Conclusions: Features related to pulmonary hypertension are fast and easily measurable on pre-TAVR CT and offer great potential regarding non-invasive detection of pulmonary hypertension in patients with severe AS and can support the echocardiographic diagnosis. In this study, the diameter of the main pulmonary artery with the additionally determined ratios were superior to the values of the right and left pulmonary artery. Additional indexing to body surface area and thus further individualization of the parameters with respect to height and weight can further improve the diagnostic quality.Background: Computed tomography (CT) of the aorta and cardiac vessels, which is performed in patients with severe aortic valve stenosis (AS) before transcatheter aortic valve replacement (TAVR), offers the possibility of non-invasive detection of pulmonary hypertension (PH), for example, by determining the diameter of the main pulmonary artery (PA), the right pulmonary artery (RPA) or the left pulmonary artery (LPA). An improvement of the significance of these radiological parameters is often achieved by indexing to the body surface area (BSA). The aim of this study was to compare different echocardiographic systolic pulmonary artery pressure (sPAP) values with radiological data in order to define potential clinical cut-off values for the presence or absence of PH. Methods: A total of 138 patients with severe AS undergoing TAVR underwent pre-interventional transthoracic echocardiography with determination of sPAP values and performance of CT angiography (CTA) of the aorta and femoral arteries. Radiologically, the PA, RPA, LPA, and ascending aorta (AA) diameters were obtained. Vascular diameters were not only indexed to BSA but also ratios were created with AA diameter (for example PA/AA-ratio). From these CT-derived vascular parameters, AUROC curves were obtained regarding the prediction of different sPAP values (sPAP 40–45–50 mmHg) and finally correlation analyses were calculated. Results: The best AUROC and correlation analyses were generally obtained at an sPAP ≥ 40 mmHg. When considering diameters alone, the PA diameter was superior to the RPA and LPA. Indexing to BSA generally increased the diagnostic quality of the parameters, and finally, in a synopsis of all results, PA/BSA had the best AUC 0.741 (95% CI 0.646–0. 836;  Pre-interventional computed tomography (CT) diagnostics in patients with severe aortic valve stenosis (AS) is currently standard practice for planning a transcatheter aortic valve replacement (TAVR) procedure . In thisIn addition to accurate preoperative/pre-interventional planning, CT diagnostics are also able provide evidence for the presence of pulmonary hypertension (PH) in patients with severe AS ,4,5. In Since right heart catheterization is no longer routinely performed prior to TAVR, transthoracic echocardiography is currently used in clinical practice as the gold standard to assess the presence of PH ,9. In moThus, the aim of the retrospective multi-center study design presented here was to compare CT morphological vascular parameters potentially associated with PH with different echocardiographically obtained sPAP values in order to draw further noninvasive conclusions about PH in TAVR patients. On the one hand, this is to strengthen the validity of echocardiography and, on the other hand, to establish cut-off values for various radiological vascular parameters in TAVR patients with PH.This study population originally included 163 patients undergoing TAVR procedure between 2016 and 2018 at Paracelsus Medical University Hospital Salzburg and Kepler University Hospital Linz. Twenty-five patients had to be excluded due to missing weight or height data, missing CT data, or inadequate CT quality. Finally, 138 patients were recommended for inclusion in the study. The study protocol was authorized by the local ethics committees of Paracelsus Medical University Salzburg (415-E/1969/5-2016) and Johannes Kepler University Linz (E-41-16) and conducted in accordance with principles of the Declaration of Helsinki and Good Clinical Practice. Written informed consent was available from all study participants.Transthoracic echocardiography was routinely performed before TAVR by using common ultrasound devices .2 for definition of severe AS. Left ventricular ejection fraction (LVEF) was calculated by usage of the Simpson’s method. Graduation of mitral, aortic, and tricuspid valve regurgitation in minimal, mild (I), moderate (II), and severe (III) was done by spectral and color-Doppler images. Maximum tricuspid regurgitant jet velocity (TRV) was obtained by continuous wave Doppler over the tricuspid valve. Pulmonary artery pressure (PAP) was calculated using the formula 4 × TRV2. To this value the estimated right atrial pressure (RAP) was added, which was determined by the diameter of the inferior vena cava (IVC). An IVC diameter ≥ 21 mm and a respiratory caliber fluctuation < 50% led to a RAP of 15 mmHg. For an IVC diameter < 21 mm as well as a respiratory caliber fluctuation ≥ 50%, a RAP of 3 mmHg was assumed. Other scenarios not corresponding to these constellations were provided with an intermediate value of 8 mmHg. The simplified Bernoulli equation (4 × TRV2) + RAP was applied to obtain a sPAP result. Different sPAP  values were used to determine PH in accordance with the current literature [Severe AS was categorized according to current guidelines of ESC using an AV Vmax  of 4.0 m/s, an AV dpmean  ≥ 40 mmHg and an aortic valve area ≤ 1.0 cmterature ,12,13,14Study patients at both centers—the University Hospital Salzburg and the Kepler University Linz—routinely received a pre-interventional, ECG triggered CT angiography (CTA) of the whole aorta and femoral arteries to assess, among others, the aortic annulus size, the aortic anatomy and vascular access. CT scans were performed on multidetector CT scanners  with a patient size-adapted tube voltage (80–120 kVp) and active tube current modulation. A bolus-tracking technique was applied with a 100 mL bolus of non-ionic iodinated contrast media followed by 70 mL saline solution injected at a flow rate of 3.5–5 mL/s.The widest short-axis diameter of the main pulmonary artery (PA) within 3 cm of the bifurcation of the pulmonary trunk.The widest short-axis diameter of the ascending aorta (AA) at the level of the bifurcation of the pulmonary trunk.The widest short-axis diameter of the right pulmonary artery (RPA).The widest short-axis diameter of the left pulmonary artery (LPA).A stationary workstation  was used for image analysis. Two experienced investigators, blinded to all clinical and hemodynamic information, performed the following measurements in mediastinal window settings on axial vessel cross sections on double oblique CT angiographic images as recommended previously ,16:The w0.725 × Weight0.425), thus providing PA/BSA, RPA/BSA, LPA/BSA, PA/AA/BSA, RPA/AA/BSA, and LPA/AA/BSA.An illustration of the measurements performed and the corresponding placements is shown in Statistical analysis with graphical representations was performed using SPSS .A Kolmogorov–Smirnov test was carried out to test variables for normal distribution. Normally distributed metric data was expressed as mean ± standard deviation (SD). Not-normally distributed metric data was expressed as median and interquartile range (IQR). Frequencies/percentages were used for categorial data and compared using the chi-square test.Area Under the Receiver Operator Characteristics (AUROC) curves with Area Under the Curve (AUC) were performed using different sPAP values (sPAP 40–45–50 mmHg) to obtain the cut-off values for the respective, CT morphological vascular parameters. In addition, sensitivity, specificity, and Youden Index (YI) were calculated separately.Correlation analyses were performed using Spearman’s rank-correlation coefficient to determine the strength between different sPAP-values (again sPAP 40–45–50 mmHg) to different CT-measurements mentioned above .p-value < 0.050 was considered statistically significant.A Regarding the demographics, 52.2% of the total cohort were male, with an overall mean age of 82.98 ± 5.05 years; 22.5% of the patients had diabetes mellitus, 81.9% had arterial hypertension, 34.1% had atrial fibrillation, and 8.0% had COPD. Echocardiography documented an average sPAP of 44.94 ± 16.65 mmHg. In this regard, 63.0% of patients had an sPAP of ≥40 mmHg and 50.0% had an sPAP ≥ 45 mmHg. CT morphology measured the main pulmonary artery (PA) to be 29.89 ± 5.45 mm and the ascending aorta (AA) to be 35.10 ± 4.61 mm. A PA diameter ≥ 29 mm according to the 2015 ESC guidelines .In 2  and secondly for the ratio from PA/AA/BSA with a cut off value of 0.42 . Another AUC value ≥ 0.700 was provided by the PA/AA ratio with a cut off value of 0.80 .The best results in the present constellation were obtained at an sPAP of ≥40 mmHg A, first,At an sPAP of ≥45 B or ≥50 2; AUC 0.676; 95% CI 0.569–0.783; p = 0.003; YI 0.39; sensitivity 0.63; specificity 0.76). However, no CT morphological parameter reached an AUC ≥ 0.700 in this case.Similar to With an sPAP ≥ 45 mmHg B and 50 A direct comparison between the AUROC results of the right and left pulmonary artery can be achieved by comparing Here, it is noticeable that the AUROC results of LPA behave similarly to those of RPA. The ratio of LPA/BSA remains the leading combined CT parameter for predicting sPAP ≥ 40 mmHg A, ≥45 mm2; AUC 0.698; 95% CI 0.569–0.827; p = 0.002; YI 0.45; sensitivity 0.63; specificity 0.82).The only difference from the previous results is that the highest AUC for the LPA/BSA ratio in this case is not found at an sPAP ≥ 40 mmHg but at an sPAP ≥ 50 mmHg  and CT morphological criteria of pulmonary hypertension, Spearman correlation analysis was performed .p < 0.001. This dropped significantly in the further course to sPAP ≥ 45 mmHg and ≥50 mmHg. A comparable correlation coefficient of 0.398 was exhibited by the ratio of PA/AA/BSA at an sPAP ≥ 40 mmHg. The correlations in which the isolated right or left pulmonary artery was involved never reached a value ≥ 0.300 with regard to the correlation coefficients.The best positive correlation was found between sPAP ≥ 40 mmHg and PA/BSA ratio with a Spearman correlation coefficient of 0.408 and a At an sPAP of ≥40 mmHg, this study showed the best results regarding agreement between CT-derived vascular parameters and echocardiography in both, AUROC results and correlation analyses. Accordingly, a further increase of pressure in the pulmonary circulation with, for example, an sPAP ≥ 45 mmHg or ≥50 mmHg did not lead to a further increase in the vessel diameter of pulmonary trunk or right or left pulmonary artery, respectively compare .4).Reasons for this could potentially be explained by the following pathophysiological mechanisms: In the pulmonary trunk as well as the central pulmonary arteries, chronic pressure load leads to increased fragmentation of the elastic fibers . This irA direct comparison of the diagnostic significance and agreement of PA, LPA, and RPA with respect to different sPAP values provides a superiority of the PA diameter compared with both pulmonary arteries not only with respect to AUROC results but also with respect to correlation analyses. These results were almost congruent with a work of Rehman et al. , who comReasons for this constellation can only be speculated, but are most likely to be attributed to anatomical conditions. Since the left lung, in contrast to the right lung, has only two lobes, the left pulmonary artery is in most cases the vessel with the smaller caliber. This could also be demonstrated in this work purely descriptively on the basis of the baseline characteristics, since the right pulmonary artery with a diameter of 27.55 mm has a larger caliber diameter on average by 2.1 mm than the left pulmonary artery with a diameter of 25.45 mm. Thus, already in the physiological state, there are different baseline positions between left and right pulmonary artery, which are additionally dependent on body size and weight. Accordingly, indexing to the BSA improved the diagnostic quality, but did not reach the significance of the pulmonary trunk by far.The diameter of the AA is already pathophysiologically not consistent with PH, but rather with generalized arterial hypertension. Accordingly, the almost absent correlations to echocardiographic sPAP can be interpreted.In the 2015 ESC guidelines , a pulmoIn this work, however, it is clear that almost every measurement performed on CT associated with pulmonary hypertension leads to improved significance and thus diagnostic quality by indexing to the patient’s individually calculated body surface area.2, with an AUC of 0.750. In the present study, the cut off ranged from 14.84 mm/m2 to 16.65 mm/m2, which was slightly lower. Simultaneously to the results of Sudo et al., the diagnostic predictive value of the pulmonary trunk was also significantly increased in our data after indexing to the BSA and also showed the best values in the correlation analyses (r = 0.408), which is why the BSA indexing should also be used for future, CT-morphological parameters with regard to an optimized statement.To ultimately reconcile this discrepancy and strengthen the power of noninvasive radiological imaging, numerous papers are now moving toward indexing CT-derived pulmonary hypertension parameters to BSA ,23. RegaFeatures related to pulmonary hypertension are fast and easily measurable on pre-TAVR CT and offer great potential regarding non-invasive screening for and detection of pulmonary hypertension in patients with severe AS. This knowledge can support and optimize the echocardiographic diagnosis since right heart catheterization is no longer a routine treatment. In this study, the diameter of the main pulmonary artery with the additionally determined ratios was superior to the values of the right and left pulmonary artery. Additional indexing to body surface area and thus further individualization of the parameters with respect to height and weight can further improve the diagnostic quality.The present study is based on data from a small cohort (n = 138) over a circumscribed time period (2016–2018) in two medical centers. Technical pitfalls in echocardiographic  and radiological measurements which lead to misclassifications should always be conceded, even if examinations were performed by experienced clinical investigators.


Athlete’s heart is a term describing the cardiovascular effects of long-term conditioning among highly trained athletes. It is a variation of normal standards.  Case series study at the cardiology division of a public university hospital. We studied 14 visually handicapped paralympic athletes (8 men) in the national judo team. They were 26.3 ± 6.4 years old, with body mass index 25 ± 14, and had been practicing judo for 9.2 ± 7.9 years. Clinical evaluations, electrocardiograms, exercise testing and echocardiograms were performed by independent observers.2). There were very strong correlations between left ventricular mass/body surface and endurance time (r: 0.91) and estimated peak oxygen uptake (r: 0.8). The correlations between left ventricular internal diastolic dimension and endurance time (r: 0.91) and estimated peak oxygen uptake (r: 0.8) were strong. Despite increased left ventricular dimensions (4 cases), atrial dimensions (1) and relative wall thickness (4), all athletes had normal left ventricular mass/body surface (89.98 ± 21.93 g/m²). The exercise testing was normal: exercise duration 706 ± 45 seconds and estimated peak oxygen uptake 62.70 ± 9.99 mlO2/min. Signs of athlete’s heart were found in all athletes, comprising left ventricular hypertrophy (5 cases), sinus bradycardia (5), T-wave juvenile pattern (3), T wave juvenile pattern (3), left atrial hypertrophy (2) and increased left ventricular volume (9 cases; 62.22 ± 6.46 ml/m Signs of athlete’s heart were seen frequently in the paralympic judo team. These demonstrated the presence of mild cardiac adaptations to training. Occurrences of cardiac adaptations to training among disabled athletes have been already observed. Among Brazilian elite disabled athletes, signs of athlete’s heart have been found to occur in 33% of clinical evaluations, 55% of electrocardiograms, 15% of vectorcardiograms and 5% of echocardiograms.At least one of these signs has been found to be presented by 51% of disabled athletes.The aim of the present case series study was to assess occurrences of athlete’s heart among the Brazilian paralympic judo team.2, and had been practicing judo for 9.2 ± 7.9 years. Clinical evaluations, electrocardiograms (ECG), exercise testing and echocardiograms were performed by independent observers. Examinations were performed during periods of peak training. ECG evaluations followed the third guidelines of the Brazilian Society of Cardiology regarding analysis and issuing of electrocardiographic reports and the criteria of Corrado et al. for diagnosing athlete’s heart.We studied the entire national paralympic judo team, comprising 14 athletes, who were all visually handicapped. Eight of them were men. The paralympic athletes were 26.3 ± 6.4 years old, with body mass index (BMI) = 25 ± 14 kg/mAll the subjects underwent symptom-limited evaluations on a treadmill , in accordance with the Bruce protocol . Echocardiograms were recorded on the ATL Ultramark 8 and 9 devices , using a 3.0-MHz phased-array transducer.We evaluated left ventricular volume (LVV), left ventricular mass/body surface (LVM/BS), relative wall thickness (RWT), diastolic interventricular septum thickness (IVSTd), diastolic posterior left ventricular wall thickness (PLVWTd), left ventricular internal diastolic dimension (LVIDd), left ventricular ejection fraction (LVEF), percentage of fractional shortening (PFS), left atrial dimension (LAD) and right ventricular end diastolic inner diameter (RV-EDD).Prior to the evaluation, informed consent was obtained from each patient. The study protocol conformed with the ethical guidelines of the 1975 Declaration of Helsinki, as reflected through a priori approval from our institution’s human research committee (CAAE: 62709816.2.0000.5505).Pearson correlation coefficients (r) were used to estimate relationships between the exercise test results and echocardiographic variables. The significance level was taken to be P < 0.05. All data were expressed as mean ± standard deviation (SD).The results are described in 2), ranging from 52 ml/m2 to 95 ml/m2. Despite the increased left ventricular dimensions (n = 4), atrial dimensions (n = 1) and relative wall thickness (n = 4), all the athletes had normal left ventricular mass/body surface (89.98 ± 21.93 g/m²). The right ventricular dimensions were also within normal values. The ejection fraction (66.23 ± 2.94) and the percentage of fractional shortening (36.29 ± 2.18%) were also normal. The Doppler echocardiography did not detect any significant valvular regurgitant flow.The left ventricular volume was increased in nine athletes , good (36%), regular (21%) and weak (7%). This was not assessed in 29% of the cases because these individuals were under 20 years of age.The results from exercise testing were normal for all subjects. There were no cases of ischemic ST depressions on ECG, or any cases of arrhythmias or hypotension. In the exercise testing, the exercise duration was 706 ± 45 seconds and the estimated peak oxygen uptake reached 62.70 ± 9.99 mlOThe correlations between the variables are presented in 2), slight asthma and mild recent hypertension; one had obesity (BMI = 38.5 kg/m2); and another two had mild asthma. All the other subjects had BMI ranging from 20.4 to 28.4 kg/m2. These data probably did not interfere with the myocardial findings.We studied the Brazilian paralympic judo team to assess occurrences of althlete’s heart. All the subjects were apparently health subjects and performed athletic activities national level. One subject presented obesity  to 59.62 mlO2/mg/min,2/kg/min). For 60% of our athletes, their fitness level was considered to be good/excellent.The maximal oxygen uptake in elite judo players has ranged from 45 ± 10 mlO2max did not differ (P > 0.05) between the groups: elite (VO2max = 58.13 ± 10.83 mlO2/kg/min) versus non-elite (VO2max = 63.28 ± 10.55 mlO2/kg/min).2/kg/minute.Aerobic power and capacity levels have been found to be similar between Brazilian elite and non-elite judo players. VOWe found ECG abnormalities in nine athletes and increased echocardiographic measurements in six athletes. Nine subjects presented increased left ventricular volume, although there were no increases in right ventricular end diastolic inner diameter. This measurement may differentiate between normal hearts and exercise-related right ventricular adaptations and is the only parameter recommended for measurement within athletes’ routine training.We registered very strong correlations between left ventricular mass/body surface and endurance time, thus showing the relationship between training and left ventricular hypertrophy, considering that judo is a martial art involving a high static component. There were also strong correlations between the left ventricular internal diastolic dimension of estimated peak oxygen uptake, considering that judo is also a sport involving a high dynamic component.Although intense endurance exercise may cause acute dysfunction of the right ventricle, chronic structural changes and reduced levels of right ventricle function in some athletesAthlete’s heart is a term used to describe the cardiovascular effects of long-term conditioning that is observed in highly trained athletes.Signs of athlete’s heart were highly prevalent manifestations among these paralympic judo players. This demonstrated that these disabled athletes presented mild cardiac adaptations to training.


Background: Fusion CRT pacing (FCRT) is noninferior to biventricular pacing, according to the current data. The aim of this study is to assess the response to FCRT and to identify predictors of super-responders (SRs) in a nonischemic population with normal AV conduction. Methods: LV-only CRT patients (pts) with a right atrium/left ventricle pacing system implanted in two CRT centers in Romania were included. Device interrogation, exercise tests, echocardiography, and individualized drug optimization were performed every 6 months during close follow-up. SRs pts were defined as those with left ventricular end-systolic volume (LVESV) improvement ≥30% and stable ejection fraction (LVEF) ≥45%. Results: A total of 25 out of 83 pts (31%) were SRs, with nonischemic LBBB low EF cardiomyopathy  initially included. Mean follow-up was 5 years ± 27 months. Patients were divided in two groups: SRs and non-SRs (52 responders/6 hypo-responders). Two predictors were found in the SRs group: a higher baseline LVEF  and a lower pulmonary arterial systolic pressure . Baseline severe mitral regurgitation was found in 11% of SRs vs. 64% in the non-SRs group. Conclusions: SRs in the selected NICM-FCRT group are significative high. Higher baseline LVEF and mild pulmonary arterial hypertension were independently associated with super-response.  Left Ventricular (LV) only pacing is a noninferior alternative to biventricular pacing (BiV) in patients undergoing cardiac resynchronization therapy (CRT) as a first-line treatment for symptomatic heart failure (HF), reduced ejection fraction (EF), and QRS duration >130 ms [The necessity and position of an RV lead to deliver pacing to obtain better responsiveness to resynchronisation is highly debatable. The only need to stimulate pacing through an RV lead may be in the case of AV block and permanent atrial fibrillation (AF). LV-only pacing is analogous to fusion pacing, and it provides a similar outcome in patients with moderate to severe HF CRT ,3. FusioThe AV conduction variability still remains the main concern regarding the quality of LV-only fusion pacing, both in the short and long term, due to changes in disease state, exercise capacity, and medication. The algorithm described by the investigators of the adaptive-CRT trial, which promotes intrinsic conduction and reduces RV pacing, demonstrated a high percentage of fusion pacing in patients with normal AV conduction, which was independently associated with superior clinical outcomes .The rate of non-responders to CRT is still around 30%, although the advance of resynchronization is extensively studied ,10. HeteThe aim of this study is to assess the response to fusion pacing CRT (FPCRT) in a homogeneous nonischemic population with normal AV conduction, which also allows for true FPCRT. This is a multicenter, retrospective study which included and analyzed patients between April 2011–June 2021. The study population included consecutive patients with CRT indication, dilated cardiomyopathy, New York Heart Association (NYHA) class II–III heart failure, left-ventricular ejection fraction (LVEF) ≤35%, QRS complex ≥130 ms, typical LBBB pattern, and optimal pharmacological treatment 3 months prior to CRT. Patients were excluded if any of the following were present: acute coronary syndrome or history of coronary artery disease, permanent atrial fibrillation, severe comorbidities , other causes of non-ischemic cardiomyopathy , evidence of conditions with risk of life-threating ventricular arrhythmias , or noncardiac diseases that limit physical activity .All patients were on chronic optimal medical therapy, including novel drug therapy for heart failure  according to the current HF guidelines , individThe strategy of device management followed precise steps: 1. Interrogation immediately after implant procedure; 2. A 24 h check after implantation; 3. A discharge check; 4. Programming at each follow-up visit. The following steps were performed in all patients after CRT: 1. A 12-lead ECG pacing on/off and complete interrogation. 2. All pacemakers were initially programmed at a base heart rate of 60 bpm and maximum tracking rate (MTR) of 130 bpm. 3. Check-ups included evaluation of the spontaneous AV interval, percentage of ventricular pacing, LV threshold, and adequate response of cardiac devices functioning during exercise. 4. The AV interval was programmed individually to achieve the best fusion capture. The CRT assessment during exercise test included: maximal heart rate, beat-to-beat ECG analysis of true LV fusion pacing, loss of LV capture occurrence, and improvement of exercise capacity. In the case of LV loss of capture or unsatisfactory LV fusion pacing, reprogramming was performed individualized for each patient, and BB/ivabradine dose titration was performed to achieve stability of the PR spontaneous interval . The folThe response assessment to CRT was based on the following criteria ,13: clinPatients were divided in two groups: super-responders (SRs) and non-SRs (responders and hypo-responders). Pts were defined as non-SRs-subtype responders when a decrease in LVESV of ≥15% and absolute increase of >5% in LVEF at 6 months was found. Non-SRs-subtype hypo-responders were defined when there was no echocardiographic improvement or a decrease in LVESV of <15% and an absolute increase of <5% in LVEF at 6 months was found. SRs were defined as a 2-fold or greater improvement in LVEF or a final LVEF ≥ 45% at 6 months post-CRT. Transthoracic echocardiography (TTE) was performed in all patients. Ultrasound images were explored with patients in the left lateral decubitus position, using a VIVID 9 system . An ECG was simultaneously recorded for each patient. The echocardiographic examination was performed using standard views and techniques. LV wall thickness, LV end-diastolic and end-systolic diameters  and volumes , LV ejection fraction (LVEF), LA diameter (LAd), LA area (LAA), and LA volume (LAV) were measured. Atrioventricular, interventricular, and intra-LV synchrony parameters were also assessed in all patients. All LA measurements were performed at the end-systole, just before mitral valve opening, and maximal atrium size was considered for evaluation. A complete TTE evaluation for CRT was performed in all patients.t test  or the Mann–Whitney U test . Proportions were compared using the chi-squared test and Fischer’s exact test. A p value < 0.05 was considered significant. To determine the predictors for super-responders to CRT, we employed univariate and multivariate analyses using logistic linear regression All analyses were carried out with the SPSS, version 18.0  statistical software.Data are expressed as mean ± standard deviation for continuous variables and as proportions for categorical variables. Continuous variables were compared between groups using the unpaired A total of 83 patients, 62.3 ± 9.2 y.o. , with non-ischemic dilated cardiomyopathy, HF NYHA class II-III, and CRT-P indication were included. All patients were implanted with a RA/LV pacing system between 2011–2021. All patients had a QRS complex > 130 ms with typical LBBB morphology (Strauss criteria). A comparison between the SR group and non-SR group regarding the main demographic parameters and medical treatments is found in No major complications were noted intra- or periprocedural during implantation. At baseline, all devices were programmed at a resting rate of 50 beats/min and a maximum tracking rate (MTR) of 130 beats/min. Individualized AV interval programming with an AV pace of 148 ± 21 ms and an AV sense of 119 ± 25 ms, allowed fusion pacing in all patients. A comparison regarding technical aspects and post-CRT ECG in the SR and non-SR groups are presented in The anterolateral position was predominant in the non-SR group, while the SR group had a mainly posterolateral position of the LV lead. These technical aspects were determined by the anatomy of the patients. Taking into account that there were no anterior leads, only an anterolateral position, we can assume that lead position or post-CRT ECG had no major implications regarding the outcome in our population. The average EF at baseline was 26.7 ± 5.1%. All patients had severe LV dilatation (mean LVEDV 245.7 ± 86.8 mL) associated with important LA dilatation (LAV 101.9 ± 33.1 mL) and pulmonary hypertension (sPAP 46.1 ± 15.3 mmHg). Echocardiography data are presented in The average follow-up was 5 years ± 27 months . A total of 31 patients (40%) were implanted before 2016 and have had more than 5 years of follow-up. At the end of the follow-up, NYHA class improvement was noted in 87% of patients: 38% of patients in NYHA I, 53% in NYHA II (versus 51% at baseline), 9% in NYHA III (versus 49% at baseline). The univariate analysis of the echocardiographic parameters showed that a better LVEF at baseline  were predictors for SR, while severe MR  and a higher PSAP  were predictors for NS. These three parameters were included in the multivariate analysis, and only a higher PSAP at baseline  remained an independent predictor for NS. A forest plot graph with univariate and multivariate analysis  is shown in The first patient implanted with a RA/LV DDD device has 10 years of follow-up, and he is a super-responder. An obvious super-responder profile, with a ”beautiful” fusion pacing ECG A–C was nThe exercise test was an essential method of follow-up; more than 400 ET were performed in order to ensure adequate fusion pacing CRT in all patients, both at rest and during exercise. The following interventions were done to achieve 100% fusion pacing: reprogramming sensed/paced AV delay or rate adaptive AV , increasing maximum tracking rate (MTR) because of inadequate or lost LV capture, and programming rate modulation response due to chronotropic incompetence. Device optimization was performed in 32 pts (38%), while BB and ivabradine titration to maintain and stabilize the AV interval was performed in more than 170 of the ETs. A similar number of optimizations (regarding the number of patients) were performed in the SR and non-SR groups, with an increased exercise capacity in the SR group. Specific data regarding the exercise test parameters are shown in Non-sudden cardiac death occurred in 7 patients (9%). No deaths were recorded in the super-responders group. Readmissions due to worsening heart failure were noted in 20 patients (24%): A total of 8 patients due to atrial flutter or fibrillation, and 12 patients due to medication and diet issues. Pacemaker replacement was performed in 6 patients due to an elective replacement indicator.A CRT-D upgrade was not necessary in any of our patients. Amiodarone was introduced for paroxysmal AF episodes (diagnosed at device interrogation) and persistent AF in 12 patients (14%). Direct current cardioversion for persistent AF was required in 6 patients (7%). Typical atrial flutter cavotricuspid ablation was performed in 2 patient (2%). There were 3 patients treated with betablocker and amiodarone who developed a subsequent AV block and needed an upgrade to a triple-chamber device . The final outcomes were positive, without any other complications in these patients. There are three categories of CRT response definition. The first category includes clinical measures: NYHA class, quality of life, 6 min walk test, and exercise duration. The second category is based on LV reverse remodeling assesment: increase in LV ejection fraction (LVEF), reduction in LV end systolic and dyastolic volumes , and mitral regurgitation (MR). The third category measures the outcome regarding HF hospitalizations, morbidity, and all-cause mortality reduction. A CRT evaluation in clinical trials is different from those in real life. We must manage CRT candidates without adequate evidence or consensus of opinion in LBBB nonischemic cardiomyopathy. Inappropriate selection of the CRT patients in clinical trials always raises the same questions . Due to these ambiguities, endpoints are very different in clinical trials and in daily practice. These issues should be addressed in future clinical research; perhaps genetic testing and cardiac MRI in these patients could help to assess the risk of malignant arrhythmias and choose the proper device. If a CRT-p device is needed, do we still need an RV lead, or is an LV-only lead is enough, with proper fusion pacing? Some of these issues are addressed in our study using a highly selected NICM LBBB group.The most reliable echocardiographic parameters to use are LVEF and LVES. Responder patients are defined if they show a decrease in LVESV of ≥15%, or an absolute increase of >5% in LVEF at the 6-month follow-up visit compared with the baseline echocardiogram (11). They are labeled as super-responders (SRs) if they show a 2-fold or greater improvement in LVEF or a final LVEF ≥ 45% at 12 months post-implantation ,14.Our study addresses a homogeneous group of highly selected NICM with long-term follow-ups. We know that NICM is a heterogeneous condition, and the reversibility of systolic dysfunction and overall prognosis is related to etiology (ischemic vs. nonischemic), life-shortening co-morbidity , patient selection , severe symptoms (NYHA IV), and proper follow-up . In our study population, patients with severe mitral regurgitation and pulmonary hypertension at baseline had a low chance of becoming super-responders. The small number of patients included in this analysis represents the main limitation of this study. In a paper published by H. Burri et al., on behalf of the EHRA Education Committee, LV-only pacing was associated with a better CRT outcome and a decrease in the number of non-responders ; howeverThe population included in our study was divided in two groups: super-responders (SRs) and non-SRs (responders and hypo-responders). From the non-SRs (69%) group, 52 were responders and 6 were considered hypo-responders at 6 months after CRT. In general, our population had a very positive outcome to FCRT, with more than one-third being SRs (31%). This can be explained due to strict enrollment criterias  of patients, with a high probability of respondes to CRT in the longer term. No arrhythmic deaths were recorded in this population. Indeed, new medications, such as ARNI and SGLT2I, may influence the outcome in HF patients. Nevertheless, this study analyzed the CRT response and at 6 months follow-up, all the patients were on optimal medical treatment at the moment of implantation and up to the 6 month follow-up. Being on stable medication at baseline and at 6 months follow-up decreases the chances of a possible interference with the CRT response, with the observation that we noted the most significant improvement at 6 months post CRT. On the other hand, on long-term follow-up, we are confident that medication optimization plays a key role in maximazing CRT response. Drugs such as betablockers (BBs) and ivabradine were titrated according to exercise test results in order to maintain long-term constant fusion pacing ; the conAfter the controversial Danish trial , the ICDBased on the results of a meta-analysis , the useThe individual programming of devices after CRT implantation and regular follow-up should be the aim. The key target of programming has been to deliver 100% of ventricular capture in order to achieve the maximal outcomes . AlthougVariability of AV conduction is one of the main concerns regarding proper FCRT at rest and during exercise. Our study shows the importance of periodic follow-up (including TTE and ET) in order to maximize the percentage of responders. To ensure the stability of AV conduction in our population, we used drug optimization and CRT reprogramming during follow-ups with ET. The ET check was an essential method of follow-up, performed systematically in our series with more than 400 ETs to ensure adequate fusion pacing CRT in all patients. Device optimization was needed in more than one-third of the patients, while BB and ivabradine titration was performed in almost half of ETs. Poor reprogramming of AV delays is a contributor to reduced efficacy of CRT , as we aAn ongoing trial is expected, as AdaptResponse (NCT02205359) set out to recruit approximately 3000 patients with LBBB, normal AV conduction, and LV fusion pacing with a combined primary endpoint of all-cause mortality and heart failure decompensation . We willFusion CRT pacing shows a positive outcome in a highly selected NICM group, with over one-third of patients being SRs after 6 months. Regular follow-ups  maximize the percentage of CRT responders.


To plan treatment and measure post-stroke recovery, frequent and time-bounded functional assessments are recommended. With increasing needs for neurorehabilitation advances, new technology based methods, such as virtual reality (VR) have emerged. Here, we developed an immersive VR version of the Action Research Arm Test (ARAT-VR) to complement neurorehabilitation.This study aimed to assess the validity, usability and test–retest reliability of the ARAT-VR among individuals with stroke, healthcare professionals and healthy control subjects (HCS).Among the 19 items of the ARAT, 13 items were selected and developed in immersive VR. 11 healthcare professionals, 30 individuals with stroke, and 25 HCS were recruited. Content validity was assessed by asking healthcare professionals to rate the difficulty of performing each item of the ARAT-VR in comparison to the classical Action Research Arm Test (ARAT-19). Concurrent validity was first measured using correlation (Spearman tests) between the ARAT-VR and ARAT-19 scores for the individuals with stroke, and second through correlation and comparison between the scores of the ARAT-VR and the reduced version of the ARAT (ARAT-13) for both individuals with stroke and HCS (Wilcoxon signed rank tests and Bland–Altman plots). Usability was measured using the System Usability Scale. A part of individuals with stroke and HCS were re-tested following a convenient delay to measure test–retest reliability (Intra-class correlation and Wilcoxon tests).Regarding the content validity, median difficulty of the 13 ARAT-VR items (0[0 to − 1] to 0[0–1]) evaluated by healthcare professionals was rated as equivalent to the classical ARAT for all tasks except those involving the marbles. For these, the difficulty was rated as superior to the real tasks . Regarding the concurrent validity, for paretic hand scores, there were strong correlations between the ARAT-VR and ARAT-13 (r = 0.84), and between the ARAT-VR and ARAT-19 (r = 0.83). Usability (SUS = 82.5[75–90]) and test–retest reliability  were excellent.The ARAT-VR is a valid, usable and reliable tool that can be used to assess upper limb activity among individuals with stroke, providing potential to increase assessment frequency, remote evaluation, and improve neurorehabilitation.Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04694833; Unique identifier: NCT04694833, Date of registration: 11/24/2020.The online version contains supplementary material available at 10.1186/s12984-022-01114-3. Upper limb function is commonly affected after a stroke. Around 80% of individuals with stroke present with motor impairments and activity limitations of the upper limb . To evalDuring the last decade, there has been rapid developments of technology that provide interesting new methods to deliver effective stroke rehabilitation . Among tVR also has the potential to be used as an evaluation tool. As a human–machine interface, the VR system continuously collects a full range of interesting data such as interactive movement kinematics during its use. This offers the possibility to develop quantitative and objective measures that could be used autonomously and operated without the need of clinician presence. To date, several tests have been developed to measure post-stroke upper limb functions such as motor control  and manuThis study aimed to develop and validate an immersive virtual version of the ARAT among individuals with stroke and healthy control subjects (HCS). The hypothesis was that the ARAT-VR and ARAT scores would be correlated among individuals with stroke when performed with both the paretic and less affected hand. We also expected that HCS and individuals with stroke, would obtain similar scores on both tests when performed with the less-affected hand. Secondary objectives were to assess the usability and reliability of the ARAT-VR.This observational multicentric study involved individuals with stroke, HCS and healthcare professionals. All these participants were recruited in Cliniques universitaires Saint-Luc and Cliniques universitaires UCL Mont-Godinne (Belgium) between October 2021 and April 2022. The protocol was approved by their Ethics Committee and registered on clinicaltrial.gov (NCT04694833). Written informed consent was obtained from all participants after receiving information regarding the trial. This study followed the STROBE recommendations  with 4 integrated infrared cameras capable to automatically detect the position and orientation of the individual’s hands and fingers. The headset was connected to a computer in order to stream the application, allowing the experimenter to see what the user was doing while performing the test. The ARAT-VR task contained 13 out of the 19 items of the ARAT, also subdivided in four subtests: grasp, grip, pinch and gross movement. Indeed, it was not possible to develop 6 ARAT items in VR because of limitations with the hand-tracking technology  and the second consisted of only scoring the 13 ARAT items that corresponded to the ARAT-VR (ARAT-13).For both the ARAT and ARAT-VR, individuals were asked to sit on a chair, with their feet on the ground, and with a back support, without armrests. When performing the ARAT, the experimenter first explained the test to the participant to provide instructions for each task. When performing the ARAT-VR, the experimenter first set the basic settings and installed the headset. All individuals then benefited from a practice learning period corresponding to the achievement of all ARAT-VR tasks. After that, participants performed the test autonomously, following written or verbal instructions provided by the software application. Before and during each virtual task, written and verbal instructions were delivered to the individual by the software application through the headset. The procedure of the test and the dimensions of the virtual objects were similar to those of the classical ARAT. The height and position of the virtual table was adjustable to allow for matching with a real table. When the participant was ready to start a task, he or she was asked to put both hands on the table. A timer was then started. The grasping movement was initiated when the individual reached the object with a hand opening movement, where the distance between the thumb and fingers corresponded to the size of the object. Once grabbed, the object was released if the individual opened the aperture of their thumb and fingers, or brought the thumb and fingers closer together. The timer stopped when the task was successfully completed, or the time had elapsed, or the user chose to move to the next task  . This quTo assess the test–retest reliability, a subgroup of the individuals with stroke and the HCS performed the ARAT-VR test a second time with the same assessor.To assess the timing execution of the ARAT-VR, we scored the time made to perform each ARAT-VR item for each participant, as measured by the software application. A median score with an interquartile range was then calculated for the paretic hand.Statistical analyses were performed using SIGMAPLOT 13.0 and R with alpha = 0.05. The sample size was determined to have a 0.5 correlation coefficient between the ARAT-19 and the ARAT-VR scores. The minimum number of individuals with stroke required was 30 to achieve 80% power with a 5% significance level.Given that ARAT and ARAT-VR are ordinal scales, we only performed non-parametric tests. An ordinal logistic regression model was first conducted to identify all the factors potentially influencing the ARAT-VR score: ARAT, FMA-UL, age, sex, weight, height, type of stroke, side of stroke, time since stroke onset, the presence of cognitive impairments and the hand affected by the stroke (dominant vs. non-dominant). For individuals with stroke, Spearman coefficients were computed to evaluate correlations between the ARAT-VR and the ARAT-19 and ARAT-13 scores. A Bland–Altman plot was also performed to visualize the difference in ARAT-VR and ARAT-13 scores for the paretic hand. For both HCS and individuals with stroke, Wilcoxon-signed rank tests were conducted to compare the scores of the ARAT-VR and the ARAT-13 assessments. Lastly, to understand the influence of experience with technologies on VR performance, correlations between age and the difference between ARAT-19 and ARAT-VR scores were performed using Spearman correlation tests. Correlations were rated as small (0.1 < r ≤ 0.3), medium (0.3 < r < 0.5) or large (r ≥ 0.5) according to Cohen’s interpretation .For the paretic hand, test–retest reliability was evaluated by performing a two-way mixed model Intraclass Correlation Coefficient (ICC) between the two repeated measures of the ARAT-VR. Reliability was rated as poor (ICC or r ≤ 0.40), moderate (0.40 < ICC or r < 0.75), or excellent (ICC or r ≥ 0.75)  . MinimalEleven healthcare professionals with a mean age of 30 ± 7.3 years took part in the trial. Among these, five were physical therapists, four occupational therapists and two doctors with specialization in physical medicine and rehabilitation. All were familiar with the ARAT before the experiment.Twenty-five HCS with a mean age of 43 ± 20.0 years, and 30 individuals with stroke  with a mean age of 60 ± 10.9 years participated in the study. Individuals with stroke were recruited during acute (n = 8), subacute (n = 8) and chronic phase (n = 14) with a median time since stroke onset of 2.9[0.4–14.1] months. Complementary information is presented in Table Regarding the content validity, median difficulty of the 13 ARAT-VR items (0[0 to − 1] to 0[0–1]) evaluated by healthcare professionals was rated as equivalent to the classical ARAT for all tasks except those involving the marbles. When manipulating marbles, median virtual task difficulty was rated as superior to the real tasks . More specifically, for all items, upper limb sub-movements involved in the ARAT-VR such as hand opening, releasing and object displacement were rated as equally difficult as those involved in the ARAT. However, holding of virtual objects (1[0–1]) and the dexterity needed for pinching movements (1[1–1.5]) were rated as more difficult in VR than in the classical ARAT. Lastly, professionals rated the ergonomics of the application with a median score of 4[4–5] out of 5 and the clarity of the instructions with a median score of 5[4–5] out of 5. All the scores supporting the data are presented in Additional file When individuals with stroke performed the test with their paretic hand, the ordinal logistic regression model showed that ARAT-VR score variance was exclusively explained by the variance of the ARAT score (p = 0.004) Table . The corRegarding the concurrent validity, individuals with stroke obtained an ARAT-VR score of 34.5[13–37] out of 39, an ARAT-19 score of 48.523–54] out of 57, and an ARAT-13 score of 32[16.75–36] out of 39 for responses made with the paretic hand. There were strong correlations between the ARAT-VR and ARAT-19 scores . We observed a significant negative moderate correlation between age and ARAT score difference for the non-dominant hand  but no significant correlation for the dominant hand.Concerning the usability of the ARAT-VR, all participants rated it as excellent on the SUS: 82.5[78.75–87.5] for HCS and 82.5[75–90] for individuals with stroke (Wilcoxon p = 0.946). The lowest score was shown for the 4th item of the scale . The median score obtained for to this item was of 2[1–3], corresponding to a neutral opinion.Regarding the inter-session test–retest reliability, results are presented in Table Concerning the ARAT-VR execution timing, the median duration was of 3.5[2.49–5.88] minutes for the paretic hand. The duration of the installation of the headset was ~ 1.5 min, the explanation of instructions was ~ 2.5 min, and the learning period was ~ 1 min, making the total administration time of the ARAT-VR to be around 9–10 min.To the best of our knowledge, this study is the first to provide an immersive virtual version of the ARAT using hand-tracking technology. Furthermore, the number of studies interested in validating other upper limb motor assessments in immersive VR among individuals with stroke remains limited . The preDue to limitation in the present hand-tracking technology in VR, the number of items of the ARAT had to be reduced in the ARAT-VR (from 19 to 13 items). However, despite this reduction, results confirmed that there was no loss of information. Indeed, as presented in Fig. Individuals with stroke obtained similar scores between the ARAT-VR and the ARAT-13 for the paretic hand. In addition, for all items, several specific ARAT and ARAT-VR upper limb sub-movements  were rated as equally difficult. However, most HCS and individuals with stroke using their less affected hand did not achieve the maximal score in VR, whereas all HCS obtained 57/57 on the ARAT-19. This difference between virtual and real environment assessments was further underlined by previous research conducted in immersive VR , 29. TwoThis study showed excellent test–retest reliability, with significant correlations and no significant differences between the scores of the first and second trials of the ARAT-VR when performed with the paretic hand among individuals with stroke. The MDC was 4.0 for the paretic hand and was slightly superior to the traditional ARAT (MDC = 3.0) . The relThe implementation of the virtual tests in clinical routine may offer several interesting perspectives. First, functional assessments developed in immersive VR could allow individuals to be evaluated remotely and more autonomously, potentially leading to an increased frequency of assessments as encouraged by current guidelines . The ARA~ 2.5 min) and the learning period (~ 1 min), the total administration time of the ARAT-VR could be estimated to be around 9–10 min whereas, in clinical routine, the ARAT-19 requires up to 15 min depending on the scoring methods used [The reduction of items offers interesting perspectives for clinical routine and research. Indeed, there is a growing demand for shorter and more efficient versions of the ARAT. Yet, as presented in the results, the median execution timing of the ARAT-VR was found to be around 4 min. When considering the duration of the installation of the headset (~ 1.5 min), the provisioning of instructions  could be more accurately determined according to norms obtained among healthy subjects. Third, due to hand-tracking limitations, the number of items of the ARAT-VR had to be reduced. Future research incorporating the use of other headsets comprising more accurate hand tracking or new technologies such as smart glasses or a depth motion camera might be of interest to develop a virtual version of all the 19 ARAT items. This could further improve the ARAT-VR validity.In terms of methodology, different clinimetric properties of the ARAT-VR have not been assessed during this trial . It would be worthwhile to test the ARAT-VR among a larger group of individuals, of different ages, with stroke and with other neurological or motor impairment profiles.The ARAT-VR is a valid, usable, and reliable tool to assess upper limb activity among individuals with stroke using their paretic hand. This new VR test holds potential to be used, both in clinical and research practice, as an alternative of the traditional ARAT.Additional file 1. STROBE statement checklist.Additional file 2. Movie representing the ARAT-VR.Additional file 3. Content validity questionnaire.Additional file 4. Raw data supporting the results of conclusions of this work.Additional file 5. Correlation results between the scores of each ARAT-VR and ARAT item.


Tricuspid valve pathophysiology is not well-understood. Emergence of novel transcatheter tricuspid therapies has fueled the requirements for improved imaging visualization techniques and interventional imaging physician skillsets in guiding these complex transcatheter procedures. There is growing understanding on the clinical significance of tricuspid regurgitation which expanded the interest for percutaneous tricuspid valve interventions. The present review concentrates on three essential aspects of tricuspid valve pathophysiology: anatomical considerations for tricuspid interventions, optimal timing of tricuspid interventions by imaging guidance, and the role of interventional imaging physicians’ skillset and knowledge in this field. Tricuspid regurgitation (TR) natural history is not well understood and presents challenges to clinical practice. The majority of severe TR is secondary due to annular dilatation resulting from right ventricular (RV) disease or less commonly right atrial (RA) dilatation. Severe TR if left untreated eventually results in right heart failure (RHF). Irrespective of the cause, TR is associated with worse survival regardless of left ventricular (LV) function and pulmonary hypertension . Indeed,As the heart team evolves, the growing experience of transcatheter therapies has highlighted the dilemma of optimal management of severe TR. In patients undergoing either surgical or transcatheter mitral or aortic valve interventions, severe TR is an important marker of poorer prognosis at both short- and long-term follow-up. The present era of structural heart transcatheter interventions brings to the forefront the importance of precisely defining the pathophysiology. The interventional imaging team now assumes a central role. To this end this review aims to highlight the evolving key concepts in the application of multimodality imaging in the assessment, patient selection and procedural guidance in patients undergoing transcatheter tricuspid valve interventions.coaptation zone. The coaptation length is approximately 5-10 mm, which maintains valve competency. Progressive leaflet tethering, prolapse or annular dilatation results in malcoaptation with a reduction in coaptation length. This is the basis for the mechanism of regurgitation and if severe can result in frank loss of coaptation zone resulting in a coaptation gap. Identification of a coaptation gap is pathognomonic of severe regurgitation. Landmarks are key to correct orientation and identification of valve leaflets. The coronary sinus is located near the postero-septal commissure. The antero-septal commissure is situated near the aortic valve/root (points toward the commissure between non-and right coronary cusps) and its location helps identify the position of the anterior leaflet. The ventricular/atrial septum identifies the septal leaflet. Lastly identifying the anterior papillary muscle (often joining with the moderator band) assists in locating the antero-posterior commissure , posterior (P) and septal (S), which are thin translucent structures, no more than a few millimeters in thickness. The septal leaflet is shortest in length  and least mobile. Importantly, recent 3D TEE imaging assessment has highlighted the significant variability 46%) in the number of functional leaflets % in the . Clearlymmissure . In termmmissure . A detait 2 mmHg .TV subvalvular apparatus consists of 2-3 papillary muscles (PM). Anterior, the largest gives rise to chords to the anterior and posterior leaflets. It is positioned below the antero-posterior commissure  and serves as a useful landmark and may join the moderator band. The posterior PM typically consists of 2-3 heads with chords to the posterior and septal leaflets. Lastly the septal PM may not always be present  and instead replaced by chords from the septal or anterior leaflet directly inserting into the ventricular septum .2 (2 (RV focused four chamber view in end diastole) (2 (The tricuspid annulus (TA) is D shaped. The septal leaflet inserts to the atrial/ventricular septum forming the more linear section with variable degrees of fibrous tissue. While the remainder C shaped muscular portion is demarcated at the transition between atrial and ventricular myocardium where anterior and posterior leaflets insert. The normal TA circumference is approximately 12 ± 1 cm, and area 11 ± 2cm2 , 9. Form2 . Establi2 with a regurgitant volume ≥45 ml  is limited by a number of technical and hemodynamic factors. Proximal iso-velocity surface area (PISA) method  allows quantitative assessment, where severe TR is defined as an effective regurgitant orifice (EROA)≥40 mme ≥45 ml . TR defiollow up . Evaluatollow up    , 21. A rctively) . Importactively)  includin2 may carry a worse outcome . RV global longitudinal strain provides important insights into RV performance, offering useful indicators of prognosis and functional capacity in a number of disease states  and associated pulmonary disease (such as pulmonary fibrosis or chronic obstructive airways disease) is necessary. Further differentiating between isolated post-capillary PH (IpcPH) or later stages with combined post-and pre-capillary PH (CpcPH) in the setting of chronic left heart disease is important. Particularly where the latter may have progressed to irreversible obstructive and fixed remodeling of the pulmonary arteries such that the relief of severe TR may have little positive impact on RV outcome . Non-invAn understanding of the mechanisms for TR is essential, since this directs  treatmenIn the setting of left heart (LH) valve disease, the majority of TR is functional in origin. Despite a fall in RV afterload, it does not predictably improve following correction of the LH valve lesion. Surgical correction for severe TR at the time of LH valve disease is performed routinely . FurtherIn patients with cardiac implantable electronic device (CEID), the incidence of TR has been reported between 6 and 10% , 43. CEIIsolated functional TR is associated with RA enlargement in the setting of chronic atrial fibrillation . RA remoProgressive pulmonary arterial hypertension (PAH) is associated with RV dilatation and dysfunction underlies the development of progressive secondary TR. Treatment is focused on identifying the cause of PAH and its management. Where appropriate medical therapy with pulmonary vasodilators aims to reduce RV afterload. As RV function improves, reduction in TR severity follows. Where severe TR persists, it usually reflects progressive RV disease, where residual TR may paradoxically work to off-load the failing RV. Surgical intervention is rarely considered and reserved for carefully selected patients undergoing specific disease modifying treatments. This includes pulmonary thromboendarterectomy, where the expected reduction in PAH and RV afterload will support RV remodeling and any concurrent TV intervention .Optimal management of severe TR initially involves treatment of the underlying causative disease process (see above) with concomitant HF treatment. Medical therapy with diuretics is currently the basis treatment for severe TR with right heart failure (RHF). With progression of TR, high doses or a combination of different diuretic groups is often necessary to control RHF. Concomitant neurohormonal antagonist administration can have an additional effect on diuretic therapy by reducing the negative effect of compensating mechanisms triggered by volume loss. When significant systemic venous congestion is present  oral diuretics may be ineffective, and intravenous therapy or in selected cases peritoneal dialysis or hemofiltration with addition of inotropic support may be necessary . Responsprimary severe TR who are mildly (or asymptomatic) with RV dilatation and are suitable for conventional surgery; primary moderate TR undergoing left-side valve surgery. For secondary TR isolated surgery should be considered in symptomatic patients with severe TR  in the absence of severe RV or LV-dysfunction or severe pulmonary vascular disease/hypertension; or in those with mild or moderate TR undergoing left heart valve surgery who have a dilated TV annulus. TR progression after LH valve surgery is a predictor of mortality (due to RHF) and, for this reason moderate TR or annulus dilation (>40 mm or > 21 mm/m2) should be treated during surgery. Reoperation may be an option in patients with severe secondary TR in the absence of severe pulmonary hypertension or RV systolic dysfunction. However, there is a substantial patient population beyond this narrow definition with symptomatic TR refractory to medical therapy.Surgical intervention can be considered for both primary and secondary TR. Most often this is performed as a concurrent procedure at the time of left heart surgery. Class I indication for TV intervention is recommended for severe TR (whether primary or secondary) at the time of left heart (LH) valve surgery in both American  and ESC/Surgical TV repair involves TV annuloplasty. The primary goal is to improve leaflet coaptation by correcting annular dilatation and restoring annular geometry . IncomplThe role of transcatheter interventions for TR stems from the unmet need of large patient populations with symptomatic TR deemed unsuitable for conventional surgery. Much like early TAVR device evolution, current TR technologies are in their infancy. Currently four tricuspid transcatheter technologies are CE marked. Using early generation devices Tamarasso et al.  showed iThere are many conceptual ways to tackle right heart failure secondary to TR. Novel technologies based on surgical strategies of repair and annuloplasty have been developed via a transcatheter approach –53. Out Echocardiography is the main pillar in each step of TR evaluation spanning diagnosis planning, procedural guidance, and follow-up assessment , 3. TV m2; tenting area > 3.2 cm2 (Transcatheter leaflet edge-to-edge repair (TEER): The aim of TEER technique is to target the antero-septal coaptation line starting close to the commissure and moving centrally (“Zip” technique). Some parameters have been described as predictors of unfavorable results after tricuspid TEER including: a septo-lateral coaptation gap > 7 mm ; TV EROA 3.2 cm2 ; and TR  3.2 cm2 . Optimal 3.2 cm2 , and absFor the TEER technique, the device is aligned perpendicular to the tricuspid leaflet coaptation line  using 2D, transgastric, multi-plane, and 3D enface views of the TV. The advancement of the delivery systems, and TEER device may be performed using 2D mid-esophageal biplane view (inflow-outflow view), the same view used during leaflet grasping/clasping. Application of the 3D enface view and transgastric short axis views demonstrate the position of the device along the coaptation line and allow for additional assessment of correct leaflet grasping. Upon completion of grasping, color Doppler and continuous wave Doppler flow velocities are obtained to evaluate for any significant change in TV gradient as well as residual TR. To date there have not been quantitative parameters validated to assess the results after tricuspid TEER technique. The system removal is also performed under TEE guidance using the bicaval view and 3D view from the RA to avoid right atrial wall damage. An illustrative case is presented in the Annuloplasty repair therapies (ART): The objective of transcatheter annuloplasty using the Cardioband device, is to imitate a surgical annuloplasty band . Anchors runs counter-clockwise from the antero-septal to the postero-septal commissure  to prevent damage to the conduction system in the trigonum. Intraprocedural imaging with TEE allows visualization of the delivery catheter, the device navigation at the level of the right atrium, device coaxiality and final TR assessment.Some anatomical relative contraindications should be taken into consideration for transcatheter tricuspid ART since the presence of very eccentric/lead induced regurgitant, excessive annulus dilatation, leaflet tethering or pseudo-prolapse may lead to a suboptimal result.Heterotopic transcatheter valve replacement (HTVR): Although fluoroscopy is the main imaging modality in HTVR procedures , TEE can be helpful in assessing the correct valve orientation in orthotopic procedures, the position of the leaflets on the anchors , and to evaluate the results. For HTVR the key is to visualize the superior vena cava (SVC) and inferior vena cava (IVC), identify the landmarks and the possible interference with the hepatic veins or valve displacement.TTE is the main imaging tool for follow-up evaluation. The results of transcatheter tricuspid intervention are evaluated at key intervals, 30 days, 6 months, and at 1 and 2 years. Assessment of residual or recurrent TR is evaluated using the standard multi-parameter approach similar to pre-procedure and includes a combination of EROA (derived from the volumetric and PISA methods), VC width (biplane) and VCA, and annular dimensions evaluated in two orthogonal views . Serial evaluation in right heart chamber size, volumes, function are important parameters and help determine response to therapy and outcomes.The presence of a tricuspid TEER device  make assessment TR severity more difficult post-intervention. The 30-day post procedure TTE is generally used to evaluate both TR severity and correct device position . Early data suggest potential decrease in annular dilatation at 1 to 2 years post intervention , 53.Comprehensive computed tomography (CT) may overcome many of the limitations from 2D echocardiography by providing excellent anatomical and functional analysis of the tricuspid valve apparatus and its relation to the nearby structures. CT can provide additional information allowing assessment of the anatomical regurgitant orifice area . The latA precise sizing of the TA and its alteration during the cardiac cycle is necessary to ensure suitability for current device . The Cardioband device can not cover a TA circumference >120 mm, and orthotopic valve a TA diameter >52 mm . The preferred modality is CCT since it allows accurate multi-planar annular reconstruction . While eCT plays a central role in suitability and procedure planning for heterotopic caval devices including parameters such as precise distance between surrounding structures; SVC diameter at the level of the innominate vein confluence and SVC-RA junction; IVC at the level of the junction with the RA; distance between RA and hepatic vein orifice(s) and their relationship with the IVC-RA junction (should be > 10 mm to avoid hepatic vein obstruction).Finally, CT can determine optimal fluoroscopic projections for guiding the procedures, essential in helping to reduce procedural times and radiation exposure. Four main fluoroscopic projections have been described which may be superimposed on to the principal echocardiographic views and help both interventional imaging and implanting team with fusion imaging guidance .Specific CT acquisition protocols focusing on the right-side are employed for tricuspid imaging. In general, CT scanners with a higher number of detectors enables shorter breath-hold, lower radiation and contrast utilization. In the setting of atrial fibrillation, CT scanners offering higher temporal resolution such as the Siemens dual-source CT scanners (preferably b80 ms) can improve image quality . In summCardiac magnetic resonance (CMR) provides an opportunity to assess RV dimensions, volumes, RV ejection fraction, quantification of TR and non-invasive calculation of pulmonary vascular resistance (PVR). Pulmonary hypertension (PH) is one of the Achille’s heels of tricuspid treatment and is usually diagnosed late because of the non-specificity of the symptoms. RV performance and adaptation to an increased afterload, reflects the interaction of the pulmonary artery (PA) and RV as a morphofunctional unit (PV-PA coupling) . In situMultiple challenges exist for obtaining quality imaging studies during CMR acquisition in structural heart patients. Variability in heart rates in the setting of atrial fibrillation may prevent accurate ejection fraction quantification in a gated cardiac MRI sequence. Presence of intracardiac devices such as older generation pacemakers/ICDs may create artifacts, limiting chamber evaluation. Lastly, in the setting of acute heart failure, patients may not be able to tolerate the duration of the MRI study or number of breath-holds required for each image stack acquisition. Technological CMR developments such as single-breath hold or complete free-breathing imaging acquisition , 66, in Intracardiac echocardiography (ICE) was developed as a potential alternative to TEE mitigating the need for a general anesthetic in its use during structural heart disease interventions. Two available phased-array systems are AcuNav V  and ViewFlex Xtra . There are 5 “standardized” positions for ICE probe imaging  . ICE allSeveral proof-of-concept reports have supported the use of ICE in guiding transcatheter TV annuloplasty, leaflet repair, valvuloplasty, and TV-in valve implantation , 69. AltStatic fusion imaging (roadmapping) uses 3D data-sets acquired prior to the procedure (most commonly CT) which are combined with intraprocedural fluoroscopy. During transcatheter valve implantation it may be useful to superimpose vena cavae onto the fluoroscopic image. However, deviations in pre-procedural imaging, patient positioning, malalignment with fluoroscopic images, registration errors, or cardiac cycle selection may affect the accuracy of the fusion display and associated procedural outcomes. Dynamic fusion imaging has several advantages due the combination of real-time imaging data . It facilitates greater accuracy when positioning devices within the heart. Key advantages included the ability to crop (to remove soft tissue details not relevant for the procedure), adjustment overlay translucency (to prevent fluoroscopy from being obscured) and the placing of persistent anatomic reference markers in fluoroscopic space. For tricuspid interventions such as Cardioband implantation, the fusion between the 3D TEE and fluoroscopy may give a better spatial orientation when deploying the anchors  with fluoroscopy, creating image overlay on a single screen. The Philips EchoNavigator  and Siemens Syngo TrueFusion  software both require compatible same brand echocardiography and fluoroscopy equipment along with specialized hardware and software needed to process and create hybrid images. Limitations of current fusion technology include the color volume overlay on fluoroscopic monitors.  anchors )..Treatment options for tricuspid regurgitation are now rapidly expanding as transcatheter tricuspid technologies continue to evolve. An appreciation of heterogenous patient cohort and the complex interaction with the right ventricle, pulmonary circulation and left heart disease is crucial in correctly identifying those who might benefit from intervention. Where conventional surgery is deemed high risk, transcatheter therapies may play a role. Multi-modality imaging in patient selection and device choice has assumed center stage for such procedures and as such demand expert skills from the imaging team. Echocardiography remains the first-line and main imaging modality and its widespread use facilitates diagnosis. An in-depth understanding of the physiopathology of tricuspid regurgitation and its mechanisms is critical to ensuring best outcomes. It is important to highlight that accurate and timely diagnosis, optimal heart team decision making, procedural success and long-term outcomes are firmly rooted in the expertise and experience of the interventional imaging team. Hence, central to the optimal treatment of TR will be the need to value the role of the interventional imaging physician, who is equally invested in each patient’s care side-by-side with the implanting physician in this entire process.All authors contributed to the article, read, and approved this manuscript.


Chromosome 9p deletion syndrome is a rare autosomal dominant disorder presenting with a broad spectrum of clinical features, including congenital heart defects (CHDs). To date, studies focused on a deep characterization of cardiac phenotype and function associated with this condition are lacking. We conducted a multicentric prospective observational study on a cohort of 10 patients with a molecular diagnosis of 9p deletion syndrome, providing a complete cardiological assessment through conventional echocardiography and tissue Doppler imaging echo modality. As a result, we were able to demonstrate that patients with 9p deletion syndrome without major CHDs may display subclinical cardiac structural changes and left-ventricle systolic and diastolic dysfunction. Albeit needing validation in a larger cohort, our findings support the idea that a complete cardiac assessment should be performed in patients with 9p deletion syndrome and should be integrated in the context of a long-term follow-up. Chromosome 9p deletion syndrome (MIM #158170) is a rare autosomal dominant disorder due to allelic loss of the short arm of chromosome 9 (9p−), with a still uncertain prevalence. The first report of the syndrome dates back to Alfi and colleagues , who desSince then, several case reports and case series have extended the amount of data regarding phenotype. Clinical features are highly heterogeneous and are mostly represented by developmental delay and intellectual disability (ID) ,3,4. BehCardiac involvement is frequently reported in 9p deletion syndrome, with a prevalence ranging from 35% to 50% of cases . In addiWith the aim of gaining insight into the cardiac phenotype of 9p deletion syndrome, we report here the largest cohort of patients cytogenetically diagnosed since 2008 along with their cardiac phenotype and cardiac functional evaluation. Furthermore, we delineate the chromosomal breakpoints of each patient as means to identify a potential correlation between the genotype of patients and their cardiac phenotype spectrum. Moreover, to support the cardiac features identified in our study, a narrative literature review, focused on the cardiac features in 9p deletion patients over the last 10 years, is also provided. This was a prospective observational study on a cohort of 10 patients with a molecular diagnosis of 9p deletion syndrome, recruited from three Italian centers with reputed expertise in rare diseases and pediatric cardiology disorders: Bambino Gesù Children’s Hospital, IRCCS, Fondazione Policlinico A Gemelli, IRCCS, and Pediatric Cardiology Unit of Sapienza University of Rome. Patients from all over Italy were referred to these three centers. Demographic data and echocardiographic exams were collected within the study period January 2019–May 2022. The inclusion criteria for the study were confirmed genetic diagnosis of 9p deletion syndrome with and without associated rearrangements, ability to perform a complete echocardiographic exam including tissue Doppler imaging examination, and acceptance of the informed consent. We excluded all patients without their own or parental consent and without a complete echocardiographic examination. The Ethical Committee of Bambino Gesù Children’s Hospital approved the study protocol, and written informed consent was obtained from patient or legal guardian. The control group consisted of healthy patients admitted to the pediatric cardiology units. Patients in the control group were studied using the same echocardiographic protocol for syndromic patients by a pediatric cardiologist (C.P.), and we included patients with a structurally normal heart and no echocardiographic parameters suggestive for systolic or diastolic dysfunction. Written informed consent was obtained from a patient or legal guardian. All patients recruited were assessed by clinical geneticists , a pediatrician with expertise in disability (R.O.), and pediatric cardiologists . Systematic patient interviews investigated family and personal history of genetic syndromes, metabolic disorders, known congenital heart defects, arrhythmias, systemic hypertension, cardiovascular medications, and previous cardiac surgery procedures. Physical examination included height, weight, and body mass index (BMI) at the moment of evaluation, and obtained data were compared with normative data . BMI wasBody surface area (BSA) was calculated according to Haycock formula . Blood pAll echocardiographic and Doppler examinations were performed by experienced pediatric cardiologists  and one sonographer (F.C.). An Epiq7 or iE33 ultrasound machine  with a 1–5 MHz transducer (X5-1) and a 3–8 MHz transducer (S8-3) was used for studying 9p deletion syndrome patients; A GE Vivid 9  with M5S-D (bandwidth 1.5–4.5 MHz) and 6S-D (bandwidth 2.4–8.0 MHz) was used for the control group. Conventional echocardiographic evaluations were performed according to the recommendations of American Society of Echocardiography .Through M-Mode evaluation, echocardiographic data from the long-axis parasternal view included left-ventricle (LV) internal diameter in diastole (LVIDd) and systole (LVIDs), thickness of the interventricular septum in diastole (IVSd) and systole (IVSs), and LV posterior wall thicknesses in systole (PWs) and diastole (PWd). 2.7 [Ejection fraction (EF) and fractional shortening (FS) of the LV were calculated using Teichholz’s M-mode formula. LV mass was calculated using the Devereux formula  and inde2.7 .The long-axis parasternal view was also used to assess proximal aorta diameters at four levels  and left atrium to aorta ratio (LA/Ao). All echocardiographic measures were indexed for BSA. Pulsed-wave Doppler echocardiography was used to assess transmitral and transtricuspidal flow patterns from the apical four-chamber view with the sample volume placed at the mitral and tricuspid valves leaflets tips. Early (E) and late (A) diastolic velocities, deceleration time (DT), and E/A ratio were measured for mitral valve. Right-ventricle global systolic function was assessed through tricuspid annular plane systolic excursion (TAPSE). In addition to the conventional echocardiographic measures, tissue Doppler imaging (TDI) studies were performed from the four-chamber view, with Doppler sample volume placed at the lateral  and septal  myocardial segments of the mitral annulus and at lateral border of the tricuspid annulus ; peak systolic (S’), early (e’) diastolic, and late diastolic (a’) waves were measured for both ventricles from a minimum of three cardiac cycles and averaged. Isovolumetric relaxation time (IVRT), isovolumetric contraction time (IVCT), and ejection time (ET) were measured on LMA, and the LV Tei index was calculated using the following formula: (isovolumic relaxation time + isovolumic contraction time)/ejection time.E/e′ ratios for the LV  were determined using previously estimated Doppler transmitral values.The acquired data were analyzed offline using dedicated software  was carried out on DNA extracted from peripheral blood lymphocytes for the 10 patients with nomenclature used according to the International System for Human Cytogenomic Nomenclature 2016 (ISCN). Segregation analysis of the molecular defects was performed according to parents’ availability. Except for the two analyses of SNP array-CGH (patient 7 and 9), array-CGH was performed in all the other cases using the Invitrogen pure link Genomic DNA Mini Kit (patient 2) and Agilent kit 8 × 60K . Data analysis was performed using software CytoSure Interpret Software v.4.10.35 (patient 2) and FE Agilent technologies  .SNP array-CGH was performed in patient 7 using CytoSNP-850K  and analyzed with the Bluegenome Bluefuse Multi Software Edition 4.4 software, while it was performed in patient 10 using the CytoScan HD and chromosome analysis suite v4.0 software.https://www.deciphergenomics.org/browser, assessed on 30 September 2022) and the UCSC genome browser  to build GrCh38 of the human genome. To evaluate the genomic region involved, the array-CGH and SNP-array data were mapped on Decipher software  was used for the statistical analysis. Continuous variables were expressed as the mean ± SD (range). Qualitative variables were expressed as the frequency and percentage. When two groups were compared for echocardiographic parameters, the nonparametric Mann–Whitney U test was performed to identify significant differences. A value of Demographic characteristics of the study cohort (n = 10) and the control group (N = 22) are summarized in The median age of patients in the study cohort was 18.8 years (IQR 5.5–25.5 years), and healthy patients had a median age of 17.0 years (IQR 12–18). There was no statistically significant difference in age, gender, weight, height, BMI, and BSA between the cohort patients and controls. At the time of evaluation, all patients had normal blood pressure. Moreover, none of them had a family history of CHDs or a personal history of arrhythmias, hypertension, or cardiovascular interventions. 2 or BMI > 85th percentile) and 1/10 was underweight (BMI < 5th percentile).BMI was normal in 6/10 patients, while 3/10 patients were overweight (BMI > 25 kg/mCHDs were found in 2/10 patients with 9p deletion syndrome (20%). As shown in Two septal defects were noted in our cohort. In particular, one patient showed an ASD, whereas the second patient displayed both ASD and VSD. No major CHDs were detected in our population, but 3/10 (30%) showed mild atrioventricular valve insufficiency. Two-dimensional, M-mode, and pulsed-wave Doppler conventional echocardiographic data of the patients and controls are listed in p = 0.040, p = 0.006, respectively). No difference in left-atrial and LV M-mode measurements was detected.LV mass and LV mass BSA-indexed were significantly smaller in the study group compared with controls  was significantly lower in the 9p deletion syndrome group. Moreover, echocardiographic data regarding LV diastolic function such as E/A, LMA e’, and SMA e’ were significantly lower in 9p deletion syndrome group than the controls, whereas E/e’ septal and E/e’ lateral values were similar in the two groups. Findings related to the systolic and diastolic function of the right ventricle did not differ significantly among the two groups; TAPSE and TLA TDI parameters were completely preserved in all groups.We conducted the first Italian case study focused on a global cardiac phenotype assessment in 10 patients with 9p deletion syndrome.The 9p deletion syndrome is a rare entity mainly characterized by ID and craniofacial abnormalities such as midface hypoplasia, long philtrum and trigonocephaly. Albeit less frequently described, patients may also present more severe malformations such as abdominal wall defects , congenital diaphragmatic hernia (CDH), and CHDs . Location and extension of 9p deletions can vary among affected individuals; therefore, several phenotypic characteristics, such as cardiac defects, are variably expressed ,3. While the proximal region (9p23–p22) is considered responsible for the clinical manifestation especially trigonocephaly, the distal region (9p23.3) is associated with autism, ID, delayed speech, behavioral problems, 46,XY reversed sex , and ambiguous genitalia in both sexes [CER1 and FREM1 have been suggested as responsible for trigonocephaly, DOCK8 has been proposed as a candidate gene for mental retardation and seizures, FOXD4 has been related to speech and language delay, and DMRT1 may play a role in sex reversal [With regard to non-cardiovascular aspects, deletion of specific genes on chromosome 9p has been related to the onset of well-defined phenotypic traits. According to the literature, reversal ,24,25,26However, no consensus has yet emerged about the critical region associated with CHDs in 9p deletion syndrome.KDM4C on 9p24.1 as a gene involved in cardiac differentiation [CER1 located on 9p22.3 seems to have a role in cardiac myogenesis [FOXD4 on 9p24.3 are associated with dilated cardiomyopathy [DOCK8 is involved in the reorganization of the actin filament system and is expressed in many organs, including heart and brain; therefore, its implication in pathogenesis of CHDs is yet to be defined [Previous studies on murine embryos reported ntiation ,28, wherogenesis . Furthermyopathy . Moreove defined ,13.Variable deletions sizes and heterogenous chromosomal defects are associated with the haploinsufficiency of the 9p region. The critical region involved has been studied by different groups. Christ and colleagues  studied Although several gene mapping studies within the deleted region have been extensively analyzed, genotype–phenotype correlation has not been established for this condition due to the frequent involvement of additional chromosomal rearrangements, as well as the lack of a consistent molecular characterization. Moreover, the disruption of 29 of the genes mapped in the region can potentially cause an unmasking of recessive traits and contribute to complex presentations .Heart involvement is well known and extensively reported in genetic disorders. Aneuploidies, such as Down syndrome and Turner syndrome, are commonly associated with CHDs ,34,35. SEven though the cardiac phenotype, as part of the 9p deletion syndrome spectrum, has been reported since the first description of the syndrome by Alfi et al., the functional cardiac involvement is poorly described. Ref.  Since thCardiac features in 9p deletion syndrome are highly heterogeneous and can manifest with a wide range of severity.In our cohort, septal defects were the prominent features and were present in 20% (2/10) of patients, while an additional 30% (3/10) showed mild atrioventricular valve insufficiency. Our results concerning CHDs were comparable with those reported previously , even ifIn detail, the present study showed that 9p deletion syndrome patients have significantly changed LV geometry. LV mass and LV mass indexed for BSA were significantly smaller in the 9p deletion syndrome group when compared to controls. A possible effect of cardiac exercise on these results may be speculated. Recently, Krysztofiak and coauthors, demonstrated that regular physical activity in children and young adolescents leads to progressive heart physiological changes that include increased LV myocardial thickness and LV mass . Even though hypotonia and psychomotor development delay  may contNevertheless, the prognostic significance of our findings remains unclear; in the adult population, higher LV mass/BSA has been proposed as an independent risk factor for sudden cardiac death  even thoAn additional interesting finding in our cohort is represented by aortic remodeling in terms of increased aortic dimensions when indexed for BSA.Aortic dilation represents a well-documented entity among patients with specific syndromes  and has been associated with several CHDs , but theAortic dilatation may be dependent on primary aortic medial degeneration or a secondary result from hemodynamically significant volume overload. Medial degeneration is due to fragmentation of elastic fibers, and it is clinically associated with additional abnormal features of the skeleton and connective tissue systems . In our cohort, none of these features were clinically evident, and aortic root measurements were found to be within normal limits when compared to normograms (Z-scores). Greater aortic dimensions/BSA in 9p deletion syndrome patients may be related either to the intrinsic properties of the aortic root or to hemodynamic abnormalities that deserve further investigation.The clinical significance and potential complications of these results should be assessed through a follow-up program evaluating the possible progression of structural changes within the aortic structure. Nevertheless, we are fully aware that our results need to be validated in a larger sample cohort.Our study also adds significant information regarding LV functional parameters concerning both systolic and diastolic function.Recent studies have highlighted the value of cardiac function assessment with different echo modalities (TDI and Speckle tracking echocardiography) in syndromic patients . In thisIn particular, we identified statistically significant differences in LV systolic and diastolic function compared with healthy controls, whereas RV performance remained normal. Furthermore, when using TDI parameters, 9p deletion syndrome patients showed lower S’ wave velocities for lateral mitral annulus and reduced LV diastolic performance when compared to the control group.All patients in our cohort are asymptomatic; we should, therefore, speculate a subclinical systolic and diastolic dysfunction which can possibly evolve into progressive and symptomatic heart failure, suggesting the need of a cardiac follow up for these patients.Commonly, obesity, hypertension, dyslipidemia, and altered insulin profile are well established cardiovascular risk factors in young adults .Congenital hyperinsulinism and hyperinsulinemic hypoglycemia have been previously reported among patients with 9p deletion syndrome ,52,53, aThere is a well-known close relationship between dysregulated insulin secretion and heart failure ; howeverMyocardial strain and strain rate parameters were not assessed in our population due to the poor collaboration of these subjects when a longer exam should be performed. However, we strongly suggest performing these measurements when possible because it may add valuable information about LV dysfunction in this cohort.In our cohort, the patient with the most severe cardiac phenotype (ASD and VSD) carried the largest 9p deletion (17.9 Mb) among all the patients analyzed. Notably, all the other patients with even mild cardiac involvement  had a concomitant complex rearrangement involving a second chromosomal region with at least 8 Mb in size.None of the genes mapped within the deleted region are exclusively associated with myocardial function; therefore, a definite genotype–phenotype correlation is still missing, and a prospective study with larger population is warranted.We are aware that our study shows some limitations mainly due to the limited sample size of our cohort. Our findings concerning both cardiac morphological and functional aspects have to be interpreted cautiously since such results come from a limited number of echo studies. We firmly believe that results validation in a larger cohort is necessary, and that cardiac assessment should not be underestimated and should be integrated in the context of a long-term follow-up.Even though the presence of a cardiac phenotype has been consistently associated with the condition since the first report of 9p deletion syndrome , the lonThe present study adds valuable information about cardiac features in the context of 9p deletion syndrome and demonstrates that even patients affected by this condition without major CHDs may display subclinical cardiac structural changes and LV systolic and diastolic dysfunction.Conventional echocardiography- and TDI-derived parameters are clinically useful tools for global cardiac assessment of patients with 9p deletion syndrome, and we suggest that these parameters may be used in the future for personalized clinical assessment and follow-up.