-3 months of RCR, the peak VO2 improved significantly, and the increases in the RCR group did not exhibit any significant differences compared to those in the historical controls. During follow-up, the proportion of patients whose exercise capacity increased by 10% or more was also evaluated; this finding did not indicate a statistically significant distinction between the groups. Conclusions: RCR during the recovery phase of cardiovascular diseases proved equally efficient and safe as center-based CR.

Late-onset right ventricular failure after continuous-flow left ventricular assist device implantation: case presentation and review of the literature.

With the widespread use of implantable left ventricular assist device (LVAD), right ventricular failure (RVF) has become a serious problem that becomes apparent several weeks or later after LVAD implantation. However, there are no marked preoperative signs of RVF. This is called late-onset RVF and is currently a major problem leading to long-term complications following implantable LVAD use. Pathogenically, this could be the result of left ventricular suction by LVAD that causes the septum shift to the left ventricular side. This causes a change in morphology of the right ventricle, resulting in impaired right ventricular function. Aortic insufficiency and ventricular arrhythmia, which are also important as long-term complications after LVAD implantation, are considered to be closely involved in the onset and progression of RVF. Once late-onset RVF develops, exercise capacity declines and inotrope administration may be required. Late-onset RVF was also reported to be significantly associated with increased mortality. Several predictors of RVF have been proposed such as preoperative left ventricular diastolic dimension <64 mm, tricuspid valve annulus diameter ≥41 mm, and so on. However, some reports identified no predictors. The basic treatment strategy for late-onset RVF is to optimize volume status by administering diuretics and ensuring inotrope as needed. ß-blockers and antiarrhythmic agents often need to be reduced in terms of dosage or even discontinued because these might reduce right ventricular function. Although their efficacy is unclear, pulmonary vasodilators may be used to reduce right ventricular afterload. It is better to decrease the rotation speed of LVAD to minimize the displacement of the septum; however, this is often difficult because the required flow rate cannot be secured. Progress in the prevention and management of late-onset RVF is required because the number of patients who require longer-term LVAD support will increase with the spread of LVAD use as destination therapy.

Association of ambient temperature and acute heart failure with preserved and reduced ejection fraction.

AIMS: Evidence on the association between ambient temperature and the onset of acute heart failure (AHF) is scarce and mixed. We sought to investigate the incidence of AHF admissions based on ambient temperature change, with particular interest in detecting the difference between AHF with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF). METHODS AND RESULTS: Individualized AHF admission data from January 2015 to December 2016 were obtained from a multicentre registry (Tokyo CCU Network Database). The primary event was the daily number of admissions. A linear regression model, using the lowest ambient temperature as the explanatory variable, was selected for the best-estimate model. We also applied the cubic spline model using five knots according to the percentiles of the distribution of the lowest ambient temperature. We divided the entire population into HFpEF + HFmrEF and HFrEF for comparison. In addition, the in-hospital treatment and mortality rates were obtained according to the interquartile ranges (IQRs) of the lowest ambient temperature (IQR1 <5.5°C; IQR25.5-13.3°C; IQR3 13.3-19.7°C; and IQR4 >19.7°C). The number of admissions for HFpEF, HFmrEF and HFrEF were 2736 (36%), 1539 (20%), and 3354 (44%), respectively. The lowest ambient temperature on the admission day was inversely correlated with the admission frequency for both HFpEF + HFmrEF and HFrEF patients, with a stronger correlation in patients with HFpEF + HFmrEF (R2  = 0.25 vs. 0.05, P < 0.001). In the sensitivity analysis, the decrease in the ambient temperature was associated with the greatest incremental increases in HFpEF, followed by HFmrEF and HFrEF patients (3.5% vs. 2.8% vs. 1.5% per -1°C, P < 0.001), with marked increase in admissions of hypertensive patients (systolic blood pressure >140 mmHg vs. 140-100 mmHg vs. <100 mmHg, 3.0% vs. 2.0% vs. 0.8% per -1°C, P for interaction <0.001). A mediator analysis indicated the presence of the mediator effect of systolic blood pressure. The in-hospital mortality rate (7.5%) did not significantly change according to ambient temperature (P = 0.62). CONCLUSIONS: Lower ambient temperature was associated with higher frequency of AHF admissions, and the effect was more pronounced in HFpEF and HFmrEF patients than in those with HFrEF.

Relation of the Metabolic Syndrome to Incident Colorectal Cancer in Young Adults Aged 20 to 49 Years.

Onco-cardiology is the emerging field, and the concept of shared risk factor holds an important position in this field. The increasing prevalence of colorectal cancer (CRC) in young adults is a critical epidemiological issue. Although metabolic syndrome, which is a major risk factor for cardiovascular disease, is known to be associated with CRC incidence in middle-aged and elderly individuals, it is unclear whether this association is present in young adults. We assessed whether metabolic syndrome was associated with CRC events in young adults (aged <50 years), and whether the association differed by the definition of metabolic syndrome. We retrospectively analyzed 902,599 adults (20 to 49 years of age) enrolled in the JMDC Claims Database which is a nationwide epidemiological database in Japan between January 2005 and August 2018. Participants who had a history of CRC, colorectal polyps, or inflammatory bowel disease were excluded. Study participants were categorized into 2 groups according to the presence of metabolic syndrome, defined using the Japanese criteria (waist circumference ≥85 cm for men and ≥90 cm for women, and ≥2 metabolic parameters including elevated blood pressure, elevated triglycerides, reduced high-density lipoprotein cholesterol, or elevated fasting plasma glucose). Clinical outcomes were collected between January 2005 and August 2018. The primary outcome was CRC of any stage. Median (interquartile range) age was 41 (37 to 45), and 55.4% were men. Over a median follow-up of 1,008 (429 to 1,833) days, there were 1,884 incidences of CRC. After multivariable adjustment, the hazard ratio (HR) of metabolic syndrome for CRC events was 1.26 (95% confidence interval [CI] = 1.07 to 1.49). Cox regression analysis after multiple imputation for missing values showed that metabolic syndrome was associated with CRC incidence (HR = 1.35, 95% CI = 1.17 to 1.56). Metabolic syndrome was also associated with a higher incidence of CRC in individuals with a follow-up period of ≥365 days (HR = 1.33, 95% CI = 1.10 to 1.60). This association was observed when metabolic syndrome was defined according to the International Diabetes Federation criteria (HR = 1.30, 95% CI = 1.09 to 1.55) and the National Cholesterol Education Program Adult Treatment Panel III criteria (HR = 1.39, 95% CI = 1.12 to 1.72). In conclusion, metabolic syndrome was associated with a higher incidence of CRC among individuals aged <50 years. These results could be informative for risk stratification of subsequent CRC among young adults.

Repetitive restenosis in a biodegradable polymer sirolimus-eluting stent with hypersensitivity reaction: a case report.

BACKGROUND: Hypersensitivity reaction is a classic cause of in-stent restenosis (ISR) in coronary stents, typically reported in bare-metal stents and first-generation drug-eluting stents. Biodegradable polymer sirolimus-eluting stent (BP-SES) was developed with the concept of biocompatibility, and there has been no report of ISR of BP-SES with hypersensitivity reaction. CASE SUMMARY: An 81-year-old woman presented with ST-elevation acute inferior myocardial infarction. Primary percutaneous coronary intervention was performed for the culprit lesion in the left circumflex artery with a permanent polymer everolimus-eluting stent (PP-EES), followed by BP-SES implantation in the left anterior descending artery. Eight months later, coronary angiography showed total occlusion of the PP-EES and diffuse ISR in the BP-SES, treated with a paclitaxel-eluting balloon. Fluorodeoxyglucose with positron emission tomography showed increased uptake around the BP-SES, and cardiac magnetic resonance imaging revealed a late gadolinium-enhanced area around both stents. Four months later, she developed re-ISR in the BP-SES, and optical coherence tomography demonstrated diffuse-layered neointimal hyperplasia with microvascularization and peri-strut low-intensity area. She was successfully treated with coronary artery bypass grafting. DISCUSSION: Our case demonstrated repetitive short-term ISR of the BP-SES. Observation by both intravascular and non-invasive imaging modalities suggested the presence of hypersensitivity reaction localized in the stent. Hypersensitivity to the metal may be a possible mechanism because both stents are composed of L605 cobalt-chromium alloy. This is the first report of ISR of a BP-SES with hypersensitivity reaction. Non-invasive imaging can be useful to assess this critical condition.

Benefit and harm of intravenous vasodilators across the clinical profile spectrum in acute cardiogenic pulmonary oedema patients.

BACKGROUND: The absence of high quality, large-scale data that indicates definitive mortality benefits does not allow for firm conclusions on the role of intravenous vasodilators in acute heart failure. We aimed to investigate the associations between intravenous vasodilators and clinical outcomes in acute heart failure patients, with a specific focus on patient profiles and type of vasodilators. METHODS: Data of 26,212 consecutive patients urgently hospitalised for a primary diagnosis of acute heart failure between 2009 and 2015 were extracted from a government-funded multicentre data registration system. Propensity scores were calculated with multiple imputations and 1:1 matching performed between patients with and without vasodilator use. The primary endpoint was inhospital mortality. RESULTS: On direct comparison of the vasodilator and non-vasodilator groups after propensity score matching, there were no significant differences in the inhospital mortality rates (7.5% vs. 8.8%, respectively; P=0.098) or length of intensive/cardiovascular care unit stay and hospital stay between the two groups. However, there was a substantial difference in baseline systolic blood pressure by vasodilator type; favourable impacts of vasodilator use on inhospital mortality were observed among patients who had higher systolic blood pressures and those who had no atrial fibrillation on admission. Furthermore, when compared to nitrates, the use of carperitide (natriuretic peptide agent) was significantly associated with worse outcomes, especially in patients with intermediate systolic blood pressures. CONCLUSIONS: In acute heart failure patients, vasodilator use was not universally associated with improved inhospital outcomes; rather, its effect depended on individual clinical presentation: patients with higher systolic blood pressure and no atrial fibrillation seemed to benefit maximally from vasodilators. TRIAL REGISTRATION: UMIN-CTR identifier, UMIN000013128.