Coronary microvascular disease: The "Meeting Point" of Cardiology, Rheumatology and Endocrinology.

BACKGROUND: Exertional chest pain/dyspnea or chest pain at rest are the main symptoms of coronary artery disease (CAD), which are traditionally attributed to insufficiency of the epicardial coronary arteries. However, 2/3 of women and 1/3 of men with angina and 10% of patients with acute myocardial infarction have no evidence of epicardial coronary artery stenosis in X-ray coronary angiography. In these cases, coronary microvascular disease (CMD) is the main causative factor. AIMS: To present the pathophysiology of CMD in Cardiology, Rheumatology and Endocrinology. MATERIALS-METHODS: The pathophysiology of CMD in Cardiology, Rheumatology and Endocrinology was evaluated. It includes impaired microvascular vasodilatation, which leads to inability of the organism to deal with myocardial oxygen needs and, hence, development of ischemic pain. CMD, observed in inflammatory autoimmune rheumatic and endocrine/metabolic disorders, brings together Cardiology, Rheumatology and Endocrinology. Causative factors include persistent systemic inflammation and endocrine/metabolic abnormalities influencing directly the coronary microvasculature. In the past, the evaluation of microcirculation was feasible only with the use of invasive techniques, such as coronary flow reserve assessment. Currently, the application of advanced imaging modalities, such as cardiovascular magnetic resonance (CMR), can evaluate CMD non-invasively and without ionizing radiation. RESULTS: CMD may present with a variety of symptoms with 1/3 to 2/3 of them expressed as typical chest pain in effort, more commonly found in women during menopause than in men. Atypical presentation includes chest pain at rest or exertional dyspnea,but post exercise symptoms are not uncommon. The treatment with nitrates is less effective in CMD, because their vasodilator action in coronary micro-circulation is less pronounced than in the epicardial coronary arteries. DISCUSSION: Although both classic and new medications have been used in the treatment of CMD, there are still many questions regarding both the pathophysiology and the treatment of this disorder. The potential effects of anti-rheumatic and endocrine medications on the evolution of CMD need further evaluation. CONCLUSION: CMD is a multifactorial disease leading to myocardial ischemia/fibrosis alone or in combination with epicardial coronary artery disease. Endothelial dysfunction/vasospasm, systemic inflammation, and/or neuroendocrine activation may act as causative factors and bring Cardiology, Rheumatology and Endocrinology together. Currently, the application of advanced imaging modalities, and specifically CMR, allows reliable assessment of the extent and severity of CMD. These measurements should not be limited to "pure cardiac patients", as it is known that CMD affects the majority of patients with autoimmune rheumatic and endocrine/metabolic disorders.

The effect of moderate wine consumption on cytokine secretion by peripheral blood mononuclear cells: A randomized clinical study in coronary heart disease patients.

Many studies conclude that wine consumption is related to lower risk for cardiovascular diseases partially through the amelioration of inflammatory biomarkers. The aim of the present study was to examine the effects of wine consumption on the inflammatory response and to compare these effects with the consumption of similar amount of alcohol without the wine micro-constituents in cardiovascular disease patients. Therefore, a randomized, single-blind, controlled, three-arm parallel intervention study was designed. Cardiovascular disease patients were randomly assigned to one of the three groups. In Group A participants consumed no alcohol, in Group B (ethanol group) and Group C (wine group) participants consumed 27 g of alcohol per day. Biological samples were collected at the beginning, on the 4th and 8th week and several biomarkers were measured. Peripheral blood mononuclear cells that were isolated from patients were incubated under basal and inflammatory conditions for 4 and 24 h and the secretion of interleukin 1ß (IL-1ß) and tumor necrosis factor α (TNFα) was measured. No significant difference was observed among the three groups before the initiation or during the intervention in the most soluble biomarkers. Higher TNFα secretion by peripheral blood mononuclear cells was observed at basal conditions in the ethanol group both at 4 and 24 h of incubation versus baseline secretion. Furthermore, lower secretion of the ΤNFα was observed after 8 weeks of intake in the wine group versus the ethanol group, both at 4 and 24 h of incubation. In conclusion, the light to moderate wine consumption for 8 weeks revealed an attenuation of the ethanol consumption effect on cytokine secretion at basal conditions from the patients' peripheral blood mononuclear cells.

The importance of heart and brain imaging in children and adolescents with Multisystem Inflammatory Syndrome in Children (MIS-C).

Multisystem Inflammatory Syndrome in Children (MIS-C) recently reported in a minority of children affected by SARS-CoV-2, mimics Kawasaki disease (KD), a medium vessel vasculitis of unknown cause. In contrast to acute COVID-19 infection, which is usually mild in children, 68% of patients with MIS-C will need intensive care unit. Myocarditis and coronary artery ectasia/aneurysm are included between the main cardiovascular complications in MIS-C. Therefore, close clinical assessment is need it both at diagnosis and during follow-up. Echocardiography is the cornerstone modality for myocardial function and coronary artery evaluation in the acute phase. Cardiovascular magnetic resonance (CMR) detects diffuse myocardial inflammation including oedema/fibrosis, myocardial perfusion and coronary arteries anatomy during the convalescence and in adolescents, where echocardiography may provide inadequate images. Brain involvement in MIS-C is less frequent compared to cardiovascular disease. However, it is not unusual and should be monitored by clinical evaluation and brain magnetic resonance (MRI), as we still do not know its effect in brain development. Brain MRI in MIS-C shows T2-hyperintense lesions associated with restricted diffusion and bilateral thalamic lesions. To conclude, MIS-C is a multisystem disease affecting many vital organs, such as heart and brain. Clinical awareness, application of innovative, high technology imaging modalities and advanced treatment protocols including supportive and anti-inflammatory medication will help physicians to prevent the dreadful complications of MIS-C.

Cardiac amyloidosis: in search of the ideal diagnostic tool.

BACKGROUND: Cardiac amyloidosis (CA) is due to amyloid deposition in the myocardium. Transthyretin (ATTR) and light-chain (AL) amyloidosis are the main types of CA. Here, we present the clinical and imaging findings in patients with CA and discuss the controversies with the aim of finding the ideal diagnostic tool. METHODS: Ten patients suspected of having CA on the basis of electrocardiographic (ECG) and echocardiographic findings were evaluated via cardiovascular magnetic resonance imaging (CMR; 1.5 T) using cine, late gadolinium enhancement (LGE), T1, T2 mapping, and extracellular volume fraction. N­terminal pro-B-type natriuretic peptide (NT-proBNP) levels were also assessed in all patients. RESULTS: All ten patients had an echocardiogram suggestive of CA. The CMR study documented ventricular hypertrophy leading to small ventricular volumes, as assessed by echocardiography. Diffuse subendocardial LGE, supporting the diagnosis of CA, was identified in all except one patient, who had subepicardial LGE due to myocarditis that was verified by endomyocardial biopsy (EMB). Right ventricular (RV) involvement was identified in four of the ten patients, whose condition deteriorated rapidly over the next 6 months. The NT-proBNP levels were >332 pg/ml in all except two patients. Light-chain amyloidosis was identified via fat tissue biopsy in two patients and through renal biopsy in one patient. In two patients with positive technetium-99m, EMB confirmed the diagnosis of ATTR. CONCLUSION: NT-proBNP may be a sensitive but nonspecific biomarker for assessing CA. However, CMR is the only imaging modality that can assess the pathophysiologic background of cardiac hypertrophy and the severity of CA, irrespective of NT-proBNP level.

Cardiac magnetic resonance predicts ventricular arrhythmias in scleroderma: the Scleroderma Arrhythmia Clinical Utility Study (SAnCtUS).

OBJECTIVES: Cardiac rhythm disturbances constitute the most frequent cardiovascular cause of death in SSc. However, electrocardiographic findings are not a part of risk stratification in SSc. We aimed to translate 24 h Holter findings into a tangible risk prediction score using cardiovascular magnetic resonance. METHODS: The Scleroderma Arrhythmia Clinical Utility Study (SAnCtUS) was a prospective multicentre study including 150 consecutive SSc patients from eight European centres, assessed with 24 h Holter and cardiovascular magnetic resonance, including ventricular function, oedema (T2 ratio) and late gadolinium enhancement (%LGE). Laboratory/clinical parameters were included in multivariable corrections. A combined endpoint of sustained ventricular tachycardia requiring hospitalization and sudden cardiac death at a median (interquartile range) follow-up of 1 (1.0-1.4) year was generated. RESULTS: Only T2 ratio and %LGE were significant predictors of ventricular rhythm disturbances, but not of supraventricular rhythm disturbances, after multivariable correction and adjustment for multiple comparisons. Using decision-tree analysis, we created the SAnCtUS score, a four-category scoring system based on T2 ratio and %LGE, for identifying SSc patients at high risk of experiencing ventricular rhythm disturbance at baseline. Increasing SAnCtUS scores were associated with a greater disease and arrhythmic burden. All cases of non-sustained ventricular tachycardia (n = 7) occurred in patients with the highest SAnCtUS score (=4). Having a score of 4 conveyed a higher risk of reaching the combined endpoint in multivariable Cox regression compared with scores 1/2/3 [hazard ratio (95% CI): 3.86 (1.14, 13.04), P = 0.029] independently of left ventricular ejection fraction and baseline ventricular tachycardia occurrence. CONCLUSION: T2 ratio and %LGE had the greatest utility as independent predictors of rhythm disturbances in SSc patients.

The pivotal role of cardiovascular imaging in the identification and risk stratification of non-compaction cardiomyopathy patients.

Non-compaction cardiomyopathy (NCM) is a heterogeneous myocardial disease that can finally lead to heart failure, arrhythmias, and/or embolic events. Therefore, early diagnosis and treatment is of paramount importance. Furthermore, genetic assessment and counseling are crucial for individual risk assessment and family planning. Echocardiography is the first-line imaging modality. However, it is hampered by interobserver variability, depends among others on the quality of the acoustic window, cannot assess reliably the right ventricle and the apex, and cannot provide tissue characterization. Cardiovascular magnetic resonance (CMR) provides a 3D approach allowing imaging of the entire heart, including both left and right ventricle, with low operator variability or limitations due to patient's body structure. Furthermore, tissue characterization, using late gadolinium enhancement (LGE), allows the detection of fibrotic areas possibly representing the substrate for potentially lethal arrhythmias, predicts the severity of LV systolic dysfunction, and differentiates apical thrombus from fibrosis. Conversely, besides being associated with high costs, CMR has long acquisition/processing times, lack of expertise among cardiologists/radiologists, and limited availability. Additionally, in cases of respiratory and/or cardiac motion artifacts or arrhythmias, the cine images may be blurred. However, CMR cannot be applied to patients with not CMR-compatible implanted devices and LGE may be not available in patients with severely reduced GFR. Nevertheless, native T1 mapping can provide detailed tissue characterization in such cases. This tremendous potential of CMR makes this modality the ideal tool for better risk stratification of NCM patient, based not only on functional but also on tissue characterization information.

Is There a Brain/Heart Interaction in Rheumatoid Arthritis and Seronegative Spondyloartropathies? A Combined Brain/Heart Magnetic Resonance Imaging Reveals the Answer.

PURPOSE OF REVIEW: To present the interaction between brain/heart and emphasize the role of combined brain/heart magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA) and other seronegative spondyloarthropathies (SNA). RECENT FINDINGS: Both traditional cardiovascular disease (CVD) risk factors and intrinsic RA/SNA features contribute to the increased CVD-related morbidity/mortality. CVD in RA usually occurs a decade earlier than age- and sex-matched controls, and RA patients are twice more likely to develop myocardial infarction irrespective of age, history of prior CVD, and traditional CVD risk factors. RA also increases risk of non-ischemic heart failure (HF), valvular disease, and myo-pericarditis. CVD in SNA affects more commonly patients with long-standing disease. Ascending aortitis, aortic/mitral insufficiency, conduction defects, and diastolic dysfunction are the commonest findings in ankylosing spondylitis (AS). CVD is also the leading cause of death in psoriatic arthritis (PsA), due to myopericarditis, diastolic dysfunction, and valvular disease. Brain damage, due to either ischemic or hemorrhagic stroke and silent vascular damage, such as white matter hyperenhancement (WMH), is increased in both RA/SNA and may lead to cognitive dysfunction, depression, and brain atrophy. Magnetic resonance imaging (MRI) is ideal for serial brain/heart evaluation of patients with systemic diseases. RA/SNA patients are at high risk for brain/heart damage at early age, irrespectively of classic risk factors. Until more data will be obtained, a combined brain/heart MRI evaluation can be proposed in RA/SNA with new onset of arrhythmia and/or HF, cognitive dysfunction and/or depression.

Quantifying atherogenic lipoproteins for lipid-lowering strategies: consensus-based recommendations from EAS and EFLM.

The joint consensus panel of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) recently addressed present and future challenges in the laboratory diagnostics of atherogenic lipoproteins. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), LDL cholesterol (LDLC), and calculated non-HDLC (=total - HDLC) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDLC is the primary target of lipid-lowering therapies. For on-treatment follow-up, LDLC shall be measured or calculated by the same method to attenuate errors in treatment decisions due to marked between-method variations. Lipoprotein(a) [Lp(a)]-cholesterol is part of measured or calculated LDLC and should be estimated at least once in all patients at risk of ASCVD, especially in those whose LDLC declines poorly upon statin treatment. Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDLC or apolipoprotein B (apoB), especially in patients with mild-to-moderate hypertriglyceridemia (2-10 mmol/L). Non-HDLC includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. Additional apoB measurement can detect elevated LDL particle (LDLP) numbers often unidentified on the basis of LDLC alone. Reference intervals of lipids, lipoproteins, and apolipoproteins are reported for European men and women aged 20-100 years. However, laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds.

Achieving low-density lipoprotein cholesterol targets as assessed by different methods in patients with familial hypercholesterolemia: an analysis from the HELLAS-FH registry.

BACKGROUND: Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and increased cardiovascular disease (CVD) risk. FH patients often have increased lipoprotein(a) [Lp(a)] levels, which further increase CVD risk. Novel methods for accurately calculating LDL-C have been proposed. METHODS: Patients with FH were recruited by a network of Greek sites participating in the HELLAS-FH registry. LDL-C levels were calculated using the Friedewald (LDL-CF) and the Martin/Hopkins (LDL-CM/H) equations as well as after correcting LDL-CM/H for Lp(a) levels [LDL-CLp(a)corM/H]. The objective was to compare LDL-C levels and target achievement as estimated by different methods in FH patients. RESULTS: This analysis included 1620 patients (1423 adults and 197 children). In adults at diagnosis, LDL-CF and LDL-CM/H levels were similar [235 ± 70 mg/dL (6.1 ± 1.8 mmol/L) vs 235 ± 69 mg/dL (6.1 ± 1.8 mmol/L), respectively; P = NS], while LDL-CLp(a)corM/H levels were non-significantly lower than LDL-CF [211 ± 61 mg/dL (5.5 ± 1.6 mmol/L); P = 0.432]. In treated adults (n = 966) both LDL-CF [150 ± 71 mg/dL (3.9 ± 1.8 mmol/L)] and LDL-CM/H levels [151 ± 70 mg/dL (6.1 ± 1.8 mmol/L); P = 0.746] were similar, whereas LDL-CLp(a)corM/H levels were significantly lower than LDL-CF [121 ± 62 mg/dL (3.1 ± 1.6 mmol/L); P < 0.001]. Target achievement as per latest guidelines in treated patients using the LDL-CM/H (2.5%) and especially LDL-CLp(a)corM/H methods (10.7%) were significantly different than LDL-CF (2.9%; P < 0.001). In children, all 3 formulas resulted in similar LDL-C levels, both at diagnosis and in treated patients. However, target achievement by LDL-CF was lower compared with LDL-CM/H and LDL-CLp(a)corM/H methods (22.1 vs 24.8 vs 33.3%; P < 0.001 for both comparisons). CONCLUSION: LDL-CLp(a)corM/H results in significantly lower values and higher target achievement rate in both treated adults and children. If validated in clinical trials, LDL-CLp(a)corM/H may become the method of choice to more accurately estimate 'true' LDL-C levels in FH patients.

Current understanding and future perspectives of brain-heart-kidney axis in psoriatic arthritis.

Psoriatic arthritis (PsA) patients are at a higher risk of systemic inflammatory sequelae, leading to microalbuminuria, cardiovascular (CVD) and neuropsychiatric (NPD) disease. Our aim is to present the existing literature about the relationship between CVD, kidney and NPD in PsA. The literature evaluation of PsA revealed that chronic T-cell activation and increased levels of circulating immune complexes can cause glomerular injury leading to microalbuminuria, which predicts CVD and all-cause mortality in both diabetic and non-diabetic patients. Furthermore, it is a marker of preclinical brain damage and identifies patients at higher risk of NPD/CVD events. Among the currently used imaging modalities in PsA, magnetic resonance imaging (MRI) maintains a crucial role, because it is ideal for concurrent evaluation of brain/heart involvement and serial follow up assessment. There is increasing evidence regarding the relationship between kidneys, heart and brain in PsA. Although currently there are no official recommendations about a combined brain/heart MRI in PsA, it could be considered in PsA with microalbuminuria, arrhythmia, HF, cognitive dysfunction and/or depression.

Myocardial Involvement in Rheumatic Disorders.

PURPOSE OF REVIEW: Autoimmune rheumatic diseases (ARDs) affect 8% of the population and approximately 78% of patients are women. Myocardial disease in ARDs is the endpoint of various pathophysiologic mechanisms including atherosclerosis, valvular disease, systemic, myocardial, and/or vascular inflammation, as well as myocardial ischemia and replacement/diffuse fibrosis. RECENT FINDINGS: The increased risk of CVD in ARDs leads to excess comorbidity not fully explained by traditional cardiovascular risk factors. It seems that the chronic inflammatory status typically seen in ARDs, promotes both the development of myocardial inflammation/fibrosis and the acceleration of atherosclerosis. CMR (cardio-vascular magnetic resonance) is the ideal imaging modality for the evaluation of cardiac involvement in patients with ARDs, as it can simultaneously assess cardiac function and characterize myocardial tissues with regard to oedema and fibrosis. Due to its high spatial resolution, CMR is capable of identifying various disease entities such as myocardial oedema /inflammation, subendocardial vasculitis and myocardial fibrosis, that are often missed by other imaging modalities, notably at an early stage of development. Although generally accepted guidelines about the application of CMR in ARDs have not yet been formulated, according to our experience and the available published literature, we recommend CMR in ARD patientS with new-onset heart failure (HF), arrhythmia, for treatment evaluation/change or if there is any mismatch between patient symptoms and routine non-invasive evaluation.

Pathophysiology and imaging of heart failure in women with autoimmune rheumatic diseases.

Autoimmune rheumatic diseases (ARDs) affect 8% of the population, and approximately 78% of them are women. Cardiovascular disease (CVD) in ARDs encompasses different pathophysiologic processes, such as endothelial dysfunction, myocardial/vascular inflammation and accelerated atherosclerosis with silent clinical presentation, leading to heart failure (HF), usually with preserved ejection fraction. Echocardiography and cardiovascular magnetic resonance (CMR) are the two most commonly used noninvasive imaging modalities for the evaluation of HF in patients with ARDs. Echocardiography currently represents the main diagnostic tool for cardiac imaging in clinical practice. However, the demand for more efficient and prompt diagnostic and therapeutic approach in this specific population necessitates the implementation of modalities capable of providing a more detailed and quantified information from the point of tissue characterization. Furthermore, echocardiography is an operator and acoustic window depended modality, with relatively low reproducibility and unable to perform tissue characterization. CMR is a noninvasive modality without radiation that can give reproducible and operator-independent information about both myocardial function and tissue characterization. By providing quantification of oedema, stress perfusion defects and fibrosis, CMR can diagnose myocardial inflammation, micro-macro-vascular myocardial ischemia and replacement or diffuse fibrosis, respectively. Tissue characterization allows for moving beyond the cardiac function to the assessment of intra- and inter-cellular alterations and promotes the development of personalized cardiac and anti-rheumatic treatment in ARDs with HF. ARDs are mainly female diseases. Cardiac involvement leading in HF is not unusual in ARDs and remains the main cause of death. Noninvasive, nonradiating imaging modalities such as echocardiography and CMR represent the main diagnostic tools. Specifically, echocardiography represents the first diagnostic approach; however, it is CMR that gives information about the pathophysiologic background behind HF in ARDs.

Cardio-oncology, the myth of Sisyphus, and cardiovascular disease in breast cancer survivors.

The number of breast cancer (BC) survivors has been increasing lately, due to the improvement in early detection strategies and oncological treatments. However, BC survivors are 3 times as likely to develop heart failure (HF) within 5 years of cancer diagnosis, and 7/100 of them will develop HF in a median follow-up of 8.5 years. Furthermore, HF in BC survivors has a worse prognosis compared to other causes of HF. Anthracyclines and trastuzumab have been proven to improve survival. However, they are also considered as the main causative factors of HF in BC survivors. Old patients, those with a pre-existing cardiovascular (CV) risk factors/disease, prior exposure to chemotherapy and radiotherapy are at increased risk. Serial evaluation of troponins and cardiac imaging parameters using echocardiography and cardiovascular magnetic resonance can significantly contribute to the early diagnosis of cardiac involvement before overt HF will develop. Assessment and immediate treatment of traditional CV risk factors is the first step for cardiotoxicity prevention. In BC survivors with known heart disease, the clinical stabilization is strongly recommended for cardiotoxicity prevention. Finally, in high-risk CV patients, primary prevention including cardioprotectants and/or CV drugs should be applied. According to recent studies, the early start of ACE inhibitors and ß-blockers and the modification of anti-cancer treatment can prevent the decline in left ventricular ejection fraction. However, further multicenter studies are needed to establish both prevention and treatment protocols to successfully overcome HF development in BC survivors.

Gender-related differences in side-effects and hemodynamic response to regadenoson in patients undergoing SPECT myocardial perfusion imaging.

PURPOSE: To evaluate differences in side-effects and hemodynamic response between men and women undergoing regadenoson-stress SPECT myocardial perfusion imaging (MPI). METHODS: The initial population of the study included 858 consecutive patients who underwent regadenoson-stress MPI at our institution. These patients underwent prospective assessment and classification of regadenoson-induced side-effects in six categories and recording of heart rate (HR) and blood pressure (BP) before and after regadenoson administration. From this initial population, after adjustment with 1:1 propensity matching using gender as the dependent variable and age, BMI, diabetes mellitus, hypertension, smoking, presence of coronary artery disease, LVEF, baseline systolic and diastolic blood pressure (BP) and HR, on-going use of cardio-active medications during test, and abnormal MPI scan as independent variables, a population of 279 pairs of opposite gender was formed and studied. RESULTS: Compared with men, women had a significantly higher rate of any side-effect (71% vs. 58%, p = 0.002), chest pain (23% vs. 12%, p < 0.001), gastrointestinal discomfort (20% vs. 12%, p = 0.01), dizziness (12% vs. 5%, p = 0.002), and headache (20% vs. 13%, p = 0.03) and similar rates of dyspnea and other side-effects. Women demonstrated a higher median HR-response compared with men (41% (- 8, 127) vs. 34% (- 5, 106), p = 0.001) while men demonstrated a lower median systolic BP response (- 3% (- 27, 48) vs. 0% (- 36, 68), p = 0.02) compared with women. CONCLUSIONS: Gender is independently associated with a differential response to regadenoson with regard to overall side-effects and HR-response. These observations have the potential of important management and prognostic implications respectively.

Adenosine stress myocardial perfusion imaging in octogenarians: Safety, tolerability, and long-term prognostic implications of hemodynamic response and SPECT-related variables.

BACKGROUND: Evaluation of tolerability, safety, and prognostic implications of adenosine stress myocardial perfusion imaging (MPI) in octogenarians. METHODS: 370 octogenarians (49% known coronary artery disease) were studied. Hemodynamic response, MPI-related data, and rest-left ventricular ejection fraction (LVEF) based on echocardiography were registered per patient, and prospective follow-up was performed to document all-cause death (ACD), cardiac death (CD), myocardial infarction (MI), and late revascularization. RESULTS: No deaths or MIs were observed during adenosine infusion or the short-term post-infusion period. 86% of patients were able to tolerate a 6-minute infusion. All side effects terminated spontaneously after infusion cessation, except for one case of pulmonary oedema. After 9.3 years, there were 124 ACDs, 62 CDs, 16 MIs, and 35 revascularizations. Differences between survival curves of summed stress score (SSS)-based risk groups were significant for all end points (P < .001). SSS and LVEF were independent predictors of all end points (P ≤ .01) and lung uptake of cardiac end points. ΔHR <10 bpm (OR = 1.78, P = .004) and inability to increase HR by >10 bpm and decrease systolic blood pressure by >10 mmHg (OR = 2, P = .02) during adenosine infusion were independent predictors of ACD and CD, respectively. Hemodynamic response variables, SSS, and lung uptake provided incremental prognostic value over pre-test data for ACD and CD. CONCLUSIONS: In octogenarians, adenosine stress MPI is well tolerated and provides effective long-term risk stratification.

The influence of gene polymorphisms on postprandial triglyceride response after oral fat tolerance test meal in patients with diabetes mellitus.

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 (OFTT) meal in patients with well-controlled type 2 diabetes mellitus (T2DM). METHODS: Fifty-one men underwent OFTT and according to postprandial TG response patients were divided into two subgroups (positive [TG ≥ 220 mg/dL, 31 patients] and negative [TG < 220 mg/dL, 20 patients]). All patients were genotyped, and study variants were detected using polymerase chain reaction (PCR) and restricted fragment length polymorphism (RFLP) analysis. RESULTS: Patients with genotype SS of LPL gene compared with genotype SX had more frequently positive response to OFTT (P = .04) and lower high-density lipoprotein cholesterol (HDL-C) concentration (P = .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 = .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.

Quantifying Atherogenic Lipoproteins: Current and Future Challenges in the Era of Personalized Medicine and Very Low Concentrations of LDL Cholesterol. A Consensus Statement from EAS and EFLM.

BACKGROUND: The European Atherosclerosis Society-European Federation of Clinical Chemistry and Laboratory Medicine Consensus Panel aims to provide recommendations to optimize atherogenic lipoprotein quantification for cardiovascular risk management. CONTENT: We critically examined LDL cholesterol, non-HDL cholesterol, apolipoprotein B (apoB), and LDL particle number assays based on key criteria for medical application of biomarkers. (a) Analytical performance: Discordant LDL cholesterol quantification occurs when LDL cholesterol is measured or calculated with different assays, especially in patients with hypertriglyceridemia >175 mg/dL (2 mmol/L) and low LDL cholesterol concentrations <70 mg/dL (1.8 mmol/L). Increased lipoprotein(a) should be excluded in patients not achieving LDL cholesterol goals with treatment. Non-HDL cholesterol includes the atherogenic risk component of remnant cholesterol and can be calculated in a standard nonfasting lipid panel without additional expense. ApoB more accurately reflects LDL particle number. (b) Clinical performance: LDL cholesterol, non-HDL cholesterol, and apoB are comparable predictors of cardiovascular events in prospective population studies and clinical trials; however, discordance analysis of the markers improves risk prediction by adding remnant cholesterol (included in non-HDL cholesterol) and LDL particle number (with apoB) risk components to LDL cholesterol testing. (c) Clinical and cost-effectiveness: There is no consistent evidence yet that non-HDL cholesterol-, apoB-, or LDL particle-targeted treatment reduces the number of cardiovascular events and healthcare-related costs than treatment targeted to LDL cholesterol. SUMMARY: Follow-up of pre- and on-treatment (measured or calculated) LDL cholesterol concentration in a patient should ideally be performed with the same documented test method. Non-HDL cholesterol (or apoB) should be the secondary treatment target in patients with mild to moderate hypertriglyceridemia, in whom LDL cholesterol measurement or calculation is less accurate and often less predictive of cardiovascular risk. Laboratories should report non-HDL cholesterol in all standard lipid panels.

Transplantation in patients with iron overload: is there a place for magnetic resonance imaging? : Transplantation in iron overload.

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.

Combined brain and heart magnetic resonance imaging in systemic vasculitides: fiction or real need?

Systemic vasculitides (SVs) is a group of diseases characterised by inflammation/necrosis of the blood vessel wall in various organs. Simultaneous brain and heart involvement is a cause of increased morbidity/mortality in SV. We aimed to present evidence of concurrent brain/heart involvement in SV and the role of a combined brain/heart magnetic resonance imaging (MRI) in their risk stratification. Cerebral vasculitis (CV) can be presented as focal deficits, seizures, headache, neuropsychiatric manifestations or cognitive dysfunction and cardiovascular disease (CVD) as myocardial/vascular inflammation, perfusion/function defects and fibrosis. MRI is a non-invasive, non-radiating technique that allows the reliable identification of intraparenchymal brain lesions and the detection of myocardial/vascular inflammation and fibrosis. However, its use in SV is currently hampered by high cost, lack of availability/expertise and lack of awareness among the clinicians. Although there are no clinical data supporting the combined use of brain/heart MRI in asymptomatic SV, it would be called for in cases with clinical suspicion of brain/heart involvement, especially in those at high risk for CVD/stroke such as SLE/APS. Furthermore, it may be of value in SV with multi-organ involvement, cognitive dysfunction or other neuropsychiatric symptoms with concurrent cardiac involvement, presenting as typical or atypical symptoms with normal routine cardiac evaluation, new onset of arrhythmia and/or HF.

The emerging role of cardiovascular magnetic resonance imaging in the assessment of cardiac involvement in juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the commonest rheumatic disease in childhood and presents several subtypes according to the ILAR classification. JIA, specifically in its systemic form, may seriously damage various structures of the cardiovascular system. Other JIA phenotypes are also of interest, as cardiovascular disease (CVD) is underestimated and understudied, but chronic systemic inflammation and risk factors remained important contributors for CVD development. The currently applied non-invasive modalities, although they are important for the initial evaluation of JIA patients, frequently fail to detect the silent, subclinical forms of CVD. Cardiovascular magnetic resonance (CMR), due to its multifaceted capability in the detection of cardiovascular disease, can offer early, reproducible, non-invasive information about cardiovascular disease in JIA, allowing risk stratification and timely initiation /modification of cardiologic and anti-rheumatic treatment. However, lack of availability/expertise and high cost still hamper its application in the clinical cardio-rheumatic practice. The aim of the current article is to present an overview of CVD in JIA emphasizing the emerging role of CMR in early diagnosis and treatment follow-up of CVD in JIA patients.