Aggravation Of Heart Failure Research Articles

Effect of left atrial function on cardiovascular outcome in non-dilated left ventricular cardiomyopathy

Abstract Background This study aimed to determine whether atrial function and strains can provide the greatest or joint incremental prognostic value in patients with non-dilated left ventricular cardiomyopathy (NDLVC) over a long follow-up period. Methods One hundred sixty-four NDLVC patients were included retrospectively. Comprehensive clinical evaluation and echocardiographic investigations were obtained, including measurements of strain derived left atrial (LA) reservoir, conduit, booster strain. All patients were followed up for adverse cardiac events (MACE) including all-cause mortality, hospitalization due to heart failure aggravation. The predictors of MACE were examined with univariable and multivariable Cox regression analysis. Subsequently, nested Cox regression models were built to evaluate the incremental prognostic value of strain parameters. Patient survival was illustrated by Kaplan–Meier curves and differences were evaluated by log-rank test. Results During a median follow-up of 3.8 years, MACEs were identified in 34 (21%) patients. Cox regression models showed that the predictive value of LA conduit strain was independent from and incremental to LAVi and baseline variables. Age, E/e', RASP and LA reservoir and conduit strain were univariably associated with the outcome (all P < 0.05). LA conduit strain was a stronger predictor of outcome compared with reservoir strain. LA conduit strain, age, RASP remained associated in the multivariable model (LA conduit strain HR: 2.14 [95% CI: 1.37-3.87; P < 0.007]; age HR: 1.05 [95% CI: 1.01-1.10; P = 0.020]; and RASP HR: 1.07 [95% CI: 1.01-1.14; P = 0.021]), whereas LVEF, LAVi were not. Adding LA conduit strain to other independent predictors (age and LAVi) improved the prediction of MACEs. (p < 0.05). Also, when a Kaplan Meier graph was obtained for the occurrence of MACE based on LA conduit strain 17%, a significant difference was shown between the two groups. Conclusion LA conduit strain provided the good prognostic value and added incremental value to conventional clinical predictors for patients with NDLVC.Incremental value of LA strainKM according to LA strain 17%

Effect of preoperative heart failure on arteriovenous access patency and prognosis in patients on hemodialysis.

The risk of arteriovenous (AV) access failure is associated with hemodynamic factors, clinical factors, or technical issues. Although several studies have shown the detrimental effects of AV access on heart function, few studies have assessed whether heart function affects AV access patency. We investigated the impact of cardiac function on AV access patency. Additionally, we evaluated the influence of heart failure (HF) on the prognosis of patients on dialysis. Patients who underwent dialysis and had echocardiographic reports between 2011 and 2013 were retrospectively included. Left ventricular ejection fraction (LVEF) was used to measure cardiac function. Data on demographics, clinical features, and technical factors associated with AV access surgery were collected. Univariate and multivariate analyses were performed to evaluate the risk factors for AV access patency loss and the prognosis of patients on dialysis. During the study period, 395 patients initiated on dialysis underwent echocardiography. In multivariate analysis, older age (hazard ratio (HR) 1.02 (1-1.03), p = 0.028), smoking (HR 2.05 (1.19-3.53), p = 0.01), lower LVEF (HR 0.98 (0.97-1), p = 0.015), and graft use (HR 2.29 (1.47-3.58), p = 0.001) were significant risk factors for primary patency loss. Regarding secondary patency loss, lower LVEF (HR 0.98 (0.96-1), p = 0.035) was the sole risk factor. In multivariate analysis, risk factors for cardiac events (acute coronary syndrome and aggravation of HF) in patients on dialysis were age (HR 1.06 (1.04-1.09), p = 0.001), diabetes (HR 2.46 (1.31-4.63), p = 0.005), pre-existing coronary artery disease (HR 2.84 (1.57-5.14), p = 0.001), and HF (HR 1.93 (1.05-3.56), p = 0.036). Decreased cardiac function adversely affects the primary and secondary patency of AV access, but its impact is limited. Additionally, HF is associated with future cardiac events in dialysis patients. However, HF is not independently associated with patient survival.

Heart failure with reduced ejection fraction and chronic kidney disease: a focus on therapies and interventions.

In heart failure with reduced ejection fraction (HFrEF), the presence of concomitant chronic kidney disease (CKD) predicts poorer cardiovascular outcomes, more aggravated heart failure (HF) status, and higher mortality. Physicians might be reluctant to initiate life-saving anti-HF medications out of fear of worsening renal function and a higher incidence of adverse events. Moreover, international guidelines do not give clear recommendations on managing this subgroup of patients as well as advanced CKD was always an exclusion criterion in most major HF trials. Nevertheless, in this review, we will highlight several recent clinical trials and post-hoc analyses of major trials that showed the safety and efficacy of the different therapies in HFrEF patients with CKD, besides several small-scale cohorts that tested guideline-directed medical therapies in End Stage Kidney Disease (ESKD). Regarding interventions in this subgroup of patients, we will provide up-to-date data on implantable cardioverter defibrillators, cardiac resynchronization therapy, and coronary revascularization, in addition to mitral valve transcatheter edge-to-edge repair and implantable pulmonary artery pressure sensors.

Genetic, sociodemographic, lifestyle, and clinical risk factors of heart failure aggravation events: data from the UK Biobank

Abstract Background Heart failure (HF) is the leading cause of readmission and hospitalization. Purpose This study examined the associations and clinical utilities of genetic, sociodemographic, lifestyle, laboratory, and clinical risk factors on HF aggravation. Methods Data were from 5,345 UK Biobank middle-aged adults with established HF at enrolment. We performed Cox proportional hazard regression analyses to investigate the associations related to HF admission after enrolment utilizing 24 variables encompassing sociodemographic, clinical, lifestyle, and laboratory data. To assess the impact of genetic factors, we additionally adjusted each polygenic risk score (PRS) for the three medical histories: hypertension, atrial fibrillation (AF), and coronary heart disease (CHD), where the hazard ratios were statistically significant. Results Over a median follow-up of 11.5 [10.9-12.2] years, 247 (4.6%) HF admission events occurred. Among the 24 variables, statistically significant hazard ratios were observed for 10 variables, with hypertension (3.31, 2.19-5.02), AF (2.06, 1.53-2.75), current smoking (1.63, 1.09-2.46), and coronary heart disease (1.58, 1.17-2.13) showing the highest hazard ratios, while female gender (0.65, 0.46-0.91) exhibited the smallest hazard ratio. After adjusting for each PRS individually, HTN PRS (HR 1.06, 0.94-1.21) and AF PRS (HR 1.02, 0.90-1.16) were not statistically significant, whereas CHD PRS (HR 1.15, 1.02-1.31) showed significance in relation to HF admission. In the HF admission prediction model, the C index was 0.859 (0.838-0.880) with clinical variables, and it marginally increased to 0.864 (0.843-0.885) when all factors, including the genetic factor, were applied. Conclusions Sociodemographic, clinical, laboratory, lifestyle, and genetic factors are each associated with HF aggravation with male gender, hypertension, AF, low eGFR, cigarette smoking, and CHD PRS.

Rationale, Design, and Interim Observations of the Steady Movement With Innovating Leadership for Heart Failure (SMILE HF) Registry: A Multicenter Prospective Cohort Registry for Patients With Acute Heart Failure.

Heart failure (HF) is a leading cause of hospitalization and death worldwide. The Steady Movement with Innovating Leadership for Heart Failure (SMILE HF) aims to evaluate the clinical characteristics, management, hospital course, and long-term outcomes of patients hospitalized for acute HF in South Korea. This prospective, observational multicenter cohort study was conducted on consecutive patients hospitalized for acute HF in nine university hospitals since September 2019. Enrolment of 2000 patients should be completed in 2024, and follow-up is planned through 2025. Interim analysis of 1,052 consecutive patients was performed to understand the baseline characteristics. The mean age was 69±15 years; 57.6% were male. The mean left ventricular ejection fraction was 39±15%. The prevalences of HF with reduced ejection fraction, HF with mildly reduced ejection fraction, and HF with preserved ejection fraction were 50.9%, 15.3%, and 29.2%. Ischemic cardiomyopathy (CMP) was the most common etiology (32%), followed by tachycardia-induced CMP (12.8%) and idiopathic dilated CMP (9.5%). The prescription rate of angiotensin-converting enzyme inhibitor/angiotensin receptor blockers/angiotensin receptor/neprilysin inhibitor, beta-blockers, spironolactone, and sodium-glucose cotransporter-2 inhibitors at discharge were 76.8%, 66.5%, 50.0%, and 17.5%, respectively. The post-discharge 90-day mortality and readmission rates due to HF aggravation were 2.0% and 6.4%, respectively. Our analysis reveals the current state of acute HF in South Korea. Our interim analysis provides valuable insights into the clinical characteristics, management, and early outcomes of acute HF patients in South Korea, highlighting the current state and treatment patterns in this population.

Hematopoietic loss of Y-chromosome in monocytes from heart failure patients associates with cardiac fibrosis signaling

Abstract Background Hematopoietic mosaic loss of Y chromosome (LOY) increases with age and associates with increased cardiovascular disease incidence. Furthermore, recent murine studies suggest that LOY could potentially promote cardiac fibrosis by stimulating the infiltration and activation of bone marrow-derived macrophages. Yet, specific signatures of hematopoietic LOY cells in patients with heart failure (HF) are missing. Methods and results To decode the genetic signature of circulating hematopoietic cells and assess the effects of LOY in human leukocytes, we performed single-cell RNA-sequencing (scRNA-seq) of immune cells from 10 male patients with chronic HF (mean age 67.3 years, ejection fraction 34.4%). We sorted immune cells by presence or absence of Y-chromosome-associated genes (figure 1A). Relative distribution of LOY was assessed, with monocytes having the greatest absolute count of LOY cells with no significant change in distribution among cell types. Given the abundance of monocytic LOY cells we investigated LOY monocytic cells transcriptional signatures (29810 Y-carrier monocytes, 2205 LOY monocytes) in an unbiased manner. Using a patient-specific, paired analysis, LOY monocytes showed significantly reduced expression of TGF-ß inhibiting genes (SMAD7, TGIF2) in LOY cells versus Y-carrier cells. Opposingly, from 193 upregulated genes, LOY cells showed elevated markers associated with monocyte/macrophage-mediated tissue damage and pro-fibrotic cardiac remodelling (S100A8, CLEC4D, TLR2). Gene ontology terms derived from upregulated genes in LOY cells further supported a mechanistic link to cardiac fibrosis by calling terms associated with TLR signaling, which are known to enhance cardiac fibrosis. (figure 1B). Conclusion This is the first study to decipher the genetic signature of LOY monocytes in HF patients. Our results considerably extend very recent experimental findings in mice that LOY sensitizes macrophages to enhanced profibrotic signaling. Diminished TGF-ß inhibitory molecules and enhanced TLR signaling may contribute to the aggravation of heart failure by LOY in patients with HF.HF mLOY scRNA-seq

Left Bundle Branch Pacing for Heart Failure and Left Bundle Branch Block Patients With Mildly Reduced and Preserved Left Ventricular Ejection Fraction.

Left bundle branch block (LBBB) may induce or aggravate heart failure (HF). Few data are available on patients with HF and LBBB with mildly reduced ejection fraction (HFmrEF; left ventricular ejection fraction [LVEF] 40%-50%) and those with preserved EF (HFpEF. LVEF ≥ 50%). We aimed to assess the long-term outcomes of left bundle branch pacing (LBBP) on cardiac function and remodelling in patients with LBBB and symptomatic HFmrEF and HFpEF. Nonischemic cardiomyopathy (NICM) patients with HFmrEF and HFpEF (LVEF from 40% to 60% as defined with the use of echocardiography) with LBBB who successfully underwent LBBP (n= 50) were prospectively included from 4 centres. Patient characteristics and echocardiographic and lead parameters were recorded at implantation and during follow-ups of 1, 3, 6, and 12 months. All patients completed 1-year follow up. The LVEF was significantly improved from 46.5 ± 5.2% at baseline to 60.0 ± 6.1% (n= 50; P < 0.001) after 1-year follow up. Higher ΔLVEF and super-response rate were observed in the HFmrEF group (n= 30) than in the HFpEF group (n= 20). LBBP improved symptoms and reversed remodelling in patients with LBBB and symptomatic HF at 1-year follow-up. Improvement occurred even in HFpEF patients, and the resynchronisation effect was better in HFmrEF group.

Anomalous right coronary artery originating from the aorta: a series of nine pediatric cases

BackgroundTo investigate the clinical manifestations, prognosis, and possibly related genes of anomalous right coronary artery originating from the aorta (ARCA-L) in children.MethodsThis case series study included pediatric patients diagnosed with ARCA-L at the Department of Cardiology in Beijing Children’s Hospital affiliated to Capital Medical University, between January 2017 and December 2019.ResultsNine pediatric patients (aged 3 months to 12 years, 4 boys) were included. Two cases presented with cardiac insufficiency as their primary manifestation, while the remaining seven had post-infection or post-exercise symptoms such as chest pain, chest tightness, long exhalation, lack of strength, and dizziness. Six patients displayed varying degrees of ST-T changes on the electrocardiograph, while two patients had a reduced left ventricular ejection fraction (LVEF) of 20-32% according to echocardiography. Multislice computed tomographic angiography confirmed the presence of ARCA-L in all patients. One patient underwent the unroofing technique. The remaining eight received conservative treatment. After a follow-up of 2–64 months, eight children had a good prognosis and survived. One child experienced sudden death due to aggravated heart failure. Whole exome sequencing revealed that one child tested negative, one had mutations in the RYR2 and LDB3 genes, and the remaining four patients had a mutation in the GDF1, LRP6, MEF2A, and KALRN genes, respectively.ConclusionsARCA-L in children might have a wide variation in clinical manifestations and a risk of sudden death. The occurrence of the disease might be associated with genetic defects.

Mechanism of ferroptosis in chronic heart failure based on theory of "harmful hyperactivity and responding inhibition"

Chronic heart failure is the end stage of heart diseases caused by multiple causes. Myocardial cell injury is the key cause of cardiac function deterioration. Ferroptosis, an iron-dependent programmed death mode, is characterized by iron overload and excessive accumulation of lipid peroxides. Studies have demonstrated that inhibiting ferroptosis has a protective effect on myocardial cells. The theory of &quot;harmful hyperactivity and responding inhibition&quot; is an important rule developed by physicians to explain the generation and restriction of the five elements and the pathological imbalance of the human body, and can guide medication. Correlating with the nature, humans need to rely on the law of responding inhibition to maintain the harmony of five Zang-organs and the steady state of Fu-organs. The pathogenesis of ferroptosis in chronic heart failure highly coincides with the process of failing to &quot;inhibition and hyperactivity becoming harmful&quot;. The initial factor of ferroptosis is the deficiency of heart Qi, which results in the inability to maintain the balance of cardiomyocyte redox system. The involvement of the five Zang-organs leads to the loss of distribution of body fluid and blood. As a result, the phlegm turbidity, blood stasis, and water retention in the meridians occur, which are manifested as the accumulation of iron and lipid peroxides, which is the aggravating factor of ferroptosis. The two factors interact with each other, leading to the spiral development and thus aggravating heart failure. According to the traditional Chinese medicine(TCM) pathogenesis of ferroptosis, the authors try to treat the chronic heart failure by stages in accordance with the general principle of restraining excess and alleviating hyperactivity. The early-stage treatment should &quot;nourish heart Qi, regulate the five Zang-organs, so as to restrain excess&quot;. The middle-stage treatment should &quot;active blood, resolve phlegm, dispel pathogen, and eliminate turbidity&quot;, so as to alleviate hyperactivity. The late-stage treatment should &quot;warm Yang, replenish Qi, active blood, and excrete water&quot;. Following the characteristics of pathogenesis, the TCM intervention can reduce iron accumulation and promote the clearance of lipid peroxide, thus inhibiting ferroptosis and improving cardiac function.

Clinical efficacy of angiotensin receptor-neprilysin inhibitor in de novo heart failure with reduced ejection fraction.

We aimed to analyze the efficacy of angiotensin receptor-neprilysin inhibitor (ARNI) by the disease course of heart failure (HF). We evaluated 227 patients with HF in a multi-center retrospective cohort that included those with left ventricular ejection fraction (LVEF) ≤ 40% undergoing ARNI treatment. The patients were divided into patients with newly diagnosed HF with ARNI treatment initiated within 6 months of diagnosis (de novo HF group) and those who were diagnosed or admitted for HF exacerbation for more than 6 months prior to initiation of ARNI treatment (prior HF group). The primary outcome was a composite of cardiovascular death and worsening HF, including hospitalization or an emergency visit for HF aggravation within 12 months. No significant differences in baseline characteristics were reported between the de novo and prior HF groups. The prior HF group was significantly associated with a higher primary outcome (23.9 vs. 9.4%) than the de novo HF group (adjusted hazard ratio 2.52, 95% confidence interval 1.06-5.96, p = 0.036), although on a higher initial dose. The de novo HF group showed better LVEF improvement after 1 year (12.0% vs 7.4%, p = 0.010). Further, the discontinuation rate of diuretics after 1 year was numerically higher in the de novo group than the prior HF group (34.4 vs 18.5%, p = 0.064). The de novo HF group had a lower risk of the primary composite outcome than the prior HF group in patients with reduced ejection fraction who were treated with ARNI.

Abstract P3068: Hematopoietic Loss Of Y-chromosome In Circulating Monocytes Derived From Heart Failure Patients Associates With Cardiac Fibrotic Signaling

Background: Hematopoietic mosaic loss of Y chromosome (LOY) correlates with age and associates with increased cardiovascular disease incidence. Moreover, new murine studies propose that LOY could promote cardiac fibrosis by stimulating cardiac infiltration and activation of circulating macrophages. Yet, specific profiles of hematopoietic LOY cells in patients with heart failure (HF) are missing. Methods and Results: To decipher the genetic profile of human circulating immune cells and assess the effects of LOY, we performed single-cell RNA-sequencing (scRNA-seq) with immune cells of 10 male patients having chronic ischemic HF (mean age 67.3 years, ejection fraction 34.4%). We bioinformatically sorted immune cells by presence or absence of Y-chromosome-associated genes. Relative distribution of LOY was assessed, with monocytes having the greatest absolute count of LOY cells with no significant change in distribution among cell types. Given the abundance of monocytic LOY cells, we examined LOY monocytic cells transcriptional profiles (29810 Y-carrier monocytes, 2205 LOY monocytes) in an unbiased manner. Using a patient-specific, paired analysis, LOY monocytes showed significantly diminished expression of TGF-ß inhibiting genes (SMAD7, TGIF2) in LOY cells versus Y-carrier cells. Opposingly, from 193 upregulated genes, LOY cells showed elevated markers associated with monocyte/macrophage-mediated tissue damage and pro-fibrotic cardiac remodelling (S100A8, CLEC4D, TLR2). Gene ontology terms derived from upregulated genes in LOY cells further supported a mechanistic link to cardiac fibrosis by calling terms associated with TLR signaling, which are known to enhance cardiac fibrosis. Conclusion: This is the first study to study the genetic signature of LOY monocytes in HF patients. Our results considerably extend very recent experimental results in mice that LOY sensitizes macrophages to enhanced signaling associated with cardiac fibrosis. Reduced TGF-ß inhibitory molecule expression and enhanced TLR signaling may contribute to the aggravation of heart failure by LOY in patients with HF.

Zhenwu Decoction:connotation interpretation based on severe cases and modern pathophysiological mechanisms and application in treatment of heart failure in critical care unit

Zhenwu Decoction is recorded in Treatise on Febrile Diseases by an outstanding physician ZHANG Zhong-jing in the Han dynasty. With effect of warming yang, transforming Qi, and promoting urination, Zhenwu Decoction is mainly used to treat edema due to yang deficiency. The studies of the severe and critical cases and the pathophysiological mechanisms have demonstrated that the record of Zhenwu Decoction in Treatise on Febrile Diseases describes the clinical symptoms and therapeutic regimen of acute heart failure. The syndrome treated by this formula may be related to the misdiagnosis and wrong treatment. Due to the difficult distinguishing between cardiogenic dyspnea and pulmonary dyspnea, high doses of Ephedrae Herba may be misused for inducing sweating, which may finally lead to the acute aggravation of heart failure, electrolyte disorder, and pulmonary infection. The syndrome treated by Zhenwu Decoction can illustrate the lack of experience of ancient physicians in treating acute heart failure. The description of &quot;trembling and shivering&quot; may be the clinical manifestation of heart failure, which is an upgraded version of &quot;trembling and shaking&quot; treated by Linggui Zhugan Decoction.(1)In terms of diseases, Zhenwu Decoction is suitable for the treatment of acute or chronic heart failure, cardiorenal syndrome, and diuretic resistance. The decoction is especially suitable for treating whole heart failure, acute heart failure, heart failure with reduced ejection fraction, and heart failure with the syndrome of sold and dampness. In addition, it can be used to treat both type Ⅱ and type Ⅳ cardiorenal syndrome.(2)In terms of symptoms, Zhenwu Decoction can be used for treating chest tightness, palpitations, lower limb edema, difficult urination or increased urine output, fear of cold, pale fat tongue with teeth marks, white and slippery tongue fur, and deep or slow pulse.(3)In terms of the pharmacological mechanism, Zhenwu Decoction treats heart failure following the principle of promoting urination, expanding blood vessels, and invigorating heart in modern medicine. Aconiti Lateralis Radix Praparata is the sovereign herb in the formula, with the recommended dosage of 30-60 g. However, arrhythmia may be caused by high doses of Aconiti Lateralis Radix Praparata, which should be used with concern. In addition to Zhenwu Decoction, Shenqi Pills, Renshen Decoction, Wuling Powder, and Fangji Huangqi Decoction with the effect of invigorating spleen, replenishing Qi, warming Yang, and promoting urination can be used in the recovery stage. The therapy of reinforcing Yang was the last choice for critical cases due to the lack of medical conditions, unclear clinical diagnosis in history, which should be treated objectively now.

Increased circulating uric acid aggravates heart failure via impaired fatty acid metabolism

BackgroundIncreased circulating uric acid (UA) concentration may disrupt cardiac function in heart failure patients, but the specific mechanism remains unclear. Here, we postulate that hyperuremia induces sterol regulatory element binding protein 1 (SREBP1), which in turn activate hepatic fatty acid biosynthesis response, leading to cardiac dysfunction.Methods and resultsIncreased circulating uric acid was observed in heart failure patients and inversely correlated to cardiac function. Besides, uric acid correlated to circulating lipids profile based on metabolomics in heart failure patients. Using cultured human hepatoellular carcinomas (HepG2) and Tg(myl7:egfp) zebrafish, we demonstrated that UA regulated fatty acid synthase (FASN) via SREBP1 signaling pathway, leading to FFA accumulation and impaired energy metabolism, which could be rescued via SREBP1 knockdown. In ISO treated zebrafish, UA aggravated heart failure via increased cardiovascular cavity size, decreased heart beats, pericardial edema and long-stretched heart deformation.ConclusionsOur findings suggest that UA-SREBP1-FASN signaling exacerbates cardiac dysfunction during FFA accumulation. Identification of this mechanism may help in treatment and prevention of heart failure.

Bone status in men with heart failure: results from the Studies Investigating Co-morbidities Aggravating Heart Failure.

To assess bone status expressed as hip bone mineral density (BMD) in men with heart failure (HF). A total of 141 male patients with HF underwent dual energy X-ray absorptiometry to assess their BMD. We analysed markers of bone metabolism. Patients were classified as lower versus higher BMD according to the median hip BMD (median=1.162 g/cm2 ). Survival was assessed over 8 years of follow-up. Patients with lower BMD were older (71 ± 10 vs. 66 ± 9 years, p=0.004), more likely to be sarcopenic (37% vs. 7%, p < 0.001) and to have lower peak oxygen consumption (absolute peak VO2 1373 ± 480 vs. 1676 ± 447 ml/min, p < 0.001), had higher osteoprotegerin and osteocalcin levels (both p < 0.05) compared to patients with higher BMD. Among 47 patients with repeated BMD assessments, a significant reduction in BMD was noted over 30 months of follow-up. In multivariate logistic regression analysis, serum osteocalcin remained independently related with lower BMD (odds ratio [OR] 1.738, 95% confidence interval [CI] 1.136-2.660, p=0.011). Hip BMD and serum osteoprotegerin were independent predictors of impaired survival on Cox proportional hazard analysis (hazard ratio [HR] 0.069, 95% CI 0.011-0.444, p=0.005, and HR 0.638, 95% CI 0.472-0.864, p=0.004, respectively). Patients with HF lose BMD over time. Markers of bone turnover can help in identifying patients at risk with osteocalcin being an independent marker of lower hip BMD and osteoprotegerin an independent predictor of death. HF patients with increased osteocalcin and osteoprotegerin may benefit from BMD assessment as manifest osteoporosis seems to be too late for clinically meaningful intervention in HF.

Occlusion preconditioned mice are resilient to hypobaric hypoxia-induced myocarditis and arrhythmias due to enhanced immunomodulation, metabolic homeostasis, and antioxidants defense.

Sea-level residents experience altitude sickness when they hike or visit altitudes above ~2,500 m due to the hypobaric hypoxia (HH) conditions at such places. HH has been shown to drive cardiac inflammation in both ventricles by inducing maladaptive metabolic reprogramming of macrophages, which evokes aggravated proinflammatory responses, promoting myocarditis, fibrotic remodeling, arrhythmias, heart failure, and sudden deaths. The use of salidroside or altitude preconditioning (AP) before visiting high altitudes has been extensively shown to exert cardioprotective effects. Even so, both therapeutic interventions have geographical limitations and/or are inaccessible/unavailable to the majority of the population as drawbacks. Meanwhile, occlusion preconditioning (OP) has been extensively demonstrated to prevent hypoxia-induced cardiomyocyte damage by triggering endogenous cardioprotective cascades to mitigate myocardial damage. Herein, with the notion that OP can be conveniently applied anywhere, we sought to explore it as an alternative therapeutic intervention for preventing HH-induced myocarditis, remodeling, and arrhythmias. OP intervention (6 cycles of 5 min occlusion with 200 mmHg for 5 min and 5 min reperfusion at 0 mmHg - applying to alternate hindlimb daily for 7 consecutive days) was performed, and its impact on cardiac electric activity, immunoregulation, myocardial remodeling, metabolic homeostasis, oxidative stress responses, and behavioral outcomes were assessed before and after exposure to HH in mice. In humans, before and after the application of OP intervention (6 cycles of 5 min occlusion with 130% of systolic pressure and 5 min reperfusion at 0 mmHg - applying to alternate upper limb daily for 6 consecutive days), all subjects were assessed by cardiopulmonary exercise testing (CPET). Comparing the outcomes of OP to AP intervention, we observed that similar to the latter, OP preserved cardiac electric activity, mitigated maladaptive myocardial remodeling, induced adaptive immunomodulation and metabolic homeostasis in the heart, enhanced antioxidant defenses, and conferred resistance against HH-induce anxiety-related behavior. Additionally, OP enhanced respiratory and oxygen-carrying capacity, metabolic homeostasis, and endurance in humans. Overall, these findings demonstrate that OP is a potent alternative therapeutic intervention for preventing hypoxia-induced myocarditis, cardiac remodeling, arrhythmias, and cardiometabolic disorders and could potentially ameliorate the progression of other inflammatory, metabolic, and oxidative stress-related diseases.

S-53-3: DEVELOPMENT OF RISK SCORES TO PREVENT CARDIOVASCULAR DISEASES

There are still many places where medical care does not reach. In this abstract, from the perspective of the SDGs, we can see that we should tackle the world through the problems that Japan has. Social inequality faces many challenges that must be resolved in the future. First of all, as for income disparity, while absolute difficulties are declining worldwide, the number of relatively poor people in poverty compared to their standard of living is still increasing. Although Japan is the world’s third-largest economy, it is the worst in eight of the 41 OECD member countries. Regional disparities and their associated population disparities are also major issues. When the population flows out, it becomes depopulated, and the town’s infrastructure deteriorates. The medical system in depopulated areas is a serious problem. Educational disparities are caused by poverty, creating a chain of poverty. The digital divide is associated with educational inequality and can lead to health problems due to difficulty obtaining correct health and preventive information. The need for a nutritionally balanced diet to improve health is learned through education. Gender inequality is also a serious problem that causes employment inequality, income inequality, and education inequality. Japan’s Gender Gap Index in 2019 was the lowest in the G7 and 121st among the 153 countries in the world. Japan needs to improve the gender gap radically. As for the intergenerational disparity, Japan’s aging rate is about 30%, which is the largest in the world. Although it will continue to increase, the population will decrease sharply. As a result, the medical services received will become increasingly difficult for the elderly. Medical staff will be available when they really need it. We have created a model for predicting incident cardiovascular disease and its subtypes. The results are returned to the participants as a joint project between Suita City and its Medical Association to prevent the aggravation of heart failure, and the results are returned on a paper basis as a personal health record. As for health guidance, we developed Lifelong Health Support 10 (LHS10) so that the examinee can objectively understand where to improve in their daily lives. We are considering creating a mechanism that allows multi-worker intervention, such as incorporating such tools on smartphones. By utilizing LHS10, it is possible to contribute to reducing social disparity as health information that is objectively simple and easy for anyone to understand.

Predictors for NYHA recovery and 1-year mortality after mitral TEER

Abstract Background Mitral regurgitation (MR) is the second-most frequent valvular heart disease in Europe and frequently aggravates heart failure (HF) symptoms. Mitral transcatheter-edge-to-edge repair (TEER) can be considered in eligible patients, for both primary (in inoperable cases) or secondary severe MR. However, intervention is not advised in severe comorbid patients in whom it is not expected to prolong survival for over 1 year. Purpose Evaluate characteristics associated with HF New York Heart Association (NYHA) class recovery, and one-year all-cause mortality after mitral TEER for severe MR. Methods All mitral TEER procedures for primary and secondary MR conducted in a single-centre between 2014 and 2020 were retrospectively analyzed. The primary endpoint was defined as a reduction of at least one NYHA class in the first month after intervention, and a secondary endpoint considered a recovery of at least two NYHA classes. Survival status 12 months after mitral TEER was also consulted. Clinical, echocardiographic and blood-analysis data were explored as characteristics associated with the endpoints defined, using Pearson's Chi-squared test, Wilcoxon rank sum test and Fisher's exact test, as appropriate. A p&amp;lt;0.05 was considered statistically significant. Results From 103 mitral TEER procedures, 86 (83%) had full information about pre- and post-intervention NYHA class, as well as survival status at 12 months. There was a higher proportion of primary MR among NYHA non-responders (47% versus 25%, p=0.034), but no differences for secondary MR. Higher surgical risk patients (EuroSCORE II) tended to have exhibit more NYHA recovery, though not reaching statistical significance (p=0.068). Both a more advanced NYHA class at baseline and lower N-terminal pro-brain natriuretic peptide (NTproBNP) levels were linked to a higher symptomatic recovery (2048 versus 5676pg/ml, p&amp;lt;0.001). Also, persisting MR after TEER of at least grade 3/4 was more frequent in non-NYHA responders. Regarding NYHA improvement of at least two classes, it was observed in 13% patients, and these also had a more advanced NYHA class at baseline and lower NTproBNP basal levels, and exhibited a lower estimated systolic pulmonary artery pressure and inferior vena cava (IVC) diameter. Finally, 10 (11.6%) of mitral TEER patients died in the first 12 months, and no statistically significant associations were found regarding pre-intervention characteristics and survival. Conclusions This study suggests that three-fifths of severe MR improve their NYHA class after TEER, but only one-fourth for primary MR. Earlier intervention – with lower NTproBNP levels, less severe pulmonary hypertension, and lower IVC diameters – is associated with more symptomatic HF improvement. All-cause mortality in the first year is still significant, exposing a need for better patient selection. However, these findings represent exploratory deductions of a relatively low number, single-centre, patients. Funding Acknowledgement Type of funding sources: None.

Acute sleep deprivation increases inflammation and aggravates heart failure after myocardial infarction.

Sleep disorders have been observed among patients with heart failure. The aim of this study was to investigate whether acute sleep deprivation (SD) aggravates left heart function. Male C57B/L6 mice were assigned to four experimental groups. Ligation of the left anterior descending branch (LAD) caused myocardial infarction (MI) in mice in the LAD group and the LAD+SD group, while mice in the sham and sham+SD groups underwent the same surgery without ligation. Echocardiography was performed before and 8 weeks after ligation of the LAD to evaluate the left ventricular internal diameter at diastole (LVIDd), left ventricular internal diameter at systole (LVIDs), ejection fraction (EF), and fractional shortening (FS). Seven days of sleep deprivation induced using the modified single platform method resulted in a lower EF and FS and a higher LVIDd and LVIDs, as well as increased expression of the IL-1β, IL-18, and IL-10 mRNAs in the left ventricular tissue of MI mice. ELISA also indicated higher levels of IL-1β and IL-10 in the LAD+SD group. It was concluded that acute sleep deprivation induced cardiovascular alterations in cardiac structure and function in HF mice, accompanied by increased levels of inflammatory cytokines.

Tanshinone IIA improves cardiac function via regulating miR-499-5p dependent angiogenesis in myocardial ischemic mice

Background/aimsMyocardial ischemia-reperfusion injury leads to aggravated cardiac remodeling and heart failure. After myocardial infarction (MI), angiogenesis plays a vital role in the repair and regeneration of tissue. The purpose of the current study was to determine the effect of Tanshinone IIA (Tan IIA) on angiogenesis and elucidate its related mechanism. MethodsThe C57BL/6 mice MI model was established to evaluate the therapeutic effect of Tan IIA in vivo. MicroRNA (miRNA) microarray and bioinformatics analysis were performed to determine the differential expressions of miRNAs after Tan IIA administration. Cell proliferation, migration, and angiogenesis capacity were detected by EdU, Transwell, and Tube formation assay in vitro, respectively. The relationship between miR-499-5p (miR-499) and paired phosphate and tension homolog deleted on chromosome ten (PTEN) was confirmed by using a Dual-luciferase reporter assay. ResultsOur results showed that Tan IIA administration improved cardiac function after MI by activating angiogenesis. Further miRNA microarray and bioinformatics analysis revealed that miR-499 was significantly down-regulated, while PTEN was remarkably upregulated after Tan IIA administration post-MI. In addition, we found that miR-499 knock-down effectively promotes cell proliferation, migration, and tube formation ability of HUVECs. Dual-luciferase reporter assay demonstrated that PTEN contains a direct binding site for miR-499-5p. ConclusionTan IIA improves cardiac function post-MI by inducing angiogenesis. In terms of the mechanism, Tan IIA promotes therapeutic angiogenesis by regulating miR-499-5p/PTEN signaling pathway.

Cardiorenal Syndrome: An Updated Classification Based on Clinical Hallmarks.

Cardiorenal syndrome (CRS) is defined as progressive, combined cardiac and renal dysfunction. In this mini review, a historical note on CRS is presented, the pathomechanisms and clinical hallmarks of both chronic heart failure and chronic kidney disease are discussed, and an updated classification of CRS is proposed. The current consensus classification relies on the assumed etiology and the course of the disease, i.e., acute or chronic CRS. Five types are described: type-I CRS presenting as acute cardiac failure leading to acute renal failure; type-II CRS presenting as chronic cardiac failure leading to chronic renal failure; type-III CRS presenting as acute kidney injury aggravating heart failure; type-IV CRS presenting as chronic kidney failure aggravating heart failure; and type-V CRS presenting as concurrent, chronic cardiac and renal failure. For an updated classification, information on the presence or absence of valvular heart disease and on the presence of hyper- or hypovolemia is added. Thus, CRS is specified as “acute” (type-I, type-III or type-V CRS) or “chronic” (type-II, type-IV or type-V) CRS, as “valvular” or “nonvalvular” CRS, and as “hyper-” or “hypovolemia-associated” CRS if euvolemia is absent. To enable the use of this updated classification, validation studies are mandated.