Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation Sequencing.

INTRODUCTION: Acute cellular rejection (ACR) of heart allografts represents the most common reason for graft failure. Endomyocardial biopsies (EMB) are still subject to substantial interobserver variability. Novel biomarkers enabling precise ACR diagnostics may decrease interobserver variability. We aimed to identify a specific subset of microRNAs reflecting the presence of ACR. PATIENTS AND METHODS: Monocentric retrospective study. A total of 38 patients with the anamnesis of ACR were identified and for each patient three consecutive samples of EMB (with, prior and after ACR) were collected. Sixteen trios were used for next-generation sequencing (exploratory cohort); the resting 22 trios were used for validation with qRT-PCR (validation cohort). Statistical analysis was performed using R software. RESULTS: The analysis of the exploration cohort provided the total of 11 miRNAs that were altered during ACR, the three of which (miR-144, miR-589 and miR-182) were further validated in the validation cohort. Using the levels of all 11 miRNAs and principal component analysis, an ACR score was created with the specificity of 91% and sensitivity of 68% for detecting the presence of ACR in the EMB sample. CONCLUSION: We identified a set of microRNAs altered in endomyocardial biopsies during ACR and using their relative levels we created a diagnostic score that can be used for ACR diagnosis.

Viral genome changes and the impact of viral genome persistence in myocardium of patients with inflammatory cardiomyopathy.

INTRODUCTION: Viral infections are considered the most frequent cause of myocarditis and dilated cardiomyopathy (DCM). MATERIAL AND METHODS: We investigated the changes in viral presence and the impact of viral genome persistence in the myocardium on echocardiographic parameters, functional status and some laboratory parameters in a 6-month follow-up. Fifty-four patients with recent onset DCM, left ventricular ejection fraction < 40% and biopsy-proven myocarditis (> 14 mononuclear leukocytes/mm2 and/or > 7 T-lymphocytes/mm2) were enrolled. Polymerase chain reaction (PCR) was performed to detect pathogens in the myocardium. Patients were divided according to the administered therapy: standard heart failure medication (46 patients) and immunosuppressive therapy (8 patients). RESULTS: In the standard heart failure medication group viral clearance was observed in 13 patients and viral persistence in 24 patients in the follow-up period. Comparing both groups, there was no statistically significant difference - LVEF improvement of 12.0 ±11.4% vs. 18.3 ±12.6%, decrease in NYHA class of 0.7 ±0.7 vs. 1.0 ±0.7, decline in NT-proBNP of 1335 ±1933 ng/l vs. 1942 ±3242 ng/l and decrease in infiltrating leukocytes of 11.1 ±15.8 vs. 6.7 ±23.0 cells/mm2 and T-lymphocytes of 5.8 ±15.1 vs. 1.8 ±10.9 cells/mm2 (all p = NS). A decrease in PCR positive patients from 37 to 29 was observed. The number of PVB19 positive PCR findings decreased from 5 to 4 in patients with immunosuppressive therapy. CONCLUSIONS: A decrease in the number of positive PCR findings in control endomyocardial biopsy was observed. Viral genome persistence was not associated with worse outcome in short-term follow-up.

[Heart transplantation and infection]. / Transplantace srdce a infekce.

Heart transplantation (HTx) is a method of treatment for patients with end-stage heart failure with severe symptoms despite complex therapy. Post-transplant difficulties include acute rejection and infectious complications, which are the most common reason of morbidity and mortality in the first year after heart transplant. It requires the patient to remain on immunosuppressive medication to avoid the possibility of graft rejection. Therefore the range of infection is much larger. The diagnosis and treatment of viral, bacterial and fungal infections is often difficult.Key words: heart transplantation - immunosuppression - infection.

Improvement of left ventricular systolic function in inflammatory cardiomyopathy: What plays a role?

AIMS: To compare the differences between patients with inflammatory cardiomyopathy (ICM) with and without improvement in left ventricular (LV) systolic function and to identify the relevant predictors of LV improvement. PATIENTS AND METHODS: The study included 63 patients with biopsy-proven ICM and heart failure symptoms of at least NYHA II, symptom duration ≤ 6 months, LV ejection fraction (LVEF) ≤ 40% assessed by echocardiography and presence of >14 mononuclear leukocytes (LCA+ cells)/mm2 in biopsy samples. Patients were evaluated at baseline and after 6 months. RESULTS: In the group with LVEF improvement of ≥ 10% (I+ group, n = 41), LVEF increased from 24 ± 7% to 47 ± 8% (P < 0.001). In 22 patients (group I-), there was no or minimal LVEF increase (< 10%). In the I+ group, there were more LCA+ cells/mm2 at baseline (25.1 ± 16.5 vs. 18.5 ± 4.4 cells/mm2; P = 0.032) and a more significant decrease in LCA+ cells in the follow-up (reduction of 13.6 ± 14.3 cells/mm2 vs. 5.0 ± 7.7 cells/mm2 in the I- group; P = 0.009). The univariate logistic regression showed a possible association of number of LCA+ cells, LV end-diastolic diameter and N-terminal fragment of pro-brain natriuretic peptide (NTproBNP) value with LVEF improvement. In the multivariate analysis, only NTproBNP at diagnosis was confirmed as an independent predictor of LVEF improvement (OR=1.2; 1.003 to 1.394; P = 0.046). CONCLUSION: The LV systolic function improvement was observed in 65% of the patients. In these patients, the number of inflammatory cells at baseline was higher and decreased more but the higher baseline NTproBNP value was the only independent predictor of LVEF improvement.

Correlations of the changes in bioptic findings with echocardiographic, clinical and laboratory parameters in patients with inflammatory cardiomyopathy.

Patients with myocarditis and left ventricular (LV) dysfunction may improve after standard heart failure therapy. This improvement seems to be related to retreat of myocardial inflammation. The aim of the present study was to assess changes in clinical, echocardiographic and some laboratory parameters and to correlate them with changes in the number of inflammatory infiltrating cells in endomyocardial biopsy (EMB) samples during the 6-month follow-up, and to define predictors of LV function improvement among baseline parameters. Forty patients with biopsy-proven myocarditis and impaired LV function (LV ejection fraction-LVEF <40 %) with heart failure symptoms ≤ 6 months were evaluated. Myocarditis was defined as the presence of >14 mononuclear leukocytes/mm(2) and/or >7 T-lymphocytes/mm(2) in the baseline EMB. The EMB, echocardiography and clinical evaluation were repeated after 6 months of standard heart failure therapy. LVEF improved on average from 25 ± 9 to 42 ± 12 % (p < 0.001); LV end-systolic volume and LV end-diastolic volume (LVEDV) decreased from 158 ± 61 to 111 ± 58 ml and from 211 ± 69 to 178 ± 63 ml (both p < 0.001). NYHA class decreased from 2.6 ± 0.5 to 1.6 ± 0.6 (p < 0.001) and NTproBNP from 2892 ± 3227 to 851 ± 1835 µg/ml (p < 0.001). A decrease in the number of infiltrating leukocytes (CD45+/LCA+) from 23 ± 15 to 13 ± 8 cells/mm(2) and in the number of infiltrating T lymphocytes (CD3+) from 7 ± 5 to 4 ± 3 cells/mm(2) (both p < 0.001) was observed. The decline in the number of infiltrating CD45+ cells significantly correlated with the change in LVEF (R = -0.43; p = 0.006), LVEDV (R = 0.39; p = 0.012), NYHA classification (R = 0.35; p = 0.025), and NTproBNP (R = 0.33; p = 0.045). The decrease in the number of CD3+ cells correlated with the change of systolic and diastolic diameters of the left ventricle (R = -0.33; p = 0.038 and R = -0.45; p = 0.003) and with the change in LVEDV (R = -0.43; p = 0.006). Tricuspid annular plane systolic excursion (TAPSE) (OR 0.61; p = 0.005) and early transmitral diastolic flow velocity (E wave) (OR 0.89; p = 0.002) were identified as predictors of LVEF improvement. Improvements in clinical status, LV function and NTproBNP levels correlated with decrease in the number of infiltrating inflammatory cells. TAPSE and E wave velocity were significant predictors of improvement in multivariate regression. Our observations suggest that contemporary guidelines-based therapy of heart failure is an effective treatment option in patients with recent onset biopsy-proven inflammatory cardiomyopathy.

Variability of post-exercise pulmonary capillary wedge pressure recovery. Implications for noninvasive echocardiographic diagnostics.

AIM: The aim of our study was to assess the course of immediate post-exercise pulmonary capillary wedge pressure (PCWP) changes to identify the optimal time window for the noninvasive diagnostics of exercise-induced PCWP elevation. METHODS AND RESULTS: Seventy-one patients at risk of heart failure with normal left ventricular ejection fraction underwent simultaneous exercise echocardiography and right heart catheterization. The ratio of early left ventricular filling velocity (E) to early diastolic mitral annular velocity (e') was used to predict noninvasively exercise-induced PCWP elevation. Fifty-one patients had exercise-induced PCWP elevation ≥ 8 mmHg and reached peak exercise PCWP ≥ 20 mmHg. Rapid post-exercise recovery of PCWP within 2 min was achieved in 18 (35.3%) patients. Intermediate post-exercise PCWP recovery at 3 and 4 min was found in 16 (31.4%) patients while late post-exercise PCWP recovery (≥ 5 min) was achieved in 17 (33.3%) patients. CONCLUSION: The course of post-exercise PCWP recovery is highly variable, and a significant proportion of patients have only a brief period (≤ 2 min) of exercise-induced PCWP elevation. This fact should be taken into account in noninvasive assessment of exercise-induced PCWP.

Pilot study of sex differences in QTc intervals of heart transplant recipients.

BACKGROUND: Repolarization processes in female and male are different. This study provided pilot data on automatic measurements of QT intervals in heart transplant (HT) recipients stratified according to the sex of the recipient and the donor. METHODS AND RESULTS: The following groups were analyzed: Group A-20 males with male heart, group B-14 females with male heart, group C-13 females with female heart, group D-11 males with female heart, group E-20 healthy males, and group F-20 healthy females. Twelve-lead electrocardiograms were digitally captured during autonomic provocative test of five postural 8-minute stages-supine, unsupported sitting, supine, unsupported standing, and supine. Fridericia formula was used for heart rate correction together with a generic correction for QT/RR hysteresis. Neither female nor male HT recipients exhibit any differences in QTc interval duration related to the sex of the donor. There was, however, a trend towards longer QTc intervals in female HT recipients compared to male HT recipients irrespective of the sex of the donor. The QTc differences between healthy control females and males were highly statistically significant proving the assay sensitivity of the study. CONCLUSION: The available pilot data suggest that in HT patients, the sex of the donor has little influence on the QTc interval of the transplanted heart.

High prevalence of exercise-induced heart failure with normal ejection fraction in post-heart transplant patients.

AIM: Post-heart transplant patients are at increased risk of diastolic dysfunction. The aim of this study was to assess the prevalence of isolated only exercise-induced heart failure with normal ejection fraction (HFNEF) in heart transplant recipients. METHODS AND RESULTS: To determine pulmonary capillary wedge pressure (PCWP) at rest and during exercise, 81 patients after orthotopic heart transplantation with normal left ventricular ejection fraction (LVEF) underwent exercise right heart catheterization with simultaneous exercise echocardiography. Based on PCWP values, the patients were divided into three groups. Twenty-one patients had no evidence of HFNEF (PCWP at rest < 15 mmHg, maximal PCWP during exercise < 25 mmHg, prevalence 26%). Forty-seven subjects were found to have only exercise-induced HFNEF (PCWP at rest < 15 mmHg, maximal PCWP during exercise ≥ 25 mmHg, prevalence 58%). Thirteen patients had HFNEF already at rest (PCWP ≥ 15 mmHg at rest, prevalence 16%). Of the noninvasive parameters obtained at rest, multivariate regression analysis identified LV mass index adjusted for allograft age to be an independent predictor of exercise-induced HFNEF. CONCLUSIONS: In heart transplant recipients with normal LVEF, there is a high prevalence of exercise-induced HFNEF. LV mass index adjusted for allograft age is predictive of exercise-induced HFNEF.

The variable clinical course of peripartum cardiomyopathy.

BACKGROUND: In Europe, peripartum cardiomyopathy (PPCM) is a rare disorder, often difficult to diagnose and it has a variable clinical course. The aim of this report was to describe and discuss the individual variability of this disorder and its management. PATIENTS AND METHODS: Three cases of PPCM manifesting as severe heart failure are compared. Common was the presence of myocardial inflammation detected by endomyocardial biopsy. Different were treatment methods and clinical course. Modern therapeutic concepts such as immunosuppressive therapy and bromocriptin administration are discussed, as well as non-pharmacological approaches. CONCLUSION: In the differential diagnostics of dyspnea associated with pregnancy and childbirth, PPCM should be considered. The potentially severe course of the disease requires hospitalization with the possibility of comprehensive heart failure treatment, including non-pharmacological approaches such as device therapy and heart transplantation.

Exercise training combined with electromyostimulation in the rehabilitation of patients with chronic heart failure: A randomized trial.

AIM: Both aerobic training (AT) and electromyostimulation (EMS) of leg muscles improve exercise tolerance in patients suffering from chronic heart failure (CHF). It was speculated that combination of both methods might have an additive effect. This study was performed to evaluate the effects of a combination of AT and EMS in rehabilitation (RHB) of CHF patients. PATIENTS AND METHODS: Patients (n=71; age 59 ± 10.2 yrs, NYHA II/III, EF 32 ± 7.1%) were randomized into 3 groups: a) group AT, b) group EMS, and c) group AT+EMS. AT protocol included standard activity on bicycle 3x a week at the level of individual anaerobic threshold. EMS (10 Hz, mode 20s "on"/20s "off") was applied to leg extensors for 2 h/day. Total time of given type of RHB was 12 weeks. RESULTS: Data analysis revealed statistically significant improvements of patients in all experimental groups (averaged difference after 12 weeks of exercise as related to initial value: ∆VO2peak: +12.9%, ∆VO2AT: +9.3%, ∆Wpeak: +22.7%). No statistically significant difference among experimental groups was found. Quality of life (Minnesota Living with Heart Failure - MLHF) global score was significantly improved in all 3 groups: AT (∆MLHF: -27.9%; P=0.001), AT+EMS (∆MLHF: -29.1%; P=0.002), and EMS (∆MLHF: -16.6%; P=0.008). MLHF score in EMS group showed the smallest time-related improvement compared to AT and AT+EMS groups, and this difference in improvement between the groups was statistically significant (P=0.021). CONCLUSION: No significant difference was found between the two types of exercise training.and nor did, their combination have any significant additional improvement.

Noninvasive prediction of the exercise-induced elevation in left ventricular filling pressure in post-heart transplant patients with normal left ventricular ejection fraction.

OBJECTIVES: At present, there are conflicting data on the ability of echocardiographic parameters to predict the exercise-induced elevation of left ventricular (LV) filling pressure. The purpose of the present study was to validate the ratio of early diastolic transmitral (E) to mitral annular velocity (e') obtained at peak exercise in its capacity to determine the exercise-induced elevation of pulmonary capillary wedge pressure (PCWP) and to reveal new noninvasive parameters with such capacity. METHODS: Sixty-one patients who had undergone heart transplantation with normal LV ejection fraction underwent simultaneous exercise echocardiography and right heart catheterization. RESULTS: In 50 patients with a normal PCWP at rest, exercise E/e' ≥8.5 predicted exercise PCWP ≥25 mmHg with a sensitivity of 64.3% and a specificity of 84.2% (area under the curve [AUC]=0.74). A comparable or slightly better prediction was achieved by exercise E/peak systolic mitral annular velocity (s') ≥11.0 (sensitivity 79.3%; specificity 57.9%; AUC=0.75) and exercise E/LV systolic longitudinal strain rate ≤-105 cm (sensitivity 78.9%; specificity 78.6%; AUC=0.87). Combined, exercise E/s' and exercise E/e' resulted in a trend toward a slightly more precise prediction (sensitivity 53.6%; specificity 89.5%; AUC=0.78) than did either variable alone. CONCLUSIONS: Exercise E/e', used as a sole parameter, is not sufficiently precise to predict the exercise-induced elevation of PCWP. Exercise E/s', E/LV systolic longitudinal strain rate or combinations of these parameters may represent further promising possibilities for predicting exercise PCWP elevation.

Impact of pulmonary hypertension on early hemodynamics, morbidity and mortality after orthotopic heart transplantation. A single center study.

AIMS: To determine the effect of pre-existing pulmonary hypertension (PHT) on early hemodynamics, morbidity and mortality after heart transplantation (HTx). METHODS: Data were prospectively collected from 149 patients, who underwent HTx between January 2000 and December 2007. The subjects were divided into 3 groups: Group A (n=84) without PTH, group B (n=50) with mild to moderate PTH and group C (n=15) with severe PTH. We studied hemodynamic profile, tricuspid valve regurgitation (TR), incidence of acute cellular rejections (AR), infections, duration of hospitalization, 30-day mortality and a long-term survival. RESULTS: Baseline characteristics were similar in all groups. Using vasodilator treatment PVR was successfully brought down to normal range 2.5 ± 0.6 Wood' units (WU) on the day 1 following the surgery in all groups. Over 80% of patients were treated in Group C, 32% in Group A and 46% in Group B. There was no significant difference in the severity of TR among the 3 groups early after HTx (severe TR was observed in 46%, 54%, 33%, respectively). There was no significant difference in incidence of AR (G ≥ 2 Banff classification) (23%, 23%, 33%, respectively), infections (28%, 32%, 33%, respectively) or duration of hospitalization (30, 30, 28 days, respectively). There was no correlation between pre-transplant PHT and 30-day mortality or a long-term survival. CONCLUSIONS: In our cohort, PHT dropped very quickly after HTx, and was not associated with acute right heart failure following the surgery. Reversible PTH does not have a negative impact on short- or long-term survival after HTx.

Effects of neuromuscular electrical stimulation and aerobic exercise training on arterial stiffness and autonomic functions in patients with chronic heart failure.

Neuromuscular electrical stimulation (NMES) of leg muscles has been introduced in clinical practice as a rehabilitation (RHB) method in patients with chronic heart failure (CHF); however, the role of NMES on the reduction of arterial stiffness and autonomic disbalance in these patients has not yet been studied. Sixty-one patients with stable CHF (mean age 58.9 [2.1] years; mean ejection fraction 31 [4.2]%, New York Heart Association II-III) were randomly assigned into two groups. Patients in (i) exercise training group (ET; n = 30) underwent 12 weeks of bicycle ET (3 × 40 min/week); (ii) group NMES (n = 31) performed 12 weeks of NMES of quadriceps and calf muscles (frequency 10 Hz, mode "20 s on-20 s off," intensity 60 mA), 2 × 60 min/day. Noninvasive assessment of arterial stiffness was done using the cardio-ankle vascular index (CAVI). CAVI and heart rate variability (HRV) and ·VO(2peak) were evaluated before and after RHB program. Both types of RHB reduced significantly CAVI (ET from 9.6 [0.2] to 8.9 [0.2], P < 0.012; NMES from 9.3 [0.2] to 8.7 [0.2], P < 0.013), increased high frequency (HF) component of HRV (+65.6%; P = 0.001) and decreased ratio of low frequency (LF) component with HF component (LF/HF ratio) in group ET (-39.8%; P < 0.001). Changes of HRV parameters in group NMES were not significant; however, a marked tendency to autonomic stabilization was present. Both types of RHB led also to significant increase of ·VO(2peak) (ET from 18.7 [0.7] to 20.8 [0.7] mL/kg/min, P < 0.004; NMES from 17.3 [0.7] to 19.0 [0.7] mL/kg/min, P < 0.001). ET or NMES has been shown to improve significantly arterial stiffness and to stabilize autonomic balance.

Estimation of left ventricular filling pressures by speckle tracking echocardiography in patients with idiopathic dilated cardiomyopathy.

AIMS: the ratio of early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (E(a)) is frequently used to predict an increase in left ventricular filling pressure (LVFP). However, this approach has several limitations. The aim of this study was to test whether additional information is gained by new echocardiographic indexes utilizing strain and strain rate (SR) derived from 2-dimensional speckle tracking echocardiography (2D-STE) for the estimation of LVFP. METHODS AND RESULTS: fifty-one patients with idiopathic dilated cardiomyopathy (IDC) underwent pulsed-wave tissue Doppler echocardiography and 2D-STE performed simultaneously with right heart catheterization. Receiver operating characteristic analysis showed that circumferential strain and the SR during late diastolic LV filling (0.956 and 0.951, both P = 0.001), E/circumferential SR at early diastolic LV filling (0.949, P = 0.001), and E/circumferential strain at the time of peak E-wave (0.948, P = 0.001) had greater area under the curve than the E/E(a) ratio (0.911, P = 0.001) for the prediction of pulmonary capillary wedge pressure > 12 mmHg. CONCLUSION: when compared with the E/E(a) ratio, several 2D-STE-derived parameters better estimated the increase in LVFP in patients with IDC.

Does the resynchronization therapy lead to reduction of symptoms and to improvement of left ventricular functions in patients with chronic heart failure?

AIM: To evaluate the therapeutic effect of resynchronization in patients with chronic heart failure who are symptomatic despite adequate pharmacological medication. SAMPLE AND METHODOLOGY: 118 patients with chronic heart failure, mostly dilated cardiomyopathy and ischaemic heart disease, with depressed systolic function, decreased left ventricular ejection fraction (LVEF) and left bundle branch block wide QRS complex, underwent implantation of the biventricular system between the years 2000-2006. We assessed changes in the NYHA functional class, hemodynamic parameters acquired during right heart catheterization, the maximum oxygen consumption during stress spiroergometric examination, as well as echocardiographic parameters. RESULTS: A statistically significant improvement was found in the NYHA functional class (from 2.8 +/- 0.4 to 2.3 +/- 0.5 after 3 m, p < 0,001 and to 2.5 +/- 0.6 after 12 m, p < 0,01 respectively), as well as an increase in the maximum oxygen consumption during spiroergometric examination (VO2 max from 14.1 +/- 3.1 ml/kg/min to 15.3 +/- 3.1 ml/kg/ min, p < 0,001 and to 15.3 +/- 2.5 ml/kg/min, p = NS respectively). In regard to hemodynamic parameters, there were increases in cardiac output and cardiac index after three months. After 12 months the change was not statistically significant (CO from 3.9 +/- 1 l/min to 4.2 +/- 0.9 l/min, p < 0,05, and to 4.1 +/- 0.9 l/min, p = NS, CI from 2 +/- 0.5 l/kg/min to 2.2 +/- 0.4 l/kg/min, p < 0,05, and to 2.1 +/- 0.4 l/kg/min, p = NS). Mean pulmonary artery pressure, as well as pulmonary capillary wedge pressure was reduced after 3, as well as after 12 months to a statistically significant degree (MPA from 29.1 +/- 11.5 mm Hg to 23.9 +/- 10.3 mm Hg, p< 0,001, and to 24.9 +/- 11.8 mm Hg, p < 0,01 respectively, and PCWP from 19.9 +/- 9.5 mm Hg to 15.2 +/- 9.2 mm Hg, p < 0,01, and to 15.6 +/- 9 mm Hg, p < 0,01 respectively). In regard to echocardiographic parameters, there was an increase in LVEF, a reduction in the end-diastolic diameter of the left ventricle, as well as a statistically significant reduction in severity of mitral regurgitation after 3, as well as 12 months (LVEF from 20.5 +/- 5.3%, to 23 +/- 6.5%, p < 0,001, and to 24.5 +/- 8%, p < 0,001, LVEDD from 69 +/- 9 mm to 68 +/- 9 mm, p < 0.01 and to 65 +/- 12 mm, p< 0.01 respectively, mitral regurgitation from 2.2 +/- 0.8 to 1.9 +/- 0.8, p< 0.001, and to 2 +/- 0.8, p < 0.001. CONCLUSIONS: In patients with chronic heart failure, resynchronization therapy leads to reduced symptoms, reduction in dyspnea and to improvements in cardiac performance due to increase in the systolic function of the left ventricle and hemodynamic changes.

Left ventricular mechanics in idiopathic dilated cardiomyopathy: systolic-diastolic coupling and torsion.

BACKGROUND: In idiopathic dilated cardiomyopathy (IDC), myocardial deformational parameters and their mutual relationships remain incompletely characterized. METHODS: Thirty-seven patients with IDC underwent two-dimensional speckle-tracking echocardiography (2D-STE) to assess left ventricular rotation, torsion, and longitudinal, circumferential, and radial systolic and diastolic strains and strain rates. Additionally, 2D-STE was performed in 14 controls. RESULTS: All deformational parameters on 2D-STE were significantly lower in patients with IDC compared with controls. Seven patients exhibited opposite basal (positive, counterclockwise) and 11 patients exhibited opposite apical (negative, clockwise) rotation at end-systole. Circumferential, radial, and longitudinal early diastolic strain rates were correlated most strongly with the corresponding spatial components of systolic deformation. CONCLUSION: In patients IDC, all torsional, systolic, and diastolic deformational parameters were decreased. Corresponding three-dimensional components of systolic and diastolic deformations were closely coupled. Considerable variation in the direction of basal and apical rotation exists in a subset of patients with IDC.

Impact of diabetes mellitus on survival rates after heart transplantation.

AIMS: Heart transplantation (HTx) is the most effective therapy in patients with end-stage heart failure. Diabetes-related complications are relative contraindications for heart transplantation. The aim of our study was to analyse the impact of DM (diabetes mellitus) at the time of heart transplantation and new-onset post-transplantation DM on long-term survival. METHODS: A retrospective database analysis was performed on all patients who had undergone HTx at our institution between 4/1997 and 9/2007. Patients were divided into three groups: Group A--patients without DM; Group B--patients with new onset of DM after HTx; Group C--patients with DM prior to HTx. RESULTS: Patients with DM before the surgery were more obese, their BMI was 27.7 +/- 2.90, compared to groups A and B with BMI of 24.7 +/- 3.37 and 25.3 +/- 3.64 respectively (p = 0.0003). Patients in group B had statistically significantly higher risk of developing acute rejection (G 1B and more according to International Society of Heart and Lung Transplantation--ISHLT--classification) (p = 0.0350). The incidence of infections between individual groups showed no statistically significant differences (p = 0.5839). Five-year survival in group A was 82%, 10-year survival was 73%. Corresponding numbers for group B were 86% and 78%, for group C 86% and 83%. Differences between groups were not statistically significant (p = 0.2560). CONCLUSIONS: DM in patients after heart transplantation in our study had no effect on long-term survival of patients. Post-transplantation DM increases risk of acute rejections. Pre-transplantation DM was associated with excessive bodyweight or obesity.

Combined right ventricular systolic and diastolic dysfunction represents a strong determinant of poor prognosis in patients with symptomatic heart failure.

BACKGROUND: The presence of right ventricular systolic dysfunction is known to significantly worsen prognosis of patients with heart failure. However, the prognostic impact of right ventricular diastolic dysfunction and of its combination with right ventricular systolic dysfunction and with other prognostic markers has not yet been systematically studied. The aim of this study was to assess the prognostic impact of combined right ventricular systolic and diastolic dysfunction in patients with symptomatic heart failure due to ischemic or idiopathic dilated cardiomyopathy. METHODS: The study included 177 consecutive patients with symptomatic heart failure (mean left ventricular ejection fraction of 23%). All patients underwent clinical and laboratory examination, standard echocardiography completed by Doppler tissue imaging of the tricuspid annular motion, and right-sided heart catheterization. They were followed up for a mean period of 16 months (range, 1-48 months). RESULTS: During the follow-up, there were 28 cardiac-related deaths and 35 non-fatal cardiac events (31 hospitalizations for heart failure decompensation and 4 hospitalizations for malignant arrhythmias requiring the implantation of a cardioverter-defibrillator). The multivariate stepwise Cox regression modeling revealed the right ventricular systolic (represented by the peak systolic tricuspid annular velocity-Sa) and diastolic (represented by the peak early diastolic tricuspid annular velocity-Ea) function to be the independent predictors of event-free survival or survival (p<0.01). The Sa separated better between patients with and without the risk of cardiac events (p<0.05), while the Ea appeared to further distinguish patients with increased risk (those at risk of late event from those at risk of early non-fatal event and early death). The strongest predictive information was obtained by the combination of Sa and Ea creating the Sa/Ea categories. The Sa/Ea I category of patients (Sa>or=10.8 cm s(-1) and Ea>or=8.9 cm s(-1)) had excellent prognosis. On the other hand, the Sa/Ea IV category (Sa<10.8 cm s(-1) and Ea<8.9 cm s(-1)) was found to be at a very high risk of cardiac events (p<0.001 vs. Sa/Ea I). Imbalanced categories of patients (Sa/Ea II and III) with only one component (Sa or Ea) pathologically decreased were at medium risk when assessing event-free survival. However, a significantly better survival (p<0.05) was found in patients with Ea>or=8.9 cm s(-1) (Sa/Ea I and III categories) as compared with those having Ea<8.9 cm s(-1) (Sa/Ea II and IV categories). Thus, in contrast to event-free survival, the survival pattern was determined mainly by the Ea value with only little additional contribution of Sa. CONCLUSIONS: The assessment of right ventricular systolic and diastolic function provides complementary information with a very high power to stratify prognosis of patients with heart failure. The combination of right ventricular systolic and diastolic dysfunction identifies those with a very poor prognosis.

Right ventricular dysfunction in chronic heart failure patients.

AIM: To evaluate any differences in haemodynamic and echocardiographic parameters in patients with both left (LV) and right ventricular (RV) systolic dysfunction and in patients with isolated LV systolic dysfunction. STUDY GROUP: One hundred patients with RV systolic dysfunction defined as peak velocity of tricuspid annular motion in systole (Sa)<11.5 cm/s, and 55 patients without RV systolic dysfunction Sa>11.5 cm/s. All patients had LV systolic dysfunction, LV ejection fraction (EF) below 40%, NYHA II-IV. METHODS: LV diameters, volumes and EF were measured by echocardiography. Patients underwent tissue Doppler imaging (TDI) of tricuspid annular motion with measurement of peak systolic velocity (Sa), peak early (Ea) and peak late (Aa) diastolic velocities. Right heart catheterization was also performed. RESULTS: Patients with RV systolic dysfunction did not differ from those without RV systolic dysfunction in terms of LV function. Patients with RV systolic dysfunction had larger RV dimension 30.6+/-5.8 vs. 33.9+/-6.7 mm, p<0.002. The patients with RV systolic dysfunction had higher values on right heart catheterization: MPAP 29.6+/-12.1 vs. 24.9+/-11.4 mm Hg, p<0.02, PCWP 20.8+/-10.0 vs. 17.3+/-9.3 mm Hg, p<0.03, PVR 189.9+/-123.3 vs. 137.7+/-94.9 dyn s cm(-5), p<0.008, CVP 7.7+/-5.6 vs. 5.1+/-3.9 mm Hg, p<0.002. The patients with RV systolic dysfunction had more pronounced diastolic dysfunction measured by TDI: Ea 9.9+/-2.3 vs. 11.4+/-2.5 cm/s, p<0.0001 and Aa 13.1+/-4.0 vs. 16.5+/-4.7 cm/s, p<0.000007. CONCLUSION: Patients with heart failure and both left and right ventricular systolic dysfunction showed more serious findings on central haemodynamics as well as more pronounced right ventricular diastolic dysfunction than those with isolated left ventricular systolic dysfunction.

Prognostic importance of various echocardiographic right ventricular functional parameters in patients with symptomatic heart failure.

Little is known about the prognostic importance of right ventricular (RV) systolic and diastolic function. The purpose of this study was to determine the prognostic power of systolic and diastolic RV functional parameters derived from Doppler tissue imaging of tricuspid annular motion and to assess whether their combination might improve the risk stratification of patients with heart failure. In all, 140 patients with symptomatic heart failure and left ventricular ejection fraction of 40% or less underwent standard echocardiography, Doppler tissue imaging of tricuspid annular motion, and right heart catheterization. They were followed up for a mean period of 17 months for cardiac-related death and nonfatal cardiac events including the implantation of cardioverter-defibrillator and hospitalization for heart failure decompensation. A total of 48 cardiac events occurred; 19 patients died, 26 were hospitalized for heart failure decompensation, and 3 because of the need for implantation of a cardioverter-defibrillator. The peak tricuspid annular velocity during systolic ejection of 10.8 cm/s or less, peak early diastolic tricuspid annular velocity of 8.9 cm/s or less, tricuspid annular acceleration during isovolumic contraction of 2.52 m/s 2 or less, and Doppler RV index (Tei index) of 1.20 or more were found to significantly worsen survival or event-free survival. However, their combination significantly exceeded the predictive potential of individual parameters. The worst survival was predicted by the combination of peak tricuspid annular velocity during systolic ejection of 10.8 cm/s or less plus peak early diastolic tricuspid annular velocity of 8.9 cm/s or less plus tricuspid annular acceleration during isovolumic contraction of 2.52 m/s 2 or less (relative risk 6.17, P < .001), whereas the worst event-free survival was identified by the combination of peak tricuspid annular velocity during systolic ejection of 10.8 cm/s or less plus peak early diastolic tricuspid annular velocity of 8.9 cm/s or less plus Doppler RV index (Tei index) of 1.20 or more (relative risk 3.62, P < .001). In conclusion, the combination of RV systolic and diastolic functional parameters represents a very powerful tool for risk stratification of patients with symptomatic heart failure.