Due to numerous links between trimethylamine-N-oxide (TMAO) and various disorders and diseases, this topic is very popular and is often taken up by researchers. TMAO is a low molecular weight compound that belongs to the class of amine oxides. It is formed by the process of oxidation of trimethylamine (TMA) by the hepatic flavin monooxygenases (FMO1 and FMO3). TMAO is mainly formed from nutritional substrates from the metabolism of phosphatidylcholine/choline, carnitine, betaine, dimethylglycine, and ergothioneine by intestinal microflora in the colon. Its level is determined by many factors, such as age, gender, diet, intestinal microflora composition, kidney function, and also liver flavin monooxygenase activity. Many studies report a positive relationship between the level of TMAO concentration and the development of various diseases, such as cardiovascular diseases and cardiorenal disorders, including atherosclerosis, hypertension, ischemic stroke, atrial fibrillation, heart failure, acute myocardial infarction, and chronic kidney disease, and also diabetes mellitus, metabolic syndrome, cancers , as well as neurological disorders. In this review, we have summarized the current knowledge on the effects of TMAO on human health, the relationship between TMAO and intestinal microbiota, the role of TMAO in different diseases, and current analytical techniques used in TMAO determination in body fluids.  TMAO is an oxidized form of trimethylamine (TMA)  is a dietary component that belongs to the class of amine oxides with the formula . One ofal., 2020). Accordal., 2020; Sarma aal., 2020). The aim of this review was to summarize the current state of knowledge about TMAO, biological properties, metabolic pathways, and essential metabolism nutrients which act as precursors of TMAO. The importance of TMAO metabolism and its role in human health are also highlighted. We provided and discussed the potential relationships between TMAO and intestinal microbiota. Attention was also paid to the potential contribution of intestinal microbiota-derived production of TMAO from the metabolism of nutrients, which has been associated with an increased risk of major adverse disorders in humans. Then we presented the potential role of TMAO in the etiology of various diseases, and the possible mechanisms that could explain their association. Finally, we analyzed the current analytical techniques which are used in TMAO determination in biological fluids.TMA is formed from the dietary compounds present in the diet, which is then immediately absorbed and converted into TMA by various enzymes , and fish  is oxidized to TMAO, which is transported to the tissues for accumulation as an osmolyte or, more frequently, cleared by kidneys , which The intestinal microbiota is shaped from birth and plays a key role in the immune system. One of the main functions of the intestinal microbiota is to form systemic immunity and maintain immune homeostasis. Factors affecting the intestinal microbiota are diet, type of labor, antibiotic use during infancy, and age, because the composition of the intestinal microbiota changes with age.Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria and Verrucomicrobia are the dominant phyla, with Firmicutes and Bacteroidetes accounting for over 90 % of the gut bacteria . An incues, 2020). Bacterher, 2018).Firmicutes to Bacteroidetes demonstrating a greater response to the dietary precursor of TMAO which suggests that the production of TMAO may be a function of individual differences in the intestinal microbiota . Studieher, 2018). The prher, 2018).Understanding the role of human intestinal microbiota has led to the identification of a large number of metabolites which are produced in the gut. These metabolites may play a role in human health and possible diseases. One of these is TMAO, whose elevated concentration increases the risk of developing renal failure, diabetes mellitus, heart failure, atherosclerosis, hypertension, metabolic syndrome, dyslipidemia which may lead to serious cardiovascular events  suggestAcinetobacter can convert lecithin and carnitine into TMAO. Analysis of fecal specimens suggested that participants with enriched bacteria of the genus Prevotella, as a result of a high-fat diet, were characterized by higher levels of TMAO compared to participants with the enrichment of the genus Bacteroides .Akkermansia mucinophilia in colon biopsies and concentration levels of TMAO . As it al., 2019).Firmicutes and Proteobacteria, which are capable of producing TMA. The strains of these bacteria show an increased proportion in patients with HF. This indicates that changes in intestinal microbiota may affect TMAO levels by regulating TMA synthesis in the intestines . HF causes changes in the composition of the intestinal microflora, which may affect the circulating levels of TMAO in human body. Researchers suggested intestinal strains, such as al., 2021).As we know, many factors influence the level of TMAO concentration in the human body. Such factors include gender, diet, gut microbiome composition, and kidney function. Unfortunately, there is no clear answer if gender can have an influence on TMAO concentrations. Some studies indicate a relationship between gender and metabolite concentration in a healthy study group . HigherGriffin et al. (2019) examineIn another study, Van Hecke and colleagues (2016) examineMoreover, the high-salt diet is indicated as a cardiovascular risk factor. High salt intake increases the level of TMAO concentration in plasma, which is associated with the reduction of urinary TMAO excretion . MoreovSome studies indicate that fish intake would contribute to the increased production of TMAO. In the research conducted by Lenz et al. (2004) the proOne of the metabolites produced by the intestinal microflora is TMAO. Researchers pay a lot of attention to the intestinal microbiome because of its possible role as a promoter of chronic diseases, cancers and even neurological disorders . IntestUntil now, high concentrations of TMAO have been combined with the development of atherosclerosis, which is one of the major causes of CVD. Increased concentrations of TMAO and also TMAO precursor in plasma have been observed in participants at risk of CVD . The liResearch conducted by Wilson et al.  indicIn research conducted by He et al. (2020) 451 peoSchneider et al. (2020) analyzeTMAO is linked to impaired renal function. In patients with compromised renal function absorbed from the intestine, TMA and TMAO may accumulate. Elevated levels of TMAO in patients with an impaired renal function may result from higher production or reduced clearance. Elevated levels of TMAO may be associated with type 2 diabetes (T2D) or atherosclerosis mediated renal dysfunction. This reduces the excretion of TMAO, thus increasing the levels of plasma TMAO . It meaResearchers observed that levels of TMAO increased along with the body mass index, visceral adiposity index and fatty liver index in metabolic syndrome. The levels of TMAO concentration in the serum with values ≥ 8. 74 µM may be considered predictive of metabolic syndrome .A correlation between increased TMAO levels and neurological disorders has been also hypothesized, but the role of TMAO in the central nervous system (CNS) has not been fully explored. Due to the importance of TMAO as a mediator of inflammatory processes, the possible participation of this compound in the etiology of neurological disorders is presumed. In the literature, there are very few studies demonstrating the relationship between brain disease and TMAO levels. The research conducted by Liu and Huang (2015) suggest1H-NMR). Table 1Various methods have been established to demonstrate TMAO and its related metabolites in body fluids . The analytical methods often used are chromatographic techniques, including liquid chromatography-mass spectrometry (LC-MS), high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), ultra-performance liquid chromatography-mass spectrometry (UPLC-MS), liquid chromatography/differential ion mobility spectrometry tandem mass spectrometry (HPLC/DMS-MS/MS), stable-isotope dilution-hydrophilic interaction liquid chromatography-time of flight mass spectrometry with multiple reaction monitoring (LC-ToF-MRM), gas chromatography-mass spectrometry (GC-MS), and also spectroscopic techniques such as proton nuclear magnetic resonance spectroscopy (In conclusion, experimental findings constantly suggest that there is a potential link between the metabolites produced by the gut flora and the risk factors for diseases. Production of TMA and TMAO relies on intestinal microbiota, and also on host genetics, co-metabolism, and diet. To broaden our knowledge on nutrient metabolism and the ways diet may influence health, the research on the relationship between TMAO and intestinal microflora should be continued. If it was possible to fully exploit the potential of TMAO, it could become a new therapeutic target for improving the outcomes of patients. A better understanding of the specific role of bacteria in regulating the levels of TMAO concentration and their mechanism and reaction to dietary modulation, in combination with the factors determining the TMAO concentration is essential and necessary before the potential benefits of TMAO manipulation may be realized under the selected disease conditions.The authors declare no conflict of interest.


OLD-CMR has successfully been used for the diagnosis of perfusion deficits caused by coronary stenosis. New BOLD-CMR sequences show improved image quality for assessing myocardial oxygenation with excellent spatial resolution, offering a distinct advantage over other image modalities. We hypothesized that these new BOLD-CMR techniques can detect differences in oxygenation throughout the myocardial wall.To investigate the epicardial and endocardial oxygenation with a new BOLD-CMR sequence in healthy volunteers compared to patients with suspected coronary artery disease (CAD).R/TE 5.8/2.9 ms; flip angle 90°; typical breath-hold duration 14 s. Images were analyzed using clinically validated software . After automatic definition of the subendocardial 50% and the subepicardial 50% of the wall thickness, the BOLD signal intensity (SI) for each was analyzed and the relative change from baseline during adenosine infusion was calculated. Late enhancement was performed to ensure that patients did not have an infarct in the selected slice for analysis.11 healthy volunteers (mean age 29 ± 4 years) and 11 patients with suspected CAD (mean age 59 ± 8 years) who all had abnormal perfusion results on SPECT were recruited for scanning. Using a clinical 1.5 T MRI system , SSFP BOLD-CMR was performed on a mid left ventricular short axis slice at baseline and during adenosine infusion (140 micro-g/kg). Typical scan parameters were: Field-of view 193 × 280 mm; matrix size 106 × 192; slice thickness 10 mm; TImage quality was excellent in 8 patients and all healthy volunteers. Three patients were excluded due to motion artifacts on the stress portion of the exam. Results are illustrated in Figure A state-of-the-art BOLD-sensitive MRI sequence, with its improved image quality and excellent spatial resolution, can detect differences in epicardial and endocardial myocardial oxygenation and are feasible for the clinical setting.


To compare the amount of remaining cement excess after cementation of implant-supported zirconia crowns with zinc phosphate or calcium aluminate glass ionomer cement.n = 10) and zinc phosphate cement (n = 10). After removal of cement excess, remaining cement excess were measured with pixel area calculation method and by weighing. Differences in amount of remaining cement excess were analyzed using Independent Samples t-Test. Level of significance was set at p = 0.05.Twenty zirconia crowns were cemented on dental implant abutments using a calcium aluminate glass ionomer cement (p = 0.002) and amount in grams (p = 0.005).Zinc phosphate cement had a significantly greater amount of remaining cement excess than calcium aluminate glass ionomer cement in terms of total number of pixels (The study suggests that the amount of remaining cement excess can be affected by the type of cement. Calcium aluminate glass ionomer cement may be a more suitable choice for cement-retained dental implant restorations, and possibly reduce the risk of complications related to cement excess such as peri-implant disease. Further studies are needed to verify the results from the present study. Moreover, Sailer et al.10 observed bone loss over 2 mm more frequently around cement-retained dental implant restorations in comparison with screw-retained dental implant restorations. Wilson et al.7 evaluated dental implants with signs of peri-implant disease. Remaining cement excess was associated with 81% of the affected implants.7 In addition, signs of inflammation disappeared when cement excess were eliminated.7 These findings suggest a potential significant detrimental effect of cement excess on the peri-implant tissues.7 Other groups such as Korsch et al.11 and Linkevicius et al.8 have found similar results.Dental implants have become a widely used treatment for the rehabilitation of partially and completely edentulous patients.13 Other factors such as undercuts, low cement viscosity5 and wider implant diameter14 can also result in a greater amount of remaining cement excess.5 It is possible that the type of cement may influence the process of cement removal. A water-based hybrid glass ionomer cement, composed of calcium aluminate and glass ionomer (CAGIC),15 is said to have a rubber-like consistency during setting. This property may allow for easier removal than conventional cements such as zinc phosphate (ZNPH). CAGIC is intended for cementation of fixed dental restorations and fulfils the requirements of the ISO standard (9917:1[2003]).16 The short setting time and strength are obtained from the glass ionomer components.15 The mean setting time for CAGIC is 4.8 ± 0.1 min,16 which is reduced compared to ZNPH (5.5 min), glass ionomer (7.0 min) and increased compared to resin cement (2.0–4.0 min).15 The material has good flowability which gives a thin film thickness, 16.8 ± 0.9 μm,16 which is thinner than ZNPH (20 μm), glass ionomer (24 μm) and resin cement (<25 μm).15 The calcium aluminate contributes to reduced microleakage, adequate biocompatibility and long-term strength and stability.15 Compressive strength for CAGIC is ~160 MPa and thereby higher than the ISO requirements for water-based cements (50 MPa) and higher than ZNPH and glass ionomer cement (104 MPa respectively 86 MPa).16 Hardness is higher for CAGIC (VHN 68.3 ± 17.2) than ZNPH (VHN 51.4 ± 10), which could influence ease of removal.16Previous studies have shown that there are difficulties in removing cement excess. The removal process of the cement excess is particularly difficult when the finish line of the preparation is below the mucosal margin.Few studies have compared how effectively cement excess can be removed comparing different types of cement. Therefore, the aim of this study was to compare the amount of remaining cement excess after cementation of implant-supported zirconia crowns with CAGIC and ZNPH cement. The hypothesis was that cementation with CAGIC will leave less remaining cement excess than ZNPH cement, due to CAGIC’s handling properties.A dental technician produced 22 identical dental casts  which were provided with implant analogs  in the position of the maxillary right central incisor. Twenty-two identical gingival masks  were produced. Each implant analog was provided with an abutment  with a guide chute placed distally and a finish line placed ~1.5 mm below the gingival margin , scanned  and thereafter milled  in zirconia (DD cube ONE® – High Translucent Plus (HT+), Dental Direkt, Germany) at a milling center (Implant Solutions West AB Sweden). The crowns were milled with a cement gap of 0.35 μm. Before choosing 0.35 μm cement gap, various test crowns with different cement gaps ranging from 0 to 0.5 μm were tested in a pilot trial. Two models were used in this pilot. Three tests were performed, in the first test, an a-silicone impression material was used to replicate the interfaces between the crowns and the abutments finish line to check if each respective gap size allowed correct seating, where the crowns reached the intended finish lines. In the second test, test crowns were cemented with CAGIC  and ZNPH . The finish lines were probed to check proper seating of the crowns onto the abutments. In the third test, all crowns were set with a passive fit on the abutments and rotated by hand mesially and distally around the abutment’s axis of rotation. Thereafter, two crowns with the cement gap of 0.35 μm were cemented onto the two models used in the pilot trial, to test the method of this study. The remaining 20 crowns and dental casts were divided into two groups; 10 crowns cemented onto 10 titanium abutments with CAGIC in one group (test) and 10 crowns cemented onto 10 titanium abutments with ZNPH in the other (control).Before cementation, teflon tape  and a-silicone impression material  were applied in the screw access holes to protect the abutment screws during cementation. The crowns were designed with venting holes to facilitate the removal of the crown and the abutment in one piece, from now on called specimen, after cementation. The venting holes were covered with a composite lid  to prevent any leakage of cement during cementation Fig. .Fig. 2CoTo obtain a comparable and even inner surface of composite on all crowns, one crown was overfilled with a-silicone and allowed to set. Thereafter the occlusal excess silicone was removed with a scalpel  and the remaining silicone inside the crown formed a silicone replica that was used on all crowns to prevent composite from interfering with the cement gap  before cementation in order to be able to determine the weight of the cement at a later stage. Cement capsules were activated according to the manufacturer’s recommendations. Immediately after activation, the CAGIC and ZNPH capsules were mixed for 8 and 10 s respectively with a high-frequency (4500 rpm) oscillating mixer . The time was recorded from end of mixing until the cement had been set. The capsules were inserted into an applicator  and the cement was pressed out and filled approximately one third of the crowns. With the help of a brush , the cement was applied on the intaglio surface of the crowns. The crowns were thereafter weighed to achieve approximately the same amount of cement in all crowns and to determine the weight of the cement that was used for each crown. After 1 min, the crowns were placed on the abutments with maximal finger pressure of approximately 55 N for 3 min for CAGIC and 10 min for ZNPH. The time recommended by the manufacturer for removal of cement excess, was doubled as a precaution as cementation was performed outside the mouth. After 4 min CAGIC reached a rubber-like consistency and at this stage the cement excess was removed with a straight stainless-steel probe  and dental floss  to imitate the clinical situation. Thereafter an axial load of 52 N was applied with a loading device with prefabricated controlled weights for 5 min. After applying a maximal finger pressure for 10 min, ZNPH was also subjected to a load of 52 N with the loading device for 5 min. The cement excess was also removed with a probe and dental floss. The cement excess removal process was completed when the operator perceived that the cement excess had been completely removed. After 24 h, when the cements were fully hardened, a hole was drilled through the composite lid to access the abutment screw and the specimen was removed from the dental cast using a screwdriver . To avoid inter-observer variations, each step was carried out by the same operator.Six molds of dental impression putty  and a-silicone impression material  were made to fixate the specimen in six different positions to facilitate measurements of the remaining cement excess. The molds were made based on each hexagonal side of the abutment’s internal connection. A small amount of putty was mixed according to the manufacturers’ recommendations and placed on two flat surfaces at a right angle to each other Fig. . The speAfter the specimens were removed from the casts, the remaining cement excess was measured using two methods, pixel area calculation and weighing. Each specimen was inserted in all six putty molds Fig.  and photWith the selection brush tool in Photoshop, the cement excess in the pictures was manually marked. Cement excess smaller than pixel size 8 were not measured due to difficulties in determining the border of the cement excess. The total amount of marked pixels was obtained with the histogram function. Thereafter, the cement excess on the specimens and in the gingival masks were removed with a probe and weighed.6 and Linkevicius et al.13 The results were analyzed with SPSS version 25  with the help of a statistician. Mean values and standard deviation were calculated. Thereafter, an Independent Samples t-Test was carried out in SPSS version 25 to investigate if there was a statistically significant difference between the two groups, in terms of weight and number of pixels. Level of significance was set at p = 0.05.The sample size was determined by comparison to other studies, such as Chee et al.t-Test revealed a statistically significant difference, where ZNPH had a greater amount of remaining cement excess than CAGIC, in terms of mean of total number of pixels    Fig.  and mean05) Fig. .Fig. 8Re17 However, it also led to ZNPH cement breaking down into several pieces during removal. CAGIC showed a different consistency compared to ZNPH and the removal process of CAGIC was simpler and more effective. The timing of cement removal could also have influenced the results as the cements were removed at different times during their setting process. The recommended timing of removal differs between cements. CAGIC was removed at an earlier stage than ZNPH, at a point where it reached a rubber-like consistency and could be removed as one entity. Similar findings regarding the removal process of CAGIC, were observed in Jefferies et al.18 Several different cements are used to cement implant-supported restorations. In the present study CAGIC was chosen for testing as it has properties that suggest easier removal. As ZNPH cement is a well-tried conventional water-based cement that has been called the “gold standard”, it was chosen as control. Cements such as resin and glass ionomer are also removed at an earlier stage during their setting process, in order to prevent it from adhering to surrounding surfaces.17 At this stage, the cements have obtained some strength, enough for larger pieces to be removed easily.17 The removal process of resin and glass ionomer cement resembles that of CAGICs. For this reason, it could be of interest to compare the different materials consistency during the removal process and amount of remaining cement excess in future studies.The hypothesis was accepted as a statistically significant difference in amount of remaining cement excess between the groups was observed. These differences are most likely explained by differences in mechanical properties between the two types of cement where e.g., the reduced setting time and increased hardness of CAGIC could be beneficial and facilitate removal. The brittle properties of zinc phosphate cement were thought to be favorable as the cement does not adhere to the circumjacent surfaces.13 In the present study, the finish line was placed ~1.5 mm below the mucosal margin. This is likely to be the main explanatory factor as Linkevicius et al.13 found significant amounts of cement excess at submucosal margins despite operators considering that all the cement was eliminated.13 In the present study, more cement excess remained mesially and distally rather than buccally and palatally, in both cement types. This could be due to the proximity of neighboring teeth which made the removal process of cement excess in the interproximal areas specifically challenging. Similar results were found in a study by Lee et al.19 The gingival mask was perceived to have a snugger fit on the mesial side compared to the distal side. This, in combination with the consistency of ZNPH, could possibly be the reason why the cement showed significantly more remaining cement excess mesially. Apart from the snugger fit, half the papilla was made of gingival mask while the other half was made of dental stone, which made it more difficult to remove cement excess in interproximal areas. This may be considered a limitation. If the whole papilla had been made of gingival mask, it could have had better resemblance to the clinical situation.After specimens were removed from the dental casts, it was observed that neither cement was completely removed. This finding is in agreement with a similar study.20 Future studies need to apply and evaluate other techniques.In the present study, dental floss was used as a complement to dental probe during the removal process. These instruments are often used in the clinical situation to facilitate the removal process. Another way to eliminate cement excess is with a scaler. This technique was used in another study but did not lead to complete removal of cement remnants.When the specimens were removed for pixel area calculation, it was discovered that some remaining cement excess was left in the gingival masks instead of the specimens’ surfaces. The cement that remained in the gingival mask was not included in the pixel area calculation, which thus did not represent the total amount of the remaining cement excess. Weighing on the other hand included the cement excess from both the specimen and the gingival mask, which gave a more representative result of the total amount of remaining cement excess but did not reveal if more remaining cement excess was left in the interproximal areas. This could have been illustrated for example by taking a picture of the gingival mask before the removal and weighing of remaining cement excess. However, the choice of method of establishing the total amount of remaining cement excess did not affect the outcome of the study as ZNPH cement showed significantly more remaining cement excess in both measurements.19 A problem that can arise when using only four measurement areas is that part of the same area is calculated twice. For example, cement excess measured on the distal side of the abutment could also be seen from the buccal side and can therefore be measured twice. This problem can be avoided when using six measurement areas, as in the present study. However, this method also has sources of error, since the measurement lines are straight, and the abutment shape is conical. This led to small areas of the abutment being left unmeasured. Therefore, guiding lines could have been drawn on the specimen before cementation to avoid measuring areas twice or leaving areas unmeasured. However, this is not likely to have affected the outcome of the present study as this limitation would affect both groups in a similar way.When measuring the pixel area, six measuring areas were chosen instead of four  which were used in previous studies.Within the limitations of this in vitro study, the findings suggest that the amount of remaining cement excess can be affected by the type of cement and that CAGIC leaves less remaining cement excess compared to ZNPH cement. CAGIC may thus be a more suitable choice for cement-retained dental implant restorations and could possibly lead to reduced biological peri-implant complications. This latter hypothesis must however be tested in further clinical studies.


Multimodality imaging is of imperative value for the planning and guidance of transcatheter mitral valve interventions. This review employs the value of different imaging modalities and future implications for clinical practice. Transcatheter mitral interventions (TMVI) have exceeded the expectations oftechnical progress over the last decade. The recent explosion of technological advances that allows the personalized management of every patient with mitral valve disease, highlights the pivotal role of multimodality imaging in the decision making process. Specific challenges include the large spectrum of underlying pathology, the multidimensional feature of mitral annulus, the interaction with the left ventricle and its outflow tract, the constantly raising number of different devices which are available on the market, and the prevention of thromboembolism. Despite multiple challenges, the tremendous value of TMVI is offering a solution to these patients who almost a decade ago would be considered inoperable , 2.There are 5 different categories of TMVI: balloon valvotomy, mitral valve leaflet repair , transcatheter mitral valve replacement, mitral annuloplasty, and paravalvular leak closure.There has been a vast development of transcatheter valves which managed to address the issue of durability . Most imAt the latest AHA/ACC guidelines on valvular heart disease , it is cTransthoracic (TTE) and 3D transesophageal (TEE) echocardiography are the first line imaging tools for the assessment of mitral valve. For the purposes of this review, we will separate echocardiographic imaging into 3 parts: (i) pre-procedural, (ii) intra-procedural, and (iii) post-procedural.(i) Pre-proceduralThe role of the imager in guiding further management, in close collaboration with the interventionist and surgeon, is crucial. TTE as well as 3D TEE will identify the etiology and mechanisms of mitral pathology . It is iTechnical considerations when obtaining the basic measurements for mitral valve assessment, such as the appropriate alignment of continuous wave Doppler with the jet and the appropriate settings for proximal isovelocity surface area (PISA) /EROA/regurgitant volume assessment, should be applied .In addition, assessment of interatrial septum and the best anatomical position for transeptal puncture will facilitate the operator during TMVI. An incidental finding of a patent foramen ovale is of no hemodynamic significance. On the contrary, it may act in favor of the interventionist during the advancement of the guiding catheter.For balloon valvotomy, the most common imaging tool for mitral stenosis assessment is the Wilkins score which consists of scoringleaflet mobility, valve and subvalvular thickening as well as calcification. A score of ≤ 8 predicts a more favorable procedural, short, intermediate and long-term outcome . Other important predictors of procedural success and long-term outcome include commissural calcification or fusion, pre-procedure mitral regurgitation >2+, post-procedure mitral regurgitation >3+, age, prior surgical commissurotomy, NYHA functional class IV, and higher post-procedure pulmonary artery pressure .For mixed MVD or pure mitral regurgitation, the development of 3D TEE has allowed us the reconstruction of the mitral valve in a similar way as the surgeon would view this in the operating room . Another(ii) Intra-procedural echocardiographyCare should be taken in the evaluation of MR during general anesthesia as the degree of regurgitation as well as Doppler values may be underestimated. The echocardiographic views differ depending on the intervention which is taking place.COAPT trial , 12 and For edge to edge repair, the bicaval view is important for the advancement of the steerable guide catheter while all TEE planes focusing on the mitral valve are important for the advancement of MitraClip in the left ventricle and the grasping of the leaflets. It is recommended to initially close the MitraClip only up to 60–90° and aim for a full closure of the Clip only after determination of proper leaflet insertion and demonstration of MR reduction. For assessment of proper leaflet insertion into the MitraClip multiple planes are useful. The insertion of the posterior leaflet is commonly best seen in the LVOT view, and the insertion of the anterior leaflet in the four-chamber view. The intercommissural view can add information such as entrapped chordae tendinae which may be visible at the free edges. Once the leaflets appear securely inserted and well-positioned in between the Clip arms and the grippers and some reduction in mitral regurgitation is documented, the MitraClip can be fully closed. An example of preprocedural imaging for MitraClip is demonstrated on After MitraClip positioning, the evaluation of residual mitral regurgitation is important in deciding the number of clips to be employed. With implantation of a second MitraClip, the orientation of the second Clip should be optimized by 2D and 3D echocardiography in the left atrium. During advancement of the MitraClip from the left atrium into the left ventricle, the Clip should be closed to avoid any interference or entanglement with the chordae tendinae then re-opened in the ventricle. In general, fluoroscopy is more helpful than TEE for the positioning of a second MitraClip which should be aligned as parallel as possible to the first Clip. Folding of leaflet tissue between two MitraClips should be avoided as this may cause irreparable residual mitral regurgitation.For color quantification , 18, theTranscatheter mitral valve replacement may be performed either trans- septal or trans-apical. TEE guidance to ensure the guide wire and device delivery system are centrally located (between A2 and P2) is important to avoid chordal rupture as well as to avoid interference with the anterior mitral leaflet and acute severe MR. After deployment of the device, multiplane 2D and 3D TEE are fundamental for device positioning, stability and function . The imager should carefully identify central MR jets through the bioprosthesis due to cusp malfunction, which would be assessed with correct alignment of the continuous wave Doppler. Paravalvular leak  may resuAnother important part of TMVR is to avoid LVOT obstruction. 3D TEE and CT software simulations add invaluable information in procedure planning, predicting the risk of post-operative LVOT obstruction. The LVOT size, aorta- LVOT angulation, the length of anterior mitral valve leaflet as well as the distance between the aorto-mitral continuity and basal ventricular septum should be monitored at all times during the mitral valve positioning and deployment procedure.Each native valve has its own anatomical and physiological characteristics therefore, an individualized approach should be adopted . Color DAs a summary of the echocardiographic assessment post-procedurally, Dr. Zoghbi et al.  suggesteComputed tomography (CT) and cardiac magnetic resonance (CMR) are complementary tools to echocardiography that provide valuable information on mitral valvular structure, function, and associated chamber volumes , 22. CT Multidetector CT adds precision to planning the optimal intervention by determining annular size, landing zone characteristics, and predicting the risk of post-operative LVOT obstruction . Left ve2 had the greatest discriminatory value for predicting LVOT obstruction post TMVR  . Surgeryost TMVR . Furtherost TMVR .Patients not suitable for completely interventional TMVI in MAC, can be treated with the adoption of a hybrid technique, where a trans-catheter aortic valve is implanted in mitral position during open heart surgery. The advantages in this setting would be multiple. An extensive annular decalcification will not be needed, with the consequent reduction of the surgical risk; the trans-catheter valve will allow a greater EROA even in small mitral valve annuli with good hemodynamic results; the technique will be easily reproducible also in a minimally invasive setting. Most importantly, the possibility of surgically removing the anterior mitral leaflet during an open operation reduces drastically the risk of LVOT obstruction which is still matter of significant concern.Complications due to mitral valve intervention are also well-suited for assessment by CT and CMR. CT has the advantage of increased spatial resolution and is less prone to artifact from metal and prosthesis artifact . FurtherCoronary CT is valuable for preoperative planning in young patients. In this category of patients, the etiology of mitral valve disease is often myxomatous in nature and associated with mitral regurgitation secondary to valve prolapse. In this setting, coronary CT allows for pre-operative, non-invasive visualization of coronary arteries in low-risk patients .CMR provides valuable functional data and allows accurate quantification of chamber volumes. It is particularly helpful in quantifying MR  Figures, 9. CMR In cases of severe MR, CMR can provide guidance on the optimal time to intervene . CMR is While CMR has good concordance with echocardiography to localize leaflet pathology in mitral valve prolapse, an important limitation is the suboptimal assessment of small structures such as chordae or vegetations due to the partial volume effect from limited CMR resolution of finer voxels .As a conclusion, while echocardiography remains the cornerstone imaging methodology, integrated CT and CMR are increasingly becoming the standard of care in mitral valve assessment prior to intervention. This provides operators with the best chance of procedural success.The future of imaging lays on hybrid imaging which fuses the advantages and overcomes the disadvantages of all the above mentioned imaging modalities. Pascual et al.  describeAs CT and CMR gain more wide-spread use, it will be important to standardize protocols and evaluate the most reliable measurements. To this end, Garg et al. recently published a consensus statement supporting a standardized CMR protocol which includes the assessment of MR . Future While CT assessment provides a high degree of precision, it comes at the cost of radiation and risk of contrast injury. Decreasing the radiation associated with CT and the time required for obtaining the optimal image are future directions of research which will allow us to more safely provide CT assessment of mitral valve pathology. Moreover, contrast-associated renal injury remains an important concern given its association with increased mortality, so further studies in reducing contrast injury are needed .Finally, an exciting area of research is in the hybrid modality approach . For exaTranscatheter mitral valve interventions have overcome multiple limitations and have a bright future: the future is standing on the rapid development of imaging and the greater application of hybrid modalities. Furthermore, transcatheter procedures will expand in areas beyond the current guidelines such as in dilated left ventricles, . We alsoAs a conclusion, TMVI multimodality imaging is expanding fast and in all dimensions. New valves and devices, but also large studies with long term results of the existing one, will shed light in the management of mitral valve pathology.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


An increased incidence of myocardial infarction (MI) has recently emerged as the cause of cardiovascular morbidity and mortality worldwide. In this study, cardiac function was investigated in a rat myocardial ischemia/reperfusion (I/R) model using echocardiography. Metformin administration significantly increased ejection fraction and fractional shortening values on Days 3 and 7 when MI occurred, indicating that metformin improved left ventricular systolic function. In the Sham + MET and MI + MET groups, the E’ value was significantly different up to Day 3 but not at Day 7. This may mean that left ventricular diastolic function was effectively restored to some extent by Day 7 when metformin was administered. These results suggest that diastolic dysfunction, assessed by echocardiography, does not recover in the early phase of ischemic reperfusion injury in the rat myocardial I/R model. However, administering metformin resulted in recovery in the early phase of ischemic reperfusion injury in this model. Further gene expression profiling of left ventricle tissues revealed that the metformin-treated group had notably attenuated immune and inflammatory profiles. To sum up, a rat myocardial I/R injury model and ultrasound-based assessment of left ventricular systolic and diastolic function can be used in translational research and for the development of new heart failure-related drugs, in addition to evaluating the potential of metformin to improve left ventricular (LV) diastolic function. Myocardial infarction (MI) is the leading cause of morbidity and mortality worldwide. Acute myocardial infarction (AMI) is strongly related to metabolic syndrome, including dyslipidemia, smoking, diabetes mellitus, and hypertension , and it Rodents remain the most commonly used animal models in cardiovascular research . AlthougMetformin, a dimethyl biguanide, is a first-line oral treatment for patients with type II diabetes, as directed by the guidelines of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) . The carThis study aimed to show the effectiveness of metformin on left ventricular diastolic function using echocardiography in a rat myocardial I/R injury model.p < 0.05 and p < 0.01, respectively). As seen in p < 0.01).A representative gross photograph of a heart 7 days after MI surgery is shown in Echocardiographic results and the representative echocardiographic images are shown in n = 3; 23.72 ± 4.06, n = 3, in SAX and apex, respectively) was higher than that seen in group D , although these differences did not reach statistical significance.Representative gross morphology of representative cardiac tissue sections stained with 1% TTC are shown in To investigate genes affected by metformin, gene expression profiling of the A (Sham), B (MI) and D (MI + MET) group was performed and a total of 2924 differentially expressed genes (DEGs) were identified  from the comparisons : 2501 DETo identify reliable set of metformin associated genes, the DEGs were categorized into 8 clusters (C1-8) based on their differential expressions in the two comparisons . Among tp < 0.01) (To understand cellular processes represented by these two clusters (C2 and C3), the enrichment analysis of gene ontology biological processes (GOBPs) were performed using DAVID software. The analysis revealed that the genes in C2 were mainly involved in immune/inflammation responses and apoptosis C, while  < 0.01) C,E. To e < 0.01) F. The ne < 0.01) F,G 19]..p < 0.01In this in vivo model, the positive effect of metformin on the early stage of MI was confirmed by assessing total weight change over the study period, the relative heart weight, left ventricular systolic and diastolic function using echocardiography on Days 1, 3, and 7 as well as the degree of fibrosis. These data demonstrate that metformin successfully attenuated left ventricular diastolic dysfunction induced by MI in this animal model.MI, including AMI, remains the leading cause of morbidity and mortality worldwide ,2,3, andIn humans, the pathologic consequences of MI are mainly seen in the coronary arteries and myocardium . Early pMetformin is a first-line anti-diabetic agent , and thiThe current study highlighted the positive effects of metformin on acute MI; the weight loss associated with metformin treatment was confirmed, and the increased heart weight/body weight (%) in the MI-induced groups reflects cardiac hypertrophy, as reported in previous studies . EchocarThe alteration of molecular signatures by metformin in rat myocardial I/R injury model has not been systematically explored despite its clinical importance. In this study, gene expression profiles of rat myocardial I/R injury model were examined. Our approach of transcriptome profiling provides a list of DEGs, thus extending the current list identified by conventional experiments. Furthermore, the gene ontology biological processes (GOBP) and network model can provide a molecular basis for understanding immune/inflammation and cardiovascular system alteration in myocardial I/R. The network model further suggested fatty acid metabolism, mitochondrial biogenesis, Tgf-β/BMP and Jak/Stat signaling pathways associated with positive effects of metformin in a myocardial I/R injury. To the best of our knowledge, the current study is the first to demonstrate the promising positive effects of metformin on left ventricular diastolic dysfunction in a rat myocardial I/R injury model using echocardiography. The rat myocardial I/R injury model is a good representation of human AMI, allowing the cardio-protective effects of metformin to be evaluated. These data provide additional understanding of the effects of metformin on the development of AMI and provide a clear rationale for the use of metformin in high-risk patients.Sprague–Dawley rats  were purchased from Koatech ; the study design was approved by the Institutional Animal Care and Use Committee of Daegu-Gyeongbuk Medical Innovation Foundation . The rats were housed at a temperature of 22 ± 1°C and relative humidity of 50% ± 10%, using 12 h light/dark cycles, illumination at 150–300 Lux and with ventilation 10–20 times/hour. These conditions were monitored every hour for 24 h and maintained within an acceptable range throughout the study. The rats were housed three per cage at the beginning of the study and fed an autoclaved pellet diet  ad libitum.The experimental design is shown in Animals were anesthetized with alfaxlaone  and xylazine . After anesthetization, rats were intubated and ventilated by respirator  with a tidal volume of 3.0 mL/kg and at a rate of 60 bpm. Throughout the surgery, the rats were placed on a heated plate and monitored by ECG . The ratEchocardiography was performed on Days 1, 3 and 7 after the induction of MI, using Vevo2100 . The rats were anesthetized with alfaxalone  and xylazine , and were placed in a supine position. They were monitored by ECG and maintained at 37 °C.Echocardiographic parameters were recorded in accordance with the American Society of Echocardiography guidelines . Images After echocardiographic evaluation on Day 7, the rats were euthanized under isoflurane anesthesia and their hearts were excised. Following reperfusion with 0.9% normal saline, the hearts were sectioned into 2 mm transverse slices and the slices were immersed in 1 % solution of 2,3,5-triphenyltetrazolium chloride  at 37 °C for 15 min in the dark. The images of these slices were obtained using a digital camera. The infarct area and total area were analyzed by the Image J program (provided by NIH). For the histopathological analysis, the heart tissue was fixed in 10% neutral buffered formalin . A tissue processor  was used to prepare samples from the formalin-fixed tissue for analysis by fixing, dehydrating and staining. The paraffin-embedded tissue blocks were cut at a 4 μm thickness and mounted onto glass slides. Staining was performed with hematoxylin  and eosin  using an autostainer . In addition, tissue sections were stained using a Masson’s trichrome staining kit according to the manufacturer’s instructions . After staining, parasternal short axis with papillary muscle and apex area of the left ventricle were scanned with a slide scanner  and were captured by slide viewer . The morphometric analysis of fibrosis was performed using image J program (provided by the NIH). The red and blue color was designated in the MT stained section, and the blue area (collagen fiber) was measured compared to the total red area. Histopathological inspection was performed in a blinded manner by two investigators.2-values.For RNA sequencing, total RNAs were obtained from left ventricle tissues of three rat groups  using Trizol reagent . The integrity of the total RNA was analyzed using an Agilent Bioanalyzer. The RNA integrity values for all of the samples were larger than 7. Poly (A) mRNA isolation from total RNA and fragmentation were performed using the Illumina TruSeq Stranded mRNA Sample Prep Kit, according to the manufacturer’s instructions. The adaptor ligated libraries were sequenced using an Illumina NovaSeq 6000 . In each condition, the mRNA-sequencing analysis was performed for two biological replicates obtained from independent rats. From the resulting read sequences for each sample were aligned to the Rattus_norvegicus reference genome (Rnor_6.0) using STAR software (version 2.7) with the default parameters . After tp-values ≤ 0.05 and absolute log2-fold-changes ≥ 0.58 (1.5-fold). To identify cellular processes represented by the DEGs, the enrichment analysis of GOBPs was performed using DAVID software [To identify DEGs between three conditions, the previously reported statistical hypothesis test was performed . Brieflysoftware  and the P < 0.05 was considered statistically significant.Statistical significance was determined using GraphPad Prism 6 . All data are presented as mean ± standard deviation (SD). The results for each group were compared by one-way analysis of variance (ANOVA) with Tukey’s multiple comparisons test, Dunnett’s multiple comparisons test and a two-tailed unpaired t-test. A


Background: Electromechanical heterogeneities due to marked dispersion of ventricular repolarisation and mechanical function have been associated with symptoms in long QT syndrome (LQTS) patients; Aim: To examine the exercise response of longitudinal LV systolic and diastolic myocardial function and synchronicity in LQTS patients and its relationship with symptoms; Methods: Forty seven  LQTS patients and 35 healthy individuals underwent an exercise test (Bruce protocol). ECG and echo parameters were recorded at rest, peak exercise (p.e.), and recovery; Results: LQTS patients had prolonged and markedly dispersed myocardial contraction, delayed early relaxation phase, and significantly decreased filling time at all exercise phases. Unlike controls, these electromechanical disturbances deteriorated further with exercise, during which additional decrease of the LV diastolic myocardial function and attenuated LV stroke volume were noted. Such abnormal responses to exercise were seen to a greater degree in symptomatic patients and in the LQT1 subgroup and improved with B-blocker therapy. Worsening myocardial contraction dispersion at p.e. was the strongest discriminator for previous clinical events, and its discriminating power excelled further by adding early relaxation delay; Conclusions: Electromechanical disturbances were shown to worsen during exercise in LQTS patients and were more pronounced in those with previous arrhythmic events. One of the greatest challenges in cardiology practice remains the prompt identification of long QT syndrome (LQTS) mutation carriers who are at highest risk of developing adverse cardiac events such as arrhythmias, syncope, or sudden cardiac death . This haTo investigate the combined effect of prolonged myocardial contraction and increased mechanical dispersion on myocardial diastolic function and symptoms in LQTS, we used two-dimensional speckle-tracking echocardiography. We adopted this approach to examine the exercise response of longitudinal LV systolic and diastolic myocardial function and synchronicity in a group of LQTS patients, in an attempt to identify high risk carriers who have had previous cardiac events.The study group included 47 genetically confirmed LQTS patients, who have been regularly followed-up with at the Umeå University Hospital. The control group consisted of 37 age- and gender-matched healthy individuals, selected from a local database of healthy people who were not on any medical treatment. Subjects with evidence of ischaemic heart disease or at high risk of atherosclerosis were not included in the study. LQTS patients were categorized as asymptomatic or if there was documented history of cardiac events such as syncope, cardiac arrest, and ventricular tachyarrhythmias, as symptomatic. Two independent operators blinded to subjects’ clinical and demographic details performed the measurements and analysed the studied parameters.All participating subjects underwent a bicycle exercise test in a semi-supine position  using a General Electric—GE ergometer  with an increasing workload of 10 Watts every 2 min. Arterial blood pressure (BP), ECG, and full Doppler-echocardiogram were recorded and analysed in three phases: (1) at rest, just before exercise; (2) at peak exercise (p.e.), when 85% of the maximum predicted heart rate (HR) for age was achieved; and (3) at 4 min into recovery.A 12-lead ECG was continuously recorded, throughout exercise, at 25 mm/s speed using a conventional electrocardiograph. At the end of each of the three study phases, manual measurements of RR, QT, and QRS intervals were made. The QRS duration was measured from the onset of the QRS complex to its end. The QT interval was measured from the start of the QRS to the end of the T-wave, at the intersection point of the descending limb of the T-wave with the isoelectric line. QT measurements were corrected for HR using the Bazett formula (QTc = QT/√RR).Two-dimensional echocardiograms were performed in the semi-supine position using a Vivid 7 echocardiograph , Horten, Norway) and interfaced to an adult 1.5–4.3 MHz phased array transducer. At the end of each exercise stage, digital loops of three cardiac cycles were consecutively acquired from the standard apical four- and two-chamber and parasternal long- and short-axis views. ECG (lead II) was superimposed on and acquired from all 2D and Doppler recordings. The analysis was blindly performed offline using a dedicated workstation .The Simpson’s biplane method was used to estimate the LV ejection fraction. LV stroke volume (SV) was estimated as the product of the LV outflow velocity time integral (VTI) and cross-sectional area . LV fillSR) were defined as the 16 LV segments’ average value of peak longitudinal negative systolic S and peak positive early-diastolic SR, respectively  and strain rate (SR) assessment by STE was performed at basal, mid, and apical levels (16 LV segments) from parasternal long axis and apical four- and two-chamber views . On the ectively .SR) was similarly measured from the QRS onset to peak positive early-diastolic SR . LV longitudinal contraction dyssynchrony (SD-tGLS) was assessed by the standard deviation of tGLS intervals derived from the 16 LV segments. Early diastolic temporal discordance (E-ESR), as a reflection of potential discoordination between early LV ventricular filling and myocardial relaxation, was assessed by the time difference between tE and tESR   at all phases . Opposit(E-ESR)] .p < 0.0001).The stroke volume was lower in LQTS patients than in controls only at p.e. . Moreovep = 0.001), which showed positive correlation with tGLS  and tESR . However, prolonged tESR correlated with reduced FT , which in turn correlated with lower SV .QTc correlated modestly with SD-tGLS  intervals were longer and SD-tGLS of a greater degree in symptomatic patients (p = 0.8)).LV GLS and Epatients . In addipatients . Finallypatients . The maxp < 0.0001), stronger than QTc . The combination of tESR and SD-tGLS improved this discriminator ability .Mechanical dispersion (SD-tGLS) at p.e. was the strongest discriminator of previous clinical events , greater SD-tGLS , and longer tESR  than those of LQT2 patients. However, at rest or during recovery, these parameters were not different between the two genotype subgroups (p > 0.3).During exercise, LQT1 patients showed longer QTc  but not different during recovery . Additionally, at p.e., mechanical contraction increased in LQT1 but remained almost unchanged in LQT2 patients , whereas it increased more in LQT2 patients during recovery . The degree of tGLS and tESR prolongation at p.e. and recovery was similar for the two groups (p > 0.5).At peak stress, the QTc prolongation was greater in LQT1 than in LQT2 patients  but of similar magnitude during recovery . Finally, at p.e., SV response was more attenuated in LQT1 patients , but at recovery it was more attenuated in LQT2 patients .FT shortening was also greater at p.e. in LQT1 than that of LQT2 patients  at p.e. was the strongest discriminator for previous clinical events. To the best of our knowledge, this is the first study that examines the relationship between repolarization, mechanical dyssynchrony, and diastolic function during dynamic exercise and the potential haemodynamic consequences in genetically confirmed symptomatic and asymptomatic LQTS patients.In LQTS subjects and opposite to that seen in controls, the already prolonged QTc interval did not shorten but increased further with exercise. Such electrical disturbances were related to mechanical changes; QTc correlated with the degree of mechanical contraction dispersion (SD-tGLS) and the duration of myocardial contraction (tGLS). These were also increased at rest and worsened during exercise in LQTS patients.SR interval. This was longer in LQTS patients, indicating significant delay of the early relaxation phase within the cardiac cycle. The degree of this delay increased further during exercise in patients. Moreover, tESR correlated inversely with LV filling time, which was shorter and shortened further with exercise in LQTS patients.Such myocardial contraction disturbances may potentially affect diastolic function and LV filling at rest and to a greater extent during exercise . In our SR)], suggesting significant dis-coordination between LV filling and myocardial relaxation. These may also be reflected by the lower transmitral flow velocities and the higher E/e’ noted in LQTS patients during exercise.However, shortening of LV filling duration during exercise may adversely affect the LV filling volume . Indeed,Of particular interest is the relationship between the above mechanical disturbances and the development of symptoms in this group of patients. Dispersion of myocardial contraction and delayed early relaxation, especially during stress, were shown to be the stronger discriminators of previous clinical events, even stronger than QTc interval. LQTS patients usually develop symptoms with stress, at the time when all systolic and diastolic disturbances were shown in our patients to worsen and when SV response was also attenuated. However, an amplified SV response during stress states may also be associated with reduced and insufficient subendocardial flow . This maB-blockers are used in the management of LQT1 and LQT2 patients in an effort to reduce the incidence of cardiac events 14). They decrease sympathetic over stimulation and shorten the QTc interval [. They deIn our study, LQT1 and LQT2 subgroups showed different patterns of EM response to exercise. QTc was prolonged and myocardial contraction dispersion was exaggerated at p.e. more so in the LQT1 than LQT2 patients. Such differences in EM response to exercise may reflect the different effects of adrenergic stimulation triggers in the two genotypes . In LQT1Identifying LQTS patients who are at risk for developing arrhythmia remains a challenge. In our study, EM disturbances were shown to be more pronounced in symptomatic LQTS mutation carriers, especially during exercise. In fact, myocardial contraction dispersion during exercise was the strongest discriminator of previous clinical events, over and above QTc. Such abnormal EM response to exercise was less pronounced in patients receiving B-blocker therapy. Therefore, additional assessment of EM response to exercise may contribute towards identifying LQTS mutation carriers at risk of arrhythmias and may play a role when deciding optimal management strategy.A modest number of LQTS subjects were included in this study and our results need to be reproduced in larger cohorts of carriers with better representation of genotype subgroups. Although between controls and patients there was no significant difference in peak exercise heart rate, this value was below that predicted for age in both groups. Lower achieved heartrate could be explained by decreased fitness levels in controls whereas B-blockers may be responsible for the attenuated heart rate response in patients. Cardiac events were identified based on the previously documented history.LQTS carriers present marked LV electromechanical dispersion, which is associated with impaired longitudinal systolic and diastolic function and inadequate stroke volume response during exercise. These disturbances are more pronounced in patients with previous arrhythmic events. Assessment of LV myocardial dispersion and relaxation properties using myocardial deformation imaging techniques may be of additional value in risk stratification and management of LQTS carriers.


The correlation between ΔZva and ΔLVMI/LVEDVI was statistically significant ; in contrast, that of ΔMPG and ΔLVMI/LVEDVI was not. The improvement in Zva after TAVR was more closely related to LVMI and LVMI/LVEDVI reduction than MPG reduction.Increase in left ventricular (LV) mass develops as a compensatory mechanism against pressure overload in aortic valve stenosis. However, long-standing LV geometrical changes are related to poor prognosis. The LV geometrical change occurs after transcatheter aortic valve replacement (TAVR). The present study aimed to investigate the relationship between improvement in valvuloarterial impedance (Zva) and change in LV mass index (LVMI) and the ratio of LVMI to LV end-diastolic volume index (LVMI/LVEDVI). We compared these relationships to that between Zva and mean pressure gradient (MPG). Baseline and follow-up transthoracic echocardiograms of 301 patients who underwent TAVR from November 2011 to December 2015 were reviewed. Spearman correlation coefficient (ρ) was used to compare ΔLVMI and ΔLVMI/LVEDVI with Zva or MPG. The correlation between ΔZva and ΔLVMI (ρ = 0.47,  Aortic valve stenosis (AS) imposes pressure overload on the left ventricle (LV) and leads to LV geometrical alterations, such as increased LV mass relative to the LV cavity ,2. TheseValvuloarterial impedance (Zva) has been proposed as a new index to represent LV global load and consists of both systemic and valvular loads . Zva canLV mass reduction, considered as a reverse-remodeling, occurs after transcatheter aortic valve replacement (TAVR) ,11,12,13n = 58); moderate and severe aortic regurgitation (n = 130); moderate and severe mitral regurgitation (n = 172); moderate and severe mitral stenosis (n = 23); moderate and severe paravalvular leakage (n = 25); concomitant coronary artery stenting with TAVR (n = 10); transapical approach (n = 8); old myocardial infarction (n = 66); diagnosed ischemic, dilated, or hypertrophic cardiomyopathy (n = 7); and procedure-related myocardial infarction (n = 1). This left 301 patients were eligible for our analysis  at baseline and follow-up (≥90 days from TAVR). From these patients, we excluded 500 participants who met the following exclusion criteria: valve in valve TAVR 3)) + 0.6, in which LV end-diastolic diameter (LVDd), interventricular septum thickness (IVSth), and posterior wall thickness in diastole (PWTh) [TTE was performed at baseline and follow-up 426 327, 788) (median with interquartile range) days after TAVR with the iE33 system  by experienced technicians. A cardiologist reviewed results and performed the off-line measurements . The fol5 cm2/m2 . LVMI/LV5 cm2/m2 ,17. The 5 cm2/m2 . LV masse (PWTh) . Continue (PWTh) . MPG wase (PWTh) ,20. Peake (PWTh) . Zva was, 788 (mee (PWTh) ,22.2) and low mean pressure gradient (<40 mmHg) is known as low-flow low-gradient AS (LFLG-AS). LFLG-AS has been reported to be associated with higher baseline Zva [2 and MPG<40mmHg, and performed subgroup analysis. We also examined the relationship between baseline LV geometry and baseline Zva or baseline MPG and that between the change of LV geometry and ΔZva or ΔMPG.Severe aortic valve stenosis with low stroke volume  at baseline was performed using a dual-source CT scanner . These datasets were processed using commercially available software .Continuous variables with normal distribution and skewed distribution are expressed as mean ± SD and median , respectively. Categorical variables are expressed as numbers and percentages. A Wilcoxon rank-sum test was used for the comparison of Zva, hemodynamics, and TTE parameters between baseline and follow-up.Spearman correlation coefficient (ρ) was used to compare LVMI and LVMI/LVEDVI with Zva or MPG at baseline and on change. We used the Hittner, May, and Silver’s test to compare the two overlapping correlations in the dependent group .To identify the factors associated with ΔLVMI and ΔLVMI/LVEDVI, we employed univariate linear regression models to examine the following 15 factors: ΔZva, ΔMPG, ΔSVI, clinical characteristics including age, sex, body mass index, past medical history (diabetes mellitus and hypertension), medications , systolic and diastolic blood pressure at follow-up, baseline LV geometry (LVMI or LVMI/LVEDVI), mild paravalvular leakage, and mild patient–prosthesis mismatch ,24,25,26LVMI, LVEDVI, and SV values assessed using echocardiography were compared with those using cardiac CT to validate echo parameters, and Spearman correlation coefficient (ρ) was used for analysis.p value < 0.05 was considered statistically significant. Statistical analysis was performed using R 3.4.1 , EZR 1.3.6  [All statistical tests were two-sided, and a  Center) , and R p Center) .The mean age was 82 ± 8 years. There were 174 men and 127 women. The risk of mortality based on a predictive model proposed by the Society of Thoracic Surgeons was 4.5 . 2, p < 0.001; LFLG-AS, baseline 5.61 ± 0.86 vs. follow-up 4.14 ± 0.98 mmHg/mL/m2, p < 0.001; Overall Zva and LFLG-AS values were significantly reduced after TAVR .In the overall population, LVMI reduction was observed after TAVR  vs. follow-up 86  g/mThe same findings—LVMI and LMVI/LVEDVI decrease—were obtained in the subgroup analysis of LFLG-AS as obtained in the overall population .p = 0.001; There were no significant relationships between baseline MPG and LVMI nor LVMI/LVEDVI . There wIn LFLG-AS, there was no significant relationship between baseline MPG and LVMI or LVMI/LVEDVI . There wp = 0.009; p < 0.001; p for comparison of correlations < 0.001). There was no significant relationship between ΔMPG and ΔLVMI/LVEDVI. In contrast, ΔZva also correlated with ΔLVMI/LVEDVI .ΔMPG had a weak correlation with ΔLVMI .In the LFLG-AS sub-group, a trend indicating a positive correlation between ΔZva and ΔLVMI was observed but was not statistically significant .There were good correlations between echocardiographic and CT measurements  was reportedly related to poor two-year survival after TAVR [The present study had several limitations. First, echocardiographic follow-up duration might be short for evaluating left ventricular change after TAVR . Second,ter TAVR . We coulter TAVR . TherefoOur study design was a single-center retrospective observational study. Therefore, a well-designed further study  is warranted to support the conclusions of our study.The improvement in Zva after TAVR was more closely related to LV mass and LVMI/LVEDVI reduction than to MPG reduction. Zva should be evaluated before and after TAVR as well as MPG, because the improvement in Zva may induce favorable LV remodeling.


Recent studies have described the occurrence of complex ventricular arrhythmias and sudden cardiac death among patients with mitral valve prolapse (MVP). The reported incidence rate of sudden cardiac death or ventricular tachycardia is about 1–1.5% among patients with MVP. Various imaging markers have been associated with this increased risk, including mitral annular disjunction, replacement fibrosis by late gadolinium enhancement, and mechanical dispersion. In this review, we briefly discuss how multimodality cardiac imaging can be applied to identify MVP patients with high risk of sudden cardiac death and complex ventricular arrhythmias. Mitral valve prolapse (MVP) has received renewed attention due to several studies documenting its association with scar substrate and increased risk of complex ventricular arrhythmias (VA) and sudden cardiac death (SCD) –3. OtherThe current echocardiographic definition of MVP is displacement of one or both mitral leaflets in the left atrium below the annulus by at least 2 mm in the parasternal long-axis view . The preThis review will focus on MVP due to myxomatous valvular degeneration. In myxomatous valve degeneration, diffuse thickening, redundancy, and elongation of mitral valve leaflets occur in association with an abnormality of the chordae. Barlow's disease and fibroelastic deficiency (FED) are ends of the myxomatous MVP spectrum. Barlow's disease is often found in middle-aged patients with severe annular dilatation, excessive valvular tissue, thickened or thin chordae, and prolapse of most of the mitral leaflet segments . On the In addition to diagnosing MVP and quantifying associated mitral regurgitation, cardiac imaging is emerging as a tool to risk stratify for malignant VA and SCD. In this review, we briefly discuss recent studies which have identified cardiac imaging-based risk markers of these adverse events in patients with MVP.There are two broad sets of data on MVP and SCD in the literature: one is from autopsy studies of subjects with SCD and the other is from observational studies on the incidence of SCD among living patients with MVP. The cause of SCD in MVP patients is assumed to be malignant VA , 17. In N = 177), where MVP was diagnosed by cardiac magnetic resonance (CMR), reported 1.2% annual event rate of SCD or malignant VA (n = 595) with MVP and 24-h ambulatory Holter monitoring finding nearly 43% having either PVC burden >5% or ventricular tachycardia  found the presence of T-wave inversion/ST-segment depression to be associated with a nearly 2-fold increased risk of mild–moderate VA and 8-fold increased risk of severe VA  remodeling. Recently, CMR has gained traction for the assessment of valvular heart disease. It can provide more accurate quantification of regurgitation volume and LV remodeling . This isThe presence of bileaflet prolapse on echocardiography with redundant valve leaflets is one of the major markers of increased incidence of VA and SCD among patients with MVP. It is reported that nearly 70% of cases with MVP and SCD had bileaflet prolapse, while only 26% had posterior leaflet prolapse . A similAutopsy studies have demonstrated the presence of myocardial fibrosis among patients with MVP , 28. Hown = 177) over a median period of 3.7 years. In his cohort, eight patients had either ventricular tachycardia (VT) or aborted SCD  in the Veneto region in Italy between 1982 and 2013  with SCD   is a separation of the posterior mitral annular hinge point from the LV wall while the attachment to the atrium and mitral valve is preserved . The detn = 900) . They den = 900) . Angelinn = 900) .n = 90) for the presence of MAD  and CMR –47 Tabl. A systee of MAD . They noFurther study and understanding of the concept of MAD are warranted. There is a need to further characterize changes in MAD between systole and diastole. Mechanistic data is required as to why MAD may cause an increased risk of VT. Moreover, the impact of surgical mitral valve repair on MAD is unknown and warrants further investigation.Mechanical dyssynchrony is associated with VA in patients with cardiomyopathies , 51. In Besides mechanical dispersion, the magnitude of longitudinal strain can be used to identify early signs of subclinical cardiomyopathy among patients with MVP. One study described decreased longitudinal LV strain in patients with classical MVP (>5 mm leaflet thickness) . AnotherMuthukumar et al. using pulsed-wave Doppler measured mitral annular velocity in a series of 21 patients with MVP . They noMVP is widely prevalent in the community. Although the risk of SCD may be low, it is of serious concern due to its devastating consequences. A risk stratification strategy is needed to identify patients at high risk of this consequential complication. There are many small series demonstrating SCD and malignant VA among patients with MVP , 2. HoweMVP is a widely prevalent disease and studies have shown the increased risk of SCD and complex VA in these patients. Several imaging markers are shown to be related to this arrhythmic risk. Aside from its role as a cornerstone for identifying MVP, echocardiography can serve as a gatekeeper for further investigations if bileaflet prolapse or signs of any cardiomyopathy are noted. The strength of CMR is its ability to perform tissue characterization to identify focal myocardial fibrosis in the posterior papillary muscle and adjacent LV wall. The presence of fibrosis has one of the most compelling mechanistic basis and supporting evidence in the literature. Patients presenting with syncope, pre-syncope, palpitations, or evidence of VA should be investigated with CMR for further risk stratification.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In planimetric measurement of left ventricular (LV) mass and volumes, selection of the most basal short-axis cine MR image plane is generally not standardized and may affect calculation of relative infarct size in post-myocardial infarct (MI) patients.To study the effect of LV base-plane selection on MR measures of LV mass, volumes, ejection fraction (EF) and relative infarct size in post-MI patients.SSFP cardiac cine and multi-shot inversion recovery spoiled gradient echo delayed enhancement (DE) images were acquired in 14 patients with documented MI , at 1.5 T. Cine and DE images were acquired in corresponding short-axis planes  from LV base  to apex. An expert observer used Argus software  to manually outline LV epi- and endomyocardial contours on cine images at end-diastole (ED) and end-systole (ES) using each of 3 methods for choosing the most basal LV slice: #1 base-plane showing 100% of myocardium at ED and corresponding ES plane, #2 base-plane selected separately for ED and ES, with 100% of myocardium visible at both phases, #3 base-plane showing 100% of myocardium at ES and corresponding ED plane. LV mass was averaged over ED and ES for each method. EF, and ED and ES-volumes were also calculated. Infarct borders were manually outlined on DE images. Infarct size (Infarct%) was expressed as a percentage of LV mass measured on the cines (in each method). Comparisons were made using repeated measures ANOVA, with Bonferroni-corrected post-hoc P-values.LV mass was largest in method #1 and smallest in #3 . Method #2 produced a larger EF (51.3 ± 8.9%) vs. #1 (43.8 ± 9.4%) or #3 (43.9 ± 10.8%); P < 0.01. Infarct% was smallest in method #1 and differed significantly between all methods . ED volume was lower in #3 than in #1 or #2 (P < 0.01) and ES volume was higher in #1 than in #2 or #3 (P < 0.01).Selecting the base-plane based on the anatomy visible in only one phase, will lead to miscalculation of MRI measures of LV mass, volumes and relative infarct size, due to through-plane motion of the heart over the cycle. To standardize measurements and to ensure that the same tissue is being measured at both phases, the most basal slice should be selected independently for ED and ES based on the visible anatomy.


To demonstrate safety and efficacy of using different generations of softer Amplatzer™ devices for ventricular septal defect (VSD) closure to avoid serious complications at follow-up.  Transcatheter closure of perimembranous ventricular septal defects (PmVSD) is a well-established procedure; however, it is associated with unacceptable incidence of complete heart block. Great advantages have been achieved by using softer devices for VSD transcatheter closure. The first and second generation of Amplatzer™ occluders  seem to offer a safe and attractive alternative for this procedure. These devices can be delivered using either an arterial (retrograde) or venous (prograde) approach.  Patients with congenital PmVSD who underwent transcatheter closure using ADO, ADO II, and AVP II devices were included. Primary end point was to determine efficacy and safety of these generations of devices and to determine the incidence of complications at follow-up . One hundred and nineteen patients underwent VSD closure at a median age of 5 years (8 months–54 years). During the catheterization, there were only minor complications and at follow-up of 36 ± 25.7 months (up to 99 months), the closure rate was high of 98.3% and freedom from AV block was 100%.  The use of softer Amplatzer™ devices is a good alternative to achieve PmVSD closure safely with no risk of AVB during the procedure or at midterm follow-up. Ventricular septal defects (VSD) are the most common congenital heart malformation accounting for almost one-fifth of all defects and can be located in membranous or muscular septum. Eighty percent of these are perimembranous .Surgical closure has been regarded as the gold standard treatment. However, transcatheter closure of congenital VSD for specific and selected patients has been advocated as an alternative to surgical repair as it avoids the risks of cardiopulmonary bypass, postoperative discomfort, and the need for sternotomy and a residual scar , 3.Percutaneous closure of VSD was first described by Lock et al.  in 1988,For a successful VSD closure, an anatomic delineation of the defect with its relation to other cardiac structures is needed, so that the development of new aortic/tricuspid regurgitation or conduction defects can be avoided . The preWith the development of the self-centering Amplatzer™ devices, an increasing number of defects could be closed with specially designed occlusion devices , 11, incInitial attempts at percutaneous closure of PmVSD resulted in heart block in 3% to 5% of patients in some reports . GreaterA retrospective study was conducted at 4 cardiac centers of all patients who underwent perimembranous ventricular septal defects closure with different generations of Amplatzer devices . Institutional review board approval was obtained. Procedures performed from January 2011 through June 2019 were included. Patients were included if they  had VSD An informed consent form was given to the relatives of the patients, and a complete left and right heart catheterization with exclusive femoral arterial access in procedures with the retrograde approach and femoral arterial and venous access for the arteriovenous loop in procedures with the prograde approach were performed. All procedures were performed under general anesthesia. VSD was thoroughly investigated with left ventricular angiography in four chambers view ; transesIn the patients with retrograde approach (58 cases), after having crossed the VSD from the femoral artery, the hydrophilic coated Terumo™ guidewire was positioned in the RV or PA, and then a Terumo™ 5Fr Judkins right guiding catheter was advanced over the 0.035 inch Terumo™ guidewire into the RV. AVP II or ADO II was loaded on the guiding catheter and advanced to the tip of the catheter. Under fluoroscopy, the distal disk of the device was deployed in the RV; then, the catheter and device were pulled slowly, and the waist and the proximal disk of the device were deployed just in the LV side of the defect .Proper position and residual shunt were confirmed with LV angiography and with TEE or TTE in some cases. After achieving good position of the device, we evaluated for any evidence of regurgitation of the aortic valve with angiography at the aortic root, and finally, device was released, and LV angiography was repeated. Next morning, electrocardiogram and TTE were performed.Prophylactic antibiotics were used previous to the procedure, and intravenous heparin was used during the whole procedure at a dose of 100 U/Kg (maximum dose of 5000 UI).Patients left the hospital 24 hours after the procedure with prophylactic antibiotics and aspirin at a dose of 5 mg/kg (maximum dose of 100 mg) for 6 months. Follow-up visits at 1, 3, 6, and 12 months and then yearly to perform clinical examination, electrocardiogram, and a TTE. We chose this scheme of visits for the purpose of assessing the position of the device, possible residual shunt, presence of aortic, tricuspid, or mitral regurgitation, and to document cardiac rhythm.Frequencies and percentages expressed categorical variables. Continuous variables were summarized as mean (SD) or median (range) as appropriate, depending on normally of distribution. The statistical analysis was performed using the SPSS version 19.0 and Microsoft Excel 2016 for Mac.A total of 119 patients who met the inclusion criteria, were treated by catheterization at 4 cardiac centers (México and Egypt). In all the procedures for transcatheter PmVSD closure, ADO I was attempted in 55 patients; ADO II in 51 patients; and AVP II in 12 patients. The prograde approach was used in 62 patients and the retrograde approach in 58 patients; it was chosen depending on the anatomy of the defect. From the complete group of studied patients, 88 patients (74%) had aneurysmal defects and 31 patients (26%) had just the PmVSD with no aneurysm. A total of 10 patients had aneurysmal defects with multiple exit sites. This group included 62 female patients (52.5%) with a group median age of 5 years (ranged from 8 months to 54 years) and weight of 18 kg (6.5–87). Demographic data are shown in Qp/Qs) was of 1.8 ± 0.8, and the mean diameter of the septal defect was of 4.9 ± 1.5 mm.The mean systolic pulmonary arterial pressure was of 31.7 ± 7.9 mmHg. The mean of the pulmonary and systemic flow , and the median procedure time was 80 minutes (range 25–210). All patients were discharged 24 hours after the procedure. At a mean follow-up of 36 ± 25.7 months, 115 patients showed complete closure of the defect and 3 patients had trivial residual shunt across the device. A patient in whom we used an ADO I 10/8 mm device presented late embolization of the device to the right pulmonary artery (RPA) discovered by TTE examination 3 months after procedure, and he went to surgery. No AV block was found in electrocardiogram, and no increase in previous aortic, tricuspid, or mitral regurgitation was found by TTE.The VSD is the most common congenital heart disease, comprising 10% of all forms of congenital cardiac defects . The perst century, the availability of Amplatzer™ VSD occluders, which was specially designed for occluding muscular and PmVSD, improved the success rate of this kind of procedures in regard to its safety profile and occlusion rates [At the end of the 90s and the beginning of the 21on rates , 17. HowA conventional VSD closure technique involves complex steps. Occasionally, the delivery sheath is difficult to pass through a small defect or be positioned into the LV apex. These difficulties can make a difficult and challenging procedure with the conventional AMVO. Moreover, PmVSD closure using the APMVSDO device has largely been abandoned because of the risk of AV block. In a review published in 2005 by Carminati et al.  where 12Since this early experience, many authors have published case series data on VSD closure using different generations of smaller Amplatzer™ devices in offlabel application. Behnke et al.  publisheFor an appropriate selection of these percutaneous devices, Behnke  used 3–5Percutaneous closure of PmVSD remains a real challenge; however, with the use of softer and smaller devices, we think that VSD closure can be more safe and effective. Dilawar et al.  informedUsing Amplatzer VSD devices, serious complications during and postprocedure have been presented. However, using these softer Amplatzer devices, only eventual and minor complications have been reported in regard to aortic, tricuspid, or mitral regurgitation. Dilawar  informedUse of ADO I, ADO II, and AVP II devices for closure of VSD seems to be safe and effective. They can be used as an offlabel therapy for VSD closure with good midterm outcomes. To date, they are preferable over devices designed exclusively for VSD closure.It is known that the use of offlabel occluders for ventricular septal defect closure is becoming an emerging practice with high global success rate and encouraging outcomes. Now, this study demonstrates outstanding results in VSD closure referring to the use of softer devices with acceptable complication rate. However, there were certain limitations. Being a retrospective study, some of the obtained data were missing which reduce the impact of this work. In regard to the complications at follow-up, complete heart block was not observed in any patient; furthermore, it is important to know that all the patients were evaluated only by conventional electrocardiogram. So, we know that it is very important to have holter data for the correct exclusion of complete AVB. This study probably opens gates to future directions in the evaluation of the conductance disturbances after percutaneous PmVSD closure.


Mitral annular disjunction (MAD) is an under-recognized cause of arrhythmic sudden cardiac death, especially in young women. The relation between MAD and the occurrence of arrhythmia during pregnancy has not yet been explored. We would like to stress the importance of careful echocardiographic examination and the vulnerable peripartum period.A 29-year-old woman survived an out of hospital cardiac arrest 4 months after delivery of her first child. The diagnosis was not clear and an implantable cardioverter-defibrillator (ICD) as secondary prevention was implanted. Her second pregnancy and delivery were uneventful. The 12-lead electrocardiogram demonstrated sinus rhythm with right bundle branch block, ventricular extra systoles (premature ventricular contractions), and a right superior axis, i.e. origin in the inferolateral basal left ventricle. Transthoracic 2D echocardiography showed myxomatous mitral valve disease with moderate mitral valve insufficiency with normal left and right heart dimensions and function. However, 4 weeks after delivery she experienced a sudden syncope at home. Implantable cardioverter-defibrillator reading revealed primary ventricular fibrillation, induced by a ventricular premature beat (VPB), terminated with a successful ICD shock. A frame-by-frame echocardiographic analysis of the mitral valve using biplane echocardiographic analysis allowed diagnosis of MAD with detachment of the root of the annulus from the posterolateral ventricular myocardium during systole.Mitral annular disjunction is an under-recognized cause of arrhythmic sudden cardiac death. Biplane echocardiographic analysis of the mitral annulus can identify MAD and as such may help for risk stratification and sudden cardiac death prevention. Careful follow-up is necessary especially during pregnancy and the postpartum period. Mitral annular disjunction (MAD) is an under-recognized cause of arrhythmic sudden cardiac death, especially in young women.Careful frame-by-frame echocardiographic analysis of the mitral annulus with use of biplane may help for risk stratification and sudden cardiac death prevention.Women with MAD, planning pregnancy, should receive complete work-up with transthoracic echocardiography, exercise test, 24 h-Holter monitoring and cardiovascular magnetic resonance for adequate risk assessment and need extensive counselling before pregnancy.P < 0.0001].,Pregnancy is complicated by maternal disease in 1–4% of cases.Mitral annular disjunction (MAD) is characterized by an abnormal atrial displacement or detachment of the roots of the annulus away from the ventricular myocardium. Mitral annular disjunction has been associated with mitral valve prolapse and malignant ventricular arrhythmias.Despite the fact that MAD is considered an under-recognized cause of arrhythmic sudden cardiac death, especially in young women, the relation between MAD and occurrence of arrhythmia during pregnancy has not yet been described. We would like to present a case of a young woman who experienced two episodes of aborted sudden cardiac death in the postpartum period.The aims of this case report areTo include MAD in the differential diagnosis of a young woman suffering from ventricular arrhythmias.To stress the importance of careful echocardiographic analysis and to introduce biplane echocardiographic imaging at the level of the mitral annulus as a useful tool to identify MAD.To draw the attention to a potential increased risk of life-threatening arrhythmia during pregnancy and the postpartum period.A 29-year-old woman with a history of out of hospital cardiac arrest with underlying ventricular fibrillation 4 months after delivery of her first child was referred to our centre to evaluate the risk of a second pregnancy. After her first pregnancy, the differential diagnosis of dilated cardiomyopathy vs. peripartum cardiomyopathy or primary electrical disease was made and an implantable cardioverter-defibrillator (ICD) was implanted as secondary prevention. Extensive investigations, including echocardiography and cardiac magnetic resonance imaging (MRI) revealed no abnormalities apart from mild mitral prolapse and mild left ventricular dysfunction.Figure 1). Exercise-ECG illustrated regular PVCs, no ST-segment changes, and moderate exercise capacity . Echocardiography showed a myxomatous mitral valve with some prolapse and mild to moderate regurgitation with normal left and right ventricular dimensions and function.When she presented in our centre for counselling, she happened to be already 2 weeks pregnant. She had no complaints, no recent history of (pre)syncope’s. Clinical examination showed a lean woman , with normal blood pressure 112/76 mmHg and an oxygen saturation of 98%. On auscultation, an apical mild systolic murmur was present with no signs of heart failure. The 12-lead electrocardiogram (ECG) demonstrated sinus rhythm with right bundle-branch block and ventricular extra systoles (PVC) . A reversible cause like deterioration of left ventricular function or electrolyte imbalance was not found. Echocardiography revealed no new abnormalities. Medical treatment with metoprolol 100 mg/day was continued.However, 4 weeks later, she experienced a sudden syncope at home, while taking a shower. ICD interrogation revealed primary ventricular fibrillation, induced by a premature ventricular beat, terminated with a successful ICD shock. The morphology of the inducing beat could not be determined, since the recording of the intracardiac EGM starts after detection . A frame-by-frame echocardiographic analysis allowed the diagnosis of a MAD with detachment of the root of the annulus from the posterolateral ventricular myocardium during systole .She mentioned having PVCs as an adolescent. Reviewing her ECGs showed the presence of regular right bundle-branch block ventricular extra systoles and a right superior axis, i.e. with an origin in the inferolateral basal left ventricle  .Mitral annular disjunction is an under-recognized cause of arrhythmic sudden cardiac death, especially in young women. One-tenth of MAD patients have life-threatening arrhythmic events and PVCs are the most common cause for seeking medical advice.P < 0.0001) and increased frequencies of maternal and foetal complications.,P = 0.01) especially during the postpartum period.,,Although the presented patient was already known for many years with PVCs and mitral valve prolapse, the only two episodes of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) occurred in the early postpartum period. Life-threatening VT and VF are very rare during pregnancy or after delivery, but are associated with elevated odds for mortality  and associated text has been obtained from the patient in line with COPE guidance.Conflict of interest: none declared.ytaa135_Supplementary_Slide-SetClick here for additional data file.


Our objective was to determine the degree of myocardial scarring in diabetic and non-diabetic patients with ischemic heart disease (IHD).not be related to increased infarct size with accompanying negative remodeling and systolic dysfunction.Diabetic patients with IHD are more likely to develop congestive heart failure (CHF) than non-diabetics, but the mechanism responsible for this is unclear. Recent evidence suggests that this may We retrospectively evaluated 54 consecutive patients  who underwent both cardiac magnetic resonance (CMR) imaging and coronary angiography for evaluation of IHD between April 2006 and July 2008. Patients were evaluated for presence of CHF symptoms and degree of coronary artery disease (CAD) . Myocardial scar was measured by late gadolinium enhancement on CMR for each patient using a 17-segment model of the left ventricle (LV), and was graded according to transmural extent on a semi-quantitative scale . Total scar burden (mean grade per segment) and spatial extent (number of segments with any scar and number of segments with grades 3–4 scar) were recorded along with LV volume and ejection fraction.More diabetics than non-diabetics had CHF symptoms , and diabetics had a greater burden of CAD . Diabetics and non-diabetics did not differ, however, in total scar burden , number of segments with any scar , or grade 3–4 scar . LV ejection fraction  and end diastolic volume  were similar for both diabetics and non-diabetics, respectively.Despite a higher incidence of CHF and a greater burden of CAD in diabetics, there was no significant difference in the amount of myocardial scar, LV size or ejection fraction compared to non-diabetics. These findings are consistent with recent literature suggesting that the higher incidence of CHF in diabetics with IHD may not be due to larger infarcts with negative remodeling and systolic dysfunction, but rather to diastolic dysfunction or other factors yet to be accounted for.