News from the field of cardiology and cardiovascular drug discovery.
Cardiology Spotlight | Bentham Science
Cardiology research is progressing rapidly, with discoveries of new therapeutic drugs, metabolic processes, and the use of AI in diagnosis, to mention just a few. Here we take a look at some recent developments in the field published in Bentham journals.
Fatty acid oxidation can help hearts regrow
Researchers from the Max Planck Institute for Heart and Lung Research and Heidelberg University studied the effect of fatty acid metabolism on cardiomyocytes. Their study illuminates the potential of metabolic reprogramming and its interplay with fatty acid oxidation.
During the postnatal maturation of cardiomyocytes, there is a metabolic shift from glycolysis to fatty acid oxidation. This brings alterations in mitochondrial homeostasis, cellular structure, and electrophysiological attributes. This metabolic transformation significantly reduces cell division, which slows heart regeneration in adults.
Researchers perturbed fatty acid oxidation through inactivation of the Cpt1b gene. This brought many promising outcomes. Notably, cardiomyocytes exhibited heightened resistance to hypoxia and a pronounced surge in proliferation post ischemia‒reperfusion injury. Intriguingly, metabolic analysis revealed a substantial accumulation of α-ketoglutarate (αKG), a pivotal intermediate in the Krebs cycle, in the mutant cardiomyocytes. This excess αKG activated the enzyme KDM5, a lysine demethylase, instigating the demethylation of H3K4me3 histones in genes crucial for cardiomyocyte maturation. This orchestrated alteration steered the cardiomyocytes toward a less mature state, promoting proliferation and potentially aiding in cardiac regeneration.
This study underscores the intricate interplay between metabolism, epigenetics, and cellular behavior. Disabling fatty acid oxidation causes a complex metabolic rewiring that induces transcriptional changes. These changes effectively revert the developmental pattern and give cardiomyocytes renewed proliferative potential.
Beyond merely expanding the pool of cardiomyocytes, this metabolic alteration led to various cardioprotective changes. The team has yet to ascertain the factors that affect the precision of αKG-dependent demethylase activity. They hypothesize that there are potential docking sites that can be studied.
Ultimately, this research highlights the critical role of αKG and the KDM5 enzyme family in modulating the transcriptional landscape. It points toward future cardiac regeneration strategies that manipulate fatty acid metabolism and epigenetic regulation.
FGF-23: A potential biomarker for RV dysfunction
Heart failure with reduced ejection fraction (HFrEF) is a condition in which the left ventricle (LV) does not function properly. Treatment of this condition naturally involves a focus on the LV. However, the proper function of the right ventricle (RV) is equally vital for managing symptoms, disease progression, and the overall prognosis of individuals with this condition. Problems with RV activity can lead to lung congestion and other issues.
There is currently no biomarker reflecting right ventricular dysfunction in HFrEF patients in the clinic. A team of researchers from the Czech Republic tried to search for a biomarker for right ventricular (RV) dysfunction in such patients. The team discovered that fibroblast growth factor-23 (FGF-23) was significantly upregulated in the plasma of patients with severe RV dysfunction.
An ELISA-based analysis in a larger patient cohort revealed that FGF-23 levels strongly correlated with the degree of RV dysfunction and were not significantly affected by left ventricular (LV) function or congestion status. Furthermore, the study demonstrated that FGF-23 could effectively distinguish severe RV dysfunction, even improving predictive value when combined with B-type natriuretic peptide (BNP).
Importantly, FGF-23 was associated with adverse outcomes, independent of other significant factors. The study suggests FGF-23 as a specific biomarker for RV dysfunction, potentially aiding in diagnosis, prognosis, and tailoring heart failure therapy.
Serum Uric Acid, gout flares, and cardiovascular implications
The relationship between serum uric acid (sUA) levels and cardiovascular (CV) disease (CVD) risk is intricate. It is influenced by various confounders, such as sex, kidney function, obesity, medication, diet, and alcohol intake. Recent research highlights gout flares significantly increase the risk of CV events due to the substantial inflammatory response associated with gout. Thus, we should consider recent gout flares as a confounding factor in epidemiological studies examining the link between sUA levels and CVD.
Additionally, assessing CVD risk in patients with hyperuricemia becomes even more complex when considering 'intercritical' gout.
Crystal deposition from gout can lead to subclinical inflammation and vascular implications, as observed through studies correlating crystal aggregates with measures such as carotid intima-media thickness.
Asymptomatic hyperuricemia has also been linked to subclinical monosodium urate crystal deposits. Treating intercritical gout, as per guidelines, has been shown to reduce systemic inflammation and improve arterial endothelial function.
However, determining the clinical relevance of subclinical monosodium urate crystal deposits remains a crucial task, particularly in the context of asymptomatic hyperuricemia. Lowering these deposits through sUA-lowering treatments may attenuate the associated inflammatory response. This may potentially decrease the risk of gout flares and thus reduce the risk of CV events.
Despite the potential significance, evaluating the role of intercritical gout and gout flares in epidemiological studies linking sUA levels with CVD risk poses considerable challenges.
Understanding Polyvascular Disease
Polyvascular disease (PolyvascDis) involves atherosclerosis affecting more than two vascular areas (coronary, carotid, aortic, visceral, or peripheral arteries). It is prevalent in 15-30% of patients with heightened rates of major adverse cardiovascular events.
A recent review in Current Vascular Pharmacology presents guidelines for clinicians for treating potential cases of PolyvascDis. The review outlines protocols for diagnosis and screening, clinical implications for medical professionals and guidelines for management.
Individuals with multiple cardiovascular risk factors or existing cardiovascular disease in one arterial region should undergo clinical and noninvasive assessments for PolyvascDis before invasive angiography.
This comprehensive approach to understanding and managing polyvascular disease is essential for optimizing patient care and improving long-term outcomes.
Researchers recommend that PolyVascDis management protocols should involve aggressive control of modifiable risk factors through lifestyle changes and appropriate drug therapy. Patients with peripheral arterial disease deserve particular attention, as they are often undertreated.
The review also recommends that revascularization should focus on symptomatic vascular beds, employing the least aggressive strategy and a multidisciplinary vascular team approach.
AI in Cardiology: A Heartbeat Toward Precision and Efficiency
While AI is seeing increasing use in medicine, its complete use in cardiology clinics is limited. In a recent study, researchers conducted a blinded, randomized trial to evaluate the effectiveness of artificial intelligence (AI) compared to sonographer assessment in determining left ventricular ejection fraction (LVEF) in echocardiography.
The researchers used 3,769 echocardiographic studies and randomized them into AI or sonographer groups. The researchers looked at the change in LVEF between the initial AI or sonographer assessment and the final cardiologist assessment.
To train the AI model, researchers used 144,184 echocardiogram videos from Stanford Healthcare and included features for view classification, LV annotation and LVEF assessment. The mean absolute difference between final cardiologist assessment and independent previous cardiologist assessment was 6.29% in the AI group and 7.23% in the sonographer group.
The AI saved time for both sonographers and cardiologists. Cardiologists were also unable to distinguish between the initial AI and sonographer assessments, indicating the effectiveness of the AI-guided approach.
The study demonstrated that AI tools can enhance the precision and speed of cardiac function assessment, paving the way for efficient and accurate diagnoses in cardiology clinics.
Valve Repair in Aortic Insufficiency
Aortic valve insufficiency (AI) is a condition in which blood leaks through the aortic valve in the heart during a specific time. It can be mild, moderate, or severe, based on how much blood is leaking.
When AI is severe enough to cause problems, intervention is needed. For a long time, replacing the aortic valve has been the best solution. Now, however, there are newer methods that have better long-term efficacy.
The best method depends on what is causing the AI and the individual patient's heart structure. This article by Sassis et al. reviews different AI pathologies, the surgeries used to treat them, and explains their effectiveness for patients.
Also read our Bentham Cardiovascular Disorders Collection.