Mitral Valve Surgery for Mitral Regurgitation Results in Reduced Left Ventricular Ejection Fraction in Barlow's Disease as Compared with Fibro-Elastic Deficiency.

Surgical correction of severe mitral regurgitation (MR) can reverse left ventricular (LV) remodeling in patients with mitral valve prolapse (MVP). However, whether this process is similar to the case in Barlow's Disease (BD) and Fibro-elastic Deficiency (FED) is currently unknown. The aim of this study is to evaluate post-operative LV reverse remodeling and function in patients with BD versus FED. In this study, 100 MVP patients (BD = 37 and FED = 63) with severe MR who underwent mitral valve surgery at three Belgian centers were retrospectively included. Transthoracic echocardiography was used to assess MR severity, LV volumes and function before surgery and 6 months thereafter. Baseline MR severity, LV ejection fraction (LVEF), indexed LV end-diastolic (LVEDVi) and end-systolic volumes (LVESVi) were not different between the groups. After a median follow-up of 278 days, there was a similar decrease in LVEDVi, but a trend towards a smaller decrease in LVESVi in BD compared to FED (-3.0 ± 11.2 mL/m2 vs. -5.3 ± 9.0 mL/m2; p = 0.154). This resulted in a significantly larger decrease in LVEF in BD (-8.3 ± 9.6%) versus FED (-3.9 ± 6.9%) after adjusting for baseline LVEF (p < 0.001) and type of surgical intervention (p = 0.01). These findings suggest that LV (reverse) remodeling in BD could be affected by other mechanisms beyond volume overload, potentially involving concomitant cardiomyopathy.

Tumour necrosis factor-alpha serum level is an independent predictor of medium-term all-cause mortality after transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a suitable treatment for patients with severe aortic stenosis and severely increased operative risk. There is need for a better preoperative risk assessment for TAVI candidates. AIM: To determine whether Tumour necrosis factor-alfa (TNFα) is an independent predictor of survival 500 days after TAVI. METHODS: Sixty patients undergoing TAVI were enrolled in the study. TNFα was determined. The CT measured low-density muscle fraction (LDM%) of the psoas muscle was determined. Operative risk assessment by Logistic EuroSCORE, EuroSCORE II, and STS score was performed. Frailty scores (FRAIL scale and Barthel index) were determined. RESULTS: Mean age was 81.01 ± 7.54 years. Twenty-six (43.3%) of the patients were males. In the univariable analyses, FRAIL scale and Barthel index were no predictors of survival after TAVI. In the multivariable analysis, including EuroSCORE II, LDM% and TNFα serum concentration, TNFα serum level was an independent predictor of survival 500 days after TAVI (HR: 3.167; 95%: 1.279-7.842; p = 0.013). The multivariable analysis, including TNFα as a categorical variable, showed that compared to patients in the conjugated first and second TNFα serum level tertile, patients in the third tertile had a hazard ratio (HR) of 10.606 (95%CI: 1.203 - 93.467) (p = 0.033). CONCLUSION: TNFα is an incremental independent predictor of long-term survival after TAVI.

Computed tomography measured epicardial adipose tissue and psoas muscle attenuation: new biomarkers to predict major adverse cardiac events and mortality in patients with heart disease and critically ill patients. Part II: Psoas muscle area and density.

Sarcopenia is a syndrome characterised by loss of skeletal muscle mass, loss of muscle quality, and reduced muscle strength, resulting in low performance. Sarcopenia has been associated with increased mortality and complications after medical interventions. In daily clinical practice, sarcopenia is assessed by clinical assessment of muscle strength and performance tests and muscle mass quantification by dual-energy X-ray absorptio-metry (DXA) or bioelectrical impedance analysis (BIA). Assessment of the skeletal muscle quantity and quality obtained by abdominal computed tomography (CT) has gained interest in the medical community, as abdominal CT is performed for various medical reasons, and quantification of the psoas and skeletal muscle can be performed without additional radiation load and dye administration. The definitions of CT-derived skeletal muscle mass quantification are briefly reviewed: psoas muscle area (PMA), skeletal muscle area (SMA), and transverse psoas muscle thickness (TPMT). We explain how CT attenuation coefficient filters are used to determine PMA and SMA, resulting in the psoas muscle index (PMI) and skeletal muscle index (SMI), respectively, after indexation to body habitus. Psoas muscle density (PMD), a biomarker for skeletal muscle quality, can be assessed by measuring the psoas muscle CT attenuation coefficient, expressed in Hounsfield units. The concept of low-density muscle (LDM) is explained. Finally, we review the medical literature on PMI and PMD as predictors of adverse outcomes in patients undergoing trauma or elective major surgery, transplantation, and in patients with cardiovascular and internal disease. PMI and PMD are promising new biomarkers predicting adverse outcomes after medical interventions.

Computed tomography measured epicardial adipose tissue and psoas muscle attenuation: new biomarkers to predict major adverse cardiac events (MACE) and mortality in patients with heart disease and critically ill patients. Part I: Epicardial adipose tissue.

Over the last two decades, the potential role of epicardial adipocyte tissue (EAT) as a marker for major adverse cardiovascular events has been extensively studied. Unlike other visceral adipocyte tissues (VAT), EAT is not separated from the adjacent myocardium by a fascial layer and shares the same microcirculation with the myocardium. Adipocytokines, secreted by EAT, interact directly with the myocardium through paracrine and vasocrine pathways. The role of the Randle cycle, linking VAT accumulation to insulin resistance, and the relevance of blood flow and mitochondrial function of VAT, are briefly discussed. The three available imaging modalities for the assessment of EAT are discussed. The advantages of echocardiography, cardiac CT, and cardiac magnetic resonance (CMR) are compared. The last section summarises the current stage of knowledge on EAT as a clinical marker for major adverse cardiovascular events (MACE). The association between EAT volume and coronary artery disease (CAD) has robustly been validated. There is growing evidence that EAT volume is associated with computed tomography coronary angiography (CTCA) assessed high-risk plaque features. The EAT CT attenuation coefficient predicts coronary events. Many studies have established EAT volume as a predictor of atrial fibrillation after cardiac surgery. Moreover, EAT thickness has been independently associated with severe aortic stenosis and mitral annular calcification. Studies have demonstrated that EAT volume is associated with heart failure. Finally, we discuss the potential role of EAT in critically ill patients admitted to the intensive care unit. In conclusion, EAT seems to be a promising new biomarker to predict MACE.

Pheochromocytoma-induced cardiogenic shock: A multicentre analysis of clinical profiles, management and outcomes.

OBJECTIVE: There is still uncertainty about the management of patients with pheochromocytoma-induced cardiogenic shock (PICS). This study aims to investigate the clinical presentation, management, and outcome of patients with PICS. METHODS: We collected, retrospectively, the data of 18 patients without previously known pheochromocytoma admitted to 8 European hospitals with a diagnosis of PICS. RESULTS: Among the 18 patients with a median age of 50 years (Q1-Q3: 40-61), 50% were men. The main clinical features at presentation were pulmonary congestion (83%) and cyclic fluctuation of hypertension peaks and hypotension (72%). Echocardiography showed a median left ventricular ejection fraction (LVEF) of 25% (Q1-Q3: 15-33.5) with an atypical- Takotsubo (TTS) pattern in 50%. Inotropes/vasopressors were started in all patients and temporary mechanical circulatory support (t-MCS) was required in 11 (61%) patients. All patients underwent surgical removal of the pheochromocytoma; 4 patients (22%) were operated on while under t-MCS. The median LVEF was estimated at 55% at discharge. Only one patient required heart transplantation (5.5%), and all patients were alive at a median follow-up of 679 days. CONCLUSIONS: PICS should be suspected in case of a CS with severe cyclic blood pressure fluctuation and rapid hemodynamic deterioration, associated with increased inflammatory markers or in case of TTS progressing to CS, particularly if an atypical TTS echocardiographic pattern is revealed. T-MCS should be considered in the most severe cases. The main challenge is to stabilize the patient, with medical therapy or with t-MCS, since it remains a reversible cause of CS with a low mortality rate.

Prevalence, Characteristics, and Outcomes of COVID-19-Associated Acute Myocarditis.

BACKGROUND: Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19-associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe. METHODS: A total of 112 patients with suspected AM from 56 963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19-associated AM. RESULTS: AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19-associated pneumonia. Twenty-one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia (P=0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47; P<0.0001) similarly in patients with or without pneumonia. Corticosteroids were frequently administered (55.5%). CONCLUSIONS: AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.

Immunomodulating Therapies in Acute Myocarditis and Recurrent/Acute Pericarditis.

The field of inflammatory disease of the heart or "cardio-immunology" is rapidly evolving due to the wider use of non-invasive diagnostic tools able to detect and monitor myocardial inflammation. In acute myocarditis, recent data on the use of immunomodulating therapies have been reported both in the setting of systemic autoimmune disorders and in the setting of isolated forms, especially in patients with specific histology (e.g., eosinophilic myocarditis) or with an arrhythmicburden. A role for immunosuppressive therapies has been also shown in severe cases of coronavirus disease 2019 (COVID-19), a condition that can be associated with cardiac injury and acute myocarditis. Furthermore, ongoing clinical trials are assessing the role of high dosage methylprednisolone in the context of acute myocarditis complicated by heart failure or fulminant presentation or the role of anakinra to treat patients with acute myocarditis excluding patients with hemodynamically unstable conditions. In addition, the explosion of immune-mediated therapies in oncology has introduced new pathophysiological entities, such as immune-checkpoint inhibitor-associated myocarditis and new basic research models to understand the interaction between the cardiac and immune systems. Here we provide a broad overview of evolving areas in cardio-immunology. We summarize the use of new imaging tools in combination with endomyocardial biopsy and laboratory parameters such as high sensitivity troponin to monitor the response to immunomodulating therapies based on recent evidence and clinical experience. Concerning pericarditis, the normal composition of pericardial fluid has been recently elucidated, allowing to assess the actual presence of inflammation; indeed, normal pericardial fluid is rich in nucleated cells, protein, albumin, LDH, at levels consistent with inflammatory exudates in other biological fluids. Importantly, recent findings showed how innate immunity plays a pivotal role in the pathogenesis of recurrent pericarditis with raised C-reactive protein, with inflammasome and IL-1 overproduction as drivers for systemic inflammatory response. In the era of tailored medicine, anti-IL-1 agents such as anakinra and rilonacept have been demonstrated highly effective in patients with recurrent pericarditis associated with an inflammatory phenotype.

Stress Echo 2030: The Novel ABCDE-(FGLPR) Protocol to Define the Future of Imaging.

With stress echo (SE) 2020 study, a new standard of practice in stress imaging was developed and disseminated: the ABCDE protocol for functional testing within and beyond CAD. ABCDE protocol was the fruit of SE 2020, and is the seed of SE 2030, which is articulated in 12 projects: 1-SE in coronary artery disease (SECAD); 2-SE in diastolic heart failure (SEDIA); 3-SE in hypertrophic cardiomyopathy (SEHCA); 4-SE post-chest radiotherapy and chemotherapy (SERA); 5-Artificial intelligence SE evaluation (AI-SEE); 6-Environmental stress echocardiography and air pollution (ESTER); 7-SE in repaired Tetralogy of Fallot (SETOF); 8-SE in post-COVID-19 (SECOV); 9: Recovery by stress echo of conventionally unfit donor good hearts (RESURGE); 10-SE for mitral ischemic regurgitation (SEMIR); 11-SE in valvular heart disease (SEVA); 12-SE for coronary vasospasm (SESPASM). The study aims to recruit in the next 5 years (2021-2025) ≥10,000 patients followed for ≥5 years (up to 2030) from ≥20 quality-controlled laboratories from ≥10 countries. In this COVID-19 era of sustainable health care delivery, SE2030 will provide the evidence to finally recommend SE as the optimal and versatile imaging modality for functional testing anywhere, any time, and in any patient.

Iron Deficiency Impacts Diastolic Function, Aerobic Exercise Capacity, and Patient Phenotyping in Heart Failure With Preserved Ejection Fraction: A Subanalysis of the OptimEx-Clin Study.

AIMS: Iron deficiency (ID) is linked to reduced aerobic exercise capacity and poor prognosis in patients with heart failure (HF) with reduced ejection fraction (HFrEF); however, data for HF with preserved ejection fraction (HFpEF) is scarce. We assessed the relationship between iron status and diastolic dysfunction as well as aerobic exercise capacity in HFpEF, and the contribution of iron status to patient phenotyping. METHODS AND RESULTS: Among 180 patients with HFpEF (66% women; median age, 71 years) recruited for the Optimizing Exercise Training in Prevention and Treatment of Diastolic HF (OptimEx-Clin) trial, baseline iron status, including iron, ferritin, and transferrin saturation, was analyzed (n = 169) in addition to exercise capacity (peak oxygen uptake [peak V̇O2]) and diastolic function (E/e'). ID was present in 60% of patients and was more common in women. In multivariable linear regression models, we found that diastolic function and peak V̇O2 were independently related to iron parameters; however, these relationships were present only in patients with HFpEF and ID [E/e' and iron: ß-0.19 (95% confidence interval -0.32, -0.07), p = 0.003; E/e' and transferrin saturation: ß-0.16 (-0.28, -0.04), p = 0.011; peak V̇O2 and iron: ß 3.76 (1.08, 6.44), p = 0.007; peak V̇O2 and transferrin saturation: ß 3.58 (0.99, 6.16), p = 0.007]. Applying machine learning, patients were classified into three phenogroups. One phenogroup was predominantly characterized by the female sex and few HFpEF risk factors but a high prevalence of ID (86%, p < 0.001 vs. other phenogroups). When excluding ID from the phenotyping analysis, results were negatively influenced. CONCLUSION: Iron parameters are independently associated with impaired diastolic function and low aerobic capacity in patients with HFpEF and ID. Patient phenotyping in HFpEF is influenced by including ID. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT02078947.

Steadily Increasing Inversion Time Improves Blood Suppression for Free-Breathing 3D Late Gadolinium Enhancement MRI With Optimized Dark-Blood Contrast.

MATERIALS AND METHODS: Fifty consecutive patients with previous cardiac arrhythmias, scheduled for high-resolution 3D LGE MRI, were prospectively enrolled between October 2017 and February 2020. Free-breathing 3D dark-blood LGE MRI with high isotropic resolution (1.6 × 1.6 × 1.6 mm) was performed using a conventional fixed TI (n = 25) or a dynamic TI (n = 25). The average increase in blood nulling TI per minute was obtained from Look-Locker scans before and after the 3D acquisition in the first fixed TI group. This average increment in TI was used as input to calculate the dynamic increment of the initial blood nulling TI value as set in the second dynamic TI group. Regions of interest were drawn in the left ventricular blood pool to assess mean signal intensity as a measure for blood pool suppression. Overall image quality, observer confidence, and scar demarcation were scored on a 3-point scale. RESULTS: Three-dimensional dark-blood LGE data sets were successfully acquired in 46/50 patients (92%). The calculated average TI increase of 2.3 ± 0.5 ms/min obtained in the first fixed TI group was incorporated in the second dynamic TI group and led to a significant decrease of 72% in the mean blood pool signal intensity compared with the fixed TI group (P < 0.001). Overall image quality (P = 0.02), observer confidence (P = 0.02), and scar demarcation (P = 0.01) significantly improved using a dynamic TI. CONCLUSIONS: A steadily increasing dynamic TI improves blood pool suppression for optimized dark-blood contrast and increases observer confidence in free-breathing 3D dark-blood LGE MRI with high isotropic resolution.

Fulminant Versus Acute Nonfulminant Myocarditis in Patients With Left Ventricular Systolic Dysfunction.

BACKGROUND: Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists. OBJECTIVES: This study sought to provide additional evidence on the outcome of FM and to ascertain whether patient stratification based on the main histologic subtypes can provide additional prognostic information. METHODS: A total of 220 patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms <30 days) all presenting with left ventricular systolic dysfunction were included in a retrospective, international registry comprising 16 tertiary hospitals in the United States, Europe, and Japan. The main endpoint was the occurrence of cardiac death or heart transplantation within 60 days from admission and at long-term follow-up. RESULTS: Patients with FM (n = 165) had significantly higher rates of cardiac death and heart transplantation compared with those with NFM (n = 55), both at 60 days (28.0% vs. 1.8%, p = 0.0001) and at 7-year follow-up (47.7% vs. 10.4%, p < 0.0001). Using Cox multivariate analysis, the histologic subtype emerged as a further variable affecting the outcome in FM patients, with giant cell myocarditis having a significantly worse prognosis compared with eosinophilic and lymphocytic myocarditis. In a subanalysis including only adults with lymphocytic myocarditis, the main endpoints occurred more frequently in FM compared with in NFM both at 60 days (19.5% vs. 0%, p = 0.005) and at 7-year follow up (41.4% vs. 3.1%, p = 0.0004). CONCLUSIONS: This international registry confirms that patients with FM have higher rates of cardiac death and heart transplantation both in the short- and long-term compared with patients with NFM. Furthermore, we provide evidence that the histologic subtype of FM carries independent prognostic value, highlighting the need for timely endomyocardial biopsy in this condition.

Safety of centrifugal left ventricular assist device in patients previously treated with MitraClip system.

INTRODUCTION: No data regarding the safety of continuous-flow left ventricular assist device (CF-LVAD) implantation in patients with previous MitraClip have been reported. Thus, it remains unknown whether an initial treatment strategy with MitraClip therapy might complicate future heart failure management in patients who are also considered for CF-LVAD. METHODS: We retrospectively identified 6 patients (median age of 62 years; 2 women) who had been treated with MitraClip, that were eventually implanted with a CF-LVAD (all Heartware HVAD) in 3 hospitals between 2013 and 2018. RESULTS: Patients were treated in 4 cases with 2 clips, and in 2 cases with 1 clip. Median time from MitraClip implantation to CF-LVAD implant was 282 days (interquartile range 67 to 493), and median time on CF-LVAD support was 401 days (interquartile range 105 to 492 days). Two patients underwent a heart transplant, 3 patients died on support, and 1 is alive on support. In all cases, there was a reduction of functional mitral regurgitation without MitraClip-related complications. CONCLUSIONS: Based on this small case series, implantation of a CF-LVAD appears safe in patients with a previously positioned MitraClip system, at least, with 1 or 2 clips in place, with no need for additional mitral valve surgery.

Validation of transcatheter aortic valve implantation risk scores in relation to early and mid-term survival: a single-centre study.

OBJECTIVES: The aim of this study was to validate recently proposed risk scores for the prediction of mortality up to 1 year after transcatheter aortic valve implantation (TAVI), using a self-expandable valve (CoreValve). METHODS: In this single-centre study, 225 consecutive patients with severe symptomatic aortic valve stenosis, who underwent TAVI between December 2007 and January 2015, were included. Conventional surgical risk scores (logistic EuroSCORE, EuroSCORE II and STS score) were calculated as well as newly proposed TAVI risk scores (TAVI2-SCORe, STT Score and OBSERVANT score). Medium-term survival of the patients was assessed up to 1 year after TAVI. RESULTS: The median age was 82 (77-86) years and 45.3% were male. Patients were categorized into 'non-high risk' or 'high risk' according to logistic EuroSCORE >20%, EuroSCORE II >8%, STS score >10%, TAVI2-SCORe >2, STT score >12% and OBSERVANT score >6. Thirty-day and 1-year survival rates were significantly different between 'non-high-risk' and 'high-risk' patients according to the STS score (1 year: low: 84.4% vs high: 67.0%, P = 0.010) and according to OBSERVANT score (1 year: low: 85.2% vs high: 68.4%, P = 0.005). In contrast, TAVI2-SCORe and STT score did not discriminate 'non-high-risk' and 'high-risk' patients. This was confirmed by Cox regression analysis [STS score >10%: hazard ratio: 2.484 (1.206-5.115), P = 0.014; OBSERVANT score >6: hazard ratio: 2.532 (1.295-4.952), P = 0.007]. CONCLUSIONS: In this single-centre study, OBSERVANT and STS score most accurately predicted early and mid-term survival in patients undergoing TAVI, using a self-expandable valve (CoreValve).

Late gadolinium enhancement CMR in primary mitral regurgitation.

AIMS: The appropriate timing for surgery in severe asymptomatic primary mitral regurgitation (MR) remains controversial. It has been shown that late gadolinium enhancement on cardiovascular magnetic resonance (LGE CMR), which may identify myocardial fibrosis, is associated with a worse outcome in various cardiomyopathies. We sought to investigate the prevalence and significance of delayed enhancement in primary MR. METHODS: We prospectively included 41 patients with at least moderate primary MR and without overt signs of left ventricular (LV) dysfunction. Patients with evidence of coronary artery disease, arrhythmias or significant concomitant valvular disease were excluded. All patients were scheduled for transthoracic echocardiography and LGE CMR. RESULTS: A total of 39 patients had interpretable LGE CMR images. Among them, 12 (31%) had late contrast uptake of the LV wall. LGE CMR showed an infarct pattern in three patients, a pattern of mid-wall fibrosis in seven patients and two patients had a combined pattern. Patients with delayed enhancement on CMR had significant higher LV diameters (LV end-systolic diameter 39 ± 4 vs. 34 ± 5 mm, P = 0·002; LV end-diastolic diameter 57 ± 5 vs. 50 ± 5 mm, P = 0·001). There was a trend towards a higher indexed left atrial volume (55 ± 21 vs. 44 ± 13 mL/m², P = 0·06). By contrast, there was no significant association between myocardial contrast uptake and age, LV ejection fraction and MR severity. CONCLUSION: Left ventricular remodelling seems to be associated with the presence of delayed enhancement on CMR in primary MR. Further data are needed to determine whether LGE CMR can predict a less favourable outcome or could improve risk stratification in asymptomatic primary MR.

The importance of exercise echocardiography for clinical decision making in primary mitral regurgitation.

Primary mitral regurgitation is generally an insidious disease with late onset of symptoms. Current European and American guidelines recommend surgery in severe primary mitral regurgitation when symptoms, overt left ventricular dysfunction, pulmonary hypertension or atrial fibrillation, occur. However, recent large studies reported an improved outcome in asymptomatic patients with severe mitral regurgitation referred for early mitral valve repair despite the risk of operative mortality or mitral valve replacement. Moreover, primary mitral regurgitation appears to have an important dynamic character in up to one-third of patients. This article provides an overview of the incremental evidence of the ability of exercise echocardiography to assess the functional repercussions of mitral regurgitation and the identification of high-risk patients who might benefit from early referral for surgery.