Christian Vahlhaus

Magnetic resonance imaging in individuals with cardiovascular implantable electronic devices

Magnetic resonance (MR) imaging has unparalleled soft-tissue imaging capabilities. The presence of devices such as pacemakers and implantable cardioverter-defibrillators (ICDs), however, was historically considered a contraindication to MR imaging. We summarize the potential hazards of the device-MR environment interaction, and present updated information regarding in vitro and in vivo experiments suggesting that certain pacemaker and ICD systems may indeed be MR-safe. Recent reports on several hundred patients with implantable pacemakers and ICDs who underwent MR scan safely indicate that, under certain conditions, individuals with these implanted systems may benefit from MR imaging. We believe that, on a case-by-case basis, the diagnostic benefit from MR imaging outweighs the presumed risks for some pacemaker and ICD patients. Thus for some patients, the risks presented by MR imaging under specific, characterized scanning and monitoring conditions may be acceptable given the diagnostic benefit of this powerful imaging modality. This may have major clinical implications on current imaging practice. A strategy for the performance of MR imaging in these individuals is proposed.

Optimal Systolic and Diastolic Reconstruction Windows for Coronary CT Angiography Using Dual-Source CT

OBJECTIVE The purpose of this study was to determine the position of the optimal systolic and diastolic reconstruction intervals for coronary CT angiography using dual-source CT. SUBJECTS AND METHODS In 90 patients, coronary dual-source CT angiography was performed without beta-blocking agents. Data were reconstructed in 5% steps throughout the R-R interval. Two independent readers selected optimal systolic and diastolic reconstruction windows for each major coronary vessel--the right coronary artery (RCA), left anterior descending artery (LAD), and left circumflex artery (LCX)--using a 3D viewer and volume-rendering displays. The motion score for each vessel was graded from 1 (no motion artifacts) to 5 (severe motion artifacts over entire vessel). RESULTS The average heart rate of all patients was 68.7 beats per minute (bpm) (range, 43-119 bpm). The median optimal systolic reconstruction windows were at 35%, 30%, and 35% for the RCA, LAD, and LCX, respectively. The median optimal diastolic reconstruction window was at 75% for all vessels. The mean motion scores (+/- SD) in the systolic reconstructions were 1.9 +/- 0.8 (RCA), 1.7 +/- 0.5 (LAD), and 2.0 +/- 0.6 (LCX). The mean motion scores for the diastolic reconstructions were 1.7 +/- 0.9, 1.5 +/- 0.6, and 1.6 +/- 0.7, respectively. In patients with a heart rate of < 70 bpm, motion scores were significantly lower in diastole versus systole (1.3 +/- 0.4 and 1.9 +/- 0.5, respectively; p < 0.01). In most patients with a heart rate of > 80 bpm, motion scores were lower in systolic than in diastolic reconstructions (2.1 +/- 0.6 and 2.6 +/- 0.8, respectively; p < 0.05). CONCLUSION Using dual-source CT, the overall optimal reconstruction window is at 75% of the R-R interval in patients with low or intermediate heart rates. In patients with heart rates of > 80 bpm, systolic reconstructions often yield superior image quality compared with diastolic reconstructions.

Fetoscopic Direct Fetal Cardiac Access in Sheep An Important Experimental Milestone Along the Route to Human Fetal Cardiac Intervention

BackgroundFetal cardiac interventions by direct ultrasound-guided approaches or open fetal cardiac surgery have been fraught with technical difficulties, as well as with significant maternal and fetal morbidity in humans. Therefore, the purpose of our study in sheep was to assess the feasibility and potential of fetoscopic direct fetal cardiac access. Methods and ResultsIn 15 anesthetized pregnant ewes (88 to 109 days of gestation; term, 145 days), 3 to 4 trocars were percutaneously placed in the uterus. Using videofetoscopic equipment, we assessed the feasibility of achieving direct fetal cardiac access. Minimally invasive direct fetal cardiac access by operative fetoscopy was achieved in 10 of the 15 fetal sheep. In 7 fetuses, the approach was successfully tested for fetal cardiac pacing (n=5) or antegrade fetal cardiac catheterization (n=2). Access was not achieved in 5 fetuses because of bleeding complications (n=2) or because the fetoscopic setup could not be established (n=3). All but 2 fetal sheep were alive at the end of the procedure. Acute fetal demise resulted from maternal hypotension or kinking of the fetal inferior caval vein by sternal suspension. Six ewes continued gestation; 3 of these went to term, with a normal fetal outcome. Two ewes died from septicemia 3 and 7 days after the procedure, and 1 ewe aborted 1 month after the procedure. ConclusionsMinimally invasive direct fetal cardiac access by operative fetoscopy is feasible in fetal sheep. The fetoscopic approach carries important potential for fetal cardiac pacing, antegrade fetal valvuloplasties, and resection of fetal intrapericardial teratomas in human fetuses.

Pre-operative prediction of post–VAD implant mortality using easily accessible clinical parameters

BACKGROUND Mortality rates are high after implantation of a ventricular assist device (VAD), occurring mainly in the early phase post-implant during the time in the intensive care unit (ICU). Pre-operative selection criteria, which predict successful outcome, are difficult to evaluate. We implemented a pre-operative risk score to predict mortality in the ICU after VAD implantation by using easily obtained and quickly accessible clinical parameters. METHODS In 241 VAD patients, 100 pre-operative markers were related to mortality in the ICU using univariate analysis and ROC curves, followed by multinomial logistic regression analyses. RESULTS The mortality rate in the ICU was 32.0%. Univariate statistical analysis revealed 34 parameters that were significantly associated with mortality in the ICU. Of these, multinomial logistic regression identified 13 markers as significant risk factors. These included demographic data (age >50 years); clinically/procedurally relevant data (ischemic cardiomyopathy [ICM], re-do surgery, on extracorporeal membrane oxygenation [ECMO], on intra-aortic balloon pump [IABP], previous cardiac surgery, ventilation, emergency implant, inotropic support, renal replacement therapy, pre-operative resuscitation, transfusion) and laboratory values (blood urea nitrogen [BUN] >40 mg/dl, creatinine >1.5 mg/dl, lactate >3 mg/dl, platelets <100 x 10(3)/microl, white blood cell [WBC] count >13 x 10(3)/microl, C-reactive protein [CRP] >8 mg/dl, hemoglobin <12 g/dl, hematocrit <35%, lactate dehydrogenase [LDH] >500 U/liter, creatine kinase [CK] >200 U/liter, troponin >20 ng/ml). A weighted risk score was implemented with a maximum of 50 points. The risk for mortality in the ICU was as follows: low (15.8%), <15 points; medium (48.2%), 16 to 30 points; and high (65.2%), >30 points. CONCLUSIONS Easily obtained and quickly accessible clinical parameters can inform potential patients, relatives, and physicians pre-operatively about the risk of death in the ICU after VAD implantation.

Diastolic filling pattern and left ventricular diameter predict response and prognosis after cardiac resynchronisation therapy

Objective: To investigate predisposing factors for cardiac resynchronisation therapy (CRT) response. Design: Single-centre study. Setting: University hospital in Germany. Patients: 122 consecutive patients with heart failure (mean (SD) age 65 (11) years; ischaemic/non-ischaemic 41%/55%; New York Heart Association (NYHA) class 3.1 (0.3); left ventricular ejection fraction 24.4 (8.1)%; QRS width 170 (32) ms, quality of life (QoL) 43.5 (19.2)) with an indication for CRT and demonstrated left ventricular dyssynchrony by echocardiography including tissue Doppler imaging. Interventions: Besides laboratory testing of clinical variables, results of ECG, echocardiography including tissue Doppler imaging, invasive haemodynamics, measures of QoL and of exercise capacity were obtained before CRT implantation and during follow-up. Main outcome measure: Responders were predefined as patients with improvement by one or more NYHA functional class or reduction of left ventricular end-systolic volume by 10% or more during follow-up. Mean (SD) follow-up was 418 (350) days. Results: Overall, 70.5% of patients responded to CRT. Responders had a significantly improved survival compared with non-responders (96.2% vs 45.5%, log-rank p<0.001). On univariate analysis, left ventricular end-diastolic diameter, left ventricular end-systolic diameter (LVESD), E/A ratio, a restrictive filling pattern, mean pulmonary artery pressure, pulmonary capillary pressure, N-terminal pro-brain natriuretic peptide and Vo2max were significant predictors of outcome. On multivariate analyses, LVESD (p = 0.009; F = 7.83), pulmonary capillary pressure (p = 0.015, F = 6.61) and a restrictive filling pattern (p = 0.026, F = 5.707) remained significant predictors of response. Conclusions: Despite treatment according to present guidelines nearly 30% of patients had no benefit from CRT treatment in a clinical setting. On multivariate analyses, patients with an increased left ventricular end-systolic diameter and concomitant diastolic dysfunction had a significantly worse outcome.

Body surface potential mapping in patients with Brugada syndrome: right precordial ST segment variations and reverse changes in left precordial leads

OBJECTIVE The aim of this study was to perform quantitative signal analysis of high-resolution body surface potential mapping (BSPM) recordings to assess its usefulness for the electrocardiographic characterization of patients with Brugada syndrome. The diagnostic value of the QRS integral and of the gradient of the ST segment have not been elucidated in Brugada syndrome. METHODS In 27 subjects (16 with Brugada syndrome and 11 healthy subjects), 120-lead BSPMs were recorded at baseline and after pharmacological provocation with intravenous administration of ajmaline (1 mg/kg). The recordings were analyzed for two regions outside the positions of the standard ECG leads: the right precordial leads (RPL) on the second and third intercostal space (high RPL) and the left precordial leads (LPL) between the fifth and seventh intercostal space (low LPL). RESULTS At baseline, in high RPL regions, patients with Brugada syndrome showed more positive QRS integrals (-5+/-8 vs. -16+/-8 mV ms) and a steeper negative ST segment gradient (-0.62+/-0.41 vs. -0.29+/-0.40 mV/s) compared to healthy subjects, P<0.001. In contrast, in low LPL regions, reduced QRS integrals and positive ST segment gradients were observed. These ECG signs were even more pronounced after intravenous ajmaline and showed a better discrimination for patients with Brugada syndrome than differences in RPL or LPL during baseline, respectively. CONCLUSIONS In the left precordial leads, patients with Brugada syndrome showed ECG changes which were reversed in relation to the ECG changes observed in right precordial leads. BSPM measurement is a useful tool to improve the understanding of the electrocardiographic changes in the Brugada syndrome.

Safe Performance of Magnetic Resonance Imaging on a Patient with an ICD

This is a report on a patient with an implanted cardioverter defibrillator (ICD) who intentionally underwent magnetic resonance imaging (MRI) of a malignant brain tumor. To avoid inadequate detection of ventricular tachycardia (VT) or ventricular fibrillation (VF), the ICD was inactivated by programming the VT‐detection and VT/VF‐therapy status off. The patient came through the protocol safely and without any difficulty or discomfort. There was no arrhythmic event. MRI affected neither programmed data nor the function of the ICD system.

Reversible regulation of the retinoblastoma protein/E2F-1 pathway during “reverse cardiac remodelling” after ventricular unloading

BACKGROUND Cyclin D1, the retinoblastoma (Rb) protein, and the E2F transcription factors are involved in the pathogenesis of cardiac hypertrophy. Cyclin D1/cdk4 complexes, by phosphorylation, inactivate Rb, thereby abrogating its growth-inhibitory effect. Ventricular unloading is associated with reversible regulation of numerous cardiomyocyte molecular systems and decreased hypertrophy. Accordingly, the hypothesis whether the Rb/E2F-1 pathway is altered by ventricular unloading was tested, and correlations with the cyclin D1 protein expression and cardiomyocyte diameters were explored. METHODS In 21 paired myocardial samples (before and after unloading) from patients with congestive heart failure (CHF), cyclin D1, phosphorylated Rb (pRb), its homologues p107 and p130 (pocket proteins), and E2F-1 were immunohistochemically investigated and morphometrically quantified. Cardiomyocyte diameters were morphometrically determined. RESULTS Cyclin D1 and the proteins of the Rb/E2F-1 pathway were significantly increased during CHF compared with controls and were significantly decreased after unloading. Cyclin D1, pRb, and p130 protein expression correlated significantly with cardiomyocyte diameters. A significant positive correlation was noted between the pocket proteins, E2F-1, and cyclin D1. CONCLUSION Increased protein expression of phosphorylated (inactivated) Rb and the pocket proteins is associated with cardiomyocyte hypertrophy in CHF. Rb inactivation might be explained by phosphorylation by increased numbers of cyclin D1/cdk4 complexes associated with cardiomyocyte hypertrophy. However, ventricular unloading can reversibly regulate this process. These data underscore the importance of cell cycle regulatory proteins in the pathogenesis of CHF-associated (maladaptive) cardiomyocyte hypertrophy and might offer novel clues for pharmacologic approaches of congestive heart failure.

Ischemic preconditioning by unstable angina reduces the release of CK-MB following CABG and stimulates left ventricular HSP-72 protein expression.

Abstract  Background and Aim: Whether the CK‐MB reducing effect of ischemic preconditioning (IP) by unstable angina within 24 to 48 hours before CABG is achieved by early or by delayed preconditioning of left ventricular myocardium in humans is unknown. We investigated whether IP is associated with phosphorylation of p38 MAPK (characteristic for early preconditioning) or with increased protein expression of HSP‐72 (characteristic for delayed preconditioning) at the time of CABG in patients. Methods: Nineteen patients were grouped according to the occurrence of ischemic episodes within 48 hours before CABG. The patients without angina were assigned to the control group (CON, n = 10) whereas patients who had experienced angina within 48 hours before CABG were assigned to the preconditioned group (IP, n = 9). The effect of IP on the CABG induced maximal release of creatine kinase (CK) and CK‐MB was examined. Left ventricular biopsy specimens taken immediately before cross clamping from ischemic (ISCH) and from reference (REF) areas were processed to analyze p38 MAPK phosphorylation and HSP‐72‐protein expression. Results: While IP significantly reduced CK‐MB (18.7 ± 1.3 vs. 13.8 ± 1.5 U/L, mean ± SEM, p < 0.05), it only tended to reduce CK (292.7 ± 32.8 vs. 274.1±31.1 U/L, p = NS, mean ± SEM). CK‐MB release for any given cross‐clamp time was significantly reduced by IP (regression lines: CON, y= 0.4x+ 2, r= 0.8; IP, y= 0.1x+ 10, r= 0.2; p < 0.01, ANCOVA). There was no effect of IP on left ventricular p38 MAPK phosphorylation. IP increased left ventricular HSP‐72‐protein expression in ischemic areas when compared to reference areas (1.78 ± 0.35 vs. 2.58 ± 0.65, REF vs. ISCH, PhosphorImager units ×106, mean ± SEM, p < 0.05, ANCOVA). Conclusions: Thus, in the human left ventricular myocardium there is a second window of protection lasting for at least 48 hours, while at that time the early phase of preconditioning has already gone.

Aortic dissection associated with cogans's syndrome: deleterious loss of vascular structural integrity is associated with GM-CSF overstimulation in macrophages and smooth muscle cells

BackgroundCogans syndrome is a rare disorder of unknown origin characterized by inflammatory ocular disease and vestibuloauditory symptoms. Systemic vasculitis is found in about 10% of cases.Case presentationA 46-year-old female with Coganss syndrome and a history of arterial hypertension presented with severe chest pain caused by an aneurysm of the ascending aorta with a dissection membrane located a few centimeters distal from the aortic root. After surgery, histopathological analysis revealed that vascular matrix integrity and expression of the major matrix molecules was characterized by elastolysis and collagenolysis and thus a dramatic loss of structural integrity. Remarkably, exceeding matrix deterioration was associated with massively increased levels of granulocyte macrophage colony stimulating factor (GM-CSF).ConclusionOur data suggest that the persistently increased secretion of the inflammatory mediator GM-CSF by resident inflammatory cells but also by SMC may be the trigger of aortic wall structural deterioration.