PURPOSE To assess if real-time magnetic resonance (MR) imaging-guided radiofrequency (RF) ablation for atrial flutter is feasible in patients. MATERIALS AND METHODS The study complied with the Declaration of Helsinki and was approved by the local ethics committee. All patients were informed about the investigational nature of the procedures and provided written informed consent. Ten patients (six men; mean age ± standard deviation, 68 years ± 10) with symptomatic atrial flutter underwent isthmus ablation. In all patients, two MR imaging conditional steerable diagnostic and ablation catheters were inserted into the coronary sinus via femoral sheaths and into the right atrium with fluoroscopic guidance. The patients were then transferred to a 1.5-T whole-body MR imager for an ablation procedure, in which the catheters were manipulated by an electrophysiologist by using a commercially available interactive real-time steady-state free precession MR imaging sequence. RESULTS All catheters were placed in standard positions successfully. Furthermore, simple programmed stimulation maneuvers were performed. In one of 10 patients, a complete conduction block was performed with MR imaging guidance. In nine of 10 patients, creating only a small number of additional touch-up lesions was necessary to complete the isthmus block with conventional fluoroscopy (median, three lesions; interquartile range, two to four lesions). CONCLUSION Real-time MR imaging-guided placement of multiple catheters is feasible in patients, with subsequent performance of stimulation maneuvers and occasional complete isthmus ablation.

Comparing the diagnostic value of multi-sequential cardiac magnetic resonance imaging (CMR) with endomyocardial biopsy (EMB) for sub-clinical cardiac allograft rejection.

Purpose: Endomyocardial biopsy (EMB) is the considered gold standard to diagnose acute cellular rejection (ACR) but it is often limited by sampling error, interobserver vaiability or the wide variability of frequency and duration to use this invasive interventional tool. Thus, we assessed cardiac function and inflammation parameters cardiac magnetic resonance imaging (CMRI) in correlation with EMB results after heart transplantation (HTx) over 24 months. Methods: In total 14 HTx patients (11male; median age 49±10years) were diagnosed with 1.5Tesla-MRI using the following parameters: T2 weighted STIR-, T1-weighted spin echo sequences (SE) for “early enhancement” and PSIR-sequences for “delayed enhancement”. Specific “cut-off” values for relative water content (≥2) and the global relative enhancement (gRE; ≥4.5) were determined according to an established CMRI myocarditis protocol and the “delayed enhancement” was visualized. All MRI-results were correlated with results of EMB performed on the same day. EMB was classified according the guidelines of the International Society for Heart and Lung Transplantation (ISHLT) using the original classification as well as rejection scores were defined from 0 (no rejection) to 4 (severe rejection). Results: Volumetric analysis of 86 CMRIs showed between the 1 month and 24 months post-transplant showed a significantly change (p<0.05) of the following: end-diastolic volume (LV-EDV) from 108±18 ml to 156±63 ml, end-systolic volume (LV-ESV) from 42±11 ml to 76±56 ml, and left ventricular ejection fraction (LV-EF) from 59±10% to 55±14%. Inflammatory CMRI parameters like gRE increased from 3.6±1.2 to 5.8±3.6 ml. EMB rejection scores increased in the same time from 0.6±0.5 to 1.3±1.6. Conclusion: Our results showed that multi-sequentialCMRI is useful to detect functional and inflammatory changes in correlation with EMB over time after HTx. Of course, future studies in large cohorts are needed to proof that CMRI is a robust diagnostic tool to detect ACR.

Verlaufskontrolle kardialer Funktions- und Inflammationsparameter mittels der Magnetresonanztomografie (cMRT) über 24 Monaten nach Herztransplantation (HTx) zur Erfassung einer frühen Abstoßung, in Korrelation zu den Ergebnissen der Endomyokardbiopsie (EMB).

Die kardiale MRT stellt die primäre nichtinvasive bildgebende Modalität bei Verdacht auf Myokarditis dar, insbesondere auch nach Ausschluss eines akuten Koronarsyndroms (ACS) zur Differenzialdiagnose. Verschiedene MR-Parameter mit unterschiedlicher Wertigkeit stehen zur Verfügung. Die Beurteilung der Volumetrie und Ventrikelfunktion weisen ebenso wie der Nachweis eines Perikardergusses alleine nur eine geringe Sensitivität und Spezifität auf. Die spezifischeren MRT-Inflammationsparameter stellen die T2-Ratio (Ödemnachweis), die frühe Kontrastmittelanreicherung bzw. das globale relative Enhancement (gRE) und die späte Kontrastmittelanreicherung, das so genannte Late-Gadolinium-Enhancement (LGE) als Zeichen eines irreversiblen Myokardschadens dar. Alle MR-Parameter zeigen die beste diagnostische Genauigkeit bei einer „infarktähnlichen“ akuten Myokarditis und eine insgesamt schlechtere Sensitivität und Spezifität bei chronischer Myokarditis. Aus diesem Grunde sollte immer ein multisequentieller Ansatz (mindestens 2 von 3 MRT-Parametern positiv) gewählt werden. Die Beurteilung der Wertigkeit neuer quantitativer Sequenzen wie des T1- und T2-Mappings steht noch aus.

Cardiovascular magnetic resonance imaging (CMRI) has become the primary tool for the non-invasive assessment in patients with suspected myocarditis, especially after exclusion of acute coronary syndrome (ACS) for the differential diagnosis. Various MRI parameters are available which have different accuracies. Volumetric and functional ventricular assessment and the occurrence of pericardial effusion alone demonstrate only a poor sensitivity and specificity. The calculation of the T2-ratio (edema assessment), the early or global relative myocardial enhancement (gRE) and the late gadolinium enhancement (LGE), which represents irreversibly injured myocardium, are more specific parameters. All MRI parameters demonstrate the best accuracy in infarct-like acute myocarditis, whereas in chronic myocarditis sensitivity and specificity are less accurate. Therefore, a multisequential (at least two out of three parameters are positive) approach is recommended. The assessment of the value of newer, more quantitative MRI sequences, such as T1 and T2-mapping is still under investigation.

Ziele: Ziel dieser Studie war die Evaluation der diagnostischen Wertigkeit der MRT nach Herztransplantation mittels verschiedener Sequenzen zur Erfassung einer Transplantatabstoßung. Als Referenz dienten die EMB-Ergebnisse. Methode: Es wurden an insgesamt 54 Patienten (10f, 44m; mittleres Alter 52±12 Jahre) 104 MRT-Untersuchungen an einem 1.5T-MRT nach einem Standard-Myokarditis-Protokoll unter Verwendung einer T2-gewichteten STIR-, einer T1-gewichteten Spinechosequenz (SE) für das frühe „enhancement“ und einer PSIR-Sequenz für das „delayed enhancement“ durchgeführt. Unter Anwendung der in unserem Zentrum für die Myokarditisdiagnostik gültigen „cut–off“-Werte wurden der relative Wassergehalt (≥2) und das globale relative Kontrastmittelenhancement (≥4,5) bestimmt und das „delayed enhancement“ visualisiert. Alle MR-Ergebnisse wurden mit den Resultaten der Endomyokardbiopsien korreliert. Ergebnis: Bei 73 (70%) von 104 Biopsien zeigte sich eine milde Abstoßung. Eine höhergradige Abstoßungsreaktion trat bei keinem der untersuchten Patienten auf. Die Sensitivität und Spezifität für eine histologisch gesicherte milde Abstoßungsreaktion betrug für den relativen Wassergehalt 29%/69%, für das relative enhancement 32%/69%, für das „delayed enhancement“ 69%/55% (bei Einzelbetrachtung). Bei Kombination der Parameter ergaben sich Sensitivitäten und Spezifitäten für das Vorliegen von mindestens einem positiven Kriterium von 85%/31%, für mindestens zwei Kriterien von 40%/72% und für drei positive Kriterien von nur 7% bzw. 90%. Schlussfolgerung: Die für die Myokarditisdiagnostik gängigen MRT-Parameter sind nur mit deutlichen Einschränkungen zur Evaluation milder Abstoßungsreaktionen nach Herztransplantation geeignet; das „delayed enhancement“ zeigt hierbei die besten diagnostischen Einzelergebnisse. Es empfiehlt sich deshalb die Kombination der Parameter. Bei der Forderung des Vorliegens von mindestens 1 von 3 positiven MR-Parametern für die Diagnose Abstoßung wird die höchste Sensitivität erzielt.

Introduction: Sub-clinical acute cellular rejection (ACR) after heart transplantation (HTx) is a major cause of cardiac allograft vasculopathy. But with endomyocardial biopsy (EMB), the considered gold standard to diagnose ACR, the detection of sub-clinical ACR is often limited by sampling error, interobserver vaiability or the wide variability of frequency and duration to use this invasive interventional tool. Thus, we used cardiac magnetic resonance imaging (CMR) as non-invasive tool to identify sub-clincal ACR after HTx. Methods: In total 73 patients (58 male) with a mean age of 53±12 years were scanned 167 times with a 1.5T-MRI scanner using a standard myocarditis protocol to detect sub-clinical ACR. Myocardial edema and myocyte damage was determined by using specific “cut-off” values to determine inflammatory parameters of early- and delayed- enhancement as well as to determine water content. All MRI-results were correlated with results of EMB performed on the same day. EMB was classified according the guidelines of the International Society for Heart and Lung Transplantation (ISHLT) using the original classification, which is considered to be more accurate to determine sub-clinical ACR. Results: In 87 (52%) out of 167 biopsies a rejection grade of 1A was diagnosed, whereas 16 biopsies (10%) were graded 1B, 2 biopsies (1.1%) 2A and 1 biopsy (0.5%) 3A, respectively. No rejection was diagnosed in 61 biopsies (36%). Sensitivity, specificity and negative predictive value for rejection grade >1B were for (1) early-enhancement 64%, 70% and 93%; (2) delayed-enhancement 43%, 38% and 82%; (3) water content: 60%, 79% and 93%. In combination of all 3 parameters sensitivity, specificity and negative predictive value were: 71%, 66% and 94%. Conclusion: In this study we showed that CMR can be helpful to diagnose sub-clinical ACR after HTx using a myocarditis protocol. Especially, the combination of the parameters early- and delayed enhancement as well as water content imply a high negative predictive value of sub-clinical ACR. Future studies in large cohorts need further to evaluate CMR as an evolving tool in ACR.

Background No-reflow after primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) is associated with poor prognosis. Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor that might aggravate reperfusion injury. The aim of our study was to assess the relationship between systemic ET-1 levels and the occurrence of no-reflow as well as to evaluate the prognostic value of ET-1 in a high-risk STEMI population.Methods We examined 128 consecutive patients undergoing primary PCI in acute STEMI <12 hours after symptom onset. Endothelin-1 was assessed before and immediately after primary PCI. Patients were categorized into 2 groups defined by the median ET-1 level on admission. No-reflow was assessed by 3 different methods after PCI: angiographic Thrombolysis in Myocardial Infarction (TIMI) flow and myocardial blush grade, electrocardiographic ST-resolution, and microvascular obstruction (MO) measured by cardiac magnetic resonance imaging (MRI). The primary clinical end points were mortality and major adverse cardiovascular events. Clinical follow-up was conducted after a median of 19 months.Results Patients with angiographically (TIMI flow <= 2 or TIMI flow 3 with final myocardial bush grade <= 2 after PCI), electrocardiographically (ST-resolution <30%), and MRI- (presence of MO) detected no-reflow had significantly higher ET-1 levels on admission. At multivariable logistic regression analysis, ET-1 levels on admission were the only significant predictor of MRI- detected no-reflow (P = .03) together with left ventricular ejection fraction (P = .002). An elevated ET-1 level >= the median on admission was a significant predictor of long-term mortality.Conclusions Endothelin-1 on admission is associated with no-reflow and increased long-term mortality in a high-risk STEMI population reperfused by primary PCI. (Am Heart J 2010; 159: 882-90.)

ObjectivesThe aim of this randomized, single-blind, controlled trial was to assess N-acetylcysteine effects on contrast-induced nephropathy and reperfusion injury in ST-segment elevation myocardial infarction patients undergoing primary angioplasty with moderate contrast volumes.BackgroundHigh-dose N-acetylcysteine reduced the incidence of contrast-induced nephropathy in patients with high contrast volumes and reduced reperfusion injury in animal trials.MethodsPatients undergoing primary angioplasty were randomized to either high-dose N-acetylcysteine (2 x 1,200 mg/day for 48 h; n = 126) or placebo plus optimal hydration (n = 125). The 2 primary end points were: 1) the occurrence of >25% increase in serum creatinine level <72 h after randomization; and 2) a reduction in reperfusion injury measured as myocardial salvage index by magnetic resonance imaging.ResultsThe median volume of an iso-osmolar contrast agent during angiography was 180 ml (interquartile range [IQR] 140 to 230 ml) in the N-acetylcysteine and 160 ml (IQR 120 to 220 ml) in the placebo group (p = 0.20). The primary end point contrast-induced nephropathy occurred in 14% of the N-acetylcysteine group and in 20% of the placebo group (p = 0.28). The myocardial salvage index was also not different between both treatment groups (43.5; IQR 25.4 to 71.9 vs. 51.5; IQR 29.5 to 75.3; p = 0.36). Activated oxygen protein products and oxidized low-density lipoprotein as markers for oxidative stress were reduced by as much as 20% in the N-acetylcysteine group (p < 0.05), whereas no change was evident in the placebo group.ConclusionsHigh-dose intravenous N-acetylcysteine reduces oxidative stress. However, it does not provide an additional clinical benefit to placebo with respect to CIN and myocardial reperfusion injury in nonselected patients undergoing angioplasty with moderate doses of contrast medium and optimal hydration. (Myocardial Salvage and Contrast Dye Induced Nephropathy Reduction by N-Acetylcysteine [LIPSIA-N-ACC]; NCT00463749) (J Am Coll Cardiol 2010;55:2201-9) (C) 2010 by the American College of Cardiology Foundation

STEMI patients undergoing PCI are at high risk for contrast-induced nephropathy (CIN) because of hemodynamic instability and lack of effective prophylaxis. High-dose N-Acetylcystein (N-ACC) reduced the incidence of CIN in patients with high contrast volumes. In addition, previous animal trials showed that the antioxidant effects of N-ACC reduce reperfusion injury. Aim of this randomized, controlled, single-blinded trial was to assess the effects of N-ACC on CIN and reperfusion injury in patients undergoing primary PCI with moderate contrast volumes. Two hundred-fifty patients undergoing primary PCI were randomized to either high-dose N-ACC (2x1200 mg/d for 48 hours) or placebo plus optimal hydratation. The two primary endpoints were: 1) occurrence of CIN defined as an increase in the serum creatinine concentration of >25% from the baseline value within 72 h; 2) Myocardial salvage measured by T2-weighted STIR-images and delayed enhancement MRI at day 2– 4 after primary PCI. Secondary endpoints were infarct size and microvascular obstruction, ST-resolution at 90 minutes and occurrence of MACE at 30 day follow-up. The median volume of an isoosmolar contrast agent during PCI was 190 ml (IQR 130, 250 ml) in the N-ACC and 180 (IQR 143; 228 ml) in the placebo group (p=n.s.). Baseline creatinine and creatinine clearance were 88 vs 86 μmol/l and 90 vs 95 ml/min, respectively. The primary endpoint CIN occurred in 14% in the N-ACC group and in 18% in the placebo group (p=n.s.). The primary endpoint reperfusion injury measured by myocardial salvage was also not different between both treatment groups (25.4%; IQR 14.1; 38.1 versus 22.5%; IQR 16.8; 36.5; p=n.s.). In addition, no differences in infarct size and microvascular obstruction as well as in ST-segment resolution were observed. The MACE rate after N-ACC was similar to placebo (19.4% versus 19.4%, p=n.s.). Lipid peroxidation as a marker for oxidative stress was reduced by 20% in the N-ACC group (p<0.05), whereas no change was evident in placebo. High-dose N-ACC reduces oxidative stress. However, it does not provide an additional clinical benefit to placebo with respect to CIN and prevention of myocardial reperfusion injury in patients undergoing PCI with moderate doses of contrast medium and optimal hydratation.

574 The success of renal transplantation has resulted in an increased number of patients requesting a renal transplant (RT) and an increased waiting time for a RT. In addition, older patients and patients with more complex medical problems are being considered for RT. UNOS estimates that 3.5% of ESRD patients on the waiting list for RT died before transplant. Therefore, periodic re-evaluation of patients on the list for RT for prolonged periods of time may be important. However, there is a paucity of data about this issue. To determine if differences existed between patients inactivated or deleted after re-evaluation compared to patients that were kept active, we reviewed the 82 patients at our center who underwent formal re-evaluation in 1997. Patients were re-evaluated if they had been on the waiting list a minimum of 1 year. Ten patients were deleted, 10 were inactivated and remain inactive pending re-evaluation of underlying medical problems, and 2 were inactivated and subsequently reactivated. We compared patients without change in status(NoC) after re-evaluation to those who had a status change (Ch). There was no difference between groups with respect to gender, race or blood type. Patients in Ch were significantly older compared to NoC (55.1±11.4 years vs 44.6±11.5, mean±SD, p<.01) and had been on the transplant list longer (Ch=35.3±27.1 months, median 26.5 vs 22.8±12.4, median 12.4, p<.05). There was an increased incidence of diabetes in the Ch compared to NoC (Ch=41% vs NoC=14%, p<.05). There was a significant increase in coronary artery disease in Ch compared to NoC (Ch=50% vs 10%, p<.01), a trend towards an increase in past MI (Ch=27% vs 7%, p=.063), and an increased incidence of peripheral vascular disease in Ch (Ch=32% vs 7%, p<.05). We conclude: 1) Twenty seven percent of patients who underwent re-evaluation had a change in status (Ch group) with 12% being removed from the waiting list, 2) Ch patients were older, and had been on dialysis longer than NoC, 3) Ch had an increased incidence of diabetes, and 4) there was an increased incidence of coronary artery disease and peripheral vascular disease in the Ch group. The re-evaluation of certain groups of patients, such as those with markers of vascular disease, older patients, and those who have been on the waiting list for prolonged periods of time may be critical to ensure optimal outcomes in this era of organ shortages.