Publications by authors named "Alexandra Arvanitaki"

24 Publications

  • Page 1 of 1

Haemodynamic effects of PAH-targeted therapies in pulmonary hypertension due to lung disease: A systematic review and meta-analysis.

Pulm Pharmacol Ther 2021 Jun 9;68:102036. Epub 2021 May 9.

Department of Cardiology, AHEPA University Hospital, Thessaloniki, Greece. Electronic address:

Background: Pulmonary hypertension (PH) is a negative predictor in patients with lung disease and/or hypoxia (group 3 PH). Current guidelines do not endorse the use of targeted therapies for pulmonary arterial hypertension (PAH) in patients with group 3 PH, due to lack of strong evidence. However, a variety of studies have examined the effect of PAH-targeted therapies in group 3 PH with mixed methods and conflicting results.

Objective: To evaluate the effect of PAH-targeted therapies on haemodynamic parameters as assessed by right heart catheterization in patients with group 3 PH.

Methods: Search strategy included PubMed and CENTRAL databases for randomized controlled trials from inception until Jan 30, 2020. We hand searched review articles, clinical trial registries and reference lists of retrieved articles. The primary outcome was the effect of PAH-targeted therapies on haemodynamic parameters [mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index (CI) and right atrial pressure (RAP)] in patients with group 3 PH, while secondary outcomes were 6-min walking distance (6MWD), brain natriuretic peptide (BNP) and quality of life (QoL).

Results: Five studies with a total of 140 patients were included. PAH-targeted therapies improved significantly mPAP [mean difference (MD) -4.02 mmHg, 95% CI -7.95;-0.09], and PVR [standardized mean difference (SMD) -0.29, 95% CI -0.50;-0.07], but not CI (SMD 0.23, 95% CI -0.23; 0.70) or RAP (MD 0.26 mmHg, 95% CI -18.75; 19.27). PAH-targeted therapies significantly increased the 6MWD by 38.5 m (95% CI 17.6; 59.4), while they did not manage to improve QoL (SMD -3.42, 95% CI -14.74; 7.91) or BNP values. There was no effect of oxygenation by the PAH-targeted therapies compared to placebo.

Conclusion: PAH-targeted therapies slightly improved mPAP and PVR in group 3 PH, without affecting CI. Larger RCTs targeted in specific subpopulations are needed to extract more robust conclusions.

Protocol Registration: Open Science Framework 10.17605/OSF.IO/56FDW.
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http://dx.doi.org/10.1016/j.pupt.2021.102036DOI Listing
June 2021

Nailfold videocapillaroscopic changes in patients with pulmonary arterial hypertension associated with connective tissue diseases.

Rheumatol Int 2021 Jul 12;41(7):1289-1298. Epub 2021 May 12.

Fourth Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki, 49 Konstantinoupoleos Street, 54642, Thessaloníki, Greece.

Pulmonary arterial hypertension (PAH) represents one of the most devastating complications in connective tissue diseases (CTDs). The aim of this study was to investigate the presence of peripheral microangiopathy in patients with PAH associated with CTDs (CTD-PAH) by exploring nailfold videocapillaroscopic (NVC) changes and identify possible associations of NVC characteristics with markers of disease severity. Α cross-sectional study was performed in 18 CTD-PAH patients [13 PAH due to systemic sclerosis (SSc-PAH) and 5 with other types of CTD-PAH], 14 patients with SSc without PAH (SSc-non-PAH) and 20 healthy controls. NVC quantitative and qualitative parameters were evaluated using Optilia Digital Capillaroscope. To ensure inter-observer repeatability, capillaroscopic images were reviewed by two independent investigators. When compared to healthy controls, patients with CTD-PAH (77.8% women, mean age 65.9 years) presented reduced capillary density (6.5 ± 1.6 loops/mm vs. 9.7 ± 0.7 loops/mm, p < 0.001) and increased capillary loop width (23.3 ± 10.1 μm vs. 11.2 ± 2.5 μm, p < 0.001). SSc-PAH patients presented lower capillary density in comparison with other CTD-PAH patients and SSc-non-PAH subjects and abnormal and disorganized capillaries compared to controls. Patients with other CTD-PAH had also reduced capillary density and increased loop diameter compared to controls. A significant linear correlation was identified between capillary density and estimated glomerular filtration rate in the total CTD-PAH population (r = 0.63, p = 0.007). In SSc-PAH group, capillary loop diameter was positively correlated to cardiac index (r = 0.61, p = 0.02). Significant NVC microvascular changes were detected in patients with various types of CTD-PAH, suggesting an impaired peripheral microcirculation parallel to pulmonary vasculopathy.
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http://dx.doi.org/10.1007/s00296-021-04839-xDOI Listing
July 2021

Lifespan Perspective on Congenital Heart Disease Research: JACC State-of-the-Art Review.

J Am Coll Cardiol 2021 May;77(17):2219-2235

McGill Adult Unit for Congenital Heart Disease Excellence (MAUDE Unit), Department of Medicine, McGill University, Montréal, Québec, Canada. Electronic address:

More than 90% of patients with congenital heart disease (CHD) are nowadays surviving to adulthood and adults account for over two-thirds of the contemporary CHD population in Western countries. Although outcomes are improved, surgery does not cure CHD. Decades of longitudinal observational data are currently motivating a paradigm shift toward a lifespan perspective and proactive approach to CHD care. The aim of this review is to operationalize these emerging concepts by presenting new constructs in CHD research. These concepts include long-term trajectories and a life course epidemiology framework. Focusing on a precision health, we propose to integrate our current knowledge on the genome, phenome, and environome across the CHD lifespan. We also summarize the potential of technology, especially machine learning, to facilitate longitudinal research by embracing big data and multicenter lifelong data collection.
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http://dx.doi.org/10.1016/j.jacc.2021.03.012DOI Listing
May 2021

Nailfold Capillaroscopy in Systemic Sclerosis Patients with and without Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis.

J Clin Med 2021 Apr 6;10(7). Epub 2021 Apr 6.

Fourth Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece.

Systemic sclerosis (SSc)-related pulmonary arterial hypertension (SSc-PAH) is a leading cause of mortality in SSc. The extent of peripheral microvasculopathy assessed through nailfold capillaroscopy might correlate with the presence of PAH in SSc patients. We searched the PubMed, Cochrane Library, Scopus, and Web of Science databases and performed a random effects meta-analysis of observational studies comparing nailfold capillaroscopic alterations in SSc-PAH versus SSc-noPAH patients. Weighted mean differences (WMD) with the corresponding confidence intervals (CIs) were estimated. The quality of the included studies was evaluated using a modified Newcastle-Ottawa scale. Seven studies with 101 SSc-PAH and 277 SSc-noPAH participants were included. Capillary density was marginally reduced in the SSc-PAH group (WMD: -1.0, 95% CI: -2.0 to 0.0, I = 86%). This effect was strengthened once PAH diagnosis was confirmed by right heart catheterization (WMD: -1.2, 95% CI: -2.3 to -0.1, I = 85%). An increase in capillary loop width was observed in SSc-PAH compared to SSc-noPAH patients (WMD: 10.9, 95% CI: 2.5 to 19.4, I = 78%). Furthermore, SSc-PAH patients had a 7.3 times higher likelihood of active or late scleroderma pattern (95% CI: 3.0 to 18.0, I = 4%). SSc-PAH patients presented with worse nailfold capillaroscopic findings compared to SSc-noPAH patients.
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http://dx.doi.org/10.3390/jcm10071528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038744PMC
April 2021

Chronic hypertension in pregnancy: synthesis of influential guidelines.

J Perinat Med 2021 Apr 19. Epub 2021 Apr 19.

Third Department of Obstetrics and Gynaecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Chronic hypertension in pregnancy accounts for a substantial proportion of maternal morbidity and mortality and is associated with adverse perinatal outcomes, most of which can be mitigated by appropriate surveillance and management protocols. The aim of this study was to review and compare recommendations of published guidelines on this condition. Thus, a descriptive review of influential guidelines from the National Institute for Health and Care Excellence, the Society of Obstetric Medicine of Australia and New Zealand, the International Society of Hypertension, the International Society for the Study of Hypertension in Pregnancy, the European Society of Cardiology, the International Federation of Gynecology and Obstetrics, the Society of Obstetricians and Gynaecologists of Canada and the American College of Obstetricians and Gynecologists on chronic hypertension in pregnancy was conducted. All guidelines agree on the definition and medical management, the need for more frequent antenatal care and fetal surveillance and the re-evaluation at 6-8 weeks postpartum. There is also a consensus that the administration of low-dose aspirin is required to prevent preeclampsia, although the optimal dosage remains controversial. No universal agreement has been spotted regarding optimal treatment blood pressure (BP) targets, need for treating mild-to-moderate hypertension and postnatal BP measurements. Additionally, while the necessity of antenatal corticosteroids and magnesium sulfate for preterm delivery is universally recommended, the appropriate timing of delivery is not clearly outlined. Hence, there is a need to adopt consistent practice protocols to optimally manage these pregnancies; i.e. timely detect and treat any potential complications and subsequently reduce the associated morbidity and mortality.
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http://dx.doi.org/10.1515/jpm-2021-0015DOI Listing
April 2021

Reinforcing adherence to lipid-lowering therapy after an acute coronary syndrome: A pragmatic randomized controlled trial.

Atherosclerosis 2021 04 17;323:37-43. Epub 2021 Mar 17.

1st Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. Electronic address:

Background And Aims: Achieving the low-density lipoprotein cholesterol (LDL-C) goal following an acute coronary syndrome (ACS) is a milestone often missed due to suboptimal adherence to secondary prevention treatments. Whether improved adherence could result in reduced LDL-C levels is unclear. We aimed to evaluate whether an educational-motivational intervention increases long-term lipid-lowering therapy (LLT) adherence and LDL-C goal attainment rate among post-ACS patients.

Methods: IDEAL-LDL was a parallel, two-arm, single-center, pragmatic, investigator-initiated randomized controlled trial. Hospitalized patients for ACS were randomized to a physician-led integrated intervention consisting of an educational session at baseline, followed by regular motivational interviewing phone sessions or usual care. Co-primary outcomes were the LLT adherence (measured by Proportion of Days Covered (PDC); good adherence defined as PDC>80%), and LDL-C goal (<70 mg/dl or 50% reduction from baseline) achievement rate at one year.

Results: In total, 360 patients (mean age 62 years, 81% male) were randomized. Overall, good adherence was positively associated with LDL-C goal achievement rate at one year. Median PDC was higher in the intervention group than the control group [0.92 (IQR, 0.82-1.00) vs. 0.86 (0.62-0.98); p = 0.03] while the intervention group had increased odds of good adherence (odds ratio: 1.76 (95% confidence interval 1.02 to 2.62; p = 0.04). However, neither the LDL-C goal achievement rate (49.6% in the intervention vs. 44.9% in the control group; p = 0.49) nor clinical outcomes differed significantly between the two groups.

Conclusions: Α multifaceted intervention improved LLT adherence in post-ACS patients without a significant difference in LDL-C goal attainment.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.03.013DOI Listing
April 2021

Peripheral microangiopathy in Eisenmenger syndrome: A nailfold video capillaroscopy study.

Int J Cardiol 2021 Mar 16. Epub 2021 Mar 16.

Fourth Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki, 49 Konstantinoupoleos Street, 54642 Thessaloniki, Greece. Electronic address:

Background: Eisenmenger syndrome (ES) comprises a severe phenotype of pulmonary arterial hypertension characterized by angiopathy of the lung circulation. The aim of the present study was to demonstrate the presence of systemic microvascular abnormalities in patients with ES using nailfold video-capillaroscopy (NVC) and to identify potential correlations of nailfold capillaroscopic characteristics with non-invasive markers of systemic organ function.

Methods: Α cross-sectional NVC study was performed in 17 consecutive patients with ES and 17 healthy controls matched for age and sex. NVC quantitative (capillary density, capillary dimensions, haemorrhages, thrombi, shape abnormalities) and qualitative (normal, non-specific or scleroderma pattern) parameters were evaluated.

Results: Patients with ES [median age 40 (18-65) years, 11 women] presented reduced capillary density [8.8 (7.2-10.2) loops/mm vs. 9.9 (8.3-10.9) loops/mm, p = .004] and increased loop width [15.9 (10.3-21.7) μm vs. 12.3 (7.6-15.2) μm, p < .001], while they had significantly more abnormal capillaries than healthy controls [2.5 (0.9-5.4) abnormal loops/mm vs. 1.0 (0.0-1.7) abnormal loops/mm, p < .001]. NVC shape abnormalities in ES were positively correlated with NT-proBNP (r = 0.52, p = .03) and were negatively associated with estimated glomerular filtration rate (r = -0.60, p = .02). Additionally, capillary loop diameter was positively correlated with increased haemoglobin levels (r = 0.55, p = .03) and negatively correlated with reduced peripheral oxygen saturation (r = - 0.56, p = .02).

Conclusions: This study supports the hypothesis of peripheral microvascular involvement in ES parallel to pulmonary microangiopathy detected by NVC. Further longitudinal studies are needed to confirm our preliminary results.
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http://dx.doi.org/10.1016/j.ijcard.2021.03.033DOI Listing
March 2021

A new approach to modelling in adult congenital heart disease: artificial intelligence.

Rev Esp Cardiol (Engl Ed) 2021 Jan 18. Epub 2021 Jan 18.

Department of Cardiology III - Adult Congenital and Valvular Heart Disease, University Hospital Muenster, Muenster, Germany.

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http://dx.doi.org/10.1016/j.rec.2020.12.008DOI Listing
January 2021

Peripheral microangiopathy in precapillary pulmonary hypertension: a nailfold video capillaroscopy prospective study.

Respir Res 2021 Jan 21;22(1):27. Epub 2021 Jan 21.

Fourth Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki, 49 Konstantinoupoleos Street, 54642, Thessaloniki, Greece.

Background: Although pulmonary vascular bed has been the main subject of research for many years in pulmonary hypertension (PH), interest has recently started to divert towards the possibility of a co-existing peripheral microangiopathy. The aim of the current study was to investigate the presence of nailfold video-capillaroscopic (NVC) structural changes in patients with precapillary PH and to identify possible associations of NVC measurements with markers of disease severity.

Methods: Α prospective case-control study was performed in 28 consecutive patients with precapillary PH [14 with idiopathic pulmonary arterial hypertension (IPAH) and 14 with chronic thromboembolic pulmonary hypertension (CTEPH)] and 30 healthy controls. NVC quantitative and qualitative parameters were evaluated using Optilia Digital Capillaroscope. To ensure inter-observer repeatability capillaroscopic images were reviewed by two independent investigators. For multiple comparisons among continuous variables, one-way ANOVA or the Kruskal-Wallis test were used. Differences between the groups were tested with post-hoc analysis with adjustment for multiple comparisons (Bonferroni test).

Results: Both IPAH (71.4% were women, mean age 53.1 ± 13.4 years) and CTEPH (64.3% women, mean age 60.9 ± 14.4 years) groups presented reduced capillary density compared to healthy controls (8.4 ± 1.2 loops/mm and 8.0 ± 1.2 loops/mm vs. 9.7 ± 0.81 loops/mm, p < 0.001) and increased loop width (15.7 ± 3.9 μm and 15.8 ± 1.9 μm vs. 11.5 ± 2.3 μm, p < 0.001). More than half of patients with IPAH presented microhaemorrhages on capillary nailfold, while increased shape abnormalities in capillary morphology and more capillary thrombi per linear mm were detected in patients with CTEPH compared to patients with IPAH and healthy controls. All PH patients presented a non-specific NVC pattern compared to controls (p < 0.001).

Conclusion: The findings of the study reveal a degree of significant peripheral microvascular alterations in patients with IPAH and CTEPH, suggesting a generalized impairment of peripheral microvasculature in pulmonary vascular disease.
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http://dx.doi.org/10.1186/s12931-021-01622-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819216PMC
January 2021

Prediction Models and Scores in Adult Congenital Heart Disease.

Curr Pharm Des 2021 ;27(10):1232-1244

Adult Congenital Heart Centre and National Centre for Pulmonary Hypertension, Royal Brompton Hospital, United Kingdom.

Nowadays, most patients with congenital heart disease survive to adulthood due to advances in pediatric cardiac surgery but often present with various comorbidities and long-term complications, posing challenges in their management. The development and clinical use of risk scores for the prediction of morbidity and/or mortality in adults with congenital heart disease (ACHD) is fundamental in achieving optimal management for these patients, including appropriate follow-up frequency, treatment escalation, and timely referral for invasive procedures or heart transplantation. In comparison with other fields of cardiovascular medicine, there are relatively few studies that report prediction models developed in the ACHD population, given the small sample size, heterogeneity of the population, and relatively low event rate. Some studies report risk scores originally developed in pediatric congenital or non-congenital population, externally validated in ACHD with variable success. Available risk scores are designed to predict heart failure or arrhythmic events, all-cause mortality, post-intervention outcomes, infective endocarditis, or atherosclerosis-related cardiovascular disease in ACHD. A substantial number of these scores are derived from retrospective studies and are not internally or externally validated. Adequately validated risk scores can be invaluable in clinical practice and an important step towards personalized medicine. Multicenter collaboration, adequate study design, and the potential use of artificial intelligence are important elements in the effort to develop reliable risk scores for the ACHD population.
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http://dx.doi.org/10.2174/1381612827999210111181554DOI Listing
January 2021

Peripheral Microangiopathy in Patients with Precapillary Pulmonary Hypertension: Correlation with Cardiac Function and Patients' Functional Capacity. Study Design and Rationale.

Mediterr J Rheumatol 2020 Sep 10;31(3):369-373. Epub 2020 Jun 10.

Fourth Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki, Greece.

Pulmonary hypertension (PH) is a rare, heterogenous clinical entity characterised by a progressive remodelling of pulmonary arterioles, which leads to obstructive pulmonary arteriopathy, increased pulmonary vascular resistance, and eventually, right heart failure. Inflammation, endothelial dysfunction, and microvascular changes of the pulmonary vasculature constitute the hallmarks of pulmonary arterial hypertension (PAH), explaining much of the pathophysiology and clinical manifestations of the disease. Besides pulmonary vasculature, a systemic component of endothelial dysfunction and microcirculation may be involved in PAH, affecting different vascular beds. Nailfold videocapillaroscopy (NVC) is an established method for the assessment of the microvasculature with clinical implications in the diagnostic assessment of individuals with Raynaud syndrome and systemic sclerosis (SSc). Nowadays, growing amounts of evidence suggest that NVC changes in SSc are correlated with other vascular complications such as PAH, supporting a potential link between peripheral and internal organ vasculopathy. The purpose of the current prospective observational study is to explore: 1. the presence of peripheral microangiopathy in precapillary PH using NVC, 2. possible NVC differences among PH subgroups, 3. a potential relationship between NVC morphological abnormalities and clinical, functional, biochemical, echocardiographic and hemodynamic markers of cardiac dysfunction in precapillary PH.
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http://dx.doi.org/10.31138/mjr.31.3.369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641020PMC
September 2020

Risk for Recurrent Cardiovascular Events and Expected Risk Reduction With Optimal Treatment 1 Year After an Acute Coronary Syndrome.

Am J Cardiol 2020 10 28;133:7-14. Epub 2020 Jul 28.

1st Cardiology Department, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. Electronic address:

According to the latest European Society of Cardiology Guidelines for the diagnosis and management of chronic coronary syndromes, patients who suffered an acute coronary syndrome fall into a chronic stable phase after 1 year. In these patients, the estimated 10-year risk for recurrent cardiovascular events varies considerably. We applied the SMART (Second Manifestations of Arterial Disease) risk score in 281 patients 1 year after an acute coronary syndrome to estimate the 10-year risk for recurrent cardiovascular events (subsequent nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death). We assessed the distribution of the estimated risk and the potential risk reduction that might be achieved with optimal guideline-directed management of modifiable risk factors (systolic blood pressure, low-density lipoprotein cholesterol, smoking, and body mass index). In our cohort, the median SMART score was 16.1% (interquartile range [IQR] 9.7 to 27.3), particularly increased in patients with older age, diabetes, polyvascular disease or chronic kidney disease (median 28.6%, IQR 20.8 to 52.9; 23.8%, 4.8 to 41.6; 29.4%, 18.8 to 49.7; 53.8%, 26.5 to 71.6, respectively). If all modifiable risk factors met guideline-recommended targets, the median SMART risk score would be 9.6% (IQR 6.3 to 20.9), with 51% of the patients at a 10-year risk <10%, while 11% and 15% at 20% to 30% and >30% risk, respectively. In conclusion, the SMART score had a wide distribution in patients with chronic coronary syndromes. A quarter of patients remained at a >20% 10-year risk, even with optimal risk factor management, clearly underlining that residual risk is an unmet clinical challenge.
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http://dx.doi.org/10.1016/j.amjcard.2020.07.046DOI Listing
October 2020

Eisenmenger syndrome: diagnosis, prognosis and clinical management.

Heart 2020 11 20;106(21):1638-1645. Epub 2020 Jul 20.

Department of Cardiology III-Adult Congenital and Valvular Heart Disease, University Hospital Muenster, Muenster, Nordrhein-Westfalen, Germany

Eisenmenger syndrome (ES) represents the most severe phenotype of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) and occurs in patients with large unrepaired shunts. Despite early detection of CHD and major advances in paediatric cardiac surgery, ES is still prevalent and requires a multidisciplinary approach by adult CHD experts in tertiary centres. Central cyanosis is the primary clinical manifestation leading to secondary erythrocytosis and various multiorgan complications that increase morbidity and affect quality of life. Close follow-up is needed to early diagnose and timely manage these complications. The primary goal of care is to maintain patients' fragile stability. Although the recent use of advanced PAH therapies has substantially improved functional capacity and increased life expectancy, long-term survival remains poor. Progressive heart failure, infectious diseases and sudden cardiac death comprise the main causes of death in patients with ES. Impaired exercise tolerance, decreased arterial oxygen saturation, iron deficiency, pre-tricuspid shunts, arrhythmias, increased brain natriuretic peptide, echocardiographic indices of right ventricular dysfunction and hospitalisation for heart failure predict mortality. Endothelin receptor antagonists are used as first-line treatment in symptomatic patients, while phosphodiesterase-5 inhibitors may be added. Due to the lack of evidence, current guidelines do not provide a clear therapeutic strategy regarding treatment escalation. Additional well-designed trials are required to assess the comparative efficacy of various PAH agents and the benefit of combination therapy. Finally, the development of a risk score is of utmost importance to guide clinical therapy.
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http://dx.doi.org/10.1136/heartjnl-2020-316665DOI Listing
November 2020

Endocarditis as the Cause of Recurrent Fever and Brain Abscess in a Patient with Complex Congenital Heart Disease: A Case Report and Literature Review.

Case Rep Infect Dis 2020 24;2020:7894574. Epub 2020 Jun 24.

Infectious Diseases Unit, First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Introduction: Blood culture-negative infective endocarditis (BCNIE) can present subtly and is associated with a diagnostic delay leading to increased morbidity and mortality. . We present the case of an 18-year-old male with a history of complex congenital heart disease and 3-year intermittent episodes of fever of unknown origin, who was referred to our hospital for upper and lower extremity focal seizures. Laboratory blood tests were normal, blood cultures were negative, and brain imaging revealed an abscess. Cardiology consultation was requested, and transthoracic echocardiography revealed an intracardiac vegetation. Empiric antibiotic treatment with sultamicillin, gentamycin, and meropenem was initiated. Serology testing was positive for , and the diagnosis of BCNIE was established. The antibiotic course was changed to oral doxycycline for 36 months and led to resolution of IE, with no vegetation detected on TTE after 15 months.

Conclusion: BCNIE is a life-threatening disease entity that can lead to severe complications, such as valve regurgitation, emboli, and death. Patients with congenital heart disease are particularly vulnerable to IE. Timely diagnosis and antibiotic management are of paramount importance in order to avoid the potentially fatal sequelae.
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http://dx.doi.org/10.1155/2020/7894574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333052PMC
June 2020

Mildly symptomatic heart failure with reduced ejection fraction: diagnostic and therapeutic considerations.

ESC Heart Fail 2020 08 5;7(4):1477-1487. Epub 2020 May 5.

1st Department of Cardiology, AHEPA University Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, 54636, Greece.

Aims: Whereas up to about half of patients with heart failure with reduced ejection fraction (HFrEF) report no or only mild symptoms and are considered as clinically stable, the progressive nature of HFrEF, often silent, renders clinical stability a misleading situation, especially if disease progression is unrecognized. We highlight the challenges in the definition of clinical stability and mild symptomatic status in HFrEF, outline clinical characteristics and available diagnostic tools, and discuss evidence and gaps in the current guidelines for the management of these patients.

Methods And Results: This is a state-of-the-art review that focuses on clinical, diagnostic, and therapeutic aspects in mildly symptomatic HFrEF patients; summarizes the challenges; and proposes directions for future research in this group of patients. The New York Heart Association classification has been widely used as a measure of prognosis in HFrEF, but it lacks objectivity and reproducibility in terms of symptoms assessment. The definition of clinical stability as described in current guidelines is vague and may often lead to underdiagnosis of disease progression in patients who appear to be 'stable' but in fact are at an increased risk of clinical worsening, hospitalization, or death. Although an increasing number of clinical trials proved that the efficacy of HFrEF therapies was unrelated to the symptomatic status of patients and led to their implementation early in the course of the disease, clinical inertia in terms of under-prescription or underdosing of guideline-recommended medications in mildly symptomatic HFrEF patients is still a challenging issue to deal with.

Conclusions: Mildly symptomatic status in a patient with HFrEF is very frequent; it should not be ignored and should not be regarded as an index of disease stability. The application of risk scores designed to predict mortality and mode of death should be engaged among mildly symptomatic patients, not only to identify the most suitable HF candidates for cardioverter defibrillator implantation, but also to identify patients who might benefit from early intensification of medical treatment before the implementation of more interventional approaches.
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http://dx.doi.org/10.1002/ehf2.12701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373907PMC
August 2020

Epidemiology and initial management of pulmonary arterial hypertension: real-world data from the Hellenic pulmOnary hyPertension rEgistry (HOPE).

Pulm Circ 2019 Jul-Sep;9(3):2045894019877157. Epub 2019 Oct 14.

Cardiology Department, Mediterraneo Hospital, Athens, Greece.

Pulmonary arterial hypertension (PAH) is a heterogenous clinical entity with poor prognosis, despite recent major pharmacological advances. To increase awareness about the pathophysiology, epidemiology, and management of the disease, large national registries are required. The Hellenic pulmOnary hyPertension rEgistry (HOPE) was launched in early 2015 and enrolls patients from all pulmonary hypertension subgroups in Greece. Baseline epidemiologic, diagnostic, and initial treatment data of consecutive patients with PAH are presented in this article. In total, 231 patients with PAH were enrolled from January 2015 until April 2018. At baseline, about half of patients with PAH were in World Health Organization functional class II. The majority of patients with PAH (56.7%) were at intermediate 1-year mortality risk, while more than one-third were low-risk patients, according to an abbreviated risk stratification score. Half of patients with PAH were on monotherapy, 38.9% received combination therapy, while prostanoids were used only in 12.1% of patients. In conclusion, baseline data of the Greek PAH population share common characteristics, but also have some differences with other registries, the most prominent being a better functional capacity. This may reflect earlier diagnosis of PAH that in conjunction with the increased proportion of patients with atypical PAH could partially explain the preference for monotherapy and the limited use of prostanoids in Greece. Nevertheless, early, advanced specific therapy is strongly recommended.
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http://dx.doi.org/10.1177/2045894019877157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792282PMC
October 2019

Myocardial Tissue Characterization and Fibrosis by Imaging.

JACC Cardiovasc Imaging 2020 05 18;13(5):1221-1234. Epub 2019 Sep 18.

Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.

Myocardial fibrosis, either focal or diffuse, is a common feature of many cardiac diseases and is associated with a poor prognosis for major adverse cardiovascular events. Although histological analysis remains the gold standard for confirming the presence of myocardial fibrosis, endomyocardial biopsy is invasive, has sampling errors, and is not practical in the routine clinical setting. Cardiac imaging modalities offer noninvasive surrogate biomarkers not only for fibrosis but also for myocardial edema and infiltration to varying degrees, and have important roles in the diagnosis and management of cardiac diseases. This review summarizes important pathophysiological features in the development of commonly encountered cardiac diseases, and the principles, advantages, and disadvantages of various cardiac imaging modalities (echocardiography, single-photon emission computer tomography, positron emission tomography, multidetector computer tomography, and cardiac magnetic resonance) for myocardial tissue characterization, with an emphasis on imaging focal and diffuse myocardial fibrosis.
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http://dx.doi.org/10.1016/j.jcmg.2019.06.030DOI Listing
May 2020

Comorbidity burden in systemic sclerosis: beyond disease-specific complications.

Rheumatol Int 2019 Sep 12;39(9):1507-1517. Epub 2019 Jul 12.

Fourth Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki, 49 Konstantinoupoleos Str, 54642, Thessaloniki, Greece.

Systemic sclerosis (SSc) is a chronic, systemic disease characterized by fibrosis of the skin and internal organs, vasculopathy, and auto-immune activation. On the top of severe organ involvement such as interstitial lung and myocardial fibrosis, pulmonary hypertension, and renal crisis, individuals diagnosed with SSc may suffer from a number of comorbidities. This is a narrative review according to published recommendations and we searched the online databases MEDLINE and EMBASE using as key words the following terms: systemic sclerosis, scleroderma, myocardial fibrosis in combination with micro- and macro-vascular disease, cardiac involvement, atherosclerosis, cardiovascular disease and coronary arteries, infections, cancer, depression, osteoporosis, and dyslipidemia. Although data are usually inconclusive it appears that comorbidities with significant impact on life expectancy, namely cardiovascular disease, infections, and cancer as well as phycological disorders affecting emotional and mental health are highly prevalent in SSc population. Thereafter, the aim of this review is to summarize the occurrence and the clinical significance of such comorbidities in SSc population and to discuss how rheumatologists can incorporate the management of these conditions in daily clinical practice.
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http://dx.doi.org/10.1007/s00296-019-04371-zDOI Listing
September 2019

Quality of Life is Related to Haemodynamics in Precapillary Pulmonary Hypertension.

Heart Lung Circ 2020 Jan 15;29(1):142-148. Epub 2019 Jan 15.

Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, Greece. Electronic address:

Background: Precapillary pulmonary hypertension (PH) is characterised by compromised functional capacity and impaired quality of life. Assessment of haemodynamics is routinely used for initial diagnosis, follow-up, and risk stratification in these patients. The purpose of this study was to investigate the relation of health-related quality of life (HRQoL) as assessed by emPHasis-10 score, a self-assessment questionnaire assessing breathlessness, fatigue, control, and confidence, to haemodynamic and neurohormonal indices in patients with precapillary PH.

Method: This was a prospective cross-sectional study which included stable patients with precapillary PH. All patients underwent right heart catheterisation, 6-minute walk test, N-terminal pro-brain natriuretic peptide (NT-proBNP) measurement, and assessment of HRQoL with the emPHasis-10 scale.

Results: Overall, 54 patients were included (32 women; mean age, 58.4 ± 14.6 yr). Mean emPHasis-10 score was 19.2 ± 12.0. EmPHasis-10 score correlated with World Health Organization functional class (r = 0.52, p < 0.001), 6-minute walk distance (r=-0.56, p < 0.001), and log(NT-proBNP) (r = 0.41, p < 0.01). A positive correlation of emPHasis-10 score with mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) and a negative correlation with mixed venous oxygen saturation and cardiac index was observed, after adjustment for age, sex, body mass index, and PH group. In a subgroup analysis of patients with pulmonary arterial hypertension (n = 34) there was a stronger correlation of emPHasis-10 score with mPAP (r = 0.86, p < 0.001) and PVR (r = 0.69, p < 0.01), but no correlation with cardiac index and mixed venous oxygen saturation.

Conclusions: Self-assessment of quality of life with the use of the emPHasis-10 score reflects functional capacity and is correlated with haemodynamic and neurohormonal indices of right heart dysfunction in patients with precapillary PH.
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http://dx.doi.org/10.1016/j.hlc.2018.12.005DOI Listing
January 2020

Assessing the reporting quality of systematic reviews of observational studies in preeclampsia.

Arch Gynecol Obstet 2019 03 4;299(3):689-694. Epub 2019 Jan 4.

Laboratory of Biomathematics, University of Thessaly School of Medicine, Papakyriazi 22, Building "Katsigra", Larissa, Greece.

Purpose: The majority of epidemiological studies in preeclampsia are observational and the overview of these studies is expressed by systematic reviews (SRs). The aim of this study was to evaluate the reporting quality of published SRs of observational studies (OS) in preeclampsia based on Meta-analysis of Observational Studies in Epidemiology (MOOSE) statement.

Methods: PubMed and Cochrane databases were searched for SRs of OS in preeclampsia published from 1st January 2011 through 10th December 2017. The SRs were evaluated for their reporting quality according to the MOOSE statement, an evidence-based tool which consists of a checklist of 35 items, overall and according to the ranking of journals.

Results: The search identified 93 eligible SRs. Six items were reported in all the studies. Ninety percent (90%) and 70% of the studies complied with 13 (37%) and 20 (57%) items of MOOSE, respectively. Two items concerning search strategy were under-reported (< 10% of studies). High-ranked journals (impact factor ≥ 5) presented a better reporting quality (p < 0.05) of the MOOSE items, while no significant differences were identified in individual items.

Conclusions: The quality of reporting of SRs for OS in preeclampsia was considered satisfactory; though, ranking of journals may have an effect in reporting. Further improvement of reporting is necessary to enhance the validity of SRs.
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http://dx.doi.org/10.1007/s00404-018-5023-yDOI Listing
March 2019

Balloon atrial septostomy in severe precapillary pulmonary hypertension: A single-center experience.

Hellenic J Cardiol 2019 Nov - Dec;60(6):384-386. Epub 2018 May 25.

Cardiology Department, AHEPA University Hospital, Aristotle University of Thessaloniki, Greece. Electronic address:

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http://dx.doi.org/10.1016/j.hjc.2018.05.006DOI Listing
October 2020

Epidemiology and management of chronic thromboembolic pulmonary hypertension: experience from two expert centers.

Hellenic J Cardiol 2018 Jan - Feb;59(1):16-23. Epub 2017 May 17.

First Cardiology Department, AHEPA University Hospital, Aristotle University of Thessaloniki, Greece. Electronic address:

Objectives: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, distinct pulmonary vascular disease, and therefore, there is a lack of data regarding its clinical presentation, diagnosis, and management at a national basis. We aimed to describe the demographics and management of patients with CTEPH in Northern Greece.

Methods: We conducted a retrospective, observational study by a joint collaboration between two pulmonary hypertension expert centers in Greece, and the study included patients diagnosed with CTEPH. The patient population was divided into two groups depending on their operability.

Results: Overall, 27 consecutive patients were included (59% female, mean age 59.3±15.1 years). Dyspnea and fatigue were the most common presenting symptoms. History of pulmonary embolism was present in 82%. Of patients, 18 (67%) were assessed as operable, of whom 10 (55%) finally underwent pulmonary endarterectomy (PEA). There were no differences in symptoms, WHO functional class, 6-min walking test distance, and hemodynamics between the operable and nonoperable groups. At the end of follow-up, all non-operable and operable patients who did not receive surgical treatment were treated with at least one pulmonary hypertension-specific drug.

Conclusion: This is the first report that presents data of patients diagnosed with CTEPH in Greece. The percentage of patients who underwent surgical treatment is lower but approaches the reported rates in large registries. Considering that PEA is a relatively safe and potentially curative surgical procedure, we emphasize the need for establishing a designated PEA center in Greece.
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http://dx.doi.org/10.1016/j.hjc.2017.05.005DOI Listing
September 2018

An Overview of Pharmacotherapy in Hypertrophic Cardiomyopathy: Current Speculations and Clinical Perspectives.

Rev Cardiovasc Med 2016 ;17(3-4):115-123

Cardiomyopathies Center, First Cardiology Department, AHEPA Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. Its clinical course is variable, ranging from a benign asymptomatic or mildly symptomatic course throughout life, to severe symptoms (dyspnea, angina, palpitations) or cardiovascular events (syncope and thromboembolism). Sudden cardiac death (SCD) remains the most striking manifestation of the disease, affecting a minority of patients. This review focuses on the medical treatments applied according to the symptomatology in obstructive and nonobstructive HCM; a special reference is made to atrial fibrillation and arterial hypertension, which often coexist with the disease. Current literature about the pharmaceutical prevention of SCD is also analyzed and novel pharmacologic agents and approaches that may represent the future management of HCM are critically reviewed. The analysis of interventional techniques that are used in cases of medical treatment failure is avoided. Rather than enumerating clinical studies and guidelines, this review provides a concise and contemporary analysis of HCM pharmacotherapy, developing applicable algorithms for clinicians and highlighting promising future drug regimens.
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October 2018