Andrzej Jaroszyński

Bioengineered human acellular vessels for dialysis access in patients with end-stage renal disease: two phase 2 single-arm trials

BACKGROUND For patients with end-stage renal disease who are not candidates for fistula, dialysis access grafts are the best option for chronic haemodialysis. However, polytetrafluoroethylene arteriovenous grafts are prone to thrombosis, infection, and intimal hyperplasia at the venous anastomosis. We developed and tested a bioengineered human acellular vessel as a potential solution to these limitations in dialysis access. METHODS We did two single-arm phase 2 trials at six centres in the USA and Poland. We enrolled adults with end-stage renal disease. A novel bioengineered human acellular vessel was implanted into the arms of patients for haemodialysis access. Primary endpoints were safety (freedom from immune response or infection, aneurysm, or mechanical failure, and incidence of adverse events), and efficacy as assessed by primary, primary assisted, and secondary patencies at 6 months. All patients were followed up for at least 1 year, or had a censoring event. These trials are registered with ClinicalTrials.gov, NCT01744418 and NCT01840956. FINDINGS Human acellular vessels were implanted into 60 patients. Mean follow-up was 16 months (SD 7·6). One vessel became infected during 82 patient-years of follow-up. The vessels had no dilatation and rarely had post-cannulation bleeding. At 6 months, 63% (95% CI 47-72) of patients had primary patency, 73% (57-81) had primary assisted patency, and 97% (85-98) had secondary patency, with most loss of primary patency because of thrombosis. At 12 months, 28% (17-40) had primary patency, 38% (26-51) had primary assisted patency, and 89% (74-93) had secondary patency. INTERPRETATION Bioengineered human acellular vessels seem to provide safe and functional haemodialysis access, and warrant further study in randomised controlled trials. FUNDING Humacyte and US National Institutes of Health.

Effect of Haemodialysis on Regional and Transmural Inhomogeneities of the Ventricular Repolarisation Phase

Recent studies have indicated increased ventricular repolarisation dispersion in haemodialysis (HD) patients. The purpose of this study was to estimate the effect of the HD process on parameters of regional and transmyocardial repolarisation inhomogeneities. Thirty-two selected HD patients (without relevant diseases and medication known to affect the QT interval) were included. Dispersion of the QT corrected interval (QT-c-D) and the corrected interval between the peak and the end of the T wave (Tpe-c-D) were evaluated before and after HD, and in controls. Blood chemistry and extracellular body water (ECW) were evaluated before and after HD. Predialysis QT-c-D and Tpe-c-D were higher in patients (53.40 ± 17.39 and 47.50 ± 13.68 ms, respectively) than in controls (34.91 ± 17.70 ms, p < 0.001 and 31.9 ± 16.76 ms, p < 0.001, respectively). HD induced an increase in the QT-c-D (67.59 ± 19.40 ms; p < 0.001) and Tpe-c-D (62.89 ± 14.33 ms; p < 0.001). Stepwise multiple regression identified the independent risk factors of QT-c-D (the differences between pre- and postdialysis phosphorus, potassium and calcium levels and ECW values) and Tpe-c-D (the differences between pre- and postdialysis phosphorus levels, calcium levels and ECW values) increases, induced by the HD process. The HD process increases regional and transmyocardial repolarisation phase inhomogeneities in HD patients. Changes of phosphorus, calcium and potassium levels plus ECW values seem to be important predisposing factors as far as the increase in ventricular inhomogeneities in HD patients is concerned.

Takotsubo syndrome in a patient after renal transplantation

Summary Background Takotsubo syndrome (TTS) is a transient cardiomyopathy of unknown origin, clinically manifesting as acute coronary syndrome (ACS). This syndrome mainly occurs in postmenopausal women and has a temporary relationship with emotional or physical stress. Case Report TTS occurred in 46-year-old female patient on the first day after renal transplantation. The predominant symptoms were connected with ACS, performed with low grade troponin elevation and characteristic shape of left ventricle depicted in echocardiography. Taking into consideration the risk of the development of contrast-induced nephropathy, coronary angiography (CA) was delayed; myocardial perfusion scintigraphy and iodine-123 metaiodobenzylguanidine (123I-mIBG) myocardial uptake were performed to confirm the clinical suspicion. Myocardial perfusion scintigraphy (MPS) performed in rest condition showed normal perfusion but myocardial uptake of 123I-mIBG was impaired. Within 6 months after surgery, full recovery of all biochemical and functional parameters of the left ventricle were observed. At that time CA was done, depicting normal coronary arteries. Conclusions TTS could be diagnosed by the use of non-nephrotoxic tests – 123I-mIBG myocardial scintigraphy, MPS and echocardiography.

Aortic Stiffness, Left Ventricle Hypertrophy, and Homogeneity of Ventricle Repolarization in Adult Dialyzed Patients

Aim. Study was designed to assess relationship between aortic compliance and homogeneity of heart electrical activity in dialysis patients. Methods. Study group was consisted of 120 dialyzed patients; 57 (age 50,7 ± 7,1) were on continuous ambulatory peritoneal dialysis (CAPD) and 73 (age 51,6 ± 7,6) were hemodialyzed (HD). Three-dimensional vectorocardiographic (VCG) monitoring was done to assess: QRS-T angle, T el and T az. Echocardiography was performed to assess: Aomax, Aomin, ASI (aortic siffness index). Results. ASI in HD as well as in CAPD patients was significantly higher compared to controls [resp., 5,51 (±1,32), 5,83 (±1,41), 3,07 (±1,09)]. Cut-off value of ASI was 5,67. In HD patients strong correlations between ASI and QRS-T angle, T el and T az were determined (resp., r = 0,429, P < 0,001; r = 0,432, P ≤ 0,001 and r = 0,387, P = 0,001). In CAPD group were significant association between ASI and QRS-T angle, T el and T az (resp., r = 0,452, P < 0,001; r = 0,417, P < 0,001 and r = 0,390, P = 0,001). ASI was independently and markedly associated with: QRS-T angle, T elev, T az, ADMA, cTnT, CRP, Total-chol, LDL-chol in HD and CAPD patients. Conclusions. ASI and VCG indices are higher in HD and CAPD patients. Correlation between ASI and VCG parameters may reflect unfavourable influence of poor aortic compliance on the electrical activity of the heart in dialyzed patients. Hypertrophy aggravates repolarization disturbances in hemodialyzed patients.

The effect of a single dialysis session on spatial QRS-T angle in haemodialysis patients

BACKGROUND Abnormal values of the spatial angle between the directions of ventricular depolarization and repolarization (QRS-T) reflect the action potential inhomogeneities and predict cardiac events and mortality in various patient groups. The study was designed to (i) compare QRS-T in haemodialysis (HD) patients and healthy subjects, (ii) assess the influence of HD on QRS-T and (iii) evaluate the possible associations between QRS-T and echocardiography, haemodynamic as well as biochemical parameters. METHODS The angular differences between the maximum spatial QRS and T vectors were measured in 73 HD patients and in 57 controls. QRS-T in patients was estimated pre- and post-dialysis together with the evaluation of blood chemistry and haemodynamic parameters. RESULTS Pre-dialysis QRS-T was higher compared with controls (30.18 ± 9.84 and 13.65 ± 7.23, respectively; P < 0.001). HD induced an increase of QRS-T (41.09 ± 11.74; P < 0.001). Pre-dialysis QRS-T adjusted for left ventricular mass index correlated with troponin T (r = 0.398, P = 0.001) and HDL (r = -0.270, P = 0.043). The differences between pre- and post-dialysis (Δ) QRS-T correlated with Δ potassium (r = 0.453, P < 0.001), Δ calcium (r = -0.309, P = 0.011) and Δ stroke index (SI; r = 0.311, P = 0.017). On multivariate analysis, troponin T was found to be an independent predictor of pre-dialysis QRS-T, whereas independent predictors of the HD-induced increase in QRS-T were potassium and cardiac index changes. CONCLUSIONS QRS-T is high in HD patients. HD enhances the inhomogeneities of action potential. Pre-dialysis QRS-T is mainly associated with troponin T elevation. HD-induced increase in QRS-T is mainly associated with potassium and SI changes. The possible clinical importance of the higher QRS-T in HD patients remains to be confirmed in further studies.

Intra-Abdominal Pressure Correlates with Extracellular Water Content

Background Secondary increase in intra-abdominal pressure (IAP) may result from extra-abdominal pathology, such as massive fluid resuscitation, capillary leak or sepsis. All these conditions increase the extravascular water content. The aim of this study was to analyze the relationship between IAP and body water volume. Material and Methods Adult patients treated for sepsis or septic shock with acute kidney injury (AKI) and patients undergoing elective pharyngolaryngeal or orthopedic surgery were enrolled. IAP was measured in the urinary bladder. Total body water (TBW), extracellular water content (ECW) and volume excess (VE) were measured by whole body bioimpedance. Among critically ill patients, all parameters were analyzed over three consecutive days, and parameters were evaluated perioperatively in surgical patients. Results One hundred twenty patients were studied. Taken together, the correlations between IAP and VE, TBW, and ECW were measured at 408 time points. In all participants, IAP strongly correlated with ECW and VE. In critically ill patients, IAP correlated with ECW and VE. In surgical patients, IAP correlated with ECW and TBW. IAP strongly correlated with ECW and VE in the mixed population. IAP also correlated with VE in critically ill patients. ROC curve analysis showed that ECW and VE might be discriminative parameters of risk for increased IAP. Conclusion IAP strongly correlates with ECW.

Left atrial volume index as a predictor of ventricle repolarization abnormalities in adult dialyzed patients

This study was performed to investigate the relationship between left atrium (LA) volume index (LAVI) and left ventricle electrical activity presumably repolarization in end‐stage renal disease patients. Study group was consisted of 120 dialyzed patients divided into two subgroups: 57 (age 50.7 ± 7.1) were on continuous ambulatory peritoneal dialysis (CAPD) and 73 (age 51.6 ± 7.6) were hemodialyzed (HD). All patients were undergoing three‐dimensional vectorcardiographic (VCG) monitoring to assess parameters concerning T vector: QRS‐T angle, Tel, and Taz. Standard echocardiography was performed to assess: LAmax, LAshort, LAlong. LAVI was calculated due to formula: LAVI = (π/6X [LAmax × LAshort × LAlong])/m2. LAVI in HD as well as in CAPD patients was significantly higher compared with controls (respectively: 36.29 ± 10.92; 36.41 ± 11.06; 20.64 ± 6.77 mL/m2). The calculated cutoff value of LAVI was 36.32 mL/m2. In HD patients, the strong correlations between LAVI and QRS‐T angle and Tel were determined (respectively: r = 0.407, P < 0.001 and r = 0.359, P = 0.006). Similarly in CAPD group were significant associations between LAVI and QRS‐T angle and Tel (respectively: r = 0.423, P < 0.001 and r = 0.374, P = 0.004). The QRS‐T angle, Tel and Taz are independently and markedly associated with LAVI in both HD and CAPD patients. LAVI and VCG indices are higher in both HD and CAPD patients. Correlation between QRS‐T angle and LAVI may reflect unfavorable influence on the electrical activity of the heart in dialyzed patients with left ventricle diastolic dysfunction. LAVI cutoff value is useful biomarker for stratification of ventricle repolarization disturbances in those patients.

Iodine-123 metaiodobenzylguanidine myocardial imaging in haemodialysed patients asymptomatic for coronary artery disease: a preliminary report.

AimThe aim of this study was to evaluate the usefulness of iodine-123 metaiodobenzylguanidine (123I-mIBG) myocardial scintigraphy in the detection of cardiac sympathetic neuropathy in haemodialysed patients without relevant cardiovascular symptoms. Materials and methodsA group of 20 haemodialysed patients were examined. The stress/rest myocardial perfusion scintigraphy by gated single-photon emission computed tomography was performed. Cardiac sympathetic functions were evaluated by single-photon emission computed tomography and planar 123I-mIBG myocardial scintigraphy and also by 24-h Holter study, with heart rate variability (HRV) and signal-averaged electrocardiogram analysis of ventricular late potentials. Semiquantitative analysis of 123I-mIBG myocardial uptake was expressed as routine heart/mediastinum ratio (HMR) 15 [early (eHMR)] and 240 min [delayed (dHMR)] after administration and washout rate (WOR). ResultsMyocardial perfusion scintigraphy showed normal values of all parameters, but semiquantitative 123I-mIBG cardiac imaging assessment indicated low values of HMR (eHMR 1.87±0.27; dHMR 1.74±0.25) and high values of WOR (31.38±9.49) compared with normal values. In 10 patients (50%) ventricular late potential was determined, and in these patients mean values of dHMR came up to 1.59±0.20. The mean value of HRV came up to 88.40±16.05 and significant correlations were found between HRV and eHMR (P=0.01) and dHMR (P=0.007). Conclusion 123I-mIBG scintigraphy can detect very early stages of cardiac sympathetic dysfunction. Low values of HMR and high values of WOR suggest an impaired cardiac adrenergic system in patients without any relevant symptoms of heart failure. Low values of HRV may confirm cardiac autonomic neuropathy.

Left atrial volume index and aortic stiffness index in adult hemodialysed patients - link between compliance and pressure mediated by endothelium dysfunction; a cross-sectional study

BackgroundThis study was performed to investigate the relationship between elastic properties of aorta and left atrium volume index (LAVI) in hemodialyzed (HD) patients.MethodsStudy group was consisted of 73 patients (age 51,6 ± 7,6 years) treated by hemodialysis. In all patients standard echocardiography was performed. Aortic stiffness index (ASI) was calculated using formula: ASI = log (SBP/DBP)/[(Aomax-Aomin)/Aomin]. LAVI was calculated according to the formula: LAVI = [π/6 x (LAmax x LAshort x LAlong)]/m2. Additionally several indices were calculated: left ventricle mass (LVM), left ventricle mass index (LVMI), midwall fractional shortening (mFS), endsystolic stress (ESS), mFS/ESS. Additionally the laboratory parameters including lipidogram, troponin T (cTnT), NT-proBNP and asymmetric dimethylarginine (ADMA) were measured.ResultsThe ASI was strong and significantly correlated with left atrium volume (LAV) and LAVI (respectively: 0,601; p < 0,001 and 0,598; p < 0,001). The ASI was independently and markedly associated with ADMA, cTnT, CRP, T-chol, and LDL-chol. The LAVI was independently and significantly correlated with NT-proBNP and cTnT.ConclusionsThere is correlation between ASI and ADMA, marker of endothelium dysfunction. There is also association between LAVI and NT-proBNP, signs of elevated left atrium pressure. The strong correlation between ASI and LAVI, improved by associations of specific biochemical markers with these echocardiographic indices, suggests there is the link between elastic properties of aorta and left atrium pressure in hemodialysed patients mediated by endothelial dysfunction.

Intra-abdominal hypertension increases spatial QRS-T angle and elevates ST-segment J-point in healthy women undergoing laparoscopic surgery

BACKGROUND Intra-abdominal hypertension (IAH) impairs cardiovascular function, however an effect of IAH on cardiac electrophysiology has been poorly documented. The aim of this study was to evaluate the effect of IAH following pneumoperitoneum on vectorcardiographic variables reflecting cardiac repolarisation and depolarisation. METHODS Otherwise healthy women undergoing elective gynaecological laparoscopy were studied. Intra-abdominal pressure (IAP), spatial QRS-T angle and ST-segment J-point (STJ) were observed during surgery and the early postoperative period. RESULTS Forty women, ages 22 to 43 were examined. Induction of IAH to 15mmHg significantly widened the spatial QRS-T angle, whereas the Trendelenburg position subsequently reduced this widening. IAH also increased STJ voltage in leads III, aVF, V2 and V3 during surgery, with increased STJ voltage persisting in several leads through the morning of postoperative day 1. CONCLUSION Induction of IAH impacts the relationship between cardiac depolarisation and repolarisation and increases spatial QRS-T angle and STJ voltage.