A very high frequency index of heart rate variability for evaluation of left ventricular systolic function and prognosis in chronic heart failure patients using five-minute electrocardiogram

Objective A novel index based on fi-equency-domain analysis of heart rate variability （HRV） was tested on patients with reduced left ventricular systolic function. This index, namely VHFI, was defined as the very high frequency （VHF） component of the power spectrum normalized to represent its relative value in proportion to the total power minus the very low frequency component. Methods Patients （n = 130） were divided into a study group, consisting 66 patients with decreased left ventricular systolic function, and a control group, consisting 64 patients with normal heart structure and function and without severe coronary artery stenosis （〈 50%）. Results VHFI in the study group was significantly higher than that in the control group （19.17 ± 13.35 vs 11.37 ± 10.77, P 〈 0.001）. Cardiac events occurred in 18 patients during follow-up （33.34 i 3.26 months）. Defining the positive test as VHFI =15 and negative test as VHFI 〈15, achieved a sensitivity of 57.58% and a specificity of78.13% for predicting decreased left ventricular systolic function, and achieved a sensitivity of 66.67% and a specificity of 64.29% for predicting cardiac events. Univariate Cox regression analysis showed that positive VHFI test was an independent variable in predictive cardiac events. Conclusions The results suggest that VHFI is a useful tool for quick evaluation of left ventricular systolic function and prediction of prognosis

Doppler Tissue Imaging Assessment of Left Ventricular Systolic Dyssynchrony in Severe Heart Failure Patients With a Normal QRS Duration

Objectives To assess the prevalence of systolic dyssynchrony of the left ventricular （LV） walls in patients of heart failure（HF） with a normal QRS duration by Doppler tissue imaging （DTI）. Methods 20 patients of HF with a normal QRS duration and 20 healthy individuals were investigated with DTI to quantitatively analyze their pulsed-wave Doppler spectrum of basal and middle segments in six walls of left ventricle. The time between the onset of the QRS complex of the surface ECG and the onset of the systolic wave of pulsed-wave Doppler spectrum was measured （TS）. LV systolic synchronization was assessed by the maximal difference （MD） in time of TS, the standard deviation （SD） and the coefficient of variation （CV） of TS in the all 12 LV segments. Results When a TS-MD of TS〉 53.08 ms, a TS-SD of TS 〉18.08 ms and a TS-CV of TS 〉 0.91 （＋1.65 SD of normal controls） was used to define significant systolic dyssynchrony, the prevalence of systolic dyssynchrony was 55.0 %, 55.0 % and 55.0 %, respectively, in the HF patients group, significantly higher than those in the normal control and the locations of delayed contraction of these patients were different. Conclusions LV systolic dyssynchrony could be commonly demonstrated by DTI in HF patients with a normal QRS duration. This finding will support the view about the possibility that more HF patients could benefit from cardiac resynchronization therapy.

Different prognostic association of systolic blood pressure at different time points with postdischarge events in patients hospitalized for decompensated heart failure

Background The association of systolic blood pressure(SBP) with mortality in heart failure(HF) patients is paradoxical, and the time points of baseline SBP are also different across prior studies. We hypothesized that the levels of SBP at admission and at discharge had different associations with postdischarge events. Methods The study population included patients hospitalized for decompensated HF in the Heart Failure Center of Fuwai Hospital from January 1, 2009 to December 31, 2014. The primary outcome was a composite of cardiovascular(CV) death and heart transplantation. Multivariate Cox proportional-hazards and restricted cubic spline analyses were used to assess the relationships between SBP at different time points and outcomes. Results In total, 2005 patients were included with a median follow-up of 48.4 months. The median age was 59 years, and 69.9% were male. Multivariate Cox analyses showed that compared with SBP < 105 mm Hg, higher SBP at admission was associated with better long-term primary outcome(105–119 mm Hg, HR = 0.764, P = 0.005;120-134 mm Hg, HR = 0.658, P < 0.001;≥ 135 mm Hg, HR = 0.657, P = 0.001). Patients whose discharge SBP was higher than 135 mm Hg had a similar primary outcome as those with SBP < 105 mm Hg(HR = 0.969, P = 0.867), and the results remained unchanged even after adjusting for admission SBP(HR = 1.235, P = 0.291). The results of restricted cubic spline analysis indicated similar associations. Conclusions Lower but not higher SBP at admission is associated with more CV deaths/heart transplantations(a reverse J-shaped curve). In contrast, there is a U-shaped association between discharge SBP and CV mortality/heart transplantation.

Testosterone level and mortality in elderly men wit systolic chronic heart failure

Previous studies on the prognostic significance of serum levels of androgens in patients with chronic heart failure （CHF） have yielded conflicting results. The aim of this study was to examine the relationship between serum concentration of testosterone and mortality in men with systolic CHF. A total of 175 elderly men （age ≥60 years） with CHF were recruited. Total testosterone （TI＇） and sex hormone-binding globulin （SHBG） were measured, and estimated free testosterone （eFT） was calculated. The median follow-up time was 3.46 years. Of these patients, 17 had a TT level below 8 nmol I^-1 （230 ng dI^-1）, 27 had an eFT level below 0.225 nmol I^-1 （65 pg ml^-1） and 12 had both. Using the age-specific tenth percentiles of TT and eFT in healthy men in our laboratory as cutoff points, the prevalences of TT and eFT deficiency was 21.7% （38/175） and 27.4% （48/175）, respectively. Both TT and eFT were inversely associated with left ventricular ejection fraction （LVEF） and N-terminal pro-brain natriuretic peptide （NT-pro-BNP） （all P〈0.01）. Kaplan-Meier curves for patients in low, medium and high tertiles according to TT and eFT level showed significantly different cumulative survival rate （both P〈0.01 by log-rank test）. However, after adjustment for clinical variables, there were no significant associations of either TT or eFT levels with survival time （0R=0.97, 95% CI： 0.84-1.12, P=0.28 and 0R=0.92, 95% CI： 0.82-1.06, P=0.14, respectively）. Our study showed that levels of TT and eFT are commonly decreased in elderly patients with systolic CHF and related to disease severity, but they are not independent predictors for mortality.

Sleep-disordered breathing is associated with depletion of circulating endothelial progenitor cells and elevation in pulmonary arterial pressure in patients with decompensated systolic heart failure

Background Sleep-disordered breathing （SDB） is known to occur frequently in and may predict worsening progression of patients with congestive heart failure （CHF）. SDB is also known to play an important role in the development of idiopathic pulmonary arterial hyper- tension （PAH） via inducing endothelial dysfunction and vascular remodeling, a pathological process that can be significantly influenced by factors such as osteoprotegerin （OPG） and endothelial progenitor cells （EPCs）. The objective of this study is to determine if CHF with SDB is associated with changes in OPG, EPCs, and PAIl. Methods EPCs were isolated, cultured, and quantified from CHF patients with SDB （n = 52）, or without SDB （n - 68）. OPG and N-terminal pro-brain natriuretic peptide （NT-proBNP） from each group was analyzed and cor- related with EPCs and the mean pulmonary artery pressure （mPAP） measured by right heart catheterization. Results A significant decrease in circulating EPCs （29.30 ± 9.01 vs. 45.17 ± 10.51 EPCs/x 200 field; P 〈 0.05） was found in CHF patients with SDB compared to those without SDB. Both OPG （789.83 ±89.38 vs. 551.29 ± 42.12 pg/mL; P 〈 0.05） and NT-proBNP （5946.50 ± 1434.50 vs. 3028.60 ± 811.90 ng/mL; P 〈 0.05） were also significantly elevated in SDB CHF patients who also had significantly elevated mPAP （50.2 ± 9.5 vs. 36.4 ± 4.1 mm Hg; P 〈 0.05）. EPC numbers correlated inversely with the episodes of apnea and hypopnea per hour （RDI, r = -0.45, P = 0.037） and blood level of OPG （r =-0.53, P = 0.011）. Although NT-proBNP was also increased significantly in patients with SDB, it had no correlation with either EPCs or RD1. Conclusions SDBdue to hypoxemia from decompensated CHF is associated with （1） OPG elevation, （2） EPC depletion, and （3） mPAP elevation. The inverse relationship of circulating OPG with EPCs suggests a likely mechanism for hypoxemia and OPG in the development of pulmonary vascular dysfunction via depleting EPCs, thus worsening prognosis of CHF.

Ivabradine in the treatment of systolic heart failure- A systematic review and meta-analysis

AIM To perform a systematic-review and meta-analysis to compare outcomes of ivabradine combined with betablocker to beta-blocker alone in heart failure with reduced ejection fraction(HFr EF).METHODS We searched PubM ed, Cochrane, EMBASE, CINAHL and Web of Science for trials comparing ivabradine + betablocker to beta-blocker alone in HFr EF. We performed a systematic-review and meta-analysis of published literature. Primary end-point was combined end point of cardiac death and hospitalization for heart failure.RESULTS Six studies with 17671 patients were included. Mean follow-up was 8.7 ± 7.9 mo. Combined end-point of heart failure readmission and cardiovascular death was better in ivabradine + beta-blocker group compared to beta-blocker alone(RR: 0.93, 95%CI: 0.79-1.09, P = 0.354). Mean difference(MD) in heart rate was higher in the ivabradine + beta-blocker group(MD: 6.14, 95%CI: 3.80-8.48, P < 0.001). There was no difference in all cause mortality(RR: 0.98, 95%CI: 0.89-1.07, P = 0.609), cardiovascular mortality(RR: 0.99, 95%CI: 0.86-1.15, P = 0.908) or heart failure hospitalization(RR: 0.87, 95%CI: 0.68-1.11, P = 0.271). CONCLUSION From the available clinical trials, ivabradine + betablocker resulted in a significantly greater reduction in HRcoupled with improvement in combined end-point of heart failure readmission and cardiovascular death but with no improvement in all cause or cardiovascular mortality. Given the limited evidence, further randomized controlled trials are essential before widespread clinical application of ivabradine + beta-blocker is advocated for HFrEF.

Androgen deficiency in elderly men with systolic chronic heart failure

Objective Several previous studies have shown androgens deficiency in men with CHF, and 2 studies on the prognostic significance of serum levels of androgens in CHF patients have yielded conflicting results. The aim of this study was to examine the relationship between serum concentration of testosterone and mortality in men with systolic CHE Methods A total of 175 elderly （age ≥ 60 years） men with CHF were recruited. Total testosterone fiT） and sex hormone binding globulin （SHBG） were measured, and free serum testosterone （eFT） was calculated. The median follow-up time was 1262 days. Results During follow-up 54 （30.9%） patients died. TT and eFF deficiency was found in 21.7% （38/175） and 27.4% （48/175） patients, respectively. Both TT and eFT were inversely associated with LVEF and NT-proBNP （all P〈0.01）. Kaplan-Meier curves for patients in low, medium and high tertiles according to TF and eFT level showed significantly different cumulative survival rate （both P〈0.01 by log-rank test）. However, after adjustment for clinical variables, there were no significant associations between either Tr or eFT levels or survival time （OR=0.97, 95% CI, 0.84-1.12, P--0.28; and OR=0.92, 95% CI, 0.82-1.06,/＇=0.14, respectively）. Conclusion Our study showed that although levels of TT and eFT are commonly decreased in elderly patients with systolic CHF and related to disease severity, they are not independent predictors for mortality

PARADIGM-HF trial： will LCZ696 change the current treatment of systolic heart failure？

1 Introduction Heart failure （HF） is a global health problem with an estimated prevalence of over 5.8 million in the USA and over 23 million worldwide.It represents the most common cause of hospitalization in elderly patients （〉 65 years） and its incidence has a growing trend mainly due to the aging of the population. Neurohumoral activation plays a major role in the pathophysiology. So in consequence, the cornerstone of its medical treatment is based on the inhibition of the renin-angiotensin-aldosterone system （RAAS） and the sympathetic nervous system, According to this, all patients with HF and reduced ejection fraction should be treated with an angiotensin converting enzyme inhibitor （ACEI） or an angiotensin receptor blocker （ARB） plus a beta blocker （BB） and if needed, a mineralocorticoid recep- tor antagonist （MRA）.

Effects of exercise training on diastolic and systolic dysfunction in patients with chronic heart failure

BACKGROUND Chronic heart failure(CHF)is a complex syndrome characterized by a progressive reduction of the left ventricular(LV)contractility,low exercise tolerance,and increased mortality and morbidity.Diastolic dysfunction(DD)of the LV,is a keystone in the pathophysiology of CHF and plays a major role in the progression of most cardiac diseases.Also,it is well estimated that exercise training induces several beneficial effects on patients with CHF.AIM To evaluate the impact of a cardiac rehabilitation program on the DD and LV ejection fraction(EF)in patients with CHF.METHODS Thirty-two stable patients with CHF(age:56±10 years,EF:32%±8%,88%men)participated in an exercise rehabilitation program.They were randomly assigned to aerobic exercise(AER)or combined aerobic and strength training(COM),based on age and peak oxygen uptake,as stratified randomization criteria.Before and after the program,they underwent a symptom-limited maximal cardiopulmonary exercise testing(CPET)and serial echocardiography evaluation to evaluate peak oxygen uptake(VO2peak),peak workload(Wpeak),DD grade,right ventricular systolic pressure(RVSP),and EF.RESULTS The whole cohort improved VO2peak,and Wpeak,as well as DD grade(P<0.05).Overall,9 patients(28.1%)improved DD grade,while 23(71.9%)remained at the same DD grade;this was a significant difference,considering DD grade at baseline(P<0.05).In addition,the whole cohort improved RVSP and EF(P<0.05).Not any between-group differences were observed in the variables assessed(P>0.05).CONCLUSION Exercise rehabilitation improves indices of diastolic and systolic dysfunction.Exercise protocol was not observed to affect outcomes.These results need to be further investigated in larger samples.

Left ventricular systolic function assessment in patients with dilated heart failure using cardiovascular magnetic resonance

Cardiovascular magnetic resonance (CMR) has become a reference standard for the measure-ment of cardiac volumes, function, and mass. This study aims to reconstruct three dimen-sional modeling of the left ventricle (LV) in pa-tients with heart failure (HF) using CMRtools and thereby derive the LV functional indices. CMR images were acquired in 41 subjects (6 females) with heart failure (HF) and 12 normal controls (4 females). Five comparisons were made (i) nor-mal and dilated heart failure subjects, (ii) male and female normal heart, (iii) male and female dilated heart, (iv) male normal and dilated heart failure and (v) female normal and dilated heart failure. In HF, a significant higher values of EDV (320 刡 79 vs. 126 刡 22 ml, P&amp;amp;amp;amp;amp;lt;0.0001), ESV (255 刡 68 vs. 54 刡 12 ml, P&amp;amp;amp;amp;amp;lt;0.00001) and lower values of EF (20 刡 7 vs. 58 刡 5 %) were found compared that of normal control. There were significant difference on LV EDV and ESV between sex in both normal and HF subjects.

Prevalence of Atrial Fibrillation in Systolic Heart Failure, Pulsed and Tissue Doppler Echocardiographic Abnormalities

Background: Heart failure (HF) is a common clinical syndrome mostly due to the impaired ability of the Left Ventricle (LV) to eject blood with reduced cardiac output. Heart failure is called systolic (SHF) if left ventricle ejection fraction on echo-cardiogram is low (LVEF of ≤50%). Aim: To assess the echocardiographic characteristics of patients with SHF with Atrial Fibrillation (AF) and compare with those with Sinus Rhythm (SR) on 12 leads ECG. Furthermore, to evaluate the clinical and biochemical markers for the prediction of AF in SHF. Method: Over two years duration, each patient diagnosed with SHF was enrolled in the study (n = 354) based on admission code. AF or sinus rhythm on 12 leads ECG was documented on each patient. Multiple logistic regression analysis was applied to assess the risk ratio of different clinical and Doppler derived variables for the development of AF in SHF. Results: Out of the total hospital medical admissions of 14,674 patients, there were 354 patients with diagnosis of SHF, a prevalence of 2.4%. The incidence of AF on ECG was 109 (31%) patients in the whole study population and 245 (69%) in SR. M Mode echocardiogram in patients with SHF and AF compared with those in SR showed significant dilation of LV cavity in systole with LVESD of 5.72 ± 0.63 vs. 5.23 ± 0.76 cm, P < 0.001 and in Diastole LVEDD of 6.83 ± 0.51 vs. 6.58 ± 0.63 cm, P < 0.001. Pulsed Doppler echocardiogram showed a severe restrictive-pattern with shorter Decellration Time (DT) of 163.73 ± 7.42 vs. 214.9 ± 31.81msec, P < 0.001 and higher Pulse to Tissue Doppler ratio of E/Em of 14.26 ± 1.34 vs. 9.99 ± 1.27, P , and the serum level of Brain Natriuretic Peptide (BNP) hormone of 723.72 ± 13.45 vs. 686.98 ± 72.57 pg/ml, P < 0.001. The predictive risks (odd ratio) of different clinical variables for the development of AF in SHF were positive for high BNP > 500 pg/ml of 2.8, history of hypertension of 1.8, history of DM of 1.7, BMI > 28 of 1.4, LV hypertrophy on ECG of 1.3. Conclusions: The prevalence of Systolic Heart Failure in the study population was 2.4%. The prevalence of AF in the study population was 31%. The best predictors of AF in SHF were high BNP > 500 pg/ml, history of hypertension, Diabete Mellitus and LV Hypertrophy on ECG.

Sodium glucose cotransporter 2 inhibitors in the management of heart failure:Veni,Vidi,and Vici

Heart failure(HF)is a chronic disease associated with high morbidity and mortality rates.Renin-angiotensin-aldosterone system blockers(including angiotensin receptor/neprilysin inhibitors),beta-blockers,and mineralocorticoid receptor blockers remain the mainstay of pharmacotherapy for HF with reduced ejection fraction(HFrEF).However,despite the use of guideline-directed medical therapy,the mortality from HFrEF remains high.HF with preserved ejection fraction(HFpEF)comprises approximately half of the total incident HF cases;however,unlike HFrEF,there are no proven therapies for this condition.Sodium glucose cotransporter-2 inhibitors(SGLT-2is)represent a new class of pharmacological agents approved for diabetes mellitus(DM)that inhibit SGLT-2 receptors in the kidney.A serendipitous finding from seminal trials of SGLT-2is in DM was the significant improvement in renal and cardiovascular(CV)outcomes.More importantly,the improvement in HF hospitalization(HHF)in the CV outcomes trials of SGLT-2is was striking.Multiple mechanisms have been proposed for the pleiotropic effects of SGLT-2is beyond their glycemic control.However,as patients with HF were not included in any of these trials,it can be considered as a primary intervention.Subsequently,two landmark studies of SGLT-2is in patients with HFrEF,namely,an empagliflozin outcome trial in patients with chronic HF and a reduced ejection fraction(EMPEROR-Reduced)and dapagliflozin and prevention of adverse outcomes in HF(DAPA-HF),demonstrated significant improvement in HHF and CV mortality regardless of the presence of DM.These impressive results pitchforked these drugs as class I indications in patients with HFrEF across major guidelines.Thereafter,empagliflozin outcome trial in patients with chronic HF with preserved ejection fraction(EMPEROR-Preserved)and dapagliflozin evaluation to improve the lives of patients with preserved ejection fraction HF(DELIVER)trials successively confirmed that SGLT-2is also benefit patients with HFpEF with or without DM.These results represent a watershed as they constitute the first clinically meaningful therapy for HFpEF in the past three decades of evolution of HF management.Emerging positive data for the use of SGLT-2is in acute HF and post-myocardial infarction scenarios have strengthened the pivotal role of these agents in the realm of HF.In a short span of time,these classes of drugs have captivated the entire scenario of HF.

Kill two birds with one stone:Hapatologist’s approach to metabolic dysfunction-associated steatotic liver disease and heart failure

Heart failure(HF)is a major global public health concern,and one of the less commonly known risk factors for HF development is metabolic dysfunction-associated steatotic liver disease(MASLD),as they share a similar pathophysio-logical background.In this article,we evaluated a recently published review article by Arriola-Montenegro et al.This article briefly summarizes the common pathophysiology of HF and MASLD development and evaluates the available therapeutic options to treat both conditions.Clinical practice guidelines highlight the importance of initiating and titrating guideline-directed medication therapy(GDMT)for patients with HF with reduced ejection fraction.GDMT is comprised of the four pillars currently proposed in most clinical practice guidelines,namely angiotensin-converting enzyme inhibitors(ACEIs),angiotensin receptor blockers(ARBs),angiotensin receptor-neprilysin inhibitors,beta-blockers,mineralocor-ticoid receptor antagonists,and sodium-glucose co-transporter 2 inhibitors(SGLT-2i).Given the similarity of pathophysiology and risk factors,recent studies for GDMT regarding ACEIs,ARBs,mineralocorticoid receptor antagonists,and SGLT-2i have shown beneficial effects on MASLD.Nonetheless,other medications for both conditions and novel therapies require more robust data and well-designed clinical studies to demonstrate their efficacies in both conditions.

Dapagliflozin in heart failure and type 2 diabetes:Efficacy,cardiac and renal effects,safety

BACKGROUND Heart failure(HF),especially HF with reduced ejection fraction(HFrEF),presents complex challenges,particularly in the aging population where it often coexists with type 2 diabetes mellitus(T2DM).AIM To analyze the effect of dapagliflozin treatment on cardiac,renal function,and safety in patients with HFrEF combined with T2DM.METHODS Patients with T2DM complicated with HFrEF who underwent treatment in our hospital from February 2018 to March 2023 were retrospectively analyzed as the subjects of this study.The propensity score matching method was used,and a total of 102 eligible samples were scaled.The clinical efficacy of the two groups was evaluated at the end of the treatment,comparing the results of blood glucose,insulin,cardiac function,markers of myocardial injury,renal function indexes,and 6-min walk test(6MWT)before and after the treatment.We compared the occurrence of adverse effects on the treatment process of the two groups of patients.The incidence of adverse outcomes in patients within six months of treatment was counted.RESULTS The overall clinical efficacy rate of patients in the study group was significantly higher than that of patients in the control group(P=0.013).After treatment,the pancreatic beta-cell function index,left ventricular ejection fraction,and glomerular filtration rate of patients in the study group were significantly higher than control group(P<0.001),while their fasting plasma glucose,2-h postprandial glucose,glycosylated hemoglobin,insulin resistance index,left ventricular end-systolic diameter,left ventricular end-diastolic diameter,cardiac troponin I,creatine kinase-MB,N-terminal pro b-type natriuretic peptide,serum creatinine,and blood urea nitrogen were significantly lower than those of the control group.After treatment,patients in the study group had a significantly higher 6MWT than those in the control group(P<0.001).Hypoglycemic reaction(P=0.647),urinary tract infection(P=0.558),gastrointestinal adverse effect(P=0.307),respiratory disturbance(P=0.558),and angioedema(P=0.647)were not statistically different.There was no significant difference between the incidence of adverse outcomes between the two groups(P=0.250).CONCLUSION Dapagliflozin significantly enhances clinical efficacy,cardiac and renal function,and ambulatory capacity in patients with HFrEF and T2DM without an increased risk of adverse effects or outcomes.

Living biodrugs and how tissue source influences mesenchymal stem cell therapeutics for heart failure

In this editorial we comment on the article by Safwan M et al.We especially fo-cused on the cardiac function restoration by the use of mesenchymal stem cells(MSCs)therapy for heart failure(HF),which has emerged as a new treatment approach as“Living Biodrugs”.HF remains a significant clinical challenge due to the heart’s inability to pump blood effectively,despite advancements in medical and device-based therapies.MSCs have emerged as a promising therapeutic approach,offering benefits beyond traditional treatments through their ability to modulate inflammation,reduce fibrosis,and promote endogenous tissue rege-neration.MSCs can be derived from various tissues,including bone marrow and umbilical cord.Umbilical cord-derived MSCs exhibit superior expansion ca-pabilities,making them an attractive option for HF therapy.Conversely,bone marrow-derived MSCs have been extensively studied for their potential to im-prove cardiac function but face challenges related to cell retention and delivery.Future research is focusing on optimizing MSC sources,enhancing differentiation and immune modulation,and improving delivery methods to overcome current limitations.

Biomechanical Manifestations of Diastolic and Systolic Function in Rats with Heart Failure with Preserved Ejection Fraction

Objective Heart failure(HF)is divided into two types:Heart failure with reduced ejection fraction(HFrEF)and heart failure with preserved ejection fraction(HFpEF).The latter always results in diastolic dysfunction,characterized by changes in mechanical properties.The objective of this study is to build a finite element(FE)model of HFpEF and analyze diastolic and systolic function in rats.Methods Ten Dahl salt-sensitive rats were fed either a low-salt(LS)(n=5)or highsalt(HS)(n=5)diet beginning at 7 weeks of age and scanned by ultrasonic machine at 14 weeks of age.A non-linear FE model of the left ventricle(LV)was built from cardiac echo images at end-diastole and passive material properties of the LV were prescribed using Fung’s transversely isotropic constitutive law.Fiber angles of the endocardium and epicardium were prescribed as 53°°and-52°,respectively,with respect to the circumferential direction and varied linearly through the LV wall.The method developed by Krishnamurthywas used to determine the unloaded geometry to estimate the Fung passive material parameters.LV end-diastolic pressure(EDP)was determined from the measured pressure waves and applied to the endocardium at the unloaded geometry to simulate passive filling.Active material properties of the LV were prescribed using Guccione’s time-varying elastance model and maximum isometric tension was scaled to match the measured peak systolic pressure.The finite element model was then coupled to the Windkessel model,whose parameters were adjusted to the measured hemodynamics.Results Measured LVEDPs of LS and HS rats were 4.9±3.4 mmHg and 13.2±5.4 mmHg(P-0.030 8),respectively.End-diastolic Cauchy stress along the fiber direction for LS rats was significantly lower than for HS rats(0.91±0.60 kPa vs 3.00±0.63 kPa,P=0.001 4)and there was a similar trend in end-diastolic Green Strain along the fiber direction(0.058±0.003 vs 0.072±0.010,P=0.012 8,Figure 1b),as well.There was no distinctive difference between end-systolic Cauchy stress along the fiber direction for LS rats and HS rats(17.2±4.3 kPa vs 17.2±5.5 kPa,P=0.991 9)but end-systolic Green Strain along the fiber direction for LS rats was significantly higher than for HS rats(-0. 108±0.017 vs-0.065±0.024,negative sign represents direction).Conclusions For rats with HFpEF,it is the elevated LVEDP that induces the increase in end-diastolic stress and strain,thereby leading to diastolic dysfunction.Because of the preserved ejection fraction,HFpEF has less effect on systolic function.

Left bundle branch pacing vs biventricular pacing in heart failure patients with left bundle branch block:A systematic review and meta-analysis

BACKGROUND Left bundle branch pacing(LBBP)is a novel pacing modality of cardiac resynchronization therapy(CRT)that achieves more physiologic native ventricular activation than biventricular pacing(BiVP).AIM To explore the validity of electromechanical resynchronization,clinical and echocardiographic response of LBBP-CRT.METHODS Systematic review and Meta-analysis were conducted in accordance with the standard guidelines as mentioned in detail in the methodology section.RESULTS In our analysis,the success rate of LBBP-CRT was determined to be 91.1%.LBBP CRT significantly shortened QRS duration,with significant improvement in echocardiographic parameters,including left ventricular ejection fraction,left ventricular end-diastolic diameter and left ventricular end-systolic diameter in comparison with BiVP-CRT.CONCLUSION A significant reduction in New York Heart Association class and B-type natriuretic peptide levels was also observed in the LBBP-CRT group vs BiVP-CRT group.Lastly,the LBBP-CRT cohort had a reduced pacing threshold at follow-up as compared to BiVP-CRT.

Correlation analysis between lung ultrasound scores and pulmonary arterial systolic pressure in patients with acute heart failure admitted to the emergency intensive care unit

Background:No convenient,inexpensive,and non-invasive screening tools exist to identify pulmonary hypertension(PH)-left heart disease(LHD)patients during the early stages of the disease course.This study investigated whether different methods of lung ultrasound(LUS)could be used for the initial investigation of PH-LHD.Methods:This was a single-center prospective observational study which was performed in the Zigong Fourth People’s Hospital.We consecutively enrolled patients with heart failure(HF)admitted to the emergency intensive care unit from January 2018 to May 2020.Transthoracic echocardiography and LUS were performed within 24 h before discharge.We used the Spearman coefficient for correlation analysis between ultrasound scores and pulmonary arterial systolic pressure(PASP).Bland-Altman plots were generated to inspect possible bias,and receiver operating characteristic(ROC)curves were calculated to assess the relationship between ultrasound scores and an intermediate and high echocardiographic probability of PH-LHD.Results:Seventy-one patients were enrolled in this study,with an overall median age of 79(interquartile range:71.5–84.0)years.Among the 71 patients,36(50.7%)cases were male,and 26(36.6%)had an intermediate and high echocardiographic probability of PH.All four LUS scores in patients with an intermediate and high probability of PH were significantly higher than in patients with a low probability of PH(P<0.05).The correlation coefficient(r)between different LUS scoring methods and PASP was moderate for the 6-zone(r=0.455,P<0.001),8-zone(r=0.385,P=0.001),12-zone(r=0.587,P<0.001),and 28-zone(r=0.535,P<0.001)methods.In Bland-Altman plots,each of the four LUS scoring methods had a good agreement with PASP(P<0.001).The 8-zone and 12-zone methods showed moderately accurate discriminative values in differentiating patients with an intermediate and high echocardiographic probability of PH(P<0.05).

Serum cystatin C,monocyte/high-density lipoprotein-C ratio,and uric acid for the diagnosis of coronary heart disease and heart failure

BACKGROUND Coronary heart disease(CHD)and heart failure(HF)are the major causes of morbidity and mortality worldwide.Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis.However,conventional diagnostic methods such as electrocardiography,echocardiography,and cardiac biomarkers have certain limitations,such as low sensitivity,specificity,availability,and cost-effectiveness.Therefore,there is a need for simple,noninvasive,and reliable biomarkers to diagnose CHD and HF.AIM To investigate serum cystatin C(Cys-C),monocyte/high-density lipoprotein cholesterol ratio(MHR),and uric acid(UA)diagnostic values for CHD and HF.METHODS We enrolled 80 patients with suspected CHD or HF who were admitted to our hospital between July 2022 and July 2023.The patients were divided into CHD(n=20),HF(n=20),CHD+HF(n=20),and control groups(n=20).The serum levels of Cys-C,MHR,and UA were measured using immunonephelometry and an enzymatic method,respectively,and the diagnostic values for CHD and HF were evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Serum levels of Cys-C,MHR,and UA were significantly higher in the CHD,HF,and CHD+HF groups than those in the control group.The serum levels of Cys-C,MHR,and UA were significantly higher in the CHD+HF group than those in the CHD or HF group.The ROC curve analysis showed that serum Cys-C,MHR,and UA had good diagnostic performance for CHD and HF,with areas under the curve ranging from 0.78 to 0.93.The optimal cutoff values of serum Cys-C,MHR,and UA for diagnosing CHD,HF,and CHD+HF were 1.2 mg/L,0.9×10^(9),and 389μmol/L;1.4 mg/L,1.0×10^(9),and 449μmol/L;and 1.6 mg/L,1.1×10^(9),and 508μmol/L,respectively.CONCLUSION Serum Cys-C,MHR,and UA are useful biomarkers for diagnosing CHD and HF,and CHD+HF.These can provide information for decision-making and risk stratification in patients with CHD and HF.

Establishing delivery route-dependent safety and efficacy of living biodrug mesenchymal stem cells in heart failure patients

BACKGROUND Mesenchymal stem cells(MSCs)as living biopharmaceuticals with unique properties,i.e.,stemness,viability,phenotypes,paracrine activity,etc.,need to be administered such that they reach the target site,maintaining these properties unchanged and are retained at the injury site to participate in the repair process.Route of delivery(RoD)remains one of the critical determinants of safety and efficacy.This study elucidates the safety and effectiveness of different RoDs of MSC treatment in heart failure(HF)based on phase II randomized clinical trials(RCTs).We hypothesize that the RoD modulates the safety and efficacy of MSCbased therapy and determines the outcome of the intervention.AIM To investigate the effect of RoD of MSCs on safety and efficacy in HF patients.METHODS RCTs were retrieved from six databases.Safety endpoints included mortality and serious adverse events(SAEs),while efficacy outcomes encompassed changes in left ventricular ejection fraction(LVEF),6-minute walk distance(6MWD),and pro-B-type natriuretic peptide(pro-BNP).Subgroup analyses on RoD were performed for all study endpoints.RESULTS Twelve RCTs were included.Overall,MSC therapy demonstrated a significant decrease in mortality[relative risk(RR):0.55,95%confidence interval(95%CI):0.33-0.92,P=0.02]compared to control,while SAE outcomes showed no significant difference(RR:0.84,95%CI:0.66-1.05,P=0.11).RoD subgroup analysis revealed a significant difference in SAE among the transendocardial(TESI)injection subgroup(RR=0.71,95%CI:0.54-0.95,P=0.04).The pooled weighted mean difference(WMD)demonstrated an overall significant improvement of LVEF by 2.44%(WMD:2.44%,95%CI:0.80-4.29,P value≤0.001),with only intracoronary(IC)subgroup showing significant improvement(WMD:7.26%,95%CI:5.61-8.92,P≤0.001).Furthermore,the IC delivery route significantly improved 6MWD by 115 m(WMD=114.99 m,95%CI:91.48-138.50),respectively.In biochemical efficacy outcomes,only the IC subgroup showed a significant reduction in pro-BNP by-860.64 pg/mL(WMD:-860.64 pg/Ml,95%CI:-944.02 to-777.26,P=0.001).CONCLUSION Our study concluded that all delivery methods of MSC-based therapy are safe.Despite the overall benefits in efficacy,the TESI and IC routes provided better outcomes than other methods.Larger-scale trials are warranted before implementing MSC-based therapy in routine clinical practice.