Dimitrios Oikonomou

Amiodarone and cardiac arrest: Systematic review and meta-analysis

INTRODUCTION The 2015 Guidelines for Resuscitation recommend amiodarone as the antiarrhythmic drug of choice in the treatment of resistant ventricular fibrillation or pulseless ventricular tachycardia. We reviewed the effects of amiodarone on survival and neurological outcome after cardiac arrest. METHODS We systematically searched MEDLINE and Cochrane Library from 1940 to March 2016 without language restrictions. Randomized control trials (RCTs) and observational studies were selected. RESULTS Our search initially identified 1663 studies, 1458 from MEDLINE and 205 from Cochrane Library. Of them, 4 randomized controlled studies and 6 observational studies met the inclusion criteria and were selected for further review. Three randomized studies were included in the meta-analysis. Amiodarone significantly improves survival to hospital admission (OR=1.402, 95% CI: 1.068-1.840, Z=2.43, P=0.015), but neither survival to hospital discharge (RR=0.850, 95% CI: 0.631-1.144, Z=1.07, P=0.284) nor neurological outcome compared to placebo or nifekalant (OR=1.114, 95% CI: 0.923-1.345, Z=1.12, P=0.475). CONCLUSIONS Amiodarone significantly improves survival to hospital admission. However there is no benefit of amiodarone in survival to discharge or neurological outcomes compared to placebo or other antiarrhythmics.

Azilsartan as a Potent Antihypertensive Drug with Possible Pleiotropic Cardiometabolic Effects: A Review Study

Background: Hypertension related cardiovascular (CV) complications could be amplified by the presence of metabolic co-morbidities. Azilsartan medoxomil (AZL-M) is the eighth approved member of angiotensin II receptor blockers (ARBs), a drug class of high priority in the management of hypertensive subjects with diabetes mellitus type II (DMII). Methods: Under this prism, we performed a systematic review of the literature for all relevant articles in order to evaluate the efficacy, safety, and possible clinical role of AZL-M in hypertensive diabetic patients. Results: AZL-M was found to be more effective in terms of reducing indices of blood pressure over alternative ARBs or angiotensin-converting enzyme (ACE) inhibitors with minimal side effects. Preclinical studies have established pleiotropic effects for AZL-M beyond its primary antihypertensive role through differential gene expression, up-regulation of membrane receptors and favorable effect on selective intracellular biochemical and pro-atherosclerotic pathways. Conclusion: Indirect but accumulating evidence from recent literature supports the efficacy and safety of AZL-M among diabetic patients. However, no clinical data exist to date that evince a beneficial role of AZL-M in patients with metabolic disorders on top of its antihypertensive effect. Further clinical studies are warranted to assess the pleiotropic cardiometabolic benefits of AZL-M that are derived from preclinical research.

Effects of oral and non-insulin injectable antidiabetic treatment in hypertension: a systematic review

BACKGROUND Diabetes mellitus type 2 (T2DM) often co-exists with hypertension, and this aggregation of co-morbidities amplifies the risk for future cardiovascular events. Therefore, it appears crucial to understand the essence of choosing oral and non-insulin injectable anti-diabetic drugs (ADs) with a favorable hemodynamic impact that could partially attenuate the increased baseline cardiovascular risk. OBJECTIVE We sought to evaluate the effect of ADs on blood pressure (BP) indices and to assess the potential role of certain ADs towards hypertension treatment. METHOD We performed a systematic review of the literature searching MEDLINE via Pubmed for all human studies implementing ADs, either individually or in combinations. RESULTS Metformin was found to reduce BP in small cohorts but failed to confirm its beneficial effect in a metaanalysis of 41 studies. Thiazolidinediones are associated with BP lowering but are contraindicated in patients with heart failure. Sulfonylureas, on the other hand, may increase BP, while a-glucosidase inhibitors, DPP-4 inhibitors, and SGLT2 inhibitors activate favorable pathophysiologic mechanisms serving as potential BP lowering agents. Relevant BP reduction was established for GLP-1 Ras in most clinical trials. CONCLUSION The favorable hemodynamic impact of certain classes of ADs might provide synergistic or incremental therapeutic benefits in high-risk patients suffering from both T2DM and hypertension. Additional randomized trials designed under the hypothesis of the emerging beneficial hemodynamic effect of ADs are expected to provide more robust evidence and to guide the optimization of combined treatment strategies in this challenging group of patients.

Aortic Stenosis, Aortic Regurgitation and Arterial Hypertension

BACKGROUND Hypertension (HT) is an important risk factor for cardiovascular disease and might precipitate pathology of the aortic valve. OBJECTIVE To investigate the association of HT with aortic dysfunction (including both aortic regurgitation and stenosis) and the impact of antihypertensive treatment on the natural course of underlying aortic disease. METHODS We performed a systematic review of the literature for all relevant articles assessing the correlation between HT and phenotype of aortic disease. RESULTS Co-existence of HT with aortic stenosis and aortic regurgitation is highly prevalent in hypertensive patients and predicts a worse prognosis. Certain antihypertensive agents may improve haemodynamic parameters (aortic jet velocity, aortic regurgitation volume) and remodeling of the left ventricle, but there is no strong evidence of benefit regarding clinical outcomes. Renin-angiotensin system inhibitors, among other vasodilators, are well-tolerated in aortic stenosis. CONCLUSION Several lines of evidence support a detrimental association between HT and aortic valve disease. Therefore, HT should be promptly treated in aortic valvulopathy. Despite conventional wisdom, specific vasodilators can be used with caution in aortic stenosis.

Intracholecystic papillary-tubular neoplasm in a patient with choledochal cyst: a link between choledochal cyst and gallbladder cancer?

BackgroundIntracholecystic papillary-tubular neoplasms are rare precursor lesions of gallbladder cancer. They were proposed as a separate pathologic entity in 2012 by Adsay et al. for the unification of a variety of mass-forming precursor lesions including papillary adenomas, tubulopapillary adenomas, intestinal adenomas, and others. They are considered homologous to intrapapillary mucinous neoplasms of the pancreas and intrabiliary papillary neoplasms of the common bile duct. In contrast with the commoner flat-type precursor gallbladder cancer lesions, they follow a more indolent clinical course and probably different genetic pathways to carcinogenesis. They are largely uninvestigated with only a handful of studies providing biological and clinical information. Choledochal cysts are dilation of the common bile duct. Diagnosis is usually established during childhood, and only a minority of patients are diagnosed at adulthood. They are of major clinical importance as they are known predisposing factors for biliary carcinogenesis.Case presentationThe current report describes a patient with a simultaneous diagnosis of choledochal cyst and intracholecystic papillary-tubular neoplasm. The patient underwent excision of the extrahepatic biliary tree for a Todani I choledochal cyst, and histological examination of the specimen revealed an intracholecystic papillary-tubular neoplasm of the gallbladder. Authors describe diagnostic and clinical course of the patient alongside clinical and biological characteristics of these rare lesions.ConclusionsTo the best of our knowledge, this is the first report of a patient with a simultaneous diagnosis of choledochal cyst and intracholecystic papillary-tubular neoplasm. Those rare lesions shed light on different forms of gallbladder cancer carcinogenesis and its relationship with choledochal cysts and cholestasis.

Noncardioembolic Stroke in Patients with Atrial Fibrillation

Atrial fibrillation (AF) could be a coincidental finding in certain patients with ischemic stroke and increased burden of underlying cardiovascular disease. Concomitant large-vessel atheromatosis and cerebral small vessel disease may be the actual cause of stroke, and distinguishing between different pathophysiologic mechanisms could impose substantial diagnostic difficulties. Despite routine use of oral anticoagulants (OACs) in patients with AF based on their risk for embolism (ie, CHA2DS2-Vasc score), antithrombotic agents may exert differential effects depending on stroke etiology and stroke subtyping should be evaluated as an additional component of risk stratification that could facilitate optimal management. In the present study, we summarize the evidence on noncardioembolic (non-CE) stroke and treatment approaches based on different stroke subtypes in patients with AF. In particular, approximately one-third of patients with AF seem to suffer a non-CE stroke. Within this category, 11% to 24% of patients present high-grade carotid stenosis and 9% to 16% of ischemic strokes are classified as lacunar. In terms of secondary prevention, the effectiveness of OACs in preventing non-CE stroke has been disputed. Additional large-scale prospective studies are warranted to assess the pathophysiologic stroke mechanisms in patients with AF and compare the differential efficacy of antithrombotic treatment strategies in non-CE ischemic syndromes.

Hypertension and Heart Failure with Preserved Ejection Fraction: Connecting the Dots

INTRODUCTION Heart failure (HF) with preserved ejection fraction (EF) (HFpEF) accounts for approximately 50% of HF cases and its prevalence relative to HF with reduced EF is rising. Hypertension (HT) is the most common co-morbidity in HFpEF patients and it is implicated in both the pathogenesis and the prognosis of the disease. Therefore, HT is a modifiable risk factor of high yield in HFpEF. We reviewed the literature for epidemiologic data supporting the co-aggregation of the two entities as well as patho-physiologic mechanisms linking HT to HFpEF. Most importantly, we focused on treatment options targeting HT as a preventive strategy for delaying the progression of diastolic dysfunction or decreasing the odds for developing HFpEF. CONCLUSION Along this line, we summarized the evidence and efficacy associated with different classes of antihypertensive medications in HFpEF patients. Finally, non-pharmacological approaches, including renal denervation and lifestyle modifications, to achieve optimal blood pressure (BP) control in HFpEF patients are reported. Unfortunately, no specific antihypertensive treatment has established a major survival benefit in this high risk subjects. Until the results of the efficacy of the novel drug LCZ696 (valsartan/ sacubitril) are available, the continuous monitoring and lowering of the BP by pharmacological and non-pharmacological means should be considered the major preventive and treatment strategy in HFpEF patients.

Atrial fibrillation in pregnancy: a growing challenge

Abstract Background: Atrial fibrillation (AF) constitutes a relatively infrequent pregnancy complication, which may be a therapeutic Gordian knot. Indeed, sparse data exist regarding the prevalence, prognosis, and management of AF during pregnancy. In general, AF occurs as a benign, self-limited arrhythmia, but occasionally may have severe hemodynamic consequences in pregnant patients suffering from heart failure, congenital heart disease, or other comorbidities. Extra-cardiac causes of AF should always be meticulously excluded. Review: Treatment decisions are difficult, since medications may cross the placental barrier and potentially affect fetal growth and organogenesis, or even result in fetal bradyarrhythmias. Treatment goals are not differentiated in comparison to those regarding AF occurring in the general population. Still, while maternal treatment is prioritized, issues regarding fetal health must deliberately be considered. Consequently, hemodynamic instability is to be promptly treated with synchronized electrical cardioversion. In contrast, in stable patients, pharmacologic cardioversion, under appropriate antithrombotic regimen, should be attempted. Selection of appropriate antithrombotic therapy, including novel oral anticoagulants, imposes further difficulties on therapeutic decision-making. Further clinical trials are warranted in order to assess the pathophysiology and prognosis of AF in pregnancy and ameliorate the evidence-based therapeutic strategy in this specific group of the population.