Publications by authors named "Maurice Enriquez-Sarano"

270 Publications

Relationship Between Residual Mitral Regurgitation and Clinical and Quality-of-Life Outcomes After Transcatheter and Medical Treatments in Heart Failure: The COAPT Trial.

Circulation 2021 May 27. Epub 2021 May 27.

Clinical Trials Center, Cardiovascular Research Foundation, New York, NY; The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY.

In the randomized COAPT trial, among 614 heart failure (HF) patients with 3+ or 4+ secondary mitral regurgitation (MR), transcatheter mitral valve repair (TMVr) with the MitraClip reduced MR, HF hospitalizations (HFH), and mortality and improved quality of life compared with guideline-directed medical therapy (GDMT) alone. We sought to examine the prognostic relationship between MR reduction and outcomes after TMVr and GDMT alone. Outcomes in COAPT between 30 days and 2 years were examined based on the severity of residual MR at 30 days. TMVr-treated patients had less severe residual MR at 30 days than GDMT-treated patients (0/1+, 2+, and 3+/4+: 72.9%, 19.9%, and 7.2% versus 8.2%, 26.1%, and 65.8%, respectively, P<0.0001). The rate of composite death or HFH between 30 days and 2 years was lower in patients with 30-day residual MR of 0/1+ and 2+ compared with 3+/4+ (37.7% versus 49.5% versus 72.2%, respectively, P<0.0001). This relationship was consistent in the TMVr and GDMT arms (P=0.92). The improvement in KCCQ score from baseline to 30 days was maintained between 30 days and 2 years in patients with 30-day MR ≤2+ but deteriorated in those with 30-day MR 3+/4+ (-0.3±1.7 versus -9.4±4.6, P=0.0008) consistently in both groups (P=0.95). In the COAPT trial, reduced MR at 30 days was associated with greater freedom from death or HFH and improved quality of life through 2-year follow-up whether the MR reduction was achieved by TMVr or GDMT. https://www.clinicaltrials.gov Unique Identifier: NCT01626079.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.053061DOI Listing
May 2021

Electrocardiogram screening for aortic valve stenosis using artificial intelligence.

Eur Heart J 2021 Mar 22. Epub 2021 Mar 22.

Department of Cardiovascular Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.

Aims: Early detection of aortic stenosis (AS) is becoming increasingly important with a better outcome after aortic valve replacement in asymptomatic severe AS patients and a poor outcome in moderate AS. We aimed to develop artificial intelligence-enabled electrocardiogram (AI-ECG) using a convolutional neural network to identify patients with moderate to severe AS.

Methods And Results: Between 1989 and 2019, 258 607 adults [mean age 63 ± 16.3 years; women 122 790 (48%)] with an echocardiography and an ECG performed within 180 days were identified from the Mayo Clinic database. Moderate to severe AS by echocardiography was present in 9723 (3.7%) patients. Artificial intelligence training was performed in 129 788 (50%), validation in 25 893 (10%), and testing in 102 926 (40%) randomly selected subjects. In the test group, the AI-ECG labelled 3833 (3.7%) patients as positive with the area under the curve (AUC) of 0.85. The sensitivity, specificity, and accuracy were 78%, 74%, and 74%, respectively. The sensitivity increased and the specificity decreased as age increased. Women had lower sensitivity but higher specificity compared with men at any age groups. The model performance increased when age and sex were added to the model (AUC 0.87), which further increased to 0.90 in patients without hypertension. Patients with false-positive AI-ECGs had twice the risk for developing moderate or severe AS in 15 years compared with true negative AI-ECGs (hazard ratio 2.18, 95% confidence interval 1.90-2.50).

Conclusion: An AI-ECG can identify patients with moderate or severe AS and may serve as a powerful screening tool for AS in the community.
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http://dx.doi.org/10.1093/eurheartj/ehab153DOI Listing
March 2021

Aortic Stenosis Progression, Cardiac Damage, and Survival: Comparison Between Bicuspid and Tricuspid Aortic Valves.

JACC Cardiovasc Imaging 2021 Jun 17;14(6):1113-1126. Epub 2021 Mar 17.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA. Electronic address:

Objectives: This study sought to compare aortic stenosis (AS) progression rates, AS-related cardiac damage (AS-CD) indicator incidence and determinants, and survival between patients with tricuspid aortic valve (TAV)-AS and those with bicuspid aortic valve (BAV)-AS.

Background: Differences in AS progression and AS-CD between patients with BAV and patients with TAV are unknown.

Methods: We retrospectively studied consecutive patients with baseline peak aortic valve velocity (peakV) ≥2.5 m/s and left ventricular ejection fraction ≥50%. Follow-up echocardiograms (n = 4,818) provided multiparametric AS progression rates and AS-CD.

Results: The study included 330 BAV (age 54 ± 14 years) and 581 patients with TAV (age 72 ± 11 years). At last echocardiogram (median: 5.9 years; interquartile range: 3.9 to 8.5 years), BAV-AS exhibited similar peakV and mean pressure gradient (MPG) as TAV-AS, but larger calculated aortic valve area due to larger aortic annulus (p < 0.0001). Multiparametric progression rates were similar between BAV-AS and TAV-AS (all p ≥ 0.08) and did not predict age-/sex-adjusted survival (p ≥ 0.45). Independent determinants of rapid progression were male sex and baseline AS severity for TAV (all p ≤ 0.024), and age, baseline AS severity, and cardiac risk factors (age interaction: p = 0.02) for BAV (all p ≤ 0.005). At 12 years, patients with TAV-AS had a higher incidence of AS-CD than BAV-AS patients (p < 0.0001), resulting in significantly worse survival compared to BAV-AS (p < 0.0001). AS-CD were independently determined by multiple factors (MPG, age, sex, comorbidities, cardiac function; all p ≤ 0.039), and BAV was independently protective of most AS-CD (all p ≤ 0.05).

Conclusions: In this cohort, TAV-AS and BAV-AS progression rates were similar. Rapid progression did not affect survival and was determined by cardiac risk factors for BAV-AS (particularly in patients with BAV <60 years of age) and unmodifiable factors for TAV-AS. AS-CD and mortality were significantly higher in TAV-AS. Independent determinants of AS-CD were multifactorial, and BAV morphology was AS-CD protective. Therefore, the totality of AS burden (cardiac damage) is clinically crucial for TAV-AS, whereas attention to modifiable risk factors may be preventive for BAV-AS.
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http://dx.doi.org/10.1016/j.jcmg.2021.01.017DOI Listing
June 2021

Community prevalence, mechanisms and outcome of mitral or tricuspid regurgitation.

Heart 2021 Mar 4. Epub 2021 Mar 4.

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK

Objective: The study aims were (1) to identify the community prevalence of moderate or greater mitral or tricuspid regurgitation (MR/TR), (2) to compare subjects identified by population screening with those with known valvular heart disease (VHD), (3) to understand the mechanisms of MR/TR and (4) to assess the rate of valve intervention and long-term outcome.

Methods: Adults aged ≥65 years registered at seven family medicine practices in Oxfordshire, UK were screened for inclusion (n=9504). Subjects with known VHD were identified from hospital records and those without VHD invited to undergo transthoracic echocardiography (TTE) within the Oxford Valvular Heart Disease Population Study (OxVALVE). The study population ultimately comprised 4755 subjects. The severity and aetiology of MR and TR were assessed by integrated comprehensive TTE assessment.

Results: The prevalence of moderate or greater MR and TR was 3.5% (95% CI 3.1 to 3.8) and 2.6% (95% CI 2.3 to 2.9), respectively. Primary MR was the most common aetiology (124/203, 61.1%). Almost half of cases were newly diagnosed by screening: MR 98/203 (48.3%), TR 69/155 (44.5%). Subjects diagnosed by screening were less symptomatic, more likely to have primary MR and had a lower incidence of aortic valve disease. Surgical intervention was undertaken in six subjects (2.4%) over a median follow-up of 64 months. Five-year survival was 79.8% in subjects with isolated MR, 84.8% in those with isolated TR, and 59.4% in those with combined MR and TR (p=0.0005).

Conclusions: Moderate or greater MR/TR is common, age-dependent and is underdiagnosed. Current rates of valve intervention are extremely low.
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http://dx.doi.org/10.1136/heartjnl-2020-318482DOI Listing
March 2021

Clinical Outcomes of Adults With Bicuspid Aortic Valve: A European Perspective.

Mayo Clin Proc 2021 03;96(3):648-657

Department of Cardiology, Amiens University Hospital, France; EA 7517 MP3CV Université de Picardie Jules Verne, Amiens, France. Electronic address:

Objective: To describe the clinical history of patients with a wide age range diagnosed with bicuspid aortic valve (BAV) and no surgical indication and to evaluate the long-term outcome of patients with BAV referred for elective surgery.

Patients And Methods: Between 2005 and 2017, 350 consecutive patients with no surgical indication (surveillance group, mean age 53±16, 71% men) and 191 with a surgical indication (surgical group, mean age 59±13, 71% men) were prospectively included. Median follow-up was 80 (32 to 115) months.

Results: In the surveillance group, the 5-year and 10-year survival rates were 93±1% and 89±2%, respectively, with a relative survival of patients with BAV compared with an age- and sex-matched control population of 98.7%. During follow-up, the cumulative 10-year incidence of aortic valve and aorta surgery was high; of 35±4%, the incidence of native valve infective endocarditis (IE) of 0.2% per patient-year, and no cases of aortic dissection were observed. In the surgical group, the 5-year and 10-year survival rates were 97±1% and 89±3%, respectively, with a relative survival of 99.4% compared with the general population. The incidence of IE was 0.4% per patient-year, and no cases of aortic dissection were observed.

Conclusion: This regional cohort shows that the 10-year survival rates of patients with BAV and a wide age range, but mostly middle-aged adults, were similar to those of the general population with a very low rate of complications. Adherence to prophylactic surgical indications and younger age might have contributed to this lack of difference.
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http://dx.doi.org/10.1016/j.mayocp.2020.04.047DOI Listing
March 2021

Natural history observations in moderate aortic stenosis.

BMC Cardiovasc Disord 2021 Feb 19;21(1):108. Epub 2021 Feb 19.

Roger L. and Lynn C. Headrick Chair, Valve Science Center, Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, Minneapolis, MN, 55407, USA.

Background: The natural history of patients with moderate aortic stenosis (AS) is poorly understood. We aimed to determine the long-term outcomes of patients with moderate AS.

Methods: We examined patients with moderate AS defined by echocardiography in our healthcare system, and performed survival analyses for occurrence of death, heart failure (HF) hospitalization, and progression of AS, with accounting for symptoms, left ventricular dysfunction, and comorbidities.

Results: We examined 729 patients with moderate AS (median age, 76 years; 59.9 % men) with a median follow-up of 5.0 years (interquartile range: 2.0 to 8.1 years). The 5-year overall survival was 52.3 % (95 % confidence interval [CI]: 48.6 % to 56.0 %) and survival free of death or HF hospitalization was 43.2 % (95 % CI: 39.5 % to 46.9 %). Worse New York Heart Association (NYHA) functional class was associated with poor long-term survival, with mortality rates ranging from 7.9 % (95 % CI: 6.6-9.2 %) to 25.2 % (95 % CI: 20.2-30.3 %) per year. Among patients with minimal or no symptoms, no futility markers, and preserved left ventricular function, 5-year overall survival was 71.9 % (95 % CI: 66.4-77.4 %) and survival free of death or HF hospitalization was 61.4 % (95 % CI: 55.5-67.3 %). Risk factors associated with adverse events were age, NYHA class, low ejection fraction and high aortic valve velocity (all p < 0.05).

Conclusions: Patients with moderate AS are at significant risk of death. Our findings highlight the need for more study into appropriate therapeutic interventions to improve the prognosis of these patients.
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http://dx.doi.org/10.1186/s12872-021-01901-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893941PMC
February 2021

Importance of Myocardial Fibrosis in Functional Mitral Regurgitation: From Outcomes to Decision-Making.

JACC Cardiovasc Imaging 2021 Apr 10;14(4):867-878. Epub 2021 Feb 10.

Cardiovascular Imaging Research Center and Core Lab, Minneapolis Heart Institute Foundation, Minneapolis, Minnesota, USA; Valve Science Center, Minneapolis Heart Institute Foundation, Minneapolis, Minnesota, USA; Minneapolis Heart Institute, Abbott Northwestern Hospital, Minneapolis, Minnesota, USA. Electronic address:

Functional mitral regurgitation (FMR) is a common and complex valve disease, in which severity and risk stratification is still a conundrum. Although risk increases with FMR severity, it is modulated by subjacent left ventricular (LV) disease. The extent of LV remodeling and dysfunction is traditionally evaluated by echocardiography, but a growing body of evidence shows that myocardial fibrosis (MF) assessment by cardiac magnetic resonance (CMR) may complement risk stratification and inform treatment decisions. This review summarizes the current knowledge on the comprehensive evaluation that CMR can provide for patients with FMR, in particular for the assessment of MF and its potential impact in clinical decision-making.
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http://dx.doi.org/10.1016/j.jcmg.2020.10.027DOI Listing
April 2021

Prosthesis-patient mismatch defined by cardiac computed tomography versus echocardiography after transcatheter aortic valve replacement.

J Cardiovasc Comput Tomogr 2021 Jan 16. Epub 2021 Jan 16.

Cardiovascular Imaging Research Center and Core Lab, Minneapolis Heart Institute Foundation, Minneapolis, MN, USA; Valve Science Center, Minneapolis Heart Institute Foundation, Minneapolis, MN, USA; Minneapolis Heart Institute, Abbott Northwestern Hospital, Minneapolis, MN, USA. Electronic address:

Backgrounds: Evaluation of prosthesis-patient mismatch (P-PM) after transcatheter aortic valve replacement (TAVR) by transthoracic echocardiography (TTE) has provided conflicting results regarding its impact on outcomes. Whether post-TAVR computed tomography angiography (CTA) evaluation of P-PM can improve our understanding is unknown. We aimed to evaluate the inter-modality (TTE vs. CTA) agreement, inter-valve platform (balloon-expanding valve [BEV] vs. self-expandable valve [SEV]) differences in P-PM severity, and outcomes related to P-PM after TAVR.

Methods: We analyzed patients with both CTA and TTE before and after TAVR. Indexed effective orifice area was calculated using two methods: TTE-derived left ventricular outflow tract (LVOT) area from measured diameter and post-TAVR CTA-measured area. Body size specific cut-offs for P-PM severity were used: for body mass index (BMI) ​< ​30 ​kg/m, moderate ​= ​0.66-0.85 ​cm/m and severe≤0.65 ​cm/m; for BMI ≥30 ​kg/m, moderate ​= ​0.56-0.70 ​cm/m and severe≤0.55 ​cm/m.

Results: A total of 447 patients were included (median age, 83 years; 54% male). The prevalence of P-PM (moderate or severe) was lower with CTA vs. TTE (3.5% vs. 19.5%, p ​< ​0.001). The prevalence of P-PM measured by TTE was more common in BEV compared to SEV (p ​= ​0.002), while CTA assessment showed no difference in P-PM incidence and severity between TAVR platforms (p ​= ​0.40). In multivariable analysis, CTA-defined but not TTE-defined P-PM was associated with mortality after TAVR (HR:3.97; 95%CI,1.55-10.2; p ​= ​0.004). Both CTA-defined and TTE-defined P-PM were associated with the composite of death and heart failure rehospitalization.

Conclusion: Although post-TAVR CTA substantially downgraded the prevalence of P-PM compared to TTE, it identified a subset of patients with clinically relevant P-PM which associated with outcomes.
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http://dx.doi.org/10.1016/j.jcct.2021.01.001DOI Listing
January 2021

Frequency of intracranial aneurysms and sub-arachnoid hemorrhage is significantly lesser in bicuspid aortic valve than aortic coarctation.

Int J Cardiol 2021 05 28;330:229-231. Epub 2021 Jan 28.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA. Electronic address:

Background: Bicuspid aortic valve(BAV) is common. Some studies suggest that all BAV patients require screening for intracranial aneurysm(IA) in order to prevent sub-arachnoid hemorrhage(SAH). Aortic coarctation(CoA) carries high-risk of both IA and SAH. Using a nationally-representative population, we assessed the frequency of IA and SAH in admissions with BAV-without-CoA versus admissions with CoA(with or without BAV).

Methods: Between 2000 and 2016, adult admissions with a primary/secondary diagnosis of BAV and/or CoA were identified using the National Inpatient Sample. Admissions with traumatic SAH and inter-hospital transfers were excluded. Outcomes were frequency of IA and SAH, and in-hospital mortality in BAV-without-CoA versus CoA.

Results: In this 17-year period, 254,675 admissions met inclusion criteria and 236,930(93.0%) had BAV-without-CoA. BAV-with-CoA was present in 2846(1.1%) and isolated-CoA in 14,899(5.9%), for a total of 17,745(7%) with CoA. IA was noted in 405 admissions(0.2%) overall, BAV-without-CoA versus CoA having 293(0.1%) versus 112(0.6%), p < 0.001. SAH was noted in 910 admissions(0.4%) overall, with BAV-without-CoA versus CoA having 760(0.3%) versus 150(0.9%), p < 0.001.

Conclusions: In this study, BAV-without-CoA admissions had 0.1%(6-times lower than CoA) and 0.3%(3-times lower that CoA) IA and SAH, respectively, which is comparable to the general population. This suggests that BAV-without-CoA patients likely do not require routine surveillance for IA.
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http://dx.doi.org/10.1016/j.ijcard.2021.01.045DOI Listing
May 2021

Left Atrial Volumetric/Mechanical Coupling Index: A Novel Predictor of Outcome in Heart Failure With Reduced Ejection Fraction.

Circ Cardiovasc Imaging 2021 Jan 19;14(1):e011608. Epub 2021 Jan 19.

Department of Cardiovascular Diseases, Mayo Clinic, Mayo Clinic, Rochester, MN (G.B., B.E., J.M., P.T., H.I.M., M.E.-S.).

Background: Left atrial assessment is complex, particularly in heart failure with reduced ejection fraction due to interactions with functional mitral regurgitation (FMR). Pilot data suggest that left atrial volumetric/mechanical coupling index (LACI) may be useful, but large outcome data are lacking.

Methods: We enrolled a comprehensively characterized cohort of patients in sinus rhythm with heart failure with reduced ejection fraction diagnosis at Mayo Clinic from 2007 to 2011. Routinely measured left atrial volume index and tissue-doppler-imaging a' allowed LACI calculation as (left atrial volume index)/(tissue-doppler-imaging a'). Survival was the outcome measured.

Results: The cohort's 4196 patients (69 [58-77] years, ejection fraction 40 [31-45]%) had mild FMR in 1505 and moderate-severe FMR in 1068. LACI was overall 5.06 (3.50-8.10) and increased with each FMR grade (3.86 [2.94-5.29] without FMR, 5.38 [3.80-8.02] with mild, 5.45 [1.49-8.07] with moderate/severe FMR; <0.0001). At diagnosis, higher LACI was independently determined by more severe FMR and by higher left ventricular mass index, lower ejection fraction, higher E/e', and lower glomerular filtration rate (all <0.0001). During follow-up 1588 (38%) patients died. In spline modeling, excess mortality appeared around LACI=6 and steeply increased thereafter (5-year survival 72±1% with LACI<6 and 49±2% with LACI ≥6, <0.0001). Multivariable comprehensive adjustment showed LACI strong association with excess mortality (adjusted hazard ratio, 1.41 [1.23-1.61], <0.0001 for LACI ≥6). Independent link to mortality persistent across FMR grades (adjusted hazard ratio, 1.45 [1.13-1.86], =0.004 without FMR, 1.42 [1.16-1.77], =0.0008 with mild FMR, and 1.38 [1.01-1.66], =0.04 with moderate/severe FMR) without interaction (=0.3). LACI independent impact on outcome was incremental to that of left atrial volume index, tissue-doppler-imaging a', or any other characteristic including the Meta-Analysis Global Group in Chronic-score (least significant =0.02).

Conclusions: In this large cohort, left atrial volumetric/mechanical coupling measured by LACI in routine practice integrates the influence of several morphological/hemodynamic determinants but displays progressive deterioration with increasing FMR severity in heart failure with reduced ejection fraction. About outcome, higher LACI is strongly, independently, and incrementally associated with excess mortality, irrespective of FMR grade and in all subsets. Hence, LACI is a novel and critical measure in heart failure with reduced ejection fraction, quantifiable in routine practice, which should be integrated in prognostication and decision-making.
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http://dx.doi.org/10.1161/CIRCIMAGING.120.011608DOI Listing
January 2021

Excess Mortality and Undertreatment of Women With Severe Aortic Stenosis.

J Am Heart Assoc 2021 Jan 29;10(1):e018816. Epub 2020 Dec 29.

Division of Cardiology Mayo Clinic Rochester MN.

Background Although women represent half of the population burden of aortic stenosis (AS), little is known whether sex affects the presentation, management, and outcome of patients with AS. Methods and Results In a cohort of 2429 patients with severe AS (49.5% women) we aimed to evaluate 5-year excess mortality and performance of aortic valve replacement (AVR) stratified by sex. At presentation, women were older (<0.001), with less comorbidities (=0.030) and more often symptomatic (=0.007) than men. Women had smaller aortic valve area (<0.001) than men but similar mean transaortic pressure gradient (=0.18). The 5-year survival was lower compared with expected survival, especially for women (62±2% versus 71% for women and 69±1% versus 71% for men). Despite longer life expectancy in women than men, women had lower 5-year survival than men (66±2% [expected-75%] versus 68±2% [expected-70%], <0.001) after matching for age. Overall, 5-year AVR incidence was 79±2% for men versus 70±2% for women (<0.001) with male sex being independently associated with more frequent early AVR performance (odds ratio, 1.49; 1.18-1.97). After age matching, women remained more often symptomatic (=0.004) but also displayed lower AVR use (64.4% versus 69.1%; =0.018). Conclusions Women with severe AS are diagnosed at later ages and have more symptoms than men. Despite prevalent symptoms, AVR is less often performed in women and 5-year excess mortality is noted in women versus men, even after age matching. These imbalances should be addressed to ensure that both sexes receive equivalent care for severe AS.
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http://dx.doi.org/10.1161/JAHA.120.018816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955469PMC
January 2021

Management and Outcome of Patients Admitted With Tricuspid Regurgitation in France.

Can J Cardiol 2020 Dec 25. Epub 2020 Dec 25.

Division of Cardiovascular Disease, Mayo Clinic and Mayo Medical School, Rochester, Minnesota, USA.

Background: Growing evidence shows a major outcome impact and undertreatment of tricuspid regurgitation (TR), but large and comprehensive contemporary reports of management and outcome at the nationwide level are lacking.

Methods: We gathered all consecutive patients admitted with a diagnosis of likely functional TR in 2014-2015 in France from the Programme de Médicalisation des Systèmes d'Information national database and collected rate of surgery, in-hospital mortality, 1-year mortality, or heart failure (HF) readmission rates.

Results: In 2014-2015, 17,676 consecutive patients (75 ± 14 years of age, 51% female) were admitted with a TR diagnosis. Charlson index was ≥ 2 in 56% of the population and 46% presented with HF. TR was associated with prior cardiac surgery, ischemic/dilated cardiomyopathy, or mitral regurgitation in 73% of patients. Only 10% of TR patients overall and 67% of those undergoing mitral valve surgery received a tricuspid valve intervention. Among the 13,654 (77%) conservatively managed patients, in-hospital mortality, 1-year mortality, and 1-year mortality or HF readmission rates were 5.1%, 17.8%, and 41%, respectively, overall, and 5.3%,17.2%, and 37%, respectively, among those with no underlying medical conditions (8-fold higher than predicted for age and gender).

Conclusions: This nationwide cohort of patients admitted with TR included elderly patients with frequent comorbidities/underlying cardiac diseases. In patients conservatively managed, mortality and morbidity were considerably high over a short time span. Despite this poor prognosis, only 10% of patients underwent a tricuspid valve intervention. These nationwide data showing a considerable risk and potential underuse of treatment highlight the critical need to develop strategies to improve the management and outcomes of TR patients.
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http://dx.doi.org/10.1016/j.cjca.2020.12.012DOI Listing
December 2020

Association of Echocardiographic Left Ventricular End-Systolic Volume and Volume-Derived Ejection Fraction With Outcome in Asymptomatic Chronic Aortic Regurgitation.

JAMA Cardiol 2021 Feb;6(2):189-198

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.

Importance: Volumetric measurements by transthoracic echocardiogram may better reflect left ventricular (LV) remodeling than conventional linear LV dimensions. However, the association of LV volumes with mortality in patients with chronic hemodynamically significant aortic regurgitation (AR) is unknown.

Objective: To assess whether LV volumes and volume-derived LV ejection fraction (Vol-LVEF) are determinants of mortality in AR.

Design, Setting, And Participants: This cohort study included consecutive asymptomatic patients with chronic moderately severe to severe AR from a tertiary referral center (January 2004 through April 2019).

Exposures: Clinical and echocardiographic data were analyzed retrospectively. Aortic regurgitation severity was graded by comprehensive integrated approach. De novo disk-summation method was used to derive LV volumes and Vol-LVEF.

Main Outcome And Measures: Associations between all-cause mortality under medical surveillance and the following LV indexes: linear LV end-systolic dimension index (LVESDi), linear LVEF, LV end-systolic volume index (LVESVi), and Vol-LVEF.

Results: Of 492 asymptomatic patients (mean [SD] age, 60 [17] years; 425 men [86%]), ischemic heart disease prevalence was low (41 [9%]), and 453 (92.1%) had preserved linear LVEF (≥50%) with mean (SD) LVESVi of 41 (15) mL/m2. At a median (interquartile range) of 5.4 (2.5-10.1) years, 66 patients (13.4%) died under medical surveillance; overall survival was not different than the age- and sex-matched general population (P = .55). Separate multivariate models, adjusted for age, sex, Charlson Comorbidity Index, and AR severity, demonstrated that in addition to linear LVEF and LVESDi, LVESVi and Vol-LVEF were independently associated with mortality under surveillance (all P < .046) with similar C statistics (range, 0.83-0.84). Spline curves showed that continuous risks of death started to rise for both linear LVEF and Vol-LVEF less than 60%, LVESVi more than 40 to 45 mL/m2, and LVESDi above 21 to 22 mm/m2. As dichotomized variables, patients with LVESVi more than 45 mL/m2 exhibited increased relative death risk (hazard ratio, 1.93; 95% CI, 1.10-3.38; P = .02) while LVESDi more than 20 mm/m2 did not (P = .32). LVESVi more than 45 mL/m2 showed a decreased survival trend compared with expected population survival.

Conclusions And Relevance: In this large asymptomatic cohort of patients with hemodynamically significant AR, LVESVi and Vol-LVEF worked equally as well as LVESDi and linear LVEF in risk discriminating patients with excess mortality. A LVESVi threshold of 45 mL/m2 or greater was significantly associated with an increased mortality risk.
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http://dx.doi.org/10.1001/jamacardio.2020.5268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643045PMC
February 2021

Contemporary differences between bicuspid and tricuspid aortic valve in chronic aortic regurgitation.

Heart 2021 Jun 27;107(11):916-924. Epub 2020 Oct 27.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester Minnesota, Rochester, New York, USA

Objective: To comprehensively explore contemporary differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients with chronic haemodynamically significant aortic regurgitation (AR).

Methods: Consecutive patients with chronic ≥moderate-severe AR from a tertiary referral centre (2006-2017) were included. All-cause mortality, surgical indications and aortic valve surgery (AVS) were analysed.

Results: Of 798 patients (296 BAV-AR, age 46±14 years; 502 TAV-AR, age 67±14 years, p<0.0001) followed for 5.5 (IQR: 2.9-9.2) years, 403 underwent AVS (repair in 96) and 154 died during follow-up. The 8-year AVS incidence was 60%±3% versus 53%±3% for BAV-AR and TAV-AR, respectively (p=0.014). The unadjusted (real-life) 8-year total survival was 93%±7% versus 71%±2% for BAV-AR and TAV-AR, respectively (p<0.0001), and became statistically insignificant after sole adjustment for age (p=0.14). The within-group relative risk of death in BAV-AR patients demonstrated a large age-dependent increase (two fold at 50-55 years, up to 10-fold at 70 years). The presence of baseline symptoms was significantly associated with death for both BAV-AR (p=0.039) and TAV-AR (p<0.0001), but the strength of the association decreased with age adjustment for BAV-AR (age-adjusted HR 2.43 (0.92-6.39), p=0.07) and not for TAV-AR (age-adjusted HR, 2.3 (1.6-3.3), p<0.0001). As compared with general population, TAV-AR exhibited baseline excess risk which further increased at left ventricular ejection fraction (LVEF) <60% and left ventricular end-systolic dimension index (LVESDi) >20 mm/m; similar thresholds were observed for BAV-AR patients.

Conclusion: BAV-AR patients were two decades younger than TAV-AR and underwent AVS more frequently, resulting in a considerable real-life survival advantage for BAV-AR that was determined primarily by age and not valve anatomy. Pragmatically, regardless of valve anatomy, patients with haemodynamically significant AR and age >50-55 years require a low-threshold for surgical referral to prevent symptom development where LVEF <60% and LVESDi >20 mm/m seem appropriate referral thresholds.
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http://dx.doi.org/10.1136/heartjnl-2020-317466DOI Listing
June 2021

Presentation and outcomes of mitral valve surgery in France in the recent era: a nationwide perspective.

Open Heart 2020 08;7(2)

Surgery, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.

Objectives: Unbiased information regarding the surgical management of patients with mitral regurgitation (MR) at the nationwide level are scarce and mainly US-based. The Programme de Médicalisation des Systèmes d'Information, a mandatory national database, offers the unique opportunity to assess the presentation and outcomes of all consecutive mitral valve (MV) surgeries performed in France in the contemporary era.

Methods: We collected all MV surgeries performed for MR in France in 2014-2016. MR aetiology was classified as degenerative (DMR), secondary (SMR) or Other (rheumatic or congenital disease and infective endocarditis).

Results: During the 3-year period, 18 167 MV surgeries were performed in France (55% repair and 45% replacement; 52% isolated). Age was 66±12 years and 59% were male. Aetiology was DMR in 42%, SMR in 16% and other in 42% including 19% with uncertain aetiologies. Overall, in-hospital mortality was 6.5% and increased with age, female gender, Charlson Comorbidity Index, type of surgery (replacement vs repair), associated surgery (combined vs isolated) and MR aetiology (all p<0.01). In-hospital mortality and rate of death/readmission for heart failure (HF) at 1 year were 3.4% and 13%, respectively for DMR (2.4% and 11% for isolated DMR) and 7.8% and 27%, respectively for SMR (5.5% and 23% for isolated SMR). Repair rate was 55% overall, 68% in DMR and 72% for isolated DMR surgery (70% of all DMR). Repair rates decreased with age, Charlson Comorbidity Index and female sex (all p<0.0001).

Conclusion: In this cross-sectional contemporary prospective nationwide database, in-hospital mortality and 1 year rate of death and HF readmission were considerable overall and in all subsets. Repair rates were suboptimal overall especially in the elderly and women subsets. These results underline the need to develop strategies to improve management and outcomes of patients with both DMR and SMR.
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http://dx.doi.org/10.1136/openhrt-2020-001339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422639PMC
August 2020

Presentation and Outcome of Arrhythmic Mitral Valve Prolapse.

J Am Coll Cardiol 2020 08;76(6):637-649

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota. Electronic address:

Background: Mitral valve prolapse (MVP) is often considered benign but recent suggestion of an arrhythmic MVP (AMVP) form remains incompletely defined and uncertain.

Objectives: This study determined ventricular arrhythmia prevalence, severity, phenotypical context, and independent impact on outcome in patients with MVP.

Methods: A cohort of 595 (age 65 ± 16 years; 278 women) consecutive patients with MVP and comprehensive clinical, arrhythmia (24-h Holter monitoring) and Doppler-echocardiographic characterization, was identified. Long-term outcomes were analyzed.

Results: Ventricular arrhythmia was frequent (43% with at least ventricular ectopy ≥5%), most often moderate (ventricular tachycardia [VT]; 120 to 179 beats/min) in 27%, and rarely severe (VT ≥180 beats/min) in 9%. Presence of ventricular arrhythmia was associated with male sex, bileaflet prolapse, marked leaflet redundancy, mitral annulus disjunction (MAD), a larger left atrium and left ventricular end-systolic diameter, and T-wave inversion/ST-segment depression (all p ≤ 0.001). Severe ventricular arrhythmia was independently associated with presence of MAD, leaflet redundancy, and T-wave inversion/ST-segment depression (all p < 0.0001) but not with mitral regurgitation severity or ejection fraction. Overall mortality after arrhythmia diagnosis (8 years; 13 ± 2%) was strongly associated with arrhythmia severity (8 years; 10 ± 2% for no/trivial, 15 ± 3% for mild and/or moderate, and 24 ± 7% for severe arrhythmia; p = 0.02). Excess mortality was substantial for severe arrhythmia (univariate hazard ratio [HR]: 2.70; 95% confidence interval [CI]: 1.27 to 5.77; p = 0.01 vs. no/trivial arrhythmia), even after it was comprehensively adjusted, including for MVP characteristics (adjusted HR: 2.94; 95% CI: 1.36 to 6.36; p = 0.006) and by time-dependent analysis (adjusted HR: 3.25; 95% CI: 1.56 to 6.78; p = 0.002). Severe arrhythmia was also associated with higher rates of mortality, defibrillator implantation, VT ablation (adjusted HR: 4.68; 95% CI: 2.45 to 8.92; p < 0.0001), particularly under medical management (adjusted HR: 5.80; 95% CI: 2.75 to 12.23; p < 0.0001), and weakly post-mitral surgery (adjusted HR: 3.69; 95% CI: 0.93 to 14.74; p = 0.06).

Conclusions: In this large cohort of patients with MVP, ventricular arrhythmia by Holter monitoring was frequent but rarely severe. AMVP was independently associated with phenotype dominated by MAD, marked leaflet redundancy, and repolarization abnormalities. Long-term severe arrhythmia was independently associated with notable excess mortality and reduced event-free survival, particularly under medical management. Therefore, AMVP is a clinical entity strongly associated with outcome and warrants careful risk assessment and well-designed clinical trials.
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http://dx.doi.org/10.1016/j.jacc.2020.06.029DOI Listing
August 2020

Dismal Outcomes and High Societal Burden of Mitral Valve Regurgitation in France in the Recent Era: A Nationwide Perspective.

J Am Heart Assoc 2020 08 22;9(15):e016086. Epub 2020 Jul 22.

Mayo ClinicDivision of Cardiovascular DiseaseMayo Medical School Rochester MN.

Background Although US recent data suggest that mitral regurgitation (MR) is severely undertreated and carries a poor outcome, population-based views on outcome and management are limited. We aimed to define the current treatment standards, clinical outcomes, and costs related to MR at the nationwide level. Methods and Results In total, 107 412 patients with MR were admitted in France in 2014 to 2015. Within 1 year, 8% were operated and 92% were conservatively managed and constituted our study population (68% primary MR and 32% secondary MR). The mean age was 77±15 years; most patients presented with comorbidities. In-hospital and 1-year mortality rates were 4.1% and 14.3%, respectively. Readmissions were common (63% at least once and 37% readmitted ≥2 times). Rates of 1-year mortality or all-cause readmission and 1-year mortality or heart failure readmission were 67% and 34%, respectively, and increased with age, Charlson index, heart failure at admission, and secondary MR etiology; however, the event rate remained notably high in the primary MR subset (64% and 28%, respectively). The mean costs of hospital admissions and of readmissions were 5345±6432 and 10 080±10 847 euros, respectively. Conclusions At the nationwide level, MR was a common reason for admission and affected an elderly population with frequent comorbidities. Less than 10% of patients underwent a valve intervention. All subsets of patients who were conservatively managed incurred high mortality and readmissions rates, and MR represented a major societal burden with an extrapolated annual cost of 350 to 550 million euros (390-615 million US dollars). New strategies to improve the management and outcomes of patients with both primary and secondary MR are critical and warranted.
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http://dx.doi.org/10.1161/JAHA.120.016086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792268PMC
August 2020

Concomitant Mitral Regurgitation in Patients With Chronic Aortic Regurgitation.

J Am Coll Cardiol 2020 07;76(3):233-246

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota. Electronic address:

Background: Etiology, mechanisms, and survival of mitral regurgitation (MR) plus hemodynamically-significant chronic aortic regurgitation (AR) are mostly unknown.

Objectives: The purpose of this study was to investigate the prevalence, mechanisms, etiologies, and survival impact of coexistent ≥ moderate MR in AR patients.

Methods: Consecutive patients with ≥ moderate-severe AR were retrospectively identified between 2004 and 2019.

Results: Of 1,239 eligible patients (61 ± 18 years, 80% men), 1,072 (86%) had pure AR, and 167 (14%) had AR + MR (9% functional mitral regurgitation [FMR] [84% nonischemic] and 5% organic mitral regurgitation [OMR] [62% degenerative]). At baseline transthoracic echocardiogram, pure AR versus AR + OMR versus AR + FMR exhibited differences in age (59 ± 18, 62 ± 16, and 73 ± 14 years, respectively), female sex (18%, 27%, and 39%, respectively), symptoms (36%, 41%, and 64%, respectively), atrial fibrillation (5%, 17%, and 36%, respectively), left ventricular (LV) ejection fraction (59%, 58%, and 46%, respectively), LV end-systolic dimension and volume index, ≥ moderate tricuspid regurgitation (TR) (7%, 35%, and 53%, respectively), and right ventricular systolic pressure (32 ± 11, 45 ± 15, and 50 ± 14 mm Hg, respectively), all p < 0.0001. After a median follow-up of 5.2 years (interquartile range: 2.2 to 10.0 years) and adjusting for demographics, New York Heart Association functional class, aortic valve surgery, LV ejection fraction, LV end-systolic dimension and volume index, presence of FMR was independently associated with all-cause mortality (p ≤ 0.004). Compared with pure AR, AR + MR + TR exhibited the highest adjusted risk of death (2.4-fold; p < 0.0001). When compared with expected population survival, excess mortality risks of pure AR, AR + OMR, and AR + FMR were 1.25-fold, 1.76-fold, and 2.34-fold, respectively (all p ≤ 0.02).

Conclusions: In hemodynamically significant AR, coexistent MR is not uncommon (approximately 14%) and mostly comprises FMR and less commonly OMR. As compared with pure AR, AR + MR + TR exhibit the largest mortality risk. Both AR + OMR and AR + FMR carry a survival penalty compared with the general population, but AR + FMR is associated with the largest excess mortality and represents an advanced stage within the AR clinical spectrum.
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http://dx.doi.org/10.1016/j.jacc.2020.05.051DOI Listing
July 2020

The Congenital Bicuspid Aortic Valve Condition in 2020.

Prog Cardiovasc Dis 2020 Jul - Aug;63(4):397. Epub 2020 Jun 27.

Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States of America.

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http://dx.doi.org/10.1016/j.pcad.2020.06.010DOI Listing
October 2020

Speaking a common language: Introduction to a standard terminology for the bicuspid aortic valve and its aortopathy.

Prog Cardiovasc Dis 2020 Jul - Aug;63(4):419-424. Epub 2020 Jun 26.

Saarland University Medical Center, Homburg, Saar, Germany.

There is a growing need to develop a common language when referring to a frequent and heterogeneous condition such as the congenital bicuspid aortic valve and its aortopathy. The following short manuscript serves as an introduction to a standard terminology for the bicuspid aortic valve and its aortopathy.
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http://dx.doi.org/10.1016/j.pcad.2020.06.006DOI Listing
October 2020

Clinical presentation and outcomes of adults with bicuspid aortic valves: 2020 update.

Prog Cardiovasc Dis 2020 Jul - Aug;63(4):434-441. Epub 2020 May 30.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA. Electronic address:

The congenital bicuspid aortic valve (BAV) is a heterogeneous condition that is better understood considering 3 types of valvulo-aortopathy presentations: A typical-presentation valvulo-aortopathy, a complex-presentation valvulo-aortopathy and an uncomplicated/undiagnosed-presentation. The burden of BAV-related complications has been elucidated in patients with the typical-presentation valvulo-aortopathy and is discussed in this review. These patients enjoy an overall normal expected long-term survival as long as complications are identified and treated in a timely manner. This notion and the fact that the most dreaded complications (infective endocarditis and aortic dissection) are infrequent, represent important reassuring points for the BAV patient. Common complications such as valve dysfunction and aorta dilatation must be the subject of focused research in prevention and treatment. Conversely, BAV patients with complex-presentation valvulo-artopathy, as well as typical valvulo-aortopathy BAV patients who are older, with advanced valvular dysfunction, and possible late-referral to specialized care, may incur a survival penalty as compared to the general population. An evidence-based discussion of these concepts is provided in this review.
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http://dx.doi.org/10.1016/j.pcad.2020.05.010DOI Listing
October 2020

The elusive 'forme fruste' bicuspid aortic valve: 3D transoesophageal echocardiography to the rescue.

Eur Heart J Cardiovasc Imaging 2020 10;21(10):1169

Department of Cardiovascular Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

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http://dx.doi.org/10.1093/ehjci/jeaa094DOI Listing
October 2020

Impact of tricuspid regurgitation on survival in patients with heart failure: a large electronic health record patient-level database analysis.

Eur J Heart Fail 2020 10 5;22(10):1803-1813. Epub 2020 May 5.

Division of Cardiology, Mayo College of Medicine, Mayo Clinic, Rochester, MN, USA.

Aims: More evidence is needed to quantify the association between tricuspid regurgitation (TR) and mortality in patients with heart failure (HF).

Methods And Results: Between 2008-2017, using the Optum longitudinal database, a patient-level database that integrates multiple US-based electronic health and claim records from several health care providers, we identified 435 679 patients with new HF diagnosis and both an assessment of the left ventricular ejection fraction and at least 1 year of history. TR was graded as mild, moderate or severe and classified as prevalent (at the time of the initial HF diagnosis) or incident (subsequent new cases thereafter). For prevalent TR, the analysis was performed using a Cox proportional hazards model with adjustment for patient covariates. Incident TR was modelled as a time-updated covariate, as were other non-fatal events during follow-up. Prevalence of mild, moderate and severe TR at baseline was 10.1%, 5.1% and 1.4%, respectively. Over a median follow-up of 1.5 years, 121 273 patients (27.8%) died and prevalent TR was independently associated with survival. Compared to patients with no TR at baseline, the adjusted hazard ratios for mortality were 0.99 [95% confidence interval (CI) 0.97-1.01], 1.17 (95% CI 1.14-1.20) and 1.34 (95% CI 1.28-1.39) for mild, moderate and severe TR, respectively. In the 363 270 patients free from TR at baseline, incident TR (at least mild, at least moderate, or severe) developed during follow-up in 12.1%, 5.1% and 1.1%, respectively. Adjusted mortality hazard ratios for such new cases were 1.48 (95% CI 1.44-1.52), 1.92 (95% CI 1.86-1.99) and 2.44 (95% CI 2.32-2.57), respectively. Findings were consistent across all patient subgroups based on age, gender, rhythm, associated comorbidities, prior cardiac surgery, B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide, and left ventricular ejection fraction.

Conclusions: In this large contemporary patient-level database of almost half-million US patients with HF, TR was associated with a marked increases in mortality risk overall and in all subgroups. Future randomized controlled trials will evaluate the impact of TR correction on clinical outcomes and the causal relationship between TR and mortality.
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http://dx.doi.org/10.1002/ejhf.1830DOI Listing
October 2020

Functional tricuspid regurgitation of degenerative mitral valve disease: a crucial determinant of survival.

Eur Heart J 2020 05;41(20):1918-1929

Department of Cardiovascular Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.

Aims: To assess functional tricuspid regurgitation (FTR) determinants, consequences, and independent impact on outcome in degenerative mitral regurgitation (DMR).

Methods And Results: All patients diagnosed with isolated DMR 2003-2011, with structurally normal tricuspid leaflets, prospective FTR grading and systolic pulmonary artery pressure (sPAP) estimation by Doppler echocardiography at diagnosis were identified and long-term outcome analysed. The 5083 DMR eligible patients [63 ± 16 years, 47% female, ejection fraction (EF) 63 ± 7%, and sPAP 35 ± 13 mmHg] presented with FTR graded trivial in 45%, mild in 37%, moderate in 15%, and severe in 3%. While pulmonary hypertension (PHTN-sPAP ≥ 50 mmHg) was the most powerful FTR severity determinant, other strong FTR determinants were older age, female sex, lower left ventricle EF, DMR, and particularly atrial fibrillation (AFib) (all P ≤ 0.002). Functional tricuspid regurgitation moderate/severe was independently linked to more severe clinical presentation, more oedema, lower stroke volume, and impaired renal function (P ≤ 0.01). Survival (95% confidence interval) throughout follow-up [70% (69-72%) at 10 years] was strongly associated with FTR severity [82% (80-84%) for trivial, 69% (66-71%) for mild, 51% (47-57%) for moderate, and 26% (19-35%) for severe, P < 0.0001]. Excess mortality persisted after comprehensive adjustment [adjusted hazard ratio 1.40 (1.18-1.67) for moderate FTR and 2.10 (1.63-2.70) for severe FTR, P ≤ 0.01]. Excess mortality persisted adjusting for sPAP/right ventricular function (P < 0.0001), by matching [adjusted hazard ratios 2.08 (1.50-2.89), P < 0.0001] and vs. expected survival [risk ratio 1.79 (1.48-2.16), P < 0.0001]. Within 5-year of diagnosis valve surgery was performed in 73% (70-75%) and 15% (13-17%) of severe and moderate DMR and in only 26% (19-34%) and 6% (4-8%) of severe and moderate FTR. Valvular surgery improved outcome without alleviating completely higher mortality associated with FTR (P < 0.0001).

Conclusion: In this large DMR cohort, FTR was frequent and causally, not only linked to PHTN but also to other factors, particularly AFib. Higher FTR severity is associated at diagnosis with more severe clinical presentation. Long term, FTR is independently of all confounders, associated with considerably worse mortality. Functional tricuspid regurgitation moderate and even severe is profoundly undertreated. Thus careful assessment, consideration for tricuspid surgery, and testing of new transcatheter therapy is warranted.
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http://dx.doi.org/10.1093/eurheartj/ehaa192DOI Listing
May 2020