Andreas Rück

NOGA-Guided Analysis of Regional Myocardial Perfusion Abnormalities Treated With Intramyocardial Injections of Plasmid Encoding Vascular Endothelial Growth Factor A-165 in Patients With Chronic Myocardial Ischemia Subanalysis of the EUROINJECT-ONE Multicenter Double-Blind Randomized Study

Background—The aim of this substudy of the EUROINJECT-ONE double-blind randomized trial was to analyze changes in myocardial perfusion in NOGA-defined regions with intramyocardial injections of plasmid encoding plasmid human (ph)VEGF-A165 using an elaborated transformation algorithm. Methods and Results—After randomization, 80 no-option patients received either active, phVEGF-A165 (n=40), or placebo plasmid (n=40) percutaneously via NOGA-Myostar injections. The injected area (region of interest, ROI) was delineated as a best polygon by connecting of the injection points marked on NOGA polar maps. The ROI was projected onto the baseline and follow-up rest and stress polar maps of the 99m-Tc-sestamibi/tetrofosmin single-photon emission computed tomography scintigraphy calculating the extent and severity (expressed as the mean normalized tracer uptake) of the ROI automatically. The extents of the ROI were similar in the VEGF and placebo groups (19.4±4.2% versus 21.5±5.4% of entire myocardium). No differences were found between VEGF and placebo groups at baseline with regard to the perfusion defect severity (rest: 69±11.7% versus 68.7±13.3%; stress: 63±13.3% versus 62.6±13.6%; and reversibility: 6.0±7.7% versus 6.7±9.0%). At follow-up, a trend toward improvement in perfusion defect severity at stress was observed in VEGF group as compared with placebo (68.5±11.9% versus 62.5±13.5%, P=0.072) without reaching normal values. The reversibility of the ROI decreased significantly at follow-up in VEGF group as compared with the placebo group (1.2±9.0% versus 7.1±9.0%, P=0.016). Twenty-one patients in VEGF and 8 patients in placebo group (P<0.01) exhibited an improvement in tracer uptake during stress, defined as a ≥5% increase in the normalized tracer uptake of the ROI. Conclusions—Projection of the NOGA-guided injection area onto the single-photon emission computed tomography polar maps permits quantitative evaluation of myocardial perfusion in regions treated with angiogenic substances. Injections of phVEGF A165 plasmid improve, but do not normalize, the stress-induced perfusion abnormalities.

Effects of intramyocardial injection of phVEGF‐A165 as sole therapy in patients with refractory coronary artery disease – 12‐month follow‐up: Angiogenic gene therapy

Abstract. Sarkar N, Rück A, Källner G, Y‐Hassan S, Blomberg P, Islam KB, van der Linden J, Lindblom D, Nygren AT, Lind B, Brodin L‐Å, Drvota V, Sylvén C (Karolinska Institute, Huddinge University Hospital, Novum, Stockholm, Sweden). Effects of intramyocardial injection of phVEGF‐A165 as sole therapy in patients with refractory coronary artery disease: 12‐month follow‐up. Angiogenic gene therapy. J Intern Med 2001; 250: 373–381.

Meta-analysis of the impact of mitral regurgitation on outcomes after transcatheter aortic valve implantation.

Significant mitral regurgitation (MR) constitutes an important co-existing valvular heart disease burden in the setting of aortic valve stenosis. There are conflicting reports on the impact of significant MR on outcomes after transcatheter aortic valve implantation (TAVI). We evaluated the impact of MR on outcomes after TAVI by performing a meta-analysis of 8 studies involving 8,927 patients reporting TAVI outcomes based on the presence or absence of moderate-severe MR. Risk ratios (RRs) were calculated using the inverse variance random-effects model. None-mild MR was present in 77.8% and moderate-severe MR in 22.2% of the patients. The presence of moderate-severe MR at baseline was associated with increased mortality at 30 days (RR 1.35, 95% confidence interval [CI] 1.14 to 1.59, p = 0.003) and 1 year (RR 1.24, 95% CI 1.13 to 1.37, p <0.0001). The increased mortality associated with moderate-severe MR was not influenced by the cause of MR (functional or degenerative MR; RR 0.90, 95% CI 0.62 to 1.30, p = 0.56). The severity of MR improved in 61 ± 6.0% of patients after TAVI. Moderate-severe residual MR, compared with none-mild residual MR after TAVI, was associated with significantly increased 1-year mortality (RR 1.48, 95% CI 1.31 to 1.68, p <0.00001). In conclusion, baseline moderate-severe MR and significant residual MR after TAVI are associated with an increase in mortality after TAVI and represent an important group to target with medical or transcatheter therapies in the future.

Impact on image quality and radiation exposure in coronary CT angiography: 100 kVp versus 120 kVp

Background: The risk of radiation-induced cancer has become a major concern with the increasing use of computed tomography (CT). Purpose: To compare image quality and radiation doses when decreasing X-ray tube peak kilovoltage (kVp) from 120 to 100 kVp in patients undergoing coronary CT angiography (CCTA). Material and Methods: Patients referred for evaluation of suspected coronary artery disease (CAD) underwent 64-channel detector CCTA using a tube voltage of either 120 kVp (n = 46) or 100 kVp (n = 82). The individual volume CT dose index (CTDIvol) and dose length product (DLP) were recorded and effective radiation dose was estimated on the basis of DLP. Subjective image quality was assessed by two radiologists on per-patient based consensus. Vascular density and image noise were quantified in the left main coronary artery (LMCA) and proximal ascending aorta (AA). Mean density in the adjacent perivascular tissue was also quantified. Contrast-to-noise ratio (CNR) was calculated. Corresponding invasive coronary angiography (ICA) was performed, which constituted the gold standard. Results: Mean values in the 100/120 kVp cohorts regarding CNR in the LMCA were 12.7/16.0 (P<0.0001)) and in the AA 13.2/17.2 (P<0.0001), CTDIvol 34.4/57.4 mGy (a 40% reduction, P<0.0001), DLP 578/1125 mGy × cm (P<0.0001), and estimated effective dose 9.6/20.2 mSv (P<0.0001). There was no statistically significant difference in subjective image quality between the two cohorts. The sensitivity to detect significant coronary stenoses was 88% (120 kVp) and 84% (100 kVp) and the specificity was 71% (120 kVp) and 74% (100 kVp), respectively. Conclusion: By reduction of tube voltage from 120 to 100 kVp at CCTA, while keeping all other scanning parameters unchanged, the radiation dose to the patient can be almost halved while keeping the diagnostic image quality at a clinically acceptable level.

Early clinical outcome of aortic transcatheter valve-in-valve implantation in the Nordic countries.

OBJECTIVE Transcatheter valve-in-valve implantation has emerged as an option, in addition to reoperative surgical aortic valve replacement, to treat failed biologic heart valve substitutes. However, the clinical experience with this approach is still limited. We report the comprehensive experience of transcatheter valve-in-valve implantation in the Nordic countries from May 2008 to January 2012. METHODS A total of 45 transcatheter aortic valve-in-valve implantations were performed during the study period in 11 centers. The mean age of the patients was 80.6 years (range, 61-91), 26 were male and 19 were female, and the mean EuroSCORE, EuroSCORE II, and Society of Thoracic Surgeons score was 35.4, 16.3, and 14.6, respectively. The type of failure was stenosis and combined in 58% (mean and peak aortic valve gradient, 77 and 45 mm Hg, respectively) and regurgitation in 42% of cases. The SAPIEN/XT (Edwards LifeSciences, Irvine, Calif) and CoreValve (Medtronic Inc, Minneapolis, Minn) system was used in 33 and 12 cases, respectively. The access route was transapical in 25, transfemoral in 17, transaortic in 2, and subclavian in 1 case. The mean follow-up was 14.4 months. The periprocedural and postoperative outcomes were assessed using the Valve Academic Research Consortium criteria. RESULTS No intraprocedural mortality occurred. The technical success rate was 95.6% (1 second valve implantation, 1 conversion to open surgery). The all-cause 30-day mortality was 4.4% (1 cardiac-related and 1 aspiration pneumonia). The major complications within 30 days included stroke in 2.2%, periprocedural myocardial infarction in 4.4%, and major vascular complication in 2.2% of patients. At 1 month, all but 1 patient had either no or mild paravalvular leakage, with a mean and peak valve gradient of 17 mm Hg (range, 4-38) and 30 mm Hg (range, 7-68), respectively. The mean gradient was greater than 20 mm Hg in 17% of patients and remained unchanged at 12 months. The 1-year survival was 88.1%. CONCLUSIONS Transcatheter valve-in-valve implantation is widely performed, albeit in small numbers, in most centers in the Nordic countries. The short-term results were excellent in this high-risk patient population, demonstrating a low incidence of device- or procedure-related complications. However, a considerable number of patients were left with suboptimal systolic valve performance with unknown long-term effects, warranting close surveillance after transcatheter valve-in-valve implantation.

Heart rate variability and heat sensation during CT coronary angiography: Low-osmolar versus iso-osmolar contrast media

Background: During computed tomography coronary angiography (CTCA) unexpected changes in heart rate while scanning may affect image quality. Purpose: To evaluate whether an iso-osmolar contrast medium (IOCM, iodixanol) and a low-osmolar contrast medium (LOCM, iomeprol) affect heart rate and experienced heat sensation differently. Material and Methods: One hundred patients scheduled for CTCA were randomized to receive either iodixanol 320 mgI/ml or iomeprol 400 mgI/ml. Depending on their heart rate, the patients were assigned to one of five scanning protocols, each optimized for different heart rate ranges. During scanning the time between each heart beat (hb) was recorded, and the corresponding heart rate was calculated. For each contrast medium (CM) the average heart rate, the variation in heart rate from individual mean heart rate, and the mean deviation from the predefined scanning protocol were calculated. Experience of heat was obtained immediately after scanning by using a visual analog scale (VAS). Examination quality was rated by two radiologists on a three-point scale. Results: The mean variation in heart rate after IOCM was 1.4 hb/min and after LOCM it was 4.4 hb/min (NS). The mean deviations in heart rate from that in the predefined scanning protocol were 2.0 hb/min and 4.7 hb/min, respectively (NS). A greater number of arrhythmic hb were observed after LOCM compared with IOCM (P<0.001). There was no statistically significant difference in image quality. The LOCM group reported a stronger heat sensation after CM injection than the IOCM group (VAS =36 mm and 18 mm, P<0.05). Conclusion: At clinically used concentrations the IOCM, iodixanol 320 mgI/ml, does not increase the heart rate during CTCA and causes less heart arrhythmia and less heat sensation than the LOCM, iomeprol 400 mgI/ml.

Transesophageal echocardiography measurements of aortic annulus diameter using biplane mode in patients undergoing transcatheter aortic valve implantation

BackgroundAortic stenosis (AS) is a relevant common valve disorder. Severe AS and symptoms and/or left ventricular dysfunction (EF <50%) have the indication for aortic valve replacement (AVR). Majority of the patients with AS are elderly often with co-morbidities and generally have high preoperative risk. Transcatheter aortic valve implantation (TAVI) is offered in this group. Four different sizes of Corevalve prosthesis are available. Correct measurement of aortic size prior to TAVI is of great important to choose the right prosthesis size to avoid among others paravalvular leak or prosthesis patient mismatch.Aim of the study is to assess the aortic annulus diameter in patients undergoing TAVI by biplane (BP) mode using transesophageal echocardiography (TEE) and compare it to two-dimensional (2D) transthoracic echocardiography (TTE) and 2DTEE using three-dimensional (3D) TEE as reference method.MethodsThe study population consisted of 50 patients retrospectively (24 men and 26 women, mean age 85±8 years of age) who all had undergone echocardiography examination prior to TAVI.ResultsThe mean aortic annulus diameter was 20.4±2.2 mm with TTE, 22.3±2.5 mm with 2DTEE, 22.9±1.9 mm with BP-mode and 23.1±1.9 mm with 3DTEE. TTE underestimated the mean aortic annulus diameter in comparison to transesophageal imaging modalities (p<0.001). Using 3DTEE, 2% of patients were unsuitable for TAVI due to a too-small AoA (n=1). This figure was similar with BP (4%, n=2; p=1.00) but considerably larger with 2DTTE (36%, n=18; p < 0.001) and 2DTEE (12%, n=6; p=0.06). There was a strong correlation between BP-mode and 3DTEE for assessment of aortic annulus diameter (r-value 0.88) with small mean difference (−0.2±0.9 mm) whereas the other modalities showed larger 95% confidence interval and modest correlation (2DTTE vs. 3DTEE, –6.3 to 0.9 mm, r=0.64 and 2DTEE vs. 3DTEE, –4.8 to 3.2 mm, r=0.61).ConclusionA multi-dimensional method is preferred to assess aortic annulus diameter in TAVI patients since there is risk of underestimation using single plane. Biplane mode is the method of choice in view of speedy post-processing with no need for expensive dedicated software. Lastly, single plane methods lead to misclassification of patients as unsuitable for TAVI. This may be of major clinical importance.

Transcatheter aortic valve implantation is feasible and safe in nonagenarians.

To the Editor: Aortic valve stenosis (AS) is a common disease, with greater prevalence with age. It is associated with poor quality of life and high morbidity and mortality. One-third of individuals with symptomatic severe AS evaluated for surgical aortic valve replacement (AVR) are denied surgery, and advanced age is the most common reason for decline. Over the past decade, transcatheter aortic valve implantation (TAVI) has been established as an alternative method to AVR in individuals with severe AS who are denied surgical AVR because they are at high risk. The shortand medium-term results of TAVI in these individuals are comparable with those of surgical AVR, but the results of TAVI in very elderly adults are largely unknown.

The relationship between electrocardiographic left ventricular hypertrophy criteria and echocardiographic mass in patients undergoing transcatheter aortic valve replacement

INTRODUCTION Calcific aortic stenosis (AS) is a common valvular disease among the elderly. Often, AS leads to left ventricular hypertrophy (LVH) and symptoms of heart failure. Severe AS can be treated by transcatheter aortic valve replacement (TAVR). Previous studies have shown that electrocardiogram (ECG) criteria for LVH correlate poorly with left ventricular mass (LVM) in echocardiography. However, such correlations have not been studied in TAVR patients. AIMS To evaluate ECG LVH criteria as a method of diagnosing and quantifying LVH in patients with AS undergoing TAVR. MATERIAL AND METHODS Twenty-four patients, with neither pacemaker nor bundle branch block, who had undergone pre-TAVR ECG and echocardiography were included. The ECGs were evaluated using the Sokolow-Lyon, Romhilt-Estes and Cornell Voltage criteria for LVH as well as spatial maximal QRS-T angle and 3D QRS maximal spatial vector. The LVM was measured by echocardiography. RESULTS 15 (63%) patients met the echocardiographic threshold for LVH. 7 patients (29%) were positive by the Sokolow-Lyon, 5 (21%) by the Romhilt-Estes and 12 (50%) by the Cornell Voltage criteria for LVH. There was no correlation between LVM and conventional ECG LVH criteria or spatial parameters. QRS duration correlated with LVM (r=0.56, R(2)=0.31, p=0.005). However, there was no correlation between QRS duration and LVM index or relative wall thickness (RWT). CONCLUSIONS In TAVR patients, none of the ECG LVH criteria should be used for evaluation of LVM. QRS duration is moderately correlated to LVM and is the most useful ECG estimate of LVM.

Is training essential for interpreting cardiac computed tomography

Background: Cardiac computed tomography (CT) has gained increasing acceptance for diagnosing obstructive coronary artery disease (CAD). Several guidelines have been published on required education for proficiency in the interpretation of these examinations. Purpose: To describe the learning-curve effect of the interpretation of 100 consecutive cardiac CT examinations aimed at diagnosing CAD. The diagnostic accuracy of radiologists and radiographers was also compared. Material and Methods: Two radiologists and two radiographers, all with no prior experience in evaluation of cardiac CT, independently underwent a dedicated training program of 100 examinations randomized into 10 blocks (sessions), with 10 cases in each. They independently evaluated the coronary arteries regarding significant obstructive CAD. After every session, individual feedback on diagnostic accuracy and comparison with the corresponding invasive coronary angiography (currently regarded as the gold standard to detect coronary lesions) was given. The time required for interpretation was recorded. Results: The mean review time decreased (P<0.0001) successively during the 10 sessions for all the observers together. The first session had a mean review time of 32 min, and the last session 16 min. No significant improvement in sensitivity, specificity, or negative predictive value (NPV) was observed. For positive predictive value (PPV), there was an improvement for the radiologists (P<0.05), but not for the radiographers. The radiographers had a higher total specificity compared to the radiologists (P<0.01). Conclusion: The review time for novices in cardiac CT was approximately halved during the first 100 cases, with maintained accuracy. There was a learning-curve effect in PPV for the radiologists. The diagnostic accuracy of dedicated radiographers indicates that they might be considered to be included as part of the evaluation team.