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  1. Solomon SD, Ostrominski JW, Vaduganathan M, Claggett B, Jhund PS, Desai AS, et al.
    Eur J Heart Fail, 2024 Jun;26(6):1334-1346.
    PMID: 38733212 DOI: 10.1002/ejhf.3266
    AIMS: To describe the baseline characteristics of participants in the FINEARTS-HF trial, contextualized with prior trials including patients with heart failure (HF) with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF). The FINEARTS-HF trial is comparing the effects of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo in reducing cardiovascular death and total worsening HF events in patients with HFmrEF/HFpEF.

    METHODS AND RESULTS: Patients with symptomatic HF, left ventricular ejection fraction (LVEF) ≥40%, estimated glomerular filtration rate ≥ 25 ml/min/1.73 m2, elevated natriuretic peptide levels and evidence of structural heart disease were enrolled and randomized to finerenone titrated to a maximum of 40 mg once daily or matching placebo. We validly randomized 6001 patients to finerenone or placebo (mean age 72 ± 10 years, 46% women). The majority were New York Heart Association functional class II (69%). The baseline mean LVEF was 53 ± 8% (range 34-84%); 36% of participants had a LVEF <50% and 64% had a LVEF ≥50%. The median N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 1041 (interquartile range 449-1946) pg/ml. A total of 1219 (20%) patients were enrolled during or within 7 days of a worsening HF event, and 3247 (54%) patients were enrolled within 3 months of a worsening HF event. Compared with prior large-scale HFmrEF/HFpEF trials, FINEARTS-HF participants were more likely to have recent (within 6 months) HF hospitalization and greater symptoms and functional limitations. Further, concomitant medications included a larger percentage of sodium-glucose cotransporter 2 inhibitors and angiotensin receptor-neprilysin inhibitors than previous trials.

    CONCLUSIONS: FINEARTS-HF has enrolled a broad range of high-risk patients with HFmrEF and HFpEF. The trial will determine the safety and efficacy of finerenone in this population.

    Matched MeSH terms: Ventricular Function, Left/drug effects
  2. Kim JD, Son I, Kwon WK, Sung TY, Sidik H, Kim K, et al.
    J Korean Med Sci, 2018 01 22;33(4):e28.
    PMID: 29318795 DOI: 10.3346/jkms.2018.33.e28
    BACKGROUND: Isoflurane, a common anesthetic for cardiac surgery, reduced myocardial contractility in many experimental studies, few studies have determined isoflurane's direct impact on the left ventricular (LV) contractile function during cardiac surgery. We determined whether isoflurane dose-dependently reduces the peak systolic velocity of the lateral mitral annulus in tissue Doppler imaging (S') in patients undergoing cardiac surgery.

    METHODS: During isoflurane-supplemented remifentanil-based anesthesia for patients undergoing cardiac surgery with preoperative LV ejection fraction greater than 50% (n = 20), we analyzed the changes of S' at each isoflurane dose increment (1.0, 1.5, and 2.0 minimum alveolar concentration [MAC]: T1, T2, and T3, respectively) with a fixed remifentanil dosage (1.0 μg/min/kg) by using transesophageal echocardiography.

    RESULTS: Mean S' values (95% confidence interval [CI]) at T1, T2, and T3 were 10.5 (8.8-12.2), 9.5 (8.3-10.8), and 8.4 (7.3-9.5) cm/s, respectively (P < 0.001 in multivariate analysis of variance test). Their mean differences at T1 vs. T2, T2 vs. T3, and T1 vs. T3 were -1.0 (-1.6, -0.3), -1.1 (-1.7, -0.6), and -2.1 (-3.1, -1.1) cm/s, respectively. Phenylephrine infusion rates were significantly increased (0.26, 0.22, and 0.47 μg/kg/min at T1, T2, and T3, respectively, P < 0.001).

    CONCLUSION: Isoflurane increments (1.0-2.0 MAC) dose-dependently reduced LV systolic long-axis performance during cardiac surgeries with a preserved preoperative systolic function.

    Matched MeSH terms: Ventricular Function, Left/drug effects
  3. Cao Y, Lu Z, Wang D, Tan KS, Liu W, Wu Q, et al.
    Eur J Pharmacol, 2021 Nov 15;911:174539.
    PMID: 34599913 DOI: 10.1016/j.ejphar.2021.174539
    Ischemia heart disease, one of the lethal cardiovascular diseases, irreversibly impairs cardiac function and is recognized as the primary risk factor for mortality in industrialized countries. The myocardial ischemia treatment still faces a considerable degree of increasing unmet needs. Isosteviol sodium (STVNa) and its derivatives have been proven to effectively alleviate metabolic diseases, hypertension, and heart hypertrophy. Little is known about how STVNa confers the cardioprotective effect during acute myocardial ischemia (AMI). In the present study, a rat model of acute ST-segment-elevation myocardial ischemia by left anterior descending (LAD) ligation was established. Compared to the AMI model group, STVNa administration (4 mg/kg, twice a day) well preserved left ventricle function by ejection fraction (45.10 ± 10.39 vs. 73.64 ± 13.15, p = 0.0013) and fractional shortening (22.94 ± 6.28 vs. 44.00 ± 11.05, p = 0.0017). Further analysis shows that high-dose STVNa (4 mg/kg) significantly improved the hemodynamics in AMI rats, with LVSP (88.25 ± 12.78 vs 99.75 ± 5.10, p = 0.018), max dP/dt (2978.45 ± 832.46 vs 4048.56 ± 827.23, p = 0.096), LVEDP (19.88 ± 2.00 vs 22.26 ± 3.21, p = 0.04) and left ventricular relaxation time constant (Tau) (0.030 ± 0.006 vs 0.021 ± 0.004, p = 0.021). Mechanically, STVNa administration retained the myocardial levels of phosphorylated AMPK, and CPT1b. Moreover, STVNa significantly increased the total energy expenditure, and reduced fatty acid accumulation through mitochondrial oxidative phosphorylation, which was supported by the indirect calorimetry and cellular energy analysis. Taken together, these findings suggest that STVNa is a potential cardioprotection agent for ischemic cardiomyopathy, likely through improving energy homeostasis, left ventricular hemodynamics, and heart function.
    Matched MeSH terms: Ventricular Function, Left/drug effects
  4. Bonsu KO, Reidpath DD, Kadirvelu A
    Cardiovasc Ther, 2015 Dec;33(6):338-46.
    PMID: 26280110 DOI: 10.1111/1755-5922.12150
    Statins are known to prevent heart failure (HF). However, it is unclear whether statins as class or type (lipophilic or hydrophilic) improve outcomes of established HF.
    Matched MeSH terms: Ventricular Function, Left/drug effects
  5. Ramalingam A, Mohd Fauzi N, Budin SB, Zainalabidin S
    Basic Clin Pharmacol Toxicol, 2021 Feb;128(2):322-333.
    PMID: 32991780 DOI: 10.1111/bcpt.13500
    This study investigated the impact of prolonged nicotine administration on myocardial susceptibility to ischaemia-reperfusion (I/R) injury in a rat model and determined whether nicotine affects mitochondrial reactive oxygen species (ROS) production and permeability transition in rat hearts. Sprague-Dawley rats were administered 0.6 or 1.2 mg/kg nicotine for 28 days, and their hearts were isolated at end-point for assessment of myocardial susceptibility to I/R injury ex vivo. Rat heart mitochondria were also isolated from a subset of rats for analysis of mitochondrial ROS production and permeability transition. Compared to the vehicle controls, rat hearts isolated from nicotine-administered rats exhibited poorer left ventricular function that worsened over the course of I/R. Coronary flow rate was also severely impaired in the nicotine groups at baseline and this worsened after I/R. Nicotine administration significantly increased mitochondrial ROS production and permeability transition relative to the vehicle controls. Interestingly, pre-incubation of isolated mitochondria with ROS scavengers (superoxide dismutase and mitoTEMPO) significantly abolished nicotine-induced increase in mitochondria permeability transition in isolated rat heart mitochondria. Overall, our data showed that prolonged nicotine administration enhances myocardial susceptibility to I/R injury in rats and this is associated with mitochondrial ROS-driven increase in mitochondrial permeability transition.
    Matched MeSH terms: Ventricular Function, Left/drug effects
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