Aggravation Of Heart Failure Research Articles

Clinical Implications of Heart Rate Control in Heart Failure With Atrial Fibrillation: Multi-Center Prospective Observation Registry (CODE-AF Registry).

BackgroundAtrial fibrillation (AF) is treated by heart rate (HR) control. However, the optimal HR target in AF patients with heart failure (HF) remains unclear. To evaluate the clinical implication of the resting HR in AF patients with HF accompanied by preserved, mid-range, or reduced ejection fraction (HFpEF, HFmrEF, or HFrEF, respectively).MethodsEchocardiographic data from June 2016 to April 2020 in a prospective, multicenter, observational registry from 11,104 patients were analyzed. The follow-up duration was 2.2 years. The main outcome was composite of death and hospitalization. We categorized patients according to the HF type and resting HR: ≤ 60 bpm, 61–80 bpm, 81–110 bpm, and >110 bpm.ResultsA total of 1,421 patients were enrolled in the study: 582 in the HFpEF group, 506 in the HFmrEF group, and 333 in the HFrEF group. The patients had a mean age of 69 ± 11 years and consisted of 872 (61.4%) men. Primary endpoint rates among HFpEF patients with 60 < HR ≤ 110 bpm were lower than those with HR ≤ 60 bpm (61–80 bpm group: hazard ratio, 0.66; 95% CI, 0.46–0.94; p = 0.021; 81–110 bpm group: hazard ratio, 0.60; 95% CI, 0.40–0.90; p = 0.013). Especially, HFpEF patients with HR 81–110 bpm had a lower incidence of hospitalization caused by HF aggravation than those with other HR strata (HR ≤ 80bpm strata or HR >110 bpm strata). In HFmrEF and HFrEF patients, the survival rates did not differ significantly among patients in the three groups with HR ≤ 110 bpm. Moreover, the event rates increased significantly in HFmrEF patients with HR >110 bpm (hazard ratio, 1.91; 95% CI, 1.16-3.14, p = 0.011).ConclusionIn patients with AF and HFpEF, the resting HR has U-shaped associations with the overall primary endpoint. A lower or higher resting HR is associated with increased cardiovascular outcomes, especially in patients with HFpEF and AF.

An updated systematic review on heart failure treatments for patients with renal impairment: the tide is not turning.

Advanced chronic kidney disease (CKD) frequently aggravates heart failure (HF). However, these patients have inherently been excluded from most HF trials. We aim to provide updated estimates of the representation of patients with advanced CKD and the provision of baseline renal function indices in HF trials with a focused interest on the landmark trials. Updated systematic review wasperformed from the inception of MEDLINE to 31 December 2019 to identify all chronic HF randomized trials published in the three major cardiology and medical journals, respectively, which included mortality endpoint. The included studies were analysed based on the representativeness of the advanced CKD population and the reporting of baseline renal function. A total of 187 eligible randomized trials with 322,374 participants were included in our analysis. One hundred and six trials (56.7%) had exclusion criteria related to renal function, which remained a continuing trend-55.1% (27/49) from inception-2000, 53.4% (39/73) from 2001-2010 and 61.5% (40/65) from 2011 (P = 0.64). The exclusion criteria, however, have become less restrictive. There was a temporal improvement in the likelihood of HF trials in providing baseline renal function indices (28.6% from inception-2000 versus 53.4% from 2001-2010 and 83.1% from 2011, P < 0.001). Concordant findings were observed in the landmark trials. Patients with advanced CKD remain underrepresented in HF trials in the contemporary era, even though the exclusion criteria have become less restrictive, and the quality of renal function monitoring has improved. The continued underrepresentation of patients with advanced CKD in HF trials merits measured broadening of eligibility in further trial studies.

Management of heart failure with reduced ejection fraction: challenges in patients with atrial fibrillation, renal disease and in the elderly.

Heart failure with reduced ejection fraction (HFrEF) is an increasing global pandemic affecting more than 30 million individuals worldwide. Importantly, HFrEF is frequently accompanied by the presence of cardiac and non-cardiac comorbidities that may greatly influence the management and prognosis of the disease. In this review article, we will focus on three important comorbidities in HFrEF; atrial fibrillation (AF), advanced renal disease, and elderly, which all have a paramount impact on progression of the disease, management strategies, and response to therapy. AF is very common in HFrEF and shares many risk factors. AF aggravates heart failure and contributes to HF-related adverse clinical outcomes; hence it requires special consideration in HFrEF management. The kidney function is largely affected by the reduced cardiac output developed in the setting of HFrEF, and the neurohormonal feedback effects create a complex interplay that pose challenges in the management of HFrEF when renal function is significantly impaired. Cardiorenal syndrome is a challenging sequela with increased morbidity and mortality thereby reflecting the delicate and complex balance between the heart and the kidney in HFrEF and renal failure conditions. Furthermore, patients with advanced renal failure have poor prognosis in the presence of HFrEF with limited treatment options. Finally, aging and frailty are important factors that influence treatment strategies in HFrEF with greater emphasis on tolerability and safety of the various HFrEF therapies in elderly individuals.

Device treatment of heart failure

Background: The incidence of heart failure (HF) is rapidly increasing, introducing a significant burden and challenges in clinical practice. Non-pharmacological cardiac device therapy has been established as an essential component of optimal HF management, particularly for the prevention of sudden cardiac death and the improvement of HF symptoms, left ventricular (LV) systolic function, quality of life, and eventually survival.Current Concepts: Cardiac resynchronization therapy (CRT) can correct atrioventricular or inter/intraventricular dyssynchrony, thereby improving LV systolic function. Recently, the concept of CRT is being expanded, including His bundle (HB), HB-optimized LV, left bundle branch (LBB), and LBB optimized LV pacing CRTs. Newly introduced CRT approaches by stimulating the cardiac conduction system are expected to correct dyssynchrony better and consequently exhibit better CRT outcomes than the conventional biventricular pacing CRT. The current versions of implantable cardioverter-defibrillators (ICDs) or CRT devices can continuously monitor multiple biosignals. CRT/ICD can calculate a single index by combining these multiple bio-signal data for early detection of HF aggravation. Recently, subcutaneous and transvenous ICDs showed comparable safety and efficacy in HF patients. In drug-refractory HF patients without LV dyssynchrony, cardiac contractility modulation therapy provides some promising results.Discussion and Conclusion: Recent technological advancements have improved the efficacy and safety of cardiac device therapy. Therefore, cardiac device therapy should be used more actively to manage HF patients better.

Clinical Experience of Liang Junzhao in the Treatment of Premature Ventricular Contractions

Premature ventricular contraction is a common disease of cardiovascular diseases, its incidence increases with the age of the current western medicine treatment of premature ventricular easy to produce bradycardia heart block, aggravating heart failure and other side effects, while traditional Chinese medicine for the treatment of premature ventricular has definite curative effect, small side effects, good prognosis and other unique advantages Liang Junzhao, the name of traditional Chinese medicine combined with many years of clinical experience, that the disease because of Qi deficiency and blood stasis, mind loss, clinical to Yi qi and blood circulation, fumaianshen prescription and curative effect is significant for the treatment of ventricular premature beats to provide a new dialectical thinking.

Impact of Catheter Ablation on Quality of Life and Healthcare Utilisation.

Impairment of quality of life (QoL) is a well-known complication of AF. Because of the association of AF with older age and many other cardiovascular comorbidities, there are multiple factors that could influence QoL score even after successful AF intervention. However, substantial improvement in QoL has been reported following catheter ablation for AF regardless of ablation outcomes. In terms of healthcare resource utilisation, the expenses associated with AF are very high because of the hospitalisations for AF-related thromboembolic complications, aggravation of heart failure, AF interventions, and emergency room visits for incessant arrhythmia episodes, and they represent a large economic burden worldwide. Several trials have shown a drastic reduction in healthcare costs following successful AF ablation. In this review, the authors discuss this evidence systematically.

Regulatory Mechanism of LINC00152 on Aggravating Heart Failure through Triggering Fibrosis in an Infarcted Myocardium.

Objective To elucidate the role of LINC00152 in the progression of heart failure following myocardial infarction. Patients and Methods. Serum levels of LINC00152 in acute myocardial infarction (AMI) patients were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) curves were depicted for assessing the diagnostic value of LINC00152 in AMI. Subsequently, an in vivo AMI model was generated in mice. LINC00152 level in a mouse infarcted myocardium was detected. Echocardiogram was conducted to evaluate the influence of LINC00152 on cardiac function in AMI mice. Primary cardiac fibroblasts were isolated from neonatal mice. After knockdown of LINC00152, proliferative and migratory changes in primary cardiac fibroblasts were assessed by cell counting kit-8 (CCK-8) and transwell assay, respectively. The regulatory effect of LINC00152 on Smad7 level was determined by qRT-PCR. Finally, the involvement of Smad7 in LINC00152-regulated proliferative and migratory abilities in primary cardiac fibroblasts was explored by rescue experiments. Results Serum level of LINC00152 was elevated in AMI patients. ROC curves demonstrated the diagnostic potential of LINC00152 in AMI (95% CI: 0.806-0.940, p = 0.034). In myocardial tissues collected from AMI mice, LINC00152 level was higher than those collected from mice of the sham group. LVEF and FS markedly decreased in AMI mice overexpressing LINC00152 on the 4th week of AMI modeling. After knockdown of LINC00152 in primary cardiac fibroblasts, proliferative and migratory abilities were declined, which were abolished by Smad7 intervention. Conclusions By downregulating Smad7, LINC00152 aggravates heart failure following AMI via promoting the proliferative and migratory abilities in cardiac fibroblasts.

Essentials in the diagnosis of postoperative myocardial lesions similar to or unrelated to rejection in heart transplant

Abstract Background, objectives: Histological diagnosis of control biopsies in patients with heart transplant represents a significant step of monitoring, with a great influence on adjusting immunosuppressive treatment. Histological lesions are usually related to ischemia and reperfusion, with varying degrees of intensity. This study aimed to highlight the most important aspects of the histological diagnosis and differential diagnosis of postoperative myocardial lesions associated or unrelated to rejection in heart transplant. Materials and Methods: This retrospective study involved 53 patients who received cardiac transplant between 2000 and 2017. Patients were monitored by lesion quantification of endomyocardial biopsies, with diagnoses established based on biopsy material in the early, medium and late post-transplant periods. Hematoxylin eosin, Masson’s trichrome, and Van Gieson stains were used; immunohistochemical determinations used CD4, CD20, CD45, CD68, HLA-DR, VEGF and CD31. Results: Ischemia and reperfusion lesions were diagnosed on all biopsies in the first 6 weeks post-transplant. Nine cases of the Quilty effect were identified, and in 12 cases, the biopsies were performed on the same spot as previous biopsies. A significant number of transplanted patients presented cytomegalovirus that was difficult to diagnose on endomyocardial biopsies. Conclusions: The detailed study of ischemia and reperfusion lesions, as well as of changes un-related to rejection becomes a major objective in the short, medium and late post-transplant period. Overdiagnosis of rejection induces changes of the immunosuppressive therapeutic protocol, with alarming repercussions on cytomegalovirus reactivation, and risks of potentiating inflammation, myocyte destruction and the recurrence of disorders related to both inducing and aggravating heart failure.

Lateral Wall Dysfunction Signals Onset of Progressive Heart Failure in Left Bundle Branch Block

ObjectivesThis study sought to investigate if contractile asymmetry between septum and left ventricular (LV) lateral wall drives heart failure development in patients with left bundle branch block (LBBB) and whether the presence of lateral wall dysfunction affects potential for recovery of LV function with cardiac resynchronization therapy (CRT). BackgroundLBBB may induce or aggravate heart failure. Understanding the underlying mechanisms is important to optimize timing of CRT. MethodsIn 76 nonischemic patients with LBBB and 11 controls, we measured strain using speckle-tracking echocardiography and regional work using pressure-strain analysis. Patients with LBBB were stratified according to LV ejection fraction (EF) ≥50% (EFpreserved), 36% to 49% (EFmid), and ≤35% (EFlow). Sixty-four patients underwent CRT and were re-examined after 6 months. ResultsSeptal work was successively reduced from controls, through EFpreserved, EFmid, and EFlow (all p < 0.005), and showed a strong correlation to left ventricular ejection fraction (LVEF; r = 0.84; p < 0.005). In contrast, LV lateral wall work was numerically increased in EFpreserved and EFmid versus controls, and did not significantly correlate with LVEF in these groups. In EFlow, however, LV lateral wall work was substantially reduced (p < 0.005). There was a moderate overall correlation between LV lateral wall work and LVEF (r = 0.58; p < 0.005). In CRT recipients, LVEF was normalized (≥50%) in 54% of patients with preserved LV lateral wall work, but only in 13% of patients with reduced LV lateral wall work (p < 0.005). ConclusionsIn early stages, LBBB-induced heart failure is associated with impaired septal function but preserved lateral wall function. The advent of LV lateral wall dysfunction may be an optimal time-point for CRT.

Causes, management and complications of severe adult dehydration in the emergency room

This literature review aims to highlight the possible causes, complications, and management of this event from previously published studies discussing dehydration in critically-ill patients admitted to the emergency room (ER). In general, the administration of fluids has been used in the ER for critically-ill patients for many purposes. These include the optimization and adjustment of body fluids and electrolytes, increase renal protection against contrast, enhance uric acid, globins, caloric intake, and as an adjuvant to ameliorate the potentiality of certain medications or to dilute them. Many etiologies have been accused to cause dehydration in critically-ill patients. These include the fasting strategy that patients are obliged to whenever undergoing a surgical operation. Kidney, heart, and liver injuries have also been associated with patients’ dehydration. Old age and the presence of other co-morbidities diabetes insipidus and uncontrolled diabetes can also aggravate the condition. Mental affection is the main complication that patients with severe dehydration might complain about. Other complications might include aggravation of heart failure, and skin diseases, and deterioration of the kidney functions and other cellular processes that require adequate nourishment for their daily normal functions. Mortality is also a serious common complication, especially within elderly patients. Although the management of dehydration can be easily achieved by fluid administration, fluid overload can aggravate the underlying complications and develop others. Therefore, the main challenge here would be to frequently monitor patients during fluid administration and resuscitation to prevent this side effect.

Clinical Outcomes of Transcatheter Aortic Valve Implantation for Native Aortic Valves in Patients with Low Coronary Heights.

PurposeAcute coronary occlusion is a rare but fatal complication that may occur during trans-catheter aortic valve implantation (TAVI) and appears more frequently in patients with low coronary heights. We evaluated the feasibility of self-expanding valves in patients with low coronary heights undergoing TAVI.Materials and MethodsTAVI for native aortic valve stenosis was conducted in 276 consecutive patients between 2015 and 2019 at our institute. Using multi-detector computed tomography (MDCT), information on the aortic valve, coronary arteries, and vascular anatomy in 269 patients was analyzed. Patients with low coronary heights were defined as those with coronary heights of 10 mm or less during MDCT analysis.ResultsAmong the 269 patients, 29 (10.8%) patients had coronary arteries with low heights. The mean coronary height was 8.9±1.2 mm in the left coronary artery. These patients with low coronary heights were treated with self-expandable (n=28) or balloon-expandable (n=1) valves. Prophylactic coronary protection with a guidewire, balloon, or stent prepositioned down at-risk coronary arteries was not pursued in all patients. No acute coronary occlusion occurred in any of these patients during TAVI. Five patients (17.9%) died during follow-up (average of 553.8 days), including four from non-cardiogenic causes and one from a cardiogenic (aggravation of heart failure) cause.ConclusionA considerable number of patients with low coronary heights were observed among TAVI candidates in this study. Use of a self-expandable valve may be feasible for successful TAVI without acute coronary occlusion in patients with low coronary heights.

Long Non-Coding RNA SOX2 Overlapping Transcript Aggravates H9c2 Cell Injury via the miR-215-5p/ZEB2 Axis and Promotes Ischemic Heart Failure in a Rat Model.

Heart failure is a common cardiovascular disease, which has been regarded as one of the highest health care costs with high morbidity and mortality in the western countries. Long noncoding RNAs have been widely reported to regulate the initiation or progression of cardiovascular diseases. However, the specific role of SOX2 overlapping transcript (SOX2-OT) in ischemic heart failure remains uncharacterized. The present study aimed to explore the function and mechanism of SOX2-OT in ischemic heart failure. The starBase website was used to predict potential miRNAs or target mRNAs. Western blot assay was implemented to test collagen protein levels. Functional assays were conducted to evaluate the effects of SOX2-OT on H9c2 cell viability and apoptosis. RNA pull down and luciferase reporter assays were used to confirm the combination between miR-215-5p and SOX2-OT. We found out that SOX2-OT level was increased by oxygen glucose deprivation/reoxygenation treatment in H9c2 cells. Silencing of SOX2-OT ameliorated cell injury by promoting cell viability, inhibiting cell apoptosis and reducing productions of collagens. Mechanistically, miR-215-5p was confirmed to bind with SOX2-OT after prediction and screening. In addition, we discovered that miR-215-5p negatively regulated zinc finger E-box binding homeobox 2 (ZEB2) protein level by directly binding with ZEB2 3' untranslated region. Finally, we verified that SOX2-OT aggravated cell injury by targeting ZEB2 in H9c2 cells. In conclusion, SOX2-OT aggravated heart failure in vivo and promoted H9c2 cell injury via the miR-215-5p/ZEB2 axis in vitro, implying a novel insight into heart failure treatment.

The Role of Neprilysin Inhibitors in the Treatment of Heart Failure with Preserved Ejection Fraction.

Clinical and hemodynamic aggravation of heart failure with preserved ejection fraction (HFpEF) is largely due to progression of left ventricular (LV) diastolic dysfunction. The key role in the normal maintenance of diastolic function is played by a high level of activity of the intracellular signaling axis, cyclic guanosine-monophosphate-protein kinase G, the activity of which is significantly reduced in HFpEF. The activity of this axis can be increased by increasing the bioavailability of natriuretic peptides by blocking the enzyme neutral endopeptidase (neprilisin), which is responsible for the destruction of natriuretic peptides.This review presents experimental and clinical data on the use of neprilysin inhibitors in HFpEF and addresses prospects of this treatment.

English

BACKGROUND Restriction of fluid is widely adopted as a strategic non-pharmacological therapy for patients with heart failure (HF). However, insufficient fluid leads to intravascular volume contraction further causing hypoperfusion of vital organs. Renal dysfunction and cardiac ischemia caused by hypoperfusion can further aggravate heart failure. Therefore, the authors decided to study the effect of fluid intake on various functional and cardiac parameters of patients of HF. METHODS 50 patients with a diagnosis of heart failure with reduced ejection fraction who had been discharged from the hospital since last 6 months and who were on restricted fluid therapy were included in the study. Patients were advised to visit the OPD once every 4 weeks and provide a record of their fluid intake. All patients irrespective of functional class were advised a fluid intake of 30 mL / day / Kg body weight. Functional status, biochemical parameters and clinical parameters were measured regularly until the end of 12 weeks. RESULTS There was marked improvement in the functional status of patients and statistically significant number was shifted from NYHA III and IV to NYHA I and II. PFI (Prescribed Fluid Intake) was associated with improvement of exercise tolerance in all NYHA Classes. Creatinine levels declined in all NYHA Classes with very high drop from 2.32 to 1.0 in NYHA Class IV. CONCLUSIONS Compensated HF patients should be prescribed physiologically correct dietary fluid intake based on body weight. This improves their functional capacity, biochemical parameters and left ventricular ejection fraction. KEYWORDS Heart Failure, Diet, Sodium-Restricted, Diuretics, Exercise Tolerance

C3a, C4a, and C5a Complement Anaphylatoxins Are Paradoxically Decreased in Acute and Chronic Heart Failure

Background Inflammation is a prerequisite for healing after physical insult or microbial invasion. However, sustained and chronic inflammation often leads to deleterious effects. Especially in heart failure (HF), inflammation plays a causative role in adverse cardiac remodeling and functional decline. An important part of the innate immune system, the complement cascade is associated with the initiation and propagation of inflammation for the purpose of clearing bacterial pathogens. Specifically, the anaphylatoxins C3a, C4a, and C5a are integral in the complement cascade, initiating and amplifying inflammation that may exacerbate HF. Hypothesis In light of prior evidence linking innate immune system activation to inflammation and the aggravation of HF, we hypothesize that increased complement activation, evidenced by higher concentrations of circulating anaphylatoxins, are indicative of HF severity and track with traditional HF risk factors. Method Blood and clinical values were obtained from healthy (non-HF), acute HF, and chronic HF subjects. To compare anaphylatoxin levels, serum from non-HF and HF subjects were assayed for circulating C3a, C4a, and C5a concentrations by cytometric bead array, then compared to clinical parameters. C3, the major complement initiating factor for the anaphylatoxins, was measured in serum by ELISA assay. Additionally, data from RNAseq analysis on cardiac tissue isolates from non-HF and dilated cardiomyopathy (DCM) patients were compared for differential expression in 22 complement-related genes. Results Compared to non-HF, Serum C3a was found to be decreased by 24.3% in chronic HF and 20.5% among all HF cohorts (P Conclusions Although inflammation is increased in HF, C3, C3a, and C4a were found to be paradoxically decreased in HF cohorts, while C5a conversely increased in acute HF alone. The significant decreases in anaphylatoxins may be explained by the decreased C3 expression observed in HF subjects. While contrary to our hypothesis, our findings suggest differential complement dynamism, dependent on acute versus chronic HF status.

Muscle mass, muscle strength, and functional capacity in patients with heart failure of Chagas disease and other aetiologies.

AimsPatients with Chagas disease and heart failure (HF) have a poor prognosis similar to that of patients with ischaemic or dilated cardiomyopathy. However, the impact of body composition and muscle strength changes in these aetiologies is still unknown. We aimed to evaluate these parameters across aetiologies in two distinct cohort studies [TESTOsterone‐Heart Failure trial (TESTO‐HF; Brazil) and Studies Investigating Co‐morbidities Aggravating Heart Failure (SICA‐HF; Germany)].Methods and resultsA total of 64 male patients with left ventricular ejection fraction ≤40% were matched for body mass index and New York Heart Association class, including 22 patients with Chagas disease (TESTO‐HF; Brazil), and 20 patients with dilated cardiomyopathy and 22 patients with ischaemic heart disease (SICA‐HF; Germany). Lean body mass (LBM), appendicular lean mass (ALM), and fat mass were assessed by dual energy X‐ray absorptiometry. Sarcopenia was defined as ALM divided by height in metres squared <7.0 kg/m2 (ALM/height2) and handgrip strength cut‐off for men according to the European Working Group on Sarcopenia in Older People. All patients performed maximal cardiopulmonary exercise testing. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Chagasic and ischaemic patients had lower total fat mass (16.3 ± 8.1 vs. 19.3 ± 8.0 vs. 27.6 ± 9.4 kg; P < 0.05) and reduced peak oxygen consumption (VO2) (1.17 ± 0.36 vs. 1.15 ± 0.36 vs. 1.50 ± 0.45 L/min; P < 0.05) than patients with dilated cardiomyopathy, respectively. Chagasic patients showed a trend towards decreased LBM when compared with ischaemic patients (48.3 ± 7.6 vs. 54.2 ± 6.3 kg; P = 0.09). Chagasic patients showed lower handgrip strength (27 ± 8 vs. 37 ± 11 vs. 36 ± 14 kg; P < 0.05) and FBF (1.84 ± 0.54 vs. 2.75 ± 0.76 vs. 3.42 ± 1.21 mL/min/100 mL; P < 0.01) than ischaemic and dilated cardiomyopathy patients, respectively. There was no statistical difference in the distribution of sarcopenia between groups (P = 0.87). In addition, FBF correlated positively with LBM (r = 0.31; P = 0.012), ALM (r = 0.25; P = 0.046), and handgrip strength (r = 0.36; P = 0.004). In a logistic regression model using peak VO2 as the dependent variable, haemoglobin (odds ratio, 1.506; 95% confidence interval, 1.043–2.177; P = 0.029) and ALM (odds ratio, 1.179; 95% confidence interval, 1.011–1.374; P = 0.035) were independent predictors for peak VO2 adjusted by age, left ventricular ejection fraction, New York Heart Association, creatinine, and FBF.ConclusionsPatients with Chagas disease and HF have decreased fat mass and exhibit reduced peripheral blood flow and impaired muscle strength compared with ischaemic HF patients. In addition, patients with Chagas disease and HF show a tendency to have greater reduction in total LBM, with ALM remaining an independent predictor of reduced functional capacity in these patients. The percentage of patients affected by sarcopenia was equal between groups.

Diffuse Myocardial Fibrosis and Diastolic Function in Aortic Stenosis

ObjectivesThe aim of this study was to investigate the relationship between extracellular volume fraction (ECV), a noninvasive parameter that quantifies the degree of diffuse myocardial fibrosis on cardiac magnetic resonance (CMR), and left ventricular diastolic dysfunction (LVDD) in patients with aortic stenosis (AS). BackgroundMyocardial fibrosis on invasive myocardial biopsy is associated with LVDD. However, there is a paucity of data on the association between noninvasively quantified diffuse myocardial fibrosis and the degree of LVDD and how these are related to symptoms and long-term prognosis in patients with AS. MethodsPatients with moderate or severe AS (n = 191; mean age 68.4 years) and 30 control subjects without cardiovascular risk factors underwent CMR. LVDD grade was evaluated using echocardiography according to the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Clinical outcomes were defined as a composite of all-cause mortality or hospitalization for heart failure aggravation. ResultsPatients in higher ECV quintiles had a significantly higher prevalence of LVDD. Higher ECV was particularly associated with decreased myocardial relaxation (septal e′ <7 cm/s) and increased LV filling pressure (E/e′ ratio ≥15). Although both impaired diastolic function and higher ECV were significantly associated with a worse degree of dyspnea, patients with higher ECV showed greater dyspnea within the same grade of LVDD. During a median follow-up period of 5.6 years, 37 clinical events occurred. Increased ECV, as well as lower septal e′ and higher E/septal e′ ratio, were independent predictors of clinical events, irrespective of age, AS severity, aortic valve replacement, and left ventricular (LV) ejection fraction. ECV provided incremental prognostic value on top of clinical factors and LV systolic and diastolic function. ConclusionsDiffuse myocardial fibrosis, assessed using ECV on CMR, was associated with LVDD in patients with AS, but both ECV and LV diastolic function parameters provided a complementary explanation for dyspnea and clinical outcomes. Concomitant assessment of both LVDD and diffuse myocardial fibrosis may further identify patients with AS with greater symptoms and worse prognosis.

Muscle wasting as an independent predictor of survival in patients with chronic heart failure

BackgroundSkeletal muscle wasting is an extremely common feature in patients with heart failure, affecting approximately 20% of ambulatory patients with even higher values during acute decompensation. Its occurrence is associated with reduced exercise capacity, muscle strength, and quality of life. We sought to investigate if the presence of muscle wasting carries prognostic information.MethodsTwo hundred sixty‐eight ambulatory patients with heart failure (age 67.1 ± 10.9 years, New York Heart Association class 2.3 ± 0.6, left ventricular ejection fraction 39 ± 13.3%, and 21% female) were prospectively enrolled as part of the Studies Investigating Co‐morbidities Aggravating Heart Failure. Muscle wasting as assessed using dual‐energy X‐ray absorptiometry was present in 47 patients (17.5%).ResultsDuring a mean follow‐up of 67.2 ± 28.02 months, 95 patients (35.4%) died from any cause. After adjusting for age, New York Heart Association class, left ventricular ejection fraction, creatinine, N‐terminal pro‐B‐type natriuretic peptide, and iron deficiency, muscle wasting remained an independent predictor of death (hazard ratio 1.80, 95% confidence interval 1.01–3.19, P = 0.04). This effect was more pronounced in patients with heart failure with reduced than in heart failure with preserved ejection fraction.ConclusionsMuscle wasting is an independent predictor of death in ambulatory patients with heart failure. Clinical trials are needed to identify treatment approaches to this co‐morbidity.

ST2 silencing aggravates ventricular remodeling and chronic heart failure in rats by mediating the IL-33/ST2 axis.

Heart failure appears to be a severe public health problem affecting millions of people worldwide. Knowledge of the molecular mechanism contributing to ventricular remodeling would allow for earlier prevention of heart failure. Evidence exists reporting the involvement of IL-33 and ST2 and in heart remodeling. Thus, this study aims to delineate the effects of ST2 on chronic heart failure (CHF) via the IL-33/ST2 axis. Coronary artery ligation was employed to simulate CHF in rats, which were characterized by transthoracic echocardiography for cardiac function. After that, ST2 silencing and IL-33 overexpression were induced in rat models to evaluate apoptosis and pathological alterations in myocardial tissues and serum levels of biochemical indices. It was revealed that cardiac function was impaired in response to ST2 silencing. Furthermore, ST2 knockdown suppressed the activities of the mitochondrial respiratory chain and accelerated cardiomyocyte apoptosis via blockade of the IL-33/ST2 axis. These findings suggest an inhibitory role of ST2 silencing on the IL-33/ST2 axis, which consequently increases the risk of cardiac dysfunction, accelerates ventricular remodeling, and aggravates heart failure in rats. This study highlights that ST2 silencing may be a novel potential preventive or therapeutic target for CHF.

Prognostic Value of Leg Muscle Strength in Acute Heart Failure Syndrome.

Leg muscle strength (LMS) may be useful as a frailty index in patients with heart failure. However, LMS, until recently, has been indirectly estimated, and its prognostic value in acute heart failure syndrome (AHFS) is unclear. Therefore, we evaluated the prognostic value of direct LMS assessment and its relationship with proinflammatory mediators in patients with AHFS. We directly measured LMS at predischarge using a dynamometer in 110 prospectively and consecutively enrolled patients with AHFS (75 male; 60 ± 14 yr; mean ejection fraction, 29.9% ± 14.6%). The primary end point was cardiovascular (CV) events, defined as CV mortality, cardiac transplantation, or rehospitalization due to heart failure aggravation. Patients were divided into impaired and preserved LMS groups according to Contal and O'Quigley's method. CV events occurred in 28 patients (25.5%) (including 5 CV deaths and 6 cardiac transplantations) during follow-up (median, 246 d; range = 11-888 d). Impaired LMS was associated with significantly higher levels of serum monokine induced by gamma interferon and poor clinical outcomes (P < 0.001). Multivariable Cox proportional hazard analysis (controlling for age, sex, body mass index, heart failure type, hemoglobin level, N-terminal pro-b-type natriuretic peptide level, and beta-blocker use) revealed LMS as an independent predictor of CV events (P = 0.017). Impaired LMS, which might be used as a marker of frailty, is associated with increased levels of a proinflammatory chemokine and independently predicts clinical outcomes in patients with AHFS. The direct measurement of LMS is simple and feasible and might have important implications for the risk stratification of patients with AHFS.