Most myocardial T1 mapping techniques, such as modified Look–Locker inversion recovery (MOLLI), generate one T1 map per breath‐held acquisition (9–17 heartbeats), which prolongs multislice protocols and may be unsuitable for patients with breath‐holding difficulties.Myocardial T1 mapping schemes of 2–5 heartbeats.To develop and characterize novel shortened inversion recovery based TProspective.2 phantom, 16 healthy volunteers, and 24 patients.Numerical simulations, agarose/NiCl1.5T/MOLLI.1 mapping schemes were characterized and compared with a conventional MOLLI scheme (5‐(3)‐3) in terms of accuracy, precision, spatial variability, and repeatability.All shortened Tt‐tests, Bland–Altman analysis, and Pearson correlation analysis.Kruskal–Wallis, Wilcoxon rank sum tests, analysis of variance, Student's 1 time variations (≤2% for T1 times ≤1200 msec) and limited penalty of precision (by a factor of ~1.4–1.5) when compared with MOLLI in numerical simulations. In phantom, differences between all schemes in terms of accuracy, spatial variability, and repeatability did not reach statistical significance (P > 0.71). In healthy volunteers, there were no statistically significant differences between all schemes in terms of native T1 times and repeatability for myocardium  and blood . All shortened schemes led to a limited increase of spatial variability for native myocardial T1 mapping with respect to MOLLI (by a factor of 1.2) (P < 0.0001). In both healthy volunteers and patients, the two‐heartbeat scheme and MOLLI led to highly linearly correlated T1 times (correlation coefficients ≥0.83).All shortened schemes provided limited T1 mapping scheme yields a 5‐fold acceleration compared with MOLLI, with highly linearly correlated T1 times, no significant difference of repeatability, and limited spatial variability penalty at 1.5T. This approach may enable myocardial T1 mapping in patients with severe breath‐holding difficulties and reduce the examination time of multislice protocols.The proposed two‐heartbeat TLevel of Evidence: 1Technical Efficacy Stage: 3J. Magn. Reson. Imaging 2019;50:641–654. The combination of native and postcontrast myocardial and blood T1 times enables the estimation of the extracellular volume (ECV) fraction,Native myocardial longitudinal relaxation time T is sensi1 mapping and often use magnetization preparation pulses such as inversion,1‐weightings is acquired and followed by voxel‐wise fitting to a model of the measured signal to generate a T1 map.1 times have been shown to be dependent on several parameters including T2,1 mapping due to its high reproducibility/high repeatability, high precision/low spatial variability, and high map quality/low artifact level.A variety of imaging sequences have been proposed for myocardial T1‐weighted images and inversion pulses.1 map reconstruction of MOLLI sequences commonly uses a three‐parameter (3P) fitting model of the inversion recovery signalTypical MOLLI sequences consist of several inversion pulses, each followed by a series of electrocardiogram (ECG)‐triggered single‐shot acquisitions. A variety of MOLLI schemes have been proposed using different amounts of T1 map per breath‐hold, thus limiting the total measurement time. Most MOLLI schemes acquire data over 9–17 heartbeats.1 mapping (from single slice to full ventricular coverage) may also depend on the pathology being assessed.1 mapping with full ventricular coverage requires repeated breath‐held acquisitions, each for a single slice, thus increasing patient discomfort and prolonging scan time. Therefore, shorter breath‐holding requirement for myocardial T1 mapping would be advantageous for multislice T1 mapping protocols.The common acquisition manner in MOLLI sequences is a single T1 mapping schemes of 2–5 heartbeats.In this work, we sought to develop and characterize novel shortened inversion recovery based TAll imaging was performed using a 1.5T MR scanner . This work was conducted according to the Declaration of Helsinki and Good Clinical Practice guidelines and was approved by a local Research Ethics Committee . Informed consent was obtained from all participants.1 mapping schemes were evaluated using two, three, four, or five ECG‐triggered single‐shot images following a single inversion pulse  fitting model and a standard 3P fitting model were evaluated. 2P‐n (n = 2–5) and 3P‐n (n = 3–5), hereafter referred to as T1 mapping using n images following a single inversion pulse with the 2P and 3P fitting models, respectively. These schemes were compared with a conventional 5‐(3)‐3 MOLLI scheme . Note that 3P‐5 can be seen as an approximation of ShMOLLI for native myocardial T1 mapping.Two T1 fitting, an exhaustive search was performed over a normalized signal dictionary created using the proposed following model:1 strength of 14.4 μT) over typical native and postcontrast myocardial T1 ranges , B0 field inhomogeneity , B1 field inhomogeneity  and a typical myocardial T2 time of 45 msec.1/T2/B0/B1 regimes. The average inversion factor δ was estimated as 0.9633. The signal dictionary Sdict(TI) was created for a 1‐msec‐step T1 range of  msec, which covers the entire range of native and postcontrast myocardial and blood T1 times.For Trestored(TIj)  was computed from the measured signal Smeas(TIj)  using a modified PSIR approach. The first image with the shortest TI (TI1 = TImin = 100 msec), which is one of the only two common images among all schemes, was chosen as the reference phase image with "negative" polarity  = –Smeas(TI1)). Using Bloch equations simulation of the sequence, this assumption was valid for any T1 time > 172 msec (in the presence of any T2 times ≥30 msec and imaging flip angles ≤85°), thus including the entire physiological ranges of native/postcontrast T1 times in myocardium, blood, and fat  as:1‐weighted images in the 2P‐n scheme, Sdict¯ and Srestored¯ are the signal amplitude averages over all TIs (TI1‐TIn) of a dictionary entry and the polarity‐restored measured signal, respectively. Dictionary matching was finally performed by minimizing the L2‐norm between Srestoredscaled and each dictionary entry.Before dictionary matching, the polarity‐restored measured signal S1 times were subsequently HR‐corrected as described in the second next section.This reconstruction was implemented on an affordable graphics processing unit (GPU)  using the compute unified device architecture (CUDA) to enable high‐performance computing. The parallelization level was set to the pixel level. This implementation was compared with a central processing unit (CPU)‐only implementation entirely developed in C++. The resulting TT1* are the model parameters.T1* is often referred to as the apparent T1 time. A PSIR reconstruction was employed to restore the signal polarity as described above. A Levenberg–Marquardt solver, provided previously,T1*. T1 times were then approximated as:1 times with δ, the inversion factor of the inversion pulse as described above.1 times was performed as described in the next section.The signal of the 3P fitting model is defined as:1 times using MOLLI have been shown to be HR‐dependent.1 errors is proposed for each of the eight evaluated T1 mapping scheme 2P‐n (n = 2–5) and 3P‐n (n = 3–5) as well as MOLLI. This correction approach was created using phantom experiments in nine agarose/NiCl2 vials with different T1/T2 times representing typical T1/T2 ranges of native and postcontrast myocardium and blood . Imaging parameters are described in the next section. The T1 dependence on HR of each T1 mapping scheme is shown in 1 over physiological HR (40–120 bpm) was observed for different T1 mapping schemes, which is vial‐ and thus T1‐dependent. Individual linear regressions were performed for each T1 mapping scheme and each vial, leading to different slopes and offsets for each T1 mapping scheme and vial  and blood , respectively. Each correction model was created as follows. An empirical method was established to correct the HR‐dependent T1 errors by aligning measured T1 times to the value at a theoretical HR of 60 bpm (T1(corr)) based on:Note that this relationship is also T1 times (and not limited to the ones corresponding to the phantom), a parabolic relationship between slope, offset, and T1 was empirically defined as:1, a2, and a3 are the coefficients of the parabolic function and were obtained from least square fitting (see To make this model applicable to any Tting see . Using E1 (T1(corr)) can be computed from Eqs. In such case, the offset can be derived as:offsetT1=1 accuracy and precision of the proposed shortened T1 mapping schemes and the conventional 5‐(3)‐3 MOLLI scheme. The Bloch equations were used to simulate the signal of each sequence by measuring the simulated transverse magnetization at the k‐space center of each imaging readout. All numerical simulations used a simulated HR of 60 bpm and the following imaging parameters: TR/TE/TI1/TI2 = 2.7/1.1/100/180 msec, 62 phase encoding lines in linear ordering, partial Fourier factor = 7/8, and five start‐up pulses. The slice profile of the employed excitation pulse  was estimated by Bloch equations simulation over the same T1/T2 ranges and B0/B1 inhomogeneities as used for the inversion pulse. A resulting average excitation flip angle of 26° was obtained and used for the simulations. An average inversion flip angle of 164° corresponding to δ = 0.9633 was also used for the simulations.Numerical simulations were used to study the T1 times (300–1500 msec in steps of 50 msec) and myocardial T2 times (30–70 msec in steps of 5 msec). Monte‐Carlo simulation  were performed for each pair of simulated T1/T2 times using random noise corresponding to a signal‐to‐noise ratio (SNR) of 50 in the longest‐TI image of the conventional MOLLI scheme (TImax = 4100 msec). Accuracy was assessed as the average over the N repetitions of the difference between the simulated and estimated T1 times. Precision was defined as the standard deviation (SD) of the estimated T1 times over the N repetitions.Numerical simulations were performed over a range of typical myocardial T1 accuracy and precision, additional numerical simulations were performed for different SNR  and T1 range (300–1500 msec in steps of 50 msec), and a fixed T2 times of 45 msec.To evaluate the influence of SNR on T1 mapping schemes and the conventional 5‐(3)‐3 MOLLI scheme in a phantom with nine agarose/NiCl2 vials of different T1/T2 times in the ranges for native and postcontrast myocardium and blood . To this end, the conventional 5‐(3)‐3 MOLLI acquisition scheme was used. The first two to five ECG‐triggered single‐shot images following the first inversion pulse were used for 2P‐n (n = 2–5) and 3P‐n (n = 3–5). The conventional MOLLI reconstruction using all images  was also performed. The 2D balanced steady‐state free precession (bSSFP) imaging readout used the following parameters: TR/TE/flip angle = 2.7 msec/1.1 msec/35°, field of view (FOV) = 360 × 306 mm2, voxel size = 1.4 × 2.1 mm2, three slices, slice gap = 8 mm, slice thickness = 8 mm, GRAPPA factor = 2, partial Fourier factor = 7/8, bandwidth = 1085 Hz/px, 62 phase‐encoding lines in linear ordering, and five start‐up pulses.The proposed 2P fitting model was characterized and compared with the conventional 3P fitting model using different shortened T1 accuracy, spatial variability, and repeatability. The 5‐(3)‐3 MOLLI acquisition scheme with a simulated HR of 60 bpm was repeated five times for assessment of T1 accuracy, spatial variability, and repeatability of all schemes. The reference T2 times were obtained from the manufacturer. The reference T1 times were obtained using inversion recovery based spin echo T1 mapping . A region of interest (ROI) was manually drawn for each vial. Measured T1 times were obtained for each vial as the averages over the five repetitions of the mean T1 times in the corresponding ROI. T1 accuracy was measured as the difference between measured and reference T1 times. T1 spatial variability was measured for each vial as the average over the five repetitions of the SD of T1 times in the corresponding ROI. T1 repeatability was estimated for each vial as the SD over the five repetitions of the mean T1 times in the corresponding ROI.Experiment #1: Characterization of T2 and long‐T2 vials. Note that the data used for creating the HR correction models were obtained from a separated study performed earlier on a different day. T1 variation as the average absolute differences with respect to the value at the reference HR of 60 bpm, described as:1 mapping sensitivity to HR of each evaluated T1 mapping schemes.Experiment #2: Characterization of the proposed HR correction. The performance of the proposed HR correction was evaluated using a second dataset of measurements where the 5‐(3)‐3 MOLLI scheme was acquired with different simulated HRs ([40–120] bpm in steps of 10 bpm). All 2P‐n and 3P‐n reconstructions were performed without and with HR correction using the two different correction models for short‐T1 mapping was performed using the 5‐(3)‐3 MOLLI acquisition scheme and the imaging parameters described in the phantom study. This protocol was modified to acquire three slices in the short axis orientation, each in a separated breath‐hold. This acquisition was repeated twice for each healthy volunteer. All 2P‐n and 3P‐n reconstructions were performed without and with HR correction using the short T2 and long T2‐based correction models for myocardial and blood T1 analyses, respectively.In vivo characterization was performed in 16 healthy volunteers . Native myocardial T1 analysis was based on a 16‐myocardial‐segment model,1 analysis was based on a single ROI drawn inside the left ventricular blood pool in the basal slice with careful exclusion of the papillary muscles. A representative example of ROIs used for myocardial and blood T1 quantification is shown in 1‐weighted images. Myocardial segments with apparent severe artifacts in the MOLLI T1 maps were discarded from quantitative myocardial T1 analysis of all schemes. Myocardial and blood T1 times, spatial variability, and repeatability were assessed for each subject. A segment‐wise T1 time was calculated as the average over the two repetitions of the T1 mean in each myocardial segment and blood pool. Segment‐wise T1 spatial variability was measured as the average over the two repetitions of the T1 spatial SD in each myocardial segment and blood pool. Segment‐wise T1 repeatability was estimated as the absolute difference between the two repetitions of the T1 mean in each myocardial segment and blood pool. The corresponding subject‐wise T1 time, spatial variability, and repeatability were computed as the averages over all nondiscarded segments, respectively.Myocardial T1 mapping was performed in all patients. Eighteen of these patients  received an injection of 0.1 mmol/kg of gadobutrol  as part of the clinical protocols. Postcontrast T1 mapping was thus also performed in these patients. Native and postcontrast myocardial T1 mapping were performed using the same 5‐(3)‐3 MOLLI acquisition scheme and imaging parameters described in the healthy volunteer study. Three slices were acquired in the short axis orientation, each in a separated breath‐hold. All 2P‐n and 3P‐n reconstructions were performed without and with HR correction using the short T2 and long T2‐based correction models for myocardial and blood T1 analyses, respectively. Subject‐wise myocardial and blood T1 times were measured as described in the healthy volunteers section.Twenty‐four consecutive patients  referred for clinical cardiac MRI in our center were recruited. Native myocardial T1 mapping schemes in phantom and in vivo, respectively. A result was considered statistically significant at the 5% significance level  and all tests were two‐tailed. When the Kruskal–Wallis or one‐way ANOVA test demonstrated statistical significance, Wilcoxon rank sum tests or Student's t‐tests were performed for each pair of T1 mapping schemes using Bonferroni correction, which resulted in a statistical significance threshold of 0.05/C28 ≈ 0.0018. Correlation and agreement analyses in the form of Pearson correlation analysis and Bland–Altman plots with limits of agreement, respectively, were performed between each shortened T1 mapping scheme and MOLLI in terms of subject‐wise native/postcontrast myocardial/blood T1 times. Bland–Altman limits of agreement were calculated as the mean difference between methods  ± 1.96 × (SD of differences); ~95% of differences between methods should lie within these limits.Kruskal–Wallis test and a one‐way analysis of variance (ANOVA) test were used to compare all T1 map (256 × 256 matrix size) were 7, 8, 11, and 13 seconds using a CPU‐based implementation, respectively. These reconstruction times were reduced to 0.2 seconds for all 2P reconstructions using the proposed GPU‐based implementation. Reconstruction times for all CPU‐based implementations increased linearly with the number of slices, while GPU‐based reconstruction times increased at a slower rate. For example, 2P‐2, 2P‐3, 2P‐4, and 2P‐5 reconstruction times for 10 T1 maps (256 × 256 × 10 matrix size) were 65, 83, 104, and 130 seconds using the CPU‐based implementation, and were reduced to 1, 1.3, 1.7, and 2 seconds using the proposed GPU‐based implementation, respectively.2P‐2, 2P‐3, 2P‐4, and 2P‐5 reconstruction times for one T1 mapping schemes are shown in Fig. 1 time variation (≤2%) with respect to MOLLI for the entire range of T1 times . All 2P‐n schemes provided limited T1 time variations (≤2%) with respect to MOLLI for T1 times ≤1200 msec but resulted in reduced accuracy for longer T1 times. All shortened T1 mapping schemes led to a precision penalty with respect to MOLLI by a factor of ~1.4–1.5. All studied schemes were T2‐dependent. Lower T2 times were associated with decreased accuracy for all schemes.Accuracy and precision of all evaluated T1 time estimates of all schemes  are shown in Fig. 1 times for long‐T2 vials  with an average error of <11 msec for all schemes. All schemes led to underestimated T1 times for short‐T2 vials  with respect to the reference T1 times. Although MOLLI tended to provide slightly lower underestimation than shortened T1 mapping schemes , these differences were not statistically significant (P = 1.00). For a typical native myocardial T1 range , 2P‐2 and 2P‐5 led to an underestimation of 25 msec and 22 msec with respect to MOLLI, while the other shortened T1 mapping schemes led to an underestimation of <10 msec. The 2P‐n (n = 2–5) schemes tended to provide lower spatial variability than the 3P‐n (n = 3–5) schemes for typical postcontrast T1 range (<450 msec), while 2P‐2 and 3P‐3 tended to show higher spatial variability than other schemes for long T1 times (>1400 msec). Although all schemes tended to provide higher spatial variability than MOLLI , and lower repeatability than MOLLI , these differences were not statistically significant .Experiment #1: Characterization of T1 times. After the proposed HR correction, T1 variation over all HR was reduced from a maximum of 55 msec to a maximum of 7 msec for all vials and T1 mapping schemes.Experiment #2: Characterization of the proposed HR correction. 1 maps of a healthy volunteer using all T1 mapping schemes are shown in Fig. 1 ranges for myocardium and blood. The perceived noise, however, was higher in the left ventricular blood pool for all shortened T1 mapping schemes.Example native myocardial TThe average HR over all healthy volunteers was 68 ± 12 bpm (51–90 bpm). On average, over all healthy volunteers, the magnitude of HR correction for native myocardium ranged from 0.03 ± 0.05 msec (≤0.17 msec) using 2P‐5 to 12 ± 9 msec (≤30 msec) using 2P‐2, while the magnitude of HR correction for native blood ranged from 3 ± 2 msec (≤8 msec) using 2P‐5 to 14 ± 12 msec (≤41 msec) using 2P‐2.1 times (P = 0.21), which were all in the range of 977–997 msec . However, they all had increased spatial variability by a factor of 1.2 with respect to MOLLI    was discarded from the analysis. There were no statistically significant differences between all schemes in terms of native myocardial T% was dis1 times, which were in the range of 1583–1623 msec (P = 0.79) , which were all inferior to MOLLI  , which were in the range of 7–15 msec for all schemes  Fig. d. 2P‐2 a1 times, spatial variability, and repeatability of 2P‐2 and MOLLI are shown in Fig. 1 times, spatial variability, and repeatability was of similar range between 2P‐2 and MOLLI ).Segment‐wise assessment of native myocardial T1 maps obtained in two patients using all the evaluated T1 mapping schemes are shown in Figs. 1 range were obtained for all schemes, although a higher perceived noise level can be observed in the left ventricular blood pool using shortened T1 mapping schemes.Example native and postcontrast myocardial T1 mapping and 11 of 288 myocardial segments (4%) from two patients for postcontrast T1 mapping were discarded from the quantitative analysis due to substantial artifacts and/or motion. HR correction of native myocardial T1 times led to changes from 0.04 ± 0.06 msec (≤0.25 msec) using 2P‐5 to 13 ± 12 msec (≤43 msec) using 2P‐2, while HR correction of native blood T1 times led to changes from 3 ± 3 msec (≤11 msec) using 2P‐5 to 14 ± 13 msec (≤47 msec) using 2P‐2. The magnitude of HR correction for postcontrast myocardial and blood T1 times was <4 msec using all schemes.Over all patients, the average HR was 68 ± 14 bpm (36–98 bpm). In all, 34 of 384 myocardial segments (9%) from five patients for native T1 times for myocardium and blood using all schemes are shown in Fig. 1 ranges  (P ≥ 0.19).Subject‐wise native and postcontrast T1 times  and postcontrast myocardial/blood T1 times (patients only) are shown in Fig. 1 times was 0.83, and was ≥0.96 for all other T1 ranges. All other shortened T1 mapping schemes were also strongly correlated with MOLLI for each T1 range (Pearson correlation coefficient ≥ 0.90). For native blood T1 times, 2P‐2 and MOLLI were in moderate agreement . For other T1 ranges, 2P‐2 and MOLLI were in good agreement with limited bias magnitude (≤17 msec) and narrow width of 95% limits of agreement (<43 msec). All other shortened T1 mapping schemes were in good agreement with MOLLI for native myocardial T1 mapping, with limited bias magnitude (≤19 msec) and narrow width of 95% limits of agreement (<39 msec).The Pearson correlation and Bland–Altman analyses in terms of subject‐wise native myocardial/blood T1 maps obtained in a patient who was unable to sustain a stable breath‐hold for the entire duration of the acquisition. MOLLI led to substantial T1 map artifacts in both mid‐ventricular and apical slices, which were then discarded for all schemes from the quantitative analysis. All shortened T1 mapping schemes provided improved map quality in this patient.1 mapping schemes combined with a novel 2P fitting model for myocardial T1 mapping. These methods were successfully evaluated in numerical simulations, phantom, healthy volunteers, and patients. Compared with the conventional MOLLI 5‐(3)‐3 scheme, shortened T1 mapping schemes (down to two heartbeats only) combined with the proposed 2P fitting model resulted in no significant differences in terms of T1 estimates and repeatability and had similar T1 ranges as well as limited reduction of precision/increase of spatial variability. Importantly, the resulting native/postcontrast myocardial/blood T1 times measured by all shortened T1 mapping schemes were highly linearly correlated with the corresponding values measured using MOLLI. Finally, the proposed GPU implementation of the exhaustive search‐based optimization of the 2P fitting model enables fast T1 map reconstruction, which is suitable for clinical application.In this work, we proposed and evaluated shortened T1 times, precision, and repeatability of MOLLI were in good agreement with previous works.1 mapping schemes provided T1 times in a similar range as MOLLI for all native/postcontrast myocardial/blood T1 ranges. Moreover, all proposed shortened T1 mapping schemes have the same acquisition manner as 5‐(3)‐3 MOLLI. These observations suggest that, similar to MOLLI, these shortened T1 mapping schemes are also sensitive to T2 relaxation,1 mapping schemes at higher fields such as 3T remains to be demonstrated and will be the focus of future work.In vivo myocardial T1 mapping schemes for postcontrast myocardial T1 mapping was demonstrated in numerical simulations, phantom, and patients. The spatial variability penalty of shortened T1 mapping schemes was more pronounced for typical short postcontrast T1 times than typical native myocardial T1 times, which could be interpreted as a consequence of lacking a second short‐TI image. For short T1 times , all 2P‐n schemes had higher precision and lower spatial variability than the shortened 3P‐n schemes. Therefore, 2P‐n schemes may be advantageous over shortened 3P‐n schemes in the context of ECV mapping.The feasibility of the shortened T1 mapping schemes resulted in an increase of T1 spatial variability (by a factor of 1.2) for native myocardial T1 times when compared with MOLLI. This increase in spatial variability between 3P‐5 (approximated ShMOLLI for native T1) and MOLLI is in good agreement with previous comparison of ShMOLLI and MOLLI at 1.5T.n = 2/3/4) did not result in a further increase of spatial variability  of native myocardial T1 time estimates when compared with 3P‐5. This suggests that the impact of each T1‐weighted image in the fitting process is dependent on its corresponding TI, similar to findings observed for saturation recovery‐based techniques.1 range of interest) have reduced T1‐weighted contrast and may thus have reduced contributions to the precision of T1 estimates.The healthy volunteer study demonstrated that all proposed shortened T1 times such as in vivo native blood T1 times, 2P‐2 led to a larger increase of spatial variability by a factor of 1.7 with respect to MOLLI, while other 2P‐n schemes still maintained a limited increase of T1 spatial variability by a factor < 1.28. This could be explained by the lack of sampling of long TI times in the 2P‐2 scheme. Therefore, 2P‐3 could be a valuable alternative to 2P‐2 for native T1 mapping, as it offers lower spatial variability for blood T1 quantification. However, blood T1 time is usually measured as the spatial average over a large ROI, which may mitigate this effect for 2P‐2, as no statistically significant differences were found in terms of repeatability for blood T1 quantification among all methods.For long T1 mapping based on the acquisition of only two images has been previously proposed using the AIR technique, which is based on saturation recovery.1 mapping by a factor of 2.5 when compared with MOLLI.1 mapping by a factor of 1.2 when compared with MOLLI, and may thus be a valuable alternative for myocardial T1 mapping, as the acquisition can be performed in just two heartbeats.Myocardial T1 times guarantees finding the global minimum of the cost function over a least‐square optimization, and was successfully used with the 2P model. Although such an approach is more computationally intensive, the proposed GPU‐based implementation substantially reduced the computation time to the subsecond scale per map, which is suitable for clinical application. Our results demonstrate that GPUs are particularly well suited for the reconstruction of T1 maps. This finding is in good agreement with prior studies where GPU‐based reconstruction substantially reduced the computation time of standard MOLLI reconstructions.The proposed 2P model‐based fitting technique enables correction for surface coil sensitivity variations using the normalization step of the dictionary matching. Exhaustive search‐based optimization over the entire range of physiological myocardial and blood native/postcontrast TAlthough 2P‐2 provides a 5‐fold acceleration with respect to MOLLI, the overall acceleration rate in multislice protocols may be reduced by the required rest‐periods between breath‐holds. However, the repetition of two‐heartbeat breath‐holds may enable the use of shortened recovery periods, improve patient comfort, and increase the probability of successful breath‐holds.1 estimates, which will be the focus of future work.Bloch equations simulation was only performed on the employed inversion pulse to determine the inversion factor in the proposed 2P fitting model. However, Bloch equations simulation could also be used for the whole pulse sequence to generate the signal dictionary.0 range if fatty tissues are considered. The use of a weighted average over the B0 and B1 ranges could also be considered to further improve the accuracy of the inversion factor estimates.In this work, the slice profile of the inversion pulses was approximated by one flip angle. Alternatively, the use of subslice‐based simulations may improve the accuracy of the slice profile correction.1 times. Although this technique was found robust for the 2P fitting model with all T1 ranges, we decided to use the PSIR approach for uniformity consideration.In this work, PSIR was employed for all reconstructions. Alternatively, a multifitting approach could have been used for all these reconstructions.1 spatial variability and repeatability, we decided to discard the registration step of the reconstruction and discard datasets with inappropriate breath‐hold. Nevertheless, retrospective image registration has been shown to improve the robustness of myocardial T1 mapping.1 mapping schemes will be the focus of future work. Finally, the use of shortened T1 mapping schemes has the potential to improve the native registration of the T1‐weighted images in patients unable to sustain long stable breath‐hold. This will be evaluated in future work in a larger patient cohort.No in‐plane motion correction was employed in this work. Image registration algorithms may provide different performance based on the amount and contrast of images used during the registration process. Therefore, to prevent such bias during in vivo evaluation of T1 mapping schemes showed varying degrees of HR dependence. These results are aligned with previous studies that demonstrated the HR dependence of MOLLI T1 times.1 variation to <10 msec for the entire T1 ranges. Alternative HR correction models have been proposed previously using a linear correction model based on measured T1 and HR.1‐independent. Although we showed that a linear relationship between HR and measured T1 times is valid for a given T1 range, the linear regression slope and offset are also T1‐dependent. Therefore, T1‐dependent correction models were found more accurate than a simple T1‐independent linear model.The evaluated shortened T1 times is mainly due to the inaccuracies of the employed fitting models, partly caused by their T2 dependence.1 times were different, which could be explained by their large T2 difference (>150 msec vs. ~45 msec). Therefore, we decided to reconstruct two differently HR‐corrected T1 maps per slice: one with myocardium‐based HR correction and one with blood‐based HR correction. Automatic segmentation of the blood pool based on thresholding of T1 maps has been previously proposed for ECV quantification.1 map for both the myocardium and blood.The HR dependence of T1 mapping schemes have been evaluated from a subset of a conventional 5‐(3)‐3 MOLLI scheme. This choice was made to minimize the number of required breath‐holds per subject. Second, the spatial variability measured as the SD over an ROI was used as a surrogate of the T1 precision, as commonly reported in prior studies.1 time estimates. Third, trends were visually observed between MOLLI and the proposed shortened T1 mapping schemes in terms of spatial variability and repeatability in phantom. However, the differences did not reach statistical significance, which may be due to insufficient statistical power related to the limited number of vials available in our phantom. Fourth, the patient study was based on a small cohort of consecutive patients referred for clinical cardiac MRI. The benefit of these techniques in a larger patient cohort including patients with breath‐holding difficulties remains to be demonstrated and will be the focus of future studies. Furthermore, evaluation of this technique would be required in a cohort of patients with proven cardiac disease where mapping has clinical utility, such as with hypertrophic cardiomyopathy and Anderson‐Fabry's disease.This work has some limitations. First, the shortened T1 mapping scheme yields a 5‐fold acceleration compared with MOLLI, with highly linearly correlated native/postcontrast myocardial/blood T1 times, no significant difference of repeatability, and a limited spatial variability penalty at 1.5T. This approach may be a valuable alternative for myocardial T1 mapping in patients with severe breath‐holding difficulties and reduce examination time of multislice protocols.In conclusion, the proposed two‐heartbeat TSupplementary Material 1 5‐(3)‐3 MOLLI pulse sequence and PSIR T1 map reconstruction schemes. In the pulse sequence, ECG‐triggered 2D bSSFP multi‐TI imaging is performed for each slice. 2P‐n/3P‐n represent the T1 map reconstruction schemes using the proposed 2P/3P fitting models with the first n images in the acquisition order, respectively.Supplementary Material 2. Simulated inversion recovery signal polarity as a function of T1 and T2 times for different flip angles (FAs). Bloch equations simulation of the sequence were used to determine the signal polarity of the shortest inversion time (TI) image . Simulations were performed for different T1 times (range: 100‐300 ms), T2 times (range: 30‐300 ms) and FAs (range: 10‐85°). Red and blue regions indicate "positive" and “negative” polarities of the shortest TI image, respectively. Areas with negative polarity (blue) indicate conditions where the proposed PSIR assumption is valid. The minimum T1 times satisfying the proposed PSIR assumption increases with higher FAs and shorter T2 times. A T1 time of 172 ms was the lower bound ensuring the validity of the proposed PSIR assumption for the entire ranges of studied FAs/T2 times, which is smaller than the lower limit of the physiological ranges of native/post‐contrast T1 times in myocardium, blood and fat.Supplementary Material 3. HR dependence of T1 estimates using 2P‐2 and MOLLI in phantom experiments. Each subfigure represents a different vial. The reference T1 and T2 values are given for each vial. Vial‐wise linear regression (dashed lines) of T1 vs. HR was performed for 2P‐2 (green) and MOLLI (black). Individual linear dependence of T1 on HR was observed for each vial. A stronger HR dependence was observed in the presence of long T1 times and short T2 times.Supplementary Material 4. Dependence of T1‐HR linearity on T1 for 2P‐2 and MOLLI in phantom experiments. Parabolic regression (dashed curves) of slopes vs. offsets  was performed for 2P‐2 (green) and MOLLI (black) on both short‐T2 and long‐T2 vials mimicking myocardium and blood, respectively.Supplementary Material 5. Representative example of ROIs used for myocardial and blood T1 quantification. The blue contours represent the segmented myocardial region while the black contour represents the area used for blood T1 analysis.Supplementary Material 6. Simulated T1 accuracy and precision as a function of T1 for different SNR. Although SNR had limited impact on T1 accuracy of all techniques, lower SNR resulted in precision penalty for all techniques as expected. However, SNR had limited influence on the relative precision penalty of all shortened T1 mapping schemes with respect to MOLLI which remained by a factor of 1.4‐1.5 for all SNR.Supplementary Material 7. T1 variation over different HRs (40‐120 bpm) before and after the proposed HR‐correction using all T1 mapping schemes. Each subfigure represents a different vial. The reference T1 and T2 values are given for each vial. The proposed HR correction reduced T1 variations to a maximum of 7 ms in all cases.Supplementary Material 8. Example native myocardial T1 maps obtained in a 32 yr female patient (HR 61 bpm) with severe left ventricular systolic dysfunction and pericardial effusion using all T1 mapping schemes (same patient as shown in Figure Click here for additional data file.


The aim of this study was to determine non-invasive diagnostic markers by echocardiography that differentiate ischemic dilated (ICM) from non-ischemic dilated cardiomyopathy (NICM) in patients with new onset heart failure. We identified 100 consecutive new heart failure patients with dilated cardiomyopathy . Clinical risk factors, medication history, serum biomarkers, ECG and echocardiographic variables were compared between the ICM and NICM groups (as confirmed by coronary angiography). Mean age, left ventricular size and ejection fraction were 56 years, 6.1 cm and 26% respectively. A total of 24% had ICM. Patients with ICM were older . No significant difference was observed between ICM and NICM among 18 clinical variables, 7 laboratory tests, 6 EKG parameters and 10 of the 13 echocardiographic markers evaluated. Segmental wall thickness variability, regional wall motion abnormality and RV enlargement on echocardiogram (echo) differentiated ICM from NICM. Segmental thickness variability outperformed wall motion abnormality in diagnosing ICM with a sensitivity and specificity of 79.2 and 98.7% versus 62.5 and 84.2% respectively. RV enlargement was not sensitive but 90.6% specific for predicting NICM. Myocardial segmental thickness variability on echo, resulting from thinned infarcted or hibernating myocardium, is a highly sensitive and specific marker to differentiate ICM from NICM in new onset heart failure. Echocardiography (echo) constitutes initial diagnostic work-up of patients presenting with new onset heart failure . FurtherWe retrospectively identified one hundred consecutive patients over a period of 3 years (2011–2014) admitted to a single center for new-onset systolic heart failure, who had dilated cardiomyopathy on echo (dilated left ventricle with an ejection fraction less than 40%), and underwent angiographic evaluation for ICM. After excluding those with (1) known history of dilated cardiomyopathy; (2) previous diagnosis of heart failure ; (3) previous diagnosis of CAD ; (4) acute coronary syndrome presentation; and (5) missing echo or angiographic data; 118 patients were identified. Further, those with (6) severe primary valvular heart disease that could contribute to LV dilatation (n = 2); (7) non-dilated cardiomyopathy  (n = 9); and (8) poor quality echo images precluding accurate segmental wall thickness/wall motion assessment (n = 7) were excluded. A total of 100 patients were included in the final analysis.A thorough review of electronic medical records was conducted to collect demographics information, co-morbidities, clinical presentation, laboratory markers, pre-hospital medications, ECG, and the echo parameters at baseline. Myocardial segmental analysis was confirmed by the consensus read of two National Board of Echocardiography certified cardiologists. Investigators collecting baseline data and reviewing echo were blinded to the results of angiography. A single investigator, who was not involved in data collection, had access to angiography results. On the completion of data collection, this investigator categorized the patients into two groups (ICM and NICM) for statistical analysis. ICM was defined as severe ≥ 70%) stenosis in the left anterior descending or a multi-vessel coronary distribution. NICM had no angiographic stenosis, mild to moderate coronary stenosis (< 70% stenosis), or severe single-vessel stenosis in a coronary vessel other than the left main or left anterior descending artery [0% stenosAmerican heart Association’s sixteen-segment model was used for regional left ventricular (LV) wall analysis –10. BasaRWMA was defined as per American Society of Echocardiography guidelines; hypokinesis, akinesis, dyskinesis, and aneurysmal segments were considered abnormal , 11. IsoCardiac chamber quantification and function was estimated per ASE guideline statement . BiplaneDemographic, clinical, laboratory, ECG, and echo parameters were compared between the ICM and NICM groups. Continuous variables were reported as mean and standard deviation and discrete variables as percentage. Analysis of variance (ANOVA) and Chi square tests were used to compare these variables, respectively. A two-sided P-value less than 0.05 was considered statistically significant. Variables that were significantly different between the comparison groups were evaluated for their sensitivity, specificity, negative and positive predictive values, and diagnostic accuracy for the diagnosis of ICM with invasive coronary angiography as the gold standard. Receiver operating characteristic curve analysis was performed. The intra-class correlation coefficient (ICC) was calculated as a measure of the intra- and inter-observer variability of the STV. A P value < 0.05 was considered significant.SPSS 20  was used for all statistical analysis.The mean age of the study population was 56 years with 68% males. Mean LV size and LV ejection fraction were 6.1 cm and 26%, respectively. A total of 24% had ICM confirmed by coronary angiogram. Patients with ICM were older (65 vs. 53 years)  but RV systolic function and RV systolic pressures were similar. Using the pre-specified cut-off, significant STV was observed in 79% of ICM (mean STV 63%) and only 1% of NICM (mean STV 89%) (P < 0.001). ICM patients also had more RWMA than NICM patients .Diagnostic test evaluations for STV, RWMA, and RV enlargement are elaborated in Table Heart failure is a frequently diagnosed condition and a common cause of significant morbidity and mortality . A thoroTo distinguish ICM from NICM, ACCF/AHA heart failure guidelines suggest that coronary angiogram be performed in patients presenting with de novo heart failure  . HoweverIn this study, we evaluated 18 clinical variables, 7 laboratory tests, 6 EKG parameters, and 13 echocardiographic markers with the goal of finding a diagnostic market that would reliably distinguish ICM from NICM (Table Wall motion is a dynamic motion of the ventricular wall in systole and diastole that may be impaired by ischemia/infarction resulting in RWMAs. Wall thickness, on the other hand is more objective as measured at a single point in time, such as end systole or end-diastole. We measured end-diastolic wall thickness in this study as end-diastole represents true resting physiologic state of the myocardium. End-systolic measurement may be more prone for artefactual errors due to inclusion of the adjacent structures such as chordae and papillary muscle. Mechanisms of ischemic wall thinning are well described. Myocardial infarction causes myocyte necrosis and replacement with collagen scar resulting in thinning of the wall in the distribution of culprit coronary vessel , 20. SimWe systemically evaluated pre-angiographic non-invasive markers in new onset heart failure with dilated cardiomyopathy and found the presence of STV, RWMA, and normal RV size on echo to correspond to coronary vascular etiology. Among these parameters, STV by itself was the most sensitive and specific diagnostic marker of ICM with a predictive accuracy of 94%. Using STV in conjunction with RWMA could further increase the diagnostic test performance of STV. Visualization of either STV or RWMA could increase the sensitivity of identifying ICM, whereas the presence of both STV and RWMA in a patient made the test 100% specific for ICM. RV enlargement was found to be a sensitive but non-specific marker for NICM Table .To our knowledge, this is the first study to report STV on echocardiography as a diagnostic marker of ICM. RWMA on the other hand has been studied previously, albeit with disparate findings –6. In thOur study has a few limitations. The use of coronary angiography as the reference standard for distinguishing the cardiomyopathies may be a potential limitation. Further studies are needed to assess the reproducibility of this single center experience with a small number of patients and overcome potential reader bias in the interpretation of segmental wall analysis. Our study findings are not applicable to patients with suboptimal echo image quality from poor ultrasongraphic windows and technique. This may be overcome partially with the use of echocardiographic contrast agent. Prospective validation of this retrospective study would be desirable.Dilated cardiomyopathy is a common disease process in patients presenting with new onset heart failure. In this patient population, STV as estimated by transthoracic echocardiography can accurately distinguish ICM from NICM. RWMA in isolation is a less accurate marker to make this distinction. Used in conjunction, these two parameters can reliably delineate ICM from NICM.These echocardiographic markers to distinguish the underlying etiology of new onset heart failure may provide additional guidance to cardiac imagers and clinicians and guide appropriate therapy.


Errors in identifying the etiology of cardiomyopathy have been described in patients undergoing cardiac transplantation. There are increasing data that cardiovascular magnetic resonance imaging (CMR) provides unique diagnostic information in heart failure. We investigated the association of the performance of CMR prior to cardiac transplantation with rates of errors in identifying the etiology of cardiomyopathy. We compared pre-transplantation clinical diagnoses with post-transplantation pathology diagnoses obtained from the explanted native hearts. Among 338 patients, there were 23 (7%) errors in identifying the etiology of cardiomyopathy. Of these, 22 (96%) occurred in patients with pre-transplantation clinical diagnoses of non-ischemic cardiomyopathy (NICM). Only 61/338 (18%) had CMRs prior to transplantation. There was no significant association between the performance of CMR and errors in the entire study cohort (p = 0.093). Among patients with pre-transplantation clinical diagnoses of NICM, there was a significant inverse association between the performance of CMR and errors . In conclusion, CMR was underutilized prior to cardiac transplantation. In patients with pre-transplantation clinical diagnoses of NICM – in whom 96% of errors in identifying the etiology of cardiomyopathy occurred – the performance of CMR was associated with significantly fewer errors. Etiology-specific treatment, in addition to standard heart failure therapies, can slow disease progression, reverse myocardial remodeling, and delay or preclude the need for advanced therapies such as cardiac transplantation2. Examples of such etiology-specific therapies include: coronary revascularization for ischemic cardiomyopathy (ICM), immunosuppression for inflammatory cardiomyopathies such as cardiac sarcoidosis and giant cell myocarditis, and exercise restriction and implantable cardioverter defibrillators for arrhythmogenic cardiomyopathy2. Thus, accurate identification of the etiology of cardiomyopathy may result in improved heart failure outcomes.Heart failure is associated with significant mortality, morbidity, and healthcare costs. An important prognostic factor in heart failure is the etiology of the underlying cardiomyopathy7. The error rates were 8–21%, with the majority of errors involving non-ischemic cardiomyopathies (NICM)7.Errors in identifying the etiology of cardiomyopathy have been described in patients undergoing cardiac transplantation through comparisons of pre-transplantation clinical diagnoses with post-transplantation diagnoses obtained by pathology examination of the explanted native hearts9. Tissue characterization of the myocardium using the late gadolinium enhancement technique (LGE CMR) frequently helps identify the etiology of a cardiomyopathy13. Whether CMR could help lower the rates of errors in identifying the etiology of cardiomyopathy is unknown. To investigate the impact of CMR, we studied consecutive patients that underwent cardiac transplantation and examined whether the performance of CMR any time prior to transplantation (hereon noted as pre-transplantation CMR) was associated with fewer errors in identifying the etiology of cardiomyopathy.Cardiovascular magnetic resonance imaging (CMR) has an important role in the evaluation of cardiomyopathy14 and the Cardiac Transplantation Registry. We hypothesized that performance of pre-transplantation CMR would be associated with fewer errors. The study was approved by University of Minnesota’s Institutional Review Board with a waiver of informed consent. It was performed in accordance with relevant guidelines and regulations.We performed a retrospective, observational study using the University of Minnesota’s Cardiovascular Magnetic Resonance RegistryConsecutive adult patients who underwent cardiac transplantation at the University of Minnesota from January 1, 2004 through December 31, 2017 were included. This time period was selected to match that of ready clinical availability of CMR at our institution.16 and included cine CMR for the assessment of left and right ventricular structure and function, and tissue characterization of the myocardium using the late gadolinium enhancement technique (LGE CMR).CMRs were performed on a Siemens 1.5T scanner as per standardized protocolsDemographic and clinical data, and pre- and post-transplantation cardiomyopathy diagnoses were independently extracted from patient records by two investigators (L.Q.L. and C.S.). Differences between the investigators were resolved by consensus. Data collected on pre-transplantation diagnostic testing included the performance of: echocardiography, coronary angiography, endomyocardial biopsy, pathology evaluation of the apex of the left ventricle (LV) obtained at the time of left ventricular assist device (LVAD) implantation, and CMR.Since patients are often referred to our institution for cardiac transplantation, referral records were also reviewed to identify diagnostic testing performed outside of our institution prior to cardiac transplantation. Five (1.5%) patients with CMRs did not have LGE CMR and were excluded from the final analysis.Pre-transplantation diagnoses were defined as those made by the cardiac transplantation team using clinical, hemodynamic and diagnostic testing data, and documented in the patients’ records prior to transplantation. Post-transplantation diagnoses were defined as those made by pathologists on routine pathology analyses of explanted hearts. ICM by pathology was recognized by the presence of ischemic-pattern  replacement fibrosis, and the absence of findings suggestive of a non-ischemic etiology .7, errors were defined as discordances between pre-transplantation clinical diagnoses and post-transplantation pathology diagnoses. For patients with NICM diagnoses, the specific etiology of NICM was compared.As in previous studiesStatistical analyses were performed using Stata 13 . Parametric continuous variables were expressed as means with standard deviation (SD). Categorical variables were expressed as counts with percentages. Comparison between groups was performed with a 2-sample Student t test for continuous, normal variables, and Wilcoxon rank sum test for continuous, non-normal data. Categorical data were compared using either chi-squared test or Fisher’s exact test. All tests were two-tailed, and p < 0.05 was considered statistically significant.During the study period, 341 patients underwent cardiac transplantation. Of these, three (0.9%) patients were excluded because their pathology reports for explanted hearts were not available. The pre-transplantation clinical diagnoses for the excluded patients were: idiopathic dilated cardiomyopathy, idiopathic restrictive cardiomyopathy and complex congenital heart disease. The remaining 338 patients comprised the study cohort.Details of pre- and post-transplantation cardiomyopathy diagnoses are provided in Table Among patients with pre-transplantation clinical diagnoses of ICM, one (0.5%) had a post-transplantation diagnosis of idiopathic dilated cardiomyopathy. Among the 186 (55%) patients with pre-transplantation clinical diagnoses of NICM, there were errors in identifying the etiology of cardiomyopathy in 22 (12%). Thus, 22/23 (96%) of all errors occurred in patients with clinical diagnoses of NICM.Among patients with errors after clinical diagnoses of NICM, ICM was the most common missed diagnosis, accounting for 30% (7/23) of errors. NICM diagnoses that were missed include: three cases each of myocarditis, idiopathic dilated cardiomyopathy and arrhythmogenic cardiomyopathy, two cases each of cardiac amyloidosis and hypertrophic cardiomyopathy, and one case each of cardiac sarcoidosis, giant cell myocarditis and left ventricular non-compaction cardiomyopathy.Patient characteristics stratified by performance of pre-transplantation CMR are listed in Table There was no significant association between the performance of pre-transplantation CMR and errors overall – 1.6% in patients with pre-transplantation CMR vs. 7.9% in those without transplantation CMR; p = 0.093. Among patients with pre-transplantation clinical diagnoses of ICM, there was no association between the performance of pre-transplantation CMR and errors. Among patients with pre-transplantation clinical diagnoses of NICM, there was a significant inverse association between the performance of pre-transplantation CMR and errors – 2.4% in patients with pre-transplantation CMR vs. 14.6% in those without transplantation CMR; p = 0.030. Thus, patients with pre-transplantation clinical diagnoses of NICM and pre-transplantation CMRs had 86% lower odds of having an error in identifying the etiology of cardiomyopathy compared with those with pre-transplantation clinical diagnoses of NICM and no pre-transplantation CMRs.In a contemporary comparison of pre-transplantation clinical diagnoses of cardiomyopathy with post-transplantation pathology diagnoses, there were errors in 7% of the study cohort. While the performance of CMR pre-transplantation was not associated with fewer errors overall, it was associated with significantly fewer errors in the subgroup with pre-transplantation clinical diagnoses of NICM. The latter accounted for 96% of all errors.17. This may explain errors in the six patients with pre-transplantation diagnoses of NICM after coronary angiography, but with post-transplantation diagnoses of ICM. Conversely, the presence of obstructive CAD in a patient with cardiomyopathy does not always signify ICM and may simply be incidental. This may explain the error in the patient with pre-transplantation clinical diagnosis of ICM. Through identification of the ischemic pattern of LGE characterized by involvement of the subendocardium  and location in the perfusion territory of an epicardial coronary artery, CMR can accurately distinguish between ICM and NICM18.Coronary angiography is conventionally used to identify ICM versus NICM. However, this approach is limited because the absence of obstructive coronary artery disease (CAD) does not always rule out ICM; in a recent systematic review of myocardial infarction with non-obstructive coronary arteries, 24% of patients had late gadolinium enhancement (LGE) in an ischemic pattern, possibly due to spontaneous healing of acute thrombotic occlusion from atherosclerotic CAD or thromboembolic disorders, or coronary vasospasm21. Additionally, all these studies investigated the role of CMR in distinguishing ICM from NICM, and none have systematically investigated its role in identifying the specific etiology of NICM.Although multiple studies have previously demonstrated the role of CMR for the identification of the etiology of cardiomyopathy, they have all defined ICM based on the presence of significant CAD by coronary angiography12. Examples include diffuse transmural LGE for cardiac amyloidosis, and multifocal, epicardial LGE with involvement of the right ventricular aspect of the basal interventricular septum for cardiac sarcoidosis (Fig. Identification of the specific etiology of NICM by CMR relies on the recognition of specific LGE phenotypes based on locations and patterns22. Patients fulfilling criteria for left ventricular non-compaction cardiomyopathy have previously been described to have left-dominant arrhythmogenic cardiomyopathy23.The lone NICM case missed despite a pre-transplantation CMR had a pre-transplantation clinical diagnosis of left ventricular non-compaction cardiomyopathy and on post-transplantation pathology examination was found to have arrhythmogenic cardiomyopathy with biventricular involvement, related to a mutation in the LMNA gene Fig. . The pat7 (Table 26.Our overall error rate is on the lower end of the range seen in prior studies of errors in identifying the etiology of cardiomyopathy in patients undergoing cardiac transplantation7 Table . This ma2.While our study findings are based on patients with end-stage cardiomyopathy that subsequently underwent cardiac transplantation, they carry a greater implication for patients with newly-diagnosed cardiomyopathy. CMR was only performed in 18% of our study cohort, highlighting that it is greatly underutilized for the identification of the etiology of cardiomyopathy. Early and accurate diagnosis of the etiology of cardiomyopathy can guide etiology-specific treatment, with the potential for reversal of myocardial remodeling and recovery of systolic function, and avoidance of advanced treatments such as implantable cardioverter defibrillator therapy, cardiac resynchronization therapy, LVAD therapy and cardiac transplantationOur study is limited by its retrospective, single-center design. Pre-transplantation diagnostic testing was performed at the discretion of the transplantation team. CMR was performed infrequently; many patients did not receive CMR because they were referred for cardiac transplantation from hospitals without CMR programs with implantable cardioverter-defibrillators in place, limiting the use of CMR. Newer CMR techniques such as T1 mapping were performed only in a recent minority of CMRs since the study period spanned 14 years. Patients with CMRs had a higher rate of endomyocardial biopsies; however, whether these were a consequence of CMR findings is not known. Post-transplantation pathology interpretations were not blinded to pre-transplantation clinical diagnoses. With regard to the implications, it may not be feasible to perform CMR in patients that present in a hemodynamically unstable state and require ventricular assist devices or cardiac transplantation before they are stable enough to undergo a CMR.Comparing pre-transplantation clinical diagnoses of cardiomyopathy with post-transplantation pathology diagnoses, there were errors in 7% of the study cohort. Ninety-six percent of all errors occurred in patients with pre-transplantation clinical diagnoses of NICM. In these patients, the performance of CMR pre-transplantation was associated with 86% lower odds of having an error. Prospective studies are needed to investigate whether routine use of CMR in patients with clinical diagnoses of NICM could improve clinical outcomes by decreasing errors in identifying the etiology of cardiomyopathy.


Patients suffering from heart failure and left bundle branch block show electrical ventricular dyssynchrony causing an abnormal blood pumping. Cardiac resynchronization therapy (CRT) is recommended for these patients. Patients with positive therapy response normally present QRS shortening and an increased left ventricle (LV) ejection fraction. However, around one third do not respond favorably. Therefore, optimal location of pacing leads, timing delays between leads and/or choosing related biomarkers is crucial to achieve the best possible degree of ventricular synchrony during CRT application. In this study, computational modeling is used to predict the optimal location and delay of pacing leads to improve CRT response. We use a 3D electrophysiological computational model of the heart and torso to get insight into the changes in the activation patterns obtained when the heart is paced from different regions and for different atrioventricular and interventricular delays. The model represents a heart with left bundle branch block and heart failure, and allows a detailed and accurate analysis of the electrical changes observed simultaneously in the myocardium and in the QRS complex computed in the precordial leads. Computational simulations were performed using a modified version of the O'Hara et al. action potential model, the most recent mathematical model developed for human ventricular electrophysiology. The optimal location for the pacing leads was determined by QRS maximal reduction. Additionally, the influence of Purkinje system on CRT response was assessed and correlation analysis between several parameters of the QRS was made. Simulation results showed that the right ventricle (RV) upper septum near the outflow tract is an alternative location to the RV apical lead. Furthermore, LV endocardial pacing provided better results as compared to epicardial stimulation. Finally, the time to reach the 90% of the QRS area was a good predictor of the instant at which 90% of the ventricular tissue was activated. Thus, the time to reach the 90% of the QRS area is suggested as an additional index to assess CRT effectiveness to improve biventricular synchrony. Heart failure (HF) constitutes a major public health problem worldwide and much attention has been paid to the understanding of the arrhythmogenic mechanisms in the failing heart induced by the structural, electrical, and metabolic remodeling. Heart failure is also characterized by a compromised ventricular contraction, which is fundamental for an optimal cardiac function. Lack of synchrony in heart contraction is worsened when the failing heart is also affected by left bundle branch block (LBBB). These patients present electrical and mechanical ventricular dyssynchrony causing pump dysfunction, reduced functional capacity, and myocardial remodeling. In particular, LBBB is associated with delayed contraction of the left ventricle (LV), reduced ventricular performance and widening of the QRS complex.The relative QRS duration (QRSd) provides a powerful prognostic value for patients with HF and is a primary indicator of eligibility for cardiac resynchronization therapy (CRT). CRT helps to reduce mortality and morbidity associated with HF , and the other one on the epicardium of the LV lateral wall. Patients with positive therapy response present QRS shortening and an increased LV ejection fraction (LVEF) . However, the electromechanical modeling study by Pluijmert et al. . Regarding the ethical considerations, the protocol was approved by the Ethics Committee for Clinical Research of the Hospital Clinic Universitari de Valencia, which certifies that the present study was conducted in accordance with the recommendations gathered in the Declaration of Helsinki, originally adopted by the General Assembly of the World Medical Association in 1964, and in its subsequent revisions. Furthermore, the patient, who underwent the standard clinical protocol, gave written informed consent for the use of his anonymized clinical data in this study.Manual image segmentation was performed using Seg3D software  , including papillary muscles and main endocardial trabeculations . From thh) and transmural (αt) angles. In papillary muscles and endocardial trabeculations, fibers are known to be aligned parallel to the longitudinal axis of those anatomical structures  network  was deveThe biventricular mesh was fit into a human torso mesh  formulation was modified. Firstly, the steady state inactivation (hss and jss) and activation (mss) gates were changed as in Passini et al. (Na) was decreased to 23% of its original value to obtain approximately a maximum upstroke velocity (dV/dtmax) of 260 V/ms as in the original O'Hara et al. (NaL) conductance (GNaL) was duplicated to maintain the relationship between INaL and peak INa observed in voltage-clamp experiments as described in Mora et al.  using ELVIRA FEM software  and transversal (σT) conductivity, respectively. This resulted in a CV of 0.61 m/s along the fiber direction and of 0.29 m/s in transverse direction. These values are consistent with experimental measurements in human ventricles  in the heart domain, we performed a set of test simulations on a 3D slab model (20 × 20 × 6 mm) composed of regular hexahedral elements (voxels) with an edge length of 0.4 mm, matching the average length in the ventricular model. As a result, we set the conductivity values to 0.5 S/m and 0.1 S/m for longitudinal . Four scenarios of CRT pacing were defined for HF + LBBB conditions with different combinations of atrioventricular delay (AVD) and interventricular delay (VVD) for each lead location configuration .For the present study a 3D anatomical model of the ventricles was generated, which does not include the geometry of the atria. Therefore, the intrinsic activation from the sinoatrial node was simulated by applying an electrical stimulus to the His bundle, either in healthy or HF + LBBB conditions see . CRT leaAVD is the time delay between the instant of initial activation of the sinoatrial node  and the instant of time of external CRT stimulation of the ventricles. To set the value of AVD in our simulations, several considerations were taken into account. Firstly, the typical duration of PR interval observed in LBBB patients is 200 ms . Thus, an AVD of 100 ms was modeled by applying an electrical stimulus to the His bundle of 80 ms after ventricular leads activation. Indeed, when we applied the external CRT ventricular stimulation, 100 ms after initial activation of the sinoatrial node (AVD of 100 ms), this intrinsic activation had reached the atrial side of the AV node (this takes 100 ms) and needed still 80 ms to reach His bundle (delay needed in the AV node). In the case of an AVD of 140 ms, the electrical stimulus in the His bundle was applied 40 ms after ventricular leads activation. Indeed, when we applied the external CRT ventricular stimulation, 140 ms after initial activation of the sinoatrial node, this intrinsic activation had reached the AV node in 100 and 40 ms of delay in the AV have also elapsed, the stimulus needed 40 ms more to reach the His bundle, and this is why we stimulated the His bundle 40 ms after the ventricles. Additionally, VVD was set to 0 ms (stimulation in both ventricles simultaneously) and 30 ms (the RV was stimulated 30 ms after the LV), according to the time ranges used in clinical practice  for the application of the CRT protocol.QRS complex was computed in the precordial leads location on the torso surface for each CRT configuration and QRSd was measured using an algorithm implemented in Matlab software . This algorithm determines the beginning and end of the QRS complex based on the first and second derivate of the electrocardiographic signal see . The QRS90) are other important parameters that have been used to evaluate CRT response. For this reason, three linear correlations between these parameters were performed using Pearson correlation method. Values of p < 0.05 were considered statistically significant. Values for the analysis are shown in Shortest QRSd was the criterion applied to evaluate the optimal location of the LV lead for different positions of the pacing lead in the RV. However, the total activation time (TAT), QRS area (QRSa) and the time to 90% of activated tissue  are shown in Under HF + LBBB conditions, activation began in the RV endocardium and reached the LV endocardium in the apical septal region after 46 ms from the onset of the RV depolarization. This is in agreement with the data recorded experimentally by Auricchio et al. . The lasA total of 54 electrode placement configurations with four different delays (two AVD and two VVD configurations) settings were tested for the CRT simulations. QRSd values are shown in Firstly, we analyzed the optimal lead placement. The shortest QRSd among all configurations tested was obtained when the RV lead was placed in the upper septum near the outflow track (third row). Furthermore, for all RV lead placement the optimal location of the LV lead, both in the epicardium and endocardium, was the LV mid posterior wall.Secondly, we analyzed the effect of the delay between pacing leads and intrinsic activation in a fixed location. The best configurations for the RV lead placed in the apex are depicted in the first row. QRSd was reduced from 172 ms  to 157 mWhen the RV lead was located in the middle of the septum (second row), the QRSd was reduced from 161 ms  to 146 mIf the RV lead was placed in the upper septum, the QRSd was reduced from 149 ms  to 143 mFinally, the influence of LV epicardial vs. endocardial pacing was assessed. QRSd was decreased in all cases after CRT application, but the reduction was greater for LV leads placed in the endocardium (column 2) compared to epicardium (column 1).Summarizing, the optimal location in terms of shortest QRSd was obtained when the RV lead was placed in the upper septum and the LV lead was located in the mid posterior wall region. Once the optimal lead location was selected for both RV and LV leads, the shortest QRSd was measured for different intrinsic and biventricular delays, without highlighting a particular optimal setting. Finally, the shortest QRSd was obtained in all configurations when the LV lead was placed in the endocardium compared with those in the epicardium.Another helpful parameter to assess CRT outcome is the total activation time (TAT) of the ventricles. This parameter is not directly accessible in clinical practice during CRT procedures, but simulations can provide additional information to achieve the ideal configuration. Ideally, within normal physiological ranges, the shorter the QRS the shorter TAT, leading to an increase in ventricular synchrony. In Finally, after applying the CRT protocol, the TAT was decreased by 15, 14, 12, 15, 19, 22%, with respect to HF + LBBB conditions, as shown in 90), , . This pa90 values for a configuration with the RV lead placed in the apex, mid septum, and upper septum, and the LV lead located in the epicardium , respectively.90 (7% reduction) for an AVD of 140 ms. On the other hand, when VVD was increased (column 1 vs. column 2 and column 3 vs. column 4) t90 increased up to 19% for all the RV lead locations.On the one hand, when AVD was modified (column 1 vs. column 3 and column 2 vs. column 4) similar results were obtained, except when the RV lead was located in the upper septum area. The electrical propagation of the intrinsic stimulus contributed to decrease tWhen the RV lead was located in the apex, the optimal location of the LV lead in the epicardium was the LV anterior wall at basal level . For theFinally, for the RV lead location in the upper septum, the optimal placement of the LV pacing lead in the epicardium was in the LV mid lateral wall, while the optimal placement of the LV lead in the endocardium was the apex of the LV lateral wall (R = 0.78 and p < 0.05). This moderate correlation could justify the difference between the optimal AVD and VVD values for the simulations with a shortest QRSd and with a shortest TAT.To better highlight the relationship between QRSd and TAT, a correlation analysis was carried out . Resultsp-value (R = −0.12 and p = 0.076). Thus, a linear relationship between QRSa and TAT was not observed in this study.A similar correlation analysis was made between area of the QRS (QRSa) and TAT . We firs90QRSa) and time to 90% of the ventricular activation (t90) for each CRT simulations. A significant correlation with a high linear dependence was observed (R = 0.94 and P < 0.05). Simulations with shorter t90QRSa correspond to the simulations with shorter t90. Therefore, a new biomarker based on time up to 90% of the QRS area can be used as an indicator of electrical synchrony.Finally, when correlating the curves of percentage of activated tissue and percentage of QRS area as a function of time, a direct relationship between both variables was observed. 90QRSa) was a good predictor of the instant at which 90% of the ventricular tissue had been activated (t90). This indicator could be used in clinical trials to complement QRSd criterion to select the optimal delay of the pacing leads to obtain a faster ventricular activation of most of the ventricular muscle.In this study, biophysical 3D multiscale simulations were conducted to assess alternative locations of the RV lead for a better CRT response in LBBB HF patients. The major findings of this study can be summarized as follows: (i) the optimal leads location based on shortest QRS criterion was the RV upper septum and the LV mid posterior region minimizing also TAT; (ii) for the optimal lead location, the delay configuration leading to the shortest QRSd was AVD = 140 ms, VVD = 30 ms. However, the AVD and VVD setting leading to the shortest TAT was different, suggesting that minimizing QRSd is a good criterion to select leads location but not to select the pacing delay; iii) the time to 90% of the QRS area . On the other hand, in the recent study of Sipal and coworkers  of response (>15% reduction in LV end-systolic volume) to CRT as well as a shorter QRSd (p < 0.001) and a greater QRS shortening for the surface ECG guided group. Furthermore, the optimal site for LV lead placement was the posterior and posterolateral region, in agreement with our simulations. For all RV lead locations tested in our study, when the LV lead was placed in the latest activated area of the LV, none of those configurations led to the shortest QRSd.The study of Zanon et al.  determinIn our study, we also showed that when pacing in the latest electrically activated area of the LV, that area did not provide the shortest TAT. Similar results were observed in the simulation study by Pluijmert et al. . In thatOptimization of AVD and VVD is crucial during CRT application. A longer inter-lead electrical delay was associated with more pronounced LV reverse remodeling in CRT patients with a presumed optimal LV lead position concordant or adjacent to the latest mechanically activated non-scarred segment  and this method is avoided, setting the shortest AVD based on echocardiography  and vice versa. Normalizing the QLV by QRS duration, termed LV lead electrical delay (LVLED), was also shown to correlate with Doppler-derived dP/dt values. LVLED greater than or equal to 50 % was associated with significantly greater reductions in all-cause death or HF hospitalization at 12 months of follow-up in patients with non-ischemic cardiomyopathy  study further reinforced the importance of QRSd over mechanical dyssynchrony as the most important indicator for CRT responses  is a good predictor of the instant at which 90% of the ventricular tissue has been activated (t90). This indicator could be used in clinical trials to complement QRSd measurements in defining the optimal location and delay of the pacing leads to produce faster ventricular activation of most of the ventricular muscle.To our knowledge, and given the benefits of using a model where all variables are accessible, our study is the first to systematically explore the correlation between the activated portion of tissue  and the QRS complex in the torso surface. Thus, we found that an index based on time to 90% of the QRS area  may affect QRSd and TAT measurements, especially when pacing on the RV upper septal area. Although our results have been compared to other related studies, the specific findings observed in this study should be carefully validated against clinical studies and complemented with a set of computational models of different patients. In addition, two isolated stimuli were employed to assess CRT efficiency. The development of strategies that allow multi-site pacing should be taken into account in future studies. Additionally, the incorporation of levels of HF in different ventricular areas could modify simulation results.In conclusion, our study showed that the optimal location for the RV lead in CRT site as an alternative to RV apex, is the upper septum close to the outflow tract, based on the shortest QRSd criterion. Furthermore, LV endocardial pacing leads improve CRT outcome, with respect to epicardial stimulation, and areas with a higher density of PMJ are suggested for better CRT response.90 (time elapsed to 90% of ventricular activation) could be used to determine the optimal VVD value. The time to reach the 90% of the QRS area (t90QRSa) is related to the time at which 90% of the ventricles are already activated (t90). Thus, t90QRSa is suggested as an additional index to assess CRT effectiveness to improve biventricular synchrony.CRT optimization based only on the shortest QRSd criterion may not be totally effective to reach the maximum TAT reduction, or to optimize biventricular pacing delay. However, a biomarker based on minimizing the value of tEFC, EC, JA, JF, and BT contributed to the conception and design of study. AL-P created the anatomical model and Purkinje system was developed by RS and JG. Computational simulations were performed by EFC and JG. The analysis/interpretation of results was performed by EFC, JG, RS, and BT. All authors contributed to draft the manuscript and all authors revised and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


To evaluate the sequential changes of hemodynamic and metabolic parameters inpatients who underwent aorta no-touch off-pump coronary artery bypasssurgery (OPCAB).2). The parameters were assessed 5min before, during and 5 min after each anastomosis . Postoperative lactate was also evaluated.Prospective study involving twenty-seven consecutive patients who underwentaorta no-touch OPCAB. The FloTrac/PreSep/Vigileo™ system (EdwardsLifesciences) was used to continuously record heart rate (HR), mean arterialblood pressure (MABP), central venous pressure (CVP), continuous cardiacindex (FCI), stroke volume (SV), stroke volume variation (SVV), and centralvenous oxygen saturation (ScvOP=0.03). There was a significant decrease inScvO2 only during PD and OM anastomoses . CVP drop after PD manipulation was strongly associated with ahigher lactate during the first hours after surgery . These hemodynamic changes were transient andentirely recovered after the heart was returned to its anatomical position.No significant differences were observed in FCI, SVV, or the systemicvascular resistance index (SVRI) during all anastomoses, except for a dropin SVRI during PD grafting . SVtended to decrease during the procedure in all territories, but withstatistically significant drop only in PD and OM grafting .There was no significant change in HR and MABP for all anastomoses, exceptfor MABP during PD grafting (-10.1±2.7 mmHg,Heart displacement for performing aorta no-touch OPCAB is well tolerated,with transient and endurable hemodynamic variations. The conceptstems from avoiding any ascending aorta manipulation, virtually eliminating the riskof embolism of aortic wall debris into the brain circulation, utilizing the off-pumpbeating heart surgery technique.However, the displacement of the heart to achieve suitable exposure for graftconstruction elicits hemodynamic changes, potentially requiring conversion toon-pump surgery and increasing morbimortality risk. Early detection of premonitory hemodynamicalterations leading to conversion may help avert this dreadful complication.The aorta no-touch off-pump coronary artery bypass surgery (OPCAB) has been therecommended technique for treatment of patients with high risk for neurologicaldamage or stroke2) assessment.The FloTrac/PreSep/Vigileo™ system  isa less invasive monitoring device allowing continuous determination of cardiacoutput (CO) and other hemodynamic variables using pulse wave analysis, coupled withmixed central venous oxygen saturation  who underwent elective first-time aortano-touch OPCAB. After the Institutional Ethical Committee's approval, informedconsent was obtained from all the patients. All operations were performed by asingle surgeon (WJG) to eliminate technical variability.In the operating room, electrocardiogram (ECG) leads were monitored, the radialartery was cannulated for continuous monitoring of arterial blood pressure and bloodgas analysis and connected to a FloTrac™ pressure transducer. ThePreSep™ central venous oximetry catheter was inserted through the rightjugular vein, the Vigileo™ system was next loaded with the patient'sdemographic data, pressure was zeroed and set to display variables' measurementwithin the past 60 seconds.2 0.6) to maintain end-tidal CO2 in35–38 mmHg. For preventing hypothermia, the operating room's temperature wasmaintained above 24˚C and the patients were continuously rewarmed with warmmattress. After median sternotomy, the internal thoracic arteries (ITAs) weretaken-down from the inner chest wall in skeletonized fashion and heparin was givento attain activated clotting time > 250 seg. After pericardial longitudinalopening, the heart was inspected, and pericardial stay sutures were placed, deeperin the left side than in the right. Additionally, one or two deep pericardialstitches were placed close to the left inferior pulmonary vein. All these suturestogether, once forcefully pulled up, improved the exposure of the lateral andinferior aspects of the heart. The application of a suction-type tissue stabilizer completedthe task of a suitable exposure of the coronary arteries to be grafted. The leftanterior descending (LAD) is the first coronary artery in the grafting sequence,followed by the posterior descending (PD), obtuse marginal (OM), and diagonal (Dg)arteries. No distal coronary snaring, CO2 blower, or intra-coronaryshunts were used in this series, in accordance with our usual OPCAB practice.Anesthetic technique was standardized for all patients. Anesthesia was induced with2.0–3.0 mg of midazolam, 1.0–3.0 mg/kg of sufentanil, and 50 mg of rocuronium and itwas maintained with 0.2–0.5 vol% of isoﬂurane and continuous intravenous infusion of0.5–1.5 mg/kg/min of sufentanil and vecuronium. Ventilation was controlled withoxygen-air mixture , vasopressors , and volume expansionwith crystalloid solutions. During graft anastomosis to OM and PD, patients wereplaced in the Trendelenburg position, and the table was rotated slightly to theright.in situ routed through the transverse sinus or as afree graft attached end-to-side to the left internal thoracic artery (LITA). Thevein graft to PD was connected to the RITA's proximal stump (17/27). The OM was always revascularized using right internal thoracic artery (RITA) grafts(16/27), either All proximal grafts were attached to the ITAs, and the ascending aorta remaineduntouched throughout all the operations; most of the times, the pericardium over theaorta was not split to completely avert any aorta manipulation.Protamine was administered to fully reverse the heparin effect after the completionof revascularization.2. Thesystemic vascular resistance index (SVRI) derived from collected parameters wascalculated. The FloTrac™ system utilizes the radial artery line for analysisof the arterial waveform to calculate CO and other parameters derived from CO data.The PreSep™ central venous oximetry catheter provides a central venous linefor volume administration and once connected to the Vigileo™ monitor, itallows continuous measurement of CVP and ScvO2.The FloTrac/PreSep/Vigileo system™ (Edwards Lifesciences) was utilized tocontinuously record hemodynamic variables: heart rate (HR), mean arterial bloodpressure (MABP), central venous pressure (CVP), continuous cardiac index (FCI),stroke volume (SV), stroke volume variation (SVV), and ScvOThe hemodynamic variables were assessed 5 minutes before the heart's displacement foranastomosis, during graft construction, and 5 minutes after each anastomosis . The last measurement was performed with the heart returned to itsanatomical position. Postoperative lactate was also evaluated.P-value<0.05. Statistical analyzes were carried out byGraphPrism 7.0 Software .Categorical data were presented in absolute (n) and relative (%) frequencies. Allhemodynamic data were expressed as the mean value ± standard deviation.The Shapiro-Wilk test was applied to tested variables for normalitydistribution. Hemodynamic changes during the heart's displacement for eachcoronary anastomosis were compared using ANOVA for repeated measures. The dropin hemodynamic variables was presented by the difference between the initial orafter the procedure value minus the during the heart's displacement value. Astatistically significant level was considered whenAll patients were successfully operated on according to the scheduled protocol.Demographic data are listed in P=0.03; 2 were variable, but no change above 10% was observed.There was a significant decrease in ScvO2 only during PD and OManastomoses .These hemodynamic changes were transient and entirely recovered after the heart wasreturned to its anatomical position.The mean number of anastomoses was 2.7 per patient and the left ventricular ejectionfraction (LVEF) varied between 0.31 and 0.71 (mean 0.61±0.10); four patientshad LVEF below 0.45. There was no significant change in HR and MABP for allanastomoses, except for MABP during PD grafting , but these weretransient and well tolerated, with the heart fully recovering when it was returnedto its anatomical place. The heart displacement for LAD anastomosis is the leastaffected by hemodynamic changes, that is why it is performed first in the sequence.Moreover, early revascularization of the left ventricle (LV) anterior wall affordsprotection to the bulk of the LV myocardium, therefore allowing for safer heartdisplacement to accomplish the operation.,6 and advanced methods for heartpositioning and anastomotic site stabilization,8 improved safety andtechnical quality, resulting in wider acceptance and extended use of thisoperation.The hemodynamic compromise is an important concern with this technique, caused bydisplacement of the beating heart, which is vital for optimal exposure of thecircumﬂex and PD artery. However, innovative improvements for coronary arteryvisualization. However, theincreased risk of stroke following CABG remains a major drawback for surgicalrevascularization compared with PCI, which is mostly related to the aortamanipulation.Coronary artery bypass grafting (CABG) has consistently been demonstrated to be themost effective therapy for the treatment of patients with advanced obstructiveatherosclerotic coronary artery disease, providing reduction of the long-term riskof death and myocardial infarction, compared to percutaneous coronary intervention(PCI),11, although an increased risk still persists owing to theneed of ascending aorta clamping to construct the proximal anastomosis.Several meta-analyses revealed that OPCAB significantly reduces the incidence ofpostoperative neurological complications compared to on-pump CABG.More than 60 randomized trials so far have compared OPCAB with on-pump CABG, allowingfor construction of several meta-analyses of these trials, all coming to a similarconclusion: OPCAB significantly reduced short-term rates of stroke and renal failurebut did not reduce the risk of mortality or myocardial infarction in low and mixedrisk patients. Specific studies targeting high-risk patients found a significantreduction in mortality with OPCAB compared with on-pump CABG, although with higherrates of repeat revascularization, thelargest prospective randomized trial performed so far comparing on- and off-pumpsurgery, the rate of the composite outcome of death, stroke, myocardial infarction,renal failure, or repeat revascularization at 5-years follow-up was similar amongpatients who underwent OPCAB and on-pump CABG.In the CORONARY trial. Therefore, the aorta no-touchOPCAB means a step forward and a refinement of the outcomes provided by the earliestOPCAB technique.Recent network meta-analysis demonstrated that avoidance of aortic manipulation inOPCAB may decrease the risk of post-operative stroke, especially in higher-riskpatients. Additionally, the study pointed out that the elimination ofcardiopulmonary bypass may reduce the risk of short-term mortality, renal failure,atrial fibrillation, bleeding, and length of intensive care unit stay. An additionalstrategy to overcome this pitfall, the technique for anastomosis of the top end ofthe vein graft to the proximal stump of RITA in the anaortic (aorta no-touch) OPCAB,has been developed and extensively employed in this case series.In another seminal study, the no-aortic touch technique afforded the lowest risk forpostoperative stroke in patients undergoing CABG. Clamping the aorta during CABGincreased the risk of postoperative stroke, regardless of the severity of aorticdisease-20.In Brazil, off-pump surgery has been demonstrated to reduce short-term costs of theprocedure in 25% compared to the on-pump CABG, as well as it is cost-effective inthe 5-years follow-up comparative analysis of the MASS-III trial. In our country,with severe health budget constraints, this savings could increase the ability tocare for patients by one quarter,22, in trialsincluding less experienced surgeons, the OPCAB short- and long-term outcomes wereinferior and led to high intraoperative conversion rates, as reported in the ROOBYtrial. Similarly,experienced surgeons tend to achieve higher rates of complete revascularization inthe OPCAB technique.OPCAB surgery has been questioned regarding its efficacy and safety in comparison tothe conventional technique, especially with the outcomes related to incompleterevascularization and quality of grafts. However, the quality of anastomosis inoff-pump surgery is directly related to the surgeon's experience. While experiencedsurgeons performing the technique reported the same degree of patency of thetechniques over 8-years follow-upBased in these recent evidences, the aorta no-touch OPCAB has been the recommendedtechnique for patients with cerebrovascular disease and/or calciﬁcation oratheromatous plaque in the ascending aorta. Furthermore, it should be favored inpatients with high-risk factors such as old age, left ventricular impairment, andrenal failure..Postoperative complications and mortality are markedly higher in patients withhemodynamic instability who underwent a delayed switch to an on-pump CABG.Worsening of cardiac function due to heart's dislodgement during OPCAB can result inobstruction of the right ventricular outflow tract and failure in LV pumpingmechanism. These changes elicit reduced CO, hypotension, and myocardial ischemia,potentially leading to cardiac arrest and urgent need to on-pump conversion. Then,likely benefits could be provided by real-time less invasive monitoring systemallowing continuous determination of CO and other hemodynamic variables in OPCAB,and letting promptly correction or earlier conversion to on-pumptechnique2 reﬂects hemodynamic changes earlier compared to the CO measuredevery 60 seconds and it has critical signiﬁcance since it represents both deliveryand consumption of oxygen. Although measurement of the CO level is too slow formonitoring the cardiac status during the manipulation and tilting of the heart, theCO is still useful as a trend monitor during the entire surgical period. Ultimately,the hemodynamic changes during OPCAB are also heavily dependent on the surgicaltechnique, surgeon's skill, and the operative team's experience.The number of coronary artery anastomoses during OPCAB is increasing, more arterialgrafts are being performed, and then the requirement of proper and accuratemanagement of hemodynamic and metabolic parameters during coronary anastomosisemerges. Apart from intravenous ﬂuid loading and head-down (Trendelenburg) positionto compensate the drop of mean arterial pressure and CO, the use of a combination ofinotropic drugs should be more intensively evaluated in this setting. Particularly,ScvO2 monitoring, alongwith patient's anthropometric data, skipping the necessity of calibration bythermodilution. Broch et al.comparatively evaluated the accuracy of FCI determination based on arterial waveformanalysis with transpulmonary thermodilution in patients scheduled for elective CABG,showing a moderate, but signiﬁcant correlation between pulse contour FCI andthermodilution FCI, both before and after cardiopulmonary bypass. Not only theuncalibrated semi-invasive monitoring system was capable to reliably measure FCIcompared with transpulmonary thermodilution in patients undergoing elective CABG,but additionally the semi-invasive monitoring device was able to detect hemodynamicchanges and trends.In recent years, the FloTrac/Presep/Vigileo™ has been introduced intoclinical practice, establishing a new concept of a semi-invasive device based onarterial waveform analysis for FCI evaluation and ScvO compared the FCImeasured by the FloTrac/Vigileo™ system to that obtained by a pulmonaryartery catheter in patients with decreased LVEF and low CO status during OPCAB. TheFCI was reliable at all points of measurement and the authors concluded that the COmeasured by the FloTrac/Vigileo™ system was consistent in patients withdecreased LVEF and low CO status during OPCAB, even during the period of heart'sdisplacement and OM grafting.Conversely, other studies reported lower accuracy of uncalibrated arterial waveformanalysis of SVV to predict ﬂuid responsiveness in patients with impaired LVEF andlow CO, especially those with FCI < 2.2 L/min/m2,28.Yet, Jo et al.2 monitoringfor OPCAB is still a matter of debate, related to the question of whether increasingthe degree and complexity of invasive monitoring will lead to improved outcomes.These devices may provide valuable information from a trending viewpoint, which maybe useful for hemodynamic management in intra- and postoperative period. Accurateand timely data regarding these endpoints may signify the difference betweencarry-on the case off-pump or urgently convert it to on-pump surgery. In this case series, nopremonitory changes that could trigger an alarm for shifting the operative strategywere detected and that might be related to the number of patients included, sofurther increasing the caseload may be of help in elucidating this question.The routine use of continuous cardiac output (CCO) and ScvOThe heart displacement for performing aorta no-touch OPCAB in all main coronaryarteries is well tolerated, with transient and endurable hemodynamic variations andno substantial influence on metabolic parameters or adverse clinical events. Closemonitoring using the FloTrac/PreSep/Vigileo™ system may be valuable forprompt identification of significant hemodynamic and metabolic changes andimplementation of proper intervention at the time of coronary artery anastomosis inpatients undergoing aorta no-touch OPCAB.