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  1. Pharmacological treatments for heart failure with preserved ejection fraction-a systematic review and indirect comparison
    Bonsu KO, Arunmanakul P, Chaiyakunapruk N
    Heart Fail Rev, 2018 03;23(2):147-156.
    PMID: 29411216 DOI: 10.1007/s10741-018-9679-y
    Pharmacological interventions for heart failure with preserved ejection fraction (HFpEF) have failed to reduce mortality and hospitalization. Evidence for mineralocorticoid antagonists (MRAs), β-adrenoceptor blockers (β-blockers), and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs)-to reduce clinical outcomes in HFpEF remains unclear. We conducted a systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov for randomized controlled trials (RCTs) assessing pharmacological treatments in HFpEF diagnosed according the recommendations of the European Society of Cardiology (ESC) 2016 guidelines from inception to August, 2017. The study outcomes were mortality, hospitalization, changes in indexes of cardiac structure and function, biomarkers, and indexes of functional capacity-quality of life (QoL) assessment and 6-min walk distance test (6-MWD). The random-effects models were used to estimate pooled relative risks (RRs) for the binary outcomes and standardized mean differences for continuous outcomes, with 95% CI. A network meta-analysis using a random-effects model was employed to estimate the comparative efficacy of treatments. We included data from 15 RCTs comprising 5930 patients. There was no significant effect seen with all treatments compared with placebo and comparative efficacy of any two treatments on all outcomes assessed. However, mineralocorticoid antagonist spironolactone demonstrated a trend towards reducing mortality compared with placebo (RR 0.92; 95% CI 0.79-1.08), sildenafil (0.14; 0.01-2.78), perindopril (0.87; 0.59-1.28), and eplerenone (0.91; 0.25-3.33). Similar trends in treatment effect were observed with spironolactone on surrogate outcomes while eplerenone demonstrated a trend of superior effect in reduction of hospitalizations compared with all other drug treatment. No drug treatment demonstrated statistically significant improvement in clinical and surrogate outcomes in HFpEF diagnosed according to the ESC 2016 guideline. Spironolactone and eplerenone showed clinically relevant reduction in mortality and hospitalization respectively compared with other drug treatments. Further trials with MRAs are warranted to confirm treatment effects in HFpEF.
    Matched MeSH terms: Stroke Volume/drug effects*
  2. Fulltext SKA-31, an activator of Ca2+-activated K+ channels, improves cardiovascular function in aging
    John CM, Khaddaj Mallat R, Mishra RC, George G, Singh V, Turnbull JD, et al.
    Pharmacol Res, 2020 01;151:104539.
    PMID: 31707036 DOI: 10.1016/j.phrs.2019.104539
    Aging represents an independent risk factor for the development of cardiovascular disease, and is associated with complex structural and functional alterations in the vasculature, such as endothelial dysfunction. Small- and intermediate-conductance, Ca2+-activated K+ channels (KCa2.3 and KCa3.1, respectively) are prominently expressed in the vascular endothelium, and pharmacological activators of these channels induce robust vasodilation upon acute exposure in isolated arteries and intact animals. However, the effects of prolonged in vivo administration of such compounds are unknown. In our study, we hypothesized that such treatment would ameliorate aging-related cardiovascular deficits. Aged (∼18 months) male Sprague Dawley rats were treated daily with either vehicle or the KCa channel activator SKA-31 (10 mg/kg, intraperitoneal injection; n = 6/group) for 8 weeks, followed by echocardiography, arterial pressure myography, immune cell and plasma cytokine characterization, and tissue histology. Our results show that SKA-31 administration improved endothelium-dependent vasodilation, reduced agonist-induced vascular contractility, and prevented the aging-associated declines in cardiac ejection fraction, stroke volume and fractional shortening, and further improved the expression of endothelial KCa channels and associated cell signalling components to levels similar to those observed in young male rats (∼5 months at end of study). SKA-31 administration did not promote pro-inflammatory changes in either T cell populations or plasma cytokines/chemokines, and we observed no overt tissue histopathology in heart, kidney, aorta, brain, liver and spleen. SKA-31 treatment in young rats had little to no effect on vascular reactivity, select protein expression, tissue histology, plasma cytokines/chemokines or immune cell properties. Collectively, these data demonstrate that administration of the KCa channel activator SKA-31 improved aging-related cardiovascular function, without adversely affecting the immune system or promoting tissue toxicity.
    Matched MeSH terms: Stroke Volume/drug effects
  3. CMR imaging biosignature of cardiac involvement due to cancer-related treatment by T1 and T2 mapping
    Haslbauer JD, Lindner S, Valbuena-Lopez S, Zainal H, Zhou H, D'Angelo T, et al.
    Int J Cardiol, 2019 Jan 15;275:179-186.
    PMID: 30360992 DOI: 10.1016/j.ijcard.2018.10.023
    BACKGROUND: Cancer-related treatment is associated with development of heart failure and poor outcome in cancer-survivors. T1 and T2 mapping by cardiovascular magnetic resonance (CMR) may detect myocardial injury due to cancer-related treatment.

    METHODS: Patients receiving cancer-related treatment regimes underwent screening of cardiac involvement with CMR, either within 3 months (early Tx) or >12 months (late Tx) post-treatment. T1 and T2 mapping, cardiac function, strain, ischaemia-testing, scar-imaging and serological cardiac biomarkers were obtained.

    RESULTS: Compared to age/gender matched controls (n = 57), patients (n = 115, age (yrs): median(IQR) 48(28-60), females, n = 60(52%) had reduced left ventricular ejection fraction (LV-EF) and strain, and higher native T1 and T2. The early Tx group (n = 52) had significantly higher native T1, T2 and troponin levels compared to the late Tx group, indicating myocardial inflammation and oedema (p 

    Matched MeSH terms: Stroke Volume/drug effects*
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