Left ventricular noncompaction (LVNC) is characterized by a bilayered appearance of the myocardium with excessive trabeculations and deep intertrabecular recesses. Manifestations of this condition are widely variable, ranging from incidental findings in asymptomatic individuals to symptomatic heart failure, conduction abnormalities, tachyarrhythmia, and sudden cardiac death. Heart failure, ventricular arrhythmias, and systemic embolisms are the most frequent cardiovascular complications.We describe a case of a 53-year-old woman who presented to the emergency department with acute presentation of previously unknown heart failure with reduced ejection fraction and was diagnosed with LVNC. During hospitalization, the patient presented a defibrillated cardiac arrest rhythm, which was resuscitated after six minutes, and then treated with the placement of an implantable cardioverter defibrillator. After two years of follow-up with optimized medical therapy, the patient currently is asymptomatic and with a preserved ejection fraction. The pathogenesis of left ventricular noncompaction (LVNC) has been regarded as an arrest in myocardium compaction during embryogenesis due to genetic causes . It is cThe main cardiac symptoms are related to heart failure (HF), which occurs in half of the patients; atrial fibrillation and ventricular tachyarrhythmias are also frequent . LVNC is2 21%, and respiratory rate of 22 breaths per minute. The physical examination showed positive hepatojugular reflux, without jugular vein distention at 45º, no murmurs were identified on cardiac auscultation, and diffuse bilateral inspiratory wet pulmonary crackles and moderate wheezes were heard on pulmonary auscultation. Laboratory evaluation showed hypochromic microcytic anemia, normal kidney, liver, and thyroid function, elevated C-reactive protein (102 mg/L), and no elevation in myocardial injury markers, although an elevated B-natriuretic peptide (BNP) level of 4270 pg/mL was noted. An electrocardiogram (ECG)  with shortness of breath on minimal exertion for two months, worsened in the six days prior to admission and progressing to dyspnea at rest, and orthopnea, associated with scanty dry cough. The patient denied fever, myalgias, chest pain, paroxysmal nocturnal dyspnea, and lower limb swelling. On admission to the ED, the patient had a blood pressure of 130/60 mmHg, pulse rate of 99 beats/minute, regular rate and rhythm, a body temperature of 37.8ºC, pulse oximetry of 96% at FiODue to decompensated non-stratified HF diagnosis and a community-acquired tracheobronchitis, empiric antibiotic therapy was initiated with amoxicillin/clavulanic acid and azithromycin and the patient was admitted to the internal medicine unit.An echocardiogram performed during admission revealed severe dilatation of the left ventricle, with left ventricular ejection function (LVEF) estimated at 31%, and also described as left eccentric ventricular hypertrophy; inferior vena cava was not dilated. During hospitalization, the patient remained symptomatic despite high-dose diuretics, associated with an increase in BNP of 10712 pg/mL.Cardiac magnetic resonance imaging (MRI) Figure  was perfThe following day, a cardiorespiratory arrest was witnessed and resuscitated promptly. Ventricular fibrillation was identified and a shock was administered, with spontaneous circulation recovery after, with a total arrest time of six minutes. The patient was admitted to a cardiac care unit and an implantable cardioverter defibrillator (ICD) was placed. When clinically stable, therapy with an angiotensin receptor-neprilysin inhibitor (ARNI) was initiated. After 19 days of admission, the patient was discharged and referred to a cardiology consultation. Smoking cessation was advised.The genetic study was negative and included a search for mutations in the following genes: LIM domain-binding protein 3, α-dystrobrevin, tafazzin, MYH7, ACTC1, TNNT2, TPM1, TNNI3, and MYBPC3. The patient started anticoagulation due to a deep vein thrombosis.During the first 16 months of follow-up under optimized tolerance-based ARNI, bisoprolol, and spironolactone therapy, an improvement in left ventricular function was achieved with transthoracic echocardiography revealing an ejection fraction of 55%.LVNC is characterized by the excessive formation of trabeculae and intertrabecular recesses in the uncompressed inner myocardial wall associated with the mesocardium, mostly affecting the apical region of the left ventricle, but in rare cases, it can affect the right ventricle . It was The main cause of LVNC is the mutation of genes encoding sarcomeric proteins, but also mutations in genes encoding cytoskeletal, Z-line, and mitochondrial proteins may be identified . The mosNine subtypes are described: isolated or benign, the arrhythmogenic form, the dilated form, the hypertrophic form, the “mixed” form, the restrictive form, the biventricular form, the right ventricular hypertrabeculation with normal left ventricular (LV) form, and the congenital heart disease form . In someThere is a mismatch between myocardial mass and the number of capillaries, leading to hypoperfusion of the endocardium, despite normal epicardial coronary arteries, with hypokinetic areas observed both in compacted and noncompacted segments . Also, tInitial ECG’s most common findings are intraventricular conduction delay, including left branch block, auriculoventricular block, and repolarization abnormalities such as QTc prolongation; also, LV hypertrophy is often present, although it can be normal in 13% of cases ,9,10. ECManifestations of this condition are widely variable, ranging from incidentally identified cardiac findings in asymptomatic individuals with or without cardiovascular risk factors to symptomatic HF, conduction abnormalities, tachyarrhythmia, and sudden cardiac death . MalignaManagement and treatment of LVNC are centered on the prevention of major complications, namely, stroke and sudden cardiac death . ICD is Prognosis is heterogeneous, and HF, ventricular arrhythmias, and systemic embolisms are the most frequent cardiovascular complications . LVEF < LVNC is a genetic disease with a wide variety of clinical presentations. HF and cardiac arrest secondary to ventricular arrhythmias are severe manifestations of the disease and determine a poor prognosis. We highlight an interesting case of LVNC, which was treated with ICD for secondary prevention and combined medical therapy with ARNI, beta-blockers, and mineralocorticoid receptor antagonists, and was noted to have a good long-term outcome. However, per current evidence, it is still unclear which patients respond well to appropriate treatment, and it is difficult to predict improvement in cardiac function. We reported a brief discussion and literature review on the current evaluation, management, and prognosis of patients with LVNC.


Bronchopulmonary dysplasia (BPD) is still a major concern in preterm infants and adequate screening methods for secondary right ventricle (RV) failure are needed. Early detection could be aided by taking measurements of RV deformation using speckle tracking echocardiography. A prospective longitudinal study was carried out over 28 months at a tertiary care pediatric cardiology center. Preterm infants < 32 weeks gestational age (GA) were eligible for the study. Enrolled patients were separated in two groups: NO-BPD or BPD. At three timepoints over the first year of life, echocardiogram measurements were performed. Right ventricle strain was studied using speckle tracking analysis and compared to conventional function parameters.Fifty patients were enrolled in the study, 22 in the NO-BPD group and 28 in the BPD group. RV strain showed no statistical differences between groups. However, the BPD group showed worse RV function than the NO-BPD group, using speckle tracking analysis and other conventional parameters. During the study follow-up, an improvement trend is shown in RV strain.RV longitudinal strain and strain rate derived by speckle tracking is feasible in preterm infants. Although there seems to be a good correlation between RV strain and BPD severity, the results of this study were not conclusive. More studies should be carried out to investigate the optimum echocardiographic screening model of RV dysfunction in BPD patients.The online version contains supplementary material available at 10.1186/s43044-023-00336-7. Perinatal medicine has experienced many advances over the last two decades. Despite this, bronchopulmonary dysplasia (BPD) is still one of the most common and worrying diseases in the preterm newborn . BPD is BPD indicates the presence of perturbations on the lung alveolar septation with varying degrees of lung fibrosis and inflammation. BPD is usually associated with abnormalities in lung microvascular development, which may contribute to the modified alveolar septation. Furthermore, lung capillary and arterioles are usually affected in BPD patients, with thicker-walled pulmonary arteries. In view of this, it is possible to consider that BPD patients not only suffer from alterations in lung structure and function but also may have increased vascular resistance and pulmonary arterial pressures . TherefoRV myocardial deformation during the cardiac cycle can be studied through strain analysis. 2D speckle tracking (STE) is a recent application software for strain study. STE imaging provides frame-by-frame tracking of ultrasound markers, is angle independent, is less sensitive to signal noise, and is not influenced by breathing movement or by the interaction with the adjacent myocardium. This technique has enabled earlier detection of subtle RV dysfunction . The aimThis prospective longitudinal study was carried out over 28 months (from April 2019 to July 2021) at a tertiary care pediatric cardiology referral center. All preterm infants (PTI) < 32 weeks who were born before July 2020 were eligible for the study. Twenty-eight days after birth, all enrolled patients were included in one of two groups: no bronchopulmonary dysplasia (NO-BPD) or bronchopulmonary dysplasia (BPD). They were screened during routine follow-up at a tertiary care pediatric referral center, which routinely includes several cardiac evaluations. Follow up data was collected at three timepoints: at 36 PMA or discharge (T1), between 5 and 9 months of life (T2), and between 11 and 16 months of life (T3)  if the variable did not meet the assumptions for data normality. Categorical variables were expressed by absolute frequency as well as percentage. The association between parametric variables was measured using Pearson correlation and for non-normal variables, the spearman correlation coefficient instead. For assessed normal samples, mean differences were tested by t-Student test. In other cases, U-Mann–Whitney test was performed. Pearson's Chi-square test was used for comparisons between categorical variables. The relationship with time was determined by the Friedman test. The reproducibility of GLS measurements was assessed using intra and interobserver reliability using 10 blinded images randomly sampled from the study. Intraobserver reliability was good, with an intraclass correlation coefficient (ICC) above 0.77. Interobserver reliability was relatively good, with an ICC above 0.69.SPSS software version 25.0  was used for performing statistical analysis. Any difference was considered statistically significant in all tests when the Fifty patients were enrolled in the study, 22 in the NO-BPD group and 28 in the BPD group . Characteristics are revealed in Table Ultrasound parameters of cardiac function were measured. The results are expressed as mean and standard deviation, or median and interquartile range Table . At T1, R = 0.617) and between GLS-RV vs. GLS-LV (R = 0.403). A small positive correlation was found between GLS-RV vs. TAPSE (R =  + 0.303). No correlation was found between GLS-RV and SW . No differences were found in strain variables of both ventricles , RV-FS, RA index and PAAT / RVET ratio. However, an improvement trend is shown in GLS-RV  represents the most common and reliable method to evaluate the presence and severity of PH . In our Ventricular function derivates from the contraction and relaxation of a complex architecture of myocardial fibers. As a result, the assessment of myocardial deformation by two-dimensional speckle tracking echocardiography gained greater acceptance. It has been proved that strain measurements can be used as an early marker of cardiac dysfunction. It is also known that RV strain is a feasible technique , 16. RV Xie et al. evaluated strain in children between 3 and 5 years old. They found some differences in RV strain between preterm BPD patients and term infants, and that duration of invasive ventilation was independently linked with GLS-RV . In our Haque et al. also studied RV function in BPD patients. They did not find differences in traditional echocardiographic parameters, but using speckle tracking they discovered that infants with severe BPD had lower peak global systolic strain than infants with moderate BPD or mild/none BPD . HoweverBlanca et al. designed a similar study to ours . They inAs for the GLS-LV data in the BPD group at T1, we propose a correlation with RV function. When echocardiographic measurements were taken, the septum took part in LV strain so RV movement may be related to these findings. Czernik et al. (2014) studied LV strain over the first month of life in BPD patients. They found higher values of LV strain in the BPD group during the first two weeks of life, which disappeared at one month of life. They suggest their findings reflect the hemodynamic changes that appear within the first days of life and the volume overload that generates a patent ductus permeable . In our This study has several strengths and limitations. The main strengths include the longitudinal follow-up over the first year of life and the standardized collection of data. We used the same equipment and protocol for all patients and echocardiographic images and measurements were made by the same investigators. The study was limited by offline speckle tracking analysis. The dependence of 2D-STE imaging on the frame-by-frame tracking of the myocardial pattern means it is influenced by image factors, including reverberation artefacts and attenuation. Thus, we lost too many cases at T3, due to the requirement of a very good loop imagen to complete a reliable strain analysis. Our study was also limited by the small sample size which makes difficult to find significant differences and generates large variances. It is possible that incorporating patients with PH in this study may have given further insight into the clinical presentation of patients with BPD.Our study demonstrates that, even though it is challenging, measuring RV longitudinal strain and strain rate derived by speckle tracking is feasible in preterm infants. Although the authors of this study did not find any statistical differences between the groups, good correlation between RV strain and BPD severity was observed. More studies should be carried out to investigate the optimum echocardiographic screening model of RV dysfunction in BPD patients (including strain measurements or not) and to confirm that non-PH patients who suffered from BPD maintain normal RV function with age.Additional file 1. Echocardiographic measurements at the three timepoints. Classification according to the presence of a significant patent ductus arteriosus (PDA) which needed treatment (drugs or surgery). Mean (Standard Deviation) for parametric variables and T-Student test for comparison between groups . Median  for non-parametric variables and U-Mann-Whitney test for comparison between groups .


Coronary angiography and viability testing are the cornerstones of diagnosing and managing ischemic cardiomyopathy. At present, no single test serves both needs. Coronary wave intensity analysis interrogates both contractility and microvascular physiology of the subtended myocardium and therefore has the potential to fulfil the goal of completely assessing coronary physiology and myocardial viability in a single procedure. We hypothesized that coronary wave intensity analysis measured during coronary angiography would predict viability with a similar accuracy to late-gadolinium–enhanced cardiac magnetic resonance imaging.Patients with a left ventricular ejection fraction ≤40% and extensive coronary disease were enrolled. Coronary wave intensity analysis was assessed during cardiac catheterization at rest, during adenosine-induced hyperemia, and during low-dose dobutamine stress using a dual pressure-Doppler sensing coronary guidewire. Scar burden was assessed with cardiac magnetic resonance imaging. Regional left ventricular function was assessed at baseline and 6-month follow-up after optimization of medical-therapy±revascularization, using transthoracic echocardiography. The primary outcome was myocardial viability, determined by the retrospective observation of functional recovery.−2 s−1, P<0.001), and had comparable accuracy to cardiac magnetic resonance imaging for predicting viability ; a threshold of −2500 W m−2 s−1 had 86% sensitivity and 76% specificity.Forty participants underwent baseline physiology, cardiac magnetic resonance imaging, and echocardiography, and 30 had echocardiography at 6 months; 21/42 territories were viable on follow-up echocardiography. Resting backward compression wave energy was significantly greater in viable than in nonviable territories (−5240±3772 versus −1873±1605 W mBackward compression wave energy has accuracy similar to that of late-gadolinium–enhanced cardiac magnetic resonance imaging in the prediction of viability. Coronary wave intensity analysis has the potential to streamline the management of ischemic cardiomyopathy, in a manner analogous to the effect of fractional flow reserve on the management of stable angina. Myocardial viability testing is an important diagnostic consideration in patients with ischemic cardiomyopathy.Coronary wave energy predicts functional recovery in patients with non–ST-segment–elevation myocardial infarction‚ but its use as a viability test in ischemic cardiomyopathy is unknown.Backward compression wave energy, measured with coronary wave intensity analysis, can be used to assess myocardial viability during cardiac catheterization.The accuracy of wave intensity analysis is similar to late-gadolinium–enhanced cardiac magnetic resonance imagingWith further validation and technical development, coronary wave energy could be a useful index for routinely assessing viability in the catheterization laboratory.1 The prognosis of these patients remains poor, with mortality rates of approximately 50% at 5 years, often preceded by recurrent hospitalizations for decompensated heart failure.2 Improving left ventricular function is a key therapeutic goal in ICM, which is associated with improved survival and quality of life; optimal medical therapy, device therapy, and revascularization may all have roles in achieving such improvements, with recent data suggesting that optimal medical therapy is the primary driver of improved left ventricle function.4Ischemic cardiomyopathy (ICM) accounts for 50% to 70% of cases of heart failure in North America and Europe.3 Furthermore, the REVIVED-BCIS2 trial (Revascularization for Ischemic Ventricular Dysfunction) showed no benefit to viability-guided percutaneous coronary intervention (PCI), where most of the testing was performed with LGE-CMR and dobutamine stress echocardiography.4 A vessel-specific index of ischemia and viability may allow the identification of the substrate of hibernation and patients who may benefit from revascularization.3Myocardial viability testing aims to prospectively identify regions of myocardium where function is likely to recover. At present, testing is achieved with noninvasive imaging methods, including late-gadolinium–enhanced cardiac magnetic resonance imaging (LGE-CMR), stress echocardiography, and nuclear imaging. Although well validated for the prediction of functional recovery, noninvasive viability testing has several limitations: it requires resources that are not universally available, certain modalities are frequently contraindicated in patients with ICM (such as CMR with cardiac devices), and the distribution of viability is not co-registered to the coronary anatomy. An analysis of viability testing in the STICH trial  showed no incremental benefit to coronary artery bypass grafting in patients with extensive viability defined by dobutamine stress echocardiography or single photon emission computed tomography.5 We have previously demonstrated that the energy of the backward originating waves (backward expansion wave [BEW] and backward compression wave [BCW]) predict recovery of regional function in patients presenting with large non–ST-segment–elevation myocardial infarction.6At present, there is no established technique for assessing myocardial viability in a vessel-specific manner at the time of angiography. Coronary wave intensity analysis (cWIA) is a promising solution. cWIA uses simultaneous intracoronary pressure and Doppler flow data to measure the energy fluxes that drive or impede myocardial perfusion, characterized as forward (originating from the aorta) or backward (originating from the microcirculation) waves.In the current study, we investigated whether cWIA could accurately assess myocardial viability in patients with stable ischemic cardiomyopathy treated with optimal medical therapy (with or without revascularization). Furthermore, we hypothesized that cWIA derived during dobutamine stress would improve the prediction of viability compared with measurements in resting conditions.7 Exclusion criteria were acute coronary syndrome within 4 weeks, contraindication to LGE-CMR, and severe valvular heart disease. All participants gave written informed consent in accordance with the protocol approved by the UK National Research Ethics Service (18/LO/0171). The study was registered with the National Institute for Health Research UK Clinical Research Network Portfolio database .The data that support the findings of this study are available from the corresponding author upon reasonable request. Patients with a recent diagnosis of ICM who were scheduled for coronary angiography and/or percutaneous coronary intervention at one of the following UK centers were enrolled in the study: St Thomas’ Hospital, London; King’s College Hospital, London; Bristol Heart Institute, Bristol. Inclusion criteria were impaired left ventricular systolic function (ejection fraction ≤40%) and extensive coronary artery disease (British Cardiovascular Intervention Society Jeopardy Score ≥8).8 Aortic pressure was measured from the guide catheter. Measurements were performed in all vessels with a visually significant stenosis unless the operator felt that a pressure wire study could not be safely performed without disrupting the lesion or if the vessel was occluded. Hemodynamic measurements were recorded under resting conditions, during intracoronary adenosine-mediated hyperemia (up to 120 mcg in the left coronary and 96 mcg in the right coronary) and at the end of each stage of an incremental low-dose dobutamine infusion . The myocardial segments subtended by each diseased vessel was determined using a prespecified algorithm based on the American Heart Association 17 segment model, by 2 independent observers who were blinded to the physiological, echocardiographic, and CMR data .9 This segmental attribution was used to determine regional viability. Angiographic stenosis severity was measured by quantitative coronary angiography.Cardiac catheterization was performed using 6Fr catheters from either the radial or femoral arteries. Intracoronary isosorbide dinitrate  was administered. After assessment of the coronary anatomy, a dual pressure-Doppler flow sensing 0.014” coronary guidewire  was used to measure distal coronary pressure and instantaneous peak flow velocity, as previously described.d/Pa during hyperemia, CFR=average peak velocity (APV)hyperemia/APVrest). Wave intensity was calculated as the product of the derivatives of distal coronary pressure (P) and flow velocity (U), (dP/dt × dU/dt), and wave separation performed as previously described .11Pressure and flow data were exported and analyzed using custom-made software . Fractional flow reserve (FFR) and coronary flow reserve (CFR) were determined using pan-cycle pressure and flow data  . Where this was not possible , a 1.5 T scanner was used . The same protocol was used on the 2 scanning platforms, with a dual-RF transmission and a 32-channel phased array body coil. LGE images were acquired at least 10 minutes after the administration of a 0.15 mmol/kg bolus of gadobutrol. Scar quantification was performed using the PSIR-LGE images in the short-axis; voxels with a signal intensity 5 standard deviations greater than normal myocardium were identified as scar. The standard clinical threshold of ≤25% LGE across the subtended territory was used to predict viability.12 Wall motion was scored qualitatively using a 5-point standard scale  and averaged across the territory subtended by each vessel, as above. The primary end point was myocardial viability, defined by a ≥0.5 reduction in average wall motion score between baseline and 6-month follow-up. All patients received maximally tolerated optimal medical therapy: the quality of optimal medical therapy was assessed at baseline and at follow-up (Table S2). Revascularization was performed with PCI, as clinically indicated or as per randomization in the REVIVED-BCIS2 trial,13 either during the same procedure or at a subsequent procedure following multidisciplinary discussion.All 2-dimensional transthoracic echocardiography studies were performed according to the British Society for Echocardiography standard protocol.t-tests. Nonnormally distributed continuous data were reported as median [first quartile–third quartile] and compared using the Mann-Whitney-U and Wilcoxon signed rank tests as appropriate. All analyses were performed in a 2-tailed manner, with a P value <0.05 taken to indicate statistical significance. The ability of each wave to identify viability was assessed by receiver operator characteristic curve analysis and compared with the predictive accuracy of LGE-CMR using the DeLong method14 with optimum sensitivity, specificity, positive predictive value, and negative predictive value determined by Youden index.15 All authors had access to the data and take responsibility for its integrity and analysis.Statistical analyses were performed using SPSS, version 27. After visually assessing for the normality of data, continuous and normally distributed data were reported as mean±standard deviation and compared using paired (within groups) and unpaired (between groups) −2 s−1 had a sensitivity of 0.91 for predicting viability.6 Assuming a 75% rate of the primary end point, we calculated that a sample size of 40 territories would give an absolute precision of 0.1 for the 95% CIs for the same point estimate of 0.91.16In the previously described acute coronary syndrome study, a BEW threshold of 2800 W m4Forty participants were recruited Figure . Sixty-oThirty participants had follow-up echocardiography after a median of 223 175–346] days accounting for 42 vascular territories; 29 of these territories were revascularized with PCI, the remaining 13 were not revascularized. The quality of medical therapy improved in 14 participants (22 territories). The follow-up population did not differ significantly from the population who underwent baseline testing (Table 75–346 daP<0.001). There was no significant difference between viable and nonviable territories in the number of segments subtended  or baseline wall motion . Viability at follow-up was similar in revascularized and non-revascularized territories .Myocardial viability was observed in 21/42 territories (50%); the change in WMSI was −0.75 [−0.55 to −1.13] in the viable territories versus 0 [0 to 0.33] in the nonviable territories , but there was no significant difference in the magnitude of the BEW or the forward waves .The resting BCW had good overall accuracy for the prediction of viability . Of the 42 territories in which remodeling was assessed, 31 territories had ≤25% scar burden. Viability was observed more frequently in territories with ≤25% scar burden . LGE-CMR was an effective predictor of viability on receiver operator characteristic analysis . The optimal cut-off was a scar burden of 12.1%, which provided a sensitivity of 0.86, specificity of 0.57, positive predictive value of 0.67, and negative predictive value of 0.80. The area under the curve for scar percentage was comparable to BCW . CFR was similar between viable and nonviable territories . Multivariate logistic regression analysis demonstrated that resting BCW magnitude and improvement of medical therapy were the only independent predictors of functional recovery, whereas BEW, FFR, revascularization, and wall motion score at baseline were not predictive .Details of the hemodynamic effects of dobutamine across the whole study population are included in the Figure S3).In 33 territories assessed with dobutamine where follow-up echocardiography data were available, there was a strong trend toward higher wave BCW energy in viable territories but no significant difference in other wave energies, whether expressed as absolute values during dobutamine administration or as changes in wave energy from resting conditions. BCW energy during dobutamine stress was predictive of viability, with accuracy comparable to assessment at rest .Although adequately powered for the prespecified primary end point, the study has a relatively small sample size and experienced significant loss to follow-up because of the COVID-19 pandemic, although analysis of demographic features suggest no systematic difference in those patients who were lost to follow-up. Physiological assessment was not possible in around 10% of vessels attempted, due to challenging anatomy or procedural factors. Furthermore, this method cannot be used to assess the viability of territories subtended by chronic total occlusions or vessels with critical stenoses, a subset of coronary lesions to which viability testing is relevant. However, these limitations would not prevent the adoption of invasive assessment as part of a wider armamentarium of testing strategies, with multiple modalities available for different clinical circumstances.22 External validation of these findings in a separate cohort of patients would be a valuable next step.The present study included few territories with extensive infarction, with 90% having <50% scar burden. This likely represents a degree of selection bias in a population who were being considered for revascularization, a consistent issue identified in prior studies and clinical trials including STICH and PARR-2.The acquisition and processing of cWIA are currently limited to academic institutions with specific expertise. Through our multi-center design, we have demonstrated the wider feasibility of this technique, though the general trend in coronary physiology is toward simpler streamlined clinical tools. Increasing interest in the coronary microvasculature, as well as the development of clinical utilities for cWIA as demonstrated in this study, shows the potential for Doppler-based assessment to accurately and efficiently identify patients who would benefit from individualized, physiology-guided therapies, and may stimulate development. Following echocardiography, patients might undergo a full assessment of etiology, coronary disease severity, and viability in a single procedure; a factor that may be of particular benefit to those in whom other imaging is contraindicated. Finally, cWIA demonstrates the potential to separate patients with low scar burden by LGE-CMR, where specificity for viability is low, likely related to the presence of longstanding hibernation, which is irreversible despite the absence of infarction.Backward compression wave energy measured with cWIA accurately predicts myocardial viability at medium-term follow-up in patients with ischemic cardiomyopathy. Invasive coronary physiology may therefore provide a useful adjunct to diagnostic angiography in the assessment of patients with suspected ischemic cardiomyopathy. The administration of dobutamine does not increase the accuracy of invasive assessment in predicting viability.This work was supported by the British Heart Foundation through a clinical research training fellowship award (FS/18/16/33396). The authors are further supported through grants from the British Heart Foundation  and from the National Institute for Health Research (NIHR130593 and 10/57/67). From the British Heart Foundation Centre of Excellence at the School of Cardiovascular and Metabolic Medicine and Sciences, King’s College London, London, United Kingdom and the School of Biomedical Engineering and Imaging Sciences, King’s College London, London, United Kingdom, and the National Institute for Health Research via the Biomedical Research Centre award to Guy’s and St. Thomas’ Hospital and King’s College London.Figures S1–S3Tables S1–S2


All management guidelines of ovarian hyperstimulation syndrome (OHSS) recommend daily monitoring of women's body weight, waist circumference and note that as indicators increase, the severity OHSS also increases. However, the dynamics of abdominal size and its relationship with markers of OHSS severity have not been highlighted. The purpose of this study is to assess the usefulness of various anthropometric indicators for determining the degree of OHSS severity as well as paracentesis indications.Observational study including 76 women complaining with OHSS. Clinical history, physical examination, laboratory tests, and ultrasound measurement of the ovarian volume (OV) and ascites index (AsI) were done in all cases. Intra-abdominal pressure (IAP) was assessed using an intravesical manometer. The anteroposterior diameter of the abdomen (APD) and transverse diameter of the abdomen (TS) were measured with a pelvimeter. The APD/TS ratio was calculated.p < 0.001). The median APD/TS was significantly lower in patients with mild OHSS  compared with severe OHSS  or critical OHSS . Similarly, the median APD/TS of the moderate OHSS group  was significantly lower than that of the severe (p < 0.001) and critical OHSS group (p = 0.001). There was a strong positive correlation between APD/TS and IAP . The APD/TS ratio showed a significant positive correlation with AsI  and OV . No significant differences were observed in age, height, weight, body mass index, hip circumference or waist circumference between moderate, severe and critical OHSS groups.The APD/TS ratio increased progressively and tended to be the highest in the most symptomatic stage of OHSS (Kruskal–Wallis test, The APD/TS ratio is related to the severity of OHSS. Monitoring APD/TS dynamics could be a method of indirectly controlling intra-abdominal volume, compliance of the abdominal wall and IAP. In conjunction with clinical and laboratory data, APD/TS might be an indicator for paracentesis.The online version contains supplementary material available at 10.1186/s12905-022-01701-5. Ovarian hyperstimulation syndrome (OHSS) is a largely iatrogenic condition, associated with significant morbidity and even mortality of healthy women undergoing fertility treatment , 2. GeneAscites progression and ovarian enlargement with OHSS leads to an increase in intra-abdominal pressure (IAP), and in severe and critical formsto the abdominal compartment syndrome (ACS) and associated severe organ dysfunction, which is the main factor of poor outcome among women with this syndrome , 7. Our All OHSS management guidelines recommend daily monitoring of women's body weight, waist circumference (WC) and note that as indicators increase, the severity of OHSS also increases , 10–12. The purpose of this study is to assess the usefulness of various anthropometric indicators in determining degree of OHSS severity as well as indications for paracentesis.2.A total of 76 infertile women who were in an in vitro fertilization program and presented OHSS were included in this study. Sample size was established based on the fact that according to the Ministry of Health of the Saratov Region, during the period from 2015 to 2019, 4800 cycles of ART were performed in all medical institutions of the region. Complications presented by various forms of OHSS requiring outpatient monitoring and hospitalization, were recorded in 95 cases (1.9%). Thus, using the statistical software to calculate the sample size with a 5% maximum acceptable error, 95% confidence level, we obtained a sample size of 76 women with OHSS. All of them were admitted into the gynaecological department of the city clinical hospital No.1 named after Yu.Ya. Gordeev . Anthropometrical, laboratory and clinical data were recorded in all included subjects  using 3.5 MHz sectoral sensors. The ovarian volume (OV) using the prolate ellipsoid formula  and the p-value of < 0.05 was considered significant.The data were analysed using a personal computer-based software package . The Shapiro–Wilk test was used to determine the normal distribution of the sample. Data for non-normally distributed variables are given as the median [interquartile range]. Homogeneity of within-group variances was evaluated by Levene's test. The Kruskal–Wallis test was used to analyse differences between groups. Statistically significant results were followed by Mann–Whitney U-tests with Bonferroni adjustment to detect subgroup differences. Spearman’s correlation coefficients were used to check the association between continuous variables. All probability tests were two-sided and a 2.Anthropometrical data are given in Additional file p < 0.001). The median APD of the mild OHSS group  was found to be significantly lower than that of the severe  and critical OHSS group . Besides that, the median APD of the moderate OHSS group  was significantly lower than that of the severe (p < 0.005) and critical OHSS group (p < 0.05). However, there was no significant difference in APD between mild and moderate or severe and critical OHSS groups (p > 0.05).Significant differences between groups were observed regarding APD measurements (p < 0.001). Figure p < 0.001) or critical OHSS . Similarly, the median APD/TS of the moderate OHSS group  was significantly lower than that of the severe (p < 0.001) and critical OHSS group (p = 0.001). There was no significant difference in APD/TS between mild and moderate or severe and critical OHSS groups (p > 0.05).As expected, APD/TS increased progressively and tended to be the highest in the most symptomatic stage of OHSS p < 0.00. Figure No significant differences were observed in age, height, weight, body mass index, hip circumference or waist circumference between moderate, severe and critical OHSS groups . A significant but weak inverse correlation was observed between APD/TS and the age .Correlation analysis was used to identify whether the APD/TS was independently associated with other anthropometric indicators and IAP, AsI or OV. As anticipated, there was a strong positive correlation between APD/TS and IAP  in IAV . This liIn a study assessing the IAV physiology during pregnancy, the authors confirm that the IAV capacity and the tensile properties of pregnant women's abdominal wall can be predicted by the dynamics of the anteroposterior and transverse abdominal diameters . It shouThe APD/TS ratio and its dynamics are important markers of OHSS severity. The APD/TS ratio increases progressively, reaching the highest values in the most symptomatic stage of OHSS.IAP showed the strongest positive correlation with the APD/TS ratio; however, significant correlations were also found between APD/TS and AsI and OV.When the ratio APD/TS is approaching to 1, and the anteroposterior and transverse abdominal dimensions become equal, the abdomen changes from an ellipse to a sphere, the reserve of abdominal wall stretching is depleted, and IAP exponential growth is observed with the transition from severe to critical OHSS. The APD/TS monitoring can be a method of indirectly controlling IAP, Cab and IAV reserve, without using complex and expensive techniques. The inclusion of APD/TS monitoring in the standard for the management of OHSS might be useful in specifying the severity and timely initiation of treatment, including methods to reduce IAP, prevent further organ dysfunction, and avoid the transition to a more severe stage of IAH and ACS. Finally, in the absence of IAP monitoring capabilities, the APD/TS ratio in conjunction with clinical and laboratory data might be an additional tool for indication for paracentesis.Additional file 1: Table S1. Baseline patients’ characteristics.Additional file 2: Table S2. Clinical and laboratory data according to the severity of ovarian hyperstimulation syndrome.Additional file 3: Table S3. Anthropometric markers according to the degree of severity of the ovarian hyperstimulation syndrome.


Despite numerous benefits of physical activity for cancer patients, the majority is insufficiently active. Previous research has shown that structural barriers negatively affect patients’ physical activity behavior. Identifying underlying mechanisms could help to develop effective strategies that alleviate those barriers and increase physical activity levels. In the current survey study, we investigated whether cancer patients’ self-efficacy, i.e., their confidence in their ability, and their intention to exercise mediated the relationship between structural barriers and physical activity. The results revealed a negative relation between structural barriers and patients’ self-efficacy. Lower self-efficacy, in turn, decreased patients’ intention and their likelihood to engage in physical activity. This mediating effect especially applied to those individuals who were sufficiently active before the diagnosis. Thus, the findings suggest that interventions directly addressing the perception of structural barriers or patients’ self-efficacy in dealing with these barriers might be effective in improving the physical activity levels of cancer patients.Previous research has shown that structural barriers negatively influence the physical activity (PA) behavior of cancer patients, but underlying mechanisms are unclear. The aim of the current study was to explore the potential mediating role of social-cognitive factors, namely PA self-efficacy and PA intention in this context. A total of 856 cancer patients completed a questionnaire on sociodemographic and medical characteristics, pre- and post-diagnosis PA, PA self-efficacy, PA intention, and PA impediment by structural barriers. A serial mediation model was used to test whether the association between structural barriers and post-diagnosis PA was mediated by PA self-efficacy and/or PA intention, in the overall sample and in subsamples defined by individuals’ pre-diagnosis PA. The results confirmed that structural barriers were not directly  but indirectly associated with post-diagnosis PA. Higher impediment by structural barriers decreased the likelihood of sufficient post-diagnosis PA via lower PA self-efficacy  and via the serial pathway of lower PA self-efficacy and lower PA intention . Investigating differences in these mediations by pre-diagnosis PA yielded significance only among previously active cancer patients. Both structural barriers and PA self-efficacy might hence be relevant target points for interventions aiming to improve PA behavior, especially among pre-diagnosis active cancer patients. The benefits of physical activity (PA) for the physical and mental health of people with cancer are widely acknowledged. Previous research has demonstrated that PA is not only associated with increased physical functioning and fitness ,2, reducA better understanding of the mechanisms through which structural barriers impede the activity behavior of people with cancer could help to identify target points for successful interventions. In this context, social-cognitive factors may play an important role as they are not only considered highly relevant for the initiation and maintenance of PA behavior but are also amenable to interventions . Many wiIt is conceivable that cancer patients’ confidence and motivation to engage in PA depend on whether the exercise environment and infrastructure support the specific needs of this target group. Thus, a perceived lack of essential structural preconditions that enable PA during as well as after cancer treatment could negatively affect the individual’s self-efficacy and intention to exercise. Previous studies among patients with chronic diseases, including breast cancer, suggested that the perception of barriers was significantly negatively associated with PA self-efficacy, which in turn was directly related to PA behavior ,31,32. TThus, the aims of the present study were to (a) investigate whether PA self-efficacy and PA intention serve as mediating factors for the association between structural barriers and sufficient PA after the cancer diagnosis and (b) explore whether the proposed mediation model equally applies to the maintenance of PA levels among previously sufficiently active individuals and the increase in PA levels among previously insufficiently active individuals.The present cross-sectional study was part of the large-scale Momentum project Heidelberg, which has been registered under NCT02678832 at clinicaltrials.gov. The survey study focused on social cognitions and norms regarding PA among people with cancer and was conducted between January 2017 and May 2018. Eligible were individuals ≥18 years with breast, prostate, or colorectal cancer whose latest diagnosis of the primary tumor, recurrence, or metastases was no longer than 30 months ago. This target group was addressed since breast, prostate, and colorectal cancer constitute prevailing cancer types, for which the beneficial effects of PA during and shortly after cancer treatment have been extensively investigated ,36. FurtAll information was assessed in a paper-and-pencil or congruent online survey as self-reported data by participants. Sociodemographic and medical items included age, sex, educational degree, height and weight to determine the body mass index (BMI), cancer type and the corresponding date of diagnosis, type and status of cancer treatment, and co-morbidities based on the Charlson co-morbidity index . PerceptPA assessment was adapted from the Godin-Shepard Leisure-Time Physical Activity Questionnaire . ParticiPA impediment by structural barriers was inquired with seven items that were developed from our preceding qualitative and quantitative study among healthcare professionals ,43. EachM) and standard deviations (SD) for metric variables and counts and percentages for nonmetric variables) were used to determine sociodemographic and medical characteristics of the study sample, their pre- and post-diagnosis PA behavior, perceived PA impediment by structural barriers, as well as their self-efficacy and intention to be physically active. Pearson’s correlation coefficient r and point biserial correlations (rpb) were calculated to ensure significant bivariate correlations between the main variables of the following mediation analysis.All statistical analyses were conducted with IBM SPSS version 25. Descriptive statistics . The structural barrier score served as the predictor (X), PA self-efficacy as the first mediator (M1), PA intention as the second mediator (M2), and meeting PA guidelines post-diagnosis as the outcome variable (Y) .As such serial mediation model with two mediators comprises three criterion variables , direct associations with their specified predictors can be determined in three separate regression analyses. Accordingly, in the current model, the first regression analysis examined the association of the first mediator PA self-efficacy with its antecedent structural barrier score, the second one tested the associations of the second mediator PA intention with its antecedents PA self-efficacy and structural barrier score, and the third one analyzed the associations of the outcome sufficient post-diagnosis PA with its antecedents PA intention, PA self-efficacy, and structural barrier score.Finally, the hypothesized pathways for direct and indirect effects in the full serial mediation model were evaluated. The applied model allowed to probe three mediation pathways for indirect effects: (a) the indirect effect of the structural barrier score on sufficient post-diagnosis PA through PA self-efficacy (X → M1 → Y), (b) the indirect effect of the structural barrier score on sufficient post-diagnosis PA through PA intention (X → M2 → Y), and (c) the indirect effect of the structural barrier score on sufficient post-diagnosis PA through PA self-efficacy and PA intention in serial (X → M1 → M2 → Y). The analyses were adjusted for age, sex, and sociodemographic, medical, and behavioral covariates that were shown to be significantly associated with sufficient post-diagnosis PA in the same sample, i.e., educational level, BMI, cancer type, time since latest diagnosis, co-morbidities, 5A score, and sufficient pre-diagnosis PA ,39. EstiFollowing the mediation analysis in the overall sample, the same procedure was applied separately in subsamples defined by whether or not participants were meeting PA guidelines pre-diagnosis to explore potential differences in the proposed associations between previously sufficiently and previously insufficiently active individuals.SD = 12.4), and 60% were female. Half of the participants were diagnosed with breast (51%) and about one-quarter with either prostate (25%) or colorectal cancer (24%). The mean time since diagnosis was 14.8 months (SD = 7.6), and 45% of patients were receiving treatment at the time of study completion (SD = 1.3) for their intention to perform 150 min MVPA per week and an average value of 4.4 out of 6 (SD = 1.7) for their self-efficacy to be sufficiently active. The mean structural barrier score describing the perceived impediment by seven structural barriers was 0.7 (SD = 0.7). Bivariate correlation analyses revealed that the structural barrier score was negatively correlated with PA self-efficacy , PA intention , and sufficient post-diagnosis PA . The correlation matrix further showed a strong correlation between PA self-efficacy and PA intention  as well as medium-sized correlations of both PA self-efficacy  and PA intention  with sufficient post-diagnosis PA.The overall sample consisted of 1299 people with cancer, of which 856 provided complete information on the variables included in the current analyses . Particimpletion . PA measp < 0.001, 95% CI ), but not with PA intention  or sufficient post-diagnosis PA . PA self-efficacy turned out as the strongest predictor of PA intention  and was further related to sufficient post-diagnosis PA . Additionally, PA intention emerged as a significant predictor of sufficient post-diagnosis PA .Results of the separate regression analyses testing the proposed associations within the mediation model are displayed in Analyzing the direct and indirect effects of the proposed mediation model in subgroups defined by whether or not participants were meeting PA guidelines before the diagnosis revealed that the effects indeed differed depending on patients’ pre-diagnosis PA . While tThe current study corroborated the mediating role of cancer patients’ self-efficacy and intention to exercise for the association between structural barriers and sufficient PA levels after the cancer diagnosis. The results indicated that a higher impediment by structural barriers was significantly associated with lower PA self-efficacy but did not directly influence the intention to exercise or activity behavior itself. As proposed, the effect of structural barriers on sufficient post-diagnosis PA was mediated through PA self-efficacy as well as a serial mediation pathway via both PA self-efficacy and PA intention. Subgroup analyses defined by patients’ pre-diagnosis PA levels revealed that the results were mainly driven by individuals who were sufficiently active before the cancer diagnosis, pointing towards the central role of patients’ self-efficacy beliefs about exercise for the maintenance of PA levels in the presence of structural barriers.It has long been known that one’s self-efficacy can be influenced by environmental factors , potentiIn contrast, the results of this study did not show a direct association between structural barriers and the intention to exercise, which is, however, consistent with a study that distinguished different types of barriers to PA in cancer patients, i.e., global, practical, and health barriers . Among tAn important aim of this study was to determine whether the discussed social-cognitive factors, i.e., PA self-efficacy and PA intention, can mediate the known association of structural barriers with activity behavior in cancer patients ,16. IndeThere are numerous behavior change techniques that are targeted at increasing PA self-efficacy . In lineIn attempting to reduce structural barriers, it is essential to consider that cancer patients encounter diverse psychosocial and disease-related challenges after their diagnosis . In a miThe results of this study further highlight the necessity of simultaneously considering structural barriers and self-efficacy for PA, as they seem to be closely related. Consequently, focusing on the concept of barrier self-efficacy , particuThis study further revealed that the mediation of structural barriers to the PA behavior of cancer patients did not apply equally to all individuals in our study population but primarily to those who were sufficiently active before the cancer diagnosis. In previous studies, we already showed that different determinants are associated with PA change patterns after cancer diagnosis  and thatTo our knowledge, this was the first study to explore the relationship between structural barriers, PA self-efficacy, PA intention, and post-diagnosis PA in a sample of cancer patients, and the results revealed valuable insights. However, some limitations need to be considered when interpreting the findings. As data were assessed as self-reports by cancer patients, they may be biased in the sense of socially desirable answers or recall biases. This could explain the relatively high number of sufficiently active individuals in the present sample as well as high mean values for PA self-efficacy and PA intention. Accordingly, the perception of structural barriers was low on average. Further, although PA self-efficacy and PA intention have been revealed as the strongest social-cognitive determinants of cancer patients’ activity levels, it might be important for future research to also consider other social-cognitive and behavioral factors as potentially relevant for the perception of structural barriers for PA. In this context, it also has to be noted that the cross-sectional design of the current study does not allow causal inferences. Thus, the proposed mechanisms underlying the association between structural barriers and post-diagnosis PA should be validated in longitudinal studies.In conclusion, this study suggests that the relationship between structural barriers and PA after the cancer diagnosis is mediated by social-cognitive constructs via different indirect pathways. In this regard, cancer patients’ self-efficacy to be physically active plays a central role in mitigating the perception of structural barriers. The mediation, however, was only found for the group of pre-diagnosis active individuals, which points to the importance of tailoring PA interventions to patients’ previous PA experience. While future research should evaluate additional ways to effectively increase inadequate activity levels in inactive cancer patients, previously active cancer patients appear to benefit from interventions that address the perception of structural barriers. Strategies to directly reduce structural barriers or increase patients’ self-efficacy in dealing with these barriers could thus make a valuable contribution to sustained PA behavior after the cancer diagnosis.


GLASED progressively decreased in the hypertension, dilated cardiomyopathy and cardiac amyloid cohorts indicating that mechanical work done and systolic performance is severely reduced in cardiac amyloid despite the relatively preserved ejection fraction. GLASED provides a new technique for assessing left ventricular myocardial health and contractile function.The left ventricular ejection fraction does not accurately predict exercise capacity or symptom severity and has a limited role in predicting prognosis in heart failure. A better method of assessing ventricular performance is needed to aid understanding of the pathophysiological mechanisms and guide management in conditions such as heart failure. In this study, we propose two novel measures to quantify myocardial performance, the global longitudinal active strain energy (GLASE) and its density (GLASED) and compare them to existing measures in normal and diseased left ventricles. GLASED calculates the work done per unit volume of muscle (energy density) by combining information from myocardial strain and wall stress . Magnetic resonance images were obtained from 183 individuals forming four cohorts . GLASE and GLASED were compared with the standard ejection fraction, the corrected ejection fraction, myocardial strains, stroke work and myocardial forces. Myocardial shortening was decreased in all disease cohorts. Longitudinal stress was normal in hypertension, increased in dilated cardiomyopathy and severely decreased in amyloid heart disease. GLASE was increased in hypertension. GLASED was mildly reduced in hypertension (1.39 ± 0.65 kJ/m EF predicted prognosis following myocardial infarction in the thrombolysis era6 but is unreliable in modern times9.Left ventricular (LV) ejection fraction (EF) does not accurately predict symptom severity15 show that midwall circumferential myocardial shortening, longitudinal shortening, myocardial mural thickness, ventricular internal diameter, and ventricular length each influence the EF independently 19.The limitations of EF described above have resulted in a search for improved measures of ventricular performance. For example, the influence of confounding structural changes on the EF can be removed by calculating the corrected ejection fraction , hypertensive heart disease, aortic stenosis, hypertrophic cardiomyopathy and concentric hypertrophy despite the usually preserved EF21 However, the major drawback of strain analysis is that it fails consider haemodynamic load and, therefore, would not be expected to accurately measure myocardial function20.Myocardial strain is an improvement on EF at measuring actual myocardial functionHaemodynamic load can be assessed by calculating contractile stress. Contractile stress measures the active force generated per unit cross-sectional area and results in cardiomyocyte contraction with associated longitudinal and circumferential shortening, radial thickening, and intraventricular pressure generation. Contractile stress incorporates information from LV mural thickness, cavity size and, crucially, pressure generation but does not provide information on the resultant deformation.Combining the information from stress and strain should provide a superior measure of systolic function. The elastic strain energy density is the energy per unit volume stored in a material under external loading and is calculated by integrating data from both the stress and strain. We can define myocardial active strain energy (ASED) as the mechanical energy (work done) per unit volume of muscle necessary to deform the myocardium and generate systolic pressure.Global longitudinal active strain energy density (GLASED) and midwall circumferential strain energy density (CASED) provide an estimate of the mechanical work done per unit volume of myocardium in association with the stress and strain in the longitudinal and circumferential directions, respectively. Active strain energy (ASE) estimates the energy produced by the whole LV myocardium. Global longitudinal active strain energy (GLASE) and midwall circumferential strain energy (CASE) estimates the energy produced in the longitudinal and circumferential directions, respectively. The measurement of ASE and ASED would be expected to be excellent measures of ventricular and myocardial health and performance because they combine data from contractile stress  and percent shortening while also supplying an estimation of the energy produced by the myocardium during systole.3 and a recent editorial declared that it is ‘time to leave diagnostics based on ejection fraction’4 because of the significant limitations described above. The search for better measures of LV performance is extremely important, as such knowledge would have a major impact on understanding conditions such as heart failure, modify treatment recommendations and provide valuable prognostic information.The EF has been described as ‘a measure of desperation’Measuring ASED avoids the weaknesses of both EF and strain by accounting for both the confounding effect of abnormal geometric patterns  and the pressure generation (loading conditions).Our primary hypothesis was that ASED (i.e. GLASED and CASED) would be significantly different between the disease cohorts and be more closely aligned to previously published mortality data compared to current methods. Therefore, we assessed ASED in individuals with DCM, hypertension, and amyloid heart disease, and contrasted them with healthy controls, as each of these cohorts have distinct geometric differences and haemodynamic loading conditions. We employed cardiac magnetic resonance (CMR) for the study because it is the gold standard for assessing left ventricular structure.Current measures of left ventricular performance such as ejection fraction and myocardial strain have important shortcomings. These limitations are attributable to the confounding effects of abnormal geometric changes and the loading conditions. This study introduces a novel measure of left ventricular systolic function called the global longitudinal active strain energy density (GLASED). GLASED combines information from left ventricular structural pattern , systolic pressure and myocardial strain and calculates the work done  per unit volume of myocardium during systole. GLASED should prove to be more accurate than the ejection fraction and myocardial strain in assessing left ventricular myocardial function.17. The demographic details are shown in Table We investigated 183 subjects, of whom 39 were healthy controls: 55 had resistant hypertension, 53 had idiopathic DCM, and 36 had probable cardiac amyloidosis. We have previously published data on this populationThe authors confirm that this study complies with the Declaration of Helsinki and that the Research Ethics Committee at the University of Bristol has approved the research protocol. We obtained informed consent from the subjects .17. MRI analysis was completed by a single reader, with > 5 years MRI experience, using cvi42 software. LV volumes, mass, and EF were measured blinded to the other results. Changes in LV longitudinal length between end-diastole and end-systole were measured manually to calculate myocardial shortening accurately using the 4-point mitral annular plane systolic excursion relative to LV end-diastolic length from the 4-chamber and 2 chamber views22. End-diastolic wall thickness (EDWT), end-systolic wall thickness (ESWT) and internal dimensions in diastole and systole were measured in the middle of each of the basal and mid  LV myocardial segments on the long-axis cines perpendicular to the LV wall whilst allowing for effects of through plane motion. Papillary muscles and trabeculae were excluded from the measurements. Each of these measurements was made 3 times and the means were calculated. Reproducibility (intraclass correlation) for these measurements was excellent (see Appendix). The myocardial contraction fraction was calculated by dividing the stroke volume by the muscle volume.CMR was undertaken as outlined in an earlier study and performed at 1.5 T  using a spine coil, an 8-element surface array coil and retrospective ECG triggeringc, using a five-variable regression equation derived from the whole study group  was derived using the benchmark of direct measurement rather than estimated using potentially less reliable built-in software.23. Proportional radial thickening was calculated as the absolute mural thickening divided by the end-diastolic mural thickness and expressed as a percentage.There is a significant difference in epicardial, midwall and endocardial circumferential strains , giving a large shear strain gradient, and making it difficult to quote a single value for circumferential strain. To compensate for the strain gradient, we used a standard analytic method to obtain the midwall circumferential shortening  was calculated using the longitudinal Laplace wall stress calculation and longitudinal shortening  would differ in the four cohorts. We assessed normality using the Shapiro–Wilk Test. Means were compared between all cohorts using one-way ANOVA with Tukey HSD/Kramer test or Kruskal–Wallis test with Nemenyi test as appropriate to correct for multiple comparisons. Correlations were performed using Pearson’s method. All continuous variables are displayed in Table Detailed results are shown in Table Stroke volume was significantly increased in the hypertension cohort, but significantly decreased in DCM and amyloid when compared with controls. The LV muscle mass was increased in hypertension, DCM, and amyloid. End-diastolic wall thickness was increased in hypertension and amyloid but was unchanged in DCM. The mean EF was not significantly different in the controls compared with hypertension but was decreased in the DCM and in amyloid Fig. A. The myc was significantly reduced in amyloid, but this was not significantly different from the DCM cohort  based on sound engineering principles; (ii) calculates the fundamental measure of energy production (i.e. work done) per unit volume of myocardium; (iii) accounts for the known confounding variables such as haemodynamic load and ventricular remodelling; (iv) matches the anticipated symptom severity, brain natriuretic peptide (BNP) and mortality in our cohorts.The synopsis of results for each cohort was as follows:c, a moderately reduced myocardial contraction fraction and longitudinal strain with a normal longitudinal stress. The greater stroke volume/height2.7 was consistent with a high-output state. Both the TIN and longitudinal generated forces were moderately increased. Pressure-strain loop was unchanged. Stroke work and CASE were moderately increased, and GLASE was mildly elevated, consistent with the extra work needed to generate the elevated blood pressure. A significant reduction in GLASED would suggest early hypertensive heart disease that was driven by the fall in longitudinal shortening of 30%. CASED, however, was not reduced as midwall circumferential shortening did not fall significantly. The explanation for difference between CASED and GLASED is uncertain but may reflect subendocardial ischaemia in the hypertension cohort due to microvascular disease.The hypertension cohort had a normal EF, a mildly reduced EFc, myocardial contraction fraction, longitudinal and midwall shortening were all severely reduced in the DCM cohort. The cohort also had a normal mural thickness, with remarkably high longitudinal and TIN force production. The EFc was higher than the EF. All the stresses in dilated cardiomyopathy were higher than healthy controls. Stroke work, pressure-strain loop, GLASE, GLASED, CASE and CASED were all moderately reduced, consistent with both a reduced LV energy production and reduced energy production per unit muscle volume.The EF, EFc, myocardial shortening, proportional radial thickening and all the stresses were severely decreased. The peak longitudinal force and TIN force were increased compared to the control group. Myocardial contraction fraction in the amyloid and DCM cohorts were the same. Stroke work per myocardial mass was also markedly decreased. Pressure-strain loop was reduced to a similar degree as DCM. In contrast, the GLASE, GLASED, CASE, CASED and SSP were extremely low. The amyloid cohort had the lowest ASE and ASED of the four groups, suggesting the worst systolic dysfunction and poorest contractile function. This suggests that the notion of amyloid heart disease being the archetypal form of diastolic dysfunction with relatively preserved “systolic function”, as defined by EF, needs re-evaluation.The EF was mildly reduced in the amyloid cohort, but the EFc was better at quantifying abnormalities compared with the EF. GLASED provided a sensitive means of detecting mild hypertensive heart disease and was different between the amyloid and DCM cohorts. A finding that contrasted with the alternative methods. Clear distinctions existed between the EF and GLASED in the four cohorts. The EF is emergent from, and contingent upon, known variables  and the pressure-strain loop methodsMyocardial forces such as TIN and longitudinal forces were increased in each of the disease cohorts especially so in DCM. Correcting these forces for LV mass improved their utility although they remained high in DCM. Using myocardial stress alone missed the abnormalities in hypertension and was misleading in assessing the contractile abnormalities of DCM. Myocardial strains were reduced in all the disease cohorts apart from midwall shortening in the hypertensive cohort. Importantly, myocardial strains alone did not differentiate amyloid from DCM.The GLASED values provide a more exact assessment for ASED compared with SSP, since it uses the more appropriate Lamé equation to calculate the stress for a thick-walled chamber. The simpler SSP gave comparable results, albeit with a slight underestimate in the amyloid cohort and an overestimate in the DCM cohort. SSP, however, is an alternative with a simpler equation to use.27. This trend is reflected by our GLASED data 36 are individually associated with an increased risk, and each of these risk factors reduces GLASED , followed by DCM ~ 170 pg/mL), hypertension (~ 26 pg/mL) and normal individuals (~ 10 pg/mL)ata Fig. A. The exata Fig. B28–30. R70 pg/mL,39. The left ventricle achieves this through remodelling39. Tissue and organ perfusion is, however, independent of the EF, since resting stroke volume and cardiac output are often preserved in heart failure39. There is a high incidence of hypertension, concentric hypertrophy, reduced wall stress and reduced myocardial strain in heart failure with a preserved EF40. Assessment of suspected HFpEF patients using GLASED would provide additional insight to the complicated mechanisms of this enigmatic and heterogenous condition by establishing the contribution of myocardial contractile abnormalities in HFpEF subgroups.A key physiological requirement of the heart is to maintain adequate tissue perfusion both at rest and with exercise, even in the presence of myocardial disease41. We recently introduced the term contractance as a measure of myocardial function, which is defined and quantified by myocardial ASED41. The definitions of ventricular performance and myocardial function are simplified and unified by the term contractance. We suggest that myocardial ASED could be used in clinical practice to assess the health of the myocardial muscle, since it identifies myocardial systolic and contractile dysfunction more accurately than current methods.The phrase “myocardial contractility” is used ubiquitously in both clinical and experimental studies. Despite this widespread use, contractility remains ill-defined 125 years after being introduced. GLASED provides a quantifiable definition of myocardial function by combining its known features, namely force generation, active stress, and deformation. Furthermore, changes in contractile function so defined would allow for the definition of inotropy to be clarified and, importantly, quantified. To date, there are no current measures of contractility that are applicable to in vitro, ex vivo and in vivo studies. Myocardial ASED, however, is applicable to both types and provides a method to compare in vivo and in vitro studiesOur cohorts were of limited size and were not age or sex matched as our aim was to explore distinct disease cohorts with different, yet near symmetrical, LV geometric patterns. Details of their cardioactive medication were not available. We did not use the current recommended criteria for diagnosis of amyloid as this was a historical cohort. These limitations would not alter the conclusions of this study as the analyses are centred around the structural and haemodynamic changes. Indeed, we think that this is a strength of the methods used as they consider the structural changes that may occur with age, sex or previous hypertension as well as the haemodynamic effects of any drug therapy. We were unable to provide information from the time-volume curves as the software necessary was unavailable when the study was performed. Further studies will be required to validate our findings.43. The calculations for ASE and ASED ignored the small amount of work performed in deforming myocardium alone and the minor component of kinetic energy imparted on the ejected blood’s motion. This is also a limitation of other methods such as stroke work calculations. Our study lacks external validation and direct prognostic data although the indirect evidence is highly promising  per unit volume of myocardium, and, therefore, gives important mechanistic insight into the pathophysiology of heart failure syndromes and has the potential to provide prognostic information.Supplementary Information 1.Supplementary Information 2.


The ability to opacify the left ventricle and delineate the endocardium after intravenous injection of microbubble ultrasound enhancing agents is of established value to quantify volumes and function in suboptimal unenhanced images, particularly in stress echocardiograms. However, applications other than quantitation of left ventricle structure and function exist for contrast enhanced left ventricular opacification. Contrast agents enable recording of Doppler velocity signals in patients with poor ultrasound transmission, providing estimates of aortic stenosis gradient and pulmonary artery pressures. Contrast echo is of value in detecting apical hypertrophic cardiomyopathy and accompanying apical aneurysms. Most importantly, ultrasound enhancing agents can identify apical and left atrial masses when they cannot be visualized in unenhanced images, and can distinguish thrombi from tumors by visualizing the vascularity inherent in tumors. Contrast agents distinguish trabecular from compacted myocardium in noncompaction syndrome, and hypertrabeculation with other abnormal conditions. A major potential application of ultrasound enhancing agents is myocardial opacification, which can assist in identifying nonviable myocardium. Also, the delayed reappearance of myocardial perfusion after microbubble destruction identifies impaired contrary flow and can diagnose coronary stenosis. Innovative applications of ultrasound contrast agents currently under investigation, include visualizing the vaso vasorum to identify plaques and assess their vulnerability, and theranostic agents to deliver drugs and biologists and to assist in sonothrombolysis. It is anticipated that the role of ultrasound contrast agents will continue to increase in the future. Richard (Dick) Conti was an “impact player.” He made an impact on everything that he engaged in, changing it for the better and leaving his imprint. He was a superb clinician, productive clinical investigator, gifted teacher, and effective administrator. His influence upon the University of Florida, the American College of Cardiology, and of course on Clinical Cardiology is easily visible. He succeeded one of us (AND) as President of the American College of Cardiology. We worked closely together, traveled extensively, and shared many experiences, some serious and some humorous. His advice was always sage and of great value. Dick was a giant intellect, an indefatigable worker, and a “tell it like it is” person; it was impossible not to like him. It is truly our honor to have the opportunity to contribute a manuscript to this issue in his memory.2The first significant clinical description of contrast echocardiography is usually credited to Drs. Gramiak and Shah who in 1969 traced the cloud of echo signals produced by the left atrial injection of indocyanine green as it opacified the left atrium and subsequently the aorta by m‐mode echocardiography.3As previously stated, ultrasound enhancing agents, referred to in the vernacular as contrast agents, have achieved an established role for left ventricular opacification and identification of the endocardial border. A number of studies have demonstrated the ability of contrast enhanced echocardiograms to yield measures of left ventricular volume and ejection fraction that correlate well with other techniques such as magnetic resonance imaging in patients in whom the unenhanced echocardiogram is technically inadequate.Ultrasound enhancing agents may also be of value in defining endocardial landmarks on three‐dimensional echocardiography which is less sensitive in imaging low intensity targets than conventional two‐dimensional imaging.Despite documentation that ventricular opacification by contrast echo could accurately identify left ventricle volumes and ejection fraction and thereby influence patient management, implementation of these recordings in echo laboratories has been slow and variable. Evidence exists to indicate that, although 15%−30% of echocardiographic studies are marginal or inadequate, especially stress echo and those performed in the intensive care unit, only approximately 5% of echo studies employ ultrasound enhancing agents.While the ability to enhance endocardial border definition by contrast echo is well established and integrated into practice, a number of other applications other than border definitions are often encountered. The injection of microbubbles produced by agitated saline to identify right to left cardiac or intrapulmonary shunts is well established and will not be further discussed.4The injection of contrast agents can be utilized to enhance Doppler recordings of flow in the central and peripheral circulation in patients with suboptimal studies. Accurate measurement of transvalve velocities from Doppler velocity recordings has played a major role in the ability of echocardiography to eliminate the need for cardiac catheterization. The initial application of this technique was in the setting of aortic stenosis Figure , where i5An important use of left ventricular opacification has been the diagnosis of apical hypertrophic cardiomyopathy. It is often impossible to delineate the endocardial border of the apex in patients in whom examinations are technically difficult. The administration of contrast can provide such identification and thereby diagnose apical hypertrophic cardiomyopathy if present (Figure and video 6Probably the major application of ultrasound enhancing agents derived from left ventricular opacification other than border delineation is the identification of cardiac masses, particularly left ventricular thrombi. Numerous examples exist of patients with sizable and protruding left ventricular thrombi that are not adequately visualized by unenhanced images that are well delineated after the administration of contrast Figures .10 TheCardiac tumors are less frequently encountered on echocardiogram than thrombi and are usually well detected even without the administration of contrast agents. However, contrast agents can be of value in distinguishing tumors from thrombi. Tumors are usually well vascularized while thrombi are not, typically yielding sonolucent thrombus images versus tumors with scattered reflectances Figure . However7Noncompaction cardiomyopathy is an uncommon congenital abnormality.82 was capable of intensely opacifying the myocardium, thereby providing the potential to assess myocardial perfusion and coronary blood flowPreclinical studies initially demonstrated that the direct intracoronary injection of CODemonstration of myocardial opacification following intravenous injection of ultrasound enhancing agents led to an immediate enthusiasm and anticipation that this methodology could be applied clinically. In fact, several multicenter trials have demonstrated that myocardial contrast echo yields similar accuracy in identifying coronary atherosclerotic stenosis as does radionuclide methods.9Several innovative applications of ultrasound enhancing agents are currently being investigated. It is well documented that atherosclerotic plaques are often accompanied by proliferation of vasa vasorum on the epithelial surface of the vessel that provide nutrient blood flow to the plaque. It has now been demonstrated that ultrasound enhancing microbubbles can be detected in plaques as evidence of proliferation of the vasa vasorum.The use of ultrasound enhancing agents, or contrast echocardiography, has now been utilized in clinical cardiology for 50 years. The primary use of contrast echo to opacify the left ventricle and delineate the endocardial border is well established to be of value and is commonly applied in clinical laboratories. Left ventricular opacification is of proven value in assessing volumes, ejection fraction, and wall motion, and in achieving reproducibility of findings. It has been demonstrated to be capable of altering patient management in those with technically suboptimal recordings. Nevertheless, available data indicate that there is generally an underutilization of ultrasound enhancing agents, even for this well‐established application. There are a number of important applications of left ventricular opacification other than for delineation of the endocardial border. Among them, amplification of Doppler echo and color flow signals, detection of hypertrophic cardiomyopathy, particularly when apical in location, detection of cardiac masses and distinguishing tumors from blood clots, establishing the presence of hypertrabeculation and assisting in the diagnosis of the noncompaction syndrome are critical to the optimal performance of echocardiography. Opacification of the myocardium by intravenous injection of ultrasound enhancing agents is feasible and has the potential to become a first line modality to assess myocardial perfusion. Technical advances will be important to achieving widespread application for this indication. The potential applications of ultrasound contrast agents continue to grow and be explored both for diagnosis and therapy. It is anticipated that the use of contrast agents will continue to play an increasingly important role in the echocardiography laboratory of the future.


There was also a significant difference concerning the hs-cTnI level between central and peripheral venous drug administration routes (p = 0.034). Due to differences in the hs-cTnI level, it appears that the administration of caspofungin may be associated with myocardial injury. Our findings also showed a higher possibility of cardiotoxicity via the central venous administration route.Echinocandins selectively inhibit fungal cell wall synthesis and, therefore, have few side effects. However, there are reports of hemodynamic and cardiac complications. We conducted this study to investigate the effects of caspofungin both on the noninvasive echocardiographic indices of myocardial function and myocardial injury based on serum high-sensitivity cardiac troponin I (hs-cTnI) levels. This study was conducted on patients treated for candidemia. The hs-cTnI level and echocardiographic parameters were measured before and 1 h after the infusion of the induction dose of caspofungin. Data were compared between central and peripheral venous drug administration routes. Fifteen patients were enrolled in the study. There were no significant differences in the echocardiographic parameters between the baseline and post-treatment period. The mean hs-cTnI level exhibited a significant rise following drug administration (0.24 ± 0.2 ng/mL vs 0.32 ± 0.3 ng/mL;  Echinocandins are deemed efficacious and safe agents in the armamentarium against fungal infections. The mechanism of action of this pharmacological group of fungicides, comprised of caspofungin, micafungin, and anidulafungin, is the inhibition of 1,3-β-D-glucan synthesis in the fungal cell wall . FurtherThe major complication of echinocandin use is hypersensitivity, which can also present as anaphylactic shocks . There hThe present interventional study was conducted in Imam Khomeini Hospital Complex between the years 2019 and 2020. The study population was comprised of 15 participants who were being treated with caspofungin at the discretion of infectious disease specialists either for confirmed or suspected candidemia in keeping with the IDSA’s guidelines. The exclusion criteria consisted of concurrent treatment with other cardiotoxic drugs, especially anthracyclines, and a history of heart failure with a left ventricular ejection fraction (LVEF) of less than 50%. Through the use of a questionnaire, the subjects’ demographic characteristics and underlying medical conditions, including a family history of cardiovascular disease and a history of coronary artery disease, hypertension, dyslipidemia, and renal failure, were collected. Additionally, an electrocardiogram (ECG) at baseline was obtained from all the patients to investigate the presence or absence of atrial fibrillation.In animal studies, the effects of echinocandin use on the heart were dose-dependent and were observed in higher doses ,8,9. In ® hs-cTnI immunoassay . The upper level of the normal limit of hs-cTnI was considered to be 0.1 ng/mL. This timeframe was considered based on our interest in assessing the acute hemodynamic effect of the drug, which was reported immediately or within 1 h in previous studies [Cardiac function was assessed noninvasively via echocardiography, conducted by a single operator on a GE VIVID E9 machine, prior to caspofungin infusion. The echocardiographic parameters investigated comprised systolic function indices, including LVEF via the eyeball and Simpson methods, the global longitudinal strain, the Tei index, and diastolic function indices, including the ratio between the early mitral inflow velocity and the mitral annular early diastolic velocity (E/E′) and the left atrial volume index. All the patients once again underwent echocardiography 1 h following caspofungin infusion for the measurement of the aforementioned parameters. Additionally, 1 h before and 1 h after the infusion of caspofungin, blood samples were obtained to measure hs-cTnI levels via Elecsys studies ,10.Given the association between echinocandin injection via the central venous route and cardiac effects in animal studies ,11, in tThe study protocol was approved by the Ethics Committee of Tehran University of Medical Sciences (Code: IR.TUMS.IKHC.REC.1396.3453). Before study enrollment, informed written consent was obtained from all the study patients, who were reassured concerning the confidentiality of their data and were permitted to withdraw collaboration at their own choice.p-value of less than 0.05 was considered statistically significant. The quantitative data were presented as the mean ± the standard deviation, and the qualitative data were presented as numbers and percentages. Due to the small size of the study population, the Kolmogorov–Smirnov test was carried out in the first step to determine whether any distribution was normal or not. Thereafter, based on the results, the 2 variables of eyeball LVEF and E/E′, given their non-normal distributions, were compared using the Wilcoxon rank-sum test, and the other variables were compared using the paired t-test.The statistical analyses were conducted using the SPSS software, version 22.0, and a The study population was comprised of 15 patients at a mean age of 32 ± 14 years, with the youngest patient aged 22 and the oldest 53. Ten (66.6%) patients were male. Diabetes and hypertension were reported in one patient each. None of the patients had a history of dyslipidemia, renal failure, coronary artery disease, or a family history of cardiovascular disease. ECG showed the sinus rhythm in all the patients; no evidence of atrial fibrillation was detected in any patient’s ECG. p-value of less than 0.001 and 0.001, respectively. Consequently, the Wilcoxon signed-rank test was used to compare the values of E/E′ and eyeball LVEF before and after the intervention: no significant difference was observed . The p-values for the other variables were greater than 0.05. Thus, the paired sample t-test was applied to compare the values before and after the intervention for the variables with normal distributions. Our results illustrated that the mean hs-cTnI level before and after the infusion of caspofungin was 0.24 ± 0.2 ng/mL and 0.32 ± 0.3 ng/mL, respectively; the rise constituted statistical significance (p = 0.006).According to the Kolmogorov–Smirnov test, E/E′ and eyeball LVEF had a 2r was used to show the degrees of these correlations. The variables of hs-cTnI and left atrial volume exhibited a significant correlation before and after caspofungin injection .None of the echocardiographic parameters exhibited a statistically significant change following caspofungin infusion compared to its respective baseline value . Table Sp = 0.034).Vis-à-vis the administration route, nine (60%) patients received caspofungin via the peripheral venous route and six (40%) patients through the central venous route. The mean hs-cTnI level showed a 0.17 ± 0.22 ng/mL rise in the peripheral vein subgroup and a 0.53 ± 0.36 ng/mL increase in the central vein subgroup; the difference between the two subgroups was statistically significant (The use of fungicides such as azoles and amphotericin B is associated with cardiac complications. For instance, amphotericin B consumption can cause hypokalemia and increase risk of cardiac arrhythmias, and itraconazole use is accompanied by cardiotoxicity . The litSuch evidence prompted further animal studies on the effects of caspofungin on cardiomyocytes and cardiac function. Arens et al.  observedFew human studies have thus far been undertaken on the hemodynamic effects of echinocandins. Lahmer et al.  studied The Fourth Universal Definition of Myocardial Infarction guideline defines myocardial injury as elevated cardiac troponin above the 99th percentile upper reference limit . The meaWe observed a significant rise in the mean hs-cTnI level after caspofungin infusion, which may denote cardiomyocyte damage. This finding chimes in with the results obtained in animal studies. Nonetheless, none of the noninvasive indices of systolic and diastolic cardiac indicesexhibited a meaningful change. Considering that hs-cTnI measurement is capable of distinguishing even slight damage to cardiomyocytes and that alterations in echocardiographic indices of systolic and diastolic functions need the involvement of a more extensive area of the heart, our findings may indicate that the extent of the acute injury caused by caspofungin administration is not sufficient to result in acute cardiac dysfunction. Be that as it may, some degree of cardiotoxicity is inevitable, which may be exacerbated by the subsequent doses of the drug and may, in the long term, lead to cardiac dysfunction.With respect to the mechanism of echinocandin-induced cardiotoxicity, various hypotheses have been propounded. Taking into account the absence of complications following micafungin, which is a hydrophilic agent, cardiotoxicity may be linked with the lipophilicity of the other two echinocandins ,18. It hThe salient limitations of the present study are its small sample size which limits statistical power, and the absence of a long-term follow-up, precluding robust conclusions regarding the long-term effects of echinocandin use on cardiac function, including the possible heart failure occurrence. Caspofungin is metabolized by the liver, and its plasma level can be affected by liver enzyme inducer drugs. The level can be increased in critically ill patients in the ICU, especially with low serum albumin . Our patThe results of the present study demonstrated a significant rise in the mean hs-cTnI level following the intravenous infusion of caspofungin; consequently, it appears that the administration of this antifungal agent may be associated with myocardial dysfunction. Our findings also showed a high possibility of echinocandin-induced cardiotoxicity via the central venous administration route in comparison with the infusion through the peripheral venous route.