In this study, we investigated the role of gated myocardial glucose metabolic imaging in assessing left ventricular (LV) systolic dyssynchrony after myocardial infarction (MI) and explored the influencing factors. Bama mini-pigs were divided into normal group and MI group and subjected to gated myocardial metabolic imaging (GMMI) and gated myocardial perfusion imaging (GMPI). The phase bandwidth (BW), standard deviation (SD) and the latest activation site of left ventricle were obtained using program Cedars QGS. The results showed that (1) BW and SD obtained in GMMI and GMPI showed significant correlation in pigs with MI, but not in the normal pigs, (2) BW and SD obtained in GMMI and GMPI had good consistency in both normal pigs and MI pigs, (3) GMMI and GMPI had a 66.7% identity in determining the latest activation site of left ventricle in the normal pigs and 77.8% identity in determining the latest activation site of left ventricle in pigs with MI. Multivariate stepwise regression analysis showed that total perfusion deficit and summed motion score were independent factors affecting BW and SD in GMMI. In conclusion, phase analysis of GMMI images could objectively reflect LV systolic dyssynchrony resulted from interactions of multiple factors. Series of studies showed that location of myocardial scars4, amount of viable myocardium5, left ventricular (LV) motion patterns6 and LV systolic synchrony7 were important factors affecting patients’ response to CRT.Cardiac resynchronization therapy (CRT) is an effective treatment for severe heart failure. But according to the existing guidelines8. Cardiovascular magnetic resonance has been used to assess LV myocardial scar and systolic dyssynchrony, but it is time-consuming and involves significant user interaction9. Gated myocardial perfusion imaging (GMPI) is widely accepted, and a single resting GMPI scan can simultaneously assess the global and regional functions, scar burden and location, systolic synchrony and latest activation site of left ventricle. Zhou et al.10 applied GMPI to guide the placement of CRT electrodes and obtained good reproducibility and high response rate. GMPI phase analysis now has become the standard reference for assessing LV systolic dyssynchrony11. Compared with GMPI, 18F-fluorodeoxyglucose (FDG) gated myocardial metabolic imaging (GMMI) has higher spatial resolution and is more accurate for assessing extent of scar and myocardial viability13. Pilot studies14 indicated that clinical non-responders to CRT could benefit from assessment of 18F-FDG positron emission tomography (PET)/computed tomography (CT). However, very few clinical investigations compared phase analyses of these two methods16 and no consistent conclusions were reached possibly due to relative confounding factors of these retrospective studies. Therefore, in this study we strictly controlled the influencing factors and used GMPI phase analysis as the reference standard to evaluate the feasibility of GMMI phase analysis for clinical utilization. We also analyzed the influencing factors for improving CRT responsiveness of heart failure patients.Theoretically, techniques that could be used to simultaneously assess scar burden and location, myocardial viability, LV function and systolic dyssynchrony will help guide the placement of CRT electrodes and solve non-response problems. Echocardiography is non-invasive, cost-effective and easy to access, but there were significant inter-observer (4–24%) and intra-observer variations (7–72%) among many parametersThe heart rate and QRS duration of the 9 pigs in the normal group were 72.8 ± 23.3 bpm and 61.0 ± 7.8 ms, respectively. Phase analysis of their GMMI images showed that LV end-diastolic volume (EDV) was 46.3 ± 8.3 ml, end-systolic volume (ESV) was 9.6 ± 5.6 ml and LV ejection fraction (LVEF) was 80.1 ± 8.2%.P > 0.05), respectively, as shown in Fig. P > 0.05 for all) as shown with Pearson’s correlation coefficients rBW = 0.03 and rSD = −0.17. Bland-Altman analysis showed that BW and SD values obtained from GMMI were in rough agreement with those obtained from GMPI with differences of −1.33 ± 5.83° and 0.02 ± 1.81° for BW and SD, respectively, indicating no significant difference from the value 0 (P > 0.05). The 95% limits of agreement were −12.76° to 10.10° for BW and −3.53° to 3.57° for SD, as shown in Fig. Phase analysis of pigs in the normal group showed a uniform color-scale distribution in the bull’s eye plot and a narrow and sharp peak with two sides being symmetrical in the phase histogram obtained from either GMMI or GMPI, as shown in Fig. The latest activation site of left ventricle in GMMI was 55.6% (5/9) in the anterior, 22.2% (2/9) in the anteroseptal, 11.1% (1/9) in the inferoseptal and 11.1% (1/9) in the anterolateral wall. The latest activation site of left ventricle in GMPI was 44.4% (4/9) in the anterior, 22.2% (2/9) in the anteroseptal, 22.2% (2/9) in the inferoseptal and 11.1% (1/9) in the inferior wall, showing an agreement of 66.7% (6/9).P < 0.05 for all), and (2) SD had a significant negative correlation to LVEF (P < 0.05), but not EDV and ESV (P > 0.05 for both), as shown in Table The analysis of possible factors affecting LV systolic dyssynchrony in GMMI showed that 1) BW and SD had a significant negative correlation to the ratio (SUVm/b) of standard uptake values of myocardium (SUVmyo) and mediastinal blood pool (SUVbp) ( BW and SP < 0.05); LVEF of pigs with MI was 53.2 ± 16.6%, which was significantly less than that of normal group (P < 0.05). The summed motion score (SMS) of pigs with MI was 23.2 ± 13.9, summed thickening score (STS) was 13.6 ± 12.0, the total scar score was 9.4 ± 4.7, and the number of viable myocardial segments was 10 ± 4, respectively. The general pathological examination of left ventricle of pigs with MI showed slightly enlarged LV cavity, slightly thinned infiltration area and no thrombosis formation. Both Hematoxylin-Eosin (HE) and Masson staining showed infarcted fibrous tissue and a small amount of viable myocardium in the infarcted area, coexistence of infarcted fibrous tissue and viable myocardial tissue in the infarcted area margin, and normal myocardial tissue in the distal end, as shown in Fig. MI was successfully established in the 9 pigs in the MI group. No pig died till 30 to 35 days after modeling. The heart rate of pigs with MI was 72.1 ± 10.1 bpm and QRS duration was 83.3 ± 47.7 ms. The total perfusion deficit (TPD) of left ventricle caused by modeling was up to 43.9 ± 14.0%, mainly present in the blood-supplying myocardium of left anterior descending (LAD) artery, and the level of troponin I was 267.88 ± 86.96 ng/ml. LV EDV and ESV of pigs with MI was 54.4 ± 17.1 ml and 16.9 ± 16.6 ml, respectively. The LV cavity of pigs with MI was significantly greater than that of the normal group (P < 0.05), indicating significant intra-LV systolic dyssynchrony after MI, but showing no significant differences from BW of 80.0 ± 51.9° and SD of 23.7 ± 16.1° obtained using GMPI , as shown in Fig. BW = 0.74 and rSD = 0.84 , as shown in Fig. P < 0.05 for both). Bland-Altman analysis showed that the values obtained with GMMI phase analysis were slightly higher than those with GMPI one, with difference of 15.33 ± 40.37° in BW and 3.38 ± 8.85° in SD, respectively, but there was no significant difference compared to the value 0 (P > 0.05) and the 95% limits of agreement were −63.80° to 94.46° for BW and −13.97° to 20.72° for SD, as shown in Fig. Phase analysis of pigs with MI showed an inhomogeneous color-scale distribution in the bull’s eye plot and an evidently widened and asymmetrical peak in the phase histogram, as shown in Fig. GMMI showed that the latest activation sites of left ventricle counted for 44.4% (4/9) in apical region, 22.2% (2/9) in the anterior, 22.2% (2/9) in the inferolateral and 11.1% (1/9) in the inferoseptal wall, while GMPI showed that the latest activation sites of left ventricle counted for 55.6% (5/9) in apical region, 22.2% (2/9) in the inferior, 11.1% (1/9) in the inferoseptal and 11.1% (1/9) in the anterolateral wall, showing 77.8% (7/9) of agreement.R2 = 0.59, F = 12.63, P = 0.009), whereas SMS was an independent factor affecting SD in GMMI .Univariate analysis of possible factors affecting post-MI LV systolic dyssynchrony showed that (1) BW in GMMI had significant, positive correlations with TPD, ESV, SMS and total scar score, but negative correlations with LVEF and the number of viable myocardial segments; and 2) SD in GMMI had significant, positive correlations with TPD, ESV, SMS and STS, but significant, negative correlations with LVEF and number of viable myocardial segments, as listed in Table  SD in GM17, it is impossible to demonstrate their correlation. For the MI group, BW and SD values obtained by GMMI and GMPI phase analysis were in a good agreement and had a significant correlation (rBW = 0.74 and rSD = 0.84). Furthermore, for both normal and MI groups, BW and SD values obtained through GMMI phase analysis were not overestimated or underestimated. In previous studies comparing GMMI and GMPI phase analyses16, all enrolled patients had coronary heart disease. However, due to differences in the accompanied diseases, degrees of LV remodeling and cardiac function impairment, as well as image qualities and reconstruction methods, the correlations of BW and SD values obtained from GMMI and GMPI phase analyses were different . Compared with these studies, we mainly utilized mini-pigs, which have been shown to have a better translational bridge between preclinical and clinical studies compared with other animals18, to simulate the clinical situations of patients with MI not accompanied with other diseases  and assessed the accuracy of GMMI phase analysis technique.Whether GMMI phase analysis is clinically feasible depends on its accuracy for quantitative determination of BW and SD values. In this study, we performed animal experiments and compared the consistency and linear correlation of BW and SD obtained by using GMMI phase analysis with those by GMPI one. The results showed that for normal group, BW and SD values obtained by GMMI and GMPI phase analyses were in a good agreement, but had no significant correlation, possibly due to that there was a narrow and sharp peak in phase histogram and narrow normal ranges of BW and SD of the normal group. Thus, under the time resolution (5.6°)19 found that placement of the LV lead to the latest sites of contraction and away from the scar could significantly reduce mortality of patients with heart failure and heart-failure-related hospitalization rate. Therefore, accurate assessment of the latest activation sites is particularly necessary. In this study, we showed that GMMI phase analysis had slightly higher consistency with GMPI one in determination of the latest activation sites of left ventricle in MI group than in normal group (77.8% vs 66.7%), roughly consistent with that of Wang et al.15. In addition, we also found that the latest activation sites were located in LAD artery distribution area in 88.9% of pigs with MI using GMMI phase analysis, while in 66.7% of pigs with MI using GMPI phase analysis. The underlying mechanism may be related to that the occlusion-induced MI of LAD artery distribution could lead to loss of metabolic activity of cardiomyocytes and weakening/disappearance of local myocardial systolic function, presenting as delayed mechanical contraction.Implantation of CRT electrodes in the latest activation sites of left ventricle can rectify LV systolic dyssynchrony to the greatest degree. KhanThe results showed that BW and SD of the normal group, but not the MI group, in the GMMI were significantly and negatively correlated with SUVm/b. Thus, it is clear that the quality of GMMI images is related to the accuracy of phase analysis. When the quality of images is poor, the ratio of SUV values of myocardial and mediastinal blood pools is low, indicating that there are risks of overestimating BW and SD.20 analyzed resting GMPI images of 2331 patients with heart failure and found that SD was significantly and positively correlated with summed rest score , but negatively correlated with LVEF , being consistent with our findings. Our study also found that after MI, the higher the total scar score is, the fewer the viable myocardial segments are and the more obvious the LV systolic dyssynchrony is. CRT can ameliorate LV systolic dyssynchrony. But too great myocardial scar burden can also cause nonresponse to CRT. Adelstein et al.3 studied patients with ischemic cardiomyopathy and found that when LV summed rest score ≥27, the improvement of post-CRT LV function was not obvious and the prognosis of patients was poor. Ypenburg et al.21 found that the sensitivity and specificity of predicting clinical response to CRT with the viable myocardial segments ≥11 were 74% and 87%, respectively.This study showed that both BW and SD in the MI group were significantly and positively correlated with TPD of left ventricle, but evidently and negatively correlated with LVEF. Multivariate linear regression analysis showed that TPD was an independent factor affecting BW in GMMI. After MI, the greater the extent and degree of myocardial perfusion defects are, the more obvious the LV systolic dyssynchrony is and the more severe the damage to LV systolic function is. HF-Action study22.This study also found that after MI, (1) BW was significantly and positively correlated with ESV and SMS, (2) SD was obviously associated with ESV, SMS and STS of left ventricle, and (3) SMS was an independent factor affecting SD in GMMI. These results indicate that post-MI LV systolic dyssynchrony is related not only to global systolic function but also to ESV as well as regional systolic function decline . Although the factors affecting BW and SD in GMMI phase are not exactly the same, both of them can be used to determine the presence of LV systolic dyssynchrony and assess the prognosis of patients with MI23. Because of higher spatial resolution and accuracy for assessing myocardial viability , PET GMMI detects LV contour more accurately than GMPI, which has emerged as a suitable modality to study the metabolic mechanisms of LV systolic dyssynchrony and the effects of CRT. PET/CT is not cost effective. But if this non-invasive imaging technology can significantly improve CRT response rate, it would be still acceptable, which needs further verification of multicenter clinical trials. Our findings may provide some evidences for development of such clinical trials.Although GMPI has been widely accepted to assess LV systolic dyssynchrony automatically and reproducibly, it still faces several challenges, such as limited temporal resolution as well as noise and artifact from areas with significantly reduced perfusion due to scar24. Second, the experimental animals used in this study were Guangxi Bama mini-pigs with a heart smaller than that of an adult. Thus, there is partial volume effect in the imaging process, especially in GMPI. Although 128 × 128 matrix, 1.45-fold amplification and an increased acquisition time were used in imaging, there was still possibility of overestimating cardiac function. Nevertheless, a previous study18 showed the experimental data on mini-pigs were more similar to those of humans. Third, many factors could affect myocardial substrate metabolism and myocardial glucose metabolism varies greatly. Although hyperinsulinemic -euglycemic clamp could promote glucose uptake in myocardia to the maximum degree and help obtain images with excellent quality, it requires longer operative time under anesthesia, which may affect cardiac function of the experimental animals. Therefore, glucose load plus intravenous insulin injection method was adopted to regulate glucose before GMMI. This method has been clinically proven to be a simple and effective glucoregulation regimen and recommended by ASNC and SNMMI25.First of all, the study is not a self-control study because repeated anesthesia can easily affect cardiac function and potentially lead to reduction of myocardial glucose metabolism of experimental pigsBW = 0.74, rSD = 0.84). In addition, BW and SD of the normal group were significantly affected by the quality of PET images. After MI, left ventricle had evident systolic dyssynchony. Both BW and SD values were affected by multiple factors including TPD, cardiac function , myocardial scar burden, and number of viable myocardial segments, indicating that LV systolic dyssynchrony after MI was the result of multi-factor interaction. Overall, GMMI phase analysis could accurately assess LV systolic dyssynchrony and could be promoted in clinics under assurance of image quality.No matter in the normal group or MI group, BW and SD values derived with GMMI phase analysis were in good agreements with those derived with GMPI. Especially in the MI group, both had a significant positive correlation  GMPI and 18F-FDG GMMI at 30–35 days after modeling. Upon the completion of imaging, pigs in the MI group, but not in the normal group, were sacrificed under anesthetic state for histopathological examination. The study was conducted in accordance with the Declaration of Helsinki and with the guide for care and use of laboratory animals. The experiment was approved by the Animal Ethics Committee of Soochow University and all efforts were made to minimize the suffering of animals. All methods were carried out in accordance with the approved protocols.Based on our preliminary experiments, LV function and the degree of LV remodeling in pigs with MI change in a dynamic process and are in a stable state at 4 weeks after MI. Therefore, pigs in the MI group were subjected to 12-lead electrocardiogram, To establish an animal model of MI, pigs in the MI group were deprived of water and feed for 12 h, intramuscularly injected 35 mg/kg ketamine and 1.5 mg/kg diazepam to induce anesthesia and 4–6 ml/h propofol to maintain anesthesia, and intravenously perfused 75 mg/h amiodarone to prevent malignant ventricular arrhythmia. The modeling was conducted under anesthesia as the following: (1) Perform tracheal intubation, connected pig to a ventilator to assist respiration, and subject pig to electrocardiogram and blood pressure monitoring throughout the operation; (2) MI was induced by catheter based 90-minute balloon occlusion of the LAD immediately after the origin of the first diagonal branch; and (3) Perform postoperative analgesia and anti-infection treatment. The successful establishment of pigs with MI was confirmed using electrocardiogram and the level of hypersensitive troponin I.99mTc-MIBI with radiochemical purity >95%; (2) 45 min after injection, fix pig and place electrodes upon the heart with two detectors setting at 90°; (3) Acquire images every 35 s and 6° clockwise from 45° at the right anterior oblique position to 45° at the left anterior oblique position with acquisition matrix of 128 × 128 and magnification of 1.45; (4) Perform the gated acquisition with electrocardiographic R-wave as the acquisition trigger signal and 8 frames/RR interval; and (5) Reconstruct images using filtered back projection method with cutoff frequency of 0.35 and order of 5 to obtain heart images in short axis, horizontal long axis and vertical long axis.At 30–35 days after modeling, the pigs in the normal and MI groups were deprived of water and feed for 12 h and subjected to GMPI using a Siemens Symbia T16 SPECT/CT Scanner equipped with a low-energy, high-resolution collimator (Germany). The procedure of GMPI was as follows: (1) Intravenously inject 370–555 MBq of 25 to adjust blood glucose to 5.55–7.77 mmol/l, 30 min later, re-measure blood glucose; (5) Intravenously inject 111–185 MBq of 18F-FDG; (6) At 45–60 min after injection, perform GMMI with 8 images per R-R interval, 3D acquisition, and 10 min/bed position; (7) Reconstruct images using algorithm of ultra high definition PET with 2 iterations and 21 subsets to obtain heart images in short axis, horizontal long axis and vertical long axis; and (8) Apply the Syngo TureD software to extract the ROI of myocardium and mediastinal blood pool, obtain their standard uptake value (SUVmyo and SUVbp), and calculate their ratio SUVm/b = SUVmyo/SUVbp.GMMI was performed after GMPI at the same day using Siemens Biograph mCT-s (64) PET/CT Scanner (Germany). The procedure of GMMI was as follows: (1) Measure fasting blood glucose of each pig; (2) Intravenously inject 20–30 ml of 50% glucose solution (10–15 g glucose); (3) 30 min after injection, re-measure blood glucose level, (4) Intravenously inject insulin based on the glucose level according to the 2016 ASNC imaging guidelines/SNMMI procedure standard for PET nuclear cardiology procedures15.The reconstructed GMMI and GMPI images were subjected to phase analysis using Cedars QGS software  to obtain LV systolic synchronization parameters including phase BW and SD. Phase BW is defined as the range of degree of the cardiac cycle that encompasses 95% of the phase distribution, and phase SD is defined as the SD of the phase distribution. According to the initial phase angles of various LV myocardial segments, the segment with the maximum initial angle was defined as the latest activation site and its corresponding positions in LV anterior, anteroseptal, inferoseptal, inferior, inferolateral, anterolateral and apical region were recordedGMPI images were also analyzed using software, Cedars QPS, to determine TPD, and GMMI images were analyzed using software, Cedars QGS, to obtain the entire LV functional parameters including EDV, ESV, and LVEF and LV regional functional parameters including SMS and STS.22: Point 0 was defined as tracer activity >75% ; Point 1 as tracer activity = 50–75% ; Point 2 as tracer activity = 25–50% (moderate scar); and Point 3 as tracer activity <25% (extensive scar). The number of viable  segments per pig was noted. In addition, the summation of various segmental scores yielded the total scar score. The higher the score was, the more the scar tissue existed.The reconstructed short-axis GMMI images were displayed in the polar map format after normalized to the maximum activity and analyzed using a 17-segment model. Tracer uptake was quantitatively analyzed and categorized on a 4-point scaleUpon the completion of imaging, the pigs in the MI group, but not in the normal group, were sacrificed under anesthetic state for histopathological examination using the following procedure: (1) Remove the heart immediately and rinse with saline; (2) Evenly cut the left ventricle into 6–8 pieces from the apex to the base, immerse these pieces in TTC at 37 °C for 10 min and subject them to pathological staining; (3) cut off tissues at infarct segment, infarct margin segment and normal myocardial segment, fix them in 10% formalin, embed them with paraffin and prepare as 5 μm sections; and (4) Stain these sections with HE and Masson so as to confirm the successful modeling and observe morphological changes in myocardial tissues.P < 0.05 was considered as statistically significant.Statistical analysis was performed using SPSS 23.0 software and two-sided test. All count data were expressed as ratio and compared using chi-square test or Fisher exact probability method. Shapiro-Wilk test was performed to determine whether the measurement data follow a normal distribution. The measurement data were presented as mean ± standard deviation and compared using Mann-Whitney U test to examine the synchronization between MI and normal groups. Differences in LV systolic dyssynchrony of GMMI and GMPI were examined by comparing BW and SD using Wilcoxon symbol rank test. The correlation between their absolute value was analyzed by Pearson linear correlation analysis and Bland-Altman analysis. Intraclass correlation coefficient with absolute agreement definition was used to assess the degree of agreement between the two imaging methods. Multivariate stepwise regression analysis was used to analyze independent factors affecting BW and SD in GMMI.


A 47-year-old man was admitted for acute heart failure. The ECG had low voltage criteria. Transthoracic echocardiogram showed bi-atrial dilation, left ventricular concentric hypertrophy with reduced ejection fraction (LVEF of 48%) and hypertrophy of the right ventricular free wall. There was no valve dysfunction. Two-dimensional speckle-tracking echocardiography showed an apical sparing pattern of longitudinal strain Fig. . ElectroAmyloidosis is a multi-systemic disease characterised by the deposition of amyloid fibrils, cardiac involvement being usually associated with poor prognosis , 2. Rela


This study was performed to compare the associations of brachial-ankle pulse wave velocity (baPWV) and central blood pressure (CBP) measurements with left ventricular (LV) geometry and diastolic function.A total of 77 subjects  without documented cardiovascular disease were prospectively recruited. All subjects underwent transthoracic echocardiography, baPWV and noninvasive measurement of CBP on the same day.P > 0.05 for each). Although baPWV significantly correlated with septal e´ velocity in simple linear correlation analyses , the significance was lost after controlling for potential confounder (P = 0.881). In simple linear correlation analyses, central systolic blood pressure (CSBP) and central pulse pressure (CPP) significantly correlated with both septal e´ velocity or E/e´ (P <  0.05 for each); however, neither central diastolic nor mean arterial pressures was associated with both septal e´ velocity and E/e´ (P > 0.05 for each). After controlling for confounders, including age, sex and body mass index, CSBP correlated with septal e´ velocity , but not with E/e´ (P = 0.074). CPP correlated with both septal e´ velocity  and E/e´  in the same multivariable model.In simple linear correlation analyses, neither baPWV nor CBP was associated with LV mass index or relative wall thickness (In subjects without documented cardiovascular disease, CSBP and CPP may be more strongly associated with LV diastolic function than baPWV. Further studies with a larger sample size are needed to confirm our results. Arteries stiffen with age, and cardiovascular diseases progress . InformaCentral blood pressure (CBP) is the pressure in the ascending aorta, just outside of the left ventricle (LV). Based on the fact that major vital organs, such as the heart and the brain, are more closely exposed to CBP than to brachial blood pressure (BrBP), emerging evidence has suggested that CBP is more predictive of future cardiovascular events than BrBP –8. Also,It has been suggested that there was a close interaction between the LV and the aorta –15. ArteBetween January and March 2018, consecutive adult subjects (≥ 18 years) who visited Seoul Metropolitan Government Seoul National University Boramae Medical Center  for cardiovascular examinations were prospectively enrolled in this study. Subjects were eligible if they had been never diagnosed with myocardial infarction, angina requiring revascularization, heart failure, peripheral arterial disease or stroke. Subjects with the following clinical conditions were also excluded: 1) unstable vital signs, 2) left ventricular ejection fraction < 50%, 3) valvular regurgitation or stenosis of mild degree and greater, 4) uncontrolled arrhythmia, and 5) ankle-brachial index < 0.9 or > 1.4. The study protocol was approved by the Institutional Review Board of Boramae Medical Center . Written informed consent was obtained from each study subject.Body mass index (BMI) was calculated by dividing body weight (kg) by the square of body height (m). Hypertension was defined as systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, previous diagnosis of hypertension, or the use of antihypertensive medications. Diabetes mellitus, was defined as fasting glucose ≥ 126 mg/dL, previous diagnosis of diabetes mellitus or the use of anti-diabetic medications. Dyslipidemia was defined as low-density lipoprotein cholesterol ≥ 160 mg/dL, previous diagnosis of dyslipidemia, or the use of anti-dyslipidemic medications. Subjects were classified as smokers if they had smoked within the recent 12 months. All subjects underwent laboratory tests with venous blood taken in the morning after overnight fasting. White blood cell (WBC) count and hemoglobin concentration as well as serum levels of fasting glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, glycated hemoglobin (HbA1c) creatinine, and C-reactive protein were measured by an automated enzymatic procedure. Estimated glomerular filtration rate was calculated using the 4-component Modification of Diet in Renal Disease (MDRD) study equation incorporating age, race, sex, and serum creatinine level [The volume-plethysmographic apparatus  was used for the measurement of baPWV. Each baPWV was measured in accordance with the manufacturer’s instructions , 18. CafImmediately after baPWV measurement, CBP measurement was conducted using a commercially available radial artery applanation tonometry  . Left raTTE was performed on the same day of CBP measurement. TTE was performed using commercially available devices  according to the recommendations of the current guidelines , 23. LV Z test [P value of < 0.05 was considered statistically significant. All statistical analyses were conducted using SPSS 22.0 .The continuous variables are presented as mean ± SD, and categorical variables are expressed as percentages. Univariate associations between 2 parameters were assessed using simple linear regression analyses. Multivariable linear regression analysis was subsequently applied to examine independent relationships between individual parameters that had significant associations in univariate analyses. Age, sex, and BMI were adjusted during multivariable analyses. Scatter plots were used for the demonstration of linear correlations between 2 parameters. Correlations were compared using Meng’s Z test . A P valClinical characteristics of the study subjects are presented in Table P > 0.05 for each). It correlated with e′ velocity in simple correlation analysis ; however, the statistical significance disappeared in multivariable analysis (P = 0.881). CSBP correlated with e′ velocity  and E/e′ , but not with RWT (P = 0.768) or LVMI (P = 0.869) in simple correlation analyses. In multivariable analysis after controlling for confounding effects of age, sex, and BMI, the statistical significance remained in the association between CSBP and e′ velocity , but not in the association between CSBP and E/e′ . Neither CDBP nor CMAP was not associated with RWT, LVMI, e′ velocity, or E/e′ in simple correlation analyses (P > 0.05 for each). CPP correlated with e′ velocity  and E/e′ , but not with RWT (P = 0.984) or LVMI (P = 0.333) in simple correlation analyses. The statistical significances in the associations of CPP with e′ velocity  and E/e′  remained even after controlling for age, sex, and BMI in multivariable analyses. The linear correlations of baPWV and CPP with E/e′ are demonstrated in Fig. r = 0.454, P <  0.001). The correlation coefficient was numerically smaller between brachial PP and E/e′ than between CPP and E/e′, although it was statistically insignificant (P for difference = 0.111)  there were lack of associations of both baPWV and CBP with LV geometry; and 2) CSBP and CPP, but not baPWV, were associated with LV diastolic function. To the best of our knowledge, this is the first report showing more powerful association of CBP with LV diastolic function compared to arterial stiffness in the same subject.The association between CBP and LV diastolic function has been reported. Previously, our group has reported a significant association between invasively measured pulsatile pressure of the central aorta and LV diastolic parameters in 153 patients undergoing invasive coronary angiography . Shim etThere have been several studies reporting the association of arterial stiffness measured by baPWV with LV diastolic function. Analysis of 320 subjects with various abnormalities of cardiac structure and function have suggested that baPWV correlates with parameters of LV structure and function such as LV mass and mitral e′ velocity . Wang etA novel finding of our study is that CBP more affects LV diastolic function than arterial stiffness. This may suggest the importance of CBP as an indicator of LV diastolic dysfunction, which provides an additional insight in the interaction between LV and the arterial system. Given that LV diastolic dysfunction is associated with worse clinical outcomes , 36, CBPThere are several limitations to this study. First, it is difficult to prove the causal relationship between CBP and LV diastolic function in this cross-sectional study. Secondly, there was the possibility that the small sample size of our study could not draw statistical significance in the relationships between baPWV and LV diastolic parameters, and between baPWV/CBP and LV geometry. For the same reason, some potential confounders, such as medications, could not be controlled during multivariable analyses. Also, although sex differences in ventricular-arterial relationships have been an issue , 26, sexIn middle-aged or older subjects without overt cardiovascular disease, CSBP and CPP were more strongly associated with LV diastolic function than baPWV. Measurement of CBP rather than baPWV may be more useful for the risk stratification and management of these age groups of subjects. Further studies with a larger sample size are warranted.


The objective of this study was to assess, whether right atrial (RA) and ventricular (RV) size is related to RV pump function at rest and during exercise in patients with pulmonary arterial hypertension (PAH).exercise). Patients were classified according to the median of RA and RV-area. RV pump function and further clinical parameters were compared between groups by student’s t-test. Uni- and multivariate Pearson correlation analyses were performed.We included 54 patients with invasively diagnosed PAH that had been stable on targeted medication. All patients underwent clinical assessments including right heart catheterization and echocardiography at rest and during exercise. RV output reserve was defined as increase of cardiac index (CI) from rest to peak exercise  showed significantly lower ∆CIexercise, higher mean pulmonary arterial pressure, pulmonary vascular resistance at rest and NT-proBNP levels. Furthermore, patients with higher RV-areas presented with a significantly lower RV stroke volume and pulmonary arterial compliance at peak exercise than patients with smaller RV-size. RV area was identified as the only independent predictor of RV output reserve.Patients with larger RA and/or RV-areas (above a median of 16 and 20cmRV and RA areas represent valuable and easily accessible indicators of RV pump function at rest and during exercise. Cardiac output reserve should be considered as an important clinical parameter. Prospective studies are needed for further evaluation. Pulmonary arterial hypertension (PAH) is a complex cardiopulmonary disorder, characterized by progressive changes affecting both the pulmonary vasculature and the right heart , 2. AlthRight atrial (RA) –9 and RVexercise) defined as increase of cardiac output/cardiac index (CI) during exercise with normal or elevated PVR measured by right heart catheterization (RHC) is an emerging parameter which has shown to be prognostically important in patients with PAH [4. Pulmonary arterial compliance (PAC) reflects the elasticity of the pulmonary arteries. For estimation of pulmonary arterial compliance (or capacitance) the measurement of SV/pulse pressure (cardiac output/heart rate)/(systolicPAP-diastolicPAP) by RHC has been shown to be the most simple and practical method [RV output reserve  and RV pump function at rest and during exercise (assessed by RHC) and further hemodynamic and clinical parameters. Furthermore, this study aimed to detect correlations and determining factors of RV pump function.We retrospectively reviewed all incident (i.e. newly diagnosed) patients aged ≥18 to 80 years with idiopathic, heritable or drug- and toxin-induced or connective tissue disease associated PAH who were diagnosed at the PH-center in Heidelberg between January 1st, 2016 and November 31st, 2016. Inclusion required RHC at rest  under standardized conditions , laboratThe hemodynamic values have been obtained by the charts. The right heart catheterization has been performed in a standardized way in a supine position using the transjugular access with a triple-lumen 7F-Swan-Ganz thermodilution catheter at rest and during exercise as previously described . PatientResting two dimensional transthoracic echocardiography (TTE) Doppler examinations were performed by experienced cardiac sonographers  with commercially available equipment  according to standardized protocol as described previously , 22. TTE2 was defined as the highest 30-s average value of oxygen uptake during the last minute of the exercise test.Patients were examined on a variable load supine bicycle ergometer  in Heidelberg as described previously . WorkloaThe Ethics Committee of the Medical Faculty, University of Heidelberg had no obligation against the conduct of the study . All data were anonymized and the study was conducted in accordance with the amended Declaration of Helsinki.2 for RV area according to the cut-off proposed by the guidelines17 was performed.Statistical analyses were conducted by two biometricians . Data are described as means ± standard deviations or number and respective percentage. Patients were divided into two groups according to their RV size . A receiver operating characteristic (ROC) curve analysis for RA and RV area with CI increase below the median of the sample as outcome parameter for further validation of the cut-off values was performed. Quantitative characteristics between the two groups including demographics, hemodynamics and parameters of echocardiography and cardiopulmonary exercise testing were compared by two-sided student’s t-tests and nonparametric tests if needed. Frequency distributions were compared by chi-square test or Fisher’s exact test. A sensitivity analysis with a threshold of 18 cmexercise (according to the median of the complete sample).Right heart size (RA and RV area) was compared between patients with higher vs. lower ∆CIexercise) as outcome variable. Parameters for correlation analysis included demographics, hemodynamics, echocardiographic parameters and measures of cardiopulmonary exercise testing according to clinical significance.Differences of the course of CI and SV increase during exercise between patients with smaller vs. larger RA and RV area were analysed with mixed ANOVA. To investigate the associations between clinical parameters, right heart size and output reserve, Pearson’s correlation analysis was performed. To identify independent predictors of RV output reserve, multivariate analysis was performed by stepwise forward selection method of logistic regression with the dichotomous variable of the two groups  was calculated according the formula PAC = SV/ pulse pressure with SV = CO/Heart rate and pulse pressure = sPAP-dPAP. Stroke volume index was calculated with SVI = CI / heart rate.p-value of 0.05 was considered statistically significant. All analyses have been performed using IBM SPSS 23 .All tests were two-sided and a pointwise We included 54 patients diagnosed with moderate to severe PAH who fulfilled the inclusion criteria  further supported these proposed cutoff-values of 16cm2 for RA and 20cm2 for RV area  “enlarged right heart size”  and 2) “normal/smaller right heart size” , 6MWD, diffusion capacity and peak VOn = 21) and/or RV-area (n = 24) had significantly higher mean, systolic and diastolic pulmonary arterial pressures, mean pulmonary vascular resistance, and NT-proBNP levels than patients with normal or smaller right heart size.Patients with enlarged RA-  and/or RV area . Furthermore, patients with smaller RV, but not RA, presented with significantly higher peak PAC than patients with RV area above the median .SV failed to increase in accordance with the exposed exercise level in patients with large RA- p = 0.01 and/or 2 for RV area led to the same differences between groups with small and large right heart size. Furthermore, CI increase showed a statistically significant difference for each workload level.Sensitivity analysis with a threshold of 18 cmexercise) echocardiography showed considerable differences in RV and RA area , hemodynamics  and lung diffusing capacity (transfer factor DLCOc SB and transfer coefficient DLCOc / VA)  and hemodynamics at rest .∆CIA) Table . A negatPeak .Stepwise forward selection of multivariate logistic regression analysis showed RV area to be the single independent predictor for high or low ∆CIexercise) measured by right heart catheterization. Furthermore, the study revealed that PAH-patients with larger size of the right heart had higher pulmonary arterial pressures, pulmonary vascular resistance and NT-proBNP levels. Patients with higher RV-areas presented with a significantly lower stroke volume index and pulmonary arterial compliance at peak exercise than patients with smaller RV-size. RV area was identified as the only independent predictor of RV output reserve (lower ∆CIexercise). Thus, this study gives further evidence that assessing the right heart size by imaging techniques as echocardiography gives further important clues to RV pump function and cardiopulmonary hemodynamics.To the best of our knowledge this is the first study showing that in patents with PAH enlarged RV- or RA areas (measured by echocardiography) were associated with a significantly reduced RV pump function during exercise  in order to maintain SVThe retrospective, single-center design of this study with a rather small number of subjects limits the study results. A higher sample size may have led to identification of more independent factors in the multivariate analysis.Echocardiographic assessments of the right heart are complicated by its complex shape and morphology. Especially in obese patients, patients with chest wall deformities or COPD, the correct assessment of RV size and function becomes a challenging task. In this respect, cardiac MRI becomes particularly appealing, as it does provide a thorough assessment of right heart size and function even in complicated conditions. In our cohort, high quality recordings were used and no comorbidities were interfering the test results. As the determination of RA and RV area is a readily available assessment which is practicable in a good quality, its application in clinical practice is more common compared to cardiac MRI. Unfortunately, no MRI data is available for this patient cohort to confirm the hemodynamic data.Invasive measurements, cardiopulmonary exercise testing and echocardiographic parameters could not be assessed in one single examination. In order to reduce the influence of inter-exam variations, we only included patients that underwent all measures within a time frame of 48 h. The assessment of CI may be complicated by tricuspid insufficiency in patients with PH. Due to the bidirectional blood flow through the tricuspid valve CI may be overestimated in some patients, which may have influenced the results.The correlation of right heart size and function to TAPSE and other parameters and their prognostic value should be investigated in a larger-scale study.The study shows that assessment of right heart size is important for RV functional characterization and may be helpful since it reflects RV pump function and RV output reserve. RV and RA area by 2-D echocardiography represented a valuable and easily accessible indicator of RV pump function at rest and during exercise. Therefore, these results may be relevant for clinical practice. RV output reserve should be considered as an important clinical parameter. However, prospective studies are needed for further evaluation.


Introduction: Adult survivors of the atrial switch operation for transposition of the great arteries present with a systemic morphologic right ventricle and a subpulmonary morphologic left ventricle. This physiology can be considered a model for the effects of long-term right ventricular pressure overload and of decreased left ventricular afterload. We aimed to determine the impact of these chronically altered loading conditions on myocardial deformation of the ventricles.Materials and methods: Two-dimensional steady state free precession cine images of 29 patients after atrial repair (age 29 ± 7 years) and 19 controls  were post-processed with feature tracking software (TomTec 2D CPA). Volumes, ejection fractions, global and free wall longitudinal and circumferential strains of both ventricles were compared between both groups.Results: Systemic right ventricular global longitudinal strain was decreased in patients compared to controls , while right ventricular circumferential strain was unchanged . Left ventricular longitudinal strain was similar in both groups , but global left ventricular circumferential strain was lower in patients . The systemic right ventricle, compared to the systemic left ventricle, showed decreased global longitudinal (p < 0.001) and circumferential strain (p < 0.001). The subpulmonary left ventricle, compared to the subpulmonary right ventricle, demonstrated similar longitudinal (p = 0.223) but higher circumferential strain (p < 0.001).Conclusions: In patients after atrial switch repair for transposition of the great arteries, the systemic right ventricle shows poor longitudinal strain, but maintains normal right ventricular circumferential strain. The left ventricle shows higher circumferential strain than the right ventricle, in both systemic and subpulmonary positions. The atrial switch operation according to Senning or Mustard has been the surgical repair technique of choice for transposition of the great arteries (TGA) for many years . In the Cardiac magnetic resonance (CMR) has evolved to be the reference method for calculation of RV volumes and function, due to its high accuracy and reproducibility .Magnetic resonance feature tracking (MRFT) enables quantification of the segmental and global motion of the myocardium from CMR cine images . MRFT isThe aim of this study was to examine regional deformation of the ventricles in patients after atrial repair (Senning) and to compare it with that of individuals with normal cardiac anatomy (controls). We hypothesized that the RV and LV in Senning patients show different deformation patterns than normal ventricles due to their reversed pressure loads.All consecutive patients with TGA after atrial switch operation undergoing a CMR examination between June, 2009 and March, 2016 were considered for inclusion in the study. Exclusion criteria consisted of evidence of chronic tachyarrhythmias or arrhythmias at the time of image acquisition, significantly impaired function with an ejection fraction (EF%) of either ventricle of <30%, significant baffle leak with a pulmonary to systemic blood flow ratio > 1.3: 1, significant baffle stenosis with evident venous dilation and/or reversed flow in the azygous vein, subpulmonary LV outflow tract obstruction. Baseline characteristics, CMR data including ventricular volumes, EF%, flow volumes, and strains in longitudinal and circumferential direction, as well as follow up cardiopulmonary exercise (CPEX) data were collected / measured.Healthy volunteers and patients in whom cardiac pathology was ruled out by CMR, such as patients who were imaged for suspected vascular rings, were recruited as normal controls.All subjects underwent CMR on a 1.5 Tesla system  using a 32-channel phased-array cardiac coil and vector cardiogram for retrospective cardiac gating.Cine Steady State Free Precession (SSFP) images were acquired in a horizontal long-axis plane showing both ventricles and both atria as well as in a stack of 12–13 adjacent short-axis slices through both ventricles from the cardiac base to the apex, with a slice thickness of 8 mm and gap of 0–2 mm. All images were acquired in end-expiratory breath-holding.The parameters of the SSFP sequence were as follows: 40 reconstructed phases/cardiac cycle, TE 1.5–1.8 ms, TR 2.8–3.1 ms, flip angle 45°, bandwidth 125 kHz, matrix 224 × 224, number of excitations 1, field of view 250–350 mm, views per segment 6–12 depending on heart rate. Parameters were optimized for obtaining a temporal resolution of <30 ms (mean 26.7 ms). Cine phase contrast images were obtained in through planes perpendicular to the ascending aorta and main pulmonary artery, in breath-holding technique, for internal validation of stroke volumes.Ventricular volumes and ejection fractions were calculated offline on a separate workstation with a dedicated software . The endsystolic and enddiastolic phases were identified visually in a midventricular short axis slice, the endocardial contours were manually traced; volumes and ejection fractions were calculated as previously described and indexed to body surface area . On phasFeature tracking analysis was performed using a dedicated software . Endocardial contours of both ventricles were traced manually on an end-diastolic image frame , and subLongitudinal strain analysis was performed on the horizontal long-axis view (four chamber view) of both ventricles. For the LV, the endocardial border was traced beginning at the septal mitral annulus, along the apex, and ending at the lateral mitral ring in a clockwise direction. For the RV, a mirror image was created in order to similarly trace from the septal tricuspid annulus, along the apex, and ending at the lateral tricuspid ring in a clockwise direction.Circumferential strain was measured for both ventricles on one midventricular slice on short axis images. Midventricular location was chosen to minimize the out-of-plane motion of the region of interest .The software provided values of global longitudinal and/or circumferential strain for the LV and the RV by averaging all segmental values. Regional segmental values were provided for the LV following the American Heart Association 17-segment model. We used a “mirror image” nomenclature for defining the segments of the RV . SystemiImage quality was assessed for each slice and classified as: 2 = good, 1 = moderate, 0 = inadequate. Images of inadequate quality were excluded from analysis.Intraobserver variability was tested by one investigator (BB) measuring twice, on different days at least 8 weeks apart. Interobserver variability was assessed from measurements of two independent investigators  blinded to each other's results.t-test was used to compare data between groups. For parameters that were not normally distributed, the Mann-Whitney U-test was used for comparison statistics. Correlations were calculated using Pearson's correlation coefficient. Intra- and interobserver variability was examined with Bland-Altman analyses , was used for statistical analyses.Continuous data are expressed as mean and standard deviation (SD). The one-sample Kolmogorov-Smirnoff test was used to test for normal distribution. The Student's analyses  and intrTwenty-nine patients after the atrial switch operation (Senning group) and 19 healthy normal controls (control group) were recruited in the study. Subject characteristics did not differ in terms of age, sex, height, weight, or heart rate . In 4 pap < 0.001) and lower RV EF% (p < 0.001) than controls (Senning patients presented larger RV end-diastolic volumes (RV EDV) (controls .p < 0.01). No difference was observed for LV EF% (p = 0.43).LV volumes were smaller in end-diastole (LV EDV) in the Senning group than in the control group (p < 0.001). The systemic RV had lower EF% than the systemic LV (p < 0.001).Comparing the ventricles in their functional positions, RV in systemic position were larger than the normal systemic LV (p < 0.05) and showed higher EF% (p = 0.001).The subpulmonary LV in the Senning group were smaller than the subpulmonary RV in the control group (p < 0.001), while mitral APSE was not significantly different . Senning patients showed lower APSE of their systemic  and also lower APSE of their subpulmonary ventricles .Tricuspid annular plane systolic excursion (APSE) was lower in the Senning than in the control group  compared to normal RV. No difference was found for RV global circumferential strain (The systemic RV (Senning) showed lower global longitudinal strain (l strain .p < 0.001).The subpulmonary LV (Senning) had similar global longitudinal strains but lower global circumferential strains than the normal systemic LV (p < 0.001)  .p < 0.001).Both ventricles in subpulmonary position, i.e., the RV in normal subjects and the LV in Senning patients, showed similar global longitudinal strain, however circumferential strain was higher in the LV than in the RV (p < 0.001) and reduced torsion  compared to the systemic LV in controls.The systemic RV in Senning patients showed significantly reduced twist , as well as with LV EF% . Circumferential strain of the systemic RV correlated with RV EDV , LV EDV , and RV EF% . LV longitudinal or circumferential strains did not correlate with ventricular volumes or EF%.In Senning patients, longitudinal RV strain correlated with RV EF%  and with LV EF% .In the control group, RV longitudinal strain correlated with RV EF% (n = 16) had worse RV global (p = 0.03) and free wall (p = 0.008) longitudinal and worse RV global (p = 0.002) and free wall (p = 0.008) circumferential strain. LV strain values were not influenced by RV EF%.Comparing subgroups of patients with RV EF% < 40% vs. ≥ 40%, those with lower RV EF% , but not in controls.RV longitudinal strain correlated with RV circumferential strain in Senning patients  and circumferential  strains in normal subjects, but not in Senning patients.LV longitudinal strain did not correlate with other strain parameters; LV circumferential strain correlated with RV longitudinal (Twenty of 29 (69%) Senning patients underwent CPEX within a median interval to CMR of 7 days (range −343 to 346 days). Additionally, the latest CPEX during follow up was considered for further functional assessment and was available in 20 of 29 (69%) patients. Most CPEX were performed as bicycle ergometries using a ramp protocol. Work load [Watts], maximal oxygen consumption [ml/kg/min], and the slope of VE/VCO2  were recorded. Patients were stratified into Weber class (A to D) according to Guazzi et al. , analogo*min) peak oxygen consumption, corresponding to 74.9 ± 14.2% predicted. VE/VCO2 was available in 17/29 (59%) of patients, with a mean ± SD of 25.7 ± 3.9. All patients attained Weber class A. VO2max at the time of CMR did not correlate with any ventricular strain. VE/VCO2 correlated weakly with global  and free wall  circumferential RV strain.At the first CPEX, patients attained a work load of 158 ± 48 Watts and 28.9 ± 5.3 ml/(kg*min) peak oxygen consumption, corresponding to 72.8 ± 13.7% predicted. All patients except one (Weber class B) were still in Weber class A at the most recent CPEX. VE/VCO2 was measured in 15/20 (52%) of patients at the most recent follow up, with a mean ± SD of 26.7 ± 3.4. No correlations with RV or LV strain were found. Exercise performance was unchanged over a follow-up period of 3.2 ± 1.4 years.At the most recent CPEX, mean performance was 170 ± 56 Watts and 28.4 ± 6.7 ml/(kgn = 16) were not performing worse than those with RV EF% ≥ 40% (n = 13). Performance in Watts, peak oxygen uptake, or percent predicted peak oxygen uptake were not correlated to RV EF%. Long-term exercise performance was not correlated with RV strain values.During follow up, patients with an RV EF% < 40% (n = 28) were still alive after a follow up time of 53 ± 25 months (range 2–108 months).One patient moved abroad after the CMR. All others (n = 8) had higher end-diastolic ventricular volumes than their counterparts . Medicated patients also differed from other Senning patients in that they had lower circumferential strains in their systemic RV . Senning groups did not differ in biventricular EF%, APSE, systemic RV twist or torsion.Senning patients taking ACE inhibitors or angiotensin receptor blockers .BB and EV contributed to conception and design of the study and made measurements. BB acquired ethics approval. BB, CK, JG, AO, and EV acquired data. BB performed the statistical analysis and drafted the manuscript. CK, JG, FF, AO, and EV revised it critically for important intellectual content. All authors provided approval for publication of the manuscript.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.


We sought to explore whether fetal hypoxia exposure, an insult of placental insufficiency, is associated with left ventricular dysfunction and increased aortic stiffness at early postnatal ages.2) from embryonic day E15‐21 or normoxic conditions (controls). After delivery, left ventricular function and aortic pulse wave velocity (measure of aortic stiffness) were assessed longitudinally by echocardiography from day 1 through week 8. A mixed ANOVA with repeated measures was performed to compare findings between groups across time. Myocardial hematoxylin and eosin and picro‐sirius staining were performed to evaluate myocyte nuclear shape and collagen fiber characteristics, respectively.Pregnant Sprague Dawley rats were exposed to hypoxic conditions (11.5% FiOp < .008). In contrast, diastolic dysfunction progressed following fetal hypoxia exposure beginning weeks 1–2 with lower early inflow Doppler velocities, and less of an increase in early to late inflow velocity ratios and annular and septal E’/A’ tissue velocities compared to controls (p < .008). As further evidence of altered diastolic function, isovolumetric relaxation time was significantly shorter relative to the cardiac cycle following hypoxia exposure from week 1 onward (p < .008). Aortic stiffness was greater following hypoxia from day 1 through week 8 . Hypoxia exposure was also associated with altered nuclear shape at week 2 and increased collagen fiber thickness at week 4.Systolic function parameters transiently increased following hypoxia exposure primarily at week 2 (Chronic fetal hypoxia is associated with progressive LV diastolic dysfunction, which corresponds with changes in nuclear shape and collagen fiber thickness, and increased aortic stiffness from early postnatal stages. In the this study, the impact of chronic fetal hypoxia exposure on myocardial function and aortic stiffness was explored at early postnatal developmental stages using a previously described fetal hypoxia rat model. Fetal hypoxia exposure was associated with progressive LV diastolic dysfunction from 1‐2weeks, which evolved concomitant with changes in nuclear shape and collagen fiber thickness, and with increased aortic stiffness from day 1. These findings are likely relevant to long‐term cardiovascular disease observed following fetal growth restriction. A vaginal smear obtained the following morning was examined for the presence of sperm, which we signified as day 0 of pregnancy (term ≈21 days). Throughout pregnancy, rats were housed in standard rat cages with ad libitum access to water and food (standard laboratory rat chow). On day 15 of pregnancy, rats were randomized to control (2.2®) with 30–70 MHz transducers. LV dimensions, LV systolic and diastolic function, and aortic stiffness were assessed using 2‐dimensional and M‐mode imaging and pulsed and tissue Doppler‐based modalities.Normoxia and hypoxia‐exposed pups were evaluated longitudinally by echocardiography on day 1 and day 3, week 1, week 2, week 4, and week 8 after birth. The rats were anesthetized with 1.5% isoflurane and placed in a supine position on a controlled heating pad. The chest and abdomen were shaved, and the extremities were gently fixed to the electrodes on the pad surface using tape and a highly conductive electrode gel. A single‐channel electrocardiogram signal and respiratory rate were continuously recorded on the imaging system. Body temperature was monitored by a rectal probe. Echocardiography evaluations were performed using a high‐resolution Vevo‐2100 ultrasound microscope  as previously described in humans  staining was performed to evaluate nuclear size and shape for assessment of cardiomyocyte hypertrophy . Longitudinal changes of parameters were estimated by using a mixed‐ANOVA  design with repeated measures. The effect of litter was analyzed using mixed‐effects models considering the pups to be clustered into litters to determine if the outcomes from the mixed repeated ANOVA, with pups being considered independent of litter, were different. Comparisons between week 2 and week 4 hypoxia and control pups for nuclear characteristics and collagen fiber counts and dimensions were assessed by 2‐way ANOVA and Tukey post hoc test. We used licensed copies of SPSS v24 and GraphPad Prism for performing the statistical analysis.Means and standard errors were calculated for the 2D and Doppler parameters of LV function and aortic PWV at the different developmental ages. Comparison between the normoxia and hypoxia‐exposed groups at each age was performed with two‐sided Student's 33.1In control rat pups, LV lateral (posterior) wall and septal (not shown) wall thickness in diastole corrected for weight were constant between day 1 and day 3 and subsequently decreased. LV end‐diastolic diameter corrected for weight decreased with age. Heart rate increased progressively with age to week 4. LV stroke volume corrected for weight decreased with age. With respect to systolic function, ejection fraction remained constant from day 1 to week 8, whereas rate‐corrected velocity of circumferential fiber shortening (VCFc) and systolic myocardial velocities (S’) of the lateral wall and septum progressively increased with age Table . Althoug3.2LV lateral and septal (not shown) wall thickness in diastole and LV end‐diastolic diameter corrected for weight did not differ between prenatal hypoxia‐exposed and control pups. LV stroke volume corrected for weight also did not differ. Heart rates were significantly lower in the fetal hypoxia rats at day 1 compared to controls but did not differ at any other stage. LV systolic function parameters  with age after week 2. In contrast, intrauterine hypoxia‐exposed pups demonstrated significantly increased aortic PWV at the earliest developmental stages, approaching controls by week 2, and remaining stable but higher thereafter Figure , suggest3.4With age in both hypoxia‐exposed and control rat pups, there was a decrease in nuclei counts, total nuclei area, and the percentage of nuclear area relative to the cardiomyocyte area Figure . AlthougWith respect to collagen fibers, there was a decrease in the total number of fibers in both groups with age, the extent of which did not differ between hypoxia‐exposed and control pups; however, collagen fiber perimeter and thickness increased significantly more so with age in the hypoxia‐exposed pups Figure . Changes4Our longitudinal study is the first to document in vivo the evolution of myocardial function in the healthy developing rat and the impact of exposure to a hypoxic intrauterine environment on myocardial function and aortic stiffness during early postnatal stages. Rodent models are increasingly used to study diseases of infancy and childhood. The availability of specialized ultrasound biomicroscopes with high frequency, high‐resolution transducers that permit in vivo assessments using state‐of‐the‐art echocardiography‐based modalities has made it now possible to investigate developmental changes in myocardial function longitudinally from very early stages in a way that is comparable to techniques used clinically in humans. Understanding the evolution of myocardial function and differences in function compared to that of humans provides insight into the translational capabilities of rodent models for pediatric and adult cardiovascular disease Chien, .Only one previous report has documented postnatal developmental changes in myocardial function in murine models using echocardiographic techniques, and this particular study only focused on LV inflow Doppler in mice from day 1 to week 12  and annular (E’) velocities acutely increase through the first year of life and continue to increase at a slower rate through adolescence  and others more progressive (LV diastolic dysfunction). We observed a brief period of bradycardia in the hypoxia‐exposed pups only on day 1 which normalized thereafter. The observed bradycardia could relate to altered fetal parasympathetic activity , the neonatal period (week 1), early infancy (week 2), early childhood (week 4), and early adolescence (week 8) in humans (Sengupta, 4.3There are limitations of our study that warrant consideration. Our model examined fetal hypoxia derived through maternal hypoxia rather than primary placental insufficiency. This model is associated with increased maternal blood pressure and altered vascular reactivity and late gestation reduction in uterine arterial resistance (Aljunaidy, Morton, Cooke, & Davdige, One other limitation of our study was the small number of litters used, despite which, when examined accounting for litter, the majority of variables remained unchanged from our initial analysis. That only the LV lateral wall E’ at 2 weeks lost significance between groups accenting for the impact of the litter did not significantly impact our observations of progressive LV diastolic function changes. Although pup weight was no longer significantly smaller at day 1, the model used has been previously shown to be associated with variable IUGR. That we were unable to show a difference in pup size yet still demonstrated important differences in cardiac function suggests hypoxia alone, even in the absence of growth restriction contributes to important cardiovascular changes that impact longer‐term cardiovascular health.5In conclusion, prenatal exposure to hypoxia results in transient changes in heart rate and LV systolic function, more progressive changes in LV diastolic dysfunction from early developmental stages that suggest combined relaxation and compliance abnormalities, and increased aortic stiffness from the newborn period to preadult stages. Alterations in LV diastolic function could be explained at least in part by altered collagen deposition which may evolve secondary to increased aortic stiffness. Ongoing work is needed to link these early functional changes with later life cardiovascular disease and to the histological, cellular, and molecular changes that are the consequence of hypoxia exposure.None of the authors have a conflict of interest related to this work.


Myocardial recovery after primary percutaneous coronary intervention in acute myocardial infarction is variable and the extent and severity of injury are difficult to predict. We sought to investigate the role of cardiovascular magnetic resonance T1 mapping in the determination of myocardial injury very early after treatment of ST-segment elevation myocardial infarction (STEMI).STEMI patients underwent 3 T cardiovascular magnetic resonance (CMR), within 3 h of primary percutaneous intervention (PPCI). T1 mapping determined the extent  and severity  of acute myocardial injury, and related these to late gadolinium enhancement (LGE), and microvascular obstruction (MVO). The characteristics of myocardial injury within 3 h was compared with changes at 24-h to predict final infarct size.P = 0.003) and at 6-months , higher incidence and larger extent of MVO  & . The average T1 value was an independent predictor of acute LGE , extent of MVO  and final infarct size . Receiver-operating-characteristic analysis showed that T1 value of AAR obtained within 3-h, but not at 24-h, predicted large infarct size (LGE > 9.5%) with 100% positive predictive value at the optimal cut-off of 1400 ms .Forty patients were included in this study. Patients with average T1 values of AAR ≥1400 ms within 3 h of PPCI had larger LGE at 24-h  predict a larger extent of MVO and infarct size at both 24 h and 6 months follow-up. Delayed CMR scanning for 24 h could not substitute the significant value of hyper-acute average T1 in determining infarct characteristics. One year mortality remains high at ~ 10% in patients presenting with ST-segment elevation myocardial infarction (STEMI), despite emergency revascularisation by primary percutaneous coronary intervention (PPCI) . ExistinCardiovascular magnetic resonance (CMR) is widely used to characterise injured myocardium . IschaemRecently, native T1 mapping was demonstrated to reflect tissue composition, with changes in T1 relaxation times reflecting pathological processes at the level of myocardial tissue , 11. MorAccordingly, we designed a proof-of-concept study using CMR T1 mapping for myocardial tissue characterisation, to test whether very early CMR imaging, within 3 h after PPCI, could provide prospective useful information to predict the evolution of myocardial injury, and final infarct size, in STEMI patients.Patients presenting with STEMI to the John Radcliffe Hospital, Oxford who underwent PPCI for an occluded coronary artery were prospectively enrolled as part of the Oxford Acute Myocardial Infarction (OxAMI) project  within 3 h of stent implantation (hyper-acute), at 24 h (acute) and at 6 months (follow-up). The scan protocol comprised cine balanced steady state free precession (bSSFP) for functional images, native T1 mapping using the shortened modified Look-Locker inversion recovery (ShMOLLI) for characterisation of area-at-risk (AAR) , T2* mapTypical acquisition parameters for bSSFP retrospectively gated cine images were TE / TR =1.4/3.2 ms; flip angle 50°; voxel size: 2.4 × 1.8 × 8.0 mm. To shorten the hyper-acute scan, the cine sequence at TP1 were acquired in a single breath hold using real time electrocardiogram (ECG)-triggered and at lower resolution (160 × 72) compared to other time points (224 × 137).T2 weighted (T2w) was performed using a T2-prep-bSSFP single shot sequence with surface coil correction .ShMOLLI T1 maps were generated from 5 to 7 bSSFP images with variable inversion preparation S2 time as described previously . Typicaln = 5), TE 22.14 ms, FOV 340 × 225 mm, bandwidth 5260 Hz/Px, matrix = 192 × 144, voxel size = 1.8 × 1.8 × 3.0 mm, flip angle 20°.T2* maps were obtained using a gradient echo sequence. Typical imaging parameters were: TR 600 ms, echo numbers (LGE was performed with a T1- weighted segmented inversion recovery gradient echo-phase sensitive-inversion recovery (GRE PSIR) sequence . LGE images were collected 10–15 min after the administration of 0.1 mmol/kg contrast agent   (Table P = 0.44), or regression in extent of LGE .There were significant differences in acute 24 h) CMR parameters using the pre-specified 1400 ms T1 cut-off obtained at the hyper-acute scan. Patients with hyper-acute T1>1400 ms in the injured myocardium had larger LV end diastolic volume (LVEDV)  with a trend towards larger LVESV  in patients with hyper-acute T1 values of AAR > 1400 ms. Final infarct size  was also larger while the myocardial salvage index was smaller (45% (37–54) vs. 71% (47–90), P = 0.021) .At the hyper-acute time point, there was a significant relationship between average T1 value and AAR  and ESV ], ejection fraction  and LGE  , ejection fraction , final infarct size   and extent of MVO   or LGE .Hyper-acute average T1 is Table . On multβ 3.07, 95% CI 1.11 to 5.02; P = 0.003 for LVEDV) and , MSI  and final infarct size  , ejection fraction  or final infarct size  at 6 months follow-up.Hyper-acute average T1 value of the AAR predicted follow-up LV volumes, EF, MSI and final infarct size Table . On multP = 0.006. By contrast, acute average T1 values of AAR (at 24 h post PPCI) did not predict large follow-up infarct size   in STEMI patients undergoing PPCI. The key findings of this study are: (1) Hyper-acute average T1 values of AAR were associated with infarct characteristics, whereby patients with higher average T1 values (> 1400 ms) had a larger extent of MVO and larger infarct size at both 24 h and 6 months follow-up; (2) hyper-acute average T1 value within the AAR, but not the extent (LV%) of AAR, independently predicted acute LGE myocardium and final infarct size at 6 months; (3) the significant value of hyper-acute average T1 value of AAR could not be substituted by delaying scan for 24 h and the utility of average T1 value exists only when CMR is performed at very early time point post STEMI.Tools to identify patients at increased risk post STEMI are needed for prognostic and therapeutic purposes, in addition, to guide clinical pathways and safe resource allocation . Our stuNotably, the ability of T1 mapping to differentiate high risk patients did not persist following the hyper-acute time point. Indeed, T1 value of AAR did not predict acute infarct size when obtained 24 h post STEMI. This may be related to inter-individual variations in the response to acute ischaemia and reperfusion, in addition to the dynamic changes of the severity of injured myocardium post reperfusion therapy , 9. HumaDifferent imaging biomarkers have been proposed to stratify STEMI patients, including LGE myocardium and MSI , 16. HowNative T1 mapping can provide a quantitative assessment of myocardial tissue composition in the setting of acute STEMI, without the need for contrast agents , 10. TheInfarct size and ejection fraction are considered as surrogates of infarct severity, nonetheless, their relationship with hyper-acute T1 value was not similar. The lack of correlation between ejection fraction and infarct size in non-large infarcts suggest a complex interaction between these two imaging biomarkers and may explain their association with T1 value . IMH wasThe sample size in our study is relatively small and the implications for clinical outcomes cannot be derived from a study of 40 patients. Early CMR imaging assessment precludes high risk and hemodynamically unstable patients. Those patients were excluded from our study, nonetheless, they have already declared themselves as high risk individuals and so stratification with imaging is less pressing. CMR analysis was performed using a threshold of 2SD for AAR and 5SD for LGE. While these image post-processing approaches are endorsed by expert consensus from the Society for Cardiovascular Magnetic Resonance (SCMR) , the SD Hyper-acute T1 values of the AAR  predicted a larger extent of MVO and infarct size at both 24 h and 6 months follow-up. Delaying CMR scanning for 24 h could not substitute the significant value of hyper-acute average T1 in determining infarct characteristics.Additional file 1. Study population and electrocardiographic analysis.


Ventricular arrhythmia (VA) in autoimmune rheumatic diseases (ARD) is an expression of autoimmune inflammatory cardiomyopathy (AIC), caused by structural, electrical, or inflammatory heart disease, and has a serious impact on a patient’s outcome. Myocardial scar of ischemic or nonischemic origin through a re-entry mechanism facilitates the development of VA. Additionally, autoimmune myocardial inflammation, either isolated or as a part of the generalized inflammatory process, also facilitates the development of VA through arrhythmogenic autoantibodies and inflammatory channelopathies. The clinical presentation of AIC varies from oligo-asymptomatic presentation to severe VA and sudden cardiac death (SCD). Both positron emission tomography (PET) and cardiovascular magnetic resonance (CMR) can diagnose AIC early and be useful tools for the assessment of therapies during follow-ups. The AIC treatment should be focused on the following: (1) early initiation of cardiac medication, including ACE-inhibitors, b-blockers, and aldosterone antagonists; (2) early initiation of antirheumatic medication, depending on the underlying disease; and (3) potentially implantable cardioverter–defibrillator (ICD) and/or ablation therapy in patients who are at high risk for SCD. Ventricular arrhythmia (VA) is associated with high morbidity and mortality . SpecifiVA is also commonly associated with autoimmune rheumatic diseases (ARDs). Seferovic et al.  describeThe term “arrhythmogenic inflammatory cardiomyopathy” (AIC) was recently proposed and includes a group of patients with nonischemic cardiomyopathy (NICM), who were referred for management of VA and were found to have evidence of active myocardial inflammation. Our aim in this review is to describe the profile of AIC in patients with ARD, suggest a diagnostic algorithm, and propose a “cardiorheumatic” therapeutic approach.Structural heart disease includes all causes of underlying myocardial fibrotic substrate (scar). The most common heart disease in ARDs leading to fibrotic substrate is ischemic cardiomyopathy (ICM)/heart failure (HF), which is caused by atherosclerotic coronary artery disease . HoweverRe-entry is the most common mechanism responsible for ventricular tachycardia (VT) in AIC and is due to the presence of anisotropic conduction occurring in a mixture of healthy myocardial tissue interspersed with scar tissue. These different types of tissue also have different conduction and refractory period properties. The post-myocardial infarction scar is a complex heterogenous mixture of viable myocardial cells interspersed with fibrotic tissue . In NICMThe role of cardiac inflammation as a causative factor of AIC in autopsy/biopsy-proven inflammatory cell infiltration in ARDs is well documented ,10,11,12+ channels [Cardiac or systemic inflammation may promote QTc-interval prolongation via cytokine-mediated intracellular pathways, increasing the risk for SCD . This ischannels .+ channels. Anti-Ro/SSA antibodies can be the cause of a novel form of acquired LQTS via cross-reaction and blockade of the hERG-K+ channel [All these disorders are caused by the dysfunction of specific cardiomyocyte ion channels, leading to a disruption of the cardiac action potential (AP) . The ele channel  Anti-Ro/ channel ,28. Pati channel . Althoug channel ,30. Neve channel ,30, we mAlthough multicenter studies about VA in ARDs are still missing, there are some publications presenting evidence of AIC in various ARDs. In rheumatoid arthritis (RA), the most common cause of SCD is atherosclerotic coronary artery disease (CAD) that may lead to acute coronary syndrome and VT . AdditioIn systemic lupus erythematosus (SLE), although supraventricular tachycardia is the most common finding, VT is not uncommon and is mainly due to CAD . ChloroqIn systemic sclerosis (SSc), non-sustained VT was described in 7–13%, while SCD was reported in 5–21% of unselected SSc patients VT and SCD can be also assessed during polymyositis (PM) and dermatomyositis (DM), although their incidence has been poorly defined ,40,41,42There is a great spectrum of clinical manifestations of AIC in ARDs, starting from clinically silent presentation and extending to overt acute or chronic HF ,45,46,47The diagnostic algorithm of AIC still remains a real challenge for the clinician. Electrocardiogram (ECG), echocardiogram (Echo), positron emission tomography imaging (PET), and cardiovascular magnetic resonance (CMR) are important for the diagnosis of AIC. ECG can show specific and nonspecific findings, including any type of arrhythmias, changes of PQ and ST interval, prolongation of QRS complex, and the presence of Q waves. Some findings, especially the presence of rhythm disorders, i.e., VT or atrioventricular block, may be suggestive of giant-cell myocarditis and/or cardiac sarcoidosis.The baseline diagnostic modality is conventional echocardiography (ECHO). There are no typical ECHO findings that can support the diagnosis of AIC. Both global and regional kinetic disorders of the left or right ventricle, diastolic dysfunction, left ventricle hypertrophy, and pericardial effusion should be taken under serious consideration. Newer echocardiographic modalities, like 2D–3D speckle tracking imaging derived by transthoracic echocardiography, should be offered more accurate data for the early diagnosis of the myocardial involvement. Furthermore, several studies ,50 suppoAlthough clinical, ECG, and conventional ECHO evaluation is the very first approach in AIC, new advances of echocardiographic imaging techniques such as 2D or 3D global longitudinal strain (GLS) can detect early myocardial involvement and select patients for further evaluation. However, only positron emission tomography imaging (PET) and cardiovascular magnetic resonance (CMR) can provide reliable diagnostic information about inflammation/scar by performing tissue characterization.The proposed diagnostic algorithm for AIC using PET includes the following : (1) nonDiffuse uptake was excluded from the diagnostic algorithm, because the inadequate fasting/physiologic uptake may reduce its specificity . AIC canCurrently, there is no specific algorithm for AIC using CMR. However, there is a diagnostic algorithm, by an expert consensus, using CMR for assessment of acute and chronic inflammatory cardiomyopathy . AccordiWhile having both a positive T2-based marker and a T1-based marker will increase specificity for diagnosing acute myocardial inflammation, having only one  marker may still support a diagnosis of acute myocardial inflammation in an appropriate clinical scenario, but with less specificity . SpecifiNearly 50% of patients referred with unexplained cardiomyopathy and VA demonstrate ongoing focal myocardial inflammation on FDG PET. These data suggest that a significant proportion of patients labeled “idiopathic” may have occult AIC, which may benefit from early detection and immunosuppressive medical therapy .Coronary angiography (CA) has a role only for the exclusion of coronary artery disease.Endomyocardial biopsy (EMB) is an invasive approach that can provide tissue for histopathologic evaluation and is still considered to be the gold standard to diagnose myocarditis and/or inflammatory cardiomyopathy. Unfortunately, the patchy distribution of the disease does not allow an accurate diagnosis . TherefoCardiac troponins are specific for myocardial cell damage, but not myocardial infarction, and can be elevated in numerous other disease states, such as renal failure, sepsis, pulmonary embolism, and cardiac injury after chemotherapy, such as with trastuzumab and doxorubicin. In these cases, myocardial injury can be diagnosed independently of myocardial ischemia. Therefore, in these cases, its clinical significance in both diagnosis and prognosis remain questionable. In a study of 215 patients with increased troponin and normal coronary arteries, the spectrum of disease identified by CMR was myocarditis (32%), small area infarction (22%), nonischemic cardiomyopathy (20%), and stress cardiomyopathy (9.3%). This study documents the great clinical value of CMR as a tool to identify various pathophysiologies in patients with an increase of troponin A current meta-analysis showed the moderate sensitivity and specificity of F-18 FDG PET or PET/CT for diagnosis of cardiac sarcoidosis (CS). The presence of combined myocardial perfusion imaging could improve diagnostic accuracy of F-18 FDG PET or PET/CT for diagnosis of CS. At present, the literature regarding the use of F-18 FDG PET for detection of CS remains limited; thus, further large multicenter studies would be necessary to substantiate the diagnostic accuracy of F-18 FDG PET for the diagnosis of CS .While CMR and FDG-PET provide complementary information in CS evaluation, current guidelines do not recommend which advanced imaging modalities are essential in suspected CS and, if so, which modality should be performed first. The utility of hybrid imaging combining both advanced imaging modalities in a single scan is currently being explored, although not yet widely available .The treatment of AIC in ARDs should include both a cardiologic and a rheumatologic approach. The cardiologic approach includes a pharmacologic and an interventional aspect.Beta blockers are of great value in the management of HF with reduced ejection fraction (HFrEF). Furthermore, carvedilol was found to be cardioprotective, due to suppression of inflammatory cytokines, while both metoprolol and propranolol were not . Beta blAngiotensin-converting enzyme (ACE) inhibitor and angiotensin-receptor blocker (ARB) treatment is well established in HFrEF. Their early initiation is of great help to minimize the ventricular remodeling and improve survival.Aldosterone antagonists play an important role in the management of HFrEF patients, irrespective of the etiology of primary myocardial disease. Although there are small mouse model studies supporting the anti-inflammatory benefits in viral myocarditis, there have not been studies in AIC patients.Implantable cardioverter–defibrillator (ICD) treatment is currently the cornerstone of HFrEF management since the multicenter automatic defibrillatorImplantation Trials (MADIT and MADIT-II) and Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) had demonstrated reduced mortality over 1-to-5-year follow-ups ,60,61. HThe role of radiofrequency ablation in patients with AIC is not well evaluated. It is known that there is a clear discordance regarding the long-term effect of ablation in ICM and NICM. This difference was attributed to a lack of modifiable substrate (scar) in NICM patients that may have a combination of scar-based re-entrant VT and functional VT not directly related to myocardial scar or fibrosis. Kumar et al. investigated the characterization of substrate and outcomes after ablation in 435 patients with cardiac sarcoidosis. They identified that the mechanism of cardiac sarcoid-related VT is likely to be the result of re-entry involving confluent regions of scarring in the RV endocardium and epicardium along with patchy LV endocardial scarring affecting the basal septum, anterior wall, and perivalvular regions. Catheter ablation was able to terminate VT storm and >1 inducible VT in the majority of patients, resulting in reduction in ICD shocks. However, recurrences were common, and the failure to abolish all VT episodes was attributed to intramural circuits . It seemAmiodarone remains the most efficacious therapy for the reduction of appropriate and inappropriate shocks in patients with ICD. No therapy resulted in mortality reduction, but amiodarone showed a trend toward increased mortality .Rheumatologic treatment depends mainly on the underlying autoimmune disease. SLE myocarditis/AIC, although uncommon, is a serious complication, with a clinical prevalence of 9%. However, it was present in 57% of postmortem analyses, suggesting a high prevalence of subclinical disease . MyocardVasculitis-induced AIC, apart from cardiac supportive medication, should be also treated with novel biologics, such as abatacept, tocilizumab, and ustekinumab, that offer more precise treatment in large-vessel vasculitis and promise to minimize the glucocorticoid dose. Novel therapies for B-cell in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis are based on rituximab. Finally, mepolizumab demonstrated the key role of interleukin-5 in eosinophilic granulomatosis with polyangiitis .In SSc patients who develop myocarditis/AIC, timely initiation of immunosuppressive treatment, such as cyclophosphamide and corticosteroids , in paraA schematic presentation of the interaction between cardiology and rheumatology in the development of AIC is presented in AIC in ARDs is a recently recognized entity that can explain the presence of VA/SCD in ARDs without coronary artery disease. Clinical assessment and evaluation with ECHO-GLS, PET, and CMR can facilitate both early diagnosis, effective treatment, and follow up. AIC treatment should include a combination of cardiac and antirheumatic medication. However, in life-threatening cases, circulatory support with external devices, and/or implantable pacemakers/defibrillators can be life-saving.