Ethnicity Differences in Geometric Remodeling and Myocardial Composition in Hypertension unveiled by Cardiovascular Magnetic Resonance.

AIMS: Hypertensive patients of African-ancestry (Afr-a) have higher incidences of heart failure and worse clinical outcomes than hypertensive patients of European-ancestry (Eu-a), yet the underlying mechanisms remain misunderstood. This study investigated right (RV) and left (LV) ventricular remodeling alongside myocardial tissue derangements between Afr-a and Eu-a hypertensives. METHODS AND RESULTS: Sixty-three Afr-a and forty-seven Eu-a hypertensives underwent multi-parametric cardiovascular-magnetic-resonance. Biventricular volumes, mass, function, mass/end-diastolic volume (M/V) ratios, T2- and pre/post-contrast T1-relaxation-times, synthetic-extracellular-volume (s-ECV) and myocardial fibrosis (MF) were measured. Three-dimensional shape modeling was implemented to delineate ventricular geometry.LV and RV-mass (indexed to body-surface-area) and M/V ratios were significantly greater in Afr-a than Eu-a hypertensives (67.1±21.7 vs. 58.3±16.7g/m2, 12.6±3.48 vs. 10.7±2.71g/m2, 0.79±0.21 vs. 0.70±0.14g/ml, 0.16±0.04 vs. 0.13±0.03g/ml, respectively; P<0.03) mirroring LV remodeling. Afr-a patients showed greater basal-interventricular-septum thickness than Eu-a patients, which may influence LV hypertrophy and RV cavity changes. This biventricular remodeling was associated with prolonged T2-relaxation-time (47.0±2.2 vs. 45.7±2.2ms, P=0.005) and higher prevalence (23% vs. 4%, P=0.001) and extent of MF (2.3[0.6-14.3] vs. 1.6[0.9-2.5] % of LV-mass, P=0.008) in Afr-a patients. Multivariable linear regression showed modifiable cardiovascular risk-factors and greater end-diastolic volume were independently associated with greater LV or RV-mass. Furthermore, ethnicity was independently associated with greater RV-mass, supporting our hypothesis of ethnic-specific hypertensive remodeling. CONCLUSIONS: Afr-a hypertensives had distinctive biventricular remodeling, including increased RV-mass and septal thickening, and subtle myocardial tissue abnormalities compared to Eu-a hypertensives. From this study, modifiable cardiovascular risk-factors, and ventricular geometry, but not ethnicity, were independently associated with higher LV mass.

Bileaflet Tethering With Preserved LV Geometry and Function: An Unusual Mechanism of Functional Mitral Regurgitation.

An 81-year-old woman presented with acute pulmonary edema. Echocardiography revealed severe functional mitral regurgitation, the mechanism of which was unusual. An atypical bileaflet tethering caused by disharmonic annular remodeling, concomitant aortic dilatation, and reduced aorto-mitral angle without left ventricular dysfunction or dilatation was found. A transcatheter edge-to-edge repair was nonetheless successfully performed.

CMR Mapping: The 4th-Era Revolution in Cardiac Imaging.

Cardiac magnetic resonance (CMR) imaging has witnessed substantial progress with the advent of parametric mapping techniques, most notably T1 and T2 mapping. These advanced techniques provide valuable insights into a wide range of cardiac conditions, including ischemic heart disease, cardiomyopathies, inflammatory cardiomyopathies, heart valve disease, and athlete's heart. Mapping could be the first sign of myocardial injury and oftentimes precedes symptoms, changes in ejection fraction, and irreversible myocardial remodeling. The ability of parametric mapping to offer a quantitative assessment of myocardial tissue properties addresses the limitations of conventional CMR methods, which often rely on qualitative or semiquantitative data. However, challenges persist, especially in terms of standardization and reference value establishment, hindering the wider clinical adoption of parametric mapping. Future developments should prioritize the standardization of techniques to enhance their clinical applicability, ultimately optimizing patient care pathways and outcomes. In this review, we endeavor to provide insights into the potential contributions of CMR mapping techniques in enhancing the diagnostic processes across a range of cardiac conditions.

Fabry Disease: More than a Phenocopy of Hypertrophic Cardiomyopathy.

Fabry disease (FD) is a genetic lysosomal storage disease with frequent cardiovascular involvement, whose presence is a major determinant of adverse clinical outcomes. As a potentially treatable cause of left ventricular hypertrophy (LVH) and heart failure with preserved ejection fraction, the early recognition of FD is crucial to initiate enzyme replacement therapy and improve long-term prognosis. Multimodality imaging plays a central role in the evaluation of patients with FD and helps in the differential diagnosis of other conditions presenting with LVH. In the present review, we explore the current applications of multimodality cardiac imaging, in particular echocardiography and cardiovascular magnetic resonance, in the diagnosis, prognostic assessment, and follow-up of patients with FD.

Percutaneous suture-based patent foramen ovale closure: A state-of-the-art review.

Percutaneous closure of a patent foramen ovale (PFO), a common variation of interatrial septum anatomy, is a commonly performed procedure in the catheterization laboratory to reduce the risk of recurrent stroke in selected patients and to treat other PFO-related syndromes. In the last twenty years, disc-based devices have represented the armamentarium of the interventional cardiologist; recently, suture-based devices have become an attractive alternative, despite limited data regarding their long-term performance. The present review gives an overview of the current evidence regarding suture-based PFO closure, the device's characteristics, the echocardiographic evaluation of the PFO anatomy, and recommendations for patient selection. A detailed procedural guide is then provided, and potential complications and future developments in the field are discussed.

Deep Learning Image Reconstruction Algorithm for CCTA: Image Quality Assessment and Clinical Application.

OBJECTIVE: The increasing number of coronary computed tomography angiography (CCTA) requests raised concerns about dose exposure. New dose reduction strategies based on artificial intelligence have been proposed to overcome limitations of iterative reconstruction (IR) algorithms. Our prospective study sought to explore the added value of deep-learning image reconstruction (DLIR) in comparison with a hybrid IR algorithm (adaptive statistical iterative reconstruction-veo [ASiR-V]) in CCTA, even in clinical challenging scenarios, as obesity, heavily calcified vessels and coronary stents. METHODS: We prospectively included 103 consecutive patients who underwent CCTA. Data sets were reconstructed with ASiR-V and DLIR. For each reconstruction signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) was calculated, and qualitative assessment was made with a four-point Likert scale by two independent and blinded radiologists with different expertise. RESULTS: Both SNR and CNR were significantly higher in DLIR (SNR-DLIR median value [interquartile range] of 13.89 [11.06-16.35] and SNR-ASiR-V 25.42 [22.46-32.22], P < 0.001; CNR-DLIR 16.84 [9.83-27.08] vs CNR-ASiR-V 10.09 [5.69-13.5], P < 0.001).Median qualitative score was 4 for DLIR images versus 3 for ASiR-V (P < 0.001), with a good interreader reliability [intraclass correlation coefficient(2,1)e intraclass correlation coefficient(3,1) 0.60 for DLIR and 0.62 and 0.73 for ASiR-V].In the obese and in the "calcifications and stents" groups, DLIR showed significantly higher values of SNR (24.23 vs 11.11, P < 0.001 and 24.55 vs 14.09, P < 0.001, respectively) and CNR (16.08 vs 8.04, P = 0.008 and 17.31 vs 10.14, P = 0.003) and image quality. CONCLUSIONS: Deep-learning image reconstruction in CCTA allows better SNR, CNR, and qualitative assessment than ASiR-V, with an added value in the most challenging clinical scenarios.

Multimodality imaging in cardio-oncology: the added value of CMR and CCTA.

During the last 30 years, we have assisted to a great implementation in anticancer treatment with a subsequent increase of cancer survivors and decreased mortality. This has led to an ongoing interest about the possible therapy-related side-effects and their management to better guide patients therapy and surveillance in the chronic and long-term setting. As a consequence cardio-oncology was born, involving several different specialties, among which radiology plays a relevant role. Till the end of August 2022, when European Society of Cardiology (ESC) developed the first guidelines on cardio-oncology, no general indications existed to guide diagnosis and treatment of cancer therapy-related cardiovascular toxicity (CTR-CVT). They defined multimodality imaging role in primary and secondary prevention strategies, cancer treatment surveillance and early CTR-CVT identification and management. Cardiac computed tomography angiography (CCTA) has acquired a central role in coronary assessment, as far as coronary artery disease (CAD) exclusion is concerned; but on the side of this well-known application, it also started to be considered in left ventricular function evaluation, interstitial fibrosis quantification and cardiac perfusion studies. Cardiac magnetic resonance (CMR), instead, has been acknowledged as the gold standard alternative to trans-thoracic echocardiography (TTE) poor acoustic window in quantification of heart function and strain modifications, as well as pre- and post-contrast tissue characterization by means of T1-T2 mapping, early Gadolinium enhancement (EGE), late Gadolinium enhancement (LGE) and extracellular volume (ECV) evaluation. Our review is intended to provide a focus on the actual role of CMR and CCTA in the setting of a better understanding of cardiotoxicity and to draw some possible future directions of cardiac imaging in this field, starting from the recently published ESC guidelines.

Nebivolol versus placebo in patients undergoing anthracyclines (CONTROL Trial): rationale and study design.

AIMS: Anthracyclines are the chemotherapeutic agents most frequently associated with cardiotoxicity, while remaining widely used. Different neurohormonal blockers have been tested as a primary prevention strategy to prevent or attenuate the onset of cardiotoxicity, with mixed results. However, prior studies were often limited by a nonblinded design and an assessment of cardiac function based only on echocardiographic imaging. Moreover, on the basis of an improved mechanistic understanding of anthracycline cardiotoxicity mechanisms, new therapeutic strategies have been proposed. Among cardioprotective drugs, nebivolol might be able to prevent the cardiotoxic effects of anthracyclines, through its protective properties towards the myocardium, endothelium, and cardiac mitochondria. This study aims to evaluate the cardioprotective effects of the beta blocker nebivolol in a prospective, placebo-controlled, superiority randomized trial in patients with breast cancer or diffuse large B cell lymphoma (DLBCL) who have a normal cardiac function and will receive anthracyclines as part of their first-line chemotherapy programme. METHODS: The CONTROL trial is a randomized, placebo-controlled, double-blinded, superiority trial. Patients with breast cancer or a DLBCL, with a normal cardiac function as assessed by echocardiography, scheduled for treatment with anthracyclines as part of their first-line chemotherapy programme will be randomized 1 : 1 to nebivolol 5 mg once daily (o.d.) or placebo. Patients will be examined with cardiological assessment, echocardiography and cardiac biomarkers at baseline, 1 month, 6 months and 12 months. A cardiac magnetic resonance (CMR) assessment will be performed at baseline and at 12 months. The primary end point is defined as left ventricular ejection fraction reduction assessed by CMR at 12 months of follow-up. CONCLUSION: The CONTROL trial is designed to provide evidence to assess the cardioprotective role of nebivolol in patients undergoing chemotherapy with anthracyclines. CLINICAL TRIAL REGISTRATION: The study is registered in the EudraCT registry (number: 2017-004618-24) and in the ClinicalTrials.gov registry (identifier: NCT05728632).

Solving the Riddle of Sudden Cardiac Death in Hypertrophic Cardiomyopathy: The Added Role of Cardiac Magnetic Resonance.

Cardiac magnetic resonance (CMR) has been recently implemented in clinical practice to refine the daunting task of establishing the risk of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). We present an exemplificative case highlighting the practical clinical utility of this imaging modality in a 24-year-old man newly diagnosed with an apical HCM. CMR was essential in unmasking a high risk of SCD, which appeared low-intermediate after traditional risk assessment. A discussion examines the essential role of CMR in guiding the patient's therapy and underlines the added value of CMR, including novel and potential CMR parameters, compared to traditional imaging assessment for SCD risk stratification.

Long-term prognostic impact of subclinical myocardial dysfunction in patients recovered from COVID-19.

BACKGROUND: Cardiovascular sequelae may occur in patients recovered from coronavirus disease 2019 (COVID-19). Recent studies have detected a considerable incidence of subclinical myocardial dysfunction-assessed with speckle-tracking echocardiography-and of long-COVID symptoms in these patients. This study aimed to define the long-term prognostic role of subclinical myocardial dysfunction and long-COVID condition in patients recovered from COVID-19 pneumonia. METHODS: We prospectively followed up 110 patients hospitalized at our institution due to COVID-19 pneumonia in April 2020 and then recovered from SARS-CoV-2 infection. A 7-month clinical and echocardiographic evaluation was performed, followed by a 21-month clinical follow-up. The primary outcome was major adverse cardiovascular events (MACE), a composite of myocardial infarction, stroke, heart failure hospitalization, and all-cause mortality. RESULTS: A subclinical myocardial dysfunction-defined as an impairment of left ventricular global longitudinal strain (≥-18%)-was identified at a 7-month follow-up in 37 patients (34%), was associated with an increased risk of long-term MACE with a good discriminative power (area under the curve: .73) and resulted in a strong independent predictor of extended MACE in multivariate regression analyses. Long-COVID condition was not associated with a worse long-term prognosis, instead. CONCLUSIONS: In patients recovered from COVID-19 pneumonia, a subclinical myocardial dysfunction is present in one-third of the whole population at 7-month follow-up and is associated with a higher risk of MACE at long-term follow-up. Speckle-tracking echocardiography is a promising tool to optimize the risk-stratification in patients recovered from COVID-19 pneumonia, while the definition of a long-COVID condition has no prognostic relevance.

The use of dedicated long-axis views focused on the left atrium improves the accuracy of left atrial volumes and emptying fraction measured by cardiovascular magnetic resonance.

BACKGROUND: The use of apical views focused on the left atrium (LA) has improved the accuracy of LA volume evaluation by two-dimensional (2D) echocardiography. However, routine cardiovascular magnetic resonance (CMR) evaluation of LA volumes still uses standard 2- and 4-chamber cine images focused on the left ventricle (LV). To investigate the potential of LA-focused CMR cine images, we compared LA maximuml (LAVmax) and minimum (LAVmin) volumes, and emptying fraction (LAEF), calculated on both standard and LA-focused long-axis cine images, with LA volumes and LAEF obtained by short-axis cine stacks covering the LA. LA strain was also calculated and compared between standard and LA-focused images. METHODS: LA volumes and LAEF were obtained from 108 consecutive patients by applying the biplane area-length algorithm to both standard and LA-focused 2- and 4-chamber cine images. Manual segmentation of a short-axis cine stack covering the LA was used as the reference method. In addition, LA strain reservoir (εs), conduit (εe) and booster pump (εa) were calculated using CMR feature-tracking. RESULTS: Compared to the reference method, the standard approach significantly underestimated LA volumes (LAVmax: bias - 13 ml; LOA = + 11, - 37 ml; LAVmax i: bias - 7 ml/m2; LOA = + 7, - 21 ml/m2; LAVmin; bias - 10 ml, LOA: + 9, - 28 ml; LAVmin i: bias - 5 ml/m2, LOA: + 5, - 16 ml/m2), and overestimated LA-EF (bias 5%, LOA: + 23, - 14%). Conversely, LA volumes (LAVmax: bias 0 ml; LOA: + 10, - 10 ml; LAVmax i: bias 0 ml/m2; LOA: + 5, - 6 ml/m2; LAVmin: bias - 2 ml; LOA: + 7, - 10 ml; LAVmin i: bias - 1 ml/m2; LOA: + 3, - 5 ml/m2) and LAEF (bias 2%, LOA: + 11, - 7%) by LA-focused cine images were similar to those measured using the reference method. LA volumes by LA-focused images were obtained faster than using the reference method (1.2 vs 4.5 min, p < 0.001). LA strain (εs: bias 7%, LOA = 25, - 11%; εe: bias 4%, LOA = 15, - 8%; εa: bias 3%, LOA = 14, - 8%) was significantly higher in standard vs. LA-focused images (p < 0.001). CONCLUSION: LA volumes and LAEF measured using dedicated LA-focused long-axis cine images are more accurate than using standard LV-focused cine images. Moreover, LA strain is significantly lower in LA-focused vs. standard images.

Comparison of Demographic, Clinical, Biochemical, and Imaging Findings in Hypertrophic Cardiomyopathy Prognosis: A Network Meta-Analysis.

BACKGROUND: Despite hypertrophic cardiomyopathy (HCM) being the most common inherited heart disease and conferring increased risk for heart failure (HF) and sudden cardiac death (SCD), risk assessment in HCM patients is still largely unresolved. OBJECTIVES: This study aims to synthesize and compare the prognostic impact of demographic, clinical, biochemical, and imaging findings in patients with HCM. METHODS: The authors searched PubMed, Embase, and Cochrane Library for studies published from 1955 to November 2020, and the endpoints were: 1) all-cause death; 2) an arrhythmic endpoint including SCD, sustained ventricular tachycardia, ventricular fibrillation, or aborted SCD; and 3) a composite endpoint including (1) or (2) plus hospitalization for HF or cardiac transplantation. The authors performed a pairwise meta-analysis obtaining the pooled estimate separately for the association between baseline variables and study endpoints. A random-effects network meta-analysis was subsequently used to comparatively assess the prognostic value of outcome associates. RESULTS: A total of 112 studies with 58,732 HCM patients were included. Among others, increased brain natriuretic peptide/N-terminal pro-B-type natriuretic peptide, late gadolinium enhancement (LGE), positive genotype, impaired global longitudinal strain, and presence of apical aneurysm conferred increased risk for the composite endpoint. At network meta-analysis, LGE showed the highest prognostic value for all endpoints and was superior to all other associates except New York Heart Association functional class >class II. A multiparametric imaging-based model was superior in predicting the composite endpoint compared to a prespecified model based on conventional risk factors. CONCLUSIONS: This network meta-analysis supports the development of multiparametric risk prediction algorithms, including advanced imaging markers additively to conventional risk factors, for refined risk stratification in HCM. (Long-term prognosis of hypertrophic cardiomyopathy according to genetic, clinical, biochemical and imaging findings: a systemic review and meta-analysis; CRD42020185219).

Myocardial Fibrosis at Cardiac MRI Helps Predict Adverse Clinical Outcome in Patients with Mitral Valve Prolapse.

Background Patients with mitral valve prolapse (MVP) may develop adverse outcomes even in the absence of mitral regurgitation or left ventricular (LV) dysfunction. Purpose To investigate the prognostic value of mitral annulus disjunction (MAD) and myocardial fibrosis at late gadolinium enhancement (LGE) cardiac MRI in patients with MVP without moderate-to-severe mitral regurgitation or LV dysfunction. Materials and Methods In this longitudinal retrospective study, 118 144 cardiac MRI studies were evaluated between October 2007 and June 2020 at 15 European tertiary medical centers. Follow-up was from the date of cardiac MRI examination to June 2020; the minimum and maximum follow-up intervals were 6 months and 156 months, respectively. Patients were excluded if at least one of the following conditions was present: cardiomyopathy, LV ejection fraction less than 40%, ischemic heart disease, congenital heart disease, inflammatory heart disease, moderate or worse mitral regurgitation, participation in competitive sport, or electrocardiogram suggestive of channelopathies. In the remainder, cardiac MRI studies were reanalyzed, and patients were included if they were aged 18 years or older, MVP was diagnosed at cardiac MRI, and clinical information and electrocardiogram monitoring were available within 3 months from cardiac MRI examination. The end point was a composite of adverse outcomes: sustained ventricular tachycardia (VT), sudden cardiac death (SCD), or unexplained syncope. Multivariable Cox regression analysis was performed. Results A total of 474 patients (mean age, 47 years ± 16 [SD]; 244 women) were included. Over a median follow-up of 3.3 years, 18 patients (4%) reached the study end point. LGE presence (hazard ratio, 4.2 [95% CI: 1.5, 11.9]; P = .006) and extent (hazard ratio, 1.2 per 1% increase [95% CI: 1.1, 1.4]; P = .006), but not MAD presence (P = .89), were associated with clinical outcome. LGE presence had incremental prognostic value over MVP severity and sustained VT and aborted SCD at baseline (area under the receiver operating characteristic curve, 0.70 vs 0.62; P = .03). Conclusion In contrast to mitral annulus disjunction, myocardial fibrosis determined according to late gadolinium enhancement at cardiac MRI was associated with adverse outcome in patients with mitral valve prolapse without moderate-to-severe mitral regurgitation or left ventricular dysfunction. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Gerber in this issue.

Normal ranges of left atrial volumes and ejection fraction by 3D echocardiography in adults: a systematic review and meta-analysis.

Increased sizes and dysfunction of the left atrium have been related to adverse outcomes. 3D-echocardiography is more accurate than 2D-echocardiography in estimating LA volumes and ejection fraction. However, the use of 3DE for LA analysis is limited by the absence of established reference values. We performed a systematic review and meta-analysis to provide reference ranges of LA maximum and minimum volumes indexed for body surface area (LAVi max and LAVi min, respectively), and LA-EF assessed by 3DE in healthy adults. Data search was conducted from inception through September 15, 2021, using the following Medical Subject Heading terms: left atrial/atrium, three-dimensional/3D echocardiography. The study protocol was registered in the PROSPERO database (CRD42021252428). 15 studies including 4,226 healthy adults (51% males) and reporting 3DE values of LAVi max, LAVi min and LA-EF were selected. LAVi max, LAVi min and LA-EF mean and reference values were equal to 25.18 ml/m2 (95% CI 23.10, 27.26), 11.10 ml/m2 (10.01, 12.18) and 55.94% (51.92, 59.96), respectively. No influential studies were identified. Pooled estimates per age group- and sex were also estimated. By meta-regression analyses, we identified variability in LA volumes and LA-EF depending on participants' age, ethnicity and number of heart cycles at 3D multi-beat acquisition. At individual patient data analysis conducted on 374 subjects, a software effect on LA-EF was shown. This systematic review and meta-analysis provides reference values of LAVi max, LAVi min and LA-EF assessed by 3DE in healthy adults, encouraging 3DE evaluation of the LA evaluation in daily practice.

Effective Study: Development and Application of a Question-Driven, Time-Effective Cardiac Magnetic Resonance Scanning Protocol.

Background Long scanning times impede cardiac magnetic resonance (CMR) clinical uptake. A "one-size-fits-all" shortened, focused protocol (eg, only function and late-gadolinium enhancement) reduces scanning time and costs, but provides less information. We developed 2 question-driven CMR and stress-CMR protocols, including tailored advanced tissue characterization, and tested their effectiveness in reducing scanning time while retaining the diagnostic performances of standard protocols. Methods and Results Eighty three consecutive patients with cardiomyopathy or ischemic heart disease underwent the tailored CMR. Each scan consisted of standard cines, late-gadolinium enhancement imaging, native T1-mapping, and extracellular volume. Fat/edema modules, right ventricle cine, and in-line quantitative perfusion mapping were performed as clinically required. Workflow was optimized to avoid gaps. Time target was <30 minutes for a CMR and <35 minutes for a stress-CMR. CMR was considered impactful when its results drove changes in diagnosis or management. Advanced tissue characterization was considered impactful when it changed the confidence level in the diagnosis. The quality of the images was assessed. A control group of 137 patients was identified among scans performed before February 2020. Compared with standard protocols, the average scan duration dropped by >30% (CMR: from 42±8 to 28±6 minutes; stress-CMR: from 50±10 to 34±6 minutes, both P<0.0001). Independent on the protocol, CMR was impactful in ≈60% cases, and advanced tissue characterization was impactful in >45% of cases. Quality grading was similar between the 2 protocols. Tailored protocols did not require additional staff. Conclusions Tailored CMR and stress-CMR protocols including advanced tissue characterization are accurate and time-effective for cardiomyopathies and ischemic heart disease.

Recent advances in multimodality imaging of the tricuspid valve.

INTRODUCTION: The tricuspid valve (TV) and the right heart chambers are complex three-dimensional structures that are difficult to assess using tomographic imaging techniques. The progressive aging of the general population and the advancements in treating left-sided heart diseases by transcatheter procedures have contributed to the tricuspid regurgitation (TR) becoming a major public health problem associated with progression to refractory heart failure and poor outcome. Recent advances in multimodality cardiac imaging allow a better understanding of the pathophysiology of TR that may translate in better management of patients. AREAS COVERED: Three-dimensional echocardiography, cardiac magnetic resonance, and computed tomography provide complementary information to i. assess the TV complex; ii. identify the etiology and the mechanisms of TR; iii. evaluate its severity and hemodynamic consequences; iv. explore the remodeling of the right heart chambers; and v. properly plan, guide, and monitor the transcatheter interventions aimed to reduce the severity of TR. EXPERT OPINION: We need thorough understanding of both the TV and the right heart chamber geometry and function to understand the pathophysiology of TR. The integrated use of multimodality cardiac imaging is pivotal to assess patients with TR and to identify tailored and timely treatment of TR in properly selected patients.