Improvement In Cardiac Function Research Articles

Rationale and design of a randomised trial of trientine in patients with hypertrophic cardiomyopathy

AimsHypertrophic cardiomyopathy (HCM) is characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, enhanced oxidative stress and energy depletion. Unbound/loosely bound tissue copper II ions are powerful catalysts of oxidative stress...

The effect of early substitution of subclinical hypothyroidism on cardiovascular function

Abstract Funding Acknowledgements Type of funding sources: None. Background / Aim Current controversies related to the treatment of subclinical hypothyroidism (SCH) with thyrotropin (TSH) < than 10 mU/L are based on the lack of evidence that levothyroxine therapy has beneficial effects. The aim of this study was to examine the effect a 3-month LT4 treatment on cardiovascular function in symptomatic SCH with TSH < 10 mIU/L. Methods Electro and echocardiographic indices were measured in 35 patients with persistent symptomatic SCH before the intervention (TSH 7.0±2.1 mIU/L), and 3 months after the euthyroid state had been achieved. Results Significant reduction in PR (before: 0.16 ± 0.02, after: 0.15 ± 0.02; p<0.001), QT (before: 389.58 ± 10.12, after: 383.54 ± 8.62; p<0.001) and QT corrected (before: 428.77 ± 20.11, after: 411.77 ± 14.73; p<0.001) intervals as well as increase in heart rate (p=0.001) were recorded in the group on levothyroxine therapy. The following parameters of the left and right ventricle were significantly decreased in the treatment group: left ventricular mass index (before: 76.81 ± 13.52, after: 70.62 ± 16.45; p<0.001 respectively), ESV (before: 38.86 ± 9.6, after: 36.95 ± 9.25; p<0.001), EDV (before: 114.83 ± 20.6, after: 108.43 ± 18; p<0.001), MAPSE 2D (before: 1.67 (1.55-1.89), after: 1.53 (1.34-1.65); p<0.001). systolic and diastolic time intervals: IVCT (before: 53.23 ± 11.07, after: 46.54 ± 11.13; p<0.001), IVRT (before: 78.71 ± 11.35, after: 72.69 ± 10.1; p<0.001), IVCT/ET (before: 0.18 ±0.04, after: 0.16 ±0.04; p<0.001). The increase was recorded as fractional shortening (before: 39.40 (35.40-46.80), after: 42.40 (38.80-47.20), p<0.001) and pressure rise in early systole (dP/dt: before: 2163.29 ± 454.48, after: 2385.17 ± 542.83; p<0.001), right atrial wall thickness and diameters (RA long axis (before: 4.59 (4.18-5.11), after: 4.81 (4.31-5.70); p<0.001) and short axis (before: 3.67 (3.16-3.87), after: 3.88 (3.38-4.14); p<0.001)), wall thickness (before: 0.43 (0.40-0.46), after: 0.44 (0.40-0.48); p<0.001). After the levothyroxine therapy, there was a statistically significant decrease in ESV and EDV (p<0.001, p<0.001 respectively). LT4 therapy significantly increased values of EF (p<0.001) as well as global longitudinal circumferential and radial strains (p<0.001, p<0.001, p<0.001 respectively). There is a moderate, positive, statistically significant correlation between the change in the titre of anti TPO antibodies and the change in global longitudinal strain values after the therapy (p = 0.027). Conclusions Our study confirmed an echocardiographic improvement of cardiac structure and function in treated individuals. The findings suggest electrocardiographic and echocardiographic screening in monitoring the therapeutic effect.

Comparison between levosimendan versus beta agonists in preservation of renal function in cardiac surgery patients with low cardiac output syndrome

ABSTRACT Background Post cardiac surgery acute kidney injury (AKI) secondary to postoperative low cardiac output syndrome (LCOS), is a serious complication. Positive inotropic agents are the main line of treatment for LCOS with different degrees of improvement of cardiac function & nephroprotective efficacy Levosimendan is a calcium sensitizer in cardiac muscles, which has a comparable positive inotropic and nephroprotective effects to that of classic beta2 agonists. Objective To evaluate the possible nephroprotective effect of levosimendan as compared to beta agonists in cardiac surgery patients with LCOS. Patients and Methods It is a prospective, randomized and comparative study conducted at Ain Shams University Hospitals over the period from December 2020 to May 2021. A total of 60 patients with post cardiac surgery low cardiac output syndrome were divided into two groups of 30 patients each. Group A (control) received beta-agonists (dobutamine or adrenaline) and Group B (study) received levosimendan. The incidence of AKI at the diagnosis of LCOS & its progression to renal failure in both groups were assessed. Results The incidence of AKI at diagnosis of LCOS postoperative was 30% (n = 9) in each group; 44% of them in the control group (n = 4) developed renal failure at discharge from ICU and none of the study group patients developed renal failure at discharge. At the time of discharge from ICU, the incidence of renal failure in beta-agonist group was 13.3%, while the incidence in the levosimendan group was 0% with statistically significant P value of 0.038. Conclusion In comparison to beta-agonists, Levosimendan may have a better nephroprotective effect that plays a role in decreasing the incidence of kidney failure in patients with post cardiac surgery LCOS. A larger randomized, controlled trials are recommended to prove such a beneficial nephroprotective effect and its exact mechanism.

Long term in vivo Dlk1 gene transfer protects against myocardial fibrosis-induced cardiac dysfunction

Introduction: Cardiac fibrosis can independently contribute to the impairment of cardiac function and development of heart failure. Early activation of pro-fibrotic genetic pathways has been suggested to occur well before adverse ventricular remodeling occurs in fibrosis as it progresses to heart failure. Delta-like homolog 1 (Dlk1), a paternally imprinted gene that encodes a transmembrane protein that contains multiple epidermal growth factor repeats, has been shown to play a critical role as a regulator of cell differentiation, neuronal differentiation, bone differentiation, and hematopoiesis. We hypothesize that Dlk-1 could regulate myocardial fibrosis via inhibition of fibroblast-myofibroblast conversion and therefore restrain cardiac fibrosis progression. Methods: Wildtype (WT) and Dlk1 knockout (Dlk1-/-) mice were subjected to myocardial infarction (MI) by permanent ligation of the left anterior descending artery to induce heart failure. A recombinant adeno-associated virus 9 (AAV9) was used to deliver Dlk1 into the myocardium in vivo. Cardiac function and hemodynamic changes were measured by echocardiography and left ventricular catheterization. Immunohistochemistry and confocal microscopy were used to determine the expression of pro-fibrotic markers. Total RNA was prepared from left ventricular (LV) tissue or cardiomyocytes and fibroblasts from Dlk1-/- and WT hearts. Masson trichrome staining was used to determine abnormal collagen deposition in the heart. Result: Myocardial fibrosis was demonstrated by increased expression of alpha-smooth muscle actin (αSMA), collagen, fibronectin, connective tissue growth factor, along with a substantial increase in the deposition of collagen as evident from Masson's trichrome staining. We observed downregulated Dlk-1 mRNA and protein expression in ischemic tissues from human patients and infarcted pigs’ hearts. The reduced levels of Dlk1 were associated with increased mRNA expression of pro-fibrotic molecules, collagen1a, LOX and αSMA in the scar area. Echocardiographic analysis revealed substantial LV chamber dilatation and reduced fractional shortening (FS %) in Dlk1 null mice as compared to WT, whereas the mice treated with AAV9-Dlk1 for 8-10 weeks showed a significant improvement in cardiac function. Consistently, Dlk1-deficient mice exhibited impairment in heart function, cardiac fibrosis and myocyte hypertrophy and increased expression of atrial natriuretic peptide, and B-type natriuretic peptide, while AAV9-Dlk1-treated mice significantly reduced cardiac remodeling and myocardial fibrosis. Conclusion: Restoration of Dlk1 in the heart following MI-induced heart failure improved cardiac function and attenuated myocardial fibrosis. The findings from the current study suggest a critical role for Dlk1 in myocardial fibrosis-induced cardiac remodeling, indicating that Dlk1 gene therapy may be a viable therapeutic approach for heart failure. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

PO-04-049 PATIENT CHARACTERISTICS AND FIVE-YEAR CLINICAL OUTCOMES OF PATIENTS WITH HEART FAILURE WITH MID-RANGE EJECTION FRACTION.

Clinical outcomes of patients presenting with heart failure and mid-range ejection fraction (HFmEF) between 35-50% is less defined. Cardiac risk factors are associated with increased risk of disease progression. To define patient clinical characteristics associated with worsening and improvement in cardiac function and clinical outcomes. Between July 2017 and December 2022, 250 patients (pts) were identified with newly diagnosed heart failure with HFmEF. Clinical characteristics, comorbidities, outcomes and prognosis among these pts who improved (Group-1: left ventricular ejection fraction (LVEF) >50%) remain stable (Group-2: LVEF 35-50%) and worsened (Group-3: LVEF <35%) were analysed. At a mean follow up of 55±6 months, LVEF improved in 146 (58.4%) pts, 69 pts (27.6%) remained stable and 35pts (14%) worsened. All pts were started on guideline directed optimal heart failure medication. At final follow up, in group 1, 9 (6.16%) had sustained Ventricular Arrhythmias VAs, none were hemodynamically significant VA, 8 (5.48%) needed ICD and 1 (0.68%) needed CRTD. Group 2, 16 (23.18%) had sustained VAs, 1 (1.45%) hemodynamically significant VA, 12 (17.39%) needed ICD and 4 (5.79%) needed CRTD. Group 3, 21 (60%) had sustained VAs, 5 (14.28%) hemodynamically significant VA, 16 (45.71%) needed implantable cardioverter defibrillator (ICD) and 5 (14.28%) needed cardiac resynchronisation therapy defibrillator (CRTD). Table 1 shows clinical characteristics of the three distinct subgroups and clinical outcomes. Mid-range cardiomyopathy is not a benign condition. Aggressive targeted treatment strategies should be embarked to improve outcomes. Careful monitoring and routine follow up needs to be undertaken. Diabetes, CAD, scar at baseline on MRI and VAs are adverse predictors of left ventricular function improvement and prognosis.

The role of purine nucleotide metabolism in cardiac failure

Normal cardiac function requires ATP to be synthesized at a sufficient rate to drive the molecular processes underlying electromechanical coupling. Myocardial metabolic dysfunction observed during heart failure leads to reductions in the chemical potential at which ATP is synthesized. We have observed reductions in oxidative capacity, and total adenine nucleotide (TAN) levels in a rat aortic constriction (TAC) induced heart failure model that parallel changes seen in large mammal models and humans with heart failure. Computer simulations of cardiac mechano-energetics also predict a marked increase in inorganic phosphate levels in diseased hearts compared to healthy control hearts. Furthermore, simulations predict that restoring the impaired energetic dysfunction of TAC rats improves systolic function. Metabolomic and proteomic analysis reveal increases in purine degradation by-products and AMP deaminase 3 (AMPD3) levels in failing versus control hearts. AMPD activity has been hypothesized to play a role in skeletal muscle in type 2 diabetes, however, there is still a need to decern the role, if any, of AMPD3 in the heart and in failure. A cardiac ventricle specific AMPD3 conditional knock out (cKO) rat model was developed to test the hypothesis that decreasing AMPD3 activity in the failing heart will lead to a preservation of TAN and improvement in cardiac mechanical function. Cardiac hypertrophy and decomposition were induced by placing a clip (TAC) in three-week old female and male rats. In the cKO model, AMPD3 exon 6 is flanked by loxP sites, and are either heterozygous for cre recombinase driven by the cardiac myosin light chain promoter (cre+/-) or lack the cre enzyme (cre-/-). Tamoxifen was administered to all rats both pre-surgery and post-surgery to induce AMPD3 knock down. Echocardiography was performed at 2- and 18-weeks post-surgery. At 18 weeks post-surgery, hearts were harvested for mitochondrial capacity, metabolite measurements, AMPD activity, and protein and mRNA measurements. Knock down efficiency in cre +/- animals compared to cre -/- was assessed based on enzyme activity, mRNA expression, and protein abundance. There is a 45% decrease in total AMPD activity in the AMPD3 cKO rats, where measured AMPD activity reflects the sum activity of all present AMPD isoforms. Additionally, there is 52% decrease in protein abundance and a 72% reduction in AMPD3 mRNA expression. Preliminary observations reveal significant differences in oxidative capacity and in cardiac function between TAC and sham rats, consistent with the hypothesis that knock down of AMDP3, an enzyme that is upregulated during TAC induced heart failure in rodents, results in preservation of myocardial nucleotide pools and improve cardiac mechanical function. Research is supported by the NIH grants HL144657 and F31-HL154605 (RL). We are grateful for support from the post-baccalaureate research program (2R25GM086262-09), the Systems and Integrative Biology (T32-GM008322) training grant and the Cardiovascular Research and Entrepreneurship training grant (T32-HL125242) and the University of Michigan Rackham Merit Fellowship. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

NADPH oxidase 4 contributes to oxidative stress in a mouse model of myocardial infarction

Oxidative stress closely related to the progression and severity of myocardial infarction (MI). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) is one of the major enzymes that generate reactive oxygen species (ROS) in cardiovascular system. Here, we aim to elucidate the pathological role of NOX4 in MI. MI mouse model was created by the coronary artery ligation. NOX4 was specifically knocked down in heart through intramyocardial injection of siRNA. NOX4 expression and oxidative stress indicators were determined at different time points using qRT-PCR, Western blot, and ELISA, and then analyzed by Pearson’s correlation. Cardiac function was evaluated by using echocardiographic technique. NOX4 was upregulated in myocardial tissues of MI mice, which positively correlated with the elevation of oxidative stress indicators. Knockdown of NOX4 in heart significantly reduced the production of ROS and the level of oxidative stress in left ventricle tissues, which was accompanied by significant improvement of cardiac function in MI mice. Selective knockdown of NOX4 in heart attenuates MI-induced oxidative stress and improves cardiac function, suggesting inhibition of NOX4/ROS axis in heart using siRNA is a potential therapeutic treatment for MI-induced cardiac dysfunction.

Finerenone attenuates myocardial apoptosis, metabolic disturbance and myocardial fibrosis in type 2 diabetes mellitus

BackgroundFinerenone is a third-generation mineralocorticoid receptor antagonists, which has shown good cardiac function improvement in patients with type 2 diabetes in large-scale clinical trials. However, its specific role in diabetic cardiomyopathy remains unclear. We explored the potential functions and mechanisms of finerenone in diabetic cardiomyopathy.MethodsThe type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin (n = 6, each group). Next the drug group was treated with finerenone (1 mg/kg/day) for 8 weeks. Then we detected the cardiac structure and function and relevant indicators. Neonatal rat cardiomyocytes were used for in vitro culture to determine the direct effect of finerenone on cardiomyocytes stimulated by high glucose and high fatty acid.ResultsCompared with the control group, rats in the type 2 diabetes group exhibited hyperglycemia, hyperlipidemia, and impaired cardiac function. Myocardium showed increased fibrosis and apoptosis. Finerenone attenuated these impairments without changing blood glucose levels. In neonatal rat cardiomyocytes, the stimulation of high concentrations of palmitic acid increased fatty acid uptake, as well as increased reactive oxygen species and apoptosis. Finerenone significantly improved fatty acid metabolism, reduced cellular inflammation levels, and decreased apoptosis.ConclusionsBy blocking the mineralocorticoid receptor, finerenone attenuates cardiac steatosis, myocardial fibrosis and apoptosis, and subsequent myocardial remodeling and diastolic dysfunction in type II diabetic rats.

Immunomodulatory amnion-derived mesenchymal stromal cells preserve muscle function in a mouse model of Duchenne muscular dystrophy

BackgroundDuchenne muscular dystrophy (DMD) is an incurable genetic disease characterized by degeneration and necrosis of myofibers, chronic inflammation, and progressive muscle weakness resulting in premature mortality. Immunosuppressive multipotent mesenchymal stromal cell (MSC) therapy could be an option for DMD patients. We focused on amnion-derived mesenchymal stromal cells (AMSCs), a clinically viable cell source owing to their unique characteristics, such as non-invasive isolation, mitotic stability, ethical acceptability, and minimal risk of immune reaction and cancer. We aimed to identify novel immunomodulatory effects of AMSCs on macrophage polarization and their transplantation strategies for the functional recovery of skeletal and cardiac muscles.MethodsWe used flow cytometry to analyze the expression of anti-inflammatory M2 macrophage markers on peripheral blood mononuclear cells (PBMCs) co-cultured with human AMSCs (hAMSCs). hAMSCs were intravenously injected into DMD model mice (mdx mice) to assess the safety and efficacy of therapeutic interventions. hAMSC-treated and untreated mdx mice were monitored using blood tests, histological examinations, spontaneous wheel-running activities, grip strength, and echocardiography.ResultshAMSCs induced M2 macrophage polarization in PBMCs via prostaglandin E2 production. After repeated systemic hAMSC injections, mdx mice exhibited a transient downregulation of serum creatin kinase. Limited mononuclear cell infiltration and a decreased number of centrally nucleated fibers were indicative of regenerated myofibers following degeneration, suggesting an improved histological appearance of the skeletal muscle of hAMSC-treated mdx mice. Upregulated M2 macrophages and altered cytokine/chemokine expressions were observed in the muscles of hAMSC-treated mdx mice. During long-term experiments, a significant decrease in the grip strength in control mdx mice significantly improved in the hAMSC-treated mdx mice. hAMSC-treated mdx mice maintained running activity and enhanced daily running distance. Notably, the treated mice could run longer distances per minute, indicating high running endurance. Left ventricular function in DMD mice improved in hAMSC-treated mdx mice.ConclusionsEarly systemic hAMSC administration in mdx mice ameliorated progressive phenotypes, including pathological inflammation and motor dysfunction, resulting in the long-term improvement of skeletal and cardiac muscle function. The therapeutic effects might be associated with the immunosuppressive properties of hAMSCs via M2 macrophage polarization. This treatment strategy could provide therapeutic benefits to DMD patients.

Predictive value of the proportion of hibernating myocardium in total perfusion defect on reverse remodeling in patients with HFrEF underwent coronary artery bypass graft

Objective: To evaluate the predictive value of the proportion of hibernating myocardium (HM) in total perfusion defect (TPD) on reverse left ventricle remodeling (RR) after coronary artery bypass graft (CABG) in patients with heart failure with reduced ejection fraction (HFrEF) by 99mTc-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) combined with 18F-flurodeoxyglucose (FDG) gated myocardial imaging positron emission computed tomography (PET). Methods: Inpatients diagnosed with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2016 to January 2022 were prospectively recruited. MPI combined with 18F-FDG gated PET was performed before surgery for viability assessment and the patients received follow-up MPI and 18F-FDG gated PET at different stages (3-12 months) after surgery. Δ indicated changes (post-pre). Left ventricular end-systolic volume (ESV) reduced at least 10% was defined as RR, patients were divided into reverse remodeling (RR+) group and the non-reverse group (RR-). Binary logistic regression analysis was used to identify predictors of RR. Receiver operating characteristic (ROC) curve analysis was performed and the area under the curve (AUC) was calculated to assess the cut-off value for predicting RR. Additionally, we retrospectively enrolled inpatients with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2021 to January 2022 as the validation group, who underwent MPI and 18F-FDG gated PET before surgery. Echocardiography was performed before CABG and after CABG (3-12 months). In the validation group, the reliability of obtaining the cut-off value for the ROC curve was verified. Results: A total of 28 patients with HFrEF (26 males; age (56.9±8.7) years) were included in the prospective cohort. HM/TPD was significantly higher in the RR+ group than in the RR- group ((51.8%±17.9%) vs. (35.7%±13.9%), P=0.016). Binary logistic regression analysis revealed that HM/TPD was an independent predictor of RR (Odds ratio=1.073, 95% Confidence interval: 1.005-1.145, P=0.035). ROC curve analysis revealed that HM/TPD=38.3% yielded the highest sensitivity, specificity, and accuracy (all 75%) for predicting RR and the AUC was 0.786 (P=0.011). Meanwhile, a total of 100 patients with HFrEF (90 males; age (59.7±9.6) years) were included in the validation group. In the validation group, HM/TPD=38.3% predicted RR in HFrEF patients after CABG with the highest sensitivity, specificity and accuracy (82%, 60% and 73% respectively). Compared with the HFrEF patients in the HM/TPD<38.3% group (n=36), RR and cardiac function improved more significantly in the HM/TPD≥38.3% group (n=64) (all P<0.05). Conclusions: Preoperative HM/TPD ratio is an independent factor for predicting RR in patients with HFrEF after CABG, and HM/TPD≥38.3% can accurately predict RR and the improvement of cardiac function after CABG.

Effects of dapagliflozin on cardiac function indexes and serum MCP-1 levels in patients with Type 2 diabetes mellitus complicated with heart failure

ABSTRACT Type 2 diabetes mellitus (T2DM) and heart failure (HF) are common in clinic, and they often coexist, triggering poor prognosis of patients and increasing hospitalization rates and mortality. Due to some common pathophysiological mechanisms between T2DM and HF, the two have synergistic effects and require collaborative management . In terms of the treatment of T2DM combined with HF, the effects of drugs on both diseases need to be considered to prevent the impact of HF drugs on glycometabolism. As an SGLT2 inhibitor, dapagliflozin can excrete glucose through the kidneys, reduce blood volume, decrease cardiac load to some extent, improve HF symptoms, and better control blood glucose . Therefore, this study selected 60 HF patients complicated with T2DM as the research subjects, and divided them into control group (CLG, conventional medical treatment) and observation group (ONG, dapagliflozin treatment) to explore the effects of dapagliflozin through comparative analysis. According to the results, compared with CLG, ONG had better improvement of blood glucose, cardiac function, and serum levels (P < 0.05), and a lower rehospitalization rate (P < 0.05), with no obvious between-group differences in the incidence of hypotension and emaciation (P > 0.05). These results showed that dapagliflozin in the treatment of T2DM with HF can improve blood glucose levels, cardiac function indexes and inflammatory factor levels, and decrease rehospitalization rates, presenting good clinical efficacy.

Physiological ischemic training improves cardiac function through the attenuation of cardiomyocyte apoptosis and the activation of the vagus nerve in chronic heart failure.

This study investigated the functional outcomes of patients with chronic heart failure (CHF) after physiological ischemic training (PIT), identified the optimal PIT protocol, evaluated its cardioprotective effects and explored the underlying neural mechanisms. Patients with CHF were randomly divided into experimental group (n = 25, PIT intervention + regular treatment) and control group (n = 25, regular treatment). The outcomes included the left ventricular ejection fraction (LVEF), brain natriuretic peptide (BNP) and cardiopulmonary parameters. LVEF and cardiac biomarkers in CHF rats after various PIT treatments (different in intensity, frequency, and course of treatment) were measured to identify the optimal PIT protocol. The effect of PIT on cardiomyocyte programmed cell death was investigated by western blot, flow cytometry and fluorescent staining. The neural mechanism involved in PIT-induced cardioprotective effect was assessed by stimulation of the vagus nerve and muscarinic M2 receptor in CHF rats. LVEF and VO2max increased while BNP decreased in patients subjected to PIT. The optimal PIT protocol in CHF rats was composed of five cycles of 5 min ischemia followed by 5 min reperfusion on remote limbs for 8 weeks. LVEF and cardiac biomarker levels were significantly improved, and cardiomyocyte apoptosis was inhibited. However, these cardioprotective effects disappeared after subjecting CHF rats to vagotomy or muscarinic M2 receptor inhibition. PIT improved functional outcomes in CHF patients. The optimal PIT protocol required appropriate intensity, reasonable frequency, and adequate treatment course. Under these conditions, improvement of cardiac function in CHF was confirmed through cardiomyocyte apoptosis reduction and vagus nerve activation.

Hypothermia as an Adjunctive Therapy in Cardiogenic Shock: A Systematic Review and Meta-Analysis.

In the setting of out-of-hospital cardiac arrest, therapeutic hypothermia (TH) has been shown to improve clinical outcomes. However, trials showing the advantage of TH did not include patients with cardiogenic shock (CS). We performed a comprehensive literature search for studies that evaluated the efficacy and safety of adjunctive TH compared with the standard of care (SOC) in patients with CS. The primary outcome was the mortality rate (in-hospital, short-, and mid-term). The secondary outcomes were the TH-related complications, duration of Intensive Care Unit (ICU) stay, duration of mechanical ventilation (MV-days), and improvement in cardiac function. Relative risk (RR) or the standardized mean difference (SMD) and corresponding 95% confidence intervals (CIs) were calculated using the random-effects model. A total of 7 clinical studies (3 RCTs included), and 712 patients (341 in the TH group and 371 in the SOC group) were included. As compared with the SOC, TH was not associated with a statistically significant improvement in the in-hospital (RR: 0.73%, 95% CI: 0.51-1.03; p = 0.08), short-term (RR: 0.90%, 95% CI: 0.75-1.06; p = 0.21), or mid-term (RR: 0.93%, 95% CI: 0.78-1.10; p = 0.38) mortality rates. Despite the improvement in the cardiac function in the TH group (SMD: 1.08, 95% CI: 0.02-2.1; p = 0.04), the TH strategy did not significantly shorten the MV days, or the ICU stay (p-values >0.05). Finally, there was a trend toward higher risks for infection, major bleeding, and the need for blood transfusion in the TH group. According to our meta-analysis of published clinical studies, TH is not beneficial in patients with CS and has a marginal safety profile. Larger-scale RCTs are needed to further clarify our results.

Relationship between coronary blood flow and improvement of cardiac function after catheter ablation for persistent atrial fibrillation.

The relationship between coronary blood flow during atrial fibrillation (AF) and improvement of cardiac function after catheter ablation (CA) for persistent AF (PeAF) is not prominent; this study was conducted to evaluate this relationship. This was a retrospective case-control study. Eighty-five patients with PeAF (resting heart rate < 100bpm) and heart failure with reduced ejection fraction (left ventricular ejection fraction (LVEF) < 40%) who had undergone coronary angiography within 1week before CA were included. All patients could maintain a sinus rhythm for > 6months after CA. The primary outcome was improvement of cardiac function with an LVEF cutoff value of > 50% during sinus rhythm 6months after CA. In the LVEF improvement group (N = 57), patients were younger, with a higher baseline diastolic blood pressure and lower baseline brain natriuretic peptide level than the no LVEF improvement group (N = 28). Heart rate at baseline and 6months after CA and AF duration did not differ between the two groups. Thrombolysis in myocardial infarction frame count parameters was significantly higher in the LVEF improvement (P < 0.001) than in the no LVEF improvement group. Multivariate logistic regression analysis revealed mean thrombolysis in myocardial infarction frame count as an independent factor for LVEF improvement (odds ratio, 1.72 (95% confidence interval 1.17-2.54); P = 0.006). Coronary blood flow in patients with PeAF is strongly associated with improved left ventricular systolic function after the restoration of sinus rhythm by CA for PeAF and heart failure with reduced ejection fraction.

Sacubitril/Valsartan Improves Left Atrial and Ventricular Strain and Strain Rate in Patients with Heart Failure with Reduced Ejection Fraction.

Data on the impact of sacubitril/valsartan (SV) therapy on phasic left atrial (LA) and left ventricular (LV) strain in heart failure with reduced ejection fraction (HFrEF) are limited. The aim of this study was to evaluate changes in two-dimensional speckle tracking (2D-STE) parameters with SV therapy in HFrEF patients. Prospective evaluation of HFrEF patients receiving optimized medical therapy. Two-dimensional speckle tracking (2D-STE) parameters were assessed at baseline and after 6 months of SV therapy. LA strain and strain rate (SR) in reservoir, conduit, and contraction phases were compared with LV longitudinal, radial, and circumferential strain and SR and stratified according to heart rhythm and HFrEF etiology. A total of 35 patients completed the 6-month follow-up, with a mean age of 59 ± 11 years, 40% in atrial fibrillation, 43% with ischemic etiology, and LVEF of 29 ± 6%. There were significant improvements in LA reservoir, conduit, and contractile strain and SR following SV therapy, particularly among patients in sinus rhythm. There were significant improvements in longitudinal, radial, and circumferential LV function indices. SV therapy in HFrEF was associated with improved longitudinal, radial, and circumferential function, particularly among patients in sinus rhythm. These findings can provide insights into the mechanisms underlying the improvement of cardiac function and help assess subclinical responses to the treatment.

Dose titration of sacubitril/valsartan for heart failure with reduced ejection fraction: a real-world study.

The study aims to explore the real-world titration patterns of sacubitril/valsartan in a chronic heart failure (HF) follow-up management system and the effect on the recovery of ventricular remodelling and cardiac function in China. This is a single-centre, observational study of 153 adult outpatients with HF and reduced ejection fraction who were managed in the chronic HF follow-up management system and prescribed with sacubitril/valsartan from August 2017 to August 2021 in China. All patients tried to titrated sacubitril/valsartan to the tolerant dose during follow-up. The primary outcome was the proportion of patients who reached and maintained the target dose of sacubitril/valsartan. The main secondary outcomes were the changes in left atrium diameter, left ventricular end-diastolic diameter (LVEDD), and left ventricular ejection fraction (LVEF) from baseline to 12months. Among the patients, 69.3% were male, with a median age of 49years. The baseline systolic blood pressure (SBP) was 117.6±18.3mmHg before starting the treatment of sacubitril/valsartan. Benefiting from the management system, 117 (76.5%) patients achieved the target dose of sacubitril/valsartan, and the median time to reach the target dose was 3 (IQR 1-5) months. Advanced age and lower SBP may be predictors of failure to reach the target dose. Compared with baseline, standard treatment resulted in a pronounced improvement in left ventricular geometry and cardiac function. The patients showed a significant increase in LVEF [28 (IQR 21-34) % vs. 42 (IQR 37.0-54.3) %, P<0.001], with a great reduction in left atrium diameter [45 (IQR 40.3-51.0) mm vs. 41 (IQR 37.0-45.3) mm, P<0.001] and LVEDD [65 (IQR 60.0-70.3) mm vs. 55 (IQR 52-62) mm, P<0.001] during 12month follow-up. Of patients, 36.5% had a LVEF ≥50%, 54.1% had LVEF >40%, and 81.1% experienced an increase in LVEF of ≥10%. After 12month follow-up, the proportion of patients with New York Heart Association classification I or II increased from 41.8% to 96.4%. Additionally, there was a significant improvement in N-terminal pro-B-type natriuretic peptide (P<0.001). At Month 12, 50% of patients achieved the target dose of beta-blockers. No serious adverse events caused by sacubitril/valsartan were observed during the follow-up. Optimising HF follow-up management was essential and effective in a real-world clinical setting; the majority could reach the target dose of sacubitril/valsartan within the management system and achieve a remarkable improvement in cardiac function and ventricular remodelling.

Obstructive Sleep Apnea and Right Ventricular Remodeling: Do We Have All the Answers?

Obstructive sleep apnea (OSA) syndrome is a very important sleep-related breathing disorder related to increased cardiovascular and overall morbidity and mortality. It is associated with multisystemic target organ damage due to micro- and macrovascular changes, resulting in carotid and coronary atherosclerosis, increased arterial stiffness, retinal damage, microalbuminuria, and cardiac remodeling. The latter consists of left ventricular (LV) hypertrophy, as well as diastolic and systolic dysfunction. The increasing burden of evidence shows that OSA also induces right ventricular (RV) remodeling that is more difficult to diagnose, but may also contribute to cardiovascular morbidity and mortality in these patients. Conventional echocardiographic parameters for assessment of RV systolic and diastolic functions are often not sensitive enough to detect subclinical and subtle changes in the RV function. Data published over last decade showed that the RV function, particularly systolic, is impaired in OSA patients and related with its severity. However, the introduction of speckle tracking echocardiography and the particularly longitudinal strain enabled the earlier detection of functional and mechanical changes even when conventional echocardiographic parameters of RV systolic function remained unchanged. The 3D echocardiography provided the possibility to evaluate the entire RV, with its unique shape, and determine 3D RV ejection fraction, which is comparable with results obtained by cardiac magnetic resonance. The use of this modality also provided a new insight into RV systolic (dys)function in OSA patients. In addition to weight loss, which has been proven very helpful in OSA patients, the only approved therapeutic approach is continuous positive airway pressure (CPAP) therapy. It is very important to assess if this therapy induces any improvement in cardiac structure and function. Limited data on this topic show that RV longitudinal strain is a more sensitive parameter rather than other conventional RV indexes in the detection of improvement in RV systolic function and mechanics. The aim of this review article is to summarize the current understanding of RV structural, functional, and mechanical changes in patients with OSA. Furthermore, we sought to provide the current knowledge regarding the effect of CPAP therapy on RV reverse remodeling in OSA patients.

Left-atrial volume reduction reflects improvement of cardiac sympathetic nervous function in patients with severe aortic stenosis after transcatheter aortic valve replacement.

Trans-catheter aortic valve replacement (TAVR) is an excellent alternative intervention for surgical aortic valve replacement. Cardiac sympathetic nervous (CSN) function and left atrial (LA) volume are both important prognostic factors in patients with aortic stenosis (AS) after TAVR. The relationship between the two clinical factors is unknown, however. This retrospective observational study aimed to assess the correlation between CSN function and LA volume in 48 symptomatic patients with severe AS (median age: 85years, IQR 82-88years; 81% female) before and after TAVR. CSN function was assessed by performing 123I-metaiodobenzylguanidine (MIBG) scintigraphy before and 6months after TAVR, and the delayed heart-to-mediastinum ratio (dHMR) and washout rate (WR) were calculated. We also performed transthoracic echocardiography near the same time. TAVR improved the dHMR, WR, and LA volume index (LAVI) (dHMR: median 2.89 [IQR 2.62-3.23] vs. 2.98 [2.49-3.25], p = 0.0182; WR: 28% [24-38] vs. 23% [16-32], p < 0.0001; LAVI: 47.7mL/m2 [37.8-56.3] vs. 41.2mL/m2 [33.7-56.1], p = 0.0024). In multiple linear regression analysis, the percentage change in LAVI from baseline to post-TAVR (∆LAVI%) was an independent predictor of change in dHMR from baseline to post-TAVR (β = - 0.35, p = 0.0110). In conclusion, LA volume reduction reflected CSN functional improvement after TAVR. In patients with TAVR, ∆LAVI% might be a valuable parameter for evaluating CSN functional recovery.

The association of serum uric acid/albumin ratio with the development of coronary collateral circulation in patients with chronic total occluded coronary arteries.

Introduction: Coronary collateral circulation (CCC) develops in chronic total occluded (CTO) vessels and protects the myocardium against ischemia in addition to the improvement of cardiac functions. Poor CCC is related to adverse cardiac events as well as poor prognosis. Serum uric acid/albumin ratio (UAR) has emerged as a novel marker associated with poor cardiovascular outcomes. We aimed to investigate whether there was an association between UAR and poor CCC in CTO patients. Methods: This study was comprised of 212 patients with CTO (92 with poor CCC and 120 with good CCC). All patients were graded based on Rentrop scores to poor CCC (Rentrop scores 0 and 1) and good CCC (Rentrop scores 2 and 3). Results: Poor CCC patients had higher frequencies of diabetes mellitus, triglyceride levels, Syntax and Gensini scores, uric acid, and UAR and lower lymphocyte, high-density lipoprotein cholesterol, and ejection fraction when compared to good CCC patients. UAR was an independent predictor of poor CCC in CTO patients. Furthermore, UAR had a better discriminative ability for patients with poor CCC from good CCC compared to serum uric acid and albumin. Conclusion: Based on the results of the study, the UAR could be used to detect poor CCC in CTO patients.

Unlocking the Pragmatic Potential of Regenerative Therapies in Heart Failure with Next-Generation Treatments.

Patients with chronic heart failure (HF) have a poor prognosis due to irreversible impairment of left ventricular function, with 5-year survival rates <60%. Despite advances in conventional medicines for HF, prognosis remains poor, and there is a need to improve treatment further. Cell-based therapies to restore the myocardium offer a pragmatic approach that provides hope for the treatment of HF. Although first-generation cell-based therapies using multipotent cells (bone marrow-derived mononuclear cells, mesenchymal stem cells, adipose-derived regenerative cells, and c-kit-positive cardiac cells) demonstrated safety in preclinical models of HF, poor engraftment rates, and a limited ability to form mature cardiomyocytes (CMs) and to couple electrically with existing CMs, meant that improvements in cardiac function in double-blind clinical trials were limited and largely attributable to paracrine effects. The next generation of stem cell therapies uses CMs derived from human embryonic stem cells or, increasingly, from human-induced pluripotent stem cells (hiPSCs). These cell therapies have shown the ability to engraft more successfully and improve electromechanical function of the heart in preclinical studies, including in non-human primates. Advances in cell culture and delivery techniques promise to further improve the engraftment and integration of hiPSC-derived CMs (hiPSC-CMs), while the use of metabolic selection to eliminate undifferentiated cells will help minimize the risk of teratomas. Clinical trials of allogeneic hiPSC-CMs in HF are now ongoing, providing hope for vast numbers of patients with few other options available.