Visual myocardial edema was present in 10 patients (59%). LGE was positive in 2 patients (12%). A total of 13 patients (76%) showed full LVEF recovery. The absence of visual myocardial edema and impairment of strain parameters were associated with delayed LVEF recovery. Multivariable Cox regression analysis revealed global longitudinal strain as an independent prognostic factor for LVEF recovery. In conclusion, biventricular systolic dysfunction with diffuse myocardial edema seems to be present in acute PPCM. Myocardial edema and strain may have prognostic value for LVEF recovery.This study aimed to evaluate the diagnostic and prognostic value of cardiac magnetic resonance in acute peripartum cardiomyopathy (PPCM). A total of 17 patients with PPCM in the acute stage and 15 healthy controls were retrospectively analyzed regarding myocardial function, edema, late gadolinium enhancement (LGE), and T1 and T2 mappings . Echocardiographic follow-ups were performed. Functional recovery was defined as a left ventricular ejection fraction (LVEF) of ≥50%. Patients with PPCM displayed biventricular dysfunction with reduced myocardial strain parameters and left ventricular and atrial dilatation, as well as diffuse myocardial edema (T2 signal intensity ratio: 2.10 ± 0.34 vs. 1.58 ± 0.21,  Peripartum cardiomyopathy (PPCM) is a rare and potentially life-threatening condition. It is defined as development of new-onset cardiomyopathy during the peripartum episode  with an initial left ventricular (LV) ejection fraction (EF) of <45% and without other identifiable cause of heart failure ,2. The iAlthough transthoracic echocardiography (TTE) is the first-line diagnostic imaging modality in case of suspected PPCM , cardiacThe purpose of our study was (1) to evaluate the diagnostic value of CMR in the acute stage of PPCM and (2) to find prognostic indicators for recovery.Patients with acute PPCM and healthy control participants were included in this study. From February 2010 to January 2020, the department’s CMR registry contained 17 comprehensive scans of patients with clinical diagnosis of PPCM. All CMR scans were performed postpartum. Acute PPCM was diagnosed based on recent diagnostic criteria (occurrence of heart failure with an LVEF of <45% during the peripartum without other identifiable cause of heart failure) [Due to ethical reasons, the control group consisted of healthy female controls instead of females with a normal pregnancy. All included controls were volunteers or outpatients presenting with nonspecific symptoms. All control participants had an unremarkable past medical history of cardiovascular disease. Electrocardiographic (ECG) results were unremarkable, and no cardiac risk factors were present. All control participants had normal cardiac MRI results without structural abnormalities.All investigations were performed on a clinical whole-body MRI system . A 32-channel torso coil with a digital interface was used for signal reception. Cardiac scan protocol included ECG-gated steady-state free precession cine images in short-axis, four-chamber, three-chamber, and two-chamber views. T2-weighted short-tau inversion-recovery (STIR) sequence was acquired in short-axis, two-chamber, and transversal views for the visualization of myocardial edema and for the calculation of the T2 signal intensity ratio, as previously described . LGE imaImages were evaluated by two radiologists  using dedicated software . Ventricular and atrial volume and mass parameters were calculated according to recent guidelines and indexed to body surface area using the Mosteller method . The pret-test. Due to the exploratory study design, no adjustments for multiple comparisons were made [2 test (with a cell count > five) or Fisher exact test (with a cell count ≤ five). For intraindividual comparisons, paired Student’s t-test and McNemar’s test were used. Univariable and multivariable Cox regression analyses were applied to test the impact of imaging variables for the prediction of LVEF recovery. After forward selection, significant covariates with p < 0.05 at univariable analysis were added to a multivariable cox regression model to further fit the impact of variables. The results are presented as hazard ratios (HRs) with 95% confidence interval (95% CIs). The cohort was also binarized based on the prevalence of visual myocardial edema and based on median values of LV myocardial dysfunction . The Kaplan–Meier method with log-rank tests was used to compare the “time to LVEF recovery” between these groups. p < 0.05 was defined to indicate statistical significance.Prism  and SPSS Statistics  were used for statistical analysis. The Kolmogorov–Smirnov test was applied for the assessment of normal distribution. Continuous patient characteristics are presented as mean ± standard deviation or as absolute frequency. Continuous variables between two groups were compared by using Student’s ere made . Dichotop = 0.077) or heart rate (p = 0.052)  and 15 female control subjects (33 ± 8 years) were included in this study. No difference between patients and healthy controls was observed in body mass index (= 0.052) . Clinica= 0.052) . Accompap < 0.001) and right ventricular ejection fraction (RVEF) , increased LV end-diastolic volume index , higher left atrium volume index , and higher LV mass index  when compared with healthy controls (p = 0.300) or in the cardiac index . Myocardial strain parameters were impaired in PPCM patients . A total of 4/17 patients (24%) had moderate pericardial effusion (10–20 mm), and 8/17 patients (47%) had small pericardial effusion (<10 mm). Pleural effusion was present in 11/17 patients (65%). None of the patients in our cohort had evidence of LV thrombus.Patients with PPCM displayed reduced LVEF , and T2 signal intensity ratio was increased in the PPCM group . Visual LGE was present in 2/17 patients  and showed a predominantly patchy pattern of enhancement in the subepi- and midmyocardium. Quantified LGE percentages were higher in patients than in healthy controls . Myocardial native T1 relaxation times  and T2 relaxation times  were increased in the PPCM group when compared with the control group. However, there was no significant difference in ECV between the two groups .Visual myocardial edema was observed in 10/17 patients  and RVEF  was observed (see p = 0.047). On CMR follow-up, no visual myocardial edema was detected in any of the patients . One focal LGE lesion was still visible on follow-up CMR. Myocardial strain parameters improved between baseline and follow-up CMR . T1 and T2 mappings were only available in two follow-up cases and were therefore excluded from the follow-up subgroup analysis. However, the presented clinical example showed a tendency towards decreasing T1 and T2 relaxation times at follow-up, indicating myocardial recovery . Between baseline and follow-up CMR, improvement in LVEF , initial LVEF , p = 0.023), GLS , p = 0.007), GCS , p = 0.010), and GRS , p = 0.010). On multivariable Cox regression analysis, only GLS , p = 0.010) remained as an independent predictive variable for LVEF recovery (p = 0.014), in patients with initially highly reduced GLS , and in patients with initially highly reduced GCS  (p = 0.125), in patients with bromocriptine added to standard heart failure therapy , or in patients with concomitant preeclampsia .LVEF recovery was defined by an LVEF of ≥50% on TTE follow-up. The mean TTE follow-up time was 563 days (median: 320 days). A total of 13/17 patients (76%) recovered by the end of follow-up . No patient deceased during follow-up time . Univariable Cox regression analysis showed an association between LVEF recovery and visual myocardial edema , recovery . Accordi= 0.010) , but notThis case-control CMR study revealed biventricular systolic dysfunction and signs of diffuse myocardial edema in the acute stage of PPCM. Prolonged myocardial T1 and T2 relaxation times in the predominant absence of LGE lesions indicate a mainly diffuse pattern of myocardial edema and emphasize the diagnostic benefit of quantitative myocardial parameters in patients with PPCM. Furthermore, the absence of myocardial edema was associated with delayed LVEF recovery. At long-term follow-up, 76% of the patients showed LVEF recovery (median time to LVEF recovery: 45 days). However, some patients showed prolonged recovery times (up to 40 months). RVEF reduction and RV dilatation were present in our PPCM cohort, indicating the presence of right ventricular involvement in the acute stage of PPCM. Furthermore, LV strain parameters, especially GLS and GCS, were markedly reduced and associated with LVEF recovery in our cohort. Impaired baseline GLS (≥−11.2%) and GCS (≥−9.5%) were associated with delayed recovery times, while no significant difference was observed for impaired baseline LVEF (≤27%). Multivariable analysis revealed GLS as an independent prognostic factor for LVEF recovery.Recovery times in the present literature vary depending on the patient cohort and the definition of recovery. High recovery rates were described by Ersbøll et al. (85% recovered to an LVEF of ≥55% at 12 months after diagnosis) and McNamara et al. (72% recovered to an LVEF of ≥50% at 12 months), and relatively low recovery rates were observed by Mahowald et al. (37% recovered to an LVEF of ≥55% by 12 months) ,23. VariThe etiology of PPCM is still not fully understood and is suggested to be multifactorial. However, noninfectious inflammatory pathways and oxidative stress could play an important role . Renz etOur study has several limitations. Because of the retrospective design, clinical data assessment was limited. The single-center cohort is small due to the extremely low incidence of PPCM. Thus, the generalizability of regression models is limited, and this study should be considered to be hypothesis generating. There was no histopathological reference standard available; however, clinical use of endomyocardial biopsy has generally become very rare due to “sampling error” and periprocedural risks, and performance is especially avoided during pregnancy or the peripartum period. Due to ethical reasons, the control group consists of nonpregnant women. However, a previous study of myocardial mapping and strain analysis in healthy women during pregnancy showed LV remodeling with mild to moderate LV hypertrophy, but no evidence of functional impairment, dilatation, edema, or fibrosis of the ventricles .


During the last decade, medical methods for second trimester abortion have considerably improved and become safe and more accessible. The combination of mifepristone and misoprostol is now an established and highly effective method for second trimester abortion. But where mifepristone is not available or affordable, misoprostol alone has also been shown to be effective. The objective of this study is to compare the efficacy of mifepristone with misoprostol and misoprostol alone for second trimester termination of pregnancy.It is a comparative study conducted on 60 patients from 13 to 18 weeks of gestation admitted for second trimester termination on legal indications.Mean induction abortion interval was comparable in both the groups. Of the 30 cases in each group, nine cases in each Group A and six cases in Group B had incomplete/failed expulsion. Among these 15 cases, only nine required check curettage for complete evacuation while others received oxytocics only for completion. The distribution of these cases was also comparable in both the groups. Only one patient in Group B had complete failure of expulsion and underwent surgical evacuation. However, the difference in dosage of misoprostol required for complete expulsion and incidence of side effects were significantly higher in the group B.Mifepristone and misoprostol combined together is now an established, highly effective and safe method for medical method of second trimester termination. However, when mifepristone is not available or affordable, misoprostol alone can also be used effectively, although a higher total dose is needed and side effects are higher than with the combined regimen. Second trimester abortions constitute 10–15% of all induced abortions worldwide but are responsible for two-thirds of major abortion-related complications.1 If the efficacy of misoprostol alone is found to be comparable to misoprostol combined with mifepristone, second trimester termination will be a cheaper procedure and will require shorter hospital stay as mifepristone is a much expensive drug (NPR 600 per tablet compared to NPR 20 per tablet) and needs to be administered 24 hours prior to misoprostol. The aim of this study was to compare both the regimens and their efficacy.The combination of mifepristone and misoprostol is now an established and highly effective method for second trimester abortion. Where mifepristone is not available or affordable, misoprostol alone has also been shown to be effective, although a higher total dose is needed and efficacy is lower than for the combined regimen.A comparative study was conducted to compare the efficacy of misoprostol alone with misoprostol and mifepristone in the Department of Obstetrics and Gynaecology, BPKIHS, Dharan, from August 2015 to July 2016. The study population was cases admitted to the inpatient department for termination of second trimester pregnancy on legal indications from 13 to 18 weeks of gestation. Patients with known contraindication to the use of mifepristone or misoprostol, prolonged corticosteroid therapy, chronic adrenal failure, inherited porphyrias or hypersensitivity reaction to mifepristone or misoprostol were excluded from the study.The sample population was randomly divided into 2 groups using computer-generated random number table. Group A received tablet mifepristone 200 milligrams (mg) per oral stat followed by tablet misoprostol 400 micrograms (mcg) per vaginum four hourly till establishment of active labor or up-to five doses. Group B received tablet misoprostol 400 mcg per vaginum four hourly till the establishment of active labor or up-to five doses. In case of failure in either group, the patient was given rest for 24 hours and received the next cycle of tablet misoprostol thereafter. In case of failure again, the patient underwent surgical management (dilatation and evacuation).This study considered 95% confidence interval and 90% power for sample size estimation.2 considering the mean induction abortion interval, the sample size was calculated using the formula given below.Based on the literature,n=14 in each groupAdding 10% in calculated sample size to reduce various types of biases, sample was calculated to be 16 in each group. But because the large sample theory of statistics recommends >30 samples, this study considered 30 sample in each arm .The ethical clearance was received from Institutional Ethical Review Board of B.P. Koirala Institute of Health Sciences, Dharan. Informed written consent was obtained from each participant. Data were entered in Microsoft Excel 2007 and converted into SPSS 11.5 version for statistical analysis. Data were analyzed by using percentage, proportion, mean, SD, median, interquartile range to describe it. Chi-square test, independent t-test or Mann Whitney U test were applied to find out the significant differences between the two groups (at 95% CI where the level of significance is 0.05).All the baseline characteristics and obstetric profile of cases in both the groups were comparable as shown .Majority of cases were terminated for maternal mental health indications and the distribution of cases was similar in both the groups. Maternal mental health indication included cases with contraception failure and failed medical abortion/ manual vacuum aspiration .The analyzed data of both the groups were compared in terms of the mean induction-abortion interval, completeness of the expulsion of the fetus along with placenta, the dosage of misoprostol required for complete expulsion in both groups, need of additional intervention and side effects of drugs.The induction-abortion interval was found to be higher in misoprostol alone group but the difference was not statistically significant . Of the Amongst the 15 cases with incomplete/failed expulsion, only nine patients required additional methods of evacuation i.e. check curettage for completion of expulsion. The remaining received other oxytocics like oxytocin and had spontaneous expulsion thereafter and did not require any additional intervention. Again, the cases with failed/incomplete expulsion were comparable in both the groups.3Second trimester medical abortion regimens have evolved greatly over the past 20 years with increasing availability of prostaglandin analogs and anti-progesterone agents such as mifepristone. Older regimens such as instillation of hypertonic saline or prostaglandin F2a although effective in provoking abortion were associated with higher rates of serious adverse events that are modern methods.4 Aim of this study was to investigate misoprostol alone or in combination with mifepristone is effective in second trimester abortion.Medical abortion (MA) involves the use of misoprostol and mifepristone. Combination of mifepristone and misoprostol has become the most adopted regimes nowadays. Misoprostol, a newer synthetic prostaglandin E1, has proven its efficacy as an abortifacient for second trimester termination since 1987.5 in Piparia, India amongst 50 cases, 25 in each group, using tablet misoprostol 200 mcg 6 hours apart and the induction abortion interval was found to be 18.94 hours among the women in the first group and 24.29 hours in the women who were in the second group, the difference being statistically significant.In this study, the median induction-to-abortion interval in the group receiving both mifepristone and misoprostol was 12.32 hours whereas that in the group receiving misoprostol only was 14.75 hours. A similar study was conducted by Patel U et alAlthough the difference in the interval was not found to be statistically significant in this study, the shorter induction-abortion interval in the group receiving mifepristone combined with misoprostol could be because of the anti-progesterone action of mifepristone blocking the progesterone receptors and sensitizing the uterus to the activity of the prostaglandins, thus, improving the efficacy of the misoprostol in the process of termination. This difference in the results between the two studies could be due to the difference in the dosage of misoprostol used and the difference in the dosing interval between two dosages. Lower dose of misoprostol and greater interval between two dosages could be a reason for longer induction abortion interval in the later study.2 also concluded that the cases receiving mifepristone also required additional methods of evacuation less frequently but the difference was not statistically significant. In contrast, Patel U et al5 stated that no case who received mifepristone had incomplete expulsion and 4 cases who did not receive mifepristone expelled incompletely.The results of this study brought out that 60% of the incomplete abortion occurred in the group receiving mifepristone, but the difference was not statistically significant. Similarly, Nagaria et al2 and Patel U et al.5 All the studies concluded that there was statistically significant difference in the occurrence of side effects in both the groups. This difference could be because of the higher dosage of misoprostol required for expulsion of the products of conception.Also, this study found that the side effects were significantly lower in the cases receiving mifepristone than their counterparts not receiving it. A similar difference in side effects was noted in the studies by Nagaria et alWith this, it can be safely articulated that pre-treatment with tablet mifepristone 200 mg provides an effective, non-invasive medical second trimester termination and significantly reduces the dosage of misoprostol and its side effects.As this study was carried out in a small scale with a small sample size, further studies with larger sample size are required to draw definitive conclusion on the efficacy of misoprostol with or without mifepristone. Therefore, whenever possible, the combined regimen should be used until further studies are available to support the efficacy of misoprostol without the use of mifepristone. But both the regimens are feasible as far as end results are concerned and misoprostol-only regimen can be used when mifepristone is not available or affordable.The combination of mifepristone and misoprostol is now an established and highly effective and safe method for medical method of second trimester abortion. The combination of misoprostol reduces the induction-abortion interval, dosage of misoprostol required for complete expulsion and also has fewer side effects. But at instances, where mifepristone is not available or affordable, misoprostol alone has also been shown to be effective, although a higher total dose is needed and has side effects which are higher than with the combined regimen.None.


Cardiac cachexia (CC) represents a serious complication of heart failure (HF). This condition could be directly related to mortality. The weight or muscle mass loss has to be monitored in our patients with HF to avoid potential complications.We report a case of an elderly patient with a history of aortic stenosis (AS) who presented with progressive shortness of breath limiting his daily activities associated with weight loss. Signs of heart failure were evident on physical examination, and valvulopathy was also evident. His echocardiogram showed reduced ejection fraction (EF) with structural changes and severe aortic stenosis. He was not a candidate for cardiothoracic surgery, and a transcatheter aortic valve replacement (TAVR) was performed. After the procedure, his symptoms improved, and during the outpatient follow-up, his cardiac function and dry weight improved.Cardiac cachexia could be caused by reversible cardiomyopathy. Early assessment and approach are critical for the outcome of our patients, impacting their quality of life and outcome in terms of morbidity and mortality consequences. Cachexia has been associated with multiple conditions: infectious, acute, and chronic conditions, including malignancies, cerebrovascular accidents, pulmonary disease, and heart failure (HF) ,2. CacheThe patient was a 68-year-old Hispanic male who presented to our office due to progressive shortness of breath limiting his daily activity  and orthopnea, associated with a weight loss of 60 pounds in four months. He has a history of diabetes mellitus, severe aortic stenosis s/p valvuloplasty (seven years ago), and pulmonary edema due to heart failure decompensation. The physical examination showed a cachectic elderly male with an increased jugular venous pulsation; third and fourth sounds were also present. A telescopic aortic murmur was appreciated; his legs had pitting edema up to the hip, and his pulses were delayed.2, peak gradient 51 mmHg, and mean gradient 30 mmHg. An angiotomography showed an aortic annulus of 25.95 mm (AVG) with an area of 5.25 cm2. Thyroid and autoimmune studies did not show any abnormalities, and he denied a history of dysphagia, odynophagia, epigastralgia, or rheumatic fever.His ECG showed left ventricular hypertrophy (LVH) with nonspecific ST changes Figure , and theThis patient was not a candidate for cardiothoracic surgery, and a transcatheter aortic valve replacement (TAVR) was performed Figure . He was After the procedure, the patient tolerated a supine position without orthopnea. During his follow-up visits, no pedal edema was noted, and his dry weight (10 pounds) increased after the procedure; also, his echocardiogram showed an ejection fraction of 46%.In the elderly population, congestive heart failure (CHF) is the leading cause of morbidity and mortality, accounting for the majority of hospitalizations . As the The prevalence of CHF is exponentially related to age, and it duplicates approximately every 10 years in males and every seven years in female patients .2) in the presence of chronic illness in addition to three of the following: decreased muscle strength, fatigue, anorexia, low fat-free mass index, abnormal biochemistry characterized by increased inflammatory markers (C-reactive protein (CRP) and interleukin (IL)-6), hemoglobin < 12 g/dL, or hypoalbuminemia [Cardiac cachexia is a pathological condition associated with worsening outcomes independent of other sociodemographic variables or CHF class . It is duminemia . Anker euminemia .Muscle wasting is an essential component of cachexia that usually precedes cachexia progression and predicts a worse prognosis in heart failure . The exaAnother possibility in a patient with chronic CHF and tricuspid regurgitation is passive congestion of blood into the liver and intestines, which causes hepatomegaly and ascites, leading to decreased gastric capacity with feelings of abdominal fullness, nausea, satiety, and anorexia .Patients with advanced heart failure have an activation of the catecholamines, pro-inflammatory cytokines, cortisol, and renin-angiotensin-aldosterone system (RAAS) that can further increase the metabolic rate and burning of more calories . The effAngiotensin II and aldosterone are thought to be a factor in cellular changes, including death and fibrosis, through the activation of the ubiquitin-proteasome pathway . AngioteImprovement of bowel perfusion with agents such as angiotensin-converting enzyme (ACE) inhibitors (-)/angiotensin receptor blockers (ARBs) could assist in minimizing and preventing mucosal injury.Other possible therapeutic options include agents that inhibit TNF-α such as pentoxifylline, reducing C-reactive protein through statins, and altering adiponectin or leptin levels .Adequate nutrition in addition to diet, avoiding sedentarism, and regular exercise could avoid tissue wasting . In educEarly diagnosis and prompt treatment of cardiac conditions are essential in the prevention of cardiac cachexia and its complications . ValvulaThe most crucial point is distinguishing between primary heart failure and AS versus HF due to other etiologies, including severe ischemic cardiomyopathy ,34. SuppIn AS, the LV will respond to the elevation of the pressure load with adaptive concentric wall hypertrophy keeping wall stress and LVEF . In advaAortic outflow obstruction can be relieved mechanically via surgical aortic valve replacement (SAVR), which can improve symptoms, LV function, and outcomes in patients with advanced AS. However, the prognosis of SAVR depends on ventricular function prior to the surgery. In patients with ventricular function impairment or poor surgical candidates, SAVR is associated with high perioperative mortality and morbidity .Reduced LVEF has been associated with increased operative mortality risk. According to the Euro Heart Survey, up to one-third of the patients with severe AS and reduced LVEF was deemed not acceptable for surgery. However, TAVR has changed the management of nonsurgical candidates with AS. TAVR has evolved to the standard in high-risk patients that are not suitable for surgery. Moreover, TAVR is related to more significant ventricular function improvement compared with surgical patients due to the lack of stress during the procedure that helps avoid inflammation, ischemia, and oxidative injury, which lead to apoptosis and dysfunction ,41.Literature has established the improvement of EF and outcomes after valve replacement due to aortic stenosis ,43.Cardiac cachexia could be caused by reversible cardiomyopathy. Besides, it is poorly understood; it plays an essential role in the outcome of our patients and leads to potential complications in heart failure patients. Early assessment and approach are critical for our patients, impacting their quality of life, and morbidity and mortality, the reason why these patients should be closely followed and their nutritional status needs to be monitored frequently.


QFR ≤ 0.80). These data could be confirmed by other parameters assessing extent of ischemia. In addition, QFR was also associated with severity of ischemia, assessed by the relative signal intensity of ischemic areas. Finally, QFR predicts a clinically relevant ischemic burden ≥ 10% with good diagnostic accuracy . QFR may be a feasible tool to identify not only the presence, but also extent and severity of myocardial ischemia in non-culprit lesions of patients with myocardial infarction.Quantitative flow ratio (QFR) is a novel method to assess the relevance of coronary stenoses based only on angiographic projections. We could previously show that QFR is able to predict the hemodynamic relevance of non-culprit lesions in patients with myocardial infarction. However, it is still unclear whether QFR is also associated with the extent and severity of ischemia, which can effectively be assessed with imaging modalities such as cardiac magnetic resonance (CMR). Thus, our aim was to evaluate the associations of QFR with both extent and severity of ischemia. We retrospectively determined QFR in 182 non-culprit coronary lesions from 145 patients with previous myocardial infarction, and compared it with parameters assessing extent and severity of myocardial ischemia in staged CMR. Whereas ischemic burden in lesions with QFR > 0.80 was low , there was a significant increase in ischemic burden in lesions with QFR ≤ 0.80 (16.6 ± 15.6%;  Quantitative flow ratio (QFR) is a novel method to assess hemodynamic relevance of coronary lesions based on a three-dimensional vessel reconstruction and estimation of its contrast media flow velocity ,2,3,4. IWhereas the association of QFR with the sheer presence of myocardial ischemia has been consistently reported, it is still unclear whether this novel modality is also able to predict the extent of ischemia. This is of major clinical relevance since previous studies showed that the extent of ischemia correlates with patient outcome ,18,19,20We retrospectively enrolled 145 patients with previous myocardial infarction who underwent staged stress perfusion CMR within 1 year after intervention of the culprit lesion to determine hemodynamic relevance of the remaining coronary lesion(s) at the Department of Cardiology, University Hospital of the RWTH Aachen, Germany between the 1 January 2016 and the 1 June 2020. Previous studies partly included patients in this study cohort .The main inclusion criterion was a previous myocardial infarction with one (or more) non treated, angiographically at least intermediate (with a lumen diameter stenosis ≥ 40%) non-culprit lesion, which was then further analyzed by stress-CMR to assess its hemodynamic relevance. Exclusion criteria were absence of CAD at baseline angiography, presence of 1-vessel CAD, absence of non-culprit lesions as defined above, relevant left main disease, previous CABG, cardiogenic shock during acute coronary angiography or direct indication to revascularization of the non-culprit vessel(s) by CABG or PCI without previous ischemia testing.The study was approved by the local Ethics Committee and is in accordance with the Declaration of Helsinki on ethical principles for medical research involving human subjects.A blinded certified investigator performed offline QFR using commercial software  according to a previously described protocol . In shorCMR image acquisition was accomplished on a 1.5 Tesla magnetic resonance scanner . After standard cine imaging, contrast enhanced first pass perfusion imaging , 0.1 mmol/kg followed by 30 mL of saline flush at 4 mL/s) during vasodilator-stress with adenosine (140 µg/kg/min intravenously for 4 min) took place. Standard late gadolinium enhancement (LGE) imaging was performed 10 min after contrast injection (a second portion was given to add up to 0.2 mmol/kg).An experienced, board-certified CMR cardiologist, blinded to the results of the QFR examination, performed CMR image analysis on a dedicated CMR workstation , as previously described .The dynamic of the first pass perfusion sequence with the greatest extent of ischemia was chosen and the apical, mid-ventricular and basal short axis (SA) slice of this dynamic were established for further analysis. Single analyses were strictly separated when several ischemic areas attributable to different coronary artery supply territories were detected. For scar quantification, a corresponding SA-slice of late gadolinium enhancement (LGE)-imaging for each slice of perfusion was defined. For each SA-slice, myocardial area was calculated by manually tracking the endocardial and the epicardial borders. Classification of the myocardium of each slice relied on the standardized AHA 16 segment model . For eacCategorical variables were summarized as count (percentage), continuous variables as mean ± standard deviation. Analysis of variance (ANOVA) was used to analyze the distribution of various parameters assessing extent and severity of ischemia among predefined groups of QFR-values . In order to test the distribution of extent and severity of ischemia expressed as ordinal variables throughout these predefined groups of QFR-values, we employed Kruskal–Wallis H-test; the results of the following post hoc analyses are reported after Bonferroni correction for multiple testing.Receiver operating curve (ROC) analysis was performed to identify the diagnostic efficiency of QFR in predicting a clinically relevant myocardial ischemia, defined as an ischemic burden ≥10% of viable myocardium, as previously described ,23. The p-value < 0.05 indicated statistical significance.All statistical analyses were performed with SPSS software v 26.0 . A We retrospectively analyzed a total of 182 non-culprit lesions of at least intermediate severity (mean percent diameter stenosis: 46 ± 9%) from 145 patients with preceding myocardial infarction who underwent staged stress perfusion CMR to assess hemodynamic relevance of the remaining non-culprit lesion(s). For patient and lesion characteristics please refer to p < 0.001 for distribution, p < 0.001 for group 1 vs. group 3). These data were confirmed by all other parameters defining extent of ischemia , as shown in n = 8) with very low QFR lesions (QFR ≤ 0.70), 50% demonstrated extensive ischemia with ischemic burden > 20% and 62.5% even presented an ischemia with a transmurality > 66%.First, we aimed to study whether QFR is associated with CMR parameters assessing extent of ischemia in our study population. Whereas ischemic burden in both groups with QFR > 0.80 was low , there was a significant increase in ischemic burden in lesions with QFR ≤ 0.80   . The disp < 0.001). Optimal cut-off for QFR in the prediction of myocardial ischemia ≥10% was 0.81 , as shown in After demonstrating a robust association of QFR with CMR-derived parameters assessing extent and severity of ischemia, we aimed to test the diagnostic efficiency of QFR for the detection of a clinically relevant ischemia, defined as an ischemic burden ≥10% ,23. QFR The main finding of our study is that QFR is associated with both extent and severity of myocardial ischemia in non-culprit lesions of patients with myocardial infarction.QFR represents a reliable, non-invasive tool in the assessment of hemodynamic relevance of coronary lesions not only in the setting of chronic, but also acute coronary syndromes ,26,27,28Our data represent a further, independent validation of QFR as a method to quantitatively assess coronary flow. In fact, one of the main determinants of a larger ischemic area is represented by the magnitude of flow reduction determined by a coronary stenosis; this more pronounced flow reduction is characterized by lower QFR values. In spite of the good association of QFR with extent and severity of ischemia in CMR, it has to be noticed that a complete overlap cannot be expected. In fact, QFR does not consider some determinants of myocardial ischemia, such as coronary artery dominance, presence of collaterals or ischemic preconditioning, which may partly explain some diverging results. In particular, in our study a relevant proportion (29%) of patients with a pathologic QFR does not show any relevant ischemia in CMR; this may be due to the factors mentioned above and may also represent a limitation of QFR in the setting of acute myocardial infarction. Furthermore, as previously reported, a diffuse coronary artery disease, which may bear a worse prognosis, can result in a comparatively small extent of ischemia visible in CMR  in comparison with a single high-grade coronary stenosis with a larger area of ischemia .As QFR allows a good estimation of extent and severity of ischemia may prompt clinicians to use this tool in order to select lesions with a more urgent need for treatment. In fact, the presence of large ischemic areas is a predictor of adverse outcome ,18,19,20Although being, to the best of our knowledge, the first study assessing the association of QFR with both extent and severity of ischemia, some limitations have to be reported. First, due to the study design we only included non-culprit lesions of patients with myocardial infarction; although previous data suggest a similar accuracy of QFR in both chronic and acute coronary syndromes, we are unable to generalize our conclusions to the population with chronic coronary syndromes. Although showing a good association of QFR with extent and severity of ischemia, we cannot exclude a potential selection bias, due to the inclusion of the lesions which were deemed relevant at the interventionalists’ discretion, which naturally exclude very peripheral or very small vessels. Moreover, our data need to be confirmed in larger prospective cohorts.QFR is associated not only to the presence, but also the extent and severity of myocardial ischemia in non-culprit lesions of patients with myocardial infarction.


To determine whether left ventricular (LV) global longitudinal strain (GLS) measured by feature-tracking (FT) cardiac magnetic resonance (CMR) improves after kidney transplantation (KT) and to analyze associations between LV GLS, reverse remodeling and myocardial tissue characteristics. This is a prospective single-center cohort study of kidney transplant recipients who underwent two CMR examinations in a 3T scanner, including cines, tagging, T1 and T2 mapping. The baseline exam was done up to 10 days after transplantation and the follow-up after 6 months. Age and sex-matched healthy controls were also studied for comparison. A total of 44 patients  completed the two CMR exams. LV GLS improved from − 13.4% ± 3.0 at baseline to − 15.2% ± 2.7 at follow-up (p < 0.001), but remained impaired when compared with controls . We observed significant correlation between improvement in LV GLS with reductions of left ventricular mass index . Improvement in LV GLS paralleled improvements in LV stroke volume index , ejection fraction , global circumferential strain  and global radial strain . There were no significant correlations between LV GLS, native T1 or T2 measurements (p > 0.05). In this study, we demonstrated that LV GLS measured by FT-CMR improves 6 months after KT in association with reverse remodeling, but not native T1 or T2 measurements. Cardiovascular disease (CVD) remains the leading cause of death in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) . This inCardiac magnetic resonance (CMR) is the gold standard to measure cardiac structure and function, having the further advantage to non-invasively characterize myocardial tissue using T1 and T2 mapping , withoutThis is a single-center prospective cohort study in a university hospital with ESRD patients who received a kidney transplant and underwent two CMR examinations. The first exam (baseline) was performed between the 1st and the 10th postoperative days. The second one was performed 6 months after renal transplantation. We included consecutive patients over 18 years-old who received a kidney transplant from a living or deceased donor. We excluded patients with a contraindication to CMR  or inability to perform breath hold. For comparison a group of age- and sex-matched healthy controls was selected from the hospital records. Healthy subjects had normal kidney function, no known chronic disease, and were not on regular medication.This study complied with the Declaration of Helsinki, and the institutional review board of Botucatu Medical School-UNESP approved the research protocol . All participants provided witnessed, written, informed consent. Siemens Healthineers  provided the use of work-in-progress #448B (VB17A) quantitative cardiac parameter mapping (T1|T2|T2*) in this study. No person from this company had access to study data or was involved in image analysis, manuscript preparation, or any part of the study. The authors had full control of the data submitted for publication.All patients underwent their examination on a 3.0-T Magnetom Verio Scanner  with a phased array chest coil, according to study protocol. A cardiac cine balanced steady-state free precession (bSSFP) sequence was acquired using retrospective cardiac gating. Typically, 25 phases were acquired in 2-, 3-, and 4-chamber long axis views and a stack of short axis views. Scan parameters: field of view (FOV) 37 cm, repetition time (TR) 43.54 ms, echo time (TE) 1.38 ms, flip angle (FA) 50°, slice thickness 6 mm, in-plane image resolution 1.6 × 1.6 mm. Myocardial tissue tagging was performed with an ECG-gated line tagging sequence with complementary spatial modulation of magnetization (CSPAMM). Image parameters were: FOV 32 cm, TR 48.15, TE 2.54, FA 10°, slice thickness 7 mm with a tag spacing of 7 mm. Short-axis tissue tagging was performed on three levels of the LV, positioned at 25%, 50% and 75% of the distance between the mitral valve annulus and the apex on a LV 4-chamber view in end-systole, and in 2- and 4-chamber long axis views. Quantitative T2 mapping was performed using a T2-prepared SSFP sequence in a mid-ventricular short axis view with the following imaging parameters: FOV 36 cm, TR 254.32, TE 1.07 ms, flip angle 35°, slice thickness 8 mm, in-plane image resolution 2.5 × 1.9 mm, acquisition in late diastole on every fourth heartbeat; T2 preparations: 0 ms, 25 ms and 55 ms. Quantitative T1 mapping was performed with a Modified Look-Locker Inversion-Recovery (MOLLI) sequence in mid-ventricular short axis view without intravenous contrast injection (Native T1). Scan parameters: FOV 36 cm, TR 316.09, TE 1.12 ms, flip angle 35°, slice thickness 8 mm, in-plane image resolution 2.1 × 1.4 mm, acquisition in late diastole on every other heartbeat, minimal inversion time 120 ms; increment 80 ms. The T1 mapping scheme included 5 acquisitions after the first inversion pulse, followed by a 3-heartbeat pause and a second inversion pulse followed by three acquisitions [5(3)3].2.The biventricular end-diastolic volume (EDV) and end-systolic volume (ESV) were measured by manual segmentation of the short axis cine images, using Argus function software . The endocardial borders were traced at end-diastole and end-systole, including trabeculations and papillary muscles in the blood pool. EDV and ESV were calculated for each ventricle using the disc summation method. Ventricular stroke volume (SV) was calculated as the difference between the EDV and ESV, and ventricular ejection fraction (EF) was (SV/EDV) × 100. LV epicardial borders were drawn only at end-diastole to calculate LV mass (LVM). All volume measurements were indexed for the body surface area (BSA) and expressed in ml/mMyocardial feature-tracking analysis was performed processing cine images using strain module of Segment Medviso software, which was previously validated in a clinical setting . CircumfT1 and T2 maps were automatically generated on the MR scanner with motion corrected images using a novel non-rigid registration algorithm , 21. A rAn experienced reader (ACVM) measured ventricular volumes, mass and EF, while another experienced reader (MFB) independently performed T1, T2 and strain analysis, blinded to former results.To determine the intraobserver reproducibility of LV GLS measured by FT-CMR, 15 exams were randomly selected and the analysis repeated by the same observer about 6 months after the initial assessment. These exams were also used to validate LV GLS measured by FT-CMR against the reference standard tagging.The Kolmogorov–Smirnov test was applied to determine appropriate parametric or nonparametric tests. Quantitative variables were expressed as mean ± standard deviation or median (interquartile range) and compared by t test or Wilcoxon signed-rank test, whereas qualitative variables were expressed by their frequencies and percentages, and compared by the chi-square test or Fisher’s exact test. The relationship between changes in LV GLS and variables of interest were assessed using Pearson’s correlation coefficients for continuous normally distributed variables and Spearman’s correlation for categorical or non-normally distributed data. Linear regression analysis was used to evaluate the influence of clinical variables in LV GLS changes. Intraobserver reproducibility was assessed by analyzing Bland–Altman plot. All data were analyzed using SAS Studio 3.8 or Microsoft Excel software. A p value of ≤ 0.05 was considered significant.We consented 47 patients of whom 44  completed the two CMR exams (n = 88 CMR studies). One patient died on the 11th day after transplant surgery and two patients refused to undergo a second CMR exam. The median time from transplant to the first exam (baseline) was 5 days and to the second exam (follow-up) was 189 days. During the study period, no patient developed a graft loss or a cardiovascular event . Control group was composed by 10 age- and sex-matched healthy controls selected from the hospital records. Table There were no significant changes in LV volumes, mass or EF. The mean native T1 decreased from 1331 ± 52 to 1298 ± 42 ms at 6 months (p < 0.001), but still remained higher than controls  , LV basal global circumferential strain (GCS) improved from − 16.7% ± 3.5 to − 18.2% ± 2.0 (p = 0.002) and RV GLS improved from − 11.5% ± 3.9 to − 14.1% ± 4.1 (p < 0.001) after 6 months of KT. The other strain variables remained unchanged. Besides these improvements, LV GLS and RV GLS remained impaired at follow-up when compared to controls . Improvement in LV GLS paralleled improvements in left ventricular stroke volume index (LVSVi) [Pearson’s r = − 0.429 p = 0.004], left ventricular ejection fraction (LVEF) , LV GCS  and LV global radial strain (GRS)   of − 1.3 to 1.7 Fig. . There wIn this prospective study we demonstrated a favorable impact of KT on LV GLS measured by FT-CMR 6 months after surgery, in concordance with previous echocardiographic studies , 18. AltFT-CMR derived LV GLS is a powerful independent predictor of mortality in patients with ischemic or non-ischemic dilated cardiomyopathy , reducedStrain measures are susceptible to changes in preload and afterload , but in Cardiac remodeling, as assessed by LV mass and geometry, is also a strong predictor of cardiovascular and all-cause mortality in studies of asymptomatic populations  and in CLVH may be associated with cardiac fibrosis that leads to conduction disturbances and probably provides the link between UC, arrhythmia and sudden death. The use of newer T1 mapping techniques without gadolinium (native T1) has demonstrated increased myocardial T1 relaxation times indicative of diffuse interstitial fibrosis in ESRD , 14 and Our study has some limitations. First, the baseline CMR was performed after transplantation surgery. Although performing CMR at the pre-transplant period would be more appropriate, this is not possible with deceased donors due to long waiting list times. However, all patients were clinically and hemodynamically stable at the moment of the CMR exam. Second, we did not perform histological confirmation of myocardial fibrosis because of the inherent risks and decreasing use of endomyocardial biopsy in daily practice, however T1 mapping is a well validated CMR technique to this end. Third, this is a single-center study with a small number of patients, and may have been underpowered to show associations between native T1 and GLS. Fourth, we did not measure serum biomarkers of heart failure, however, previous study has found associations between B‐type natriuretic peptide (BNP) and those CMR indices in hemodialysis patients . FinallyOverall, our findings reinforce the potential role of multiparametric CMR in monitoring important biomarkers of UC in ESRD patients after KT. Early detection of individuals at higher risk for CVD after KT could allow identification of those who might benefit from closer cardiovascular follow-up or more aggressive therapies. Future studies with increased number of patients and longer follow-up are needed to determine which of these CMR parameters will be helpful in predicting mortality or guiding therapy.In this prospective study we demonstrated that LV GLS measured by FT-CMR improves 6 months after KT in association with reverse remodeling but not native T1 or T2 measurements.


T1, T2, and T2∗ for comprehensive tissue characterization of the myocardium in a single scan using a multi‐gradient‐echo readout with saturation and T2 preparation pulses.To implement a free‐breathing sequence for simultaneous quantification of T2‐prepared Relaxometry with Navigator‐gating (SATURN) technique, a series of multi‐gradient‐echo (GRE) images with different magnetization preparations was acquired during free breathing. A total of 35 images were acquired in 26.5 ± 14.9 seconds using multiple saturation times and T2 preparation durations and with imaging at 5 echo times. Bloch simulations and phantom experiments were used to validate a 5‐parameter fit model for accurate relaxometry. Free‐breathing simultaneous T1, T2, and T2∗ measurements were performed in 10 healthy volunteers and 2 patients using SATURN at 3T and quantitatively compared to conventional single‐parameter methods such as SASHA for T1, T2‐prepared bSSFP, and multi‐GRE for T2∗.In the proposed Saturation And T1, T2, and T2∗ times acquired with SATURN and single‐parameter methods was shown in quantitative measurements Simulations confirmed accurate fitting with the 5‐parameter model. Phantom measurements showed good agreement with the reference methods in the relevant range for in vivo measurements. Compared to single‐parameter methods comparable accuracy was achieved. SATURN produced in vivo parameter maps that were visually comparable to single‐parameter methods. No significant difference between T1, T2, and T2∗ in the myocardium for comprehensive tissue characterization with co‐registered maps, in a single scan with good agreement to single‐parameter methods.SATURN enables simultaneous quantification of  T1 mapping is most commonly performed based on a series of inversion or saturation recovery images and has shown promise for the assessment of ischemic and nonischemic cardiomyopathies.T1 maps insensitive to the heart rate, the magnetization evolution, and other confounders.A wide variety of mapping sequences was proposed in the last decades for noninvasively studying the myocardial tissue state.T1 mapping, myocardial T2 mapping is increasingly used for the reliable assessment of myocardial edema.T2 mapping is performed by acquiring at least 3 T2‐prepared balanced steady‐state free precession (bSSFP) images to provide robust and reproducible T2 maps.In addition to T2∗ quantification has demonstrated high clinical value for the assessment of myocardial iron accumulation.T2∗ measurements in the myocardium is most commonly performed by acquiring 8 echoes with a multi‐gradient‐echo readout and performing an exponential fit.Myocardial T1 and T2 were proposed to improve patient comfort and shorten measurement time.T1 and T2 mapping was obtained in a single breath‐hold by combining saturation/inversion pulses and T2 preparation modules to improve the detection of abnormalities by inherently co‐registered parametric maps.T1 and T2 in the entire myocardium in a single scan avoiding deviations due to incorrect breath‐holds.T1 and T2 based on undersampled non‐Cartesian readouts with varying preparations.The methods described above each require one breath‐hold per slice. Therefore, free‐breathing methods and simultaneous quantification of T1, T2, and T2∗) requires multiple sequences in clinical practice, expanding the scan protocol and prolonging examination duration. Furthermore, many recently developed methods rely on implicit or explicit model‐based regularization.However, the lack of a combined method for assessment of all 3 clinically relevant tissue characteristics  sequence. The sequence is based on a single‐shot multi‐gradient‐echo readout generating 5 echoes for each end‐diastolic imaging window. We used a prospective navigator on the diaphragm of the liver with a gating window of 4‐5 mm depending on the subject’s breathing pattern. Navigator gating is performed with the following accept‐reject scheme: The first contrast without preparation was repeated if the navigator was rejected. Saturation prepared images were also immediately re‐attempted in the next heartbeat. No navigator was played during the rest periods before the T2 preparation. For T2‐prepared images, T2 preparation was only performed if the navigator was accepted. In this way, if the navigator was rejected the T2‐prepared image could be re‐attempted immediately, without the need of additional rest‐periods. However, in this way, navigator rejections lead to an increase in effective rest periods. We used saturation and T2 preparation pulses before the readouts to generate T1 and T2 contrasts. Therefore, we combined the SASHA 3‐parameter fit model with the T2‐prepared bSSFP 3‐parameter fit model. Since we only use short echo times (TE) for the gradient‐echo readout and the noise floor for the T2∗ decay is not corrected, we used a truncation model for T2∗ as previously suggested.T1 offset. Thus, T2∗ is reconstructed with a truncation model. The first contrast is performed without any preparation representing full magnetization recovery  and T2 preparation time of T2p=0. The second block consists of 2 different T2‐weighted contrasts using preparation durations of 25 and 50 ms, respectively, as previously recommended.T2 preparation. The third block acquires images with saturation preparation to sample the T1 recovery curve. The fourth and sixth image is performed with a saturation pulse before the readout to mimic the effect of a very long T2 preparationTS and T2p was set to TSmin and 0. Image 5 and 7 are acquired with saturation preparation with a maximum TS for maximum precision.Figure T1‐effects” (WET) pulse to reduce the sensitivity to B1.T2 preparation module consist of a 90∘ rectangular flip‐down pulse, a 270∘ rectangular flip‐up pulse and composite 180∘ MLEV refocusing pulses in between.The full acquisition comprises 7 different contrast preparations followed by imaging at 5 echo times, yielding a total of 35 images. Saturation pulses were performed using a composite “Water suppression Enhanced through 2.2All measurements were performed on a 3T MRI scanner  with a 28‐channel receiver coil array. Sequence parameters are listed in Table R = 3. Additionally, GRAPPA with acceleration R = 4 was explored for the use in subjects with higher heart rates. SPIRiTR = 4, as previously proposed.SATURN was performed using GRAPPA with acceleration factor 2.3T1 (1200‐1700 ms), T2 (20‐70 ms), and T2∗ (5‐60 ms) were varied and the magnitude was fitted with the proposed 5‐parameter fit model given in Equation . GRE was performed for T2∗ quantification with 12 contrasts ranging from TE = 2‐60 ms, TR = 10 000 ms and 1 k‐space line per readout with the same imaging parameters listed above. All measurements were additionally compared with single‐parameter methods for myocardial mapping  and a 3‐parameter fit model,T2∗ with 8 echoes ranging from 1.6 to 16.3 msPhantom measurements were performed to evaluate the accuracy and precision of the proposed SATURN sequence. Reference measurements for 2.5In vivo measurements were performed in 10 healthy volunteers , 1 patient  with hypertrophic cardiomyopathy (HCM), and 1 patient  with suspected hypertensive heart disease (HHD) after written consent was obtained. All images were acquired in the mid‐ventricular short‐axis view using the parameters described in the previous section.TS adjusted to the subject’s heart rate. Motion between images from different heartbeats was reduced by retrospective image registration. Rigid registration was performed with mutual information in the region of interest as the similarity metric. Voxel‐wise fitting was performed using the 5‐parameter model.SATURN was performed with a maximum Regions of interest were manually drawn in the entire myocardium, with careful distancing to the epi‐ and endocardial borders. Bullseye plots were generated for the 6 mid‐ventricular segments of the American Heart Association (AHA) segment model.Standard deviation maps (SD maps) were generated by calculating all partial derivatives of the fit function as previously proposed.2.6T1, T2, and T2∗ times were averaged across all subjects. Additionally, the within‐segment means of the SD T1, T2, and T2∗ times were calculated using the corresponding voxel‐wise SD maps. Intersubject variability was calculated as the SD of the within‐segment mean across all subjects. Pair‐wise comparison was performed using Student’s t‐tests using the Bonferroni correction for multiple comparisons along T1, T2, and T2∗. Values of p less than 0.05 were considered significant. Significance between segments of the myocardium was tested using the ANOVA test. Relative deviations were compared by dividing the absolute difference between reference and SATURN with the reference.The within‐segment mean and the within‐segment SD of the 33.1T1, T2, and T2∗. Figure T1, T2, and T2∗ across the relevant in vivo range  was achieved in simulations. One source of deviation for T2 was incomplete recovery during the rest‐periods leading to very slight deviations in T2  as shown in Supporting Information Figure T2∗ quantification was found to be more susceptible to higher noise levels than T1 and T2. T1, T2, and T2∗ accuracy were independent of the heart rate. T2 accuracy was additionally compromised by an imperfect T2 preparation efficiency resulting in a strong underestimation, especially for longer T2 times.Figure 3.2T1 times compared with the inversion recovery spin‐echo, yielding accuracy comparable to SASHA. T2 times were accurate in the relevant range (5.2% deviation) and decreased when exceeding 100 ms with relative deviations of up to 20%. For T2∗ of less than 100 ms T2∗ accuracy (7.7% deviation) was slightly higher compared with the conventional single‐parameter method, where a decrease of up to 11 ms was measured compared with the reference GRE. SATURN overestimates long T2∗ times compared with the GRE and multi‐GRE.Phantom measurements Figure  showed g3.326.5±14.9 seconds, which corresponds to an average gating efficiency of 54%±30%. The minimal TSmin was 7 ms for every subject and the maximal TSmax was 601±65 ms. An example of magnitude data acquired with SATURN in 1 healthy subject is shown in Figure T1 and T2. Artifacts are observed in T2∗ maps  and image quality is visually improved (only 5.4% lower within‐segment SDs). SATURN T1 maps appear smoother and more homogeneous when using R=3 with smaller variations within the myocardium. Additional artifacts appear in T2∗ maps using R=4, which are largely alleviated using regularization.Supporting Information Figure T1, T2, and T2∗ and the corresponding within‐segment SD. The relaxation times in the healthy myocardium measured with SATURN averaged over all 6 AHA segments were T1=1573±86ms, T2=33.2±3.6ms, comparable to the conventional methods . T2∗ obtained with SATURN was 25.3±6.1ms, corresponding to a 5.9% increase compared to the conventional method  with both methods suffering from artifacts. No significant differences were found between the in vivo times measured with SATURN and the conventional methods for neither T1, T2 or T2∗.Figure T1 (P=.36) but significant differences for T2 (P=.037) and T2∗ (P=.038), with the lowest T2/T2∗ times being observed in the mid‐inferior segment. The same trend is observed for the conventional methods. For SASHA T1, no significant difference among the segments (P=.83) was observed, but significant differences for the single‐parameter T2 (P=.033) and T2∗ (P<.01), depicting a similar drop in the mid‐inferior segment. Intersubject variability of 57.9 ms  was observed in T1, which is higher than for SASHA (42.3 ms (2.7%)). Intersubject variability of 3.3 ms (9.9%) for T2 obtained with SATURN were in the range of the T2‐prepared bSSFP with 3.2 ms (9.6%), and 3.6 ms (14.2%) for T2∗ compared with the multi‐GRE 3.2 ms (13.4%) were observed.No significant differences among segments were measured for SATURN σ(T1)=68ms, σ(T2)=1.1ms and σ(T2∗)=3.3ms and for the conventional methods σ(T1)=39.3ms, σ(T2)=1.9ms and σ(T2∗)=1.5ms. Examples of SD maps are shown in Figure T1, SATURN achieved 23.3% lower within‐segment SDs and improved precision compared with SASHA T1 map. T2 shows comparable precision between SATURN and the single‐parameter method (5.1% deviations). Increased within‐segment SDs of 8.3% are observed for SATURN T2∗ compared with the reference multi‐GRE.SD maps are calculated for all healthy subjects for SATURN and the conventional methods and resulted in mean values of T1, T2, and T2∗ maps for a patient with HCM, and 1 patient with suspected HHD and the corresponding bullseye plots. Increased T1, T2, and T2∗ times (1607/47.0/35.5 ms vs 1487/38.5/26.5 ms) are observed in the septal regions compared with the lateral myocardium in the patient with HCM. SATURN shows increased T1 times and patchy structures in the patient with HHD. T2∗ times are substantially elevated.Figure 4T1, T2, and T2∗ in the myocardium based on a gradient‐echo readout in combination with saturation pulses and T2 preparation pulses. We demonstrated good agreement with Bloch simulations and phantom experiments yielding generally accurate T1 times. However some biases for T2 and T2∗ are observed. In vivo measurements provided robust image quality comparable to reference methods for all segments in the mid‐ventricular short‐axis view.In this study, we proposed the SATURN sequence for free‐breathing simultaneous quantification of T1 measurements resulted in good accuracy compared to spin‐echo sequences and SASHA in the phantom and in vivo. Mean T1 times in the 6 segments are comparable to previously reported values for saturation based T1 mapping at 3T.T1 maps yielded similar image quality and smaller within‐segment standard deviations compared with SASHA. Similar inter‐subject variability was found between SATURN and the reference method.T2 mapping is compromised for long T1/T2 combinations due to insufficient recovery during the rest‐period. However, as this effect is only marked at values outside the relevant in vivo range, a choice of 4 seconds rest periods seemed justified. In vivo T2 measurements resulted in lower T2 times than reported in literature,T2‐prepared bSSFP. The lower T2 times obtained in this study as compared to previous literatureT2 times . However, this can be alleviated by using regularization (SPIRiT + LLR) at the cost of inducing complexity in the post‐processing. T2 maps reconstructed using acceleration factors of R = 3 and R = 4 resulted in visually similar T2 maps with only slight deviations of 2.1% in the T2 times and 1.9% in the within‐segment standard deviations. Similar to T1, for the T2∗ the use of R = 4 increases the within‐segment standard deviation by 52.4%, which might be due to the low SNR for images with long TEs.Higher accelerations might be necessary for patients with high heart rates to reduce the time per single‐shot acquisition. The variability in T1, T2, and T2∗ time as reported in literature. T1 and T2∗ was observed in the septal region and patchy structures in the T1 map as typically observed in HHD.In the patient with HCM we observed an increased T1, T2, and T2∗ is more time‐efficient since all parameters are acquired in 1 scan (average acquisition time was 26.5±14.9seconds). Additionally, they share the same volume and are, therefore, inherently co‐registered. This eases the fusion of imaging information as corresponding regions are easy to identify. Furthermore, the assessment of multiple quantitative measures increases the specificity for diagnosis.Simultaneous measurements of Free‐breathing imaging was achieved by using a prospective navigator on the liver diaphragm. This may minimize the susceptibility to incomplete breath‐holds as often observed in patients suffering from dyspnea. Residual motion is compensated by the use of image registration. We used rigid‐registration as previously reported to yield satisfactory results in healthy subjects  and the reference SE and GRE methods for all single tubesTABLE S2T1, T2, and T2∗ times for the in vivo measurements for SATURN compared with the conventional cardiac mapping sequences  across all healthy subjects. Per‐subject relaxation times are summarized as means and within‐segment standard deviation, as highlighted in blue. The corresponding P‐values for the t‐test with Bonferroni correction are shown belowFIGURE S1 Simulations for the proposed SATURN sequence for varying T1 (left), T2 (middle), and T2∗ (right) for different sources of error as (A) the rest period before the T2 preparations, (B) Rician noise on the signal with corresponding SNR, (C) the heart rate in beats‐per‐minute (bpm) and (D) the T2 preparation efficiency as a scale factor of the flip down and flip up 90∘ pulses of the T2 preparation module. The relative deviation between simulated and true quantitative measures is depicted for each source of error. All simulations are performed with the common parameters  and only the source of error was varied. In A, only deviations in T2 are observed for a rest period of shorter than 5 seconds. In B, major deviations are observed for T2∗ dependent on the Rician noise. T2 is less impacted and T1 only slightly. C, no effect in neither T1, T2, and T2∗ was observed dependent on the heart rate. Deviations would be assumed for T1 only if noise was added. In D, a strong drop in T2 is observed for a decreased T2 preparation efficiencyFIGURE S2 A, In vivo T1, T2, and T2∗ maps acquired with single‐parameter reference methods (left) and the proposed SATURN sequence (right) for 2 healthy subjects. Visually homogeneous mapping is achieved throughout the myocardium for T1 and T2, minor artifacts appear in T2∗ maps. Image quality appears visually comparable to the reference methods. B, Below the standard deviation (SD) maps are shown for the 3 relaxation times and the same subjects for SATURN and the reference methodsFIGURE S3T1, T2, T2∗, and R2∗ maps are shown for the acquisition with acceleration factor R=3 (left), R=4 (middle) and for R=4 with additional regularization using SPIRiT + locally low rank (LLR) regularization (right). Quantitative measures with the standard deviation (shaded area) extracted from the SD maps along the myocardial wall are shown on the right side for R=3 (blue), R=4 (orange), and SPIRiT + LLR (yellow). Visual image quality is improved and precision is regained after the use of SPIRiT + LLR for R=4. The color bar and the y‐axis of the plot have the same ranges. The corresponding quantitative times for the pixel‐wise curve are windowed the same as the color bar left of the axis. The LLR algorithm takes around 200 seconds on a single coreFIGURE S4 In vivo T2 times acquired with the T2‐prepared bSSFP using a 3‐parameter fit model and 4 dynamics and a 2‐parameter fit model without the fourth dynamic (saturation). A, On the left side the mean T2 times per healthy subject are correlated between the 2‐parameter fit model and the 3‐parameter fit model. B, On the right side, the Bland‐Altman plot between 2 and 3 parameters is shown with a significant difference and an average bias of 5.85 ms increased T2 when using the 2‐parameter model. C, The representative T2 maps are depicted with the corresponding bullseye plots (D) showing the within‐segment mean and within‐segment standard deviation across all subjectsFIGURE S5 A, Native T1, T2, and T2∗ maps without (top) and with motion correction using rigid registration (bottom). B, Magnitude images which indicate the difference encoded in blue and red between 2 images and the corresponding registered images below. On the left side contrast number 5 (max TSmax) was motion corrupted as also seen in the resulting T1 map above. In the center image contrast number 3 (second T2 preparation) was corrupted and on the right image along the different gradient echoes small translation was corrected. C, Signal intensity for a region of interest in the septal myocardium across 3 repetitions of the SATURN sequenceClick here for additional data file.


In the past 20 years, Cardiac Computed Tomography (CCT) has become a pivotal technique for the noninvasive diagnostic work-up of coronary and cardiac diseases. Continuous technical and methodological improvements, combined with fast growing scientific evidence, have progressively expanded the clinical role of CCT. Recent large multicenter randomized clinical trials documented the high prognostic value of CCT and its capability to increase the cost-effectiveness of the management of patients with suspected CAD. In the meantime, CCT, initially perceived as a simple non-invasive technique for studying coronary anatomy, has transformed into a multiparametric “one-stop-shop” approach able to investigate the heart in a comprehensive way, including functional, structural and pathophysiological biomarkers. In this complex and revolutionary scenario, it is urgently needed to provide an updated guide for the appropriate use of CCT in different clinical settings. This manuscript, endorsed by the Italian Society of Medical and Interventional Radiology (SIRM) and by the Italian Society of Cardiology (SIC), represents the first of two consensus documents collecting the expert opinion of Radiologists and Cardiologists about current appropriate use of CCT. Cardiac Computed Tomography (CCT) was historically adopted as a tool to rule-out coronary artery disease (CAD) due to the well-established very high negative predictive value. Recently, the results of multicenter randomized clinical trials have changed the perception of CCT in the clinical world, leading the scientific community to recognize CCT as the first line diagnostic test for most of the patients with suspected chronic coronary syndrome  and in sIn this complex and revolutionary scenario, in which guidelines help the translation of evidences into clinical practice , there iThis manuscript, endorsed by the Italian Society of Medical and Interventional Radiology (SIRM) and by the Italian Society of Cardiology (SIC), represents the first of two consensus documents collecting the expert opinion of Radiologists and Cardiologists about current appropriate use of CCT and integrates the guidelines for appropriate use of cardiovascular magnetic resonance (CMR) recently published by the same working group .The writing committee discussed the table of content and assigned referrals for each chapter.A.Strong recommendation: there is evidence, general agreement, or both, that the test is useful (benefit >  >  > risk).B.Moderate recommendation: there is conflicting evidence or opinion about the usefulness of the test; the weight of evidence/opinion, however, is strongly in favor of the test’s usefulness. (benefit >  > risk).C.Weak recommendation: the test’s usefulness is less well established; there is a small net benefit (benefit ≥ risk)D.No recommendation: there is evidence or general agreement that the risk/harm outweighs benefits (benefit = or < risk).E.Expert opinion: there is insufficient evidence or evidence is unclear or conflicting, but this is what the working group recommends. Further research is recommended in this area.Each referral conducted literature review and drafted the assigned section highlighting indications and rating them according to the following score:Assigned scores were discussed in consensus by all authors and unanimously approved.In pre- and post-surgical complex congenital heart diseases (CHD), multimodality imaging is required for both the detailed evaluation of cardiovascular anatomy and for the functional characterization of cardiac chambers and flows. Catheterization is required for pulmonary vascular resistances calculation, whereas for most types of CHD and congenital coronary artery anomalies (CAAs) CCT is adopted as a complementary imaging modality  Table 11.Table 1Echocardiography is the initial imaging tool for morpho-functional evaluation; however, a frequently limited acoustic window hampers the assessment of the mediastinal vessels, extra-cardiac surgical conduits, and intra-cardiac complex anatomy, particularly in adults with grown-up congenital heart diseases (GUCH).The use of CCT has been described in patients of all ages and with CHD of all levels of complexity, especially when echocardiography is not exhaustive. CCT is generally recommended in complex conditions that require investigation of coronary vessels or complex vascular and thoracic anatomy , 16. CCTIn patients with suspected vascular rings and slings or tracheobronchial narrowing for complete cartilaginous rings, CCT is the method of choice for the pre-surgical evaluation of tracheobronchial tree and pulmonary parenchyma . CongeniCMR remains the method of choice in the follow-up of complex CHD due to the absence of ionizing radiation and for its capability to quantify vessel flows and ventricular function and to identify myocardial fibrosis. However, CMR is time consuming and image quality may be reduced in patients with metallic devices. CCT provides better visualization of stents, conduits, and metallic objects and is safe in patients with implanted pacemakers and defibrillators . MoreoveFinally, CCT may provide useful morphological information to avoid external coronary artery compression related to device release in transcatheter pulmonary valve replacement  and to iThe main limitation of CCT is ionizing radiation exposure; however, low-dose acquisition protocols can be adopted .Coronary Artery Calcium Score (CACS), reported as Agatston score , measureRecent studies , 29 haveCACS may have a role also in individuals aged 45-to-75 years with low cardiovascular risk but with strong family history of premature CAD and in diabetics patients aged > 40 years or at intermediate-risk of early CAD , 32.The absence of CACS carries a favorable 5-year and 15-year prognosis for patients with and without diabetes, respectively .Finally, CACS is considered useful for guiding preventive medical therapy , avoidinAccording to 2019 ESC guidelines on chronic coronary syndromes, coronary CT Angiography (CCTA) is not recommended for extensive screening of asymptomatic individuals . MoreoveThis is reflected in 2019 ESC guidelines that suggest that asymptomatic diabetic subjects with CACS > 400 may be referred for functional imaging or CCTA . HoweverFinally, some evidence suggests that CCTA could enhance screening in asymptomatic individuals in specific sporting  , 44 or wNon-cardiac surgery is associated with an incidence of complications from 7 to 11%, with a mortality rate of 0.8% to 1.5%, largely driven (42% of cases) by cardiac complications. Based on the rate of cardiovascular events , surgical procedures are classified at low, intermediate, or high risk . The current guidelines recommend coronary functional testing for patients with an unknown or impaired functional status undergoing intermediate-to-high risk non-cardiac planned surgery , 47. NevIn a recently published meta-analysis, CCTA was found to safely predict freedom from perioperative MACEs in a cohort of patients at high risk according to clinical indices . The sevCAD needs to be screened in patients scheduled for cardiac surgery for pre-operative risk assessment. In particular, a thorough cardiological evaluation is indicated in patients with severe valve disease with history of CAD, suspected ischemia, systolic dysfunction, male with age > 40 years, post-menopausal women, and patients with one or more risk factors. Several studies indicated that CCTA can reliably replace invasive coronary angiography (ICA) as a screening tool before valve interventions –52, espeIn the recent past, stable symptomatic patients with chest pain were non-invasively assessed using different functional tests, including mainly treadmill testing, stress echocardiography and single photon emission computed tomography (SPECT). Stress perfusion cardiac magnetic resonance (stress-CMR) and positron emission tomography (PET) were less used due to availability and costs concerns, albeit showing a higher diagnostic accuracy. Unfortunately, despite routine use of these tests, only one-third of the patients with a positive functional test turns out to be affected by obstructive CAD at ICA , revealiIn the recent years, CCTA was found to detect with high accuracy non-obstructive CAD defined by ICA, and to reduce unnecessary ICAs when compared to functional testing .CT), it is comparable to ICA with invasive FFR in targeted revascularization , be, be61], In past studies adopting old technology, it was found that the accuracy of CCTA was influenced by the pre-test probability (PTP) of CAD , being pHowever, CCTA is to be avoided in the presence of conditions which cannot ensure good image quality related to local availability and expertise, scanner technology, and patient characteristics, including extensive coronary calcification, irregular heart rate, severe obesity, and inability to breath-hold (Class III) .CCTA has the unique capability to non-invasively quantify coronary atherosclerosis and to characterize plaque morphology and composition with high accuracy compared to histology and intravascular ultrasound (IVUS) . This isPatients with obstructive CAD have worse outcomes compared to patients with nonobstructive or absent CAD . HoweverOther plaque characteristics, such as extent and location , have been associated with clinical outcome , 83, andThese data support the reporting of HRP features presence (if more than 2 HRP features are evident) even for non-obstructive lesions, as suggested by CAD-RADS guidelines .Some technical limitations may impact on CCTA-based plaque characterization, most importantly spatial resolution and other factors such as a certain degree of density overlap in lipid-rich and fibrous-rich non-calcified plaques. Dual-energy CT may overcome these limitations thanks to tissue decomposition algorithms. However, this approach is still limited to research and initial results need to be validated .Pericoronary adipose tissue is emerging as an imaging biomarker to identify plaque instability. Increased epicardial adipose tissue (EAT) attenuation was detected around inflamed plaques . MoreoveCT and stress-CTP allow to integrate information about the hemodynamic significance of coronary lesions to angiographic evaluation of CAD, thus potentially avoiding additional examinations and costs. In fact, data coming from iFFR show that only 35% of anatomically obstructive lesions have positive iFFR reflecting hemodynamic significance of a stenosis. Thus, iFFR is a key parameter to guide revascularization, improving the outcome and reducing health care costs [FFRre costs , 92  due to software constraints and offsite analysis [CT is strictly related to image quality. Imaging artifacts caused by low contrast, cardiac and respiratory motion, blooming due to severe calcification, and image noise due to low radiation exposure or high body mass index hamper FFRCT performance [Despite the advantages, FFRanalysis  and currformance .CT [Also, stress-CTP is capable of detecting functionally relevant stenosis, improving the diagnostic performances of CCTA, with similar performance in comparison with CCTA combined with FFRCT .Stress-CTP depicts perfusion defects as a hypo-attenuating myocardial region using either a static protocol (single scan acquired both at rest and during stress at the peak of iodine concentration in the coronaries) or a dynamic protocol in which several datasets are acquired during first pass perfusion. Dynamic stress-CTP has the advantage of providing quantitative evaluation of perfusion by estimating the myocardial blood flow .Regardless of the acquisition protocol, stress-CTP requires the administration of pharmaceutical stressors and notably increases both radiation exposure and iodinated contrast agent dose.Stress-CTP shows similar performance with respect to stress-CMR  and slightly better performance than single photon emission computed tomography (AUC 0.91 vs. 0.87)  and has CT, data on clinical utility and outcome have not been reported [However, these data need to be confirmed on larger populations. Furthermore, differently from FFRreported .


The purpose of this study was to explore the prognostic significance of PTT and PBVi using an automated, inline method of estimation using CMR.Pulmonary transit time (PTT) and pulmonary blood volume index (PBVi) (the product of PTT and cardiac index), are quantitative biomarkers of cardiopulmonary status. The development of cardiovascular magnetic resonance (CMR) quantitative perfusion mapping permits their automated derivation, facilitating clinical adoption.In this retrospective 2-center study of patients referred for clinical myocardial perfusion assessment using CMR, analysis of right and left ventricular cavity arterial input function curves from first pass perfusion was performed automatically , allowing estimation of PTT and subsequent derivation of PBVi. Association with major adverse cardiovascular events (MACE) and all-cause mortality were evaluated using Cox proportional hazard models, after adjusting for comorbidities and CMR parameters.2 = 0.57). Over a median follow-up period of 28.6 months (IQR: 22.6 to 35.7 months), MACE occurred in 61 (6.2%) patients. After adjusting for prognostic factors, both PTT and PBVi independently predicted MACE, but not all-cause mortality. There was no association between cardiac index and MACE. For every 1 × SD (2.39-s) increase in PTT, the adjusted hazard ratio for MACE was 1.43 . The adjusted hazard ratio for 1 × SD (118 ml/m2) increase in PBVi was 1.42 .A total of 985 patients : 52 to 71 years]) were included, with median left ventricular ejection fraction (LVEF) of 62% (IQR: 54% to 69%). PTT increased with age, male sex, atrial fibrillation, and left atrial area, and reduced with LVEF, heart rate, diabetes, and hypertension (model rPulmonary transit time (and its derived parameter pulmonary blood volume index), measured automatically without user interaction as part of CMR perfusion mapping, independently predicted adverse cardiovascular outcomes. These biomarkers may offer additional insights into cardiopulmonary function beyond conventional predictors including ejection fraction.  The pulmonary circulation is inextricably linked with cardiac physiology, but our understanding of the cardiopulmonary axis in various disease states is limited. Use of noninvasive imaging biomarkers as surrogate indicators of cardiopulmonary status may facilitate risk stratification and outcome prediction, potentially contributing to personalized clinical care.Pulmonary transit time (PTT) and pulmonary blood volume (PBV) are physiological parameters reflective of cardiopulmonary hemodynamics . Both arDespite extensive research supporting a clinical utility of PTT and PBV, at-scale analysis and clinical adoption have been hindered by challenges in data acquisition, requiring either invasive catheterization  or manuaIn this study, a fully automated machine learning approach for identification of RV and LV arterial input functions during first-pass perfusion imaging was deployed, allowing in-line estimation of PTT and subsequent calculation of PBV. Using a large, 2-center patient cohort, we investigated the potential clinical utility of PTT and PBV by assessing correlations with other parameters and any independent prognostic significance.This was a retrospective cohort study of patients referred for adenosine stress CMR at 2 centers , between March 2016 and August 2018. This cohort has been used to explore the prognostic effect of myocardial blood flow (MBF) and myocardial perfusion reserve (MPR), and has been previously described . In brieThe primary outcome was the incidence of major adverse nonfatal cardiovascular events . All-cause mortality was defined as a secondary outcome in view of the sample size and the broadly unselected patient population, which meant that the cause of death was often unrelated to cardiorespiratory disease and included sepsis and cancer-related deaths. Mortality data was obtained from the National Health Service Spine portal, with data on the cause of death being available for only a small number of patients. Clinical data were retrieved from the electronic patient records, with follow-up starting from the date of the perfusion CMR examination. Outcomes for the primary analysis were censored at death and end of follow-up period. Comorbidities recorded included history of hypertension, dyslipidemia, diabetes mellitus, atrial fibrillation, stroke or transient ischemic attack, smoking, history of previous myocardial infarction, percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG), and cancer .The study was approved by the National Health Service Research Ethics Committee and Health Research Authority . The study conformed to the principles of the Helsinki Declaration, and all patients provided written, informed consent.CMR studies were carried out on 1 of 4 1.5-T (Aera) or 3-T scanners . A standard clinical protocol, including cine imaging and stress and rest perfusion followed by late gadolinium enhancement, was used for all studies. Stress myocardial perfusion was performed, using adenosine as pharmacological stressor according to guidelines . The myoImage analysis for cardiac volume parameters and presence and distribution of late gadolinium parameters was performed using commercially available software . The perfusion sequence deployed  involvesNon-invasive methods of volume estimation are based on the indicator dilution principle and have been previously validated against invasive thermodilution methods . The PTTPulmonary blood volume was estimated as the product of PTT and cardiac output as originally described from indicator dilution methods :(eq. 2)PThis was indexed to body surface area (BSA), allowing calculation of pulmonary blood volume index (PBVi):The LV stroke volume was estimated using steady state free precession (SSFP) cine images from manual planimetry of a full short-axis stack in end-diastole and -systole, and the patient’s heart rate at rest was used to derive cardiac output (cardiac output = stroke volume × heart rate). Rest PTT was used for the primary analysis, including estimation of PBV as cardiac output data was only available during rest. Associations between stress PTT and outcomes were performed as a secondary exploratory analysis.t-test or a Mann-Whitney U test depending on normality, and categorical variables were compared with a chi-square test. Correlations were assessed using Spearman’s rank correlation coefficient. Predictors of rest PTT were evaluated using a multivariate regression analysis, the model of which included parameters either known to correlate with rest PTT as shown in previous studies  when not. Normality was assessed by visual inspection of the frequency histograms and quantified using a Kolmogorov-Smirnov test. Categorical variables were summarized as frequencies and percentages. Comparisons between MACE and non-MACE groups were performed for continuous variables using a 2-tailed unpaired Student’s  studies , or that studies . A sensiA total of 1,049 patients with CMR myocardial perfusion imaging data were available for inclusion as previously described . Of thesMedian age of the patients was 62 years (IQR: 52 to 71 years) and 660 (67%) were men. There were 281 (28.6%) patients with diabetes mellitus, and 306 (31%) patients had a prior history of either PCI or CABG. The median LVEF across the cohort was 62% (IQR: 54% to 69%). Baseline characteristics are summarized in 2 (IQR: 335 to 475 ml/m2). Rest PTT correlated with LV end-diastolic volume index (r = 0.37) and left atrial area index (r = 0.33), and negatively correlated with LVEF (r = −0.39), heart rate (r = −0.51), and myocardial blood flow at rest (r = −0.43) (e PTT (Median rest PTT was 7.7 s (IQR: 6.4 to 9.2 s). The median PBV index was 400 ml/m= −0.43) . In a mu) . A similar difference was observed with rest PTTn . Patients with MACE were also older, and more frequently had a history of diabetes, hypertension, previous revascularization, and stroke (Data on MACE was available over a median period of 28.6 months (IQR: 22.6 to 35.7 months) during which period there were 71 (7.2%) MACE in 61 (6.2%) patients. These included 29 (2.9%) myocardial infarctions, 10 strokes (1%), 23 (2.3%) hospitalizations for heart failure, and 9 cases of ventricular tachycardia or appropriate ICD treatment (0.9%). Patients with MACE had longer rest PTT  and larger PBVi  between patients who survived and those who died during the follow-up period.All-cause mortality data was available over a median of 31.4 months (IQR: 26.7 to 38.3 months), and during this period, 53 (5.4%) patients died. There was no statistically significant difference in rest PTT , rest PTTn  and PBVi (402 ml/m2) increase in PBVi was 1.42 . A sensitivity analysis across various models was performed, with inclusion of variables in the multivariable models limited to prevent overfitting. Both rest PTT and PBVi remained predictive of MACE in additional models with different variables, including MPR, left atrial area index, history of dyslipidemia, and history of previous myocardial infarction/PCI/CABG  (n = 17), with both rest PTT and PBVi remaining independently predictive of MACE. After adjusting for the same variables as those used in PTT was also extracted during adenosine stress first pass perfusion, and an exploratory analysis between stress PTT and outcomes was performed. A total of 963 cases with stress PTT data were available for analysis, following exclusion of cases with incomplete or erroneous stress perfusion data. As expected, median stress PTT was shorter than rest PTT 6.2 s (IQR: 5.1 to 7.7 s) versus 7.7 s (IQR: 6.4 to 9.2 s), although they were highly correlated . Stress PTT also correlated with LVEF (r = −0.37), stress MBF (r = −0.31), LV end-diastolic volume index (r = 0.24), and LA area index (r = 0.32) . Over the follow-up period, 57 patients from this cohort had MACE. Stress PTT was predictive of MACE (p = 0.020) but not all-cause mortality (p = 0.064). The HR for 1-SD (2.64-s) increase in stress PTT was 1.34  after adjusting for age, LVEF, hypertension, diabetes, sex, and presence of LGE .This study investigated the prognostic power of pulmonary transit time and PBV measured automatically, in-line, during routine quantitative myocardial perfusion CMR. We demonstrate that PTT and PBVi are independently associated with adverse cardiovascular events in patients clinically referred for perfusion CMR, with a prognostic power incremental to established clinical risk factors and imaging biomarkers.PTT represents the average time it takes for a bolus of intravenous contrast to pass from the right to the left side of the heart . The potRecently, a number of noninvasive imaging modalities, including echocardiography , compute2) was independently associated with adverse outcomes in heart failure outpatients. Similarly, Swift et al. , Ricci et al. , both of which are known to affect PTT. Stroke volume was calculated from planimetry of short-axis stack cine images rather than phase contrast velocity measurement, as the latter was not available. Although this may introduce a degree of error, particularly in the context of valve disease, this is not believed to alter the conclusion, as the PTT and PBVi varied over a much larger dynamic range than cardiac output. Furthermore, the study was designed primarily to assess the prognostic value of biomarkers (PTT and PBVi) that could be automatically derived from CMR sequences obtained as part of routine clinical imaging protocols. Although all first-pass perfusion studies rely on the indicator dilution principles, there are important variations between different methods of PTT estimation. Different sampling locations have been described, including the pulmonary trunk to left atrium , the RV PerspectivesCOMPETENCY IN MEDICAL KNOWLEDGE: PTT can be derived automatically from rest perfusion CMR imaging, without the need for additional image acquisition or user input. Both PTT and PBVi encode prognostic information which is independent of established imaging parameters including LVEF and the presence of LGE.TRANSLATIONAL OUTLOOK: Further research is needed to establish whether PTT metrics can serve as noninvasive biomarkers for risk stratification and early warning signals in specific disease models and whether these can be altered with treatment.PTT and PBV, measures of the cardiopulmonary system, can now be derived automatically without user input from latest-generation CMR perfusion mapping studies. Here, we show that these metrics are independently associated with adverse cardiovascular events over and above conventional factors, potentially providing clinically feasible imaging biomarkers of cardiopulmonary physiology.This study was supported by a Clinical Training Research Fellowship (to Dr Seraphim) from the British Heart Foundation (FS/18/83/34025) and directly and indirectly from the National Institute for Health Research Biomedical Research Centres at University College London Hospitals and Barts Health National Health Service Trusts. This study was also supported by the National Heart, Lung and Blood Institute, National Institutes of Health by the Division of Intramural Research (Z1A- HL006214-05 and Z1A- HL006242-02). This work forms part of the research areas contributing to the translational research portfolio of the Biomedical Research Centre at Barts, which is supported and funded by the National Institute for Health Research. Prof. Petersen has served as a consultant for and is a shareholder of Circle Cardiovascular Imaging Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.