The role of cardiopulmonary exercise testing in risk stratification and prognosis of atrial fibrillation: a scoping review of the literature.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is a significant tool for evaluating exercise capacity in healthy individuals and in various pulmonary and cardiovascular conditions, quantifying symptoms and predicting outcomes. Atrial fibrillation (AF) poses a significant burden on patients and health systems; a research marathon is ongoing for discovering the pathophysiologic substrate, natural history, prognostic tools and optimal treatment strategies for AF. Among the plethora of variables measured during CPET, there is a series of parameters of interest concerning AF. METHODS: We conducted a scoping review aiming to identify significant CPET-related parameters linked to AF, as well as indicate the impact of other cardiac disease-related variables. We searched PubMed from its inception to 12 January 2022 for reports underlining the contribution of CPET in the assessment of patients with AF. Only clinical trials, observational studies and systematic reviews were included, while narrative reviews, expert opinions and other forms of manuscripts were excluded. RESULTS: In our scoping review, we report a group of heterogeneous, thus noteworthy parameters relevant to the potential contribution of CPET in AF. CPET helps phenotype AF populations, evaluates exercise capacity after cardioversion or catheter ablation, and assesses heart rate response to exercise; peak VO2 and VE/VCO2, commonly measured indices during CPET, also serve as prognostic tools in patients with AF and heart failure. CONCLUSIONS: CPET seems to hold a clinically important predictive value for future cardiovascular events both in patients with pre-existing cardiac conditions and in healthy individuals. CPET variables may play a fundamental role in the prediction of future AF-related events.

Cardiovascular efficacy and safety of dipeptidyl peptidase-4 inhibitors: A meta-analysis of cardiovascular outcome trials.

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors are a generally safe and well tolerated antidiabetic drug class with proven efficacy in type 2 diabetes mellitus (T2DM). Recently, a series of large, randomized controlled trials (RCTs) addressing cardiovascular outcomes with DPP-4 inhibitors have been published. AIM: To pool data from the aforementioned trials concerning the impact of DPP-4 inhibitors on surrogate cardiovascular efficacy outcomes and on major cardiac arrhythmias. METHODS: We searched PubMed and grey literature sources for all published RCTs assessing cardiovascular outcomes with DPP-4 inhibitors compared to placebo until October 2020. We extracted data concerning the following "hard" efficacy outcomes: fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, hospitalization for heart failure, hospitalization for unstable angina, hospitalization for coronary revascularization and cardiovascular death. We also extracted data regarding the risk for major cardiac arrhythmias, such as atrial fibrillation, atrial flutter, ventricular fibrillation and ventricular tachycardia. RESULTS: We pooled data from 6 trials in a total of 52520 patients with T2DM assigned either to DPP-4 inhibitor or placebo. DPP-4 inhibitors compared to placebo led to a non-significant increase in the risk for fatal and non-fatal myocardial infarction [risk ratio (RR) = 1.02, 95%CI: 0.94-1.11, I 2 = 0%], hospitalization for heart failure (RR = 1.09, 95%CI: 0.92-1.29, I 2 = 65%) and cardiovascular death (RR = 1.02, 95%CI: 0.93-1.11, I 2 = 0%). DPP-4 inhibitors resulted in a non-significant decrease in the risk for fatal and non-fatal stroke (RR = 0.96, 95%CI: 0.85-1.08, I 2 = 0%) and coronary revascularization (RR = 0.99, 95%CI: 0.90-1.09, I 2 = 0%), Finally, DPP-4 inhibitors demonstrated a neutral effect on the risk for hospitalization due to unstable angina (RR = 1.00, 95%CI: 0.85-1.18, I 2 = 0%). As far as cardiac arrhythmias are concerned, DPP-4 inhibitors did not significantly affect the risk for atrial fibrillation (RR = 0.95, 95%CI: 0.78-1.17, I 2 = 0%), while they were associated with a significant increase in the risk for atrial flutter, equal to 52% (RR = 1.52, 95%CI: 1.03-2.24, I 2 = 0%). DPP-4 inhibitors did not have a significant impact on the risk for any of the rest assessed cardiac arrhythmias. CONCLUSION: DPP-4 inhibitors do not seem to confer any significant cardiovascular benefit for patients with T2DM, while they do not seem to be associated with a significant risk for any major cardiac arrhythmias, except for atrial flutter. Therefore, this drug class should not be the treatment of choice for patients with established cardiovascular disease or multiple risk factors, except for those cases when newer antidiabetics (glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors) are not tolerated, contraindicated or not affordable for the patient.

Is miRNA-375 a promising biomarker for early detection and monitoring of patients with type 2 diabetes?

miRNAs are small, non-coding RNAs, functioning as negative suppressors of target gene expression. A significant proportion of the transcriptome is subject to miRNA modulation. A single miRNA determines the expression of hundreds of genes, while miRNAs are relatively stable in biological fluids. Thus, they have attracted scientific interest regarding their use as biomarkers for several diseases. miRNA-375 mainly influences ß-cell function and insulin secretion. Several studies, primarily experimental, have assessed its role as a biomarker in type 2 diabetes, while recently obtained human evidence supports this potential role. Besides its diagnostic potential, miRNA-375 may also have therapeutic implications. In view of the growing epidemic of type 2 diabetes, there is an unmet need for identification of biomarkers for early recognition and monitoring of these patients. Long-term, prospective human studies are required to elucidate whether miRNA-375 can evolve as a key player in diagnosis and prognosis of type 2 diabetes.