Detection of T2 hyperintensities in suspected degenerative cervical myelopathy (DCM) is done subjectively in clinical practice. To gain objective quantification for dedicated treatment, signal intensity analysis of the spinal cord is purposeful. We investigated fully automated quantification of the T2 signal intensity (T2-SI) of the spinal cord using a high-resolution MRI segmentation.Matched-pair analysis of prospective acquired cervical 3D T2-weighted sequences of 114 symptomatic patients and 88 healthy volunteers. Cervical spinal cord was segmented automatically through a trained convolutional neuronal network with subsequent T2-SI registration slice-by-slice. Received T2-SI curves were subdivided for each cervical level from C2 to C7. Additionally, all levels were subjectively classified concerning a present T2 hyperintensity. For T2-positive levels, corresponding T2-SI curves were compared to curves of age-matched volunteers at the identical level.p < 0.001) and range  compared to matched controls. Percentage of the range from the mean absolute T2-SI per cervical level, introduced as “T2 myelopathy index” (T2-MI), was correspondingly significantly higher in T2-positive segments . ROC analysis indicated excellent differentiation for all three parameters (AUC 0.865–0.920).Forty-nine patients showed subjective T2 hyperintensities at any level. The corresponding T2-SI curves showed higher signal variabilities reflected by standard deviation  and DRKS00017351 (28.05.2019) The radiological assessment in degenerative cervical myelopathy (DCM) is still challenging and requires further improvement due to restricted correlation of imaging alterations and clinical severity of affected patients as well as controversial prognostic utilization . MagnetiIn clinical routine, the evaluation of such intramedullary signal changes is done subjectively, predominantly resulting in a binary categorization for T1 hypointensities , 21–23. Therefore, a more precise and completely objective graduation of intramedullary signal alterations seems to be purposeful for an optimal treatment planning in affected patients. We investigated a fully automated quantification of the T2 signal intensity (T2-SI) of the entire cervical spinal cord based on a high-resolution T2 MRI segmentation.This is a matched-cohort analysis of DCM patients and healthy volunteers out of two separate trials, who prospectively underwent identical cervical MRI protocols between July 2018 and Jan 2022. Patients were included through the local outpatient clinic if showing a cervical spinal canal compromise with at least radiological contact of degenerative tissue to the spinal cord in combination with symptoms of degenerative cervical spine disease. Healthy volunteers were recruited through a clinical announcement. Details on inclusion and exclusion criteria have been already published . Both trThe whole cervical spine was depicted using a common clinically applied T2-weighted 3D sequence acquired on a 3 Tesla scanner (SIEMENS Magnetom Prisma) with a 64-channel head-neck coil .https://bitbucket.org/reisert/patchwork/wiki/Home). The analyses have been implemented in a special internal software . Ground truth segmentations were manually delineated for 15 cases by two examiners, splitting into ten training and five validation cases. Each of the two examiners provides more than 10 years of experience in spinal MRI evaluation. The segmentation reached a Dice coefficient of 0.91. All segmentations were checked for apparent errors by two examiners independently. Additionally, an automated annotation of the vertebral bodies C2 to C7 was trained by another patchwork CNN as anatomical reference. The cross-sectional areas  of the spinal cord were computed, and the T2-SI was averaged for each CSA slice-by-slice and depicted as T2-SI curve in arbitrary units (a.u.). The spinal cord segmentation and associated T2-SI curve is exemplary shown in Fig. The next step was a fully automated segmentation of the spinal cord from C2 to C7 based on these 3D T2-weighted images using a trained deep convolutional neural network (CNN). The applied approach involved using nested patches of a fixed matrix size that decrease in physical size. An U-net type architecture was utilized in each scale, with the U-net matrix size set at 32 × 32 × 32 voxels for all scales. A scale pyramid with a depth of four was employed. The architecture of the U-net used was similar to the default U-net configuration presented in the literature . The netTo compare the particular cervical segments, the mean, standard deviation (SD), and range of the T2-SI of all slices were calculated from the center of the upper to the center of the lower cervical body, respectively.Representing the extent of T2-SI variability, we introduced the “T2 myelopathy index” (T2-MI) as a new parameter. It was defined as percentage of the T2-SI range in relation to the mean absolute T2-SI within every single cervical segment:The complete post-processing including segmentation, T2-SI curve generation, and calculation of the evaluated parameters takes about 3 min.For definition of the ground truth, the presence of a T2 hyperintensity within the spinal cord was subjectively evaluated in each cervical level from C2 to C7, receiving five ratings per MRI scan . Accordingly, all segments were classified in a binary fashion as “T2-positive” if a hyperintensity occurred or as “T2-negative” if it did not. To raise reliability, the categorization was done by three independent, blinded, experienced observers. Each of the three observers provides at least 10 years of experience in spinal MRI evaluation. The agreement of all three observers was evaluated through Fleiss’ kappa statistics . For furFor all segments that were subjectively categorized as T2-positive, we generated a control group with age- and level-matched segments out of the healthy volunteers (T2-negative).U test for unpaired samples was applied. Gender distribution between both groups was checked through exact binomial test. Overall, p-values < 0.05 were assumed to be statistical significant. Normal distribution was evaluated by Shapiro-Wilk-test. In case of non-normal distributed values, median and interquartile range (IQR) were stated. The diagnostic accuracy for the established parameters was defined by ROC analysis. An area under the curve (AUC) of 0.8–0.9 was considered as “excellent” and of > 0.9 as “outstanding” [For group comparison, Mann-Whitney tanding” . We additanding” , 32. ForOverall, 202 MRI datasets were included for analysis, of which 114 (56.4%) were symptomatic patients and 88 (43.6%) asymptomatic volunteers. Median age of all included participants was 61.0 (IQR 15.2) years and 94 (46.5%) were female.p < 0.001), representing a “substantial” agreement [Every cervical segment was categorized subjectively by each of the three observers, resulting in 1010 ratings per observer. Inter-rater reliability analysis revealed an absolute agreement of all three observers concerning the T2 hyperintensity categorization in 963 segments (95.3%). Fleiss-Kappa was 0.674 (greement .n = 15) and C5/6 (n = 22). There were six T2-positive patients for each level C3/4 and C6/7, and none showing a T2 hyperintensity in C2/3. None of the healthy volunteers showed a T2 hyperintensity.After forced consensus between the raters, 49 segments were classified as T2-positive, expectedly all out of the patients group. Therefore, 43.0% of the 114 included patients showed a T2 hyperintensity at any level. The predominantly affected levels were C4/5  a.u. vs. 24.34 (IQR 17.12) a.u., p < 0.001; Table The absolute T2-SI values revealed no significant differences between the T2-positive and T2-negative group . For the particular cervical levels C3/4, C4/5, and C5/6, this significant difference was reproducible (p < 0.001–0.002), whereas level C6/7 showed only a trend , was correspondingly significantly different between both groups (T2-positive segments 23.99% (IQR 15.21) vs. T2-negative segments 10.85% IQR 7.14); ; p < 0.0We present a new quantification procedure for the T2-SI of the spinal cord that was able to differentiate between cervical segments of DCM patients with a present T2 hyperintensity and healthy volunteers based on the variability of the signal intensity. This fully automated process has the potential for diagnosing radiological DCM objectively and standardized, thus optimizing the recommendation for treatment. The received sufficient diagnostic accuracy of the established parameters and their cut-off values have to be confirmed through further investigations and correlated to clinical symptoms of affected patients.This T2-SI quantification tool is based on a fully automated segmentation procedure of the spinal cord, based on a trained deep CNN showing sufficient accuracy. Minor interferences of compromising degenerative tissue and spinal cord in high-grade stenosis are conceivable due to nearly iso-intense signaling at those borders. However, two independent observers did not detect any apparent segmentation error. The next step was the generation of a T2-SI curve for the whole cervical spinal cord, averaging the T2-SI within every slice Fig. . The advThe exact position of the T2 signal alteration within the spinal cord and the type of their boundaries was not addressed in our evaluation due to averaging of every cross-section. However, the sharp or blurry demarcation of T2 hyperintense areas was a relevant prognostic factor in previous subjective classifications, which has to be considered as limitation –14. A rep = 0.093). Nevertheless, even at level C6/7, both groups showed clearly distant values for the T2-MI of 11.6% (T2-negative) versus 24.8% (T2-positive).The absolute T2-SI values are not interindividually comparable due to known specific imaging conditions for each MRI scan . That coFigure To summarize the main limitations of our study, we predominantly have to mention the still limited patient population as basis for our analysis. Additionally, it has to be taken into account that the applied parameters standard deviation, range, and T2-MI are arbitrary. The extent, position, and the boundary type of the T2 signal alteration within the spinal cord was not addressed in this evaluation, which, however, should be relevant for the characterization of DCM patients.For the future, diagnostic accuracy and prognostic information for affected patients should be improved by combining different MRI modalities. Especially diffusion-based techniques, such as diffusion microstructural imaging (DMI) or diffusion tensor imaging (DTI), may allow conclusions about alterations of the axonal integrity and intramedullary free water distribution , 36–38. This evaluation represents one step for this approach with implementation of a routinely applicable, fast and observer-independent assessment of intramedullary T2 signal alterations and transferring this into a quantifiable setting.This fully automated T2 signal quantification of the spinal cord was able to reveal a significantly different variability of the T2-SI in patients with DCM and present T2 hyperintensities compared to healthy volunteers. Whilst the absolute T2-SI values are not applicable due to known individual imaging conditions, we introduced the new, inter-individually comparable T2 myelopathy index (T2-MI), showing corresponding significances to the extent of signal variability represented by the standard deviation and range of T2-SI at every cervical level.This automated, innovative procedure has the potential for diagnosing radiological DCM more objectively and standardized, thus optimizing the recommendation for treatment. The determination of more detailed cut-off values associated to the different stages of DCM and its diagnostic accuracy is under further investigation.


Mitral regurgitation is the most common form of valvular heart disease. The anatomy and pathophysiology of mitral valve regurgitation are very complex, and dedicated devices are required for transcatheter mitral valve replacement in patients with a high or prohibitive surgical risk. In the United States, all transcatheter mitral valve replacement devices are still being studied and are not yet approved for commercial use. Early feasibility studies have demonstrated good technical success and short-term outcomes, but larger samples and longer-term outcomes still need to be assessed. Furthermore, significant advances in device technology, delivery systems, and implantation techniques are essential to avoid left ventricular outflow tract obstruction, and valvular and paravalvular regurgitation as well as ensuring good anchoring of the prosthesis. This has led to the development of transcatheter options including transcatheter-edge-to-edge repair (TEER) and transcatheter mitral valve replacement (TMVR).2Mitral regurgitation (MR) is the most common form of valvular heart disease. In the current era, the management of MR is determined by several factors, including etiology, severity, and surgical risk of the patient. Untreated severe MR can result in high mortality rates.Early advancements in transcatheter aortic valve replacement (TAVR) contributed to the use of aortic transcatheter heart valves in the mitral position. Successful implantations were noted in patients with failed bioprosthetic valves , annuloplasty rings , and mitral annular calcification (MAC), but not in native mitral valves without MAC. For this reason, significant efforts were undertaken for designing new devices that implanted into the native mitral annulus. Dedicated TMVR devices are needed to provide anchoring, eliminate MR, and reduce the risk of paravalvular regurgitation and left ventricular outflow tract (LVOT) obstruction.TMVR devices face several challenges. The mitral annulus is a large D-shaped structure defined anteriorly by the aortomitral curtain, making device sizing a challenging process. The annulus size is larger than the aortic, thus larger devices are needed that have higher-profile delivery systems. This translates into larger iatrogenic atrial septal defects for transseptal delivery systems with possible right to left shunting and resulting hypoxia. The delivery catheter needs flexibility to reach the mitral implant position. In the absence of mitral annular calcification, an anchoring mechanism is required, especially since the anterior aortomitral curtain is a dynamic and flexible structure. Finally, the proximity of the device to the LVOT and the presence of the anterior mitral valve leaflet during TMVR can induce LVOT obstruction, which appears to be the Achilles heel of TMVR.Clinical trial design for TMVR poses several challenges. The obvious major benefit of TMVR is MR elimination, which is in contrast to TEER; however, this needs to be evaluated against its risks. Randomized controlled trials have provided the highest quality data for safety and effectiveness of novel transcatheter devices over the last decade. For TMVR, standard of care treatment that can serve as appropriate control group in a randomized controlled trial is evolving. For TMVR in patients with primary MR, randomization must be considered against surgical mitral valve repair or TEER for patients at high surgical risk. For secondary MR, TMVR must be randomized against guideline-directed medical therapy or TEER, depending on the clinical situation and anatomy, given that TEER now has a class 2A guideline recommendation in this setting.Randomization of patients with secondary MR to surgery is difficult given lack of guideline recommendations and favorable surgical data. Single arm TMVR evaluation may be appropriate in the context of overall randomized controlled trial design when randomization to surgery or TEER is not feasible or possible due to clinical or anatomic reasons. An important consideration of TMVR trials is the appropriate evaluation of surgical candidacy, contemporary guideline directed medical therapy , and evaluation of TEER suitability, which is supported by guidelines for high-risk primary MR and medically optimized secondary MR patients. With regard to trial end points, the primary end point for TMVR trials should include those related to heart failure, such as mortality and/or heart failure hospitalizations. Quality of life end points (Kansas City Cardiomyopathy Questionnaire score) may be considered as a component of a composite primary end point as suggested in the Mitral Valve Academic Research Consortium document. Randomized trials with TEER as the control group can be designed to demonstrate superiority or noninferiority; however, those against guideline-directed medical therapy must be designed to demonstrate superiority. Secondary end points should include those pertaining to safety, measures of success, left ventricular remodeling, and functional capacity.Currently, several TMVR systems  are being evaluated in multiple feasibility studies and pivotal trials. The delivery mechanism, deployment, and anchoring mechanisms vary significantly between devices. Devices can be annular, supra or subannular, with or without a docking system , and with or without (annular or ventricular) anchors. We hereby discuss TMVR devices that are currently being studied .4The Tendyne TMVR system (Abbott Vascular) is an intra-annular, self-expanding nitinol bioprosthesis with a trileaflet porcine pericardial valve. The system consists of an outer frame that serves as a supra-annular cuff to prevent paravalvular MR. It is a retrievable and repositionable device delivered transapically via a 36F sheath and anchored to the left ventricular apex by an epicardial pad tether. It is possible to tighten the tether for a few days up to weeks after implantation to decrease any significant development of paravalvular leak.7 The device was founded in 2010, acquired by Abbott in 2015, and approved for CE mark in Europe since January 2020 after the publication of the largest early feasibility, multinational, nonrandomized study. This study included 100 patients with ≥ 3+ MR at high to prohibitive surgical risk who underwent implantation of the Tendyne valve.8 According to the Mitral Valve Academic Research Consortium definitions, technical success was achieved in 96% of the patients, along with 94% and 72.4% 30-day and 1-year survival rates, respectively. The majority of patients had NYHA I/II at 1 year (88.5%).The Tendyne TMVR system is the most studied device thus far, with the largest published cohort of 100 patients followed up to 2 years.9 Patients with severe MAC (≥ 3+ MR or severe MS or moderate MR with at least moderate MS) will be enrolled in a nonrandomized arm. The primary outcome includes 1-year survival free of heart failure hospitalization and the composite of all-cause mortality, cardiovascular-related hospitalizations, stroke, or mitral valve reintervention or reoperation.9The SUMMIT trial  is an ongoing large randomized study to compare Tendyne TMVR with TEER using MitraClip in patients with ≥ 3+ MR.10 The system is delivered via a 35F straight or a 37F curved sheath and can be implanted via a transapical or transseptal approach.The Intrepid TMVR system was developed by Foundry Newco XII, Inc, and was acquired by Medtronic in 2015. It consists of a 27-mm trileaflet bovine pericardial valve surrounded by an internal frame as well as an outer fixation frame with a flexible atrial segment and a stiffer ventricular segment in sizes of 42 and 48 mm, with a 54-mm valve in development.11 Important exclusion criteria included LVEF < 20% and severe pulmonary hypertension with systolic pulmonary pressure > 70 mm Hg. All patients underwent a transapical approach with the Intrepid valve TMVR and had Society of Thoracic Surgeons (STS) and EuroSCORE scores of 6.4% +/- 5.5% and 7.9% +/- 6.2%, respectively. One patient did not receive the valve due to left ventricle apical bleeding. The majority of patients (72%) had secondary MR, while 16% had primary MR and 45% had at least moderate TR. Technical success was achieved in 98% of patients, and there were no device malfunctions or failures or conversions to open cardiac surgery. The survival rate at 30 days was 86%, with the majority having less than mild MR.11The first early feasibility study, the Intrepid Global Pilot study, was published in 2018 and included 50 patients at high surgical risk who had compatible anatomy for the device.12In addition, a prospective, multicenter, nonrandomized study enrolled 15 patients from six different sites and demonstrated a procedural success rate of 93% (14 out of 15 patients) and a 30-day survival rate of 100% with a transfemoral, transseptal insertion approach.13 The study evaluates the outcomes of TMVR in native valves and the outcomes of TMVR in patients with MAC in a separate arm. The primary outcome includes a composite of all-cause mortality, heart failure hospitalization at 30 days, and KCCQ improvement.13The APOLLO trial  is an ongoing large nonrandomized open-label trial.The AltaValve  is a supra-annular valve delivered transapically via a 32F sheath. A transfemoral delivery system has been developed and now is being studied. The system is comprised of a 27-mm trileaflet bovine pericardial valve encased in a spherical nitinol frame and a fabric skirt on the bottom at the level of the annular ring . Due to its unique supra-annular position, the risk of LVOT obstruction and embolization may be lower than other devices.15The AltaValve is being evaluated in an early feasibility study. Limited results were presented in the American Association for Thoracic Surgery AATS 2022 Mitral Conclave Workshop and demonstrated 100% technical success rate in 10 patients. Several successful cases of AltaValve implant have been described in the literature.The Tiara valve (Neovasc Inc.) is a self-expanding, nitinol-based frame with bovine leaflets requiring a 32F or 36F delivery sheath. The available valve sizes include 35 mm and 40 mm. The valve stability relies on ventricular anchoring tabs.16 Neovasc has filed for CE mark in 2020 but still remains under clinical investigation.The Tiara-I study enrolled 27 patients with severe MR who underwent implantation of the Tiara valve system and demonstrated an 89% survival rate at 30 days.17 The docking system encircles the mitral chordae to provide support for valve implantation.The SAPIEN M3 TMVR system (Edwards Lifesciences) is a balloon expandable bovine pericardial valve implanted in a nitinol docking system via a transseptal approach.15 There was significant MR reduction  in all patients without a significant increase in mitral valve gradient (mean gradient of 2.3 mm Hg).The results of the first-in-human study demonstrated successful implantation of the Sapien M3 system in 9 out of 10 patients.18 Thirty-five patients with severe MR and high surgical risk underwent TMVR using the Sapient M3 system, with successful implant seen in 89% (31/35 patients). Paravalvular regurgitation occurred in 2.8% (1/35 patients) requiring intraprocedural closure.18 The 30-day survival rate was 97.1%, and 93.8% of the patients had ≤ 1+ MR with a mean mitral gradient of 5.36 mm Hg.18The results of the early feasibility study were presented in the Transcatheter Cardiovascular Therapeutics 2019 meeting.17 It is implanted transeptally using a 28F sheath. Available sizes include 44 mm and 48 mm.The EVOQUE TMVR system (Edwards Lifesciences) consists of a bovine pericardial valve in a nitinol frame with ventricular anchors and an intra-annular sealing skirt to decrease the risk of paravalvular leak.19 The technical success of the procedure was around 93%. The majority of PVL cases were mild except in one patient requiring percutaneous closure and another requiring conversion to surgical mitral valve replacement. Only one patient developed LVOT obstruction. Survival rate at 30 days was 93%. There was significant symptomatic improvement seen in NYHA classification and KCCQ-12 score.19The first-in-human experience using the EVOQUE TMVR system studied 14 patients with severe MR with at least high surgical risk.20The safety and performance of the valve is currently being evaluated in the MISCEND study—Edwards EVOQUE Eos Mitral Valve Replacement: Investigation of Safety and Performance After Mitral Valve Replacement With Transcatheter Device.21 The anchoring mechanism is based on axial compression force.The Cephea TMVR system (Abbott Vascular) consists of a self-expanding bovine pericardial valve  encased in a nitinol double disc frame and delivered via a transseptal approach.22 Subsequently, three patients with severe degenerative MR and prohibitive surgical risk underwent successful implantation of the Cephea device. There was a significant MR improvement (≤ mild MR) with significant increase in transmitral gradient (mean gradient of 3 mm Hg) and no LVOT obstruction. To our knowledge, 10 patients have received the Cephea TMVR device. An early feasibility study is currently ongoing in the US.The first valve was implanted in 2019.The HighLife TMVR system (HighLife SAS) is a self-expanding nitinol subannular valve with bovine pericardial leaflets implanted in a ring. It is available in a 31-mm valve size. Transseptal delivery is achieved using a 39F sheath. The subannular ring is implanted via a transaortic retrograde approach.23 Surgical conversion was described in one patient. At 30 days, the mortality rate was 10%, and 75% had less than mild MR.23 Currently, an ongoing early feasibility trial is underway.24The first interim data was presented during the Transcatheter Cardiovascular Therapeutics 2021 meeting and demonstrated a 90% technical success rate (27/30 patients).25 The TWIST-EFS study aims to enroll 15 participants with significant MR and high operative risk to undergo TMVR with the Innovalve system.26 This system has the potential of reducing LVOT risk by holding the anterior leaflet away from the LVOT by way of the rotation and chordal wrapping mechanism.The Innovalve TMVR system is a novel transseptal TMVR system consisting of an atrial flange and a cylinder with six arms designed for grasping and wrapping the chordae followed by positioning, anchoring, and delivery of the valve.Mitral regurgitation is a common valvular disease with complex anatomy and pathophysiology. Despite significant advances in transcatheter aortic devices, dedicated devices in the mitral position are essential and currently being studied. Success in the TMVR field requires excellence in cardiac imaging and patient selection in addition to future advances in valve anchoring, decreases in delivery sheath profiles, and formation of prediction models to decrease LVOT obstruction.Transcatheter mitral valve replacement (TMVR) in high-risk surgical patients with severe native mitral valve regurgitation is feasible using dedicated devices.To date, the Tendyne TMVR system is the only system with CE Mark.In the United States, all TMVR systems are being studied and are not ready for commercial use outside of clinical trials.Significant advances in device technology, delivery systems, and implantation techniques are essential to avoid vascular complications, left ventricular outflow tract obstruction, and achieve good anchoring to reduce paravalvular regurgitation.


Heart failure, a complex cardiovascular condition, is a huge burden on patients, caregivers, and healthcare systems and it is prevalent worldwide. Heart failure is caused by a wide variety of underlying conditions that include both cardiac and non-cardiac pathologies. Identifying the underlying cause enables us to apply etiology-based interventions. The spectrum of heart failure management ranges from classification to transplantation. In addition to its classification and monitoring, this article reviews various management strategies, including both conventional methods and the latest innovations. These include lifestyle interventions, pharmacotherapy, device therapy, transplantation, and regenerative medicine. Heart failure occurs when the heart is unable to pump enough blood to fit the body’s requirements. Classification systems for this condition have been provided by the New York Heart Association and the American College of Cardiology/American Heart Association. These classifications can be used to evaluate the functional status and to stage heart failure. Treatment strategies can then be tailored. The goal of these treatments is to reduce associated morbidity and mortality.Heart failure is caused by a variety of conditions, and identifying the underlying cause helps us to optimize treatment. It is also imperative to monitor the disease. In this review, we discuss various evaluation and monitoring strategies that form the core elements of managing heart failure. Signs of disease progression and early decompensation detected on monitoring necessitate modifications in therapeutic interventions to reduce morbidity and mortality.To manage heart failure, it is essential to adopt a multifaceted approach. Conventional methods of managing heart failure include lifestyle changes and pharmacotherapy, whereas, interventional heart failure therapy utilizes minimally invasive procedures to improve outcomes . CardiacMethodsA comprehensive review of the literature related to heart failure management was conducted. Data were collected from electronic databases (PubMed and Scopus) to identify relevant peer-reviewed articles. The following search terms were used: “heart failure’’, “management”, “classification”, “monitoring”, “lifestyle”, “medication”, “device therapy”, “transplant” and “regenerative medicine”. We included articles in the English language only. The inclusion criteria were not exclusive to any specific study design, and 288 relevant articles were included in the review. Findings were presented using a narrative approach. The data were summarized to highlight the classification, causes, and management options.Classification of heart failureThe most common classification system is the New York Heart Association classification system. This classification categorizes patients into four classes based on symptoms and limitations of activity. Class I and II are considered mild heart failure, whereas, class III and IV are considered severe/advanced heart failure. These four levels are presented in Table The American College of Cardiology/American Heart Association staging system includes four stages Table .According to the latest guidelines, heart failure is classified based on the ejection fraction into the following classes. In heart failure with reduced ejection fraction, the left ventricular ejection fraction is ≤40%. If the ejection fraction improves later on, it is then called heart failure with improved ejection fraction. In heart failure with mildly reduced ejection fraction, the left ventricular ejection fraction ranges from 41% to 49%. In heart failure with preserved ejection fraction, the left ventricular ejection fraction is ≥50% [CausesOver two-thirds of the total cases of heart failure can be attributed to ischemic heart disease, hypertensive heart disease, chronic obstructive pulmonary disease, and rheumatic heart disease . IschemiThe causes of heart failure vary between developing and developed countries. The underlying causes in developed countries are usually ischemic heart disease and chronic obstructive pulmonary disease, whereas, in developing countries, hypertensive heart disease, cardiomyopathies, myocarditis, and rheumatic heart disease are prevalent . The INTEvaluation and monitoringDiagnosing heart failure requires examining both clinical features and objective findings.History and ExaminationThe evaluation should start with a thorough history and physical examination. The symptoms of heart failure include orthopnea, paroxysmal nocturnal dyspnea, lethargy, fatigue, reduced exercise tolerance, nocturnal cough, wheezing, and ankle swelling. The signs are displaced apex beat, right ventricular heave, third heart sound, tachycardia, pulsus alternans, elevated jugular venous pressure, wheezing, crepitations, cachexia, muscle wasting, edema, hepatomegaly and ascites . Daily wElectrocardiographyElectrocardiographic abnormalities are common in suspected cases; therefore, an abnormal test has very little predictive value. On the other hand, if the electrocardiography findings are normal, an alternative diagnosis should be carefully considered .BiomarkersTesting for cardiac biomarkers is commonly carried out as they are a cost-effective means of ruling out heart failure. Cardiac biomarkers associated with myocardial stretch are brain or b-type natriuretic peptide (BNP), n-terminal pro-b-type natriuretic peptide (NT-proBNP), and mid-regional pro atrial natriuretic peptide (MR-proANP). Biomarkers associated with myocyte injury are high-sensitivity troponin T (hsTnT) and heart-type fatty acid-binding protein (H-FABP). Biomarkers associated with fibrosis, inflammation, and matrix remodeling are soluble growth-stimulating gene 2 (sST2), galectin-3 , and growth differentiation factor-15 (GDF-15) . Among aImagingChest X-ray can identify cardiomegaly and pulmonary congestion. Using transthoracic Doppler echocardiography, we can measure the left ventricular ejection fraction. This enables us to determine whether the systolic function is preserved or reduced. Fast breath-hold cardiovascular magnetic resonance (CMR) is the reference standard for the measurement of cardiac volumes, function, and mass in heart failure. The results are accurate and reproducible .Remote MonitoringRemote monitoring can either be invasive or non-invasive.Non-invasive remote monitoring is simple and cost-effective. It enables consistent monitoring of blood pressure, physical activity, and weight. It also improves medication adherence . Some stAlternatively, remote hemodynamic monitoring requires an invasive procedure and may not be cost-effective. It has shown the strongest ability to reduce heart failure readmissions and is currently approved for this purpose .LifestyleDietThe American College of Cardiology/American Heart Association recommendations include restricting salt intake to less than 2 grams per day and fluid intake to less than 2 liters per day .Alcohol ConsumptionAlthough light/moderate consumption of alcohol may confer some cardiovascular benefits, excessive drinking should be avoided as it is known to cause alcoholic cardiomyopathy .SmokingCigarette smoking is an important risk factor for left ventricular hypertrophy, systolic dysfunction, and incident heart failure hospitalization and is associated with higher mean BNP levels (p<0.05). Current smoking , smoking intensity among current smokers , and smoking burden among ever smokers  were significantly associated with incident heart failure hospitalization in comparison with never smoking [Weight ManagementTreatment of heart failure also includes weight reduction in obese patients. Sudden unexpected weight gain of greater than 2 kilograms in three days should either be discussed with a healthcare provider or patients can adjust their diuretic dose accordingly (increase the dose if a sustained increase in weight is noted) . On the ActivityAlthough destabilization of congestive heart failure necessitates bed rest, patients are otherwise encouraged to carry out activities that do not induce symptoms.PharmacotherapyTable Angiotensin-Converting Enzyme InhibitorsAngiotensin-converting enzyme inhibitors are used as first-line therapy in patients with reduced left ventricular ejection fraction. They inhibit the conversion of angiotensin I to angiotensin II. By reducing vasoconstriction and fluid retention, they decrease the workload on the heart. They improve symptoms, functional capacity, and survival while reducing hospitalization. The commonly used drugs are enalapril, lisinopril, and ramipril. The common side effects include cough, hypotension, renal insufficiency, hyperkalemia, syncope, and angioedema. Angioedema and bilateral renal artery stenosis are contraindications to the use of angiotensin-converting enzyme inhibitors. Enalapril is also recommended in patients with asymptomatic left ventricular dysfunction .Angiotensin Receptor BlockersAlternatively, angiotensin receptor blockers  can also be used. They are particularly beneficial in patients who cannot tolerate the side effects  of angiotensin-converting enzyme inhibitors. They improve symptoms and reduce hospitalizations. They also reduce mortality, similar to angiotensin-converting enzyme inhibitors .DiureticsIn patients with symptomatic heart failure, diuretics  are recommended. Diuretics increase urine production and relieve congestion. They rapidly improve dyspnea and increase exercise tolerance . Loop diSpironolactone, an aldosterone antagonist, effectively reduces morbidity and mortality . It is iBeta-BlockersBeta-blockers reduce heart rate, decrease myocardial oxygen demand and improve cardiac function. They are recommended for all patients with heart failure from cardiomyopathies and reduced left ventricular ejection fraction who are on pharmacotherapy unless contraindicated. They reduce morbidity and mortality .DigoxinDigoxin improves ventricular function and symptoms but does not reduce mortality. It is used as a second-line drug for mild to moderate heart failure management.Angiotensin Receptor-Neprilysin InhibitorsAngiotensin receptor-neprilysin inhibitors have increasingly gained popularity in the management of heart failure. In a double-blind trial, the angiotensin receptor-neprilysin inhibitor LCZ696 was proven superior to enalapril in reducing morbidity and mortality in patients with heart failure with reduced ejection fraction .Sodium-Glucose Co-Transporter 2 (SGLT2) InhibitorsSimilarly, in another double-blind trial, sodium-glucose co-transporter 2 (SGLT2) inhibitors were proven to reduce morbidity and mortality (regardless of the presence of diabetes) .Interventional heart failure therapyPatients on the above-mentioned therapies with refractory symptoms are usually treated with additional invasive procedures. Device therapy is not meant to replace pharmacotherapy, but rather complement it. There has been a surge in the use of several device-based therapies for managing heart failure. The most commonly used devices are described below.Cardiac Resynchronization TherapyThe cardiac resynchronization therapy device, also known as a biventricular pacemaker, has leads that are positioned in the right atrium, right ventricle, and coronary sinus vein on the left side of the heart. Rhythmic generation of electrical impulses synchronizes cardiac contractions and improves cardiac function. It is particularly useful in patients with heart failure and electrical dyssynchrony. This device improves exercise tolerance, quality of life, New York Heart Association class, and left ventricular ejection fraction .Implantable Cardioverter-DefibrillatorThe implantable cardioverter-defibrillator is useful for treating ventricular tachycardia and ventricular fibrillation. This device, implanted under the skin, detects an abnormal cardiac rhythm and delivers electrical shocks to restore sinus rhythm. Implantation of implantable cardioverter-defibrillator in addition to cardiac-resynchronization therapy with a pacemaker should be considered in symptomatic patients with severe heart failure with left ventricular ejection fraction ≤35% and QRS duration ≥120 milliseconds, as this strategy reduces morbidity and mortality .Intra-aortic balloon pump and extracorporeal membrane oxygenation are mechanical support systems that can be used as a temporary bridge to cardiac transplantation.Intra-Aortic Balloon PumpIntra-aortic balloon pump places an inflatable balloon through the femoral artery into the aorta using a catheter. Once placed, the balloon inflates and deflates in synchronization with the cardiac cycle. It improves cardiac output via inflation and reduces afterload via deflation.Extracorporeal Membrane OxygenationExtracorporeal membrane oxygenation is a cardiopulmonary support system that takes blood out of the body, replaces the carbon dioxide with oxygen, then pumps the oxygenated blood back into the body. The veno-arterial (VA) extracorporeal membrane oxygenation configuration is used in patients with heart failure. It functions similarly to a heart-lung machine (bypass used in cardiac surgeries). The major difference is that, unlike the heart-lung machine, it can be used for longer periods. Extracorporeal membrane oxygenation and intra-aortic balloon pump may have synergistic effects in the management of acute heart failure .Ventricular Assist DevicesVentricular assist devices are electromechanical devices that assist in cardiac circulation. They can partially or completely replace the function of the heart. Ventricular assist devices can increase exercise capacity, and improve symptoms and overall quality of life. The most commonly used device is the left ventricular assist device, which improves left ventricular function. In some cases, where there is significant impairment of right ventricular function as well, biventricular assist devices are used. Ventricular assist devices can be used as a bridge or alternative to cardiac transplantation . ComplicHeart TransplantHeart transplant is performed in patients with advanced heart failure who have failed to respond to other treatment strategies. It can significantly increase survival and exercise capacity and improve the recipient’s quality of life. The sparse availability of donor hearts is a limitation to this treatment option. The median survival of adult recipients is 10.7 years. Factors associated with early mortality are graft failure and multiple organ dysfunction. Factors associated with late mortality are malignancy, infection, rejection, and cardiac allograft vasculopathy .Regenerative medicineStem Cell TherapyOnly a small proportion of patients with ventricular assist devices have demonstrated reverse structural remodeling of the myocardium with significant functional improvement. As a result, cell therapy for heart failure has gained popularity due to its potential to induce reverse remodeling of the myocardium . Stem ceGene TherapyThrough this approach, cardiac tissue repair can be induced through the introduction of therapeutic genes (genes encoding growth factors and anti-apoptotic factors) and proteins. It has certain similar challenges as stem cell therapy (including the need to optimize delivery methods). Viral vectors (adeno-associated viruses) are usually used; however, immune response to the vector is a major concern. Some methods for transducing the cells such as the retrograde delivery approach and using cardiac-specific adeno-associated virus vectors are promising .Tissue EngineeringTissue engineering refers to constructing cardiac tissue in vitro. This tissue can then be transplanted into the heart to restore damaged areas, promote regeneration, and improve cardiac function. One approach is to seed cells onto porous, biodegradable scaffolds. Another approach is to cast cells into synthetic hydrogels or create scaffold-free tissues composed exclusively of the cells and matrix secreted by them . AlthougHeart failure is a significant burden with various underlying etiologies. Monitoring enables early detection of progression, which necessitates adjustments in therapeutic interventions. Managing heart failure requires a multifaceted approach. Lifestyle changes and pharmacotherapy play a vital role in its management, whereas interventional heart failure therapy utilizes minimally invasive procedures to improve outcomes in advanced and refractory cases. Cardiac transplantation remains the gold standard, and it is employed when all other options have been exhausted. Advancements in novel pharmacological agents and regenerative medicine are promising. However, further studies need to be conducted.


In repaired tetralogy of Fallot (ToF) patients with residual right ventricular (RV) outflow tract obstructions (RVOTO), risk stratification and timing of re-interventions are based on RVOTO gradients. However, this might be insufficient to prevent RV dysfunction. Instead, assessment of RV to pulmonary arterial (RV-PA) coupling allows integrated assessment of RV function in relationship to its afterload and could be of additional value in clinical decision-making.Two patients with repaired ToF and residual RVOTO without pulmonary regurgitation underwent right heart catheterization (RHC) and cardiac magnetic resonance imaging. We determined RV end-systolic elastance (Ees), arterial elastance (Ea) and RV-PA coupling (Ees/Ea) using single-beat RV pressure–volume analysis. Patient 1 was asymptomatic despite severely increased RV pressures and a left pulmonary artery (LPA) stenosis (invasive gradient 20 mmHg). Right ventricular volumes and function were preserved. The Ea and Ees were increased but RV-PA coupling was relatively maintained. Of interest, RV end-diastolic pressure and RV diastolic stiffness were increased. After LPA plasty, RV function was preserved during long-term follow-up. Patient 2 was symptomatic despite mildly elevated RV pressures and a supravalvular RV-PA conduit stenosis (invasive gradient 30 mmHg). The RV showed severe RV dilatation and dysfunction. The Ea was increased but Ees was decreased leading to RV-PA uncoupling. Despite balloon angioplasty, RV function was unchanged during long-term follow-up.Development of RV dysfunction might be insufficiently predicted by RVOTO severity in patients with repaired ToF. Assessment of RV remodelling and function in relationship to its afterload might help to optimize risk stratification. Right ventricular (RV) pressures do not always inform us properly about the extent of RV adaptation and RV function.This case series is the first to perform single-beat RV pressure–volume analysis in patients with ToF and provides new insights that linking indexes of RV function to its afterload might be of additional value for risk stratification, monitoring, and optimizing timing of re-interventions in patients with repaired ToF.1 Right ventricular dysfunction is independently associated with reduced survival, and therefore, maintenance of RV function is of great importance.2 Timing of re-interventions for the relief of RVOTO remains challenging. According to the guidelines, decision-making should be guided by RVOTO gradients.4 However, a recent study found no association between peak RVOT gradient on echocardiography and the severity of RV dysfunction.5 Therefore, integrated assessment of RV remodelling and function in relationship to its afterload could be of additional value in clinical decision-making. The interaction between the RV and pulmonary arterial load can be assessed using pressure–volume loops. Within this framework, RV end-systolic elastance (Ees), which is considered a load-independent measure of ventricular contractility, can be calculated as the slope of the end-systolic pressure–volume relationship (ESPVR) using /stroke volume. The multi-beat RV pressure–volume analysis, in which multiple pressure volume loops during changing preload conditions are being used to calculate the slope of the ESPVR, is the gold standard to assess Ees.6 However, due to the preload alterations, this is often not feasible in patients and the single-beat RV pressure–volume analysis from Brimioulle et al.7 can serve as an applicable alternative.7 During this single-beat RV pressure–volume analysis, the slope of the ESPVR is being assessed using the maximal isovolumetric pressure of the RV, which can be extrapolated from RV pressure curves .8Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart disease. Although survival has improved, patients suffer from residual pulmonary regurgitation (PR) and right ventricular (RV) outflow tract obstruction (RVOTO) leading to RV dysfunction.9 The RV to pulmonary arterial (RV-PA) ‘coupling’ is calculated as the ratio of Ees/Ea and represents the efficiency of mechanical energy transfer from the RV to the pulmonary vasculature. In addition, diastolic stiffness can be assessed using RV end-diastolic elastance (Eed). End-diastolic elastance can be calculated as the slope of the end-diastolic pressure–volume relationship (EDPVR) at end-diastole.10 Here, we present two cases with repaired ToF and a supravalvular RVOTO who underwent right heart catheterization (RHC) and cardiac magnetic resonance (CMR) imaging. In addition, single-beat RV pressure–volume analysis was performed.In addition to Ees, the pulmonary arterial elastance (Ea), which is mainly a reflection of pulmonary vascular resistance, can be calculated as RV afterload using RV systolic pressure/stroke volume.Timeline clinical course of two repaired ToF patients with RV pressure overloadTable 1). Right heart catheterization demonstrated a moderate LPA origin stenosis (invasive gradient LPA-PA 20 mmHg). In addition, a subvalvular RVOTO with an aneurysm was found (invasive gradient PA-RV 24 mmHg). The RPA showed a minimal stenosis (invasive gradient RPA-PA 10 mmHg). Right ventricular pressure was severely increased (RV systolic pressure 65 mmHg vs. LV systolic pressure 91 mmHg), but RV volumes and function were preserved (2). Right ventricular pressure–volume analysis showed increased pulmonary Ea and RV Ees, but RV-PA coupling was relatively preserved . Furthermore, RV end-diastolic pressures and RV Eed (a measure of RV diastolic stiffness) were increased. Three months later, an infundibulectomy and LPA plasty were performed. The post-operative course was complicated by a superior caval vein (SCV) tear for which resuscitation and emergency reoperation were required. During 6 years of follow-up, the patient did not develop any symptoms and RV function remained preserved .In a patient with trisomy 21, ToF was repaired by a commissurotomy for a bicuspid pulmonary valve, a mean pulmonary artery, and right ventricular outflow tract (RVOT) patch, atrial septal defect and ventricular septal defect closure, and mitral valve plasty at the age of 23 months. At the age of 13, he was asymptomatic with no signs of venous congestion , but echocardiography showed a moderate left pulmonary artery (LPA) stenosis  and mild pulmonary valve regurgitation (peak gradient 2.3 m/s). Cardiac magnetic resonance demonstrated a perfusion mismatch with a four times higher perfusion to the right lung compared with the left lung. Biventricular volumes and function were preserved and RV mass was increased (Table 1). A surgical closure of the residual VSD was performed, and a valved RV-PA conduit (Contegra 18 mm) was implanted. However, exercise capacity remained unchanged. Six years later, she was still symptomatic with no signs of venous congestion and had impaired exercise capacity , NYHA class II). Echocardiography revealed a stenosis of the Contegra RV-PA conduit (estimated echocardiographic gradient 23 mmHg) and mild PR. Right heart catheterization showed the following invasive pressures and gradients at rest: LV systolic pressure 98 mmHg, RV systolic pressure 31 mmHg, mean arterial pressure (MPA) systolic pressure 20 mmHg, and LPA/RPA systolic pressure 15 mmHg. A minimal LPA and RPA stenosis (invasive gradient both 5 mmHg) and a trivial Contegra stenosis (invasive gradient 11 mmHg) were found. Because of hypotension under general anaesthesia, an adrenaline challenge was performed . This revealed a moderate Contegra stenosis (invasive gradient 30 mmHg). Right ventricular pressure was mildly increased . However, there was severe RV dilatation and RV systolic dysfunction (2). Right ventricular pressure–volume analysis showed that Ea was increased but Ees was severely reduced leading to severe RV-PA uncoupling. Furthermore, RV end-diastolic pressures and RV Eed were preserved . The Contegra stenosis was corrected using balloon angioplasty because of the lack of an ideal landing zone for stenting. After the balloon angioplasty, there was a mild decrease in the Contegra gradient (invasive gradient pre-intervention 30 mmHg vs. 20 mmHg post-intervention). No pulmonary valve regurgitation was present after balloon angioplasty . Despite this intervention, exercise capacity remained impaired during follow-up. Right heart catheterization revealed a good Contegra function and unchanged mild LPA stenosis 2 years after Contegra balloon angioplasty. However, CMR revealed persistent LV dysfunction (LVEF 40%) and unchanged RV function (RVEF 39%) 4 years after Contegra balloon angioplasty .A female patient with ToF was corrected with a transannular patch and a ventricular septal defect (VSD) closure at the age of 10 months. At the age of 6 years, she was symptomatic. She suffered from complains of fatigue and showed reduced exercise capacity and shortness of breath when walking the stairs during daily life. A residual VSD with negligible L-R shunt was found on echocardiography. Since there was no perfusion mismatch, management was conservative. Three years later, she remained symptomatic. Physical examination was unremarkable. Cardiopulmonary exercise testing showed reduced exercise capacity , and CMR demonstrated left ventricular (LV) and RV dilatation and systolic impairment  might be achieved by the increase in wall thickness as well as changes in muscle properties. Similar findings of a supranormal Ees and hypercontractile RV have been found in patients with pulmonary hypertension (PH).15 Despite high RV pressures, Patient 1 showed preserved RV volumes and systolic function and a relatively maintained RV-PA coupling. Of interest, RV function remained preserved during long-term follow-up. In contrast, in Patient 2, we found that despite mildly increased RV pressures, significant RV-PA uncoupling occurred, with no to little improvement in RV function after RVOTO intervention. This is in line with literature showing that RV function may be unchanged after surgical pulmonary valve replacement and underlines the importance of early detection of RV dysfunction.16 In addition, severe RV dilatation, low relative wall thickness, and increased RV wall stress were observed. Our findings are in line with previous studies which estimated RV-PA coupling non-invasively or after the application of inotropes in patients with repaired ToF.18 However, these studies were performed in repaired ToF patients with mainly residual volume overload. In addition to increased RV pressure and volume overload, RV-PA uncoupling might be explained by different disease stages, gender, age and differences in (the history of) PR.19 Therefore, a complex combination of factors might have impact on RV-PA coupling in repaired ToF. Of interest, Patient 1 showed increased RV end-diastolic pressures and RV diastolic stiffness. This might be a consequence of stiffening of the cardiomyocytes due to compensatory RV hypertrophy in response to pressure overload. Right ventricular hypertrophy might protect against progressive RV dilatation and reduces ventricular wall stress.20Our case series is the first that performed single-beat RV pressure–volume analysis in patients with repaired ToF. We present two cases with a supravalvular RVOTO but a different response of the RV to the elevated afterload. This is in line with the study from Latus et al.20 In addition, this case series is the first to perform single-beat RV pressure–volume analysis in patients with ToF and provides new insights in this extra tool that might help to optimize the timing of re-interventions. We found that linking indexes of RV function to its afterload, in addition to RVOT gradients as recommended by the guidelines, might be of additional value for risk stratification, monitoring, and optimizing timing of re-interventions in patients with repaired ToF.4Right ventricular function determines long-term outcome in patients with repaired ToF, and therefore, preservation is of great importance. However, timing of re-interventions for the relief of RVOTO remains challenging. In line with previous literature, our case series shows that RV pressures do not always inform us properly about the extent of RV adaptation and RV function.7 However, a disadvantage of this method is that it is based on a few assumptions.7 Despite these assumptions, the single-beat RV pressure–volume analysis is a good and applicable alternative in patients for the multi-beat RV pressure–volume analysis. This multi-beat technique requires preload alterations using  vena cava occlusion or the Valsalva manoeuver, which might not be feasible in all circumstances. In addition, Ea was used to determine RV afterload. However, Ea mainly represents pulmonary vascular resistance, which was only mildly increased in this case series. Therefore, other factors such as pulmonary arterial compliance might also have an impact on RV afterload. Finally, we solely report on single time point RV pressure–volume analysis. Future studies with multiple time point RV pressure–volume analysis would be of great interest. This supports future larger and prospective studies about RV pressure–volume analysis in repaired ToF.In this case series, we present two patients with differences in age, gender, and surgical history, which might have impact on our results. Right ventricular pressure–volume analysis was performed using the single-beat method from Brimioulle et al.This case series illustrates that development of RV dysfunction might not be predicted by the severity of RVOTO in patients with repaired ToF. Linking indexes of RV function to its afterload might be of additional value for risk stratification, monitoring, and optimizing timing of re-interventions in patients with repaired ToF


Tricuspid regurgitation (TR) is commonly seen in surgically palliated patients with hypoplastic left heart syndrome, and when significant, is associated with an increase in both morbidity and mortality. Tricuspid valve dysfunction appears to be the result of a combination of inherent structural malformations and the unique physiological circumstances resulting from right ventricular pressure and volume overload. Valve dysfunction evolves rapidly, and manifests early on in the surgical pathway. Whilst traditional echocardiographic imaging can identify anatomical defects and dysfunction resulting in varying degrees of regurgitation even at early stages, more sophisticated investigations such as 3D echocardiography, strain imaging and transesophageal 3DE might prove useful to better demonstrate the complex interactions between abnormal anatomy of the valve complex, ventricular function, mechanical synchrony, and TR. Recognition of specific mechanisms of TR can enhance patient-specific care by directing precise surgical interventions and by informing the best timing for intervention on the valve. Hypoplastic left heart syndrome (HLHS) represents a spectrum of congenital malformation of the left heart and left-sided vascular structures , 2. A seThe tricuspid valve (TV) therefore must perform in the systemic circulation, and experiences haemodynamic conditions that are quite different to its circumstances in a normal, biventricular circulation.Tricuspid regurgitation (TR) is commonly seen in surgically palliated patients. TR of at least moderate degree is associated with poorer outcomes for patients with functionally univentricular circulations, with an increase in both morbidity and mortality –8. HenceThe mechanisms of dysfunction of the tricuspid valve are often difficult to fully elucidate using traditional imaging, and also evolve over relatively short periods of time, including in the interval between palliative surgical stages. Additionally, there are complex interactions between ventricular function, mechanical synchrony, and TR.The multifactorial nature of the aetiology of TR makes it difficult to tease out specific mechanisms in individual patients. Effective surgical intervention can improve patient outcomes , but relA normal tricuspid valve is composed of four components, namely the leaflets, the papillary muscles, the chordal apparatus and the valve annulus  Figure .Usually there are three leaflets, described in an attitudinally appropriate manner (relative to the anatomic position in the body) as anterior-superior, septal and inferior, with the anterior-superior being the largest. Papillary muscle arrangement is highly variable; generally, there are two main muscles, the anterior and the posterior. The third, the septal papillary muscle, displays the most inconsistency, being often absent, or alternatively, multiple. The chordae attach to the papillary muscles, and together these form the tensor apparatus for the TV. The normal tricuspid annulus is D shaped, and is a dynamic structure, changing shape considerably during the cardiac cycle. It is mainly fibrous, but contains muscle bands, especially in the anterosuperior portion, and is less distinct than the mitral annulus.In hearts with HLHS, the TV anatomy is extremely variable. A study of 82 pathological specimens of HLHS  showed tIt is valuable for both the echocardiographer and the surgeon to be aware of these anatomical differences and variability, enabling surgical planning and also aiding in prognostication.Surgical intervention to the TV can reduce TR severity and may improve functional outcomes of patients with HLHS , 11, 12.Surgical inspection of the TV does not facilitate appreciation of the contribution of dynamic changes in the annulus, nor of motion abnormalities of the valve . It can Echocardiography can demonstrate TV structural abnormalities that may be amenable to surgical techniques, and also, notably, is able to demonstrate the valve in motion and therefore reveal the functional importance of valve pathology . The funAn echocardiographic study  sought t):•annular dilatation•valve prolapse due to either chordal elongation or rupture of a papillary muscle•leaflet restriction or “tethering”•valve leaflet dysplasia including presence of clefts in the leaflets•papillary muscle abnormality•presence of endocardial fibroelastosis•right ventricular dysfunctionAnatomical factors noted by the echocardiographer which contributed to TR included , 3:•ann3Ventricular dilatation caused by chronic volume overload and leading to progressive annular dilatation, was also noted.This study showed that echocardiography commonly detects annular dilatation and valve prolapse as primary mechanisms of TR, and also often identifies leaflet dysplasia, but not clefts, and leaflet tethering. During surgery, a different subset of abnormalities, namely annular dilatation and valve dysplasia, were identified as being the most common mechanisms of TR. These findings underline that it is important to obtain detailed echocardiographic studies prior to surgery, in particular to elucidate valve motion abnormalities, which the surgeon does not have the opportunity to view in the flaccid heart attached to cardiopulmonary bypass ; howeverThree-dimensional echocardiography (3DE) provides several insights into TV structure and function that cannot be elucidated by 2D echocardiography alone , 21. 3DE3DE also has been used to demonstrate considerable evolution of the TV in the “interstage” period between the first and second palliative surgical stages. A very informative study by Takahashi and colleagues  used 3DEEarly recognition of these abnormalities utilising 3DE has potential to help with prognosis; early leaflet tethering, identified prior to any intervention, is associated with the development of TR . GreaterThese progressive changes in TV features appear to be an adaptive response to the unique loading conditions in the functionally single ventricle circulation. Colen and colleagues used 2DE and 3DE to investigate this adaptation of the TV during the surgical palliation pathway . They obEven as early as fetal life, and before and after the first stage of palliation, the RV experiences significant volume loading as compared to a two-ventricle circulation. This significant volume load drives secondary compensatory changes in the RV, including hypertrophy and dilatation , 27. TheUgaki and colleagues  report aDysfunction of the RV at the time of the Norwood operation is an independent predictor of poor outcome . There iModern echocardiographic techniques provide additional detail regarding the effects of abnormal contraction patterns and the progressive development of TR. We assessed the presence and degree of asymmetry of contraction between the septal and lateral RV walls using peak strain and difference in time to peak strain  in patiePatients with more significant TR had more disparity in the degree of developed strain and delay in time to peak strain around the TV annulus. RV mechanical dyssynchrony and asymmetry in contraction around the TV annulus contribute to changes in the TV shape and motion, and the development or exacerbation of TR. The rate at which changes in ventricular function and severity of TR develop, as monitored on serial echocardiography, is an important marker of poor outcome .). We observed in this group a negative effect on regional and global RV function as assessed by RV longitudinal strain, with a pronounced effect on regional dysfunction compared to patients without apical bulging. Severe TR in the apical bulging group was associated with death or transplant, and we hypothesize that ventricles with this geometry may be compromised in their ability to compensate for the additional volume loading that is imposed by the presence of higher degrees of TR.Differences are observed between HLHS patients in the geometry of the RV and septum, and in their consequent ability to tolerate or compensate for TR . Across Figure 7We have discussed the insights of echocardiography into the evolution of TR in early infancy. The presence of TR remains a risk factor for patients with HLHS as they progress along the single ventricle palliation surgical pathway , 8, 12, In adult cardiac surgery, repair of mitral valves is greatly aided by the use of transoesophageal 3DE , and aut3D printing is beneficial in planning of complex congenital cardiac surgical procedures, but mainly relies on data obtained from CT scans. Developments using transoesophageal 3DE as the substrate for 3D printed models allow the creation of bespoke models of congenitally malformed valves, including in patients with HLHS . These mTR is common in HLHS at all stages of palliation, and is the result of a combination of anatomical abnormalities of the TV and of the haemodynamic circumstances of its role in the systemic RV in the functionally univentricular heart. Variations in the geometry of the RV and the TV annulus, and the influence of the rudimentary LV, have an important impact on the mechanical function of the TV. The TV adapts and evolves during the course of surgical palliative treatment. 2D and 3D echocardiography, together with newer techniques including strain imaging, provide insight into the morphology of the TV, mechanisms of TR, and the interactions with the unique loading conditions of HLHS. TR has a detrimental effect on patient outcomes and is a potential surgical target, with effective surgical treatment conferring a survival benefit. Recognition of specific mechanisms of TR can direct precise surgical interventions and inform the best timing for intervention on the valve, and therefore enhance patient-specific care.


While conventional electrocardiogram monitoring devices are useful for detecting atrial fibrillation, they have considerable drawbacks, including a short monitoring duration and invasive device implantation. The use of patch-type devices circumvents these drawbacks and has shown comparable diagnostic capability for the early detection of atrial fibrillation.2DS2-VASc) score had increased detection rates.We aimed to determine whether a patch-type device (AT-Patch) applied to patients with a high risk of new-onset atrial fibrillation defined by the congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, age 65-74 years, sex scale . When a CHA2DS2-VASc score ≥4 was combined with previous heart failure, the detection rate was significantly increased to 24.4%. Comparison of the recorded electrocardiogram data revealed that supraventricular and ventricular ectopic rhythms were significantly more frequent in the new-onset atrial fibrillation group compared with nonatrial fibrillation group , respectively.Atrial fibrillation was detected by the AT-Patch in 3.4% (11/320) of patients, as diagnosed by both cardiologists. Interestingly, when participants with or without atrial fibrillation were compared, a previous history of heart failure was significantly more common in the atrial fibrillation group (n=4/11, 36.4% vs n=16/309, 5.2%, respectively; This study detected a moderate number of new-onset atrial fibrillations in high-risk patients using the AT-Patch device. Further studies will aim to investigate the value of early detection of atrial fibrillation, particularly in patients with heart failure as a means of reducing adverse clinical outcomes of atrial fibrillation.ClinicalTrials.gov NCT04857268; https://classic.clinicaltrials.gov/ct2/show/NCT04857268 Stroke prevention, which is frequently associated with atrial fibrillation, is currently a leading global health concern . ImportaWhile conventional electrocardiogram (ECG) monitoring devices, including multilead portable ECG monitoring devices, event-detection monitoring devices, and implantable ECG monitoring devices, are useful for the early detection of atrial fibrillation, they also have considerable drawbacks including the requirement for multiple outpatient visits as well as invasive device implantation . To overIn addition to these devices, the AT-Patch (ATsens) is a single-lead ECG monitoring device that is capable of continuously monitoring an ECG signal for up to 14 days and also enables the correlation of ECG changes and patient symptoms via a smartphone connection. Moreover, it has recently been demonstrated to have comparable diagnostic capability and safety to conventional ECG monitoring systems . Despite2DS2-VASc) score to predict new-onset atrial fibrillation, with over 10% of patients with CHA2DS2-VASc scores ≥2 having new-onset atrial fibrillations [2DS2-VASc score for the early detection of new-onset atrial fibrillation in high-risk patients using the AT-Patch.Furthermore, several studies have indicated high performance rates when using the validated congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, age 65-74 years, sex scale . The protocol was registered with the Clinical Research Information Service of the Korea Centers for Disease Control and Prevention, Ministry of Health and Welfare, Republic of Korea (KCT0005650) on December 2, 2020. It was registered at ClinicalTrials.gov (NCT04857268) for international access to the protocol on April 23, 2021.2DS2-VASc scores ≥2. The CHA2DS2-VASc score was calculated as follows: congestive heart failure, hypertension, diabetes mellitus, aged between 65 and 75 years, vascular disease, and female sex (1 point for each parameter), and stroke or transient ischemic attack and age >75 years (2 points for each). The maximum CHA2DS2-VASc score was 9 points. Congestive heart failure was defined as a previous diagnosis of heart failure (signs or symptoms of heart failure or objective evidence of reduced left ventricular ejection fraction ≤40%). Hypertension was defined as a systolic blood pressure greater than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg, or prior antihypertensive drug use. Diabetes mellitus was defined as fasting glucose levels greater than 126 mg/dL or the presence of previous antidiabetic drug treatment. Vascular disease was defined as the prior occurrence of myocardial infarction, peripheral vascular disease, or aortic plaque [We enrolled 320 adults aged ≥19 years who visited 2 tertiary hospitals in Korea. Inclusion criteria were as follows: (1) patients who provided written and informed consent to participate and (2) those with CHAc plaque . The excThe AT-Patch is a single-use device that can continuously record the electrical activity of the heart. This single-lead, noninvasive ECG recorder is indicated for ambulatory ECG monitoring for up to 14 days (11 days if the device is connected to a smartphone via Bluetooth). It weighs only 13 g, has a size of 95.0 × 50.6 × 8.3 mm, and allows for uninterrupted recording during sleep and light physical activity, thereby offering user comfort and increased patient adherence.A study coordinator placed this device on the patient’s left pectoral region, tilted 45° inward. To prevent noise or signal loss, the skin was cleansed using a 70% ethanol solution prior to attachment. Participants were instructed to wear the adhesive patch for as long as possible in order to obtain ECG data for up to 11 days. A continuous ECG signal was recorded for 11 days and stored on a memory card. Following this, the device was linked to a computer, and the data were subsequently downloaded and analyzed using AT-report, a specific program provided by ATsens Co, Ltd.Clinical assessments were scheduled for baseline and days 11, 90, and 180. During the baseline assessment, we obtained the participants’ demographic data, past and present medical and drug administration history, and conducted physical examinations , laboratory parameters, and 12-lead ECG results . For eligible participants, we attached the experimental AT-Patch device according to the institutional Good Clinical Practice for medical devices and recorded the date and time. During the following visit (day 11±5), we detached the device from the patient and analyzed the recorded data for atrial fibrillation detection. During the third visit (day 90±15), routine physical examinations (blood pressure and pulse) and 12-lead ECG were performed. Finally, during the last visit (day 180±15), the participants repeated the clinical assessments performed during the third visit. If atrial fibrillation or other types of arrhythmias were detected via either the AT-Patch or 12-lead ECG, the investigator scheduled the individual for further assessment.The primary end point was the incidence of newly diagnosed atrial fibrillation as defined by ≥30 seconds of atrial fibrillation or flutter detected by the device. ECG data were reviewed by 2 independent cardiologists, and the diagnosis was confirmed when both reviewers were in agreement. The secondary end points were (1) a new clinical diagnosis of atrial fibrillation by 12-lead ECG at a scheduled or unscheduled follow-up visit and (2) death, acute myocardial infarction, stroke, or systemic embolic events during the 6-month monitoring period.2DS2-VASc score [2DS2-VASc score ≥2. This is more than 8 times the expected incidence rate in these patients. We set the type I error to 0.05 and the confidence limit to 3% which resulted in 315 participants. Finally, we set the attrition rate to 1.5% which resulted in the final sample size of 320 participants.Previous studies reported the incidence of new-onset atrial fibrillation as 0.76 per 100 person-years in adults aged ≥50 years which gradually increased to 0.17-6.71, according to the CHASc score  We hypotP value of <.05 was considered statistically significant. The Cohen κ coefficient was applied to evaluate interobserver reliability between the 2 independent cardiologists’ interpretations. McNemar’s test was applied to a 2 × 2 contingency table to determine the detection power of the AT-Patch device in comparison with the 12-lead ECG. For comparisons between patients with or without atrial fibrillation, the chi-square test (or Fisher’s exact test when any expected count was <5 for a 2 × 2 or 2 × 4 table) was performed for categorical variables, and a 2-sample t test or the Wilcoxon rank sum test was applied for continuous variables, dependent upon whether the data followed a normal distribution. Statistical analyses were performed using R software .Data are presented as numbers and frequencies for categorical variables and as means and SDs for continuous variables. The incidence of newly diagnosed atrial fibrillation is described as the proportion and 95% CI. A 2-sided A total of 320 participants were enrolled in this study. The incidence of arrhythmias, as detected by the AT-Patch and subsequently confirmed by 2 cardiologists (C1 and C2), is shown in It was determined that atrial fibrillation occurred in 4.4% (14/320) and 3.8% (12/320) of patients by cardiologist 1 (C1) and cardiologist 2 (C2), respectively, with example recordings of a detected episode shown in Overall, the total number of patients with new-onset atrial fibrillation was 4.4% (14/320). Interestingly, none of the participants presented with atrial fibrillation with both the patch monitor and 12-lead ECG. Moreover, the cardiologists determined that nonsustained ventricular tachycardia occurred occasionally, in 4.1% (13/320) of patients, and supraventricular tachycardia occurred more frequently, in 46.6% (149/320) of patients . No sust2DS2-VASc score ≥2, the mean age was 73.3 (SD 7.8) years, and the average CHA2DS2-VASc score was 3.6 . Interestingly, among the administered medications, the use of angiotensin-converting enzyme inhibitors was significantly different between patients with and without episodes of atrial fibrillation as detected by the AT-Patch device alone . When we evaluated patients with new-onset atrial fibrillation detected by AT-Patch or 12-lead ECG, those with previous heart failure were significantly different .Across the 320 participants with a CHA SD 1.2; . This st2DS2-VASc score ≥4 increased the detection rate of atrial fibrillation (P=.29). However, when we combined a CHA2DS2-VASc score ≥4 and previous heart failure, the detection rate significantly increased to 24.4% (P=.003).We determined that a CHAillation , but notThe average recording time for the patch ECG monitors was 263.8 (SD 15.6) hours and of them, 84.3% of ECG signals were valid for appropriate interpretation, with noise or missing signals disregarded for accurate diagnosis of arrhythmic events .P=.001 and 4.6% vs 1.2%; P<.001, respectively) and ventricular  ectopic rhythms were significantly more frequent in the new-onset atrial fibrillation group.According to the patch analysis system, normal sinus rhythm was detected in 98.2% of patients, and the average heart rate of this study’s population was 67.8 (SD 8.6) per minute. The participants were divided into atrial fibrillation and the nonatrial fibrillation groups as classified by AT-Patch only and by AT-Patch or 12-lead ECG. When comparing the recorded ECG data of the atrial fibrillation and the nonatrial fibrillation groups classified by AT-Patch only and by AT-Patch or 12-lead ECG, both classifications similarly showed that supraventricular  of participants were affected by itching during the patch monitoring period, and only 2.2% (7/320) of patients experienced a mild rash . All par2DS2-VASc components that were highly correlated with atrial fibrillation. As the AT-Patch has been shown to be comparable to conventional devices in detecting arrhythmia, it is now essential to find predictors associated with high diagnostic identification of new-onset atrial fibrillation among high-risk patients [2DS2-VASc score ≥4, including a history of heart failure. The pathophysiological relationship between heart failure and atrial fibrillation is not yet completely understood. However, many disease processes that predispose patients to heart failures, such as hypertension, diabetes mellitus, ischemic heart disease, and valvular heart disease, are risk factors for the development of atrial fibrillation [2DS2-VASc score ≥4 and a history of heart failure.This study aimed to demonstrate the diagnostic value of the AT-Patch, a wearable ECG monitoring device, for the detection of new-onset atrial fibrillation in high-risk patients. The results demonstrate the detection of a moderate number of new-onset atrial fibrillations among high-risk participants, with very few dermatologic reactions reported. These findings support previous studies that indicate that prolonged conventional ECG monitoring increases the detection rate of paroxysmal atrial fibrillations . Furtherpatients . With reillation . Moreoveillation , with seillation ,20. TherThe ECG data showed that the baseline electrical rhythm was more unstable in the atrial fibrillation group and that the occurrence of supraventricular and ventricular ectopic signals was more frequent in the new-onset atrial fibrillation group than in the nonatrial fibrillation group. Previous studies have indicated that episodes of atrial tachycardia potentially promote the remodeling of pulmonary vein cardiomyocytes and the left atrium, which may in turn be related to the arrhythmogenesis of paroxysmal atrial fibrillation . Althoug2DS2-VASc score is ≥4 and who have a history of heart failure are candidates that should be investigated in relation to atrial fibrillation.It is thought that the increasing incidence and prevalence of atrial fibrillation is in part due to the rapidly growing number of older adults in Korea . A largeDespite our study being statistically designed to demonstrate a higher diagnostic yield of new-onset atrial fibrillation, it is possible that the sample size may not be sufficient to prove the diagnostic value of this wearable device. To overcome this limitation, we employed the Firth logistic regression for rare variant association tests to generate a more accurate and reliable estimate of the predictor variables (Table S2 in This study was designed to be completed after the follow-up period at 6 months and as such, we were unable to investigate the late clinical outcomes for the participants. Some studies have reported a substantially increased risk of stroke in patients discharged from the hospital with a diagnosis of atrial fibrillation in the first year after diagnosis . HoweverThis study successfully detected a moderate number of new-onset atrial fibrillations using the AT-Patch device. This noninvasive, continuous ambulatory ECG monitor, which is less cumbersome to wear than conventional ECG monitors, is potentially beneficial for the early detection of atrial fibrillation and the prevention of subsequent adverse outcomes. Further studies will aim to investigate the relationship between heart failure and atrial fibrillation and use longer follow-up periods to determine how effectively prolonged monitoring with this patch device reduces adverse clinical outcomes of atrial fibrillation.


The potential of cardiac magnetic resonance to improve cardiovascular care and patient management is considerable. Myocardial T1-rho (T1ρ) mapping, in particular, has emerged as a promising biomarker for quantifying myocardial injuries without exogenous contrast agents. Its potential as a contrast-agent-free (“needle-free”) and cost-effective diagnostic marker promises high impact both in terms of clinical outcomes and patient comfort. However, myocardial T1ρ mapping is still at a nascent stage of development and the evidence supporting its diagnostic performance and clinical effectiveness is scant, though likely to change with technological improvements. The present review aims at providing a primer on the essentials of myocardial T1ρ mapping, and to describe the current range of clinical applications of the technique to detect and quantify myocardial injuries. We also delineate the important limitations and challenges for clinical deployment, including the urgent need for standardization, the evaluation of bias, and the critical importance of clinical testing. We conclude by outlining technical developments to be expected in the future. If needle-free myocardial T1ρ mapping is shown to improve patient diagnosis and prognosis, and can be effectively integrated in cardiovascular practice, it will fulfill its potential as an essential component of a cardiac magnetic resonance examination. A significant amount of modern cardiovascular magnetic resonance (CMR) research is the quest for new methodologies that would further improve contrast beyond established T1- and T2-weighted techniques [1H would occur at the Larmor frequency of approximately 64 MHz. However, to study biological processes such as the proton exchange between water and macromolecules, which occur at lower frequencies (in the order of 100 Hz to a few kHz), conventional T1- or T2-weighting imaging may not be sufficient. The low main magnetic field strength B0 that would be needed to resonate at these frequencies would be impractical for clinical imaging due to its inherently low signal-to-noise ratio (SNR).At the clinical magnetic field strength of 1.5 T for example, the precession of In this context, T1-rho (known as “T1ρ” and pronounced “T-one-rho”) imaging provides a viable approach to study low-frequency processes without sacrificing SNR . T1ρ is Evidence is also accumulating that endogenous T1ρ mapping of the myocardium can provide important molecular information about diseased myocardial tissue . In factIn this review, we aim at providing researchers and clinicians with an overview of the most-widely used myocardial T1ρ mapping tools from a more technical viewpoint with an emphasis on physical characteristics, sequence design, standardization, and influencing factors. We then discuss clinical applications and provide an insight to some of the emerging developments that may help bring myocardial T1ρ mapping closer to clinical practice.One of the first applications of T1ρ to magnetic resonance imaging (MRI) was investigated by Sepponen et al.  nearly 40 magnetic field is rotated by 90º (tip-down) RF pulse into the transverse—Mxy—plane. A spin-lock RF pulse with amplitude B1 is then applied parallel to the magnetization to lock the spins in the rotating frame. Then a tip-up 90º pulse is applied to flip the magnetization back to the longitudinal plane  [In biological tissues with proteins, proton exchange is expected to contribute to T1ρ relaxation. Several groups have explored the relationship and positive correlation between T1ρ and tissue water  content , 18. Mäk content . In the  content , 20. On  radian) . One canRegarding collagen content, Zhao et al.  found a There have been few studies undertaken that have shown the contributions of chemical exchange to T1ρ dispersion in tissue models , 24. TheUsing phantoms at 4.7-T, Kettunen et al. showed that T1ρ of blood was linearly related to oxygen saturation , which aDiffusion effects also affect the rate of spin–lattice relaxation in the rotating frame. This contribution can be mitigated by increasing the spin-locking field. Spear et al. , 40 deriInfarct/Remote = 74 ms at 500 Hz vs. ∆T1ρInfarct/Remote = 137 ms at 2500 Hz) [Data that links the previous findings to the in vivo heart are limited. Witschey et al.  found th2500 Hz) . A fast 2500 Hz) .To further investigate the evolution of T1ρ relaxation times for different myocardial tissue compositions, we correlated histology data and T1ρ obtained in a pig model of myocardial infarction on a 1.5-T system, three months after the infarction was induced. The study found that T1ρ elevation (72 ms vs. 51 ms) in the apical septal region corresponded well with the collagenous zone identified on histological data . The second approach, proposed by Qi et al. in 2020 [3 spatial resolution).Two-dimensional T1ρ-weighted images are usually reconstructed with a conventional generalized autocalibrating partially parallel acquisitions (GRAPPA) reconstruction, which is widely available on commercial systems . Typical in 2020 , combineOnce the images have been reconstructed, the fitting procedure should be carefully considered. In most studies, T1ρ maps are computed on a pixel-by-pixel basis using the monoexponential decay model defined in Eq.  or root mean square error (uncertainty) maps should be included in the interpretation and evaluated during scanning to allow for repeated acquisitions if quality is deemed insufficient. R2 maps are calculated on a pixel-by-pixel basis and are dependent on a wide range of factors including respiratory-related motion, off-resonance artifacts, slice profiles, dark banding-like artifacts, or aliasing interference. Figure 2 maps. Myocardial segments with low R2 values  must beAny reported relaxation time is the result of the combination of the subject, hardware, acquisition, reconstruction and fitting algorithms, and map analysis that are being used ; consequOn the physiological side several factors can influence myocardial T1ρ values. Gender, age, heart rate, temperature, body mass index and disease are important factors to consider [consider –62. MultOn the hardware and acquisition sides, and besides obvious magnetic field strength dependence, spin-lock pulse efficiency must be considered. Compared to standard Malcolm Levitt (MLEV) schemes [+ inhomogeneities [ schemes , self-coeneities , 65. Theeneities –71, but eneities .Giri et al.  have alsOn the reconstruction and analysis sides, the appropriate choice of the fitting model  is of utmost importance as it may impact the accuracy and precision of myocardial T1ρ values [ρ values , 72. Besρ values . FinallyConsiderations. A number of published articles have raised specific absorption rate (SAR) concerns related to spin-locking pulses [g pulses , 75. RF g pulses , 77. ParPublications reporting normal healthy values of the left ventricle obtained across different system vendors, field strengths, pulse sequences, and imaging sites are listed in Table To date, only ten studies have reported myocardial T1ρ values in patients, six of them being oriented towards specific populations Table : hypertrThere are two studies reporting the use of myocardial T1ρ mapping in patients with chronic myocardial infarction. Both studies were performed on a 1.5 T system in patients with a first episode of reperfused ST segment-elevated myocardial infarction. In the first cohort of 9 patients , van OorHypertrophic cardiomyopathy (HCM) is a genetic cardiovascular disease characterized by an inappropriately increased left ventricular wall thickness in the absence of an obvious cause for the myocardial hypertrophy, such as systemic hypertension or aortic stenosis. The estimated prevalence of HCM is 1 in 500 people , 84. LGEDCM refers to a heterogeneous group of myocardial diseases with poor outcomes and with an estimated prevalence of 40 in 100 000 individuals , 88. It At present, myocardial T1ρ mapping has been limited to the above-mentioned myocardial disorders and clinical applications are still in their infancy. These preliminary findings warrant additional studies to investigate the clinical value and prognostic utility of T1ρ mapping in a host of other cardiomyopathies. Examples of subjects likely to benefit from such mapping technology are patients with Takotsubo cardiomyopathy . Velasco et al. [Even though clinical studies have demonstrated the value of single mapping  techniques, and more recently T1ρ mapping, they are unable to provide a complete assessment of myocardial disease if they are applied and analyzed in silos. Multi-parametric mapping can provide a superior insight of myocardial tissue characteristics, more accurately identify myocardial injuries, while promoting knowledge and discovery. Magnetic resonance fingerprinting (MRF) and multitasking allow simultaneous measurement of multiple parameters (such as T1 and T2) in a single time-efficient scan and could thus provide a comprehensive assessment of the heart –98. One o et al.  recentlyThe application of AI to CMR mapping is a very recent phenomenon. For myocardial T1ρ mapping, AI technologies could come in several flavors, including smarter acquisition schemes that lower scan times; advanced reconstructions that improve T1ρ map quality; automated segmentation that drives easier and more efficient analysis; and radiomics applications  to gain The clinical studies discussed above provide exciting preliminary insights into contrast-agent-free quantification of myocardial injuries with myocardial T1ρ mapping. However, they also highlight important issues. First, and perhaps most importantly, widespread clinical adoption of myocardial T1ρ mapping is challenged by a lack of standardization and transferability  and the Quantitative MR Study group of the International Society for Magnetic Resonance in Medicine (ISMRM). Both initiatives have put up much-needed roadmaps for the development of new quantitative imaging techniques that may help accelerate their uptake in routine clinical practice.The advances presented in this Review have shown the promising performance of myocardial T1ρ mapping for the quantification of myocardial injuries without the injection of contrast agents. The relatively early stage of the technique also leaves plentiful space for future work, both for technological and clinical research. On the technological side, myocardial T1ρ mapping can be further enhanced by encoding for 3D information; by integrating multiparametric technologies such as MRF; by exploiting AI-driven tools for faster, easier, and more efficient analysis with the potential of removing error-prone manual processes; and by exploring the parameter space of T1ρ mapping in terms of resolution, SNR, accuracy, and precision. On the clinical side, applications of myocardial T1ρ mapping are still in the early stages. However, the lack of clinical evidence from prospective and randomized trials should not be considered as a barrier to further technical developments and to the translation of already existing methods. Given the unique potential of the mapping technology, it is likely that there will soon be an multitude of clinical studies assessing the performance of T1ρ mapping in a wide range of clinical scenarios. And only when myocardial T1ρ mapping is fully tested, standardized, and released, will its true impact in healthcare become apparent.