Newly detected diabetes mellitus patients with acute coronary syndrome have an adverse cardiometabolic profile similar to patients with prior diabetes and a more extensive ischemic myocardial insult.

AIMS: The impact of newly detected diabetes mellitus (NDDM) on metabolic parameters and extent of myocardial necrosis in patients with acute coronary syndrome (ACS) is not fully explored. We examined the impact of NDDM on cardiometabolic characteristics and myocardial necrosis in ACS patients. METHODS: CALLINICUS-Hellas Registry is an ongoing prospective multicenter observational study evaluating the adherence to lipid-lowering therapy (LLT) among ACS patients in Greece. Three groups were created: a) patients with NDDM (abnormal fasting glucose, HbA1c ≥ 6.5 % and no previous history of DM), b) patients without known DM and HbA1c < 6.5 % (non-DM) and c) patients with prior DM. RESULTS: The prevalence of NDDM among 1084 patients was 6.9 %. NDDM patients had lower HDL-C [38 (32-45) vs 42 (36-50) mg/dL] and higher triglycerides levels [144 (104-231) vs 115 (87-152) mg/dL] compared to non-DM patients (p < 0.05). NDDM patients featured both higher body mass index [29.5 (26.4-34.3) vs 27.1 (24.9-29.9) kg/m2] and waist circumference [107 (100-114) vs 98 (91-106) cm] compared to non-DM patients (p < 0.05). In addition, NDDM patients had more extensive myocardial necrosis than patients with prior DM. CONCLUSIONS: ACS patients with NDDM have an adverse cardiometabolic profile similar to patients with prior DM and have more extensive myocardial insult.

Incidence and causal association of functional atrial mitral regurgitation in HFpEF.

Heart failure with preserved ejection fraction (HFpEF) is as common as heart failure with reduced ejection fraction. Atrial fibrillation (AF), as well as the presence of mitral regurgitation (MR), is highly prevalent in these patients. Atrial functional MR (AFMR) is a type of functional MR characterized by severe left atrial dilatation and remodeling with normal left ventricular (LV) dimensions and function. Dilatation of the mitral annulus is considered to be the main underlying mechanism, though the leaflets and the rest of the mitral apparatus play significant role in the development of MR, mainly in patients with long standing AF. There are several echocardiographic differences between atrial and ventricular functional MR, better identified with 3D echocardiography. Significant AFMR impairs prognosis, especially of patients with HFpEF, and this is important while they represent a group of under-diagnosed and under-treated patients. Finally, because focused medical evidence-based approach is not available yet, it seems that the prevention of left atrial dilatation and early restoration of sinus rhythm (SR) is the best therapeutic option.

Pathophysiological alterations of left ventricular myocardial systolic function during normal pregnancy assessed by speckle tracking echocardiography: a prospective cohort echocardiography study.

PURPOSE: By using conventional echocardiographic indices, cardiac pumping function remains unaltered during pregnancy. However, two-dimensional speckle tracking echocardiography (2D-STE) can detect subclinical changes of myocardial function even in patients with normal and stable left ventricular ejection fraction (LVEF).The aim of this study was to evaluate LV systolic performance during normal low risk pregnancy by using both conventional 2D and 3D echo indices and 2D-STE. METHODS: One hundred and twelve pregnant women without any history of heart disease were prospectively recruited. They underwent serial echocardiographic evaluation in each pregnancy trimester and 6 months after delivery (time indicated as 1,2,3 and 4). 2D LVEF, 3D LVEF, LV global longitudinal strain (LVGLS), LV global circumferential strain (LVGCS) and LV-twist were measured and compared to the control group (c). RESULTS: 2D-LVEF and 3D-LVEF were not significantly different among the three trimesters, postpartum and controls. LVGLS progressively decreased during pregnancy (1st :21.71 ± 2.13%, 2nd : 21.20 ± 2.30%, 3rd : 19.82 ± 2.10%, 4th : 21.81 ± 2.05%, c: 21.71 ± 2.2%, overall p < 0,001) which receded during puerperium. No significant difference was noted in LVGCS (1st : 18.08 ± 5.54%, 2nd : 18.57 ± 3.41%, 3rd :18.20 ± 3.33%, 4th : 17.95 ± 3.39%, c: 18.8 ± 2.2%, p > 0.3). LV-Twist was significantly higher in the 1st trimester compared to controls (p = 0.04) and remained constantly high during the rest of the pregnancy and puerperium (1st :13.80 ± 5.09°, 2nd :13.46 ± 5.35°, 3rd :13.58 ± 4.32°, 4th :13.37 ± 4.26°, c: 11.5 ± 4.3°). CONCLUSIONS: In low risk individuals with normal pregnancy, a redistribution of force occurs especially in the 3rd trimester. Longitudinal strain decreases, while torsional movement of the heart increases and counterbalances the temporal change of longitudinal systolic function. These changes would probably reflect the pathophysiological alterations related to pregnancy.

Segmentally impaired left ventricular longitudinal strain: a new predictive diagnostic parameter for asymptomatic patients with severe aortic stenosis and preserved ejection fraction.

INTRODUCTION: This study aims to investigate the correlation between severe aortic stenosis (sAS) and impairment of left ventricular global longitudinal strain (LVGLS) in particular segments, using two-dimensional speckle tracking echocardiography in patients with sAS and normal ejection fraction of left ventricle (LVEF). METHODS: The study included 53 consecutive patients with asymptomatic sAS and preserved LVEF. The regional longitudinal systolic LV wall strain was evaluated at the area opposite of the aorta as the median strain value of the basal, middle, and apical segments of the lateral and posterior walls and was compared to the average strain value of the interventricular septum (IVS) at the same views. RESULTS: LVGLS was decreased and was not statistically different between three- and four-chamber views (-12.5 ± 3.6 vs -11.4 ± 5.5%, p = 0.2). The average strain values of the lateral and posterior walls were statistically reduced compared to the average value of the IVS (lateral vs IVS: -7.8 ± 3.7 vs -10 ± 5.3%, p = 0.005, posterior vs IVS: -7.7 ± 4.2 vs -10.3 ± 3.8%, p < 0.0001). There was no significant difference between lateral and posterior walls (-7.8 ± 3.7 vs -7.7 ± 4.2%, p = 0.9). CONCLUSIONS: The strain of lateral and posterior walls of left ventricle, which lay just opposite to the aortic valve seem to be more reduced compared to other walls in patients with sAS and preserved LVEF possibly due to their anatomical position. This impairment seems to be the reason of the overall LVGLS reduction. Regional strain could be used as an extra tool for the estimation of the severity of AS as well as for prognostic information in asymptomatic patients.

Biventricular myocardial function in Covid-19 recovered patients assessed by speckle tracking echocardiography: a prospective cohort echocardiography study.

Although severe acute respiratory syndrome coronavirus 2 causes respiratory disease, it may also lead to cardiovascular involvement with unknown long-term consequences. The aim of our study was to evaluate prospectively cardiac involvement in patients after the recovery from Covid-19, using two-dimensional speckle tracking echocardiography. 100 Covid-19 recovered patients with preserved left ventricular ejection fraction, were included, divided based upon clinical manifestation into two groups, those who were treated ambulant and those who were hospitalized. All patients underwent echocardiographic evaluation after their recovery. Although overall LV systolic function expressed by EF was normal, left ventricular global longitudinal strain (LVGLS) was significantly lower in Covid-19 recovered patients (33.28 ± 9.4 days after diagnosis) compared to controls (- 18.47 ± - 2.4 vs. - 21.07 ± - 1.76% respectively, p < 0.0001). Εspecially the lateral wall longitudinal strain (LATLS) and posterior wall longitudinal strain (POSTLS) were significantly reduced in all patients compared to controls (- 17.77 ± - 3.48 vs. - 20.97 ± - 2.86%, p < 0.0001 and - 19.52 ± - 5.3 vs. - 22.23 ± - 2.65%, p = 0.01). right ventricular global longitudinal strain (RVGLS) was significantly diminished only in the hospitalized group of Covid-19 recovered patients, compared to controls (- 18.17 ± - 3.32 vs. - 26.03 ± - 4.55% respectively, p < 0.0001). LVGLS is affected in almost all individuals after Covid-19 infection independently of the infection severity, with LATLS being the most sensitive marker of LV impairment and with POSTLS to follow. RV shows impaired GLS in severely ill patients highlighting RVGLS as a helpful tool of prognosis. Recovered patients from Covid-19 infection have to be monitored for a long time, since the term "long Covid disease" might also include the cardiac function.

Left ventricular ejection fraction and Global Longitudinal Strain variability between methodology and experience.

INTRODUCTION: Although ejection fraction (EF) is the cornerstone of the assessment of left ventricular (LV) systolic function, its measurement faces a number of challenges related to image quality, assumptions of LV geometry, and expertise. The aim of this study was to test the inter-observer variability of EF and GLS measurement in patients with a broad spectrum of LV function, between physicians and investigators (Inv) with different levels of expertise. METHODS: In 122 patients, EF and GLS were measured by 4 Inv blinded to each other with different level of experience in echocardiography; EF was measured using 3 methods: visual assessment, biplane Simpson's method, and auto-EF method. GLS was measured from the 3 apical views. A significant difference for LVEF and for LVGLS was considered to be >10 and >2 absolute values, respectively. RESULTS: Intra-observer agreement was excellent for visually assessed EF (ICC = 0.87, P < .001) and GLS (ICC = 0.82, P < .001) and good for EF measured by Simpson's method (ICC = 0.70, P < .001) and auto-EF (ICC = 0.72, P < .001). Intra-observer and inter-observer agreements were excellent for GLS with ICCs above 0.8. GLS discordance between the 4 Inv was not significant. Discordance in EF and GLS measurements among the Inv was not related to image quality or wall motion abnormalities. CONCLUSION: Although EF has proved its prognostic value in various cardiovascular entities, GLS seems to be more reliable for serial assessment of LV function, demonstrating lower intra- and inter-observer variability, even by different physicians with variant level of expertise.

Cardio-oncology: a new and developing sector of research and therapy in the field of cardiology.

Cardio-oncology is a new field of interest in cardiology that focuses on the detection, monitoring, and treatment of cardiovascular disease occurring as a side effect of chemotherapy and radiotherapy. Both cancer treatment modalities can cause cardiac dysfunction, a major cause of morbidity and mortality in the oncologic population. It is necessary to periodically monitor cancer patients under treatment, especially those receiving anthracyclines and trastuzumab (monoclonal antibody), using mainly 3D echocardiography to calculate left ventricular ejection fraction and to estimate myocardial deformation. Additionally, measuring various biomarkers, such as natriuretic peptides, could facilitate early identification and appropriate response to potential cardiotoxicity. In this regard, cardiological assessment before starting cancer treatment is essential and should be continued throughout, since cardiac dysfunction can occur at any time, even several years after therapy onset. High-risk individuals, in particular, should receive a detailed management plan designed in collaboration between an oncology and a cardiology specialist. If heart failure develops, even in the absence of overt clinical symptoms, standard heart treatment is to be followed and causal agent discontinued if possible. One important question is whether and when to stop cardiac medication in case of heart dysfunction reversal, after completion of cancer treatment. Further cardio-oncology evolution can lead to a deeper understanding of the adverse mechanisms and effects causing heart failure, as well as the development of personalized treatment regimens in order to limit cardiotoxicity.

Subclinical left ventricular dysfunction and correlation with regional strain analysis in myocarditis with normal ejection fraction. A new diagnostic criterion.

BACKGROUND: The diagnosis of myocarditis is challenging, especially in case of normal left ventricular systolic function. The aim of this study is to test the hypothesis that 2D speckle tracking echocardiography (2DSTE) can detect subclinical left ventricular (LV) dysfunction in patients with myocarditis and preserved LV function without regional wall motion abnormalities and that regional strain analysis can correlate with cardiac magnetic resonance (CMR) findings. METHODS: Study population consisted of 25 consecutive patients with myocarditis and 19 controls. All patients underwent a full echocardiographic study at the first day of their admission and in addition to conventional echocardiographic measurements, global longitudinal and circumferential strain of the left ventricle (LVGLS, LVCS accordingly), as well as regional strains of the lateral wall, were estimated. Moreover, all patients underwent a CMR scan during the first week from their admission. RESULTS: Although there was no statistical difference between the two groups of patients in systolic function, myocarditis patients demonstrated significantly impaired LVGLS (-16.5 ±â€¯2.2 vs -20.5 ±â€¯1.3%, p < 0.0001) and LVCS (-16.4 ±â€¯3.7 vs -20.9 ±â€¯2%, p = 0.002), as well as segmental longitudinal strains of the lateral wall. CMR in all myocarditis patients revealed late gadolinium enhancement in the lateral left ventricle free wall. CONCLUSIONS: In patients with acute myocarditis with preserved ejection fraction, 2DSTE evaluation appears to be a promising, useful noninvasive and inexpensive tool in addition to existing methods used for the diagnosis of acute myocarditis, since it seems to be able to identify myocardial fibrosis early in the setting of the disease.

Lipoprotein (a) Evolution: Possible Benefits and Harm. Genetic and Non-Genetic Factors Influencing its Plasma Levels.

The limited distribution of lipoprotein (a) (Lp(a)) to humans, Old World primates and to the European hedgehog, has raised considerable interest and speculation regarding its possible physiological role. Lp(a) has variable circulating concentrations (<0.1 - >100 mg/ml) which are highly genetically determined in humans. These characteristics gave rise to several theories concerning the origins and evolution of Lp(a). Lp(a) has a protective role after injury since Lp(a) particles bind to macrophages and platelets membrane receptors, leading to fibrin activation and injury healing. On the other hand, Lp(a) seems to be implicated in the formation of atheromatic plaques but also in cerebrovascular events and stenosis of the aortic valve. The main genetic factor determining plasma Lp(a) levels is the Lp(a) gene (LPA). Most Caucasian people have normal plasma Lp(a) concentrations, but there is important distribution variation according to race. Women seem to have increased Lp(a) levels compared with men, while diabetes mellitus type 2 favours lower plasma Lp(a) levels. Nutrition, hormones and several drugs may also influence circulating Lp(a) levels.

A safety radiation marker in the cardiac catheterization lab.

OBJECTIVE: Nowadays, in order to deal with cardiovascular disease, coronary angiography (CRA) is the best tool and gold standard for diagnosis and assessment. CRA inevitably exposes both patient and operator to radiation. The purpose of this study was to calculate the radiation exposure in association with the radiation absorbed by interventional cardiologists, in order to estimate a safety radiation marker in the catheterization laboratory. METHODS AND RESULTS: In 794 successive patients undergoing CRA and in three interventional cardiologists the following parameters were examined: radioscopy duration, radiation exposure during fluoroscopy, total radiation exposure and the number of stents per procedure. Every interventional cardiologist was exposed to 562,936 µGym2 of total radiation during CRA procedures, to 833,371 µGym2 during elective CRA + percutaneous coronary intervention (PCI) procedures and to 328,250 µGym2 during primary CRA + PCI. Hence, the total amount of radiation that every angiographer was exposed to amounted to 1,724,557.5 µGym2 (median values). During the same period, the average radiation that every angiographer absorbed was 15,253 while the average dose of radiation absorbed during one procedure was 0.06 mSv for each operator. Therefore, the ratio between radiation exposure and the radiation finally absorbed by every operator was 113:1 µGym2/mSv. CONCLUSIONS: The present study, indicating the ratio above, offers a safety marker in order to realistically estimate the dose absorbed by interventional cardiologists, suggesting a specified number of permitted procedures and an effective level of radiation use protection tools.

Study of common variants of the apolipoprotein E and lipoprotein lipase genes in patients with coronary heart disease and variable body mass index.

OBJECTIVE: In the present study, we evaluated the influence of lipoprotein lipase (LPL) and apolipoprotein (apo) E polymorphisms on lipid concentrations of 178 Greek men of similar age with coronary heart disease (CHD), but varying body mass index (BMI). DESIGN: Patients were divided according to their BMI (in kg/m²) into three groups: lean (BMI = 20-24.9), overweight (BMI = 25-29.9), and obese (BMI ≥ 30). Polymorphisms of LPL (HindIII, S447X) and apo E (ε2, ε3, ε4), and lipid parameters were studied. RESULTS: There was a negative correlation between BMI and high-density lipoprotein cholesterol (HDL-C) concentration (r = -0.272, p < 0.001), as has already been described. Lean homozygotes for the HindIII(+) allele had higher HDL-C levels compared to lean homozygotes for the HindIII(-) allele (p = 0.012). No correlation was found between S447X or apo E polymorphisms and BMI or plasma lipids in any group. Overweight men with the ε3/ε3 and SS genotypes had higher triglycerides concentration compared with overweight men with ε3/ε3 and SX (p = 0.002). CONCLUSIONS: The HindIII polymorphism alone may influence HDL-C concentration in lean men, in contrast to S447X alone, which has no influence on any lipid parameters. However, the S447X and apo E polymorphisms may have a synergetic effect and alter plasma triglyceride concentration in overweight men.

Familial hypercholesterolemia and triglyceride metabolism.

Familial hypercholesterolemia (FH) is a common autosomal disorder associated with hypercholesterolemia which usually results from a mutation in the coding region of the low density lipoprotein (LDL) receptor (R) activity. Only 20% of untreated heterozygote (h) FH men reach 70 years of age. Therefore, the diagnosis of hFH is a better predictor of coronary heart disease than risk-based algorithms. Fasting and postprandial hypertriglyceridemia are also considered as risk factors for atherosclerosis. The plasma triglycerides (TG)s are formed from two major sources; intestinally-derived chylomicrons and hepatically-derived very low density lipoproteins (VLDL). Potentially, atherogenic remnants of TG-rich lipoproteins accumulate in the postprandial state. In addition, TG-rich lipoproteins may promote the formation of atherogenic small dense LDL. In FH subjects, lipoprotein metabolism seems to be impaired and may contribute to premature atherosclerosis. This was documented in many studies in which mice lacking LDLR present hypercholesterolemia, increased plasma TG-rich lipoprotein remnants and develop premature spontaneous atherosclerosis. In this review, we focus on the current knowledge regarding TG metabolism on a selected clinically condition such as FH. Variation in clinical characteristics has been described between studies which may occur due to dissimilarity in the molecular defect of FH. Additionally, the relationship between TG levels in FH subjects and the development of atherosclerosis, as well as the appropriate treatment for these patients is analysed.

Sex-associated effect of CETP and LPL polymorphisms on postprandial lipids in familial hypercholesterolaemia.

BACKGROUND: This study assessed the gender-specific influence of the cholesteryl ester transfer protein (TaqIB, I405V) and lipoprotein lipase (S447X) polymorphisms on the response to an oral fat tolerance test in heterozygotes for familial hypercholesterolaemia. METHODS: We selected and genotyped 80 men and postmenopausal women heterozygous for familial hypercholesterolaemia (main group) as well as 11 healthy control subjects. Patients were subgrouped based on their response to oral fat tolerance test. The oral fat tolerance test was defined as pathological when postprandial triglyceride concentration was higher than the highest triglyceride concentration observed in healthy subjects (220 mg/dl) at any time (2, 4, 6 or 8 h). RESULTS: In the pathological subgroup, men had significantly higher incremental area under the curve after oral fat tolerance test than postmenopausal women. Furthermore, multivariate analysis revealed a gender association of TaqIB and I405V influence on postprandial lipaemia in this subgroup. CONCLUSION: In conclusion, it seems that gender and TaqIB polymorphism of the cholesteryl ester transfer protein gene were both associated with the distribution of triglyceride values after oral fat tolerance test, only in subjects with a pathological response to oral fat tolerance test. Specifically, men carrying the B2 allele of the TaqIB polymorphism showed a higher postprandial triglyceride peak and a delayed return to basal values compared with women carrying B2. However, further investigations in larger populations are required to replicate and confirm these findings.

Primary and secondary hypertriglyceridaemia.

Familial hypertriglyceridaemia is inherited in an autosomal dominant manner. The responsible genetic abnormality is unknown but recently, a novel gene encoding apolipoprotein AV has been linked to familial hypertriglyceridaemia. All patients develop the same phenotype with elevated levels of very low density lipoproteins (VLDL) in plasma. The main disorder of this dyslipidaemia is decreased intestinal absorption of biliary acids, leading to a compensatory increase of VLDL production. In familial hypertriglyceridaemia, a marked increase in plasma triglyceride (TG) levels can cause acute pancreatitis. Moreover, patients with other genetic factors, like familial chylomicronaemia, familial combined hyperlipidaemia, familial dysbetalipoproteinaemia and other rare disorders (e.g. Tangier disease and fish eye disease) may present increase of TG levels or cholesterol levels or both. Secondary hypertriglyceridaemias include hypothyroidism, kidney abnormalities (e.g. nephrotic syndrome or chronic kidney failure), diabetes mellitus, heavy alcohol consumption and obesity. In men and postmenopausal women, it seems that estrogen deficiency is responsible for higher TG levels compared with premenopausal women postprandially. In every state -fasting or postprandial-, women demonstrate lower plasma TG levels compared with men. This fact is due not only to increased muscular TG uptake and storage but also to higher TG clearance. Many studies demonstrated an age impact on plasma TG increase and larger variation of fasting TG levels caused by age. Also, hypertriglyceridaemia (TG >150 mg/dl; 1.7 mmol/l) is one of the diagnostic criteria of metabolic syndrome. Finally, several drugs may increase TG levels (e.g. chlorthalidone or beta-blockers).

Gender differences in the lipid profile of dyslipidemic subjects.

OBJECTIVE: We evaluated the gender-associated differences in lipid profile of subjects intended to receive lipid-lowering therapy with emphasis on the associations between triglycerides (TG) and other plasma lipid variables. DESIGN: Lipid profiles of 1385 patients [aged 55+/-11 years, 549 women (40%)] were evaluated. Eligible subjects fulfilled one or more of the following criteria: total cholesterol (TC)>or=6.2 mmol/l, TG>or=1.7 mmol/l, and high-density lipoprotein cholesterol (HDL-C)<1.0 mmol/l. Patients were divided into subgroups according to TG and HDL-C levels. RESULTS: Women aged on average 3.5 years older, had higher TC and HDL-C, lower TG and a correspondingly lower TC/HDL-C ratio than men. High TG and low HDL-C in tandem appeared twice more frequently in men. Inverse correlations between HDL-C and TG levels were found to exist in the entire cohort (r=-0.354, p<0.001) and in all various subgroups. In the subgroup with TG<1.7 mmol/l, women had higher TC and HDL-C, lower TG levels and lower TC/HDL-C ratio compared with men. In the subgroup with TG>or=1.7 mmol/l, women had higher TC and HDL-C levels and lower TC/HDL ratio compared with men. In the subgroup with HDL-C>or=1.0 mmol/l women had higher HDL-C, lower TG levels and lower TC/HDL-C ratio compared with men. CONCLUSIONS: Elevated TG levels and low HDL-C in tandem are common lipid abnormalities in the clinical setting of primary and secondary preventions. Gender-associated differences in the lipid profile are evident in subjects presenting with dyslipidemia and might be of potential relevance for diagnostics and therapy for the prevention of atherosclerosis.

Therapeutic effects of fibrates in postprandial lipemia.

Hypertriglyceridemia is observed in many metabolic diseases such as the metabolic syndrome, diabetes mellitus, or mixed dyslipidemia frequently leading to premature coronary heart disease (CHD). Additionally, several studies have shown that postprandial hypertriglyceridemia is pronounced in patients with CHD, metabolic syndrome, hypertension, and other pathologic conditions. The triglyceride-rich lipoprotein remnants accumulating in the postprandial state seem to be involved in atherogenesis and in events leading to thrombosis. Since abnormal postprandial lipemia is associated with pathologic conditions, its treatment is of clinical importance.Fibrates are of significant help in managing hypertriglyceridemia. This review summarizes the effect of fibric acid derivatives on postprandial lipemia. Fibrates decrease the production of and enhance the catabolism of triglyceride-rich lipoproteins through the activation of peroxisome proliferator-activated receptor-alpha. Results of clinical studies with fibrates have confirmed their action in decreasing postprandial triglyceride levels by increasing lipoprotein lipase activity, decreasing apolipoprotein CIII production, and by increasing fatty acid oxidation in the liver.It is concluded that fibrates are effective agents in lowering the postprandial increase in remnant lipoprotein particles and retinyl palmitate. Furthermore, fibrates can also affect the postprandial lipid profile by increasing hepatic lipase levels and in some cases, by reducing cholesterol ester transfer protein activity. The main target of fibrate therapy is to improve fasting hypertriglyceridemia, which is an essential component associated with improving postprandial lipemia. Fibrates are well tolerated by patients and adverse effects have been reported rarely after their administration.