Detection of myocardial ischemia due to clinically asymptomatic coronary artery stenosis at rest using supervised artificial intelligence-enabled vectorcardiography - A five-fold cross validation of accuracy.

BACKGROUND: Coronary artery disease (CAD) is a leading cause of death and disability. Conventional non-invasive diagnostic modalities for the detection of stable CAD at rest are subject to significant limitations: low sensitivity, and personal expertise. We aimed to develop a reliable and time-cost efficient screening tool for the detection of coronary ischemia using machine learning. METHODS: We developed a supervised artificial intelligence algorithm combined with a five lead vectorcardiography (VCG) approach (i.e. Cardisiography, CSG) for the diagnosis of CAD. Using vectorcardiography, the excitation process of the heart can be described as a three-dimensional signal. A diagnosis can be received, by first, calculating specific physical parameters from the signal, and subsequently, analyzing them with a machine learning algorithm containing neuronal networks. In this multi-center analysis, the primary evaluated outcome was the accuracy of the CSG Diagnosis System, validated by a five-fold nested cross-validation in comparison to angiographic findings as the gold standard. Individuals with 1, 2, or 3- vessel disease were defined as being affected. RESULTS: Of the 595 patients, 62·0% (n = 369) had 1, 2 or 3- vessel disease identified by coronary angiography. CSG identified a CAD at rest with a sensitivity of 90·2 ± 4·2% for female patients (male: 97·2 ± 3·1%), specificity of 74·4 ± 9·8% (male: 76·1 ± 8·5%), and overall accuracy of 82·5 ± 6·4% (male: 90·7 ± 3·3%). CONCLUSION: These findings demonstrate that supervised artificial intelligence-enabled vectorcardiography can overcome limitations of conventional non-invasive diagnostic modalities for the detection of coronary ischemia at rest and is capable as a highly valid screening tool.

The Effect of LVAD Pressure Sensitivity on the Assisted Circulation Under Consideration of a Mitral Insufficiency: An In Vitro Study.

Current left ventricular assist devices (LVADs) differ with respect to their pump characteristics as described by the pump characteristic curve (also called HQ-curve). Pressure sensitive LVADs depict a flat characteristic curve while most available LVADs have a steep, less pressure sensitive characteristic curve. This in vitro study investigated the effect of LVAD pressure sensitivity with a focus on the afterload of the right ventricle (RV) which is one out of many factors influencing right heart failure (RHF). To this end, two laboratory pumps differing in pressure sensitivity were tested as LVAD in an established, active mock circulation loop (MCL). The MCL represented patients with left heart failure and mitral insufficiency as another contributing factor to RV afterload. The results show that the pressure-volume loop (PV-loop) of the left ventricle (LV) undergoes a leftward and thus somewhat of a downward-shift for highly pressure sensitive support. Consequently, the LV is unloaded to a higher degree at comparable arterial blood pressure and identical cardiac output, pulmonary and systemic vascular resistance and ventricular contractility. This causes a concomitant decrease of RV afterload. This effect seems to be due to increased unloading during systole. In case of a severe concomitant mitral insufficiency and looking at left atrial pressure, the difference is 18.5%. Without mitral insufficiency, the difference is reduced to 10.2%.

Diagnosis of obstructive coronary artery disease by cardiogoniometry: a field test in a real-life setting.

Cardiogoniometry is an electrocardiographic and vectorcardiographic method utilizing computer-assisted analysis of cardiac potentials focusing on T-wave abnormalities resulting from myocardial malperfusion. We describe a case of diagnosis of obstructive coronary artery disease with this method and discuss the possible implications for the clinical setting.

Nocardiosis in Heart Transplant Recipients.

Nocardia has emerged as an important opportunistic pathogen, especially in organ transplant recipients. Heart transplant (HT) recipients initially had an especially high rate of Nocardia infection, but this could be reduced by the routine use of cyclosporine. Our objective was to clarify the prevalence and presentation of Nocardiosis in HT recipients in a retrospective cross-sectional analysis.

Normothermic ex vivo allograft blood perfusion in clinical heart transplantation.

BACKGROUND: Cold ischemia associated with cold static storage is an independent risk factor for primary allograft failure and survival of patients after orthotopic heart transplantation. The effects of normothermic ex vivo allograft blood perfusion on outcomes after orthotopic heart transplantation compared to cold static storage have been studied. METHODS: In this prospective, nonrandomized, single-institutional clinical study, normothermic ex vivo allograft blood perfusion has been performed using an organ care system (OCS) (TransMedics, Andover, MA, USA). Included were consecutive adult transplantation patients who received an orthotopic heart transplantation (oHTx) without a history of any organ transplantation, in the absence of a congenital heart disorder as an underlying disease and not being in need of a combined heart-lung transplantation. Furthermore, patients with fixed pulmonary hypertension, ventilator dependency, chronic renal failure, or panel reactive antibodies >20% and positive T-cell cross-matching were excluded. Inclusion criteria for donor hearts was age of <55 years, systolic blood pressure >85 mmHg at the time of final heart assessment under moderate inotropic support, heart rate of <120 bpm at the time of explantation, and left ventricular ejection fraction >40% assessed by an transcutaneous echo/Doppler study with the absence of gross wall motion abnormalities, absence of left ventricular hypertrophy, and absence of valve abnormalities. Donor hearts which were conventionally cold stored with histidine-tryptophan-ketoglutarate solution (Custodiol; Koehler Chemie, Ansbach, Germany) constituted the control group. The primary end point was the recipients' survival at 30 days and 1 and 2 years after their heart transplantation. Secondary end points were primary and chronic allograft failure, noncardiac complications, and length of hospital stay. RESULTS: Over a 2-year period (January 2006 to July 2008), 159 adult cardiac allografts were transplanted. Twenty-nine were assigned for normothermic ex vivo allograft blood perfusion and 130 for cold static storage with HTK solution. Cumulative survival rates at 30 days and 1 and 2 years were 96%, 89%, and 89%, respectively, whereas in the cold static storage group survival after oHTx was 95%, 81%, and 79%. Primary graft failure was less frequent in the recipients of an oHTx who received a donor heart which had been preserved with normothermic ex vivo allograft blood perfusion using an OCS (6.89% versus 15.3%; P = .20). Episodes of severe acute rejection (23% versus 17.2%; P = .73), as well as, cases of acute renal failure requiring haemodialysis (25.3% versus 10%; P = .05) were more frequent diagnosed among recipients of a donor heart which had been preserved using the cold static storage. The length of hospital stay did not differ (26 days versus 28 days; P = .80) in both groups. CONCLUSIONS: Normothermic ex vivo allograft blood perfusion in adult clinical orthotopic heart transplantation contributes to better outcomes after transplantation in regard to recipient survival, incidence of primary graft dysfunction, and incidence of acute rejection.

Image based evaluation of mediastinal constraints for the development of a pulsatile total artificial heart.

BACKGROUND: Good anatomical compatibility is an important aspect in the development of cardiovascular implants. This work analyzes the interaction of the pump unit of an electrically driven pulsatile Total Artificial Heart (TAH) and the mediastinum. For an adequate compliance, both overall dimensions and alignment of inlets and outlets must be matched. METHODS: Cross-sectional medical image data of 27 individuals, including male and female patients suffering from end stage heart failure, was segmented and reconstructed to three dimensional (3D) surface models. Dimensions and orientations of relevant structures were identified and analyzed. The TAH surface model was virtually placed in orthotopic position and aligned with atrioventricular valves and big vessels. Additionally seven conventional cadaver studies were performed to validate different pump chamber designs based on virtual findings. Thereby 3D-coordinates were captured and introduced to the virtual environment to allow quantitative comparison between different individuals. RESULTS: Spatial parameters varied more in male patients with higher values if heart failure persists. Good correlation of the virtual analysis both to literature data and conventional cadaver studies could be shown. The full data of the 27 individuals as well as the summarized values found in literature are enclosed in the appendix. By superimposing the TAH-volume model to the anatomy, various misalignments were found and the TAH-design was adjusted. CONCLUSIONS: Virtual fitting allows implant design adjustments in realistic anatomy which has not been influenced by thoracotomy. Higher numbers of relevant individuals can be reasonably investigated in the virtual environment and quantitatively correlated. Using this approach, conventional cadaver studies can be significantly reduced but not obviated, due to the unavailable haptic feedback and immobility of potentially compressed structures.

K201 improves aspects of the contractile performance of human failing myocardium via reduction in Ca2+ leak from the sarcoplasmic reticulum.

In heart failure, intracellular Ca2+ leak from cardiac ryanodine receptors (RyR2s) leads to a loss of Ca2+ from the sarcoplasmic reticulum (SR) potentially contributing to decreased function. Experimental data suggest that the 1,4-benzothiazepine K201 (JTV-519) may stabilise RyR2s and thereby reduce detrimental intracellular Ca2+ leak. Whether K201 exerts beneficial effects in human failing myocardium is unknown. Therefore, we have studied the effects of K201 on muscle preparations from failing human hearts. K201 (0.3 microM; extracellular [Ca2+]e 1.25 mM) showed no effects on contractile function and micromolar concentrations resulted in negative inotropic effects (K201 1 microM; developed tension -9.8 +/- 2.5% compared to control group; P < 0.05). Interestingly, K201 (0.3 microM) increased the post-rest potentiation (PRP) of failing myocardium after 120 s, indicating an increased SR Ca2+ load. At high [Ca2+]e concentrations (5 mmol/L), K201 increased PRP already at shorter rest intervals (30 s). Strikingly, treatment with K201 (0.3 microM) prevented diastolic dysfunction (diastolic tension at 5 mmol/L [Ca2+]e normalised to 1 mmol/L [Ca2+]e: control 1.26 +/- 0.06, K201 1.01 +/- 0.03, P < 0.01). In addition at high [Ca2+]e) K201 (0.3 microM) treatment significantly improved systolic function [developed tension +27 +/- 8% (K201 vs. control); P < 0.05]. The beneficial effects on diastolic and systolic functions occurred throughout the physiological frequency range of the human heart rate from 1 to 3 Hz. Upon elevated intracellular Ca2+ concentration, systolic and diastolic contractile functions of terminally failing human myocardium are improved by K201.

Circulating calcitriol concentrations and total mortality.

BACKGROUND: Evidence is accumulating that vitamin D supplementation of patients with low 25-hydroxyvitamin D concentrations is associated with lower cardiovascular morbidity and total mortality during long-term follow-up. Little is known, however, about the effect of low concentrations of the vitamin D hormone calcitriol on total mortality. We therefore evaluated the predictive value of circulating calcitriol for midterm mortality in patients of a specialized heart center. METHODS: This prospective cohort study included 510 patients, 67.7% with heart failure (two-thirds in end stage), 64.3% hypertension, 33.7% coronary heart disease, 20.2% diabetes, and 17.3% renal failure. We followed the patients for up to 1 year after blood collection. For data analysis, the study cohort was stratified into quintiles of circulating calcitriol concentrations. RESULTS: Patients in the lowest calcitriol quintile were more likely to have coronary heart disease, heart failure, hypertension, diabetes, and renal failure compared to other patients. They also had low 25-hydroxyvitamin D concentrations and high concentrations of creatinine, C-reactive protein, and tumor necrosis factor alpha. Eighty-two patients (16.0%) died during follow-up. Probability of 1-year survival was 66.7% in the lowest calcitriol quintile, 82.2% in the second quintile, 86.7% in the intermediate quintile, 88.8% in the fourth quintile, and 96.1% in the highest quintile (P < 0.001). Discrimination between survivors and nonsurvivors was best when a cutoff value of 25 ng/L was applied (area under the ROC curve 0.72; 95% CI 0.66-0.78). CONCLUSIONS: Decreased calcitriol levels are linked to excess midterm mortality in patients of a specialized heart center.

Up-regulation of nestin in the infarcted myocardium potentially indicates differentiation of resident cardiac stem cells into various lineages including cardiomyocytes.

To identify proteins involved in cardiac regeneration, a proteomics approach was applied. A total of 26 proteins, which displayed aberrant expression in mouse hearts infarcted through ligation of the left anterior descending coronary artery, were identified. These included the intermediate filament protein nestin, which was up-regulated in the infarct border zone. Corresponding changes were observed for its mRNA. Nestin mRNA was also up-regulated in hearts from 17 of 19 patients with end-stage heart failure, including 4 with acute myocardial infarction in comparison with 8 donor hearts. Immunofluorescence confocal laser scanning microscopy revealed that nestin is expressed, on the one hand, in small proportions of cardiomyocytes, endothelial cells, smooth muscle cells, neuronal cells, and fibroblasts. On the other hand, it was found to be coexpressed with the stem cell markers c-kit, Sca-1, Mdr-1, and Abcg2 in small interstitial cells. In infarcted hearts from chimeric mice transplanted with bone marrow from enhanced green fluorescent protein (EGFP) transgenic mice, less than 1% of nestin-positive cells coexpressed EGFP, although EGFP-positive cells were abundant in these. Consequently, enhanced expression of nestin in the injured myocardium might reflect spontaneous regenerative processes supposedly based on the differentiation of resident cardiac stem cells into diverse cardiac cell types.

Long-term results of heart transplantation for end-stage valvular heart disease.

BACKGROUND: In general, heart transplantation for patients with heart failure improves survival. However, the outcomes of heart transplantation for patients with end-stage valvular heart disease are less well reported. This is a substantial group of patients, many of whom have had previous cardiac surgery. They therefore may be considered a subgroup with a poor prognosis. This study reports on the outcomes of heart transplantation for patients with end-stage valvular heart disease. PATIENTS AND METHODS: From March 1989 to December 2004, 75 consecutive adult heart transplantations were performed for end-stage valvular heart disease. Clinical characteristics were retrieved from a computerized database. RESULTS: The early mortality risk in heart transplantation for end-stage valvular heart disease was 13%, compared to 8% for other indications (p = 0.12). The main causes of early death were rejection (20%) and right ventricular failure (20%). The total follow-up time was 415 patient-years. During the follow-up, another 23 patients died (55/1000 patient-years of late mortality rate), mostly due to infection (43%) and multiorgan failure (22%). Multivariable analysis demonstrated that increased waiting time to heart transplantation correlated with increased survival (HR = 0.998, p = 0.04). The survival at 1, 5, 10, and 15 years was 70%, 64%, 56%, and 46% compared to 78%, 68%, 53%, and 41% for other indications, respectively (p = 0.5). CONCLUSION: The outcomes of heart transplantation for patients with end-stage valvular heart disease are similar to those for other patients. Apparently, the longer the waiting time to heart transplantation the better the outcome becomes.

Ranolazine improves diastolic dysfunction in isolated myocardium from failing human hearts--role of late sodium current and intracellular ion accumulation.

The goal of this study was to test the hypothesis that the novel anti-ischemic drug ranolazine, which is known to inhibit late I(Na), could reduce intracellular [Na(+)](i) and diastolic [Ca(2+)](i) overload and improve diastolic function. Contractile dysfunction in human heart failure (HF) is associated with increased [Na(+)](i) and elevated diastolic [Ca(2+)](i). Increased Na(+) influx through voltage-gated Na(+) channels (late I(Na)) has been suggested to contribute to elevated [Na(+)](i) in HF. In isometrically contracting ventricular muscle strips from end-stage failing human hearts, ranolazine (10 micromol/L) did not exert negative inotropic effects on twitch force amplitude. However, ranolazine significantly reduced frequency-dependent increase in diastolic tension (i.e., diastolic dysfunction) by approximately 30% without significantly affecting sarcoplasmic reticulum (SR) Ca(2+) loading. To investigate the mechanism of action of this beneficial effect of ranolazine on diastolic tension, Anemonia sulcata toxin II (ATX-II, 40 nmol/L) was used to increase intracellular Na(+) loading in ventricular rabbit myocytes. ATX-II caused a significant rise in [Na(+)](i) typically seen in heart failure via increased late I(Na). In parallel, ATX-II significantly increased diastolic [Ca(2+)](i). In the presence of ranolazine the increases in late I(Na), as well as [Na(+)](i) and diastolic [Ca(2+)](i) were significantly blunted at all stimulation rates without significantly decreasing Ca(2+) transient amplitudes or SR Ca(2+) content. In summary, ranolazine reduced the frequency-dependent increase in diastolic tension without having negative inotropic effects on contractility of muscles from end-stage failing human hearts. Moreover, in rabbit myocytes the increases in late I(Na), [Na(+)](i) and [Ca(2+)](i) caused by ATX-II, were significantly blunted by ranolazine. These results suggest that ranolazine may be of therapeutic benefit in conditions of diastolic dysfunction due to elevated [Na(+)](i) and diastolic [Ca(2+)](i).

Negative inotropy of the gastric proton pump inhibitor pantoprazole in myocardium from humans and rabbits: evaluation of mechanisms.

BACKGROUND: Proton pump inhibitors are used extensively for acid-related gastrointestinal diseases. Their effect on cardiac contractility has not been assessed directly. METHODS AND RESULTS: Under physiological conditions (37 degrees C, pH 7.35, 1.25 mmol/L Ca2+), there was a dose-dependent decrease in contractile force in ventricular trabeculae isolated from end-stage failing human hearts superfused with pantoprazole. The concentration leading to 50% maximal response was 17.3+/-1.3 microg/mL. Similar observations were made in trabeculae from human atria, normal rabbit ventricles, and isolated rabbit ventricular myocytes. Real-time polymerase chain reaction demonstrated the expression of gastric H+/K+-adenosine triphosphatase in human and rabbit myocardium. However, measurements with BCECF-loaded rabbit trabeculae did not reveal any significant pantoprazole-dependent changes of pH(i). Ca2+ transients recorded from field-stimulated fluo 3-loaded myocytes (F/F0) were significantly depressed by 10.4+/-2.1% at 40 microg/mL. Intracellular Ca2+ fluxes were assessed in fura 2-loaded, voltage-clamped rabbit ventricular myocytes. Pantoprazole (40 microg/mL) caused an increase in diastolic [Ca2+]i by 33+/-12%, but peak systolic [Ca2+]i was unchanged, resulting in a decreased Ca2+ transient amplitude by 25+/-8%. The amplitude of the L-type Ca2+ current (I(Ca,L)) was reduced by 35+/-5%, and sarcoplasmic reticulum Ca2+ content was reduced by 18+/-6%. Measurements of oxalate-supported sarcoplasmic reticulum Ca2+ uptake in permeabilized cardiomyocytes indicated that pantoprazole decreased Ca2+ sensitivity (Kd) of sarcoplasmic reticulum Ca2+ adenosine triphosphatase: control, Kd=358+/-15 nmol/L; 40 microg/mL pantoprazole, Kd=395+/-12 nmol/L (P<0.05). Pantoprazole also acted on cardiac myofilaments to reduced Ca2+-activated force. CONCLUSIONS: Pantoprazole depresses cardiac contractility in vitro by depression of Ca2+ signaling and myofilament activity. In view of the extensive use of this agent, the effects should be evaluated in vivo.

Poor outcome in end-stage heart failure patients with low circulating calcitriol levels.

BACKGROUND: Vitamin D receptor knockout mice develop typical signs of congestive heart failure (CHF). In approximately 20% of stable CHF patients, frankly low concentrations of the vitamin D hormone calcitriol are found. AIMS: We investigated whether serum calcitriol concentrations predict clinical outcome in end-stage CHF. METHODS AND RESULTS: We collected blood samples in 383 end-stage CHF patients who were on a waiting list for cardiac transplantation. We assessed associations of calcitriol with disease severity and freedom from event (death or cardiac transplantation) during 1-year follow-up. In electively listed patients (n=325), 31% had deficient calcitriol levels (<43 pmol/l) compared to 47% in urgently/high urgently listed patients (n=58; P<0.001). As determined by multivariable logistic regression, calcitriol was an independent predictor of the listing status 'urgent/high urgent' (P<0.001). Calcitriol concentrations were also significantly lower in patients with an event (n=233) compared to those who survived on the waiting list (P<0.001). Cox regression analysis revealed that patients in the highest calcitriol tertile had a hazard ratio (95% CI) for an event of 0.506 (0.334-0.767) compared with patients in the lowest calcitriol tertile (P=0.005), after adjustment for potential confounders. CONCLUSION: Data indicate that low serum calcitriol concentrations are independently associated with poor clinical outcome in end-stage CHF.

Survival analysis in heart transplantation: results from an analysis of 1290 cases in a single center.

BACKGROUND: The clinical profiles of recipients and donors eligible for the procedure as well as the procedure itself have changed over time. We determined the impact of changes in baseline risk profiles at different transplant periods on outcome, and the time-specific distribution of causes of death. PATIENTS AND METHODS: Adult heart transplantations were performed consecutively on 1290 patients. Three transplant periods were defined: 1989-1993, 1994-1998, and 1999-2004. RESULTS: Recipient age and body mass index, previous cardiac surgery, high urgency status, need of ventricular assist device, waiting time (to transplantation and on ventricular assist device), donor age and body mass index, donor-recipient body mass index mismatch, and ischemic and cardiopulmonary bypass time were significantly different over the three transplant periods. There was, however, no significant difference in mortality risk. The major causes of deaths were: acute rejection, multiorgan failure, and right heart failure (1-5 years); cardiac allograft vasculopathy and malignancy (>5-10 years); and malignancy and infection (>10 years). The overall 1-, 5-, 10- and 15-year survival was respectively 77%, 67%, 53% and 42%. There was no difference in survival by different transplant periods (p=0.68). CONCLUSION: Despite clearly increased baseline risk profiles over time, the outcome of adult heart transplantation remains stable and encouraging. Cardiac allograft vasculopathy, malignancy, and infection threaten the long-term survival.

Long-term experiences on cardiac retransplantation in adults.

BACKGROUND: It remains disputed whether cardiac retransplantation should be performed. This study aimed to evaluate our long-term experiences on cardiac retransplantation in adults. PATIENTS AND METHODS: Between March 1989 and December 2004, 2% (28/1290) of cardiac retransplantations were performed. RESULTS: The reasons for cardiac retransplantation were cardiac allograft vasculopathy (n=13; 47%), primary graft failure (n=11; 39%), and refractory acute rejection (n=4; 14%). The 30-day mortality risk was 29% (acute rejection: 50%; primary graft failure: 36%; cardiac allograft vasculopathy: 15%, p=0.324), compared to 8.5% for primary cardiac transplantation (p<0.001). The causes of early death were acute rejection (n=3; 37%), multiorgan failure (n=3; 37%), primary graft failure (n=1; 13%), and right ventricular failure (n=1; 13%). The late mortality rate was 96/1000 patient-years. The causes of late death were acute rejection (n=4; 50%), cardiac allograft vasculopathy (n=2; 25%), multiorgan failure (n=1; 13%), and infection (n=1; 13%). The 1-, 5-, 10-, and 15-year survival was respectively 78, 68, 54, and 38% (primary cardiac transplantation), and 46, 41, 32, and 32% (cardiac retransplantation) (p=0.003). The short-term survival for cardiac retransplantation due to cardiac allograft vasculopathy was likely better than primary graft failure and refractory acute rejection (p=0.09). CONCLUSION: The overall outcomes of cardiac retransplantation are significantly inferior to primary cardiac transplantation. Cardiac retransplantation should be only performed for selected patients.

Patients with congestive heart failure and healthy controls differ in vitamin D-associated lifestyle factors.

We have recently hypothesized that low vitamin D status may contribute to the pathogenesis of congestive heart failure (CHF). This study was aimed at evaluating, in a pilot study, whether CHF patients have indications for a low vitamin D status during earlier periods of their lives. We performed a case-controlled study in 150 CHF patients and 150 controls. Study participants had to answer a questionnaire that included several items concerning vitamin D-associated lifestyle factors during childhood, adolescence, and adulthood. A vitamin D score was constructed. This score takes into consideration that ultraviolet-B (UVB) exposure is the major vitamin D source for humans and that those lifestyle factors, which are associated with regular UVB exposure, can guarantee an adequate vitamin D status at best. The vitamin D score was significantly higher in controls than in patients (p < 0.001). Compared with the controls, more patients lived in large cities (p < 0.001), fewer patients were members of a sport club (p < 0.001), and fewer patients had summer holidays every year (p < 0.01). Patients also reported significantly less alcohol consumption during adulthood than controls (p < 0.001). Our results demonstrate that CHF patients and controls differed in several vitamin D-associated lifestyle factors and in alcohol consumption during earlier periods of their lives.

Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Elevated circulating concentrations of proinflammatory cytokines may contribute to the pathogenesis of congestive heart failure (CHF). In vitro studies suggest that vitamin D suppresses proinflammatory cytokines and increases antiinflammatory cytokines. OBJECTIVE: We evaluated the effect of vitamin D supplementation on the survival rate and different biochemical variables in patients with CHF. DESIGN: One hundred twenty-three patients randomly received either 50 mug vitamin D(3)/d plus 500 mg Ca/d [D(+) group] or placebo plus 500 mg Ca/d [D(-) group] for 9 mo. Biochemical variables were assessed at baseline and after 9 mo. The survival rate was calculated for a follow-up period of 15 mo. RESULTS: Ninety-three patients completed the study. Significant treatment effects were observed on logarithmic-transformed serum concentrations of 25-hydroxyvitamin D (P = 0.001), parathyroid hormone (P = 0.007), tumor necrosis factor alpha (P = 0.006), and interleukin 10 (P = 0.042). 25-Hydroxyvitamin D increased by 26.8 ng/mL in the D(+) group but increased only by 3.6 ng/mL in the D(-) group. Compared with baseline, parathyroid hormone was significantly lower and the antiinflammatory cytokine interleukin 10 was significantly higher in the D(+) group after 9 mo. The proinflammatory cytokine tumor necrosis factor alpha increased in the D(-) group but remained constant in the D(+) group. The survival rate did not differ significantly between the study groups during the follow-up period. CONCLUSIONS: Vitamin D(3) reduces the inflammatory milieu in CHF patients and might serve as a new antiinflammatory agent for the future treatment of the disease. Our data provide evidence for the involvement of an impaired vitamin D-parathyroid hormone axis in the progression of CHF.

[Predictive value of ECG changes for acute cardiac rejections in heart transplant recipients]. / Diagnostische Wertigkeit von EKG-Veränderungen bei akuten kardialen Abstossungsreaktionen nach orthotoper Herztransplantation.

BACKGROUND AND PURPOSE: Currently, endomyocardial biopsy is the most reliable method to detect an acute rejection after heart transplantation. However, as an invasive procedure it is associated with a definite risk for complications. Therefore, it was examined whether changes in QT time and QT dispersion on the surface ECG are able to predict an acute cellular rejection. PATIENTS AND METHODS: During the first 3 months after heart transplantation, QT time, heart rate-corrected QT time (QTc time), QT dispersion, and heart rate-corrected QT dispersion (QTc dispersion) were analyzed in 100 patients with acute cellular rejection grade > or = II according to the International Society for Heart and Lung Transplantation (ZA group), and in 100 patients without or with only mild rejection episodes (< or = grade I; MA group). Results were obtained by determining the difference in the ZA group between the QT interval in the presence of a rejection and the QT interval at other time points, which were then compared with the results of the MA group at matched time points. RESULTS: At the time point of rejection, the ZA group showed a mean prolongation in both QTc time and QTc dispersion of > 40 ms compared with other time points. Such differences were not seen in the MA group (p < 0.001 for comparisons between study groups). If prolongations in QTc time and QTc dispersion of > 25 ms were used as predictors for an acute rejection, sensitivity was 77% and 70%, respectively, and specificity was 96% and 95%, respectively. CONCLUSION: Provided that ECGs are performed regularly, measurements of QTc time and QTc dispersion can reliably be used to detect an acute rejection in the early phase after heart transplantation.

Liver failure in total artificial heart therapy.

BACKGROUND: Congestive hepatopathy (CH) and acute liver failure (ALF) are common among biventricular heart failure patients. We sought to evaluate the impact of total artificial heart (TAH) therapy on hepatic function and associated clinical outcomes. METHODS: A total of 31 patients received a Syncardia Total Artificial Heart. Preoperatively 17 patients exhibited normal liver function or mild hepatic derangements that were clinically insignificant and did not qualify as acute or chronic liver failure, 5 patients exhibited ALF and 9 various hepatic derangements owing to CH. Liver associated mortality and postoperative course of liver values were prospectively documented and retrospectively analyzed. RESULTS: Liver associated mortality in normal liver function, ALF and CH cases was 0%, 20% (P=0.03) and 44.4% (P=0.0008) respectively. 1/17 (5.8%) patients with a normal liver function developed an ALF, 4/5 (80%) patients with an ALF experienced a markedly improvement of hepatic function and 6/9 (66.6%) patients with CH a significant deterioration. CONCLUSIONS: TAH therapy results in recovery of hepatic function in ALF cases. Patients with CH prior to surgery form a high risk group with increased liver associated mortality.

Applicability of cardiogoniometry as a non-invasive screening tool for the detection of graft vasculopathy in heart transplant recipients.

Currently available diagnostic modalities for the detection of graft vasculopathy following orthotopic heart transplantation are subject to various restrictions. We hypothesized that cardiogoniometry, a novel non-invasive diagnostic tool for the detection of atherosclerotic coronary vessel disease, is applicable in the graft vasculopathy setting. Cardiogoniometric results were obtained during routine follow-up in 49 consecutive, unselected heart transplant recipients and then retrospectively correlated blindly by an independent reader to recent angiographic findings. Sensitivity of cardiogoniometry was 100%, specificity 62.3%, positive predictive value 68.75%, negative predictive value 100%, negative likelihood ratio 0 and positive likelihood ratio 2.888. Cardiogoniometry is potentially applicable as an easy-to-perform, non-invasive screening tool predominantly for the exclusion but also for the detection of graft vasculopathy in heart transplant recipients.