Determinants of the heart rate variability in type 1 diabetes mellitus.

Background: Evaluation of heart rate variability (HRV) detects the early subclinical alterations of the autonomic nervous system. Thus, impaired HRV is the earliest subclinical marker of cardiac autonomic neuropathy (CAN) in type 1 diabetes mellitus (T1DM). Objectives: We aimed to explore the HRV parameters in asymptomatic T1DM patients and compare them with the results obtained in healthy subjects. Potential associations between HRV parameters and the established risk factors for CAN and cardiovascular diseases were also investigated. Methods: Seventy T1DM patients (38 ± 12 years, 46 females) and 30 healthy subjects were enrolled into the study. For HRV analysis, beat-to-beat heart rate was recorded for 30 min. The less noisy 5-min segment of the recording was analyzed by Bittium Cardiac Navigator HRV analysis software. Time domain, frequency domain, and nonlinear indices were calculated. Results: Regarding ratio of low to high frequency component (LF/HF), no differences were found between the two populations (p = 0.227). All the further, time domain, frequency domain, and nonlinear HRV indices were significantly lower in T1DM patients (each p < 0.001). In multiple linear models, disease duration remained the only independent predictor of LF/HF ratio (p = 0.019). HbA1c was found to be significant independent predictor of all further time domain (SDNN, p < 0.001; rMSSD, p < 0.001), frequency domain (VLF, p < 0.001; LF, p = 0.002; HF, p = 0.006; Total Power, p = 0.002), and nonlinear indices (SD1, p = 0.006; SD2, p = 0.007), alone, or in combination with other factors, such as age or body mass index. Conclusion: Asymptomatic T1DM patients have significantly reduced overall HRV as compared with healthy subjects, indicating subclinical CAN. Quality of the glycemic control is important determinant of HRV among T1DM patients. This relationship is independent of other risk factors for CAN or cardiovascular diseases.

Cardiovascular outcomes in patients treated with sodium-glucose transport protein 2 inhibitors, a network meta-analysis of randomized trials.

Background: Gliflozins altering the sodium-glucose transport protein 2 (SGLT2) in the nephron, represent alone or in combination a promising treatment option for patients with type II diabetes mellitus. In addition to glucose control, these drugs provide benefits including reduced risk of long-term cardiovascular (CV) and renal complications. Several trials evaluated gliflozins in patients with various degrees of cardiac dysfunction with heterogeneous results. Objectives: We aimed to perform a comprehensive analysis of the effect of gliflozins on CV outcomes. Methods: Systematic searches of electronic databases were conducted until September 2022. Multiple treatment network meta-analysis was performed in R. Random-effects model was used to combine risk estimates across trials calculating risk ratio (RR) with 95% confidence intervals as summary statistics. The primary endpoint of interest was the rate of heart failure-related hospitalization (HHF) and the composite of HHF with CV mortality (HHF + CVD). Secondary outcomes included major adverse cardiac events (MACE), CV- and overall mortality, myocardial infarction (MI), and stroke. Results: Twenty-nine studies randomizing 88,418 patients were identified. Gliflozins reduced the risk of HHF (RR: 0.72 [0.69; 0.76]) and HHF + CVD (RR: 0.78 [0.75; 0.82]). The risk of MACE and its component also improved significantly except for stroke. The network analyses did not explore major differences among the individual substances. The only exception was sotagliflozin which appeared to be more effective regarding HHF + CVD, stroke, and MI compared to ertugliflozin, in HHF + CVD and stroke compared to dapagliflozin, and in stroke endpoint compared to empagliflozin. Conclusion: Our meta-analysis supports a group effect of gliflozins beneficial in a wide spectrum of patients with a risk of heart failure (HF) development. In addition to the improvement of HF-related outcomes, the risk of major adverse events is also reduced with SGLT2 inhibition. Systematic review registration: [www.ClinicalTrials.gov], identifier [CRD42022358078].

Quality of glycemic control has significant impact on myocardial mechanics in type 1 diabetes mellitus.

The potential associations between disease duration, glycemic control, and the echocardiographic markers of the myocardial mechanics were investigated in asymptomatic T1DM patients. Seventy T1DM patients (38.2 ± 11.7 years, 46 female) and 30 healthy volunteers were investigated. Besides the conventional and tissue Doppler measurements, left ventricular global longitudinal (GLS) and circumferential (GCS) strain as well as left and right atrial strain parameters were measured with 2D speckle tracking technique. Median HbA1c level was 7.4 (1.8)%. Even when added age and hypertension to the model, current HbA1c level remained independent predictor of left ventricular GLS (p = 0.002), GCS (p < 0.001), mitral e' (p = 0.018), tricuspid e' (p = 0.018) and left (p = 0.039) and right atrial conduit strain (p = 0.047) in multiple linear regression models. Correlations between disease duration and the echocardiographic variables lost their significance in multiple models. In patients with a combination of HbA1c ≤ 7.4% and no hypertension, echocardiographic findings did not differ from those in healthy volunteers. Patients with HbA1c > 7.4% and no hypertension and especially patients with coexisting hypertension and HbA1c > 7.4%, exhibited significantly impaired myocardial mechanics. Quality of glycemic control has a significant impact on myocardial mechanics in T1DM patients. Regarding disease duration this relationship was not proved.

Prognostic value of right atrial stiffness in systemic sclerosis.

OBJECTIVES: We hypothesised that right atrial (RA) size and mechanics may have prognostic role in systemic sclerosis (SSc) patients without manifest pulmonary arterial hypertension (PAH), thus we aimed to investigate the prognostic power of RA volume, strain and stiffness parameters alone and when added to the echocardiographic marker of RV longitudinal systolic function. METHODS: Seventy SSc patients (57±12 years) were enrolled into our follow-up study. They underwent standard echocardiographic and tissue Doppler measurements at baseline. In addition to maximal RA volume index, RA reservoir, conduit and contractile strain were measured with 2D speckle tracking technique. RA stiffness was calculated as ratio of TriE/e' to reservoir strain. Survival was assessed after 5 years. All-cause mortality was chosen as outcome. Sequential χ2 analysis was used to evaluate the incremental prognostic benefit of adding RA volume, strain or stiffness to tricuspid S (TriS). RESULTS: During the follow-up period of 4.7±0.9 years, 6 patients (8.6%) died. When added to TriS in sequential Cox model, RA stiffness significantly improved the diagnostic performance of the model (Δχ2= 3.950; p=0.047) and remained independent predictor of the outcome (HR 2.460 (1.005-6.021); p=0.049). Vmax index and strain parameters did not show incremental prognostic value over TriS. Using ROC analysis, RA stiffness ≥0.156 was the best predictor of mortality (sensitivity=83.3%, specificity =89.1%, AUC=0.859). CONCLUSIONS: RA stiffness is associated with all-cause mortality in SSc patients without PAH independent of and incremental to the RV longitudinal systolic function. It may be proposed as non-invasive marker for identifying patients with high mortality risk.

The Genetic Architecture of Hypertrophic Cardiomyopathy in Hungary: Analysis of 242 Patients with a Panel of 98 Genes.

Hypertrophic cardiomyopathy (HCM) is a primary disease of the myocardium most commonly caused by mutations in sarcomeric genes. We aimed to perform a nationwide large-scale genetic analysis of a previously unreported, representative HCM cohort in Hungary. A total of 242 consecutive HCM index patients (127 men, 44 ± 11 years) were studied with next generation sequencing using a custom-designed gene-panel comprising 98 cardiomyopathy-related genes. A total of 90 patients (37%) carried pathogenic/likely pathogenic (P/LP) variants. The percentage of patients with P/LP variants in genes with definitive evidence for HCM association was 93%. Most of the patients with P/LP variants had mutations in MYBPC3 (55 pts, 61%) and in MYH7 (21 pts, 23%). Double P/LP variants were present in four patients (1.7%). P/LP variants in other genes could be detected in ≤3% of patients. Of the patients without P/LP variants, 46 patients (19%) carried a variant of unknown significance. Non-HCM P/LP variants were identified in six patients (2.5%), with two in RAF1 (p.Leu633Val, p.Ser257Leu) and one in DES (p.Arg406Trp), FHL1 (p.Glu96Ter), TTN (p.Lys23480fs), and in the mitochondrial genome (m.3243A>G). Frameshift, nonsense, and splice-variants made up 82% of all P/LP MYBPC3 variants. In all the other genes, missense mutations were the dominant form of variants. The MYBPC3 p.Gln1233Ter, the MYBPC3 p.Pro955ArgfsTer95, and the MYBPC3 p.Ser593ProfsTer11 variants were identified in 12, 7, and 13 patients, respectively. These three variants made up 36% of all patients with identified P/LP variants, raising the possibility of a possible founder effect for these mutations. Similar to other HCM populations, the MYBPC3 and the MYH7 genes seemed to be the most frequently affected genes in Hungarian HCM patients. The high prevalence of three MYBPC3 mutations raises the possibility of a founder effect in our HCM cohort.

Galectin-3 and sST2: associations to the echocardiographic markers of the myocardial mechanics in systemic sclerosis - a pilot study.

BACKGROUND: Progressive cardiac fibrosis is the central aspect of the myocardial involvement in systemic sclerosis (SSc). We hypothesized that circulating biomarkers of the cardiac fibrosis may be useful in the early diagnosis of the cardiac manifestation in this disease. Thus, we investigated the potential correlations between the levels of galectin-3, soluble suppression of tumorigenicity-2 (sST2) and the echocardiographic markers of the myocardial mechanics in SSc patients. METHODS: Forty patients (57.3 ± 13.7 years, 36 female) were investigated. In addition to the conventional echocardiography, tissue Doppler and speckle tracking-derived strain techniques were used to assess the function of both ventricles and atria. To estimate the correlations between galectin-3 and sST2 levels and the echocardiographic variables, partial correlation method was used with age as correcting factor. RESULTS: In age adjusted analysis galectin-3 level showed significant correlation with left ventricular global longitudinal strain (r = 0.460, p = 0.005); grade of left ventricular diastolic dysfunction (r = 0.394, p = 0.013); septal e' (r = - 0.369, p = 0.021); septal E/e' (r = 0.380, p = 0.017) and with the grade of mitral regurgitation (r = 0.323, p = 0.048). No significant correlation was found between sST2 levels and the echocardiographic variables. CONCLUSIONS: Galectin-3 levels, but not sST2 levels show significant correlation with the parameters of the left ventricular systolic and diastolic function. Galectin-3 may be a useful biomarker for the screening and early diagnosis of SSc patients with cardiac involvement.

Minimal Clinically Important Differences (MCID) for the Functional Assessment of Chronic Illness Therapy Fatigue Scale in Patients with Systemic Sclerosis.

(1) Background: Systemic sclerosis (SSc) is characterized by significant fatigue, causing diminished quality of life (QoL). The aim of this study was to examine fatigue levels and their associations with clinical factors and determine the minimal clinically important difference (MCID) value for the Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-FS). (2) Methods: A total of 160 SSc patients and 62 individuals without SSc were followed-up over a 12-month period by measuring the FACIT-FS and the Visual Analogue Scale and the Short Form 36 Vitality Score analyzing changes in exhaustion. (3) Results: Fatigue was strongly correlated with HRQoL, level of pain, emotional disorders, physical capability and functionality. The MCID values for FACIT-FS were calculated as -3 for deterioration and +4 for improvement after a 12-month follow-up. The predictors of improvement of fatigue from baseline parameters were the significant disease activity, the patients' poorer functionality and the short disease duration. Patients with scleroderma-related interstitial lung disease at baseline had approximately tripled risks for worsening fatigue. The independent influential factors regarding the changing of FACIT-FS were improving or worsening in the same direction in reference to physical condition, gastrointestinal and emotional factors. (4) Conclusions: Fatigue is a multi-dimensional symptom, which is strongly correlated to HRQoL. MCID values of FACIT-FS can be useful tools in monitoring the changes of HRQoL in clinical trials and in daily practice among patients with SSc.

Screening for precapillary pulmonary hypertension in chronic myeloproliferative disorders: the role of N-terminal pro-B-type natriuretic peptide and vascular endothelial growth factor - a pilot study.

INTRODUCTION: Precapillary pulmonary hypertension (PH) implies a worse prognosis in myeloproliferative neoplasms (MPN). N-terminal pro-B-type natriuretic peptide (NT-proBNP) is elevated in cardiopulmonary involvement. In MPN patients with precapillary PH, elevated vascular endothelial growth factor (VEGF) values, but in left heart (LH) disease patients, decreased values were reported. Our aim was to determine whether a combination of NT-proBNP and VEGF is suitable for the detection of the precapillary forms of PH in MPN patients. MATERIAL AND METHODS: Eighty-one MPN patients were investigated. Pulmonary hypertension was defined as Doppler-derived systolic pulmonary artery pressure (sPAP) ≥ 40 mm Hg. Patient groups with cardiopulmonary involvement (precapillary PH, PH due to LH disease, left ventricular ejection fraction < 50%, atrial fibrillation) or LH disease (PH due to LH disease, left ventricular ejection fraction < 50%, atrial fibrillation) were identified. RESULTS: In 9 patients PH was associated with LH disease. In 2 patients precapillary PH was found with extremely high NT-proBNP values. NT-proBNP significantly correlated with sPAP (r = 0.550; p < 0.001). NT-proBNP ≥ 466 pg/ml was the best predictor of cardiopulmonary involvement (AUC: 0.962, sensitivity: 86.7%, specificity: 93.9%). No correlation was found between VEGF levels and sPAP values. VEGF ≤ 431 pg/ml was the best predictor of LH disease (AUC: 0.609, sensitivity: 76.9%, specificity: 62.7%). CONCLUSIONS: NT-proBNP levels reflect cardiopulmonary involvement with high accuracy, but the combination of NT-proBNP and VEGF is not suitable for the detection of precapillary PH as the diagnostic power of VEGF is limited. Highly elevated NT-proBNP levels may suggest precapillary PH but further investigation is necessary for the exclusion of LH disease or atrial fibrillation.

Successful termination of ventricular arrhythmias with implantable cardioverter defibrillator in a patient with myotonic dystrophy / Implantálható kardioverter-defibrillátor által sikeresen megszüntetett malignus kamrai ritmuszavar dystrophia myotonicában szenvedo betegben.

Összefoglaló. A dystrophia myotonica (DM) multiszisztémás, autoszomális domináns módon öröklodo, többségében felnottkori izombetegség, melynek incidenciája 1 : 8000. A betegség kapcsán fellépo izomszöveti degeneráció a harántcsíkolt izomszövet átépülése mellett a szívizomszövetet is érinti, ami fontos oki szerepet játszik az érintett betegek csökkent várható élettartamában. A DM-ben szenvedok halálozásának közel egyharmadáért a cardiovascularis okok tehetok felelossé. Esetriportunkban egy 52 éves, korábban kritikus bradycardia és I. fokú atrioventricularis blokk miatt pacemakerimplantáción átesett, DM-mel diagnosztizált nobeteg kardiológiai utánkövetését mutatjuk be. A hirtelen szívhalál rizikóstratifikációja céljából elvégzett invazív elektrofiziológiai vizsgálat során kamrafibrilláció lépett fel, így a korábban implantált pacemakerelektródák mellé sokkelektróda került beültetésre, a pacemakerkészüléket implantálható kardioverter-defibrillátorra (ICD) cseréltük. Az 1 éves ICD-kontrollvizsgálat során azt találtuk, hogy a beültetés óta 22, tartós kamrai tachycardiával járó epizód lépett fel, melyek közül a készülék valamennyit sikeresen terminálta. Az eset bemutatásával szeretnénk rámutatni arra, hogy a magas cardiovascularis rizikócsoportba tartozó DM-betegek azonosítása kiemelkedo fontosságú lehet a hirtelen szívhalál megelozése érdekében. Orv Hetil. 2021; 162(46): 1856-1858. Summary. Myotonic dystrophy (DM) is one of the most frequent adulthood diseases of the skeletal muscles, which develops multisystemic features and shows autosomal dominant trait. In DM, tissue degeneration affects not only the skeletal, but the cardiac muscle, too. In one third of the patients, the cause of death is of cardiac origin. We report on our patient's case, who was diagnosed with DM at the age of 52, in whom episodes of critical bradycardia with first-degree atrioventricular block was detected, resulting in a pacemaker implantation. Invasive cardiac electrophysiological study was performed, during which ventricular fibrillation was registered. A shock electrode was added to the previously implanted pacemaker, enabling defibrillation in case of detection of a sustained ventricular arrhythmia. During the 1-year follow-up, 22 episodes of sustained ventricular tachycardia were identified, with the device successfully terminating the malignant arrhythmias. Our case shows that electrophysiological study and the succeeding implantation of an implantable cardiac defibrillator is highly important in identifying and terminating ventricular arrhythmias in high-risk DM patients. Orv Hetil. 2021; 162(46): 1856-1858.

Management of acutely decompensated chronic thromboembolic pulmonary hypertension in late pregnancy: a case report.

BACKGROUND: Pregnancy in patients with pulmonary hypertension is associated with increased risk of maternal and fetal death. Physiological changes during pregnancy, labor and the postpartum period may all lead to acute decompensation of chronic right heart failure with rapid progression to circulatory collapse. As such, guidelines discourage planned pregnancies in women suffering from pulmonary hypertension. There are, however, rare cases of pulmonary hypertension which have previously been undiagnosed and only become apparent during late stage pregnancy. These individuals require close monitoring and multidisciplinary management. CASE PRESENTATION: We describe the case of a 34-year-old female who presented with acute decompensation of previously undiagnosed pulmonary hypertension during the 30th week of her second pregnancy. Echocardiography and CT scan confirmed severe pulmonary hypertension and right heart failure with no new thromboembolic component. Following stabilization of cardiorespiratory parameters with high FiO2 noninvasive ventilation, intravenous epoprostenol and levosimendan treatment, Cesarean section was performed under epidural anesthesia. Close monitoring was continued in the postoperative period and cardiovascular parameters were managed with ongoing inotropic and escalating vasodilator therapy. The findings were consistent with chronic thromboembolic pulmonary hypertension. Persistent hypoxia was found to be a result of right bronchial obstruction caused by blood clots, which resolved with bronchoscopic intervention. Ongoing postpartum management resulted in improved cardiovascular parameters and oxygenation. Epoprostenol treatment was successfully converted to subcutaneous treprostinil therapy and the patient was discharged home to care for her healthy baby girl. Optimal timing of pulmonary endarterectomy will be chosen based upon functional status and patient preference. CONCLUSIONS: The case described is the first published report of previously undiagnosed pulmonary hypertension presenting with acute right heart failure in late pregnancy successfully managed by pharmacological therapy, noninvasive ventilation and a Cesarean performed under epidural anesthesia. The case illustrates that despite the challenges, acutely discovered right heart failure can be successfully managed with a comprehensive multidisciplinary treatment plan.

Left atrial stiffness is superior to volume and strain parameters in predicting elevated NT-proBNP levels in systemic sclerosis patients.

Heart failure with preserved ejection fraction (HFpEF) is common in systemic sclerosis (SSc) and implies a worse prognosis therefore non-invasive assessment of left ventricular (LV) filling pressure is pivotal. Besides E/e' the use of maximal left atrial volume (LA Vmax index) is recommended. LA reservoir strain was also reported to be useful. The utility of LA stiffness, however, was never investigated in SSc. Thus we aimed to compare the diagnostic power of LA Vmax index, reservoir strain and stiffness in predicting elevated LV filling pressure in SSc patients. 72 SSc patients (age: 57 ± 11 years) were investigated. LA stiffness was calculated as ratio of E/e' to LA reservoir strain. Elevated LV filling pressure was defined as NT-proBNP > 220 pg/ml. Receiver-operating characteristic (ROC) curves were used to estimate the diagnostic performance of the investigated parameters. Average NT-proBNP level was 181 ± 154 pg/ml. NT-proBNP > 220 pg/ml was found in 21 SSc patients. LA stiffness showed the highest diagnostic performance in predicting NT-pro-BNP > 220 pg/ml, with a cut off value of 0.314 (Area under the curve: 0.719, specificity: 89.4%, sensitivity: 42.1%). AUC values for LA reservoir strain and Vmax index were 0.595 and 0.521, respectively. LA stiffness was superior to Vmax index and reservoir strain in predicting elevated NT-proBNP levels in SSc patients. Although invasive validation studies on larger samples are required, our data suggest, that the use of LA stiffness may significantly contribute to diagnostic precision in populations with a high suspicion of HFpEF.

Relation of Right Atrial Mechanics to Functional Capacity in Patients With Systemic Sclerosis.

Cardiac involvement in systemic sclerosis (SSc) implies a worse prognosis. Little is known about the right atrial (RA) mechanics in this disease, but recent data suggest that it correlates well with the functional capacity of the patients in conditions with known right heart involvement. Thus we aimed to investigate the abnormalities of the RA function as compared with healthy subjects and to assess the potential correlations between RA mechanics and the functional capacity in SSc patients using 2D speckle tracking technique. A total of 70 SSc patients (age: 57 ± 12 years) were investigated. Functional capacity was measured with 6-minute walk test (6MWT). Echocardiographic parameters of the right ventricular (RV) systolic function (TAPSE, RVFAC), parameters of the tricuspid inflow (E, A), and tricuspid annular systolic (S), early- (e') and late- (a') diastolic myocardial velocities were measured. RV wall thickness was obtained. RA reservoir (εR), conduit (εCD), and contractile (εCT) strain were measured. RA stiffness was calculated as ratio of E/e' to εR. Echocardiographic data were compared with an age- and gender-matched group of 25 healthy volunteers. RA εR (49.3 ± 10.7 vs 59.6 ± 9.9%, p = 0.000) and εCD (26.8 ± 8.1 vs 34.3 ± 7.3%, p = 0.000) were significantly lower in SSc patients. No significant difference was found in εCT (22.9 ± 5.8 vs 25.3 ± 5.7%, p = 0.082). RA stiffness was significantly increased in SSc patients (0.11 ± 0.04 vs 0.08 ± 0.02, p = 0.001). 6MWT distance was 391 ± 95m. In stepwise multiple linear regression analysis RV wall thickness (r = -0.289, p = 0.030) and RA stiffness (r = -0.418, p = 0.002) became independent predictors of 6MWT distance. In conclusion, RA εR and εCD are impaired, while RA stiffness is increased in SSc compared with healthy subjects. Speckle tracking-derived RA stiffness is turned out to be one of the main determinants of the functional capacity in SSc patients.

Impairment of Left Atrial Mechanics Is an Early Sign of Myocardial Involvement in Systemic Sclerosis.

BACKGROUND: Left ventricular (LV) diastolic dysfunction is common in systemic sclerosis (SSc). Less is known, however, about left atrial (LA) mechanics in this context. The aim of this study was to investigate the correlation between LV diastolic function and LA mechanics in SSc patients with the use of volumetric and 2-dimensional speckle tracking-derived strain techniques and to compare the results with those obtained in healthy subjects. METHODS AND RESULTS: Seventy-two SSc patients and 30 healthy volunteers (H) were investigated. LV diastolic function was classified as normal (I), impaired relaxation (II), and pseudonormal pattern (III). LA reservoir (H: 51.8 ± 7.4%; I: 45.1 ± 8.1%; II: 42.2 ± 6.6%; III: 36.6 ± 7.3%; analysis of variance: P < .001) and contractile strain (H: 24.8 ± 4.9%; I: 18.2 ± 4.4%; II: 21.5 ± 2.8%; III: 16.8 ± 3.6%; P < .001) already showed significant worsening in SSc patients with preserved LV diastolic function compared with healthy subjects. LA conduit strain (H: 27.1 ± 4.6%; I: 26.9 ± 5.7%; II: 20.6 ± 6.1%; III: 19.5 ± 5.3%; P < .001) was preserved in this early phase. Further deterioration of reservoir strain was pronounced in the pseudonormal group only. LA contractile strain increased significantly in the impaired relaxation group and then decreased with the further worsening of the LV diastolic function. Regarding phasic volume indices, the differences between groups were not always statistically significant. CONCLUSION: LA mechanics strongly reflects the changes in LV diastolic function in SSc. On the other hand, strain parameters of the LA reservoir and contractile function already show significant worsening in SSc patients with preserved LV diastolic function, suggesting that impairment of the LA mechanics is an early sign of myocardial involvement in SSc.

The presence of small joint contractures is a risk factor for survival in 439 patients with systemic sclerosis.

OBJECTIVES: Analysis of risk factors and mortality of 439 patients with systemic sclerosis (SSc) in a tertiary care centre. METHODS: The mean follow up time was 8.4±5.6 years. Lost to follow up rate was 6.4%. Female to male ratio was 366 to 73. Two hundred sixty patients had limited and 179 diffuse cutaneous SSc (dcSSc). A standard protocol including musculoskeletal examinations was used for the assessment of patients. RESULTS: By Kaplan-Meier analysis the overall 5-, 10- and 15 year survival were 88.2%, 79.9% and 73.6%, respectively. Univariate analysis showed that dcSSc, male gender, presence of small joint contractures, pulmonary interstitial, cardiac, oesophageal involvement, scleroderma renal crisis, arterial hypertension, anti-topoisomerase antibody, anemia, hypalbuminemia, coexistent malignancies and elevated erythrocyte sedimentation were associated with poor survival. Lack of giant capillaries, avascular zones or neo-angiogenesis on capillaroscopy, and presence of anti-centromere antibodies were associated with favourable outcome. Multivariate regression analysis showed presence of small joint contractures, history of arterial hypertension, male gender, diffusing capacity of carbon monoxide <50%, right ventricular pressure >40 mmHg on echocardiography, less than 50% ejection fraction, anti-topoisomerase I positivity, anemia, and serum albumin concentration < 35 g/l as well as current or history of coexistent malignancy were independent poor prognostic factors. CONCLUSIONS: In addition to well-known factors predicting poor outcome in SSc, the presence of small joint contractures was a newly identi ed independent risk factor of mortality. Our data also confirmed a recent finding showing that history of arterial hypertension was also a poor prognostic factor.

[Hungarian Heart Failure Registry 2015-2016. Preliminary results]. / Magyar Szívelégtelenség Regiszter 2015­2016. Kezdeti eredmények.

Heart failure is associated with a poor prognosis despite significant advances in the pharmacological and device therapy and incurs very high cost because of frequent hospitalizations. Therefore, professional high-quality care is essential for both patients and the healthcare system. The best way to evaluate the quality of care for a particular disease is the use of disease-specific registries. Until now, there has not been a registry evaluating characteristics and management of heart failure patients in Hungary. For that reason, the Hungarian Society of Cardiology initiated the set-up of the Hungarian Heart Failure Registry. The Aim of this paper is to present the goals, methods and first year results of the Hungarian Heart Failure Registry. The goal of the Registry is to create a modern, web-based database that summarizes the data of large number of patients who are currently or were previously admitted to hospital or who are currently or were previously patients in an outpatient department due to severe heart failure (NYHA III-IV). Currently 17 cardiology departments participate in the development of the Registry. The planned number of patients is 2000. Initially follow-up was planned for one year (pilot study). After the evaluation of the relevant experiences of the pilot study, long-term follow-up is planned. The Registry collects information about the type of heart failure (heart failure with reduced - LVEF≤45% - vs. preserved - LVEF>45% - ejection fraction), etiology, co-morbidities, diagnostic methods, treatment as well as morbidity and mortality. After the first year, assessing the baseline parameters of 698 patients enrolled in the Registry we found that the majority of patients (87.8%) has heart failure with reduced ejection fraction and in 39.8% of the patients heart failure has an ischaemic origin. The most frequent co-morbidity was hypertension followed by diabetes, renal insufficiency and COPD. The patients were treated with ACE inhibitors or ARBs in 94.4%, with beta blockers in 95.9%, and mineralocorticoid receptor antagonists in 73.9%. The mean dose of neurohormonal antagonists was higher than half of the target dose defined by current guidelines. The use of cardiac resynchronisation therapy was 11.7% and implantable cardioverter defibrillator was 25.8%. The pharmacological and device therapy of patients who were enrolled in the Registry until now was fit the current guidelines' recommendations. This, however, does not mean that the management of heart failure is without problems in our country but that high quality patient care is available with adequate heart failure treatment in cardiology departments dedicated to heart failure care. Orv. Hetil., 2017, 158(3), 94-100.

Galectin-3 is an independent predictor of survival in systemic sclerosis.

BACKGROUND: Galectin-3 is a beta-galactoside-binding lectin that may be related to tissue sclerosis or aberrant activation of angiogenesis in systemic sclerosis (SSc). The aim of our study was to determine the associations between galectin-3 levels and patient characteristics, as well as to investigate the long term prognostic value of galectin-3 in a large cohort of SSc patients. METHODS: 152 patients with SSc (55±11years, 138 female) were included in our follow-up study. Blood samples and clinical data were collected at baseline. Primary and secondary outcomes were all-cause and cardiovascular mortality, respectively. RESULTSS: Galectin-3 levels showed positive correlation with the grade of left ventricular diastolic function (r=0.193; p=0.026), erythrocyte sedimentation rate (r=0.172; p=0.036) and serum level of C-reactive protein (r=0.200; p=0.015) while negative correlation with diffusing capacity for carbon monoxide (r=-0.228; p=0.006), in age, gender and BSA adjusted analyses. During the follow-up of 7.2±2.3years, 35 SSc patients (23%) died. In multivariate Cox regression analyses adjusted for age, gender, BSA, creatinine and NT-proBNP levels, galectin-3 was an independent predictor both of the all-cause mortality (HR: 2.780, 95% CI: 1.320-5.858, p=0.007) and cardiovascular mortality (HR: 3.346, 95% CI: 1.118-10.012, p=0.031). Using receiver-operating characteristic analysis, galectin-3>10.25ng/ml was found to be the best predictor of the all-cause mortality. CONCLUSIONS: Our results suggest that galectin-3 is an independent predictor of all-cause and cardiovascular mortality in SSc. Validation studies are required to establish whether galectin-3 may be proposed as simple biomarker for identifying patients with high mortality risk in SSc.

Early morphologic and functional changes of atherosclerosis in systemic sclerosis-a systematic review and meta-analysis.

OBJECTIVE: Cardiopulmonary manifestations have an important impact on the life expectancy of SSc patients. Functional and morphological macrovascular changes may appear early before the development of ischaemic symptoms. Several non-invasive methods are used in cardiovascular risk assessment. Heterogeneous data are available regarding these in SSc. We aimed to perform a systematic review and meta-analysis to characterize the importance of atherosclerosis in SSc. METHODS: A systematic literature search was performed to identify controlled studies on carotid intima-media thickness, flow- or nitrate-induced vasodilatation (flow-mediated dilatation, nitroglycerine-mediated dilatation), pulse wave velocity, augmentation index and ankle-brachial pressure index. Outcomes were pooled with the random-effects model. RESULTS: Thirty-five studies comprising a total of 1292 SSc patients qualified. Intima-media thickness, pulse wave velocity and ankle-augmentation index were higher and flow-mediated dilatation lower in SSc patients [standardized mean difference (SMD) 0.65 (95% CI: 0.29, 1.01), 0.62 (95% CI: 0.35, 0.88), 0.96 (95% CI: 0.45, 1.47) and -0.68 (95% CI: -1.39, -0.34), respectively, P < 0.01 for each]. Nitroglycerine-mediated dilatation and ankle-brachial pressure index were lower, but not significantly [SMD: -0.16 (95% CI: -0.50, 0.18) and -0.39 (95% CI: -0.91, 0.13), respectively]. Data showed high to moderate inconsistency and significant heterogeneity. Meta-regression analysis of the SMD and the disease duration found a regression coefficient of 0.086, P = 0.014, confirming that parameters of the included SSc population may have contributed to the heterogeneity. CONCLUSION: Meta-analysis of the published observational studies confirms that abnormalities attributable to macrovascular involvement are significantly more prevalent in SSc patients compared with controls. Considering the increasing importance of cardiovascular disease in SSc, a more widespread use of cardiovascular risk assessment is warranted.

Mutations in NEBL encoding the cardiac Z-disk protein nebulette are associated with various cardiomyopathies.

INTRODUCTION: Transgenic mice overexpressing mutated NEBL, encoding the cardiac-specific Z-disk protein nebulette, develop severe cardiac phenotypes. Since cardiomyopathies are commonly familial and because mutations in a single gene may result in variable phenotypes, we tested the hypothesis that NEBL mutations are associated with cardiomyopathy. MATERIAL AND METHODS: We analyzed 389 patients, including cohorts of patients with dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), and left ventricular non-compaction cardiomyopathy (LVNC). The 28 coding exons of the NEBL gene were sequenced. Further bioinformatic analysis was used to distinguish variants. RESULTS: In total, we identified six very rare heterozygous missense mutations in NEBL in 7 different patients (frequency 1.8%) in highly conserved codons. The mutations were not detectable in 320 Caucasian sex-matched unrelated individuals without cardiomyopathy and 192 Caucasian sex-matched blood donors without heart disease. Known cardiomyopathy genes were excluded in these patients. The mutations p.H171R and p.I652L were found in 2 HCM patients. Further, p.Q581R and p.S747L were detected in 2 DCM patients, while the mutation p.A175T was identified independently in two unrelated patients with DCM. One LVNC patient carried the mutation p.P916L. All HCM and DCM related mutations were located in the nebulin-like repeats, domains responsible for actin binding. Interestingly, the mutation associated with LVNC was located in the C-terminal serine-rich linker region. CONCLUSIONS: Our data suggest that NEBL mutations may cause various cardiomyopathies. We herein describe the first NEBL mutations in HCM and LVNC. Our findings underline the notion that the cardiomyopathies are true allelic diseases.

Diastolic Dysfunction Is a Contributing Factor to Exercise Intolerance in COPD.

Right ventricular (RV) systolic failure is rare in patients with COPD, but they often develop RV diastolic dysfunction. Left ventricular (LV) diastolic dysfunction is also common in this population. Nevertheless, data are scarce regarding the effect of diastolic dysfunction on the functional capacity in patients with COPD. We investigated the correlation between echocardiographic parameters of RV and LV diastolic function and the exercise capacity in COPD, by using conventional echocardiographic methods and tissue Doppler imaging. 65 patients with COPD (61 ± 9 years) in stages GOLD II-IV were investigated. Functional capacity was measured with 6-minute walk test (6MWT). Right (RA) and left atrial (LA) area index were measured; collapsibility index inferior vena cava was calculated. Parameters of the mitral and tricuspid inflow (E, A) as well as annular systolic (S), early- (e') and late- (a') diastolic myocardial longitudinal velocities were measured. E/A, E/e' and e'/a' ratios were calculated. 6MWT distance was 330 ± 76 m. LV diastolic dysfunction was found in 48 (74%) patients. LV and RV filling pressures were elevated in 28 (43%) and in 29 (45%) patients, respectively. In the left heart, LA area index showed significant correlation with the functional capacity (r = -0.319; p = 0.011). In stepwise multiple linear regression analysis tricuspid e'/a' (r = 0.611; p = 0.000), collapsibility index (r = 0.505; p = 0.000), RA area index (r = -0.445; p = 0.000) and body surface area (r = 0.314; p = 0.011) were independent predictors of 6MWT distance. Right ventricular diastolic function and filling pressure have strong influence on the functional capacity in patients with COPD.

Echocardiographic abnormalities in new-onset polymyositis/dermatomyositis.

OBJECTIVE: To identify early echocardiographic abnormalities at the time of diagnosis of polymyositis (PM) and dermatomyositis (DM) and follow the echocardiographic findings during the first 3 months of therapy. METHODS: We included 30 PM/DM patients (23/7) with a mean age of 42.3 ± 1.6 years and without cardiovascular symptoms. Age-matched healthy patients served as controls. Clinical characteristics were recorded. Traditional echocardiography and tissue Doppler imaging (TDI) were performed to measure systolic [ejection fraction, right ventricular fractional area change (RV FAC), lateral and tricuspid annulus s velocities] and diastolic echocardiographic variables (mitral inflow velocities: E, A; deceleration time: DT; lateral and tricuspid annulus e', a' velocities, lateral E/e'). RESULTS: The left and right ventricular systolic dysfunction detected by TDI at the time of the PM/DM diagnosis improved, and characteristic values at the end of the followup period were comparable to those of the controls (lateral s: 10.6 ± 0.2, 8.7 ± 0.4, 9.6 ± 0.3, 11.3 ± 0.2 cm/s; RV FAC: 45.2 ± 2.3, 36.9 ± 1.5, 42.2 ± 1.3, 46.9 ± 1.2%; tricuspid s: 13.3 ± 0.2, 9.5 ± 0.4, 10.3 ± 0.3, 11.6 ± 0.5 cm/s; control, 0, 1, and 3 mos, respectively). Measurements indicated the development of diastolic dysfunction at 3 mos (E/A: 1.4 ± 0.1, 1.29 ± 0.05, 1.03 ± 0.05, 0.92 ± 0.05; DT: 148.6 ± 3.6, 157.3 ± 5.7, 168.3 ± 6.0, 184.3 ± 6.2 ms; lateral e': 12.8 ± 0.3, 12.1 ± 0.5, 10.2 ± 0.6, 10.8 ± 0.8 cm/s; E/e': 5.6 ± 0.1, 5.0 ± 0.22, 6.92 ± 0.46, 7.64 ± 0.47; control, 0, 1, and 3 mos, respectively). CONCLUSION: TDI is a useful method to detect early cardiac abnormalities complementing the conventional echocardiographic measurements. LV and RV systolic dysfunction found in the acute phase significantly improved during the first 3 months of therapy; however, deterioration of diastolic dysfunction was also observed.