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Background: Right ventricular dysfunction (RVD) and pulmonary hypertension have been recognized as two important prognostic features in patients with left side heart failure. Current literature does not distinguish between right heart failure (RHF) and RVD, and the two terms are used indiscriminately to describe pulmonary hypertension and RVD as well as clinical sign of RHF. Therefore, the right ventricle (RV) adaptation across the whole spectrum of left ventricular ejection fraction (LVEF) values has been poorly investigated., Methods: This is a multicenter observational prospective study endorsed by the Italian Society of Cardiology aiming to analyze the concordance between the signs and symptoms of RHF and echocardiographic features of RVD. The protocol will assess patients affected by chronic heart failure in stable condition regardless of the LVEF threshold by clinical, laboratory, and detailed echocardiographic study. During the follow-up period, patients will be observed by direct check-up visit and/or virtual visits every 6 months for a mean period of 3 years. All clinical laboratory and echocardiographic data will be recorded in a web platform system accessible for all centers included in the study., Results: The main study goals are: to investigate the concordance and discordance between clinical signs of RHF and RVD measured by ultrasonographic examination; to evaluate prognostic impact (in terms of cardiovascular mortality and heart failure hospitalization) of RVD and RHF during a mean follow-up period of 3 years; to investigate the prevalence of different right ventricular maladaptation (isolated right ventricular dilatation, isolated pulmonary hypertension, combined pattern) and the related prognostic impact., Conclusions: With this protocol, we would investigate the three main RVD patterns according to heart failure types and stages; we would clarify different RVD and pulmonary hypertension severity according to the heart failure types. Additionally, by a serial multiparametric analysis of RV, we would provide a better definition of RVD stage and how much is it related with clinical signs of RHF (ClinicalTrials.gov Identifier: NCT06002321)., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Exercise-induced mitral regurgitation (Ex-MR) is one of the mechanisms that contribute to reduced functional capacity in heart failure (HF). Its prevalence is not well defined across different HF subtypes. The aim of the present study was to describe functional phenotypes and cardiac response to exercise in HFrEF, HFmrEF, and HFpEF, according to Ex-MR prevalence. A total of 218 patients with HF [146 men, 68 (59-78) yr], 137 HFrEF, 41 HFmrEF, 40 HFpEF, and 23 controls were tested with cardiopulmonary exercise test combined with exercise echocardiography. Ex-MR was defined as development of at least moderate (≥2+/4+) regurgitation during exercise. Ex-MR was highly prevalent in the overall population (52%) although differed in the subgroups as follows: 82/137 (60%) in HFrEF, 17/41 (41%) in HFmrEF, and 14/40 (35%) in HFpEF ( P < 0.05). Ex-MR was associated with a high rate of ventilation (VE) to carbon dioxide production (VCO 2 ) in all HF subtypes [31.2 (26.6-35.6) vs. 33.4 (29.6-40.5), P = 0.004; 28.1 (24.5-31.9) vs. 34.4 (28.2-36.7), P = 0.01; 28.8 (26.6-32.4) vs. 32.2 (29.2-36.7), P = 0.01] and with lower peak VO 2 in HFrEF and HFmrEF. Exercise right ventricle to pulmonary circulation (RV-PC) uncoupling was observed in HFrEF and HFpEF patients with Ex-MR [peak TAPSE/SPAP: HFrEF 0.40 (0.30-0.57) vs. 0.29 (0.23-0.39), P = 0.006; HFpEF 0.44 (0.28-0.62) vs. 0.31 (0.27-0.33), P = 0.05]. HFpEF with Ex-MR showed a distinct phenotype characterized by better chronotropic reserve and peripheral O 2 extraction. NEW & NOTEWORTHY Ex-MR is a common mechanism across the spectrum of HF subtypes and combines with ventilatory inefficiency and RV-PC uncoupling. Interestingly, in HFpEF, Ex-MR emerged as unexpectedly prevalent and peculiarly associated with increased chronotropic response and peripheral O 2 extraction as potential adaptive mechanisms to backward flow redistribution.

Background: Cardiac resynchronization therapy (CRT) is an established treatment in patients with heart failure and prolonged QRS duration. A biventricular device is implanted to achieve faster activation and more synchronous contraction of the ventricles. Despite the convincing effect of CRT, 30-40% of patients do not respond. We decided to investigate the role of multipoint pacing (MPP) in a selected group of patients with right ventricle (RV)-to-left ventricle (LV) intervals less than 80 ms that do not respond to traditional CRT., Methods: We will enrol 248 patients in this patient-blinded, observational, clinical study aiming to investigate if MPP could decrease LV end-systolic volume (ESV) in patients with RV-to-LV interval less than 80 ms. MPP will be activated ON at implant in patients with RV-to-LV delay less than 80 ms and OFF in RV-to-LV at least 80 ms. At follow-up the activation of MPP will be related to CRT response. The primary study endpoint will be the responder rate at 6 months, defined as a decrease in LV ejection fraction, LV end-diastolic volume, LV end-systolic volume (LVESV) at least 15% from baseline. Secondary outcomes include 12 months relative percentage reduction in LVESV and a combined clinical outcome measure of response to CRT defined as the patient being alive, no hospitalization due to heart failure, and experiencing an improvement in New York Heart Association functional class (Composite-Score)., Conclusion: Reducing the nonresponder rate continues to be an important goal for CRT.If an increase in reverse remodelling can be achieved by MPP, this study supports the conduct of larger trials investigating the role of MPP on clinical outcomes in selected patients treated, right now, only with traditional CRT., Trial Registration: ClinicalTrials.gov, NCT02713308. Registered on 18 March 2016.

Tricuspid annular (TA) size, assessed by 2D transthoracic echocardiography (TTE), has a well-established prognostic value in patients undergoing mitral valve surgery, with TA dilatation triggering simultaneous tricuspid annuloplasty. While TA dilatation is common in patients with dilated atria secondary to atrial fibrillation, little is known about the mechanisms of TA dilatation in patients with sinus rhythm (SR). This study aimed to identify echocardiographic parameters most closely related to the TA size as a potential tool for identification of patients prone to developing TA enlargement. 120 patients with SR underwent clinically indicated TTE, including 30 patients with normal hearts and 90 patients diagnosed with at least one right heart abnormality, defined as: right ventricular (RV) or right atrial (RA) dilatation, ≥ moderate tricuspid regurgitation (TR) and elevated systolic pulmonary artery pressure (sPAP). RA and RV end-diastolic and end-systolic volumes (EDV, ESV) and function were measured using commercial 3D software (TomTec). 3D RV long and short axes were used as surrogate indices of RV shape. Degrees of TR and sPAP were estimated by 2D TTE. 3D TA sizing was performed at end-diastole using 3D custom software. Linear regression analysis was used to identify variables best correlated with TA size, followed by multivariate analysis to identify independent associations. The highest correlations were found between TA area and: RA ESV (r = 0.73; p < 0.01), RV EDV (r = 0.58; p < 0.01), RV end-diastolic long and short axes (r = 0.53, 0.42; both p < 0.01), TR degree (r = 0.40; p < 0.01) and sPAP (r = 0.32; p < 0.01). Multivariate analysis revealed that RA ESV was the only parameter independently associated with TA area (p < 0.05, r = 0.85). In conclusion, RA volume plays an important role in TA dilatation even in patients with normal SR. Understanding of annular remodeling mechanisms could aid in identifying patients at higher risk for TA dilatation, especially those scheduled for mitral valve surgery.

Background: Right heart catheterization (RHC) is recommended by guidelines for the diagnosis of pulmonary hypertension, the definition of hemodynamic impairment and responsiveness to drug therapy. However, RHC is an invasive test with associated risk of complications. Noninvasive echocardiographic tools, possibly predictive of pulmonary hypertension at RHC, could be therefore extremely useful., Methods: Sixty-four consecutive patients with suspected pulmonary hypertension were enrolled in the study and assessed by echocardiography and RHC. Diagnosis of pulmonary hypertension was based on mean pulmonary artery pressure (≥25 mmHg) at RHC., Results: Of 64 consecutive patients enrolled, 77% were diagnosed as having pulmonary hypertension after RHC. On the basis of significant differences between patients with pulmonary hypertension at RHC and those without on echocardiographic assessment, a multiple logistic regression model was constructed to predict the presence of pulmonary hypertension at RHC. The score was calculated using right atrium and ventricular diastolic area, tricuspid regurgitation Vmax, tricuspid regurgitation severity degree and left ventricular ejection fraction. The score area under the curve was therefore 0.786 (P = 0.0001), higher than for tricuspid regurgitation Vmax (P = 0.06). A score value more than 57 was associated with a 93% sensitivity, a 67% specificity, a 91% positive predictive power, a 73% negative predictive power, and an odds ratio 27 (P < 0.001) of pulmonary hypertension at RHC, significant even after correction at multivariable analysis. Accuracy of the prediction model was assessed in a validation cohort with comparable results (P = n.s.)., Conclusion: A simple noninvasive echocardiographic score can be useful in predicting the diagnosis of pulmonary hypertension at RHC and may be considered for the selection of patients who should undergo or could avoid RHC.

Background: Right ventricular (RV) function plays a pivotal prognostic role in multiple cardiac diseases. Echocardiography guidelines recommend that RV quantification be performed in the RV-focused view, which is theoretically more reproducible than the four-chamber (4Ch) view. However, differences between views in RV size and function measurements have never been systematically studied. Accordingly, the aim of this study was to compare (1) RV size and function parameters obtained from the RV-focused and 4Ch views and (2) test-retest variability between these two views., Methods: Fifty patients (26 men; mean age, 63 ± 18 years) undergoing clinically indicated transthoracic echocardiography were prospectively enrolled. Each patient underwent three repeated acquisitions of the 4Ch and RV-focused views by two sonographers. The first operator performed two acquisitions at the beginning and the end of the clinical transthoracic echocardiographic study, and the second operator performed the third acquisition afterward. RV size and function measurements were obtained from the two views and compared using paired t-test analysis and Bland-Altman analysis. Intra- and interoperator test-retest and intra- and interreader variability for both views were assessed using intraclass correlations and coefficients of variation., Results: All RV size parameters were significantly larger when measured in the RV-focused view compared with the 4Ch view. Also, all RV function parameters, including RV free wall and global longitudinal strain, were larger in magnitude when measured in the RV-focused view. Measurements variability was consistently better for the RV-focused view., Conclusions: RV size and function measurements obtained from the RV-focused and 4Ch views are not interchangeable. RV size and function parameters measured from the RV-focused view are more reproducible than from 4Ch acquisitions. Therefore, only the RV-focused view should be used for quantitative assessment of the right ventricle., (Copyright © 2018 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Patients with an open ventricular septal defect (VSD) after repair of pulmonary atresia (PA), VSD, and major aortopulmonary collaterals (MAPCAs) are the most vulnerable subgroup. We analyzed the impact of concomitant versus delayed VSD closure on survival and intermediate-term right ventricular (RV) function., Methods: Between October 1996 and February 2017, 96 patients underwent a pulmonary flow study-aided repair of PA/VSD/MAPCAs. For patients who underwent either concomitant or delayed intracardiac repair, echocardiographic RV systolic function was retrospectively calculated to assess (1) RV fractional area change (RVFAC) and (2) two-dimensional RV longitudinal strain (RVLS) of the free wall of the right ventricle. QLAB cardiac analysis software version 10.3 (Philips Medical Systems, Andover, MA) was used for analysis., Results: A total of 64 patients underwent concomitant VSD closure at the time of unifocalization, and 16 patients underwent delayed VSD closure at a median of 2.3 years (range: 3 days to 7.4 years). At a median follow-up of 8.1 years (range: 0.1 to 19.5 years) for the concomitant repair group versus 7.4 years (range: 0.01 to 15.3 years) for the delayed repair group, no differences in RVFAC and RVLS were observed (RVFAC: 41.0% ± 6.2% versus 41.2% ± 7.6%, p = 0.91; RVLS: -18.7 ± 4.3 versus -18.9 ± 4.0, p = 0.87)., Conclusions: Patients (83%) with PA/VSD/MAPCAs underwent complete repair at intermediate-term follow-up with preserved RV function. Delayed VSD closure was accomplished in 50% of the patients initially deemed unsuitable for repair. Delayed VSD closure did not affect survival and did not portend impaired RV systolic function., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Proper integration of multiple imaging modalities in the routine follow-up of patients with repaired tetralogy of Fallout (TOF) is poorly supported by data. We report our single center comparative study between cardiac magnetic resonance (CMR) and echocardiography to assess equipoise in the clinical utility of these two imaging methods in an unselected consecutive cohort of TOF patients referred to our outpatient clinic., Material and Methods: In this cross-sectional study, repaired TOF patients who underwent CMR and echocardiography within a 4-week period between 2010 and 2011 at our Center were included. Linear regression was used to analyze degree of inter modality correlation. A prediction model tested the association between functional data/probrain natriuretic peptide (Pro-BNP) with CMR., Results: Fifty patients were included in the study (mean age 31 ± 18 years). The best predictors of right ventricle (RV) ejection fraction at CMR were tricuspid anular plane systolic excursion (tricuspid valve anular plane systolic excursion, R 0.37, P < 0.0001) and RV peak S-wave velocity (R 0.40, P < 0.001). Pro-BNP levels did present weak correlation with New York Heart Association functional class (R 0.31, P < 0.002) and QRS duration (R 0.32, P < 0.002) and a moderate correlation with right atrium area at CMR (R 0.46, P < 0.0001)., Conclusion: We found limited correlation between the two imaging modalities in the evaluation of RV after intracardiac repair of TOF. Pro-BNP level presents moderate correlation with right atrium area measured with echocardiography. Serial CMR evaluations are needed in this patient population, but they may be interchanged by routine echocardiography in particular in patients with normal or stable echocardiographic parameters.

Objectives: This study sought to investigate how right ventricular (RV) contractile function and its coupling with pulmonary circulation (PC) stratify clinical phenotypes and outcome in heart failure preserved ejection fraction (HFpEF) patients., Background: Pulmonary hypertension and RV dysfunction are key hemodynamic abnormalities in HFpEF., Methods: Three hundred eighty seven HFpEF patients (mean age 64 ± 12 years, 59% females, left ventricular ejection fraction 59 ± 7%) underwent RV and pulmonary hemodynamic evaluation by echocardiography (entire population) and right heart catheterization (219 patients). Patients were investigated by tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) relationship and stratified according to TAPSE/PASP ratio tertiles (1: <0.35; 2: 0.35 to 0.57; 3: >0.57). Specifically, TAPSE/PASP ratio was taken as a noninvasive index of RV to PC coupling based on the correlation with invasively evaluated RV systolic elastance/arterial elastance (r = 0.35; p < 0.0001)., Results: Groups had similar prevalence of comorbidities except for a higher prevalence of atrial fibrillation and kidney dysfunction in tertile 1. Progressively increasing levels of natriuretic peptides, worse systemic and pulmonary hemodynamics, abnormal exercise aerobic capacity and ventilatory inefficiency were observed from the highest to lowest TAPSE/PASP tertile. TASPE/PASP correlated with pulmonary artery compliance (r = 0.69; p < 0.0001). Remarkably, the tertile 1 group distributed along the worse portion of the curve at lower pulmonary artery compliance and higher pulmonary vascular resistances. In addition, the TAPSE/PASP ratio emerged as an independent predictor of worse outcomes., Conclusions: A thorough assessment of RV-PC coupling and RV contractile function stratify HFpEF phenotypes at different level of risk. These observations shift the interest toward therapeutic strategies that may benefit the right heart as primary unmet need in the complex pathophysiology of the HFpEF syndrome., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Cardiovascular magnetic resonance (CMR) plays a key role in the management of thalassemia major patients, but few data are available in pediatric population. This study aims at a retrospective multiparametric CMR assessment of myocardial iron overload, function, and fibrosis in a cohort of pediatric thalassemia major patients., Methods and Results: We studied 107 pediatric thalassemia major patients (61 boys, median age 14.4 years). Myocardial and liver iron overload were measured by T2* multiecho technique. Atrial dimensions and biventricular function were quantified by cine images. Late gadolinium enhancement images were acquired to detect myocardial fibrosis. All scans were performed without sedation. The 21.4% of the patients showed a significant myocardial iron overload correlated with lower compliance to chelation therapy (P<0.013). Serum ferritin ≥2000 ng/mL and liver iron concentration ≥14 mg/g/dw were detected as the best threshold for predicting cardiac iron overload (P=0.001 and P<0.0001, respectively). A homogeneous pattern of myocardial iron overload was associated with a negative cardiac remodeling and significant higher liver iron concentration (P<0.0001). Myocardial fibrosis by late gadolinium enhancement was detected in 15.8% of the patients (youngest children 13 years old). It was correlated with significant lower heart T2* values (P=0.022) and negative cardiac remodeling indexes. A pathological magnetic resonance imaging liver iron concentration was found in the 77.6% of the patients., Conclusions: Cardiac damage detectable by a multiparametric CMR approach can occur early in thalassemia major patients. So, the first T2* CMR assessment should be performed as early as feasible without sedation to tailor the chelation treatment. Conversely, late gadolinium enhancement CMR should be postponed in the teenager age., (© 2015 American Heart Association, Inc.)

Background: The mechanism of cardiac resynchronization therapy (CRT)-induced proarrhythmia remains unknown. We postulated that pacing from a left ventricular (LV) lead positioned on epicardial scar can facilitate re-entrant ventricular tachycardia. The aim of this study was to investigate the relationship between CRT-induced proarrhythmia and LV lead location within scar., Methods and Results: Twenty-eight epicardial and 63 endocardial maps, obtained from 64 CRT patients undergoing ventricular tachycardia ablation, were analyzed. A positive LV lead/scar relationship, defined as a lead tip positioned on scar/border zone, was determined by overlaying fluoroscopic projections with LV electroanatomical maps. CRT-induced proarrhythmia occurred in 8 patients (12.5%). They all presented early with electrical storm (100% versus 39% of patients with no proarrhythmia; P<0.01), requiring temporary biventricular pacing discontinuation in half of cases. They more frequently presented with heart failure/cardiogenic shock (50% versus 7%; P<0.01), requiring intensive care management. Ventricular tachycardia was re-entrant in all. The LV lead location within epicardial scar was significantly more frequent in the proarrhythmia group (60% versus 9% P=0.03 on epicardial bipolar scar, 80% versus 17% P=0.02 on epicardial unipolar scar, and 80% versus 17% P=0.02 on any-epicardial scar). Ablation was performed within epicardial scar, close to the LV lead, and allowed CRT reactivation in all patients., Conclusions: CRT-induced proarrhythmia presented early with electrical storm and was associated with an LV lead positioning within epicardial scar. Catheter ablation allowed for resumption of biventricular stimulation in all patients., (© 2014 American Heart Association, Inc.)

Introduction: The left ventricular (LV) pacing site and the magnitude of the electrical delay within the LV, as expressed by prolonged QRS duration, are major determinants of cardiac resynchronization therapy (CRT) efficacy. We investigated the incremental value of positioning the LV lead in areas of late activation in order to enhance the response to CRT in patients with different degrees of QRS complex lengthening., Methods and Results: This analysis was performed on 301 heart failure patients who received a CRT defibrillator. On implantation, the right ventricular (RV)-to-LV interval was measured as the delay between local activations recorded through the RV and LV leads in the final position. After 1 year, 171 (57%) patients displayed reverse LV remodeling, as measured by a ≥15% reduction in the LV end-systolic volume. Both the RV-to-LV interval and its percentage value corrected for the QRS duration were significantly associated with a positive response to CRT. An RV-to-LV interval >80 milliseconds and an RV-to-LV interval/QRS >58% yielded the best prediction of reverse remodeling. Although the response to CRT decreased with shorter QRS duration in the overall population, patients with an RV-to-LV interval >80 milliseconds showed a response rate >65% in all QRS subgroups., Conclusion: A longer RV-to-LV interval is associated with reverse LV remodeling after CRT. On implantation attempts could be made to maximize it when selecting the LV lead position, especially in patients with shorter QRS duration, and thus less likely to respond positively to CRT., (© 2014 Wiley Periodicals, Inc.)

Introduction: Right ventricular (RV) systolic dysfunction is a strong prognostic predictor in chronic heart failure (HF). However, assessment of RV function remains difficult. We investigated the prognostic value of different echocardiographic parameters for evaluating RV function in 60 patients with chronic HF and a low left ventricular ejection fraction (<40%) who were on optimal medical treatment., Methods: RV function was assessed using standard and tissue Doppler echocardiography. The following parameters were measured: tricuspid annular plane systolic excursion (TAPSE), right ventricular fractional area change (RVFAC), right myocardial performance index (MPI), tissue Doppler peak myocardial velocity (Sm) and longitudinal strain of the right ventricular wall in the basal and middle segments., Results: During a mean follow-up of 32 ± 13 months, 6 patients died and 16 were hospitalised for HF. TAPSE, RVFAC, right MPI and Sm did not predict cardiovascular events. The only variable associated with either cardiac death or HF hospitalisation (p=0.002), or HF hospitalisation only (p<0.0001) was systolic longitudinal strain in the basal and middle segments of the RV wall., Conclusion: Our study demonstrates that longitudinal RV strain is a powerful prognostic variable for the prediction of major cardiac events in patients with chronic HF.

Objectives: To detect right ventricular myocardial function in dilated cardiomyopathy (DCM) using two-dimensional strain echocardiography (2DSE) and to evaluate the relationship between right ventricular dysfunction and response to cardiopulmonary exercise test (CPET)., Methods: Seventy-five DCM patients (44 idiopathic and 31 ischemic) without clinical signs of right ventricular failure underwent standard echo, 2DSE analysis of right ventricle and bicycle CPET., Results: The two groups were comparable for clinical and standard two-dimensional echocardiographic and Doppler variables, except for right ventricular diameters that were mildly increased in patients with idiopathic DCM. Right ventricular global longitudinal strain (RV GLS) and regional peak myocardial right ventricular strain were significantly impaired in patients with idiopathic DCM compared with ischemic DCM (both P<0.001). A significant correlation was detectable among RV GLS and VO2 peak percentage (r= -0.65, P<0.0001), VE/VCO2 slope (r=0.35, P<0.01), maximum work rate percentage (r= -0.55, P<0.001) and peak circulatory power (r=0.53, P<0.001). These correlations with RV GLS remained significant even in multivariate analysis., Conclusion: 2DSE represents a promising noninvasive technique to assess right ventricular myocardial function in patients with DCM. Reduced right ventricular myocardial deformation is related to decreased ability to perform aerobic exercise and work rate, and to impaired ventilatory response.