In critically ill patients, hemodynamic disturbances are common and often lead to a detrimental outcome. Frequently, invasive hemodynamic monitoring is required for patients who are hemodynamically unstable. Although the pulmonary artery catheter enables a comprehensive assessment of the hemodynamic profile, this technique carries a substantial inherent risk of complications. Other less invasive techniques do not offer a full range of results to guide detailed hemodynamic therapies. An alternative with a lower risk profile is transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE). After training, intensivists can obtain similar parameters on the hemodynamic profile using echocardiography, such as stroke volume and ejection fraction of the right and left ventricles, an estimate of the pulmonary artery wedge pressure, and cardiac output. Here, we will review individual echocardiography techniques that will help the intensivist obtain a comprehensive assessment of the hemodynamic profile using echocardiography. These tools are often used in cardiac critical care due to the comprehensive evaluation of cardiac and circulatory function. In particular, pulmonary artery catheters carry a high inherent risk of complications, some of which are fatal. They also lose diagnostic detail in settings where only parts of the myocardium are affected . Changes will only be shown when they affect overall cardiac function. In daily practice, most of the parameters of the Swan–Ganz catheter can also easily be assessed less invasively with the 21st relative of the Swan–Ganz catheter: echocardiography.Invasive hemodynamic disturbances are common in intensive care medicine. During the past four decades, monitoring has evolved from simple manual blood-pressure measurement, to continuous invasive arterial blood-pressure monitoring, to thermodilution techniques using transpulmonary thermodilution . However, even in less dramatic situations, echocardiography can provide the same information as advanced hemodynamic monitoring, generating beneficial effects for patient management. This is clearly seen in scenes wherein echocardiography has become part of the mainstay of therapy as it is in adult cardiac surgery, where it improves perioperative outcomes . Beyond Ultrasound-based cardiac imaging has transformed clinical care in intensive care medicine, as well as in the operating room, and today forms an important column of comprehensive cardiac care. Theoretically, ultrasound machines use two different modes of image acquisition: M- and B-modes. M-mode is the oldest mode and records images along a sound axis over time. The B-mode represents the classical representation of tissue-specific sound conduction properties in a two-dimensional (2D) image. Both techniques are regularly used to characterize both right ventricular (RV) and left ventricular (LV) functions. In addition to image acquisition, blood flow and tissue velocity can be visualized and quantified using two different modes of Doppler echocardiography: pulsed-wave (PW) and continuous-wave (CW) Doppler. Both record flow velocities over time but with intrinsic differences between the two techniques. The PW Doppler mode can record flow velocities with high spatial resolution in a defined range but fails in the setting of higher velocities (up to ~150–170 cm/s). CW Doppler can resolve high-flow velocities but lacks spatial resolution. To assess flow velocity in relation to anatomical structures, one relies on color Doppler. Here, different colors are coded for the flow velocities depending on the direction of the blood flow and the velocity. Typically, red is used for flow directed towards the ultrasound probe, and blue is used for flow directed away from the ultrasound probe. All image acquisition can be applied as transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE). TTE offers the intrinsic advantage of being noninvasive and rapidly available, and most guidelines, reference values, and scientific evidence refer to data from studies with TTE. Unfortunately, TTE requires access to the thorax, an anatomical site that is not easily accessible during surgery and can be challenging in patients after cardiothoracic surgery or under mechanical ventilation. Therefore, in the perioperative setting, physicians are more commonly relying on TEE, which commonly provides excellent high-resolution image quality due to proximity of the ultrasound probe to cardiac structures. Currently, mainly multiplanar TEE probes are used, allowing all degrees of freedom  for image acquisition. Ultrasound devices and probes have progressed steadily, and the latest generations allow for more advanced measurements, using three-dimensional (3D) echocardiography and semiautomatic endocardial and myocardial tracking . Evaluation of systolic LV function is probably the most common investigation in perioperative echocardiography. There are numerous well-validated parameters to assess LV systolic function, which predicts perioperative morbidity and mortality ,5,6. FurLeft ventricular function can now to a large extent be assessed with non-invasive echocardiography measurements, often replacing the more invasive technique such as left heart catheter. Modern echocardiographic machines have integrated various complex echocardiographic assessments into their software, but they still require a high level of training and are typically time-consuming. However, time is a precious resource for the acutely deteriorating patient in the ICU. Therefore, clinicians frequently rely on eyeballing techniques in the decision-making process. For the inexperienced user in a time restraint setting, eyeballing techniques can be “supercharged” using basic imaging modalities in echocardiography. The following paragraphs show several easy-to-learn parameters that can help to quickly assess the left ventricular function without using complex measurement tools.Systolic left ventricular function is an integral part of the point-of-care assessment of hemodynamically unstable patients. Some views (in TTE or TEE) help to confirm or exclude numerous pathologies as the cause of clinical deterioration. However, all examinations, regardless of the underlying imperative, should include a statement about the systolic LV function, which represents the approach recommended by International Guidelines .Especially in emergencies, the investigator should not spend too much time on differentiated diagnostic algorithms but focus on the elimination of potentially life-threatening conditions. For this reason, most of the following techniques allow even the inexperienced examiner to quickly obtain information on left ventricular systolic function by “eyeballing.” As a first step in the examination, it is recommended to obtain an overview of the diameters and wall thicknesses of the left ventricle. The M-mode offers the best temporal resolution of all ultrasound modalities with a sampling rate of at least 1000 frames per second, making fast or subtle movements optimally visible. Furthermore, the rather abstract image of the M-mode contains less ‘optical noise’ than a B-mode image for the inexperienced examiner.To eject blood into the aorta, the left ventricle must also contract circumferentially. This change in diameter is described by fractional shortening (FS) and expresses the change in the diameter of the LV in M-mode from diastole to systole as a percentage C. CalculLVID = left ventricular internal diameterAn FS of <25% indicates systolic dysfunction of the LV. Values above the upper reference limit of 45% may indicate a hyperdynamic circulatory state.To eject blood volume into the systemic circulation, the LV describes a pronounced longitudinal shortening in the direction of the cardiac basis in addition to circumferential narrowing . This longitudinal movement can be quantified diagnostically by determining the mitral annular plane systolic excursion (MAPSE). MAPSE is a simple and well-validated marker. It is derived from the M-mode of the summative longitudinal function of the LV and closely correlates with the global function of the LV A. EspeciWhen mitral annulus calcifications are present, MAPSE should be interpreted with caution, because this condition might limit the movements of the mitral annulus and thus reduce MAPSE. Furthermore, wall abnormalities of the mitral valve annulus could also contribute to a reduced MAPSE. This is important to keep in mind when evaluating LV function, especially when values are different from other measurements or the overall look of ventricular function.During early diastole, the mitral valve opens fully, and the leaflet of the anterior mitral valve moves toward the interventricular septum. This movement of the anterior mitral valve leaflet is only possible when the ejection of blood into the ascending aorta is intact. If the ejection fraction is reduced, the blood volume within the left ventricle will remain elevated at early diastole. This, in turn, will reduce the movement of the anterior mitral valve leaflet. This can be used diagnostically . For thiEPSS should be interpreted with caution in the setting of impaired mitral valve opening, as it occurs in mitral valve stenosis. Here, the ejection fraction may be intact, but the EPSS is reduced because the mitral valve cannot open fully due to limited motion of the anterior leaflet. There are situations in a clinical setting where patients deteriorate over time. Here, repetitive measurements of cardiac outcome can influence the clinical management and guide vasopressor or inotropic therapy . Cardiac output (CO) determination by echocardiography is an important alternative to more invasive methods, such as pulmonary catheterization or transpulmonary thermodilution. To measure the stroke volume and therefore cardiac output, Doppler echocardiography or 2D measurements can be used.Conceptually, the LV ejects blood into a cylinder (ascending aorta) with each contraction. The base of this cylinder is the systolic cross-sectional area of the left ventricular outflow tract (LVOT), while its height is the distance the blood travels during ejection for that beat. From this, the volume per beat can be calculated, reflecting stroke volume. First, the diameter of the LVOT is measured. Assuming that the base of the LVOT cylinder is circular, the radius can be used to calculate its area. However, care must be taken, as small errors in 2D diameter measurements will lead to large errors in calculating the cross-sectional area, as the radius  is squared in the calculations. The LVOT diameter can be measured in long-axis or three-chamber views. Thereafter, the bloody flow velocity in the LVOT is measured using the PW Doppler at roughly the same spot as the diameter measurement, and the velocity–time integral (VTI) is formed D. The st2). Theoretically, stroke volume can also be determined using volumetric methods (see below).Multiplying the stroke volume by the heart rate at the time of measurement yields CO (L/min). Normalized to the patient’s body surface area, the result is the so-called cardiac index  also give away the stroke volume of the ventricle, which can serve as an alternative method of cardiac output measurement (please see above). To determine LV volume, the sum of a series of parallel slices from the apex to the base is calculated electronically. The advantage of this technique is that, even in the presence of altered ventricular geometry , volume determination produces reliable values compared to cardiac magnetic resonance  imaging.Although 2D volumetry usually provides results that correlate well with reference technologies, more accurate measurements are achieved by using 3D echocardiography . For thiDespite being the cornerstone for the evaluation of left ventricular systolic function, 2D measurements of left ventricular ejection fraction have some inherent shortcomings, such as interobserver variability. Structural damage to the heart is only given away when an impairment of LVEF is involved. Tools to evaluate subclinical left ventricular function can close the diagnostic gap. Left ventricular deformation measurements, such as left ventricular strain measurements from STE, close this diagnostic window, and offer additional advantages over 2D measurements of the left ventricle. The 2D STE of the LV measures the radial and circumferential shortening of the LV, while global longitudinal strain measures lengthening, shortening, thickening, and rotation capacity of the myocardium. Thus, it provides a more thorough assessment of the function of the left ventricle with a deeper understanding of the disease states.The strain describes the relative change in myocardial length from end-diastole to end-systole and is expressed as a percentage. Negative values represent shortening, while positive values describe elongation. In fact, its prognostic value appears to be incrementally superior to LVEF E–G 12]..12]. WitAll the mentioned parameters can be used to assess the left ventricular systolic function. However, they differ in clinical use and in the situation when they should be used. On a practical ground, we subdivide the above parameters into practicability and use. The parameters presented here can be categorized into parameters that can be used for estimation or parameters that highly correlate or even substitute invasive gold-standard measurement techniques. ‘Estimation’ parameters include FS, MAPSE, and EPSS; more exact evaluation parameters include stroke volume measurement by VTI, 2D or 3D volume measures (and ejection fraction), or left ventricular strain . Parameters such as FS, MAPSE, and EPSS provide the advantage that no advanced calculation package is necessary for their measurement. As such, they can be used in simple bedside ultrasound machines, as long as the appropriate ultrasound probe is present. Thus, from a clinical and practical approach, we can use these parameters in acute deteriorating patients, or in the emergency of patients in shock. Here, they can help us to rule in or rule out certain differential diagnosis of patients in shock. In rapidly deteriorating patients, speed trumps perfection, and this is where the advantage of these parameters resides. For example, in patients with shock of unclear origin, we can quickly assess if cardiac function is impaired , or if the patients are hypovolemic .More exact parameters come into play when a thorough assessment of cardiac function is required. This is the case in patients with underlying cardiac disease who undergo therapy for a separate clinical condition  or patients admitted for cardiac conditions. Here, 2D or 3D volumetry stroke volume measurement or left ventricular strain measurement provide detailed information on cardiac function, sometimes even with beat-to-beat resolution. To measure these parameters, we require ultrasound machines that provide state-of-the-art speckle tracking-based calculation packages to semi-automatically determine the individual values. Otherwise, the values need to be measured offline with separate software packages. In summary, all left ventricular systolic parameters provide information for the clinical environment, but they always come with a trade-off. Simple parameters lose detail but gain ‘practicability’; advanced parameters provide accuracy but might take longer to be determined.Relaxation of the left ventricle during diastole is an active process. In an adenosine triphosphate (ATP)-dependent process, the muscle fibers within the cardiac myocytes relax, which decreases the left ventricular intracavitary pressure significantly. When cardiac myocytes are depleted from ATP, this relaxation process is impaired. Physiologically, this process begins in late systole  and ends with mitral valve closure (end of diastole) and is known as the isovolumic relaxation period. It creates a suction from blood from the pulmonary veins from the left atrium into the left ventricle, without an increase in left ventricular chamber pressures. In diastolic dysfunction, this process is impaired, leading to an increased in left ventricular filling pressures. The evaluation of this in the perioperative setting is important, since LV diastolic dysfunction (heart failure with preserved ejection fraction) has a severe impact on patient prognosis and has an impact on catecholamine therapy .As mentioned above, the diastolic function (or dysfunction) is represented by the kinetics of ventricular filling. Therefore, it is important to look at ventricular filling dynamics when assessing the left ventricle works during diastole. The normal Doppler pattern of ventricular inflow is characterized by a short time interval between aortic valve closure and the onset of ventricular filling (isovolumetric relaxation time). After the opening of the mitral valve, there is a rapid inflow of blood from the left atrium into the ventricle. Blood flow velocities of 60 to 80 cm/s are achieved in healthy adults. This early maximum fill velocity  occurs simultaneously with the peak pressure gradient between the atrium and the ventricle. After this peak velocity, the flow slows in healthy individuals. This time interval, defined as the deceleration time between the peak of the E wave and the intersection of a line following the deceleration slope with the baseline, is between 140 and 200 ms. Atrial contraction again causes an acceleration of flow through the mitral valve, which is expressed in the flow profile of the A wave, which reaches lower flow velocities (20 to 60 cm/s) under physiological conditions. In the case of impaired ventricular filling and increased filling pressures (diastolic dysfunction), atrial filling remains of greater importance, which is reflected in a decrease in the E/A ratio  A.Due to ventricular filling during diastole, there is a geometric change in the left ventricle from the base to the apex. The velocity of this longitudinal myocardial lengthening can be measured by Doppler tissue imaging (TDI) and used for diagnostic purposes. The annulus of the lateral and septal mitral valves is used as a measurement site. Following Doppler measurement of blood flow velocities across the mitral valve, the TDI velocities of the mitral valve annulus are defined as e′ and a′, respectively B. The raUsing the E/e′ ratio, the end diastolic pressure of the LV can be estimated non-invasively  as follolateral ≥ 10 cm/s: normal diastolic functione′lateral < 10 cm/s: diastolic dysfunctione′For the diagnosis of diastolic function, all above parameters are usually used and evaluated using complex schemes. However, in the perioperative setting, a precise classification of the diastolic function is achieved using a simple algorithm :e′lateraE/e′ ≤ 8: diastolic dysfunction grade I (impaired relaxation)E/e′ 9–12: diastolic dysfunction grade II E/e′ > 13: diastolic dysfunction grade III (restriction).The morphology, duration, and relative velocity of the pulmonary venous flow velocities are directly influenced by the left atrial pressure, as well as the compliance and contraction of the left ventricle. Therefore, the pulmonary venous flow profile indirectly reflects the dynamics of LV filling. Pulmonary venous flow velocities are measured by PW Doppler C. This irev. If diastolic function decreases, left atrial pressure increases. As a result, the S wave of the systolic filling flattens, and the D wave increases proportionally. Due to increased resistance in the context of diastolic relaxation and disturbance of blood flow through the mitral valve during atrial contraction, the flow velocity of Arev increases.The flow profile is basically divided into two segments: the flow profile S during systole and D during diastole. In late diastole, even under physiological conditions, there is a slight reversal of flow back into the pulmonary veins, which is called AAlthough the left atrium (LA) is easily characterized by echocardiography in dimensions and function, these measurements are rarely used perioperatively. An enlarged LA  or LA dysfunction (LA strain ~<20%) both reflect advanced chronic diastolic LV dysfunction and are associated with increased end-diastolic LV pressures D. STE-baDiastolic dysfunction has received less attention than systolic impairment in critically ill patients. However, the evaluation of diastolic function is essential in patients in the ICU whenever an echocardiography is performed. Diastolic dysfunction, in essence, leads to an increase in filling pressure, such as end-diastolic LV pressure (EDLVP). In the past, these measurements required invasive techniques, such as Swan–Ganz catheter placement, that carry substantial risks such as pulmonary artery rupture. Essentially, echocardiographic evaluation of EDLVP or wedge pressure estimation is less accurate but still provides integral information for patient management. The clinical scenarios where diastolic LV evaluation could be useful in the ICU could be cardiac deterioration, or post-surgical evaluation after valve surgery. In patients with a history of arterial hypertension, diastolic functional measurement can also help gauge the severity of impairment. In patients with pulmonary edema, the flow profile of the pulmonary vein provides additional information, because a blunted signal indicates incomplete decongestion of the pulmonary circulation . We regularly use a repetitive assessment of the pulmonary vein flow profile to guide the extent of diuretic therapy and fluid restriction. In summary, at least a brief evaluation of left ventricular diastolic function  should be part of every echocardiography in the ICU, because it completes cardiac function in each individual patient and helps guide therapy.Since the RV differs from the LV in its complex three-dimensional structure and physiological properties, echocardiography poses a greater challenge for the inexperienced investigator. Due to its size and thin wall, the RV serves as a volume reservoir and therefore can tolerate preload increases  much better than afterload increases . RV dysfunction can have many causes and is associated with a dramatic worsening of patient prognosis. The following sections will provide an overview of the possibilities of echocardiographic RV analysis.To measure the dimensions of the right ventricle, a plane should be selected in which the RV is optimally visualized along its long axis and as circumferentially as possible. Transthoracically, this is typically achieved in the RV-focused four-chamber view, which in TEE can be approached from the mid-esophageal four-chamber view by slightly rotating the probe to the right side of the patient. Here, the end-diastolic diameter of the right ventricular (RVEDD) can be determined basally  and midventricular (at the level of the papillary muscles) A. Due toIn addition to dimensions, 2D echocardiography rapidly provides simple and robust parameters of RV function. The most important and still widely used parameter is the TAPSE (tricuspid annular plane systolic excursion). In its original form, it can only be obtained from the four-chamber transthoracic view using an M-mode sector through the lateral tricuspid annulus C. The TAValues of <35% are considered pathological in patients awake and spontaneously breathing. In patients with severely abnormal RV configurations, the FAC can sometimes deviate significantly from the ‘true’ right ventricular ejection fraction (RVEF), usually due to ‘blind spots’ in the FAC .The complex geometry of the RV can be fully visualized only using 3D imaging techniques. TEE is typically associated with optimal examination conditions , allowing high-resolution 3D data sets to be generated using multi-beat recordings triggered by ECG . Therefore, 3D-based real-time methods make volumetry feasible at the bedside and provide a relevant prognostic RVEF in addition to right ventricular end-diastolic volume (RVEDV) and right ventricular end-systolic volume (RVESV) D–F. The RV strain analysis was initially mainly experimental in nature and was often performed using LV strain software. Currently, there are many studies that highlight the prognostic importance of RV strain in various settings, including perioperative medicine ,28,29,30The echocardiographic evaluation of right ventricular function has gained increasing interest in recent years, as fundamental evidence for the crucial prognostic impact of RV dysfunction in various cardiac and non-cardiac conditions exists. Analogously to the left ventricular function, parameters of the right ventricular function can be divided into parameters that are easy to measure at the bedside, but less predictive, and parameters that require off-line calculation packages.Parameters, such as right ventricle dimensions, TAPSE, and RV FAC can be measured with most ultrasound machines with the appropriate probe and thus provide a rather quick assessment of the right ventricle. The parameters are useful in clinical situations where a quick assessment of the right ventricle is necessary, for example, in patients where a sudden increase in right ventricular afterload is suspected .For a full-scale assessment of right ventricular function, for example in progressive right heart failure, the more elaborate measurements such as 2D RV ejection fraction or RV strain can provide a complete picture of the patient situation. This might be helpful in patients after cardiac surgery or with chronic pulmonary hypertension. Today, 3D-based quantification of RV function has emerged as the echocardiographic gold standard, but its routine use is currently limited to a few centers with the necessary expertise and equipment.In summary, all functional parameters of the right ventricle provide information for the clinical environment. In the acute situation, we recommend using fast and accessible functional parameters; when a thorough assessment is required to monitor therapy measurements for RV strain, it might provide a better picture of the clinical situation.Because acute and chronic elevations of afterload are often associated with RV dysfunction, determining systolic pulmonary artery pressure (sPAP) plays a critical role in initiating appropriate therapy. The invasive procedure of choice, right heart catheterization using Swan–Ganz catheters, is complex and can be associated with life-threatening complications. On the contrary, if RV dysfunction has been detected by echocardiography, a non-invasive Doppler-estimate can assess sPAP. Two important conditions must be met for measurement: (1) the presence of tricuspid regurgitation (TR) and (2) the CW Doppler beam must be parallel to the tricuspid insufficiency jet to avoid dramatic underestimation of sPAP. For this measurement, the TR is best visualized in the apical four-chamber view in TTE or in an atypical bi-caval view in TEE. According to the modified Bernoulli equation, echocardiography devices can automatically calculate a systolic pressure from the maximum flow velocity of the TR jet, which corresponds to the difference in pressure between RV and RA A,B. By aPW Doppler can be used to record the inflow profile through the tricuspid valve in suitable sections . This can provide valuable information on the diastolic function. Diastolic RV dysfunction is often a consequence of acute myocardial ischemia, in the context of volume challenge or increased pressure in the pulmonary circulation. Echocardiography can detect even mild deterioration of right heart failure. Determining the E/A can be easily acquired and helps to gauge the severity of impairment of right ventricular function.The unique feature of TDI of the RV is that it provides parameters to evaluate both the systolic and diastolic functions of the RV. Doppler focus is placed on the lateral tricuspid annulus. Maximum systolic velocity (S′), as well as early (e′) and late (a′) diastolic tissue velocities, can be measured. Comparison of these parameters with reference values can be used to detect RV systolic or diastolic dysfunction. Furthermore, the so-called myocardial performance index (MPI or Tei index) can be used to determine a TDI-based measure of the global RV function. For this purpose, different times are measured from the recorded TDI course of a cardiac cycle, and the MPI is calculated .Echocardiographic evaluation of the inferior vena cava (VCI) provides valuable information on volume status and central venous pressure (CVP). For this purpose, the maximum diameter of the VCI is measured in a subxiphoid view, and the collapsibility during (active) inspiration is observed. A decrease in diameter with spontaneous collapsibility indicates an intravascular volume deficiency in the systemic venous circulation . On the contrary, increases in diameter (>2.1 cm) and reduced collapsibility (<50%) indicate an increase in CVP (10–20 mmHg). Although diastolic RV dysfunction can therefore be suspected, this method is suitable for using the estimated CVP to determine the sPAP as mentioned above. Intraoperatively, CVP estimation is obsolete, as invasive CVP measurement can be performed, and the collapse of the VCI does not produce meaningful results in ventilated patients.Doppler assessment of RV should be performed in all patients undergoing echocardiography for hemodynamic deterioration because the measurements are crucial for macro dynamics. As such, Doppler sonographic measurements of tricuspid valve pressure gradient can be used in patients who undergo invasive mechanical ventilation for respiratory failure (such as acute respiratory distress syndrome). Here, the measure can provide an excellent estimate of the right ventricular after load of the right ventricle.If hypovolemia such as that in acute hemorrhage is suspected, the assessment of the vena cava is helpful, because with a little training, even the novice can detect changes that might affect the patient’s macrohemodynamics.In summary, Doppler measurements complete the assessment of the right ventricular function because they put functional measurements in context with hemodynamic parameters.Echocardiographic measurements can substitute advanced hemodynamic measurements in many settings. It comes with the advantage that even TEE carries a substantially lower risk of complications than, e.g., Swan–Ganz catheter placement.


Gadolinium-enhanced cardiovascular magnetic resonance (CMR) is the most widely used approach for diagnosing myocardial fibrosis with late gadolinium enhancement (LGE) in cardiomyopathy associated with Duchenne muscular dystrophy. Given the limitations and safety of gadolinium use, we wanted to develop and evaluate multi-parametric pre-contrast CMR models for the diagnosis of LGE and investigate whether they could be utilised as surrogates for LGE in DMD patients.A total of 136 DMD patients were prospectively recruited and separated into LGE − and LGE + groups. In the first subset of patients (derivation cohort), regression models for the diagnosis of LGE were built by logistic regression using pre-contrast sequence parameters. In a validation cohort of other patients, the models’ performances were evaluated.EF, native T1 and longitudinal strain alone, as well as their combinations form seven models. The model that included EF, native T1 and longitudinal strain had the best diagnostic value, but there was no significant difference in diagnostic accuracy among the other models except EF. In the validation cohort, the diagnosis outcomes of models were moderate consistent with the existence of LGE. The longitudinal strain outperformed the other models in terms of diagnostic value .Pre-contrast sequences have a moderate predictive value for LGE. Thus, pre-contrast parameters may be considered only in a specific subset of DMD patients who cannot cooperate for long-time examinations and have contradiction of contrast agent to help predict the presence of LGE.ChiCTR180001834020180107The online version contains supplementary material available at 10.1186/s13023-023-02931-y. DMD is a fatal X-linked recessive muscular degenerative disorder caused by defective dystrophin synthesis, resulting in fibrosis and fat replacement of muscles throughout the body, including skeletal and cardiac muscles, and affects 1 in about every 3500–5000 boys  and cardNon-invasive cardiovascular imaging is indispensable for the early detection of myocardial abnormalities, which can develop early in DMD patients . CurrentNot only cardiac structure and function parameters but also myocardial strain , native T1 and T2 values can be obtained by pre-contrast CMR sequences. Previous studies have also shown that LGE is correlated with strain alterations in a variety of diseases, including DMD . The strThe study complied with the Declaration of Helsinki and was approved by the Biomedical Research Ethics Committee of our medical centre. This study has been registered in clinical trial. And each participant signed an informed consent form prior to the examination. From July 2018 to January 2021, we prospectively collected imaging and clinical data of DMD patients who could undergo standard gadolinium-enhanced CMR scanning in our medical centre. The diagnosis of DMD was confirmed by gene detection or muscle biopsy according to the guideline . The exc2) was executed to assess the LV structure and function parameters and tissue-tracking indices were obtained based on 8–12 continuous cine imaging in the short-axis view from the mitral valve level to the LV apex, as well as the horizontal four-chamber and vertical two-chamber long-axis. Native T1 mapping, T2 mapping and LGE images were acquired at the basal, middle and apical standard short-axis levels of the LV. LGE images were obtained 5–10 min after the intravenous injection of gadolinium  at a dose of 0.1 mmol/kg body weight and a flow rate of 1.2-2.0 ml/s using a single-shot phase-sensitive inversion recovery (PSIR) sequence . Native T1 mapping was performed using the Modified Look-Locker inversion recovery (MOLLI) sequence (scanning pattern 5(3)3, slice thickness = 6 mm, slice gap = 3 mm, TR = 2.71 ms, TE = 1.1 ms, flip angle = 35°, matrix = 128 × 192 pixels, FOV = 280 × 224 mm2) in combination with motion correction (MOCO) was used to perform T1 mapping quantification before contrast administration [2) to obtain three single-shot images with different T2-preparation times .Standard gadolinium-enhanced CMR scanning was conducted by using a clinical 3.0-T whole-body scanner , with the participant supine, by using the two-element cardiac phased-array coil. All images were acquired during end-expiration breath-holding, and dynamic changes in the ECG and breathing were monitored using the manufacturer’s standard ECG-triggering device and the breath-hold technique. Balanced steady-state free precession (SSFP) sequence  and analyzed by an experienced cardiac radiologist with more than 3 years of CMR experience who was blinded to the clinical information. Parameters were calculated automatically by the software or manually according to formulas. In all series, the epi- and endocardial boundaries were delineated manually and papillary muscles were excluded from the myocardium. In order to eliminate the interference of artifacts, LGE was deemed present if myocardial enhancement was confirmed by using a signal intensity threshold of 5SD above the mean signal of the remote normal myocardium through enhanced sequences Fig. -A, B. AcAll statistical analyses were performed using SPSS 22.0 software  and MedCalc 19.7. Continuous variables were presented as the mean ± standard deviation (SD). Categorical variables were expressed as the frequency and percentage. The normality of the data was determined using Kolmogorov–Smirnov test, and the homogeneity of variance was determined using Levene’s test. Student t-test, Wilcoxon test, and χ2 test were used to compare the variables between groups in baseline and CMR characteristics. All tests were two-sided, and p < 0.05 was considered statistically significant.Derivation cohort. —A subset of patients was used as a derivative cohort to derive models to predict the presence of LGE. Univariate and multivariate logistic regression analyses were performed to calculate the OR and 95% CI. Covariates were incorporated in multivariate logistic regression when p < 0.1 or considered clinically relevant. Any independent factors were combined to calculate a linear regression equation to predict LGE and each regression equation and independent factors were used as a prediction model. ROC curves of different models were constructed to assess appropriate diagnostic thresholds, and the AUC was compared using the Delong method.Validation cohort. —Another subset of patients was used for validation. The threshold value of each model obtained in the derivation cohort was used to determine whether each patient in the validation cohort had LGE, and the results were compared with the imaging diagnostic results. The sensitivity, specificity, negative and positive predictive values of each model in the validation cohort were calculated to evaluate their predictive performance. Kappa test was used to assess the consistency of each model and LGE diagnosis.A total of 136 patients were enrolled in this study, including 63 LGE + patients. All subjects were male. The derivation cohort contained 96 patients and the remaining 40 DMD boys were included in the validation cohort. In the derivation and validation cohorts, there were 45 and 18 LGE + patients, respectively. In terms of age, height, weight and other baseline characteristics, there were no significant differences between the derivation and validation cohorts , while the absolute value of PS-L decreased . And the basic demographic characteristics as well as the three pre-contrast parameters in the multivariate logistic regression of the validation cohort are shown in Additional file 1: Supplementary Table Table Our study found that pre-contrast sequence parameters, including LVEF, native T1 and global longitudinal strain, may be independent predictors for LGE presence in DMD patients. Based on the three parameters, we derived different linear regression models. In the derivation cohort, the model combining the EF, native T1 and longitudinal strain exhibited the best diagnostic value, pre-contrast sequences offer a moderate predictive value for the presence of LGE. Compared with single index models, composite multi-parameter regression models had increased diagnostic efficiency, but not statistically significantly. In addition, we introduced the validation cohort for the first time in such studies of pre-contrast sequence performance to predict LGE in DMD patients. In the validation cohort, we further confirmed that these three parameters and their composite regression models can moderately predict LGE for individual CMRs, and good sensitivity can be obtained by using global longitudinal strain only. Furthermore, the performance of these models derived from the pre-contrast sequence parameter was mediocre, suggesting that non-contrast sequence imaging in DMD patients could not completely replace LGE imaging. Nonetheless, these models might be applied when the GBCAs CMR was contradicted and could not be finished for the reasons stated in the introduction.Different from previous studies, we included models that incorporated different parameters through multivariable regression screening and compared the predictive efficiency to assess whether fewer, simpler CMR parameters might be employed as a substitute for LGE. Compared with the segmental CMR parameters patterns demonstrated by Raucci Jr. and colleagues , the resIn our study, the performance of multi-parameter models, such as LVEF and global native T1, LVEF and longitudinal strain, in predicting LGE had not been significantly improved. EF and global native T1 primarily reflect global myocardial abnormalities, while previous studies have demonstrated that myocardial fibrotic change in individuals with DMD mostly begins and focuses on the lateral free wall, which is typically patchy –26. The Interestingly, compared with the multi-parameter models, single-index prediction models, such as longitudinal strain, had better sensitivity in the prediction of LGE. According to several studies, myocardial longitudinal strain decreases sooner in the early stage of DMD, and has a good correlation with myocardial injury, including myocardial fibrosis and heart failure , 31. In Despite predictive results in the validation cohort being unsatisfactory, these models are still important in DMD patients. DMD patients will find it challenging to maintain supine postures for long periods of examination time because of severe dyskinesia, scoliosis and respiratory dysfunction caused by progressive muscle damage , 34. In There are some limitations of our study. First, the derivation and validation cohorts introduced in the study were not real machine learning, but rather basic manual verification. Given the rarity of DMD incidence and the long time it took to recruit enough DMD participants in a single center, the small number of instances may contribute to the low prediction accuracy and the small number of cases in our validation cohort cannot support machine learning with a large sample size. However, our results had shown some predictive trends and value in the relatively small sample, so in subsequent studies, we will expand the number of examples and consider applying artificial intelligence machine learning for prediction model research. Second, this was a single-centre design study, with some bias in case selection and a lack of prospective longitudinal evaluation of the occurrence of LGE. Third, given the focal patchy manifestations of fibrosis in DMD myocardial damage, segmental pre-contrast parameters may be more predictive in areas where LGE is commonly observed . InsteadThrough the derivation and validation cohorts, we considered that pre-contrast sequences models had moderate predictive value for the presence of LGE in young DMD patients. Although the predictive efficacy of models were restricted, longitudinal strain might be used as a surrogate for LGE in DMD patients with absolute contraindications to GBCAs, no intravenous access and poor compatibility requiring reduced examination time. However, given the critical information that LGE imaging can provide, non-contrast imaging protocol still cannot completely replace LGE imaging at present, and DMD patients without exceptional circumstances should continue to have standard gadolinium-enhanced CMR scanning performed regularly.Below is the link to the electronic supplementary material.Supplementary Material 1: Supplementary Table Supplementary Material 2: Supplementary Table Supplementary Material 3: Supplementary Table


Ebstein’s anomaly occurs when there is an apical displacement of the tricuspid valve with septal and posterior valve leaflets tethering. This condition often occurs in association with other congenital, structural, or conduction system diseases, including intracardiac shunts, valvular lesions, arrhythmias, accessory conduction pathways, and first-degree atrioventricular (AV) block. We present for the first time a case of a patient with Ebstein’s anomaly who presented with second-degree Mobitz II AV block and was successfully treated with conduction system pacing (CSP) due to her young age and the likelihood of a long-term high percentage of pacing.We present a case of a 42-year-old lady with a background of complex congenital heart disease, including severe pulmonary stenosis, Ebstein anomaly, and atrial septal defect (ASD). She required complex surgical intervention, including tricuspid valve (TV) repair and subsequently replacement, ASD closure, and pulmonary balloon valvuloplasty. She presented to our hospital with symptomatic second-degree Mobitz II AV block  and right bundle branch block (RBBB) on her baseline ECG. Her echocardiogram showed dilated right ventricle (RV) and left ventricle (LV) with low normal LV systolic function. Due to her young age and the likelihood of a long-term high percentage of RV pacing, we opted for CSP after a detailed discussion and patient consent. The distal HIS position is the preferred pacing strategy at our centre. We could not cross the TV with the standard Medtronic C315 HIS catheter, so we had to use the deflectable C304 HIS catheter. Mapping and pacing of the distal HIS bundle were achieved by Medtronic Selectsecure 3830, 69 cm lead. HIS bundle pacing led to the correction of both second-degree Mobitz II AV block and pre-existing RBBB. The implantation was uneventful, and the patient was discharged home the next day without any acute complications.Distal HIS pacing is feasible in patients with surgically treated complex Ebstein anomaly and heart block. This approach can normalize the QRS complex with a high probability of preserving or improving LV function. Crossing the tricuspid valve could be problematic, so that a deflectable C315 HIS catheter can facilitate the process.Distal HIS pacing is achievable and safe in patients with surgically treated complex Ebstein’s anomaly and heart block.This approach can normalize the QRS complex with a high probability of preserving or improving LV function.1 In patients with narrow QRS complexes, His bundle pacing allows similar ventricular activation pattern with preservation of QRS duration and morphology.2Conduction system pacing (CSP) gained popularity in the last decade as a more physiological alternative to right ventricular pacing for treating bradycardia or as an alternative to biventricular pacing for cardiac resynchronization therapy (CRT). It is divided into His bundle pacing (HBP) and left bundle branch area pacing. The current European Society of Cardiology guidelines for pacing and CRT present HBP as a class IIb indication (level of evidence C) and a left ventricular ejection fraction > 40% who require frequent (more than 20%) ventricular pacing or as part of a ‘pace and ablate’ strategy for rapidly conducted supra-ventricular arrhythmias. It also has a class IIa indication (level of evidence B) in CRT candidates in case of failed coronary sinus lead implantation.To the best of our knowledge, we report the first case of HBP in a patient with corrected Ebstein’s anomaly, second-degree Mobitz II AV block, and RBBB.Figure 1A). Lung sounds were clear bilaterally in all lobes anteriorly and posteriorly. There was a variation in the intensity of the first heart sound consistent with a 2:1 atrioventricular (AV) block. Vital signs were stable, and laboratory tests did not show any abnormality.We present a case of a 42-year-old lady with a background of complex congenital heart disease, including severe pulmonary stenosis, Ebstein anomaly, and atrial septal defect (ASD). She required open pulmonary valvotomy in 1982, transcatheter device closure of ASD , tricuspid valvuloplasty incorporating 28 mm Carpentier-Edwards annuloplasty ring , and modified right-sided maze and tricuspid valve replacement using 29 mm Carpentier-Edwards PERIMOUNT Magna Ease bioprosthetic valve . Her medical history also includes heterozygous factor V Leiden deficiency, benign intracranial hypertension and previous vitreous haemorrhage with bilateral papilloedema. She presented to our hospital with newly developed dizziness and previously reported shortness of breath and exercise intolerance. Her resting ECG showed a right bundle branch block, QRS of 152 ms, 2:1 heart block, and normal QRS axis .Ultrasound-guided axillary venous access was obtained for both atrial and CSP lead. A Medtronic SelectSecure 3830 lead, 69 cm lead, and C315 HIS catheter were used to map and pace the HIS bundle. We encountered difficulties crossing the TV, so we used the deflectable C304 HIS catheter. The distal HIS position is the preferred pacing strategy at our centre. An anatomical approach was targeted at the basal RV septal site after crossing the prosthesis with a small HIS, far-field, and a large ventricular signal . The patient was discharged home the next day without any acute complications.We managed to achieve full correction of right bundle branch block (RBBB) with non-selective HIS pacing throughout. Pacing parameters were satisfactory with sensing of 8 mV, threshold of 1 mV at 0.4 ms, and local RV capture of 0.375 V at 0.4 ms with a paced QRS of 114 ms (She came for her device follow-up 6 weeks post-implantation. Symptoms improved, the device check showed 98% RV/HIS pacing, and threshold improved to 0.5 V at 0.4 ms. Atrial parameters are stable. There is a good biventricular function and trivial tricuspid regurgitation on echocardiography.3 High-degree AV block is a rare presentation.4 Tricuspid valve surgeries and challenging morphological abnormalities in these patients often demand exceptional skills during pacemaker implantation.5 Sharma et al.6 demonstrated the feasibility of HBP in patients with RBBB allowing further widening the potential benefits of CSP. His bundle pacing can significantly benefit the physiological ventricular activation pattern. Nevertheless, it presents challenges such as the difficulty of lead implantation, reduced R-wave amplitudes, and high and unstable pacing thresholds. His bundle pacing in patients with Ebstein’s anomaly could be even more challenging as in some cases, His-potentials could be demonstrated only in the atrialized portion of the ventricle7 or because of a possible intra- and infra-hisian conduction delay.8Ebstein’s anomaly occurs when there is an apical displacement of the tricuspid valve with septal and posterior valve leaflets tethering. This condition often occurs in association with other congenital, structural, or conduction system diseases, including intracardiac shunts, valvular lesions, arrhythmias, accessory conduction pathways, and first-degree AV block.In this case, the HBP was confirmed by as follows:HIS signal on the lead intracardiac electrogram.Two different thresholds on threshold testing; first at 1 V with correction of the RBBB and second is local RV septal capture at a lower output, broader QRS notched, and LBBB morphology.We achieved full correction of RBBB with non-selective HIS pacing accompanied by the disappearance of the patient’s symptoms.9 Alternatives to transvalvular lead implantation in patients with tricuspid valve replacement are described in the literature. Lead placement in the lateral and anterolateral veins also provides the benefit of resynchronization and presents good lead parameters.10–12 Paravalvular lead placement is achievable13 as well as leadless permanent pacemaker implantation.14The effect of transvalvular lead placement on tricuspid regurgitation in patients with tricuspid valve repair or replacement is an important factor to be considered before the decision for pacemaker implantation. Cardiovascular implantable electronic device-related tricuspid regurgitation due to lead placement is a possible complication of pacemaker implantation secondary to direct trauma or further interaction of the electrode leading to impingement of the leaflets and malcoaptation. In addition, leaflet adhesion, fibrosis, and encapsulation could contribute to tricuspid regurgitation.In conclusion, pacemaker implantation is challenging in patients with surgically treated complex Ebstein’s anomaly and heart block. We demonstrated that distal HIS pacing is feasible in these patients. This approach can normalize the QRS complex with a high probability of preserving or improving LV function.ytad531_Supplementary_DataClick here for additional data file.


Obtaining prior authorization (PA) before treatment is becoming increasingly burdensome in oncology, especially in radiation oncology. Here, we describe the impact of a strategic novel operational PA redesign to shorten authorization time and to improve patient access to cancer care at a large United States academic proton therapy center. We ask whether such a redesign may be replicable and adoptable across oncology centers.Our PA redesign strategy was based on a 3-tiered approach. Specifically, we (1) held payors accountable to legally backed timelines, (2) leveraged expertise on insurance policies and practices, and (3) updated the submission, appeal writing, and planning procedures for PA. Metrics were compared at the following 3 time points: 6 months before, at phase-in, and at 6 months after intervention.P < .001). The proportion of commercially insured patients treated with proton beam therapy also increased by 6.2%, and the number of new starts rose by 11.7 patients/mo. Overall patient census increased by 13 patients/d. Median authorization time was 1 week, and 90% of surveyed providers reported reduced PA burden and improved patient care.In analyzing the impact of improving PA access to care, the percentage of approvals for commercial proton beam therapy improved by an absolute 30.6% postintervention (This is the first validated, comprehensive operational strategy to improve access to cancer therapy while reducing the burden of PA. This novel approach may be helpful for addressing barriers to PA in medical and surgical oncology because the redesign is predicated on laws that regulate PA across disciplines. The need for prior authorization (PA) by health insurance companies is increasingly recognized as a burden for providers and a barrier to patients seeking access to cancer care. Ostensibly, health insurers use PA to evaluate the appropriateness of a medical service to disincentivize costly procedures that do not provide comparable patient benefits , 2. HoweRecognizing these challenges and the increasing use of PA by payors over time, the University of Florida Health Proton Therapy Institute (UFHPTI) undertook a strategic redesign of its administrative PA process with the goals of reducing delays, denials, and costs while providing patients with more timely and appropriate access to care. This approach was based on a successful model described previously by another large cancer center  that useIn June 2021, recognizing shifts in payor denial patterns and increased barriers to PA, UFHPTI executive leadership approached the developers of the prior strategy with the goal of redesigning the PA team and processing structure to minimize delays in PA and inappropriate denials  review based on national and state mandates. The federal mandate is based on the Employee Retirement Income Security Act (ERISA) , which gSecond, for traditional fully funded plans, state laws frequently mimic the ERISA or require payors to devise their own procedures and impose penalties if those PA procedures are not followed . These sThird, for all plans (self- or fully funded) with a history of violated procedures or timelines or those with low approval rates, applicable state or federal laws were applied to skip internal payor appeals and move directly to IRO . IRO isUFHPTI had an initial PA team consisting of 7 full-time-equivalent (FTE) members to shepherd coverage claims through the PA process. The redesign involved supplementing these 7 FTEs with another 4 individuals, including 2 new medical dosimetrists and 2 seasoned experts in PA navigation , 6 months after (June 2021 to November 2021), and 6 months after that (December 2021 to May 2022) . The following metrics were analyzed and compared before versus after the intervention involved the patient populations affected by PA: (1) commercial-insurance approval rates for proton therapy; (2) IRO approval rate; (3) median time to an authorization decision; (4) daily census (on treatment) of commercially insured proton patients; (5) daily census of all proton patients; and (6) overall daily census and change in net revenue. A financial analysis was conducted to evaluate the value of the redesign on operations. This included a net present value  calculation over a 3-year period to represent a short-term valuation of the PA redesign investment based on the first year’s discounted free cash flow and assessment of the modified internal rate of return . The NPV and MIRR used standard financial methods and incorporated excess net patient revenues resulting from additional approvals from the PA redesign over year 1, fixed and variable PA team costs, effort costs, and opportunity costs, as well as time period 0 costs. A constant discounted free cash flow model was subsequently used.2 tests were used to compare the overall commercial proton approval rate after the redesign . For all analyses, the threshold for statistical significance was P = .05. A provider survey was furnished at 12 months postintervention to ascertain the redesign’s effect on clinical flow and reduction in PA burden.Pearson’s χP < .001), amounting to a 30.6% absolute increase in the approval rate overall. Similarly, the IRO approval rate began at 0% and increased by 11% during phase-in and another 10% by postintervention, for an absolute increase of 21% overall.Changes in operational metrics over the 3 intervals are shown in The number of new commercially insured proton starts, daily proton patient census, percentage of all patients receiving proton therapy, and percentage of commercially insured patients receiving proton therapy increased after the redesign. Specifically, the number of commercially insured proton new starts increased by 8.9 patients/mo; the daily census of all patients receiving proton therapy increased by 16.5 patients; and the percentage of patients receiving proton therapy (as opposed to photon or other types of radiation therapy) increased by 6.4%. Of note, the percentage of commercially insured patients receiving proton therapy increased by 6.2%  and an MIRR of 197%.Last, a provider survey was sent to all 10 UFHPTI treating physicians 1 year after the redesign adjuvant treatment .From a value perspective, our analysis showed an impressive NPV of more than 7-figures and an MIRR of 197%. Unlike the original pilot study, we did not replace any PA team members or reduce the number of FTEs in that team. Although doing so led to cost savings in the pilot study , we inveAnother aspect of the success of our redesign is its generalizability to other US centers and specialties because the framework of our timeline is based on federal and state laws that would apply in any applicable US jurisdiction. For example, medical or surgical oncology practices could recruit advanced practice nurses to their PA teams who would have the clinical expertise for writing letters of medical necessity and drafting appeals; this would also lift the administrative burden of PA on providers in those specialties. Overall, our results indicate that this strategy can be extended beyond radiation oncology to medical and surgical oncology services because the redesign is predicated on laws and procedures that regulate PA for health services across disciplines, which is one of the most important effects of our findings.However, crucial future directions for PA reform for proton therapy and other advanced treatment modalities in oncology include practice-level adoption of operational strategies to improve immediate access (as described here), as well as guidance on legislation to modify the regulation of PA with policymakers to prevent long-term detrimental effects on patient care. Reforming PA regulation may be necessary to achieve congruence between evidence-based national guideline recommendations  and payoOur study had several important limitations. First, the improvement from the phase-in through postintervention periods may have been influenced by COVID-19 surges during the study. Although this would not directly affect approval rate metrics (the focus of the redesign), it could well have affected patient census. Similar COVID-19 spikes were experienced at our center’s location  during the preintervention and phase-in periods and, to a lesser extent, during postintervention. Despite these spikes, the trends seen in census improvement illustrate that the census benefits were likely related to redesign effects. Second, some benefits could have resulted from changes in payor policy, proton coverage expansion, disease site, or payor mix. However, no substantial changes were noted, and a review of the PA policies instead tended to become more restrictive over time , 17, 20.In closing, our redesign of the PA process confirmed that quality improvement efforts and operational research on factors related to initial PA approval and successfully appealed denials can produce practical data allowing practices to successfully navigate PA, thereby creating increased access to appropriate and justified care.


A 37-year-old woman, previously known to have severe airplane phobia, develops panic disorder-like symptoms in the second hour of the flight. After a while, panic disorder was accompanied by chest pain and syncope. An ECG showed no abnormalities. Transthoracic echocardiogram demonstrated decreased left ventricular ejection fraction (EF: 30), large apical akinesis, and characteristic regional wall motion abnormalities involving the middle and apical segments of the left ventricle. Findings were consistent with Takotsubo cardiomyopathy. But in the emergency department, Brain Diffusion MRI showed cortical and subcortical vasogenic edema in the posterior regions, predominantly on the left, bilaterally, compatible with posterior reversible encephalopathy. This case highlights the Takotsubo cardiomyopathy-related posterior reversible encephalopathy syndrome (PRES) syndrome and managing the disease. Although Takotsubo is cardiomyopathy that mimics myocardial infarction, it differs in its pathophysiology in that the microvascular spasm that occurs after emotional stress leads to a reversible clinical scenario. This condition may rarely affect the cerebrovascular circulation, simultaneously leading to posterior reversible encephalopathy syndrome (PRES). Aerophobia is an extreme fear of flying by airplane. People with aerophobia may fear different aspects of flight, such as taking off, landing, or being trapped in an airplane. This case report aimed to demonstrate the Takotsubo cardiomyopathy (TC) associated with PRES in a patient with aerophobia.A 37-year-old woman with previously known severe airplane phobia developed panic-like symptoms during the second hour of the flight. After a while, the panic disorder was accompanied by chest pain and syncope. She was rushed to the emergency room in a disoriented state, exhibiting notable limitations in orientation and cooperation and diffusing myoclonic spasms throughout her body. Afterward, the patient began to experience agitation. ECG and troponin follow-ups are performed to exclude the considering acute coronary syndrome in the foreground. The initial troponin level was 489 ng/L  but then normalized in four hours, which helped rule out myocardial infarction. Echocardiography shows decreased left ventricular ejection fraction, large akinesia of the apex, and characteristic regional wall motion abnormalities of the middle and apex of the left ventricle. Brain diffusion magnetic resonance imaging (MRI) is performed in the emergency department. It is consistent with cortical and subcortical vasogenic edema in the posterior regions, predominantly on the left side and bilateral, compatible with posterior reversible encephalopathy (PRES) Figure . ClinicaTakotsubo Cardiomyopathy (TC), initially reported in 1990 . As per Patients typically present with chest pain, dyspnea, dizziness, generalized weakness, and syncope. Physical examination findings resembling acute systolic heart failure include jugular vein distension, an S3 gallop, tachycardia (rapid heart rate), hypotension (low blood pressure), and reduced pulse pressure. Additionally, there is a possibility of developing a systolic ejection murmur caused by obstruction of the left ventricular outflow tract and mitral regurgitation due to ventricular ballooning. Most patients display elevated levels of troponin T, I or creatine kinase-MB (CK-MB), ST elevation, T-wave inversion on electrocardiograms (ECGs), and increased brain natriuretic peptide (BNP) .The exact pathophysiology of Takotsubo cardiomyopathy remains unclear; however, several pathological mechanisms have been proposed. The correlation between stressful triggers and TC indicates the significant involvement of the adrenergic system in its pathophysiology. It is believed that catecholamines, including epinephrine and norepinephrine, released during times of stress, play a role in the development of apical ballooning, potentially leading to myocardial toxicity and/or disruption of the cardiac microvasculature -7. HowevIncreased serum and cardiac nerve catecholamines in the acute period are believed to contribute to vasospasm in both epicardial and cardiac vessels. Vasospasm increases cardiac workload, impairs tissue perfusion, and leads to symptoms similar to ischemia . VasculaAlthough the treatment of Takotsubo cardiomyopathy remains uncertain, patients are usually monitored in cardiology wards for 21 days to assess left ventricular systolic function. Mild to moderate cases are managed symptomatically, while severe cases may require mechanical ventricular support .Despite the generally good prognosis associated with TC, complications carry a higher mortality risk. Currently, no standardized guidelines exist for the diagnostic and management approach to TC. Conservative management is generally effective . InitialWhen admitting a patient with Takotsubo cardiomyopathy, clinicians should know the high risk (7%) of cerebrovascular events in the first 30 days . Atrial Posterior reversible encephalopathy syndrome (PRES) is a cerebrovascular event characterized by acute onset of altered consciousness, headache, visual loss , and sometimes epileptic seizures . Risk faIncreased hydrostatic pressure disrupts the blood-brain barrier, leading to extravasation of intravascular fluid into the brain tissue and brain tissue edema. Parietooccipital regions are commonly affected, less commonly temporal and frontal lobes, brainstem, and deep white matter. The posterior system is more affected than the anterior system due to its limited adaptive mechanisms to regulate the blood-brain barrier .The clinical and radiological features give PRES its name. The gold standard for diagnosis is to demonstrate vasogenic edema on non-contrast MRI as T2 hyperintense, predominantly in the parieto-occipital lobes . CranialTreatment is usually directed toward the underlying cause. In the presence of hypertension, a standard protocol has not been established. It is recommended to initiate antihypertensive treatment when blood pressure reaches 160/100 mm Hg. Sudden blood pressure lowering may increase the risk of cerebral hypoperfusion and ischemia. Therefore, blood pressure should not be reduced by more than 10-20 mm Hg every 10-20 minutes ''.Patients experiencing chest pain and dyspnea following physically or mentally stressful triggers; should exercise caution for TC, a condition that imitates acute myocardial infarction. Close monitoring is essential to ensure early diagnosis and promptly address cerebrovascular events' potential occurrence. Risk factors should be rapidly identified, and the underlying etiology should be treated. Our case is one of the rare cases in which TC is associated with PRES. The pathogenesis is believed to involve adrenergic discharge triggered by aerophobia. When recent cases are examined, the cause-effect relationship between Takotsubo and PRES is not clearly established. Therefore, more clinical research is needed.


Reversal of torrential tricuspid regurgitation is rarely seen. We describe a case in which effective immunosuppression alongside conventional heart failure therapies lead to reversibility of torrential tricuspid regurgitation in a patient with cardiac sarcoidosis. We also discuss the diagnostic challenge in distinguishing cardiac sarcoidosis from other myocardial diseases in a patient presenting with biventricular failure. A 48-year-old man presented with a 2-week history of worsening exertional dyspnea, abdominal distension, and fatigue. His past medical history included hypertension, Gilbert’s syndrome, pulmonary embolism in 2014 and 2020 for which he was taking apixaban and candesartan. Physical examination revealed a heart rate of 88 bpm, BP of 96/67 mmHg, raised JVP, mild ascites, and bilateral leg edema. A pan-systolic murmur was audible and air entry at the right lung base was reduced. 12-lead electrocardiogram demonstrated sinus rhythm with 1st degree atrioventricular block (AVB), PR interval 273 ms, right bundle branch block with QRS duration 131 ms, and left axis deviation. Inpatient rhythm monitoring detected episodes of second degree (Mobitz II) AVB. Echocardiography revealed severe impairment of biventricular systolic function.−1, PCV 0.51) with normal inflammatory markers , mild renal impairment , and elevated bilirubin (56 μmol·L−1). Liver transaminases, corrected calcium, and thyroid function tests were normal. High-sensitivity troponin-I , brain natriuretic peptide , and serum angiotensin converting enzyme  were elevated. Tuberculosis Elispot test was negative. Despite the polycythemia, molecular diagnostics detected no mutations in JAK2, CALR, and MPL genes.Serologic work-up revealed polycythemia  with severely reduced ejection fraction (EF) of 14% and multiple regional wall motion abnormalities, not compatible with a coronary distribution. Moderate functional mitral regurgitation (MR) was noted. The myocardium had a speckled appearance especially of the right side of the interventricular septum. The right ventricle (RV) was dilated with severely reduced systolic function . There was non-coaptation of the tricuspid valve (TV) leaflets due to tricuspid annular dilatation causing torrential tricuspid regurgitation (TR) and a dilated inferior vena cava. Because of the severe RV dysfunction and torrential TR, the RV systolic pressure could not be estimated.Cardiac magnetic resonance (CMR) imaging confirmed severe biventricular dysfunction with no regions of T2 signal-hyperintensity. Delayed gadolinium imaging revealed near circumferential subendocardial and subepicardial enhancement in the septum, anterior, and inferior walls which became transmural in the basal-mid lateral wall  of 14. Patchy intense FDG activity was seen throughout the myocardium (SUVmax 11.9) involving the septum, anterior, inferior, and RV free walls, both atria and the inter-atrial septum  positron emission tomography (PET) revealed intense thoracic and abdominal lymphadenitis with a maximal standardized uptake value . The hilar lymph nodes remained mildly enlarged and inflamed with a reduction in SUVmax to 6.5 .The fluid overload resolved with aggressive intravenous diuresis alongside oral heart failure medications. The patient was treated with induction therapy using intravenous methylprednisolone infusions (1 g on 3 consecutive days). Following this, prednisolone (40 mg daily weaned to 15 mg over 10 weeks) and methotrexate  were initiated. Due to episodes of high-grade AVB and severe LV systolic impairment, a defibrillator with cardiac resynchronization therapy (CRT-D) was implanted. Device follow-up at 6 weeks demonstrated 97% biventricular pacing with the underlying QRS duration 135 ms. Six-months later, repeat FDG-PET imaging revealed almost complete resolution of myocardial inflammation with only low-grade FDG uptake in the basal septum  and the TR remained moderate.1 The patient had severe TR prior to transplantation and histopathology revealed non-caseating granulomas within the TV leaflets, moderator band, RV septum, and the right atrium. Extensive fibrosis of the TV causing adherence to the RV wall was responsible for the valvular regurgitation. In our case, primary myocardial involvement of the RV likely resulted in chamber and TV annular dilation, although it is possible that concomitant TV leaflet and papillary muscle inflammation may have contributed to malcoaptation. Reduction in TR was therefore felt to be predominantly due to immunosuppressive therapy, as the improvement in RV function and TV leaflet coaptation corresponded with resolution of RV inflammation on FDG-PET. However, CRT implantation also played an important role in promoting LV remodeling.TV incompetence in CS is rare and usually secondary to chamber dilatation. Direct valvular granulomatous infiltration was described in a case following cardiac transplantation.2 Other causes include left-sided valvular and myocardial disease, pulmonary hypertension and increased RV afterload from pulmonic stenosis.3 Regurgitation occurs due to TV annular dilation, leaflet tethering, and RV +/− right atrial remodeling. Therefore, treatment of the primary cause often improves TR. Reversibility of torrential TR in the presence of severe RV dilatation and dysfunction, as in our case, has rarely been described. Reversible severe TR has been noted in association with thyrotoxicosis, wherein dilatation of the RV cavity and TV annulus was ascribed to a hyperdynamic circulatory state. Following beta-blockade and restoration of euthyroid status, only trivial TR was detectable.4 In the majority of cases, however, TR-reversibility is seen in the context of medical therapy for HF and atrial fibrillation whereby chronic right atrial dilatation is the core mechanism.In 90% of cases the most frequent mechanism of TR is secondary rather than primary. De novo TR following device implantation is associated with recurrent HF hospitalization and increased mortality.5 Key echocardiographic differentiators include thinning and aneurysmal transformation of the RV free wall or interventricular septum in CS compared to hypertrophy in CA.6 Diffuse thickening of the interatrial septum or cardiac valves may also be seen in CA. With CMR, LGE in a patchy, multifocal distribution is common to both diseases. In our case, the global subendocardial LGE pattern that is a hallmark of CA, was present in addition to transmural and subepicardial fibrosis. Expansion of the interstitial space with abnormal amyloid protein accumulation causes increased extracellular volumes. An elevated native T1 relaxation time > 1164 ms yields a 98% positive predictive value for CA.7 However, myocardial inflammation on FDG-PET, in particular the high signal with the RV free wall, tilted the balance toward CS. Due to differences in likelihoods on advanced imaging findings, endomyocardial biopsy was performed and, in this case, the histology clarified the diagnosis.Distinguishing between cardiac sarcoidosis and amyloidosis was a clinical challenge. When advanced, both diseases may display biventricular infiltration manifesting as granular speckling and thickening of the myocardium on echocardiography.This was a clinical case with several learning points including understanding of the mechanisms of valvular disease in cardiac sarcoidosis. We discussed how prompt immunosuppression combined with medical and device-related heart failure therapy can aid reversal in severe tricuspid regurgitation. Finally, we discussed the importance of multimodality imaging in distinguishing between cardiac sarcoidosis and amyloidosis.


Mechanical thrombectomy has been shown to reduce thrombus burden and pulmonary artery pressure (PAP) and to improve right ventricular (RV) function in patients with high-risk or intermediate-high-risk pulmonary embolism (PE). As hemodynamic data after mechanical thrombectomy for PE are scarce, we aimed to assess the hemodynamic effects of mechanical thrombectomy in acute PE with right heart overload.In this prospective, open-label study, patients with acute symptomatic, computed tomography-documented PE with signs of right heart overload underwent mechanical thrombectomy using the FlowTriever System. Right heart catheterization was performed immediately before and after thrombectomy and after three months. Transthoracic echocardiography was performed before thrombectomy, discharge, and at three months. This analysis was done after 20 patients completed three months of follow-up.Twenty-nine patients  underwent mechanical thrombectomy, of which 20 completed three months follow-up with right heart catheterization. Most patients were at high (17%) or intermediate-high (76%) risk and had bilateral PE (79%). Before thrombectomy, systolic PAP (sPAP) was severely elevated (mean 51.3 ± 11.6 mmHg). Mean sPAP dropped by -15.0 mmHg  immediately after the procedure and continued to decrease from post-thrombectomy to three months . RV/left ventricular (LV) ratio immediately reduced within two days by -0.37 . The proportion of patients with a tricuspid annular plane systolic excursion (TAPSE)/sPAP ratio < 0.31 mm/mmHg decreased from 28% at baseline to 0% before discharge and at three months (p = 0.007). There were no procedure-related major adverse events.Mechanical thrombectomy for acute PE was safe and immediately reduced PAP and improved right heart function. The reduction in PAP was maintained at three months follow-up. Pulmonary embolism (PE) remains the leading cause of preventable death in hospitalised patients , 2. The Whenever systemic lysis fails or is contraindicated, catheter-directed reperfusion treatment should be considered in patients with high-risk PE , 8–10. IHerein, we assessed the safety and the hemodynamic effects of mechanical thrombectomy in acute PE with right heart overload through three months of follow-up.This prospective, open-label, single-arm, single-center study assessed the hemodynamic effects of transcatheter mechanical thrombectomy using the FlowTriever System in acute symptomatic PE with right heart overload. This analysis was done after the first 20 patients completed their three months follow-up. Adults (≥ 18 years) with symptoms and clinical signs of acute (symptom duration < 30 days) PE, computed tomography-documented proximal filling defects in at least one main or lobar pulmonary artery, and signs of right heart overload in transthoracic echocardiography or computed tomography were included. Exclusion criteria were inability to receive anticoagulation and life expectancy < 30 days (as determined by the investigator). All patients provided written informed consent. The trial was approved by the local ethics committee (ethic committee of the Ärztekammer des Saarlandes) and complied with the Declaration of Helsinki.All patients had computed tomography to confirm the diagnosis of pulmonary embolism. Transthoracic echocardiography was performed before the thrombectomy.Mechanical thrombectomy was achieved using the FlowTriever System via large-bore transfemoral venous access. Full details of the procedure have been reported previously . In brieRight heart catheterization and transthoracic echocardiography were repeated at three months of follow-up.The primary safety outcomes were the number of patients with major adverse events, including major bleeding and periprocedural device- or procedure-related adverse events, between baseline to 48 h and survival at 30 days of follow-up. The efficacy outcomes were changes in sPAP between baseline and three months and changes in RV/LV ratio determined by transthoracic echocardiography from baseline to 48 h. Other outcomes included changes in echocardiographic parameters (tricuspid annular plane systolic excursion (TAPSE), TAPSE/sPAP ratio, and LV ejection fraction), and biomarkers, such as high-sensitivity (hs) troponin T and N-terminal B-type natriuretic peptide (NT-proBNP), as well as lengths of in-hospital stay, and time spent at intensive care unit (ICU).Statistical analyses were done using Stata 16.1 . Categorical variables are summarized as counts (percentages). Continuous variables are presented as means (standard deviations [SD]) or median (interquartile range [IQR]). The paired t-test or the Wilcoxon signed-ranks test was used to analyze matched pairs. Before-after changes are summarized as means . McNemar’s (two paired samples) or Cochran’s Q test (more than two paired samples) were used to compare the proportion of patients with mean PAP (mPAP) > 20 mmHg within groups. Pearson’s correlation coefficient was calculated for systolic PAP before thrombectomy and its change during follow-up. All tests were two-sided, and p-values < 0.05 were considered significant.From April 2021 to August 2022, 29 patients 34% female) were included. The patients’ baseline characteristics are summarized in Table 4% femaleTable From post-thrombectomy to three months, mean sPAP p = 0.002) continued to decrease Table . Compare continueHeart rate decreased significantly by -27 b.p.m.  during the procedure, while systolic and diastolic blood pressure (BP) remained unchanged. Of note, patients in the lowest quartile of systolic BP before thrombectomy  had an increase in systolic BP by 23 mmHg  on table, whereas in those in the upper quartile , systolic BP decreased by -18 mmHg . Patients in the second and third quartiles did not have a change in systolic BP (both p > 0.189).Before thrombectomy, the RV/LV ratio was increased Table  and immeThe peripheral oxygen saturation increased from 93 ± 7% to 97 ± 2% (p = 0.006) from pre- to post-procedure, whereas the supplemental oxygen was reduced from 7 ± 5 l/min to 2 ± 2 l/min (p < 0.001). The arterial lactate level decreased  on table. The perceived exertion, as measured using the original Borg CR10 scale,  improvedMedian hs-troponin T decreased from 80 pg/ml (IQR: 55–128) to 25.5 pg/ml (IQR: 18–42) before discharge  and to 11 pg/ml (IQR: 8–27) at three months . Before thrombectomy, hs-troponin T was increased (> 14 pg/ml) in 97% (28/29) of the patients. Following thrombectomy, the proportion of patients with increased hs-troponin T decreased from 90% (20/22) before discharge to 38% (5/13) at three months (Cochran’s Q for change from baseline to three months p = 0.006).Likewise, NT-proBNP substantially decreased from 2327 pg/ml (IQR: 1341–4167) to 344 pg/ml (IQR: 140–716) before discharge  and to 166 pg/ml (IQR: 82–260) at three months .There were no procedure-related major adverse events between baseline to 48 h and survival from baseline to 30 days of follow-up. Importantly, no patient died during 30 days of follow-up.This study assessed whether the hemodynamic effects of mechanical thrombectomy using the FlowTriever System are maintained through three months post-procedure in acute PE with right heart overload. The key findings are: (i) mechanical thrombectomy for acute PE was safe, (ii) immediately reduced PAP, improved right heart function and clinical symptoms, and (iii) mean sPAP continued to decrease through three months of follow-up.The 2019 ESC Guidelines for the Diagnosis and Management of Acute PE recommend catheter-directed treatment for reperfusion in patients with high-risk PE, in case systemic thrombolysis fails or is contraindicated , 7. The 2 l /min), (ii) arterial lactate level decreased, (iii) heart rate was lowered by 27 bpm, and (iv) hs-troponin T levels normalised. However, mPAP remains elevated in about a third of the patients. This group may include patients with previously undiagnosed pulmonary hypertension and those at increased risk for chronic thromboembolic pulmonary hypertension (CTEPH), requiring further follow-up.Compared with baseline, where 90% of the patients had pulmonary hypertension as defined by mPAP > 20 mmHg, about 35% had sustained mPAP > 20 mmHg at three months. This is of relevance since mPAP elevations > 20 mmHg predict mortality –20. TherFurther, mechanical thrombectomy improved RV function and RV-arterial coupling, assessed using the TAPSE/sPAP ratio. The ratio of TAPSE/sPAP, where TAPSE estimates contractility and sPAP reflects afterload, represents a non-invasive surrogate of end-systolic/arterial elastance (Ees/Ea) ratio and associates with functional class and prognosis in pulmonary hypertension , 21, 22.None of the patients included in this study died within 30 days post-thrombectomy. In FLASH, all-cause mortality at 30 days was 0.8%,  which isIn contrast to systemic thrombolysis, recommended in high-risk PE but associated with increased bleeding risk, particularly in elderly patients,  we obserThis study adds to previous single-arm studies and registries showing that mechanical thrombectomy using large-bore thrombus aspiration is feasible and safe, reduces thrombus burden, and immediately improves hemodynamics in intermediate and high-risk PE , 12. Mora priori power calculation to assess hemodynamic effects. All procedures herein were performed using the FlowTriever System, so the findings cannot be extrapolated to other catheter systems. The procedures were performed by only two experienced operators trained in structural interventions, which may explain the low rate of adverse events observed herein.Several limitations of this analysis need to be acknowledged. Because of the non-randomized study design and the lack of a comparator treatment group, we cannot exclude selection bias and unspecific treatment effects. Therefore, the data should be interpreted with caution and as hypothesis-generating. This feasibility study’s size was small and not based on an Mechanical thrombectomy for acute intermediate and high-risk PE with RV overload was safe and immediately reduced PAP, improved right heart function and RV-arterial coupling. Moreover, the reduction in PAP was maintained for three months. Randomized, controlled trials are required to finally assess the role of mechanical thrombectomy in the management of acute PE.


Methods forty SSc patients were examined using CPET and resting transthoracic echocardiography. CPET parameters analyzed were minute ventilation/carbon dioxide production (VE/VCO2) slope and maximum oxygen uptake (VO2 max); echocardiographic parameters were systolic pulmonary artery pressure (sPAP), tricuspid annular plane systolic excursion (TAPSE), and TAPSE/sPAP ratio. Results a positive correlation was observed between VE/VCO2 slope and age  and sPAP , conversely, a negative correlation was found between VE/VCO2 slope and TASPE/sPAP ratio . VO2 max showed an inverse correlation with age  and sPAP  and a positive correlation with TAPSE/sPAP ratio . On stepwise linear regression analysis, VE/VCO2 slope was significantly correlated with TAPSE/sPAP ratio , as well as VO2 max was significantly correlated with TAPSE/sPAP ratio . Conclusion in SSc patients, TAPSE/sPAP ratio is the echocardiographic parameter of RV function which showed the best correlation with ventilatory efficiency and exercise capacity.The aim of the study was to evaluate the correlation between cardiopulmonary exercise testing (CPET) parameters and right ventricular echocardiographic parameters for pulmonary arterial hypertension screening in a cohort of systemic sclerosis (SSc) patients.  CO) and natriuretic peptides is recommended by current guidelines. Right heart catheterization (RHC) is required to confirm PAH diagnosis and to assess the severity of haemodynamic impairment  were enrolled in the study. Twenty-three patients (57.5%) had lcSSc. Clinical, echocardiographic and CPET parameters of SSc patients are reported in Table 2 slope and VO2 max median values were 29.2 (IQR 25.3–32.7) and 19.7 (IQR 17.85–24.21) mL/min/kg, respectively. sPAP and TAPSE/sPAP ratio median value were 28 (25–32) mmHg and 0.87 (IQR 0.75–1.05) mm/mmHg, respectively.VE/VCO2 slope and age  and sPAP , conversely, a significant negative correlation was observed between VE/VCO2 slope and TAPSE/sPAP ratio  .A significant positive correlation was found between VE/VCO2 max showed a significant negative correlation with age  and sPAP  and a significant positive correlation with TAPSE/sPAP ratio  .VO2 slope and VO2 max showed a correlation with age, sPAP and TAPSE/sPAP ratio. Therefore, in multiple regression analysis TAPSE/sPAP ratio is the only variable, which shows a significant correlation with exercise capacity (VO2 max) and ventilatory efficiency (VE/VCO2 slope).In this study, VE/VCOReducing the time to PAH diagnosis can significantly improve patients’ survival. Current guidelines recommend resting echocardiography as a screening test in SSc patients. Although elevated sPAP values are associated with an increased probability of PAH, sPAP estimation may be inaccurate in the individual patient. In the ESC/ERS guidelines, CPET was performed to reduce unnecessary invasive procedures and in PAH risk assessment .2 slope and VO2 max. In clinical practice, sPAP is the most used echocardiograpic parameter to evaluate PAH. In our previous study, we demonstrated that in SSc patients with a DETECT algorithm step 2 total score > 35 TAPSE/sPAP ratio can be used to further select patients requiring RHC to confirm PAH diagnosis [. investigated the role of CPET in early PAH detection in a prospective study of 173 SSc patients, without known PAH, who also underwent RHC. PeakVO2 and VE/VCO2 were the CPET parameters, which showed the highest correlations with pulmonary haemodynamics. PeakVO2 was the most accurate parameter for diagnosis  and a peakVO2 of > 18.7 mL/kg/min excluded PAH . In addition, a nadir VE/VCO2 ratio of > 45.5 showed a positive predictive value of 1.0 [2 slope showed the best performance to predict PAH at RHC [2 slope and VO2 max has already been reported. In heart failure, higher sPAP and lower RV fractional area change (FAC) were correlated with worse percent predicted VO2 max and higher VE/VCO2 slope [In our study, we demonstrated that TAPSE/sPAP ratio is the best echocardiographic parameter of RV function which correlates with VE/VCOiagnosis . Dumitree of 1.0 . SantaniO2 slope . In PAH,O2 slope . To dateIn conclusion, in SSc patients TAPSE/sPAP ratio is the echocardiographic parameter of RV function which showed the best correlation with ventilatory efficiency and exercise capacity. Future larger studies are needed to confirm our preliminary data.


Mild uptake in the left ventricular wall was detected on the oncology 18FDG PET/CT. True myocardiac-involvement could not be distinguished with physiological uptake. The following 68Ga-FAPI-04 showed intense heterogeneous uptake in the left ventricular wall, particularly in the septum and apex area, corresponding with the late gadolinium enhancement regions shown by cardiac MR. Intense uptake was also noted in the mediastinal and bilateral hilar lymph nodes. Endomyocardial biopsy demonstrated sarcoidosis.A 47-year-old female with cardiac dysfunction and lymphadenopathy underwent