European Journal of Cardiovascular Medicine

Rheumatic fever (RF) is an inflammatory disease affecting heart, joints, skin, and brain. It develops typically two to four weeks succeding a streptococcal upper respiratory infection.   Clinically it is presence of fever with painful affection of more than one joints, muscle movements which are involuntary and a non-itchy rash - erythema marginatum. Heart is involved in about fifty percent of cases. Rheumatic heart disease (RHD) which is damage to heart valves, happens after multiple attacks but can sometimes occur after one. The damaged valves lead to atrial fibrillation and infection of the valves and heart failure. ^[1]

Rheumatic heart disease is a systemic immune process that is a sequelae to beta-haemolytic streptococcal infection of the pharynx and is most common in developing countries. The incidence of RHD is maximum in Oceania, Central sub-Saharan Africa, and South Asia. It is estimated 15.6 to 19.6 million people are living with RHD ^{[2, 3],} with almost 80 % of these residing in low and middle-income countries. The estimated population prevalence in these countries is 2.5 to 3.2 cases per 1000. ^{[4, 5]}

On an average 1 to 5 % of people with RHD die every year accounting for 2,33,000 to 2,94, 000 RHD-related deaths per year ^{[6, 7]}, almost all (95 %) of deaths occurring in low- and middle income countries. RHD is now almost rare in high income countries, except affecting population of migrant and old age residents. Still RHD is a vital cause of preventable heart disease in indigenous populations. ^[8]

Surgery is the most important management strategy for severe forms. Factors important for outcomes of valve surgery for RHD patients are age, pre-operative clinical status as per New York Heart Association (NYHA) functional class assessment, atrial fibrillation (AF) if preexisting, left ventricular functional status and type of underlying valve lesion . ^[8]    

Outcomes vary as per treatment choice, prosthetic valve type and timing of referral, type of valve lesions, single/ multiple valve affection, pre-operative right and left ventricular function. Knowledge regarding how these factors interact is limited and also on how they might be anticipated to influence outcomes and treatment recommendations.

We therefore aimed to identify factors associated with early left ventricular dysfunction after mitral and/or tricuspid valve surgery in RHD by analyzing data.

The present prospective observation study included all the patients with rheumatic heart disease having Mitral valve replacement with or without Tricuspid repair or replacement at UN Mehta Institute of Cardiology and Research Center, Ahmedabad from March 2021 to February 2023. The study was approved by institutional ethics committee (UNMICRC/CVTS/2021/03). The informed consent was taken from each participants in the study.

Demographic data, risk factors, Echocardiographic parameters, clinical data, pre & post-operative data were taken from all participants in the study. The study assessed Post-surgery LV function once patients were off ionotropic support.

Patients with isolated mitral and/or tricuspid valve lesion due to RHD, MVR and/or TV REPAIR / TVR for rheumatic valvular disease with Pre-operative normal LV function (EF 55% or more) were included in the study. Patient with Redo MVR, MVR for Non-Rheumatic valvular disease, MVR associated with surgically non-significant Aortic and/or pulmonary valve lesion, MVR associated with Surgery like AVR, CABG (TV Repair/ Replacement included), Pre-operative LV dysfunction (EF less than 55%) were excluded from the study.

Statistical Analysis:

Data were analysed as range; mean ± standard deviation (±SD), frequencies (number of cases), and relative frequencies (percentages) as appropriate. Categorical data variables were expressed as number percentage and compared using chi square analysis. Continuous data variables were represented as mean ± SD and compared using independent sample t-test. A probability value (p-value) less than 0.05 was considered statistically significant. All statistical analysis was carried out using the SPSS (Statistical Package for the Social Science) program vs 20.

250 patients with rheumatic valvular disease with pre-operative normal biventricular function undergoing mitral valve and/or tricuspid valve surgery were included in this study from March 2021 to February 2023.

Table 1 shows the baseline characteristics of the study population. Majority of patients (92%) were from age group <60 years. Elderly patients (more than 60years of age) were only 8%. Mean age in this study is 44.41 ± 11.57 years. 65.2% patients were female that is almost 2/3 of total no. of patients. 1/3 of patients that is 34.8% were male. Male: female ratio is 1.1.87

The most common presentation was dyspnoea on exertion. 42.4% patients had atrial fibrillation. Among them approx 1/3rd patients had atrial fibrillation with fast ventricular rate and 2/3rd had controlled ventricular rate. 35.6% patients had history of palpitation. All patients with palpitation had atrial fibrillation. 25.2% patients had history of chest pain. 10.4% patients had previous history of stroke. All the patients with history of stroke had clots in left atrium or in appendage. And all those patients had atrial fibrillation.

Table 1: Baseline Charecteristics

Table 2: Pre-Op Echo Evaluation

Table 3: Post Operative Echo Evaluation

Table 4: Surgical Parametrs

Table 5: Post Operative Outcome

Table 6: Lv Dysfunction Outcome

Table 7: Predictor That Associated For Lv Dysfunction

Figure 1: Forest plot of predictors associated with postop early LV dysfunction

And 2/3 patients (68.8%) out of 250 had NYHA Class III symptoms. 14% of patients had symptoms belong to NYHA Class II. NYHA Class IV symptoms seen in 17.2% of patients. Most common presentation at time of surgery was NYHA Class III.

Table 2 shows that in pre-operative 2D Echo evaluation 85.2% patients had severe mitral stenosis and 26.4% patients had severe mitral regurgitation. 34.4% patients had moderate MR, among them half of patients has associated severe MS.

42% patients had moderate tricuspid regurgitation. 33.6% of patients had severe and 24.4% patients had mild TR. 3.6% patients had tricuspid stenosis.

33.6% patients had severe PAH and 35.6% patients had moderate PAH. Only 2% patients had moderate RV dysfunction, rest all had mild or no RV dysfunction. 19.6% patients had LA/LAA clots, 2/3rd of patients among them had history of stroke. Average LA size was 60.12 ± 12.38mm. Average LV diastolic diameter was 48.63± 8.92mm. Average LV systolic diameter was 34.84 ± 8.20mm.

In Table 3 Post-operative 26.4% of patients had developed early left ventricular dysfunction. 13.6% patients had mild LV dysfunction. 9.6% patients had moderate LV dysfunction and 3.2% patients had severe LV dysfunction. 73.6% patients had normal LV function. 53.6% patients had mild PAH, 38.4% had moderate and 8% patients had severe PAH.

57.2% patients had mild RV dysfunction and 7.2% patients had moderate RV dysfunction, rest of patients had normal RV function. 54.4% patients had post-operative mild TR. 36% patients had moderate and 9.6% had severe TR. Out of 24 patients with post-operative severe TR, 14 patients had severe TR during pre-operative and 10 patients had moderate TR during pre-operative.

83.2% patients underwent MVR, 14.8% underwent MVR + TV REPAIR and 2% patients underwent MVR + TVR. In all patient partial posterior mitral leaflet was preserved.

27mm (34 patients) and 29mm (30.4% patients) sized valve commonly used for replacement. 25mm size valve used in 14.4% patients and 31mm size valve used in also 16% patients. In 6.4% patients tissue valve was implanted in mitral position and in 93.6 % patient mechanical valve was implanted. In 2% patient tricuspid valve was replaced and in 14.8% patients tricuspid valve repair (De Vega or ring annuloplasty) was done. Average CPB time was 53.79 ± 17.42min. Average aortic cross clamp time was 38.05 ± 13.91min as shown in Table 4.

Table 5 shows 8.8% patients had post-operative stroke. All of had LA/LAA clot and all had atrial fibrillation, few of them had pre-operative history of CVA. 3.6% patients went into sepsis post-surgery. 2.8% patients had development of AKI, all had sepsis induced AKI and all recovered fully at time of discharge. 2.8% patients were re-explored in ICU for high drain output. 2% patients were known case of CKD. No in hospital mortality.

Average time for ventilation was 13.42 ± 4.12 hours. There was no re-intubation. Average time for ICU stays was 6.49 ± 4.01 days. Average time for hospitalisation was 12.01 ± 61 4.57 days. Prolong hospitalisation required for the patients who had post-operative stroke and AKI.

LV dimension, severity of PAH, severity of MR have found statistically significant in post-operative patients with lv dysfunction compared to post-operative normal lv function shown in table 6. Other pre-operative factors like RV function, LA size, AF, aortic cross clamp time and CPB time had not significant association with post-operative lv dysfunction in my study. Overall ventilation hours, ICU and hospital stays were prolonged in patients with post-operative left ventricle dysfunction.

Table 7 shows the univariate logistic regression analysis to find out the risk factor that are significantly associated with LV Dysfunction. The current study results show that Left Ventricular End Diastolic Diameter, left ventricular End Systolic Diameter, Severe pulmonary artery hypertension and severity of mitral regurgitation were significantly associated for postoperative LV dysfunction.

In developing countries, first presentation may be time with poor prognostic echocardiographic markers such as an EF < 60% or an ESD > 45 mm. ^{[9, 10, 11]}  Suri et al. have concluded that a preserved LV function postoperatively can be predicted by pre-operative EF > 65% or LVESD < 36 mm. An EF < 60% indicating contractile dysfunction in MR, is associated mostly with poor survival post-surgery.

Tribouilloy et al. in their work have demonstrated that LVESD > 40 mm can independently predict higher mortality in medically managed patients and also those who underwent mitral valve surgery. Paired analysis of 83 patients showed that majority had EF > 55% but only 60% (n = 43) showed improvement in postoperative EF to pre-operative values (EF > 55%) at six months. This suggests some degree of LV impairment as reflected by the median postoperative EF of 42%, which reflects true EF on removal of low-pressure run-off into LA in case of MR after MVR .^[12]

In Enriquez-Sarano’s work, EF declined significantly from 58 ± 13% prior to surgery to 50 ± 14% following MVR. LV dysfunction gets masked by ventricular loading conditions in severe MR which are, increased preload and reduced afterload because of run-off into the low-pressure LA during systole. ^{[13, 14]} These loading conditions change immediately following mitral valve surgical intervention as the leak gets corrected and LV gets synchronised to systemic pressure which unmasks true state of LV contractility. Ischemic cardioplegic arrest also adds to transient fall in early postoperative EF.

Prolonged cardioplegic arrest leads to myocardial ischaemia which gets reflected by prolonged CPB duration and postoperative LV dysfunction and contributes to persistent LV dysfunction. Lastly, Essop stressed on the importance of preserving chords and valve apparatus at surgery to avoid any discontinuity of chordal–mitral apparatus which will eventually lead to progressive dilatation and LV dysfunction after surgery. Chordal preservation is now the standard practice during MVR. ^{[15, 16]}

Heart failure due to annular dilatation and chordal elongation causing valve prolapse and severe MR during active carditis is the predominant mode of death in rheumatic carditis. Early surgery is lifesaving and causes slow ventricular improvement in majority. ^{[17, 18]}

Wisenbaugh et al. have documented that in developing world first time presentation may be EF < 60% or ESD > 45 mm. ^[13] Hence they suffer poorer outcomes following MVR and will benefit from mitral valve repair if possible, even though repair in RHD is technically more demanding than with degenerative MR.

Delayed surgery is a concerning issue as clinicians may not be working as per established guidelines for making timely surgical referrals. Mostly moderate to severe MR are assessed by junior clinicians and as these patients are not that symptomatic their echocardiographic work up gets deferred in a busy clinic assuming such patients are doing well and are given follow up appointments .^[19]

Pathophysiologically, MR becomes symptomatic in later course due to excellent compliance properties of the LA allowing it to accommodate larger volumes of blood before back pressure changes are noticed in pulmonary circulation. As regurgitation increases, contractile dysfunction also increases preceding the onset of dyspnoeic symptoms. Hence, timing of surgery in severe MR is very vital for preservation of myocardial function.

Wisenbaugh et al. concluded pre-operative ESD as only independent predictor of postoperative mortality. ^[20] ESD < 40 mm in preoperative evaluation predicted favourable outcomes, risk of severe heart failure and/or death sharply rose when it was 51 mm. Hence, recommended optimal time for surgery is at LVESD between 40 to 50 mm, MV repair being the preferred surgery at LVESD of 50 mm. ^[13]

Saleem W et al., proved that mean age of patients was 37 ± 10 years, LVEDD: 51.1 ± 9.1mm, PASP: 44 ± 11mmHg, LVESD: 34.7 ± 8.4 mm and EF of 55 ± 9%. Patients having Left ventricular end-systolic dimension (LVESD) > 38 mm had postoperative left ventricular dysfunction after MVR than patients with pre-operative LVESD < 38mm (p= 0.003) . ^[21]

Witkowski et al. believed that the LVEF of patients with mitral regurgitation is overestimated due to the increased ventricular preload (end‐diastolic volume), and the removed excess preload leads to a reduction in the LVEF and lowered end‐diastolic volume after mitral valve operations. ^[22]

Quintana et al showed that: Postoperative outcomes were comparable between patients; however, those with an EF of 60% in only one third of patients with post repair EF 49% and left ventricular end-systolic diameter>36 mm were independently associated with a 4.4- and 6.5-fold increased risk of developing a postoperative EF. ^[23]

Lastly, after the exhaustive discussion of exhaustive works by the above mentioned esteemed authors we can say that our results are well in synchrony with the already available literature. LV End Systolic Diameter/ End Diastolic diameter and Severe MR on pre-op echocardiography stand as the predictive risk factors for early left ventricular dysfunction after mitral valve replacement for rheumatic valvular disease with most significant association (p-value) mentioned in Table - 7. Moderate MR on pre-op echo doesn’t appear to have significance as a predictive risk factor. Severe PAH (pulmonary artery hypertension) also has significance as a predictive risk factor.

Majority of patients who are symptomatic were receiving heart-failure treatment, including ACE inhibitors. Symptomatic therapy believing that LV function and cavity size are stable in these subjects is a misinterpretation of the evidence-based guidelines for surgery, which recommends surgery in symptomatic severe MR regardless of chamber dimensions. ^{[24, 25]} Severe MR should be operated early because of difficulty in diagnosing underlying LV dysfunction and also because of poor long-term outcomes even in good EF patients.

Pre-operative EDD and ESD and pre-operative severity of mitral regurgitation and severity of PAH were the predictors of postoperative LV dysfunction. Figure - 1 shows the strength of association of these factors. Chronic MR therefore requires careful clinical surveillance and prompt referral for regular echocardiographic assessment to enable early detection of LV dilatation and timely surgery in order to preserve ventricular function. We acknowledge the importance of echocardiography for preoperative LV function quantification and need to be confirmed by further studies conducted in asymptomatic patients.

Financial support and sponsorship

Nil

Conflicts of interest

There are no conflicts of interest.

Ethical approval

Prior ethics committee approval was taken by approaching the Institutional Review Board. The approval number being - UNMICRC/CVTS/2021/03

Author’s contributions

• Dr. Sandeep Lukhi: Concept, Design, Acquisition, Draft
• Shobhit Mathur: Design, Acquisition, Draft
• Chirag Doshi: Literature review
• Mrs Himani Pandya: Acquisition, Draft, Statistics

Figure legends:

Figure 1: Forest plot of predictors associated with postop early LV dysfunction

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