Right Ventricular Longitudinal Shortening is not Associated with Left Ventricular Rotational Mechanics in Healthy Adults - Insights from the Three-dimensional Speckle-tracking Echocardiographic MAGYAR-Healthy Study.

Background: The left ventricle (LV) not only contracts, but its rotational mechanics have a significant role in systolic ejection, whereas the right ventricle (RV) is substantially different in shape and function, and its contractility is not accompanied by rotational features. Simple M-mode echocardiography-based tricuspid annular plane systolic excursion (TAPSE) reflects RV longitudinal contraction or shortening. The aim of the present study was to examine the relationship between the parameters characterizing the rotational mechanics of the LV as assessed by three-dimensional speckle-tracking echocardiography (3DSTE) and the TAPSE. The effects of different degrees of these parameters on each other were also examined. Methods: The present retrospective analysis evaluated the results of 80 healthy adult individuals with an average age of 28.1 ± 6.3 years (33 males) with LV rotational mechanics being directed normally. All cases have undergone complete two-dimensional Doppler echocardiography with the measurement of TAPSE and 3DSTE. Results: None of the LV volumes and rotational parameters showed any differences in healthy cases with TAPSE 18-21 mm vs. TAPSE > 22 mm. Similarly, right atrial (RA) volumetric parameters did not differ either. TAPSE showed no associations with the degree of basal LV rotation. RA volumes were slightly increased with higher basal LV rotation. Similar to basal LV rotation, TAPSE did not change with the degree of apical LV rotation and a tendentious increase of RA volumes could be demonstrated with increasing apical LV rotation. No correlation could be demonstrated between apical and basal LV rotations and TAPSE. Conclusions: 3DSTE-derived LV rotational parameters and TAPSE are not associated suggesting that LV twist is independent of RV longitudinal shortening in healthy circumstances.

Autonomic function and specific right atrial functions - Is there a relationship? Correlations from the three-dimensional speckle-tracking echocardiographic MAGYAR-Healthy Study.

INTRODUCTION: Similarly to the ventricles, the atria are under sympathetic/parasympathetic neural regulation. Accordingly, correlations were investigated between Ewing's standard cardiovascular reflex tests (SCRTs) and three-dimensional speckle-tracking echocardiography (3DSTE)-derived right atrial (RA) volumes and strains in healthy subjects. MATERIALS AND METHODS: The study comprised 45 healthy adults, but 5 subjects were excluded due to inferior image quality for 3DSTE-derived RA assessments. The remaining 40 individuals being in sinus rhythm had a mean age of 35.1 ± 3.5 years (20 men). Two-dimensional, Doppler, 3DSTE and SCRTs were performed in all cases. RESULTS: RA maximum volume and total and passive RA stroke volumes correlated with the Valsalva ratio. Active RA stroke volume and emptying fraction showed correlations with 30/15 ratio. Peak global and mean segmental RA circumferential (CS) and longitudinal strains (LS) showed correlation with the Valsalva ratio. At atrial contraction, global RA-LS and mean segmental RA-CS showed correlations with the Valsalva ratio. Moreover, mean segmental RA-CS correlated with 30/15 ratio and mean segmental RA radial strain showed correlations with systolic blood pressure in response to standing. Autonomic neuropathy score correlated with peak global RA-LS. CONCLUSIONS: Autonomic function parameters have significant associations with specific RA functions in healthy adults, making the latter possible indicators of autonomic dysregulation.

Similarities and Differences between Three-Dimensional Speckle-Tracking Echocardiography-Derived Left and Right Atrial Volumes and Volume-Based Functional Properties in the Same Healthy Adults-A Detailed Analysis from the MAGYAR-Healthy Study.

Background and Objectives: It would be important to know what happens to the volume and volume-based functional properties of one atrium if the size of the other atrium is larger or smaller than the average. Therefore, the present study aimed to perform three-dimensional speckle-tracking echocardiography (3DSTE)-derived quantification of left atrial (LA) and right atrial (RA) volumes and volume-based functional properties to examine these associations in healthy adults with mean and lower or higher than mean atrial volumes. Materials and Methods: The present study consisted of 179 healthy volunteers with a mean age of 32.3 ± 12.3 years (92 males). Three-dimensional speckle-tracking echocardiography-derived LA and RA volumes and volume-based functional properties were determined in all cases. Results: When different LA or RA volume groups were evaluated, both LA and RA showed the same pattern of volume changes in all phases of atrial function with higher LA or RA volumes. In case of low and mean LA volumes, RA volumes were higher compared to their LA counterpart. In case of mean and high RA volumes, RA volumes proved to be higher as well. In case of mean LA or RA volumes, differences between LA and RA stroke volumes (SVs) could not be detected, but all atrial emptying fractions (EFs) were lower for RA than for LA. Some differences were detected in counterpart LA/RA total, passive, and active atrial SVs and EFs values in the presence of lower/higher than mean LA/RA volume. Conclusions: In case of mean LA or RA volumes, RA volumes are higher compared to their LA counterpart, LA-SVs and RA-SVs are similar, but atrial EFs are lower for RA than for LA. If lower/higher than mean LA or RA volumes are present, some differences in patterns of changes in counterpart atrial volumes-SVs and EFs-could be detected.

Associations between Mitral Annular and Left Atrial Volume Changes in Healthy Adults-Detailed Analysis from the Three-Dimensional Speckle-Tracking Echocardiographic MAGYAR-Healthy Study.

Background: Three-dimensional (3D) speckle-tracking echocardiography (3DSTE) is one of the newest development in non-invasive imaging offering simultaneous 3D evaluation of atria and valvular annuli. 3DSTE was used to analyze correlations between left atrial (LA) volume changes and mitral annular (MA) dimensions and functional properties in healthy adult subjects. Methods: A total of 297 healthy subjects were enrolled in this retrospective cohort study, from which insufficient quality of images was responsible for the exclusion of 98 cases (33%). The remaining study population consisted of 199 healthy adults without valvular regurgitation/stenosis in sinus rhythm (mean age: 33.5 ± 12.7 years, 104 males, body mass index: 24.7 ± 1.2 kg/ m 2 , systolic and diastolic blood pressure: 118.2 ± 3.4 mmHg and 78.3 ± 4.5 mmHg, respectively). Two-dimensional Doppler echocardiography and 3DSTE were performed in all cases. Results: Larger LA volumes were associated with more dilated MA dimensions with its reduced function. Elevated LA stroke volumes could be demonstrated only in systole and end-diastole, while increased LA emptying fraction was present only in end-diastole. Reduced MA fractional area change was associated with larger diastolic LA volumes, smaller early diastolic LA stroke volume, in addition all LA emptying fractions were smaller as well. Correlations could be demonstrated between LA and MA parameters. Conclusions: 3DSTE is suitable not only for chamber quantifications, but also for the assessment of valvular annular dimensions. Strong relationship exists between LA volumes and MA dimensions and functional properties.

Left ventricular deformation in the presence of left ventricular 'rigid body rotation' in healthy adults-three-dimensional speckle-tracking echocardiographic insights from the MAGYAR-Healthy Study.

Background: During the heart cycle, the left ventricle (LV) not only shows a contraction-relaxation pattern, but LV has a rotational mechanics, as well. It is a known fact that certain pathologies may be associated with an absence of LV twist, when LV basal and apical regions rotate in the same clockwise (cw) or counterclockwise (ccw) direction called LV 'rigid body rotation' (LV-RBR), but it can also occur in healthy subjects. The present cohort study aimed to examine LV strains in healthy subjects with LV-RBR versus with normally directed LV rotational mechanics by three-dimensional speckle-tracking echocardiography (3DSTE). Methods: The study consisted of 181 healthy individuals, from which 171 cases had normally directed LV rotational mechanics (mean age: 32.5±12.3 years, 79 males) and 10 healthy subject showed LV-RBR (mean age: 35.4±11.3 years, 3 males). Complete two-dimensional (2D) Doppler echocardiography and 3DSTE were performed in all healthy individuals. Results: None of routine 2D Doppler echocardiographic parameters showed differences between the groups examined. There were no subjects with ≥ grade 1 regurgitation on any valves or with significant stenosis on any valves. 3DSTE-derived LV volumes, global and mean segmental strains did not differ between the groups examined. Apical anterior and lateral segments showed reduced segmental LV circumferential strain (CS) (-18.9%±8.5% vs. -26.7%±10.7%, P=0.02; -27.3%±12.6% vs. -34.8%±13.2%, P=0.08, respectively) and LV area strain (AS) (-26.8%±9.8% vs -36.8%±12.0%, P=0.01; -35.7%±13.2% vs. -45.0%±14.6%) in healthy subjects having LV-RBR as compared to cases with normally directed LV rotational mechanics. These abnormalities were present only in subjects having cwLV-RBR. Conclusions: Although global LV deformation is normal in the presence of LV-RBR in healthy adults, reduction of apical anterior and lateral LV-CS (and LV-AS) are present in cases with cwLV-RBR only suggesting segmental deformation abnormalities.

Global left ventricular strains and left atrial volumes are not associated in healthy adults - Detailed analysis from the three-dimensional speckle-tracking echocardiographic MAGYAR-Healthy Study.

Introduction: During the heart cycle, left ventricular (LV) contractility is characterized by complex deformation and rotational mechanics, resulting in LV ejection. The present study seeks to expand our knowledge by examining dependence of LV strains representing LV deformation on left atrial (LA) volumes in healthy circumstances. Therefore, the aim of this study was to evaluate the associations between LA volumes and LV strains as assessed simultaneously by three-dimensional speckle-tracking echocardiography (3DSTE) in normal healthy adults. Methods: The present study consisted of 302 healthy adults, but according to exclusion criteria, 137 subjects were excluded due to inferior image quality. The final population comprised 165 individuals (mean age: 33.1 ±â€¯12.3 years, 75 males) who were voluntarily recruited for screening. Two-dimensional echocardiography extended with 3DSTE was performed in all subjects for detailed LV/LA analysis. Results: Overall feasibility for simultaneous assessment of LV strains and LA volumes proved to be 55 % with excellent intra- and interobserver correlations. All global LV strains were similar, regardless of the LA volumes examined. All LA volumes and volume-based functional properties respecting the cardiac cycle were similar, regardless the global LV strains examined. Conclusions: LV strains and LA volumes can be simultaneously assessed by 3DSTE. Global LV strains and LA volumes are not associated in healthy adults.

Right ventricular longitudinal shortening and right atrial volumes are not associated in healthy adults-detailed analysis from the three-dimensional speckle-tracking echocardiographic MAGYAR-Healthy Study.

Background: There is a close relationship between volumes of the right atrium (RA) and dimensions and derived functional sphincter-like features of the tricuspid annulus (TA). However, its relation to longitudinal TA motion is not clear, which can even be considered to be a characteristic of the longitudinal shortening of the right ventricle (RV) and represented by TA plane systolic excursion (TAPSE). Therefore, the aim of this cohort study was to perform a detailed analysis of the relationship of three-dimensional speckle-tracking echocardiography (3DSTE)-derived RA volumes and RV longitudinal shortening in healthy individuals. These parameters were also examined in case of average values and larger/smaller than mean values. Methods: The present study comprised 93 healthy adults (mean age: 27.7±6.3 years, 46 men), who participated in a complete medical investigation including two-dimensional, TAPSE, Doppler and 3DSTE-derived RA volumetric echocardiographic assessments. Results: RA volumes, stroke volumes and emptying fractions were not related to TAPSE. In case of low, mean and high TAPSE, maximum [50.4±22.4 vs. 49.5±15.5 vs. 49.0±15.8 mL, P= not significant (ns)], preatrial contraction (36.9±16.8 vs. 34.5±10.4 vs. 35.6±10.5 mL, P= ns) and minimum (28.7±13.6 vs. 27.2±9.4 vs. 26.6±9.3 mL, P= ns) RA volumes did not differ. Higher RA volumes showed no associations with TAPSE either. Conclusions: 3DSTE-derived RA volumes and M-mode echocardiography-derived TAPSE representing RV longitudinal shortening are not associated in healthy adults. None of the RA volumes showed correlations with TAPSE.

Trends and regional differences in antidiabetic medication use: a nationwide retrospective observational study.

BACKGROUND: The prevalence of diabetes is increasing, and several new drug groups have been authorized and used successfully in the treatment of diabetes, while older drug groups are still in use. Our aim was to assess the utilization tendencies and regional differences in antidiabetic medication consumption in Hungary between 2015 and 2021 and to identify the possible determinants of regional differences in antidiabetic medication use. METHODS: For this retrospective drug utilization study, yearly wholesale database was used, which provides total coverage for ambulatory antidiabetic drug sales in Hungary, including both reimbursed and non-reimbursed medications. Data were expressed as Defined Daily Dose per 1000 inhabitants per day (DDD/TID), percentage of total use and the ratio of the highest and lowest utilization values among the counties (max/min ratio). To assess the potential reasons for regional differences in antidiabetic drug use, we analyzed the associations between regional drug utilization data and possible determinants. RESULTS: The total national antidiabetic medication use has increased by 7.6% and reached 94.8 DDD/TID in 2021. Regarding antidiabetic subgroups, the use of metformin and novel antidiabetics (DPP4Is, GLP1As and SGLT2Is) and their combinations increased in all counties, while sulfonylurea consumption decreased, and insulin use was stable. In 2021, 19.2-24.1% of the total antidiabetic medication consumption was novel antidiabetics, 39.1-47.2% metformin, 14.8-25.8% sulfonylureas and 23.6-30.5% were insulins. Regional differences in antidiabetic medication consumption were considerable mainly in the case of GLP1As (max/min ratio:3.00), sulfonylureas (2.03) and SGLT2Is (1.92) in 2021. The association between antidiabetic medication use and possible determinants was confirmed in the case of unemployment rate and sulfonylurea use, the number of public medical card holders per ten thousand inhabitants and human insulin and sulfonylurea use. GLP1As were the only antidiabetic drug group that did not correlate with any of the investigated factors. CONCLUSIONS: Although novel antidiabetic drug use was growing dynamically in Hungary, sulfonylurea use is still considerable. Differences in antidiabetic drug consumption were substantial between the regions.

Three-Dimensional Speckle-Tracking Echocardiography-Derived Tricuspid Annular Properties in Acromegaly-Results from the MAGYAR-Path Study.

INTRODUCTION: Acromegaly is an endocrine pathology characterized by the overproduction of human growth hormone. The present study aimed to analyze three-dimensional speckle-tracking echocardiography (3DSTE)-derived tricuspid annular (TA) properties in detail in patients with acromegaly and to compare the findings to those of matched healthy controls. METHODS: The present study consisted of 29 patients with acromegaly (mean age: 55.9 ± 14.5 years, 21 males), of which 13 had an active disease. The control population comprised 57 healthy subjects (mean age: 53.2 ± 8.4 years, 38 males). RESULTS: In the presence of acromegaly, left atrial and end-diastolic left ventricular (LV) sizes were dilated, and LV ejection fraction was increased, which was accompanied by thickened interventricular septum and LV posterior wall as compared with matched healthy controls. The presence of grade 1 mitral (MR) and tricuspid (TR) regurgitations were more frequent in acromegaly than in controls, regardless of disease activity. Higher than grade 1 MR/TR was uncommon in acromegaly. The 3DSTE-derived all end-diastolic (2.47 ± 0.27 cm vs. 2.23 ± 0.27 cm; 8.73 ± 1.77 cm2 vs. 6.67 ± 1.40 cm2; 11.56 ± 1.34 cm vs. 10.20 ± 1.10 cm, p < 0.001 for all) and end-systolic (1.97 ± 0.27 cm vs. 1.77 ± 0.28 cm; 6.24 ± 1.61 cm2 vs. 5.01 ± 1.42 cm2; 9.80 ± 1.35 cm vs. 8.72 ± 1.10 cm, p < 0.001 for all) TA diameters, areas, and perimeters proved to be dilated, while TA functional parameters including TA fractional area change (28.77 ± 9.80% vs. 27.64 ± 15.34%, p = 0.720) and fractional shortening (20.60 ± 9.08% vs. 20.51 ± 8.81%, p = 0.822) were normal in acromegaly regardless of whether acromegaly was active or not. RA volumes respecting the cardiac cycle were dilated in acromegaly as compared with those of healthy controls regardless of disease activity and were associated with respective changes in TA dimensions. CONCLUSIONS: In the presented acromegaly patients, significant TA dilation with preserved function could be detected regardless of disease activity. RA volumes and TA dimensions are correlated in acromegaly.

Incident Cancer Risk of Patients with Prevalent Type 2 Diabetes Mellitus in Hungary (Part 2).

(1) Background: Among the chronic complications of type 2 diabetes mellitus, cancer has become the leading cause of death in several countries. Our objective was to determine whether prevalent type 2 diabetes mellitus is associated with a higher incidence of cancer. (2) Methods: This study comprised a nationwide analysis conducted in Hungary. The study population was divided into two groups: a type 2 diabetes mellitus group vs. a non-diabetic group. The primary outcome was the risk related to overall cancer incidence; a key secondary outcome was the overall incidence of cancer in distinct study years; and a further outcome was the annual percent changes. (3) Results: The odds ratio related to the overall incidence of cancer was 2.50 (95% confidence interval: 2.46-2.55, p < 0.0001) in patients with diabetes as related to non-diabetic controls. The odds ratio was higher in males than in females [ORmales: 2.76 (2.70-2.82) vs. ORfemales: 2.27 (2.22-2.33), p < 0.05 for male-to-female comparison]. The annual cancer incidence rate declined in non-diabetic controls, but not in patients with diabetes [-1.79% (-2.07--1.52%), p < 0.0001] vs. -0.50% (-1.12-+0.10%), p = 0.0991]. Several types of cancer showed a decreasing tendency in non-diabetic controls, but not in patients with type 2 diabetes. (4) Conclusions: Type 2 diabetes is associated with a higher risk of cancer. While the cancer incidence decreased for non-diabetic individuals with time, it remained unchanged in patients with T2DM.

Incident Cancer Risk in Patients with Incident Type 2 Diabetes Mellitus in Hungary (Part 1).

(1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal of this study was the assessment of the overall incidence of cancer among patients with newly diagnosed T2DM in Hungary. (2) Methods: A nationwide, retrospective, longitudinal study was performed using a Hungarian database. After exclusion of cases of age < 18 years, with gestational diabetes, with polycystic ovary syndrome, and with type 1 and prevalent type 2 diabetes mellitus, the incident T2DM (approx. 50,000 cases yearly) and for comparison, the diabetes-free Hungarian adult population (approx. 7,000,000 cases yearly) was included in the study. The primary endpoints were the overall and site-specific incidence and annual percentage change of the incidence of cancer in both populations. (3) Results: The overall incidence of cancer in patients amounted to 29.4/1000 and 6.6/1000 with or without T2DM, respectively, and the OR (95%CI) of cancer of the T2DM group was 4.32 (4.14-4.53), p < 0.0001. The risk of having cancer was age dependent. The incidence of cancer was declining in the non-diabetic but was unchanged in the T2DM population. The average lag time of diagnosing cancer after the detection of T2DM was 3.86 months. (4) Conclusions: Incident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months.

D-dimer levels to exclude pulmonary embolism and reduce the need for CT angiography in COVID-19 in an outpatient population.

OBJECTIVES: Emerging results indicate that, in COVID-19, thromboembolic complications contribute to the high mortality and morbidity. Previous research showed that the prevalence of pulmonary embolism (PE) is between 25-50% in COVID-19 patients, however, most of these reports are based on data from patients with severe pneumonia, treated in intensive care units. MATERIALS AND METHODS: We conducted a retrospective, single-center, observational study to estimate the prevalence of PE in COVID-19 patients who underwent CT angiography and to identify the most important predictors. Adult outpatients with COVID-19, who presented at our COVID Outpatient Clinic between 1st and 31st of March in 2021 and underwent CTA examination were included in this study. Multiple linear regression analysis was used to identify predictors of PE in COVID-19 patients. The predictors were: age, gender, disease duration, CT severity index and log-transformed quantitative D-dimer (logQDDIM) value. RESULTS: 843 COVID-19 patients were included into the study. 82.56% (693 patients) of the infected patients had a pulmonary CTA examination and D-dimer levels (mean age: 59.82 years ± 15.66). 7.61% (53 patients) of the patients had PE. 2.02% (14 patients) of the patients had main branch or lobar PE. The multiple regression analysis found that only logQDDIM was a significant predictor. A logQDDIM cut-off value of 0.0169 (1.0171 ug/ml serum D-dimer) predicted PE with 99% sensitivity (p<0.0001, degree-of-freedom = 570, AUC = 0.72). CONCLUSIONS: We demonstrated in a large cohort of COVID-19 patients that a cut-off value of QDDIM of 1ug/ml can exclude pulmonary embolism in an outpatient setting, implicating that QDDIM might potentially supersede CTA as a screening approach in COVID-19 outpatient clinics.

Cardiovascular autonomic and peripheral sensory neuropathy in women with obesity.

Introduction: A higher incidence of neural dysfunction in people with obesity has been described. We determined the prevalence of neuropathic lesions in obese women and evaluated their potential association with anthropometric and laboratory parameters. Patients and methods: In our cross-sectional study, we enrolled female patients with obesity and without diabetes before obesity treatment. Voluntary female subjects were controls with a normal body mass index (BMI). Autonomic function was assessed by Ewing's cardiovascular reflex tests, while comprehensive peripheral neuropathic assessments were conducted utilizing the Neurometer®, Tiptherm®, Monofilament®, and Rydel-Seiffer tuning fork tests. Sudomotor function was assessed by the Neuropad®-test. Body composition was examined using the InBody 770. Results: 71 patients (mean ± SD; age: 36.1 ± 8.3 years; BMI: 40.2 ± 8.5 kg/m2) and 36 controls (age: 36.4 ± 13.3 years; BMI: 21.6 ± 2.1 kg/m2) were enrolled. Patients had significantly higher systolic (patients vs. controls; 137.5 ± 16.9 vs. 114.6 ± 14.8 mmHg, p<0.001) and diastolic (83.0 ± 11.7 vs.69.8 ± 11.2 mmHg, p<0.001) blood pressure compared to controls. Among autonomic tests, only the heart rate response to Valsalva maneuver (Valsalva-ratio) revealed significant impairment in patients (1.4 ± 0.2 vs. 1.7 ± 0.4, p<0.001). Neurometer® at the median nerve revealed increased current perception threshold (CPT) values at all stimulating frequencies in patients (CPT at 2000 Hz: 204.6 ± 70.9 vs. 168.1 ± 66.9, p=0.013; 250 Hz: 84.4 ± 38.9 vs. 56.5 ± 34.8, p<0.001; CPT at 5 Hz: 58.5 ± 31.2 vs 36.9 ± 29.1, p<0.001). The Rydel-Seiffer tuning fork test has revealed a significant impairment of vibrational sensing on the lower limb in patients (right hallux: 6.8 ± 0.9 vs. 7.4 ± 0.8, p=0.030; left hallux: 6.9 ± 0.8 vs. 7.3 ± 0.9, p=0.029). The Neuropad® testing showed a significant impairment of sudomotor function in women with obesity. A negative correlation was found in patients between BMI and the 25-hydroxy-D3/D2-vitamin levels (r=-0.41, p=0.00126) and a positive correlation between the BMI and resting systolic blood pressure (r=0.26, p=0.0325). Conclusion: Peripheral sensory neuronal and sudomotor function impairments were detected in female patients with obesity compared to the controls with normal BMI. Cardiovascular autonomic dysfunction was also revealed by the Valsalva-ratio in these patients, suggesting the presence of parasympathetic dysfunction. The negative correlation between BMI and the 25-hydroxy-D3/D2-vitamin highlights the potential deficiency of vitamin D in the population affected by obesity.