Meta-analysis addressing the impact of cardiovascular-acting medication on peak oxygen uptake of patients with HFpEF.

As our therapeutic armamentarium for HFpEF is insufficient, research has been focusing on the potential beneficial effect of existing pharmaceutical regimens on this specific patient population. A series of RCTs have recently examined the impact of various pharmaceutical treatments with proven benefit in HFrEF, on the improvement of symptoms of HFpEF patients. This systematic review and meta-analysis comprised studies of adult patients with HFpEF and evaluated the impact of different cardiovascular acting medication on cardiorespiratory fitness, reflected by peak VO2 values measured during CPET. The primary outcome was difference between groups in the change of peak VO2 (ΔpeakVO2). Literature search involved PubMed/MEDLINE, Scopus and Web of Science databases. Our search identified 3634 records and 19 studies were included in qualitative analysis; 12 studies with 1341 patients were finally included in primary outcome analysis. ΔpeakVO2 between baseline and study-end did not significantly change after treatment with spironolactone, ivabradine, sildenafil, or oral inorganic nitrate and neither did difference in 6MWT distance after treatment with spironolactone. Spironolactone led to statistically significant reduction in E/E' ratio study-end values (WMD - 1.64, 95%CI - 2.42 to - 0.86, I2 = 87%, p < 0.0001), as well as to a significant increase in MLHFQ values (WMD 0.75, 95%CI 0.02 to 1.48, I2 = 0%, p = 0.65), indicating deterioration in HRQoL among HFpEF patients. A series of established cardiovascular acting medication in HFrEF seems not to confer significant benefit in peak VO2 and 6MWT distance in HFpEF. Spironolactone is associated with improvements in diastolic function and with a significant deterioration in HRQoL of this population.

Cardiopulmonary exercise testing in patients with end-stage kidney disease: principles, methodology and clinical applications of the optimal tool for exercise tolerance evaluation.

Chronic kidney disease (CKD), especially end-stage kidney disease (ESKD), is associated with an increased risk for cardiovascular events and all-cause mortality. Exercise intolerance as well as reduced cardiovascular reserve is extremely common in patients with CKD. Cardiopulmonary exercise testing (CPET) is a non-invasive, dynamic technique that provides an integrative evaluation of cardiovascular, pulmonary, neuropsychological and metabolic function during maximal or submaximal exercise, allowing the evaluation of functional reserves of these systems. This assessment is based on the principle that system failure typically occurs when the system is under stress and thus CPET is currently considered to be the gold standard for identifying exercise limitation and differentiating its causes. It has been widely used in several medical fields for risk stratification, clinical evaluation and other applications, but its use in everyday practice for CKD patients is scarce. This article describes the basic principles and methodology of CPET and provides an overview of important studies that utilized CPET in patients with ESKD, in an effort to increase awareness of CPET capabilities among practicing nephrologists.

Cardiorespiratory fitness assessed by cardiopulmonary exercise testing between different stages of pre-dialysis chronic kidney disease: A systematic review and meta-analysis.

AIM: The burden of several cardiovascular risk factors increases in parallel to renal function decline. Exercise intolerance is common in patients with chronic kidney disease (CKD) and has been associated with increased risk of adverse outcomes. Whether indices of cardiorespiratory capacity deteriorate with advancing CKD stages is unknown. METHODS: We conducted a systematic review and meta-analysis of studies assessing cardiorespiratory capacity in adult patients with pre-dialysis CKD using cardiopulmonary exercise testing (CPET) and reporting data for different stages. Our primary outcome was differences in peak oxygen uptake (VO2 peak) between patients with CKD Stages 2-3a and those with Stages 3b-5(pre-dialysis). Literature search was undertaken in PubMed, Web of Science and Scopus databases, and abstract books of relevant meetings. Quality assessment was undertaken with Newcastle-Ottawa-Scale. RESULTS: From 4944 records initially retrieved, six studies with 512 participants fulfilling our inclusion criteria were included in the primary meta-analysis. Peak oxygen uptake (VO2 peak) was significantly higher in patients with CKD Stages 2-3a versus those with Stages 3b-5(pre-dialysis) [weighted-mean-difference, WMD: 2.46, 95% CI (1.15, 3.78)]. Oxygen consumption at ventilatory threshold (VO2 VT) was higher in Stages 2-3a compared with those in Stages 3b-5(pre-dialysis) [standardized-mean-difference, SMD: 0.59, 95% CI (0.06, 1.1)], while no differences were observed for maximum workload and respiratory-exchange-ratio. A secondary analysis comparing patients with CKD Stages 2-3b and Stages 4-5(pre-dialysis), yielded similar results [WMD: 1.78, 95% CI (1.34, 2.22)]. Sensitivity analysis confirmed the robustness of these findings. CONCLUSION: VO2 peak and VO2 VT assessed with CPET are significantly lower in patients in CKD Stages 3b-5 compared with Stages 2-3a. Reduced cardiorespiratory fitness may be another factor contributing to cardiovascular risk increase with advancing CKD.

Using ChatGPT to perform a systematic review: a tutorial.

This tutorial provides a comprehensive guide on leveraging ChatGPT for systematic literature reviews, leveraging actual applications in cardiovascular research. Systematic reviews, while essential, are resource-intensive, and ChatGPT offers a potential solution to streamline the process. The tutorial covers the entire review process, from preparation to finalization. In the preparation phase, ChatGPT assists in defining research questions and generating search strings. During the screening phase, ChatGPT can efficiently screen titles and abstracts, processing multiple abstracts simultaneously. The tutorial also introduces an intermediate step of generating study summaries that leads to the generation of reliable data extraction tables. For assessing the risk of bias, ChatGPT can be prompted to perform these tasks. Using each tool's explanation document to generate an appropriate prompt is an efficient method of reliable risk of bias assessments using ChatGPT. However, users are cautioned about potential hallucinations in ChatGPT's outputs and the importance of manual validation. The tutorial emphasizes the need for vigilance, continuous refinement, and gaining experience with ChatGPT to ensure accurate and reliable results. The methods presented have been successfully tried in several projects, but they remain in nascent stages, with ample room for improvement and refinement.

Identifying the Role of Flow-Mediated Dilatation Assessment in Acute Coronary Syndromes: A Systematic Review.

In the context of the global burden of cardiovascular disease, the development of novel, patient-targeted diagnostic and therapeutic strategies is of paramount importance. Acute coronary syndromes (ACS) comprise a subset of cardiovascular disease, with constantly increasing prevalence requiring urgent attention. Flow-mediated dilatation (FMD), a noninvasive method for the evaluation of endothelial function, has been previously implemented in patients with ACS. A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in order to identify all relevant studies assessing the implementation of FMD among patients with ACS. Our review reflects an effort to present all available data regarding the role of FMD to date, a valuable noninvasive and easy accessible diagnostic tool, in the prognosis of patients with ACS. FMD evaluation in patients with ACS reveals a decline in values, indicative of the presence of endothelial function among this distinct patient group. FMD has also been used to assess the response to various treatments, as well as to predict major adverse cardiovascular events. Dynamic responses to interventions highlights its potential in the evolving field of interventional cardiology.

Does the long-term administration of proton pump inhibitors increase the risk of adverse cardiovascular outcomes? A ChatGPT powered umbrella review.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed for the treatment of acid-related disorders. In the context of coronary artery disease (CAD), PPIs are commonly prescribed along with antiplatelet medications. In fact, the potential interaction between these two classes of medications has been subject to much debate. This review aimed to summarise the findings from systematic reviews and meta-analyses on the casual relationship between PPI use (alone) and major adverse cardiovascular events (MACE). Furthermore, the recent release of ChatGPT has provided reviewers with a powerful natural language processing tool. We therefore aimed to assess the utility of ChatGPT in the systematic review process. METHODS: A comprehensive search of PubMed was conducted to identify relevant systematic reviews and meta-analyses published up to March 2023. Two independent reviewers assessed the eligibility of the studies, extracted the data, and assessed the methodological quality using AMSTAR 2.0. The population of interest was adults that received the medications of interest (PPIs) for a minimum of three months, regardless of indication. Control groups were defined as placebo or active comparators. The outcomes of interest were described under the general term MACE, which include cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. There were no restrictions with regards to time, but we only included reports in English. A different group of independent reviewers simultaneously ran the same process using ChatGPT. The results were then compared with the human generated results. RESULTS: Seven systematic reviews and meta-analyses were included, involving a total of 46 randomised controlled trials and 33 observational studies. The studies examined the association between PPI use and MACE, including stroke, myocardial infarction, and all-cause mortality. The results of the individual studies were conflicting, with some showing a positive association between PPI use and MACE, some showing no association, and others showing mixed results. However, the majority of the studies that included observational data reported a positive association between PPI use and MACE. Sensitivity analyses conducted in some studies did not significantly alter the primary results, suggesting that the findings were robust. Furthermore, ChatGPT was successfully prompted to execute most tasks involved in this review. We therefore present text that was generated by ChatGPT, including the abstract, introduction, results, and discussion sections. CONCLUSION: The findings of this umbrella review suggest that a causal relationship between PPI use and an increased risk of MACE cannot be ruled out. Further research is needed to better understand this relationship, particularly the underlying mechanisms and potential confounding factors. Healthcare professionals should consider the long-term use of PPIs and carefully weigh the risks and benefits for each patient. Finally, ChatGPT was successfully prompted to execute most of the tasks involved in this review. We therefore feel that this tool will be of great assistance in the field of evidence synthesis in the near future.

Meta-analysis of cardiovascular outcome trials assessing the impact of glucagon-like peptide-1 receptor agonists on major cardiac arrhythmias.

OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), a group of novel antidiabetic agents, demonstrated beneficial cardiovascular effects in recent large, placebo-controlled randomised clinical trials (RCTs); their clear antiarrhythmic benefit has not been yet underlined. The purpose of the present meta-analysis is to clarify the impact of GLP-1RAs on different types of cardiac arrhythmias. METHODS: We searched PubMed from its inception up to 8 October 2020 for all available cardiovascular and renal outcome, placebo-controlled RCTs utilising GLP-1RAs versus placebo. The present meta-analysis is reported according to the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) statement. RESULTS: We included data from 7 RCTs with GLP-1RAs in a total of 55,943 participants. Treatment with GLP-1RAs did not provide significant benefit in the risk for atrial fibrillation (RR = 0.81, 95%CI; 0.78-1.15, I2 = 51%), atrial flutter (RR = 0.79, 95%CI; 0.53-1.16, I2 = 0%), ventricular fibrillation (RR = 0.99, 95%CI; 0.48-2.04, I2 = 0%), ventricular tachycardia (RR = 1.41, 95%CI; 0.87-2.28, I2 = 10%), atrial tachycardia (RR = 0.63, 95%CI; 0.10-3.90, I2 = 24%), sinus node dysfunction (RR = 0.70, 95%CI; 0.40-1.23, I2 = 0%), ventricular extrasystoles (RR = 1.37, 95%CI; 0.56-3.30, I2 = 0%), second-degree atrioventricular block (RR = 0.96, 95%CI; 0.52-1.74, I2 = 0%) or complete atrioventricular block (RR = 0.78, 95%CI; 0.39-1.54, I2 = 38%). CONCLUSIONS: In patients with type 2 diabetes mellitus, treatment with GLP-1RAs does not significantly affect the risk for major cardiac arrhythmias.

Cardiopulmonary Exercise Testing in Heart Failure With Preserved Ejection Fraction: Technique Principles, Current Evidence, and Future Perspectives.

Heart failure with preserved ejection fraction (HFpEF) is a multifactorial clinical syndrome involving a rather complex pathophysiologic substrate and quite a challenging diagnosis. Exercise intolerance is a major feature of HFpEF, and in many cases, diagnosis is suspected in subjects presenting with exertional dyspnea. Cardiopulmonary exercise testing (CPET) is a noninvasive, dynamic technique that provides an integrative evaluation of cardiovascular, pulmonary, hematopoietic, neuropsychological, and metabolic functions during maximal or submaximal exercise. The assessment is based on the principle that system failure typically occurs when the system is under stress, and thus, CPET is currently considered to be the gold standard for identifying exercise intolerance, allowing the differential diagnosis of underlying causes. CPET is used in observational studies and clinical trials in HFpEF; however, in most cases, only a few from a wide variety of CPET parameters are examined, while the technique is largely underused in everyday cardiology practice. This article discusses the basic principles and methodology of CPET and studies that utilized CPET in patients with HFpEF, in an effort to increase awareness of CPET capabilities among practicing cardiologists.

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.

The Impact of Metabolic Syndrome Components on Erectile Function in Patients with Type 2 Diabetes.

Erectile dysfunction is commonly encountered in diabetic patients and in patients with metabolic syndrome; however, only a few studies have assessed patients with metabolic syndrome and type 2 diabetes mellitus (T2DM) regarding their sexual function. The purpose of this study is to examine the effect of metabolic syndrome and its components on the erectile function of T2DM patients. A cross-sectional study including T2DM patients was conducted from November 2018 until November 2020. Participants were evaluated for the presence of metabolic syndrome and their sexual function was assessed using the International Index of Erectile Function (IIEF) questionnaire. A total of 45 consecutive male patients participated in this study. Metabolic syndrome was diagnosed in 84.4% and erectile dysfunction (ED) in 86.7% of them. Metabolic syndrome was not associated with ED or ED severity. Among metabolic syndrome components, only high-density lipoprotein cholesterol (HDL) was associated with ED [x2 (1, n = 45) = 3.894, p = 0.048; OR = 5.5 (95% CI: 0.890-33.99)] and with the IIEF erectile function scores (median 23 vs. 18, U = 75, p = 0.012). Multiple regression analyses showed that HDL was non-significantly associated with the IIEF erectile function scores. In conclusion, among T2DM patients HDL is associated with ED.

5-Fluorouracil, capecitabine and vasospasm: a scoping review of pathogenesis, management options and future research considerations.

BACKGROUND: 5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent that can cause cardiotoxicity manifesting, among others, as chest pain. Capecitabine is an oral prodrug of 5-FU, with reported preferential activation in malignant cells that may also cause cardiotoxic reactions. Standard treatment of 5-FU and capecitabine induced chest pain with vasodilators is mostly effective, but there are several cases of patients unresponsive to these agents. METHODS: We performed a PubMed search on 31st May 2020. We used a three keyword search strategy using Boolean search operators. More specifically, we included fluorouracil or 5-FU or capecitabine and chest pain or angina and mechanism or treatment or management. We included primary reports of clinical and non-clinical data, as well as systematic reviews. Narrative reviews, expert opinions, letters to the editor and other forms of non-primary literature were excluded. RESULTS: Our search yielded a total of 1595 reports. Of these, 1460 were narrative reviews or irrelevant to the topic and were excluded. A total of 135 reports were used for our review. We used 81 reports for data extraction, which included 13 clinical trials, 4 retrospective reports, 61 case reports, and 3 systematic reviews. CONCLUSION: We report the incidence and predisposing factors, the value of available diagnostic procedures, and standard medical and invasive treatments. We also speculate on the potential benefit of arginine as a promising option both in prevention as well as treatment of 5-FU-induced chest pain. Finally, gaps of evidence are identified and proposals are made in terms of future research.

Homocysteine as a Predictor of Paroxysmal Atrial Fibrillation-Related Events: A Scoping Review of the Literature.

High levels of homocysteine (Hcy) have been linked with adverse cardiovascular outcomes, such as arrhythmias and stroke. In the context of paroxysmal atrial fibrillation (PAF), hyperhomocysteinemia has been demonstrated to be an independent predictor of future events. The aim of this report was to address the potential value of Hcy levels in predicting future paroxysms of atrial fibrillation (AF), as well as to identify the potential mechanisms of action. We searched PubMed and the Cochrane Database on 16 January 2022. Keywords used were homocysteine or hyperhomocysteinemia paired with a total of 67 different keywords or phrases that have been implicated with the pathogenesis of AF. We included primary reports of clinical and non-clinical data in the English language, as well as systematic reviews with or without meta-analyses. We placed no time constraints on our search strategy, which yielded 3748 results. Following title review, 3293 reports were excluded and 455 reports were used for title and abstract review, after which 109 reports were finally used for full-text review. Our review indicates that Hcy levels seem to hold a predictive value in PAF. Herein, potential mechanisms of action are presented and special considerations are made for clinically relevant diagnostic procedures that could complement plasma levels in the prediction of future PAF events. Finally, gaps of evidence are identified and considerations for future clinical trial design are presented.

Effects of different exercise programs on the cardiorespiratory reserve in HFpEF patients: a systematic review and meta-analysis.

HFpEF represents a heterogeneous syndrome with complex pathophysiological substrates and multiple clinical manifestations. Recently, much attention has been focused on cardiac rehabilitation programs for HFpEF patients, and several studies have examined the effects of exercise training on this specific population. This systematic review and meta-analysis included studies on adult patients with HFpEF and evaluated the impact of exercise on the cardiorespiratory fitness variables measured during CPET. The primary outcome was the difference in the change in the peak oxygen uptake (Δpeak VO2) between the groups. Literature search involved PubMed/MEDLINE, Cochrane/CENTRAL and Scopus databases. From an initial 5,143 literature records, we identified 18 studies fulfilling the inclusion criteria; 11 studies with 515 patients were finally included in the primary outcome analysis. Δpeak VO2 between baseline and study end was significantly higher in the groups of exercise training versus control (WMD 2.25 ml/kg/min, 95% CI 1.81-2.70). Exercise training resulted in greater change in the 6-minute walking test (6MWT) distance (WMD 2.25 m, 95% CI 1.81-2.70). Health-related quality of life (HRQoL) (WMD: -3.36, 95% CI -9.42 to 2.70, I2 = 14%, p = 0.33) and echocardiographic indices of diastolic function showed no differences between exercise and control groups at study end. In the subgroup analysis, no difference between resistance versus aerobic exercise was noted in Δpeak VO2, but high-intensity interval training showed a greater increase in peak VO2 versus aerobic exercise (WMD 1.62 ml/kg/min, 95% CI 0.96-2.29, I2 = 0%, p = 0.82). Exercise training in HFpEF results in significant improvements in peak VO2 and 6MWT distance as compared to those for controls. High-intensity interval training may offer greater enhancement of the exercise capacity of these patients than standard aerobic exercise.

Cardiac geometry, function, and remodeling patterns in patients under maintenance hemodialysis and peritoneal dialysis treatment.

Cardiovascular disease is the leading cause of mortality in patients with end-stage-kidney disease. Evidence on the possible echocardiographic differences between hemodialysis and peritoneal dialysis (PD) is scarce. This study aimed to evaluate differences in left (LA) and right atrial (RA), left (LV) and right ventricular (RV) geometry, systolic and diastolic function in hemodialysis, and PD patients. Thirty-eight hemodialysis and 38 PD patients were matched for age, sex, and dialysis vintage. Two-dimensional and tissue-Doppler echocardiography, and lung ultrasound were performed during an interdialytic day in hemodialysis and before a programmed follow-up visit in PD patients. Vena cava diameter (11.09 ± 4.53 vs. 14.91 ± 4.30 mm; p < 0.001) was significantly lower in hemodialysis patients. Indices of LA, RA, LV, and RV dimensions were similar between the two groups. LVMi (116.91 [38.56] vs. 122.83 [52.33] g/m2 ; p = 0.767) was similar, but relative wall thickness was marginally (0.40 [0.14] vs. 0.45 [0.15] cm; p = 0.055) lower in hemodialysis patients. LV hypertrophy prevalence was similar between groups (73.7% vs. 71.1%; p = 0.798), but hemodialysis patients presented eccentric and PD patients concentric LVH. Regarding ventricular systolic function, stroke volume (p = 0.030) and cardiac output (p = 0.036) were higher in hemodialysis, while RV systolic pressure (RVSP) (20.37 [22.54] vs. 27.68 [14.32] mm Hg; p = 0.009) was higher in PD. No significant differences were evidenced in diastolic function indices and lung water excess between the two groups. A moderate association was noted between ultrasound B-lines score and LA volume index (r = 0.465, p < 0.001), RVSP (r = 0.431, p < 0.001), and E/e' ratio (r = 0.304, p = 0.009). Hemodialysis and PD patients present largely similar echocardiographic indices reflecting cardiac geometry, systolic, and diastolic function, but different patterns of abnormal LV remodeling.

Cardiopulmonary reserve examined with cardiopulmonary exercise testing in individuals with chronic kidney disease: A systematic review and meta-analysis.

BACKGROUND: Patients with chronic kidney disease (CKD) often present reduced physical activity and exercise tolerance due to factors relevant to co-existing disturbances of the cardiac, nervous and muscular systems. Cardiopulmonary exercise testing (CPET) is used for clinical evaluation of exercise limitation and related symptoms (i.e., dyspnea, fatigue) in several medical fields. OBJECTIVES: This is a systematic review and meta-analysis of studies using CPET technology to examine cardiopulmonary reserve in individuals with versus without CKD. METHODS: Literature search involved PubMed, Web of Science and Scopus databases; manual search of article references and of gray literature was also performed. Observational studies and randomized trials that used CPET for patients with CKD stage 1-5 versus controls were eligible. The primary outcome was peak oxygen uptake (VO2peak). The Newcastle-Ottawa Scale was used to evaluate the quality of retrieved studies. RESULTS: From an initial 4944 literature records, we identified 29 studies fulfilling the inclusion criteria; of these, 25 studies (2,213 participants) with complete data were included in the final meta-analysis. VO2peak was significantly lower in CKD patients than controls without CKD [standardized mean difference (SMD) -1.40, 95% confidence interval (CI) -1.68; -1.13)]. Values were lower for CKD than non-CKD individuals for oxygen consumption at anaerobic threshold (SMD -1.06, 95% CI -1.34; -0.79) and maximum workload [weighted mean difference (WMD) -58.26, 95% CI 74.14; -42.38]. In 3 studies, CKD patients had higher VO2peak than controls with heart failure without CKD (WMD 6.60, 95% CI 3.02; 10.18). Sensitivity analyses confirmed the robustness of these findings. CONCLUSIONS: VO2peak and other commonly analyzed CPET variables were lower in patients with CKD than controls, which indicates reduced functional cardiopulmonary reserve in CKD. In contrast, patients with CKD performed better than controls with heart failure without CKD. Overall, rehabilitation programs should be more widely applied to individuals with CKD. PROSPERO REGISTRATION NUMBER: CRD42021227805.

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.

Reinforcing adherence to lipid-lowering therapy after an acute coronary syndrome: A pragmatic randomized controlled trial.

BACKGROUND AND AIMS: Achieving the low-density lipoprotein cholesterol (LDL-C) goal following an acute coronary syndrome (ACS) is a milestone often missed due to suboptimal adherence to secondary prevention treatments. Whether improved adherence could result in reduced LDL-C levels is unclear. We aimed to evaluate whether an educational-motivational intervention increases long-term lipid-lowering therapy (LLT) adherence and LDL-C goal attainment rate among post-ACS patients. METHODS: IDEAL-LDL was a parallel, two-arm, single-center, pragmatic, investigator-initiated randomized controlled trial. Hospitalized patients for ACS were randomized to a physician-led integrated intervention consisting of an educational session at baseline, followed by regular motivational interviewing phone sessions or usual care. Co-primary outcomes were the LLT adherence (measured by Proportion of Days Covered (PDC); good adherence defined as PDC>80%), and LDL-C goal (<70 mg/dl or 50% reduction from baseline) achievement rate at one year. RESULTS: In total, 360 patients (mean age 62 years, 81% male) were randomized. Overall, good adherence was positively associated with LDL-C goal achievement rate at one year. Median PDC was higher in the intervention group than the control group [0.92 (IQR, 0.82-1.00) vs. 0.86 (0.62-0.98); p = 0.03] while the intervention group had increased odds of good adherence (odds ratio: 1.76 (95% confidence interval 1.02 to 2.62; p = 0.04). However, neither the LDL-C goal achievement rate (49.6% in the intervention vs. 44.9% in the control group; p = 0.49) nor clinical outcomes differed significantly between the two groups. CONCLUSIONS: Α multifaceted intervention improved LLT adherence in post-ACS patients without a significant difference in LDL-C goal attainment.

Colchicine as a Potential Therapeutic Agent Against Cardiovascular Complications of COVID-19: an Exploratory Review.

Coronavirus disease-19 (COVID-19) may result in serious complications involving several organ systems, including myocardial tissue. An exaggerated host inflammatory response, described as a cytokine storm, has been linked to play a major role in these complications. Colchicine and other pharmaceutical agents have been proposed to counter the cytokine storm and improve outcomes. In this exploratory review, we utilized a PubMed and Cochrane Database search aiming to identify the biochemical characteristics of the cytokine storm as well as to identify the potential effect of colchicine on these inflammatory biomarkers. The research yielded 30 reports describing the characteristics of the cytokine storm and 44 reports describing the effect of colchicine on various inflammatory biomarkers. According to our research, colchicine may be an agent of interest in the treatment of COVID-19 via its anti-inflammatory properties. However, there are potential drug interactions with cytochrome P450 3A4 inhibitors resulting in acute colchicine toxicities. Additionally, there is scarce evidence regarding the efficacy of colchicine in the acute phase of disease, since most trials evaluated its effect in chronic conditions. In this direction, our team proposes three different hypotheses for evaluating the place of colchicine in the treatment of COVID-19.

Spontaneous Coronary Artery Dissection (SCAD): Case Series and Mini Review.

Spontaneous coronary artery dissection (SCAD) has gained recognition in recent years as a non-atherosclerotic cause of acute coronary syndrome (ACS), especially in young and middle-aged women without any of the classic risk factors for cardiovascular disease. The booming use of coronary angiography in patients presenting with ACS combined with new, revolutionary methods of intravascular imaging, have led to increased rates of SCAD diagnosis. We aim to present a brief, up-to-date review of the existing literature, along with our experience as reflected in the recent management of nine SCAD cases in three tertiary care hospitals.