Ventricular dysfunction may be found in 40% of newborns with CDH, and is not only a predictor of disease severity, but also mortality and need for ECMO. We conducted this study to assess the utility of serial echocardiography in management of newborns with CDH and their survival outcomes. This is a retrospective study, wherein the demographic, clinical and echocardiographic data from our local CDH registry and hospital clinical database were analyzed to study the correlation of timed echocardiographic findings with mortality and other outcomes. Fourty-two newborns with CDH were admitted during the study period (M/F:19/23), with median gestation of 38 weeks (IQR:36–39) and birth weight of 2.83 kg (IQR 2.45–3.17). Thirty-one were left-sided, seven right, one central, and three bilateral hernias. Twelve infants (28%) died in early infancy. Three infants were excluded from analysis due to either palliation at birth or significant cardiac anomaly. A total of 137 echos from 39 infants were analyzed. Seventy percent of newborns who died and had an echo within the first 72 h, were noted to have suffered from moderate to severe PH. Birth weight < 2.8 kg, RVSP > 45.5 in the first 72 h and postoperative VIS > 23.5 and RSS > 4.3 were good predictors of mortality. Markers of elevated pulmonary pressures and cardiac function were useful in guiding therapy. Serial timed functional echocardiography (f-Echo) monitoring allows targeted therapy of patients with CDH. Birth weight, initial severity of pulmonary hypertension and postoperative RSS and VIS may be useful in predicting mortality.The online version contains supplementary material available at 10.1007/s00246-022-03002-y. Congenital diaphragmatic hernia (CDH) is a life-threatening defect in the developing diaphragm's integrity , with a Patients with CDH have varying degrees of pulmonary hypoplasia and abnormal pulmonary vascular disease, often leading to various degrees of pulmonary hypertension. In CDH patients, persistent pulmonary hypertension of the newborn (PPHN) is associated with adverse outcomes, and therefore its management remains crucial in the care of these infants . Up to 3Advances in our understanding of cardiovascular physiology in CDH patients has allowed for the optimization of hemodynamics and management of pulmonary hypertension (PH) . Timed fNon-response to pulmonary arterial vasodilators in CDH patients may be related to abnormal ventricular function, and it is important to improve cardiac function in addition to reducing pulmonary arterial pressures in this situation .Sidra Medicine is a greenfield children’s hospital in Doha, Qatar. The neonatal intensive care unit (NICU) is a quaternary referral center for national and international patients with medical, surgical, and cardiac conditions. A national CDH-Qatar (CDH-Q) program was established and standard clinical guidelines for the management of CDH were developed based on recent literature and international guidelines. This study was conducted at Sidra Medicine to test the hypothesis that routine serial echocardiography is an important tool in the standardized management of newborns with CDH, and may improve survival outcomes.This is a retrospective, observational, single center study conducted at Sidra Medicine hospital, from April 2018 to January 2022. A retrospective review of echocardiography images and clinical charts of all eligible CDH patients admitted to the NICU was done using the hospital's electronic medical record system.The NICU at Sidra Medicine hospital has facilities for ECMO, and is well supported by a neonatal hemodynamics team of consultant neonatologists, with expertise in functional echocardiograph. The CDH-Qatar (CDH-Q) program was established with a vision to develop a national quaternary referral center for pre-and post-natal referrals of CDH patients in Qatar and further afield. A local CDH registry was created at Sidra Medicine in 2019 on REDCap® (Research Electronic Data Capture) software  for dataTo assess the impact of standardized management, utilizing serial echocardiography, on mortality amongst newborns with CDH.To identify echocardiography predictors of mortality.Primary Objectives:To study the correlation of echocardiography markers with respiratory severity score (RSS) and inotropic scores in predicting disease severity and mortality.To evaluate trends in f-echo and cardiorespiratory parameters used in decision-making for timing of surgical correction.To study the use of inotropes and milrinone in the treatment of ventricular dysfunction and various pulmonary vasodilators in treatment of acute or chronic pulmonary hypertension related to CDH.Secondary Objectives:Inclusion Criteria All infants admitted to Sidra NICU with a diagnosis of CDH from April 2018 till January 2022.Exclusion Criteria Infants who received palliative care from birth and those with significant associated congenital cardiac anomalies, other than atrial septal defect (ASD), ventricular septal defect (VSD), and persistent ductus arteriosus (PDA), were excluded from f-Echo analysis but were included in the basic demographic data analysis.Study data were collected and managed using secure, web-based software-REDCap® electronic data capture tools hosted at Sidra Medicine, Qatar. Patient demographic data included infants’ sex, gestational age, birth weight, prenatal MRI and ultrasound scan results, postnatal treatment, side and size of the defect, age at repair, cardiovascular therapies, ECMO, duration of ventilation, and non-invasive ventilatory support. For size of CDH defect, Congenital Diaphragmatic Hernia Study Group (CDHSG) Staging System was utilized . In addiAll echocardiograms were performed using the EPIC 7 Philips machine with a S12-4 Hz/ S8-3 multi-frequency sector probe. The first, structural scans, were performed by pediatric cardiology. Functional echocardiography scans were thereafter performed by clinicians from the neonatal hemodynamics team. Researchers collected echocardiography data from the Philips Intellivue® database. Two researchers measured some of the missing f-Echo parameters offline, wherever possible, and cross-verified them to minimize inter-observer variability in reporting.within 72 h of birth24–48 h pre-operative24–48 h post-operativeA total of three echocardiograms was studied for each patient at the set time points:A standard Echo protocol as per published guidelines was followed, and all possible functional Echo parameters were collected as listed in Appendix IIA.The following measurements were taken:PPHN was diagnosed by assessment of right ventricular systolic pressure (RVSP) , the presence of right-to-left or bidirectional shunting at atrial level or ductus arteriosus, septal wall flattening or paradoxical motion. PH was defined as moderate if RVSP ≥ 45, with or without bidirectional /right-to-left ductal shunting and severe if RVSP ≥ 70 and bidirectional /right-to-left ductal shunting , 30 PulmMarkers of LV function – systolic function is assessed by fractional shortening (FS), ejection fraction (EF) of LV with the biplane Simpson's method, and left ventricular output (LVO). Markers of LV diastolic function are early to late ventricular filling velocities (E/A ratio) and isovolumic relaxation time (IVRT)  The meanRight ventricular systolic function was assessed using Tricuspid Annular Plane Systolic Excursion (TAPSE) and Fractional Area Change (FAC).TAPSE was evaluated by measuring total excursion of tricuspid annulus during ventricular systole on M-mode using apical four-chamber view with cursor aligned in the direction of movement of tricuspid annulus. Three measurements were taken, and an average value at two decimal points was recorded for analysis.FAC was measured using the 2D recording of RV in a four-chamber view by measuring RV area in systole and diastole.Relevant cardiorespiratory parameters were collected at the time of Echo at corresponding time points.Respiratory severity score (RSS) was calculated using mean airway pressure (MAP) x fractional inspired oxygen (FiO2), and was considered as a marker of severity of illness . SubgrouVasoactive Inotropic score (VIS) was calculated using the following formula :VIS = (dopamine dose (μg/kg/min) + dobutamine dose (μg/kg/min) + 100 × epinephrine dose (μg/kg/min) + 10 × milrinone dose (μg/kg/min) + 10 000 × vasopressin dose (unit/kg/min) + 100 × norepinephrine dose (μg/kg/min).Data were also collected for inhaled nitric oxide (iNO) and other pulmonary vasodilators, alprostadil and hydrocortisone.The following outcome data were recorded from Cerner and REDCap®-death, need for ECMO, duration of ventilation, respiratory support or oxygen, inhaled nitric oxide (iNO), other pulmonary vasodilators, various types of inotropic support, day of CDH surgical repair, and length of hospital stay.Institutional Review Board (IRB) approval for this project was obtained from Sidra Medicine (IRB No-1696088-4). STROBE criteria were followed for reporting this observational study .U-test was used. For calculating the p-values of association between categorical variables, the Chi-square or Fisher's Exact test was used as appropriate. Freeman's coefficient of differentiation was used as a measure of association between defect size and mortality where 0 represents no association and 1 represents perfect association. Serial TAPSE measurements were analyzed using the rstatix package and a one-way repeated measures ANOVA, which is an extension of the paired-samples t-test for comparing the means of three or more levels of the within-subjects variable. To build ROC curves, the pROC package was used. The Youden Index was used to determine the appropriate cut-off point for the parameters of interest. Survival Analysis was performed using the Kaplan–Meier Model. All statistical analyses were performed using the statistical software R version 4.1.1. Any association with a p-value less than 0.05 was considered significant.Descriptive statistics were used to describe the study population, including gender, age (in days), gestation at birth, birth weight, and singleton/multiple births. Categorical and continuous variables were represented by frequencies, mean ± SD or median (Inter quartile range). To compare continuous variables between groups, the Mann–Whitney Fourty-two newborns with CDH were admitted during the specified study period (M/F:24/18), with median gestation age of 38 weeks (IQR:36–39) and median birth weight of 2.83 kg (IQR 2.45–3.17). Thirty-one were left-sided, 7 right-sided, 1 central and 3 bilateral diaphragmatic hernias. Three patients had D type and 9 had C type defect, 20 had either A or B defects. Information on defect size was unavailable in 10 patients, where they were either not operated upon or the surgeon had not clearly stated the size of defect. Descriptive data were collected for all 42 infants, but three infants were excluded from analysis, as per exclusion criteria, due to either palliation at birth or significant cardiac anomaly—one infant with transposition of great arteries (TGA) and ASD, VSD, hypoplastic tricuspid valve and another with TGA and atrioventricular septal defect.A total of 12 out of 42 infants admitted with CDH died in NICU/CICU, of which 5 had abnormal genetics. Our overall mortality rate was 28%, and after excluding genetic anomalies was 19%. Mortality amongst preterm infants (< 37 weeks gestation) was 45%; that in term infants was 22%. A total of 37 infants underwent surgical repair for CDH, out of which 3 died within 30 days and 4 more died at later stages. Of the 2 patients that required ECMO, 1 survived. Both the infants with significant heart anomalies died . Mortality amongst infants with milder congenital heart defects was 33%.Demographic data was compared based on survivors and non-survivors; no significant difference was found amongst these two groups, apart from side of defect, where those with bilateral hernias had a higher mortality Table . ClinicaA total of 137 echocardiograms in 39 newborns were analyzed, where available, at the specified time intervals. A review of patient scans and notes confirmed that serial echocardiography findings were consistently used in all patients to influence decisions regarding initiation and choice of inotropes and use of milrinone, inhaled nitric oxide, sildenafil, inhaled iloprost, vasopressin, alprostadil. ECHO markers of moderate to severe pulmonary hypertension  influenced use of pulmonary vasodilators like inhaled nitric oxide (iNO) and IV/oral sildenafil. INO was mainly used if RVSP > 60 mm Hg and FiO2 requirement > 60% either during initial stabilisation, perioperative period or during episodes of acute deterioration over chronic pulmonary hypertension (PH).Subnormal TAPSE with or without low RVO/LVO were particularly useful in guiding use of Milrinone alone or with epinephrine. However, no statistical correlation could be made with these outcome data. Fluid boluses were used with caution for intravascular fluid depletion, upon ECHO guided assessment.In addition, echocardiography was used to influence discussions and decisions regarding initiation of ECMO, readiness for surgery and pre-and post-operative stabilization. Seventy percent (7/10) of the newborns that died and had serial echo assessments, were found to have suffered from moderate to severe PH in the first 72 h.We studied the utility of a number of demographic characteristics, RSS and f-Echo parameters with regards to predicting mortality.Correlation of defect size with mortality was analyzed. A value of 0.16 was obtained for Freeman's coefficient of differentiation between defect size and mortality, indicating no association.Receiver Operating Curve (ROC) curves were used for analyzing all other parameters Fig. . The staBirth weight less than 2.8 kg (specificity of 81.8% and sensitivity of 76.7%) was identified to be a significant marker in predicting mortality with AUC of 77.9%.RVSP of more than 45.5  in the first 72 h, suggesting moderate pulmonary hypertension, was a good predictor of mortality with AUC of 75.4%, this cut-off value was found to be only slightly lower in the pre-operative period, at 42.5 .VIS in post-operative period, showed two significant values that were predictive of mortality . With AUC of 78.9%, VIS of 10.5 had a sensitivity of 83.3% and specificity of 66.7% and VIS of 23.5 was 100% sensitive but only 50% specific.RSS of ≥ 4.3 in the postoperative period (AUC 73.3%) was predictive of mortality with a specificity of 83.3% and sensitivity of 73.3%.Mortality prediction based on RV dysfunction:Kaplan–Meier plot of all the patients showed increased trends towards early mortality in those having RV dysfunction compared to those who didn’t; however, this was not statistically significant Fig. .Fig. 2EfWe compared the echo parameters of babies with low respiratory severity scores (RSS < 4) with those of higher scores (RSS > 4) and found significant correlation with certain echo parameters in first 72 h, pre- and post-op Table . OverallWe also compared the Echo parameters for babies with lower inotropic scores (VIS < 15) versus higher scores (VIS ≥ 15) . There wRespiratory severity score (RSS) was high initially in first 72 h, but stabilized in the pre-operative period, and had a modest rise post-operatively.TAPSE was initially low, improved in the pre-op stage and continued to improve post-operatively.RVSP as a surrogate for pulmonary pressures was elevated in the early 72 h, stabilized pre-operatively and further improved post-operatively.The frequency of use of milrinone, inotropes and pulmonary vasodilators for our patients with CDH is shown in Table . MilrinoThis is the first study from Middle Eastern population describing echocardiographic findings in CDH patients. Our calculated estimated prevalence of CDH is 3.82 per 10,000 births, based on average annual births  in Qatar,  as compaOur overall mortality is comparable to internationally reported rates (20–40%), but after excluding confirmed genetic anomalies, the mortality was even lower, which is comparable to reports from many high-volume centers . The mor, RVSP of more than 45.5 in the first 72 h was found to be a good predictor of mortality. Similar cut-off values are reported by Derya et al.[Pulmonary hypertension is a known predictor of mortality in CDH patients . In our ya et al.. In otheya et al..Birth weight less than 2.8 kg was a significant predictor of mortality in our cohort. Previous studies have similarly reported birth weight cut-offs of 2.755 kg as a predictor for mortality . Higher The improved trends pre-operatively for RSS, TAPSE, and RVSP indicate that clinicians endeavored to achieve cardiovascular stability in patients prior to surgery with regards to need for respiratory support, right ventricular systolic function, and pulmonary pressures. Pre-operative high RSS, pulmonary pressures and poor right ventricular function are important factors associated with mortality and morbidity in patients with CDH, and therefore the stability of these parameters is commonly practiced , 53, 54.Use of Milrinone in our cohort (62%) is higher than in international reports. Milrinone, a phosphodiesterase-III inhibitor with lusitropic and vasodilator effects, was used in up to 30% of CDH infants across the USA. No randomized trials have tested the efficacy or safety of milrinone in CDH neonates, but retrospective studies demonstrated that its use was associated with neither improved OI, PAP, or left ventricular measurements nor adverse events . The useStrengths: Standardised echo schedule and timelines as per protocol were used. The hemodynamic team consists of a group of experienced clinicians. Standardization of technique was emphasized amongst the group by regular hemodynamic meetings and case discussions.Weaknesses: This is an observational study where stored data were analyzed. Missing images or information could therefore not be obtained retrospectively. Some variation in acquired images and measurements may be present as echocardiograms were performed by several experienced members of the team. In the sicker patients, clinicians prioritized the assessment of only certain important echo parameters, in the interest of maintaining patient stability. Patients with any cardiac anomalies were mainly scanned by cardiologists and therefore did not always have complete functional echocardiography measurements performed at the set time points.CDH is a complex, multiorgan disease which has a large spectrum and whose prognosis is not easily predictable. Serial timed functional Echo monitoring allows targeted therapy of patients with CDH. Birth weight, initial pulmonary pressures and postoperative respiratory stability and inotropic scores may be useful predictors of mortality, but further validation is required. Early RSS, pulmonary pressures and right ventricular function are important factors associated with mortality and morbidity in patients with CDH and therefore can be utilized for assessing pre-operative stability and decision-making in timing of surgery. Large prospective clinical studies in CDH patients are needed to identify predictive functional markers and for optimizing management.Supplementary file1 (DOCX 96 kb)Supplementary file2 (DOCX 484 kb)Supplementary file3 (MP4 4511 kb)Below is the link to the electronic supplementary material.


The aim of this study was to provide insights into myocardial adaptation over time in myocyte injury caused by acute myocarditis with preserved ejection fraction. The effect of myocardial injury, as defined by the presence of late gadolinium enhancement (LGE), on the change of left ventricular (LV) segmental strain parameters was evaluated in a longitudinal analysis. Patients with a first episode of acute myocarditis were enrolled retrospectively. Peak radial (PRS), longitudinal (PLS) and circumferential (PCS) LV segmental strain values at baseline and at follow-up were computed using feature tracking cine cardiac magnetic resonance imaging. The change of segmental strain values in LGE positive (LGE+) and LGE negative (LGE−) segments was compared over a course of 89 ± 20 days. In 24 patients, 100 LGE+ segments and 284 LGE− segments were analysed. Between LGE+ and LGE− segments, significant differences were found for the change of segmental PCS (p < 0.001) and segmental PRS (p = 0.006). LGE + segments showed an increase in contractility, indicating recovery, and LGE− segments showed a decrease in contractility, indicating normalisation after a hypercontractile state or impairment of an initially normal contracting segment. No significant difference between LGE+ and LGE− segments was found for the change in segmental PLS. In the course of acute myocarditis with preserved ejection fraction, regional myocardial function adapts inversely in segments with and without LGE. As these effects seem to counterbalance each other, global functional parameters might be of limited use in monitoring functional recovery of these patients. Acute myocarditis represents an inflammation of the myocardium, mostly caused by viral infection and frequently affecting young individuals. The clinical presentation is often unspecific, varying from subclinical disease and flu-like symptoms to a fulminant, infarct-like presentation with acute heart failure, arrhythmia, and sudden cardiac death , 2. MyocCardiac magnetic resonance imaging (MRI) is the most sensitive imaging modality for the diagnosis and follow-up of patients with myocarditis, as it enables the combination of functional and morphological data in a multiparametric approach with high accuracy –11. MoreMyocardial dysfunction, as a typical characteristic of an inflammatory process, can be detected by visual assessment on cardiac MRI cine imaging; however, it is not always apparent in segments with LGE and is unspecific. Due to the frequent multifocal, patchy distribution of LGE, it was assumed that the surrounding myocardium might compensate the focal defect by increasing its own contractility, resulting in preserved regional and global function . HoweverIn current cardiac MRI practice, evaluation of myocardial contractility is generally performed by visual assessment on cine images, with inherent observer dependency . Over thThe aim of this study was to provide insights into myocardial adaptation caused by myocyte injury over the course of acute myocarditis in a longitudinal analysis. The effect of myocardial injury, as defined by the presence of LGE, on change of left ventricular (LV) segmental strain parameters by feature tracking cardiac magnetic resonance (MRI) was evaluated.We retrospectively enrolled consecutive patients who underwent baseline and follow-up cardiac MRI due to suspected myocarditis between January 2016 and December 2019 at our institution. Individuals treated as inpatients with their first clinical episode of myocarditis were included. Myocarditis was defined by the current European Society of Cardiology (ESC) guidelines . SimultaClinical data and laboratory values were collated from the patients’ electronic records. For the acute phase of myocarditis, peak inflammatory laboratory values and peak cardiac enzymes from serial blood sampling during hospitalisation were obtained. Clinical and laboratory follow-up was performed close to the follow-up MRI examination.3, in addition to three standard long axis views (2 chamber (CH), 3 CH and 4 CH). To visualise myocardial edema, fat saturated T2-weighted images were acquired in short axis orientation. Mapping sequences were only acquired in part of the population, which is why the data is not displayed under results. LGE imaging was performed 10 min after administration of 0.2 mmol/kg contrast agent  using a gradient-spoiled turbo fast-field-echo sequence with a non-selective 180° inversion pre-pulse in end diastole. The optimal inversion time was obtained from a Look Locker sequence.Cardiac MRI investigations were performed on a 1.5T system  using a dedicated cardiac 5-channel phased array coil. For functional and feature tracking strain analysis, retrospectively triggered balanced steady-state free precession (b-SSFP) sequences in expiratory breath hold technique were acquired as a short axis stack covering the whole LV; repetition time 3.3 ms, echo time 1.6 ms, flip angle = 60°, spatial resolution = 8 × 1.5 × 1.5 mmCardiac MRI data was analysed on a commercially available post-processing software . Volumetric analysis was performed according to the current guidelines of the Society of Cardiovascular Magnetic Resonance (SCMR). LV and right ventricular (RV) volumes, as well as LV myocardial mass were indexed to the calculated body surface area . Global A dedicated software  was used for feature tracking strain analysis of cardiac MRI cine images, known for its excellent intra- and interobserver reproducibility , 28. TheLongitudinal strain was assessed using 2-chamber, 3-chamber, and 4-chamber long axis slides. Endo- and epicardial contours were drawn manually, and propagated automatically throughout the cardiac cycle. The quality of propagation was checked visually, and if necessary, manual contouring was adapted and propagation was repeated. Segmental strain parameters were derived according to the 16-segment model of the AHA.Late gadolinium enhancement imaging and strain analysis are illustrated in Fig. Population characteristics are presented using means and standard deviations (SD) for continuous variables as well as counts and percentages for categorical variables. Descriptive statistics (histograms) were applied to test the normality of data. The Student’s t test for paired samples was used to compare clinical characteristics between baseline and follow-up.Strain values of specific segments are displayed as means and standard deviations of their absolute values. Since segmental strain values are known to show different distributions in different segments , 29, theChange in segmental strain values from baseline to follow-up was computed by subtracting baseline values from follow-up values. These changes were expressed as their standardised mean difference (SMD) with 95% confidence intervals (CI). The strain values of all LGE+ and LGE− segments were compared using a Student’s t test for unpaired samples.Statistical significance was set as a two-sided p-value of < 0.05. All statistical analyses were computed using the STATA version 15.0 .We included 24 patients  with acute myocarditis. Baseline demographic and clinical characteristics of the study population are displayed in Table Consistent with the study inclusion criteria, LGE was present in all patients. At baseline, a total of 100 LGE+ and 284 LGE− segments were detected. This corresponds to an average of 4.2 ± 2.8 affected segments per patient. The segmental distribution of LGE is listed in Table At follow-up, the number of LGE+ segments had decreased to an average of 2.8 ± 2.5 per patient with no new segments detected. The pattern of affected segments remained similar, with inferolateral basal and midventricular segments being most frequently affected.The summarised amount of LGE, calculated by the FWHM method, was inter-individually highly variable (mean at baseline = 6.5 ± 3.9%), and declined significantly from baseline to follow-up (p = 0.023).LV ejection fraction as well as global strain values are displayed in Table Absolute values of segmental strains at baseline and at follow-up are displayed in Table Changes in peak segmental strain values from baseline to follow-up for LGE+ and LGE− segments are displayed in Fig. To the best of our knowledge, this is the first study focusing on the regional effect of myocyte injury on myocardial function during the course of acute myocarditis with preserved ejection fraction, using feature tracking strain analysis. Thus, the study provides insights into the potential mechanisms of myocardial dysfunction and its compensatory mechanisms.Feature tracking strain analysis was able to depict differences in LGE+ segments compared to LGE− segments for PCS and PRS. On the one hand, LGE+ segments showed a significant improvement in PCS and a trend towards improvement in PRS, indicating recovery. On the other hand, LGE− segments showed a reduction in PCS and PRS indicating normalisation from an initially hypercontractile state or impairment of an initially normal contracting segment. For PLS, no significant change could be observed.Our data supports the hypothesis that myocyte injury in the acute stage of myocarditis leads to regional myocardial dysfunction and recovers over time. Adjacent myocardium, which was affected to a lesser extent or completely unaffected, seems to react with an initial hypercontractility to compensate and seems to normalise once recovery sets in. An alternative explanation for the inverse reaction of initially unaffected segments would be the development of a scar, however in the absence of progression of LGE, this appears less likely.There is limited data in the literature on the correlation between presence of LGE and segmental myocardial strain parameters. However, as a proof of concept for this study, Tahir et al.  found reRegarding the course of global peak strain values in acute myocarditis, Luetkens et al.  found siThe present data shows that compensatory mechanisms of the LV myocardium occurs over the course of acute myocarditis in patients with preserved ejection fraction. At the segmental level, LGE + and LGE− segments adapt inversely in PCS and PRS. Meanwhile global strain parameters remain unchanged over time, underlining the limited utility of global function parameters to track functional recovery over the course of acute myocarditis in patients with preserved ejection fraction.PLS shows no significant changes at either segmental or global level. Whether the lack of change is due to a limitation of the software used in the study, or a lack of remodelling possibilities cannot be determined from our data.In the acute phase of myocarditis, reduced global strain values have been observed in several studies , 30–32. Since circumferential strain is thought to contribute more to the LVEF than longitudinal strain , this coLV end-diastolic volume decreased significantly from baseline to follow-up in our study. Importantly, LV dilatation has an influence on strain values due to the change in the fibre course , 35. HowOur study has several limitations, foremost the retrospective design. While accurate diagnosis of myocarditis remains a challenge, the gold standard of endomyocardial biopsy (EMB) was not performed in this study. However, EMB also has its limitations, mostly resulting from sampling error. Therefore, we applied narrow inclusion criteria and considered only patients with high clinical suspicion of acute myocarditis, according to the ESC Guidelines and positive cardiac MRI criteria for myocardial inflammation, renowned for improving diagnostic accuracy , 36. To This study provides insights into the potential mechanisms of myocardial dysfunction and its compensatory mechanisms over the course of acute myocarditis with preserved ejection fraction derived from segmental feature tracking strain analysis. Our results indicate that compensatory mechanisms are highest for circumferential segmental strain parameters and lowest for longitudinal segmental strain parameters. LGE+ segments show an increase in contractility, indicating recovery. LGE− segments show a decrease in contractility, indicating normalisation after a hypercontractile state or an impairment of an initially normal contracting segment. These effects seem to counterbalance each other, resulting in unchanged global function parameters , which suggests that these parameters might be of limited use in monitoring functional recovery in these patients. Future studies with a larger number of patients and a longer follow-up period are required to further improve our understanding of the underlying pathophysiological process, as well as assessing the long-term effects of the disease on myocardial function.


Heart failure (HF) is a common disease that requires appropriate tools to correctly predict cardiovascular outcomes. Echocardiography represents the most commonly used method for assessing left ventricular ejection fraction and a cornerstone in the detection of HF, but it fails to procure an optimal level of inter-observer variability, leading to unsatisfactory prediction of cardiovascular outcomes. In this review, we discuss emerging clinical tools  that permitted an improvement in the diagnosis and ameliorated the risk stratification across different HF phenotypes. The review analyzes the speckle-tracking contributions to the field, discussing the limitations and advantages in clinical practice. Heart failure (HF) is a pathophysiological condition with signs and symptoms due to abnormal cardiac function, resulting in the inability of the heart to pump the blood required to meet the needs of metabolic tissues, or due to the high left ventricular filling pressure, despite preserved contraction. According to the European guidelines, HF is classified based on the left ventricular (LV) systolic function: HF with preserved ejection fraction (HFpEF) (ejection fraction (EF) > 50%), HF with mid-range EF (HFmEF) (EF 40–49%), HF with reduced EF (HFrEF) (EF < 40%), and improved EF (HFimpEF) with a baseline EF ≤ 40% and a subsequent improvement of at least 10% from the baseline EF [Despite this classification, the prognosis is similar between the LVEF groups , which u0 indicates the baseline length. It is important to consider the normal values of the left ventricular global longitudinal strain (GLS) in terms of clinical applications which varied form −15.9% to −22.1% [Analysis of longitudinal deformation could detect subclinical dysfunction and identify the initial alteration of LV myocardial contraction. This analysis could be performed using strain-based imaging techniques (speckle-tracking echocardiography): an operator-friendly, less angle-dependent, post-processing computer algorithm that measures the deformation of the left ventricle in the longitudinal, circumferential, and radial planes . During Moreover, GLS analysis could be applied to the RV, with a better diagnostic capability compared to standard echo measures, and the LA, in order to obtain additional diagnostic information regarding diastolic function, through the analysis of atrial strain .These approaches are, however, far from faultless, and there are important limitations that need to be acknowledged, such as the absence of large-scale, independent randomized studies. GLS may be influenced and flawed by geometric assumptions, poor acoustic windows, inappropriate measures due to imprecise customization, or inaccurate tracking of the LV myocardium throughout systole. Moreover, GLS may have different values depending on the age, sex, and loading conditions. There are small differences between different vendors; subsequently improved software versions were released to improve the inter-vendor agreement .Nonetheless, GLS can be a useful clinical tool to improve risk stratification in patients with HF, as this parameter correlates with the severity of HF, and it can help identify different cardiomyopathy phenotypes suggesting disease causes and severity.GLS demonstrated to be superior to LVEF in assessing the likelihood of all-cause mortality in patients with acute congestive HF, regardless of clinical characteristics and systolic function . This meThe GLS enables the evaluation of mechanical dispersion, namely the peak strain dispersion (PSD), which represents the contractile dispersion defined as the standard deviation of the contractile duration compared to the regional strain curves. PSD accurately reflects the dyssynchrony between different LV regions, functional heterogeneity of contraction, and effective LV global work .PSD proved to be a good predictor of ventricular arrhythmias independent of LVEF . SimilarThis feature appeared to be beneficial in patients with ischemic heart disease and HF-identifying patients, who could most benefit from implantable cardioverter–defibrillator (ICD) implantation. However, this has not been confirmed in any independent, randomized, large study .RV systolic dysfunction remains an important predictor of major events in patients with congestive HF . The quaA preserved EF does not guarantee the absence of clinical HF. Almost half of the patients that presented with signs and symptoms of HF displayed a preserved EF on the echocardiogram . ConversThe diagnosis of HFpEF can also be improved by assessing LA function. Strain analysis can be applied to the LA providing an accurate estimation of the LV filling pressure and the LA function. All phases of the LA loop, reservoir, conduit, and booster pump were analyzed. It was detected using 2D speckle-tracking echocardiography, placing a region of interest (ROI) on the LA in Four- and two-chamber views . TraditiWhen invasive LV filling pressures were evaluated, LA strain correlated better than standard parameters; the existing data showed only a modest correlation between E/e’ and invasive filling pressures . AbnormaIncreasing evidence indeed suggests that the LA remodeling is distinct from the LA enlargement because it involves LA changes, such as fibrosis, even before atrial enlargement .Despite these promising results, LA strain has some important limitations: a lack of generally accepted standard validation, a standardized methodology, limited software distribution, and it is a preload-dependent method, even if to a lesser degree than LA volume, which makes the interpretation of the atrial function index more difficult due to the interaction between atrial and ventricular functions .This method needs to be validated in randomized trials, and the correlation between LA strain and LV filling needs to be evaluated in a plethora of different scenarios, e.g., restrictive cardiomyopathy, mitral regurgitation, HCM, patients suffering from hyperdynamic states.HFmEF is defined as the presence of typical HF symptoms and an EF of 41–49%, encompassing 3–24% of patients suffering from HF . The novWithin the HFmEF spectrum, there is another clinical entity, distinct from HFrEF and HFpEF: HFimpEF.Several subsequent studies have identified HF patients with improved EF (HFimpEF) as the new clinical entity, distinct from HFrEF and HFpEF. HF with a second measurement of LVEF > 40% and a ≥10% increase from the baseline LVEF of ≤40% is defined as HFimpEF . PreviouA typical conundrum during clinical practice could be to differentiate between physiological characteristics, such as in the athlete’s heart, and left ventricular hypertrophy (LVH), a hallmark frequently described in patients with HFpEF. LV-GLS may be useful because there are typical regional alterations distinctive to specific diseases.HCM is characterized by symptoms typically attributed to HF, and is associated with a normal EF (except during the later stage) and an impaired LV-GLS. Given the several subtypes of HCM, characteristic regional alterations have been described, such as reduction in the septal segments in sigmoid HCM, or by a diffuse reduction in the apical segments, with global reduction of an absolute LV-GLS (15.1% versus 20.3%) . After aPSD seems to be especially useful in identifying patients at risk of ventricular arrhythmia. A >67 ms increase in PSD in patients with HCM was significantly associated with a future risk of ventricular tachycardia .These patients also usually experience paroxysmal atrial fibrillation and left atrial structural remodeling, thus putting them at an increased risk of adverse cardiovascular outcomes. It is pivotal to consider any modifications that could affect the LA function, and therefore LA strain, allowing for the categorization of the LV diastolic function and the forecasting of HF events. In 104 HCM patients, the best cutoffs for poor cardiovascular outcomes  were absolute values < 23.8% for reservoir strain, and <10.2% for conduit strain . In anotHowever, attention should be paid to possible confounders, such as Fabry cardiomyopathy (FC), a disorder caused by deficient enzyme activity of α-galactosidase A : in affected individuals, the principal enzyme substrate, globotriaosylceramide (Gb3), accumulates in cytoplasmic lysosome, leading to organ dysfunction and symptoms .Cardiac involvement in Fabry disease has multiple manifestations, including HF and progressive LVH. It is therefore recommended to be included in the differential diagnosis of adults with unexplained LVH .Strain analysis has been shown to be a useful tool in the detection of systolic dysfunction in patients with FC, especially for early detection, as reduced GLS  may be a marker of early FC . HoweverCardiac amyloidosis is another cause of HFpEF, often diagnosed late. When this condition is suspected , LV-GLS could improve the diagnosis through the detection of specific patterns, such as the “apical sparing” pattern, characterized by preserved LV-GLS values on an apical region, along with reduced values in the basal segment, showing a high discriminatory power, with a sensitivity of 93% and specificity of 82%, between these two conditions from controls  Figure . MoreoveHowever, it could be challenging to differentiate between hypertensive heart disease and cardiac amyloidosis because both share an increased left ventricular wall thickness. In one study, when the LA function was assessed, LA strain in confirmed cases of cardiac amyloidosis was significantly reduced compared to the control group of hypertensive patients, irrespective of amyloid light chain or amyloid transthyretin subgroup. Despite similar LV wall thicknesses, a reservoir strain cut-off value of 20% was 86.4% sensitive and 88.6% specific for identifying cardiac amyloidosis in this cohort .Sarcoidosis is a systemic granulomatous disease that can involve the myocardium . Sudden The role of LV-GLS in identifying early subclinical myocardial injury has become central in cardio-oncology, although it is not effectively used clinically. Early identification of adverse effects on myocardial tissue is pivotal to improve the effectiveness of chemotherapy and to adjust the correct cardiovascular therapy as soon as possible, to avoid further deterioration. The superiority of LV-GLS over LVEF, in these patients, was confirmed in a trial of patients who underwent anthracycline therapy . After oRV systolic dysfunction remains an important predictor of major events in patients with HF . The quaAlthough few studies have examined the prognostic importance of RV systolic dysfunction in patients with HFpEF, it is important to emphasize that the prevalence of this condition ranges from 37% to 19%, and is considered a poor prognostic by multiple mechanisms not yet completely understood . In a stFinally, as we already described the pathognomonic apical sparing in cardiac amyloidosis, the analysis of RV strain seems to contain more insights into the mechanisms and the clinical manifestations in these patients. More specifically, the RV-free wall strain correlates with the functional status of amyloid patients, because amyloid deposits infiltrate the RV in later stages, leading to progressive terminal HF . We haveThe objective of this clinical review was to analyze the strengths and weaknesses of GLS in the evaluation of patients with HF. We can consider whether 2D LVEF should be replaced by LV-GLS; the latter, provides pivotal information on prognosis and LV function, but should be intended as complementary. Every new development in diagnostic tools is often time-consuming, and this expenditure should be justified in an improvement of diagnostic and prognostic definitions in clinical practice. The study of LV-GLS in echocardiography proved to have a robust justification in HFpEF patients, to identify pathological versus physiological LV hypertrophy in the initial form of cardiac amyloidosis, and following a cancer patient who is at risk of cardiotoxicity due to chemotherapy.The study of LA or RV strain seems to be a very promising field for clinical research, and further studies are necessary to translate these results into clinical practice.In addition, several recent studies have shown that changes in LV and LA strain over time reflect the response to therapy, suggesting their potential value in guiding the optimal management of patients with HF . FinallyGiven all these issues, we may wonder why these approaches are not routinely implemented in our clinical practice: as demonstrated, there are some important limitations to be aware of. Despite providing promising data, these methods are still considered time-consuming, have known limitations and a lack of standard in large studies: a summary of all potential limitations is presented in In conclusion, we are moving in the right direction, improving the prognostic and diagnostic role of the echocardiography with complementary methods, as previously stated. Our hope is that in the future, the accuracy will be improved by technological development, allowing a prevailing use of the method with an accepted standard validation.


Estimation of pulmonary pressures is of key importance in acute cardiovascular and respiratory failure. Pulmonary artery acceleration time (PAAT) has emerged as reliable parameter for the estimation of systolic pulmonary artery pressure (sPAP) in cardiological population with preserved right ventricular function. We sought to find whether PAAT correlates with sPAP in critically ill patients with and without right ventricular (RV) systolic dysfunction.Observational study. We measured sPAP using continuous-wave Doppler analysis of tricuspid regurgitation velocity peak method and we assessed the validity of PAAT in estimating sPAP in patients admitted to adult intensive care unit (ICU) for acute cardiovascular and respiratory failure.p 0.0035) was observed in overall population, which was confirmed in those with preserved RV systolic PAAT and sPAP . In patients with impaired RV systolic function no statistically significant correlation between PAAT and sPAP was demonstrated (p 0.2737). Adjusting PAAT values for log10, heart rate and RV ejection time did not modify the abovementioned correlations.We enrolled 236 patients admitted to cardiothoracic ICU for cardiovascular and respiratory failure . 114 (48.3%) had preserved RV systolic function (defined as TAPSE ≥ 17 mm), whilst 122 (51.7%) had RV systolic impairment (defined as TAPSE < 17 mm). A weak inverse correlation between PAAT and sPAP (ρ–0.189, PAAT measurement to derive sPAP is not reliable in cardiothoracic critically ill patients, particularly in the coexistence of RV systolic impairment. Pulmonary hypertension (PH) is a condition defined by an increase in afterload leading to a mean pulmonary artery pressure (mPAP) ≥ 25 mmHg at rest . The premax) is considered the cornerstone of non-invasive assessment of systolic pulmonary artery pressure (sPAP) [A number of echocardiographic parameters have been validated to assess RV morphology and function and to estimate pulmonary pressures . Continue (sPAP) . Althouge (sPAP) , 5.Pulmonary artery acceleration time (PAAT) has demonstrated good reliability in estimating mPAP , 7 and, We sought to investigate whether PAAT estimation of sPAP is reliable also in critically ill patients admitted to intensive care unit (ICU) for acute cardiovascular failure and respiratory failure related to moderate-to-severe acute respiratory distress syndrome (ARDS), with and without RV systolic dysfunction, defined as tricuspid annular plane systolic excursion (TAPSE) < 17 mm .2 on FiO2 ratio below 200).The project has been approved by the ethical committee of Royal Brompton Hospital NHS Foundation Trust , where it was carried out. Written informed consent was acquired for all patients. The study was conducted on consecutive patients admitted to adult cardiothoracic ICU for post-cardiac surgery and respiratory failure related to at least moderate ARDS . Images were recorded in multiple views thus obtaining optimal imaging for the primary analysis.TAPSE and tissue Doppler S’ was measured in the apical four-chamber view during systole with cursor placed through the lateral tricuspid annulus. In accordance with current guidelines, TAPSE < 17 mm and S’ < 9.5 cm/sec were regarded as pathological .max. sPAP was determined from the TR jet velocity using the simplified Bernoulli equation adding the right atrial pressure (RAP), directly measured from central venous pressure (at end-expiration) or estimated from inferior vena cava (IVC) diameter and respiratory collapsibility [Continuous-wave Doppler was used to measure the peak velocity of the TRVsibility , 12.Doppler interrogation of the proximal pulmonary artery was performed either in parasternal long-axis outflow and/or the parasternal short-axis Fig. A in ordeAll values used for analysis represented the average of three consecutive cardiac cycles, with the exception of patients with atrial fibrillation, in whom five-beat averages were obtained. Continuous-wave Doppler was used with a sweep speed of 100 mm/s to achieve a satisfactory envelope.All measurements were made offline. Echocardiograms were interpreted by fully certified physicians who were blinded to the patients’ medical history and diagnosis.Results of continuous data were expressed as mean ± standard deviation for normally distributed data and median (interquartile range) for values not normally distributed; normal distribution of data was assessed with D’Agostino–Pearson test. Categorical variables were expressed as percentage.χ2 test with Yates correction or Fisher’s exact test when appropriate. Continuous variables were compared with Mann–Whitney U-test for unpaired data. Relationships between PAAT and haemodynamic indexes were evaluated by Spearman correlation coefficient. A two-sided p-value < 0.05 was assumed as statistically significant.Categorical data were compared by Pearson’s max were expressed as intra-class correlation coefficient (ICC), which was derived using a one‐way random‐effects model.Statistical analyses were performed by using SPSS software . The intra-observer and inter-observer variability of PAAT and TRVWe consecutively enrolled 255 adult patients admitted to cardiothoracic ICU. Nineteen subjects were excluded for inadequate echocardiographic windows, thus 236 patients were considered for the final analyses. The mean age was 63 ± 17 years, and 150 (63.5%) were males. 114 (48.3%) had preserved RV systolic function (defined as TAPSE ≥ 17 mm), whilst 122 (51.7%) had RV systolic impairment (defined as TAPSE < 17 mm). One hundred and twenty-nine patients (54.7%) were admitted after cardiac surgery, while 107 (45.3%) for respiratory failure related to moderate-to-severe ARDS. Amongst those undertaking cardiac surgery: 78 (60.5%) underwent mitral valve replacement, 32 (24.8%) aortic valve replacement and 19 (14.7%) coronary artery bypass graft. Two hundred and twenty patients had RAP derived from invasive measurements.p < 0.001). Need for positive-pressure ventilation (both invasive and non-invasive) and respiratory gas exchanges (PaO2 on FiO2 ratio and PaCO2) did not differ between the two cohorts. No patients required mechanical circulatory support nor inhaled nitric oxide at time of echocardiographic assessment.Stratifying for the cause of ICU admission, a statistically significant difference in the incidence of RV dysfunction was observed: 69.8% of patients affected by acute cardiovascular failure experienced RV dysfunction, while only 29.9% had RV dysfunction in the respiratory failure subgroup  and the inter‐observer variability was 0.94 .p 0.0035) was observed in overall population  and HR did not increase the strength of this relation ; PAAT adjusted for RVET did not correlate with sPAP (p 0.8110).A weak inverse correlation between PAAT and sPAP . Adjustment of PAAT for log10PAAT, HR and RVET did not yield significative increase in the strength of relationship with TAPSE .PAAT had also a weak-positive correlation with TAPSE   and HR ; no statistically significant correlation was found between PAAT adjusted for RVET and sPAP (p 0.1164). We did not find any statistically significant correlation between PAAT and TAPSE (p 0.2594), even after adjustment of PAAT for log10 (p 0.2876), HR (p 0.5873) and RVET (p 0.5565). The same applied for correlation between S’ and PAAT (p 0.134).In patients with preserved RV systolic function, defined as TAPSE ≥ 17 mm and S’ ≥ 9.5 cm/sec, a weak inverse correlation between PAAT and sPAP was found . Additionally, PAAT did not correlate with TAPSE (p 0.4515) neither with S’ (p > 0.5). Only adjustment of PAAT for HR yielded a weak inverse correlation with TAPSE .In the cohort of patients with impaired RV systolic function, no statistically significant correlation between PAAT and sPAP was demonstrated p 0.2737) .The strength of abovementioned correlations was not influenced by the addition of RAP to TRV2 was observed , PAAT had a weak-negative correlation with PaCO2 , and a weak-positive correlation between TAPSE and PaCO2 was found .In overall population, a weak-positive correlation between sPAP and PaCO2 in patients with preserved and impaired RV systolic function.Table The results of our study demonstrate that PAAT is not a reliable parameter to estimate sPAP in patients admitted to cardiothoracic ICU with and without RV systolic dysfunction.max is considered the non-invasive parameter of choice for establishing the suspicion of PH. However, TR-methods of estimation of pulmonary artery pressure are burdened with some limitations: (1) difficult measurement of TVRmax in trivial or mild TR; (2) sub-optimal Doppler signal alignment with TR jet; (3) underestimation of RA–RV gradient in severe TR, due to the early equalization of chamber pressures [.According to the current guidelines, TVRressures ; 4) the themax iGiven the non-negligible pitfalls of TR-derived methods, alternative TR-independent methods, have been proposed for the evaluation of pulmonary artery pressure. It has previously been shown that PAAT should be possible to measure in 99% of patients out of which 25% has no measurable TR and thus provide a way of estimating the pulmonary pressure non-invasively . DiffereThe evaluation and treatment of RV dysfunction is particularly challenging in critically ill and the coexistence of RV failure and PH is burdened by an increased mortality , 20. WhiNormal PAAT interval values in adults range from 136 to 153 ms . PAAT maOur results are partially in contradiction with the previous literature, as also patients without RV dysfunction did not prove strong relation between Doppler-derived PAAT and TR-estimated sPAP. One of the potentially explaining difference is the admission underlying pathology. Respiratory pathologies may highly influence the interaction between RV and pulmonary circulation system both in settings of normal and impaired RV systolic function . An eleg2) has a well-defined role in determining pulmonary vascular resistances [2. However, no correlation between PAAT and PaCO2 was found in patients with impaired RV systolic function suggesting further caution in the use of PAAT to estimate pulmonary artery pressure.Arterial partial pressure of carbon dioxide  the limited sample size; (2) the heterogeneous population; and (3) sPAP has been assessed only with echocardiography and no validation with pulmonary artery catheter was performed .Although echocardiography presents well-known limitations, which are listed in the manuscript, it is considered a reliable diagnostic tool in PH. Additionally, the same methodology has been used in other studies already published and included in the referenced meta-analyses , 16.sPAP evaluation may be extremely useful in patients with acute respiratory failure, although its estimation based on TR jet may be unfeasible. PAAT measurement to derive sPAP is not reliable in cardiothoracic critically ill patients, particularly in the coexistence of RV systolic impairment. Non-invasive echocardiographic estimation of pulmonary artery pressure in suspected and proven PH remains a challenge, especially in ICU patients. In this specific clinical setting, echocardiographic parameters validated in outpatient population should be adopted with caution.


Potentially fatal arrhythmia is one of the causes of premature death in acromegalic cardiomyopathy patients who are not properly treated. Implantable cardioverter-defibrillator (ICD) is one of the most effective and established treatments to prevent sudden cardiac death due to potentially fatal tachyarrhythmia. However, since the indication of ICD changes depending on whether it is ischemic cardiomyopathy or non-ischemic cardiomyopathy, proper diagnosis is important in patients with these diseases. Cardiac magnetic resonance (CMR) is a convenient and useful tool for diagnosing these. Both potentially fatal arrhythmias and coronary artery disease (CAD) are known to be important complications of acromegaly. Herein, we present a case of potentially fatal tachyarrhythmia due to acromegalic cardiomyopathy with the acute coronary syndrome. Furthermore, we mention the usefulness of CMR in the case which is difficult to determine the indication for an ICD. Cardiovascular disease is a principal cause of premature mortality in acromegalic patients. The fundamental physiologic derangements in acromegaly are a pathologically elevated serum concentration of growth hormone (GH), and insulin-like growth factor-1 (IGF‐1) . The hig We report the case of a 69-year-old Japanese male, who suffered out-of-hospital cardiac arrest (OHCA) due to ventricular fibrillation (VF) caused by acromegalic cardiomyopathy, despite undergoing appropriate treatment. His medical history included a surgical resection of a pituitary adenoma for acromegaly at the age of 60 years, and subsequent octreotide long-acting repeatable therapy, after which his serum insulin-like growth factor-1 (IGF-1) levels were under control. He was noted to have diminished left ventricular (LV) function; however, he had no symptoms of dyspnea. After ruling out other secondary cardiomyopathies, he was diagnosed with LV dysfunction due to acromegaly cardiomyopathy. A transthoracic echocardiogram (TTE) showed a gradual improvement of his ejection fraction (EF) value from 34% to 43% over a period of nine years  detected VF. He achieved a return of spontaneous circulation (ROSC) after three unsynchronized defibrillations (200J), and three epinephrine injections. Post ROSC, his blood pressure was 112/59 mmHg, heart rate 70 bpm, and oxygen saturation 99% under intubation on a fraction of inspiratory oxygen of 100%. Physical examination revealed coldness of the extremities, but not pulmonary rales and heart murmur. The ECG after ROSC showed the same AF rhythm as before, as well as new ST depression in leads V4-6 and ST elevation in leads aVR and V1 , but no regional wall motion abnormalities. He immediately underwent coronary angiography (CAG) to evaluate for the acute coronary syndrome (ACS). A 90% stenosis in the proximal LAD artery was diagnosed Figure , and optCreatine kinase (CK) and CK-MB peaked at 2452 and 63 U/L, respectively. It seemed that a high value of CK compared to CK-MB was due to muscle injury of cardioversion. He was extubated on day 7, and his neurological function fully recovered to his baseline. Subsequently, the patient underwent a clinical examination to determine the etiology of potentially fatal arrhythmias. CMR imaging which took place about a week later revealed late gadolinium enhancement (LGE) in the interventricular septum (IVS) Figure , and theCardiovascular disease is known to be an important complication of acromegaly, accounting for increased morbidity and reduced life expectancy in these patients , 4. ThisImplantable cardioverter-defibrillator is one of the most effective and established treatments to prevent sudden cardiac death due to potentially fatal tachyarrhythmia, and improve survival regardless of the type of heart disease. Japanese guidelines recommended that ICD may be considered for patients with non-ischemic cardiomyopathy even if VT/VF was "due to reversible acute causes , but whose possibility of re-exposure to the same conditions is high." In this case, we diagnosed fatal arrhythmia due to non-ischemic cardiomyopathy accompanied by ACS and, therefore, decided to implant an ICD as secondary prevention according to Japanese guidelines . HoweverThe precise diagnosis in patients with CPA by VF is important because the indication for ICD must be determined by the underlying cardiac disease. In patients with acromegaly, approximately 3% have been reported to have a unique cardiomyopathy characterized by biventricular hypertrophy, myocardial necrosis, lymphocytic infiltration, and interstitial fibrosis . The mecMoreover, in addition to optimal medical therapy for heart failure, the normalization of GH and IGF-1 levels, whether by surgical or pharmacological therapy, is essential to prevent or improve cardiovascular complications. Because the diagnosis of acromegaly is often delayed by many years due to the silent progression of the disease, the necessity of early recognition and management is paramount to avert chronic cardiovascular damage . PatientIn conclusion, the prognosis of cardiac complications caused by acromegaly is poor, and ICD is one of the most effective and established treatments. Although it may be difficult to determine the indication for ICD in some cases, it is necessary to make an appropriate decision by making full use of diagnostic imaging such as CMR.


Dilated cardiomyopathies (DCMs) are a heterogenous group of primary myocardial diseases, representing one of the leading causes of heart failure, and the main indication for heart transplantation. While the degree of left ventricular dilation and dysfunction are two key determinants of adverse outcomes in DCM patients, right ventricular (RV) remodeling and dysfunction further negatively influence patient prognosis. Consequently, RV functional assessment and diagnosing RV involvement by using an integrative approach based on multimodality imaging is of paramount importance in the evaluation of DCM patients and provides incremental prognostic and therapeutic information. Transthoracic echocardiography remains the first-line imaging modality used for the assessment of the RV, and newer techniques such as speckle-tracking and three-dimensional echocardiography significantly improve its diagnostic and prognostic accuracy. Nonetheless, cardiac magnetic resonance (CMR) is considered the gold standard imaging modality for the evaluation of RV size and function, and all DCM patients should be evaluated by CMR at least once. Accordingly, this review provides a comprehensive overview of the anatomy and function of the RV, and the pathophysiology, diagnosis, and prognostic value of RV dysfunction in DCM patients, based on traditional and novel imaging techniques. Dilated cardiomyopathies (DCMs) are primary myocardial disorders characterized by left ventricular or biventricular dilation and systolic dysfunction in the absence of either abnormal pressure or loading conditions or coronary artery disease ,2. DCM sSeveral anatomic features distinguish the RV from the LV. Being the most anteriorly situated cardiac chamber, the RV has a complex shape, which partially explains the more difficult imaging evaluation of the RV compared to the LV. With a crescent shape when viewed in cross-section, and triangular when looking from the side, the RV consists of three components: (1) the inlet, containing the tricuspid valve, chordae tendinae, and the papillary muscles; (2) the trabeculated apical myocardium; and (3) the infundibular or conal region, which accommodates the outflow tract and supports the pulmonary valve  6,7]. D,7. D6,7]The distinct hemodynamic environment  explains the organized fashion in which the RV contracts. The contraction of the RV resembles a peristaltic motion, with the inlet and apical regions contracting first, and the conal one 20 to 50 ms later . The floThe RV performance is the result of the interaction between contractility, afterload, and preload. Through the concept of ventricular interdependence, the size, shape, and compliance of one ventricle affect the other. Consequently, RV function is directly influenced by the systolic ventricular interdependence, through the IVS. The diastolic ventricular interdependence is mostly related to the degree of pericardial constraint . The twoOn one end, the development of PAH secondary to left-sided cardiac disease has a complex pathophysiology that involves the interplay between the LV, the left atrium (LA), and the mitral valve (MV) apparatus . The enlOn the other end, the myopathic involvement of the RV in DCM is multifactorial and depends on the underlying etiology. Thirty to forty percent of patients with DCM have biventricular involvement, with the same myopathic process affecting both ventricles. One strong predictor of RV dysfunction is a reduced LVEF . FurtherRV function has been shown to significantly impact patient prognosis in several cardiac conditions ,34,35,36Although not considered the gold-standard technique for the evaluation of the RV due to multiple considerations , transthoracic echocardiography (TTE) remains the first-line imaging modality used for the assessment of the RV due to its wide availability and cost-efficiency. The functional evaluation of the RV by TTE is usually based on two-dimensional echocardiography (2DE). However, advanced echocardiographic techniques, such as speckle-tracking echocardiography (STE) and three-dimensional echocardiography (3DE), have become mandatory for the accurate quantification of the RV function ,39,40,41TA plane systolic excursion (TAPSE) measurement by M-mode echocardiography evaluates the systolic motion of the TA towards the RV apex at the level of the lateral TA  42]. Ho. Ho42]. A TAPSE < 16 mm is considered suggestive of RV systolic dysfunction . The proThe systolic velocity of the lateral TA by tissue Doppler imaging (TDI) is another measurement of RV longitudinal function  43]. Fu. Fu43]. The RV myocardial performance index (RV MPI) or Tei index is a unitless parameter which provides information about global systolic and diastolic RV function. It can be measured either with TDI or pulsed Doppler (PW) by dividing the total isovolumic time  to the ejection time (ET). The TDI method has the advantage of simultaneously recording time intervals from the same cardiac cycle. Since this measurement is based only on time intervals, it surpasses the limitations of RV shape and geometry. However, it is less useful in irregular heart rhythms. Proposed cut-offs for an abnormal RV MPI are >0.43 (PW) and >0.54 (TDI) . ImpaireRV fractional area change (FAC) is obtained by measuring RV end-diastolic and end-systolic areas after manually tracing the RV endocardial borders in the RV-focused apical 4 chamber (A4C) view  53]. RV. RV53]. The systolic performance of the RV can be evaluated with the use of myocardial deformation imaging techniques. The current recommendation in clinical practice is to evaluate the RV free wall longitudinal strain (FWLS) in the RV-focused A4C view by STE  53,58].,58.53,58The aforementioned limitations of classical RV function parameters assessed by 2DE  can be overcome by the use of 3DE . FurtherA 3DE RVEF < 45% is consistent with RV dysfunction . DespiteAll the aforementioned echocardiographic parameters, each with several advantages and limitations, have proven useful in diagnosing RV dysfunction in DCM patients, especially when the evaluation follows a multiparametric approach. Furthermore, recent studies suggest that the presence and pattern of RV dysfunction influence the response to HFrEF therapies. Yanis Bouali et al. evaluated two HFrEF phenotypes undergoing treatment with sacubitril/valsartan (S/V). Among the dissimilarities between the phenotypes, TAPSE (16 ± 4 mm vs. 19 ± 4 mm), RVFWLS (−19 ± 5% vs. −21 ± 4%), and RVFAC (31 ± 9% vs. 38 ± 9%) were found to be significantly lower at the initiation of therapy compared to follow-up. The phenotype with more significant RV failure at baseline had worse prognosis during the treatment period. However, the evolution of RV function was characterized by a significant improvement in TAPSE, RVFAC, and RVFWLS in both groups. Moreover, the improvement in TAPSE was correlated with both LVEF and LV GLS. These findings support the belief that there is a connection between LV and RV reverse remodeling in patients undergoing HF therapies which have been mainly attributed to LV dysfunction . A systeFinally, dimensional and functional RV parameters obtained by echocardiography are helpful in differentiating physiological RV remodeling found in athlete’s heart from the pathological RV remodeling encountered in conditions such as arrhythmogenic right ventricular cardiomyopathy (ARVC). Although the RV dimensional remodeling has a dissimilar pattern in the two conditions , with thPressure–volume loops (PVL) derived from right heart catheterization (RHC) are considered the gold-standard methods for the evaluation of RV function in relation to the afterload. The relationship between RV contractility and afterload is described as right ventriculo-arterial coupling (RVAC), and is defined as the ratio between end-systolic elastance (Ees) and arterial elastance (Ea). A normal Ees/Ea reflects an optimal balance between RV mechanical work and oxygen consumption ,84. In lThe assessment of RV systolic function in patients with DCM started more than 2 decades ago, with the evaluation of RVEF by invasive techniques with limited clinical applicability, such as thermodilution or contrast ventriculography ,94,95. NRV dysfunction is common and yields an unquestionable prognostic significance in DCM patients. In several studies, RV dysfunction emerged as a predictor of adverse events both at baseline and during long-term follow-up. Compared to the classical echocardiographic parameters such as TAPSE, S’ wave velocity, Tei index, and RVFAC, more advanced imaging techniques, namely RV strain by STE, RVEF by 3DE and CMR, and non-invasive echocardiographic surrogates of RVAC, provide improved risk stratification in DCM patients. Multimodality cardiac imaging is of paramount importance for the accurate evaluation of RV systolic function in DCM patients, providing diagnostic, prognostic, and therapeutic implications.


The probability of hospital discharge was 34% lower (HR 0.66/95% CI 0.47–0.93) for subjects with diastolic dysfunction based on selected TEE parameters, independent of potential confounders, including a baseline diagnosis of heart failure. There was a dose–response relation between severity of diastolic dysfunction and probability of discharge. LV diastolic dysfunction based on those selected TEE parameters was also associated with postoperative cardio-respiratory complications; however, these complications did not fully account for the relation between LV diastolic dysfunction and prolonged length of hospital stay. (9) Conclusions and Relevance: In patients with normal systolic function undergoing CAB, diastolic dysfunction based on selected TEE parameters is associated with prolonged duration of postoperative hospital stay. This association cannot be explained by baseline comorbidities or common post-operative complications. The diagnosis of diastolic dysfunction can be made by TEE.(1) Importance: Abnormal left ventricular (LV) diastolic function, with or without a diagnosis of heart failure, is a common finding that can be easily diagnosed by intra-operative transesophageal echocardiography (TEE). The association of diastolic function with duration of hospital stay after coronary artery bypass (CAB) is unknown. (2) Objective: To determine if selected TEE parameters of diastolic dysfunction are associated with length of hospital stay after coronary artery bypass surgery (CAB). (3) Design: Prospective observational study. (4) Setting: A single tertiary academic medical center. (5) Participants: Patients with normal systolic function undergoing isolated CAB from September 2017 through June 2018. (6) Exposures: LV function during diastole, as assessed by intra-operative TEE prior to coronary revascularization. (7) Main Outcomes and Measures: The primary outcome was duration of postoperative hospital stay. Secondary intermediate outcomes included common postoperative cardiac, respiratory, and renal complications. (8) Results: The study included 176 participants ; 105 (60.2%) had LV diastolic dysfunction based on selected TEE parameters. Median time to hospital discharge was significantly longer for subjects with selected parameters of diastolic dysfunction (9.1/IQR 6.6–13.5 days) than those with normal LV diastolic function (6.5/IAR 5.3–9.7 days) ( Risk scoring systems for cardiac surgery patients first became popular with the Parsonnet score to calculate mortality risk . Though Heart failure (HF) is increasingly becoming a worldwide health burden, and the USA is no exception ,7,8. A s2), a marker of diastolic dysfunction recommended by American society of Echocardiography was elevated in only 18% of the study patients [Coronary artery disease and myocardial ischemia can affect diastolic function and often precedes systolic dysfunction. That is why many patients who have severe CAD requiring coronary artery bypass (CAB) may have diastolic dysfunction yet preserved EF . Kim et patients ,21.Many patients for CAB in our institution were referred from other peripheral hospitals with TTE or cardiac catheterization reports indicating significant multivessel CAD without actual images of TTE or catheterization. In those that did, very few had complete evaluations of nonsystolic function. However, all these patients would receive a TEE intraoperatively during CAB as standard protocol unless there is active contraindication. This prompted us to conduct a prospective cohort study involving subjects with normal systolic function undergoing CAB surgery to evaluate the association between intraoperative TEE metrics of LV performance during diastole and postoperative outcomes. The TEE algorithm depends on a limited number of metrics of performance during diastole and is validated to predict 5-year composite outcomes following CAB . We hypoPatients who underwent CAB using cardiopulmonary bypass (CPB) at the Johns Hopkins Hospital (JHH) from September 2017 to June 2018 and underwent a TEE examination to assess diastolic function were eligible for inclusion. Individuals were excluded for any of the following: left ventricular ejection fraction <50%; preoperative electrical pacing; inotropic support; or mechanical ventricular support. Institutional approval by the Johns Hopkins Medical Institutional Review Board was received, and requirement for written informed consent was waived. All study patients underwent CAB using CPB with cardioplegic arrest. None of the patients in the study had an off pump or beating heart surgery.A protocol for evaluating performance during diastole by intraoperative TEE was introduced at JHH in January 2017 and intended for all patients undergoing CAB surgery. Examinations were performed after induction of anesthesia and prior to coronary artery revascularization, i.e., prior to CPB, though timing in relation to sternotomy or phase of respiratory cycle were not standardized. All TEEs were performed by physicians certified by the National Board of Echocardiography (NBE) in advanced perioperative TEE or by cardiac anesthesia fellows under the direct supervision of a certified physician. Metrics of performance during diastole were interpreted by a single physician (JMD) blinded to each subject’s preoperative comorbidities and postoperative course. The TEE evaluation of performance during diastole was modified from that of Swaminathan et al.  and inclBaseline (prior to surgery) demographic characteristics, comorbidities, and laboratory data were extracted from the medical record. Medical care throughout the hospital course was at the direction of the clinical team, who recorded diagnoses (ICD-10 codes), laboratory tests, and medications as part of routine care. The clinical team was not blinded to results of the evaluation of performance during diastole. Follow-up included the intraoperative and postoperative care phases until the time of hospital discharge. Complications were determined from abstraction of data routinely recorded in the medical record. Intravenous fluids and red blood cells administered volumes were abstracted from the medical record from time of surgery through the 4th postoperative day.The primary outcome, time to hospital discharge, was defined as the time from end of surgery to hospital discharge. Secondary outcomes were: interval until extubation (requiring greater than 6 h following end of surgery), interval until free of supplemental oxygen (days from end of surgery to breathing room air), composite cardio-respiratory morbidity , new atrial fibrillation, postoperative hypotension, hypervolemia, acute kidney injury  , stroke,t-test, Kruskal–Wallis, and chi-square test. Distinct clusters (heterogenous groups) within a patient sample were evaluated using latent class analysis (LCA) to classify subjects into multiple comorbidity groups based on comorbidities present at admission. LCA uses the joint distribution of observed responses across all individuals on a set of items  to characterize an underlying categorical latent variable that subdivides the given population into a smaller number of groups using modal class assignment. LCAs were conducted using the 12 baseline variables representing comorbidities based on cardiovascular diseases, chronic lung diseases, obesity, and baseline ASA score. Since the number of clusters is unknown a priori, statistical comparisons of model fit, based primarily on the log likelihood value and Bayesian Information Criterion (BIC), were used to compare models with an increasing number of clusters. An LCA is particularly suitable because of its ability to specify unobserved (latent) subgroups of individuals [Continuous variables were summarized using mean ± SD. Categorical variables were summarized using percentage. Variables were compared across subjects with normal and diastolic dysfunction using ividuals .coxph” function.Cox Proportional Hazard models, with the response variable being ‘time to discharge’ and the event variable being ‘discharge’, were used to evaluate the association between time to discharge and diastolic dysfunction with and without adjustment for confounding variables. Additional Cox models were used to determine the role of secondary outcomes in mediating the relationship between diastolic dysfunction and time to discharge. Survival analyses were performed using the R programming environment. All estimates and confidence intervals (CIs) were obtained using the “n = 105) vs. normal (n = 71) baseline performance during diastole are shown in The mean number of grafts that were revascularized was 3.35 ± 1 . TEE evaluation of function during diastole was inconsistently completed, but consistency increased over the course of the study, approaching 90% of eligible patients by the end of the study. Relative frequency of reasons for incomplete evaluation  could not be determined. Data were captured on 176 eligible subjects . Baseline characteristics of study participants with abnormal . Probability of hospital discharge on any given postoperative day (hereafter referred to as “daily probability of discharge”) was significantly lower for those with diastolic dysfunction  (function . There wfunction .Model 1), duration of CPB , severity of illness latent class  history of heart failure and myocardial infarction (Model 3), the daily probability of discharge remained significantly lower for those with diastolic dysfunction.Adjusting for age, sex , Model 1farction , Model 3p < 0.001); (2) tended to be lower in the group with diastolic dysfunction and low severity of illness ; (3) had no pattern of relation for the two strata with normal performance during diastole (Model 3), the association between abnormal e′ and discharge was unchanged (RR 0.61/95% CI 0.42–0.88). Abnormal E was also independently associated with discharge (RR 0.61/95% CI 0.39–0.94), but E/e′ was not (RR 0.85/95% CI 0.48–1.52).A sensitivity analysis excluding five subjects with more than mild valvular disease  did not affect these results (RR 0.63/95% CI 0.45–0.90). Our propensity analysis successfully matched 42 subjects with and without selected parameters of diastolic dysfunction , and showed that daily probability of discharge was 37% lower (RR 0.63/95% CI 0.40–1.00) for those with diastolic dysfunction. Our LCA showed the daily probability of discharge: (1) was significantly lower for the group with both diastolic dysfunction and high severity of illness latent class  or transfusion of packed red blood cells  between subjects with and without diastolic dysfunction. Secondary intermediate outcomes are shown in There were no significant differences in intravenous fluid administration  associated with a significantly longer postoperative hospital stay; (2) associated with a greater baseline comorbidity burden. Still, multivariate analysis showed their 35–40% lower daily probability of discharge  was independent of baseline comorbidities, including heart failure and myocardial infarction; (3) dose-dependently related to daily probability of discharge; and (4) associated with numerous complications after surgery, particularly heart failure and respiratory insufficiency/failure. These complications did not fully account for the relationship between diastolic dysfunction and daily probability of discharge.Compared to patients with normal performance during diastole, we observed a 31% longer mean hospital stay in patients with diastolic dysfunction based on intraoperative TEE assessment of LV performance during diastole. This does not appear to be an artifact driven by outliers, given the nature of the nonparametric Kruskal–Wallis evaluation performed. The unadjusted ratio for daily probability of discharge in a patient with selected parameters of diastolic dysfunction is 0.54. This suggests a 46% lower daily probability of discharge if a patient has any degree of diastolic dysfunction . We have previously demonstrated that, independent of systolic function, preoperative TTE-measured diastolic dysfunction is associated with prolonged hospitalization as part of a combined endpoint in patients undergoing CAB, aortic valve replacement, or combined CAB and aortic valve replacement . Severe The graded association between abnormal nonsystolic TEE metrics and prolonged post-CAB hospital stay that we observed in this study mimics the graded association between diastolic dysfunction and event-free five-year survival reported following CAB surgery . Both stThe relevance of the E/e′ ratio as an indicator of left sided filling pressures ,35,36,37There are several limitations to our prospective cohort study. First, protocol adherence was inconsistent over the course of the study. Limited feedback with respect to obstacles to adherence prohibits a true understanding as to the breadth of the protocol’s utility. The small study population restricts subgroup size, preventing utilization of a more robust statistical analysis. Thus, while our LCA and the propensity score analyses indicate that co-morbidities do not account for the entire effect of baseline diastolic dysfunction on hospital stay, a large number of our propensity score subjects did not have good matches. The study population size may also obscure the identification of an interaction between diastolic dysfunction and a perioperative morbidity. Finally, the true value of E/e′ remains unclear. Although originally defined as a noninvasive approach to evaluate left heart filling pressures , this coIn conclusion, we found that, compared to normal intraoperative TEE metrics during diastole prior to CPB, abnormal nonsystolic echocardiographic parameters are associated with a 31% longer hospital stay following CAB surgery in patients with normal baseline left ventricular systolic function. In this case, diastolic dysfunction is indicated by the presence of selected parameters—either E > 50 cm/s or e′ < 10 cm/s. The daily probability of discharge is inversely related to the severity of performance abnormality during diastole in a dose-dependent manner. The prolongation in hospital stay could be accounted for neither by baseline comorbidities nor by post-op complications. Larger studies are needed to confirm the consistency of these results and to elucidate a modifiable cause of the prolonged hospital stay.