Hans-Joachim Nesser

Guidelines on the management of stable angina pectoris: executive summary

We thank the authors for raising the interesting discussion regarding the treatment of hypertension in patients with concomitant coronary disease. The J-shaped association between on-treatment blood pressure and risk has been described in longitudinal cohorts of patients with treated hypertension as well as in clinical trial populations, both in on-treatment and control arms. However, it is not absolutely clear that the association is treatmentrelated; in fact, one meta-analysis of seven randomized controlled trials including data on more than 40 000 patients has shown that the J-shaped relationship between blood pressure and mortality was not related to antihypertensive treatment. In this meta-analysis, noncardiovascular death was inversely related to blood pressure (both systolic and diastolic) in contrast to the J-shaped relationships for cardiovascular and total mortality, leading the authors to hypothesize that poor health conditions leading to low blood pressure and an increased risk of death might in part explain the J-shaped curve. Secondly, as discussed in the full-text version of the guidelines, there is accumulating evidence that blood pressure lowering in the ‘normal’ range is associated with improved cardiovascular outcomes in the population with known coronary disease. In the CAMELOT study, patients with coronary disease and mean blood pressure of 129/78 were randomized to enalapril, amlodipine, or placebo. Blood pressure reductions were similar (5/2 mm) in both treatment groups and associated with similar relative reductions in the composite endpoint of cardiovascular death, MI, and stroke, although not statistically significant in either group because of the small sample size. An intravascular ultrasound substudy demonstrated a significant inverse correlation between progression of atherosclerosis and blood pressure reduction even in this normal blood pressure range, with the greatest benefit observed in patients whose blood pressure fell below 120/80. Thus, the task force has felt it important, in the absence of unequivocal evidence to the contrary, to preserve consistency between guidelines on prevention and angina with regard to targets for institution of therapy for hypertension in the presence of coronary disease. No lower limit has yet been identified as a definite cutoff beyond which blood pressure should not be lowered further, although, clearly, symptomatic hypotension or postural hypotension will limit aggressive blood pressure lowering in the lower range.

Quantitative Assessment of Left Ventricular Size and Function Side-by-Side Comparison of Real-Time Three-Dimensional Echocardiography and Computed Tomography With Magnetic Resonance Reference

Background— Cardiac CT (CCT) and real-time 3D echocardiography (RT3DE) are being used increasingly in clinical cardiology. CCT offers superb spatial and contrast resolution, resulting in excellent endocardial definition. RT3DE has the advantages of low cost, portability, and live 3D imaging without offline reconstruction. We sought to compare both CCT and RT3DE measurements of left ventricular size and function with the standard reference technique, cardiac MR (CMR). Methods and Results— In 31 patients, RT3DE data sets (Philips 7500) and long-axis CMR (Siemens, 1.5 T) and CCT (Toshiba, 16-slice MDCT) images were obtained on the same day without β-blockers. All images were analyzed to obtain end-systolic and end-diastolic volumes and ejection fractions using the same rotational analysis to eliminate possible analysis-related differences. Intertechnique agreement was tested through linear regression and Bland-Altman analyses. Repeated measurements were performed to determine intraobserver and interobserver variability. Both CCT and RT3DE measurements resulted in high correlation (r2>0.85) compared with CMR. However, CCT significantly overestimated end-diastolic and end-systolic volumes (26 and 19 mL; P<0.05), resulting in a small but significant bias in ejection fraction (−2.8%). RT3DE underestimated end-diastolic and end-systolic volumes only slightly (5 and 6 mL), with no significant bias in EF (0.3%; P=0.68). The limits of agreement with CMR were comparable for the 2 techniques. The variability in the CCT measurements was roughly half of that in either RT3DE or CMR values. Conclusions— CCT provides highly reproducible measurements of left ventricular volumes, which are significantly larger than CMR values. RT3DE measurements compared more favorably with the CMR reference, albeit with higher variability.

Quantification of left ventricular volumes using three-dimensional echocardiographic speckle tracking: comparison with MRI

AIMS Although the utility of two-dimensional (2D) speckle tracking echocardiography (STE) to quantify left ventricular (LV) volume has been demonstrated, this methodology is limited by foreshortened views, geometric modelling, and the assumption that speckles can be tracked from frame to frame, despite their out of plane motion. To circumvent these limitations, a three-dimensional (3D) speckle tracking algorithm was recently developed. Our goal was to evaluate the accuracy of the new 3D-STE side by side with 2D-STE using cardiac magnetic resonance (CMR) as a reference. METHODS AND RESULTS Apical two- and four-chamber views (A2C and A4C) and real-time 3D datasets (Toshiba Artida 4D System) obtained in 43 patients with a wide range of LV size and function were analysed to measure LV end-systolic and end-diastolic volumes (ESV and EDV) using 2D and 3D-STE techniques. Short-axis CMR images (Siemens 1.5T scanner) acquired on the same day were analysed to obtain ESV and EDV reference values using the method of disks approximation. Reproducibility of both STE techniques was assessed using repeated measurements. While 2D-STE correlated well with CMR (r: 0.72-0.88), it underestimated LV volumes with relatively large biases (10-30 mL) and wide limits of agreement (SD: 36-51 mL), with A2C-derived measurements being worse than A4C values. The 3D-STE measurements showed higher correlation with CMR (0.87-0.92), and importantly smaller biases (1-16 mL) and narrower limits of agreement (SD: 28-37 mL). In addition, 3D-STE showed lower inter- and intra-observer variability (11-14% and 12-13%), than 2D-STE (16-17% and 12-16%, respectively). CONCLUSION This is the first study to validate the new 3D-STE technique for LV volume measurements and demonstrate its superior accuracy and reproducibility over previously used 2D-STE technique.

Quantitative evaluation of regional left ventricular function using three-dimensional speckle tracking echocardiography in patients with and without heart disease.

Although 2D speckle tracking echocardiography (STE) has been shown useful for the assessment of regional left ventricular (LV) function, it is limited by its 2D nature. Our goal was to evaluate new 3D-STE software by comparing regional wall motion (RWM) measurements against 2D-STE, and testing its ability to identify RWM abnormalities. 2D and real-time 3D datasets obtained in 32 subjects were analyzed to measure radial, longitudinal and rotational indices of displacement and strain. Segments were classified as normal or abnormal using cardiac MRI. 3D-STE and 2D-STE indices did not correlate well and showed wide limits of inter-technique agreement despite the minimal biases. In normal segments, 3D-STE showed: (1) higher displacements, due the out-of-plane motion component; (2) smaller SDs, indicating tighter normal ranges; (3) gradual decrease in displacement and reversal in rotation from base to apex. In abnormal segments, all 3D-STE indices were reduced. In conclusion, this is the first study to evaluate the new 3D-STE technique for measurements of RWM indices and demonstrate its superiority over 2D-STE.

Multimodality Comparison of Quantitative Volumetric Analysis of the Right Ventricle

Real-time 3D echocardiography (RT3DE), cardiac magnetic resonance (CMR) and cardiac computed tomography (CCT) can quantify right ventricular (RV) volume and overcome the limitations 2D echocardiography that stem from the unique geometry of the right ventricle. We tested a new technique for volumetric analysis of the right ventricle designed for RT3DE, CMR and CCT (TomTec) on images obtained in RV-shaped phantoms and in 28 patients with a range of RV geometry who underwent RT3DE, CMR and CCT imaging on the same day. In-vitro measurements showed that: (1) volumetric analysis of CMR images yielded the most accurate measurements; (2) CCT measurements showed slight (4%) but consistent overestimation; (3) RT3DE measurements showed small underestimation, but considerably wider margins of error. In patients, both RT3DE and CCT measurements correlated highly with the CMR reference (r-values 0.79–0.89) and showed the same trends noted in-vitro. In conclusion, eliminating analysis-related inter-modality differences allowed fare comparisons and highlighted the unique limitations of each modality. Understanding these differences promises to aid in the functional assessment of the right ventricle.

Real-time 3D echocardiographic quantification of left atrial volume: multicenter study for validation with CMR

OBJECTIVES We studied in a multicenter setting the accuracy and reproducibility of 3-dimensional echocardiography (3DE)-derived measurements of left atrial volume (LAV) using new, dedicated volumetric software, side by side with 2-dimensional echocardiography (2DE), using cardiac magnetic resonance (CMR) imaging as a reference. BACKGROUND Increased LAV is associated with adverse cardiovascular outcomes. Although LAV measurements are routinely performed using 2DE, this methodology is limited because it is view dependent and relies on geometric assumptions regarding left atrial shape. Real-time 3DE is free of these limitations and accordingly is an attractive alternative for the evaluation of LAV. However, few studies have validated 3DE-derived LAV measurements against an accepted independent reference standard, such as CMR imaging. METHODS We studied 92 patients with a wide range of LAV who underwent CMR (1.5-T) and echocardiographic imaging on the same day. Images were analyzed to obtain maximal and minimal LAV: CMR images using standard commercial tools, 2DE images using a biplane area-length technique, and 3DE images using Tomtec LA Function software. Intertechnique comparisons included linear regression and Bland-Altman analyses. Reproducibility of all 3 techniques was assessed by calculating the percentage of absolute differences in blinded repeated measurements. Kappa statistics were used to compare 2DE and 3DE classification of normal/enlarged against the CMR reference. RESULTS 3DE-derived LAV values showed higher correlation with CMR than 2DE measurements (r = 0.93 vs. r = 0.74 for maximal LAV; r = 0.88 vs. r = 0.82 for minimal LAV). Although 2DE underestimated maximal LAV by 31 ± 25 ml and minimal LAV by 16 ± 32 ml, 3DE resulted in a minimal bias of -1 ± 14 ml for maximal LAV and 0 ± 21 ml for minimal LAV. Interobserver and intraobserver variability of 2DE and 3DE measurements of maximal LAV were similar (7% to 12%) and approximately 2 times higher than CMR (4% to 5%). 3DE classified enlarged atria more accurately than 2DE (kappa: 0.88 vs. 0.71). CONCLUSIONS Compared with CMR reference, 3DE-derived LAV measurements are more accurate than 2DE-based analysis, resulting in fewer patients with undetected atrial enlargement.

Stress-induced cardiomyopathy (Tako-Tsubo syndrome) in Austria

Background: Tako-Tsubo syndrome (TS) is a still rarely diagnosed clinical syndrome, which is characterized by acute onset of chest pain, transient cardiac dysfunction with (frequently) reversible wall motion abnormalities (WMAs), but with no relevant obstructive coronary artery disease. Methods and results: Among 179 consecutive patients with proven diagnosis of TS that were retrospectively analysed in this multicentre registry, women represented the majority of patients (94%) while only 11 men (6%) developed TS. Mean age was 69.1±11.5 years (range 35–88 years). Cardinal symptoms of TS, which led to admission, were acute chest pain (82%) and dyspnoea (32%), respectively. All patients demonstrated typical WMAs, whereby four different types of WMAs could be defined: (1) a more common apical type of TS (n=89; 50%); (2) a combined apical and midventricular form of TS (n=23; 13%); (3) the midventricular TS (n=6; 3%); and (4) an unusual type of basal WMAs of the left ventricle (n=3). Only in 101 patients (57%), a clear causative trigger for onset of symptoms could be identified. In-hospital cardiovascular complications occurred in 25 patients (14%) and consisted of cardiac arrhythmias in 10 patients (40%), cardiogenic shock in six patients (24%), cardiac decompensation in eight patients (32%) and cardiovascular death in one patient, respectively. Echocardiographic control of left ventricular function after the initial measurement was available in almost 70% of the patients: complete recovery of WMAs was found in 73 patients (58.87%); 49 patients (39.52%) showed persistent WMAs. Recurrences of TS were only seen in four patients. During the follow-up period, 13 patients died: three of cardiovascular causes and 10 of non-cardiac causes. In-hospital mortality was 0.6%, 30-day mortality was 1.3% and 2-year mortality was 6.7%. Conclusions: This study represents to date the largest series of patients suffering from TS in Austria and worldwide. Similar to others, in our series the prevalence of TS was significantly higher in women than in men, while in contrast to other studies, the apical type of TS was detected most frequently. The similar clinical presentation of TS patients to the clinical picture of acute myocardial infarction demonstrates the importance of immediate coronary angiography for adequate differential diagnosis of TS. TS is not necessarily a benign disease due to cardiovascular complications as well as persistent WMAs with delayed recovery.

Endovascular thrombectomy for acute ischemic stroke patients anticoagulated with dabigatran.

For the treatment of acute ischemic stroke (AIS), IV recominant tissue plasminogen activator (rtPA) has proven efficacy n eligible patients, but carries an increased risk of intracereral hemorrhage [1]. Preexisting anticoagulation, including the irect thrombin inhibitor dabigatran, usually contraindicates the se of rtPA. This notwithstanding, several single cases of IV tPA treatment in patients with AIS under dabigatran have een reported, with mixed results [2]. Endovascular therapy has merged as a potential, yet still experimental, alternative treatment ption for a number of clinical scenarios with contraindications o IV rtPA [3]. We report successful rescue thrombectomy in two patients who uffered AIS under treatment with dabigatran for atrial fibrillation AF).

Three-dimensional analysis of regional left ventricular endocardial curvature from cardiac magnetic resonance images.

Left ventricular (LV) remodeling is usually assessed using changes in LV volume, while disregarding regional changes that may occur independently of volume. We hypothesized that 3D analysis of regional endocardial curvature could provide useful information on localized remodeling. Cardiac magnetic resonance (CMR) images were acquired in 44 patients: 14 normal controls (NL), 15 with dilated cardiomyopathy (DCM), and 15 ischemic heart disease (IHD). LV endocardial surface was reconstructed throughout the cardiac cycle and used to calculate for each point the curvedness, normalized by instantaneous LV size (Cn). Normalized curvedness was compared between groups of segments: NL (N=401), DCM (N=255) and IHD (N=92). While in NL segments, Cn values were comparable in basal and mid-ventricular segments, they were higher in the apical segments (p&#60;0.05). Also, % change in Cn was higher in mid and apical compared to basal segments (p&#60;0.05). At all LV levels, Cn in DCM segments was lower (p&#60;0.05) than in NL and IHD. In contrast, % change in Cn was lower in both IHD and DCM segments compared to NL (p&#60;0.05). 3D analysis of regional LV endocardial curvature from CMR images provides quantitative information, which is consistent with the known pathophysiology, and may prove useful in the evaluation of LV remodeling.

Left Atrial Diameter and Survival among Renal Allograft Recipients

BACKGROUND AND OBJECTIVES Sequential echocardiography is routinely performed in patients with ESRD listed for transplantation. The benefit of this labor- and time-intensive measure, however, remains unclear. Thus, this study elucidated the various obtained routine echocardiography parameters that best predicted mortality and graft survival after renal transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study investigated 553 first renal transplant recipients listed in the Austrian Dialysis and Transplant Registry between 1992 and 2011 who had echocardiographic analysis at transplantation and survived at least 1 year. Cox proportional hazards models with the purposeful selection algorithms for covariables were used to identify predictors of mortality and graft loss. A Fine and Gray model was used to evaluate cause-specific death. RESULTS During a median follow-up of 7.14 years, 81 patients died, and 59 patients experienced graft loss after the first year. The Kaplan-Meier analysis showed that 85% of patients with a left atrial diameter below the median of 53 mm were alive 10 years after transplantation, whereas only 70% of those patients with a left atrial diameter equal to or above the median had survived (P<0.001). In the multivariable model, left atrial diameter (per millimeter) independently predicted overall mortality (hazard ratio, 1.06; 95% confidence interval, 1.03 to 1.08; P<0.001) and cause-specific cardiac death (hazard ratio, 1.04; 95% confidence interval, 1.00 to 1.08; P=0.04). Functional graft loss was predicted by the right atrial diameter (hazard ratio, 1.04; 95% confidence interval, 1.02 to 1.07; P=0.001). CONCLUSION The left atrial diameter determined at transplantation predicted overall and cardiac mortality. Patients with widely enlarged left atria exhibit a considerably reduced life expectancy. It remains to be determined, however, whether renal transplantation is futile in these patients.