Cardioprotective and Antianginal Efficacy of Nicorandil: A Comprehensive Review.

ABSTRACT: Angina pectoris remains a significant burden despite advances in medical therapy and coronary revascularization. Many patients (up to 30%) with angina have normal coronary arteries, with coronary microvascular disease and/or coronary artery vasospasm being major drivers of the myocardial demand-supply mismatch. Even among patients revascularized for symptomatic epicardial coronary stenosis, recurrent angina remains highly prevalent. Medical therapy for angina currently centers around 2 disparate goals, viz secondary prevention of hard clinical outcomes and symptom control. Vasodilators, such as nitrates, have been first-line antianginal agents for decades, along with beta-blockers and calcium channel blockers. However, efficacy in symptoms control is heterogenous, depending on underlying mechanism(s) of angina in an individual patient, often necessitating multiple agents. Nicorandil (NCO) is an antianginal agent first discovered in the late 1970s with a uniquely dual mechanism of action. Like a typical nitrate, it mediates medium-large vessel vasodilation through nitric oxide. In addition, NCO has adenosine triphosphate (ATP)-dependent potassium channel agonist activity (K ATP ), mediating microvascular dilatation. Hence, it has proven effective in both coronary artery vasospasm and coronary microvascular disease, typically challenging patient populations. Moreover, emerging evidence suggests that cardiomyocyte protection against ischemia through ischemic preconditioning may be mediated through K ATP agonism. Finally, there is now fairly firm evidence in favor of NCO in terms of hard event reduction among patients with stable coronary artery disease, following myocardial infarction, and perhaps even among patients with congestive heart failure. This review aims to summarize the mechanism of action of NCO, its efficacy as an antianginal, and current evidence behind its impact on hard outcomes. Finally, we review other cardiac and emerging noncardiac indications for NCO use.

Strategies for combating antibiotic resistance in bacterial biofilms.

Biofilms, which are complexes of microorganisms that adhere to surfaces and secrete protective extracellular matrices, wield substantial influence across diverse domains such as medicine, industry, and environmental science. Despite ongoing challenges posed by biofilms in clinical medicine, research in this field remains dynamic and indeterminate. This article provides a contemporary assessment of biofilms and their treatment, with a focus on recent advances, to chronicle the evolving landscape of biofilm research.

A Rare Case of ST-Segment Elevation Myocardial Infarction and Left Ventricular Thrombus in a Dextrocardia Patient With COVID-19 Infection.

Acute coronary syndrome (ACS) is an increasingly common finding among patients presenting with Coronavirus Disease 2019 (COVID-19) pneumonia. While cardiovascular disease alone remains one of the most common causes of death among COVID-19 patients in the United States, its heightened prevalence with COVID-19 pneumonia has been well documented. Here we present the case of a 58-year-old male with an extensive cardiac history including coronary artery disease (CAD) with multiple drug-eluting stents (DES) placed and an episode of cardiac arrest requiring implantable cardioverter defibrillator (ICD) placement. He presented to the Emergency Department originally complaining of chest pain, shortness of breath, and fatigue, and was found to be positive for COVID-19 pneumonia. Cardiac catheterization demonstrated extensive CAD and evaluation for coronary artery bypass grafting (CABG) was warranted. Shortly after, the patient experienced an acute thrombotic episode in the left anterior descending (LAD) coronary artery and underwent successful emergent high-risk percutaneous coronary intervention (PCI) with DES placement. The patient was also found to have a left ventricular thrombus requiring anticoagulation. Despite his complex course, the patient had a very favorable outcome.

Impact of Atrial Fibrillation on In-hospital Outcomes and Healthcare Resource Utilization of Women With Peripartum Cardiomyopathy: A Study From National Inpatient Sample.

There is limited data on the impact of atrial fibrillation (Afib) on hospital outcomes in females with peripartum cardiomyopathy (PPCM). The National Inpatient Sample (NIS) 2011-2019 was used to find patients with PPCM. PPCM patients were divided into 2 groups: with and without Afib. Baseline characteristics were compared between both groups. Logistic regression was used to find independent predictors of Afib. Out of 13,840 PPCM patients, 249 (1.8%) also had a diagnosis of Afib. The Afib group was older and had a high burden of comorbidities. PPCM patients with Afib had higher in-hospital mortality (4-vs-0.7%, P=0.02), mean length of stay (11.3-vs-4.3 days, P<0.001) and healthcare resource utilization. Old age, low-income quartile, liver disease, obstructive sleep apnea, and acute posthemorrhagic anemia were significant predictors of Afib. In conclusion, Afib is associated with higher in-hospital mortality and worse outcomes in females with PPCM. Further research is needed to improve these outcomes.

Diabetes, stroke, and neuroresilience: looking beyond hyperglycemia.

Ischemic stroke is a leading cause of morbidity and mortality among type 2 diabetic patients. Preclinical and translational studies have identified critical pathophysiological mediators of stroke risk, recurrence, and poor outcome in diabetic patients, including endothelial dysfunction and inflammation. Most clinical trials of diabetes and stroke have focused on treating hyperglycemia alone. Pioglitazone has shown promise in secondary stroke prevention for insulin-resistant patients; however, its use is not yet widespread. Additional research into clinical therapies directed at diabetic pathophysiological processes to prevent stroke and improve outcome for diabetic stroke survivors is necessary. Resilience is the process of active adaptation to a stressor. In patients with diabetes, stroke recovery is impaired by insulin resistance, endothelial dysfunction, and inflammation, which impair key neuroresilience pathways maintaining cerebrovascular integrity, resolving poststroke inflammation, stimulating neural plasticity, and preventing neurodegeneration. Our review summarizes the underpinnings of stroke risk in diabetes, the clinical consequences of stroke in diabetic patients, and proposes hypotheses and new avenues of research for therapeutics to stimulate neuroresilience pathways and improve stroke outcome in diabetic patients.

Loperamide-Induced Cardiac Events: Case Reports and Review.

Reports of cardiac arrhythmia secondary to loperamide toxicity have become increasingly common in the literature. We present two patients in their mid-20s, each having overdosed on loperamide and subsequently manifesting life-threatening cardiac arrhythmias not otherwise explained by known pathology. An analysis of the limited research available indicates that loperamide's capacity to block ion channels may be responsible for these events. A better mechanistic understanding of loperamide's effects can help inform clinical management of patients with these life-threatening symptoms as at this time no set guidelines for management have yet been established.

Native valve emphysematous enterococcal endocarditis: expanding the differential diagnosis.

INTRODUCTION: Emphysematous endocarditis is caused by the gas-forming organisms Citrobacter koseri, Escherichia coli, Clostridium species, and Finegoldia magna. We report the first case of emphysematous endocarditis caused by Enterococcus faecalis. CASE REPORT: An 82-year-old man presented with fever and rapidly progressive shortness of breath. He was found to be in atrial fibrillation with rapid ventricular rates. Two-dimensional transthoracic echocardiography demonstrated severe mitral regurgitation. Subsequent two- and three-dimensional transesophageal echocardiogram revealed a large, highly mobile vegetation on the atrial surface of the anterior mitral leaflet with aneurysmal destruction of the lateral scallop requiring mitral valve replacement. Sequencing of the vegetation revealed Enterococcus faecalis, an anaerobic gram-positive coccus that, in rare cases, produces gas using a heme-dependent catalase. Histopathological analysis of the infected valve suggested interstitial gas accumulation, leading to the diagnosis of emphysematous endocarditis. CONCLUSIONS: E. faecalis-associated emphysematous endocarditis should be included in the differential diagnosis of valvular vegetation in patients with a rapidly progressing clinical course. When possible, histopathological analysis should be used alongside other imaging techniques to confirm the diagnosis of emphysematous endocarditis. This case also highlights the importance of collecting blood cultures prior to initiating antibiotic treatment.

Frog sign and AV nodal reentrant tachycardia: A case report.

Supraventricular tachycardia is one the most frequent cardiac arrhythmias seen in patients, with AVNRT being the most common subtype. Two subgroups of AVNRT have been reported, that of typical and atypical. "Frog Sign," long considered a classic physical exam sign, albeit rare, is associated with typical AVNRT. We present a case of a patient who presented with frog sign and ultimately was determined to have AVNRT. Knowledge of "frog" sign aids clinical diagnosis and correct treatment.

Temporal Trend, Prevalence, Predictors, and Outcomes of Pericardial Diseases in Patients Undergoing Transcatheter Aortic Valve Repair.

Background Pericardial disease (PD) - acute pericarditis (AP) and pericardial effusion (PE) - is a rare complication of transcatheter aortic valve repair (TAVR) although its prevalence, predictors, and outcomes are not well studied. Methods We used the National Inpatient Sample (NIS) database to find patients who received TAVR between 2011 and 2018. TAVR patients were divided into two groups: with and without PD (AP and/or PE). The baseline characteristics between the two groups were compared using the Chi-square test and student t-test. Variables with a p-value of 0.20 or less from the univariate logistic regression were included in the multivariate logistic regression to find independent predictors of PD in TAVR patients. Results Out of 218,340 TAVR hospitalizations, 4323 (1.2%) had a concurrent diagnosis of PD. TAVR patients with PD were older (81 ± 7 vs 80 ± 6 years, p < 0.05), more likely to be females (62 vs 46%, p < 0.001), white (84.2 vs 82.9%, p = 0.83), and had a higher burden of comorbidities (Table 3). TAVR patients with PD had higher in-hospital mortality rate (12.3 vs 1.9%, p < 0.001), mean length of stay (8.4 vs 5.3 days, p < 0.001), and mean total hospital cost ($283,389 vs $224,544, p < 0.001). Age > 75, female sex, atrial fibrillation (Afib), atrial flutter (Aflutter), peripheral vascular disease (PVD), coagulopathy, cirrhosis, malnutrition, percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and pacemaker (PM) implantation were the independent predictors of PD in TAVR patients. Conclusion Older, white females with a higher burden of comorbidities and cardiovascular procedures are at higher risk of pericardial complications of TAVR procedure. Sex-based disparities in the prevalence of PD after TAVR is an area of further research. Careful selection of patients for TAVR is essential to reduce the burden of these complications.

Temporal Trend, Prevalence, Predictors and Outcomes of Gastrointestinal Bleed in Hypertrophic Cardiomyopathy in the United States (from the National Inpatient Sample).

Gastrointestinal bleed (GIB) is an important complication in patients with hypertrophic cardiomyopathy (HC) although its prevalence, predictors and outcomes are unknown. The national inpatient sample 2011 to 2018 was analyzed to find hospitalizations with the diagnosis of HC. HC patients were divided into 2 groups: with and without GIB. Baseline characteristics between the 2 groups were compared (Table 2). Variables with p value of 0.2 or less from univariate logistic regression were included in the multivariate logistic regression to find an independent predictor of GIB in HC patients. Stata IC was used for all statistical analysis. Our study reported 242,172 HC hospitalizations between 2011 and 2018, out of which 13,231 (5.4%) also has a concurrent diagnosis of GIB. The GIB group was older (mean age ± SD: 70 ± 28 vs 65 ± 10, p <0.001), more likely to be female (62.5 vs 57%, p <0.001) and had higher burden of comorbidities . HC patients with GIB had higher in-hospital mortality rate (5.3 vs 3.1%, p <0.001), mean length of stay (7.8 vs 5.6 days, p <0.001) and mean total hospital cost ($100,294 vs 77,966, p <0.001). Age group >75, female, chronic kidney disease (CKD 3/4), end-stage renal disease, cirrhosis, coagulopathy and malnutrition were an independent predictor of GIB in HC patients. In conclusion, the prevalence of GIB during HC hospitalizations is increasing. Older, white, females with higher burden of comorbidities are at an increased risk of GIB in HC patients. Sex-based disparities in the prevalence of GIB in HC patients is an area of further research.

Improving the therapeutic efficiency of noncoding RNAs in cancers using targeted drug delivery systems.

The delivery of noncoding (nc)RNA to target cancer stem cells and metastatic tumors has shown many positive outcomes, resulting in improved and more efficient treatment strategies. The success of therapeutic RNA depends solely on passing cellular barriers to reach the target site, where it binds to the mRNA of the interest. By 2018, 20 clinical trials had been initiated, most focusing on cancer and diabetes, with some progressing to Phase II clinical trials testing the safety and efficacy of small interfering (si)RNA. Many challenges limit RNA interference (RNAi) and miRNA usage in vivo; therefore, various approaches have been developed to promote ncRNA efficiency and stability. In this review, we focus on targeting the tumor microenvironment (TME) via the modification of delivery systems utilizing nanotechnology-based delivery approaches.

Heart-type fatty acid-binding protein: an overlooked cardiac biomarker.

Cardiac troponins (cTn) are currently the standard of care for the diagnosis of acute coronary syndromes (ACS) in patients presenting to the emergency department (ED) with chest pain (CP). However, their plasma kinetics necessitate a prolonged ED stay or overnight hospital admission, especially in those presenting early after CP onset. Moreover, ruling out ACS in low-risk patients requires prolonged ED observation or overnight hospital admission to allow serial measurements of c-Tn, adding cost. Heart-type fatty acid-binding protein (H-FABP) is a novel marker of myocardial injury with putative advantages over cTn. Being present in abundance in the myocellular cytoplasm, it is released rapidly (<1 h) after the onset of myocardial injury and could potentially play an important role in both earlier diagnosis of high-risk patients presenting early after CP onset, as well as in risk-stratifying low-risk patients rapidly. Like cTn, H-FABP also has a potential role as a prognostic marker in other conditions where the myocardial injury occurs, such as acute congestive heart failure (CHF) and acute pulmonary embolism (PE). This review provides an overview of the evidence examining the role of H-FABP in early diagnosis and risk stratification of patients with CP and in non-ACS conditions associated with myocardial injury. Key messages Heart-type fatty acid-binding protein is a biomarker that is elevated early in myocardial injury The routine use in the emergency department complements the use of troponins in ruling out acute coronary syndromes in patients presenting early with chest pain It also is useful in risk stratifying patients with other conditions such as heart failure and acute pulmonary embolism.