Phase 3 Trial of Interleukin-1 Trap Rilonacept in Recurrent Pericarditis.

BACKGROUND: Interleukin-1 has been implicated as a mediator of recurrent pericarditis. The efficacy and safety of rilonacept, an interleukin-1α and interleukin-1ß cytokine trap, were studied previously in a phase 2 trial involving patients with recurrent pericarditis. METHODS: We conducted a phase 3 multicenter, double-blind, event-driven, randomized-withdrawal trial of rilonacept in patients with acute symptoms of recurrent pericarditis (as assessed on a patient-reported scale) and systemic inflammation (as shown by an elevated C-reactive protein [CRP] level). Patients presenting with pericarditis recurrence while receiving standard therapy were enrolled in a 12-week run-in period, during which rilonacept was initiated and background medications were discontinued. Patients who had a clinical response (i.e., met prespecified response criteria) were randomly assigned in a 1:1 ratio to receive continued rilonacept monotherapy or placebo, administered subcutaneously once weekly. The primary efficacy end point, assessed with a Cox proportional-hazards model, was the time to the first pericarditis recurrence. Safety was also assessed. RESULTS: A total of 86 patients with pericarditis pain and an elevated CRP level were enrolled in the run-in period. During the run-in period, the median time to resolution or near-resolution of pain was 5 days, and the median time to normalization of the CRP level was 7 days. A total of 61 patients underwent randomization. During the randomized-withdrawal period, there were too few recurrence events in the rilonacept group to allow for the median time to the first adjudicated recurrence to be calculated; the median time to the first adjudicated recurrence in the placebo group was 8.6 weeks (95% confidence interval [CI], 4.0 to 11.7; hazard ratio in a Cox proportional-hazards model, 0.04; 95% CI, 0.01 to 0.18; P<0.001 by the log-rank test). During this period, 2 of 30 patients (7%) in the rilonacept group had a pericarditis recurrence, as compared with 23 of 31 patients (74%) in the placebo group. In the run-in period, 4 patients had adverse events leading to the discontinuation of rilonacept therapy. The most common adverse events with rilonacept were injection-site reactions and upper respiratory tract infections. CONCLUSIONS: Among patients with recurrent pericarditis, rilonacept led to rapid resolution of recurrent pericarditis episodes and to a significantly lower risk of pericarditis recurrence than placebo. (Funded by Kiniksa Pharmaceuticals; RHAPSODY ClinicalTrials.gov number, NCT03737110.).

Immobile Leaflets at Time of Bioprosthetic Valve Implantation: A Novel Risk Factor for Early Bioprosthetic Failure: A Novel Risk Factor for Early Bioprosthetic Failure.

OBJECTIVES: The clinical implications of finding immobile leaflet(s) at the time of bioprosthetic valve implantation but with acceptable prosthetic haemodynamics are uncertain. We sought to determine the characteristics of such patients and their impact on outcome. METHODS: Patients with immobile leaflet at the time of surgical bioprosthetic valve implantation were identified retrospectively by a systematic search of an institutional echocardiography database (2010-2020). Intraoperative echocardiograms were reviewed de-novo to confirm immobile leaflet(s) at the time of implantation. Cases were matched 1:2 to controls with normal bioprosthetic leaflets motion for age, sex, prosthesis position, prosthesis model, size, year of implantation, and pre-implantation left ventricular ejection fraction. Proportional hazards method was used to analyse the composite endpoint of stroke, valve thrombosis or re-intervention. RESULTS: Immobile leaflet at the time of bioprosthetic valve implantation were found in 26 patients (median age 71 ys 39% males) following tricuspid (n=13), mitral (n=11) and aortic (n=2) valve replacements; 96% received porcine prostheses; prosthesis size was 27 mm or larger in 92%. Immobile leaflet were recorded on intraoperative reports in 16 (62%) cases. It resulted in elevated gradient or mild-moderate prosthetic regurgitation in three (12%), but none led to immediate corrective action intraoperatively. At median follow-up of 21 (4-50) months, presence of immobile leaflet was associated with composite clinical endpoint of stroke, valve thrombosis or re-intervention (hazard ratio 6.8, 95% CI 1.8-25.2, p<0.01) compared to controls. CONCLUSION: Immobile leaflet immediately post-bioprosthetic valve implantation is frequently under-recognised intraoperatively and appears to be associated with early bioprosthetic dysfunction and worse clinical outcome.

Aetiology and outcomes of severe right ventricular dysfunction.

AIMS: Right ventricular dysfunction (RVD) is an important determinant of functional status and survival in various diseases states. Data are sparse on the epidemiology and outcome of patients with severe RVD. This study examined the characteristics, aetiology, and survival of patients with severe RVD. METHODS AND RESULTS: Retrospective study of consecutive patients with severe RVD diagnosed by transthoracic echocardiography (TTE) between 2011 and 2015 in a single tertiary referral institution. Patients with prior cardiac surgery, mechanical assist devices, and congenital heart disease were excluded. Primary endpoint was all-cause mortality. In 64 728 patients undergoing TTE, the prevalence of ≥mild RVD was 21%. This study focused on the cohort of 1299 (4%) patients with severe RVD; age 64 ± 16 years; 61% male. The most common causes of severe RVD were left-sided heart diseases (46%), pulmonary thromboembolic disease (18%), chronic lung disease/hypoxia (CLD; 17%), and pulmonary arterial hypertension (PAH; 11%). After 2 ± 2 years of follow-up, 701 deaths occurred, 66% within the first year of diagnosis. The overall probability of survival at 1- and 5 years for the entire cohort were 61% [95% confidence interval (CI) 58-64%] and 35% (95% CI 31-38%), respectively. In left-sided heart diseases, 1- and 5-year survival rates were 61% (95% CI 57-65%) and 33% (95% CI 28-37%), respectively; vs. 76% (95% CI 68-82%) and 50% (95% CI 40-59%) in PAH, vs. 71% (95% CI 64-76%) and 49% (95% CI 41-58%) in thromboembolic diseases, vs. 42% (95% CI 35-49%) and 8% (95% CI 4-15%) in CLD (log-rank P < 0.0001). Presence of ≥moderate tricuspid regurgitation portended worse survival in severe RVD. CONCLUSION: One-year mortality of patients with severe RVD was high (∼40%) and dependent on the aetiology of RVD. Left-sided heart diseases is the most common cause of severe RVD but prognosis was worst in CLD.

Imaging in blunt thoracic trauma: The importance of clinical correlation.

We present the case of a 26-year-old female restrained front-seat passenger who presents following a motor vehicle accident, with CT angiogram features suggestive of possible acute aortic injury. However, clinical features including relative hemodynamic stability and absence of typical symptoms were discordant with these imaging findings. This case illustrates that even with ECG-gating, CT angiogram artifact mimicking acute aortic injury may still occur. Careful evaluation and clinical correlation is of vital importance, both to ensure acute aortic injury is not missed and that patients are not erroneously sent for aortic surgery when there is no aortic injury. Careful clinical evaluation must be combined with imaging in all cases of suspected aortic trauma, and at times multimodality imaging is indicated to direct the decision making strategy.

Advanced cardiac imaging techniques assist in characterizing a cardiac mass and directing management.

Advanced imaging techniques, including contrast echocardiography and CMR, provided valuable characterization and evaluation of a boy with an unusual cardiac mass. Imaging features assisted with differentiation of benign from malignant etiology and excluding thrombus. Accurate imaging techniques saved our patient risks associated with unnecessary surgery or anticoagulation. The ability to accurately define size serially assisted in guiding expectant management. He died from a noncardiac cause at age 28, and autopsy demonstrated a hamartoma of mature cardiac myocytes.

Absence of Pericarditis Recurrence in Rilonacept-Treated Patients With COVID-19 and SARS-CoV-2 Vaccination: Results From the RHAPSODY Long-term Extension.

Background: Rilonacept inhibits the interleukin-1 pathway, and extended treatment in patients with recurrent pericarditis (RP) reduced recurrence risk by 98% in the phase 3 trial, RHAPSODY long-term extension (LTE). Severe acute respiratory syndrome (SARS)-CoV-2 vaccination and/or infection may trigger pericarditis recurrence, and in clinical practice, it is unknown whether to continue rilonacept during SARS-CoV-2 infection. This post-hoc analysis of the RHAPSODY LTE aimed to inform rilonacept management in RP patients vaccinated against SARS-CoV-2 or who contract COVID-19. Methods: Analysis was conducted from May 2020 to June 2022. The LTE portion of RHAPSODY LTE enabled up to 24 months of additional open-label rilonacept treatment beyond the pivotal study. Rilonacept efficacy data in preventing pericarditis recurrence were assessed, and concomitant SARS-CoV-2 vaccination and COVID-19 adverse event data were evaluated. Results: No pericarditis recurrences were temporally associated with vaccination. Sixteen COVID-19 cases were reported; 10 in 30 unvaccinated or partially vaccinated patients (33%) vs 6 of 44 fully vaccinated patients (14%; P = 0.04). Twelve of 16 patients (75%) were receiving rilonacept at the time of infection, and none experienced pericarditis recurrence. One pericarditis recurrence occurred in the peri-COVID-19 period in 1 of 4 patients who had stopped rilonacept treatment > 4.5 months prior. COVID-19 severity was mild in 13 patients, moderate in 2, and severe in 1. Conclusions: Full vaccination effectively reduced COVID-19 events in patients treated with rilonacept. Vaccination or COVID-19 during rilonacept treatment did not increase pericarditis recurrence. Continued rilonacept treatment in patients contracting COVID-19 did not worsen disease severity, whereas rilonacept interruption increased pericarditis recurrence, supporting a recommendation for continued rilonacept treatment for RP during vaccination or COVID-19. ClinicalTrialsgov identifier: NCT03737110.

Contexte: Le rilonacept inhibe la voie de l'interleukine-1 et, d'après les résultats de la période de prolongation à long terme de l'essai de phase III RHAPSODY, la poursuite du traitement par cet agent chez les patients atteints de péricardite récidivante a réduit le risque de récidive de 98 %. La vaccination contre le syndrome respiratoire aigu sévère (SRAS)-CoV-2 ou l'infection à ce virus pourrait toutefois déclencher une récidive de la péricardite, et dans la pratique clinique, on ignore s'il vaut mieux poursuivre le traitement par rilonacept pendant l'infection à SRAS-CoV-2. Cette analyse post-hoc de la période de prolongation à long terme de l'essai RHAPSODY vise à orienter la gestion du rilonacept chez les patients atteints de péricardite récidivante qui sont vaccinés contre le SRAS-CoV-2 ou qui contractent la COVID-19. Méthodologie: L'analyse a été effectuée de mai 2020 à juin 2022. La période de prolongation à long terme de l'essai RHAPSODY a permis d'accumuler des données en mode ouvert pendant une période allant jusqu'à 24 mois au-delà de l'étude pivot. Les données sur l'efficacité du rilonacept en prévention de la récidive de péricardite ont été évaluées, tout comme les données sur la vaccination concomitante contre le SRAS-CoV-2 et les cas de COVID-19. Résultats: Aucune récidive de la péricardite n'a pu être associée sur le plan temporel avec la vaccination. Au total, 16 cas de COVID-19 ont été signalés, dont 10 chez les patients non vaccinés ou partiellement vaccinés sur 30 (33 %) et 6 chez les patients complètement vaccinés sur 44 (14 %; p = 0,04). De ces 16 patients, 12 (75 %) prenaient du rilonacept au moment de l'infection et aucun n'a connu de récidive de la péricardite. Une récidive de la péricardite s'est produite dans la période suivant la COVID-19 chez 1 des 4 patients qui avaient cessé de prendre le rilonacept > 4,5 mois auparavant. La COVID-19 a été légère chez 13 patients, modérée chez 2 patients et sévère chez 1 patient. Conclusions: La vaccination complète a réduit efficacement les cas de COVID-19 chez les patients traités par le rilonacept. La vaccination ou l'infection à SRAS-CoV-2 pendant le traitement par rilonacept n'a pas augmenté le risque de récidive de la péricardite. La poursuite du traitement par rilonacept chez les patients atteints de COVID-19 n'a pas aggravé la sévérité de la maladie, tandis que l'interruption du traitement a augmenté le risque de récidive de la péricardite, ce qui plaide en faveur de la recommandation de poursuivre le traitement de la péricardite récidivante par le rilonacept pendant la vaccination ou la COVID-19. Numéro d'identification ClinicalTrialsgov: NCT03737110.

Sustained Pericarditis Recurrence Risk Reduction With Long-Term Rilonacept.

BACKGROUND: Rilonacept, a once-weekly interleukin-1 alpha and beta cytokine trap, reduced pericarditis recurrence in the phase 3 study, RHAPSODY (Rilonacept Inhibition of Interleukin-1 Alpha and Beta for Recurrent Pericarditis: A Pivotal Symptomatology and Outcomes Study). The RHAPSODY long-term extension further explored recurrent pericarditis natural history and treatment duration decision-making during 24 additional months of open-label rilonacept treatment. METHODS AND RESULTS: Seventy-four patients commenced the long-term extension, with a median (maximum) total rilonacept duration of 22 (35) months. Individually, 18 months after the most proximal pericarditis recurrence, investigators decided to continue rilonacept on study, suspend rilonacept for off-treatment observation (rescue allowed), or discontinue the study. The annualized incidence of pericarditis recurrence on rilonacept up to the 18-month decision milestone was 0.04 events/patient-year versus 4.4 events/patient-year prestudy while on oral therapies. At the 18-month decision milestone, 64% (33/52) continued rilonacept, 15% (8/52) suspended rilonacept for observation, and 21% (11/52) discontinued the study. Among the 33 patients (1/33; 3.0%) continuing rilonacept (median time to recurrence could not be estimated due to too few events), a single recurrence occurred 4 weeks after a treatment interruption. Among patients suspending rilonacept, 75% (6/8) experienced recurrence (median time to recurrence, 11.8 weeks [95% CI, 3.7 weeks to not estimable]). There was a 98% reduction in risk of pericarditis recurrence among patients continuing rilonacept treatment after the 18-month decision milestone versus those suspending treatment for observation (hazard ratio, 0.02; P<0.0001). CONCLUSIONS: In the RHAPSODY long-term extension, continued rilonacept treatment resulted in continued response; treatment suspension at the 18-month decision milestone was associated with pericarditis recurrence. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03737110.

The safety profile of perflutren microsphere contrast echocardiography during rest and stress imaging: results from an Australian multicentre cohort.

BACKGROUND: Contrast enhanced echocardiography (CEE) is utilised when sub-optimal image quality results in non-diagnostic echocardiograms. However, there have been numerous safety notices issued by regulatory authorities regarding rare but potentially serious adverse reactions (AR). This multi-centre, retrospective analysis was performed to assess the short-term safety of CEE in a broad range of indications. METHODS: All CEE performed over 58 months at three institutions were assessed for AR within 30 min. RESULTS: A total of 5956 CEE were performed in 5576 patients. A total of 4903 were stress CEE and 1053 resting CCE. Bolus administration in 5719, infusion in 237 cases; 89.9% of CCE were outpatients. Commonest CEE indication was functional stress testing (82.3%). There were 16 AR related to CEE (0.27%). All AR were mild, transient and all patients made a full recovery. No cases of serious anaphylaxis or death within 30 min of contrast administration. Comparing those with and without an AR, there were no significant differences in age, gender, BMI, LVEF, patient location, exam type or RVSP. There was a slightly increased likelihood of an AR during infusion versus bolus dosing (p = 0.02). CONCLUSION: CEE is a safe investigation in a broad range of indications and clinical scenarios. AR are very rare, mild and transient.

First Australian transapical mitral valve-in-valve implant for a failed mitral bioprosthesis: how to do it.

Transcatheter aortic valve replacements lower mortality in patients not suitable for surgical valve replacement compared to conservative treatment. Transcatheter valve-in-valve implants have been shown to be feasible in failed bioprostheses in aortic, mitral, pulmonary and tricuspid positions. We report the first Australasian experience of a transapical mitral valve-in-valve placement with an Edwards Sapien(®) transcatheter valve for a failed mitral bioprosthesis, focussing on the technical aspects of this novel procedure. Whilst the evidence for this niche indication is limited currently to case reports and case series, further evaluation of its long term outcomes may justify its use in this particularly high risk group of re-do sternotomy patients.

MELD and MELD XI Scores as Predictors of Mortality After Pericardiectomy for Constrictive Pericarditis.

OBJECTIVE: To assess the association between the preoperative model for end-stage liver disease (MELD) and MELD-XI (exclude international normalized ratio) score and outcomes in patients undergoing pericardiectomy for constrictive pericarditis. PATIENTS AND METHODS: Patients >18 years of age undergoing pericardiectomy for constrictive pericarditis between January 1, 2007, and October 12, 2017, were analyzed with data for MELD and MELD-XI score calculation within 30 days preoperatively. The association between the MELD and MELD-XI scoring systems and risk of postoperative outcomes was assessed in regression models adjusting for relevant covariates. The primary outcome was operative mortality (death within 90 days or in hospital). Secondary outcomes included various measures of postoperative morbidity. RESULTS: A total of 175 and 226 patients had data for MELD/MELD-XI, respectively. Ninety-day mortality was 8.7%. When stratified into tertiles of MELD-XI, the unadjusted risk of 90-day mortality was 2.7%, 8.2%, and 16.0%, respectively. In Cox regression models fitted for MELD-XI and MELD, higher scores associated with increased risk of mortality (P<.001 for both). In secondary multivariable analyses, both MELD-XI and MELD were associated with increased incidence of renal failure and greater levels of chest-tube output and transfusion, whereas MELD-XI was additionally associated with prolonged intubation and extended intensive care unit and hospital stays. CONCLUSION: Among patients undergoing pericardiectomy for constrictive pericarditis, MELD-XI and MELD were associated with increased postoperative morbidity and mortality. Although the simpler MELD-XI score generally performed as well or better than MELD as a correlate of various outcomes, both scores can serve as a simple yet robust risk stratification tool for patients undergoing pericardiectomy for constrictive pericarditis.

Outcomes of Tricuspid Valve Operation at the Time of Pericardiectomy for Constrictive Pericarditis.

BACKGROUND: This study sought to determine the outcome effect of concomitant tricuspid valve operation for regurgitation during pericardiectomy for constrictive pericarditis. METHODS: This cohort study included 310 patients with mild or greater tricuspid valve regurgitation who underwent pericardiectomy for constrictive pericarditis from 2000 to 2016 at the Mayo Clinic in Rochester, Minnesota. Patients were divided into 2 treatment groups: tricuspid valve operation (n = 68) and no tricuspid operation (n = 242). Survival analysis, proportional odds models, and landmark analysis were carried out to estimate the treatment effects of tricuspid valve operation. RESULTS: Tricuspid valve regurgitation was graded mild in 203 (65%) patients, moderate in 69 (22%), and severe in 38 (12%). Tricuspid valve operation included repair in 54 patients (17%) and replacement in 14 (5%). Mechanical circulatory support was used more commonly in the intervention group (15% vs 5%; P = .009), but rates of stroke (3% vs 2%; P = .210) and mortality (9% vs 6%; P = .422) were similar. Tricuspid valve intervention resulted in a reduced risk of long-term mortality (hazard ratio, 0.68; 95% confidence interval [CI], 0.38 to 1.21; P = .192), less than moderate tricuspid valve regurgitation at follow-up (odds ratio vs moderate or severe, 0.093; 95% CI, 0.04 to 0.19), and less than moderate right ventricular enlargement at follow-up (odds ratio vs moderate or severe, 0.67; 95% CI, 0.35 to 1.24). Remnant severe right ventricular dysfunction resulted in increased risk of mortality (hazard ratio vs none or trivial, 4.87; 95% CI, 1.10 to 21.65; P = .037). CONCLUSIONS: Concomitant tricuspid valve operation for regurgitation can be performed without increased operative mortality during pericardiectomy for constrictive pericarditis. Operation appears protective against long-term mortality, residual tricuspid regurgitation, and right ventricular enlargement.

High Prevalence of Severe Aortic Stenosis in Low-Flow State Associated With Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a low-flow state and may underestimate aortic stenosis (AS) severity. Single-high Doppler signals (HS) consistent with severe AS (peak velocity ≥4 m/s or mean gradient ≥40 mm Hg) are averaged down in current practice. The objective for the study was to determine the significance of HS in AF low-gradient AS (LGAS). METHODS: One thousand five hundred forty-one patients with aortic valve area ≤1 cm2 and left ventricular ejection fraction ≥50% were identified and classified as high-gradient AS (HGAS) (≥40 mm Hg) and LGAS (<40 mm Hg), and AF versus sinus rhythm (SR). Available computed tomography aortic valve calcium scores (AVCS) were retrieved from the medical record. Outcomes were assessed. RESULTS: Mean age was 76±11 years, female 47%. Mean gradient was 51±12 in SR-HGAS, 48±10 in AF-HGAS, 31±5 in SR-LGAS, and 29±7 mm Hg in AF-LGAS, all P≤0.001 versus SR-HGAS; HS were present in 33% of AF-LGAS. AVCS were available in 34%. Compared with SR-HGAS (2409 arbitrary units; interquartile range, 1581-3462) AVCS were higher in AF-HGAS (2991 arbitrary units; IQR1978-4229, P=0.001), not different in AF-LGAS (2399 arbitrary units; IQR1817-2810, P=0.47), and lower in SR-LGAS (1593 arbitrary units; IQR945-1832, P<0.001); AVCS in AF-LGAS were higher when HS were present (P=0.048). Compared with SR-HGAS, the age-, sex-, comorbidity index-, and time-dependent aortic valve replacement-adjusted mortality risk was higher in AF-HGAS (hazard ratio=1.82 [1.40-2.36], P<0.001) and AF-LGAS with HS (hazard ratio=1.54 [1.04-2.26], P=0.03) but not different in AF-LGAS without HS or SR-LGAS (both P=not significant). CONCLUSIONS: Severe AS was common in AF-LGAS. AVCS in AF-LGAS were not different from SR-HGAS. AVCS were higher and mortality worse in AF-LGAS when HS were present.

Echocardiographic Assessment of Left Ventricular Systolic Function: An Overview of Contemporary Techniques, Including Speckle-Tracking Echocardiography.

Assessment of left ventricular systolic function has a central role in the evaluation of cardiac disease. Accurate assessment is essential to guide management and prognosis. Numerous echocardiographic techniques are used in the assessment, each with its own advantages and disadvantages. This review is based on a literature search of the PubMed, MEDLINE, EMBASE, and Scopus databases from inception through December 30, 2017, using the terms strain echocardiography, tissue Doppler strain, and speckle-tracking echocardiography. We provide the internist with a contemporary overview of current echocardiographic techniques used in the evaluation of left ventricular systolic function. In particular, we focus on the role of speckle-tracking echocardiography, including its utility in the detection of subclinical left ventricular dysfunction and the associated prognostic implications.

Prevalence and predictors of intracranial aneurysms in patients with bicuspid aortic valve.

OBJECTIVE: To determine the prevalence and outcomes of intracranial aneurysm (IA) in patients with bicuspid aortic valve (BAV). METHODS: Retrospective review of patients with BAV who underwent brain MR angiography at the Mayo Clinic from 1994 to 2013. RESULTS: There were 678 patients included in this study-mean age 57±13 years, men 480 (71%), mean follow-up 10±3 years (5913 patient-years). Coarctation of aorta (COA) was present in 154 (23%) patients.There were 59 IAs identified in 52 of 678 patients (7.7%). IA was present in 20/154 patients (12.9%) with COA and 32/524 patients (5.7%) without COA (p<0.001). For the patients without COA, female gender and right-left cusp fusion were risks factors for IA in women after adjustment for all potential variables (HR 1.76, CI 1.31 to 2.68, p=0.03). There was no significant trend in the risk for IA across age tertiles: age ≤40 years versus 41-60 years (HR 1.19, p=0.34), and age 41-60 years versus 61-80 years (HR 1.06, p=0.56).Among the 52 patients with IA, enlargement occurred in three patients (6%), rupture in two patients (4%) and four patients (8%) underwent coil embolisation. For the 626 patients without IA at baseline, no patient developed IA over 7±2 years of imaging follow-up. CONCLUSIONS: BAV is associated with a higher prevalence of IA compared to the general population, and this risk is higher in patients with COA, right-left cusp fusion and female gender.

Carcinoid heart disease: Diagnosis and management.

Hedinger syndrome refers to carcinoid valvular heart disease. The disease is believed to be triggered by vasoactive substances that result in valvular fibrosis. It classically occurs in patients with metastatic carcinoid and preferentially involves the right sided cardiac valves. Affected valves become thickened and retracted, exhibiting regurgitation and sometimes, stenosis. Echocardiography is recommended in patients with carcinoid syndrome and a follow up study is advisable in those who develop a murmur or other symptoms or signs of valvular heart disease. For appropriately selected patients, valve replacement surgery appears to improve outcomes.