Aims: Multimodal imaging has allowed cardiac amyloidosis (CA) to be increasingly recognised as a treatable cause of heart failure with preserved ejection fraction, but its prognosis remains poor due to late diagnosis. To assess the left ventricular diastolic function (LVDF) patterns in a large contemporary CA cohort according to the current recommendations and to identify their determinants. Methods and Results: We conducted a monocentric, observational study on a cohort of CA patients from a tertiary CA referral centre. Diastolic function was analysed using standard echocardiography and clinical, laboratory and survival parameters were collected. Four hundred and sixty-four patients with one of the three main type of CA were included: 41% had grade III diastolic dysfunction , 25% had grade II diastolic dysfunction, and 25% had grade I diastolic dysfunction; 9% were unclassified. No difference was found between the main CA types. After multivariate analyses, grades II and III were independently associated with dyspnoea, elevated NT-proBNP, cardiac infiltration and systolic dysfunction . Grade I patients had a better prognosis. Conclusions: All LVDF patterns can be observed in CA. One quarter of CA patients have grade I LVDF, reflecting the emergence of earlier stage-related phenotypes with a better prognosis.  Cardiac amyloidosis (CA) is an increasingly recognised cause of heart failure rather than a specific aetiology of rare restrictive cardiomyopathies ,2,3. IncWe conducted a monocentric, observational, retrospective study based on prospectively collected data at the French referral centre for CA . All patients with confirmed amyloidosis (light chain (AL), hereditary transthyretin (ATTRv) or wild-type transthyretin (ATTRwt)), with cardiac involvement and available echocardiographic data were included. Biomarkers, multimodality imaging, and biopsies when required were used to confirm the diagnosis as previously described ,11. PatiClinical , electrocardiographic  and laboratory parameters  were recorded at diagnosis. Amyloidosis severity was assessed using the Mayo Clinic score  for AL aEchocardiograms were performed and analysed by cardiologists blinded to clinical data using the Vivid 7 system . LV dimensions and interventricular septal thickness (IVST) were measured according to ASE recommendations from the parasternal long-axis view and were used to calculate LV mass index (LVMi) . LV ejecDiastolic function grade was assessed following the ASE/EACVI recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography , using aFollow-up began after echocardiographic evaluation. An “event” was defined as a composite of death, heart transplant or circulatory assist device. Event status and date were obtained from the usual patient follow-up visits, patient phone calls, or medical records. t-test or the Kruskal–Wallis test and categorical variables were compared using the χ2 test. We checked the linearity of continuous variables using fractional polynomial regression, and dichotomised non-linear continuous variables using their median . We performed univariate analysis to identify the LVDF determinants using a binary outcome: grade I diastolic dysfunction (non-elevated filling pressure) was compared to grades II and III (elevated). Variables associated with LV diastolic dysfunction with p value < 0.15 in univariate analysis were included in a multivariate logistic regression model. We assessed collinearity between IVST and LVMi, and between LVEF and GLS and only included IVST and GLS in the multivariate analysis model. p values less than 0.05 were considered statistically significant. Uni- and multivariate analyses were performed globally, and for each CA type . Missing data were handled using case-complete analysis. Cumulative event curves were plotted using the Kaplan–Meier survival method according to diastolic function grade. Differences between curves were tested by log-rank analysis. Survival was censored at last contact with the patient. Ten patients were excluded as they were lost of follow-up after the first diagnostic assessment. Statistical analyses were performed using STATA software version v14.0 .Continuous variables were reported as their mean +/− SD or median (interquartile range) depending on distribution, and categorical variables were expressed as numbers (percentages). Continuous variables were compared using Student’s Of the 584 AL and ATTR patients referred to our center between September 2008 and June 2017, 464 were included: 157 AL (34%), 176 ATTRwt (38%) and 131 ATTRv (28%) .p wave on the electrocardiogram) did not have any echocardiographic A wave . LVDF grading for these 371 patients in sinus rhythm according to algorithm B is depicted by LVDF was graded according to a specific algorithm for 93 patients with atrial fibrillation, revealing 23 (25%) with grade I LVDF b. Altogether, LVDF was graded for 421 (91%) patients: 115 (25%) grade I, 118 (25%) grade II, and 188 (41%) grade III . 2, mitral s’ < 8/cm/s) according to LVDF grade from grade I to III. Of note, s’ velocity was the most frequently altered LV parameter, whatever the LVDF grade, seen in 92% of the patients in Grade I, 98% in Grade II and 99% in Grade III, respectively.Multivariate analysis showed that factors independently associated with elevated LV filling pressures (LVDF Grade II–III vs. I) were NYHA class, LV septal thickness, GLS and NT-proBNP level . RegardiMedian follow-up of patients without an event was 26 (16–39) months and 168 (36%) patients experienced an event: 154 (33%) patients died , 11 received a heart transplant  and 3 had circulatory support (3 AL). This is the first study assessing the LVDF grades, defined by ASE/EACVI updated guidelines, in a large and contemporary cohort of CA patients. We showed that less than half of the study population (41%) had a restrictive mitral pattern (grade III LVDF) and a quarter (25%) had grade I LVDF, with significantly different prognoses. Four determinants of grades II and III LVDF were identified: systolic dysfunction, degree of myocardial infiltration, NT-proBNP plasma level and NYHA class. Less than half of the study population had a restrictive mitral pattern, yet CA is still perceived as the archetypal restrictive cardiomyopathy, characterised by an E/A ratio >2 . Indeed,In our study, systolic dysfunction assessed by LVEF or GLS and the degree of infiltration assessed by IVST or LVMi were independent LVDF determinants. No relationship was observed between age and LVDF grades despite a wide age range in the studied population, which is in contrast with a previous study in the general population . This inHowever, in the subtype analysis, IVST and GLS were not found to be LVDF determinants in AL, conversely to heart failure markers NYHA and NT-proBNP. This may reflect the consequence of diastolic and systolic function impairment and suggests that light chain deposits have a greater myocardial toxicity, meaning LVDF impairment can occur with fewer deposits ,11,26. NAtrial fibrillation is a diastolic dysfunction determinant in ATTRwt. This could be due to greater left atrial dilatation in this subgroup subsequent to myocardial thickening, which results in impaired LV compliance . AlternaCA prognosis is worse than other hypertrophic cardiomyopathies ,32. Our CA is rare, so our study was retrospective with a monocentric cohort. Currently, this is the largest CA cohort to represent the three main CA types and to evaluate LVDF using the recently updated definition combining multiple parameters. Some standard diastolic parameters were missing , which could have helped to grade patients with missing criteria. It also could have been of interest to analyse left atrial strain since recent literature showed its good prognostic value and diagnostic accuracy in CA. This echographical parameter might be useful in CA and will be the subject of further analyses ,37,38. MLess than half of the CA study population had a restrictive mitral pattern whatever the amyloidosis type patients with CA. Furthermore, one quarter presented with grade I LVDF, reflecting the emergence of earlier stage-related phenotypes with a better prognosis, due to well-established multimodality diagnosis criteria.


Our score showed a good performance, which is comparable to the 2010 TFC using those parameters, which are available in routine clinical practice  vs. AUC97%, p < 0.001 (95%CI 0.93–1.00). A score of 6/12 points yielded a specificity of 91% and an improved sensitivity of 67% for ARVC diagnosis as compared to a sensitivity of 41% for the abovementioned readily available 2010 TFC. Conclusions: ARVC patients present with significantly larger RA compared to athletes, resulting in a greater RAVI/LAVI ratio. Our novel diagnostic score includes readily available clinical parameters and has a high diagnostic accuracy to differentiate between ARVC and the athlete’s heart.Objective: The 2010 Task Force Criteria (TFC) have not been tested to differentiate ARVC from the athlete’s heart. Moreover, some criteria are not available  or subject to interobserver variability  in clinical practice. We hypothesized that atrial dimensions are useful and robust to differentiate between both entities and proposed a new diagnostic score based upon readily available parameters including echocardiographic atrial dimensions. Methods: In this observational study, 21 patients with definite ARVC were matched for age, gender and body mass index to 42 athletes. Based on ROC analysis, the following parameters were included in the score: indexed right/left atrial volumes ratio (RAVI/LAVI ratio), NT-proBNP, RVOT measurements (PLAX and PSAX BSA-corrected), tricuspid annular motion (TAM), precordial TWI and depolarization abnormalities according to TFC. Results: ARVC patients had a higher RAVI/LAVI ratio (1.76 ± 1.5 vs. 0.87 ± 0.2,  The athlete’s heart is a physiological condition of morphological and functional alterations induced by repetitive and intense exercise. The correct identification and recognition of exercise-induced alterations allows the differentiation of healthy subjects from patients who suffer from an underlying structural heart disease potentially mimicking the athlete’s heart. Exercise-induced changes involving both ventricles have been widely analyzed .There is a significant overlap between myocardial morphologic alterations described in arrhythmogenic right ventricular cardiomyopathy (ARVC) and the athlete’s heart, so that it is often challenging to distinguish the two conditions . The 201Until now, observational echocardiographic studies reported contrasting findings for cardiac function and dimensions in athletes compared to ARVC ,6,7. DatThe aim of our study was (1) to analyze dimensional changes of both atria in addition to conventional ventricular parameters in ARVC patients compared to a cohort of athletes, and (2) to provide a new diagnostic score developed upon readily available clinical parameters to help distinguish the athlete’s heart from ARVC in the clinical setting.www.arvc.ch (Accessed on 16 August 2021)) were matched 1:2 for age, gender and body mass index to 42 athletes referred for pre-participation screening. Athletes were defined as individuals engaging in regular exercise, training at amateur or professional levels based on a documented sports history [Twenty-one consecutive patients with definite ARVC according to the 2010 TFC from the ARVC registry at the University Hospital of Zurich . All patients prospectively included in our registry signed an informed consent prior to the study.A baseline TTE was performed at the time of first presentation and analyzed by experienced cardiologists. Left and right chamber measurements as well as RV outflow tract (RVOT) dimensions in the parasternal long axis (PLAX) and short axis (PSAX) were assessed according to current guidelines and adjusted for body surface area (BSA) ,11. AtriA baseline cycle ergometry with ramp protocol was performed at the time of first presentation. The maximal workload was calculated in Watts. Heart rate and blood pressure were measured at baseline and every minute during the test. A continuous ECG was registered. The double product factor  was calculated.Cut-off values for each variable were defined based on receiver-operating characteristic (ROC) curves. Quartiles were analyzed for parameters without normal distribution, and standard deviations were considered for parameters with normal distribution. Based on analysis of quartiles and standard deviations, 0 points were assigned for each parameter for which values were valid for >75% of athletes and for <25% of ARVC patients, 2 points were assigned for values valid for more than 75% of ARVC patients and for <25% of athletes, and 1 point was assigned for intermediate values. For dichotomic parameters (T-wave inversions (TWI) and depolarization abnormalities at baseline ECG), 1 point was assigned whenever this criterion was met. TWI were considered as pathological when present in at least two right precordial leads with extension beyond V3 in the presence of a complete right bundle branch block (RBBB). The same cut-offs values as in the 2010 TFC were considered for RVOT measurements. Sensitivity and specificity for ARVC diagnosis with the full 2010 TFC  were analyzed according to ROC curves. Our proposed novel score  ranges ft-test, Mann-Whitney U-test, Pearson Chi-square test or Fisher’s Exact test, as appropriate. Univariable analysis for relevant clinical covariates was performed by Pearson or Spearman’s test, as appropriate. A two-sided p-value of <0.05 was considered to be statistically significant. Optimal cut-off values for the score calculation were calculated using ROC curves.All statistical analyses were performed with SPSS software . Continuous variables are presented as mean (± standard deviation) and categorical variables are expressed as percentages, unless stated otherwise. Differences in baseline characteristics between the groups were assessed by independent Student’s n = 8 (67%) performed endurance sports, and n = 1 (8.3%) was a competitive endurance runner. All of them were advised to quit competition after being diagnosed with ARVC. Among the healthy athletes, n = 8 (19%) were professional, while the rest were competitive, non-professional athletes; n = 23 (54.8%) engaged in endurance sports and n = 19 (45.2%) in mixed activities.Baseline characteristics of ARVC patients and athletes are summarized in n = 8 (38%) vs. n = 1 (2.4%), p < 0.001). On ergometry, both populations performed a maximal exercise test, as highlighted by the double product factor. Athletes performed better and reached a higher maximal heart rate compared to ARVC patients.ARVC patients were more likely to have a positive family history of sudden cardiac death or ventricular arrhythmia  ARVC patients and in n = 1 (2.4%) of athletes. Despite no significant differences in LV ejection fraction, ARVC patients had a higher proportion of LV wall motion abnormalities . Similarly, ARVC patients had a worse LV diastolic function compared to athletes . A positive correlation between a higher RAVI/LAVI ratio and ARVC diagnosis, with a value of ≥1.11 being highly specific for ARVC, was found   .p < 0.001). A score value obtained by our novel score of 6/12 yielded a specificity of 91% and a sensitivity of 67% for a diagnosis of definite ARVC, while a score of 7/12 yielded a specificity of 100% and a sensitivity of 57%.Details regarding the 2010 TFC are summarized in p < 0.001, 95%CI 0.978–1.000). A sub-analysis of those 2010 TFC, which are easier to obtain  and regional wall motion abnormalities on TTE as well as repolarization and depolarization abnormalities on 12-lead ECG) revealed an AUC of 97% for definite ARVC diagnosis , with a lower sensitivity of 41% compared to our novel score (67%).ROC curves for the conventional 2010 TFC parameters  had the highest diagnostic performance  for ECG anomalies at rest, and n = 1 (2.4%) due to pre-syncopal events. Among ARVC patients, n = 4 were referred due to syncope or presyncope, n = 1 for dyspnea, n = 5 for evaluation of ventricular arrhythmias, n = 1 for ECG alterations and n = 10 for further analyses due to known positive familiarity for ARVC. Compared to ARVC patients, athletes had less abnormalities on baseline 12-lead ECG , mainly TWI in the precordial leads beyond V2 in the absence of a complete RBBB . First degree atrio-ventricular block and RBBB were similar in both groups (n = 3 (14.3%) vs. 4 (9.5%), p = 0.571 and n = 5 (23.8%) vs. 4 (9.5%), p = 0.127, respectively).Data are presented in To the best of our knowledge, this is the first study assessing the diagnostic value of atrial dimensions and serum NT-proBNP to differentiate between ARVC and the athlete’s heart, integrating these findings into a novel diagnostic score to better discriminate between both phenocopies.ARVC patients presented with significantly larger RA, but smaller LA dimensions as compared to athletes, resulting in a greater RAVI/LAVI ratio.The best novel diagnostic model to discriminate between ARVC (diagnosed by the full 2010 TFC serving as the diagnostic gold standard) and the athlete’s heart was obtained when including the following parameters: RAVI/LAVI ratio, RVOT in PLAX and PSAX, TAM, TWI and depolarization abnormalities on 12-lead ECG, and serum NT-proBNP with a diagnostic accuracy of 93%. A score value of ≥6 out of a maximum of 12 points was specific for a diagnosis of ARVC.Our novel diagnostic model showed a higher sensitivity to diagnose ARVC as compared to the 2010 TFC restricting to echocardiography and 12-lead ECG only, which are easy to obtain and readily available in daily clinical practice.We report the following main findings:The findings of this study are clinically relevant as they help cardiologists and sport medicine specialists differentiate those subjects in daily clinical practice who are more likely to suffer from ARVC and thus may need further specific investigations.There is a significant overlap between myocardial RV morphologic alterations described in ARVC and the athlete’s heart ,6,7. TheAmong the 2010 TFC criteria, the first one (RV imaging criterion) encompasses the evaluation of RV wall motion abnormalities and RVOT dilatation/RV dysfunction. This can be challenging since the echocardiographic window for the RV is narrow, particularly in dilated RVs, and lacks reproducibility ,13. CardThe second criterion of the 2010 TFC (tissue characterization by biopsy) is an invasive test usually not available in clinical routine, and often inconclusive due to the heterogeneous involvement of ventricular fibro-fatty infiltration, which spares the septum where biopsies are frequently taken from.ECG depolarization and repolarization abnormalities (third and fourth category of the 2010 TC) are easy to obtain, however, a significant overlap between ARVC and the athlete’s heart may be present, and repolarization abnormalities may disappear during the course of disease in both phenocopies ,16. In tPer study design, the 2010 TFC criteria had the highest sensitivity and specificity for ARVC diagnosis (gold standard). In routine clinical practice, often only imaging and electrocardiographic criteria are available to help in the differential diagnosis between ARVC and the athlete’s heart. However, these criteria alone have a low sensitivity for a diagnosis of ARVC vs. athlete’s heart. On the contrary, the sensitivity of our novel diagnostic score outperformed these conventional parameters.In our novel scoring system, we included well-established, readily available clinical and echocardiographic measurements that are less prone to interpretation with a very high specificity and good sensitivity with higher scores, making a diagnosis of ARVC more likely.The athlete’s heart is a physiological adaptation to repetitive and intense exercise leading to cardiac alterations. Data regarding the physiological exercise-induced alterations involving particularly the RA in athletes as compared to ARVC patients are scarce. Athletes undergo a repetitive right-sided volume overload which leads to a physiological enlargement of the right-sided cavities ,19. ThisPrevious data indicates that the RA, but also LA, are commonly affected by the disease process in ARVC, where it is driven by pressure and volume overload secondary to RV diastolic and systolic dysfunction, although a primary desmosomal impairment at an atrial level has been suggested as well . We repo2 greater than the general population, although it is associated with preserved compliance and lower LA stiffness index [LA enlargement is another key component of the athlete’s heart, which is associated with a worse cardiovascular outcome . The physs index ,24. We rRV enlargement is a common clinical feature of the athlete’s heart . AlthougNT-proBNP is an easily available blood test. Although in previous studies the suspicion for an acquired form of ARVC induced by strenuous physical activity was raised, athletes barely present NT-proBNP values exceeding 200 ng/L, while it is significantly higher in ARVC due to the underlying cardiomyopathy . We founAccording to current knowledge, TWI in precordial leads in adults correlate with RV structural anomalies and, as such, TWI beyond V2 in absence of a complete RBBB warrant further investigation . In athlWe performed our analysis based on TTE, since CMR data was not available in athletes, although it is considered the gold standard for the assessment of right-sided chambers and LA volumes. However, CMR is a time-consuming and expensive imaging modality, which is not used as a first-line screening method in clinical routine. Furthermore, this was a small observational study, and therefore the proposed clinical score needs validation in larger prospective cohorts.ARVC patients present with significantly larger RA as compared to athletes, resulting in a greater RAVI/LAVI ratio. A novel diagnostic score encompassing those clinical parameters that are easy to obtain and robust  had a high diagnostic accuracy to differentiate between ARVC and the athlete’s heart.


A 69-year-old woman with a history of hypertension and obesity, hospitalized with atypical chest pain, was diagnosed with left ventricular noncompaction. In-hospital monitoring of the cardiac rhythm revealed multiple episodes of atrial tachycardia and one episode of wide complex tachycardia (WCT) with left bundle branch block-like morphology and a right superior QRS axis. The electrocardiographic criteria were suggestive of a supraventricular origin of the WCT. Given the importance of reaching the correct diagnosis when dealing with a WCT, we tried to further define the pattern of ventricular activation using vectorcardiography (VCG). We analyzed the QRS loops during WCT in comparison to a sinus beat, a narrow complex tachycardia beat, and a premature ventricular contraction. The fast initial activation seen in the efferent limb of the QRS loop during the WCT was thought to be reflective of the fast initial activation via the conduction system seen in SVT with aberrancy, which was our final diagnosis for the WCT episode. This case illustrates a novel use of vectorcardiography as an additional diagnostic tool in the differential diagnosis of WCT. Differential diagnosis of wide complex tachycardia (WCT) represents a challenge for many physicians, given the various electrocardiographic (ECG) criteria available and, importantly, the associated therapeutic consequences of inaccurate diagnosis. Left ventricular noncompaction (LVNC) is a cardiomyopathy associated with heart failure, thromboembolism, or arrhythmias, including sudden cardiac death . Herein,A 69-year-old woman with a history of obesity and hypertension was hospitalized with atypical chest pain, palpitations, right upper quadrant pain, nausea, and weakness. Her medication included an ACE inhibitor, a thiazide-like diuretic, and aspirin. On arrival, her pulse was 94 beats/min, her blood pressure was 140/90 mmHg, and her oxygen saturation was 95% on room air. On physical examination, she appeared well, the skin was warm and dry, and there were no overt signs of congestive heart failure. An electrocardiogram A showed The echocardiogram B demonstGiven the newly diagnosed cardiomyopathy with reduced systolic function, a coronary angiogram was performed and revealed coronary arteries with no significant stenoses. The baseline rhythm was sinus, on a 48 h Holter recording that also demonstrated frequent premature atrial contractions, as well as multiple nonsustained runs of narrow complex tachycardia with an ECG pattern suggestive of SVT, likely atrial tachycardia. The recordings also included one episode of WCT with a QRS width of 150 ms, consisting of five beats, at a rate of 140 bpm, with left bundle branch block (LBBB)-like morphology and a right superior QRS axis . None of the Brugada or Vereckei criteria for VT were clearly present . Analysis of the mode of initiation of the tachycardia episode for both WCT and NCT  showed aGiven the importance of excluding VT, we tried to further define the pattern of ventricular activation during WCT using VCGs, which were generated from the 12-lead electrocardiographic monitoring tracings . We analThe timing and sequence of ventricular activation at baseline (sinus beats with narrow QRS) showed similar velocities of activation during the efferent and the afferent limbs. During NCT, ventricular activation showed a similar pattern, albeit slightly faster during the initial 20 ms than during the terminal 20 ms. During WCT, ventricular activation in the initial portion of the efferent limb was significantly faster (more widely distanced 1 ms markers) than in the afferent limb. This contrasted with the slow initial activation (closely spaced 1 ms markers) seen during the PVC. The fast initial activation seen in the efferent limb of the QRS loop during the WCT was thought to be reflective of the fast initial activation via the conduction system seen in SVT with aberrancy, which was our final diagnosis for the WCT episode.The patient was treated for heart failure with reduced ejection fraction according to the current guidelines, with a combination of a betablocker, an ACE inhibitor, a mineralocorticoid antagonist, and a loop diuretic. On this regimen, the patient improved clinically and, at her 12-month follow-up visit, reported no interval hospitalizations. There were no further WCT episodes during Holter monitoring, and the echocardiogram revealed an improvement in the LV ejection fraction to 48%.Demonstrated here as a case of a patient newly diagnosed with LVNC, who developed wide complex tachycardia with LBBB-like morphology and a superior axis. The diagnosis wzs made using the Brugada and Vereckei algorithms, as well as by analyzing the mode of onset of tachycardia. We also described a novel approach to delineate differences in ventricular activation velocity by VCG analysis, which confirmed the diagnosis of SVT with aberrant conduction.The American Heart Association classifies LVNC as a distinct primary cardiomyopathy with a genetic etiology , charactThe substrate for malignant ventricular arrhythmias and conduction disturbances in LVNC patients is multifactorial: Myocardial fibrosis, impaired flow reserve causing extended ischemia, and transmural heterogeneity with myocardial cells positioned around the deep intertrabecular recesses that may serve as slow conducting zones for re-entry . VentricThe WCT episode appeared more likely to be supraventricular in origin conducted with aberrancy. The two most established sets of criteria that help with the differential diagnosis of a WCT are included in the Brugada  and VereNone of the Verekei  criteriaWhen we analyzed the onset of the WCT, we identified a premature atrial contraction , very likely caused by a change in body position. Since the QRS axis and morphology seemed to be influenced, in part, by positional changes, we shifted our attention to the timing of ventricular activation in relationship to atrial activation to help clarify the WCT diagnosis.Perhaps one of the most compelling arguments for a supraventricular origin for the WCT episode in our patient was the analysis of the mode of tachycardia initiation . ComparaDifferences in ventricular activation velocity are extremely important when one is trying to discern the origin of a WCT. In SVT, initial activation is fast, via the conduction system, while in VT, it is slow because it occurs via muscle-to-muscle conduction. We used VCG, which is considered a complement to standard 12-lead ECG, offering a better insight into the spatial orientation and timing of the ventricular activation. VCG displays cardiac activation with a vector loop in three orthogonal planes—frontal (XY leads), horizontal (XZ leads), and sagittal (ZY leads)—and has been reported to be particularly helpful in defining ventricular activation in patients with conduction disease ,22. The Several observational studies have tried to define the VCG patterns associated with PVCs or VT ,23,24. WNote that the pattern seen in the sinus rhythm at baseline had markers relatively equally distanced on the afferent and efferent loops with fast ventricular activation via the conduction system during the initial as well as the 20 ms terminals of the QRS loop. During SVT with aberrancy, ventricular activation in the efferent loop appears to be faster than during sinus rhythm (in both cases via the conduction system), likely due to the fact that the amount of myocardium activated via the Purkinje network is significantly less than during sinus rhythm; therefore, it activates faster. Slow initial ventricular activation is one of the most important VCG criteria when diagnosing VT . This isAlthough comparative analysis of the speed of inscription in the initial portion of the QRS loop is based on a known pattern of ventricular activation in VT and SVT, the use of comparative analysis of the efferent and afferent limbs of the QRS loops, in addition to the more established ECG criteria for differentiating VT from SVT, is new. We believe that analysis of the VCG loop allows a better visualization of the three-dimensional geometry of the ventricular activation, which is ultimately one of the pillars in the SVT/VT differential.Given that reconstructed VCGs are readily available in most ECG and Holter monitoring systems, the addition of VCG analysis in the differential diagnosis of WCT could prove to be helpful when analysis of a reconstructed VCG is available.This case illustrated a novel use of vectorcardiography as an additional diagnostic tool in the differential diagnosis of WCT. If validated in future studies, this method could be incorporated into the diagnostic algorithms for WCT. This case also illustrated the need to integrate all information available and not to absolutize any criteria in the differential diagnosis process.


Functional tricuspid regurgitation (FTR) is common in left-sided heart pathology involving the mitral valve. The incidence, clinical impact, risk factors, and natural history of FTR in the setting of ischemic mitral regurgitation (IMR) are less known.We conducted a cohort study based on data collected from January 2012 to December 2014. Patients diagnosed with IMR were eligible for the study. The median follow-up was 5 years. The primary outcome is defined as FTR developing at any stage.2), LV internal diastolic diameter (LVIDD) 59.6 ± 3.94 (mm), RV fractional area change 22.3 ± 4.36 (%), systolic pulmonary artery pressure (SPAP) 48.4 ± 9.45 (mmHg). Independent variables associated with FTR development were age ≥ 65y [OR 1.2], failed revascularization, LA area ≥ 42.5 (mm2) [OR 17.1], LVEF ≤ 24% [OR 32.5], MR of moderate and severe grade [OR 419.4], moderate RV dysfunction [OR 91.6] and pulmonary artery pressure of a moderate or severe grade [OR 33.6]. During follow-up, FTR progressed in 39 (97.5%) patients. Covariates independently associated with FTR progression were lower LVEF, RV dysfunction, and PHT of moderate severity. LA area and LVIDD were at the margin of statistical significance .Among the 134 IMR patients eligible for the study, FTR was detected in 29.9% . In the FTR group, the average age was 60.7 ± 9.2 years , the mean LV ejection fraction (LVEF) was 37.3 ± 6.45 [%], LA area 46.4 ± 8.06 (mmIn our cohort study, FTR development and progression due to IMR was a common finding. Elderly patients with ischemic MR following unsuccessful PCI are at higher risk. FTR development and severity are directly proportional to LV ejection fraction, to the extent of mitral regurgitation, and SPAP. FTR tends to deteriorate in the majority of patients over a mean of 5-y follow-up.The online version contains supplementary material available at 10.1186/s12872-021-01982-y. Acute myocardial infarction directly affects myocardial viability and functionality and leads to structural remodeling and conduction changes seen immediately after an injury. The remodeling process results in valvular dysfunction and eventually hemodynamic changes. Ischemic mitral regurgitation (IMR) is a complication observed following the remodeling of the injured left ventricle –3.IMR is defined as mitral regurgitation following structural remodeling due to ischemic myocardial injury that is not directly related to valvular or sub-valvular pathologies such as mitral valve prolapse, endocarditis, autoimmune disease, medication, or direct radiation effect. The mechanism of IMR seems to be limited to leaflet motion, mainly due to shortening and limited relaxation of the ischemic papillary muscles. IMR is often classified as type IIIb of the Carpentier classification introduced in 1983, involving a restricted leaflet motion, most commonly the posterior leaflet . There cFunctional tricuspid regurgitation (FTR) is the consequence of various structural and functional changes involving the tricuspid annulus and the right ventricle. It is mostly secondary to left-sided mitral pathology in mitral regurgitation, mitral stenosis, and aortic stenosis , 9. PatiWe conducted an observational cohort study using Emek Medical Center's computerized database, a university-based secondary care center. Information regarding patient characteristics, demographics, and angiographic details were collected and analyzed using the Clalit health service database. Patients enrolled in the study were admitted to our heart institute for acute myocardial infarction (MI) from January 2012 to December 2014. Patients younger than 18 years and patients with primary mitral and tricuspid pathology and secondary pulmonary-related tricuspid regurgitation were excluded. The study population consisted of patients who developed mitral regurgitation following myocardial infarction. Patients were eligible for the study provided they met the inclusion criteria  was visually assessed  in multiple acoustic windows and calculated using the biplane Simpson method. Continuous-wave (CW) Doppler over TR peak gradient and the vena cava estimated central pressure using inferior vena cava (IVC) diameter and the respiratory fluctuation were used to estimate the systolic pulmonary artery pressures (SPAP) and the right atrial pressure followed by the categorization of severity grade and chamber size according to the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI) guidelines , 23.The planned sample size is based on multiple variables such as IMR and FTR prevalence and a group difference of at least 15% to demonstrate a statistical difference of 80% and alpha of 5% in a two-sided test. We had to include a minimum sample size of 164 patients. Preliminary analysis revealed that one out of five patients would be eligible for the study. Following these analyses, we extended the duration of recruitment for 2 years.Our institutional Ethics Committee approved the study following the Helsinki Convention. The Emek Medical Center IRB waived informed consent due to the use of anonymous patient data and the retrospective nature of the study .Continuous variables were presented using mean ± standard deviation. Categorical variables were presented using frequencies and percentages. A chi-square test was performed to analyze the association between the study groups and categorical variables. For continuous variables, we used the t-test . All confidence intervals are at the 95% level. TR progression was analyzed using the Mantel–Cox multivariant analysis, R-squared analysis, and One-way ANOVA. Multivariable models and linear regression analysis were used to estimate the predictors of FTR. Cut-off points for continuous variables as LVIDD, LA, sPAP, and LVEF were made using the highest sensitivity and specificity point in the ROC curve. The odds ratio was calculated using descriptive analysis in SPSS and linear regression models. Some variables such as age and gender were analyzed using the Cochrane-Armitage test. Forest plot and subgroup analysis for FTR Differences was done using JMP (SAS) and considered statistically significant at the 2-sided p level of 0.05. The statistical analyses were performed using the software SPSS (IBM) and SAS 9.4 (SAS).During the study period, 960 patients were admitted to the intensive cardiac unit due to acute MI. Of these, 274 patients were excluded from the study: 236 patients were excluded due to previous known MR, non-ischemic originating mitral regurgitation, and primary mitral pathology. Thirty-eight patients were excluded due to previous TR, secondary TR, and primary tricuspid pathology. Of the 686 eligible patients, 175 (25.6%) developed ischemic mitral regurgitation. Forty-one patients were excluded due to a lack of adequate follow-up TTE exams and low imaging quality. Thus, 134 patients were in the final study cohort . Older age was directly linked to FTR severity . Multivariate linear regression analysis indicated that failed revascularization during the indexed event was an independent covariate for FTR development and severity . Door-to-balloon (D2B) time of 90 min was achieved in 94% of cases and did not influence FTR development (p = 0.56). Gender, smoking, obesity, hypertension, hyperlipidemia, diabetes mellitus, peripheral vascular disease, atrial fibrillation, chronic renal failure, prior coronary bypass surgery, or the Killip class were not found to be different between patients who developed FTR and those who did not . The two groups' demographic characteristics revealed that patients who developed FTR were older .We did not find a significant statistical correlation between the infarct-related arteries involved or the existence of multiple coronary artery diseases with the development of FTR (p < 0.0001) , LV ejection fraction (LVEF), RV function , Systolic pulmonary artery pressure (SPAP) and MR severity grade with the development of FTR  Table . We inte1) Table .Table 2E‘FTR progression’ was defined as a deterioration in TR's severity at follow-up compared to the indexed event. During follow-up, FTR progressed in 39 (97.5%) of newly developed FTR patients.p = 0.001 for moderate and severe PHT), reduced LVEF (p < 0.0001), and moderate/severe RV dysfunction (p = 0.002). LA area and LVIDD were borderline significant . Moderate or severe MR was found to be statistically linked to FTR progression  . Group 2 and group 3 had mixed echocardiographic criteria . The mean survival time was 4.58 years (95% CI: 4.11–5.04 years) in the FTR group and 5.15 years (95% CI: 4.9–5.4 years) in the no-FTR group  and the interconnection between the mitral and tricuspid apparatuses –27. Our Multivalve involvement was described in the past regarding rheumatic heart disease and congenital heart disease and not extensively in the context of ischemic heart disease –32.Myocardial infarction is still the most common cause of HFrEF, and until recently, it was thought that its primary effect was directed toward left-sided pathology through an extensive remodeling process , 34.IMR is a common complication after myocardial infarction that requires adequate follow-up regardless of the appearance of clinical symptoms –37. MildOver a five-year follow-up, we could see that FTR developed in nearly a third of IMR patients, and more surprisingly, it progressed in almost all newly developed FTR patients. Elderly patients who had unsuccessful PCI seemed to be at a higher risk than others. We identify several echocardiographic predictors for FTR development and rapid FTR deterioration and a cut-off threshold for better monitoring and future management.Our findings are consistent with prior reports of left and right chamber interconnection. Deterioration of left side chambers resulting from extensive remodeling may shift volume and pressure initially toward unadjusted right-sided chambers and result in larger LA size and systolic pulmonary artery pressure. Over time, without proper optimal heart failure medical therapy, this may result in RV dysfunction and progressive development of FTR.Bivalvular regurgitation, particularly with the tricuspid valve's involvement, dramatically influences the prognosis of heart failure, limits therapeutic options, and substantially increases the overall mortality –41.IMR should be appropriately monitored and followed up regardless of symptoms. FTR should be assessed annually to avoid significant deterioration and start prompt treatment for heart failure before the first signs of heart failure appear.Our study is designed in a retrospective fashion. The data analysis was retrospectively reviewed on computerized patient medical records. Echocardiographic images were assessed according to the ASE criteria.Quantification of the severity of mitral and tricuspid regurgitation was based on qualitative grading. These assessment methods may be confounded by several technical and hemodynamic factors, including the jets' eccentricity and atrial size. However, we cannot accurately apply quantitative or semiquantitative methods because of the nature of the study.The influence of heart failure medical therapy and its contribution to valvular dysfunction could not be evaluated here due to a lack of clinical data. Larger samples are needed to evaluate these factors.In our cohort study, FTR was a common finding in IMR patients. Third of patients with ischemic mitral regurgitation developed functional tricuspid regurgitation (FTR). Elderly patients who had unsuccessful PCI are at a higher risk. FTR progression was observed in almost all patients over a 5-years follow-up period. Rapid FTR progression was observed in patients with moderate and severe MR, LVEF ≤ 24%, LA size ≥ 42.5 mm, LVIDD ≥ 56.5 mm, and RV of moderate and severe dysfunction. FTR was found to be positively linked to poor outcomes and lower survival rates.Additional file 1. Supplementary file.


The late 1990s saw the dawn of device-based treatments for HF when left ventricular assist devices were first approved by the US Food and Drug Administration as a bridge to transplant. This was followed in the early 2000s by US Food and Drug Administration approval of cardiac resynchronization therapy, where clinical benefits similar to those observed with drugs were seen in patients with medically refractory HF. Implantable cardioverter-defibrillators were also introduced for primary prevention of sudden cardiac death. The success of these device-based therapies, which are indicated to treat relatively small and specific subsets of patients with HF, inspired a generation of innovators to develop new devices to address the myriad of unmet needs encountered by patients with HF, as well as the health care systems tasked with providing their short- and long-term care.For decades, the cornerstone of heart failure (HF) treatment has focused on medical therapies, such as diuretics, afterload reducing agents, beta-blockers, and mineralocorticoid antagonists. During the 1990s, research showed the beneficial effects of these agents on hemodynamics, exercise tolerance  and Transcatheter Valve Therapies (TVT) meetings. In the same spirit, the inaugural Technologies and Heart Failure Therapeutics meeting,JACC: Basic to Translational Science includes Brief Reports summarizing the presentations delivered by all 7 companies along with video links to their presentations and the discussion by the judges. Collectively, these reports highlight the process of translational research and serve to inspire readers to join the quest to develop new devices for the treatment of HF!One of the highlights of Technologies for Heart Failure Therapeutics meeting was the “Shark-Tank” innovation competition, where 7 start-up companies presented their concepts to an esteemed panel of clinicians, regulatory experts, and investors. Company representatives summarized the fundamentals of their technology including intellectual property position, available preclinical and clinical data, regulatory strategy, and their ultimate business model, in hopes of capturing the vote of the judges as the company most likely to succeed. Technologies ranged from monitoring devices with machine learning backends to devices for acute decompensated and chronic HF. This special edition of The authors have reported that they have no relationships relevant to the contents of this paper to disclose.


CON: 29.6 ± 2.8 (mm/m2)0.5; p = 0.005). No inter-group differences were noted for peak global RV strain . Lower mid-wall strain was demonstrated in the SP compared to CON . Conclusion: Soccer training has the potential to increase RV size in pre-adolescent players. The unique segmental analyses used in this study have identified inter-group differences that were masked by global strain evaluations. The clinical and physiological implications of these findings warrant further investigation.Cardiac modifications to training are a product of the genetic pre-disposition for adaptation and the repetitive haemodynamic loads that are placed on the myocardium. Elite pre-adolescent athletes are exposed to high-intensity training at a young age with little understanding of the physiological and clinical consequences. It is unclear how right ventricular (RV) structure and function may respond to this type of stimulus. The aim of this study was to compare RV structure and strain across the cardiac cycle and within individual segments in elite soccer players (SP) and controls (CON). Methods: Twenty-two highly trained, male pre-adolescent SP and 22 age-and sex-matched recreationally active individuals CON were investigated using 2D echocardiography, including myocardial speckle tracking to assess basal, mid-wall, apical and global longitudinal strain and strain rate during systole (SRS) and diastole (SRE and SRA). Results: greater RV cavity size was identified in the SP compared to CON (RVD Pre-adolescent soccer players are exposed to high training demands at a young age, with reported intensities surpassing 85% maximal heart rate during intermittent high-intensity training and match-play  and the ensuing repetitive haemodynamic loads that are placed on the myocardium . The use of peak RV strain, both globally and segmentally, has recently been used in clinical adolescent populations and is potentially a useful diagnostic tool  in endurance trained (swimmers) compared to untrained pre-adolescents . The secondary aim was to explore the relationship between these RVindices and a surrogate measure of physical soccer performance (aerobic capacity). It was hypothesised that: (1) RV dimensions would be greater in the SP compared to the CON (2) global and temporal RV function would not be different when comparing the two groups and; (3) there would be significant relationships between RV morphology and function and aerobic capacity respectively.Twenty-two highly trained, male youth SP and 22 age- and sex-matched recreationally active individuals (CON) were recruited to participate in the study. The SP were recruited from two Category one Premier League youth soccer academies. Category one academies represent the highest achievable grade for professional youth soccer academies in the English Premier League. The CON participants were recruited from a local high school close to one of the Premier League Academy training grounds.n = 2) or a soccer related injury (n = 1). At the second club, researchers provided information to 15 U12 players and their parents, of which 2 were recovering from injury, one was released from the club after signing up from the study, and one signed up and simply did not attend the testing. This resulted in 11 participants from both clubs, with a total of 22 SP volunteering for the study. CON participants took part in compulsory physical education of 2 h per week (the same as SP), were all recreationally active and without engagement in systematic training. The CON self-reported 1.53 ± 1.77 h per week of physical activity  squad and their parents were approached, of which three were not enrolled because of either personal circumstance  and a sub-sample (n = 15) of the CON participants underwent an assessment of peak oxygen uptake  by experienced sonographers , to maximise quality control. A complete echocardiographic study was performed with an additional focus of the right-sided heart and all images were acquired and analysed in accordance with the American Society of Echocardiography (ASE)  and parasternal short axis (RVOT1), as well as distal level (RVOT2). A modified apical four chamber orientation was used to obtain measurements from the main body of the RV , mid cavity (RVD2) and RV length (RVD3). In addition, RV area was calculated in diastole (RVDarea) and systole (RVSarea) allowing the calculation of fractional area change (RVFAC). A 4 mm pulsed wave Doppler sample volume was placed at the level of the sub-pulmonary valve in the RV outflow tract allowing the assessment of the velocity time interval (RVOTVTI) and identification of pulmonary value closure (PVC), as the timing selected when the ascending side of pulmonary valve outflow trace reached baseline. Pulsed wave TDI was used to interrogate the RV lateral wall with a 2 mm sample volume positioned within the tricuspid annulus. Peak systolic (TDI-S’adj), early diastolic (TDI-E’adj) and late diastolic (TDI-A’adj) myocardial velocities were measured. RV: LV ratio was determined from basal measurements in the RV and LV taken from an apical 4 chamber view at end diastole  and early (SRE) and late ventricular diastole (SRA) were reported for the three wall segments and averaged to obtain a global value  from base-to-apex. The software automatically tracked 3 RV FW segments  and provided an interpretation on tracking quality. Furthermore, the operator provided a subjective assessment of tracking quality and segments were excluded if deemed unacceptable. The peak values for ε and SR files were imported into custom software . This software uses the speckle tracking data generated by Echopac and automates the analysis of the right ventricular changes. For each cardiac cycle, the software extracted ε data for each of the three segments of the RV FW only. Thus, the software also averaged ε values at each time point for each of the 3 FW segments  to provide an averaged value of ε and SR. For each of the 4 sets of data  the software applied a 500-point cubic spline to both the systolic and diastolic periods of the cardiac cycle (derived from PVC). The splined data was then used to identify systolic and diastolic peaks and relative timings for each of the 4 data sets. To facilitate temporal analysis, the software also calculated ε and SR values at 5% increments of the systolic and diastolic phases, respectively. Internal assessment of the software in our lab has found extremely strong agreement with peak ε and time to peak ε taken directly from Echopac’s analysis screens .Following speckle tracking analysis, the resulting raw t test was used to compare RV structure, function, ε and SR in SP and CON. TDI-A’ was not normally distributed and consequently a Mann Whitney U test was performed to evaluate inter-group differences. The relationship between RV morphology and function (ε and SR) and their relationship with D effect sizes were calculated for all inter-group comparisons. All statistical data was analysed using SPSS version 23.0, Chicago IL), with statistical significance granted at p < 0.05.Normality of data was assessed using the Shapiro–Wilk test. For normally distributed data, a Student’s independent 2 vs. CON: 1.33 ± 0.18 m2) was lower (p = 0.026) in the SP compared to CON. Resting heart rate was lower (p = 0.004) in the SP than CON . There was no significant inter-group difference in resting systolic (SP: 100 ± 8 vs. CON: 105 ± 13 mmHg) or diastolic (SP: 61 ± 9 vs. CON: 61 ± 10 mmHg) blood pressure. The SP demonstrated a higher (p = 0.0006) −1 ·min−1, respectively) although there was no inter-group difference for maximal HR (SP: 189 ± 7 vs. CON: 186 ± 9 beats.min−1).There was no inter-group difference for body mass (SP: 40.2 ± 5.8 kg vs. CON: 44.0 ± 11.7 kg) and stature (SP: 151.3 ± 6.3 cm vs. CON: 148.6 ± 7.3 cm). Body surface area  in the SP compared to the CON (Table p = 0.02) in the SP compared to the CON  0.21 ± 0.04 vs. (CON) 0.19 ± 0.04 cm.s−1.mm−1] and [TDI-A’adj: (SP) 0.11 ± 0.03 vs (CON) 0.11 ± 0.01 cm.s−1.mm−1].Larger RVDp = 0.04) time to peak for global longitudinal ε in the SP compared to CON (Table p = 0.00007) and SRA (p = 0.005) respectively were also identified in the SP compared to CON (Table p = 0.007) MW peak longitudinal ε was identified in the SP compared to the CON. Lower peak MW SRS (p = 0.0014) and MW SRA (p = 0.0039) were noted in SP compared to CON. Apical time to peak ε was longer (p = 0.02) in the SP compared to CON. Apical SRE was (p = 0.04) greater in SP compared to CON (Table p < 0.05) mid-wall ε  and 40% diastole (p = 0.0656).There was no inter-group difference in peak global longitudinal ε. There was a longer , peak MW SRS  and apical SRS , respectively. There were no other significant correlations between r =  − 0.479, p = 0.000) and MW ε and resting heart rate .Moderate, but significant correlations were derived between ε, however, interrogation of the RV using segmental ε analyses demonstrated lower peak ε in the SP compared to CON in the MW region of the RV. (4) lower MW ε was noted in mid-to-late systole and early diastole in the SP compared to CON and (5) significant correlations between The major findings from this study were: (1) larger RV dimensions in the SP compared to CON. (2) higher RVFAC in the SP compared to CON. (3) no inter-group difference for global peak longitudinal The morphological enlargements in RV cavity diameter noted in the SP in the present study are likely driven by repeated exposure to elevations in RV end-systolic wall stress from relative increases in pulmonary artery pressures  dimensions in SP compared to CON mimics the pattern seen in adult endurance athletes  has previously been seen in adult endurance athletes  towards greater lengthening at 35% diastole. This may be coupled with the enhanced SRE in SP than CON, driving the early diastolic pressure gradient between RA and RV.Similarly, interrogation of the SR segmental analyses identified the potential mechanism for globally reduced SRS in SP than CON. It would appear that the slower peak RV SRS was a product of a slower MW peak SRS in the SP, without differences in other RV FW segments between groups. Similar segmental SR findings were noted in the mid-wall segment in adult endurance athletes  and SRS global and segmental findings (lower in SP compared to CON), their subsequent relationships with The evidence of a significant relationship between As with all cross-sectional studies, the morphological and functional differences identified in this study ascribed potentially to high-intensity soccer training, could also be a product of genetic self-selection. Consequently, there is a need for a longitudinal evaluation of the effect of high-intensity soccer training on changes in RV morphology and function in males and females, as well as athletes of different ethnicities. Furthermore, the use of the cycle ergometer to obtain the ε. The use of global and segmental strain analysis may help to define the normative values in pre-adolescents who are highly trained athletes.Despite exposure to limited years of soccer training and a level of biological immaturity, this cross-sectional study demonstrated that pre-adolescent SP have larger RV dimensions than age- and sex-matched recreationally active peers. Furthermore, the novel segmental and temporal analyses adopted in this study demonstrated the first evidence of lower MW ε and SRS in SP compared to CON in this age group, despite unremarkable differences in global peak ε and SR between groups. This segmental and temporal analyses identified differences between trained and untrained groups, which would have been concealed with sole reporting of peak global longitudinal


Background: Four-dimensional automatic right ventricular quantification technology (4D auto-RVQ) is a new method that can simultaneously measure right ventricular (RV) structure and strain. The role of 4D auto-RVQ in determining RV function and hemodynamics is not clear. The role of 4D auto-RVQ in determining RV function and hemodynamics is not clear. We assessed the 4D auto-RVQ to measure right heart structure, function, and hemodynamics in patients with pulmonary hypertension (PHTN) correlated with right heart catheterization (RHC).Methods: We enrolled a prospective cohort of 103 patients with PHTN and 25 healthy controls between September 2017 and December 2018. All patients with PHTN underwent echocardiography and RHC. Patients were included if they underwent two-dimensional (2D) and 4D auto-RVQ echocardiographic sequences on the same day as RHC. We analyzed RV functional indices using 2D and 4D auto-RVQ analyses. We divided patients with PHTN into three groups according to echocardiographic image quality as follows: high (n = 24), average (n = 48), and poor (n = 4). Hemodynamic parameters were measured using RHC, including mean right atrial pressure, mean pulmonary arterial pressure, RV cardiac index (RV-CI), and pulmonary vascular resistance.Results: There were significant differences in most 2D and 4D auto-RVQ parameters between patients with PHTN and healthy controls. Interobserver variability showed significant agreement with 4D auto-RVQ for most measurements except for 4D end-diastolic volume. Indices measured by auto 4D-RVQ in the high-quality image group had a good correlation with RHC but not in the average- and poor-quality image group. Mid-RV diameter showed the best predictive power for the right RV-CI . RV end-systolic volume >121.50 mL had a 71.43% sensitivity and a 100% specificity to predict right RV-CI .Conclusions: 4D auto-RVQ may be used to estimate RV function and some hemodynamic changes compared with RHC in PHTN patients with high image quality. Furthermore, a large sample of the study is needed to evaluate RV function by 4D auto-RVQ in PHTN patients with average image quality. Echocardiography is the most commonly used imaging technique for the study of right ventricular (RV) morphology, volume, function, and tissue characterization , 2. The The right ventricle has a unique crescent shape and complex muscle moment, which influences the accurate evaluation of RV function. In patients with pulmonary hypertension (PHTN), the right heart chambers are significantly enlarged, and the scanning width of the echocardiography is insufficient to cover the entire right ventricle. The walls of the right ventricle can be difficult to identify. RV strain has been extensively used to evaluate the myocardial function and has predictive potential in patients with PHTN. RV strain is also recommended in European guidelines as part of the echocardiographic assessment of the right heart in adults , 6.Right heart catheterization (RHC) is recommended to confirm the diagnosis of pulmonary arterial hypertension (PAH) and to support treatment decisions . RV hemoRecently, 4D automatic RV quantification (4D auto-RVQ) has emerged as a new technology for comprehensive RV assessment. This technique can simultaneously measure RV volume, tricuspid annular plane systolic exertion (TAPSE), RV diameter, 4D ejection fraction (4D-EF), and longitudinal strain of the RV free wall and septum . In our Our study was a prospective cross-sectional project by design. Adult inpatients with PHTN and healthy volunteers were enrolled from September 2017 to December 2018. All patients with PHTN underwent echocardiography and RHC. Patients with PHTN were included if they had a diagnosis of idiopathic PAH, chronic thromboembolic PAH, connective tissue disease PAH, or residual PAH after surgery for congenital heart disease by RHC with a mean PAP of >25 mm Hg . All procedures were performed in accordance with the 1964 Helsinki Declaration and its later amendments.All patients underwent standard transthoracic echocardiography using a GE Vivid E9  with a 3.5-MHz phased-array transducer. Consecutive cardiac cycles were recorded during breath-holding with stable electrocardiography tracing. All patients underwent standard 2DE and Doppler echocardiography examinations with detailed evaluation of right heart function. A comprehensive evaluation of the right ventricle by 2DE obtained six standardized views, including the parasternal long-axis, RV inflow, parasternal short-axis, apical four-chamber, and subcostal views.Offline analysis was then performed on digitally stored images. Indices of 2DE included TAPSE and RV fractional area change. Right heart size was quantified as RV end-diastolic area at the end of the electrocardiogram (ECG) T-wave. RV chamber size was assessed at the apex of the ECG R-wave in the apical four-chamber view with a focus on the right ventricle. We measured pulmonary systolic pressure by Doppler tricuspid regurgitation peak velocity plus estimated right atrial pressure.Digital data were analyzed offline . Measurements using 4D auto-RVQ were acquired using the 4-V matrix-array transducer on the cardiac ultrasound GE system. Images were acquired using single beats with frame rates of ≥12 FPS. Apical RV-focused four-chamber views were acquired with patients in the lateral decubitus position. The transducer position was modified for optimal simultaneous visualization of the tricuspid valve, cardiac apex, and RV outflow tract. We visualized left ventricular apex, mid–mitral valve, aortic annulus, RV apex, mid–tricuspid valve, and RV diameter in the short-axis view  and perf2 was defined as reduced right heart function  ÷ CO [PAWP (pulmonary artery wedge pressure)]. CI <2.5 L/min/mfunction . The int2 test. Pearson correlation analysis was performed to evaluate the relationship between 4D auto-RVQ and strain, as well as those parameters measured using the reference method. Interobserver agreement for qualitative analysis score using 4D auto-RVQ manual and software assessments was calculated using the intraclass correlation coefficient. Receiver operating characteristic (ROC) curves were used to investigate and compare the predictive ability of 4D auto-RVQ parameters to evaluate right heart function. A p-value of <0.05 was considered statistically significant.Analyses were performed using SPSS version 20.0  and MedCalc 19.0.5. Continuous data are presented as mean ± standard deviation. Categorical data are presented as absolute numbers or percentages. Differences between groups were analyzed using the χn = 76) into three groups according to echocardiographic image quality as follows: high image quality (n = 24), average image quality (n = 48), and poor image quality (n = 4). Clinical and conventional echocardiographic and 4D auto-RVQ characteristics of adult patients with PHTN are described in There were 103 adult patients with PHTN and 25 healthy controls from September 2017 to December 2018. We excluded 27 patients on whom RHC was not performed on the same day as echocardiography. Finally, 76 patients diagnosed with PHTN by RHC were recruited. We divided patients with PHTN . We performed a correlation analysis of the 4D auto-RVQ indices and RHC indices in all PHTN cases .ROC curves , Table 6Despite its clinical importance, the study of RV function is technically challenging, in patients with PHTN. It is usually very difficult to evaluate RV morphology and function using 2DE. Recently, 3DE and 4DE have been introduced and are reportedly feasible and clinically applicable for RV volumetric quantification in patients with acquired RV pressure or volume overload . At presp < 0.001) was a significant determinant of all-cause mortality . Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.WW, BL, and MH drafted the manuscript. LN, YT, JL, JW, SY, and HL contributed to data collection and statistical analysis. HW, DH, CX, and ZZ provided supervision and revised the manuscript. CX contributed to the conception, design, and supervision of the study. All authors contributed to the article and approved the submitted version.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.


Selective sodium–glucose cotransporter 2 (SGLT2) inhibitors reduced the risk of hospitalization for heart failure in patients with or without type 2 diabetes (T2DM) in large-scale clinical trials. The exact mechanism of action is currently unclear. The dual SGLT1/2 inhibitor sotagliflozin not only reduced hospitalization for HF in patients with T2DM, but also lowered the risk of myocardial infarction and stroke, suggesting a possible additional benefit related to SGLT1 inhibition. In fact, several preclinical studies suggest that SGLT1 plays an important role in cardiac pathophysiological processes. In this review, our aim is to establish the clinical significance of myocardial SGLT1 inhibition through reviewing basic research studies in the context of SGLT2 inhibitor trials. As the incidence of type 2 diabetes mellitus (T2DM) is steadily increasing , sodium–Selective SGLT2 inhibitors and the dual SGLT1/2 inhibitor sotagliflozin were originally designed to aid glucose control in patients with diabetes mellitus. This pharmacological action is based on the blockade of SGLT2 in the kidney. Renal SGLT2 is a high-capacity glucose transporter that uses one sodium ion per glucose molecule to transport glucose into the intracellular space . It is lSince SGLT2 is upregulated in the kidneys of humans (and rodents) with diabetes  and at tLarge cardiovascular outcome trials have been carried out with the following selective SGLT2 inhibitors: empagliflozin ,5, dapagThe first dedicated HF trial with the SGLT2 inhibitor dapagliflozin (DAPA-HF)  showed tSeveral mechanisms have been proposed that could explain the clinically observed salutary cardiovascular effects of SGLT2 inhibitors ,29,30,31+/H+-exchanger 1 (NHE1) has recently been identified as a potential membrane transporter that is blocked by selective SGLT2 inhibitors in healthy rabbit, rat, and mouse cardiomyocytes [v1.5 channel in cardiomyocytes as a potential target for SGLT2 inhibitors [There is a growing number of studies suggesting that SGLT2 inhibitors exert direct cardioprotective effects. However, SGLT2 is not expressed in murine and human hearts to a relevant extent ,39,40,41myocytes ,43,44. Tmyocytes , whereasmyocytes . Finallyhibitors .Interestingly, a recent study using docking analysis found that the most selective SGLT2 inhibitor empagliflozin shows a relatively high binding affinity towards SGLT1, with much less affinity towards NHE1 . Given tA pivotal study established the relevance of SGLT1 inhibition on the population level, as well. Seidelmann and colleagues  found thBased on the above, it cannot be ruled out that SGLT1 inhibition could contribute to the salutary cardiorenal effects of SGLT2 inhibitors. In the following sections, we highlight how SGLT1 contributes to pathophysiological processes in the heart, so that the beneficial cardiac effects of myocardial SGLT1 inhibition could be appreciated.Several studies documented that humans with HF exhibit increased LV SGLT1 mRNA or protein expression as compared with non-failing controls, including those with dilated cardiomyopathy (DCM) , ischemiData are scarce regarding the possible regulators of myocardial SGLT1 expression in human hearts. A previous study identified that in patients with HCM or ICM, SGLT1 expression increased in conjunction with the activating phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) . HoweverIn line with data on human hearts, myocardial SGLT1 mRNA or protein expression was found to be upregulated in non-diabetic small animal models of acute myocardial ischemia–reperfusion injury  or ischeIn mice, AMPK and ERK1/2 were found to be responsible for upregulating myocardial SGLT1 during acute ischemia–reperfusion injury . In a ge+-K+-ATPase [Zhou and colleagues  were the+-ATPase . In huma+-ATPase . Therefo+-K+-ATPase in the human heart, instead it co-localized with aquaporin-1, a marker of capillaries. The authors postulated that SGLT1 expression in the heart is confined to the capillaries of the myocardium [+-K+-ATPase in the membrane of cardiomyocytes in LV sections from patients with end-stage HF [However, Vrhovac and colleagues  found thocardium . In contstage HF . Furtherstage HF . This isstage HF  showing stage HF . On the stage HF , and frostage HF  express stage HF ,74 and fstage HF  are alsoNeither global knock out ,76 nor cUnexpectedly, the increase in glucose uptake in cardiomyocytes from mice with global SGLT1 knockout was similar to that of wild-type controls during insulin stimulation or hyperglycemia . FurtherSeveral studies documented that SGLT1 plays an important pathophysiological role in the myocardium under diabetic conditions , as it m+ overload. The latter is a well-known phenomenon in HF [+ levels compared with non-diabetic controls, which could be further elevated during electric stimulation [+ uptake (while the Na+/K+-ATPase was blocked by ouabain) in cardiomyocytes originating from these diabetic rats, but not in those from healthy rats [+ uptake suggests a causal role of SGLT1, as the transporter uses the Na+ gradient to bring glucose into cells, unlike GLUTs. When extracellular glucose is absent (and the Na+/K+-ATPase is blocked by ouabain), SGLT1 is inactive and, therefore, no Na+ is transported into the intracellular space via this transporter, preventing intracellular Na+ accumulation.Importantly, SGLT1 transfers two sodium ions down the electrochemical gradient to bring one glucose molecule inside the cell. Therefore, chronic upregulation of SGLT1 in cardiomyocytes might not only result in intracellular glycogen accumulation, but also intracellular Naon in HF  and conton in HF . Lamberton in HF  found thmulation . Howeverthy rats . The facBesides cardiomyocytes, cardiac fibroblasts also express SGLT1 which might play an important role in the development of cardiac fibrosis. In human cardiac fibroblasts, high-glucose medium increased SGLT1 and matrix metalloproteinase 2 expression which was blocked by phlorizin . This waSeveral studies documented that SGLT1 contributes to cardiac perturbations under non-diabetic conditions . A recenPRKAG2 cardiomyopathy), myocardial glycogen content was increased alongside higher SGLT1 membrane expression [PRKAG2 cardiomyopathy has been established by evidencing that cardiomyocyte-specific knock down of SGLT1 in this genetic HF model rescued the cardiac phenotype [Myocardial SGLT1 not only contributes to the development of HF, but its conditional cardiomyocyte-specific overexpression for 10 weeks itself is sufficient to evoke LV dilation and systolic dysfunction coupled with increased myocardial glycogen content in mice . Howeverpression . In thespression . The cauhenotype .Apart from HF, SGLT1 has been implicated in the pathophysiology of myocardial ischemia. A recent study showed that knock down of SGLT1 increased cell viability following hypoxia–reoxygenation, and protected against acute myocardial ischemia–reperfusion injury in both in vivo and ex vivo settings, without affecting glucose uptake . As compThere is currently limited evidence that SGLT2 or SGLT1/2 inhibitors significantly interact with myocardial SGLT1, and if they indeed do so, the clinical relevance of this interaction is currently unclear. Nonetheless, SGLT1 plays a pathophysiological role in the heart under various conditions independent of diabetes, including ischemia and HF, whereas individuals with functionally limited SGLT1 are at lower risk of developing HF. Therefore, even if SGLT2 inhibitors do not significantly affect myocardial SGLT1 (which seems to be unlikely), the modulation of this transporter remains a potential target to counteract adverse processes in the heart.


Cardiovascular complications following the receipt of mRNA-based (Pfizer-BioNTech and Moderna) coronavirus disease 2019 (COVID-19) vaccines have not yet been described. In this case series, we describe two patients with clinically suspected myocarditis, one patient with stress cardiomyopathy, and two patients with pericarditis after receiving an mRNA-based COVID-19 vaccine. The two patients with clinically suspected myocarditis were otherwise healthy young men who presented with acute substernal chest pressure and/or dyspnea after receiving the second dose of the vaccine and were found to have diffuse ST elevations on electrocardiogram (ECG), elevated cardiac biomarkers and inflammatory markers, and mildly reduced left ventricular (LV) function on echocardiography. Both patients met the modified Lake Louise Criteria for acute myocarditis by cardiac magnetic resonance imaging. We subsequently discuss a case of a 60-year-old woman with known coronary artery disease (CAD) and previously normal LV function, who presented with new exertional symptoms, ECG changes, and apical akinesis following the second dose of the vaccine, and was diagnosed with a stress cardiomyopathy. Finally, we describe two patients with pericarditis who presented with chest pain, elevated inflammatory markers, and pericardial effusions after receiving the vaccine. Overall, this case series describes the first reported cases of myocarditis, stress cardiomyopathy, and pericarditis after receiving an mRNA-based COVID-19 vaccine. In December 2020, the Food and Drug Administration issued an Emergency Use Authorization (EUA) for two mRNA-based vaccines developed by Pfizer-BioNTech and Moderna for the prevention of coronavirus disease 2019 (COVID-19) . FurtherAlthough prior studies have shown that cardiovascular complications, such as myocardial infarction, myocarditis, ventricular arrhythmias, and stress cardiomyopathy, were prevalent in hospitalized patients with COVID-19 -6, cardiMyocarditisCase 1A 19-year-old male student with no significant past medical history presented to our hospital with acute substernal chest pressure and shortness of breath four days after receiving the second dose of the Pfizer-BioNTech vaccine.On presentation, he was afebrile, with a heart rate of 71 beats per minute (bpm), and blood pressure of 145/95 mmHg. Physical exam was unremarkable. His electrocardiogram (ECG) was notable for diffuse ST elevations Figure , and labCardiac magnetic resonance imaging (CMR) identified mild hypokinesis of the basal to mid lateral wall, with corresponding elevated native T1 values , elevated T2 values , and subepicardial delayed enhancement Figure -1E in thCase 2An 18-year-old male student with no significant past medical history was transferred to our hospital for management of worsening LV function following the second dose of the Moderna vaccine.He initially presented to another hospital, where he reported fevers, myalgias, and acute substernal chest pain one day after receiving the second dose. On presentation, his temperature was 101°F, heart rate was 120 bpm, and blood pressure was 110/59 mmHg. Physical examination was unremarkable. ECGs demonstrated diffuse ST elevations Figure , and labCMR revealed mild hypokinesis of the mid lateral wall, with corresponding elevated native T1 values  and T2 values , and subepicardial delayed enhancement Figure -2E in thStress cardiomyopathyA 60-year-old woman with a history of a stent placed in the left anterior descending artery (LAD) three years ago, and normal LV function and wall motion on echocardiography five months ago, presented to clinic four days after receiving her second dose of the Pfizer-BioNTech vaccine, with exertional chest pain and new inferolateral T wave inversions Figure . She wasPericarditisThe first patient was a 21-year-old woman with a history of idiopathic thrombocytopenic purpura, who presented three weeks after her first dose of the Pfizer-BioNTech vaccine with chest pain that worsened during inspiration and while supine. She was found to have sinus tachycardia, a small pericardial effusion on echocardiogram, and elevated inflammatory markers without evidence of myocardial injury. Based on the clinical presentation, the patient was diagnosed with pericarditis . Her symThe second patient was a 61-year-old woman with a history of hypertension who developed low-grade fevers, night sweats, chest discomfort and palpitations four weeks after her second dose of the Pfizer-BioNTech vaccine. She noted that her symptoms improved when leaning forward. On exam, she was found to have a friction rub. ECG revealed new-onset atrial fibrillation Figure  and echoIn this case series, we describe patients with clinically suspected myocarditis, stress cardiomyopathy, and pericarditis after receiving an mRNA-based COVID-19 vaccine. Since December 2020, over 865,000 residents in our metro area have been vaccinated .Since December 2019, SARS-CoV-2 has infected over 167 million people worldwide . CardiacWhile the definitive etiologies for these cases cannot be identified, the temporal association of the receipt of the vaccine and absence of other plausible causes suggest the vaccine as the likely precipitant of these rare events. Myocarditis and pericarditis are rare cardiovascular complications that have also been associated with vaccines such as the smallpox and influenza vaccines, and it has been postulated that the systemic inflammatory response to immunizations can lead to myocardial and pericardial inflammation ,14. TherWe report the first case series of patients with myocarditis, stress cardiomyopathy, and pericarditis after receiving the mRNA-based COVID-19 vaccines. While we cannot definitively prove association of the vaccines with these adverse events, we believe reporting these complications may enable further monitoring and investigation. However, it is crucial to emphasize that these findings are rare while SARS-CoV-2 infection is associated with a much higher incidence of cardiovascular complications.


Streptococcus pyogenes). RHD keeps position 1 as the most common cardiovascular disease in young people aged <25 years considering all the continents. The disease can lead to valvular cardiac lesions as well as to carditis. Rheumatic fever valvular injuries lead most commonly to the fusion and thickening of the edges of the cusps and to the fusion, thickening, and shortening of the chordae and ultimately to calcification of the valves. Valvular commissures can also be deeply compromised, leading to severe stenosis. Atrial and ventricular remodeling is also common following rheumatic infection. Mixed valvular lesions are more common than isolated valvular disorders. Echocardiography is the most relevant imaging technique not only to provide diagnostic information but also to enable prognostic data. Further, it presents a very important role for the correction of complications after surgical repair of rheumatic heart valvulopathies. Three-dimensional (3D) echocardiography provides additional anatomical and morphofunctional information of utmost importance for patients presenting rheumatic valvopathies. Accordingly, three-dimensional echocardiography is ready for routine use in patients with RHD presenting with valvular abnormalities.Rheumatic heart disease (RHD) remains to be a very important health issue worldwide, mainly in underdeveloped countries. It continues to be a leading cause of morbidity and mortality throughout developing countries. RHD is a delayed non-suppurative immunologically mediated inflammatory response to the throat infection caused by a hemolytic streptococcus from the A group ( Streptococcus pyogenes) can be observed in cases of throat infection after tonsillitis in high-income countries. However, such infections in developing or average-income countries can lead to carditis and permanent valve damage as a consequence of repeated attacks of RF (Rheumatic fever (RF) and rheumatic heart disease (RHD) continue to be very important health issues across different continents, affecting mainly developing or average income countries, as determined by the World Heart Federation position statement and by the Health Statistics Census from those nations , 2. Globks of RF , 3. Worlks of RF .Clinical manifestations of acute RF can be pleomorphic, including fever, arthritis, carditis, chorea, subcutaneous nodules, and erythema marginatum. The prevalence rates of RHD in school-age children in developing countries vary from one to five cases per 1,000, mainly in sub-Saharan Africa . In someIt is known that ~60% of RHD patients who present with heart failure during their first acute RF attack demonstrate valvular disease 10 years later , 12. ProThe pathogenesis of acute rheumatic carditis seems to be related to the immune-mediated response following GAS infection, the production of antibodies against GAS pharyngitis, and GAS production of aggressive elements such as streptococcal M protein, which can trigger an autoimmune response.The activation and infiltration of T cells into the valves produce a disarray of the normal valvar cell arrangement and changes in valvar collagen. There is also activation of inflammatory cytokines, granulomatous inflammation, and CD4+ T cell-mediated delayed hypersensitivity against GAS. The pathognomonic lesions of the rheumatic process in the endocardium of the heart valve and in the myocardium are called Aschoff bodies and are observed as granulomatous inflammation. Valve lesions may be progressive, leading to chronic sequelae such as valvular stenosis and insufficiency, as well as to carditis, heart failure, and pulmonary hypertension. In addition, these aggressive effects depend on evidence of a susceptible host, as well as the level of host autoimmune response.Echocardiography, in its various modalities, is a diagnostic imaging investigation technique that has clinical applications in countless scenarios for various heart diseases –48.From the first observations in M-mode, echocardiography has had several advances in technique with the advent of two-dimensional (2D) transthoracic echocardiography with the Doppler technique (and its various presentations), transesophageal echocardiography, strain from speckle-tracking technique and echocardiography, and 3D transthoracic and transesophageal echocardiography with pocket transducers and cell phone acquisition using nanotechnology and miniaturization –15.3D echocardiography results in multi-structural cardiac observation from multiple planes and the rotation of not only the observation planes but also the cardiac structure in relation to a specific investigation plane –48. 3D e3D echocardiography provides very important clinical applications for the understanding of heart valve diseases, cardiomyopathies, and congenital heart diseases; it is essential for operative planning in cardiac surgeries, for percutaneous transcatheter procedures in the operating room/hybrid room for the treatment of valvular heart disease or congenital heart disease, and for the correction of complications related to surgical treatment of valve diseases  –48.3D echocardiography was developed to overcome the limitations of conventional 2D echocardiographic analysis. 3D analysis allows the observation of cardiac structures without the use of mathematical formulae and geometric inferences for cardiac chamber measurement . 3D echocardiography makes volumetric quantification of the cardiac chambers more realistic and closer to actual anatomical observation. It provides a greater proximity to measurements made by nuclear magnetic resonance , 32–34, The idea of 3D echocardiography arises from the reports of Baum and Greenwood during their observations of the human orbit in 1954 . In 1974The mitral valve apparatus comprises a 3D complex of different structures that enables emptying of the left atrium and filling of the left ventricle during the diastolic phase of the cardiac cycle –67. It iFully understanding and detailed investigation of the normal mitral valve apparatus is key to better determining the level of RF aggression, imbalance, and distortion.RHD can affect the mitral valve, causing pure mitral stenosis  or combined mitral stenosis and regurgitation (40%) . RHD mosTwo decisive situations that can definitely change not only the mitral valve apparatus anatomy but also the function, and most importantly, impact prognosis, are RF attacks (carditis)  and infeEchocardiography was incorporated into the revised Jones criteria for the identification of rheumatic aggression in 2015 , as cardA score to predict the feasibility and success of mitral valve percutaneous valvuloplasty was originally described by Wilkins et al. in Boston, USA, in 1988, in 22 patients with mitral valve stenosis, with cross-sectional and 2D echocardiography . In the Considering percutaneous balloon mitral valvuloplasty, 3D echocardiography-based scores provided additive information that could predict post-procedural outcome and suboptimal results. 3D echocardiographic analysis enabled a more comprehensive observation of post-procedural posterior-commissural splitting when compared to 2D observation .Although non-invasive multimodality diagnostic investigation has gained tremendous new advances, invasive hemodynamic measurements still present a diagnostic hallmark concerning RHD. The comparison between non-invasive and hemodynamic evaluation is of great concern and interest to cardiac surgeons and clinical cardiologists. For patients presenting mitral valve stenosis, a combination of 3D echocardiography and invasive information  proved to provide a better correlation to invasive measurement of the mitral valve area measured by the Gorlin equation, when compared to the three-dimensional planimetry method .Another important issue that 3D echocardiography could provide additional information on is related to the analysis of the left atrium (volumes and function) , 76, 77.3D echocardiography can also provide automatic information concerning the left atrium appendage, when considered to be percutaneously closed.Mitral valve rheumatic disease regurgitation caused by rheumatic valvular lesions is observed as thickening, calcification, scarring of the cusps, chordal shortening leading to valvular lack of coaptation, and restriction of valvular movement. Complete mitral valve rheumatic disease regurgitation analysis should employ different echocardiographic techniques for complete anatomical and morphological investigation  and to grade the insufficiency. Thus, we should try to obtain parameters such as vena contracta, vena contracta area, regurgitant volume, regurgitant fraction, and regurgitant orifice.3D echocardiography enables multi-angular spatial observations, mainly in the very particular “en face” view of the mitral valve. It also allows not only the ventricular view but also the ventricular approach, as well as simultaneous observations from the left atrial and ventricular views. 3D transesophageal observation enables a perfect analysis, as in the surgical view from the operating room. In addition, 3D color flow echocardiography enables accurate identification of the origin of the regurgitant jet and the quantification of the number of jets. The quantification of 3D mitral regurgitation vena contracta is employed as a semiquantitative method to grade insufficiency and can be used to overcome two-dimensional PISA limitations , 78, 79.3D echocardiographic analysis of the mitral valve is very important and valued for transcatheter treatment of mitral disease while managing periprosthetic leaks and valve-in-valve procedures.In acute attacks of RF, the presence of small vegetations on the line of closure of the insufficient mitral valve may lead to a misleading gross and echocardiographic diagnosis of infective endocarditis, even more because the acute RF attack is a febrile disease.Also, 3D echocardiography can be currently employed to provide automatic information from the mitral valve apparatus, concerning the annulus dimensions, annulus height, tenting area, planar and non-planar angles, shape, sphericity index, intertrigonal and intercommissural distances, and information from the leaflet coaptation .2. On analysis, measurement with 3D echocardiography provides greater accuracy, showing better reproducibility. 3D echocardiographic analysis also allows better observation of the etiology of aortic valve disease, allowing for a better structural observation of anatomical changes such as rheumatic disease lesions, biscuspid valves, quadricuspid valves, degenerative changes such as Lambl's excretions, and tumors such as papillary fibroelastomas , the degree of left ventricular hypertrophy, analysis of left ventricular diastolic function, the analysis of arterial valve impedance , the analysis of associated heart valve diseases , the degree of hypertension, and the analysis of the performance of the right ventricle.Analysis of the aortic valve area is of great importance in analyzing the severity of aortic stenosis. A widely used method for measuring the aortic valve area is the continuity equation using 2D echocardiography. In this method, a circular shape is assumed for the ventricular outflow tract, which, in a large number of cases, is different from the actual elliptical anatomical shape . This inAnother method for assessing the aortic valve area consists of using the left ventricular stroke volume measured by 3D analysis . To measMeasurement of the aortic area using the 3D LV stroke volume method is as follows:Left-ventricle stroke volume, measured by 3D echocardiographyAortic valve velocity time integral (TVI)This method, using left-ventricle stroke volume for the evaluation of the aortic area, has better correlation with invasive methods (Gorlin equation) than bidimensional methods.The analysis of the severity of aortic stenosis using 3D echocardiography has better correlation with measurements using other imaging methods (computed tomography and magnetic resonance imaging), when compared with 2D echocardiographic analysis . In addiThe use of echocardiography for quantification and evaluation of the hemodynamic and anatomical impact of aortic valve insufficiency allows accurate observation and determination of the temporal moment of the natural history of patients with aortic insufficiency. The morphofunctional analysis of the patient with aortic insufficiency should take into account the etiological evaluation of the valve disease, the diameters of the ascending aorta, the diameters of the left ventricle, myocardial performance analysis (left ventricular ejection fraction), the quantification of severity of insufficiency with measurement of the contracted vena, the observation of the width of the jet in the left ventricular outflow tract, the measurement of the regurgitant fraction, the regurgitant volume, and the ERO.The use of 3D echocardiography provided new insights into the analysis of the severity of aortic valve insufficiency , 89, 91.2. Tricuspid rheumatic valve disease demonstrates similar findings to those observed in mitral valve aggression. Thus, fusion and thickening of the cusps, diastolic cuspal doming, thickening, shortening, fusion, and retraction of the chordae, commissural thickening and fibrosis, and calcification/scarring of the different elements of the valvular apparatus can be found over time after rheumatic onset .Another important condition that can be very well-visualized with the addition of 3D echocardiography is tricuspid lesions due to infective endocarditis .2 in adults, with a peak transpulmonic flow velocity of >4 m/s, along with the demonstration of restriction of leaflet mobility with a doming appearance on systole, calcification, and thickening of the leaflets. The use of 3D transesophageal echocardiography may add diagnostic information to anatomical investigation of the pulmonic valve, when compared to the 2D echocardiographic approach , atria volumes, and emptying fractions.3D echocardiography techniques are subject to the physical limitations of ultrasound, such as inadequate image quality, planar variation within the acquired image, the occurrence of image artifacts, gain adjustments , the occurrence of cardiac arrhythmias, and breathing variations during image acquisition. Also, the possible occurrence of artificial thickening of the cardiac structures displayed in volume rendering, the unreliability for tissue characterization, and the interobserver bias  are of great importance, in addition to the need for specific training to obtain and analyze the images. In developing countries, 3D echocardiography equipment is still limited by cost. In the future, a better analysis of RHD patients should be considered, taking into consideration a multimodality approach .RHD is a very important health issue worldwide, mainly in underdeveloped countries. Echocardiography is the most relevant imaging technique providing diagnostic information, enabling prognostic data, and presenting a very important role in the correction of complications after surgical repair of rheumatic heart valvulopathies. Accordingly, 3D echocardiography is ready for routine use in patients with RHD presenting with valvular abnormalities.MV, CB, AG, PV, LB, LD, PG, VA, FT, and RS: planning, conduct, and reporting. MV: guarantor. All authors contributed to the article and approved the submitted version.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.