Diastolic dysfunction was present in 70.9% (n = 88) of measurements before sternotomy and 75% (n = 93) after sternal closure. Diastolic dysfunction at either stage was associated with greater CPOMS on D5 (p = 0.009) and D8 (p = 0.009), with CPOMS scores 1.24 (p = 0.01) higher than in patients with normal function. Diastolic dysfunction was also associated with longer durations of intubation (p = 0.001), ICU length of stay (p = 0.019), and new postoperative atrial fibrillation  = 4.50 (1.22–25.17)). We were able to apply the updated ASE/EACVI guidelines and grade diastolic dysfunction in the majority of patients. Any grade of diastolic dysfunction was associated with greater all-cause morbidity, compared with patients with normal diastolic function.Diastolic dysfunction is associated with major adverse outcomes following cardiac surgery. We hypothesized that multisystem endpoints of morbidity would be higher in patients with diastolic dysfunction. A total of 142 patients undergoing cardiac surgical procedures with cardiopulmonary bypass were included in the study. Intraoperative assessments of diastolic function according to the 2016 American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines using transesophageal echocardiography were performed. Cardiac Postoperative Morbidity Score (CPOMS) on days 3, 5, 8, and 15; length of stay in ICU and hospital; duration of intubation; incidence of new atrial fibrillation; 30-day major adverse cardiac and cerebrovascular events were recorded. Diastolic function was determinable in 96.7% of the dataset pre and poststernotomy assessment ( Diastolic dysfunction refers to the inability of the ventricle to relax to its original unstressed state . It is pAnalysis of outcomes following cardiac surgery tends to focus on endpoints of immediate morbidity , majThe Cardiac Postoperative Morbidity Score (CPOMS)  is a valIn this prospective observational study, we hypothesize that morbidity is greater for patients with diastolic dysfunction, as defined by recent consensus-based international guidelines  when comIn total, 142 patients undergoing cardiac surgery from November 2014 to December 2016 provided consent for participation in this study, and a total of 124 patients were included in the final analysis  .The study population consisted of adult patients undergoing elective, urgent (surgery within the current admission) or emergency (operation before the beginning of the next working day) at high-volume UK cardiac center . A rangePatients were not premedicated. The induction of anesthesia was standardized according to the local protocol. Mean arterial pressure was maintained between 50 and 80 mmHg using metaraminol or phenylephrine. A TEE probe was introduced after induction of anesthesia. Choice of inotropic support (including the use of phosphodiesterase inhibitors), red cell and product transfusion, volume administration, pacing, and management of separation from bypass were at the discretion of the operating team.Three cardiovascular ultrasound machines using a multiplane transesophageal echo probe were available, including a Phillips iE33 , a Siemens Acuson CV70 , and a GE Vivid E9 . All echocardiographic data were collected, analyzed, and interpreted by one of three EACVI-accredited TEE operators blinded to the patients’ data. Comprehensive datasets were acquired for each patient at two stages intraoperatively: before sternotomy, and after sternal closure . Measurements were taken during hemodynamic stability and without the need for manipulation of fluids or vasoactive drugs. Sweep speeds were set at 50–100 mm/s, and measurements were recorded during apnea. To ensure high-quality data collection, all variables were measured during apnea, the average of three cardiac cycles was used for analysis, and cardiac cycles with extrasystoles on electrocardiogram were excluded. Where apnea was clinically inappropriate, several measurements were performed, and averaged values were calculated .Left ventricular diastolic function was assessed according to the 2016 American Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI) guidelines for the evaluation of Left Ventricular Diastolic Dysfunction [Data relating to patient characteristics, comorbidities, medications, intraoperative transesophageal echo findings, and postoperative outcomes were prospectively collected on case report forms and entered onto REDCap, a secure database. Prolonged length of stay was defined as 11 or more days, as described in a large UK audit of the length of stay after cardiac surgery .Initially, the primary outcome was a change in diastolic function following the use of enoximone. During this study—following recruitment of only 80 patients—our two institutions merged, leading to a change in pharmacy and formularies, replacing enoximone entirely (with milrinone.) As a result, we were unable to continue assessing the impact of enoximone and instead report the effect of diastolic dysfunction, since defined by ASE/ECAVI, on morbidity with a primary outcome of CPOMS at days 3, 5, 8, and 15. Secondary outcomes remain unchanged: length of stay in intensive care and hospital, duration of intubation, the incidence of new postoperative atrial fibrillation, and major adverse cardiac and cerebrovascular events.n = 42, D5 n = 121, D8 n = 37, and D15 n = 57 , requiring a sample size of 121, plus an additional 20 allowing for data attrition.Power calculations were made using published CPOMS data, where each unit increase in CPOMS summary score was associated with a subsequent increase in length of stay. To detect a one-unit increase in mean (SD) CPOMS, required sample sizes were D3 Descriptive statistics were applied to examine outcomes of interest. Lavene’s and the Shapiro–Wilk tests were performed to evaluate the data distribution. Normally distributed data were presented as mean ± standard deviation, whereas nonparametric data were presented as median and interquartile ranges. For continuous variables where parameters were not normally distributed, Mann–Whitney or Kruskal–Wallis test was used. For categorical variables, Fisher’s exact test was used. To examine the severity of diastolic dysfunction on composite morbidity outcomes, trends across the three groups  were assessed using a nonparametric test for trend for continuous data, and an exact logistic regression model for categorical data.p value less than 0.05 was considered significant. Statistical analyses were performed using Stata Version 14  software.To determine if the presence of diastolic dysfunction was independently associated with hospital length of stay, an all-subset regression was used to select the best model from the available covariates. Hospital length of stay was log-transformed and observed differences converted to percentages. All variables in Patients’ baseline characteristics are shown in n = 240) and were able to determine the grade of diastolic dysfunction in 85% (n = 210)  .n = 88) in the presternotomy assessment and 75% (n = 93) in the poststernal closure assessment as having diastolic dysfunction. We identified normal diastolic function (DFN) at both stages in 20.1% (n = 25). Data were indeterminate for the presence or absence of diastolic dysfunction (IDDD) in 3.2% (n = 4) at each time point.We identified 70.9%  between measurements, 20.9% changed by one grade, , and in 20%, change was considered indeterminable. Changes in diastolic function between the two measurement stages are outlined .p = 0.009) and D8 , and overall CPOMS that were higher by 1.24 (p = 0.01) unadjusted, and by 1.14  after adjustment for age, bypass time and elective vs. nonelective surgery in patients with diastolic dysfunction versus normal function. In addition, longer durations of intubation (0.25 (0.2–0.42) vs. 0.5 (0.27–1) days; p = 0.001, adjusted coefficient 0.52 ), ICU length of stay (2 (2–3) vs. 3 (2–5) days; p = 0.019, adjusted b (SE) = 1.02 (0.46) p = 0.025) and new postoperative atrial fibrillation  = 3.58 (1.06–12.13) after adjustment for age, bypass time and elective surgery) were observed in those with diastolic dysfunction (Presence of diastolic dysfunction of any grade or at either time point was associated with greater composite morbidity burden. This included greater cardiac postoperative morbidity scores (CPOMS) on postoperative D5  , versus DD1, was associated with greater morbidity burden for all morbidity outcomes except new postoperative AF . CPOMS i< 0.001) .p = 0.217. By using the length of stay as a categorical variable (>11 days versus <11 days) and fitting a logistic regression model, diastolic dysfunction was not identified as an independent predictor of prolonged length of stay: OR 2.29 (0.69–7.59) p = 0.175. No statistically significant independent predictors of prolonged length of stay (>11 days) were identified in the dataset.A multivariable regression model was fitted to identify independent predictors of prolonged length of stay. Variables found to be independently associated with hospital length of stay were age and cardiopulmonary bypass time . After aThe use of the 13-domain CPOMS at defined time points  postoperatively enabled functional indices of morbidity burden to be quantified and compared with patients without diastolic dysfunction for the first time. This study demonstrated that any grade of diastolic dysfunction was associated with greater all-cause morbidity, compared with patients with normal diastolic function. This included CPOMS on days 5 and 8, as well as the length of ICU stay, duration of mechanical ventilation, MACCE, and postoperative atrial fibrillation. In addition, at each measured time point, the CPOMS in patients with diastolic dysfunction was higher by more than one point, amounting to one extra domain or organ system of morbidity, compared with patients with normal diastolic function. CPOMS was also observed to increase by approximately one point with each stepwise increase from normal diastolic function, to diastolic dysfunction with normal left atrial pressure, to diastolic dysfunction with raised left atrial pressure in both presternotomy and poststernal closure groups. The spread of morbidity seemed to suggest a preponderance of renal, cardiovascular, and infection morbidity domains with this pattern occurring in the early and later operative assessment times. Overall, the results confirm that the presence and severity of diastolic dysfunction are associated with major morbidity.Almashrafi et al. recently observed that hospital length of stay after cardiac surgery increases monotonically with the number of postoperative complications . It coulAlthough diastolic dysfunction was not identified as an independent predictor of prolonged length of stay, a clear morbidity signal was observed in this perioperative patient population, and we believe that diastolic dysfunction should continue to be studied in this context and will benefit from ongoing analysis in larger-scale studies.The assessment of diastolic dysfunction in the perioperative environment is influenced by loading conditions, fluctuating hemodynamics, and mechanical ventilation ,22,23,24In 2016, the ASE/EACVI guidelines were updated and simplified, with emphasis given to “2D imaging”, “clinical context”, and four diastolic indices: tricuspid regurgitant jet velocity, indexed left atrial volume, annular e’ velocity, and E/e’. Clinically, diastolic dysfunction is considered present when left ventricular systolic dysfunction (LVEF < 50%) or “myocardial disease” exists. Once diastolic dysfunction is diagnosed, the guidelines place emphasis on a distinction being made between diastolic dysfunction with normal or raised left atrial pressure. Clearly, such clinical context may be observed in many patients presenting for cardiac surgery; the guidelines reference a nonapplicability to the perioperative environment but with no specific statement not to use them. A recent critical care environment meta-analysis applied these guidelines in patients with septic shock and found the identification of diastolic dysfunction was strongly associated with mortality . A patien = 15), with only a very small number of patients ultimately deemed unclassifiable (IDDD). The additional emphasis on clinical context and 2D data, together with the assessment of diastolic indices, has enabled diagnosis and classification in cases where ambiguity would otherwise exist. Importantly, we found the main outcomes of classification: normal diastolic function, diastolic dysfunction with normal left atrial pressure, and diastolic dysfunction with raised left atrial pressure are associated with multisystem morbidity outcomes. We identified the presence of perioperative diastolic dysfunction in 77.4% of our dataset, which is in line with that previously described in a CABG population [The updated 2016 ASE/EACVI approach enabled us to straightforwardly classify 97.6% of our mixed cardiac surgical dataset, including those patients with mitral valve disease (pulation . This isp = 0.02), although this is not surprising, as diastolic dysfunction is more prevalent with advancing age [It is important to acknowledge that the two groups—normal diastolic function and diastolic dysfunction—contain different patient characteristics. Age was significantly higher in patients with diastolic dysfunction p = 0.0, althougn = 48) received a phosphodiesterase inhibitor “on pump”, which may have influenced diastolic measurements acquired after sternal closure. However, we found any grade of diastolic dysfunction measured at either stage pre- or poststernotomy to have a similar effect on the outcome. Change in diastolic function (improved or worse) was observed in 20% of patients receiving phosphodiesterase inhibitors. As the study was not intended as an interventional study, the impact on the perioperative management of diastolic dysfunction needs to be evaluated in future studies. Finally, with regard to the updated ASE/EACVI guidelines on the assessment of diastolic function, we acknowledge these are validated in an outpatient rather than perioperative population and have justified applying them in the discussion above. However, we could not identify a definition of “myocardial disease” within the guidelines, and therefore, an assumption was made about this definition, which may have introduced bias.We acknowledge these findings need to be viewed in the context of limitations. Firstly, our initial primary outcome measure was to assess the effect of enoximone on change in diastolic function and provide a background for future studies of its effect. As our primary outcome measure was undeliverable, our secondary outcome was subsequently powered for this study. We performed a prospective observational study in a nonhomogeneous population of perioperative cardiac surgical patients that included assessment of diastolic function in elective and nonelective or urgent cases, isolated CABGs, isolated valves (including mitral where mitral stenosis and mitral regurgitation may require different echocardiographic diagnostic algorithm; In summary, we were able to demonstrate the feasibility to apply the updated ASE/EACVI guidelines and that grading of diastolic dysfunction could be applied to nearly every patient. Although identification of intraoperative diastolic dysfunction appears to be associated with outcome, its role in perioperative settings remains unknown. Further studies are required to determine whether manipulation and improvement of diastolic dysfunction in the intraoperative phase can result in improved postoperative recovery.


Cardiovascular magnetic resonance (CMR) myocardial strain analysis using feature tracking (FT) is an increasingly popular method to assess cardiac function. However, different software packages produce different strain values from the same images and there is little guidance regarding which software package would be the best to use. We explored a framework under which different software packages could be compared and used based on their abilities to differentiate disease from health and differentiate disease severity based on outcome.To illustrate this concept, we compared 4-chamber left ventricular (LV) peak longitudinal strain (GLS) analyzed from retrospective electrocardiogram gated cine imaging performed on 1.5 T CMR scanners using three CMR post-processing software packages in their abilities to discriminate a group of 45 patients with heart failure with preserved ejection fraction (HFpEF) from 26 controls without cardiovascular disease and to discriminate disease severity based on outcomes. The three different post-processing software used were SuiteHeart, cvi42, and DRA-Trufistrain.All three software packages were able to distinguish HFpEF patients from controls. 4-chamber peak GLS by SuiteHeart was shown to be a better discriminator of adverse outcomes in HFpEF patients than 4-chamber GLS derived from cvi42 or DRA-Trufistrain.We illustrated a framework to compare feature tracking GLS derived from different post-processing software packages. Publicly available imaging data sets with outcomes would be important to validate the growing number of CMR-FT software packages. Cardiovascular magnetic resonance imaging (CMR) is recommended as the gold standard for the assessment of left ventricular (LV) systolic function . MyocardThe strain values produced by FT analysis is vendor-dependent. There are a number of different commercial software packages available for FT and different vendors produce different strain values . There iIn this study, we propose that different CMR FT software packages be compared and used based on their abilities to differentiate disease from health and to discriminate disease severity based on patient outcome. To illustrate this concept, we compared three CMR post-processing FT software packages SuiteHeart , cvi42 , and DRA-Trufistrain  in a group of HFpEF patients. We first compared their abilities to discriminate HFpEF patients from controls using GLS. In addition, we investigated if there was a difference in the GLS derived from different software packages to associate with outcomes in HFpEF patients.We retrospectively analyzed baseline data from 45 HFpEF patients enrolled in a previous study  and 26 cControl patients were retrospectively chosen from a prospective cohort study of patients referred for a CMR at the Philadelphia Veterans Affairs Hospital . We seleAll HFpEF patients and controls were followed prospectively for HF hospitalization and death until January 2019. The incidence of death or hospitalization for HF was ascertained via medical record review by trained physicians. Incident HF was identified by: (1) a discharge diagnosis of decompensated HF; (2) presence of new onset or worsening HF symptoms; (3) clinical or radiologic evidence of pulmonary congestion, invasive evidence of increased LV filling pressures or elevated BNP (> 300 ng/L or NT-proBNP > 1000 ng/L). The protocol was approved by the institutional review boards of the Philadelphia Veterans Affairs Hospital and the Hospital of the University of Pennsylvania. All subjects provided written informed consent.2; matrix size = 192 × 192; and parallel imaging factor = 2.All participants had CMR examination on a 1.5 T CMR scanner  using an eighteen-channel phased-array body coil. Retrospective ECG gated cine CMR imaging was performed with balanced steady-state free precession (bSSFP) sequences using standard protocol covering short axis and long axis in the 2- and 4-chamber views. The bSSFP cine images were acquired continuously from the mitral annulus to the apical level without gaps on the short axis. The LV outflow track (3-chamber) view was not consistently acquired and therefore not included in the analysis. Briefly, the imaging parameters are as follows: repetition time = 2.6 ms; echo time = 1.3 ms; phases = 30; slice thickness = 8 mm; bandwidth = 898 Hz/pixel; flip angle = 70°, field of view = 300 to 340 mmShort axis cine images were used to analyze LV systolic function. The LV function analysis was performed using SuiteHeart 5.0.0 (Neosoft Inc) including all phases between end-diastole and end-systole of all slices. Papillary muscles were included in the ventricular volume and all volumetric parameters were indexed to body surface area. Longitudinal strains were analyzed on three different cardiac post-processing software packages SuiteHeart 5.0.0 (Neosoft Inc.), cvi42 5.10.3 (Circle Cardiovascular Imaging), and DRA-Trufistrain 2.1 . Long axis endocardial and epicardial contours of 2-chamber and 4-chamber cine images were automatically traced by SuiteHeart and cvi42 with manual correction. For DRA-Trufistrain, the endocardial and epicardial contours at end-diastole were manually traced and automatically propagated through the other phases based on the results of the deformable image registration. The peak global myocardial systolic strain (2-chamber and 4-chamber) was obtained for analysis. In order to delineate if contours play a role in the difference of the FT algorithms, we randomly selected 10 patients and compared the manually contoured results with the results from the automatic contours with manual correction.Continuous variables were described as mean ± standard deviation (SD) or median values based on normality of the variables. The normality of distribution of continuous variables was assessed by the Anderson–Darling test. Categorical variables were presented as percentages. The comparison of continuous parametric data was performed by Student’s t‐test and non-parametric data using Mann–Whitney test. Categorical variables were compared by Chi‐square test or Fisher’s exact test. The association of baseline clinical and imaging parameters and outcomes was evaluated by univariable Cox regression analysis and significant univariate parameters were to be adjusted in the multivariable analysis if appropriate. Receiver operating curves (ROCs) were used to determine optimal cut off values using area under the curve (AUC) and were compared using DeLong’s Test. The cut-off points were subsequently used in Kaplan–Meier curves to estimate the distribution of survival as a function of follow-up time. For all data, P < 0.05 was considered statistically significant. EmpowerStats  was used to perform statistical analysis.We randomly selected 10 HFpEF patients to assess reproducibility. For inter-observer reproducibility, the second investigator completed the analysis independently. For intra-observer reproducibility, the same investigator analyzed the same group of subjects two months later blinded to the first measurements. Reproducibility was tested by intraclass correlation coefficient (ICC) and Bland–Altman plots.Forty-five HFpEF patients  and 26 non-HFpEF patients  were included in the analysis. The mean LVEF was lower in the HFpEF group . During a median follow-up period of 3.8 years (range from: 1–5.2 years), 14 (31%) events occurred . All demographic and baseline clinical and CMR characteristics are shown in Table The mean difference and standard deviation of 4-chamber GLS determined from manual contours versus automatic contours with manual correction in 10 randomly selected patients using SuiteHeart is 0.21% and 0.87%, and using cvi42 is -0.19% and 0.61%, respectively. There was no statistical difference between SuiteHeart and cvi42 with p-values of 0.465 and 0.364, respectively. DRA-Trufistrain was not included in this comparison because it can only be manually traced.All global longitudinal strain parameters (2-chamber and 4-chamber) derived from the three software  were able to distinguish HFpEF patients from non-HFpEF controls (p < 0.05)  and DRA-Trufistrain  , cvi42  0.470–0.770, optimal cut point = -15.1%; sensitivity = 0.93, specificity = 0.48), and DRA-Trufistrain  were compared with De-Long’s test. Based on pairwise comparison of ROC curves, there was no significant difference in AUC between cvi42 and SuiteHeart (p = 0.225), cvi42 and DRA-Trufistrain (p = 0.599) and SuiteHeart and DRA-Trufistrain (p = 0.470). Using the optimal cut points determined from the ROC analysis, Kaplan Meier survival curves for the 3 software packages showed only SuiteHeart software was able to significantly differentiate the survival probabilities of the HFpEF patients  on 2-chamber and 4-chamber longitudinal strains. Bland–Altman plots for inter- and intra-observer reproducibility for 4-chamber longitudinal strains in HFpEF patients are shown in Fig. We illustrated a framework by which CMR FT postprocessing strain software packages can be compared by evaluating its ability to discriminate HFpEF from non-HFpEF controls and further differentiate patients with adverse outcome. For the three software packages examined, all were able to discriminate HFpEF patients from controls. SuiteHeart 4-chamber GLS was associated with adverse outcomes of HFpEF patients in this small cohort of patients. cvi42 and DRA-Trufistrain were limited by the small sample size, but showed trends toward discrimination for adverse outcomes. The intra-observer and inter-observer reproducibilities in all three software packages were excellent. These findings may have significant implications for the clinical usage of different software packages in myocardial strain analyses.Myocardial strain imaging techniques and analysis provide a valuable diagnostic and prognostic tool for assessing cardiac function . CMR myoCMR FT, on the other hand, is based on pattern-matching techniques of tracking “features” across multiple images in a cardiac cycle . A pixelIn addition to cvi42 and SuiteHeart, we included DRA—Trufistrain in our comparison. DRA stands for deformable registration algorithms. DRA also measures strain values from bSSFP cine images, but unlike most of the FT software which utilize optical flow methods and track endocardial features, DRA-Trufistrain method tracks the myocardium and produces layer-specific information . DRA hasIn addition to CMR, 2D speckle-tracking echocardiography (STE) has also been widely used to assess myocardial strain due to its ease of use and availability. STE has been shown to have good correlation with the strain calculated by CMR FT and MT, although the agreement is not optimal in myocardial deformation analysis . STE relLike echocardiography, strain values differ by vendor packages in CMR-FT. Worse than the problem in STE, where three main vendors differ and TomTec is the only vendor independent software, more than 10 vendor independent CMR FT software packages have emerged, which has amplified the problem of FT analysis in CMR. Each software utilizes different techniques to derive their strain measurements and because some methodologies are proprietary, it is difficult to directly compare these software methodologies. Furthermore, the selective use of different post-processing software may affect the significance of strain measurements. Although CMR is the gold standard for strain analysis using MT or DENSE, one study has found that 2D-STE provided stronger prognostic value to predict overall and CV mortality in HFpEF patients compared to CMR methods . This diOur study addresses one important concept in evaluating diagnostic and prognostic parameters or methodologies by directly examining the software package’s ability to detect and differentiate disease. Since it would be impossible to standardize individual algorithms, we propose to standardize methodology to evaluate output parameters from the different software packages. The goal is to find parameters from the analysis to differentiate disease from control and to detect more severe disease with worse prognosis from the less severe. In this particular study cohort, we have found that all three software packages investigated were able to fulfill the first requirement of differentiating disease from control, but only one was able to differentiate the more severe from the less severe disease in this small cohort of patients as evidenced by adverse outcome events. Both cvi42 and Trufistrain will likely be able to inform outcome if the sample size were larger, as evidenced by the p-value trends (Table Our study has a number of limitations. We only studied one disease to illustrate the concept. Our myocardial strain analysis also only focused on two parameters, GLS from 2-chamber and 4-chamber views. 3-chamber views were not used due to inconsistencies in slice selection in acquired images. We choose not to compare GCS on the short-axis view because when we compared GLS and GCS between HFpEF patients and controls, we found that the GLS had greater sensitivity for separation of patients and controls and thus chose to use GLS as an illustrative example. We did not perform global radial strain analysis due to its inferior reproducibility compared to GLS and GCS. Our goal is to provide a demonstration of the method of comparison of strain software using HFpEF as an illustrative example, rather than making a firm statement about strain and outcomes in HFpEF patients. Another limitation to our study is that we only included a single version of each of three software packages. We considered that these software packages to be representative to illustrate the concept as both SuiteHeart and cvi42 have artificial intelligence assisted contour tracking algorithms and are currently widely used. We also included DRA-Trufistrain as it represents a different tracking algorithm.In the setting of lacking standardization and increasing use of CMR FT in research and clinical realms, we proposed and demonstrated that the output of the CMR strain parameters can be evaluated across packages for disease discrimination and for adverse outcome differentiation. The most successful software package will be the ones that could perform well in different disease categories. Publicly available large data sets with outcomes in different disease populations by which the software developers could use to benchmark their products are urgently needed.


Pulmonary hypertension (PH) is dichotomized into pre- and post-capillary physiology by invasive catheterization. Imaging, particularly strain assessment, may aid in classification and be helpful with ambiguous hemodynamics. We sought to define cardiac MRI (CMR) feature tracking biatrial peak reservoir and biventricular peak systolic strain in pre- and post-capillary PH and examine the performance of peak left atrial strain in distinguishing the 2 groups compared to TTE.p < 0.001) as was pulmonary vascular resistance . Post-capillary patients had significantly larger left atria . There was no difference in right atrial volumes between groups , however peak RA strain was lower in post-capillary PH patients . In the post-capillary group, there was commensurately severe peak strain impairment in both atria . CMR LAVi and peak LA strain had a multivariate AUC of 0.98  for post-capillary PH diagnosis which was superior to TTE.Retrospective cross-sectional study from 1 Jan 2015 to 31 Dec 2020; 48 patients (22 pre- and 26 post-capillary) were included with contemporaneous TTE, CMR and catheterization. Mean pulmonary artery pressures were higher in the pre-capillary cohort (55 ± 14 vs. 42 ± 9 mmHg; CMR volumetric and deformation assessment of the left atrium can highly accurately distinguish post- from pre-capillary PH. Pulmonary hypertension (PH) is a hemodynamic diagnosis with diverse etiologies and variable prognoses . DichotoPre-capillary mPAWP ≤ 15 mmHg) PH encompasses most of the WHO classification groups  while post-capillary PH (mPAWP > 15 mmHg) relates to left heart disease (group 2)  performed by our service were included. Patients were excluded if any of the 3 tests were performed prior to referral and not repeated by us. This was to minimize random error and bias arising from potential methodological differences at external sites. Medical records were reviewed to determine PH classification groups according to current guidelines (This study has been approved by the Heath Research Authority (HRA) and NHS Research Ethics Service (REC) (IRAS ID 280472/Protocol 20HH5838) with waivers of informed consent due to the retrospective design.Patients were allowed only oral clear fluids prior to catheterization. This was to avoid dehydration and factitious PAWP normalization. Vascular access was via right internal jugular (ultrasound-guided) or occasionally right antecubital venous puncture. A Swan-Ganz catheter was used for all pressure measurements (mean of 3 readings recorded in sinus rhythm or 5 in AF). PAWP tracings were obtained in end-expiration. Cardiac output (CO) measurements were made using the thermodilution or Fick method. PVR (Wood units/WU) was calculated by (mPAP-mPAWP) ÷ CO.Patients were classified as having pre-capillary PH if their invasive mPAP was ≥ 25 mmHg and mPAWP ≤ 15 mmHg. A designation of post-capillary PH was applied if the mPAWP was >15 mmHg  measured in accordance with current guidelines . ePLAR wReduced medial  mitral annular e' velocities may be observed in pre-capillary PH  and can All patients underwent comprehensive CMR on a 1.5T Siemens Aera scanner  using a 32-channel phased array surface coil as part of routine care. Cine imaging was performed with breath-held steady state free precession sequences to derive contiguous parallel short axis slices of both ventricles from base to apex, as well as standard long axis slices of the heart. Slice prescription parameters were 8 mm thickness/2 mm gap for short axis imaging with 1.5–2 mm in-plane spatial resolution, and 33–45 ms temporal resolution with 25–30 reconstructed cardiac phases.CMR studies were analyzed using Circle Cardiovascular Imaging . Volumetric analysis was performed as per guidelines .Myocardial and atrial deformation FT was also performed using CVI42 . EndocarWith regard to the RV, only the free wall endo- and epicardial borders were traced to derive the RV free wall longitudinal strain (RVFWLS), with tracing and deformation of the septum assigned to the LV.Three repeat measurements of peak biatrial reservoir, LV GLS and RVFWLS were performed, and the average recorded.Ten patients were randomly selected for strain measurement by a second investigator (DG) to assess inter-observer variability. Intra-observer variability was assessed with one investigator (KL) re-measuring atrial and ventricular strain after 1 month.t-test or Mann Whitney U test for normal and non-normal data, respectively. Categorical variables are displayed as n (%) and differences assessed using Fisher's exact test. Intraclass correlation coefficient (ICC) estimates and their 95% confidence intervals for inter- and intra-observer variability in strain assessment were calculated. Correlation analysis was performed using Pearson correlation coefficient or Spearman rank test where data was non-normal. TTE and CMR measurement of LAV was compared with Bland-Altman analysis. Univariate and multivariate stepwise logistic regression was performed to identify variables that differentiated post- from pre-capillary PH. Receiver operating characteristic (ROC) curves with area under the curve (AUC) values were used to compare discriminative ability of the various parameters and the optimal cut-points were defined by the Youden index. A p-value of ≤0.05 was considered statistically significant.Continuous normal data are presented as mean (±1 standard deviation). Non-normal data are presented as median (inter-quartile range). Continuous data was compared with the two tailed Student's Measurement of FT biatrial and biventricular strain was feasible in all patients. There was excellent inter- and intra-observer agreement. Intra-observer (KL) ICC for the RA, LA, RV and LV were 0.99 (0.97–1.0), 1.0 (0.99–1.0), 0.99 (0.95–1.0) and 0.97 (0.87–0.99), respectively.Inter-observer  ICC were 0.98 for RA (0.90–0.99), 1.0 for LA (0.98–1.0), 0.99 for RV (0.96–1.0) and 0.97 for LV (0.88–0.99).p < 0.001) . Pre-capillary PH patients were mainly female and younger, with lower BMI and preserved renal function. Only 1 pre-capillary PH patient had an AF history compared to 20 (77%) post-capillary patients (< 0.001) .Mean PA pressures (mPAP) were higher in the pre-capillary cohort as was PVR. Cardiac index (CI) was similar between groups. Mean RA pressures (mRAP) were higher in post-capillary PH patients .TR Vmax was lower but transmitral E wave velocity was higher in post-capillary PH patients. ePLAR and all ePLAR variants were significantly higher in pre-capillary patients in context of greater TR Vmax and lower LV filling pressure estimates by E/e'. Lastly, TTE LAVi was smaller in the pre-capillary group .Pre-capillary PH patients had smaller left atria and ventricles relative to the right. The post-capillary group had significantly larger left atria. There was no difference in RAVi between groups, however peak RA strain was lower in post-capillary patients .Amongst post-capillary patients, there was commensurately severe biatrial impairment of peak strain .All patients had preserved LVEF however longitudinal function assessed by LV GLS was similarly impaired in both groups. RVEF was more impaired in pre-capillary patients with concomitant/proportional RVFWLS reduction.Ten parameters  were assessed for their ability to distinguish post- from pre-capillary PH.Of all (TTE and CMR) parameters, CMR LAVi had the greatest AUC (0.96) followed by peak LA strain (AUC 0.92) ; Table 5Echocardiographic parameters also had excellent, albeit smaller AUC. ePLAR  had the smallest AUC of all (0.84) while variant ePLAR  and TTE LAVi performed similarly well (AUC 0.89).2 had 85% sensitivity and 95% specificity for distinguishing post- from pre-capillary PH. Compared to CMR LAVi, a peak LA strain cut-point of <12% had excellent sensitivity at 81% and greater specificity at 100% (p < 0.001) for post-capillary PH diagnosis.Consistent with prior data , a CMR L at 100% . StepwisNon-indexed LAV was underestimated by TTE compared to CMR  .p < 0.001). A similar relationship was seen for mRAP and peak RA strain . There was however no association between mRAP and RAVi   and peak LA strain  were significantly correlated with mPAWP (both = 0.993) .p = 0.002) (p = 0.019). Lastly, there was no correlation between mRAP and mPAP in post-capillary patients    which wa= 0.365) .In this work, we have shown that CMR LA volumetric and deformation assessment can accurately distinguish post- from pre-capillary PH and was superior to TTE. LA volumetric assessment was more sensitive but deformation assessment more specific and diagnostic accuracy was enhanced with use of both parameters (multivariate AUC 0.98).TTE's predictive performance for post-capillary PH was optimized when variant ePLAR  was utilized, with an augmented AUC of 0.89 compared to ePLAR .The discriminatory ability of LAV was maximized as a CMR parameter, circumventing TTE limitations of suboptimal acoustic windows with certain body habitus. Additionally, the LA long axis plane is typically divergent from that of the LV, causing TTE volumetric underestimation without atrial-focussed imaging , 22.This is also the first study to contrast biatrial and biventricular CMR FT deformation parameters in the same PH cohort. There are several notable findings.In a canine PH model by PA banding, early compensation was characterized by preserved systolic but impaired RV diastolic function, and increased RA distensibility (increased reservoir strain) . The latBoth pre- and post-capillary PH patients had similarly severe RA dilatation however post-capillary patients had lower RA peak strain and higher mRAP despite the similar volumes.Tello et al.  have shoRight ventricular diastolic dysfunction in left heart disease is poorly characterized. Independent of RVSP elevation, Yu et al.  have demRecent data from Patel et al.  indicateSu et al.  has showSummarily, it would appear that biventricular fibrosis is seen in post-capillary PH whereas RV fibrosis predominates in pre-capillary PH.Our work adds further to these data. Our post-capillary cohort comprised mainly of HFpEF patients with commensurately severe biatrial peak strain reduction. As depicted in These observations would suggest that clinically significant RV diastolic dysfunction occurs in both pre- and post-capillary PH however in pre-capillary patients, when symptomatic, represents late stage disease (RV-RA uncoupling) following RV-PA uncoupling in the context of progressive afterload elevation . ConversIn proposing additional mechanistic hypotheses for the dissimilarity in atrial strain between both groups, it is also important to note that the majority of post-capillary patients had a history of AF. Longstanding AF leads to atrial structural change/diffuse fibrosis causing impairment of atrial phasic function and peak reservoir strain, with the magnitude of strain impairment corresponding to the degree of atrial fibrosis , 34.Beyond AF itself (“AF begets AF”), post-capillary PH patients also had multiple contributors of atrial arrhythmogenic remodeling  includinBoth groups had similarly preserved LVEF but reduced GLS. The pathophysiology underlying this subclinical dysfunction is likely disparate between groups. In pre-capillary PH patients with higher mPAP, PVR, RV volumes and greater RV dysfunction, abnormal septal configuration and reduced LV preload are likely principal mechanisms for LV GLS impairment , 37. In Lastly, our data contributes to the literature regarding determination of congruence between CMR and TTE deformation assessment. Inoue and colleagues  showed sSubsequent to this, prospective validation of the diagnostic performance of combined CMR LA volumetric and strain assessment may enhance the current PH workup algorithm. Study into the prognostic value of CMR FT strain in PH would also be invaluable in view of the present paucity of imaging prognostic markers, specifically with examination of change in deformation parameters following targeted therapy.Comprehensive CMR FT deformation assessment offers additional physiologic insights in PH beyond sole volumetric evaluation and may enhance the current PH workup algorithm.n = 48) was due to exclusion of a large proportion of patients who had part of their PH workup completed externally prior to referral. Age and gender matching of pre- and post-capillary groups was not possible due to the typical disparate demography of PAH and diastolic dysfunction/HFpEF patients. There was a significant interval between all investigations, with potential for change in loading conditions with medical therapy however this does not appear to have affected the predictive ability of assessed TTE and CMR parameters. The strength of imaging-hemodynamic correlation was also maintained and is consistent with published data. Additionally, the time interval reflects current actual service provision at our institution. Amongst post-capillary PH patients, there was a larger proportion with an AF history but this would be congruent with the post-capillary phenotype. With CMR FT LA strain, we acknowledge the limitation of single cardiac cycle atrial strain assessment in AF compared to averaging in TTE but again, this does not appear to have affected the predictive ability of CMR LA strain. Lastly, atrial strain was not assessed using a dedicated algorithm but rather by a ventricular algorithm from a specific vendor.This was a retrospective study from a single institution. The relatively small cohort size (The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Health Research Authority and NHS Research Ethics Service. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.KL, LH, DG, and SG contributed to conception and design of the study. KL organized the database and wrote the first draft of the manuscript. KL and DG performed the image analysis. HP and KL performed the statistical analysis. LH, FL, GH, and RD wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Mitral valve (MV) prolapse (MVP) is a primary valvular abnormality. We hypothesized that additionally there are concomitant abnormalities of the left ventricle (LV) and MV apparatus in this entity even in the absence of significant mitral regurgitation (MR).To characterize MV and LV anatomic and functional features in MVP with preserved LV ejection fraction, with and without significant MR, using cardiovascular magnetic resonance (CMR).Consecutive MVP patients  with preserved LV ejection fraction, and 44 controls  by CMR were included, as well as 13 additional patients with “borderline” MVP. From cine images we quantified LV volumes, MV and LV anatomic measurements  and, using feature tracking, longitudinal and circumferential peak systolic strains.Significant MR was found in 46 (56%) MVP patients. Compared with controls, MVP patients had LV enlargement, basal inferolateral hypertrophy, higher posterior annular excursion, and reduced shortening of the papillary muscles. LV basal strains were significantly increased, particularly in several basal segments. These differences remained significant in patients without significant MR, and many persisted in “borderline” MVP.In patients with MVP and preserved LV ejection fraction there is LV dilatation, basal inferolateral hypertrophy, exaggerated posterior annular displacement and increased basal deformation, even in the absence of significant MR or overt MVP. These findings suggest that MVP is a disease not only of the MV but also of the adjacent myocardium.The online version contains supplementary material available at 10.1186/s12968-021-00800-w. Mitral valve (MV) prolapse (MVP) is the most common cause of primary mitral regurgitation (MR) in developed countries . MVP is Patients with CMR-based diagnosis of MVP and preserved LVEF from 2 collaborating institutions were included: the CMR program at the Mount Sinai Hospital, New York City, New York, USA, and the Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Inclusion criteria were age ≥ 18 years, presence of MVP  during systole in the LV outflow tract long-axis view) ], prior In order to evaluate the possible evolution of MVP, we additionally analyzed a separate group of patients n = 13) with “borderline” MVP, whom we initially excluded. “Borderline” MVP was defined as morphology suggestive of prolapse but with leaflet displacement < 2 mm into the LA (a phenotype that has been linked to future MVP) , illustr3 with “bBaseline demographics, cardiovascular risk factors and electrocardiographic (ECG) findings were collected from patients’ electronic health records. The respective institutional review boards approved the study. Patients enrolled at CNIC provided written informed consent, while this requirement was waived at Mount Sinai.CMR studies were performed on 1.5 T  or 3 T  CMR units using dedicated phased-array surface coils as receivers. Sequences were acquired during end-expiratory breath holds with retrospective ECG or pulse gating. Balanced steady-state free-precession (bSSFP) cine images were acquired in three standard long-axis views  in all patients. In addition, a stack of contiguous short-axis views covering the entire ventricles was available in all patients. Cine images were obtained with in-plane spatial resolution of ≤ 2 mm and temporal resolution ≤ 45 ms following current recommendations . To dete42 , by the same observer.Short-axis cine and phase contrast images were analyzed using specialized software . All measurements of MV geometry in the LV outflow tract view and LV strain quantification were obtained with cviLV mass, biventricular volumes and ejection fractions were quantified from bSSFP-cine images by manually tracing the endocardial and epicardial contours of the short axisat end-diastole and end-systole. Papillary muscles and trabeculations were considered part of the LV cavity . In an LMVP distance: maximum displacement of the mitral leaflets beyond the annular plane during systole .Mitral annular diameters: measured from the aortomitral junction to the posterior mitral leaflet insertion point both in diastole and systole, with their difference defined as annular lengthening.Maximum leaflet thickness, measured in diastole.Length of the posteromedial papillary muscle (PM): measured in end-diastole and end-systole, with their difference defined as PM shortening.Distance of the tip of the posteromedial PM to the tip of the posterior mitral leaflet as a surrogate of “chordal length”, measured in end-diastole and end-systole.Distances from the posteromedial PM insertion point to the anterior and posterior mitral annulus. These were also measured in end-diastole and end-systole, as well as their difference.Distances from the anterior and posterior mitral annulus to external reference point  were measured in end-diastole and end-systole, as well as their difference.Mitral annular disjunction (MAD): distance from the LA wall-mitral posterior leaflet junction to the LA wall-LV inferolateral wall junction , measureMitral annulus angle: measured as the angle between the mitral annular planes at end-diastole and end-systole.Regarding MV anatomy and geometry, the following measurements were performed in the LV outflow tract long-axis view Fig. :MVP dist42 feature-tracking module. Epicardial and endocardial borders, excluding the papillary muscles, were manually drawn in the end-diastolic phase in the short axis, 4-chamber, 2-chamber and LV outflow tract long-axis views, and then automatically propagated through the cardiac cycle  or Fisher exact tests, and non-parametric tests such as Wilcoxon rank-sum for continuous variables as appropriate. To ensure that potential LV abnormalities were not secondary to volume overload in the presence of MR, a sub-analysis was performed comparing controls with MVP patients without significant MR. Similar comparisons were performed between controls and patients with “borderline” MVP.Categorical data are expressed as number (percentage) whereas continuous variables are presented as median [interquartile range], since most were not normally distributed according to the Shapiro–Wilk test. For comparisons between MVP patients and controls, differences for categorical variables were evaluated by the chi-square . The following levels of agreement were used: excellent for ICC > 0.74, good for ICC 0.6‒0.74, fair for ICC 0.4‒0.59, poor for ICC < 0.4 .p value < 0.05 was considered statistically significant. The Holm-Bonferroni correction [In all cases, a rrection  was usedThe clinical characteristics of the MVP (including MVP without significant MR), control and “borderline” MVP groups are summarized in Table In the MVP cohort 46 patients had significant (at least moderate) MR by CMR. By design, no patients in the control group had significant MR. CMR measurements of cardiac chambers are summarized in Table Myocardial LGE was available in 44 controls, 70 MVP patients, and 11 patients with “borderline MVP”. There were two control subjects with focal LGE in the inferior RV insertion point, considered nonspecific. Regarding MVP patients, 23 (33%) had myocardial LGE, being intramyocardial the most common pattern and the inferolateral segment the most commonly affected  was increased in the overall MVP group but not in those without significant MR, with no systolic differences in either group.Global strain values, as well as those segmental strains showing significant differences between controls and MVP patients (including those without significant MR) are shown in Table There were no other consistent significant differences regarding segmental peak systolic strains see Fig.  and 5.p > 0.05, for all segments). Regarding MV leaflets thickness; there was an increase of -13% and -15% in peak systolic longitudinal strain in basal segments per every increase of 1 mm in mitral valve anterior and posterior leaflet thickness, respectively (p < 0.05).In simple linear regression analysis, there was not significant correlation between global or segmental longitudinal peak systolic strain and MVP severity  appear to be a central component of MVP and may have a role in its pathogenesis.Additional file 1. Borderline mitral valve prolapse. Movies showing examples of patients with mitral leaflet morphology suggestive of prolapse but posterior displacement into the let atrium < 2 mm.Additional file 2. Borderline mitral valve prolapse. Movies showing examples of patients with mitral leaflet morphology suggestive of prolapse but posterior displacement into the let atrium < 2 mm.Additional file 3. Late gadolinium enhancement in patients with mitral valve prolapse. Examples of 4 patients with MVP and typical examples of intramyocardial LGE (asterisks) in the basal inferolateral (A and B), basal inferior (C) and basal anterolateral (D) segments. An example of papillary muscle LGE is also shown in C (arrow).Additional file 4. Left ventricle peak systolic longitudinal strain. Table including individual LV segments peak systolic longitudinal strain measurements.Additional file 5. Left ventricle peak systolic circumferential strain. Table including individual LV segments peak systolic circumferential strain measurements.Additional file 6. Geometric and myocardial strain comparison between mitral valve prolapse patients with phase contrast in the ascending aorta and controls. Table showing the comparison between controls, MVP patients, and MVP without significant MR corroborated by phase contrast.Additional file 7. Excessive apical annular displacement in MVP. Movie showing excessive apical annular displacement  in a patient with MVP.


É intrigante que na hipertensão pulmonar “idiopática”, também parece haver uma alta prevalência das mesmas características de obesidade, resistência à insulina e anormalidades nos hormônios sexuais.Nesse contexto, Abacioglu et al.2) e ausência de outros fatores de risco cardiovascular, mas a resistência à insulina era pior no grupo com SOP de acordo com sua fisiopatologia subjacente. Em geral, não houve diferenças na disfunção sistólica ou diastólica no lado esquerdo pela ecocardiografia. Entretanto, a rigidez da artéria pulmonar, a função do lado direito do coração e o acoplamento VD-AP foram piores no grupo SOP. A rigidez da artéria pulmonar se correlacionou com a resistência à insulina e apresentou tendência a ser mais elevada em pacientes que não estavam em tratamento para a SOP.A coorte do estudo com SOP e os controles foram bem pareados em idade basal e índice de massa corporal (IMC) geral. O grupo com SOP era, em média, jovem (média de idade de 22 anos), com IMC médio normal  is a complex endocrinological syndrome that presents in women with obesity, insulin resistance and sex hormone abnormalities. It is intriguing that in otherwise ‘idiopathic’ pulmonary hypertension, there also seems to be a high prevalence of the same features of obesity, insulin resistance, and sex hormone abnormalities.On this background, Abacioglu et al.2) and showed absence of other cardiovascular risk factors, but insulin resistance was worse in the PCOS group, consistent with their underlying pathophysiology. Overall, there were no differences in left-sided systolic or diastolic dysfunction by echocardiography. However, pulmonary artery stiffness, right-sided function and RV-PA coupling was worse in the PCOS group. Pulmonary artery stiffness correlated with insulin resistance and tended to be higher in patients who were not undergoing treatment for PCOS.The study cohort of PCOS and controls were well-matched regarding baseline age and overall body mass index (BMI). The PCOS group was on average young (mean age 22) with a normal mean BMI (24.9 kg/mAlthough the study sample is small, the groups were well-matched in overall demographics apart from insulin resistance, allowing assessment of subclinical impairments secondary to PCOS. However, the differences between the groups were small and the evaluation of the long-term progression of these changes in RV-PA coupling to determine clinical significance is needed. Sex hormone alterations have also been identified in patients with either PAH or PCOS, and how these influence the abnormal RV-PA coupling in this sample is unknown.These issues aside, this study provides important information on the potential role of PCOS in pulmonary hypertension in women. It is remarkable that despite modern advances, a large proportion of PAH cases remain idiopathic with a disproportionate effect on women. Given the shifting demographics of PAH to a more obese phenotype in modern times,Whether differences in visceral adiposity in PCOS may underlie some of the observed right heart changes requires future studies. Weight loss in overweight patients, even in those without heart failure, may improve pulmonary artery pressures and central hemodynamics,–,,An important caveat to echocardiographic studies such as this, is the systemic underestimation of the burden of left heart disease and early heart failure with preserved ejection fraction that is increasingly recognized in young overweight individuals.


Usually such circulation is associated with low systemic vascular resistance or arteriovenous malformation (AVM), resulting in depressurized circulation and a high-output cardiac state. Treating physicians should be cognizant of such pathology when investigating patients with heart failure. As an example, renal arteriovenous malformations are a rare vascular phenomena that are typically the result of iatrogenic, traumatic or congenital etiology. Generally, non-salient, most are detected as an incidental finding.Heart failure is usually associated with a low-cardiac-output state; however, a minority of these patients are characterized by a high-output cardiac state, described as a cardiac index of > 4 L/minute/mA 75-year-old Afro-Caribbean man with multiple comorbidities presented to the emergency department with a 6-month history of heart failure symptoms. Cardiac catheterization demonstrated a giant right renal AVM leading to a significant left-to-right, post-tricuspid shunt that was treated with transcatheter coiling.We present this case to emphasize the significance of a detailed workup in a patient with heart failure symptoms. Usually2 . General2 . The exc2 , 6–10. TA 75-year-old Afro-Caribbean man presented to the emergency department with a 6-month history of peripheral edema, dyspnea on exertion, and orthopnea. Clinical history included hypertension, gastroesophageal reflux disease, and asthma. A clinical examination revealed hypertension, oxygen saturation of 98% on room air, and hypervolemia with jugular venous distension and peripheral edema. Hematologic and biochemical investigations demonstrated normocytic normochromic anemia (hemoglobin 128 g/L) and renal insufficiency (serum creatinine 126 µmol/L).2, and increased left ventricular end-diastolic pressure with a mean capillary wedge pressure of 13 mmHg, without significant V wave. Pulmonary vascular resistance was 4 Wood units (WU) and systemic vascular resistance was 18.17 WU.A transthoracic echocardiogram revealed mixed systolic and diastolic left ventricular (LV) disease and an ejection fraction of 40%. The LV internal diameter in diastole was 6.0 cm. The right ventricle (RV) was moderately dilated with moderate to severe global systolic dysfunction. There was septal flattening in diastole, suggestive of volume overload with markedly elevated right atrial (RA) pressure  revealed a large complex AVM within the right renal sinus. Other investigations for alternative etiologies of pulmonary hypertension were explored and were non-contributory, including a ventilation–perfusion (V/Q) scan with low-dose CT showing no evidence of pulmonary embolism. CT angiogram displayed a large, ~ 2-cm-diameter renal AVM Fig. b, which The patient underwent transcatheter intervention. As we wished to occlude the renal AVM beyond a branch supplying blood to the lower half of the kidney , and we wished to avoid occluding the renal artery supplying blood to the functioning kidney, such anatomy was unsuitable for a vascular plug deployment, and hence 21 coils were deployed into the distal renal AVM . Pulmonary vascular resistance was 2.54 WU and systemic vascular resistance was 23.61 WU. The patient reported significant improvement from New York Heart Association (NYHA) class 4 to class 2 and expressed gratitude for the clinical care received.Repeat right heart catheterization showed a reduction in RA mean pressure (10 mmHg) and PA pressure , with lower cardiac output (5 L/minute) and cardiac index . This is based on the communication between the arteries and veins. In congenital AVMs, there are multiple communications, creating a vascular nidus that bypasses the capillary bed. AVFs are characterized by a single direct communication between the artery and a vein, usually resulting from iatrogenic or traumatic events, or idiopathic . The majIt is prudent to investigate each of these patients very meticulously. Initial noninvasive imaging with duplex color ultrasonography reveals turbulent flow in the IVC or renal vein. Multidetector CT and contrast-enhanced magnetic resonance angiography (MRA) demonstrate dilated enhancing vessels with attenuation or signal similar to arteries. Digital subtraction angiography has the advantage of evaluating the feeding vessels and assists in planning the management of the AVMs .Indications for invasive management strategies include hypertension, hematuria, AVM rupture, congestive heart failure, neoplasm, and renal failure . ManagemTranscatheter embolization is the intervention of choice. If unsuccessful, or if surgical intervention is indicated, tissue-sparing is preferred to total nephrectomy . In the Systemic AVM is a rare but potentially reversible cause of a high-output cardiac state. Clinical consideration and appropriate invasive and noninvasive workup led to salutary benefits.


It remains unclear as to whether polycystic ovary syndrome (PCOS) is an additional risk factor in the development of left ventricular (LV) hypertrophy in obese women. In the current study, we provide clarity on this issue by rigorously analysing patient LV geometry beyond the basic clinical measures currently used. Importantly, the cohort contained only normotensive patients that would normally be deemed low risk with no further intervention required.2, type 2 diabetes, hypertension.The study comprised 24 obese women with PCOS and 29 obese Control women. Transthoracic echocardiography was used to evaluate LV structure/function. Basic clinical and metabolic data were collected for each participant consisting of age, BMI, blood pressure, fasting glucose, LDL-C, HLD-C, cholesterol and triglyceride levels. Exclusion criteria; BMI < 30 g/m2.7 was increased patients with PCOS (45 ± 2.2 vs 37 ± 1.6) with 33% exhibiting LV mass/height2.7 above ASE guidelines, compared to 7% in Controls. Furthermore, 25% of patients with PCOS were characterised with concentric hypertrophy, an alteration in LV geometry that was not observed in the Control group.Both groups exhibited concentric remodelling of the LV posterior wall at a prevalence of ~20%, this associated with grade 1 diastolic dysfunction. Estimated LV mass/heightTo our knowledge, this is the first study to assess LV geometric patterns in obese women with PCOS. The results suggest that obese women with PCOS are at greater risk of concentric hypertrophy than obese only women and provide justification for additional cardiovascular risk assessment in normotensive obese/PCOS women. Polycystic ovarian syndrome (PCOS) is a complex endocrine/metabolic syndrome characterised by the presence of “ovarian cysts”, increased androgens and an irregular or absent menstrual cycle . With coPrevious studies have reported left ventricular (LV) geometric patterns to be predictive of future cardiovascular risk in obese and/or hypertensive patients –6. IndeeIn the current study, we provide clarity on this issue by rigorously analysing patient left ventricular structure beyond the basic clinical measures currently used in normotensive obese patients with and without PCOS. This is the first study to our knowledge that has assessed LV geometric patterns in PCOS and provides novel insight into the additive effects of PCOS in LV remodelling in obesity.This multisite study was performed in a cross sectional and retrospective format, A and comprised a total of 23 Control normotensive obese women without PCOS and 21 normotensive obese women with PCOS from the University Hospital Geelong and the Geelong Endocrinology and Diabetes Centre in Australia, as well as a further 6 Control normotensive obese women without PCOS and 3 normotensive obese women with PCOS from the University Heart and Vascular Center Hamburg, Germant. For data collection within the Australian sites the study was conducted in accordance with National Health and Medical Research Council (NHMRC) guidelines and was approved by the Human Research Ethics Committee (HREC) via the Barwon Health Research and Integrity Unit, in accordance to guidelines outlined in Section 5 of the National Statement on Ethical Conduct in Human Research. According to the declaration of Helsinki Hamburg data were obtained retrospectively from patients who underwent echocardiography at the University Heart and Vascular Center Hamburg in the years 2020–2021, all data underwent pseudonymisation prior to data collection and analysis.2, type 2 diabetes, history of hypertension or use of anti-hypertensive medication and history of cardiac disease or systemic disease. PCOS diagnosis was based on the Rotterdam criteria in which two of the following three criteria were present; 1. Oligoovulation or anovulation, 2. Hyperandrogenism, either clinical presentation or biochemical and/or 3. Polycystic ovaries detected via transvaginal ultrasound.Basic clinical and metabolic data were collected for each patient consisting of age, height, weight, blood pressure, fasting glucose, total cholesterol, LDL-C, HLD-C and triglyceride levels . Exclusion criteria included; BMI < 30 g/mIntelli sense HEM-907 or HBF-1300. As all participants were obese, it is important to note that an appropriate sized cuff bladder was used, at least 80% of the patient’s arm circumference. In the incidence of an elevated BP reading (≥ 140/90 mmHg), the measurement was repeated up to three times with the lowest measurement recorded.Blood pressure (BP) was recorded as per the American Heart Association guidelines, with the use of OMRON All echocardiograms were performed using the Phillips Ie33 with a S5-1 transducer. A combination of two-dimensional, M-mode, pulsed wave and continuous wave Doppler and tissue Doppler were used. Left ventricular diameter and wall thicknesses were measured in the parasternal long axis view using two-dimensional or M-mode measurements; left ventricular internal diameter during diastole and systole , interventricular septum diameter during diastole and systole , left ventricular posterior wall diameter during diastole and systole . Mitral inflow velocities  and deceleration times (DT) were measured using pulsed wave Doppler in the apical 4 chamber view. Echocardiographic data was analysed using proprietary software.DD was characterised according to ASE guidelines and as previously described . An E’ ≥3 - (LVIDd)3]) + 0.6). LV mass was then indexed to body surface area  and to height (g/m2.7). RWT was calculated using the formula, RWT = 2 ∙ (LVPWd)/LVIDd. LV geometry was characterised using the following criteria; Normal LV geometry, RWT ≤ 42, LVMI (g/m2.7) ≤ 51; eccentric hypertrophy, RWT ≤ 42, LVMI (g/m2.7) > 51; concentric remodelling, RWT > 42, LVMI (g/m2.7) ≤ 51 and concentric hypertrophy, RWT > 42, LVMI (g/m2.7) > 51.LV mass was estimated according ASE guidelines as previously described , in whicp<0.05 was considered significant. All statistical analysis were performed using SPSS version 23.Continuous variables were represented as means ± 1 SEM, unless otherwise stated. Means of continuous variables were analyzed via a student’s t test. Associations were determined by performing linear regression analysis, assessed with Pearson’s correlation coefficient. Categorical variables were expressed as percentages or prevalence and analysed via chi-square tests, using Fisher’s exact test. To determine independent predictors of categorical variables, multivariable logistic regression analysis was performed. As per selection criteria, women of both groups were of similar age and BMI and all women were normotensive with no differences between systolic and diastolic blood pressure . In addiTo increase confidence that our dataset was representative of the wider population, we first confirmed that the dataset exhibited normal associations between age and indices of diastolic decline and left ventricular hypertrophy (LVH). In which bivariate correlation analysis confirmed age to associate with the diastolic indices Peak A wave (p = 0.001) and E/A ratio (p = 0.002) and with the LVH indices; LV mass/BSA (p = 0.048), IVSd (p = 0.044), LVPWd (p = 0.035) and RWT (p = 0.045) .2.7 (45.07 ± 2.17 vs 37.15 ± 1.54 p<0.05)  or normalised to BSA  or height p<0.05) . Fig 1B.e of RWT . CompariDiastolic function was comparable amongst obese women without and with PCOS, with both groups exhibiting a prevalence of normal diastolic function of ~70%, as well as a comparable prevalence of Grade 1 DD (17.24% vs 16.67%) and Grade 2 and 3 DD (3.45% vs 4.17%) . BivariaThe results from the current study provide novel insights into alterations in LV geometric patterns in obese women with PCOS. The major findings from the current study are the identification of concentric hypertrophy in the PCOS group, that was not accompanied by the presence of DD, suggesting that the PCOS heart has undergone compensatory alterations in LV structure that are not present in obese only women.Clinically, LVH is commonly assessed via transthoracic echocardiography in which 2 dimensional and M-Mode measurements are used to determine the LVPWd, LVIDd and estimated LV mass . More coIt is difficult to pin point the exact mechanism/s involved in the pathogenesis of the development of concentric hypertrophy in these PCOS women. This in part due to the complex and multifaceted nature of PCOS and its associated syndromes, such as hyperlipidaemia, hypertension, insulin resistance and hyperandrogenism, thus making it difficult to dissect the individual contributions that these cardiovascular risk factors may have as well as their interacting influences in promoting LV remodelling. Interestingly, while the main cardiovascular preventative strategy in PCOS focuses on treating these commonly associated cardiovascular risk factors, the patients in the current study exhibited normal fasting glucose and lipid profiles , yet the PCOS group still presented with a type of LV remodelling not observed in the obese only group suggesting that normalising some of the associated metabolic abnormalities in PCOS may be insufficient to mitigate increased cardiovascular risk. Importantly, essential data such as fasting plasma insulin and androgen levels were missing from our study. Indeed the lack of this data reflects common clinical practice in the monitoring and treatment of PCOS in which plasma insulin levels are rarely assessed and androgen levels are assessed at the time of diagnosis and will only be reassessed if androgen blocking therapy is required. It is therefore challenging to understand the associations between insulin resistance and androgen levels with LV remodelling in PCOS patients retrospectively in a clinical setting. However, rat models with PCOS like phenotypes have helped to shed some light into the influence of these factors in LV remodelling, with testosterone treatment shown to induce LV hypertrophy with reports of increased LV mass , LVPWd aThe strengths of the current study included the inclusion of only obese and normotensive patients, thereby allowing us to tease out the additive effects of PCOS in obesity, independent of hypertension. In addition, the use of transthoracic echocardiography and its application to assess LV geometric patterns is another strength of the study as it maximises translational potential of the study, opposed to assessment of cardiac structure and function by less accessible and more intrusive methods such as Magnetic Resonance Imaging and catheterization. The main limitation however of the current study was our relatively low sample numbers, therefore in order to build confidence that the dataset were representative of the wider population we confirmed that the patients exhibited normal associations between age with diastolic decline and LV structure, thereby allowing us to exclude the presence of “outliers” that skewed the results of the study. Furthermore, the study was conducted with data obtained from multiple sites within Australia and Germany allowing us to confirm associations and LV remodelling patterns in different subpopulations thereby further strengthening the confidence in the results obtained.In summary this study has identified the presence of concentric hypertrophy in normotensive obese PCOS patients that was not observed in normotensive obese only patients, suggesting that PCOS is an independent risk factor for LV remodelling in obesity. Therefore, this study provides justification for additional cardiovascular risk assessment in normotensive obese PCOS patients.S1 File(PDF)Click here for additional data file.


To investigate the relationship between ST-segment resolution (STR) and myocardial scar thickness after percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI).Forty-two STEMI patients with single-branch coronary artery stenosis or occlusion were enrolled. ST-segment elevations were measured at emergency admission and at 24 h after PCI. Late gadolinium-enhanced cardiac magnetic resonance imaging (CMR-LGE) was performed 7 days after PCI to evaluate myocardial scars. Statistical analyses were performed to assess the utility of STR to predict the development of transmural (> 75%) or non-transmural (< 75%) myocardial scars, according to previous study.The sensitivity and specificity of STR for predicting transmural scars were 96% and 88%, respectively, at an STR cut-off value of 40.15%. The area under the curve was 0.925. Multivariate logistic proportional hazards regression analysis disclosed that patients with STR < 40.15% had a 170.90-fold higher probability of developing transmural scars compared with patients with STR ≥ 40.15%. Pearson correlation and linear regression analyses showed STR percentage was significantly associated with myocardial scar thickness and size.STR < 40.15% at 24 h after PCI may provide meaningful diagnostic information regarding the extent of myocardial scarification in STEMI patients.The online version contains supplementary material available at 10.1186/s12872-021-02269-y. Transmural myocardial scars of the left ventricle that complicate ST-segment elevation myocardial infarction (STEMI) predispose to heart failure and cardiac death. Therefore, early identification and analysis of myocardial scars are particularly important . The sizDelayed ST-segment resolution (STR) is prevalent during major adverse cardiovascular events, and is predictive of arrhythmia, heart failure, and 30-day mortality . We hypoForty-two consecutive patients with STEMI treated with coronary angiography and percutaneous coronary intervention (PCI) within 12 h of the onset of pain were enrolled between March 2017 and October 2017. Inclusion criteria were (1) single-branch coronary artery stenosis or occlusion, and (2) restoration of coronary perfusion to TIMI flow grade 3 after PCI. Exclusion criteria were a prior history of the acute coronary syndrome; coronary revascularization; severe chronic kidney disease; intracardiac pacing leads or other implants precluding CMR-LGE; hemodynamic instability; or known claustrophobia. The study was performed at the First Affiliated Hospital of Chongqing Medical University, China. Demographic and clinical characteristics including ECG STR 24 h after PCI were recorded. CMR-LGE was performed 7 days after PCI. This study was conducted in accordance with the Declaration of Helsinki. The research protocol was approved by the locally appointed Ethics Committee, and written informed consent was obtained from all study participants.Patients were examined in the supine position using a 1.5-T imaging unit  equipped with master gradients  and a 5-element cardiac phased-array receiver coil. Images were obtained using electrocardiographic gating and expiratory breath holds. A dose of 0.2 mmol/kg of body weight of gadopentetate dimeglumine  was administered intravenously at a rate of 5 ml/s with a power injector. Ten minutes after contrast agent injection, a Look-Locker sequence was performed to obtain the most appropriate inversion time to nullify the signal intensity of normal myocardium. The left ventricular short-axis imaging layer was 8 mm thick and 0 mm apart. The left ventricular 2-chamber and 4-chamber scanning imaging layers were 5 mm thick and 0 mm apart. This was immediately followed by the acquisition of LGE images, with an inversion recovery prepared T1-weighted gradient-echo sequence . Late gadolinium enhancement was interpreted as present or absent by the consensus of two CMR-trained physicians, and was considered present only if confirmed on both short-axis and matching long-axis myocardial locations.P < 0.001) [First, we marked the segments of the myocardial scar with the bull’s eye segmental comparison (17-segment model) and compared them with the results of coronary angiography. Second, we searched for the thickest myocardial scar layer-by-layer on the short axis imaging and calculated the percentage of the thickness of the myocardial scar, which was defined as a transmural myocardial scar when the percentage was > 75%, according to previous study . Beek et< 0.001) . FinallyStandard 18-lead ECGs were obtained at emergency admission and 24 h after coronary angiography and PCI. The TP segment was used as the isoelectric line in the ST-segment measurement. The ST segment was measured 20 ms after the J point. The summed ST-segment elevation was measured by adding the ST amplitude in all leads with ST-elevation at emergency admission and 24 h after PCI –16. STR t-test. All statistical analyses were performed using SPSS v.22.0 . P value < 0.05 was considered statistically significant.Basic descriptive statistics were used. CMR-LGE location data were described on a patient-by-patient basis. Statistical analyses were performed to assess the clinical utility of using of STR to predict myocardial scarification. Myocardial scars were assessed using two measures: (1) scar thickness and (2) scar size. Receiver operating characteristic (ROC) curve analysis, logistic regression analysis, and multivariate logistic proportional-hazards regression estimated transmural myocardial scar. Pearson correlation and linear regression analyses were used to investigate the coefficients of STR percentage with myocardial scar thickness and size. Myocardial scar thickness and size difference between two ST-segment resolution groups were analyzed by P < 0.001).Myocardial scars were diagnosed in 41 of 42 STEMI patients (96.7%) by using CMR-LGE. A patient-by-patient visual analysis of scar tissue location in the STEMI group, with bull’s eye segmental comparison of CMR-LGE findings is shown in Additional file A transmural scar was defined as a myocardial lesion extending > 75% of the wall thickness. All myocardial scars were classified as either non-transmural (0–75%) or transmural 76–100%) according to CMR-LGE results. The relationship of the ST-segment resolution percentage to transmural scarification was identified by the ROC curve. The ROC curve analysis demonstrated a sensitivity of 96% and a specificity of 88% to predict transmural myocardial scarification following STEMI at an STR cut-off value of 40.15%. The area under the curve was 0.925  = 0.925.Patients were divided into two groups: STR < 40.15% (n = 16) and STR ≥ 40.15% (n = 26). Compared with patients with STR ≥ 40.15%, patients with STR < 40.15% had significantly longer pain-to-balloon time; higher aspartate aminotransferase (AST), peak troponin-I, and brain natriuretic peptide (BNP) levels; lower left ventricular ejection fraction (LVEF); and a higher prevalence of diuretic therapy. Other characteristics such as age; gender; body mass index; histories of smoking, hypertension, and diabetes; hyperlipidemia; culprit artery; leukocyte, erythrocyte, and platelet counts; hemoglobin, hemoglobin A1(c), alanine aminotransferase (ALT), and creatinine levels; left ventricular diastolic diameter; the use of therapeutic drugs other than diuretics; and coronary care unit residence time were similar between the two groups , and STR < 40.15%  were significant risk factors for transmural scars (Table P = 0.020). STR < 40.15% showed significance for predicting transmural scar  and size   and 0.214% , respectively  Fig. . Linear 8, 01 FigP < 0.001) and the size of myocardial scar was larger (P = 0.001) in the STR < 40.15% group, the difference was statistically significant . Our study showed that the STR < 40.15% group had a higher incidence of transmural myocardial fibrosis, and no differences in the incidence of arrhythmias and readmission rate were found between the two groups, which may be related to the small sample size , the left ventricular ejection fraction was significantly reduced (P < 0.001), and the troponin and BNP were higher (P < 0.001) in the group with STR < 40.15%. The delay of opening time of effective coronary blood flow in STR < 40.15% group may be an important reason for the aggravation of myocardial transmural injury and the formation of transmural myocardial fibrosis. Shortening the pain to balloon time may avoid or reduce the occurrence of poor STR, thus affecting the clinical prognosis of patients.The physiology of STR is related to the restoration of myocardial perfusion. Following PCI of epicardial coronary arteries, microvascular spasm and embolism may lead to persistent coronary microvascular dysfunction (CMD) and subsequently cause myocardial and especially endocardial ischemia. In the setting of CMD, extracellular potassium ion clearance is decreased, thus prolonging repolarization and delaying STR. Poor STR reflects microvascular and left ventricular dysfunction , 37, 38,There are several limitations of this study. First, this was a cross-sectional study with a relatively small number of patients. Second, it was difficult to recruit STEMI patients who were willing or able to undergo CMR-LGE 7 days after PCI. Third, because this study was limited to STEMI patients, cross-validation analysis is needed to determine whether delayed STR can be used to predict myocardial scarification in non-STEMI patients. Fourth, to verify the clinical effects of STR, longer clinical follow-up is needed, especially for the monitoring and follow-up of malignant arrhythmias.We found that STR correlated with myocardial scar thickness following STEMI. To the best of our knowledge, this is the first study to confirm that STR < 40.15% after PCI can provide important prognostic information regarding myocardial fibrosis in STEMI patients. These results suggest that STR may represent a safe, readily accessible, easily administered, inexpensive diagnostic modality in the management of STEMI patients for whom CMR-LGE is contraindicated.Additional file 1. Eye representation of segments in which visual analysis of CMR-LGE detected scar tissue.


Cardiac amyloidosis is a rare underdiagnosed condition with increasing morbidity and mortality. Its diagnosis is challenging and requires high clinical suspicion. Several diagnostic tools aid in the diagnosis of cardiac amyloidosis such as electrocardiogram, echocardiography, and, most importantly, cardiac MRI. A wide range of clinical symptoms is associated with cardiac amyloidosis, with shortness of breath and peripheral edema being the most common presenting complaints. Here, we report a case of transthyretin cardiac amyloidosis and discuss the importance of imaging in establishing the diagnosis. Cardiac amyloidosis (CA) is a rare underdiagnosed condition with increasing morbidity and mortality. Transthyretin (ATTR) amyloidosis is currently considered the most frequent form of CA and its incidence is increasing thanks to the advances in diagnostic imaging techniques . ATTR-caA 65-year-old white male with a previous history of hypertension was referred to the Heartland Clinic for evaluation of newly diagnosed pulmonary hypertension. He reported shortness of breath with exertion for one month in addition to leg swelling. His symptoms were so severe that he could no longer work. The patient denied palpitations, dizziness, or syncope. Family history was negative for cardiac disease including cardiomyopathy. A 2D echocardiogram showed markedly increased left ventricular wall thickness without left ventricular outflow tract obstruction, mild mitral regurgitation, mild left atrial dilatation, and mildly reduced left ventricular systolic dysfunction with an estimated ejection fraction of 45-50%.On initial physical examination, blood pressure was 110/70 mmHg with heart rate (HR) of 77 beats per minute (bpm). There was jugular venous distention of 8 cm. Cardiac auscultation showed 2/6 left upper sternal murmur, normal S1S2, and regular rhythm. Lung auscultation was symmetrical, clear bilaterally. There was 2+ bilateral lower extremity edema with intact pulses. Electrocardiogram (ECG) showed normal sinus rhythm with left ventricular hypertrophy.Due to ongoing symptoms and high clinical suspicion of cardiac amyloidosis, contrast-enhanced cardiac MRI Figure  was perfNuclear imaging of 99mTechnetium pyrophosphate (99mTc-PYP) planar scintigraphy was ordered. It showed intense radiotracer uptake by the heart that was greater than normal bone uptake  and a quantitative heart to the contralateral ratio of 1.9 (>1.5 considered positive); both strongly suggestive of ATTR amyloidosis Figure . Serum aA right heart catheterization revealed severe pulmonary hypertension with mean pulmonary artery pressure of 40 mmHg, pulmonary capillary wedge pressure (PCWP) of 26 mmHg, and pulmonary vascular resistance (PVR) of 1.85 suggestive of elevated left-sided filling pressures and cardiac etiology of pulmonary hypertension (post-capillary). Subsequently, a right ventricle biopsy was performed, and six specimens were taken from the endomyocardium. Microscopic examination showed perimyocytic and nodular deposits of eosinophilic amorphous material in several of the fragments. This material stained positive for amyloid on thioflavin S stain examined under fluorescence microscopy. Immunohistochemical staining was performed for amyloid typing. ATTR immunostaining was positive in the amyloid deposits. Lambda and kappa light chains were negative. The histologic and immunostaining patterns were consistent with the ATTR type of amyloidosis.The patient was started on tafamidis 61 mg capsule daily. He has regular clinic follow-ups since diagnosis and has noted improved symptoms of shortness of breath and edema.Amyloidosis is a rare multisystemic disease caused by the deposition of misfolded proteins in various organs such as the kidney, liver, heart, and nervous system. Many types of amyloidosis exist, differentiated by the nature of the deposited proteins, however, the light chain amyloidosis (AL) and ATTR amyloidosis proteins represent the majority of CA .Most commonly, electrocardiography in CA shows left ventricular hypertrophy (LVH). Unexplained left LVH, characterized by low QRS voltage on electrocardiogram despite LVH on echocardiogram, provides valuable clues for the suspicion of CA. However, these electrocardiographic features are actually not sensitive enough to identify CA -8. Less Echocardiography is the modality of the first approach in the diagnosis of CA due to easy accessibility. The amyloid phenotype is typically characterized by biventricular wall thickening with small, non-dilated ventricles and left ventricular (LV) wall thickness, typically greater than 12 mm . HoweverCardiovascular magnetic resonance (CMR) has established a significant role in diagnosing CA when suspected. CMR is especially useful in patients with increased left ventricular wall thickness and/or hypertrophy because it can differentiate different cellular and interstitial pathologies, which is not possible on echocardiography . In CA, Nuclear imaging is a sensitive tool for the identification of the TTR subtype of CA, and it is encouraging in distinguishing between it and the AL subtype which can also involve the heart. There are many radiotracers, and the most common single-photon emission CT tracer is a 99m Technetium-phosphate derivative. The exact mechanism behind the effectiveness of this imaging modality remains somewhat elusive, though there are a few plausible theories. Of these, it suggests that phosphate in the radiotracers binds to high calcium levels in amyloidosis. Another hypothesis is based on the duration of amyloid deposition that occurs in less time frame in patients with AL relative to a more indolent course of patients with ATTR. As 99mTc-PYP preferentially binds to ATTR relative to AL fibrils, this technique can also be used to distinguish the aforementioned amyloidosis subtypes .This case demonstrates the advanced utility of current imaging modalities to better diagnose CA so that treatment options can be introduced at an earlier stage. In the future, these advanced imaging modalities may assist with avoiding invasive procedures such as endomyocardial biopsy which is considered the gold standard. In the end, the early detection of cardiac amyloidosis is critical since treatment options are currently available with the goal of improving the quality of life and survival in affected patients. Current research has shown promise that the aforementioned imaging modalities may also help assess response to therapy.


The heart is viscoelastic, meaning its compliance is inversely proportional to the speed at which it stretches. During diastolic filling, the left ventricle rapidly expands at rates where viscoelastic forces impact ventricular compliance. In heart disease, myocardial viscoelasticity is often increased and can directly impede diastolic filling to reduce cardiac output. Thus, treatments that reduce myocardial viscoelasticity may provide benefit in heart failure, particularly for patients with diastolic heart failure. Yet, many experimental techniques either cannot or do not characterize myocardial viscoelasticity, and our understanding of the molecular regulators of viscoelasticity and its impact on cardiac performance is lacking. Much of this may stem from a reliance on techniques that either do not interrogate viscoelasticity  or techniques that compromise elements that contribute to viscoelasticity . Clinically, cardiac viscoelastic characterization is challenging, requiring the addition of strain-rate modulation during invasive hemodynamics. Despite these challenges, data continues to emerge demonstrating a meaningful contribution of viscoelasticity to cardiac physiology and pathology, and thus innovative approaches to characterize viscoelasticity stand to illuminate fundamental properties of myocardial mechanics and facilitate the development of novel therapeutic strategies. Reduced cardiac compliance is associated with aging and broadly observed across multiple etiologies of heart failure . StiffenThe viscoelasticity of the myocardium is an important determinant of cardiac performance in health and disease . ViscousControlling myocardial viscoelasticity may be particularly consequential for maintaining myocardial reserve, the ability of the heart to increase its power output in response to increased demand. Viscous forces proportionally increase ventricular stiffness by the rate of ventricular filling. During exercise, reserve capacity is utilized by increasing the heart rate while maintaining the stroke volume . As hearMyocardial compliance is regulated at the myofilament, cytoskeletal and extracellular level. At the molecular level tissue viscoelasticity arises from cross-links which break and reform when the material is stretched or compressed. There are numerous such instances of slip bonds in myocardium, such as actomyosin cross-bridges, cell-cell and cell-matrix interactions, and cytoskeletal cross-linking and anchoring complexes. Thus, viscoelasticity is a multi-scale problem with tissue level, myocyte level, and myofilament level contributors.The myofilaments, which are responsible for the contractile capacity of cardiac tissue, have highly regulated mechanical behavior governed in large part by post-translational modifications and changes in sarcomere stoichiometry . The giaThe non-sarcomeric cytoskeleton consisting of microtubules and desmin intermediate filaments is critical for sarcomere organization  and reguDeposition of extracellular matrix, i.e., fibrosis, is a common feature of dilated and ischemic heart failure in particular . When thLike most biological material, myocardium is a non-linear viscoelastic material , meaningIn addition to non-linear mechanical properties, the heart expands during diastole, meaning that the myocytes are stretched along both their length and width which leads to compression along their axis normal to both the contractile axis and ventricular wall. Tensile tests only stretch the material in 1D, while compressive tests do not typically stretch sarcomeres, as compression is commonly applied orthogonal to the contractile axis. 2D stretching assays are more physiologically relevant but are highly specialized and difficult to employ. The easiest physiological approximation of diastolic compliance likely comes from stretching myocytes or myocardium in 1D with 10–20% strain in about 100–200 ms along the contractile axis. At these rates myocardial stiffness is increased by about 30–50% by viscoelastic forces .The complexity of a non-linear, anisotropic, viscoelastic material makes it difficult to extrapolate physiological implications from a single measurement technique. Yet the use of orthogonal approaches, when combined with varying strain and loading rates and modeling, enables the contributions of sarcomeres, microtubules, and extracellular matrix to be isolated.One dimensional mechanical tests are the most common form of measuring myocardial mechanics enabling assessment of both systolic and diastolic properties. Isometric force generation is a typical method to determine the contractile capacity of the heart, conducted by holding the muscle at constant length and introducing calcium to demembranated myocardium  or by elScanning probe-based force spectroscopy employs micro and nanoscale cantilevers , fluid jin vivo requires the simultaneous collection of chamber pressure and volume, as achieved using conductance catheter hemodynamic assesment  for 7 min. Following fixation, cells were exchanged into blocking buffer and incubated with primary antibodies for alpha tubulin  and desmin  for 48 h. Cells were then rinsed and exchanged into secondaries  for 48 h of incubation. Cells were then pelleted and resuspended in Prolong Diamond antifade (Invitrogen) and mounted between and glass slide and coverslip for imaging.Confocal imaging was conducted on a Zeiss 980 laser scanning confocal microscope equipped with Airyscan through a 63 × oil 1.4 NA objective lens. Image analysis was performed using Zen Black for Airyscan processing and Image J was used for image preparation.p-values were calculated using paired sample t-tests in Origin Lab 2019.Unadjusted The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The animal study was reviewed and approved by Institutional Animal Care and Use Committee.MC and BP designed the experiments, analyzed the data, and wrote and edited the manuscript. MC conducted the experiments. Both authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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