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19 pages, 1583 KB  
Article
Long-Term Outcomes in Aortic Stenosis: Mortality Analysis in a Selected Patient Group
by Olga Irtyuga, Mary Babakekhyan, Oleg Metsker, Anna Starshinova, Dmitry Kudlay and Georgy Kopanitsa
J. Pers. Med. 2025, 15(9), 410; https://doi.org/10.3390/jpm15090410 - 2 Sep 2025
Viewed by 548
Abstract
Background: Aortic stenosis (AS) is a prevalent acquired heart valve disease with increasing incidence, particularly among older adults. Gender-specific differences in AS presentation, comorbidities, and outcomes remain underexplored, necessitating further investigation to optimize personalized treatment strategies. Objective: To evaluate the clinical and demographic [...] Read more.
Background: Aortic stenosis (AS) is a prevalent acquired heart valve disease with increasing incidence, particularly among older adults. Gender-specific differences in AS presentation, comorbidities, and outcomes remain underexplored, necessitating further investigation to optimize personalized treatment strategies. Objective: To evaluate the clinical and demographic characteristics, comorbidities, and survival outcomes of patients with AS, stratified by gender and aortic valve morphology. Methods: A retrospective analysis of 145,454 echocardiographic examinations (2009–2018) at the Federal State Budgetary Institution “V.A. Almazov National Medical Research Centre” identified 84,851 patients meeting the inclusion criteria (Vmax ≥ 2.0 m/s, age ≥ 18 years). Patients were stratified by gender and valve morphology (bicuspid aortic valve [BAV] vs. tricuspid aortic valve [TAV]). Survival was assessed in 475 pts with AS over a 16-year period (2009–2025) using Kaplan–Meier analysis. Statistical comparisons utilized STATISTICA v. 10.0, with p-values derived from P-tests. Results: Of the cohort, 4998 men and 6322 women had AS. Men with AS were older (median 64 vs. 57 years, p < 0.0001) and had higher systolic blood pressure (140 vs. 130 mmHg, p < 0.0001) than men without AS. Women with AS were also older (median 70 vs. 58 years, p < 0.0001) with higher systolic (140 vs. 130 mmHg, p < 0.0001) and diastolic blood pressure (80 vs. 80 mmHg, p < 0.0001). Men with AS had higher rates of hyperlipidemia (HLP) (26.3% vs. 10.3%, p < 0.0001), while women with AS had increased coronary artery disease (CAD) (35.7% vs. 26.4%, p < 0.0001), diabetes mellitus (DM) (13.4% vs. 10.2%, p < 0.0001), and obesity (10.9% vs. 10.2%, p = 0.06). Chronic heart failure (CHF) was more frequently reported in patients with AS, regardless of gender, compared to patients without AS (in men 53.4% vs. 41.8%, p < 0.0001; in women 54.5% vs. 37.5%, p < 0.0001). BAV was associated with higher AS prevalence (54.5% in men, 66.4% in women). Survival analysis revealed higher mortality. Over the 16-year follow-up period, the mortality rate was 21.7%. Conclusions: Mortality in a representative AS cohort reached 21.7%, underscoring the progressive nature of the disease and its long-term impact. Survival was negatively affected by age over 68.5 years, as well as the presence of aortic regurgitation (AR), increased peak aortic jet velocity, and enlarged maximum aortic diameter. Aortic valve replacement demonstrates an insignificant effect on patient survival rates. Beta-blocker therapy in patients with varying degrees of aortic AS severity has not only demonstrated its safety but has also shown a positive effect on reducing mortality (improving survival). In contrast, the combination of angiotensin II receptor blockers (ARBs) with calcium channel blockers (CCBs) is quite dangerous for patients with AS and reduces their survival. Aortic valve replacement demonstrates an insignificant effect on patient survival rates. In contrast, the absence of fibrinolytic therapy and anticoagulant treatment is associated with an improved prognosis. Conversely, the administration of antiarrhythmic agents and statins is correlated with enhanced survival outcomes, potentially attributable to their influence on coexisting comorbidities. Further research is required to delineate their precise mechanisms and contributions. These results emphasize the importance of early identification, comprehensive risk assessment, and individualized management strategies in improving outcomes for patients with AS. Full article
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34 pages, 1051 KB  
Review
Atrial Fibrillation in Diabetes: Pathogenesis and Targeted Rhythm Control Strategies
by Konstantinos Grigoriou, Paschalis Karakasis, Konstantinos Pamporis, Panagiotis Theofilis, Dimitrios Patoulias, Efstratios Karagiannidis, Barbara Fyntanidou, Antonios P. Antoniadis and Nikolaos Fragakis
Curr. Issues Mol. Biol. 2025, 47(7), 559; https://doi.org/10.3390/cimb47070559 - 17 Jul 2025
Viewed by 1252
Abstract
Diabetes mellitus and atrial fibrillation (AF) frequently coexist, creating a complex bidirectional relationship that exacerbates cardiovascular risk and challenges clinical management. Diabetes fosters a profibrotic, pro-inflammatory, and proarrhythmic atrial substrate through a constellation of pathophysiologic mechanisms, including metabolic remodeling, oxidative stress, mitochondrial dysfunction, [...] Read more.
Diabetes mellitus and atrial fibrillation (AF) frequently coexist, creating a complex bidirectional relationship that exacerbates cardiovascular risk and challenges clinical management. Diabetes fosters a profibrotic, pro-inflammatory, and proarrhythmic atrial substrate through a constellation of pathophysiologic mechanisms, including metabolic remodeling, oxidative stress, mitochondrial dysfunction, ion channel dysregulation, and autonomic imbalance, thereby promoting AF initiation and progression. Conventional rhythm control strategies remain less effective in diabetic individuals, underscoring the need for innovative, substrate-targeted interventions. In this context, sodium–glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as promising agents with pleiotropic antiarrhythmic properties, modulating fibrosis, inflammation, and mitochondrial integrity. Moreover, advances in anti-inflammatory, antifibrotic, and ion channel-modulating therapeutics, coupled with novel mitochondrial-targeted strategies, are reshaping the therapeutic landscape. Multi-omics approaches are further refining our understanding of diabetes-associated AF, facilitating precision medicine and biomarker-guided interventions. This review delineates the molecular nexus linking diabetes and AF, critically appraises emerging rhythm control strategies, and outlines translational avenues poised to advance individualized management in this high-risk population. Full article
(This article belongs to the Special Issue Advances in Molecular Therapies and Disease Associations in Diabetes)
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17 pages, 2228 KB  
Article
Formulation and In Vitro Characterization of Cellulose-Based Propranolol Hydrochloride Sustained Release Matrix Tablets
by Aashish Khadka, Bhupendra Raj Giri, Rishiram Baral, Shailendra Shakya and Ashwinee Kumar Shrestha
BioChem 2025, 5(2), 14; https://doi.org/10.3390/biochem5020014 - 30 May 2025
Viewed by 1109
Abstract
Background/Objectives: Propranolol HCl (PPH), a nonselective beta-adrenergic receptor blocker, is employed as an anti-hypertensive, anti-anginal, anti-arrhythmic, and anti-migraine agent. Given its utility in chronic conditions, developing a sustained-release dosage form becomes imperative to optimize therapeutic outcomes while enhancing patient adherence and minimizing side [...] Read more.
Background/Objectives: Propranolol HCl (PPH), a nonselective beta-adrenergic receptor blocker, is employed as an anti-hypertensive, anti-anginal, anti-arrhythmic, and anti-migraine agent. Given its utility in chronic conditions, developing a sustained-release dosage form becomes imperative to optimize therapeutic outcomes while enhancing patient adherence and minimizing side effects. In this study, we employed a widely adopted matrix-based system to develop PPH sustained-release (PPH-SR) matrix tablets, ensuring the uniform dispersion of the drug within the polymeric matrix to regulate its release rate. Methods: Utilizing cellulose-based polymers, specifically HPMC K100M and ethyl cellulose (EC), as matrix formers, nine different formulations were prepared at varying drug-to-polymer ratios. We employed a wet granulation method, followed by compression of the dried granules, to fabricate round-shaped biconvex PPH-SR tablets. Results: Among these different formulations, formulation 2 (F2), comprising 40 mg PPH and 50 mg HPMC K100M (along with other excipients), showed excellent flowability, as evidenced by Carr’s index and angle of repose values of 12.50 and 28.50, respectively. Additionally, the mechanical properties of F2 tablets showed a hardness of 12.34 ± 0.91 KP, an average weight of 200.45 ± 1.87 mg, with a friability of 0.20%, and a content uniformity of 98.36%. Moreover, in vitro release characteristics of F2 tablets demonstrated a sustained-release behavior, with 94.3 ± 10.2% drug release over 24 h. A comparative analysis with marketed tablets yielded similarity and dissimilarity factors of 64 and 8, respectively. Furthermore, the release profile of F2 exhibited a high degree of linearity with the Korsmeyer–Peppas model (R2 of 0.977), showcasing its reliability and predictability. Conclusions: In essence, this in-house developed PPH sustained-release formulation can improve patient adherence, reduce side effects, and improve therapeutic outcomes. These results align with our objective of enhancing the therapeutic efficacy of PPH and affirm the broader relevance of innovative formulation strategies in addressing the challenges of chronic disease management. Full article
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24 pages, 2711 KB  
Review
Integrative Approaches in the Management of Hypertrophic Cardiomyopathy: A Comprehensive Review of Current Therapeutic Modalities
by Marco Maria Dicorato, Gaetano Citarelli, Francesco Mangini, Rossella Alemanni, Miriam Albanese, Sebastiano Cicco, Cosimo Angelo Greco, Cinzia Forleo, Paolo Basile, Maria Cristina Carella, Marco Matteo Ciccone, Andrea Igoren Guaricci and Ilaria Dentamaro
Biomedicines 2025, 13(5), 1256; https://doi.org/10.3390/biomedicines13051256 - 21 May 2025
Cited by 1 | Viewed by 2642
Abstract
Hypertrophic cardiomyopathy (HCM) is often associated with left ventricular outflow tract (LVOT) obstruction, which affects a substantial proportion of patients. This obstruction results from a range of anatomical abnormalities involving both the valvular and subvalvular structures. Pharmacological therapies play a pivotal role in [...] Read more.
Hypertrophic cardiomyopathy (HCM) is often associated with left ventricular outflow tract (LVOT) obstruction, which affects a substantial proportion of patients. This obstruction results from a range of anatomical abnormalities involving both the valvular and subvalvular structures. Pharmacological therapies play a pivotal role in the management of LVOT obstruction, with a range of drug classes exhibiting distinct mechanisms of action. Beta-blockers, including atenolol and nadolol, are considered the first-line treatment due to their ability to reduce heart rate and myocardial contractility and enhance diastolic filling. Non-dihydropyridine calcium channel blockers, such as verapamil and diltiazem, are utilized as second-line agents when beta-blockers are ineffective or contraindicated. Disopyramid, a Class 1A antiarrhythmic agent, is employed for patients who do not respond to initial therapeutic interventions and can reduce LVOT gradients. Recent advancements in cardiac myosin modulators, such as Mavacamten and Aficamten, offer targeted therapies by modulating myosin–actin interactions to reduce LVOT gradients and improve symptoms, with promising results from clinical trials. Although gene therapy is still in its nascent stages, it has the potential to address the genetic basis of HCM by employing techniques such as genome editing, gene replacement, and the modulation of signaling pathways. For patients exhibiting severe symptoms or demonstrating unresponsiveness to medical treatment, invasive therapies, such as septal reduction therapy and alcohol septal ablation, are considered. Ultimately, the treatment and prevention of atrial fibrillation and sudden cardiac death are two key points of HCM management in both obstructive and non-obstructive forms. This review aims to provide an overview of current pharmacological and invasive strategies, as well as emerging therapies, in the management of HCM. Full article
(This article belongs to the Special Issue Advanced Research in Hypertrophic Cardiomyopathy)
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17 pages, 3595 KB  
Review
Hydrocarbon Exposure in Myocarditis: Rare Toxic Cause or Trigger? Insights from a Biopsy-Proven Fulminant Viral Case and a Systematic Literature Review
by Andrea S. Giordani, Tommaso Simone, Anna Baritussio, Cristina Vicenzetto, Federico Scognamiglio, Filippo Donato, Luca Licchelli, Luisa Cacciavillani, Chiara Fraccaro, Giuseppe Tarantini, Fausto Braccioni, Stefania Rizzo, Monica De Gaspari, Cristina Basso, Renzo Marcolongo and Alida L. P. Caforio
Int. J. Mol. Sci. 2025, 26(9), 4006; https://doi.org/10.3390/ijms26094006 - 24 Apr 2025
Cited by 1 | Viewed by 1027
Abstract
Toxic myocarditis (TM) is rare, and no systematic evidence is available regarding its treatment or prognosis. Hydrocarbons even more rarely cause TM, and they are associated with severe extracardiac toxicity. Moreover, a pathogenic interaction between viral and toxic agents in TM has not [...] Read more.
Toxic myocarditis (TM) is rare, and no systematic evidence is available regarding its treatment or prognosis. Hydrocarbons even more rarely cause TM, and they are associated with severe extracardiac toxicity. Moreover, a pathogenic interaction between viral and toxic agents in TM has not been studied. We present the first case of biopsy-proven parvovirus B19 (B19V) viral fulminant myocarditis diagnosed after hydrocarbon exposure, along with a systematic literature review of hydrocarbon-TM cases. A systematic literature review was conducted by searching hydrocarbon-TM cases. Clinical and prognostic data were recorded. After screening of 937 records, 7 were included. All cases were male, with a median age of 24 years (IQR 23–25). Chest pain and dyspnea were the main symptoms, but arrhythmic presentation was also reported; endomyocardial biopsy (EMB) was performed in only one case. Overall, treatment was based on supportive measures, such as antiarrhythmic and/or vasoactive therapy. Our example (male, 47 years old) is the first reported fulminant biopsy-proven case diagnosed after a massive exposure to hydrocarbons, in which EMB molecular analysis unexpectedly revealed B19V with a high viral load. Hemodynamic and arrhythmic instability required percutaneous stellate ganglion blockade and temporary wearable defibrillator use. Left ventricular function spontaneously normalized at 3 months. In conclusion, we report the first fulminant B19V myocarditis case temporally associated with aromatic hydrocarbon exposure due to a coexistence of viral and toxic causes. Our case and the systematic review show that promptly performing EMB can provide a definitive diagnosis and guide treatment, especially in severe cases in which infectious agents may contribute to myocardial damage. Full article
(This article belongs to the Special Issue Molecular Research in Myocarditis)
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29 pages, 1152 KB  
Review
Physicochemical Characteristics of Cardiological Drugs and Practical Recommendations for Intravenous Administration: A Systematic Review
by Massimiliano Quici, Elena Martini, Davide Giustivi, Maria Calloni, Chiara Cogliati, Alba Taino, Antonella Foschi, Andrea Gori, Paolo Zappa, Francesco Casella, Arianna Bartoli, Leyla La Cava, Alessia Meschia, Rosita Celano, Francesco Urso, Dario Cattaneo and Antonio Gidaro
Sci. Pharm. 2025, 93(1), 13; https://doi.org/10.3390/scipharm93010013 - 12 Mar 2025
Viewed by 5436
Abstract
Most cardiological drugs need intravenous administration to have a fast effect in an emergency. Intravenous administration is linked to complications, such as tissue infiltration and thrombophlebitis. Aiming to supply an effective tool for the development of appropriate policies, this systematic review provides practical [...] Read more.
Most cardiological drugs need intravenous administration to have a fast effect in an emergency. Intravenous administration is linked to complications, such as tissue infiltration and thrombophlebitis. Aiming to supply an effective tool for the development of appropriate policies, this systematic review provides practical recommendations about the diluent, pH, osmolarity, dosage, vesicant properties, and phlebitis rate of the most commonly used cardiological drugs evaluated in randomized controlled trials (RCTs) till 31 August 2024. The authors searched for available IV cardiological drugs in RCTs in PUBMED EMBASE®, EBSCO-CINAHL®, and Cochrane Controlled Clinical trials. Drugs’ chemical features were obtained online, in drug data sheets, and in scientific papers, establishing that the drugs with a pH of <5 or >9, an osmolarity > 600 mOsm/L, and a high incidence of phlebitis reported in the literature, as well as vesicant drugs, require utmost caution during administration. A total of 857 papers were evaluated and 316 studies were included. A total of 84 cardiological drugs were identified, of which only 31 (37%) can be safely infused via a peripheral route. Thrombolytics and anticoagulants are considered the safest classes of drugs, with only one drug flagged as a “red flag” medication. However, a higher percentage of drugs in other categories meet the “red flag” criteria, including antiarrhythmics (52%), antiplatelet agents (67%), diuretics (67%), antihypertensives (70%), other drugs (77%), and vasoconstrictors and inotropics (89%). Understanding the physicochemical properties of cardiological drugs is essential for significantly improving patient safety and preventing administration errors and local side effects. Full article
(This article belongs to the Topic Challenges and Opportunities in Drug Delivery Research)
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16 pages, 1439 KB  
Review
Automaticity of the Pulmonary Vein Myocardium and the Effect of Class I Antiarrhythmic Drugs
by Iyuki Namekata, Maika Seki, Taro Saito, Ryosuke Odaka, Shogo Hamaguchi and Hikaru Tanaka
Int. J. Mol. Sci. 2024, 25(22), 12367; https://doi.org/10.3390/ijms252212367 - 18 Nov 2024
Viewed by 1263
Abstract
The pulmonary vein wall contains a myocardial layer whose ectopic automaticity is the major cause of atrial fibrillation. This review summarizes the results obtained in isolated pulmonary vein myocardium from small experimental animals, focusing on the studies with the guinea pig. The diversity [...] Read more.
The pulmonary vein wall contains a myocardial layer whose ectopic automaticity is the major cause of atrial fibrillation. This review summarizes the results obtained in isolated pulmonary vein myocardium from small experimental animals, focusing on the studies with the guinea pig. The diversity in the action potential waveform reflects the difference in the repolarizing potassium channel currents involved. The diastolic depolarization, the trigger of automatic action potentials, is caused by multiple membrane currents, including the Na+-Ca2+ exchanger current and late INa. The action potential waveform and automaticity are affected differentially by α- and β-adrenoceptor stimulation. Class I antiarrhythmic drugs block the propagation of ectopic electrical activity of the pulmonary vein myocardium through blockade of the peak INa. Some of the class I antiarrhythmic drugs block the late INa and inhibit pulmonary vein automaticity. The negative inotropic and chronotropic effects of class I antiarrhythmic drugs could be largely attributed to their blocking effect on the Ca2+ channel rather than the Na+ channel. Such a comprehensive understanding of pulmonary vein automaticity and class I antiarrhythmic drugs would lead to an improvement in pharmacotherapy and the development of novel therapeutic agents for atrial fibrillation. Full article
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27 pages, 1497 KB  
Review
Amiodarone Therapy: Updated Practical Insights
by Victorița Șorodoc, Lucia Indrei, Catinca Dobroghii, Andreea Asaftei, Alexandr Ceasovschih, Mihai Constantin, Cătălina Lionte, Bianca Codrina Morărașu, Alexandra-Diana Diaconu and Laurențiu Șorodoc
J. Clin. Med. 2024, 13(20), 6094; https://doi.org/10.3390/jcm13206094 - 12 Oct 2024
Cited by 6 | Viewed by 10485
Abstract
Amiodarone, a bi-iodinated benzofuran derivative, is among the most commonly used antiarrhythmic drugs due to its high level of effectiveness. Though initially categorized as a class III agent, amiodarone exhibits antiarrhythmic properties across all four classes of antiarrhythmic drugs. Amiodarone is highly effective [...] Read more.
Amiodarone, a bi-iodinated benzofuran derivative, is among the most commonly used antiarrhythmic drugs due to its high level of effectiveness. Though initially categorized as a class III agent, amiodarone exhibits antiarrhythmic properties across all four classes of antiarrhythmic drugs. Amiodarone is highly effective in maintaining sinus rhythm in patients with paroxysmal atrial fibrillation while also playing a crucial role in preventing a range of ventricular arrhythmias. Amiodarone has a complex pharmacokinetic profile, characterized by a large volume of distribution and a long half-life, which can range from several weeks to months, resulting in prolonged effects even after discontinuation. Side effects may include thyroid dysfunction, pulmonary fibrosis, and hepatic injury, necessitating regular follow-ups. Additionally, amiodarone interacts with several drugs, including anticoagulants, which must be managed to prevent adverse effects. Therefore, a deep understanding of both oral and intravenous formulations, as well as proper dosage adjustments, is essential. The aim of this paper is to provide a comprehensive and updated review on amiodarone’s indications, contraindications, recommended dosages, drug interactions, side effects, and monitoring protocols. Full article
(This article belongs to the Section Pharmacology)
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12 pages, 533 KB  
Review
The Role of Ranolazine in the Treatment of Ventricular Tachycardia and Atrial Fibrillation: A Narrative Review of the Clinical Evidence
by Kyosuke Murai, Amir Vasigh, Tamás Alexy, Kálmán Tóth and László Czopf
Biomedicines 2024, 12(8), 1669; https://doi.org/10.3390/biomedicines12081669 - 26 Jul 2024
Viewed by 4007
Abstract
Cardiac arrhythmias are among the leading causes of morbidity and mortality worldwide. While antiarrhythmic drugs traditionally represent the first-line management strategy, their use is often limited by profound proarrhythmic effects. Several studies, including randomized control trials (RCTs), have demonstrated the antiarrhythmic efficacy of [...] Read more.
Cardiac arrhythmias are among the leading causes of morbidity and mortality worldwide. While antiarrhythmic drugs traditionally represent the first-line management strategy, their use is often limited by profound proarrhythmic effects. Several studies, including randomized control trials (RCTs), have demonstrated the antiarrhythmic efficacy of ranolazine, which is registered as an antianginal agent, while also establishing its safety profile. This review compiles clinical evidence investigating the antiarrhythmic properties of ranolazine, focusing primarily on ventricular tachycardia (VT) and atrial fibrillation (AF), as they are common rhythm abnormalities with serious complications. Data from RCTs indicate that ranolazine reduces VT incidence, although this effect is not universal. Therefore, we attempt to better describe the patient population that gains the most benefit from ranolazine due to VT suppression. Additionally, ranolazine is known to enhance the conversion rate of AF to sinus rhythm when combined with other antiarrhythmic drugs such as amiodarone, highlighting its synergistic effect in the atrium without provoking ventricular dysrhythmias. Despite the heterogeneity in the currently available data, ranolazine appears to be an effective and safe option for the management of various arrhythmias. Full article
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40 pages, 6645 KB  
Review
The Benzoylpiperidine Fragment as a Privileged Structure in Medicinal Chemistry: A Comprehensive Review
by Giulia Bononi, Chiara Lonzi, Tiziano Tuccinardi, Filippo Minutolo and Carlotta Granchi
Molecules 2024, 29(9), 1930; https://doi.org/10.3390/molecules29091930 - 23 Apr 2024
Cited by 1 | Viewed by 5794
Abstract
The phenyl(piperidin-4-yl)methanone fragment (here referred to as the benzoylpiperidine fragment) is a privileged structure in the development of new drugs considering its presence in many bioactive small molecules with both therapeutic (such as anti-cancer, anti-psychotic, anti-thrombotic, anti-arrhythmic, anti-tubercular, anti-parasitic, anti-diabetic, and neuroprotective agents) [...] Read more.
The phenyl(piperidin-4-yl)methanone fragment (here referred to as the benzoylpiperidine fragment) is a privileged structure in the development of new drugs considering its presence in many bioactive small molecules with both therapeutic (such as anti-cancer, anti-psychotic, anti-thrombotic, anti-arrhythmic, anti-tubercular, anti-parasitic, anti-diabetic, and neuroprotective agents) and diagnostic properties. The benzoylpiperidine fragment is metabolically stable, and it is also considered a potential bioisostere of the piperazine ring, thus making it a feasible and reliable chemical frame to be exploited in drug design. Herein, we discuss the main therapeutic and diagnostic agents presenting the benzoylpiperidine motif in their structure, covering articles reported in the literature since 2000. A specific section is focused on the synthetic strategies adopted to obtain this versatile chemical portion. Full article
(This article belongs to the Special Issue Recent Advances in Development of Small Molecules to Fight Cancer)
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13 pages, 3451 KB  
Article
Intravenous Cavutilide for Pharmacological Conversion of Paroxysmal and Persistent Atrial Fibrillation in Patients with Heart Failure
by Maria M. Beliaeva, Khava M. Dzaurova, Yulia A. Yuricheva, Peter S. Novikov, Nikolay Yu. Mironov, Gennady S. Tarasovskiy, Maksim A. Zelberg, Sergey F. Sokolov and Sergey P. Golitsyn
J. Cardiovasc. Dev. Dis. 2023, 10(12), 487; https://doi.org/10.3390/jcdd10120487 - 6 Dec 2023
Cited by 2 | Viewed by 2297
Abstract
This work aimed to study the efficacy and safety of the class III antiarrhythmic agent cavutilide (Niferidil, Refralon) for pharmacological cardioversion in patients with paroxysmal and persistent atrial fibrillation (AF) and heart failure (HF). Methods and Results: In this retrospective cohort study, 58 [...] Read more.
This work aimed to study the efficacy and safety of the class III antiarrhythmic agent cavutilide (Niferidil, Refralon) for pharmacological cardioversion in patients with paroxysmal and persistent atrial fibrillation (AF) and heart failure (HF). Methods and Results: In this retrospective cohort study, 58 patients with stable HF (aged 69 [61;73] years, 30 males, 78% with persistent AF) and 274 patients without HF (aged 63 [57;70] years, 196 males, 56% with persistent AF) were included. The median AF duration in the group with HF was 35.5 [10.6;124] days, and that in the group without HF was 14.5 [3.6;90] days. All patients received 5–30 µg/kg cavutilide intravenously in one to four (if needed) boluses of 5–5–10–10 µg/kg at 15 min intervals. Subsequent boluses were not administered if the patient’s sinus rhythm (SR) was restored or if bradycardia, QT prolongation > 500 ms or evidence of proarrhythmia was observed. Holter electrocardiogram monitoring was started before infusion and was continued for 24 h. The main criterion for an antiarrhythmic effect was sinus rhythm restoration within 24 h of the initial bolus. Results: Cavutilide converted AF to SR in 37.9% of patients with HF after bolus 1 (5 µg/kg), in 58.6% after bolus 2 (cumulative dose = 10 µg/kg), in 74% of cases after bolus 3 (cumulative dose = 20 µg/kg) and in 92.8% of cases after bolus 4 (cumulative dose = 30 µg/kg). Cavutilide was effective in 89% of cases with persistent AF with a median duration of 70.5 [30;159] days and in 92% of cases with paroxysmal AF with a median duration of 36 [24;102] h. In the group of patients without HF, the effectiveness of bolus 1 was 36.9%, that of the bolus 2 was 58%, that of the bolus 3 was 77% and that of the bolus 4 was 90.1%. Cavutilide restored SR in 90% of patients with persistent AF with a median duration of 82.5 [28;180] days and in 90% of cases with paroxysmal AF with a median duration of 50 [24;120] h. No statistically significant difference in the probability of SR restoration or the effectiveness of each bolus of cavutilide was found between patients with and without HF. The median time to restoration of SR in patients with HF was 23 [11;55] min, and that in patients without HF was 22 [10;45] min (p = 0.424). No cases of symptomatic/severe bradycardia were observed in either group. QT prolongation over 500 ms after cavutilide injection was registered in 19% of patients without HF and in 15.5% of those with HF (p = 0.58). Short runs of Torsade de pointes tachycardia occurred in one patient (0.4%) without HF after 10 µg cavutilide administration and were successfully treated with MgSO4. Conclusions: Cavutilide demonstrated a high likelihood of AF conversion to SR in paroxysmal (92%) and persistent (89%) arrhythmia and HF. Concomitant HF and its severity do not affect the efficacy and safety of cavutilide. Full article
(This article belongs to the Special Issue Heart Failure: Clinical Diagnostics and Treatment)
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21 pages, 292 KB  
Review
Adjunctive Therapeutics in the Management of Cardiopulmonary Resuscitation: A Narrative Literature Review
by Megan Hoffer, Robert C. F. Pena, Quincy K. Tran and Ali Pourmand
J. Clin. Med. 2023, 12(23), 7374; https://doi.org/10.3390/jcm12237374 - 28 Nov 2023
Cited by 1 | Viewed by 2096
Abstract
Nearly 565,000 patients will suffer from prehospital and inpatient cardiac arrest in the United States per annum. Cardiopulmonary resuscitation and all associated interventions used to achieve it remain an essential focus of emergency medicine. Current ACLS guidelines give clear instructions regarding mainstay medications [...] Read more.
Nearly 565,000 patients will suffer from prehospital and inpatient cardiac arrest in the United States per annum. Cardiopulmonary resuscitation and all associated interventions used to achieve it remain an essential focus of emergency medicine. Current ACLS guidelines give clear instructions regarding mainstay medications such as epinephrine and antiarrhythmics; however, the literature remains somewhat controversial regarding the application of adjunctive therapeutics such as calcium, magnesium, sodium bicarbonate, and corticosteroids. The available data acquired in this field over the past three decades offer mixed pictures for each of these medications on the effects of core metrics of cardiopulmonary resuscitation (e.g., rate of return of spontaneous circulation, survival-to-hospitalization and discharge, 24 h and 30 d mortality, neurological outcome), as well as case-specific applications for each of these interventions (e.g., polymorphic ventricular tachycardia, electrolyte derangements, acidosis, post-arrest shock). This narrative literature review provides a comprehensive summary of current guidelines and published data available for these four agents and their use in clinical practice. Full article
15 pages, 2954 KB  
Review
Facilitation of hERG Activation by Its Blocker: A Mechanism to Reduce Drug-Induced Proarrhythmic Risk
by Kazuharu Furutani
Int. J. Mol. Sci. 2023, 24(22), 16261; https://doi.org/10.3390/ijms242216261 - 13 Nov 2023
Cited by 5 | Viewed by 4265
Abstract
Modulation of the human Ether-à-go-go-Related Gene (hERG) channel, a crucial voltage-gated potassium channel in the repolarization of action potentials in ventricular myocytes of the heart, has significant implications on cardiac electrophysiology and can be either antiarrhythmic or proarrhythmic. For example, hERG channel blockade [...] Read more.
Modulation of the human Ether-à-go-go-Related Gene (hERG) channel, a crucial voltage-gated potassium channel in the repolarization of action potentials in ventricular myocytes of the heart, has significant implications on cardiac electrophysiology and can be either antiarrhythmic or proarrhythmic. For example, hERG channel blockade is a leading cause of long QT syndrome and potentially life-threatening arrhythmias, such as torsades de pointes. Conversely, hERG channel blockade is the mechanism of action of Class III antiarrhythmic agents in terminating ventricular tachycardia and fibrillation. In recent years, it has been recognized that less proarrhythmic hERG blockers with clinical potential or Class III antiarrhythmic agents exhibit, in addition to their hERG-blocking activity, a second action that facilitates the voltage-dependent activation of the hERG channel. This facilitation is believed to reduce the proarrhythmic potential by supporting the final repolarizing of action potentials. This review covers the pharmacological characteristics of hERG blockers/facilitators, the molecular mechanisms underlying facilitation, and their clinical significance, as well as unresolved issues and requirements for research in the fields of ion channel pharmacology and drug-induced arrhythmias. Full article
(This article belongs to the Special Issue Cardiac Arrhythmia: Molecular Mechanisms and Therapeutic Strategies)
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28 pages, 5419 KB  
Article
Synthesis and In Vivo Antiarrhythmic Activity Evaluation of Novel Scutellarein Analogues as Voltage-Gated Nav1.5 and Cav1.2 Channels Blockers
by Wei Yang, Wenping Wang, Song Cai, Peng Li, Die Zhang, Jinhua Ning, Jin Ke, Anguo Hou, Linyun Chen, Yunshu Ma and Wenbin Jin
Molecules 2023, 28(21), 7417; https://doi.org/10.3390/molecules28217417 - 3 Nov 2023
Cited by 8 | Viewed by 2064
Abstract
Malignant cardiac arrhythmias with high morbidity and mortality have posed a significant threat to our human health. Scutellarein, a metabolite of Scutellarin which is isolated from Scutellaria altissima L., presents excellent therapeutic effects on cardiovascular diseases and could further be metabolized into methylated [...] Read more.
Malignant cardiac arrhythmias with high morbidity and mortality have posed a significant threat to our human health. Scutellarein, a metabolite of Scutellarin which is isolated from Scutellaria altissima L., presents excellent therapeutic effects on cardiovascular diseases and could further be metabolized into methylated forms. A series of 22 new scutellarein derivatives with hydroxyl-substitution based on the scutellarin metabolite in vivo was designed, synthesized via the conjugation of the scutellarein scaffold with pharmacophores of FDA-approved antiarrhythmic medications and evaluated for their antiarrhythmic activity through the analyzation of the rat number of arrhythmia recovery, corresponding to the recovery time and maintenance time in the rat model of barium chloride-induced arrhythmia, as well as the cumulative dosage of aconitine required to induce VP, VT, VF and CA in the rat model of aconitine-induced arrhythmia. All designed compounds could shorten the time of the arrhythmia continuum induced by barium chloride, indicating that 4′-hydroxy substituents of scutellarein had rapid-onset antiarrhythmic effects. In addition, nearly all of the compounds could normalize the HR, RR, QRS, QT and QTc interval, as well as the P/T waves’ amplitude. The most promising compound 10e showed the best antiarrhythmic activity with long-term efficacy and extremely low cytotoxicity, better than the positive control scutellarein. This result was also approved by the computational docking simulation. Most importantly, patch clamp measurements on Nav1.5 and Cav1.2 channels indicated that compound 10e was able to reduce the INa and ICa in a concentration-dependent manner and left-shifted the inactivation curve of Nav1.5. Taken together, all compounds were considered to be antiarrhythmic. Compound 10e even showed no proarrhythmic effect and could be classified as Ib Vaughan Williams antiarrhythmic agents. What is more, compound 10e did not block the hERG potassium channel which highly associated with cardiotoxicity. Full article
(This article belongs to the Section Medicinal Chemistry)
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Article
Development of Solid Lipid Nanoparticles for Controlled Amiodarone Delivery
by Andreea Creteanu, Gabriela Lisa, Cornelia Vasile, Maria-Cristina Popescu, Adrian Florin Spac and Gladiola Tantaru
Methods Protoc. 2023, 6(5), 97; https://doi.org/10.3390/mps6050097 - 9 Oct 2023
Cited by 7 | Viewed by 3107
Abstract
In various drug delivery systems, solid lipid nanoparticles are dominantly lipid-based nanocarriers. Amiodarone hydrochloride is an antiarrhythmic agent used to treat severe rhythm disturbances. It has variable and hard-to-predict absorption in the gastrointestinal tract because of its low solubility and high permeability. The [...] Read more.
In various drug delivery systems, solid lipid nanoparticles are dominantly lipid-based nanocarriers. Amiodarone hydrochloride is an antiarrhythmic agent used to treat severe rhythm disturbances. It has variable and hard-to-predict absorption in the gastrointestinal tract because of its low solubility and high permeability. The aims of this study were to improve its solubility by encapsulating amiodarone into solid lipid nanoparticles using two excipients—Compritol® 888 ATO (pellets) (C888) as a lipid matrix and Transcutol® (T) as a surfactant. Six types of amiodarone-loaded solid lipid nanoparticles (AMD-SLNs) were obtained using a hot homogenization technique followed by ultrasonication with varying sonication parameters. AMD-SLNs were characterized by their size distribution, polydispersity index, zeta potential, entrapment efficiency, and drug loading. Based on the initial evaluation of the entrapment efficiency, only three solid lipid nanoparticle formulations (P1, P3, and P5) were further tested. They were evaluated through scanning electron microscopy, Fourier-transform infrared spectrometry, near-infrared spectrometry, thermogravimetry, differential scanning calorimetry, and in vitro dissolution tests. The P5 formulation showed optimum pharmaco-technical properties, and it had the greatest potential to be used in oral pharmaceutical products for the controlled delivery of amiodarone. Full article
(This article belongs to the Special Issue Feature Papers in Methods and Protocols 2023)
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