New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2023.

Although cardiovascular diseases (CVDs) are the leading cause of death worldwide, their pharmacotherapy remains suboptimal. Thus, there is a clear unmet need to develop more effective and safer pharmacological strategies. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2023, including the approval of first-in-class drugs that open new avenues for the treatment of atherosclerotic CVD and heart failure (HF). The new indications of drugs already marketed (repurposing) for the treatment of obstructive hypertrophic cardiomyopathy, hypercholesterolaemia, type 2 diabetes, obesity, and HF; the impact of polypharmacy on guideline-directed drug use is highlighted as well as results from negative clinical trials. Finally, we end with a summary of the most important phase 2 and 3 clinical trials assessing the efficacy and safety of cardiovascular drugs under development for the prevention and treatment of CVDs.

New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2022.

Cardiovascular diseases (CVD) remain the leading cause of death worldwide and pharmacotherapy of most of them is suboptimal. Thus, there is a clear unmet clinical need to develop new pharmacological strategies with greater efficacy and better safety profiles. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2022 including the approval of first-in-class drugs that open new avenues for the treatment of obstructive hypertrophic cardiomyopathy (mavacamten), type 2 diabetes mellitus (tirzepatide), and heart failure (HF) independent of left ventricular ejection fraction (sodium-glucose cotransporter 2 inhibitors). We also dealt with fixed dose combination therapies repurposing different formulations of "old" drugs with well-known efficacy and safety for the treatment of patients with acute decompensated HF (acetazolamide plus loop diuretics), atherosclerotic cardiovascular disease (moderate-dose statin plus ezetimibe), Marfan syndrome (angiotensin receptor blockers plus ß-blockers), and secondary cardiovascular prevention (i.e. low-dose aspirin, ramipril and atorvastatin), thereby filling existing gaps in knowledge, and opening new avenues for the treatment of CVD. Clinical trials confirming the role of dapagliflozin in patients with HF and mildly reduced or preserved ejection fraction, long-term evolocumab to reduce the risk of cardiovascular events, vitamin K antagonists for stroke prevention in patients with rheumatic heart disease-associated atrial fibrillation, antibiotic prophylaxis in patients at high risk for infective endocarditis before invasive dental procedures, and vutrisiran for the treatment of hereditary transthyretin-related amyloidosis with polyneuropathy were also reviewed. Finally, we briefly discuss recent clinical trials suggesting that FXIa inhibitors may have the potential to uncouple thrombosis from hemostasis and attenuate/prevent thromboembolic events with minimal disruption of hemostasis.

Preliminary data of familial hypercholesterolemia (FH) patients in Romania.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is one of the most frequent monogenic cholesterol disorders. Its prevalence varies in adults between 1/500-1/217 individuals in the heterozygous form. The objective of this study was to uncover the FH prevalence in Romania to perform an adequate prevention for high risk individuals. METHODS: We have conducted an epidemiological study between January 2015 and January 2018 by recruiting patients from the CardioPrevent Foundation based on their FH score (taking into account their low density lipoprotein cholesterol (LDLc) levels, clinical characteristics such as premature coronary artery disease (CAD), and their family history of premature cardiovascular disease). We have calculated the probability of FH using the Dutch Lipid Clinic Network (DLCN) criteria and we have included patients with a score over 3 points. RESULTS: We have enrolled 59 patients, out of whom 61% were females. 8.4% of the patients recruited had a first degree relative with premature coronary artery disease and 5% had a relative with LDLc >190 mg/dl (without statin treatment). 10.16% of the patients had coronary artery disease and 15.25% peripheral vascular disease. 91.52% of the patients had a possible FH, while 6.7% had a probable FH and 1.6% a definite FH diagnosis. Based on this data, the prevalence of FH in Romania is: 1:213. CONCLUSIONS: To raise the suspicion for FH is easy at the level of the general practitioners, based on the analysis of LDLc levels and premature CAD occurrence. Diagnosis can be further refined using an available online free software.

Deceleration and Acceleration Capacities in Risk Stratification for Arrhythmias in Patients With Chronic Obstructive Pulmonary Disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk for both supraventricular and ventricular arrhythmias. Autonomic dysregulation may be responsible for the development of arrhythmias in these patients, and its analysis could be useful for identifying those at high risk for arrhythmias. STUDY QUESTION: Our purpose is to analyze the role of acceleration capacity (AC) and deceleration capacity (DC), novel markers of the autonomic balance, as potential arrhythmic risk predictors in patients with COPD. STUDY DESIGN: We prospectively included 47 patients diagnosed with COPD, and a control group of 64 age-matched subjects without COPD. AC and DC values were obtained using 24-hour Holter monitoring. The arrhythmias were isolated premature atrial complexes, supraventricular tachycardias, isolated premature ventricular beats (PVC), and combined ventricular arrhythmias consisting in ventricular tachycardias or more than 10 PVC per hour. RESULTS: Supraventricular arrhythmias and isolated PVC were more frequent in the COPD group. The DC was significantly lower (3.10 vs. 5.60, P < 0.0001) and AC higher (-4.60 vs. -6.60, P = 0.002) in patients with COPD. DC was identified as a predictor of arrhythmic events with an area under the curve (AUC) for premature atrial complexes >70/d of 0.72 (0.56-0.87, P = 0.013), for supraventricular tachycardias 0.76 (0.62-0.90, P = 0.002), and for combined ventricular arrhythmias 0.69 (0.54-0.82, P = 0.025). AC was predictor only for combined ventricular arrhythmias with an AUC of 0.74 (0.58-0.85, P = 0.002). CONCLUSIONS: Patients with COPD associate a significant autonomic imbalance and a higher incidence of arrhythmias. DC could be a strong predictor for supraventricular and ventricular arrhythmias in patients with COPD with no clinically apparent cardiac disease. AC could be useful alongside with DC regarding the risk for ventricular arrhythmias, but seems to have lesser value as a predictor for supraventricular arrhythmias.

Circulating Reticulocalbin 1 and Reticulocalbin 3 in Systemic Sclerosis Patients: Results of a Case Control Study.

BACKGROUND: Proteomic candidate biomarkers for systemic sclerosis (Ssc) useful for appropriate patient evaluation and follow-up were identified in mass-spectrometry studies; however, most of these biomarkers were not evaluated and confirmed on independent patient samples. Up-regulation of reticulocalbin 1 (RCN1) and reticulocalbin 3 (RCN3) in the dermal fibroblast secretome originating from Ssc patients was previously described. The aim of the study was to evaluate circulating RCN1 and RCN3 as candidate biomarkers for Ssc clinical expression. METHODS: 40 consecutive Ssc patients and 20 gender and age matched controls were included. Serum RCN1 and RCN3 was evaluated using commercial ELISA kits. RESULTS: Serum RCN1 and RCN3 were not statistically significant different between Ssc patients and healthy controls. Serum RCN1 and RCN3 were correlated in both Ssc and healthy control groups (p < 0.001). Serum RCN1 was positively correlated with Ssc disease activity score (EUSTAR, p = 0.02) and remained associated with EUSTAR after adjusting for disease duration in multivariate analysis. 6 Ssc patients (15%) had elevated RCN1 values compared to reference values obtained from healthy control samples. These patients had higher prevalence of digital ulcers, higher disease activity scores, and tended to have esophageal hypomotility, calcinosis, telangiectasia, and diffuse Ssc subtype. CONCLUSIONS: RCN1 and RCN3 expression was not statistically significantly different to healthy controls. However, RCN1 was associated with disease activity score and could be used as a stratification biomarker for Ssc patients, as patients with high RCN1 shared a particular disease pattern.

Prevalence and impact on survival of hepatopulmonary syndrome and cirrhotic cardiomyopathy in a cohort of cirrhotic patients.

BACKGROUND & AIMS: Extrahepatic complications of cirrhosis increase the risk for decompensation of the liver disease and death. Previous studies show common pathogenetic mechanisms involved in the development of hepatopulmonary syndrome and cirrhotic cardiomyopathy. We aimed to assess the link between these entities and their effect on disease-related patient morbidity and mortality. METHODS: Seventy-four consecutive cirrhotic patients without prior history of cardiovascular and pulmonary disease were included in a prospective observational study. Routine blood work, arterial blood gas analysis, pulse oximetry measurements, N-terminal pro-brain natriuretic peptide levels and contrast enhanced echocardiography examination with tissue Doppler imaging were performed in all patients. Patients were followed up for a median of 6 months and disease-related adverse events and death were the main outcomes tested. Statistical analysis was conducted according to the presence of hepatopulmonary syndrome or cirrhotic cardiomyopathy. RESULTS: Hepatopulmonary syndrome was diagnosed in 17 patients (23%) and cirrhotic cardiomyopathy in 30 patients (40.5%). There was no association between the presence of cirrhotic cardiomyopathy and the existence of mild or moderate hepatopulmonary syndrome. No echocardiographic parameters were useful in predicting the presence of hepatopulmonary syndrome. N-terminal pro-brain natriuretic peptide levels and length of QT interval did not aid in diagnosis of cirrhotic cardiomyopathy. Neither entity had significant influence on disease-related outcomes in the follow-up period. CONCLUSIONS: Hepatopulmonary syndrome and cirrhotic cardiomyopathy are independent complications arising in cirrhosis and have a limited influence on morbidity and mortality on a pre-liver transplantation population.