Papers by Genovefa Kolovou
Journal of Clinical Medicine
Heart failure (HF) patients frequently develop brain deficits that lead to cognitive dysfunction ... more Heart failure (HF) patients frequently develop brain deficits that lead to cognitive dysfunction (CD), which may ultimately also affect survival. There is an important interaction between brain and heart that becomes crucial for survival in patients with HF. Our aim was to review the brain/heart interactions in HF and discuss the emerging role of combined brain/heart magnetic resonance imaging (MRI) evaluation. A scoping review of published literature was conducted in the PubMed EMBASE (OVID), Web of Science, Scopus and PsycInfo databases. Keywords for searches included heart failure, brain lesion, brain, cognitive, cognitive dysfunction, magnetic resonance imaging cardiovascular magnetic resonance imaging electroencephalogram, positron emission tomography and echocardiography. CD testing, the most commonly used diagnostic approach, can identify neither subclinical cases nor the pathophysiologic background of CD. A combined brain/heart MRI has the capability of diagnosing brain/hear...
Angiology, 2018
We thank Tzovaras et al for their letter 1 regarding our previous study linking gene polymorphism... more We thank Tzovaras et al for their letter 1 regarding our previous study linking gene polymorphisms of tumor protein p53 with left main coronary artery disease. 2 In their letter, the association between cardiovascular disease (CVD) and cancer is briefly discussed. 1 In this context, apart from p53 gene, there are other genes that may contribute to the progression of both atherosclerosis and cancer. For example, the paraoxonase (PON) gene family, including 3 proteins (PON1, PON2, and PON3), has been involved in the development of CVD and cancer, thus representing potential therapeutic targets for these diseases. 3,4 Similarly, lectin-like oxidized low-density lipoprotein (LDL) receptor 1 has been reported to contribute to tumorigenesis and atherogenesis; therefore, its gene variants may affect susceptibility/protection from cancer and CVD. 5 C-reactive protein, a well-established marker of inflammation and atherosclerosis, 6-8 may also predict cancer prevalence and outcomes. 9,10 Lipoprotein lipase and cytochrome P450 CYP1A1 are also implicated in tumor progression and/or prevention, 11,12 apart from their role in atherogenesis. 13,14 These data highlight the presence of links between cancer and CVD in relation to several genes. Furthermore, modified LDL particles may act as codelivery polymers of anticancer therapy to tumor tissue. 15 Further large studies are needed to establish the clinical implications of such associations. Authors' Note N.K. has given talks, attended conferences and participated in trials sponsored by Amgen, Angelini, AstraZeneca, Boehringer Ingelheim, MSD, Novartis, Novo Nordisk, Sanofi, and WinMedica. G.K. have given talks, attended conferences, and participated in trials sponsored by Amgen, Angelini, MSD, Lilly, Vianex, and Sanofi-Aventis.
Diagnostics, 2020
Aims: T1-mapping is considered a surrogate marker of acute myocardial inflammation. However, in d... more Aims: T1-mapping is considered a surrogate marker of acute myocardial inflammation. However, in diffuse cutaneous systemic sclerosis (dcSSc) this might be confounded by coexisting myocardial fibrosis. We hypothesized that T1-based indices should not by themselves be considered as indicators of myocardial inflammation in dcSSc patients. Methods/Results: A cohort of 59 dcSSc and 34 infectious myocarditis patients was prospectively evaluated using a 1.5-Tesla system for an indication of suspected myocardial inflammation and was compared with 31 healthy controls. Collectively, 33 (97%) and 57 (98%) of myocarditis and dcSSc patients respectively had ≥1 pathologic T2-based index. However, 33 (97%) and 45 (76%) of myocarditis and dcSSc patients respectively had ≥1 pathologic T2-based index. T2-signal ratio was significantly higher in myocarditis patients compared with dcSSc patients (2.5 (0.6) vs. 2.1 (0.4), p < 0.001). Early gadolinium enhancement, late gadolinium enhancement and T2-ma...
International Journal of Clinical Practice, 2019
The influence of gene polymorphisms on postprandial triglyceride response after oral fat toleranc... more The influence of gene polymorphisms on postprandial triglyceride response after oral fat tolerance test meal in patients with diabetes mellitus Abstract Aims: We evaluated the influence of CETP (rs5882 and rs708272), APOE (rs7412, rs429358) and LPL (rs328) gene polymorphisms on triglyceride (TG) response to oral fat tolerance test meal (OFTT) in patients with well-controlled type 2 diabetes mellitus (T2DM). Methods: Fifty-one male underwent OFTT and according to postprandial TG response patients were divided to 2 subgroups [positive (TG=/>220mg/dL, 31 patients) and negative (TG <220mg/dL, 20 patients)]. All patients were genotyped, and study variants were detected using Polymerase Chain Reaction (PCR) and Restricted Fragment Length Polymorphism analysis (RFLP). Results: Patients with genotype SS of LPL gene compared with genotype SX had more frequently positive response to OFTT (p=0.04) and lower HDL cholesterol concentration (p=0.03). Patients with positive response to OFTT and genotype SS of LPL gene compared with genotype SX had lower AUC (area under the curve)-TG, 1744(368) vs 1887(807) mg/dL/h, respectively, p=0.04. CETP and APOE gene polymorphisms had no influence on postprandial TG response to OFTT. Conclusions: In patients with well-controlled T2DM, LPL but not CETP and APOE gene polymorphisms influenced TG postprandial response. Particularly, S447 allele carriers of LPL gene presented more frequently positive postprandial TG response to OFTT compared with 447X allele carriers. No differences were found between allele carriers of patients with negative response to OFTT in any other studied gene polymorphism.
Rheumatology International, 2018
Life expectancy in autoimmune rheumatic diseases (ARDs) remains lower compared to the general pop... more Life expectancy in autoimmune rheumatic diseases (ARDs) remains lower compared to the general population, due to various comoborbidities. Cardiovascular disease (CVD) represents the main contributor to premature mortality. Conventional and biologic disease-modifying antirheumatic drugs (DMARDs) have considerably improved long-term outcomes in ARDs not only by suppressing systemic inflammation but also by lowering CVD burden. Regarding atherosclerotic disease prevention, EULAR has recommended tight disease control accompanied by regular assessment of traditional CVD risk factors and lifestyle changes. However, this approach, although rational and evidence-based, does not account for important issues such as myocardial inflammation and the long asymptomatic period that usually proceeds clinical manifestations of CVD disease in ARDs before or after the diagnosis of systemic disease. Cardiovascular magnetic resonance (CMR) can offer reliable, reproducible and operator independent information regarding myocardial inflammation, ischemia and fibrosis. Some studies suggest a role for CMR in the risk stratification of ARDs and demonstrate that oedema/fibrosis visualisation with CMR may have the potential to inform cardiac and rheumatic treatment modification in ARDs with or without abnormal routine cardiac evaluation. In this review, we discuss how CMR findings could influence anti-rheumatic treatment decisions targeting optimal control of both systemic and myocardial inflammation irrespective of clinical manifestations of cardiac disease. CMR can provide a different approach that is very promising for risk stratification and treatment modification; however, further studies are needed before the inclusion of CMR in the routine evaluation and treatment of patients with ARDs.
Heart Failure Reviews, 2018
In iron overload diseases (thalassemia, sickle cell, and myelodysplastic syndrome), iron is depos... more In iron overload diseases (thalassemia, sickle cell, and myelodysplastic syndrome), iron is deposited in all internal organs, leading to functional abnormalities. Hematopoietic stem cell transplantation (HSCT) is the only treatment offering a potential cure in these diseases. Our aim was to describe the experience in the field and the role of magnetic resonance imaging in the evaluation of iron overload before and after HSCT. Magnetic resonance imaging (MRI), using T2*, is the most commonly used tool to diagnose myocardial-liver iron overload and guide tailored treatment. Currently, HSCT offers complete cure in thalassemia major, after overcoming the immunologic barrier, and should be considered for all patients who have a suitable donor. The overall thalassemia-free survival of low-risk, HLA-matched sibling stem cell transplantation patients is 85-90%, with a 95% overall survival. The problems of rejection and engraftment are improving with the use of adequate immunosuppression. However, a detailed iron assessment of both heart and liver is necessary for pre-and post-transplant evaluation. In iron overload diseases, heart and liver iron evaluation is indispensable not only for the patients' survival, but also for evaluation before and after HSCT.
European journal of clinical investigation, Jan 5, 2017
Duchenne muscular dystrophy (DMD) is an X-linked muscle disorder characterized by progressive and... more Duchenne muscular dystrophy (DMD) is an X-linked muscle disorder characterized by progressive and irreversible loss of muscular function. As muscular disease progresses, the repair mechanisms cannot compensate for cellular damage, leading inevitably to necrosis and progressive replacement by fibrous and fatty tissue. Cardiomyopathy and respiratory failure are the main causes of death in DMD. In addition to the well-described muscle and heart disease, cognitive dysfunction affects around 30% of DMD boys. Myocardial fibrosis, assessed by late gadolinium enhancement (LGE), using cardiovascular magnetic resonance imaging (CMR), is an early marker of heart involvement in both DMD patients and female carriers. In parallel, brain MRI identifies smaller total brain volume, smaller gray matter volume, lower white matter fractional anisotropy and higher white matter radial diffusivity in DMD patients. The in vivo brain evaluation of mdx mice, a surrogate animal model of DMD, showed an increas...
European journal of clinical investigation, Jan 13, 2017
Duchenne muscular dystrophy (DMD) is an X-linked muscle disorder characterized by progressive, ir... more Duchenne muscular dystrophy (DMD) is an X-linked muscle disorder characterized by progressive, irreversible loss of cardiac and skeletal muscular function. Muscular enlargement in DMD is attributed to oedema, due to the increased cytoplasmic Na+ concentration. The aim in this review is to present the current experience and emphasize the role of cardiovascular magnetic resonance (CMR) in the diagnosis of this condition. DMD patients' survival depends on ventilatory assistance, as respiratory muscle dysfunction was the most common cause of death in the past. Currently, due to improved ventilatory assistance, cardiomyopathy has become the main cause of death. even though clinically overt heart failure may be absent. CMR is the technique of choice to assess the pathophysiologic phenomena taking place in DMD, such as myocardial oedema and subepicardial fibrosis. The classic index to assess oedema is the T2-weighted short-tau inversion recovery (T2w-STIR), as it suppresses the signal ...
BMC cardiovascular disorders, Jul 24, 2017
To evaluate cardiovascular function in boys with Duchenne (DMD) and Becker (BMD) muscular dystrop... more To evaluate cardiovascular function in boys with Duchenne (DMD) and Becker (BMD) muscular dystrophy, using cardiac magnetic resonance (CMR). This is a single point cross sectional study of twenty-four boys with genetically ascertained DMD, and 10 with BMD, aged 10.5 ± 1.5 years (range 9-13), were prospectively evaluated by a 1.5 T system and compared with those of age-sex matched controls. The DMD patients were divided in 2 groups. Group A (N = 12) were under treatment with both deflazacort and perindopril, while Group B (n = 12) were under treatment with deflazacort, only. BMD patients did not take any medication. Biventricular function was assessed using a standard SSFP sequence. Late gadolinium enhancement (LGE) was assessed from T1 images taken 15 min after injection of 0.2 mg/Kg gadolinium DTPA using a 3D-T1-TFE sequence. Group A and BMDs were asymptomatic with normal ECG, 24 h ECG recording and echocardiogram. Group B were asymptomatic but 6/12 had abnormal ECG and mildly impa...
Current vascular pharmacology, Jan 28, 2017
Enhanced postprandial lipaemia has been reported in patients with obesity, hypertension, metaboli... more Enhanced postprandial lipaemia has been reported in patients with obesity, hypertension, metabolic syndrome and type 2 diabetes mellitus (T2DM). We compared 2 oral fat meal tests (LIPOLD: 149g of fat, 56g of carbohydrates and 11.7g of proteins administrated per 2m2 of body surface) and LIPOTEST: 75g of fat, 25g of carbohydrates and 10g of protein with the addition of 15g common sugar) with regard to changes in triglycerides (TGs) as well as other cardiometabolic parameters between baseline and 4 h after the meals METHODS: We studied 21 men [median age (interquartile range; IQR) = 65 (16) years] with well-controlled T2DM [median glycated haemoglobin (HbA1c) (IQR) = 6.6 (0.9) %]. All participants performed the meals with 1 week interval between the 2 meals. Median (IQR) TG differences in mg/dl were 86 (100) and 46 (60) for LIPOLD and LIPOTEST meals, respectively, whereas the % differences in TGs were 105 (105) and 48 (55), respectively. The differences (in mg/dl and %) between TGs bef...
International journal of cardiology, 2017
Peripheral Raynaud's phenomenon (RP) is either primary (PRP), without any coexisting disease ... more Peripheral Raynaud's phenomenon (RP) is either primary (PRP), without any coexisting disease or secondary (SRP), due to connective tissue diseases (CTD). We hypothesized that adenosine stress cardiovascular magnetic resonance (CMR) can assess myocardial perfusion in a population of PRP and SRP. Twenty CTDs, aged 30.6±7.5yrs., 16F/4M, including 9 systemic sclerosis (SSc), 4 systemic lupus erythematosus (SLE), 3 mixed connective tissue disease (MCTD), 2 polymyositis (PM) and 2 rheumatoid arthritis (RA), with SRP, under treatment with calcium blockers, were evaluated by stress CMR and compared with age-sex matched PRP and controls. All RP patients were under treatment with calcium blockers. Stress perfusion CMR was performed by 1.5T system using 140mg/kg/min adenosine for 4min and 0.05mmol/kg Gd-DTPA for first-pass perfusion. A rest perfusion was performed with the same protocol. Late gadolinium enhanced (LGE) images were acquired after another dose of Gd-DTPA. In both PRP, SRP, th...
International journal of cardiology, 2017
Cardiac involvement at diagnosis of connective tissue disease (CTD) has been described by echocar... more Cardiac involvement at diagnosis of connective tissue disease (CTD) has been described by echocardiography. We hypothesized that cardio-vascular magnetic resonance (CMR) detects occult lesions at CTD diagnosis. CMR was performed early after diagnosis in 78 treatment-naïve CTDs (aged 43±11, 59F/19M) without cardiac involvement [5 Takayasu arteritis (TA), 4 Churg Strauss syndrome (CSS), 5 Wegener granulomatosis (WG), 16 systemic lupus erythematosus (SLE), 12 rheumatoid arthritis (RA), 8 mixed connective tissue diseases (MCTD), 12 ankylosing spondylitis (AS), 3 polymyalgia rheumatica (PMR), 8 systemic sclerosis (SSc) and 5 dermatomyositis (DM)]. Acute and chronic lesions were assessed by T2>2 with positive LGE and T2<2 with positive LGE, respectively. In 3/5 TA, 3/4 CSS, 4/5 WG, 10/16 SLE, 9/12 RA, 6/8 MCTD, 4/12 AS, 1/3 PMR, 2/8 SSc and 2/5 DM, the T2 ratio was higher compared to normal (2.78±0.25 vs 1.5±0.2, p<0.01). Myocarditis was identified in 1 TA, 1 SLE, 1 RA, 1 SSc and...
Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese, Jan 10, 2017
Although the risk of MRI scanning on patients with conventional devices is lower than initially t... more Although the risk of MRI scanning on patients with conventional devices is lower than initially thought, the patient's safety can only be guaranteed when using MRI-conditional devices. The most important modifications in MRI-conditional devices include a) Reduction in ferromagnetic components to reduce magnetic attraction and susceptibility artifacts; b) Replacement of the reed switch by a Hall sensor in order to avoid unpredictable reed switch behavior; c) Lead coil design to minimize lead heating and electrical current induction; d) Filter circuitry to prevent damage to the internal power supply; and e) Dedicated pacemaker programming to prevent inappropriate pacemaker inhibition and competing rhythms. Although many companies claim to have MRI-conditional devices, adoption in clinical practice is limited because a) Not all companies have MRI-conditional devices approved for both 1.5 and 3T; b) Not all companies offer the option of unlimited MRI scanning (without an exclusion z...
Heart, 2016
Ankylosing spondylitis (AS) associates with various cardiac lesions, including aortitis/aortic re... more Ankylosing spondylitis (AS) associates with various cardiac lesions, including aortitis/aortic regurgitation, conduction abnormalities and myocardial involvement, due to either coronary artery disease or primary cardiomyopathy.1 The cornerstone tool for the non-invasive evaluation of heart involvement has, until recently, been echocardiography.1 Echocardiographic evaluation in AS is mainly focused on valve and ventricular function assessment, with the pattern of ‘diastolic dysfunction with preserved ejection fraction’ being the most common preclinical finding. A strong correlation has also been shown between several indices of vascular pathology associated with the development of cardiovascular disease (CVD) and increased disease activity in patients with AS.2 Cardiovascular magnetic resonance (CMR), a non-invasive, non-radiating, operator-independent technique, currently represents the gold standard for ventricular function and tissue characterisation in patients with CVD, including those in whom CVD develops in the context of a connective tissue disease (CTD).3 ,4 Recently, new CMR indices, such as native and postcontrast T1 mapping, T2 mapping and extracellular volume quantification (ECV) have been successfully used to identify preclinical cardiac lesions …
Current Medicinal Chemistry, 2015
World Journal of Cardiology, 2015
Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked muscular diseases responsible for o... more Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked muscular diseases responsible for over 80% of all muscular dystrophies. Cardiac disease is a
International journal of cardiology, Jan 15, 2014
Recent LBBB in connective tissue diseases (CTDs) is challenging, due to high incidence of underly... more Recent LBBB in connective tissue diseases (CTDs) is challenging, due to high incidence of underlying pathology that may remain undetected, due to limitations of imaging tests. We hypothesized that cardiovascular magnetic resonance (CMR) may be of diagnostic value in CTDs with recent LBBB and normal echocardiogram. 26 CTDs, aged 32 ± 7 yrs (19 F) and 26 controls without CTDs, aged 60 ± 4 yrs (10 F) with recent LBBB and normal echo were evaluated by CMR. The CTDs included 6 sarcoidosis (SRC), 4 systemic sclerosis (SSc), 6 systemic lupus erythematosus (SLE), 6 rheumatoid arthritis (RA) and 4 inflammatory myopathies (IM). CMR was performed by 1.5T. LVEF, T2 ratio (oedema imaging) and late gadolinium enhancement (LGE) (fibrosis imaging) were evaluated. Acute and chronic lesions were characterised by T2>2 and positive LGE and T2<2 and positive LGE, respectively. According to LGE, lesions were characterised as diffuse subendo-, subepicardial/intramural not following and subendocardia...
Hellenic journal of cardiology : HJC = Hellēnikē kardiologikē epitheōrēsē
We carried out an evaluation of Greek cardiovascular magnetic resonance (CMR) data in order to an... more We carried out an evaluation of Greek cardiovascular magnetic resonance (CMR) data in order to analyse the indications, safety, quality, and impact on management, in comparison with the EuroCMR registry. A retrospective analysis was performed of Greek CMR data from patients referred from 6 Greek cardiac clinics to 6 different MRI units in Athens that offer CMR services. A total of 10,000 CMR examinations carried out from 1995 to 2010 were evaluated retrospectively and included in the study. Fifty percent of patients underwent evaluation for thalassaemic syndromes. In the remaining 50%, the most important indications were: a) workup of myocarditis/cardiomyopathies (40%), b) assessment of viability (5%), and c) congenital heart disease (5%). Image quality was good in 75%, moderate in 15%, and inadequate in 10% of cases. Complications occurred in 0.02%, including allergic reactions, dyspnoea, and panic attack. No death or cardiac complication was observed during or due to CMR; however,...
European Cardiology Review, 2014
A systemic disease is one that affects a number of organs and tissues, or the body as a whole. Sy... more A systemic disease is one that affects a number of organs and tissues, or the body as a whole. Systemic diseases include endocrine, metabolic, nutritional, multisystem (rheumatic) and HIV disease. Cardiovascular involvement is a common and underestimated problem in systemic diseases, and may present with disease associated cardiac involvement at diagnosis or later in the course of the systemic disease. The cardiac involvement in these diseases is usually silent or oligo-symptomatic and includes different pathophysiological mechanisms such as, myocardial inflammation, infarction, diffuse, subendocardial vasculitis, valvular disease and different patterns of fibrosis. Furthermore, acuity of heart involvement may be underestimated due to non-specific cardiac signs, and finally, most of patients are female and unable to exercise, due to arthritis or muscular discomfort/weakness or may have limited acoustic window, due to increased breast size. Cardiovascular magnetic resonance (CMR), du...
The International Journal of Cardiovascular Imaging, 2013
Kawasaki disease (KD) is a vasculitis affecting the coronary and systemic arteries. Myocardial in... more Kawasaki disease (KD) is a vasculitis affecting the coronary and systemic arteries. Myocardial inflammation is also a common finding in KD post-mortem evaluation during the acute phase of the disease. Coronary artery aneurysms (CAAs) develop in 15-25% of untreated children. Although 50-70% of CAAs resolve spontaneously 1-2 years after the onset of KD, the remaining unresolved CAAs can develop stenotic lesions at either their proximal or distal end and can develop thrombus formation leading to ischemia and/or infarction. Cardiovascular magnetic resonance (CMR) has the ability to perform non-invasive and radiation-free evaluation of the coronary artery lumen. Recently tissue characterization of the coronary vessel wall was provided by CMR. It can also image myocardial inflammation, ischemia and fibrosis. Therefore CMR offers important clinical information during the acute and chronic phase of KD. In the acute phase, it can identify myocardial inflammation, microvascular disease, myocardial infarction, deterioration of left ventricular function, changes of the coronary artery lumen and changes of the coronary artery vessel wall. During the chronic phase, CMR imaging might be of value for risk stratification and to guide treatment.
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Papers by Genovefa Kolovou