|Year : 2018 | Volume
| Issue : 12 | Page : 963-971
Impact of preoperative pulmonary arterial hypertension on early and late outcomes in patients undergoing valve surgery for rheumatic heart disease
Deepak Prakash Borde1, Balaji Asegaonkar1, Sujit Khade1, Manish Puranik2, Antony George3, Shreedhar Joshi4
1 Department of Cardiac Anesthesia, Ozone Anesthesia Group, Aurangabad, Maharashtra, India
2 Department of Cardiac Surgery, Seth Nandlal Dhoot Hospital, Aurangabad, Maharashtra, India
3 Department of Cardiac Anesthesia, Lissie Hospital, Kochi, Kerala, India
4 Department of Cardiac Anesthesia, Narayana Institute of Cardiac Sciences, Bengaluru, Karnataka, India
|Date of Web Publication||10-Dec-2018|
Dr. Deepak Prakash Borde
Department of Cardiac Anesthesia, Ozone Anesthesia Group, Seth Nandlal Dhoot Hospital, Aurangabad - 431 001, Maharashtra
Source of Support: None, Conflict of Interest: None
Background and Aims: There is conflicting evidence on adverse effect of Pulmonary Arterial Hypertension (PAH) on outcomes after cardiac surgery for rheumatic heart disease (RHD). The authors studied Indian patients with RHD and preoperative PAH, who undergo cardiac surgery with a hypothesis that they have poor short and long-term outcomes. Methods: This was a retrospective observational study of 407 patients. The patients were divided in three groups based on PAH estimated on echocardiograph as; no or mild PAH (pulmonary artery systolic pressure (PASP) <30 mm of Hg); moderate PAH (PASP 31-55 mm of Hg) and severe PAH (PASP >55 mm of Hg). The primary endpoint was in-hospital mortality and major morbidities; while secondary endpoint was long-term survival. Results: In-hospital mortality was 24 (5.9%); and was not different in patients with severe, (9.1%), moderate (4.5%) or mild PAH (2.8%) (P = 0.09). Patients with severe PAH had higher incidence of prolonged ventilation (P = 0.007). Factors independently associated with mortality were; >2-packed cell transfusion, prolonged ventilation and acute kidney injury but not moderate and severe PAH. Patients with mitral stenosis (MS) and severe PAH had significantly higher mortality as compared to no or mild PAH (P = 0.03) on long-term follow-up [81.37% (mean duration 19.40 ± 14.10 months)], mortality was 8% and not statistically different (P = 0.25) across PAH categories. Conclusion: Moderate and severe PAH does not affect short and long term outcomes of patients undergoing valve surgery for RHD. Patients with MS with severe PAH had higher mortality compared to those with no PAH.
Keywords: Indian, pulmonary hypertension, rheumatic heart disease
|How to cite this article:|
Borde DP, Asegaonkar B, Khade S, Puranik M, George A, Joshi S. Impact of preoperative pulmonary arterial hypertension on early and late outcomes in patients undergoing valve surgery for rheumatic heart disease. Indian J Anaesth 2018;62:963-71
|How to cite this URL:|
Borde DP, Asegaonkar B, Khade S, Puranik M, George A, Joshi S. Impact of preoperative pulmonary arterial hypertension on early and late outcomes in patients undergoing valve surgery for rheumatic heart disease. Indian J Anaesth [serial online] 2018 [cited 2021 Jan 24];62:963-71. Available from: https://www.ijaweb.org/text.asp?2018/62/12/963/247116
| Introduction|| |
Rheumatic heart disease (RHD) is a major burden in developing countries where it causes most of the cardiovascular morbidity and mortality in young people, leading to about 250,000 deaths/year worldwide. Pulmonary arterial hypertension (PAH) is often found in symptomatic patients with left-sided valvular lesions. One of the most commonly used scoring system for mortality prediction after cardiac surgery, European System for Cardiac Operative Risk Evaluation II (EuroSCORE II), identifies moderate [pulmonary artery systolic pressure (PASP) 31–55 mmHg] and severe [PASP more than 55 mmHg] PAH as risk factors for mortality.
Recent studies have indicated improved outcomes in patients with severe PAH, with reduced perioperative mortality rates compared to older studies. Evidence on this topic appears to be controversial, with some studies claiming PAH as independent risk factor, whereas others conclude that mortality is unaffected by severe PAH. Indian studies on this important topic are very limited.,
The authors report their experience of impact of preoperative PAH on short- and long-term outcomes of patients undergoing mitral ± aortic valve surgery for RHD.
| Methods|| |
This was a retrospective observational data analysis. The Institutional Review Board approved the study with a waiver of consent. Consecutive adult patients, who underwent cardiac surgery at our institute for RHD from January 2010 to August 2016, were considered eligible for inclusion in the study. Exclusion criteria were isolated aortic valve replacement as they have entirely different pathophysiology for PAH, non-availability of preoperative PAH data; and incomplete records.
The primary end points were in-hospital mortality defined as all-cause mortality in the same admission of cardiac surgery and major morbidities like re-exploration for bleeding, prolonged ventilator support (for more than 24 h), cardiac surgery-related acute kidney injury (CSAKI) (defined as more than 50% increase or doubling of preoperative creatinine during 7 days or requirement of renal replacement therapy) and neurologic deficit of more than 24 h. The secondary end point was long-term survival.
Demographic and procedural data were abstracted from medical records. It included age, sex and pre-existing comorbidities, including, anaemia as per world health oragnisation (WHO) definition, New York Heart Association (NYHA) functional classification, atrial fibrillation (AF), chronic obstructive pulmonary disease (COPD) that was defined as per X-ray and clinical findings, diabetes mellitus, renal disease (abnormal creatinine level >1.5 mg/dL and/or reduced creatinine clearance <50 ml/min), previous cerebrovascular accident (CVA) as defined as neuro-deficit of >24 h, peripheral vascular disease (PVD) and previous cardiac surgery. The primary predominant lesion and associated tricuspid regurgitation (TR) with its severity were also noted.
Preoperative echocardiography imaging was performed according to guidelines of the American Society of Echocardiography. PASP was estimated by Doppler echocardiography by calculating the right ventricular to right atrial pressure gradient during systole, approximated by the modified Bernoulli equation as 4v2, where v is the velocity of the tricuspid regurgitation jet in m/s. The patients were divided in three groups based on PASP which was estimated on latest echocardiograph before surgery as (1) no or mild PAH (PASP less than 30 mmHg), (2) moderate PAH (PASP 31–55 mmHg) and (3) severe PAH (PASP more than 55 mmHg). These cut-offs were based on definitions used in EuroSCORE II system. None of the patients underwent right heart catheterisation (RHC) for estimation of PA pressure or pulmonary vascular resistance (PVR) measurements.
Intraoperative monitoring in addition to standard American Society of Anesthesiology Guidelines consisted of arterial blood pressure monitoring by femoral arterial catheter, arterial blood gas monitoring, central venous pressure monitoring and temperature monitoring at two sites, nasopharynx and skin. Induction of general anaesthesia was done with midazolam, fentanyl and propofol. Vecuronium was used as a muscle relaxant. After induction, intravenous tranexamic acid, 10-mg/kg bolus, was given to all patients. Titrated doses of sevoflurane or isoflurane and titrated boluses of fentanyl and midazolam as per haemodynamic parameters were used for maintenance of anaesthesia. All patients had surgery through median sternotomy. Cardiopulmonary bypass (CPB) was established with aortic and bicaval cannulation after adequate heparinisation (activated clotting time ACT >400 s). Moderate hypothermia (32–34°C) was maintained during conduct of CPB. The extracorporeal circuit consisted of membrane oxygenator, roller pump, tubing and crystalloid prime solution. Blood cardioplegia was used to achieve cardiac arrest and to provide myocardial protection during aortic clamping. At the end of CPB, protamine reversal was given to achieve normal ACT. All patients were transferred to the intensive care unit. Patients were extubated as per standardised institutional protocols. Operative details noted were CPB duration, aortic cross-clamping duration (ACC), concomitant procedure and selection of prosthetic valves.
Data on long-term follow-up were abstracted from hospital record; if the follow-up record was not available, the patients were contacted telephonically. Information on mortality, readmission for cardiac causes (prosthetic-valve thrombosis, congestive heart failure, arrhythmias resulting in significant haemodynamic disturbances etc.) and non-cardiac causes (anticoagulation related bleeding, neurological complications, respiratory causes etc.) was collected.
Patients were classified in three groups according to the severity of PAH according to EuroSCORE II system. Continuous variables were described as mean with standard deviation and were compared between PAH groups by using analysis of variance. Categorical data were presented as percentage and were compared using Chi-square test. Ordinal data were described as median (interquartile range, range). Univariate and multiple regression analysis were used to identify factors associated with mortality. Crude survival curves were estimated using the nonparametric Kaplan–Meier method. The log-rank test was used to compare survival among groups. All P values <0.05 were considered as significant. The Statistical Package for Social Sciences (SPSS) version 16.0.0 for Windows (SPSS Inc., Chicago, IL, USA) was used for analysis.
| Results|| |
A total of 482 patients underwent surgery during the study period. Patients excluded as per exclusion criteria were isolated aortic valve replacement (42; 8.7%), non-availability of preoperative PAH data (23; 4.8%) and incomplete records (20; 4.2%). The final analysis included 407 patients. A total of 278 patients underwent isolated mitral valve replacement (MVR), 50 patients underwent MVR + tricuspid valve repair (TV rep), 79 patients underwent double valve replacement (DVR) and 7 patients underwent DVR + TV rep.
Baseline clinical characteristics of patients are summarised in [Table 1]. Prevalence of preoperative moderate and severe PAH was 32.7% (133/407) and 40.5% (165/407), respectively, in the cohort. The groups had similar demographics and comorbidities except that there were more patients with severe PAH in NYHA III and IV class, more patients with severe PAH had severe TR and fewer patients in severe PAH category underwent concomitant aortic valve surgery. EuroSCORE II was significantly higher in moderate and severe PAH groups. As shown in [Table 1], significantly higher number of patients underwent TV repair procedure in severe PAH category, although overall CPB and ACC times were similar in all categories.
Post-operative outcomes are summarised in [Table 2]. Overall incidence of in-hospital mortality was 5.9% (n = 24), although the incidence of mortality was higher in severe PAH patients (9.1%; n = 15) as compared to patients with moderate PAH (4.5%; n = 6) and no or mild PAH (2.8%; n = 3), but it was not statistically significant (P = 0.09). As far as post-operative morbidities are concerned, patients with severe PAH had higher incidence of prolonged ventilation (P = 0.007) but incidence of other morbidities such as re-exploration for bleeding (P = 0.97), CSAKI (P = 0.53) and neurologic deficit (P = 0.9) was similar in all categories of PAH. Results of univariate and multiple regression analysis for mortality are shown in [Table 3]. Factors independently associated with mortality were more than two-packed cell transfusion, prolonged ventilation and CSAKI but not moderate (P = 0.37) and severe PAH (P = 0.43). When we compared mortality rates as per predominant lesion [mitral stenosis (MS) compared with mitral regurgitation (MR)] and PAH category, we found that patients with MS and severe PAH had significantly higher mortality as compared to no or mild PAH (P = 0.03); mortality rates were similar in all categories of PAH in patients with MR as predominant lesion (P = 0.98) [Table 4].
|Table 3: Univariate and multiple logistic regression analysis for in-hospital mortality|
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The long-term follow-up was available in 81.37% patients. Mean long-term follow-up was 19.40 ± 14.10 months. The total patient-years of follow-up were 350 patient-years. The readmission rates for both cardiac and non-cardiac reasons were similar across all PAH categories (P = 0.88). The overall mortality of the entire cohort over the follow-up period was 8% and not statistically different (P = 0.25) in patients with no or mild PAH (8%), moderate PAH (11%) and severe PAH (6%), as shown in [Table 5]. Also, long-term survival was not significantly different in the moderate and severe PAH groups compared with the normal and mild PAH groups using the Kaplan–Meier curve analysis (Chi-square value 2.47; P = 0.29, log-rank test) [Figure 1].
| Discussion|| |
The main findings of this study are that patients with moderate or severe PAH undergoing cardiac surgery for RHD have similar short and long-term mortality and morbidity compared to no or mild PAH. Patients with severe PAH experience higher incidence of prolonged post-operative ventilation. Patients with MS as predominant lesion and with severe PAH have significantly higher mortality as compared to patients with no or mild PAH (P = 0.03); mortality rates were similar in all categories of PAH in patients with MR as predominant lesion (P = 0.98).
The RHD is major burden on health care in developing countries affecting mainly young population. The development of PAH frequently complicates left-sided valve disease and is usually most pronounced in those with long-standing rheumatic mitral valve involvement. PAH reflects not only passively transmitted backpressure from left atrial (LA) hypertension but also an active increase in PVR caused by a combination of pulmonary vasoconstriction and obliterative changes in the pulmonary vascular bed. The pressure in a relatively thin-walled chamber like LA depends on several factors such as its stiffness, mechanical effects of its rhythmic contraction and relaxation, diastolic period, the quantity of blood entering and exiting it, and the net atrio-ventricular compliance which include compliance of LA and left ventricle (LV), and compliance of the pulmonary venous system. Schwammenthal et al. in a study of 20 patients reported a significant increase in PA pressure on exercise in a subgroup of patients with low atrio-ventricular compliance. Apparently, in patients of MS, a wide spectrum of atrio-ventricular compliance exists – patients with low compliance and patients with normal compliance. Patients with low compliance develop significant PAH, severe increase in LA pressure and symptoms of MS on exercise or in situations of increased cardiac output, whereas patients with normal compliance remain asymptomatic in situations of increased cardiac output as the increased RV stroke volume is accommodated in the compliant pulmonary venous bed. This probably explains that even though all patients had severe mitral valve disease, only 40% patients in our cohort developed severe PAH.
PAH has been defined as an increase in mean pulmonary arterial pressure more than 25 mmHg at rest as assessed by RHC. Echocardiography is a convenient screening tool for PAH. EuroSCORE II identifies moderate (PASP 31–55 mmHg) and severe (PASP more than 55 mmHg) PAH as risk factors for mortality. In a recent meta-analysis of 32 studies, 2604 Doppler–RHC pairings were studied. The authors concluded that correlation between echo-based and RHC assessment of PAH is high particularly in patients with left-sided heart pathology and elevated PA pressures. Echocardiography is also non-invasive, convenient and practical approach. Hence, the authors used values based on latest preoperative echocardiography with EuroSCORE II cut-offs. Like present study, previously published studies also have utilised echo-based measurements for estimation of PAH.,
Large body of literature is available on impact of PAH on outcomes in valve surgeries. These studies have studied various patient populations and used different methods for assessment of PAH with variable cut-offs and variable follow-up,,,,,,,,,,,,,,, [Table 6]. Present study assessed impact of PAH as measured by Doppler echocardiography on patients undergoing cardiac surgery exclusively for RHD as per EuroSCORE II cut-offs. The incidence of severe PAH in our study was 40%, which is in accordance to previous studies. Overall incidence of in-hospital mortality of 5.9% and 9.1% in moderate and severe PAH, respectively, are comparable to the recently published literature of cardiac surgery in RHD patients.,, The mortality in severe PAH was not statistically different than in moderate and no or mild PAH patients. Factors significantly associated with mortality were more than two-packed cell transfusion, prolonged ventilation and CSAKI. Majority of previous studies in various patient populations have concluded that mitral valve surgery can be performed with acceptable perioperative mortality in patients with severe PAH.,,,,, Our findings are similar to previous studies. In contrast, a recent large study of 1639 RHD patients undergoing cardiac surgery demonstrated that PASP >70 mmHg was an independent risk factor for in-hospital mortality (OR 2.93, 95% CI 1.61–5.32, P < 0.001), and patients with PASP >52 mmHg experienced higher 1-year mortality. Another interesting finding in our study was that when we separated patients based on predominant lesion as MS or MR, patients with MS and severe PAH had significantly higher mortality as compared to no or mild PAH in contrast to MR in which mortality was similar in all categories of PAH.
|Table 6: Studies published on impact of PAH on outcomes in valve surgeries|
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The improved survival rates in severe PAH patients can be multi-factorial. There is better understanding of pathophysiological changes due to PAH resulting in improved anaesthetic, surgical and CPB techniques and materials. Special anaesthetic considerations apply to patients with PAH in order to avert the risk of right ventricular failure. It consists of balanced anaesthetic technique, avoidance of hypoxia, hyper-carbia, avoidance of use of nitrous oxide, judicious use of vasodilator and inotrope therapy and use of post-operative ventilator support. There is realisation that PAH decreases significantly immediately after repair or replacement of diseased mitral valve., One of the important findings of our study was that patients with severe PAH experienced higher rates of post-operative mechanical ventilation. The exact reasons for prolong ventilation were not available for detailed analysis. This appears to be more likely an association rather than causative effect.
There are many reports that severe PAH returns to normal after MVR.,, This can be one of the important reasons for similar long-term outcomes in patients with severe and mild PAH. The long-term survival was comparable across all categories of PAH. This finding is in contrast to some of the previously published reports claiming reduced survival in severe PAH patients., Also, we assessed patients for incidence of readmissions for both cardiac (prosthetic valve thrombosis, congestive heart failure, arrhythmias resulting in significant haemodynamic disturbances etc.) and non-cardiac (anticoagulation related bleeding, neurological complications, respiratory causes etc.) reasons and found no significant difference in rates of readmissions.
There are various important limitations to the present study, most important being retrospective nature and single centre study. The study duration was long which might likely change the management practices related to PAH. We evaluated PA pressure based on Doppler echocardiography and not RHC, which is gold standard for its assessment. Certain patients who did not follow with our hospital were followed up by telephonic call, which is prone for some errors.
| Conclusion|| |
Moderate and severe PAH does not affect short and long-term outcomes of patients undergoing mitral ± aortic valve surgery for RHD. Patients with MS with severe PAH had higher mortality compared to those with no PAH, whereas mortality in patients with MR as primary pathology was not different across PAH categories.
The authors would like to thank Dr. Murali Chakravarthy, Fortis Hospital, Bengaluru, for his expert inputs for this manuscript.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]