You are here

Article Text

Article menu

Download PDFPDF

Valvular heart disease
Original research article
Echo-Doppler determinants of outcomes in patients with unoperated significant mitral regurgitation in current era
  1. Asim M Rafique1,
  2. Parham Zarrini2,
  3. Nirmal Singh3,
  4. Roy Beigel4,
  5. Rigved Tadwalkar1,
  6. Meshe Chonde5,
  7. Leandro Slipczuk2,
  8. Bojan Cercek2,
  9. Saibal Kar2 and
  10. Robert J Siegel2
  1. 1UCLA Medical Center, Los Angeles, California, USA
  2. 2Cedars-Sinai Heart Institute, Los Angeles, California, USA
  3. 3University of Arizona, Tucson, Arizona, USA
  4. 4Sheba—Tel Hashomer Hospital, Ramat Gan, Israel
  5. 5UPMC Presbyterian, Pittsburgh, Pennsylvania, USA
  1. Correspondence to Dr Robert J Siegel; siegel{at}cshs.org

Abstract

Objective One-half of patients with severe symptomatic mitral regurgitation (MR) do not undergo surgery due to comorbidities. We evaluated prognosticators of outcomes in patients with unoperated significant MR.

Methods In this observational study, we retrospectively evaluated medical records of 75 consecutive patients with unoperated significant MR.

Results All-cause mortality was 39% at 5 years. Non-survivors (n=29) versus survivors (n=46) were: older (77±9.8 vs 68±14, p=0.006), had higher New York Heart Association (NYHA) class (2.7±0.8 vs 2.3±0.8, p=0.037), higher brain natriuretic peptide (1157±717 vs 427±502 pg/mL, p=0.024, n=18), more coronary artery disease (61% vs 35%, p=0.031), more frequent left ventricular ejection fraction <50% (20.7% vs 4.3%, p=0.026), more functional MR (41% vs 22%, p=0.069), higher mitral E/E′ (12.7±4.6 vs 9.8±4, p=0.008), higher pulmonary artery systolic pressure (PASP; 52.6±18.7 vs 36.7±14, p <0.001), more ≥3+ tricuspid regurgitation (28% vs 4%, p=0.005) and more right ventricular dysfunction (26% vs 6%, p=0.035). Significant predictors of 5-year mortality were PASP (p=0.001) and E/E′ (p=0.011) using multivariate regression analysis.

Conclusions Patients with unoperated significant MR have high mortality. Elevated PASP and mitral E/E′ were the most significant predictors of 5-year survival in patients with unoperated significant MR. Current American College of Cardiology (ACC)/American Heart Association (AHA) guidelines provide a limited incorporation of echo-Doppler parameters in the preoperative risk stratification of patients with severe MR.

  • HEART FAILURE

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/openhrt-2015-000378

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Key questions

    What is already known about this subject?

    • Patients with uncorrected severe symptomatic mitral regurgitation (MR) have a significantly increased risk of morbidity and mortality. Several clinical and echocardiographic prognosticators of outcomes in patients with unoperated severe MR have been described in the past, but limited data exist in the current era.

    What does this study add?

    • This study provides an updated analysis of echo-Doppler parameters in determining outcomes in patients with severe MR who are not candidates for surgery or percutaneous repair in the context of current American College of Cardiology (ACC)/American Heart Association (AHA) guidelines.

    How might this impact on clinical practice?

    • This study will help clinicians to better risk stratify patients with severe MR and highlights that the current ACC/AHA guidelines provide limited incorporation of echo-Doppler parameters in the preoperative risk stratification of patients with severe MR.

    Introduction

    Patients with uncorrected severe symptomatic mitral regurgitation (MR) have a significantly increased risk of morbidity and mortality.1–4 However, in the EuroHeart survey, approximately one-half of patients with severe symptomatic MR did not undergo surgery, most frequently due to comorbidities.5 However, there are no data from the current era, which addresses the natural history of patients with unoperated severe MR to determine the prognostic value of various echo-Doppler and clinical variables. The objective of our study was to identify clinical and echo-Doppler predictors of 5-year outcomes in patients with significant symptomatic MR who did not undergo surgical intervention in the current era.

    Methods

    In this observational study, we retrospectively evaluated the medical records of consecutive patients with significant MR (≥3+) from December 2005 through December 2008, who were considered high risk and did not undergo surgery during a 5-year follow-up and were not deemed to be candidates for the MitraClip procedure.6 ,7 We excluded patients with concomitant moderate or greater aortic stenosis or aortic regurgitation, and patients with prior percutaneous or surgical repair or replacement of the mitral and/or aortic valves.6 ,7 Hospital medical records and the social security death index were used to obtain and verify the 5-year mortality data. Patients were stratified into two groups as survivors versus non-survivors at 5 years of follow-up. The Institutional Review Board approved the study, and the waiver for patient consent was granted because of the retrospective nature of the study.

    Two independent reviewers (RJS and AMR) evaluated the echocardiograms. Significant MR was defined as per the ACC/AHA guidelines, using a combination of qualitative and quantitative parameters including MR colour jet area to left atrial area ratio (JA/LAA) ≥40%, Doppler vena contracta width (VC) ≥0.7 cm, mitral regurgitant volume (Rvol) ≥60 mL/beat, regurgitant fraction ≥50%, effective regurgitant orifice area (EROA) ≥40 mm2, density and width of MR continuous wave (CW) jet, pulmonary vein flow (PVF) with systolic reversal, and enlarged left atrium (LA) and left ventricle (LV).6–8

    Transmitral early (E) peak velocity, its deceleration time (DT) and transmitral atrial (A) wave velocity were obtained with a pulsed wave sample at the tip of the mitral valve.9 Early diastolic velocity of the lateral aspect of the mitral annulus (E′) was measured by Doppler tissue imaging (TDI). PVF was obtained on an apical four-chamber view.9 ,10

    The maximum velocity of the tricuspid regurgitation (TR) jet was measured using CW Doppler as per American Society of Echocardiography (ASE) recommendations.8 ,11 Right ventricle (RV) systolic pressure was estimated based on the modified Bernoulli equation and assumed to be equal to the pulmonary artery systolic pressure (PASP) in the absence of RV outflow obstruction. PASP was calculated by adding the tricuspid valve pressure gradient to the estimated right atrial pressure (RAP).11 RAP was considered as: 3 mm Hg for inferior vena cava (IVC) diameter <1.7 cm and ≥50% collapse with inspiration; 7 mm Hg for IVC diameter ≥1.7 cm and ≥50% decrease in the diameter with inspiration; 12 mm Hg if <50% collapse on inspiration; ≥15 mm Hg if the IVC was dilated without any collapse.8 ,11

    Statistical analysis

    Statistical analysis was performed with the statistical software program IBM SPSS V.21.0 (IBM Inc). Continuous data were presented as mean±SD. Categorical data were presented as an absolute number or percentages. Between-groups comparisons of baseline data were performed using the independent-samples t-test. All categorical variables were compared between the two groups using the Pearson χ2 test. Clinical and statistical variables were entered into Cox regression models to evaluate the independent predictors of 5-year survival. Kaplan-Meier analysis was used to estimate survival. The log-rank test was used to compare survival across two groups. A p value <0.05 was considered statistically significant. Given the retrospective and observational nature of the study, the sample size was not calculated.

    Results

    Medical records of 83 patients with significant MR and available 5-year follow-up data were reviewed. Eight patients were excluded due to: prior mitral valve repair (MVR; n=2), MitraClip treatment (n=1), or MVR/mitral valve replacement (MVRe; n=3) during the follow-up period, or absence of a reliable TR signal on echocardiography (n=2). We included 75 patients (45 male) with a mean age of 72±11 years. The mean mitral EROA was 54±30 mm2, the mitral Rvol was 80±37 mL/beat, the VC was 0.6±0.2 cm and the mean mitral JA/LAA was 42.3±12 mm Hg. TDI of the lateral mitral annulus was available for 64 (85%) patients, and PVF was interpretable in 62 (83%) patients. The reasons for non-operability are shown in table 1.

    View this table:
    Table 1

    Reasons for not performing mitral valve surgery

    Overall, 29 (39%) patients died during the 5 years of follow-up. As shown in table 2, non-survivors (n=29) compared with survivors (n=46) were older (77±9.8 vs 68±14 years, p=0.006); had more coronary artery disease (61% vs 35%, p=0.031), diabetes (21% vs 6.5%, p=0.057), pulmonary hypertension (71% vs 37%, p=0.004), atrioventricular block (14% vs 2.3%, p=0.073), higher New York Heart Association (NYHA) class (2.7±0.8 vs 2.3±0.8, p=0.037), higher brain natriuretic peptide (BNP) level (1157±717 vs 427±502, p=0.024, n=18) and a trend for a higher incidence of syncope (7.1% vs 0%, p=0.066). Overall, there was no significant difference in the prevalence of symptoms between the two study groups (93.1% vs 84.8%, p=0.281). Other comorbidities and medical treatment were comparable between the two groups.

    View this table:
    Table 2

    Comparison of baseline clinical variables between non-survivors and survivors

    The use of β-blockers, ACE inhibitors or angiotensin receptor blockers, or spironolactone was significantly higher in non-survivors compared with survivors (87% vs 61%, p=0.033). The use of these medications tended to be more frequent in non-survivors compared with survivors both in functional MR (FMR; 100% vs 78%, p=0.134) and degenerative MR (DMR; 79% vs 56%, p=0.147). Patients on these medications tended to have worse: NYHA class (2.6±0.7 vs 2.1±0.9, p=0.044), left ventricular ejection fraction (LVEF; 58±17% vs 65±12%, p=0.182), forward stroke volumes (47±19 vs 71±42, p=0.051), PASP (43±16 vs 36±16, p=0.176), RAP (9±6 vs 8±6, p=0.782), BNP (896±1232 vs 491±195, p=0.561) and creatinine (2.1±2.9 vs 1.0±0.4, p=0.289).

    As shown in table 3, non-survivors compared with survivors had: similar LV systolic (36.4±13.1 vs 34.3±9.2, p=0.448) and LV diastolic (55.5±9.7 vs 53.6±6.8, p=0.369) dimensions, with a higher prevalence of an LVEF<50% (20.7% vs 4.3%, p=0.026), lower LV stroke volume (49.5±21.8 vs 66.7±47.8, p=0.038), higher mitral E velocity (116.1±28.9 vs 99.5±30.7, p=0.024), higher E/E′ (12.7±4.6 vs 9.8±4, p=0.008), higher prevalence of E/E′≥15 (32% vs 10.5%, p=0.034), higher PASP (52.6±18.7 vs 36.7±14, p<0.001), similar E/A≥2 (18.2% vs 26.3%, p=0.473), similar DT<140 ms (21.4% vs 10.9%, p=0.216), and more TR and RV dysfunction (26% vs 4%, p=0.035).

    View this table:
    Table 3

    Comparison of echocardiographic variables between non-survivors and survivors

    Non-survivors compared with survivors had: severe MR (72% vs 70%, p=0.791), FMR (41% vs 22%, p=0.069), eccentric MR jet (64% vs 78%, p=0.242), mitral annular calcification (70% vs 36%, p=0.021), JA/LAA (72.4% vs 45.7%, p 0.023), VC≥0.7 (34.5% vs 22.2%, p=0.246), Rvol≥60 mL (58.6% vs 76.1%, p=0.11), EROA≥40 mm2 (51.7% vs 76.1%, p=0.029) and mean EROA (47±23 vs 59±32, p=0.074; table 4). Of the 22 patients with FMR, the 5-year mortality was 54% compared with 32% of 53 patients with DMR (p=0.032).

    View this table:
    Table 4

    Comparison of echocardiographic variables related to MV anatomy and function

    Figure 1 shows the areas under the curve (AUC) from receiver-operator characteristic curve for the various parameters. Lateral E/E′≥8 was 92% sensitive and 39% specific; lateral E/E′≥15 was 32% sensitive and 89% specific; PASP≥50 mm Hg was 59% sensitive and 87% specific; PASP≥60 mm Hg was 28% sensitive and 89% specific; RAP≥10 mm Hg was 36% sensitive and 81% specific (AUC=0.62, 95% CI 0.48 to 0.76, p=0.098); mitral E velocity ≥120 cm/s was 43% sensitive and 80% specific (AUC 0.66, 95% CI 0.53 to 0.78, p=0.027); and mitral JA/LAA ≥40% was 66% sensitive and 60% specific (AUC 0.71, 95% CI 0.60 to 0.83, p <0.01) to predict 5-year mortality.

    Figure 1
    Figure 1

    (A) ROC for the prediction of 5-year mortality in unoperated significant MR. AUCs and corresponding p values are shown for lateral annulus E/E′ (AUC=0.69, 95% CI 0.56 to 0.83, p=0.01). (B) ROC for the prediction of 5-year mortality in unoperated significant MR. AUCs and corresponding p values are shown for PASP (AUC=0.76, 95% CI 0.64 to 0.88, p<0.001). AUC, area under curve; PASP, pulmonary artery systolic pressure; ROC, receiver-operator characteristic curve.

    Using Kaplan-Meier curves, the 5-year all-cause mortality was 67% in patients with E/E′≥15 compared with 33% in patients with E/E′<15 (p=0.008, figure 2A). Using Kaplan-Meier curves, the 5-year mortality was 74% for patients with a PASP≥50 mm Hg compared with 23% for patients with PASP<50 mm Hg (p<0.001, figure 2B).

    Figure 2
    Figure 2

    (A): Five-year mortality in unoperated patients with severe MR with E/E′≥15 was significantly higher compared with patients with E/E′<15 (67% vs 33%, p=0.008). (B): Five-year mortality in unoperated patients with severe MR with PASP≥50 was significantly higher compared with patients with PASP<50 (76% vs 23%, p<0.001). DMR, degenerative MR; EROA, effective regurgitant orifice area; FMR, functional MR; MR, mitral regurgitation; PASP, pulmonary artery systolic pressure.

    Patients with PASP≥50 mm Hg and E/E′≥15 (n=8) had a 5-year mortality of 75% while patients with PASP<50 mm Hg and E/E′<15 (n=38) had a lower 5-year mortality of 21%. Only seven patients had LVEF<50%, so further stratification was not possible. In the subgroup of patients with LVEF≥50%, patients with PASP≥50 mm Hg had a significantly worse survival than patients with PASP<50 mm Hg (22% vs 67%, p<0.001).

    In the multivariate Cox regression analysis presented in table 5, the only significant predictor predictive of 5-year mortality was a PASP≥50 mm Hg (HR 2.2, 95% CI 1.4 to 3.3, p<0.001). Age, gender, NYHA class ≥3, LVEF<50%, E/E′≥15, EROA≥40 and MR Rvol≥60, aetiology were not significant independent predictors in the multivariate model. Using the above parameters as continuous variables in the linear regression model, the significant predictors included PASP (p=0.001) and E/E′ (p=0.011).

    View this table:
    Table 5

    Cox regression model using clinical and echocardiographic variables

    Discussion

    Patients with moderate to severe or severe MR who do not undergo surgical repair or replacement because of comorbidities have a high 5-year mortality. In the multivariate analysis, significant predictors of 5-year mortality were PASP and E/E′. We did not find EROA, Rvol and VC to be predictive of mortality in patients with significant MR.

    The likely mechanisms of increased mortality in patients with elevated and persistent PASP most likely include more advanced LV and LA remodelling in response to chronic volume overload from severe MR resulting in irreversible changes in the myocardium due to fibrosis and the permanent dysfunction of endothelium in the pulmonary vasculature. Elevated filling parameters in the setting of pulmonary hypertension therefore represent a more advanced disease stage where early intervention is warranted. Early optimisation of medical therapy for congestive heart failure (CHF) is prudent to improve pulmonary hypertension (PH) and hence outcomes in patients with MR by preventing late LV irreversible remodelling.12 The role of specific therapy for PH should be evaluated in patients with MR with an elevated transpulmonary gradient. MVR/MVRe is now an alternative treatment for patients with severe symptomatic MR who are not operative candidates.13–15 It is important to carefully evaluate the patients undergoing MVR/MVRe or MitraClip as increasingly more complex and sick patients are being referred for these procedures.16–18 Swaans et al19 showed that high surgical-risk patients with severe symptomatic MR treated with transcatheter MV repair show similar survival rates comparable to patients undergoing surgery, with both groups showing a survival benefit compared with conservative treatment. Appropriate risk stratification and proper selection of these high-risk patients and optimisation of filling pressures may improve outcomes of these patients with poor surgical options and with an increased mortality with medical therapy alone.

    Conclusions

    Patients with unoperated significant MR have a high mortality rate. Elevated filling pressures as determined by PASP and mitral E/E′ were most significant predictors of 5-year survival in patients with unoperated significant MR. Optimisation of filling pressure preprocedure or earlier intervention preceding development of irreversible changes may further improve outcomes in patients undergoing evaluation for MVR/MVRe or MitraClip.

    Limitations

    This is a retrospective study; however, few studies have evaluated the prognosis of untreated MR in the modern era as most patients with severe MR undergo surgery or percutaneous intervention. This study is unique in providing an updated evaluation of echo-Doppler prognosticators in patients with severe MR. PASP was evaluated using echocardiography, which reflects the filling pressure under true resting conditions, avoiding the impact of analgesia or sedation and intravenous fluids on cardiac haemodynamics.

    Supplemental material

    References

    1. ↵
      1. Nishimura RA,
      2. Otto CM,
      3. Bonow RO, et al
      ., American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2438–88. doi:10.1016/j.jacc.2014.02.537
      OpenUrlFREE Full Text
    2. ↵
      1. Delahaye JP,
      2. Gare JP,
      3. Viguier E, et al
      . Natural history of severe mitral regurgitation. Eur Heart J 1991;12(Suppl B):5–9. doi:10.1093/eurheartj/12.suppl_B.5
      OpenUrlAbstract/FREE Full Text
    3. ↵
      1. Rosen SE,
      2. Borer JS,
      3. Hochreiter C, et al
      . Natural history of the asymptomatic/minimally symptomatic patient with severe mitral regurgitation secondary to mitral valve prolapse and normal right and left ventricular performance. Am J Cardiol 1994;74:374–80. doi:10.1016/0002-9149(94)90406-5
      OpenUrlCrossRefPubMedWeb of Science
    4. ↵
      1. Hannan EL,
      2. Racz MJ,
      3. Jones RH, et al
      . Predictors of mortality for patients undergoing cardiac valve replacements in New York State. Ann Thorac Surg 2000;70:1212–18. doi:10.1016/S0003-4975(00)01968-8
      OpenUrlCrossRefPubMedWeb of Science
    5. ↵
      1. Iung B,
      2. Baron G,
      3. Butchart EG, et al
      . A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease. Eur Heart J 2003;24:1231–43. doi:10.1016/S0195-668X(03)00201-X
      OpenUrlAbstract/FREE Full Text
    6. ↵
      1. Feldman T,
      2. Foster E,
      3. Glower DD, et al.
      , EVEREST II Investigators. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med 2011;364:1395–406. doi:10.1056/NEJMoa1009355
      OpenUrlCrossRefPubMedWeb of Science
    7. ↵
      1. Lim DS,
      2. Reynolds MR,
      3. Feldman T, et al
      . Improved functional status and quality of life in prohibitive surgical risk patients with degenerative mitral regurgitation after transcatheter mitral valve repair. J Am Coll Cardiol 2014;64:182–92. doi:10.1016/j.jacc.2013.10.021
      OpenUrlFREE Full Text
    8. ↵
      1. Lang RM,
      2. Bierig M,
      3. Devereux RB, et al.
      , Chamber Quantification Writing Group; American Society of Echocardiography's Guidelines and Standards Committee; European Association of Echocardiography. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440–63. doi:10.1016/j.echo.2005.10.005
      OpenUrlCrossRefPubMedWeb of Science
    9. ↵
      1. Nagueh SF,
      2. Appleton CP,
      3. Gillebert TC, et al
      . Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr 2009;22:107–33. doi:10.1016/j.echo.2008.11.023
      OpenUrlCrossRefPubMedWeb of Science
    10. ↵
      1. Park HS,
      2. Naik SD,
      3. Aronow WS, et al
      . Differences of lateral and septal mitral annulus velocity by tissue Doppler imaging in the evaluation of left ventricular diastolic function. Am J Cardiol 2006;98:970–2. doi:10.1016/j.amjcard.2006.04.044
      OpenUrlCrossRefPubMedWeb of Science
    11. ↵
      1. Ommen SR,
      2. Nishimura RA,
      3. Hurrell DG, et al
      . Assessment of right atrial pressure with 2-dimensional and Doppler echocardiography: a simultaneous catheterization and echocardiographic study. Mayo Clin Proc 2000;75:24–9. doi:10.4065/75.1.24
      OpenUrlCrossRefPubMedWeb of Science
    12. ↵
      1. Onorati F,
      2. Santini F,
      3. Dandale R, et al
      . Functional mitral regurgitation: a 30-year unresolved surgical journey from valve replacement to complex valve repairs. Heart Fail Rev 2014;19:341–58. doi:10.1007/s10741-013-9392-9
      OpenUrlPubMed
    13. ↵
      1. Taramasso M,
      2. Denti P,
      3. Buzzatti N, et al
      . Mitraclip therapy and surgical mitral repair in patients with moderate to severe left ventricular failure causing functional mitral regurgitation: a single-centre experience. Eur J Cardiothorac Surg 2012;42:920–6. doi:10.1093/ejcts/ezs294
      OpenUrlAbstract/FREE Full Text
    14. ↵
      1. Whitlow PL,
      2. Feldman T,
      3. Pedersen WR, et al
      ., EVEREST II Investigators. Acute and 12-month results with catheter-based mitral valve leaflet repair: the EVEREST II (Endovascular Valve Edge-to-Edge Repair) High Risk Study. J Am Coll Cardiol 2012;59:130–9. doi:10.1016/j.jacc.2011.08.067
      OpenUrlPubMed
    15. ↵
      1. Mauri L,
      2. Foster E,
      3. Glower DD, et al
      ., EVEREST II Investigators. 4-Year results of a randomized controlled trial of percutaneous repair versus surgery for mitral regurgitation. J Am Coll Cardiol 2013;62:317–28. doi:10.1016/j.jacc.2013.04.030
      OpenUrlFREE Full Text
    16. ↵
      1. Maisano F,
      2. Franzen O,
      3. Baldus S, et al
      . Percutaneous mitral valve interventions in the real world: early and 1-year results from the ACCESS-EU, a prospective, multicenter, nonrandomized post-approval study of the MitraClip therapy in Europe. J Am Coll Cardiol 2013;62:1052–61. doi:10.1016/j.jacc.2013.02.094
      OpenUrlFREE Full Text
    17. ↵
      1. Wan B,
      2. Rahnavardi M,
      3. Tian DH, et al
      . A meta-analysis of MitraClip system versus surgery for treatment of severe mitral regurgitation. Ann Cardiothorac Surg 2013;2:683–92. doi:10.3978/j.issn.2225-319X.2013.11.02
      OpenUrlPubMed
    18. ↵
      1. Conradi L,
      2. Treede H,
      3. Rudolph V, et al
      . Surgical or percutaneous mitral valve repair for secondary mitral regurgitation: comparison of patient characteristics and clinical outcomes. Eur J Cardiothorac Surg 2013;44:490–6. doi:10.1093/ejcts/ezt036
      OpenUrlAbstract/FREE Full Text
    19. ↵
      1. Swaans MJ,
      2. Bakker AL,
      3. Alipour A, et al
      . Survival of transcatheter mitral valve repair compared with surgical and conservative treatment in high-surgical-risk patients. JACC Cardiovasc Interv 2014;7:875–81. doi:10.1016/j.jcin.2014.01.171
      OpenUrlAbstract/FREE Full Text
    View Abstract

    Footnotes

    • Contributors AMR and RJS contributed to the conception and design of the study. Data were collected by AMR, PZ, NS, RT and MC. Statistical analysis and interpretation of data were performed by AMR, RJS and RB. The manuscript was drafted by AMR with further revisions by RJS, BC and SK for important intellectual content.

    • Funding This research received no grant from any funding agency in the public, commercial or not-for-profit sector.

    • Competing interests None declared.

    • Ethics approval Cedars-Sinai Institutional Review Board (IRB).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement No additional data are available.