Function In Heart Failure Patients Research Articles

Evaluation of Right Ventricular Function in Heart Failure Patients with Preserved Ejection Fraction using 2D Speckle Tracking Echocardiography

Evaluation of Right Ventricular Function in Heart Failure Patients with Preserved Ejection Fraction using 2D Speckle Tracking Echocardiography

Left atrial function in patients with heart failure

Improvement of the treatment and diagnosis of hypertension and heart failure (HF) contributes to an increase in life expectancy of the population and, accordingly, its aging. The problem of diagnosing and predicting HF with preserved ejection fraction (HFpEF) is currently one of the urgent problems. The role of left atrial function in the development and course prediction of HF are the subject of scientific study. This review provides an analysis of recent studies on left atrial function in HF patients.

Positive airway pressure therapy in heart failure patients comorbid with obstructive sleep apnea: Cardiovascular outcomes and nighttime-duration effect.

Comorbidity of obstructive sleep apnea (OSA) and heart failure (HF) is becoming increasingly common. This is a global analysis of positive airway pressure (PAP) efficacy for the cardiovascular outcomes in those HF Patients with comorbid OSA. Related randomized controlled trials were included. Analysed indicators covered primary outcomes (cardiac function, motor ability and life quality) and secondary outcomes (blood pressure and OSA-accompanying symptoms). Weighted mean difference was used to analyse the PAP-control difference in different experimental phases and the baseline-post difference in different groups. Compared with control group, PAP was associated with a 3.48% increase in left ventricle ejection fraction (LVEF) (p < .00001) and little decrease in heart rate (HR) (p=.67). Over 6h of mean nighttime use was associated with a greater increase in LVEF of 5.21% (p=.0002) and a significant reduction in HR of 3.81 bpm (p=.03). There was no significant difference between PAP and control group in their association with change in motor ability and life quality. Besides, PAP was associated with a 13.08 mm Hg decrease in systolic blood pressure and great improvements in OSA-accompanying symptoms: Apnea-Hypopnea Index, -23.73 e/h; mean oxygen saturation, 1.86%; minimum oxygen saturation, 8.78%; Epworth Sleepiness Scale, -1.39 point; arousal index, -16.41 e/h. There was also no significant difference in diastolic blood pressure. Positive airway pressure treatment improves cardiac function in HF patients with comorbid OSA, but the improved magnitude is associated with the duration of nighttime use rather than the duration of treatment.

Functional Significance of Cardiac Rehabilitation-Regulated Expression of Circulating MicroRNA-423-5p in Hypertensive Patients with Heart Failure with a Moderately Reduced Ejection Fraction.

BackgroundHypertension is a vital risk factor for heart failure, while cardiac rehabilitation can effectively improve cardiac function of heart failure patients. This study aimed to determine the impact of cardiac rehabilitation on microRNA-423-5p in hypertensive patients with heart failure with a moderately reduced ejection fraction. MethodsSixty hypertensive patients with heart failure with a moderately reduced ejection fraction were randomly divided into cardiac rehabilitation group and positive control group with 30 cases per group, while 30 hypertensive patients without heart failure were recruited as negative control group. The cardiac rehabilitation group and positive control group were treated with 1-month cardiac rehabilitation combined with the routine treatment and routine treatment only, respectively. The New York Heart Association classification, 6-minute walking test, and color Doppler echocardiography were adopted to detect cardiac function. Meanwhile, the expression of microRNA-423-5p and N-terminal pro-B-type natriuretic peptide was determined via Real-Time Fluorescence Quantitative PCR and electrochemiluminescence immunoassay. The diagnostic potential of microR-423-5p and N-terminal pro-B-type natriuretic peptide was assessed by ROC curve analysis and multivariate linear regression model. ResultsPatients in cardiac rehabilitation group displayed significantly lower expression of microR-423-5p and better results of New York Heart Association classification, 6-minute walking test, and color Doppler echocardiography than those in positive control group (P < .05). ROC analysis showed that microR-423-5p (AUC = 0.785; 95% CI: 0.686-0.865; sensitivity = 73.33%; specificity = 73.33%) had better specificity and accuracy than N-terminal pro-B-type natriuretic peptide (AUC = 0.721; 95% CI: 0.617-0.811; sensitivity = 81.67%; specificity = 63.33%). ConclusionMicroR-423-5p was implicated in left ventricular hypertrophy and might be a potential biomarker for assessing the therapeutic effect of cardiac rehabilitation on hypertensive patients with heart failure with a moderately reduced ejection fraction.

Pulmonary Capillary Recruitment Is Attenuated Post Left Ventricular Assist Device Implantation

Intoduction There is limited knowledge of pulmonary physiology and pulmonary function following continuous flow-left ventricular assist device (CF-LVAD) implantation. Therefore, the present study investigated if CF-LVAD influenced the pulmonary circulation by assessing pulmonary capillary blood volume and alveolar- capillary conductance as well as pulmonary function in heart failure patients. Methods 17 patients with severe HF who were scheduled for CF-LVAD (Heart Mate II® or Heart Ware®) implantation participated in the study. They underwent pulmonary function testing (measures of lung volumes and flow rates) and more unique measures of pulmonary physiology using a rebreathe-technique that quantified the diffusing capacity of the lungs for carbon monoxide and nitric oxide (DLCO and DLNO, respectively) pre and 3 months post CF-LVAD implantation. Results After CF-LVAD, pulmonary function was not significantly changed (p>0.05). For lung diffusing capacity, DLCO was significantly reduced (p=0.04), however, alveolar volume (VA) was not changed (p=0.47). After DLCO was corrected by VA, DLCO/VA demonstrated a trend towards reduction (p=0.08). For the alveolar-capillary component, capillary blood volume (Vc) and alveolar membrane conductance (Dm) were significantly or trended towards a reduction (p<0.04, p=0.06, respectively). However, Dm/Vc was not altered (p=0.92). Conclusions Early post CF LVAD implantation, Vc is reduced likely as a result of pulmonary capillary de-recruitment which contributes to the fall in lung diffusing capacity. There is limited knowledge of pulmonary physiology and pulmonary function following continuous flow-left ventricular assist device (CF-LVAD) implantation. Therefore, the present study investigated if CF-LVAD influenced the pulmonary circulation by assessing pulmonary capillary blood volume and alveolar- capillary conductance as well as pulmonary function in heart failure patients. 17 patients with severe HF who were scheduled for CF-LVAD (Heart Mate II® or Heart Ware®) implantation participated in the study. They underwent pulmonary function testing (measures of lung volumes and flow rates) and more unique measures of pulmonary physiology using a rebreathe-technique that quantified the diffusing capacity of the lungs for carbon monoxide and nitric oxide (DLCO and DLNO, respectively) pre and 3 months post CF-LVAD implantation. After CF-LVAD, pulmonary function was not significantly changed (p>0.05). For lung diffusing capacity, DLCO was significantly reduced (p=0.04), however, alveolar volume (VA) was not changed (p=0.47). After DLCO was corrected by VA, DLCO/VA demonstrated a trend towards reduction (p=0.08). For the alveolar-capillary component, capillary blood volume (Vc) and alveolar membrane conductance (Dm) were significantly or trended towards a reduction (p<0.04, p=0.06, respectively). However, Dm/Vc was not altered (p=0.92). Early post CF LVAD implantation, Vc is reduced likely as a result of pulmonary capillary de-recruitment which contributes to the fall in lung diffusing capacity.

Prognostic Impact of Hybrid Comprehensive Telerehabilitation Regarding Diastolic Dysfunction in Patients with Heart Failure with Reduced Ejection Fraction-Subanalysis of the TELEREH-HF Randomized Clinical Trial.

Aims: The objective of the study was to evaluate the effects of individually prescribed hybrid comprehensive telerehabilitation (HCTR) implemented at patients’ homes on left ventricular (LV) diastolic function in heart failure (HF) patients. Methods and results: The Telerehabilitation in Heart Failure Patients trial (TELEREH-HF) is a multicenter, prospective, randomized (1:1), open-label, parallel-group, controlled trial involving HF patients assigned either to HCTR involving a remotely monitored home training program in conjunction with usual care (HCTR group) or usual care only (UC group). The patient in the HCTR group underwent a 9-week HCTR program consisting of two stages: an initial stage (1 week) conducted in hospital and the subsequent stage (eight weeks) of home-based HCTR five times weekly. Due to difficulties of proper assessment and differences in the evaluation of diastolic function in patients with atrial fibrillation, we included in our subanalysis only patients with sinus rhythm. Depending on the grade of diastolic dysfunction, patients were assigned to subgroups with mild diastolic (MDD) or severe diastolic dysfunction (SDD), both in HCTR (HCTR-MDD and HCTR-SDD) and UC groups (UC-MDD and UC-SDD). Changes from baseline to 9 weeks in echocardiographic parameters were seen only in A velocities in HCTR-MDD vs. UC-MDD; no significant shifts between groups of different diastolic dysfunction grades were observed after HCTR. All-cause mortality was higher in UC-SDD vs. UC-MDD with no difference between HCTR-SDD and HCTR-MDD. Higher probability of HF hospitalization was observed in HCTR-SDD than HCTR-MDD and in UC-SDD than UC-MDD. No differences in the probability of cardiovascular mortality and hospitalization were found. Conclusions: HCTR did not influence diastolic function in HF patients in a significant manner. The grade of diastolic dysfunction had an impact on mortality only in the UC group and HF hospitalization over a 12–24-month follow-up in HCTR and UC groups.

Clinical Study of Heart Failure with Left Ventricular Ejection Fraction Regimen Treated with Entresto.

Heart failure is a group of syndromes caused by various cardiac structural or functional disorders leading to impaired ventricular filling and (or) ejection capacity. Because of decreased ventricular systolic function and impaired ejection function, the amount of cardiac output cannot meet the body's metabolic needs; organ and tissue blood perfusion is insufficient; at the same time, pulmonary circulation and (or) systemic circulation congestion; the clinical manifestations are mainly dyspnea and weakness but restricted physical activity and edema. Treatment of the disease should include preventing and delaying the onset of wails, relieving symptoms of clinical wails, improving its long-term prognosis, and reducing mortality. The aim of the study is to observe the efficacy and safety of Entresto in the treatment of left ventricular ejection fraction heart failure (HFpEF). Seventy-eight patients with HFpEF treated in our hospital from October 2017 to April 2018 were randomized into a treatment group (Entresto 50 mg + basic treatment, n = 39) and a control group (basic treatment, n = 39). The course of treatment was ten weeks. The levels of brain natriuretic peptide (BNP) and echocardiographic indicators (LVMI, LVEF, LVEDD, LVESD, E/E′ Ratio, E/A ratio, DT), 6-minute walking test (6MWD), and Minnesota Quality of Life Scale (MLHFQ) were analyzed before and after treatment. LVMI, LVEF, LVEDD, LVESD, E/E′ ratio, E/A ratio, DT, and BNP were all significantly improved in the Entresto group after treatment. In the control group, except for LVEDD, LVESD, the E/A ratio, and BNP, other indicators were significantly improved after treatment (P < 0.05). Posttreatment, both groups had significantly improved 6MWD and MLHFQ scores (P < 0.05). Differences in these parameters between the two groups were statistically significant (P < 0.05). After treatment, the levels of NE, AngII, ALD, and MMP-9 in the two groups were decreased (P < 0.05), with the lower lever in the treatment group (P < 0.05). The effective rate was 76.92% in the control group and 94.87% in the Entresto group, and this rate difference was statistically significant (P < 0.05). The number of patients re-hospitalized due to cardiovascular events was 2 (the Entresto group) vs. 7 (the control group) cases; worsening of heart failure was observed in 1 patient (the Entresto group) vs. 6 (the control group), and the difference between the two groups was statistically significant (P < 0.05). However, the incidence of adverse reactions between the two groups was not statistically significant. Entresto can significantly improve left ventricular diastolic function in heart failure patients with preserved left ventricular ejection fraction and improve quality of life. This treatment is safe and effective and worthy of clinical application. This trail is registered with ChiCTR2000031486. This trial was approved by the Chinese Clinical Trial Registry (clinical trial number: ChiCTR2000031486). The registration number of this study is 2022-R008.

Correlation Between Lipid Profile and Kidney Function in Ambulatory Heart Failure Patient

Heart failure contributes to a high number of hospitalizations. Currently, the number of outpatients is more dominant than hospitalized heart failure patients. Unfortunately, a study in the outpatient setting is still limited. This study aims to evaluate the correlation between lipid profile and kidney function in ambulatory heart failure patients. This study is a single-center cross-sectional study. Data were collected from August to September 2020. Data were extracted from 62 medical records of heart failure patients with ejection fraction 45%. Exclusion criteria were life-threatening comorbidity and patient with routine hemodialysis. Data were analyzed with Pearson or Spearman correlation test. Most of the heart failure patients in our outpatient clinic are elderly (60 years old) and male (58%). The researchers found positive correlation of total cholesterol (r 0.39; p 0.001) and triglyceride (r 0.59; p 0.001) to serum creatinine. On the other hand, LDL and blood cholesterol ratio negatively correlated with serum creatinine, r - 0.31; p 0.016; and r - 0.46; p 0.001; respectively. All of this analysis was statistically significant. It concluded that lipid profiles were correlated with kidney function in heart failure patients

EFFECT OF MODERN VERSUS STANDARD OF CARE ANTI-FAILURE MEDICATIONS ON LEFT VENTRICULAR FUNCTION IN HEART FAILURE PATIENTS WITH REDUCED EJECTION FRACTION AS DETECTED BY2D SPECKLE TRACKING ECHOCARDIOGRAPHY

Background: Heart failure (HF) is a major and growing public health problem, as 21 million adults worldwide are living with heart failure and this number is expected to rise due to aging population, increasing prevalence of risk factors and improved post myocardial infarction (MI) survival. Objective: This study was discuss the effect of modern versus standard of care anti failure medications on LV function in heart failure patients with reduced ejection fraction using 2D speckle tracking echocardiography. Patients and methods: The study population includes 100 heart failure patients with reduced ejection fraction 50 on modern anti-failure medications including angiotensin receptor neprilysin inhibitor (ARNI) and 50 controls on standard anti-failure medications including angiotensin I-converting enzyme inhibitor (ACEI) or angiotensin II receptor blockers (ARBs). All patients attended the outpatient clinic of the Cardiology Department at Al-Azhar University Hospital (Cairo) from March 2020 to March 2021. Results: There was no significant statistical difference between groups also regard sex distribution there was no significant difference between groups and male were majority in both groups. There was no significant difference between the two studied groups regarding levels of serum creatinine and serum K. Results of comparison of end systolic, end diastolic diameters of left ventricle and diameter of left atrium showed no significant difference between both groups at pre medication assessment but there was a highly significant after medications in both groups (p= 0.00, 0.038 and 0.035 respectively) also in group A there was a significant decrease from pre to post assessment (p=0.003, 0.012 and 0.004 respectively). There was a statistically significant improve in mitral regurgitation after medication in group A than in group B (p=0.00) but was of no significant in pre medication assessment (p=0.48). Conclusion: In HFrEF patients, sacubitril/valsartan significantly improves the mitral regurgitation LV remodeling and with a significant effect on LV diastolic and systolic echo parameters. Accordingly, sacubitril/valsartan could be used at an earlier time in HFrEF patients in order to further limit LV remodeling.

Preparation of Nanographene and Its Effect on the Correlation Between N-Terminal Pro Brain-Type Natriuretic Peptide, Peripheral Blood Copeptin Level and Cardiac Function Grading of Patients with Heart Failure

At present, biosensors based on nanomaterials are increasingly adopted in clinical detection of heart failure (HF) patients. This work aimed to analyze the correlation between N-terminal pro brain-type natriuretic peptide (NT-proBNP) and copeptin (CPT) levels in order to study the grading of heart function in patients with HF under the fluorescence platform built on nanographene. The and detection principle of of nanographene solution was prepared, and After its physical and chemical properties were tested, the nanographene solution was then used to detect the expression levels of NT-proBNP and CPT in patients with heart failure. Seventy-two patients with heart failure who came to hospital were selected as the observation group, and another 50 healthy people with physical examination were selected as the control group. The results showed that the constructed nanographene solution mixed with NT-proBNP didn’t exhibit fluorescence quenching. Therefore, it was feasible to detect NT-proBNP with nanographene solution. The test results obtained after the detection of different concentrations of nanographene showed that 20 μg/mL nanographene had the best fluorescence quenching effect. The ROC curve of the constructed nanographene had improved specificity in judging heart failure and had better diagnostic performance. The levels of pro-brain natriuretic peptide and copeptin in patients with heart failure were obviously higher than those in the observation group, and there was considerable difference between the two (P &lt; 0.05). After correlation analysis, it was found that the levels of terminal pro-brain natriuretic peptide and copeptin in patients with heart failure were positively correlated with the grade of heart function in patients with heart failure. In summary, the nanographene solution used in this study can accurately detect the expression level of NT-proBNP in patients with heart failure, and the accuracy and efficiency of diagnosis were improved in patients with heart failure. Moreover, the higher the grade of cardiac function in HF patients, the higher NT-proBNP and CPT levels, and there was positive correlation between cardiac function grade and NT-proBNP and CPT levels.

Improvement of Pulmonary Function in Heart Failure Patients with Restrictive Patterns Undergoing Transcatheter Aortic Valve Replacement.

BackgroundThis study aimed to investigate the improvement of pulmonary function in heart failure patients with restrictive patterns undergoing transcatheter aortic valve replacement (TAVR).MethodsA total of 80 patients with heart failure and restrictive patterns undergoing TAVR due to severe aortic stenosis were included in this study. Spirometry and gas diffusion were assessed before and 4–6 months after TAVR. Pre- and post-TAVR measures were compared using paired t-tests.ResultsSpirometry demonstrated increased absolute and percentage predicted total lung capacity (TLC), forced vital capacity (FVC), residual volume (RV), forced expiratory volume in the first second (FEV1), and forced vital capacity (FVC). FEV1/FVC decreased due to a pronounced increase in FVC. Additionally, the diffusing capacity for carbon monoxide (DLCO) increased significantly.ConclusionPulmonary function improves in heart failure patients with restrictive patterns undergoing TAVR.

Oscillatory Pattern of Sympathetic Nerve Bursts Is Associated With Baroreflex Function in Heart Failure Patients With Reduced Ejection Fraction.

Sympathetic hyperactivation and baroreflex dysfunction are hallmarks of heart failure with reduced ejection fraction (HFrEF). However, it is unknown whether the progressive loss of phasic activity of sympathetic nerve bursts is associated with baroreflex dysfunction in HFrEF patients. Therefore, we investigated the association between the oscillatory pattern of muscle sympathetic nerve activity (LFMSNA/HFMSNA) and the gain and coupling of the sympathetic baroreflex function in HFrEF patients. In a sample of 139 HFrEF patients, two groups were selected according to the level of LFMSNA/HFMSNA index: (1) Lower LFMSNA/HFMSNA (lower terciles, n = 46, aged 53 ± 1 y) and (2) Higher LFMSNA/HFMSNA (upper terciles, n = 47, aged 52 ± 2 y). Heart rate (ECG), arterial pressure (oscillometric method), and muscle sympathetic nerve activity (microneurography) were recorded for 10 min in patients while resting. Spectral analysis of muscle sympathetic nerve activity was conducted to assess the LFMSNA/HFMSNA, and cross-spectral analysis between diastolic arterial pressure, and muscle sympathetic nerve activity was conducted to assess the sympathetic baroreflex function. HFrEF patients with lower LFMSNA/HFMSNA had reduced left ventricular ejection fraction (26 ± 1 vs. 29 ± 1%, P = 0.03), gain (0.15 ± 0.03 vs. 0.30 ± 0.04 a.u./mmHg, P < 0.001) and coupling of sympathetic baroreflex function (0.26 ± 0.03 vs. 0.56 ± 0.04%, P < 0.001) and increased muscle sympathetic nerve activity (48 ± 2 vs. 41 ± 2 bursts/min, P < 0.01) and heart rate (71 ± 2 vs. 61 ± 2 bpm, P < 0.001) compared with HFrEF patients with higher LFMSNA/HFMSNA. Further analysis showed an association between the LFMSNA/HFMSNA with coupling of sympathetic baroreflex function (R = 0.56, P < 0.001) and left ventricular ejection fraction (R = 0.23, P = 0.02). In conclusion, there is a direct association between LFMSNA/HFMSNA and sympathetic baroreflex function and muscle sympathetic nerve activity in HFrEF patients. This finding has clinical implications, because left ventricular ejection fraction is less in the HFrEF patients with lower LFMSNA/HFMSNA.

Indicator of endothelial dysfunction endothelin-1 dynamics in heart failure patients with midrange ejection fractionf of ischemic etiology against the background of therapy

Background and Aims: Evaluate the influence of β-blockers bisoprolol and nebivolol in combination with eplerenone on endothelial function in heart failure patients with mid-range ejection fraction (HFmEF) of ischemic etiology and metabolic disorders.

Effect of atrial fibrillation on cognitive function in heart failure patients.

Effect of atrial fibrillation on cognitive function in heart failure patients.

Importance of epicardial adipose tissue localization using cardiac magnetic resonance imaging in patients with heart failure with mid‐range and preserved ejection fraction

BackgroundEpicardial adipose tissue (EAT) has been implicated in the pathophysiology of heart failure (HF) with left ventricular ejection fraction (LVEF) >40%, but whether this is due to a regional or global effect of EAT remains unclear.HypothesisRegional EAT is associated with alterations in local cardiac structure and function.MethodsPatients with HF and LVEF >40% were studied. Cardiac Magnetic Resonance imaging was used to localize EAT surrounding the right ventricle (RV) and LV separately, using anterior‐ and posterior interventricular grooves as boundaries. Atrial‐ and ventricular EAT were differentiated using the mitral‐valve position. All EAT depots were related to the adjacent myocardial structure.Results102 consecutive HF patients were enrolled. The majority of EAT was present around the RV (42% of total EAT, p < .001). RV‐EAT showed a strong association with increased RV mass (β = 0.60, p < .001) and remained associated with RV mass after adjusting for total EAT, sex, N‐terminal prohormone of brain natriuretic peptide (NT‐proBNP), renal function and blood glucose. LV‐EAT showed a similar association with LV mass in univariable analysis, albeit less pronounced (β = 0.24, p = .02). Atrial EAT was increased in patients with atrial fibrillation compared to those without atrial fibrillation (30 vs. 26 ml/m2, p = .04), whereas ventricular EAT was similar (74 vs. 75 ml/m2, p = .9).ConclusionsRegional EAT is strongly associated with local cardiac structure and function in HF patients with LVEF >40%. These data support the hypothesis that regional EAT is involved in the pathophysiology of HF with LVEF >40%.

Associations between kidney function and outcomes of comprehensive cardiac rehabilitation in patients with heart failure.

To investigate the impact of baseline kidney function on outcomes following comprehensive cardiac rehabilitation (CR) in patients with heart failure (HF). We reviewed a total of 3,727 patients who were admitted for HF treatment. Estimated glomerular filtration rate (eGFR), quadriceps strength (QS), and 6-min walk distance (6MWD) were measured at hospital discharge as a baseline and 5months thereafter in participants of outpatient comprehensive CR. The association between outpatient CR participation and all-cause events was evaluated using propensity score-matched analysis in subgroups across eGFR stages. The changes in QS and 6MWD following 5-month CR were compared between eGFR stages. Out of the studied patients, 1585 (42.5%) participated in outpatient CR. After propensity matching for clinical confounders, 2680 patients were included for analysis (pairs of n = 1340 outpatient CR participants and nonparticipants). The participation in outpatient CR was significantly associated with low clinical events in subgroups of eGFR ≥ 60 [hazard ratio (HR): 0.65, 95% confidence interval (CI): 0.51-0.84] and eGFR 45-60 (HR: 0.71, 95% CI: 0.55-0.92), but not in eGFR 30-45 (HR: 0.83, 95% CI: 0.64-1.08) and eGFR < 30 (HR: 0.88, 95% CI: 0.69-1.12). QS and 6MWD were significantly higher after 5-month CR than those at baseline (P < 0.001, respectively), but lower baseline eGFR correlated with lower changes in QS and 6MWD (trend P < 0.001, respectively). Although low baseline kidney function attenuates the outcomes of CR, outpatient CR seems to be associated with a better prognosis and positive change in physical function in HF patients with low kidney function.

Comparative efficacy of image-guided techniques in cardiac resynchronization therapy: a meta-analysis

BackgroundSeveral studies have illustrated the use of echocardiography, magnetic resonance imaging, and nuclear imaging to optimize left ventricular (LV) lead placement to enhance the response of cardiac resynchronization therapy (CRT) in heart failure patients. We aimed to conduct a meta-analysis to determine the incremental efficacy of image-guided CRT over standard CRT.MethodsWe searched PubMed, Cochrane library, and EMBASE to identify relevant studies. The outcome measures of cardiac function and clinical outcomes were CRT response, concordance of the LV lead to the latest sites of contraction (concordance of LV), heart failure (HF) hospitalization, mortality rates, changes of left ventricular ejection fraction (LVEF), and left ventricular end-systolic volume (LVESV).ResultsThe study population comprised 1075 patients from eight studies. 544 patients underwent image-guided CRT implantation and 531 underwent routine implantation without imaging guidance. The image-guided group had a significantly higher CRT response and more on-target LV lead placement than the control group (RR, 1.33 [95% CI, 1.21 to 1.47]; p < 0.01 and RR, 1.39 [95% CI, 1.01 to 1.92]; p < 0.05, respectively). The reduction of LVESV in the image-guided group was significantly greater than that in the control group (weighted mean difference, − 12.46 [95% CI, − 18.89 to − 6.03]; p < 0.01). The improvement in LVEF was significantly higher in the image-guided group (weighted mean difference, 3.25 [95% CI, 1.80 to 4.70]; p < 0.01). Pooled data demonstrated no significant difference in HF hospitalization and mortality rates between two groups (RR, 0.89 [95% CI, 0.16 to 5.08]; p = 0.90, RR, 0.69 [95% CI, 0.37 to 1.29]; p = 0.24, respectively).ConclusionsThis meta-analysis indicates that image-guided CRT is correlated with improved CRT volumetric response and cardiac function in heart failure patients but not with lower hospitalization or mortality rate.

Effect of Levosimendan on Ventricular Systolic and Diastolic Functions in Heart Failure Patients: A Meta-Analysis of Randomized Controlled Trials.

Levosimendan, a calcium sensitizer, exerts inotropic action through improving left ventricular ejection fraction. We noticed that only few clinical studies are published in which the effects of levosimendan on cardiac function are studied by echocardiography. When screening the literature (PubMed, Embase, and CENTRAL, from inception to August 2020), we found 29 randomized controlled trials on levosimendan containing echocardiographic data. We included those studies, describing a total of 574 heart failure patients, in our meta-analysis and extracted 14 ultrasonic parameters, pooling the effect estimates using a random-effect model. Our analysis of the diastolic parameters of the left ventricle shows that levosimendan reduce the early/late transmitral diastolic peak flow velocity ratio [standardized mean difference (SMD) -0.45 to 95% confidence interval (CI) (-0.87 to -0.03), P = 0.037] and E/e' (e': mitral annulus peak early diastolic wave velocity using tissue-doppler imaging) [SMD -0.59, 95% CI (-0.8 to -0.39), P < 0.001]. As it regards the systolic parameters of the right ventricle, levosimendan increased tricuspid annular plane systolic excursion [SMD 0.62, 95% CI (0.28 to 0.95), P < 0.001] and tricuspid annular peak systolic velocity [SMD 0.75, 95% CI (0.35 to 1.16), P < 0.001], and reduced systolic pulmonary artery pressure [SMD -1.02, 95% CI (-1.32, -0.73), P < 0.001]. As it regards the diastolic parameters of the right ventricle, levosimendan was associated with the decrease of Aa (peak late diastolic tricuspid annular velocity using tissue-doppler imaging) [SMD -0.38, 95% CI (-0.76 to 0), P = 0.047] and increase of Ea (peak early diastolic tricuspid annular velocity using tissue-doppler imaging) [SMD 1.03, 95% CI (0.63 to 1.42), P < 0.001] and Ea/Aa [SMD 0.86, 95% CI (0.18 to 1.54), P = 0.013]. We show that levosimendan is associated with an amelioration in the diastolic and systolic functions of both ventricles in heart failure patients.

MiR-132/212 Impairs Cardiomyocytes Contractility in the Failing Heart by Suppressing SERCA2a.

Compromised cardiac function is a hallmark for heart failure, mostly appearing as decreased contractile capacity due to dysregulated calcium handling. Unfortunately, the underlying mechanism causing impaired calcium handling is still not fully understood. Previously the miR-132/212 family was identified as a regulator of cardiac function in the failing mouse heart, and pharmaceutically inhibition of miR-132 is beneficial for heart failure. In this study, we further investigated the molecular mechanisms of miR-132/212 in modulating cardiomyocyte contractility in the context of the pathological progression of heart failure. We found that upregulated miR-132/212 expressions in all examined hypertrophic heart failure mice models. The overexpression of miR-132/212 prolongs calcium decay in isolated neonatal rat cardiomyocytes, whereas cardiomyocytes isolated from miR-132/212 KO mice display enhanced contractility in comparison to wild type controls. In response to chronic pressure-overload, miR-132/212 KO mice exhibited a blunted deterioration of cardiac function. Using a combination of biochemical approaches and in vitro assays, we confirmed that miR-132/212 regulates SERCA2a by targeting the 3′-end untranslated region of SERCA2a. Additionally, we also confirmed PTEN as a direct target of miR-132/212 and potentially participates in the cardiac response to miR132/212. In end-stage heart failure patients, miR-132/212 is upregulated and correlates with reduced SERCA2a expression. The up-regulation of miR-132/212 in heart failure impairs cardiac contractile function by targeting SERCA2a, suggesting that pharmaceutical inhibition of miR-132/212 might be a promising therapeutic approach to promote cardiac function in heart failure patients.

Discovery of a Hydroxypyridinone APJ Receptor Agonist as a Clinical Candidate.

Apelin-13 is an endogenous peptidic agonist of the apelin receptor (APJ) receptor with the potential for improving cardiac function in heart failure patients. However, the low plasma stability of apelin-13 necessitates continuous intravenous infusion for therapeutic use. There are several approaches to increase the stability of apelin-13 including attachment of pharmacokinetic enhancing groups, stabilized peptides, and Fc-fusion approaches. We sought a small-molecule APJ receptor agonist approach to target a compound with a pharmacokinetic profile amenable for chronic oral administration. This manuscript describes sequential optimization of the pyrimidinone series, leading to pyridinone 14, with in vitro potency equivalent to the endogenous ligand apelin-13 and with an excellent oral bioavailability and PK profile in multiple preclinical species. Compound 14 exhibited robust pharmacodynamic effects similar to apelin-13 in an acute rat pressure-volume loop model and was advanced as a clinical candidate.