Publications by authors named "Ageliki Laina"

18 Publications

  • Page 1 of 1

Permanent pacemaker implantation in unexplained syncope patients with electrophysiology study-proven atrioventricular node disease.

Hellenic J Cardiol 2022 Jan 8. Epub 2022 Jan 8.

First Department of Cardiology, National and Kapodistrian University, "Hippokration" Hospital, Athens, Greece.

Background: Syncope, whose cause is unknown after an initial assessment, has an uncertain prognosis. It is critical to identify patients at highest risk who may require a pacemaker and to identify the cause of recurrent syncope to prescribe proper therapy. Aim of this study was to evaluate the effect of permanent pacing on the incidence of syncope in patients with unexplained syncope and electrophysiology study-proven atrioventricular node disease.

Material And Methods: This was an observational study based on a prospective registry of 236 consecutive patients (60.20 ± 18.66 years, 63.1% male, 60.04 ± 9.50 bpm) presenting with recurrent unexplained syncope attacks admitted to our hospital for invasive electrophysiology study (EPS). The decision to implant a permanent pacemaker was made in all cases by the attending physicians according to the results of the EPS. 135 patients received the antibradycardia pacemaker (ABP), while 101 declined.

Results: The mean of reported syncope episodes was 1.97 ± 1.10 (or presyncope 2.17 ± 1.50) before they were referred for a combined EP guided diagnostic and therapeutic approach. Over a mean follow-up of approximately 4 years (49.19 ± 29.58 months), the primary outcome event (syncope) occurred in 31 of 236 patients (13.1%), 6 of 135 (4.4%) in the ABP group as compared to 25 of 101 (24.8%) in the no pacemaker group (p < 0.001).

Conclusion: Among patients with a history of unexplained syncope, a set of positivity criteria for the presence of EPS defined atrioventricular node disease, identifies a subset of patients who will benefit from permanent pacing.
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http://dx.doi.org/10.1016/j.hjc.2022.01.001DOI Listing
January 2022

His Bundle Pacing: A promising alternative strategy for Antibradycardic-pacing. Report of a single center-experience.

Hellenic J Cardiol 2021 Nov 26. Epub 2021 Nov 26.

Department of Cardiology, Hippokration General Hospital, 114 Vasilisis Sofias Str, Athens, Greece. Electronic address:

His Bundle Pacing (HBP) is proven to be a safe and effective alternative pacing modality that, in addition, avoids Pacemaker-induced Cardiomyopathy (PICM) by achieving a ''physiological'' ventricular stimulation, via the native conduction system. Indications include various causes of bradycardia requiring antibradycardic pacing, inadequately controlled Atrial Fibrillation requiring AV node ablation and established PICM. In addition, HBP may also be used as an alternative therapy for patients with Heart Failure (HF) and an indication for Cardiac Resynchronization Therapy. Available data show a benefit from HBP with regard to preservation or restoration of intra- and inter-ventricular synchronization, improvement in Left Ventricular Ejection Fraction, functional status and Quality of Life, decrease in atrial fibrillation incidence and improvement in HF hospitalization rates, compared to conventional pacing. Nevertheless, superiority in terms of mortality rates has not been consistently demonstrated and long-term efficacy and safety remains to be proven. In the present manuscript, we review the status of HBP and we present our current experience with this novel pacing modality.
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http://dx.doi.org/10.1016/j.hjc.2021.10.005DOI Listing
November 2021

Daratumumab May Attenuate Cardiac Dysfunction Related to Carfilzomib in Patients with Relapsed/Refractory Multiple Myeloma: A Prospective Study.

Cancers (Basel) 2021 Oct 9;13(20). Epub 2021 Oct 9.

Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece.

Carfilzomib has improved survival in patients with relapsed/refractory multiple myeloma (RRMM), but it may exert cardiovascular adverse events (CVAEs). The aim of this study was to assess whether treatment with daratumumab may ameliorate carfilzomib-related toxicity. We prospectively evaluated 25 patients with RRMM who received either daratumumab in combination with carfilzomib and dexamethasone (DaraKd) ( = 14) or Kd ( = 11). Cardiac ultrasound was performed before treatment initiation and C6D16 or at the time of treatment interruption. Patients were followed for a median of 10 months for CVAEs. The mean (± SD) age was 67.8 ± 7.6 years and 60% were men. The two treatment groups did not significantly differ in baseline demographic characteristics ( > 0.1 for all). In the DaraKd group, we did not observe any significant change in markers of ventricular systolic function. However, these markers deteriorated in the Kd group; left ventricular (LV) ejection fraction, LV global longitudinal strain, tricuspid annular plane systolic excursion and RV free wall longitudinal strain significantly decreased from baseline to second visit ( < 0.05). A significant group interaction ( < 0.05) was observed for the abovementioned changes. CVAEs occurred more frequently in the Kd than the DaraKd group (45% vs. 28.6%). DaraKd was associated with preserved post-treatment cardiac systolic function and lower CVAE rate compared with Kd. The clinical significance and the underlying mechanisms merit further investigation.
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http://dx.doi.org/10.3390/cancers13205057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533991PMC
October 2021

Additive contribution of microRNA-34a/b/c to human arterial ageing and atherosclerosis.

Atherosclerosis 2021 06 15;327:49-58. Epub 2021 May 15.

Institute of Cardiovascular Regeneration, Center of Molecular Medicine, JW Goethe University Frankfurt, Frankfurt am Main, Germany; Department of Cardiology, Center of Internal Medicine, JW Goethe University Frankfurt, Frankfurt am Main, Germany; German Center of Cardiovascular Research (DZHK), Rhein-Main Partner Site, Frankfurt am Main, Germany; Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK; Department of Cardiology, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. Electronic address:

Background And Aims: Preclinical data suggest that the ageing-induced miR-34a regulates vascular senescence. Herein we sought to assess whether the miR-34 family members miR-34a, miR-34b and miR-34c are involved in human arterial disease.

Methods: Expression levels of miR-34a/b/c were quantified by TaqMan assay in peripheral blood mononuclear cells (PBMCs) derived from a consecutive cohort of 221 subjects who underwent cardiovascular risk assessment and thorough vascular examination for aortic stiffness and extent of arterial atherosclerosis.

Results: High miR-34a was independently associated with the presence of CAD [OR (95%C.I.): 3.87 (1.56-9.56); p = 0.003] and high miR-34c with the number of diseased arterial beds [OR (95%C.I.): 1.88 (1.034-3.41); p = 0.038], while concurrent high expression of miR-34-a/c or all three miR-34a/b/c was associated with aortic stiffening (miR-34a/c: p = 0.022; miR-34a/b/c: p = 0.041) and with the extent of atherosclerosis [OR (95%C.I.) for number of coronary arteries [miR-34a/c: 3.29 (1.085-9.95); miR-34a/b/c: 6.06 (1.74-21.2)] and number of diseased arterial beds [miR-34a/c: 3.51 (1.45-8.52); miR-34a/b/c: 2.89 (1.05-7.92)] after controlling for possible confounders (p < 0.05 for all). Mechanistically, the increased levels of miR-34a or miR-34c were inversely associated with expression of SIRT1 or JAG1, NOTCH2, CTNNB1 and ATF1, respectively. The association of miR-34a/c or miR-34a/b/c with CAD was mainly mediated through SIRT1 and to a lesser extent through JAG1 as revealed by generalized structural equation modeling. Leukocyte-specific ablation of miR-34a/b/c ameliorates atherosclerotic plaque development and increases Sirt1 and Jag1 expression in an atherosclerosis mouse model confirming the human findings.

Conclusions: The present study reveals the clinical significance of the additive role of miR-34a/b/c in vascular ageing and atherosclerotic vascular disease.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.05.005DOI Listing
June 2021

Syncope associated with supraventricular tachycardia: Diagnostic role of implantable loop recorders.

Ann Noninvasive Electrocardiol 2021 Sep 6;26(5):e12850. Epub 2021 May 6.

First Department of Cardiology, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Syncope represents a relatively uncommon symptom of supraventricular tachycardia (SVT). It is likely that an impaired autonomic vasomotor response to the hemodynamic stress of tachycardia is the determinant of hemodynamic changes leading to cerebral hypoperfusion and syncope. In this regard, tilt-table test may detect abnormalities in the autonomic nervous function and predict the occurrence of syncope during SVT. Electrophysiology studies may reproduce the SVT, distinguish it from other life-threatening ventricular tachyarrhythmias, and exclude other causes of syncope. Not infrequently mixed syncope mechanisms are revealed during the above diagnostic workup raising doubts about the operating mechanism in the clinical setting. In such cases of uncertainty, an implantable loop recorder, providing long-term cardiac monitoring, may play a pivotal role in the establishment of the diagnosis, confirming the association of an arrhythmic event with the symptom. Herein, we present four such cases with recurrent unexplained syncope finally attributed to paroxysmal SVT guiding them to a potentially radical treatment through radiofrequency catheter ablation.
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http://dx.doi.org/10.1111/anec.12850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411760PMC
September 2021

Carfilzomib-induced endothelial dysfunction, recovery of proteasome activity, and prediction of cardiovascular complications: a prospective study.

Leukemia 2021 05 15;35(5):1418-1427. Epub 2021 Feb 15.

Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Carfilzomib (CFZ) improves survival in relapsed/refractory multiple myeloma but is associated with cardiovascular adverse events (CVAEs). We prospectively investigated the effect of CFZ on endothelial function and associations with CVAEs. Forty-eight patients treated with Kd (CFZ 20/56 mg/m and dexamethasone) underwent serial endothelial function evaluation, using brachial artery flow-mediated dilatation (FMD) and 26S proteasome activity (PrA) measurement in PBMCs; patients were followed until disease progression or cycle 6 for a median of 10 months. FMD and PrA decreased acutely after the first dose (p < 0.01) and FMD decreased at cycles 3 and 6 compared to baseline (p ≤ 0.05). FMD changes were associated with CFZ-induced PrA changes (p < 0.05) and lower PrA recovery during first cycle was associated with more prominent FMD decrease (p = 0.034 for group interaction). During treatment, 25 patients developed Grade ≥3 CVAEs. Low baseline FMD (HR 2.57 lowest vs. higher tertiles, 95% CI 1.081-6.1) was an independent predictor of CVAEs. During treatment, an acute FMD decrease >40% at the end of first cycle was also independently associated with CVAEs (HR = 3.91, 95% CI 1.29-11.83). Kd treatment impairs endothelial function which is associated with PrA inhibition and recovery. Both pre- and posttreatment FMD predicted CFZ-related CVAEs supporting its role as a possible cardiovascular toxicity biomarker.
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http://dx.doi.org/10.1038/s41375-021-01141-4DOI Listing
May 2021

Pegylated interferon and ribavirin treatment for chronic hepatitis C deteriorates subclinical markers of vascular function.

Hellenic J Cardiol 2019 Mar - Apr;60(2):143-145. Epub 2018 Jul 6.

2nd Department of Internal Medicine and Research Laboratory, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens, Greece.

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http://dx.doi.org/10.1016/j.hjc.2018.07.001DOI Listing
August 2020

The effect of treatment response on endothelial function and arterial stiffness in depression. A prospective study.

J Affect Disord 2019 06 9;252:190-200. Epub 2019 Apr 9.

Department of Clinical Therapeutics, Vascular Laboratory, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, 80 Vas. Sofias Str, Athens 11528, Greece; Cardiovascular Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle Upon Tyne, UK. Electronic address:

Background: Major depression is associated with endothelial dysfunction and arterial stiffening, which may mediate development of hypertension and increased cardiovascular risk. The effect of response to antidepressant treatment on these vascular parameters has not been elucidated.

Aims: We aimed to assess the net effect of antidepressant therapy on endothelial function and arterial stiffness in patients with psychotic depression.

Method: Thirty-seven patients with major psychotic depression, according to DSM-IV-TR, were treated with titrated citalopram 20-60 mg and risperidone 0.5-1 mg and were followed for 6 months. Twelve additional patients who denied treatment, or were non-compliant, were also followed for the same time period. Vascular function was assessed by flow-mediated dilatation (FMD), carotid-femoral pulse wave velocity (PWV) and augmentation index (AI), at baseline and at the end of follow-up.

Results: Aortic and peripheral blood pressure (BP), PWV, FMD and AI (p < 0.05 for all) were significantly improved in the group that received treatment. Overall, only responders to treatment (n = 24) presented significant improvements in all hemodynamic and vascular parameters (p < 0.05 for all), irrespectively of traditional cardiovascular risk factors (TRFs), vasoactive medication and BP lowering. In a secondary analysis, patients with psychotic depression presented worse endothelial function as compared to controls matched for TRFs.

Limitations: Non-randomized study.

Conclusions: Patients who respond to therapy for major psychotic depression present sustained improvement in vascular function. Given that depressed patients are considered to be at high cardiovascular risk and are often non-compliant with treatment, further research to assess cardiovascular benefits of vigilant monitoring of antidepressant therapy is warranted.
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http://dx.doi.org/10.1016/j.jad.2019.04.024DOI Listing
June 2019

Age-dependent association of pulse wave velocity with coronary artery disease and myocardial aging in high-risk patients.

J Cardiovasc Med (Hagerstown) 2019 Apr;20(4):201-209

Vascular Laboratory, Department of Clinical Therapeutics, Alexandra Hospital.

Aims: Progressive arterial stiffening, as a marker of arterial aging, may reach a plateau in elderly patients and may thus lose its clinical utility. This phenomenon may be more prominent in high-risk patients. We aimed to investigate if carotid-to-femoral pulse wave velocity (cf-PWV) is related to coronary artery disease (CAD) and diastolic dysfunction in elderly high-risk patients as compared to a control group of younger individuals.

Methods: One-hundred and ninety-two high-risk stable patients who underwent coronary artery angiography and assessment of cf-PWV were consecutively recruited. Indices of diastolic dysfunction were also measured by echocardiography, including the volume of the left atrium and the ratio of early transmitral peak velocity (E) to the mitral annular early diastolic velocity (E').

Results: Increased cf-PWV was associated with the presence of CAD [odds ratio (OR) 1.34, P = 0.02], number of diseased coronary vessels (OR 1.17, P = 0.029) and CAD severity (P = 0.023) as assessed by Gensini score, in patients less than 65 years old after adjustment for traditional risk factors. Moreover, cf-PWV correlated with E/E' (P = 0.019) and increased the odds by 16% (OR 1.16, P = 0.048) for more severe diastolic dysfunction in patients aged below 65 years old. None of these outcomes correlated with cf-PWV in the elderly.

Conclusion: In high cardiovascular risk patients, an age-dependent association of cf-PWV with CAD and diastolic dysfunction was evinced. In contrast to younger patients, these results suggest that measuring arterial stiffness in elderly high-risk patients may lack clinical value.
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http://dx.doi.org/10.2459/JCM.0000000000000769DOI Listing
April 2019

Abdominal Fat Tissue Echogenicity: A Marker of Morbid Obesity.

J Clin Endocrinol Metab 2019 02;104(2):301-311

Vascular Laboratory, Department of Clinical Therapeutics, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Purpose: Menopause-related changes may affect regional but also morphological characteristics of adipose tissue. We sought to assess the clinical value of echogenicity of subcutaneous adipose tissue (SAT) and preperitoneal adipose tissue (pPAT) in postmenopausal women without cardiovascular disease.

Methods: In 244 consecutively recruited postmenopausal women, subclinical atherosclerosis was assessed in the femoral and carotid arteries by intima-media thickness (IMT) and atheromatous plaques using high-resolution ultrasonography. In 41 women with a second visit (median follow-up 41.5 months), carotid atherosclerosis was re-evaluated. Images of SAT and pPAT were ultrasonographically acquired, and their echogenicity was evaluated by grayscale mean (GSMn) using a dedicated software. A control group of 20 healthy premenopausal women was used for comparisons in fat echogenicity.

Results: SAT GSMn but not pPAT was higher in postmenopausal as compared with healthy premenopausal women and was independently associated with metabolic markers of adiposity including body mass index (BMI) and waist circumference (WC). SAT GSMn was associated with carotid IMT and the presence and number of atheromatous plaques [adjusted OR 2.44 and 2.32 per 1-SD increase in GSMn (95% CIs 1.55 to 3.93 and 1.55 to 3.45), respectively]. SAT GSMn conferred incremental value over traditional risk factors, insulin resistance, BMI, and WC for the detection of subclinical atherosclerosis. Increased baseline SAT GSMn was associated with increased rate of progression in carotid IMT.

Conclusions: SAT echogenicity may serve as a qualitative marker of adiposity, conferring incremental clinical value over BMI and WC in postmenopausal women. Further investigation is warranted to assess the utility of ultrasonography-derived fat echogenicity as a screening method for morbid obesity.
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http://dx.doi.org/10.1210/jc.2018-01301DOI Listing
February 2019

RNA Therapeutics in Cardiovascular Precision Medicine.

Front Physiol 2018 25;9:953. Epub 2018 Jul 25.

Center of Molecular Medicine, Institute of Cardiovascular Regeneration, Goethe University Frankfurt, Frankfurt, Germany.

Since our knowledge on structure and function of messenger RNA (mRNA) has expanded from merely being an intermediate molecule between DNA and proteins to the notion that RNA is a dynamic gene regulator that can be modified and edited, RNA has become a focus of interest into developing novel therapeutic schemes. Therapeutic modulation of RNA molecules by DNA- and RNA-based therapies has broadened the scope of therapeutic targets in infectious diseases, cancer, neurodegenerative diseases and most recently in cardiovascular diseases as well. Currently, antisense oligonucleotides (ASO), small interfering RNAs (siRNAs), and microRNAs are the most widely applied therapeutic strategies to target RNA molecules and regulate gene expression and protein production. However, a number of barriers have to be overcome including instability, inadequate binding affinity and delivery to the tissues, immunogenicity, and off-target toxicity in order for these agents to evolve into efficient drugs. As cardiovascular diseases remain the leading cause of mortality worldwide, a large number of clinical trials are under development investigating the safety and efficacy of RNA therapeutics in clinical conditions such as familial hypercholesterolemia, diabetes mellitus, hypertriglyceridemia, cardiac amyloidosis, and atrial fibrillation. In this review, we summarize the clinical trials of RNA-targeting therapies in cardiovascular disease and critically discuss the advances, the outcomes, the limitations and the future directions of RNA therapeutics in precision transcriptomic medicine.
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http://dx.doi.org/10.3389/fphys.2018.00953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068259PMC
July 2018

Low Birth Weight: A Novel Cardiovascular Risk Factor?

Circ Genom Precis Med 2018 06;11(6):e002163

Cardiovascular Research Centre, Institute of Genetic Medicine, Newcastle University, United Kingdom (K.S.).

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http://dx.doi.org/10.1161/CIRCGEN.118.002163DOI Listing
June 2018

Differential associations of systolic and diastolic time rate of blood pressure variation with carotid atherosclerosis and plaque echogenicity.

J Clin Hypertens (Greenwich) 2017 Nov 22;19(11):1070-1077. Epub 2017 Aug 22.

Vascular Laboratory, Department of Clinical Therapeutics, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

In the current study, the authors sought to assess whether the time rate of systolic and diastolic blood pressure variation is associated with advanced subclinical stages of carotid atherosclerosis and plaque echogenicity assessed by gray scale median. The authors recruited 237 consecutive patients with normotension and hypertension who underwent 24-hour ambulatory blood pressure monitoring and carotid artery ultrasonography. There was an independent association between low 24-hour systolic time rate and increased echogenicity of carotid plaques (adjusted odds ratio for highest vs lower tertiles of gray scale median, 0.470; 95% confidence interval, 0.245-0.902 [P = .023]). Moreover, increased nighttime diastolic time rate independently correlated with the presence (adjusted odds ratio, 1.328; P = .015) and number of carotid plaques (adjusted odds ratio, 1.410; P = .003). These results indicate differential associations of the systolic and diastolic components of time rate of blood pressure variation with the presence, extent, and composition of carotid plaques and suggest that when blood pressure variation is assessed, both components should be considered.
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http://dx.doi.org/10.1111/jch.13070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8031346PMC
November 2017

Vascular ageing: Underlying mechanisms and clinical implications.

Exp Gerontol 2018 08 15;109:16-30. Epub 2017 Jun 15.

Department of Clinical Therapeutics, Alexandra Hospital, University of Athens, Athens, Greece. Electronic address:

Epidemiological studies have shown that ageing is a major non-reversible risk factor for cardiovascular disease. Vascular ageing starts early in life and is characterized by a gradual change of vascular structure and function resulting in increased arterial stiffening. At the present review we discuss the role of the most important molecular pathways involved in vascular ageing, their association with arterial stiffening and possible novel therapeutic targets that may delay this otherwise irreversible degenerating process. Specifically, we discuss the role of oxidative stress, telomere shortening, and ubiquitin proteasome system in endothelial cell senescence and dysfunction in vascular inflammation and in arterial stiffening. Further, we summarize the most important molecular mechanisms regulating vascular ageing including sirtuin 1, telomerase, klotho, JunD, and amyloid beta 1-40 peptide.
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http://dx.doi.org/10.1016/j.exger.2017.06.007DOI Listing
August 2018

Amiodarone and cardiac arrest: Systematic review and meta-analysis.

Int J Cardiol 2016 Oct 9;221:780-8. Epub 2016 Jul 9.

Hellenic Society of Cardiopulmonary Resuscitation, Athens, Greece; European University Cyprus, School of Medicine, Nicosia, Cyprus.

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.
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http://dx.doi.org/10.1016/j.ijcard.2016.07.138DOI Listing
October 2016

Steroid-induced hypocalcaemia with tetany in a patient with hypoparathyroidism.

BMJ Case Rep 2014 Nov 18;2014. Epub 2014 Nov 18.

Department of Internal Medicine, "A. Fleming" General Hospital, Athens, Greece.

Although glucocorticoids have a known negative effect on calcium balance, they do not normally cause clinically significant hypocalcaemia. A young woman with post-surgical hypoparathyroidism developed symptomatic hypocalcaemia on two occasions following treatment with intravenous hydrocortisone for allergic reactions. Oral calcium and vitamin D supplementation could not prevent the development of hypocalcaemia. She was treated successfully with intravenous calcium gluconate infusions and discontinuation of glucocorticoids. In patients with hypoparathyroidism, impaired parathyroid hormone response to steroid-induced negative calcium balance may result in severe symptomatic hypocalcaemia requiring hospitalisation.
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http://dx.doi.org/10.1136/bcr-2014-207562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4244442PMC
November 2014
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