The professional association has already developed guidelines on the appropriate use of handheld ultrasound devices, especially in an emergency setting. Handheld ultrasound devices are seen as the ‘stethoscope of the future’ to assist in physical examination. Our exploratory study evaluated whether the measurements of cardiovascular structures and the agreement in identifying aortic, mitral, and tricuspid valve pathology made by a resident with a handheld device  reach the results reported by an experienced examiner who used a high-end device (STD). Patients referred for cardiology examination in a single center from June to August 2022 were eligible for the study. Patients who agreed to participate underwent two heart ultrasound examinations scanned by the same two operators. A cardiology resident performed the first examination with a HH ultrasound device, and an experienced examiner performed the second examination with an STD device. Forty-three consecutive patients were eligible, and forty-two were included in the study. One obese patient was excluded because none of the examiners succeeded in performing the heart examination. The measurements obtained with HH were generally higher than those obtained with STD, with the highest mean difference of 0.4 mm, but without significant differences . For valvular disease, the lowest agreement was observed for mitral valve regurgitation , which was missed in almost half of the patients with mild regurgitation and underestimated in half of the patients with moderate mitral regurgitation. The measurements performed by the resident with the handheld Kosmos Torso-One device showed high concordance with those conducted by the experienced examiner with a larger high-end ultrasound device. The learning curve of the resident could explain the limited performance in identifying valvular pathologies between examiners. Transthoracic echocardiography is the most common cardiac imaging modality , a centrThe first handheld ultrasound device, Acuson P10 (Siemens), was launched in 2007 and commercialized as a diagnostic and screening tool for physicians and nurses. The following years have seen a decrease in both cost and dimensions of ultrasound devices. At the same time, the performance in image quality, available imaging modes, and measurement accuracy has continued to increase steadily .Increased accessibility also makes handheld ultrasound devices attractive for teaching purposes. A study performed on Johns Hopkins Medical Center medical residents found that at least 30 scans are required to develop basic skills in heart ultrasound . ReliablSeveral handheld ultrasound devices with specific features are available for performing echocardiography .The handheld devices presented in The Kosmos Torso-One (Echonous Inc.) is, as of September 2022, the only HH device that presents both pulsed wave and continuous wave capabilities . Priced Problem-oriented focus cardiac ultrasound examination (FoCUS) is recommended by international professional associations, especially in emergency settings , or other factors. All patients were older than 18 years old and hemodynamically stable. The only exclusion criterion was the patient’s refusal to participate in the study. All patients signed an informed consent document.Patients underwent two heart ultrasound examinations and were scanned by the same two operators after the physical examination. The first examination (HH) was performed on the day of the presentation by a fifth-year cardiology resident using a Kosmos Torso-One  device with a phased array probe . The cardiology resident had previously received standard echocardiography training (a six-month cardiology imaging rotation). The second examination (STD) was performed the following day by an experienced cardiologist (>10 years of experience in echocardiography) using a high-end device with a phased-array cardiac probe  in the presence of the cardiology resident. The resident participated in the STD examination for training purposes and had no input into the STD report. Observation of the experienced examiner is valuable in the learning curve process, and the possibility to ask questions allows case-based training.Regardless of the ultrasound device, we performed the ultrasound using the parasternal long and short axis views, apical 2-, 4-, and 5-chamber views, and subcostal views. In all cases, patients were positioned in the left lateral decubitus position. Images were optimized to provide optimal endocardial definition. Complete echocardiographic examination was performed in all patients, including bidimensional, color Doppler, pulsed wave Doppler, and continuous wave Doppler. Each examiner collected the measurements , along with the information regarding the presence and severity of the valvular disease. Demographic data  and referral diagnosis were also recorded for each examined patient.The Kosmos Torso-One ultrasound device automatically calculates end-systolic volume, end-diastolic volume, and stroke volume (defined as the volume of blood pumped out of the left ventricle of the heart during each systolic cardiac contraction) in apical four-chamber and apical two-chamber view and provides an average between the two evaluations . We usedVariables were reported as mean (standard deviation) for age and number (%) for sex and referral diagnosis. The echocardiographic measurements were reported as mean (standard deviation), median [Q1 to Q3], and {min to max}, where Q1 is the 25th percentile and Q3 is the 75th percentile to allow an appropriate evaluation of the concordance between HH and STD. The agreement between two paired measurements (STD and HH) was reported as the difference between the gold standard measurement (STD) and HH measurement accompanied by the associated 95% confidence interval (95%CI). The difference is not statistically significant when 0 is in the 95% confidence interval. The visual representation of the agreement between measurements was reported using the Bland–Altman plot created with Real Statistics Using Excel (©Charles Zaiontz 2013–2022). http://vassarstats.net/kappa.html, accessed on 20 October 2022). A value of Kappa between 0.21 and 0.39 indicates a minimal agreement, between 0.40 and 0.59 indicates a weak agreement, between 0.60 and 0.79 indicates a moderate agreement, and between 0.80 and 0.90 indicates a strong agreement, while a value higher than 0.90 indicates an almost perfect agreement [The concordance of findings  was evaluated with the Kappa concordance coefficient using Linear Weighting  was excluded due to the impossibility of obtaining cardiovascular images either with the handheld or high-end transthoracic ultrasound probe. The excluded patient had been admitted for atrial fibrillation ablation and received the indication for transesophageal echocardiography, which was successfully performed.Forty-three patients were consecutively included in the study with no refusal to participate, and forty-two were evaluated. One patient  with morbid obesity . The diagnoses at the presentation were as follows: coronary artery disease—referred for invasive coronary imaging , atrial fibrillation , atrial flutter , paroxysmal supraventricular tachycardia  undergoing ablation, lower limb arteriopathy for peripheral angioplasty , type 2 s-degree  or third-degree  heart block presenting for permanent heart stimulator implantation, dilated cardiomyopathy , hypertrophic cardiomyopathy with signs and symptoms of decompensated heart failure , and severe aortic stenosis (1 patient. 2.4%)Patient ages ranged from 54 to 82 years old (average 65.4 (8.2) years). Most patients were men  younger than women (men vs. women—64.2 (8.3) years vs. 67.1 (8) years; Student t-test for independent sample: A good agreement between the HH and STD measurements was observed, with only two values that exceeded the upper bound of agreement (one measurement of LV—left ventricle and one of LVEF—left ventricular ejection fraction) . The LV The smallest agreement between STD and HH was observed for the pathology of the mitral valve . Half of the cases with mild mitral regurgitation were not identified on handheld ultrasound examination (8/16). Five subjects with moderate mitral insufficiency were also underestimated (5/10). Thirteen of fifteen patients with no mitral insufficiency were correctly identified. All cases of aortic stenosis were appropriately identified by handheld ultrasound, but only 3/10 patients with mild aortic regurgitation were correctly identified  . The cardiology resident appropriately diagnosed, with HH ultrasound, 10 out of 19 patients with mild or moderate tricuspid valve insufficiency, underestimated the severity of insufficiency in 4 out of 7 patients with moderate tricuspid regurgitation, and missed tricuspid regurgitation in 5 out of 12 patients with mild regurgitation . EighteeA pleural effusion was found in one patient. It was a mild right pleural effusion in a 78-year-old male who presented for dyspnea and orthopnea and congestive heart failure with severe left ventricular systolic dysfunction, severe mitral regurgitation, and moderate tricuspid regurgitation .The examination with the handheld device missed no cases of significant left ventricular hypertrophy, dilatation, or impaired systolic function .Intracardiac devices and significant para-lead regurgitations were clearly visualized in our study .The Kosmos Torso-One ultrasound device did not allow quantitative measurements for evaluating mitral valve stenosis and mitral prosthesis function when the study was conducted. In a patient with a mitral biological prosthesis, thickened valve cusps and reduced motion suggested malfunction of the prosthetic valve but did not provide measurements for quantification of the dysfunction. Trans-mitral mean pressure and pressure half-time were performed with the high-end ultrasound device and were consistent with moderate stenosis of the mitral biological prosthetic valve .Pulsed wave and continuous wave Doppler were used to quantify blood flow through valves .Our study shows an appropriate concordance of cardiovascular structure measurements between STD and HH devices, considering the difference between the examiners (cardiology resident vs. experienced cardiologist). The concordance between diagnoses was smaller than between measurements, showing weak to moderate agreements. The observed difference could be explained not only by device performance but also by the resident’s learning curve and the experienced echocardiographer’s expertise.No studies were available in the scientific literature to report the performances of the Kosmos device used in our study  when we Our results agree with other studies that compared pocket-size devices with conventional transthoracic examinations. Jenkins et al.  reportedBlurred endocardial borders represented a common issue in our study, more frequently encountered with handheld ultrasound, leading to differences in the measurement of heart chambers between handheld (HH) and high-end (STD) devices. Generally, the cardiovascular measurements had, in our study, higher HH values than STD for LVEF, Ao, and LV, but with identical measurements for IVS . DespiteOne disadvantage of using a handheld ultrasound device is its incapacity to generate the same image quality as the larger device. Image HH quality was also more prone to artifacts than the high-end (STD) counterpart. Wilkinson and Saxhaug  raise coAccording to the Echonous representatives, when they first started developing the handheld ultrasound device, they mainly focused on providing a learning tool for medical students . This woCurrently, the main application of artificial intelligence in the Kosmos device is automated ejection fraction calculation. Papadopoulou et al.  comparedOur study has its limitations, the most important ones being the applied design, namely, exploratory study, and thus the limited number of included patients. Secondly, in every patient, the examination with the handheld ultrasound device was performed by a cardiology resident, while the sonographist performing the echocardiography with the high-end device had more than ten years of experience. The applied design of the study limited the intra-observed reliability analysis on different devices . Furthermore, the results reported on inter-observer reliability are biased by the experience of the examiners, so the difference in experience may account for some of the differences between evaluations. Cardiac ultrasound examination is operator-dependent, so differences even between two experienced examiners when using the same device are common ,22,23,24The measurements of cardiovascular structures taken by a cardiology resident with a Kosmos Torso-One device showed high concordances with the larger high-end ultrasound device used by an experienced examiner. The learning curve could explain the limited performance in identifying valvular pathologies by the resident with the Kosmos Torso-One device. Incorporating algorithms in assisting measurements and identifying pathological findings could make echocardiographic examinations less operator-dependent and assist even less-experienced examiners in daily practice to ensure timely and accurate patient triage and/or diagnosis.


Mechanical circulatory support has proven effective in managing postcardiotomy cardiogenic shock by stabilizing patients’ hemodynamics and ensuring adequate organ perfusion. Among the available device modalities, the combination of extracorporeal life support and a microaxial flow pump for left ventricular unloading has emerged as a valuable tool in the surgical armamentarium. In this publication, we provide recommendations for the application and weaning of temporary mechanical circulatory support in cardiogenic shock patients, derived from a consensus among leading cardiac centers in German-speaking countries. Cardiogenic shock (CS) in patients following cardiac surgery  is a highly relevant but complex diagnosis. CS after heart surgery refers to a critical hemodynamic state of patients where weaning from cardiopulmonary bypass (CPB) is not possible or a persistent low cardiac output syndrome occurs during or after the cardiac procedure . AlthougThe term “postcardiotomy” does not accurately encompass the range of cardiac procedures that can result in CS). While PCCS is most frequently observed after standard cardiac procedures such as coronary artery bypass grafting or heart valve surgery, it can also occur after endovascular procedures like transcatheter aortic valve implantation or interventions on the thoracic aorta. Despite the fact that these procedures do not involve opening of heart chambers, they are still broadly classified as PCCS . AdditioIn this article, we present an algorithm for the therapy allocation of patients with PCCS . This stTemporary MCS devices play a key role in the therapy of PCCS. While a wide range of different temporary MCS systems and combinations thereof are available, no single therapy approach has yet established itself as the gold standard . NeverthDiagnosis and indicationEvaluation of reversible causes of hemodynamic instabilityEvaluation of contraindications for temporary MCS (tMCS)Treatment of PCCS using tMCSDe-escalation and weaning from tMCS.The presented algorithm consists of five parts:So far, there are no uniform diagnostic criteria or recommendations regarding the indication for the treatment of patients with PCCS. The current EACTS/ELSO/STS/AATS expert consensus gives recommendations on different tMCS modalities; however, it does not provide the complete treatment pathway . DespiteDepending on the clinical scenario, a distinction can be made between intraoperative and immediate postoperative circulatory failure starting in the intensive care unit (ICU) .Criteria for intraoperative CS: Failure to wean from CPB or inability to close the thorax and/or increasing lactate level and catecholamine requirement on CPB ,11.Criteria for postoperative CS in the ICU: Increasing catecholamine requirement or/and hemodynamic instability despite high-dose inotropic support . ObjectiIn addition to the VIS score, other parameters such as arterial lactate, cardiac index, central/mixed venous saturation, and systemic vascular resistance should be taken into account. Due to the potential influence of the index cardiac procedure or the underlining pathology itself, the relation to pre- and intraoperative values is particularly important in PCCS evaluation .The VIS is a useful tool for quantifying inotropic and vasopressor support and correlates with the severity of shock . It is c* Dosage in µg/kg/minIn case of obesity, the calculation is based on the patient’s lean body weight .A VIS > 30 indicates severe PCCS, in which case mechanical circulatory support should be considered .Technical problems (Tension) pneumothoraxBleedingMyocardial ischemiaIatrogenic dissectionPericardial tamponadePulmonary embolismBefore initiating tMCS therapy, reversible causes related to the underlying disease and/or surgery should be ruled out. In addition to the common differential diagnoses of CS, these include:Signs of severe cerebral damageCritical comorbiditiesMalignancy with an anticipated life expectancy of less than 6 monthsDocumented patient wishes/patient directivespH < 6.9 mol/LLactate > 225 mg/dL (25 mmol/L) No viable treatment options availableUncontrolled bleedingIneffective resuscitation (MAP < 50 mmHg or apO2 < 50 mmHg for 30 min)Mechanical circulatory support is an invasive and resource-intensive treatment that can be associated with relevant complications . For thiExpected duration of supportAnatomical characteristics of the patient (vascular access)Complication profiles of respective tMCS devicesAvailability of the tMCS devicesThe selection algorithm for an optimal tMCS system is based on the clinical scenario and the severity of shock. The following points are taken into account when choosing the tMCS modality:In case of isolated LV dysfunction, without arrhythmia or severe lactic acidosis (<72 mg/dL or <8 mmol/L), primary implantation of an Impella pump  should be performed ,15.In patients with a mechanical aortic valve prosthesis or a free-floating thrombus in the LV, a left ventricular Impella is contraindicated. In such cases, primary implantation of v-a ECLS has to be performed. Following this, LV unloading strategies  should be discussed.The Impella CP  is usually implanted percutaneously via femoral artery and can generate a flow of up to 3.5 L/min. For patients with an expected short tMCS duration, sole percutaneous Impella CP implantation can be considered.The Impella 5.5 can provide up to 5.8 L/min depending on afterload and has to be surgically implanted through a vascular prosthesis. Axillary artery is the preferred access route, as it allows for early postoperative mobilization of the patient and uncomplicated explantation.If the axillary artery is less than 7-mm in diameter, exhibits calcifications or anatomical peculiarities (such as arteria lusoria), implantation of an Impella CP via the axillary artery, possibly on the contralateral side, may alternatively be considered.Alternative access routes such as the ascending aorta (in open-chest patients) can be considered.We recommend performing surgical implantation via a 10 (8)-mm vascular prosthesis, which is anastomosed in end-to-side fashion to the target vessel.In case of isolated RV dysfunction, it is possible to establish RV support using v-a ECLS, a temporary right ventricular assist device (RVAD), or a right-sided percutaneous microaxial pump  .In patients with an open chest, cannulation of the pulmonary artery can be performed using a vascular prosthesis (10- or 8-mm diameter), which is tunneled out of the chest cavity allowing for thoracic closure and facilitating later explantation. For venous drainage, a cannula is usually placed in the right atrium via femoral or the right internal jugular vein. Alternatively, if no peripheral access is possible and extended support duration is anticipated, direct cannulation of the right atrium can be performed. In this case, a 14 mm graft is usually anastamosed to right atrium and exteriorized and a 24–26 Fr venous cannula is directly inserted and chest is closed ,16.In patients with a closed chest, percutaneous cannulation of the pulmonary artery can be performed via the right internal jugular vein. This can be achieved through two separate cannulas , requiring two separate venous punctures .Alternatively, the insertion of a double-lumen cannula  facilitated right ventricular support through a single puncture of the jugular vein. The tip of the catheter is placed in the main stem or upper right pulmonary artery under fluoroscopic and echocardiographic guidance. This method allows for early mobilization on ongoing right ventricular support .The percutaneous Impella RP is inserted into the pulmonary artery via the femoral vein and generates a flow of up to 4.6 L/min. Disadvantages of the Impella RP are a limited support duration, impaired patient mobilization, and the lack of respiratory support . AlternaEstablishing rapid circulatory support is essential in patients undergoing CPR. In this case, immediate implantation of veno-arterial extracorporeal life support (v-a ECLS) is recommended ,11,15.In open-chest patients, cannulation of central vessels  can be considered.In patients with a closed thorax, peripheral v-a ECLS cannulation should be performed. Whether percutaneous or open surgical cannulation is chosen depends on the clinical situation, anatomical circumstances of the patient, and the surgeon’s preference.In patients with peripheral arterial occlusive disease, surgical exposure of the femoral vessels and surgical implantation should be performed as a primary approach.Placement of a peripheral perfusion cannula is recommended, but can be performed shortly after hemodynamic stabilization.In patients with biventricular heart failure, respiratory failure, and/or severe lactic acidosis , isolated Impella therapy cannot provide sufficient hemodynamic support. At the same time, sole support with v-a ECLS may lead to pulmonary congestion due to the afterload increase associated with the retrograde arterial flow of v-a ECLS ,7,8,9,17In our algorithm, we primarily recommend LV unloading for v-a ECLS using an Impella pump, the so-called ECMELLA  concept .ECMELLA combines the advantages of v-a ECLS and an Impella pump, namely: biventricular unloading through a simultaneous preload and afterload decrease, as well as pulmonary support with an oxygenator. Therapy on ECMELLA provides intensive mechanical circulatory support with high-volume flow, which is intended to ensure sufficient organ perfusion in phases of acute shock .Another important advantage of the ECMELLA concept is the easy way of de-escalation once circulatory conditions have been stabilized. In this case, v-a ECLS weaning is usually performed first while continuing Impella therapy. This enables longer support with a lower risk of complications .The ECMELLA 2.0/2.1 implantation technique represents the further development of the concept, whereby only one instead of two arterial cannulation sites is required to establish ECMELLA support ,20.In this case, arterial vascular access is achieved via a Y-shaped vascular prosthesis, which is anastomosed to the axillary artery. One branch is used for Impella implantation, the other for the arterial cannula insertion of v-a ECLS. This method enables early postoperative mobilization  and bedside de-escalation on the ICU over time ,20.Intra-aortic balloon pump (IABP)The sole use of an IABP did not show any survival benefit in the treatment of cardiogenic shock patients .In our algorithm, the IABP is used only in combination with v-a ECLS for LV unloading in patients with absolute contraindications for an Impella pump. These include mechanical aortic valve prostheses or a floating thrombus in the left ventricle ,15. HowePercutaneous ventingPassive LV unloading can also be achieved with the help of a percutaneously placed cannula that is introduced into the left atrium by transseptal puncture .The venting cannula of the TandemHeart system  enables unloading of the left ventricle. It is connected to the venous drainage .The Bio-Medicus, NextGen two-stage cannula  allows for simultaneous drainage of both atria .A percutaneous cannula is placed under fluoroscopy and echocardiographic control.In specific cases , percutaneous atrial septostomy can be performed as a last-resort option.Surgical ventingIn patients with an open thorax an additional venous cannula can be placed through the upper right pulmonary vein into the LV .Alternatively, a vent can be placed directly via the LV apex. This method does not necessarily require a median sternotomy. Apical LV venting can be performed through a left lateral mini-thoracotomy, taking into account potential complications such as coronary artery injury, ventricular perforation, and bleeding .After placement, the cannulas for passive venting are tunneled outwards, fixated, and connected to the venous drainage of the v-a ECLS using a Y-shaped connector.Systems for tMCS represent an effective therapy for PCCS but carry the risk of treatment-associated complications. Those probability increases with the duration of support; therefore, a daily evaluation of the weaning potential is of great importance. Depending on the tMCS systems used, First, the indication for re-operation or intervention is verified depending on the entity of the cardiogenic shock .The basic prerequisites for weaning are the cessation of inotropic support  and a LVEF > 30% . If the LVEF is <25%, long-term support system should be considered. In borderline cases with an LVEF of 25–30%, a detailed re-evaluation of cardiac function should be performed after optimization of heart failure therapy ,10.After hemodynamic stabilization and a significant reduction of inotropic medication (with only low-dose vasopressor therapy remaining), a stepwise reduction in support is performed until the P2 level is achieved. This is done gradually with a continuous re-evaluation of hemodynamics over at least 48 h. Support should not be reduced below the P2 level, as this can cause retrograde flow through the pump into the left ventricle.If there are no severe valve pathologies, the LVEF is at least 25–30%, there is a stable rhythm, and no continuous inotropic treatment is needed while on support at the P2 level, the Impella can be removed.If this is not the case, alternative treatment concepts such as LVAD, heart transplantation, or palliation should be discussed.In case of increasing mitral regurgitation during a reduction of Impella flow, endovascular mitral valve reconstruction can be performed under Impella support .If circulatory support is inadequate , v-a ECLS implantation for escalation to ECMELLA can be considered, but long-term LVAD therapy should be prioritized .In the event of severe respiratory failure, veno-venous extracorporeal membrane oxygenation (v-v ECMO) can be implanted.If severe hemolysis, pump thrombosis, or Impella pump failure occur, a switch to a new Impella can be performed, but long-term LVAD therapy should be simultaneously discussed depending on the cardiac recovery potential.The basic criteria for weaning from v-a ECLS are the same as for weaning from Impella support. After stabilization of the patient’s hemodynamic condition, the v-a ECLS flow is gradually reduced to 1.5–2 L over at least 48 h.If the general weaning criteria  are met, v-a ECLS can be explanted.In patients on ECLS with unclear neurological status or severe complications, switch to Impella support in setting of bridge-to-decision therapy should be considered .Harlequin syndrome  is a rare complication that can occur after onset of the unloading device or during myocardial recovery under v-a ECLS therapy. In severe respiratory failure, poorly oxygenated blood is ejected into the circulation, but remains in the supra-aortic vessels due to retrograde flow and a high afterload generated by v-a ECLS. In this situation, the therapy should be escalated to veno-veno-arterial ECLS. To do this, an additional arterial ECLS line is established in order to transport oxygenated blood to the right atrium. This counteracts differential hypoxemia and reduces the risk of cerebral and coronary hypoperfusion .The basic criteria for ECMELLA weaning correspond to those for v-a ECLS and Impella weaning. Complications on v-a ECLS are common and increase with support duration. Therefore, the concept of ECMELLA weaning focuses primarily on the reduction of v-a ECLS support with potential explantation.ECMELLA therapy with femoral cannulation and simultaneous respiratory insufficiency also bears a risk of differential hypoxemia (Harlequin syndrome). In this case, escalating to vv-a ECMELLA should be considered.If de-escalation of ECMELLA therapy is not possible, long-term LVAD implantation on ECMELLA can be performed.The right ventricle has a significant regenerative potential, but sometimes requires prolonged periods of support. Therefore, implantation of a permanent RVAD or heart transplantation should be considered only after longer periods of support (>30 days) . It shouWe recommend a stepwise flow reduction of the temporary RVAD by no more than 0.5 L/min per day until 2 L/min is reached.It is important to underline, that in case of temporary RV support with Impella RP device the flow should not be reduced below 1.5 L/min (P4 level), due to the iatrogenic tricuspid regurgitation caused by the device itself.If hemodynamics fail to stabilize at minimal flow, the optimal support level should be established and re-evaluation performed after seven days.If weaning from temporary RVAD support is not possible after a total of 30 days, switching to a permanent system and/or listing for heart transplantation should be considered .If gas exchange is impaired during temporary RVAD support, the installation of an oxygenator in the extracorporeal circuit should be considered.Despite advances in therapy, the survival of patients with CS after cardiac surgery has hardly improved in recent years . In contp = 0.044) [The protocols are based on current studies and expert recommendations in the field of mechanical circulatory support. In a retrospective analysis, Ott et al. evaluated the results of the first version of the institutional allocation protocol for selecting temporary MCS in a large cardiac surgery department. A propensity score-matched analysis demonstrated a significant improvement in 30-day survival in patients treated according to the protocol  .LV unloading for CS patients treated with v-a ECLS is a crucial component of the presented algorithm, as it is associated with a significant survival benefit ,8. HowevIn this current manuscript, we summarized the most recent recommendations on tMCS therapy and adapted them for use in the setting of PCCS. We also presented de-escalation strategies for various tMCS modalities that can be applied to common causes of cardiogenic shock. However, our expert group remains committed to continuously improving and optimizing the presented tMCS algorithms.Cardiogenic shock after cardiac surgery is a life-threatening condition associated with high mortality. Tailored therapy using temporary mechanical circulatory support is an effective and often life-saving treatment option for patients with PCCS. The algorithm-based standardization of tMCS treatment seems a useful strategy to optimize the time-sensitive care of patients with PCCS.


Cardiovascular magnetic resonance (CMR) is increasingly used in newborns with congenital heart disease. However, reporting on ventricular volumes and mass is hindered by an absence of normative data in this population.Healthy term (37–41 weeks gestation) newborns underwent non-sedated, free-breathing CMR within the first week of life using the ‘feed and wrap’ technique. End-diastolic volume (EDV), end-systolic volume (ESV) stroke volume (SV) and ejection fraction (EF) were calculated for both left ventricle (LV) and right ventricle (RV). Papillary muscles were separately contoured and included in the myocardial volume. Myocardial mass was calculated by multiplying myocardial volume by 1.05 g/ml. All data were indexed to weight and body surface area (BSA). Inter-observer variability (IOV) was performed on data from 10 randomly chosen infants.2, ESV 14.5 (2.5) ml/m2 and ejection fraction (EF) 63.2 (3.4)%. Normative RV indexed EDV, ESV and EF were 47.4 (4.5) ml/m2, 22.6 (2.9) ml/m2 and 52.5 (3.3)% respectively. Mean LV and RV indexed mass were 26.4 (2.8) g/m2 and 12.5 (2.0) g/m2, respectively. There was no difference in ventricular volumes by gender. IOV was excellent with an intra-class coefficient > 0.95 except for RV mass (0.94).Twenty healthy newborns  with a mean (SD) birth weight of 3.54 (0.46) kg and BSA of 0.23 (0.02) m2 were included. Normative LV parameters were indexed EDV 39.0 (4.1) ml/mThis study provides normative data on LV and RV parameters in healthy newborns, providing a novel resource for comparison with newborns with structural and functional heart disease.The online version contains supplementary material available at 10.1186/s12968-023-00932-1. Neonatal cardiovascular magnetic resonance (CMR) is being increasingly utilized for assessment of structural and functional cardiac conditions. CMR has the unique ability to provide a detailed assessment of cardiac anatomy, non-invasive hemodynamics, volumetric data and tissue characterization, without the use of potentially harmful ionizing radiation . In addiIn neonates and infants, accurate measurement of biventricular volumes are needed for preoperative assessment and surgical planning for patients with congenital heart disease (CHD) associated with borderline left or right heart structures . While tThe interpretation of CMR in the neonatal population is limited by the inability to compare ventricular volumes and mass to those in normal neonates. There has been a recent momentum in pediatrics to establish CMR datasets for healthy infants and children –12, alth2)] in early pregnancy were included to avoid potential effects of maternal obesity. This study was approved by the Regional Ethics Committee and written informed parental consent was obtained. CMR was performed on infants while inpatients on the postnatal ward. No infant had required admission to the intensive care unit.Healthy term (37–41 weeks gestation) newborns underwent non-sedated, free-breathing CMR within the first week of life using the ‘feed-and-wrap’ technique. Newborns were a subset of infants born to mothers with a normal body mass index (BMI) in a larger multisite study examining the impact of maternal obesity on newborn outcomes , 14. NeoAll infants were scanned using acoustic ear protection, pulse oximetry, vector electrocardiogram (ECG) monitoring and without sedation or anesthesia, as described previously . Scans wImages were transferred to the post-processing Circle Cardiovascular Imaging (cvi42) software . End-diastolic and end-systolic phases were determined on the cine bSSFP short-axis stack. Manual contouring of biventricular endocardial borders was performed. Four chamber and two chamber cine images were used for cross-referencing particularly in basal slices for accurate determination of the atrioventricular valvar plane through the cardiac cycle. Left ventricular (LV) papillary muscles were separately contoured and included in the LV mass (LVM) calculation and excluded from the ventricular volume. RV trabeculations and papillary muscles were not contoured separately and were included in RV blood pool. A smooth endocardial border was drawn for the RV volumes. Epicardial borders for both ventricles were traced in diastole to measure the myocardial volume. The interventricular septum, including the septal band was included as part of the LVM. Myocardial volume was multiplied by the factor 1.05 g/ml to obtain the myocardial mass.  for continuous variables and percentages for categorical variables. The volumetric variables were assessed for normal distribution using the Shapiro–Wilk test. The association of gestational age to ventricular volumes was assessed using Pearson correlation coefficient and a p-value of < 0.05 was considered statistically significant. The primary data analysis was performed using Excel 2019 . The comparative analysis was performed using Stata ..Ten randomly selected neonates’ CMR data were chosen for interobserver variability assessment. Post-processing was performed on each of these studies by a second independent observer using the same methodology as stated above. Intraclass coefficient (ICC) estimates and their 95% confidence interval (CI) were calculated using Stata A total of 20 healthy newborns  were included in the study. All neonates were born at term with a mean gestational age of 39.9 1.2) weeks. Average maternal age was 34.2 (5.3) years. Mean age at the time of the scan in hours was 31.8 (14.0) hours (range of 9–56). One newborn did not have height included in the dataset precluding measurement of BSA and indexed values. Demographic details of the cohort are shown in Table .2 weeks.2. The average absolute and BSA indexed LV end-systolic volume  was 3.3 (0.5) ml and 14.5 (2.5) ml/m2, respectively. LV ejection fraction (LVEF) measured 63.2 (3.4)%. The LVM was 6.0 (0.7) g with an LVM index (LVMI) of 26.4 (2.8) g/m2. LVM, LVEDV and LVESV were also indexed to body weight as shown in Table The average LV end-diastolic volume (LVEDV) was 9.0 1.2) ml. The mean LVEDV indexed by BSA (LVEDVI) was 39.0 (4.1) ml/m ml. The 2. The RV ejection fraction (RVEF) was 52.5 (3.3)%. The average RV end-systolic volume (RVESV) was 5.2 (0.9) ml with an RVEDV indexed to BSA (RVEDVI) of 22.6 (2.9) ml/m2. Absolute RVM and BSA indexed mass (RVMI) were 2.9 (0.5) g and 12.5 (2.0) g/m2, respectively. In addition, the ratio of the RVEDV to the LVEDV was 1.2 (0.2). RV parameters including values indexed to birth weight are shown in Table Similarly, the mean absolute RV end-diastolic volume (RVEDV) of the cohort was 11.0 (1.7) ml. The RVEDV indexed by BSA (RVEDVI) was 47.4 (4.5) ml/mwas 52.5 .3%. The There were 13 male and 7 female infants. Volumetric data for LV and RV are described for males and females separately in Table There was a weak relationship between LVESVI and gestational age . There was no correlation between gestational age and any other variables of biventricular volumes or mass.  estimate between individual measurements and average measurement were calculated. LVEDV, LVESV, RVEDV, RVESV and LVM had excellent inter-observer reproducibility, while that for RVM was slightly lower Table .Table 5INeonatal CMR has historically been challenging primarily due to the need for anesthesia and image optimization. With numerous recent studies reporting refined imaging techniques in neonates without sedation, –17 and wEchocardiography is usually the first line method for assessment of LV volumes and mass. Three dimensional echocardiography is superior to 2-dimensional echocardiography in this regard, although there are wide limits of agreement and it underestimates ventricular volumes when compared to CMR in adult patients . LVM is 2 or more is used in some centers as favoring biventricular surgery [2 would measure as 4.6 standard deviations below the mean, indicative of moderate LV hypoplasia. In a large multicenter study of patients with pulmonary atresia and intact ventricular septum, a higher baseline RV end-diastolic area measured by 2-dimensional echocardiography was associated with biventricular repair [Neonatal CMR is being increasingly performed for both CHD and acquired cardiac conditions . Neonate surgery , 26. Howr repair . CMR is r repair , 8. By pSimilar to other centers, neonatal CMR was safely performed without sedation in our study using multi-signal average breathing and a feed-and-wrap technique . Additio2; females, 51 ml/m2) and RVEDV  in the youngest cohort reported appear to be higher than the values we observed. However, the cohort grouped children between 0 and 6 years of age (n = 12), likely accounting for the difference. Similarly, a recent large prospective pediatric study was conducted by Olivieri et al. to assess ventricular volumes and mass in healthy children and infants [Our study showed no association between gestational age and CMR data, although all neonates were born at term within a narrow timeframe (39–41 weeks gestation) which may preclude detection of a significant correlation. LV volumes by CMR in a preterm neonatal population has been evaluated . There h infants . The stuDespite being the largest CMR study performed on healthy term newborns, the study has a relatively small sample size (n = 20) that limits detailed analysis. Of note, the study was performed on a 3T scanner. Available adult studies have shown good reproducibility in the volumetric data obtained at 1.5 and 3T, but the lack of supportive pediatric literature potentially limits the generalizability of our data . All neoUsing non-sedated, free-breathing CMR, we report the largest study of normative data on biventricular volumes and masses in a healthy neonatal population, obtained in the first few days of life. The variables in this study were highly reproducible with good inter-observer agreement. These normative data provide a reference for comparison of ventricular volumes and masses in newborns with structural and functional heart disease.Additional file 1: Table S1. Correlation between gestational age and ventricular variables.


Reports of left ventricular noncompaction (LVNC) rarely include descriptions of the right ventricle (RV). This study aimed to describe the characteristics of the RV in LVNC patients with reduced LV function (LVNC-R) compared with patients with dilated cardiomyopathy (DCM) and subjects with LVNC with normal left ventricular ejection fraction (LV-EF) (LVNC-N).Forty-four LVNC-R patients, 44 LVNC-N participants, and 31 DCM patients were included in this retrospective study . Each group was divided into two subgroups by the amount of RV trabeculation.There was no difference in the RV-EF between the groups, and the RV trabecular mass correlated positively with the RV volume and negatively with the RV-EF in all the groups. All the measured parameters were comparable between the groups with decreased LV function. The hypertrabeculated RV subgroups showed significantly higher RV volumes and lower RV-EF only in the decreased-LV-function groups. The correlation of LV and RV trabeculation was observed only in the LVNC-N group, while LV trabeculation correlated with RV volumes in both noncompacted groups. Both decreased-LV-function groups had worse RV strain values than the LVNC-N group; however, RV strain values correlated with RV trabeculation predominantly in the LVNC-R group.The presence and characteristics of RV hypertrabeculation and the correlations between LV trabeculation and RV parameters raise the possibility of RV involvement in noncompaction; moreover, RV strain values might be helpful in the early detection of RV function deterioration. Many investigations have highlighted the characteristics of the right ventricle (RV) in physiological and pathological conditions, but the connection between the RV and the left ventricle (LV) must be emphasized, as they are inseparable through their direct mechanical interactions , 2.Although some studies have revealed the relationship between RV and LV trabeculation and the effect of LV trabeculation on RV parameters in various conditions, the RV characteristics in the case of a hypertrabeculated left ventricle, e.g., noncompaction (LVNC), are less well described. In an LVNC population with good LV ejection fraction (EF), the characteristics of RV trabeculation suggested the involvement of the RV in noncompaction , 4. HoweOur study aimed to describe the characteristics of the RV and quantify the connection among RV parameters, LV function, and LV trabeculation in LVNC patients with reduced LV function (LVNC-R); furthermore, we compared these correspondences with those in both dilated cardiomyopathy (DCM) patients and LVNC subjects with normal EF (LVNC-N).Forty-four LVNC-R patients (EF<50%), 44 LVNC-N participants (EF>50%), and 31 DCM patients were included in this retrospective study.Both LVNC-R and LVNC-N were diagnosed based on the morphological criteria of Petersen . For better patient selection, Jacquier‘s criterion  was 42% in the LVNC-R group and 36% in the LVNC-N group , 6. In aThe enrolled DCM patients met the following diagnostic criteria: dilated LV chamber, increased LV volumes, and decreased systolic LV function (EF<50%) with the exclusion of other causes of LV dysfunction .The following exclusion criteria were applied in all three groups: patients with poor image quality or whose scans were performed after contrast agent administration or contained arrhythmic or respiratory artifacts were excluded, as it would have modified the postprocessing evaluation . The preTo study the hypertrabeculation of the RV, all the groups were divided into two subgroups by the amount of RV trabeculation. The patients were evaluated individually based on their sex- and age-specific reference values, and those who exceeded that range were categorized as patients with RV hypertrabeculation (HT), while those who were within the abovementioned reference range were classified as having normal RV trabeculation (NT) .All procedures in this investigation followed the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Ethical approval was obtained from the Central Ethics Committee of Hungary. Participants provided written informed consent, as they had to sign a form before the examination that their results could be used for scientific purposes.Cardiac MRI examinations were performed on a 1.5 T MRI scanners . Retrospectively gated, balanced steady-state free precession (bSSFP) cine images were acquired in conventional two-chamber, three-chamber and four-chamber long-axis views. Breath-hold short-axis cine images from base to apex were obtained with full coverage of the LV and RV.The following scanning parameters were similar for both Siemens and Philips scanners: repetition time: 2.5 and 2.7 ms, respectively; echo time: 1.15 and 1.3 ms, respectively; flip angle: 58° and 60°, respectively; spatial resolution: 1.5 ×1.5 mm for both scanners; and temporal resolution: 25 frames per cardiac cycle for both scanners. The slice thickness was 8 mm with no interslice gap, and the field of view was 350 mm on average adapted to body size. All of the images were obtained before the administration of the contrast agent .For the postprocessing analysis, Medis Suite software version 3.2  and its modules QMass and QStrain were used. Semiautomatic tracing with manual correction of the endo- and epicardial contours of the left and right ventricles was performed at end-systole and end-diastole. These contours were made by two independent observers (ZG with 6 years of experience and AS with 11 years of experience).The LV and RV volumetric, functional and myocardial mass parameters were calculated with the MassK algorithm of the QMass module. Based on the altered signal intensities, this threshold-based papillary and trabeculated muscle quantification algorithm automatically identifies all voxels within the epicardial contour as blood or myocardium; therefore, the detected myocardial voxels within the endocardial borders include the papillary and trabeculated muscles . For theBased on the above, the LV and RV end-diastolic volume , end-systolic volume , stroke volume , ejection fraction , end-diastolic total myocardial mass and end-diastolic trabecular and papillary muscle mass  were calculated. The compact myocardial mass  was calculated as the difference between the total myocardial mass and the LV-TM and RV-TM. All of the measured parameters were indexed to body surface area (i).For the LV and RV deformation analysis, the feature-tracking technique was used within the QStrain module of the software. Endocardial strain values were calculated based on the manually traced endocardial contours in end-diastole and end-systole in the short axis and the 2-, 3- and 4-chamber long-axis images of the left ventricle and in the 4-chamber view of the right ventricle. The LV global longitudinal strain (LV-GLS), LV global circumferential strain (LV-GCS), RV global longitudinal strain (RV-GLS), RV free-wall strain (RV-FWS) and RV septal strain (RV-SS) were measured.Continuous variables are represented as the mean and standard deviation (SD), and discrete parameters are described as counts and percentages. The Shapiro–Wilk test was used to assess the normality of distributions. For the comparison of the three groups, one-way analysis of variance (ANOVA) was used with Tukey’s post-hoc test in the case of normal distribution and equal variances. The Kruskal–Wallis test was used to compare nonnormally distributed data. An independent-samples t-test or the Mann–Whitney test was performed to compare the subgroups, as appropriate. Linear correlations between the studied parameters were assessed with Pearson’s or Spearman’s correlation coefficient. To compare categorical variables, the chi-squared test was performed. The intraclass correlation coefficient (ICC) and 95% confidence intervals were used to estimate the interobserver agreement. A p value <0.05 was considered statistically significant. IBM SPSS Statistics  was used for calculations. Figures were generated with GraphPad Prism version 8.0.0 on Windows .The ICCs were calculated to describe the interobserver agreement on the LV and RV parameters, and excellent values were measured for all parameters .Contrast agent was used for 84.0% of the studied patients (n = 100), and late gadolinium enhancement (LGE) with a nonischemic pattern was present in 71.4% of the DCM, 63.9% of the LVNC-R and 2.7% of the LVNC-N groups .First, we presented the baseline characteristics of the LV. The LVNC-R and LVNC-N groups were different in all of the measured parameters, while the LVNC-R and DCM groups differed significantly only in the LV-TMi. LV-TMi correlated negatively with LV-EF . The LVNC-N group had significantly better LV-GLS and LV-GCS values than the reduced-EF group .The measured RV volumetric parameters were all comparable between the LVNC-R and DCM groups, while the RV-EDVi and RV-SVi values were significantly higher in the LVNC-N group than in the LVNC-R or DCM groups. It is remarkable that independent of the LV-EF, the RV-EF was in the normal range in all of the studied groups, and no significant differences were observed between the three groups. Furthermore, there were no significant differences in either the RV-TMi or RV-CMi between the observed groups .Next, the patients were divided by RV trabecular mass into two subgroups: RV-HT and RV-NT . RV-HT wIn the comparison of the HT and NT subpopulations, not only the RV-TMi but also the RV-CMi were significantly higher in the HT groups. We did not find differences in the RV volumetric or functional parameters between the NT and HT subgroups of the LVNC-N population. In contrast, RV volumetric parameters were significantly higher and RV-EF was significantly lower in the decreased-LV-function groups with RV-HT. Unlike the other two groups, the HT subgroup of the LVNC-R group showed significantly worse RV strain values  than the NT subgroup .Regarding the deformation analysis of the RV in the total population, there were no significant differences in the RV-GLS and RV-FWS between the reduced-LV-function groups; however, relevant differences were found between the good- and decreased-LV-EF populations. RV-SS differed significantly only between the two LVNC groups .The RV-TMi showed a strong positive correlation with the RV volumes and a negative correlation with the RV-EF in all of the studied groups. Further relevant correlation between the RV-TMi and LV-TMi were observed only in the LVNC-N group, while this observation was not present in the decreased-LV-function groups. Notably, the LV-TMi showed more significant correlations with RV parameters in the LVNC groups than in the DCM group. The RV-EF was correlated with all RV parameters in all the groups, while the LV-EF showed a correlation with volumes only in the LVNC-R group .All the measured RV strain values showed significant correlations with the RV-TMi and LV-TMi and with the RV-EF, especially in the LVNC-R group. The RV-GLS and RV-FWS showed negative correlations with the LV-EF in the reduced LV function groups, and the RV-SS correlated with the LV-TMi, RV-TMi, RV-EF, RV-EDVi and RV-ESVi only in the LVNC-R group .In this study, we described the RV trabeculation and RV functional characteristics of patients with LVNC and decreased LV function.After studying the characteristics of the LV, the good- and decreased-LV-function groups differed in the volumetric and functional parameters, while the only difference between the LVNC-R and DCM populations was in the value of the LV-TMi. These findings were consistent with the literature in all aspects –16. For In contrast with the RV volumetric parameters of the good EF group, those of the LVNC-R and DCM groups were decreased but still in the normal range in our study, which might be due to LV enlargement that compresses the RV through mechanical interactions . As poteAlthough there were no differences in the RV-TMi among the groups, this parameter differed significantly between the NT and HT subgroups in each patient population. The correlations of the RV-TMi with RV volumes and RV-EF corroborate the significantly higher volumes and lower RV-EF values observed in the HT subgroups with decreased LV function (LVNC-R-HT and DCM-HT) , 21, 23.It is worth mentioning that RV and LV trabeculation were significantly correlated only in the LVNC-N group , 25. StaAs LV-TMi and LV-EF correlated with RV volumetric parameters, the former in both noncompacted groups and the latter only in the LVNC-R group, the pathological relevance of the morphological features of LVNC may arise in terms of RV.Regarding our results, in the presence of good LV function, all the RV strains were independent of LV trabeculation and LV function. However, once LV function had decreased, both RV-GLS and RV-FWS decreased, independent of the etiology. This is supported by the literature, as more decreased RV strain values were described in DCM patients with a higher risk of major cardiovascular events combined with other cardiovascular diseases –30.Not only LV function but also LV trabeculation might have an impact on RV strains: notable correlations could be observed between the RV-SS values and LV-TMi in noncompaction patients with reduced LV-EF. This could be due to ventricular interdependency, as LV contraction through the interventricular septum contributes to RV pressure by 20–40% .We must highlight that relevant correlations were observed between all measured RV strain parameters and RV trabeculation only in the LVNC-R group. Moreover, significantly lower RV strains could be observed in the HT subgroup than in the NT subgroup solely in the LVNC-R population. This is in line with a larger LVNC study with good LV-EF, which also showed these correlations and differences . InteresTo summarize, in this investigation, the characteristics of the RV and the connections between the RV and LV parameters were described, focusing on noncompaction patients with reduced LV function.According to our results, the significant differences between patients with a normal and hypertrabeculated RV, the RV strain deterioration due to RV hypertrabeculation, and the relevant correlations in both LVNC groups could presume the involvement of the RV in noncompaction.Our study suggests that similar to that of the LV, the progression of RV function deterioration might be assumed in noncompaction, although further studies with larger cohorts and genetic verification are required for an accurate assessment.S1 TableDCM: dilated cardiomyopathy, LVNC-R: left ventricular noncompaction with reduced LV function, LVNC-N: left ventricular noncompaction with good LV function, ECG: electrocardiography. The bold values indicate statistical significances (p<0.05).(DOCX)Click here for additional data file.S2 Tableother technical reasons: implanted devices, arrhythmic or respiratory artifacts. comorbidities: ischemic, valvular, or congenital heart diseases, coexisting cardiomyopathies; hypertension, diabetes mellitus, endocrine disorders, chronic kidney or systemic diseases. intense sports activity: >6 hours/week. LVNC: left ventricular noncompaction, DCM: dilated cardiomyopathy, LV: left ventricle, LVNC-R: left ventricular noncompaction with reduced LV function, LVNC-N: left ventricular noncompaction with good LV function.Exclusion criteria: (DOCX)Click here for additional data file.S3 TableICC: intraclass correlation coeffitients, RV-EDVi: right ventricular end-diastolic volume index, RV-ESVi: right ventricular end-systolic volume index, RV-SVi: right ventricular stroke volume index, RV-EF: right ventricular ejection fraction, RV-TotalMassi: right ventricular end-diastolic total myocardial mass index, RV-TMi: right ventricular end-diastolic trabecular and papillary muscle mass index, RV-GLS: right ventricular global longitudinal strain, RV-FWS: right ventricular free-wall strain, RV-SS: right ventricular septal strain.(DOCX)Click here for additional data file.S4 TableDCM-NT: dilated cardiomyopathy with normal right ventricular trabeculation, DCM-HT: dilated cardiomyopathy with right ventricular hypertrabeculation, LVNC-R-NT: left ventricular noncompaction with reduced left ventricular function and normal right ventricular trabeculation, LVNC-R-HT: left ventricular noncompaction with reduced left ventricular function and right ventricular hypertrabeculation, LVNC-N-NT: left ventricular noncompaction with good left ventricular function and normal right ventricular trabeculation, LVNC-N-HT: left ventricular noncompaction with good left ventricular function and right ventricular hypertrabeculation. RV-EDVi: right ventricular end-diastolic volume index, RV-ESVi: right ventricular end-systolic volume index, RV-SVi: right ventricular stroke volume index, RV-EF: right ventricular ejection fraction, RV-TMi: right ventricular end-diastolic trabecular and papillary muscle mass index, RV-CMi: right ventricular end-diastolic compact myocardial mass index, RV-GLS: right ventricular global longitudinal strain, RV-FWS: right ventricular free-wall strain, RV-SS: right ventricular septal strain. The bold values indicate statistical significances (p<0.05).(DOCX)Click here for additional data file.S1 File(XLSX)Click here for additional data file. 21 Mar 2023 <div> PONE-D-23-04778 </div>  <div> Characteristics of the right ventricle in left ventricular noncompaction with reduced ejection fraction </div>  <div> PLOS ONEDear Dr. Szűcs,Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.Please submit your revised manuscript by May 05 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at  </div> A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.A marked-up copy of your manuscript that highlights changes made to the original version. 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Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: We look forward to receiving your revised manuscript.Kind regards,Antoine Fakhry AbdelMassihAcademic EditorPLOS ONEJournal Requirements:When submitting your revision, we need you to address these additional requirements.https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf[Note: HTML markup is below. Please do not edit.]Reviewers' comments:Reviewer's Responses to Questions <font color="black"> Comments to the Author1. Is the manuscript technically sound, and do the data support the conclusions? </font> The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: No********** <font color="black"> 2. Has the statistical analysis been performed appropriately and rigorously?  </font> Reviewer #1: Yes********** <font color="black"> 3. 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Is the manuscript presented in an intelligible fashion and written in standard English? </font> PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: Yes********** <font color="black"> 5. Review Comments to the Author </font> Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: The Authors present the study entitled "Characteristics of the right ventricle in left ventricular noncompaction with reduced ejection fraction". The topic could be of great clinical importance. LVNC is a disease that could worsen the clinical prognosis; therefore, describing the new indices that can help prevent clinical status deterioration would be of great interest. The Reviewer appreciates the Authors' effort and notices the promising value of the study; however, at that moment, some crucial comments need to be addressed.Major comments:1. The study's title is not confirmed in the text and should be changed accordingly (the Authors compared different groups of patients but not only concentrated on LVNC-R).2. The Authors should find and precisely describe the possible clinical value of the presented results. The main differences were presented between the groups with reduced and normal LVEF; however, there were no evident differences between DCM and LVNC-R groups .3. Control group of persons is necessary for LVNC-N patients.4. The presentation of the Methods section needs to be corrected (results should be excluded from that part). The Authors include some results in the Methods section- that should be changed (the results should not be included in the methods section).5. From which patients the authors enrolled their groups retrospectively? From some Magnetic Resonance material? The flowchart with the enrollment process should be added: the Authors should write from which group of patients the enrolled groups were taken; the Authors should write precisely how many patients and why were further excluded from the analysis.6. What is the real novelty of the presented study ??? The Authors should underline that regarding their results.Minor comments:1. The inclusion criteria should be mentioned precisely (the authors included that information in different parts of the methods section).1. The Authors mentioned that "All participants provided written informed consent" – how the authors obtained written informed consent in the retrospective study? That should be clarified in the methods section.3. Information from lines 82-83  should be mentioned in the magnetic resonance description.I did not find some important citations in the manuscript:Stämpfli SF, Donati TG, Hellermann J, Anwer S, Erhart L, Gruner C, Kaufmann BA, Gencer B, Haager PK, Müller H, Tanner FC. Right ventricle and outcome in left ventricular noncompaction cardiomyopathy. J Cardiol. 2020 Jan;75(1):20-26. doi: 10.1016/j.jjcc.2019.09.003.********** <font color="black"> 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.If you choose “no”, your identity will remain anonymous but your review may still be made public.Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. </font> Reviewer #1: No**********https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool,  3 May 2023Response to ReviewerMajor comments:1. The study's title is not confirmed in the text and should be changed accordingly (the Authors compared different groups of patients but not only concentrated on LVNC-R). As the Reviewer requested, we have considered changing the study title to a more accurate form. We hope that the modified title reflects the manuscript’s content more precisely. Please see the revised title in the Manuscript file.2. The Authors should find and precisely describe the possible clinical value of the presented results. The main differences were presented between the groups with reduced and normal LVEF; however, there were no evident differences between DCM and LVNC-R groups .The Reviewer is correct that a definitive distinction could be conducted between DCM and LVNC-R patients, in which the LV trabecular mass can be helpful, according to our results. Despite the reduced LV-EF, we need to emphasize that the average RV-EF was in the normal range in both groups in our study. Although the RV strain values of the LVNC-R and DCM groups were significantly worse than those of the LVNC-N population, significant differences between the hypertrabeculated and normally trabeculated RV subgroups could be observed only in LVNC-R. This suggests that this hypertrabeculated subgroup is more vulnerable, which might indicate an even worse prognosis.Our results are strengthened by some studies, and the prognostic role of RV involvement in noncompaction might be predictable not only in addition to good LV function but also in the case of decreased LV-EF [1-3]. Nonetheless, the abovementioned results and the literature raise attention to the potential reduction of RV function and the importance of the follow-up of these patients.We have emphasized the prognostic role of RV involvement in noncompaction in the introduction section (lines 60-63); moreover, the discussion section was also modified according to the abovementioned hypothesis (lines 340-341). We hope it meets the Reviewer’s expectations.3. Control group of persons is necessary for LVNC-N patients.We would like to thank the Reviewer for the constructive comment. As we would like to focus on noncompaction patients with reduced left ventricular function, in addition to this LVNC-R population, we would have fitted two other groups for a more comprehensive analysis: one for the noncompaction phenotype (LVNC-N group) and one for reduced LV function (DCM group).During the study design process, the opportunity for a control group arose; however, it would be very similar to our previous studies, where the comparison of healthy controls and a large LVNC cohort with good LV function was thoroughly discussed . In these studies, significant differences were found between the groups in almost all LV and RV parameters, and these results were cited in our recent manuscript to give a more comprehensive picture of the role of noncompaction even with good LV function.Thus, if we had enrolled a fourth group for controls, the manuscript could have been criticized as having redundant content, and the focus of the LVNC-R group might have been lost.For all these reasons, with the greatest respect, we would like to refrain from involving a control group in this investigation. To meet your requirements, we emphasized the results and the comparison of the abovementioned studies even more in the discussion section (lines 282-284).4. The presentation of the Methods section needs to be corrected (results should be excluded from that part). The Authors include some results in the Methods section- that should be changed (the results should not be included in the methods section).The Methods section has been modified as the Reviewer needed: the Jacquier criteria were corrected for a better understanding (lines 75-76); in Table 1, the baseline characteristics were separated from LV parameters (lines 91 and 183); moreover, RV reference ranges were removed, as they were misunderstood, and only the citation was referenced (lines 98-101). Please find these changes in the modified manuscript.5. From which patients the authors enrolled their groups retrospectively? From some Magnetic Resonance material? The flowchart with the enrollment process should be added: the Authors should write from which group of patients the enrolled groups were taken; the Authors should write precisely how many patients and why were further excluded from the analysis.At the Heart and Vascular Center of Semmelweis University, we have an extensive register of cardiac MRI examinations conducted since 2009. We enrolled all the studied groups retrospectively from that pool. From that pool, our research group also created a highly detailed register of noncompaction patients, which helped in the most careful patient selection regarding the exclusion criteria.The exclusion process was complex, as several criteria were met at the same time. First, all scans taken after contrast agent administration were excluded, as based on our previous investigation, these would have distorted our results [5]. Regarding the remaining LVNC population, we excluded patients with any comorbidity; then, from the rest, we selected patients with reduced LV function, to which we matched participants with good LV-EF by sex and age individually.Regarding the DCM patients, after excluding the images taken after contrast agent administration, we selected all nonischemic, comorbidity-free DCM patients.As the Reviewer recommended, we added a flowchart in the Supplementary material (Table S2) with the enrollment process. The exclusion criteria are also seen on page 4, lines 82-88. We sincerely hope that it will meet your requirements.6. What is the real novelty of the presented study ??? The Authors should underline that regarding their results.The abovementioned study is one of our research team’s investigations. The main difference between the two studies is the study population. While the previous study focused on the characteristics of the RV in a highly selected LVNC population with good EF, we described the characteristics of the RV in patients with reduced LV function in the current study. We investigated how LV function deterioration affects RV volumetric, functional, and myocardial mass parameters, which were not previously detailed in the literature. The novelty of our study was that RV function was preserved in addition to reduced LV function; however, the hypertrabeculated RV had significantly worse strain values than the normally trabeculated RV. According to the references mentioned in the second question above, a worse long-term prognosis might be predictable in these patients. This hypothesis was highlighted more in the discussion section.Minor comments:1. The inclusion criteria should be mentioned precisely (the authors included that information in different parts of the methods section).We would like to thank the Reviewer for reminding us of this inaccuracy. All the inclusion and exclusion criteria are mentioned in the Study population part of the Methods section; however, for the Reviewer’s recommendation, we clarified both of them and completed the Manuscript with a flowchart .1. The Authors mentioned that "All participants provided written informed consent" – how the authors obtained written informed consent in the retrospective study? That should be clarified in the methods section.The Heart and Vascular Center of Semmelweis University is an educational institution where all patients must read, fill out and sign a formal document before undergoing any examination. In this form, the patients approve that their examination’s details could be used for scientific purposes. That is the reason why we have written informed consent for a retrospective investigation. Thank you for the critical comment; we have clarified this issue in the Methods section (lines 104-105).3. Information from lines 82-83  should be mentioned in the magnetic resonance description.In our investigation, the poor image quality, as scans were performed after contrast agent administration, or the presence of artifacts, e.g., arrhythmias and implanted devices, were limiting factors and resulted in false parameters during the postprocessing evaluation [5]. In other words, poor image quality would provide unusable data, and for this reason, these patients should be excluded from the investigation. As these circumstances do not influence the scanning procedure but determine the analyses of the population, we would like to mention these issues in the study population part, where the enrollment/exclusion processes were detailed, if it meets your requirements. Additionally, the ‘Image acquisition and analysis’ section was also completed with this information (lines 130-131).I did not find some important citations in the manuscript:Stämpfli SF, Donati TG, Hellermann J, Anwer S, Erhart L, Gruner C, Kaufmann BA, Gencer B, Haager PK, Müller H, Tanner FC. Right ventricle and outcome in left ventricular noncompaction cardiomyopathy. J Cardiol. 2020 Jan;75(1):20-26. doi: 10.1016/j.jjcc.2019.09.003.We would like to thank you for bringing this article to our attention. As the Reviewer suggests, it highlights the prognostic role of distinct RV parameters in LVNC, emphasizing the importance of follow-up of these patients. As discussed above in the second question, we have completed the discussion section and cited this reference (line 338).References1. Stampfli, S.F., et al., Right ventricle and outcome in left ventricular non-compaction cardiomyopathy. J Cardiol, 2020. 75(1): p. 20-26.2. Wang, W., et al., Influence of Right Ventricular Dysfunction on Outcomes of Left Ventricular Non-compaction Cardiomyopathy. Front Cardiovasc Med, 2022. 9: p. 816404.3. Kiss, A.R., et al., Impact of Right Ventricular Trabeculation on Right Ventricular Function in Patients With Left Ventricular Non-compaction Phenotype. Frontiers in Cardiovascular Medicine, 2022. 9.4. Kiss, A.R., et al., Left ventricular characteristics of noncompaction phenotype patients with good ejection fraction measured with cardiac magnetic resonance. Anatol J Cardiol, 2021. 25(8): p. 565-571.5. Szucs, A., et al., The effect of contrast agents on left ventricular parameters calculated by a threshold-based software module: does it truly matter? Int J Cardiovasc Imaging, 2019. 35(9): p. 1683-1689.AttachmentResponse to Reviewers.docxSubmitted filename: Click here for additional data file. 21 Aug 2023Characteristics of the right ventricle in left ventricular noncompaction with reduced ejection fraction in the light of dilated cardiomyopathyPONE-D-23-04778R1Dear Dr. Szűcs,We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact Kind regards,Antoine Fakhry AbdelMassihAcademic EditorPLOS ONEAdditional Editor Comments :Please during proofing, move Table 1 to results section Reviewers' comments:Reviewer's Responses to Questions <font color="black"> Comments to the Author </font> 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.Reviewer #1: (No Response)********** <font color="black"> 2. Is the manuscript technically sound, and do the data support the conclusions? </font> The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes********** <font color="black"> 3. Has the statistical analysis been performed appropriately and rigorously?  </font> Reviewer #1: Yes********** <font color="black"> 4. Have the authors made all data underlying the findings in their manuscript fully available?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. </font> The Reviewer #1: Yes********** <font color="black"> 5. Is the manuscript presented in an intelligible fashion and written in standard English? </font> PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: Yes********** <font color="black"> 6. Review Comments to the Author </font> Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: The Authors corrected their text nicely according to my previous comments. It would be helpful whether the Authors write in red color their new elements of the text additionally to information regarding lines.For that moment I have only one minor comment:The Authors should exclude ALL the results from the Methods section. (Table 1 present the results).********** <font color="black"> 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.If you choose “no”, your identity will remain anonymous but your review may still be made public.Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. </font> Reviewer #1: No********** 15 Sep 2023PONE-D-23-04778R1 Characteristics of the right ventricle in left ventricular noncompaction with reduced ejection fraction in the light of dilated cardiomyopathy Dear Dr. Szűcs:I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. onepress@plos.org.If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact plosone@plos.org. If we can help with anything else, please email us at Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staffon behalf ofProf Antoine Fakhry AbdelMassih Academic EditorPLOS ONE


Given the compelling evidence on the effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the conventional heart failure population, SGLT2i deserve exploration in systemic right ventricular (sRV) failure. The initial experience with dapagliflozin in sRV failure patients is described, with a focus on tolerability and short-term effects on clinical outcomes.p = 0.036, and 72 ± 14 vs. 66 ± 16 ml/min/1.73m2, p = 0.020, respectively). At 6 months follow-up (n = 8), median NT-proBNP decreased significantly from 736.6 [589.3–1193.3] to 531.6 [400.8–1018] ng/L (p = 0.012). Creatinine and eGFR recovered to baseline levels. There were no significant changes in echocardiographic systolic sRV or left ventricular function. New York Heart Association class improved significantly in 4 out of 8 patients (p = 0.046), who also showed an improvement in the 6-minute walk test or bicycle exercise test performance. One female patient developed an uncomplicated urinary tract infection. No patients discontinued treatment.Ten patients  with symptomatic sRV failure who received dapagliflozin 10 mg per day on top of optimal medical therapy between 04–2021 and 01–2023 were included. Within 4 weeks, no significant changes in blood pressure, electrolytes, or serum glucose occurred. Creatinine and estimated glomerular filtration rate (eGFR) showed a slight decline (88 ± 17 to 97 ± 23 µmol/L, Dapagliflozin was well-tolerated in this small cohort of sRV failure patients. While the early results on the reduction of NT-proBNP and clinical outcome parameters are encouraging, large-scale prospective studies are warranted to thoroughly evaluate the effects of SGLT2i in the growing sRV failure population. With the improved survival of congenital heart disease patients, clinicians are frequently confronted with heart failure in this heterogeneous population. Complex congenital heart disease with a systemic right ventricle (sRV) forms a distinct entity where the morphological RV functions in the subaortic position and supports the systemic circulation. This occurs in the biventricular setting of transposition of the great arteries (TGA) after the atrial switch procedure according to Mustard or Senning, or in congenitally corrected TGA (ccTGA). Failure of the sRV is a frequent long-term complication in these patients; at 45 years of age, over 50% of TGA patients who underwent the atrial switch and up to 65% of ccTGA patients will have developed symptomatic heart failure , 2. RobuRecently, sacubitril/valsartan  has been linked to reduction of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, sRV remodeling with improvement of systolic ventricular function, improvements in 6-minute walk test (6MWT) distance, New York Heart Association (NYHA) class, and quality of life in patients with sRV failure , 6. ThesSodium-glucose cotransporter 2 inhibitors (SGLT2i) are a relatively novel class of drugs that have quickly become a pillar in the treatment of “conventional” left ventricular heart failure, demonstrating a reduced risk of worsening heart failure, hospitalization, and cardiovascular-related death . Given tIn this brief report, we describe the tolerability and short-term neurohumoral, echocardiographic, and clinical effects of dapagliflozin in the treatment of sRV patients with heart failure. Moreover, we discuss the rationale for and propose a future prospective evaluation of SGLT2i effects in this patient group.Adult patients with symptomatic sRV failure who were started on dapagliflozin 10 mg p.o. q.d. on top of current optimal medical therapy as part of compassionate care between April 2021 and January 2023 were reviewed for inclusion.Inclusion criteria were: adults with an sRV in a biventricular circulation with underlying anatomy of TGA after the atrial switch procedure or ccTGA, progressive symptomatic heart failure with NYHA class ≥ II, and at least moderately reduced systolic sRV function as assessed by echocardiography. Progressive symptomatic heart failure was defined as progressive symptoms attributed to heart failure and/or a deterioration in exercise performance as assessed by bicycle exercise test, accompanied by an increase in NT-proBNP levels despite the pharmacological treatment.All patients were followed up in the outpatient clinic according to the smart technology-supported care pathway at the Leiden University Medical Center, as previously described . After bTolerability was evaluated by blood pressure and laboratory investigations , non-fasting plasma glucose, and electrolytes) after 2 to 4 weeks, discontinuation of treatment, and the occurrence of side effects or adverse events.2 max.At the structured 6 months follow-up visit, the biomarker NT-proBNP was evaluated as a surrogate for neurohumoral activation status and heart failure-related prognosis. Furthermore, hemoglobin, hematocrit, electrolytes, creatinine, eGFR, aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyltransferase (GGT), HbA1c, non-fasting serum glucose, and uric acid changes were evaluated. Systolic sRV and left ventricular (LV) function were assessed by transthoracic echocardiography as previously described , 9. ChanAll tests and procedures performed involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 2013 Helsinki declaration or comparable ethical standards. Appropriate local scientific board approval was obtained and the need for written informed consent was waived by the institutional medical ethical board (protocol N22.120). All patients provided consent for registration of their data and publication.t-tests or Wilcoxon signed-rank tests were used as appropriate. For the comparison of paired ordinal data, the Wilcoxon signed-rank test was used. A p-value < 0.05 was considered statistically significant.All statistical analyses were performed in SPSS version 25 . The figure was generated with Graphpad Prism version 9.3.1 . Normally distributed continuous data were displayed as mean (± standard deviation) and non-normally distributed continuous data were displayed as median [interquartile range Q1—Q3]. Proportions were displayed as numbers (percentages). Normality was tested with the use of the Shapiro-Wilk test. For the comparison of continuous values between time points, paired samples Ten consecutive patients were included in this retrospective cohort. Six (60%) had underlying anatomy of TGA late after the atrial switch, and 4 (40%) had ccTGA. Seven patients (70%) were female and the median age at treatment initiation was 50 years [46.5–52]. Baseline patient characteristics are shown in At baseline, 4 patients had severely reduced and 6 had moderately reduced systolic sRV function. Three patients had a mechanical tricuspid valve and the other 7 patients had grade II tricuspid regurgitation. The systolic subpulmonary LV function was good in 8 and mildly reduced in 2 patients.p = 0.509), diastolic blood pressure , non-fasting plasma glucose levels , or electrolytes were observed. Creatinine increased  and eGFR decreased  significantly. A 60-year-old female patient developed a urinary tract infection which was treated with oral antibiotics. No other side effects or adverse events were observed and none of the patients discontinued the treatment.After 2–4 weeks of treatment with dapagliflozin, no statistically significant changes in systolic blood pressure  after 4 months with mild congestion which resolved after a single intravenous administration of loop diuretics. Additionally, this patient required escalation in the dose of spironolactone and bumetanide despite treatment with dapagliflozin and was listed for heart transplantation. In the 6 months preceding SGLT2i therapy, this patient experienced 4 heart failure-related admissions. The dose of furosemide was reduced in patient 2 and triamterene could be stopped in patient 3. No concurrent changes in medical therapy occurred in the other 7 patients during follow-up.p = 0.012) (p = 0.575) and eGFR  recovered after the initial deterioration in renal function, with no significant change from baseline to 6 months (p = 0.957) or body mass index . There were no statistically significant changes in systolic sRV or LV function and dimensions as assessed with transthoracic echocardiography from baseline to 6 months follow-up (p = 0.046), and no patients experienced a clinical deterioration. These 4 patients also showed an improvement in either 6MWT distance or exercise test performance, although these changes were not statistically significant.Eight patients (80%) had a 6 months follow-up visit. From baseline to 6 months, median NT-proBNP decreased significantly from 736.6  to 531.6  ng/L (= 0.012) . Creatin6 months . There wollow-up . ChangesDapagliflozin was well-tolerated in this cohort of 10 patients with symptomatic sRV failure: (1) blood pressure, plasma glucose, and electrolytes remained stable while renal function recovered to baseline levels after an initial dip, (2) no patients discontinued treatment, (3) no relevant side effects were observed, and (4) no unexpected deterioration of heart failure was observed.In the 8 patients with a structured 6 months follow-up visit, we observed a significant median NT-proBNP reduction of 17.3% −43.5–−6.9]. To compare, a 45% reduction in NT-proBNP levels was documented at 6 months in sRV failure patients treated with sacubitril/valsartan (–−6.9. ToA comparable magnitude of NT-proBNP reduction was documented in the large randomized controlled trials investigating SGLT2i in conventional left ventricular heart failure with reduced ejection fraction. In the DAPA-HF and EMPEROR-reduced trials, median NT-proBNP reductions of 13.7% and 12.9%, respectively were reported , 11. WheNT-proBNP is released by both the ventricular and atrial myocytes as a response to elevated cardiac wall stress, and has prognostic value in sRV failure patients specifically; a decrease in NT-proBNP has been correlated with improved clinical status, reduced risk of hospitalization, and lower mortality in sRV failure patients . ElevateRegarding the short-term outcomes, a significant improvement in NYHA class was observed. Nevertheless, there were no significant changes in any of the exercise parameters nor in the echocardiographic parameters assessing systolic ventricular function. This might be attributed to the limited cohort, small effect size, or the variability in the echocardiographic assessment of sRV function.Another potential advantage of SGLT2i is the practical ease of implementation and adherence when compared to other heart failure drugs, as the target dose and starting dose are identical and can be implemented over a wide range of renal functions. When comparing SGLT2i to other drugs with more profound anti-hypertensive effects like ARNIs or beta blockers, SGLT2i might prove to be especially beneficial in relatively young adult congenital heart disease patients, in whom hypotension rather than hypertension usually is a limiting factor.The initial results seem encouraging and demonstrate that SGLT2i treatment is feasible and safe, even in advanced sRV failure patients. Although no firm conclusions can be drawn regarding the clinical effects, the current data is promising and worthy of further validation in a larger prospective setting, particularly when considering the growing unmet need for adequate heart failure treatment in the adult congenital heart disease population. Therefore, we call for international collaboration and the initiation of a prospective trial to study the effects of SGLT2i as a promising treatment option for sRV failure.