Cardiac involvement in Anderson-Fabry disease (AFD) results in myocardial lipid depositions. An early diagnosis can maximize therapeutic benefit. Thus, this study aims to investigate the potential of cardiac MRI (CMR) based parameters of left atrial (LA) function and strain to detect early stages of AFD.n = 58, age 40 (29–51) years, 31 female) with genetically proven AFD had undergone CMR including left ventricular (LV) volumetry, mass index (LVMi), T1, and late gadolinium enhancement, complemented by LA and LV strain measurements and atrial emptying fractions. Patients were stratified into three disease phases and compared to age and sex-matched healthy controls .Patients (p < 0.001). In contrast, LA volumetry, T1, and LVMi showed no significant differences between the early phase and HC (p > 0.05). In the intermediate phase, LVMi and T1 demonstrated significant differences. In advanced phase, all parameters except active emptying fractions differed significantly from HC. ROC curve analyses of early disease phases revealed superior diagnostic confidence for the LA reservoir strain  over the LV strain (AUC 0.82).A total of 19 early-, 20 intermediate-, and 19 advanced-phase patients were included. LV and LA reservoir strain was significantly impaired in all AFD phases, including early disease (both LA reservoir strain showed impairment in early AFD and significantly correlated with disease severity. The novel approach performed better in identifying early disease than the established approach using LVMi and T1. Further studies are needed to evaluate whether these results justify earlier initiation of therapy and help minimize cardiac complications.• Parameters of left atrial function and deformation showed impairments in the early stages of Anderson-Fabry disease and correlated significantly with the severity of Anderson-Fabry disease.• Left atrial reservoir strain performed superior to ventricular strain in detecting early myocardial involvement in Anderson-Fabry disease and improved diagnostic accuracies of approaches already using ventricular strain.• Further studies are needed to evaluate whether earlier initiation of enzyme replacement therapy based on these results can help minimize cardiac complications from Anderson-Fabry disease.The online version contains supplementary material available at 10.1007/s00330-022-09183-7. Anderson-Fabry disease (AFD) is a rare, hereditary, X-linked, lysosomal storage disease caused by mutations in the ɑ-galactosidase A gene, resulting in an enzymatic deficiency of alpha-galactosidase , 2. AccuClassic imaging biomarkers for advanced AFD are left ventricular (LV) hypertrophy and late gadolinium enhancement (LGE). T1 mapping on the other hand can directly visualize sphingolipid deposition in the myocardium, even in earlier disease stages , 11. In Strain analysis can be performed by speckle tracking echocardiography (STE) and cardiac magnetic resonance imaging (CMR) –21. WhilTherefore, the goal of this study was to assess atrial function and deformation using CMR-derived total (TEF), passive (PEF), and active (AEF) atrial emptying fractions and strain analysis to address the hypothesis that these parameters allow to discriminate not only between AFD patients and healthy controls (HC) but are able to evaluate disease severity.The protocol of this retrospective single-center study was approved by the responsible institutional ethics committee.A total of 58 AFD patients  were enrolled and stratified into three disease severity phases based on CMR findings  Table S, as follA group of 58 healthy subjects who were matched 1:1 with AFD patients on a basis of age and sex served as a control group. Based on their clinical history, none of the subjects have had any cardiovascular events or symptoms or cardiovascular risk factors . All healthy controls (HC) had normal LV volumes, normal myocardial T1 and T2 relaxation times according to institutional reference ranges, and no LGE.All patients underwent CMR on 3-T systems . Standard cardiac views  were acquired using a unified imaging protocol comprising a conventional balanced steady-state free-precession cine sequence with retrospective ECG gating and standard acceleration . Typical pulse sequence parameters were as follows: repetition time (TR) 3.77 ms; echo time (TE) 1.39 ms; reconstructed cardiac phases 25; field of view (FOV) 360 mm; flip angle 60°; voxel-size 1.5 × 1.5 × 8.0 mm; and cardiac cycle/slice 10.Native T1 mapping was performed in three short-axis slices predefined from the previously acquired cine stack . A commercially available modified Look-Locker inversion-recovery sequence with a 5(3)3 scheme was applied with the following pulse sequence parameters: TR/TE 331.68 / 1.12 ms; FOV 630 × 360 mm; matrix 256 × 256; slice thickness 8 mm; flip angle 35°; bandwidth 1085 Hz/Pixel; and GRAPPA 3.2, slice thickness 8 mm, inter-slice gap 2 mm, and flip angle 25°. The inversion time (TI) ranged between 260 and 320 ms and was defined based on a separately acquired TI scout. TI was increased by 10 ms for every minute of acquisition to optimally null the signal from the normal myocardium.For contrast enhancement, 0.2 mmol/kg gadoteric acid  was administered. LGE images were acquired 10 min after contrast injection using a segmented T1-weighted inversion recovery ultrafast spoiled gradient echo sequence in long- and short-axis views identical to those used for cine imaging. The following pulse sequence parameters were applied: TR 2 × RR-interval, TE 4.38 ms, in-plane resolution 1.4 × 1.8 mmImage analysis was performed by a specifically trained reader. For post-processing, a dedicated cardiovascular software  was used. Atrial strain analysis was semi-automatically performed as recently described  and manuVolumetric analysis of left atrial (LA) time–volume curves was semi-automatically performed using the biplane area-length calculation technique, which is the method of choice if the Simpsons method is not practical . As the To calculate LA strains, endocardial and epicardial borders were manually traced in a single slice at end-diastole in the 2-, 3-, and 4-chamber-views Fig. . The LA Using the LV end-diastolic frame as a zero-reference, strain curves were then analyzed to identify peaks corresponding to the following phases of the LA cycle: (1) reservoir—passive LA filling due to inflow from pulmonary veins, 2) conduit—passive flow through the LA after the opening of the mitral valve in the early LV filling phase, and (3) booster—active LA contraction during the late LV filling phase , 37. In  conduit—Statistical analyses were performed using SPSS Statistics . The Kolmogorov-Smirnov test was used to assess the normal distribution of the continuous data. Continuous variables are reported as means with standard deviations in brackets if normally distributed, and as median and the respective interquartile ranges in case of non-normal distribution. Categorical variables are reported as absolute frequencies and proportions. Differences between AFD phases and HC were compared using two-way ANOVA with post hoc testing and Bonferroni correction. Binary logistic regression models were created to evaluate multiparametric approaches.p value < 0.05 was considered significant.To evaluate differences in the ability to discriminate between HC and AFD patients, receiver operating characteristic (ROC) curve analyses were performed and areas under the curve (AUC) were evaluated. Cut-off values were determined by the highest Youden’s index from the comparison between all AFD patients and all HC, as this most closely resembles the real-world scenario where it is not known what disease phase a patient is in ahead of the CMR. These cut-offs were subsequently used for phase-specific evaluation of sensitivity, specificity, and diagnostic accuracy. Pairwise DeLong comparisons were performed to compare different approaches. A The overall study population consisted of 58 patients , LA conduit , and LA booster strain . In addition, LV global longitudinal strain (LV GLS) was significantly reduced .LA strain analyses revealed significant differences between phase I patients and respective matched HC for LA reservoir . Further details for all parameters can be found in Table LA emptying fractions, LVMi, and global T1 relaxation times did not show significant differences between the groups . In multiparametric testing, the addition of LA reservoir strain significantly increased the AUC compared to the combination of LVMi and T1 alone (0.52 vs. 0.90) as well as LVMi, T1, and LV GLS (0.79 vs. 0.90) for differentiating phase I AFD from HC. Comparison between mono- and multiparametric approaches revealed that LA reservoir strain alone was non-inferior to all tested multiparametric approaches  . Using the cut-off at 35.9 %, a sensitivity of 89 % and a specificity of 75 % were reached. LVMi (AUC 0.51) and T1 AUC 0.52) performed significantly lower when compared using the DeLong test  and phase I patients (p = 0.012). LVMi was significantly increased in comparison to matched HC  but not in comparison to phase I patients . In ROC-curve analyses, T1 showed an AUC of 0.76  and LVMi reached an AUC of 0.67 (sensitivity 67 % and specificity 57 %).As seen in Fig. p < 0.001), conduit , and booster strain . In addition, LV global longitudinal strain (LV GLS) was significantly reduced in comparison to HC  but not in comparison to phase I AFD patients (p = 1.000). ROC-curve analyses indicated that LA reservoir strain  performed superior to LVMi and T1 .LA strain analysis revealed significant differences between phase II AFD and respective matched HC for reservoir  .The comparison between multiparametric approaches showed a significant increase of the AUC when LA reservoir strain was added to the combination of LVMi and T1 (AUC 0.68 vs. 0.96) as well as LVMi, T1, and LV GLS (0.79 vs. 0.96). Comparison between mono- and multiparametric approaches revealed that LA reservoir strain alone was superior to the combination of LVMi and T1 as well as non-inferior to all tested multiparametric approaches  Fig. . Concern2 [69.6–133.6] vs. 53.3 g/m2 [46.5–60.2], p < 0.001), to phase I , and to phase II  patients. Figure p < 0.001); however, there were no significant differences between phases II and III (p = 0.706).With the progression of AFD, established parameters such as LVMi and myocardial T1 gain more importance. Thus, LVMi was significantly increased in phase III AFD compared to HC  for the differentiation between phase III patients and HC, while LVMi reached an AUC of 0.99 (sensitivity 95 % and specificity 93 %).p < 0.001)  but not in comparison to the other disease phases . ROC-curve analyses revealed non-inferior diagnostic performance of LA reservoir strain  in comparison to LVMi  and T1  and LV GLS . All multiparametric approaches reached remarkably high diagnostic confidence (AUC 1.00).All LA strain parameters showed significant differences between phase III patients and matched HC  Fig. . Again, As AFD is an x-linked disease, results must also be viewed as split by sex. Comparisons between male and female patients showed a significantly smaller LA TEF for phase I male patients, significantly younger male patients in phases II and III, and a significantly higher increase in LVMi for male patients in both phases II and III. Significantly lower  LV EF was found in male phase II patients and significantly higher LA PEF was observed in male phase III patients. The detailed comparison of sex-specific baseline characteristics for AFD patients can be found in Table In addition, Table r = 0.40  and r = 0.28 , p ≤ 0.05). In addition, there were negative correlations between LA reservoir strain and LVMi for both women  and men   Fig. .In this study, various LA parameters were analyzed in a multi-parametric CMR diagnostic workup of AFD patients. Disease severity and progression were evaluated based on novel atrial, as well as already established parameters, such as functional markers, LV strain, and myocardial T1. The results demonstrated that LA reservoir strain reliably differentiates between early-phase AFD patients and HC when atrial volumetric parameters and T1 mapping fail to do so. In addition, this study found a significant correlation between LA strains and disease severity in AFD.Previous studies have shown that abnormalities in myocardial T1 occur before LV hypertrophy develops –12, 38. The single CMR-based atrial strain study available in the literature was designed to compare AFD patients with severe LV hypertrophy  and patients with hypertrophic cardiomyopathy and thus had a different scope . HoweverAn STE-based study has shown that abnormalities of LA functional parameters occur in AFD patients before LV hypertrophy becomes evident . InteresIn addition, this study confirms prior literature findings that AEF proved to be the least diagnostically accurate in comparison to TEF and PEF , 42. ThiPrior research demonstrated that ventricular strain analysis by CMR could show AFD-related strain abnormalities even before sphingolipid deposition can be detected by mapping sequences . The resDeposition of sphingolipids in the atrial myocardiumFrom a pathophysiological viewpoint, the early impairment and gradual deterioration of LA strain with advancing disease could be explained by an accumulation of multiple pathways with abnormal atrial deformation patterns as their common outcome , 46:Dep(2)Ventricular diastolic dysfunctionHistopathological studies have proven that sphingolipid deposition does occur in the atria . UnfortuThe strain has recently been highlighted in diseases accompanied by diastolic dysfunction , 48–50. Overall, this study complements the current literature in regard to atrial strain analysis and involvement in AFD by demonstrating its diagnostic performance. It provides novel insights into atrial deformation in AFD patients, suggesting latent diastolic dysfunction pre-detectable accumulation. In addition, it was able to show a correlation between disease severity and LA reservoir strain. The careful evaluation of the atria could aid in further understanding the different pathophysiological pathways in which the disease impairs cardiac function and potentially help guide therapeutic decisions in the future .This study has several limitations. Despite the balanced sex ratio and efforts to manage an equal distribution of HC and patients with AFD, this remains a single-center, retrospective study. Several studies have already validated the reproducibility of atrial strain analyses; however, there are still significant differences between various vendors. Thus, there exists no current reference standard , 28, 54.Because of the retrospective nature of the study, patients did not undergo endomyocardial biopsy as ground truth for cardiac involvement in AFD. However, as a surrogate, thorough genetic analyses were performed, and all mutations with their respective nucleotides and protein changes are reported in Table The analysis of atrial deformation patterns by CMR feature-tracking strain analysis revealed that LA reservoir strain reliably differentiates between early-phase AFD patients and HC whereas atrial volumetric parameters and T1 mapping fail to do so. In addition, atrial strain analysis provides incremental value in the diagnosis of early AFD when compared to multiparametric approaches including ventricular strain analysis. This study also found a significant correlation between LA strains and disease severity in AFD measured by T1 and LVMi. These results suggest that the evaluation of LA deformation patterns should be an integral part of the diagnostic work-up in AFD with questionable cardiac involvement. Further studies are needed to evaluate whether earlier initiation of ERT based on these results can help minimize cardiac complications from AFD.ESM 1(DOCX 154 kb)


Objective: The knowledge of maternal cardiovascular hemodynamic adaptation in twin pregnancies is incomplete. We aimed to longitudinally investigate maternal left ventricular (LV) function in uncomplicated twin pregnancies. Methods: 30 healthy and uncomplicated twin pregnant women and 30 controls with normal singleton pregnancies were prospectively enrolled to undergo transthoracic echocardiography at 10–15 week’s gestation (w) (T1), 19–26 w (T2) and 30–38 w (T3). LV dimensions and volumes, as well as LV ejection fraction (LVEF), mass (LVM) and diastolic parameters , were calculated. Speckle-tracking imaging was also applied to evaluate LV global longitudinal (GLS), radial and circumferential 2D strains. Results: During twin pregnancy, maternal LV dimensions, volumes and LVM had an increasing trend from T1 to T3, similar to singletons, while LVEF remained stable. There was LV remodeling/hypertrophy in 50% of women at T2 and T3 in both groups. Diastolic function had a worsening trend from T1 to T3 with no differences between twins and singletons, except for higher LV filling pressure  at T2 in twins. Two-dimensional strains did not vary during gestation in either group, except for a linear trend to increase  GLS in singletons. Radial and circumferential 2D strains were impaired in about half of the women at each trimester, while GLS was altered in one-fourth/one-third of them in both groups. Conclusion: Maternal LV geometry, dimensions and function are significantly impaired during twin pregnancies, in particular in the second half of gestation, with no significant differences compared to singletons. In pregnancy, significant cardiac structural and hemodynamic changes occur. Cardiovascular (CV) remodeling involves the whole heart . Left veAs described in a previous paper on the same population , from FeA standard, calibrated, electronic sphygmomanometer  was used to measure blood pressure at each arm, at rest in a 45° reclining sitting position. Systolic blood pressure (SBP) was considered elevated if higher than 140 mmHg and diastolic blood pressure (DBP) if higher than 90 mmHg. Two more measurements were taken at the arm with the highest blood pressure, and the average value was calculated. Blood pressure was assessed by the same staff member, at the same part of the day and adopting the same device. Mean arterial pressure (MAP) was defined as (SBP + 2 × DBP)/3.2  and eccentric hypertrophy by RWT < 0.42 and LVM index > 95 g/m2  [Echocardiographic examinations were performed using a Vivid 7 machine  with a 3.5 MHz transducer. Digital loops were stored on the hard disk of the echocardiograph for on-line and off-line analyses and transferred to an EchoPac, Vingmed workstation  for off-line analysis. Participants were studied in the left lateral decubitus position and images were acquired from standard parasternal and apical windows. LV dimensions, volumes and LVM were obtained according to current guidelines and LVEF calculated by means of Simpson’s biplane method . LVM wasfemales) . LV diasfemales) . Myocardfemales) ,18.A two-dimensional (2D) strain calculates myocardial deformation from a 2D point of view. Negative strain means shortening, while positive indicates thickening of a given myocardial segment. STE analysis using a commercially available automated function image technique was applied for the assessment of LV global longitudinal strain (GLS) from apical long-axis slices (long-axis and two- and four-chamber views) . Endocarn) and percentage (%). Student’s t-test was run to compare means for continuous variables. The χ2 test (or Fisher’s exact test) was adopted to assess differences between proportions.Continuous variables were reported as mean ± standard deviation (SD) and categorical ones as frequency (i is the subject and j the time of the measure.β_0 is the fixed intercept.β_01 is the parameter related to the twin dependency.β_1 and β_2 represent the type of time trend (linear or quadratic).b_i0 〖+ b〗_i1 t_ij + e_ij is the error term expressed in terms of random intercept, random slope and residuals, where terms b_i0, 〖 b〗_i1 and e_ij have zero mean.Every clinical outcome was studied by means of multilevel mixed-effects linear regression analysis. With respect to a standard two-way ANOVA for repeated measurements, such an approach considers each outcome as a linear model with random intercepts and slopes. This assumption fits models with a general covariance matrix depending on time and also uses all nonmissing information on repeated data. The model to be fitted was:Finally, a quantile regression analysis was run to design boundary curves. This analysis extends the longitudinal mixed model, focusing on the chosen quantile.To better compare the models, they were corrected for maternal age.For every outcome, the best-fitted model was selected by means of the minimum Akaike criterion. To discover the best model, an initial linear model hypothesis, adopting the twin pregnancy as covariate, was analyzed and, if needed, its polynomial degree was elevated.R and R-Studio were utilized to analyze databases and to run traditional statistics , while longitudinal data analysis was obtained with Stata 14.2 with xtmixed function, and quantile regression was performed with the lqmm method from the lqmm R package Version 1.5.8, Marco Geraci, London, UK .p-value < 0.05 was considered significant.For every statistic, A total of 39 women with uncomplicated twin pregnancies and 34 with healthy singleton ones fitted the inclusion criteria and were enrolled in a prospective way . Among tp < 0.01), while delivery time earlier and Caesarean section rate greater (p < 0.001). Body mass index and body surface area augmented during pregnancy in both groups, with a significant quadratic trend but without intergroup differences.p = 0.04). Consequently, LVM  showed a trend to increase from T1 to T3 with no intergroup differences . RWT did not vary throughout twin gestation, similar to singleton pregnancy. LV remodeling/hypertrophy was more pronounced at T2 than T1 in both twins and singletons , but the LV geometric pattern did not differ between twin and singleton gestations at each time interval. p = 0.015) (as suggested by the quadratic trend). On the contrary, the concentric pattern (either remodeling or hypertrophy) was similar in the two groups at each trimester.Echocardiographic data are reported in As concerns diastolic function , E wave p (trend) refers to a longitudinal regression run on the subgroup of 30 patients. If reported, the model has p-value < 0.05, for details see Data are given as mean ± SD. Data are given as mean ± SD. EDV, end-diastolic volume; ESV, end-systolic volume; LVEF, left ventricular ejection fraction; IVST, interventricular septum thickness; PWT, posterior wall thickness; LVEDD, left ventricular end-diastolic diameter; LVM, left ventricular mass; BSA, body surface area; RWT, relative wall thickness; DT, deceleration time; IVRT, isovolumic relaxation time; IVCT, isovolumic contraction time; ET, ejection time; MPI, myocardial performance index; BMI, body mass index; BSA, body surface area; ESV, end-systolic volume; LVEF, left ventricular ejection fraction; IVST, interventricular septum thickness; PWT, posterior wall thickness; LVM, left ventricular mass; IVCT, isovolumic contraction time.STE data  were avaThe main findings of this study can be summarized as follows: (1) during pregnancy, particularly if multiple, LV volumes, LVM and LV filling pressure increase; (2) some diastolic parameters tend to worsen from T1 to T3 in both twin and singleton pregnancies; and (3) GLS, as well as circumferential and radial strains, did not significant vary during gestation, with no difference between twin and singleton gestation, although 2D strains are altered in a high percentage of women with twin pregnancy.Pregnancy is characterized by profound hemodynamic adaptation in order to meet the increased metabolic demands of the mother and fetus and to ensure adequate uteroplacental circulation. Indeed, systemic vascular resistance (and blood pressure) falls from the first trimester, with a nadir in the second one, while CO increases till delivery. Consequently, cardiac remodeling occurs to face these changes, principally with increased LVM ,23.Limited data are available about maternal hemodynamics during multiple pregnancies. Among these, Kametas et al. found a significantly higher CO among twins than in singletons , as did In the present paper, we assessed GLS as well as radial and circumferential LV strains, which had never been previously studied in twin pregnancies. Although we found no differences in LV strains among cases and controls, we demonstrated a high rate of LV strain alteration  since T1, in association with LV remodeling and diastolic impairment, remarking that pregnancy is a condition in which the heart faces profound hemodynamic challenges. STE has been applied to overcome the limitations of conventional echocardiography. It is angle-independent, not greatly influenced by preload or afterload and not affected by heart movements ,12. StudOutside of pregnancy, there is a well-established trend for basing treatment on hemodynamic profiling. For example, in the NICE guidance on adult hypertension , treatmeThe main strengths of this present paper lie in its prospective study design with a longitudinal assessment of maternal cardiac function from the first to the third trimester of gestation. Moreover, a whole evaluation of maternal LV function by means of STE had never been previously carried out in twin pregnancies. A detailed assessment of maternal hemodynamics in twins might offer a better insight to the process of maternal adaptation to twin pregnancy in order to also improve the understanding of the pathophysiology of CV complications occurring more frequently during twin gestations .We acknowledge the following limitations to the study. Firstly, we cannot provide accurate reference ranges for each variable due to the small number of enrolled women. Secondly, the absence of a post-delivery evaluation does allow us to show which variables eventually normalize and when they do so. Thirdly, as already discussed, a significant proportion of monochorionic twins was enrolled; considering that CO is marginally higher in dichorionic ones , this caTo conclude, pregnancy is a condition of high hemodynamic load and determines profound changes in the left ventricle. STE is able to detect a high percentage of alterations, which are the expression of the damage induced by hypertrophy and remodeling. In how many women it persists remains to be clarified. No substantial differences were found in multiple pregnancies. However, our data are limited by the small sample size. Larger studies with a postpartum assessment are needed to extend our knowledge.


MV). Transcatheter mitral valve repair (TMVr) devices have been proven to be efficient and safe, but many anatomical structures are not compatible with these technologies. The most significant advantage of transcatheter mitral valve replacement (TMVR) over transcatheter repair is the greater and more reliable reduction in mitral regurgitation. However, there are also potential disadvantages. This review introduces the newest TMVr and TMVR devices and presents clinical trial data to identify current challenges and directions for future research.Over the last two decades, transcatheter devices have been developed to repair or replace diseased mitral valves ( Mitral valve (MV) disease is the most common heart valve disease, with a prevalence in western countries of 1% to 2% in the general population and a prevalence of 10% in persons over 75 years of age [MR is a disease in which the MV does not close adequately during left ventricular systole, resulting in regurgitation of blood from the left ventricle (LV) to the left atrium, and includes primary (degenerative) MR and secondary  MR . PrimaryOptimization of pharmacological therapy is the first step in treating all patients with secondary MR, and the application of cardiac resynchronization therapy requires a comprehensive evaluation according to the relevant guidelines . The Eur(TMVr). However, there are still patients who are anatomically unsuitable for these therapies, such as patients with a high coaptation defect or severe mitral valve calcification. As a result, interest in transcatheter mitral valve replacement (TMVR) has increased over the last few years.In elderly patients and patients with comorbidities, the surgical risk is high and approximately 50% of patients with severe MR symptoms are not suitable candidates for open-heart surgery . TherefoTMVr and TMVR devices, early results of treatment, challenges to treatment, and scientific views on the future direction in this constantly evolving field.This review covers The different components of the mitral valve  and the different pathogeneses of the disease (primary and secondary) have led to a series of different therapeutic measures, such as transcatheter edge-to-edge repair (TEER), direct/indirect annuloplasty, and chordal repair. An overview of the features of transcatheter, mainly transfemoral mitral valve repair devices that have received CE make approval is indicated in TM  is based on the traditional surgical “edge-to-edge” procedure and consists of two main components: a clip and a catheter system. After transseptal puncture, and under the guidance of transesophageal echocardiography (TEE) and fluoroscopy, the clip is advanced in the left atrium through the catheter. The anterior posterior mitral leaflets are grasped together, according to the anatomical location of the regurgitant jet, to create a double-orifice outflow tract. The latest fourth-generation MitraClip (MitraClip G4) offers more clip sizes for tailored repair. It also has a new leaflet grasping technology called a Controlled Gripper ActyationTM, which allows physicians to grasp leaflets simultaneously or independently to confirm and optimize leaflet insertion. The MitraClip G4 offers four types of clips based on mitral valve anatomy: NTW, NT, XTW and XT. The recommendations of clip selection are shown in p = 0.001). A 5-year follow-up revealed no significant difference in mortality between the MitraClip and surgical groups , nor was there a significant difference in New York Heart Association (NYHA) class between the two groups [The MitraClipo groups . More reo groups  and MITRo groups  found tho groups  suggesteo groups  reportedAs TEER procedure becomes more popular, the number of patients with residual or recurrent MR is rapidly increasing ,31. In pOverall, the MitraClip has been shown to have a high safety and efficacy profile in adequately selected patients, with a low incidence of complications . Future studies will need to answer questions regarding patient selection, long-term outcomes and the importance of residual MR following MitraClip and post-procedural transmitral pressure gradients , which hPASCAL BThe PASCAL system  is another form of TEER  In contrThe first clinical trial of the PASCAL system was applied to 23 patients with severe MR who were inappropriate for surgery , of whicCardioband CThe Cardioband system  secures the annuloplasty band to the posterior annulus through small anchors under TEE and X-ray guidance, and then adjusts the annuloplasty band to reduce the diameter of the mitral annulus. In a multicenter clinical study , the CarMitralign DThe Mitralign system  is introduced from the femoral artery, retrograde through the aorta into the LV and left atrium, and paired surgical pledgets are anchored across the annulus. The pledgets are pulled together to reduce the diameter of the annulus. Nickenig et al.  reportedCarillon EThe Carillon mitral contour system  is the only device in its category, allowing indirect annuloplasty without the need for transseptal puncture. The procedure is guided by X-ray to reach the right atrium via the internal jugular vein, and the device is deployed after entering the coronary sinus. The diameter of the mitral annulus can be shortened by shortening the length of the device after insertion. In a randomized clinical trial of REDUCE-FMR , 120 patNeoChord FThe NeoChord system  is a device used to treat primary MR caused by MV prolapse/flail posterior. In contrast to the above-mentioned TMVr devices, this device is guided by TEE through an apical approach into the LV, with one end connected to the MV leaflet and the other to the left ventricular myocardium, forming an artificial chord fixed to the ventricular wall. A Trans-Apical Chordae Tendineae trial demonstrated promising immediate safety and efficacy of the NeoChord system with achieved acute procedural success (placement of at least one neo-chord and reduction of MR from 3+ or 4+ to ≤2+) in 26 patients . A cliniMV disease is complex as well as heterogeneous, and TMVr devices are difficult to fully address all variabilities in MV anatomy and patients’ conditions. The development of TMVR offers a new treatment option to address MR. TMVR and may have several theoretical advantages over TMVr, namely predictably reducing MR, and possibly being less invasive than surgical procedures . The iniIndeed, surgery is still the standard approach to MR treatment, and the transcatheter options for repeat procedures in patient with previous mitral surgery is highly relevant, as these patients are often at too high-risk for repeat surgery. To date, the current literature reports mitigated results and significant morbidity in some of these situations. Thus, the VIVID registry  reportedNevertheless, since most of MR patients do not have previous surgery or significant calcification of their mitral annulus, the valved stents used for TAVR cannot be used for TMVR.The valve-in-native valve procedure for these patients is genuine TMVR. Over 30 TMVR devices are currently in development, and the field is in constant expansion ,58. HereTendyne Mitral Valve System  AThe Tendyne mitral valve is the only TMVR device with a CE mark (since January 2020). The Tendyne mitral valve system is a self-expanding tri-leaflet porcine pericardial valve mounted on a nitinol frame, which is fully repositionable and retrievable. Its design has many advantages as follows: (1) the D-shaped design prevents left ventricular outflow tract obstruction (LVOTO); (2) it can be retrieved and re-released or adjusted when the implantation position or the efficacy is unsatisfactory; (3) the presence of an atrial cuff prevents perivalvular leakage, and (4) the reliance on the apical tether rather than clamping of leaflets or chordae is the most unusual feature of the Tendyne valve and the most unique in its design. The apical tether provides strong tensile force, virtually eliminating the risk of atrial embolization of the valve; secondly, there is no need to clamp the leaflets or chordae by using the apical tether because the stent on the ventricular portion can be narrowed towards the center. By adjusting the position of the tether, the valved stent can be drawn toward the free wall of the ventricle, mitigating the risk of LVOTO. The apical pad can also serve to seal the myocardial orifice created with transapical puncture. Thirteen sizes of this Tendyne valved stent are available. The first in-human implantation of the Tendyne valve was performed in February 2013 and was reported as a two-patient series the following year. A dramatic improvement in intracardiac pressures, along with complete elimination of MR was reported . In the Tendyne global feasibility trial, one-hundred patients were enrolled in multiple centers from November 2014 to November 2017 . This prospective non-randomized study evaluated 30-day and 1-year outcomes following transapical TMVR with the Tendyne prosthesis . The results demonstrated technical success in 97% of patients, and no perioperative mortality. At 30 days, 98.8% of patients presented with no or trace regurgitation. The all-cause mortality was 6% after one-month. Furthermore, the all-cause mortality was 26% with no MR in 98.4% at 1-year. A small study showed encouraging results of the Tendyne system in patients with severe MAC, for which treatment options are currently limited. The device was successfully implanted with correction of MR in nine patients, and there were no procedural deaths. One patient presented with LVOTO  and required alcohol septal ablation. There was one cardiac death and one non-cardiac death in the follow-up (median 12 months). Clinical improvement with mild or no symptoms occurred in all patients alive at the end of follow-up .The SUMMIT trial (NCT03433274) is an ongoing prospective, controlled, multicenter clinical investigation with three trial cohorts: Randomized , non-randomized, and MAC, designed to evaluate the safety and effectiveness of using the Tendyne mitral valve system for the treatment of symptomatic MR. This study should offer a large dataset regarding efficacy and safety of the Tendyne system. To date, 1000 Tendyne devices have been successfully implanted worldwide.Tiara TMVR System  B2; 40 mm: internal dimensions 34.2 × 40 mm, area 9–12 cm2) [The Tiara TMVR system has a self-expanding nitinol frame with three bovine pericardial leaflets. The device is D-shaped and fits geo-magnetically in the native mitral annulus. The valve features three anchors (two anterior and one posterior) on the ventricular part . The ven–12 cm2) .The first in-human implantation was reported in January 2014 . The twoIntrepid TMVR System  CThe Intrepid TMVR system integrates a self-expanding nitinol frame with tri-leaflet bovine pericardial valve, which includes an inner stent with valve attached and an independent conformable outer stent to engage the annulus and leaflets, providing fixation while isolating the inner stent from the dynamic anatomy . The outBapat et al.  describeEVOQUE TMVR System  DThe EVOQUE  valve is a transseptal self-expanding nitinol valve with bovine pericardial leaflets. The atrial part provides additional annular anchorage and contains a paravalvular sealing skirt, which is designed to minimize paravalvular leakage. Two sizes (44 and 48 mm) are currently available and are delivered via a transfemoral/transseptal approach. The delivery system allows for three planes of motion, permitting coaxial alignment and precise positioning within the annulus. To reduce the risk of LVOTO, the delivery system allows the valve to be tilted before deployment. An early feasibility trial is currently enrolling (NCT02718001). The results of the first 14 patients treated with the EVOQUE valve showed technical success in 93% of patients and one patient undergoing surgical conversion. Two patients underwent paravalvular leak closure, and one patient underwent alcohol septal ablation for LVOTO. Of the patients, 93% survived at 30-days. MR was eliminated in 80% of patients, and the remaining 20% of patients had mild MR .SAPIEN M3 System  EThe SAPIEN M3 system is a modification of the SAPIEN 3 TAVR system, including a nitinol dock with a balloon-expandable tri-leaflet bovine pericardial valve. The SAPIEN M3 valve adds a polyethylene terephthalate (PET) skirt to minimize paravalvular leakage. Early experience in 10 patients showed promising safety and efficacy, with nine successfully implanted patients with no significant adverse events . ResultsHighLife TMVR system  FThe HighLife TMVR system’s special component is a sub-annular implant ring that acts as a docking system. A transfemoral retrograde transaortic approach is used to place a sub-annular ring around the MV from the start to act as an anchor for the self-expanding tri-leaflet bovine pericardial valve. This design could theoretically reduce the risk of perivalvular leakage and LVOTO. The first two case of HighLife implantation in humans showed excellent early hemodynamic performance . Data frIn addition to the systems mentioned above, other technologies are under development and are still in their early stages, with only a few cases being reported. Other devices under development include the NAVI System ; the AltaValve TMVR system ; the Cephea TMVR System  .Different strategies should be adopted for MR with different etiologies . The TEENotably, the role of center and operator experience cannot be ignored. Reports have already illustrated that increased institutional and operator experience is associated with improvements in procedure success, procedure time, and procedural complications for TMVr with MitralClip ,85.TMVR has the potential to overcome these limitations even if some challenges remain to be solved. Based on experience with TAVR, the transfemoral approach would be the preferred interventional approach. However, due to the larger size of the MV compared to the aortic valve, TMVR devices require a large profile delivery system, and most devices still require a standard transapical approach. Thus, it is predictable that perioperative complications might be further reduced when transseptal TMVR delivery becomes more widely feasible. Therefore, the development of maneuverable low-profile delivery systems should be key in future research. This might allow reduction in the need for atrial septal defect closure following transseptal approach.(1)The mitral annulus is saddle-shaped and D-shaped, not circular, and is not in the same plane. Even if a skirt is placed on the atrial portion, paravalvular leakage may still occur.(2)In TAVR, the aortic valve is calcified, rigid, and rounder after pre-dilation, which makes it relatively easy to anchor the circular aortic valved stent to the native annulus in a tube-like area. In contrast, the mitral annulus is compliant, and its shape is constantly changing with the cardiac cycle and underlying pathological process. Thus, it generally does not provide radial support for the new valved stent because the annulus is located between the contracting left atrial and ventricular chamber. Thus, mitral fixation has to be done in a very different way than that for TAVR and engineers face significant challenges when developing new devices.(3)The intracavitary pressure from the LV contraction can be high (180 mmHg), and the prosthetic valve is at risk of atrial embolization.(4)There are about 24 chordae in the left ventricular cavity which can interfere with the implantation and fixation of the new prosthetic valve.(5)The probability of acute LVOTO after TMVR is 8.2% , rising TMVR offers some additional challenges. Indeed, compared to TAVR, the TMVR faces more problems and challenges due to the more complex anatomy of the MV apparatus: Some approaches have been proposed to overcome these challenges: the use of a D-shaped valve ring, the alcohol septal ablation method, the anterior leaflet laceration technique (Lampoon) that can minimize the impact on left ventricular outflow tract , the fixAlthough current mitral valved stents meet basic requirements, such as fixation to the mitral annulus, satisfactory valve function, no paravalvular leakages, and no short-term complications, they still face some practical problems, especially when used in patients with lower surgical risk  or at a younger age when optimal long-term results are mandatory. (1)In the vicinity of the mitral valved stent, where blood flow is maintained at a very low velocity within a relatively small circulatory area, the potential for blood clotting in the left atrium is increased. Indeed, to prevent paravalvular leakage, prosthetic valves are designed to have an atrial skirt and a complex structure aligned towards the atrial portion, where blood flow is slow and therefore prone to thrombus formation. In addition, the peripheral area of the mitral valved stent against the ventricular wall is also blinded to blood flow and is also susceptible to thrombus formation. Clinical studies have shown that thrombosis is, indeed, a problem and a major cause of postoperative death in many patients. Some studies suggest adequate oral anticoagulants as one of the main solutions ,90,91,92(2)The mitral annulus size may easily be underestimated. Nakashima et al.  reported(3)The durability of prosthetic valves may also be an issue. The prosthetic aortic valve is implanted in the aortic root where there is little local tissue activity, and therefore valve degeneration is low after TAVR (about 6.6% after 5 years ). In conThese issues include:The current medical consensus is that mitral valves should not be replaced if they can be repaired because MV replacement may damage the chordae tendineae, which are part of the ventricular systolic function. When the ventricle contracts, the chordae pull the mitral apparatus to prevent prolapse and regurgitation, as well as pull the apical tissue toward the MV to help the ventricle contract. Long-term lack of chordae inevitably leads to impaired ventricular function, which in severe cases contributes to heart-failure worsening. Therefore, there is currently a preference for MV replacement surgery that preserves the sub-valvular apparatus, such as chordae tendineae . All TMVWhether with TMVr or TMVR, patients need accurate quantification of mitral regurgitation, assessment of mitral valve anatomy, assessment of LV dimensions and systolic function, as well as left atrial dimensions. In addition, the mitral valve cannot be inspected during the intervention procedure compared with surgery, so it is more important to accurately visualize the mitral valve apparatus. Three-dimensional TEE has been shown to provide better information on valve morphology and function with assessing the mitral annulus perimeter and area ,103,104.Overall, TMVR has the theoretical advantages of being applicable to more patients and could achieve “one valve for the individual patient.” It also potentially offers a more complete and predictable MR reduction, and might be technically less challenging than TMVr. Nevertheless, TMVR comes with a potentially higher burden of complication, and long-term follow-up data are still lacking. TMVr, on the other hand, can only fit a limited number of patients and can be only performed by highly-experienced operators but has a little detrimental physiologic impact on the valve because it leaves most of its anatomical structures untouched. In the near future, it will be interesting to observe the progress of the SUMMIT trial as it compares the outcomes of the Tendyne system with those of the MitraClip system.Thus, it appears that for now, repair and replacement remain complementary rather than competitive.


Mitral atresia with normal aortic root is a rare complex congenital heart defect (CHD) and constitute less than 1% of all CHDs. In this anomaly, the mitral valve is atretic, a patent foramen ovale provides egress of the left atrial blood, either a single ventricle or two ventricles with left ventricular hypoplasia are present, and the aortic valve/root are normal by definition. Clinical, roentgenographic and electrocardiographic features are non-distinctive, but echo-Doppler studies are useful in defining the anatomic and pathophysiologic components of this anomaly with rare need for other imaging studies. Treatment consists of addressing the pathophysiology resulting from defect and associated cardiac anomalies at the time of initial presentation, usually in the early infancy. These children eventually require staged total cavo-pulmonary connection (Fontan) in three stages. Discussion of each of these stages were presented. Complications are observed in-between the stages of Fontan surgery and following completion of Fontan procedure. Attempts to monitor for early detection of these complications and promptly addressing the complications are recommended. Mitral atresia may be seen in subjects with both aortic atresia or a normal aortic root; the first lesion is commonly designated as hypoplastic left heart syndrome (HLHS) which was reviewed elsewhere ,2,3. MitMitral atresia with normal aortic root is an uncommon, complicated CHD and is typically associated with multiple other heart anomalies. The occluded mitral valve may be in the form of an imperforate valve membrane or an absent atrioventricular (AV) connection . In a stThe left atrium (LA) is small in size and may be hypoplastic. The right atrium (RA) is dilated and hypertrophied. Either a patent foramen ovale (PFO) or an atrial septal defect (ASD) is usually present; a PFO in 2/3rds of the subjects and an ASD in the remaining 1/3rd . RestricPulmonary venous blood from the LA goes through the ASD/PFO into the RA and mixes with the systemic venous blood. This produces systemic arterial desaturation in all children with mitral atresia. In patients with restrictive PFO, development of pulmonary venous congestion and edema may be seen. There appears to be a tendency for development of interatrial obstruction as these babies age. From the RA, the blood is conveyed via the tricuspid valve into the RV or single ventricle, as the case may be. This mixture of pulmonary and systemic venous returns is then distributed into the aorta and pulmonary artery dependent on their respective vascular resistances. The magnitude of arterial desaturation is inversely related to the degree of pulmonary stenosis (PS). In neonates with pulmonary atresia, the pulmonary blood flow is supplied through the PDA or rarely via the aortopulmonary collateral blood vessels.The types of clinical manifestations are largely related to the combined effect of the basic defect and associated heart abnormalities. The majority of patients manifest during the neonatal period, typically during the first week of life either with cyanosis or difficulty in breathing. Or, they may have been detected by fetal ultrasound during maternal pregnancy or by pulse oximetry screening after the baby is born.Infants with inter-atrial obstruction exhibit signs of pulmonary venous congestion, namely, tachypnea, retractions, and cyanosis. In an occasional case with an intact atrial septum, the presentation is immediately following birth.Infants who have severe pulmonary stenosis or atresia have diminished pulmonary blood flow (PBF) and their presentation is with cyanosis and dyspnea as the PDA begins to constrict. When the PBF is markedly diminished severe metabolic acidosis occurs.Infants without PS have elevated PBF and as the pulmonary vascular resistance (PVR) falls with aging , volume overload occurs and congestive heart failure (CHF) develops. Tachypnea, tachycardia and cardiomegaly are the usual findings in these babies.On physical examination, the precordial impulses either show a right ventricular heave (in patients with PS or pulmonary atresia) or a hyperdynamic RV impulse (in subjects without PS). The second heart sound is single in patients with severe PS or pulmonary atresia while it may be split in babies without PS. Infants with PS exhibit long ejection systolic murmurs along the left upper sternal border. Such murmurs are absent in babies with pulmonary atresia. Children without PS may have non-specific ejection systolic murmurs of short duration along the left sternal border. Signs of CHF are perceived in the majority of babies without PS. In subjects with severe restriction of PFO, signs of pulmonary edema may be observed instead. Femoral pulses may be decreased in babies with coarctation or interruption of the aorta and as stated above, such aortic obstructions are seen in only infants who do not have PS.There are no characteristic findings indicative of the defect on chest X-ray. However, chest roentgenographic features reflect the pathophysiologic status of PBF resulting from the combined effect of the defect itself and associated abnormalities. Mild cardiomegaly with decreased pulmonary vascular markings is seen in babies with severe PS or pulmonary atresia. Moderate to severe cardiac enlargement along with increased pulmonary vascular markings is seen in infants without PS. In babies with obstruction at PFO, pulmonary edema is seen on chest X-ray. The chest films are thus useful in assessing the status of PBF.ECG demonstrates tall, peaked P waves in lead II and right chest leads suggestive of RA enlargement. Right axis deviation and RV hypertrophy are seen in most patients. On occasion, left axis deviation is seen (12% of the babies). Presence of Q waves in the right chest leads with a qR pattern was observed in most patients in one study . The desIn contradistinction to findings on chest X-rays and ECGs, echo-Doppler studies are very valuable in making a diagnosis and in supplying suitable information for planning an appropriate treatment algorithm. The atretic left AV valve  can easiIt is also imperative to identify if the defect is a part of complete AV septal defect; if such is the case, it is unlikely to have left atrial obstruction because AV septal defects typically have large ostium primum ASDs whereas mitral atresia cases have hypoplastic left atrium and potential to have obstructed inter-atrial defect.The size of the ASD/PFO is appraised by imaging the diameter of the atrial defect by two-dimensional imaging A and by After defining the size of the LA, atretic mitral valve and the atrial septum, one should evaluate if there are two ventricles or if there is only one ventricle, i.e., single ventricle. If there are two ventricles, the nature of ventricular looping (d-loop or l-loop), the size of the VSD, and where the aorta and pulmonary artery arise should be appraised. Then, the great artery relationship should be determined. In both the above groups, the presence of stenosis or atresia or wide-open (non-stenosed) pulmonary valve should be defined. In patients with PS, the magnitude of narrowing is assessed by continuous wave Doppler recording. In patients with pulmonary atresia, patency of the ductus arteriosus should be scrutinized. Suprasternal notch views should be performed and Doppler interrogation should be undertaken to identify aortic coarctation or interrupted aortic arch.Catheterization and angiography are not necessary since the diagnosis and pathophysiology of the lesion complex can be defined by echo studies. Same thing holds true for MRI and CT studies. However, catheterization is an integral part of relief of obstruction in patients with restrictive ASD/PFO and will be reviewed in the section on “Inter-atrial Obstruction”, under “Therapy”.3); and treating respiratory acidosis with suction, intubation, and assisted ventilation as deemed appropriate. If ductal dependent situation is suspected, the intravenous prostaglandin E1 (PGE1) should be started while waiting for confirmation of the diagnosis.The management at the time of presentation, usually in the neonatal period, is similar to that used for other cyanotic CHD patients, as described elsewhere ,17,18 anAs stated in the preceding section, the clinical features are largely dependent upon the status of the PBF (presence of pulmonary outflow tract obstruction and the patency of the ductus), PVR, and the magnitude of restriction at the ASD/PFO level. Consequently, the management should address these problems. Following stabilization of the infant, the treatment is designed to address the pathophysiologic abnormality created by the defect complex, such as inter-atrial obstruction, reduced PBF, elevated PBF with or without CHF, or increased PBF combined with inter-atrial obstruction.In patients with restrictive ASD/PFO, producing pulmonary venous congestion, balloon atrial septostomy ,20,21,22Some infants, though rare, may have a very tight PFO  or even 1 intravenously should be started promptly; we usually begin with a dose of 0.05 to 0.1 mcg/kg/min and once the O2 saturation improves, the dosage is gradually reduced to 0.015 to 0.02 mcg/kg/min. Then, a more permanent way to supply pulmonary flow, usually via a modified Blalock-Taussig (BT) shunt  on  on 37] oThis combination does occur commonly in this defect complex . A fast Because of the complexity of this heart defect, it is imperative to periodically re-examine these infants. The atrial septal communication that is adequate early in the neonatal period may develop restriction with time. The atrial defect may also become restrictive even after septostomy. Consequently, intermittent clinical and echocardiographic assessment of the atrial defect is a must. Eventually, unobstructed left to right shunt across the atrial septum  should bDefinitive intracardiac repair of mitral atresia with normal aortic root is not feasible because there is either a single ventricle is present or when two ventricles are present, the left ventricle is hypoplastic. Consequently, most of these patients are addressed with single-ventricle palliation strategy by Fontan procedure . The conAfter palliation during the neonatal period and following multi-staged Fontan surgery, clinical and echocardiographic follow-up is necessary to detect interstage problems and post-Fontan complications, respectively. The inter-stage mortality rates varied from 5% to 15% ,56,57. TSimilarly, complications were observed during follow-up evaluation of patients who had all three stages of Fontan and these are arrhythmias; Fontan pathways obstruction; residual shunts; thrombo-embolic events, including, cerebro-vascular accidents or transient ischemic attacks; cyanosis; collateral vessels; and systemic venous congestion, including protein-losing enteropathy ,45,60. LMitral atresia with normal aortic root is a rare cardiac defect with hypoplastic LA and has a propensity to develop atrial septal restriction. The clinical presentation is largely dependent upon the associated heart defects. Echo–Doppler studies are useful in making the diagnosis and help guide the type of therapy. Babies with pulmonary atresia or severe pulmonary stenosis should undergo systemic to pulmonary arterial shunt, usually by a modified BT shunt. Early transcatheter or surgical atrial septostomy in patients with interatrial obstruction and placement of pulmonary artery band in patients with unrestricted pulmonary blood flow have become major components of early palliative treatment. As the infants grow, close attention should be paid to evaluate adequacy of atrial defect by serial echo studies. Atrial septostomy or septectomy may be needed later in infancy, if it was not required or not performed in the neonatal period. Then, staged Fontan, consisting of bidirectional Glenn and extra-cardiac conduit with fenestration with subsequent closure of fenestration should be undertaken, similar to those used in other single ventricle defects. Interstage and post-Fontan complications should be identified and promptly treated as appropriate.


However, the rate of unsuccessful or complicated left ventricular (LV) lead placement through coronary sinus is 5–7%, and the rate of “CRT non-response” is approximately 30%. These reasons have pushed physicians and engineers to collaborate to overcome the challenges of LV lead implantation. Thus, various alternatives to BVP have been proposed to improve CRT effectiveness. His bundle pacing (HBP) has been increasingly used by activating the His–Purkinje system but is constrained by challenging implantation, low success rates, high and often unstable thresholds, and low perception. Therefore, the concept of pacing a specialized conduction system distal to the His bundle to bypass the block region was proposed. Multiple clinical studies have demonstrated that left bundle branch area pacing (LBBAP) has comparable electrical resynchronization with HBP but is superior in terms of simpler operation, higher success rates, lower and stable capture thresholds, and higher perception. Despite their well-demonstrated effectiveness, the transvenous lead-related complications remain major limitations. Recently, leadless LV pacing has been developed and demonstrated effective for these challenging patient cohorts. This article focuses on the current state and latest progress in HBP, LBBAP, and leadless LV pacing as alternatives for failed or non-responsive conventional CRT as well as their limits and prospects.Cardiac resynchronization therapy (CRT)  Heart failure (HF) is a cardiovascular epidemic, with high morbidity and mortality and poor quality of life, especially in patients with HF and reduced ejection fraction (HFrEF) . Accordivia biventricular pacing (BVP) is non-physiological with the fusion of the epicardial LV wavefront and the endocardial wavefront from the right ventricular (RV) apex, leaving some degree of dyssynchrony. However, conventional CRT is precluded in a proportion of eligible candidates due to anatomic or technical constraints such as occluded venous access, an inappropriate coronary sinus (CS) anatomy, or a high threshold in regions of fibrosis (Cardiac resynchronization therapy (CRT) is a well-established modality that offers remarkable clinical benefits for patients with medically refractory HF . It has fibrosis , 6. In afibrosis , 8.For these reasons, physicians and engineers have been working together to overcome the challenges of LV lead implantation but have also shown increased interest in developing physiological pacing techniques to improve CRT effectiveness. His bundle pacing (HBP) has increased in use by activating the His bundle but is restricted by implant challenges, low success rates, and a high and often unstable pacing threshold –12. TherFrom CS epicardial pacing to leadless endocardial stimulation, various LV pacing alternatives reportedly improve CRT effectiveness . This reThe efficacy of CRT in patients with HF has been demonstrated in numerous trials. The Multisite Stimulation in Cardiomyopathies (MUSTIC) study was the first to assess the clinical outcomes of CRT in 67 patients with severe HF . FinallyHowever, approximately 30% of candidates respond unfavorably to CRT or even worsen , 24, 28.Despite great advances in multipolar LV electrodes and MPP, non-response due to suboptimal lead position remains a critical problem. To overcome the challenges of the CS approach, physicians have strived for alternative solutions, such as surgical LV epicardial lead placement, LV endocardial pacing, or HBP to most recently leadless LV pacing. However, surgical LV epicardial lead placement does not always deliver additional improvement in the LVEF versus conventional CRT, and it is inherently more invasive and challenging in patients with a previous history of heart surgery . MoreoveHis bundle pacing activates the His–Purkinje system (HPS) and restores physiological activation of the ventricles. HBP is defined as the presence or absence of His–Purkinje conduction disease (HPCD) according to four basic criteria : (1) relS-HBP: (1) S-QRS = H-QRS with an isoelectric interval. In patients with HPCD, S-QRS ≤ H-QRS with BBB correction and S-QRS ≤ or > H-QRS without BBB correction; (2) discrete local ventricular EGM in HBP leads with the stimulus to the local ventricle (S-V) = His to the local ventricle (H-V); (3) paced QRS = native QRS. In patients with HPCD, paced QRS < native QRS with BBB correction; paced QRS = native QRS without BBB correction; and 4) a single capture threshold (His capture) was observed. In patients with HPCD, two distinct His capture thresholds (with and without BBB correction) may be observed.NS-HBP: (1) S-QRS < H-QRS  with or without an isoelectric interval. In patients with HPCD, S-QRSend < H-QRSend with BBB correction; (2) direct capture of local ventricular EGM in HBP lead by a stimulus artifact; (3) paced QRS > native QRS. In patients with HPCD, paced QRS ≤ native QRS with BBB correction and paced QRS > native QRS without BBB correction; (4) usually, two distinct capture thresholds (His bundle capture and RV capture) are observed. In patients with HPCD, three distinct capture thresholds (with or without correction for BBB and RV capture) may be observed.Theoretically, S-HBP may be advantageous over NS-HBP in terms of clinical outcomes. Instead, few hemodynamic and clinical differences were observed between these two forms of capture, probably owing to the rapid conduction of the HPS relative to the ventricular myocardial conduction , 38.P < 0.01). Subsequently, a prospective study assessed the HBP outcomes of patients with HF and LBBB (P < 0.001) and decreased LV end-systolic volume . Similarly, the outcomes of HBP were explored in 106 CRT-eligible or -failed patients  and BVP (n = 20) groups. Compared with BVP, HBP achieved a narrower mean QRSd, regardless of TR or PP analyses . Furthermore, a non-significant trend toward a higher echocardiographic response was observed. There were also no significant intergroup differences in CV hospitalization and mortality. Another randomized trial of HBP versus BVP (His-Alternative) was performed in patients with symptomatic HF and LBBB . LVEF improved significantly  after a mean follow-up of 14 ± 10 months. Similar results with a narrower QRSd, increased LVEF, and improved NYHA were reported in other studies  –48. HOT- studies –48. In a studies . These dThese trials indicated that HBP generates a narrow paced QRS and improves clinical outcomes, which seem potential for CRT. However, HBP has some limitations. First, the major limit is the inability to map the precise location of the His bundle, which is approximately 1–2 mm in diameter . The meaIn 2017, Huang et al.  first inP < 0.001), increased LVEF , decreased LVESV , and improved NYHA class . A subsequent long-term trial with a larger sample size (N = 632) assessed LBBP feasibility and safety (N = 88). No serious complications occurred during the procedure or follow-up. A similar result was reported by another large study (N = 325)   in whichN = 325) . NonetheN = 325) . These dSeveral clinical trials have explored whether LBBAP is equal or superior to conventional CRT , 60, 61.P < 0.0001), increased LVEF , and decreased LVEDD  and N-terminal pro-hormone B-type natriuretic peptide . These results indicated that LOT-CRT provided greater electrical resynchronization and clinical benefits than BVP or LBBAP alone, but further research is needed to confirm this finding.To our knowledge, proximal LBB pacing is inherently limited by its inability to restore physiological activation of the lateral wall of the LV in patients with a distal conduction delay . Thus, iMultiple studies demonstrated the technical advantages and clinical potential of LBBAP. It has comparable LV synchrony with HBP but a high success rate of 81.1–97% , 56, 65 Despite the well-demonstrated effects of HBP and LBBAP, transvenous leads and typical pocket infections remain a non-negligible limitation , 19. LeaN = 28) showed an improved clinical composite score and 66% (N = 21) gained a ≥ 5% absolute increase in the LVEF at 6 months. Of note, serious procedure/device-related complications were observed in 8.6% of patients (N = 3) within 24 h and 22.9% of patients (N = 8) between 24 h and 1 month. A real-world experience with the WiSE-CRT system was shared in an international trial  (N = 4), 18.8% (N = 17), and 6.7% (N = 6), respectively. A total of five deaths (5.6%) occurred within 6 months. HF symptoms improved in 70% of patients. Subsequently, the Stimulation of the Left Ventricular Endocardium for Cardiac Resynchronization Therapy (SOLVE-CRT) trial assessed the short-term outcomes of the WiSE-CRT system in cases without prior implant experience (N = 1), embolization of an unanchored LV electrode (N = 1), and skin infection (N = 1). These results indicated that biventricular endo-pacing from the WiSE-CRT system was effective in cases of failed conventional CRT or non-response, but complications must be noted.In 2014, the Wireless Stimulation Endocardially for CRT (WiSE-CRT) study . The pro2610673)  in whichperience . WiSE-CRP = 0.012), and it was maintained at the 6-month follow-up. Only a significant improvement in the LVEF was achieved after WiSE-CRT implantation  without evidence of LV reverse remodeling and improved NYHA class. A current meta-analysis of leadless LV pacing for CRT (The aforementioned trials of leadless LV endocardial pacing were combined with a traditional pacemaker or ICD instead of a totally leadless CRT. The successful coexistence of Micra and the WISE-CRT system was first reported in 2019 . Also, t for CRT  includedTaken together, these data support the efficacy of leadless LV pacing as an alternative in patients in whom CRT is impossible or ineffective. It significantly reduces diaphragm stimulation, avoids mitral regurgitation, and can be performed at multiple physiological pacing positions. In addition, the receiver electrode was completely endothelialized for approximately 4 weeks; therefore, long-term anticoagulation was not required . HoweverIn summary, HBP, LBBAP, and leadless LV pacing have been demonstrated as potential alternatives for optimal CRT when conventional CRT fails. Each technique has its advantages and disadvantages . HBP andJH conducted the reference analysis and wrote the manuscript. QK contributed to the reference collection and manuscript revision. QC contributed to the topic conception, manuscript revision, and decided to submit for publication. All authors contributed to the article and approved the submitted version.


Heart failure with preserved ejection fraction is responsible for half of all heart failure and confers substantial morbidity and mortality, and yet to date, there have been no effective pharmacologic interventions. Although the pathophysiology is complex, the primary aetiology of exercise intolerance is due to an elevated left atrial pressure, particularly with exercise. In this context, device-based therapy has become a focus. Several companies have developed techniques to percutaneously create an iatrogenic left to right shunt at the atrial level, thereby reducing left atrial pressure and reducing transmitted pressures to the pulmonary circulation and reducing pulmonary congestion. In this review, we explore the pathophysiology, evidence base, benefits, and considerations of these devices and their place in the therapeutic landscape of heart failure with preserved ejection fraction. Heart failure with preserved ejection fraction (HFpEF) is now the most common cause of heart failure within the USA , in partThe dominant clinical manifestation of HFpEF is exertional dyspnoea, although fatigue, peripheral oedema, and clinical right heart failure may also co-exist. The pathophysiology of HFpEF is complex, diverse, and frequently argued ; the comPulmonary congestion, responsible for the majority of HF (heart failure) admissions, is primarily due to elevated left atrial pressure. The rapidity of the rise, and pre-existing lymphatic accommodations, leads to the variability in the relationship between left atrial pressure and the consequent development of pulmonary oedema. Prolonged elevations in left atrial pressure precede the onset of acute decompensated heart failure . ElevateSeveral studies have demonstrated the correlation of elevated left atrial pressure with exercise limitation. The 6-min walk test (6MWT) is a submaximal measure of exercise capacity frequently utilised in heart failure trials. In a study of 64 HFpEF patients  characteTo confirm the diagnosis of HFpEF, diagnostic algorithms and risk scores have been developed largely focussed on the demonstration of evidence of diastolic dysfunction and/or cardiac remodelling , 14, In Since the early 1970s, left atrial pressure has been routinely assessed via a catheter measurement of the PCWP. The current gold standard test for the diagnosis of HFpEF is exercise right heart catheterisation, whereby pulmonary pressures are measured at rest and with exercise, typically via cycle ergometry in the supine or upright position. The best surrogate for a direct left atrial pressure measurement is via measurement of the PCWP with a balloon tipped catheter; values ≥ 15 mmHg at rest or ≥ 25 mmHg with exercise are diagnostic of HFpEF .Similar to HFpEF, patients with mitral stenosis also predominantly derive symptoms from an elevated left atrial pressure. In 1916, Réné Lutembacher described the combination of mitral stenosis (MS) and a congenital atrial septal defect , a combiThese designs were then engineered to a percutaneous 8 mm nitinol interatrial shunt device . Several key design differences are to be noted; the device forms an hourglass shape across the septum, with a PTFE skirt over a nitinol frame, with the funnel shape designed to improve flow across a smaller central lumen (5.1 mm).The RELIEVE-HF trial  is a prospective, multicenter, randomised trial aiming to recruit 500 HFrEF and HFpEF patients, with a primary safety endpoint of major cardiovascular and neurological events, and a similar primary efficacy endpoint to the Corvia trial with a hierarchical composite of death, transplantation, LVAD implantation, recurrent HF hospitalisation, and change in KCCQ overall score. Importantly, the trial includes all patients with HF across the spectrum of ejection fraction. Patients with severe pulmonary hypertension (PASP > 70 mmHg) and right ventricular dysfunction will be excluded. The roll-in cohort have data reported  for 92 pOne of the key issues with both above devices is the relatively large outer diameter at 19 and 14 mm respectively, potentially limiting transseptal access for future percutaneous procedures involving left atrial access. Consequently, two systems have been created specifically to generate a shunt without leaving a device. The alleviant system excises tissue using RF energy to create a 7-mm shunt. Thirty patients have been treated thus far (83% HFpEF), with observational data demonstrating improvement in KCCQ of 24 points at 6 months, and a reduction in peak exercise PCWP of 8 mmHg.The intershunt device is a percutaneous device designed to excise a 6-mm circular section (“punch”) of tissue across the atrial septum, without leaving a permanent device in situ. This theoretically eliminates the risk of device embolisation and thrombus formation; early studies have demonstrated device patency in six patients trialled thus far .The NoYA adjustable shunting system uses a radioablation catheter with a minimum size of 4 mm; however, the waist can be adjusted to be as large as 10 mm, adapted to the individual patient. The first-in-man study has enrolled 10 patients, with increases in 6-min walk distance and improvements in functional class. A larger trial of 150 patients is currently recruiting.The Atrial Flow Regulator , 27 (OccDespite the safety profile seen thus far within the realms of the clinical trials, it is important to consider the potential for complications with these devices. All transseptal procedures carry a small but significant risk of cardiac injury, even with echocardiographic guidance. Secondly, there is a theoretical risk of right heart failure as a consequence of the shunt − early follow-up of the IASD demonstrated increased right-sided flow; however, there was no evidence of worsening RV function on follow-up out to 12 months. Atrial fibrillation, present in 30–50% of patients with HFpEF, significantly impairs exercise capacity ; interveInteratrial septal devices offer a new paradigm of treatment for patients with HFpEF by targeting the end physiologic manifestation of left atrial pressure, obviating some of the complexity around the pathophysiologic pathways leading to its development. Early pilot and randomised studies have demonstrated both safety and efficacy, with the pivotal trial of the IASD device now completed enrolment and in the follow up phase.


All patients had a positive T1-criterion, and 27 (96.4%) had a positive T2-criterion. A positive T2-criterion or T2-mapping > 50 ms could discriminate between patients with genetic and inflammatory myopathies with a sensitivity of 96.4% and a specificity of 91.3% (AUC = 0.9557). Conclusions. The vast majority of symptomatic patients with inflammatory myopathies and normal echocardiography show evidence of acute myocardial inflammation. In contrast, acute inflammation is rare in patients with genetic myopathies, who show evidence of chronic low-grade inflammation.Introduction. Myopathies are heterogeneous neuromuscular diseases of genetic and/or inflammatory etiology that affect both cardiac and skeletal muscle. We investigated the prevalence of cardiac inflammation in patients with myopathies, cardiovascular symptoms, and normal echocardiography using cardiovascular magnetic resonance (CMR). Methods. We prospectively evaluated 51 patients with various genetic (n = 23) and inflammatory (n = 28) myopathies  years, 22% girls; 61 (55–65) years, 46% women, respectively) and compared their CMR findings to corresponding age- and sex-matched controls  and to each other. Results. Patients with genetic myopathy had similar biventricular morphology and function to healthy controls but showed higher late gadolinium enhancement (LGE), native T1 mapping, extracellular volume fraction (ECV), and T2 mapping values. Collectively, 22 (95.7%) patients with genetic myopathy had a positive T1-criterion and 3 (13.0%) had a positive T2-criterion according to the updated Lake Louise criteria. Compared with healthy controls, patients with inflammatory myopathy showed preserved left ventricular (LV) function and reduced LV mass, while all CMR-derived tissue characterization indices were significantly higher ( The myopathies are a heterogeneous group of neuromuscular diseases, with the common disease characteristic being muscular weakness due to disease processes at the level of the muscle fiber . MyopathAlthough skeletal muscles are most often affected, myopathies may also involve cardiac muscle, and this may occur prior to, simultaneously with, or after the onset of skeletal muscle disease ,6. NotabCurrently, the primary diagnostic tools capable of evaluating the heart in this context are echocardiography and cardiovascular magnetic resonance (CMR). Echocardiography is widely available with widespread expertise among cardiologists, can be performed at the bedside, and is cost-effective. However, it is operator-dependent, and its efficacy can be limited by poor acoustic windows. CMR, on the other hand, is the diagnostic gold standard for the evaluation of ventricular/atrial volumes, wall motion and systolic function of both ventricles, importantly without the need for ionizing radiation. Due to its unique ability to perform tissue characterization, it offers incremental diagnostic/prognostic information in heart failure with preserved (HFpEF) or reduced ejection fraction (HFrEF) ,10,11. S(1)To examine if CMR can identify inflammatory or fibrotic loci in patients with myopathies and atypical cardiac symptoms with otherwise normal routine clinical and echocardiographic evaluation.(2)To assess if CMR findings could provide insights regarding the origin of myocardial abnormalities in patients with myopathies.(3)To compare the tissue characteristics of the myocardium in patients with genetic and inflammatory myopathies.Although CMR has been used previously to investigate myocardial inflammation both in patients with inflammatory myopathies  and geneA total of 51 patients diagnosed with a myopathy (23 with various genetic myopathies and 28 with various inflammatory myopathies) that were referred for cardiology evaluation due to atypical cardiac symptoms  and normal routine clinical and echocardiographic evaluation were prospectively evaluated using CMR. The CMR findings of each group of patients were compared with a corresponding age- and sex-matched healthy control group . The study protocol was approved by the Olympic Diagnostic/Research Center ethics committee , and all participants provided written informed consent before inclusion in the study.All individuals included in the study underwent a CMR evaluation, including biventricular function evaluation and T2 and T1 imaging assessment for the evaluation of myocardial inflammation and fibrosis using a 3.0T system .The CMR examination included standard functional imaging using a high spatial and temporal resolution and breath-held balanced steady-state precession (bSSFP) cine sequence ,16 with Black-blood short tau T2W images (STIR-T2) for edema detection were also acquired. For T2 mapping, data were acquired in basal, mid-ventricular, and apical short-axis planes using a T2-prepared single-shot SSFP technique, as was previously described .T1-weighted spin-echo early gadolinium-enhanced (EGE) and phase-sensitive inversion recovery late gadolinium-enhanced (LGE) images were acquired after intravenous injection of gadobenate dimeglumine contrast medium , as described previously .Myocardial T1 mapping measurements were acquired using a modified Look-Locker inversion recovery (MOLLI) sequence with motion correction (MOCO)  in basalTwo experienced clinicians  with >20 years of experience evaluated the images using the Syngo Siemens protocol. The following functional parameters were calculated: LV-RV end-systolic volume  and end-diastolic volume , ejection fraction , and LV mass (LVM). A normal LVEF was defined as LVEF ≥ 55% . AdditioT1-mapping was performed using a 5-3-3 modified Look-Locker inversion recovery (MOLLI) technique with a scheme on three representative short-axis positions  before and 15 min after contrast-media administration. T2-mapping was performed on the same three left ventricular (LV) short axes using a black-blood-prepared, navigator-gated, free-breathing hybrid gradient (echo planar imaging) and spin-echo multi-echo sequence.Global myocardial inflammation was assessed in STIR-T2 images by calculating the T2 signal intensity ratio as the signal intensity of myocardium divided by the signal intensity of the skeletal muscle (T2 ratio) . Global Color-coded T1 and T2 maps were generated based on inline-generated, motion-corrected raw images using built-in software in three matching short-axis slices. Motion-corrected T1 maps were examined for quality in raw T1 images, T1 maps and T2 maps. Endocardial and epicardial contours were manually drawn by two experienced observers. Global T1, ECV, and T2 values were calculated. Before the CMR examination, the hematocrit was determined in all subjects, allowing the calculation of ECV in conjunction with native and post-contrast T1-mapping measurements using a previously described equation . T2 resuTo evaluate the presence of myocardial inflammation, we made use of the updated Lake Louise criteria (LLc), which are comprised of a T1-based criterion and a T2-based criterion . A positp ≤ 0.05. Boxplots with individual data points were used for visualizing different CMR indices stratified by group. Where mentioned, sensitivity and specificity were calculated based on the true/false positive and true/false negative values from the corresponding contingency table. Receiver operating characteristic curves were plotted based on univariable logistic regression models.Data were analyzed using R-Studio (R v.4.1.2). Body surface area (BSA) was calculated using the Du Bois method, and ventricular volumes and LVM were indexed by dividing the values by the calculated BSA. The normality of continuous variables was examined visually using histograms and Q-Q plots, and all were found to be not normally distributed. Thus, comparisons between groups were performed with Mann–Whitney tests for continuous variables and with Chi-square tests for binary/categorical variables. Continuous variables are presented as median (interquartile range), and binary/categorical variables are presented as numbers (percentage). Statistical significance was considered for p < 0.001), native T1 mapping  vs. 1250.0 , p < 0.001), and ECV values  vs. 28.0 , p < 0.001). Similarly, compared to controls, patients with genetic myopathy had increased T2 mapping  vs. 46.00 , p < 0.001) but not T2 ratio (p = 0.646). Nevertheless, when investigating the number of participants with abnormal CMR values, only LGE, native T1 mapping and ECV showed significantly higher percentages in the genetic myopathy group (19 (82.6%), 10 (43.5%), and 11 (47.8), respectively, p ≤ 0.002 for all; matched controls had no occurrences of abnormal CMR values). Only 2 (8.7%) patients showed abnormal T2 ratio/T2 mapping values (p = 0.51). No controls met any of the updated LLc, while 22 (95.7%) and 3 (13.0%) of patients with genetic myopathies met either the T1-based or T2-based criterion, respectively . By extension, 3 (13.0%) patients also met both criteria, suggesting a high probability of myocardial inflammation.The majority of patients with genetic myopathies were diagnosed either with Duchenne muscular dystrophy (8 (34.8%)) or Becker muscular dystrophy (7 (30.4%)). Patients with genetic myopathies did not have significant differences in biventricular morphology, function, or LVM . Comparep < 0.001 and 68.0  vs. 53.2 , p = 0.007, respectively). In contrast, patients with inflammatory myopathy had a significantly lower indexed LVM compared with their matched controls  vs. 57.5 , p = 0.001). Compared with their matched controls, patients with inflammatory myopathy showed significantly elevated values in all T1-based indices  and T2-based indices  . None of the controls met any of the updated LLc, while all 28 patients with inflammatory myopathy met the T1-based criterion, and 27 (96.4%) met the T2-based criterion. Collectively, 27 (96.4) patients met both criteria, suggesting a high probability of myocardial inflammation.The majority of patients with inflammatory myopathies were diagnosed either with polymyositis (10 (35.7%)) or dermatomyositis (10 (35.7%)). Similar to the previous comparison, patients with inflammatory myopathies did not show significant differences in age or sex compared with their matched control group . Patientp < 0.001). Regarding T1-based indices, although there were no significant differences in LGE and ECV between the groups, patients with inflammatory myopathies had significantly higher EGE and native T1 values . Both groups also showed considerable differences in T2-based indices, with patients with inflammatory myopathies having much higher values of both T2 ratio and T2 mapping  vs. 1.50 , p < 0.001 and 58.0 ms  vs. 46.0 ms , p < 0.001, respectively). When cut-off points for normal values were examined, the proportion of patients with inflammatory myopathies that had abnormal T1- or T2-based indices was significantly higher compared with patients with genetic myopathies, with the exception of LGE (p = 0.379). Although the large majority of patients in either group met the T1-based LLc (p = 0.921), significantly more patients with inflammatory myopathies met the T2-based LLc (27 (96.4%) vs. 3 (13.0%), p < 0.001).The comparison of patients with genetic and inflammatory myopathies is presented in Comparisons of CMR indices between all of the examined groups are presented visually in In this study, we compared the CMR findings of patients with genetic and inflammatory myopathies referred for atypical cardiac symptoms to those of age- and sex-matched controls. Both myopathy groups showed largely preserved biventricular function and morphology. However, they both exhibited abnormalities in myocardial tissue characterization, with the vast majority of patients exhibiting evidence of diffuse or replacement myocardial fibrosis. Interestingly, we show that the distinguishing feature between patients with genetic and inflammatory myopathies is the presence of myocardial oedema in the latter, which could differentiate between the two groups with excellent sensitivity and specificity.To our knowledge, this is the first study in the literature that compared the CMR findings of patients with genetic and inflammatory myopathies. Our findings show that expansion of the cardiac extracellular space, consistent with myocardial fibrosis, is a shared feature of both genetic and inflammatory myopathies. However, the fact that T2-based indices can readily discriminate between the two groups implies different etiologies leading to extracellular space expansion. Namely, increases in capillary leak leading to interstitial oedema would lead to the increases in T2-based indices observed in the inflammatory myopathy group. This corresponds with endothelial activation and subsequent capillary leak, consistent with severe acute inflammation. In contrast, although patients with genetic myopathies had, on average, significantly higher T2 mapping values compared with their matched controls, elevations comparable to those seen in patients with inflammatory myopathies were not observed. Collectively, this implies that slow, low-grade inflammation is responsible for the expansion of the cardiac extracellular space in patients with genetic myopathies. This is further supported by the beneficial effect of immunomodulatory treatment with corticosteroids in both disease groups ,26.The findings of this investigation are in agreement with those of previous studies. In patients with inflammatory myopathies, the main CMR pattern found is that of myocardial inflammation, with increased values of native T1 and T2 mapping and preserved LVEF . PreviouIn patients with Duchenne muscular dystrophy, LGE-spared regions showed significantly different native T1 and ECV values compared to controls . The inc(1)The presence of abnormalities in myocardial tissue characterization indices, despite the relatively preserved biventricular structure and function in patients with both genetic and inflammatory myopathies, supports the notion that disease onset may be evident even in the absence of decrements in LVEF.(2)Whether the early initiation of renin-angiotensin system inhibitors and/or β-adrenoreceptor antagonists could modulate myocardial inflammation and prevent evolution to heart failure in these patients should be investigated.(3)Gene therapy for genetic myopathies can potentially exacerbate myocardial inflammation (24). CMR could function as a screening tool before the initiation of gene therapy in these cases, but additional research is required to demonstrate where this would lead to added benefits.Our findings have important implications:Firstly, the relatively small patient population and the single-center nature of our study should be acknowledged as limitations of this investigation. In addition, short- or long-term follow-up was not available, thus precluding the determination of the prognostic implications of CMR findings in the examined patients. Although T2 mapping could discriminate between patients with genetic and inflammatory myopathies with great accuracy, it should be acknowledged that in clinical practice, such a distinction would also be possible based on the clinical picture. Lastly, the longitudinal evaluation of myocardial inflammation and its response to targeted therapeutic interventions using CMR was not available.Myocardial inflammation is a common pathway in asymptomatic patients with either genetic or inflammatory myopathies, and therefore, they should be evaluated irrespective of cause and symptoms using CMR. However, myocardial inflammation, as assessed by CMR, often has characteristics of an acute phenomenon in inflammatory myopathies while presenting with a low-grade inflammatory pattern in genetic myopathies.