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1.
Sulfide regulation of cardiovascular function in health and disease.
Kolluru, GK, Shackelford, RE, Shen, X, Dominic, P, Kevil, CG
Nature reviews. Cardiology. 2023;(2):109-125
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Abstract
Hydrogen sulfide (H2S) has emerged as a gaseous signalling molecule with crucial implications for cardiovascular health. H2S is involved in many biological functions, including interactions with nitric oxide, activation of molecular signalling cascades, post-translational modifications and redox regulation. Various preclinical and clinical studies have shown that H2S and its synthesizing enzymes - cystathionine γ-lyase, cystathionine β-synthase and 3-mercaptosulfotransferase - can protect against cardiovascular pathologies, including arrhythmias, atherosclerosis, heart failure, myocardial infarction and ischaemia-reperfusion injury. The bioavailability of H2S and its metabolites, such as hydropersulfides and polysulfides, is substantially reduced in cardiovascular disease and has been associated with single-nucleotide polymorphisms in H2S synthesis enzymes. In this Review, we highlight the role of H2S, its synthesizing enzymes and metabolites, their roles in the cardiovascular system, and their involvement in cardiovascular disease and associated pathologies. We also discuss the latest clinical findings from the field and outline areas for future study.
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Effect of sacubitril-valsartan on the incidence of atrial fibrillation: A meta-analysis.
Mohammad, Z, Ahmad, J, Sultan, A, Penagaluri, A, Morin, D, Dominic, P
Journal of cardiovascular electrophysiology. 2023;(4):1037-1042
Abstract
INTRODUCTION Sacubitril/valsartan reduces all-cause mortality in heart failure (HF) patients compared to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). ACEIs/ARBs have been shown to decrease the incidence of atrial fibrillation (AF). We hypothesized sacubitril-valsartan decreases the incidence of AF compared to ACEis/ARBs. METHODS Clinicaltrials.gov was searched for trials by terms sacubitril/valsartan, entresto, sacubitril, valsartan. Randomized controlled human trials of sacubitril/valsartan reporting AF were included. Data were extracted independently by two reviewers. Data was pooled using a random effect model. Publication bias was evaluated by funnel plots. RESULTS A total of 11 trials including 11,458 patients on sacubitril/valsartan and 10,128 patients on ACEI/ARBs were identified. A total of 284 AF events were reported in the sacubitril/valsartan group compared to 256 AF events in ACEIs/ARBs. Patients on sacubitril/valsartan were as likely as patients on ACEIs/ARBs to develop AF (pooled odds ratio [OR] = 1.091, 95% confidence interval [CI] = 0.917-1.298, p = .324). Six atrial flutter (AFl) events were reported in six trials; 48 out of 9165 patients in the sacubitril/valsartan group developed AFl compared to 46 out of 8759 in ACEi/ARBs group. There was no difference in AFl risk between the two groups (pooled OR = 1.028, 95% CI = 0.681-1.553, p = .894). Finally, sacubitril/valsartan did not reduce the risk of atrial arrhythmias (AF + AFl) compared to ACEi/ARBs (pooled OR = 1.081, 95% CI = 0.922-1.269, p = .337). CONCLUSION Although sacubitril/valsartan reduces mortality compared to ACEIs/ARBs in HF patients, they do not reduce AF risk compared to these drugs.
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COVID-19 Vaccination and Cardiac Arrhythmias: A Review.
Pari, B, Babbili, A, Kattubadi, A, Thakre, A, Thotamgari, S, Gopinathannair, R, Olshansky, B, Dominic, P
Current cardiology reports. 2023;(9):925-940
Abstract
PURPOSE OF REVIEW In this review, we aim to delve into the existing literature, seeking to uncover the mechanisms, investigate the electrocardiographic changes, and examine the treatment methods of various cardiac arrhythmias that occur after administration of the COVID-19 vaccine. RECENT FINDINGS A global survey has exposed an incidence of arrhythmia in 18.27% of hospitalized COVID-19 patients. Furthermore, any type of COVID-19 vaccine - be it mRNA, adenovirus vector, whole inactivated, or protein subunit - appears to instigate cardiac arrhythmias. Among the cardiac adverse events reported post-COVID-19 vaccination, myocarditis emerges as the most common and is thought to be a potential cause of bradyarrhythmia. When a patient post-COVID-19 vaccination presents a suspicion of cardiac involvement, clinicians should perform a comprehensive history and physical examination, measure electrolyte levels, conduct ECG, and carry out necessary imaging studies. In our extensive literature search, we uncovered various potential mechanisms that might lead to cardiac conduction abnormalities and autonomic dysfunction in patients who have received the COVID-19 vaccine. These mechanisms encompass direct viral invasion through molecular mimicry/spike (S) protein production, an escalated inflammatory response, hypoxia, myocardial cell death, and the eventual scar/fibrosis. They correspond to a range of conditions including atrial tachyarrhythmias, bradyarrhythmia, ventricular arrhythmias, sudden cardiac death, and the frequently occurring myocarditis. For treating these COVID-19 vaccination-induced arrhythmias, we should incorporate general treatment strategies, similar to those applied to arrhythmias from other causes.
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Sacubitril/valsartan: An antiarrhythmic drug?
Huang, E, Bernard, ML, Elise Hiltbold, A, Khatib, S, Polin, GM, Rogers, PA, Dominic, P, Morin, DP
Journal of cardiovascular electrophysiology. 2022;(11):2375-2381
Abstract
INTRODUCTION Heart failure (HF) is a major cause of morbidity and mortality, with nearly half of all HF-related deaths resulting from sudden cardiac death (SCD), most often from an arrhythmic event. The pathophysiologic changes that occur in response to the hemodynamic stress of HF may lead to increased arrhythmogenesis. Theoretically, medications that block these arrhythmogenic substrates would decrease the risk of SCD. The combined angiotensin receptor and neprilysin inhibitor (ARNi; tradename Entresto) is the newest commercially available medication for the treatment of heart failure. METHODS AND RESULTS We reviewed and synthesized the available literature regarding sacubitril/valsartan and its effects on cardiac rhythm. ARNi has been shown to decrease cardiovascular mortality and hospitalization in patients with HF with reduced ejection fraction (HFrEF). Emerging evidence suggests that ARNi also may play a role in reducing arrhythmogenesis and thereby SCD. CONCLUSION This review summarizes the current data regarding this ARNi and its potential antiarrhythmic effects.
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Stimulant Drugs of Abuse and Cardiac Arrhythmias.
Dominic, P, Ahmad, J, Awwab, H, Bhuiyan, MS, Kevil, CG, Goeders, NE, Murnane, KS, Patterson, JC, Sandau, KE, Gopinathannair, R, et al
Circulation. Arrhythmia and electrophysiology. 2022;(1):e010273
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Abstract
Nonmedical use of prescription and nonprescription drugs is a worldwide epidemic, rapidly growing in magnitude with deaths because of overdose and chronic use. A vast majority of these drugs are stimulants that have various effects on the cardiovascular system including the cardiac rhythm. Drugs, like cocaine and methamphetamine, have measured effects on the conduction system and through several direct and indirect pathways, utilizing multiple second messenger systems, change the structural and electrical substrate of the heart, thereby promoting cardiac dysrhythmias. Substituted amphetamines and cocaine affect the expression and activation kinetics of multiple ion channels and calcium signaling proteins resulting in EKG changes, and atrial and ventricular brady and tachyarrhythmias. Preexisting conditions cause substrate changes in the heart, which decrease the threshold for such drug-induced cardiac arrhythmias. The treatment of cardiac arrhythmias in patients who take drugs of abuse may be specialized and will require an understanding of the unique underlying mechanisms and necessitates a multidisciplinary approach. The use of primary or secondary prevention defibrillators in drug abusers with chronic systolic heart failure is both sensitive and controversial. This review provides a broad overview of cardiac arrhythmias associated with stimulant substance abuse and their management.
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Prognostic value of cardiac biomarkers in COVID-19 infection.
Sheth, A, Modi, M, Dawson, D, Dominic, P
Scientific reports. 2021;(1):4930
Abstract
Multiple Biomarkers have recently been shown to be elevated in COVID-19, a respiratory infection with multi-organ dysfunction; however, information regarding the prognostic value of cardiac biomarkers as it relates to disease severity and cardiac injury are inconsistent. The goal of this meta-analysis was to summarize the evidence regarding the prognostic relevance of cardiac biomarkers from data available in published reports. PubMed, Embase and Web of Science were searched from inception through April 2020 for studies comparing median values of cardiac biomarkers in critically ill versus non-critically ill COVID-19 patients, or patients who died versus those who survived. The weighted mean differences (WMD) and 95% confidence interval (CI) between the groups were calculated for each study and combined using a random effects meta-analysis model. The odds ratio (OR) for mortality based on cardiac injury was combined from studies reporting it. Troponin levels were significantly higher in COVID-19 patients who died or were critically ill versus those who were alive or not critically ill (WMD 0.57, 95% CI 0.43-0.70, p < 0.001). Additionally, BNP levels were also significantly higher in patients who died or were critically ill (WMD 0.45, 95% CI - 0.21-0.69, p < 0.001). Cardiac injury was independently associated with significantly increased odds of mortality (OR 6.641, 95% CI 1.26-35.1, p = 0.03). A significant difference in levels of D-dimer was seen in those who died or were critically ill. CK levels were only significantly higher in those who died versus those who were alive (WMD 0.79, 95% CI 0.25-1.33, p = 0.004). Cardiac biomarkers add prognostic value to the determination of the severity of COVID-19 and can predict mortality.
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Aldosterone Antagonist Therapy and Mortality in Patients With ST-Segment Elevation Myocardial Infarction Without Heart Failure: A Systematic Review and Meta-analysis.
Dahal, K, Hendrani, A, Sharma, SP, Singireddy, S, Mina, G, Reddy, P, Dominic, P, Modi, K
JAMA internal medicine. 2018;(7):913-920
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Abstract
IMPORTANCE Treatment with aldosterone antagonists is recommended and has been shown to have beneficial effects in patients with ST-segment elevation myocardial infarction (STEMI) and left ventricular ejection fraction (LVEF) less than 40%. However, the role of aldosterone antagonists in patients with ejection fraction greater than 40% or without congestive heart failure is not well known. OBJECTIVES To perform a systematic review and meta-analysis using standard techniques to determine the role of therapy with aldosterone antagonists in this patient population. DATA SOURCES PubMed, Embase, CINAHL, and Cochrane Central databases were searched and a manual search for relevant references from the selected articles and published reviews was performed from database inception through June 2017. STUDY SELECTION Randomized clinical trials that evaluated treatment with aldosterone antagonists in patients with STEMI without clinical heart failure or LVEF greater than 40% were included. DATA EXTRACTION AND SYNTHESIS Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used to conduct and report the meta-analysis, which used a random-effects model. Two investigators independently performed the database search and agreed on the final study selection. A manual search was performed for relevant references from the selected articles and published reviews. MAIN OUTCOMES AND MEASURES The outcomes analyzed were mortality, new congestive heart failure, recurrent myocardial infarction, ventricular arrhythmia, and changes in LVEF, serum potassium level, and creatinine level at follow-up. RESULTS In all, 10 randomized clinical trials with a total of 4147 unique patients were included in the meta-analysis. In patients who presented with STEMI without heart failure, treatment with aldosterone antagonists compared with control was associated with lower risk of mortality (2.4% vs 3.9%; odds ratio [OR], 0.62; 95% CI, 0.42-0.91; P = .01) and similar risks of myocardial infarction (1.6% vs 1.5%; OR, 1.03; 95% CI, 0.57-1.86; P = .91), new congestive heart failure (4.3% vs 5.4%; OR, 0.82; 95% CI, 0.56-1.20; P = .31), and ventricular arrhythmia (4.1% vs 5.1%; OR, 0.76; 95% CI, 0.45-1.31; P = .33). Similarly, treatment with aldosterone antagonists compared with control was associated with a small yet significant increase in LVEF (mean difference, 1.58%; 95% CI, 0.18%-2.97%; P = .03), a small increase in serum potassium level (mean difference, 0.07 mEq/L; 95% CI, 0.01-0.13 mEq/L; P = .02), and no change in serum creatinine level (standardized mean difference, 1.4; 95% CI, -0.43 to 3.24; P = .13). CONCLUSIONS AND RELEVANCE Treatment with aldosterone antagonists is associated with a mortality benefit in patients with STEMI with LVEF greater than 40% or without heart failure.
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Non-vitamin K antagonists oral anticoagulants are as safe and effective as warfarin for cardioversion of atrial fibrillation: A systematic review and meta-analysis.
Telles-Garcia, N, Dahal, K, Kocherla, C, Lip, GYH, Reddy, P, Dominic, P
International journal of cardiology. 2018;:143-148
Abstract
BACKGROUND Current guidelines recommend anticoagulation using warfarin with bridging parenteral anticoagulation or one of the non-vitamin K antagonist oral anticoagulants (NOACs) to prevent thromboembolic events in patients undergoing cardioversion for atrial fibrillation (AF). We aimed to compare by meta-analytical techniques, the safety and efficacy of NOACs versus warfarin in patients undergoing cardioversion. METHODS PUBMED, EMBASE, Cochrane CENTRAL and CINAHL were searched electronically in addition to manual search for randomized controlled trials (RCTs) comparing NOACs and warfarin in patients undergoing cardioversion for AF. Mortality, major bleeding and ischemic and hemorrhagic stroke were compared between the two agents. RESULTS A total of 7 trials with 7588 total patients were included in the meta-analysis. NOACs, as compared to warfarin, resulted in similar risk of ischemic stroke [odds ratio (OR): 0.49 (95% confidence interval (CI): 0.20-1.19; P = 0.12], major bleeding [0.71 (0.37-1.38), P = 0.32], mortality [0.73 (0.32-1.67); P = 0.45], and hemorrhagic stroke [0.96 (0.11-8.70); P = 0.97]. The results were consistent across subgroup analyses. CONCLUSIONS Based on the current meta-analysis, NOACs and warfarin have comparable efficacy and safety in patients with atrial fibrillation undergoing cardioversion.