Targeting epicardial adipose tissue: A potential therapeutic strategy for heart failure with preserved ejection fraction with type 2 diabetes mellitus

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various comorbidities, multiple cardiac and extracardiac pathophysiologic abnormalities, and diverse phenotypic presentations. Since HFpEF is a heterogeneous disease with different phenotypes, individualized treatment is required. HFpEF with type 2 diabetes mellitus (T2DM) represents a specific phenotype of HFpEF, with about 45%-50% of HFpEF patients suffering from T2DM. Systemic inflammation associated with dysregulated glucose metabolism is a critical pathological mechanism of HFpEF with T2DM, which is intimately related to the expansion and dysfunction (inflammation and hypermetabolic activity) of epicardial adipose tissue (EAT). EAT is well established as a very active endocrine organ that can regulate the pathophysiological processes of HFpEF with T2DM through the paracrine and endocrine mechanisms. Therefore, suppressing abnormal EAT expansion may be a promising therapeutic strategy for HFpEF with T2DM. Although there is no treatment specifically for EAT, lifestyle management, bariatric surgery, and some pharmaceutical interventions (anti-cytokine drugs, statins, proprotein convertase subtilisin/kexin type 9 inhibitors, metformin, glucagon-like peptide-1 receptor agonists, and especially sodium-glucose cotransporter-2 inhibitors) have been shown to attenuate the inflammatory response or expansion of EAT. Importantly, these treatments may be beneficial in improving the clinical symptoms or prognosis of patients with HFpEF. Accordingly, well-designed randomized controlled trials are needed to validate the efficacy of current therapies. In addition, more novel and effective therapies targeting EAT are needed in the future.     

Short-term rapid weight loss induced by bariatric surgery improves ventricular ejection fraction in patients with severe obesity and heart failure

BackgroundObesity is a major risk factor for the development of metabolic syndrome, coronary artery disease, and heart failure (HF). Rapid weight loss following bariatric surgery can significantly improve outcomes for patients with these diseases.ObjectivesTo assess whether bariatric surgery improves ventricular ejection fraction in patients with obesity who have heart failure.SettingPrivate practice, United States.MethodsWe conducted a retrospective review of echocardiographic changes in systolic functions in patients with obesity that underwent bariatric surgery at our institution. Patients were divided into 2 groups, those (1) without known preoperative HF and (2) with preoperative HF. We compared the left ventricular ejection fraction (LVEF) before and after bariatric surgery in both groups. Common demographics and co-morbidities were also analyzed.ResultsA total of 68 patients were included in the analysis: 49 patients in group 1 and 19 in group 2. In group 1, 59.2% (n = 29) of patients were female, versus 57.9% (n = 11) in group 2. The excess body mass index lost at 12 months was 52.06 ± 23.18% for group 1 versus 67.12 ± 19.27% for group 2 (P = .0001). Patients with heart failure showed a significant improvement in LVEF, from 38.79 ± 13.26% before to 48.47 ± 14.57% after bariatric surgery (P = .039). Systolic function in patients from group 1 showed no significant changes (59.90 ± 6.37 mmHg) before and (59.88 ± 7.85 mmHg) after surgery (P = .98).ConclusionRapid weight loss after bariatric surgery is associated with a considerable increase in LVEF and a significant improvement of systolic function.     

Longitudinal evaluation of ventricular ejection fraction and NT-proBNP across heart failure subgroups

Objectives: Left ventricular ejection fraction (EF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are important surrogate markers of cardiac function and wall stress. Randomized trials of heart failure (HF) have shown improvements in survival in patients with reduced EF (<40%, HFrEF) but not with preserved EF (≥50%, HFpEF) or mid-range EF (40-49%, HFmrEF). Limited information is available on the trajectory of EF in contemporary heart failure management programs (HFMPs).

Design: 201 HF patients consecutively enrolled 2010–2011 in the outpatient-based HFMP of Skåne University Hospital in Lund were included in the study. Probable etiology, EF, NT-proBNP and medications were assessed at baseline and 1 year after enrollment.

Results: HFrEF was the most common heart failure subgroup (78.1% of patients) in this HFMP, followed by HFmrEF (14.9%) and HFpEF (7.0%). The most common etiology was ischemic heart disease (IHD, 40.8%).

Complete recovery of EF (>50%) was rare (14.1% of patients with HFrEF and 26.7% with HFmrEF), some degree of improvement was observed in 57.7% and 46.7% of patients. LVEF improved on average 9.1% in patients with HFrEF (p?p?Conclusions: This study provides estimates of the improvement in LVEF and NT-proBNP that can be expected with contemporary management across subgroups of HF and different etiologies in a contemporary HFMP.     

Parallel improvement of systolic function with surgical weight loss in patients with heart failure and reduced ejection fraction: a systematic review and patient-level meta-analysis

BackgroundMorbid obesity (MO) is an increasingly common condition in patients with heart failure with reduced ejection fraction (HFrEF). Although substantial weight loss in morbidly obese patients has proved to slow the progression of heart failure, parallel alteration of ejection fraction (EF) and New York Heart Association (NYHA) functional class along with post-bariatric surgery weight loss is yet to be determined.ObjectivesThis systematic review aimed to measure the effect of bariatric weight loss on EF and NYHA functional class in patients with HFrEF.MethodsA systematic literature review was performed in Medline/PubMed to identify studies in patients with MO and pre-existing HFrEF, who underwent bariatric surgery.ResultsA total of 11 studies encompassing 136 patients with HFrEF undergoing bariatric surgery for MO were included. Six studies provided patient-level data on 37 cases. Patients lost an average body mass index (BMI) of 12.9 ± 4.2 kg/m² (5.1 to 23 kg/m²) after an average follow up of 22.43 ± 18.6 months (2–89 mo). There was a direct correlation between BMI loss and EF improvement (r = 0.61, P < .0001), but not between BMI loss and NYHA functional class changes (r = 0.17, P = .4).ConclusionWeight loss induced by bariatric surgery results in parallel EF increase in patients with MO and HFrEF. However, current data does not indicate a parallel improvement of clinical symptoms (NYHA functional class) along with such an increase in EF in this population of patients.     

Improvement in ejection fraction by nocturnal haemodialysis in end-stage renal failure patients with coexisting heart failure.

BACKGROUND: Congestive heart failure (CHF) is an independent risk factor for mortality in the end-stage renal disease (ESRD) population. Nocturnal haemodialysis (NHD), a novel mode of renal replacement therapy, may be more effective than conventional haemodialysis in reducing intravascular volume or in removing uraemic toxins with vasoconstrictor or myocardial depressant actions, and may, therefore, improve the left ventricular (LV) systolic function of patients with coexisting cardiac and renal failure. METHODS: To test this hypothesis, we determined, in six patients (mean age+/-SD: 49.5+/-9 years), blood pressure (BP), ejection fraction (EF: radionucleotide angiography), left ventricular mass index (LVMI: echocardiography), LV fractional shortening (FS), and extracellular fluid volume (ECFV: bioelectrical impedance): before and after a mean of 3.2+/-2.1 years following conversion from conventional dialysis (3 days/week x 4 h) to NHD (6 nights/week x 8-10 h). RESULTS: There were significant reductions in systolic and mean arterial BP (138+/-10 to 120+/-9 mmHg, P=0.04; 99+/-6 to 86+/-7 mmHg, P=0.01). There was a significant increase in EF (28+/-12 to 41+/-18%, P=0.01) and a trend to greater LV FS (20+/-10 to 38+/-17%, P=0.06). Post-dialysis ECFV was not affected by dialysis mode (18.5+/-5.1 vs 18.2+/-3.5 l, P=0.76). The number of prescribed cardiovascular medications was reduced (2.2-0.7, P=0.02). CONCLUSIONS: In ESRD patients with systolic dysfunction, NHD leads to a sustained increase of EF and a reduction in the requirement for vasoactive medications in the absence of any reduction in post-dialysis ECFV.     

Drugs acting on the heart: heart failure and coronary insufficiency

Heart failure (HF) and coronary insufficiency are common amongst surgical and critical care patients. Both are chronic conditions interrupted by acute episodes. HF activates neurohormonal mechanisms that worsen renal and cardiac function. Acute heart failure (AHF) commonly presents with dyspnoea as a consequence of systolic and/or diastolic dysfunction. Goals of treatment are symptom relief, to maintain tissue perfusion and optimize cardiac function. Diuretics and vasodilators are used early; positive inotropic drugs are reserved for when other treatment has failed. Chronic heart failure (CHF) is treated using changes in lifestyle and drugs to manage symptoms. ACE inhibitors and beta-blockers are effective in systolic heart failure and are associated with improved mortality. HF with preserved ejection fraction (HFPEF) is less responsive to drug therapy, though outcomes are better than for systolic HF. Coronary insufficiency occurs because of an imbalance of myocardial oxygen balance, leading to symptoms of ischaemic heart disease (IHD). Treatment goals are maintaining coronary blood flow and reducing myocardial oxygen demand. Beta-blockers and anti-platelet drugs improve outcomes; modern anti-platelets are more effective but are associated with risks of haemorrhage. Statins are effective for primary and secondary prevention of myocardial infarction; they have additional anti-inflammatory properties.     

Drugs acting on the heart: heart failure and coronary insufficiency

Heart failure (HF) and coronary insufficiency are common amongst surgical and critical care patients. Both are chronic conditions interrupted by acute episodes. HF activates neurohormonal mechanisms that worsen renal and cardiac function. Acute heart failure (AHF) commonly presents with dyspnoea as a consequence of systolic and/or diastolic dysfunction. Goals of treatment are symptom relief to maintain tissue perfusion and optimize cardiac function. Diuretics and vasodilators are used early; positive inotropic drugs are reserved for when other treatment has failed. Chronic heart failure (CHF) is treated using changes in lifestyle and drugs to manage symptoms. ACE inhibitors and beta-blockers are effective in systolic heart failure and are associated with improved mortality. HF with preserved ejection fraction (HFPEF) is less responsive to drug therapy, though outcomes are better than for systolic HF. Coronary insufficiency occurs because of an imbalance of myocardial oxygen balance, leading to symptoms of ischaemic heart disease (IHD). Treatment goals are maintaining coronary blood flow and reducing myocardial oxygen demand. Beta-blockers and anti-platelet drugs improve outcomes; modern anti-platelets are more effective but are associated with risks of haemorrhage. Statins are effective for primary and secondary prevention of myocardial infarction; they have additional anti-inflammatory properties.     

In-hospital outcomes after rotational atherectomy in patients with low ejection fraction

Objectives. This study evaluated angiographic success and in-hospital outcomes of percutaneous coronary intervention (PCI) with rotational atherectomy (RA) in patients with low left ventricular ejection fraction (LVEF). Design. Between January 2010 and March 2014, 272 consecutive patients with heavily calcified lesions underwent elective PCI with RA. Of these, 33 patients had LVEF?≤35% (low LVEF group), whereas 237 patients had LVEF?>35% (preserved LVEF group). The primary endpoint was angiographic success and in-hospital major adverse cardiac events (MACE). MACE included death from any cause, postprocedure onset MI, emergency coronary artery bypass grafting, and target vessel revascularization. The secondary endpoints were MACE and the components within 30days after PCI. The components of MACE were evaluated. Results. Angiographic success, defined as <30% residual stenosis with thrombolysis in myocardial infarction flow 3 at final angiography, was achieved in all patients without fatal complications. Intra-aortic ballon pumping (IABP) was used significantly more frequently in the low LVEF group compared with the preserved LVEF group (15.2% vs. 2.1%, p?=?.003). There were no significant differences between groups regarding in-hospital and clinical outcomes within 30 days following PCI. Conclusion. If medications and mechanical support were appropriately performed, the angiographic success rate and in-hospital MACE rate of PCI with RA in patients with low LVEF could be expected to have good outcomes similar to those for patients with preserved LVEF.     

ST2 in heart failure with preserved and reduced ejection fraction

Objectives. Soluble suppression of tumorigenecity 2 (sST2) is prognostic in acute and chronic heart failure with reduced ejection fraction (HFrEF) but less studied in HF with preserved EF (HFpEF). We evaluated sST2 concentrations, correlations with biomarkers and echocardiographic measures of diastolic and systolic function, and associations with outcomes in HFpEF and HFrEF. Design and results. A total of 193 subjects from three different cohorts were included. Eighty-six HFpEF patients were obtained from the Karolinska Rennes (KaRen) study, 86 patients with HFrEF were recruited from referrals to Karolinska University Hospital for advanced assessment of HF, and 21 controls were included (ClinicalTrials.gov Identifier for KaRen: NCT01091467). HFrEF and controls cohorts did not have ClinicalTrials.gov registrations. sST2 was lower in HFpEF, median (interquartile range); 23 (17–31) compared to HFrEF; 35 (23–52) µg/L, p?_s=0.392, p?_s=0.466, p?_s=0.276, p?=?.019) but not to E/E´, nor to left ventricular mass index. sST2 was in HFpEF associated with the composite endpoint of death or HF hospitalization, adjusted hazard ratio (HR) per log increase in sST2 6.62, 95% confidence interval (CI) 1.04–42.28, p?=?.046, and in HFrEF death, heart transplant or left ventricular assist systems; 3.51, 95% CI 1.05–11.69, p?=?.041. Conclusions. In patients with HFpEF compared to HFrEF, crude levels of sST2 were lower but potentially more strongly associated with outcomes. The lower levels of sST2 in HFpEF than in HFrEF may reflect lower degrees of fibrosis, but the potentially stronger association with outcomes may reflect a greater prognostic importance of progressive fibrosis and as such a greater potential for intervention. In conclusion; this study adds to the evidence of sST2 as prognostic marker in both HFpEF and HFrEF.

Trial registration: ClinicalTrials.gov identifier: NCT01091467.     

Sleeve gastrectomy in obese Wistar rats improves diastolic function and promotes cardiac recovery independent of weight loss

BackgroundHeart failure with preserved ejection fraction is the most common cause of heart failure and is characterized by impaired diastolic relaxation. Bariatric surgery significantly improves diastolic relaxation, but a mechanism beyond weight loss remains unknown.ObjectivesWe tested the hypothesis that a sleeve gastrectomy (SG) will improve diastolic dysfunction independent of weight loss due to postoperative alterations in the enterocardiac axis.SettingUniversity research laboratory.MethodsMale Wistar rats were fed a high-fat diet (HFD) or low-fat diet (LFD) for 10 weeks and then divided into SG-HFD, pair-fed sham HFD, ad-lib sham HFD, or ad-lib sham LFD groups (n = 9–14 per group). At least 2 months postoperatively, cardiac function, meal tolerance, glucose tolerance, and cardiac gene expression were compared between groups.ResultsOnly the SG cohort showed significant improvements in postoperative diastolic relaxation (isovolumetric relaxation time pre-SG: 14.7 ± 2.3 msec, post-SG: 11.2 ± 1.8 msec, P < .001). SG significantly increased active glucagon-like peptide-1 (P = .03). Compared to pair-fed sham HFD rats, SG-HFD rats had significantly altered mRNA cardiac gene expression, including sarco/endoplasmic reticulum Ca2+-ATPase 2 a (SERCA2 a) (P < .001).ConclusionsSG improves diastolic function independent of weight loss in a rat model of obesity with beneficial alterations in cardiac gene expression of multiple known targets related to cardiac failure, including SERCA2 a. These data support that a greater curve gastrectomy induces beneficial intracellular cardiac signaling for diastolic function mediated by the enterocardiac axis that is independent of weight loss. These findings could translate to offering metabolic surgery to patients with heart failure with preserved ejection fraction.     

Antithrombin III is associated with acute liver failure in patients with end-stage heart failure undergoing mechanical circulatory support

Objective

There are few data on the role of liver dysfunction in patients with end-stage heart failure supported by mechanical circulatory support. The aim of our study was to investigate predictors for acute liver failure in patients with end-stage heart failure undergoing mechanical circulatory support.

Durable circulatory support with a paracorporeal device as an option for pediatric and adult heart failure patients

ObjectivesNot all patients in need of durable mechanical circulatory support are suitable for a continuous-flow left ventricular assist device. We describe patient populations who were treated with the paracorporeal EXCOR, including children with small body sizes, adolescents with complex congenital heart diseases, and adults with biventricular failure.MethodsInformation on clinical data, echocardiography, invasive hemodynamic measurements, and surgical procedures were collected retrospectively. Differences between various groups were compared.ResultsBetween 2008 and 2018, a total of 50 patients (21 children and 29 adults) received an EXCOR as bridge to heart transplantation or myocardial recovery. The majority of patients had heart failure compatible with Interagency Registry for Mechanically Assisted Circulatory Support profile 1. At year 5, the overall survival probability for children was 90%, and for adults 75% (P = .3). After we pooled data from children and adults, the survival probability between patients supported by a biventricular assist device was similar to those treated with a left ventricular assist device/ right ventricular assist device (94% vs 75%, respectively, P = .2). Patients with dilated cardiomyopathy had a trend toward better survival than those with other heart failure etiologies (92% vs 70%, P = .05) and a greater survival free from stroke (92% vs 64%, P = .01). Pump house exchange was performed in nine patients due to chamber thrombosis (n = 7) and partial membrane rupture (n = 2). There were 14 cases of stroke in eleven patients.ConclusionsDespite severe illness, patient survival on EXCOR was high, and the long-term overall survival probability following heart transplantation and recovery was advantageous. Treatment safety was satisfactory, although still hampered by thromboembolism, mechanical problems, and infections.     

Miniaturization of mechanical circulatory support systems

Heart failure (HF) is increasing worldwide and represents a major burden in terms of health care resources and costs. Despite advances in medical care, prognosis with HF remains poor, especially in advanced stages. The large patient population with advanced HF and the limited number of donor organs stimulated the development of mechanical circulatory support (MCS) devices as a bridge to transplant and for destination therapy. However, MCS devices require a major operative intervention, cardiopulmonary bypass, and blood component exposure, which have been associated with significant adverse event rates, and long recovery periods. Miniaturization of MCS devices and the development of an efficient and reliable transcutaneous energy transfer system may provide the vehicle to overcome these limitations and usher in a new clinical paradigm in heart failure therapy by enabling less invasive beating heart surgical procedures for implantation, reduce cost, and improve patient outcomes and quality of life. Further, it is anticipated that future ventricular assist device technology will allow for a much wider application of the therapy in the treatment of heart failure including its use for myocardial recovery and as a platform for support for cell therapy in addition to permanent long-term support.     

低射血分数非体外循环冠状动脉旁路移植术患者围术期相关危险因素分析

目的 分析术前合并低射血分数(EF)的非体外循环冠状动脉旁路移植术(OPCABG)患者围术期相关危险因素.方法 应用自制OPCABG麻醉数据库,对我院2007年11月至2009年2月2 379例OPCABG患者围术期相关资料进行回顾性分析,以术前EF＜40%定义为低EF,将患者分为EF＜40%组(n=2 224)与EF≥40%组(n=155)进行单因素分析,再分别以术后死亡、术后透析、术中室颤、术中主动脉内球囊反搏(IABP)以及术中紧急中转心肺转流(CPB)为终点事件,进行单因素与多因素逻辑回归分析.结果 术前EF＜40%组患者占所有患者的6.5%,经单因素分析,与术前低EF显著相关的危险因素有心肌梗死史、术前室早、房颤、肝功能异常、室壁瘤、合并瓣膜病;经多因素逻辑回归分析,发现术前低EF是术中室颤、IABP以及术后死亡的独立危险因素,但不是术中紧急中转CPB、术后透析的独立危险因素.结论 术前合并低EF分别是术中室颤、术中IABP及术后死亡的独立危险因素.