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Echocardiographic Estimated Pulmonary Systolic Pressure and Outcome After Noncardiac-Obstetrics Surgery in Postcapillary Pulmonary Hypertensive Patients

Open AccessPublished:January 20, 2022DOI:https://doi.org/10.1016/j.amjcard.2021.12.047
      Pulmonary hypertension is associated with increased postoperative risk. This study analyzed the relation between the preoperative echocardiographic estimated blood pressure (estimated pulmonary arterial systolic pressure [ePASP]) of noncardiac patients and postoperative cardiac outcome and tried to identify a clinically meaningful threshold for ePASP in postcapillary pulmonary hypertensive patients. This was a single-center retrospective cohort study with propensity score analysis based on patients who underwent elective noncardiac surgery from June 2012 to December 31, 2018. We evaluated the relation between ePASP and the development of postoperative major adverse cardiac events (MACEs). Multivariate logistic regression models and generalized additive models were used, and the minimum p value approach was used to identify the threshold of ePASP that independently indicated the risk of MACEs. Finally, propensity score matching was used for patients with ePASP above or below the threshold, and the exposure effect was evaluated. Of the 16,210 surgeries, 7.0% experienced postoperative MACEs. The threshold for the ePASP was 47 mm Hg. Adjusted odds ratios for MACEs before and after propensity score matching were 2.03 (1.22 to 2.83) and 1.62 (1.01 to 2.23), respectively. In conclusion, the incidence of postoperative MACEs was 7.0% in patients who underwent elective noncardiac surgery. An ePASP ≥47 mm Hg was significantly associated with an increased risk of postoperative MACEs in postcapillary pulmonary hypertensive patients.
      Severe pulmonary hypertension (PH, pulmonary arterial systolic pressure [PASP] >70 mm Hg) is often associated with a great risk of death in any circumstances.
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      However, there is no consensus on what level of mild to moderate PH (PASP 30 to 70 mm Hg) poses a risk to patients with PH during surgery
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      Whether the relation between PASP and the postoperative outcome is linear remains unprevailed. Each year, a large portion of patients with elevated PASP who underwent elective noncardiac surgery challenge both anesthesiologists and cardiologists before and after operations. This retrospective study aimed to investigate the relation of the preoperative echocardiographic PASP (ePASP) and the development of postoperative major adverse cardiac events (MACEs) and to identify an optimal threshold to evaluate the prognostic relevance of ePASP on perioperative in-hospital morbidity and mortality in adult patients with postcapillary PH who underwent noncardiac surgery with general anesthesia at a large tertiary care medical center.
      This single-center retrospective cohort study was conducted in a teaching hospital in China with 1,500 beds. This study was approved by the ethics committee. Because of the retrospective feature and lack of patient follow-up, and no involvement of patient identification information, written informed consent was waived by the institutional review board. This study used data obtained from the perioperative database, which contains the perioperative information of inpatients from 2012 onward. This study analyzed data from adults (age ≥18 years) who underwent elective noncardiac surgery between June 1, 2012, and December 31, 2018.
      Patients with pulmonary valve stenosis (transpulmonary pressure gradient >20 mm Hg) and right ventricular outflow tract obstruction (pressure gradient across the 2 chambers in the right ventricle >10 mm Hg) were removed from the acquisition of echocardiographic data because there were clinical considerations that would contribute to skewed pulmonary artery pressure. Patients with possible precapillary pulmonary hypertension (Supplementary Table 1 in the Appendix) were excluded.
      The procedures excluded cardiac surgery, obstetrics, and emergency surgery departments. Only the first procedure record was used by patients who underwent surgery >2 times a year (a small number of patients operated on in different years could be recognized as two surgeries). If the time interval between the 2 operations was <3 months, the second operation would not be registered. Surgery under local infiltration anesthesia was also omitted from this analysis.
      The different risk of cohorts was ePASP. Echocardiographic examinations were performed using a Vivid 9 ultrasound system (General Electric Vingmed Ultrasound AS, Horten, Norway) or Philips EPIC 7 (Philips Medical Systems, Andover, Massachusetts) equipped with a 2 to 4 MHz transducer with a frame rate of at least 50 frames per second. Standard 2-dimensional and Doppler images were obtained. In the absence of pulmonic valve stenosis or right ventricular outflow tract obstruction, ePASP is calculated from the peak velocity (V) of a tricuspid valvular regurgitant jet using simplified Bernoulli's equation: ePASP = 4V
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      Burden of pulmonary arterial hypertension in Germany.
       + right atrial pressure (RAP), where RAP is estimated from the diameter and respiratory changes of the inferior vena cava (IVC). An IVC diameter ≤2.1 cm that collapses >50% with a sniff suggests normal RAP (5 mm Hg), whereas IVC diameter >2.1 cm that collapses <50% with a sniff suggests high RAP of 15 mm Hg. In scenarios in which IVC diameter and collapse do not fit this paradigm, an intermediate value of 10 mm Hg is used.
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      Patients with higher or lower preoperative ePASP were defined as at different risk of the study.
      The variables collected in this study included basic characteristics of patients (body mass index, gender, age, smoking, and alcohol habits); variables of preoperative disorder (hypertension, coronary artery disease, myocardial infarction, revised cardiac risk index [rCRI]); intraoperative variables (intraoperative hypotension, blood infusion, anesthesia type, the modified Johns Hopkins Hospital Surgical Criteria, mean intraoperative heart rate);
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      pressure variables (baseline blood pressure, ePASP) and variables of heart structure and functionality such as left ventricular ejection fraction (LVEF), right ventricular enlargement and left ventricular diastolic dysfunction (definitions of variables are listed in Supplementary Table 2). According to existing literature,
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      we defined intraoperative hypotension as intraoperative systolic blood pressure <90 mm Hg or mean blood pressure <70 mm Hg for ≥5 minutes, or when the mean blood pressure decreased by >20% from the baseline for ≥5 minutes (Supplementary Table 2). The rCRI is a well-developed and validated risk index for predicting postoperative MACEs in all types of patients who underwent general surgery, including those with diabetes mellitus, active congestive heart failure, preoperative renal insufficiency.
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      The modified Johns Hopkins Hospital Surgical Criteria was used for categorizing the surgical complexity.
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      The average of 3 values recorded electronically from the preoperative ward before surgery was defined as the baseline pressure on separate days. Low LVEF was defined as LVEF <55%.
      The primary outcomes included acute myocardial infarction (ST-segment elevation myocardial infarction and non–ST-segment elevation myocardial infarction), new congestive heart failure, nonfatal cardiac arrest, and death within 7 days postoperatively in the hospital. Only the first MACE was counted for a patient who experienced multiple events during hospitalization.
      We used well-developed and validated claims algorithms for identifying MACEs, which include International Classification of Diseases, Ninth or Tenth Revision when appropriate,
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      analysis of entire perioperative laboratory test results (B-type natriuretic peptide, cardiac troponin T, creatinine), plain text analysis of drug prescriptions, medical procedures and trans-departmental medical consultation records. Furthermore, electronic records of potential events retrieved by the algorithm were manually reviewed by anesthesiologists and final adjudication was made by a senior cardiologist (L.L.).
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      • Mérie C
      • Jørgensen M
      • Gislason GH
      • Torp-Pedersen C
      • Overgaard C
      • Køber L
      • Jensen PF
      • Hlatky MA.
      Association of β-blocker therapy with risks of adverse cardiovascular events and deaths in patients with ischemic heart disease who underwent noncardiac surgery: a Danish nationwide cohort study.
      • Fleisher LA
      • Fleischmann KE
      • Auerbach AD
      • Barnason SA
      • Beckman JA
      • Bozkurt B
      • Davila-Roman VG
      • Gerhard-Herman MD
      • Holly TA
      • Kane GC
      • Marine JE
      • Nelson MT
      • Spencer CC
      • Thompson A
      • Ting HH
      • Uretsky BF
      • Wijeysundera DN
      American College of Cardiology, American Heart Association
      2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients who underwent noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
      • James PA
      • Oparil S
      • Carter BL
      • Cushman WC
      • Dennison-Himmelfarb C
      • Handler J
      • Lackland DT
      • LeFevre ML
      • MacKenzie TD
      • Ogedegbe O
      • Smith Jr, SC
      • Svetkey LP
      • Taler SJ
      • Townsend RR
      • Wright Jr, JT
      • Narva AS
      • Ortiz E.
      2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8).
      • Whelton PK
      • Carey RM
      • Aronow WS
      • Casey Jr, DE
      • Collins KJ
      • Dennison Himmelfarb C
      • DePalma SM
      • Gidding S
      • Jamerson KA
      • Jones DW
      • MacLaughlin EJ
      • Muntner P
      • Ovbiagele B
      • Smith Jr, SC
      • Spencer CC
      • Stafford RD
      • Taler SJ
      • Thomas RJ
      • Williams Sr, KA
      • Williamson JD
      • Wright Jr, JT
      2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
      • McMurray JJ
      • Adamopoulos S
      • Anker SD
      • Auricchio A
      • Böhm M
      • Dickstein K
      • Falk V
      • Filippatos G
      • Fonseca C
      • Gomez-Sanchez MA
      • Jaarsma T
      • Køber L
      • Lip GY
      • Maggioni AP
      • Parkhomenko A
      • Pieske BM
      • Popescu BA
      • Rønnevik PK
      • Rutten FH
      • Schwitter J
      • Seferovic P
      • Stepinska J
      • Trindade PT
      • Voors AA
      • Zannad F
      • Zeiher A
      • Bax JJ
      • Baumgartner H
      • Ceconi C
      • Dean V
      • Deaton C
      • Fagard R
      • Funck-Brentano C
      • Hasdai D
      • Hoes A
      • Kirchhof P
      • Knuuti J
      • Kolh P
      • McDonagh T
      • Moulin C
      • Popescu BA
      • Reiner Z
      • Sechtem U
      • Sirnes PA
      • Tendera M
      • Torbicki A
      • Vahanian A
      • Windecker S
      • McDonagh T
      • Sechtem U
      • Bonet LA
      • Avraamides P
      • Ben Lamin HA
      • Brignole M
      • Coca A
      • Cowburn P
      • Dargie H
      • Elliott P
      • Flachskampf FA
      • Guida GF
      • Hardman S
      • Iung B
      • Merkely B
      • Mueller C
      • Nanas JN
      • Nielsen OW
      • Orn S
      • Parissis JT
      • Ponikowski P
      Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology, ESC Committee for Practice Guidelines
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      • Casey Jr, DE
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      • Jaffe AS
      • Jneid H
      • Kelly RF
      • Kontos MC
      • Levine GN
      • Liebson PR
      • Mukherjee D
      • Peterson ED
      • Sabatine MS
      • Smalling RW
      • Zieman SJ
      ACC/AHA Task Force Members
      2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
      ,
      • Andersson C.
      Incorrect ICD-10 code and MACE endpoint.
      For the comparative analysis, patients were divided into 2 groups according to the occurrence of postoperative MACEs. Continuous variables with a normal distribution were compared using the Student t test, and those with non-normal distribution were compared with the Mann-Whitney U test. The Kolmogorov-Smirnov test was used to determine whether the data were normally distributed or not. Categorical variables were compared using the chi-square test or Fisher's exact test. Rank variables were compared using the Kruskal-Wallis H test. Statistical significance was defined by a two-tailed p <0.05.
      We examined the unadjusted relation between the ePASP and the risk of MACEs using a cubic spline function in general additive models. We used the inflection point to divide the ePASP into 2 clinically meaningful categories. If we observed an area of inflation, the optimal threshold for the ePASP was determined using the minimum p value approach. This approach evaluated every possible threshold of the ePASP at intervals of 1 mm Hg in the multivariate logistic regression models. The ePASP that demonstrated the smallest statistically significant p value was selected as the optimal threshold to divide the ePASP into 2 groups.
      In the multivariate models, the basic characteristics of patients such as age, body mass index, hypertension, cancer or malignant tumor, intraoperative hypotension, and blood infusion were added to the model as covariates. The rCRI was used to adjust for the preoperative risk of MACEs. Besides, variables of heart structure and functionality such as low LVEF, right ventricular enlargement, and left ventricular diastolic dysfunction were also included in the full model. Multicollinearity in these variables was assessed by the variance inflation factor, with a reference value of 2. The goodness of fit was tested using the le Cessie-van Houwelingen-Copas-Hosmer unweighted sum of squares test (p >0.05). Discrimination of the multivariate model was assessed based on the c-statistic. We assessed whether the addition of the ePASP to the model can improve the predictive ability for MACEs by calculating the net reclassification improvement (NRI) and the integrated discrimination improvement. A heterogeneity analysis was used to determine any differences in the effects of the treatments in different subgroups by covariates in the model mentioned previously. We calculated the adjusted odds ratio (OR) for MACEs in each subgroup and then tested the interaction effect of the covariates for the relation between ePASP and outcomes. Sensitivity analysis of logistic regression models was constructed as follows: (1) with MACE up to 30 days after surgery; (2) including all patients with possible precapillary PH; (3) multivariable logistic regression with a cut-off point of ePASP by maximum OR approach. The ePASP that demonstrated the ePASP cut-off point with the highest adjusted OR (also 47 mm Hg, p value <0.001) was selected as the optimal threshold to divide the ePASP into 2 groups.
      To reduce the influence of potential confounding factors, propensity score (PS) matching analysis was performed to modify intergroup differences according to the lower or higher ePASP. Tables 1 and 2 list demographic and perioperative variables used for estimating the PS. Using greedy matching algorithms, this study used a caliper of 0.25 of the logit of the PS to match patients at a ratio of 10:1. This study evaluated the balancing in demographic, surgical, and preoperative covariates of the PS-matched cohort by the standardized mean difference. All absolute standardized differences after PS were <15%. The risk of outcome variables, including the occurrence of morbidity, were re-analyzed by logistic regression in the total and PS-matched cohorts. All statistical analysis was performed using the R programing language version 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria).
      Table 1Baseline characteristics of all patients included in the total set and the propensity score match set
      All values are reported as N (%) unless otherwise specified. (no/mild/moderate/severe).
      VariablesAll (n=16,384)ePASP Total set (mm Hg)ePASP Match set (mm Hg)
      Demographic data<47 (n=16,128)≥47 (n=256)p Value<47 (n=2,540)≥47 (n=254)smd
      Age [yr; median (IQR)]68(60-76)68(60-75)76(68-84)<.00176 (68-81)76 (68-84)0.2
      Women, [n (%)]8728 (53.3%)8599 (53.3%)129 (50.4%)0.3521273(50.1%)128(50.4%)0.6
      Body mass index, kg/m224.4 ± 3.724.4 ± 3.723.1 ± 4.0<.00123.3 ± 3.723.1 ± 43.5
      Cigarette, [n (%)]1975 (12.1%)1950 (12.1%)25 (9.8%)0.257249(9.8%)25(9.8%)0.1
      Alcohol, [n (%)]1712 (10.4%)1692 (10.5%)20 (7.8%)0.165227(8.9%)20(7.9%)3.8
      Preoperative medical history
      ASA-PS (I/II/III/IV or V; n)1080/12605/2614/851077/12486/2485/803/119/129/5<.00114/1239/1251/363/119/127/58.5
      rCRI (0/I/II/III or higher; n)13300/1577/920/58713144/1538/891/555156/39/29/32<.0011624/388/281/247155/39/29/318.4
      Hypertension7726 (47.2%)7558 (46.9%)168 (65.6%)<.0011702(67%)166(65.4%)3.5
      Ischemic heart disease3213 (19.6%)3151 (19.5%)62 (24.2%)0.061639(25.2%)61(24%)2.7
      Congestive heart failure104 (0.6%)104 (0.6%)0 (0.0%)0.197429(16.9%)62(24.4%)18.7
      Arrhythmia677 (4.1%)664 (4.1%)13 (5.1%)0.443421(16.6%)49(19.3%)7.1
      Peripheral arterial disease680 (4.2%)616 (3.8%)64 (25.0%)<.001394(15.5%)42(16.5%)2.8
      Stroke931 (5.7%)881 (5.5%)50 (19.5%)<.001434(17.1%)41(16.1%)2.5
      Diabetes mellitus1591 (9.7%)1549 (9.6%)42 (16.4%)<.001835(32.9%)81(31.9%)2.1
      Chronic renal disease1914 (11.7%)1873 (11.6%)41 (16.0%)0.030310(12.2%)38(15%)8.1
      Dyslipidemia3755 (22.9%)3672 (22.8%)83 (32.4%)<.001179(7%)19(7.5%)1.7
      Anemia632 (3.9%)593 (3.7%)39 (15.2%)<.001254(10%)32(12.6%)8.2
      COPD1019 (6.2%)1000 (6.2%)19 (7.4%)0.422219(8.6%)24(9.4%)2.9
      Respiratory failure598 (3.6%)565 (3.5%)33 (12.9%)<.00112(0.5%)0(0%)9.7
      Interstitial lung diseases456 (2.8%)432 (2.7%)24 (9.4%)<.00124(0.9%)0(0%)13.8
      Preoperative laboratory data
      Serum creatinine, mmol/L98.8 ± 107.597.9 ± 104.9154.7 ± 206.4<.001138.1 ± 184.8149.7 ± 199.16
      Hemoglobin (g/dL)131.5 ± 19.5131.7 ± 19.3116.9 ± 23.0<.001118.8 ± 21.7117.2 ± 22.96.9
      Baseline systolic BP, mm Hg134.5 ± 16.2134.4 ± 16.2139.4 ± 18.3<.001140 ± 17139 ± 174.1
      Baseline diastolic BP, mm Hg76.7 ± 9.776.7 ± 9.775.9 ± 12.30.18476 ± 1076 ± 123.2
      TR Vpeak, mm Hg238(218-259)238(218-258)334(326-352)<.001248 (225-269)334 (326-352)319.7
      ePASP, [mm Hg; (IQR)]28(24-32)28(24-32)51(48-56)<.00129.6 (25.3-34.2)51.1 (48.5-56.4)331
      Low left ventricular ejection fraction947 (5.8%)873 (5.4%)74 (28.9%)<.001500(19.7%)72(28.3%)20.4
      Right ventricular enlargement363 (2.2%)329 (2.0%)34 (13.3%)<.001112(4.4%)34(13.4%)31.9
      Right ventricular front-back diameter1.9 ± 0.31.9 ± 0.32.0 ± 0.4<.0011.9 ± 0.32 ± 0.430.9
      Diastolic dysfunction, (none, I / II/ III; n)3866/12285/164/693841/12091/147/4925/194/17/20<.001940/895/70525/88/14175.6
      Mitral valve disorder303/15834/188/59302/15647/143/361/187/45/23<.001465/2001/47/2725/192/17/2047.2
      Tricuspid valve disorder8433/7589/322/408359/7424/307/3874/165/15/2<.00120/2454/50/161/186/45/2271.9
      Aortic valve disorder16379/3/2/016123/3/2/0256/0/0/0<.0011000/1460/70/1073/164/15/226.1
      Pulmonary valve disorder3866/12285/164/693841/12091/147/4925/194/17/2000
      Preoperative Medication History
      ACE inhibitors524 (3.2%)513 (3.2%)11 (4.3%)0.314122(4.8%)11(4.3%)2.3
      Angiotensin receptor blockers1805 (11.0%)1762 (10.9%)43 (16.8%)0.003444(17.5%)43(16.9%)1.5
      Beta blocker1507 (9.2%)1456 (9.0%)51 (19.9%)<.001465(18.3%)50(19.7%)3.5
      Calcium channel blocker3606 (22.0%)3524 (21.9%)82 (32.0%)<.001827(32.6%)81(31.9%)1.4
      Diuretic646 (3.9%)627 (3.9%)19 (7.4%)0.004166(6.5%)19(7.5%)3.7
      Insulin880 (5.4%)847 (5.3%)33 (12.9%)<.001316(12.4%)32(12.6%)0.5
      Sulfonylureas832 (5.1%)820 (5.1%)12 (4.7%)0.774153(6%)12(4.7%)5.8
      Metformin452 (2.8%)445 (2.8%)7 (2.7%)0.98196(3.8%)7(2.8%)5.8
      Aspirin1640 (10.0%)1594 (9.9%)46 (18.0%)<.001390(15.4%)45(17.7%)6.4
      Clopidogrel156 (1.0%)152 (0.9%)4 (1.6%)0.31146(1.8%)4(1.6%)1.8
      HMG-CoA reductase inhibitors1084 (6.6%)1063 (6.6%)21 (8.2%)0.303246(9.7%)21(8.3%)5.0
      low asterisk All values are reported as N (%) unless otherwise specified.(no/mild/moderate/severe).
      Table 2Intraoperative characteristics of all patients included in the total set and the propensity score match set
      Intraoperative dataAll (n=16,210)ePASP Total Set (mm Hg)ePASP Match set (mm Hg)
      <47 (n = 16,006)≥47 (n = 204)p Value<47 (n = 2,020)≥47 (n = 202)smd
      Surgical complexity, (low/moderate/high)3440/9977/29673384/9796/294856/181/19<.001627/1729/18456/179/196.2
      Surgery type<.0017.3
      Eye/ear/throat282 (1.7%)280 (1.7%)2 (0.8%)22(0.9%)2(0.8%)
      Integumentary531 (3.2%)521 (3.2%)10 (3.9%)90(3.5%)10(3.9%)
      Genital/urinary3396 (20.7%)3339 (20.7%)57 (22.3%)612(24.1%)56(22%)
      Musculoskeletal3321 (20.3%)3247 (20.1%)74 (28.9%)709(27.9%)74(29.1%)
      Nervous812 (5.0%)808 (5.0%)4 (1.6%)44(1.7%)4(1.6%)
      Vascular222 (1.4%)214 (1.3%)8 (3.1%)60(2.4%)8(3.1%)
      Digestive5916 (36.1%)5827 (36.1%)89 (34.8%)879(34.6%)88(34.6%)
      Respiratory1858 (11.3%)1848 (11.5%)10 (3.9%)104(4.1%)10(3.9%)
      Other46 (0.3%)44 (0.3%)2 (0.8%)20(0.8%)2(0.8%)
      Cancer surgery8337 (50.9%)8193 (50.8%)144 (56.2%)0.0841405(55.3%)142(55.9%)1.2
      Surgery time, [min; (IQR)]116(65-199)116(65-200)98(60-158)<.00195 (58-161)97 (60-158)1.9
      Anesthesia type<.0012.6
      GA ± epidural/nerve block13942 (85.1%)13764 (85.3%)178 (69.5%)1800(70.9%)177(69.7%)
      Neuraxial or nerve block2442 (14.9%)2364 (14.7%)78 (30.5%)740(29.1%)77(30.3%)
      Use of vasopressor1800 (11.0%)1764 (10.9%)36 (14.1%)0.113352(13.9%)36(14.2%)0.9
      Use of calcium channel blocker1612 (9.8%)1593 (9.9%)19 (7.4%)0.191255(10%)19(7.5%)9.1
      Use of beta blocker8120 (49.6%)8038 (49.8%)82 (32.0%)<.001994(39.1%)82(32.3%)14.3
      fluid administration, [ml kg-1; (IQR)]
      Infusion volume22(14-35)22(15-35)19(12-35)0.00820 (12.1-32.3)19.2 (11.5-34)9.5
      Crystal20(13-29)20(13-29)17(11-26)0.00218.3 (10.5-27.3)16.9 (10.9-25.7)8.4
      Colloid0(0-7)0(0-7)0(0-6)0.030 (0-6.8)0 (0-6.2)6.7
      Intraoperative blood infusion2648 (16.2%)2615 (16.2%)33 (12.9%)0.152415(16.3%)33(13%)9.5
      Intraoperative hypotension983 (6.0%)970 (6.0%)13 (5.1%)0.531112(4.4%)13(5.1%)3.3
      Mean intraoperative HR65.4 ± 10.265.4 ± 10.269.0 ± 13.0<.00168.1 ± 12.469.1 ± 137.6
      The lowest MBP (mm Hg)50.9 ± 2.650.9 ± 2.650.8 ± 1.50.36351 ± 251 ± 25.3
      The lowest pulse oximeter (%)91.1 ± 7.791.1 ± 7.789.7 ± 7.90.00591 ± 890 ± 819.3
      Mean end-tidal CO235.0 ± 10.835.0 ± 10.435.7 ± 27.50.38634 ± 4.335.8 ± 27.58.7
      For the period June 2012 to December 2018, 17,646 elective noncardiac surgeries with preoperative ePASP data were screened, and ultimately a total of 16,210 surgeries were analyzed (Figure 1). The study participants were aged 18 to 100 years old, 53.3% were women, and the mean body mass index was 24.4 ± 3.7 kg/m2, mostly American Society of Anesthesiologists Class II or III. The most common surgeries were digestive tract (36.1%) and genital/urinary surgeries (20.7%), with a median operation duration of 116 minutes (65 to 199 interquartile range). The median ePASP for the study population was 28 mm Hg (Table 1).
      Figure 1
      Figure 1Flow diagram of the study population. MACE = major adverse cardiac events.
      Of the 16,210 surgeries included in this study, 1,147 (7.0%; 95% confidence interval 6.6% to 7.4%) developed MACEs; patients with MACEs had a higher in-hospital mortality (1.2 vs 0.4%; p <0.001) and longer hospitalization (median 6 vs 5 days; p <0.001). The logistic regression showed that in addition to old age, higher rCRI, cancer surgery, intraoperative blood infusion and hypotension, abnormal heart structure (right ventricular enlargement) and functionality (low LVEF, left ventricular diastolic dysfunction) were all risk factors.
      The restricted cubic spline using the general additive models describing the ePASP to MACEs was a “J” shaped curve, with an inflection point at approximately 40 to 55 mm Hg, after which the probability of MACE leveled up (Figure 2). The multivariate analysis revealed that the best threshold of ePASP was 47 mm Hg. Multivariate analysis showed that ePASP of patients ≥47 mm Hg was independently associated with MACE development (2.03; 95% confidence interval 1.22 to 2.83; p <0.001; c-statistic = 0.894; NRI 0.592 [0.536 to 0.648]; integrated discrimination improvement 0.068 [0.059 to 0.077]) (Table 3). The relation between the ePASP and MACEs was qualitatively preserved across the subgroup analyses (Figure 3). The relation between ePASP and MACEs remained stable in the sensitivity analyses. After PS weighting, the balanced characteristics of the 2 cohorts were listed in Table 2. The recalculated logistic OR for ePASP cut-off point (ePASP <47 mm Hg as reference) was 1.62 (1.01 to 2.23); p <0.001.
      Figure 2
      Figure 2Cubic spline function curves of the unadjusted relation between ePASP and the probability of MACE. Shaded areas represent 95% CIs.
      Table 3Major adverse cardiovascular events and adjusted odds ratio in models before and after propensity score matching
      Continous ePASPePASP, IQR, mm HgePASP cut-point before PSePASP cut-point after PS
      aOR (95% CI)p ValueIQR, mm HgaOR (95% CI)p ValueaOR (95% CI)p ValueaOR (95% CI)p Value
      AllModel 11.06 (1.05∼1.07)<.001<24reference<.0015.48 (3.95∼7.01)<.0011.89 (1.33∼2.44)<.001
      24-281.42 (1.14∼1.69)
      28-321.60 (1.28∼1.92)
      >322.92 (2.39∼3.46)
      AllModel 21.05 (1.04∼1.05)<.001<24reference<.0014.08 (2.83∼5.34)<.0011.88 (1.33∼2.44)<.001
      24-281.32 (1.06∼1.58)
      28-321.34 (1.07∼1.61)
      >322.12 (1.72∼2.53)
      AllFull model1.02 (1.01∼1.03)0.001<24reference0.0102.03 (1.22∼2.83)<.0011.62 (1.01∼2.23)0.012
      24-281.17 (0.90∼1.43)
      28-321.24 (0.95∼1.53)
      >321.44 (1.11∼1.76)
      Model 1: Crude model.
      Model 2: Crude model + age, gender. Full model: Model 2 + body mass index, revised cardiac index, hypertension, right ventrical enlargement, low LVEF, diastolic dysfunction grade, cancer surgery, intraoperative blood transfusion, intraoperative hypotension. All odds ratio in stratification in this table was calculated using the full model.
      ePASP cut-point = >47 mm Hg; <47 mm Hg as reference.
      aOR = adjusted odds ratio; CI = confidence interval; ePASP = echocardiographic tricuspid valve peak regurgitation velocity; IQR = interquartile range; PS = propensity score weighting, a statistical method in observational studies to balance pretreatment characteristics of groups and to get unbiased results.
      Figure 3
      Figure 3Subgroup analyses stratified by patient and operative variables.
      In this study of 16,210 patients who underwent elective noncardiac surgery, we found that an ePASP of ≥47 mm Hg of postcapillary PH was independently associated with MACE. The NRI analysis found that ePASP of ≥47 mm Hg improved the risk stratification for MACE compared with the assessment limited to the CRI and other perioperative variables.
      More cardiologists and anesthesiologists are encountering patients with PH who underwent noncardiac surgical procedures. PH is regarded as a particularly independent risk factor with a significant burden of cardiovascular complications, regardless of the type of anesthesia administered, and despite advances in perioperative monitoring and treatment.
      • Hosseinian L.
      Pulmonary hypertension and noncardiac surgery: implications for the anesthesiologist.
      ,
      • Aguirre MA
      • Lynch I
      • Hardman B.
      Perioperative management of pulmonary hypertension and right ventricular failure during noncardiac surgery.
      During a surgical procedure, potential complications related to the consequences of right ventricular failure, arrhythmias, postoperative hypoxemia, and myocardial ischemia.
      • McGlothlin D
      • Ivascu N
      • Heerdt PM.
      Anesthesia and pulmonary hypertension.
      A common mode of death appears to be minor stimulation resulting in tachycardia or increased pulmonary vascular resistance, followed by refractory hypotension, hypoxia, and ultimately cardiovascular collapse.
      Increased perioperative morbidity and mortality of adult patients with PH who underwent noncardiac surgery have been described previously in small series and retrospective analyses of surgical databases.
      • Price LC
      • Montani D
      • Jaïs X
      • Dick JR
      • Simonneau G
      • Sitbon O
      • Mercier FJ
      • Humbert M.
      Noncardiothoracic nonobstetric surgery in mild-to-moderate pulmonary hypertension.
      ,
      • Kaw R
      • Pasupuleti V
      • Deshpande A
      • Hamieh T
      • Walker E
      • Minai OA.
      Pulmonary hypertension: an important predictor of outcomes in patients who underwent non-cardiac surgery.
      ,
      • Smilowitz NR
      • Armanious A
      • Bangalore S
      • Ramakrishna H
      • Berger JS.
      Cardiovascular outcomes of patients with pulmonary hypertension who underwent noncardiac surgery.
      ,
      • Memtsoudis SG
      • Ma Y
      • Chiu YL
      • Walz JM
      • Voswinckel R
      • Mazumdar M.
      Perioperative mortality in patients with pulmonary hypertension who underwent major joint replacement.
      • Lai HC
      • Lai HC
      • Wang KY
      • Lee WL
      • Ting CT
      • Liu TJ.
      Severe pulmonary hypertension complicates postoperative outcome of non-cardiac surgery.
      • Ramakrishna G
      • Sprung J
      • Ravi BS
      • Chandrasekaran K
      • McGoon MD.
      Impact of pulmonary hypertension on the outcomes of noncardiac surgery: predictors of perioperative morbidity and mortality.
      Each of the studies previously mentioned varied in the diagnostic methods and definitions of PH used. As we know, the golden standard for a definitive diagnosis of PH is a right heart catheterization, which is invasive. A mean pulmonary artery pressure ≥25 mm Hg at rest or ≥30 mm Hg with exercise is considered diagnostic. However, most patients would receive only 1 echo as an initial and final test, and the diagnosis of PH by echocardiogram is a reality in daily practice, especially for patients who underwent noncardiac surgery. ePASP is a well-validated measure and a reliable parameter in comparison with those obtained by cardiac catheterization.
      • Cordina RL
      • Playford D
      • Lang I
      • Celermajer DS.
      State-of-the-art review: echocardiography in pulmonary hypertension.
      The 2009 American College of Cardiology Foundation/American Heart Association expert consensus document on PH recommends further evaluation of patients with dyspnea with ePASP >40 mm Hg.
      • McLaughlin VV
      • Archer SL
      • Badesch DB
      • Barst RJ
      • Farber HW
      • Lindner JR
      • Mathier MA
      • McGoon MD
      • Park MH
      • Rosenson RS
      • Rubin LJ
      • Tapson VF
      • Varga J
      American College of Cardiology Foundation Task Force on Expert Consensus Documents, American Heart Association, American College of Chest Physicians, American Thoracic Society, Inc, Pulmonary Hypertension Association
      ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on expert consensus documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association.
      The 2009 ESC guidelines suggest a high probability of PH based on tricuspid regurgitation peak velocity >3.4 m/s or ePASP >50 mm Hg at rest (Class I, Level B).
      • Galiè N
      • Hoeper MM
      • Humbert M
      • Torbicki A
      • Vachiery JL
      • Barbera JA
      • Beghetti M
      • Corris P
      • Gaine S
      • Gibbs JS
      • Gomez-Sanchez MA
      • Jondeau G
      • Klepetko W
      • Opitz C
      • Peacock A
      • Rubin L
      • Zellweger M
      • Simonneau G
      • Committee for Practice Guidelines ESC
      Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT).
      In a study of patients with severe PH who underwent noncardiac surgery, the authors recruited patients with ePASP >70 mm Hg. Confusingly, there were different cut-off values of ePASP in various studies. This study made efforts to find an appropriate threshold of ePASP for patients who underwent noncardiac surgery, hoping to be a good alarm for surgeons, cardiologists, and anesthesiologists.
      To the best of our knowledge, this is one of the few studies focusing on postcapillary PH for noncardiac surgeries based on analyses of real-world clinical data. We presented 2 identical cut-off points, 1 was 47 mm Hg using a minimal p value approach for the association with MACEs, the other was 47 mm Hg using a maximal adjusted OR approach to best discriminate the magnitude of risk.
      Our research has some advantages. We found that after stratifying our analyses by the various patient and perioperative variables, our results remained reliable. This suggests that the relation between ePASP and MACEs does not change significantly depending on patient characteristics and time frame. We also proved the robustness of our conclusion by multiple sensitivity analyses.
      Although we tried to implement the best research methods and improve the quality of the database, various shortcomings and errors were still inevitable. These include: echocardiogram is a routine test before surgery for moderate and high-risk patients in our hospital; however, there may be a selection bias induced by only including individuals with preoperative echo data available. Linear dimensional parameters were used for right ventricle enlargement identification, which was less valuable than the area or 3-diemnsional method. As ePASP values may be impacted both by cardiac output as well as increased pulmonary vascular resistance, a small group of patients with high PASP based on high cardiac output could not be distinguished. Although the authors tried to exclude the patients with disorders possibly accounting for precapillary PH, there still might be very few unrecognized precapillary PH patients. The results of this study only draw associations and cannot imply causality. Thus, we cannot suggest that management of preoperative blood pressure to achieve an ePASP below 47 mm Hg will reduce the risk of MACEs. Further randomized trials are needed. The single-center retrospective design might limit the generalizability of the present study, and external validation is warranted. Postoperative laboratory tests and exams were not performed in every patient but were based on clinical observations when symptoms and signs were suspected, resulting in an underestimation of the rate of the primary outcome.
      In conclusion, the incidence of postoperative MACEs was 7.0% in elective noncardiac surgery. Preoperative echocardiographic ePASP ≥47 mm Hg was significantly associated with increased risk of postoperative MACE in postcapillary pulmonary hypertensive patients. Special attention should be placed on these patients.

      Disclosures

      The authors have no conflicts of interest to declare.

      Appendix. Supplementary materials

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