J. Otton

Reference values for healthy human myocardium using a T1 mapping methodology: results from the International T1 Multicenter cardiovascular magnetic resonance study

BackgroundT1 mapping is a robust and highly reproducible application to quantify myocardial relaxation of longitudinal magnetisation. Available T1 mapping methods are presently site and vendor specific, with variable accuracy and precision of T1 values between the systems and sequences. We assessed the transferability of a T1 mapping method and determined the reference values of healthy human myocardium in a multicenter setting.MethodsHealthy subjects (n = 102; mean age 41 years (range 17–83), male, n = 53 (52%)), with no previous medical history, and normotensive low risk subjects (n=113) referred for clinical cardiovascular magnetic resonance (CMR) were examined. Further inclusion criteria for all were absence of regular medication and subsequently normal findings of routine CMR. All subjects underwent T1 mapping using a uniform imaging set-up (modified Look- Locker inversion recovery, MOLLI, using scheme 3(3)3(3)5)) on 1.5 Tesla (T) and 3 T Philips scanners. Native T1-maps were acquired in a single midventricular short axis slice and repeated 20 minutes following gadobutrol. Reference values were obtained for native T1 and gadolinium-based partition coefficients, λ and extracellular volume fraction (ECV) in a core lab using standardized postprocessing.ResultsIn healthy controls, mean native T1 values were 950 ± 21 msec at 1.5 T and 1052 ± 23 at 3 T. λ and ECV values were 0.44 ± 0.06 and 0.25 ± 0.04 at 1.5 T, and 0.44 ± 0.07 and 0.26 ± 0.04 at 3 T, respectively. There were no significant differences between healthy controls and low risk subjects in routine CMR parameters and T1 values. The entire cohort showed no correlation between age, gender and native T1. Cross-center comparisons of mean values showed no significant difference for any of the T1 indices at any field strength. There were considerable regional differences in segmental T1 values. λ and ECV were found to be dose dependent. There was excellent inter- and intraobserver reproducibility for measurement of native septal T1.ConclusionWe show transferability for a unifying T1 mapping methodology in a multicenter setting. We provide reference ranges for T1 values in healthy human myocardium, which can be applied across participating sites.

Everolimus-Associated Pneumonitis in 3 Heart Transplant Recipients

Although pulmonary toxicity from sirolimus is well recognized, the biochemically homologous everolimus has until recently been thought to be free from this side effect. Emerging evidence suggests an association between high-dose everolimus and symptomatic pneumonitis. Toxicity at typical immunosuppressive doses has also been described. In support of these observations, we report the occurrence of clinical pneumonitis in 3 patients in association with everolimus therapy after heart transplantation in the absence of other causative factors. Typical onset consisted of dyspnea, hypoxemia, and bilateral diffuse pulmonary infiltrates beginning between 2 weeks and 6 months after commencement of the drug. Although uncommon, everolimus may cause pneumonitis and should be considered in the differential diagnosis of pulmonary infiltrates and hypoxemia in an appropriate clinical setting.

A method for coronary artery calcium scoring using contrast-enhanced computed tomography

BACKGROUND Limitations to the coronary calcium score include its requirement for noncontrast imaging and radiation exposure that approaches current methods for contrast-enhanced CT angiography. OBJECTIVES We sought to derive and validate a method of measuring the coronary artery calcium score (CACS) from standard contrast-enhanced CT, obviating the need for a second non-contrast calcium scan. METHODS The volume of intramural calcium of >320 HU in major coronary vessels was measured in 90 contrast-enhanced and traditional non-contrast calcium scan pairs. An empiric conversion factor was derived to convert the small voxel contrast-enhanced calcium volume to an Agatston calcium score. The accuracy of this technique was then prospectively validated in 120 consecutive patients undergoing clinical calcium scans and contrasted-enhanced coronary CT. Eleven patients were excluded from analysis because of the prespecified criteria of excessive noise in the contrast-enhanced CT or total coronary artery occlusion. RESULTS The Pearson correlation of the contrast scan-derived calcium score with the measured CACS was r2 = 0.99. With standard CACS risk bands, agreement of the contrast-enhanced calcium score estimate with the measured CAC by quadratic weighted κ was 0.96. The 95% limits of agreement (Agatston units) were given by ±(3.2 + 0.14 × CACS + 4.44 mean square root of CACS). Inter-observer and intra-observer reliability with the intraclass correlation was 0.99. CONCLUSION The calcium score can be accurately measured from contrast-enhanced cardiac CT scans with the use of a Hounsfield unit threshold of 320.

Perfusion phantom : an efficient and reproducible method to simulate myocardial first-pass perfusion measurements with cardiovascular magnetic resonance

The aim of this article is to describe a novel hardware perfusion phantom that simulates myocardial first‐pass perfusion allowing comparisons between different MR techniques and validation of the results against a true gold standard. MR perfusion images were acquired at different myocardial perfusion rates and variable doses of gadolinium and cardiac output. The system proved to be sensitive to controlled variations of myocardial perfusion rate, contrast agent dose, and cardiac output. It produced distinct signal intensity curves for perfusion rates ranging from 1 to 10 mL/mL/min. Quantification of myocardial blood flow by signal deconvolution techniques provided accurate measurements of perfusion. The phantom also proved to be very reproducible between different sessions and different operators. This novel hardware perfusion phantom system allows reliable, reproducible, and efficient simulation of myocardial first‐pass MR perfusion. Direct comparison between the results of image‐based quantification and reference values of flow and myocardial perfusion will allow development and validation of accurate quantification methods. Magn Reson Med, 2013.

Platelet expression of stromal-cell-derived factor-1 (SDF-1): An indicator for ACS?

BACKGROUND Acute coronary syndrome (ACS) along with myocardial ischemic injury are the leading causes for chest pain. Platelet surface expression of stromal-cell-derived factor-1 (SDF-1) is enhanced during ischemic events and may play an important role in trafficking hematopoietic progenitor cells for tissue regeneration and neovascularization. This study examined the platelet surface expression of SDF-1 in patients with chest pain. METHODS We consecutively evaluated 1000 patients, who were admitted to the emergency department with chest pain. Platelet surface expression of GPIb and SDF-1 was determined by two-color whole blood flow cytometry. RESULTS Patients with ACS showed significantly enhanced SDF-1 expression on admission compared to patients with other causes such as stable angina pectoris (SAP) and other origin of chest pain (CPO) (ACS vs. SAP/CPO (mean fluorescence intensity (MFI)± SD): 39.7 ± 26.3 vs. SAP: 37.6 ± 31.5;P=0.045; arterial hypertension: 27.3 ± 12.7;P=0.003; orthopedic disease: 22.1 ± 6.5;P=0.014; pulmonary embolism: 26.6 ± 19.1;P=0.003; Da Costas syndrome: 22.1 ± 12.5;P=0.021; inflammatory cardiomyopathy: 19.8 ± 11.5;P=0.025). Logistic regression analysis showed that surface expression of platelet SDF-1 was significantly associated with ACS (P=0.026), however, the superiority of troponin-I in predicting ACS remains on a high level (P=0.001). Areas under the curve of receiver operating characteristic analysis revealed 0.718 (95% confidence interval (CI):0.680-0.757) using SDF-1, and 0.795 (95%CI:0.760-0.829) applying troponin-I baseline serum levels. Patients with enhanced SDF-1 levels (cutoff:MFI ≥ 27.7) had a 1.4-fold relative risk (95%CI:1.17-1.52) for ACS. CONCLUSIONS Platelet SDF-1 surface expression was significantly enhanced in patients with ACS compared to SAP or CPO. Determination of platelet SDF-1 may be useful as an early additional biomarker for cardiovascular risk stratification.

Body position and activity, but not heart rate, affect pump flows in patients with continuous-flow left ventricular assist devices.

OBJECTIVES The aim of this study was to determine the contribution of pre-load and heart rate to pump flow in patients implanted with continuous-flow left ventricular assist devices (cfLVADs). BACKGROUND Although it is known that cfLVAD pump flow increases with exercise, it is unclear if this increment is driven by increased heart rate, augmented intrinsic ventricular contraction, or enhanced venous return. METHODS Two studies were performed in patients implanted with the HeartWare HVAD. In 11 patients, paced heart rate was increased to approximately 40 beats/min above baseline and then down to approximately 30 beats/min below baseline pacing rate (in pacemaker-dependent patients). Ten patients underwent tilt-table testing at 30°, 60°, and 80° passive head-up tilt for 3 min and then for a further 3 min after ankle flexion exercise. This regimen was repeated at 20° passive head-down tilt. Pump parameters, noninvasive hemodynamics, and 2-dimensional echocardiographic measures were recorded. RESULTS Heart rate alteration by pacing did not affect LVAD flows or LV dimensions. LVAD pump flow decreased from baseline 4.9 ± 0.6 l/min to approximately 4.5 ± 0.5 l/min at each level of head-up tilt (p < 0.0001 analysis of variance). With active ankle flexion, LVAD flow returned to baseline. There was no significant change in flow with a 20° head-down tilt with or without ankle flexion exercise. There were no suction events. CONCLUSIONS Centrifugal cfLVAD flows are not significantly affected by changes in heart rate, but they change significantly with body position and passive filling. Previously demonstrated exercise-induced changes in pump flows may be related to altered loading conditions, rather than changes in heart rate.

A direct comparison of the sensitivity of CT and MR cardiac perfusion using a myocardial perfusion phantom

Background Direct comparison of CT and magnetic resonance (MR) perfusion techniques has been limited and in vivo assessment is affected by physiological variability, timing of image acquisition, and parameter selection. Objective We precisely compared high-resolution k-t SENSE MR cardiac perfusion at 3 T with single-phase CT perfusion (CTP) under identical imaging conditions. Methods We used a customized MR imaging and CT compatible dynamic myocardial perfusion phantom to represent the human circulation. CT perfusion studies were performed with a Philips iCT (256 slice) CT, with isotropic resolution of 0.6 mm3. MR perfusion was performed with k-t SENSE acceleration at 3 T and spatial resolution of 1.2 × 1.2 × 10 mm. The image contrast between normal and underperfused myocardial compartments was quantified at various perfusion and photon energy settings. Noise estimates were based on published clinical data. Results Contrast by CTP highly depends on photon energy and also timing of imaging within the myocardial perfusion upslope. For an identical myocardial perfusion deficit, the native image contrast-to-noise ratio (CNR) generated by CT and MR are similar. If slice averaging is used, the CNR of a perfusion deficit is expected to be greater for CTP than MR perfusion (MRP). Perfect timing during single time point CTP imaging is difficult to achieve, and CNR by CT decreases by 24%–31% two seconds from the optimal imaging time point. Although single-phase CT perfusion offers higher spatial resolution, MRP allows multiple time point sampling and quantitative analysis. Conclusion The ability of CTP and current optimal MRP techniques to detect simulated myocardial perfusion deficits is similar.

Accuracy and Clinical Outcomes of Computed Tomography Coronary Angiography in the Presence of a High Coronary Calcium Score

BACKGROUND A high coronary calcium burden may adversely affect image quality of CT coronary angiography (CTCA). The ability to rule out clinically significant disease in this setting is uncertain. METHODS We examined CTCA findings in patients with a calcium score of >600. Utilising a search of death notices, structured patient interview and medical records, downstream investigations, cardiovascular events, revascularisation and mortality were recorded. RESULTS Sixty patients with a calcium score >600 had CTCA performed on the same day. Coronary disease findings were: mild 28%, moderate 33%, severe 32% and non-diagnostic 7%. During a median 1.75-year follow-up, 31 (53%) of patients underwent further assessment for coronary disease, eight patients (13%) underwent revascularisation and there were two non-cardiovascular and one cardiovascular deaths. No patient with mild or moderate disease at CTCA had subsequently demonstrated ischaemia, was deemed to require PCI or suffered cardiac mortality. The negative predictive value of CTCA for subsequent PCI and all-cause mortality was 97% (100% for cardiac mortality only). The positive predictive value of CTCA for revascularisation or CV death was 42%. CONCLUSION In patients with an elevated coronary calcium score, a negative CTCA implies an excellent short-term outcome and appears to exclude clinically significant coronary disease.

Use of 3-Dimensional Models to Optimize Pre-Procedural Planning of Percutaneous Left Atrial Appendage Closure

Percutaneous left atrial appendage closure (LAAC) has become the treatment of choice for patients with nonvalvular atrial fibrillation at high risk for stroke and contraindications to oral anticoagulant therapy. The ultimate goal of LAAC is to minimize long-term stroke and bleeding risks while

Defining the mid-diastolic imaging period for cardiac CT – lessons from tissue Doppler echocardiography

BackgroundAggressive dose reduction strategies for cardiac CT require the prospective selection of limited cardiac phases. At lower heart rates, the period of mid-diastole is typically selected for image acquisition. We aimed to identify the effect of heart rate on the optimal CT acquisition phase within the period of mid-diastole.MethodsWe utilized high temporal resolution tissue Doppler to precisely measure coronary motion within diastole. Tissue-Doppler waveforms of the myocardium corresponding to the location of the circumflex artery (100 patients) and mid-right coronary arteries (50 patients) and the duration and timing of coronary motion were measured. Using regression analysis an equation was derived for the timing of the period of minimal coronary motion within the RR interval. In a validation set of 50 clinical cardiac CT examinations, we assessed coronary motion artifact and the effect of using a mid-diastolic imaging target that was adjusted according to heart rate vs a fixed 75% phase target.ResultsTissue Doppler analysis shows the period of minimal cardiac motion suitable for CT imaging decreases almost linearly as the RR interval decreases, becoming extinguished at an average heart rate of 91 bpm for the circumflex (LCX) and 78 bpm for the right coronary artery (RCA). The optimal imaging phase has a strong linear relationship with RR duration (R2 = 0.92 LCX, 0.89 RCA). The optimal phase predicted by regression analysis of the tissue-Doppler waveforms increases from 74% at a heart rate of 55 bpm to 77% at 75 bpm. In the clinical CT validation set, the optimal CT acquisition phase similarly occurred later with increasing heart rate. When the selected cardiac phase was adjusted according to heart rate the result was closer to the optimal phase than using a fixed 75% phase. While this effect was statistically significant (p < 0.01 RCA/LCx), the mean effect of heart-rate adjustment was minor relative to typical beat-to-beat variability and available precision of clinical phase selection.ConclusionHigh temporal resolution imaging of coronary motion can be used to predict the optimal acquisition phase in cardiac CT. The optimal phase for cardiac CT imaging within mid-diastole increases with increasing heart rate although the magnitude of change is small.