The characteristics of mitral regurgitation: Data from patients admitted following acute myocardial infarction

Data were collected on patients admitted to the Queen Elizabeth Hospital Birmingham with type-1 myocardial infarction during 2016 and 2017 inclusively, who were treated by percutaneous intervention and had pre-discharge transthoracic echocardiography. The data were obtained from prospectively maintained hospital databases and records. Echocardiography was performed and reported contemporaneously by accredited echocardiographers. The purpose was to understand the prevalence and characteristics of mitral regurgitation (MR) after acute MI, including patients with ST-elevation (STEMI) and non-ST elevation MI (NSTEMI). MR was observed in 294/1000 patients with the following relative severities: mild = 76%, moderate = 21%, severe = 3% [1]. MR was graded by multiparametric quantification including proximal isolvelocity surface area (PISA), vena contracta (VC), effective regurgitant orifice area (EROA) and regurgitant volume (RVol). Amongst all patients with MR (n=294), PISA was performed in 89/294 (30%), VC 75/294 (26%), EROA in 53/294 (18%) and RVol in 26/294 (9%). Amongst patients with moderate or severe MR (n=70), PISA was performed in 57/70 (81%), VC in 55/70 (79%), EROA in 46/70 (66%) and RVol in 25/70 (36%). Characteristics of MR following acute MI were also assessed including frequency of reported leaflet thickness (259/294 = 88%) and mitral annular calcification (102/294 = 35%). Furthermore, the effect of MI on pre-existing MR was investigated and patients with pre-existing MR who continue to have MR after acute MI were found to have progression of MR by one grade in approximately 25% of cases. Finally, using Cox proportional hazards univariate analysis, significant factors associated with mortality in patients with MR post-MI include age (HR 1.065; 95% CI 1.035-1.096; p<0.001), creatinine clearance, (HR 0.981; 95% CI 0.971-0.991; p<0.001), left ventricular ejection fraction (LVEF) (HR 0.966; 95% CI 0.948-0.984; p<0.001), indexed left ventricular end-diastolic volume (LVEDVi) (HR 1.016; 95% CI 1.003-1.029; p=0.018), indexed left ventricular end-systolic volume (LVESVi) (HR 1.021; 95% CI 1.008-1.034; p=0.001), indexed left atrial volume (HR 1.026; 95% CI 1.012-1.039; p<0.001), and those with intermediate likelihood of pulmonary hypertension (pHTN) (HR 2.223; 95% CI 1.126-4.390; p=0.021); or high likelihood of pHTN (HR 5.626; 95% CI 2.189-14.461; p<0.001). Age and LVEF were found to be independent predictors of mortality on multivariate analysis [1].


Value of the Data
• These data are important because they characterise mitral regurgitation observed after acute MI. In particular, these data show that a significant proportion of patients have posteriorly eccentric jets which may explain why the use of multiparametric quantification in real world analysis of patients with MR is not ubiquitous. • This data is useful to cardiologists, echocardiographers and those shaping international guidelines, particularly as echocardiography is currently recommended as the gold standard method of assessing mitral regurgitation after acute MI. • Currently, international guidelines recommend multiparametric assessment of MR using echocardiography. These data show that despite best effort s, the recommended parameters are not universally measured in the real world and thus there may be a greater role for other imaging modalities e.g. cardiovascular magnetic resonance imaging. • These data also show that the prevalence and relative severities of MR in a combined population of Non-ST elevation and ST-elevation MI (STEMI) patients is similar to those found in a large prospective study of STEMI patients only. • Patients with pre-existing MR who continue to have MR after acute MI develop worsening of MR by one grade in approximately 25% of cases.

Experimental Design, Materials and Methods
A prospectively maintained National Institute for Cardiovascular Outcomes Research (NICOR) database maintains a record of all patients admitted with acute myocardial infarction, including type of infarction and procedure performed. This database was searched for patients fulfilling the inclusion criteria and found that a total of 1210 patients were admitted with a type-1 myocardial infarction (MI) between 2016 and 2017. Six researchers analysed 10 0 0 consecutive records of patients who were treated by percutaneous coronary intervention (PCI). These records were cross referenced with the Queen Elizabeth Hospital Birmingham (QEHB) hospital records to identify those who had pre-discharge echocardiography reports. Duplicate records (patients attending for staged PCI or further MI within the timeframe were excluded). Hospital records of patients included in the study were further interrogated to identify: • Outcomes: Mortality data was obtained from the QEHB hospital records which are linked to centralised data from the Office of National Statistics. Date of death and time from MI to death was recorded.

Measurement of echocardiographic parameters
All included patients had echocardiography performed prospectively pre-discharge by technicians accredited by the British Society of Echocardiography using CX-50 machines (Philips medical systems, Amsterdam, Netherlands) and acquiring the minimum dataset [3] .
• MR severity assessment: MR was categorized as none/trivial, mild, moderate, or severe according to established criteria [4] . Where possible, multiparametric assessment of MR was performed, as recommended [4] , which includes the assessment of the following parameters: • Proximal isovelocity surface area (PISA) -measured (cm) with reduced aliasing velocity and increased penetration depth. • Vena contracta(VC) width -measured (cm) in the parasternal long axis view in a plane parallel to the mitral annulus. • Effective regurgitant orifice area (EROA) -derived by measurement of PISA using the flow convergence method, the aliasing velocity and the velocity-time-integral of the MR jet using continuous wave doppler in the apical 4-chamber view. The EROA was then calculated using the formula below: Whereby V Alias represents the alising velocity at the radial distance (cm/s), V max represents the peak velocity of the mitral regurgitant jet (cm/s) and r represents the PISA radius (cm). • Regurgitant volume (RVol) -calculated by multiplying the EROA by the velocity-time integral (cm) dervived from a continuous wave Doppler profile of the MR jet in the apical 4-chamber view.
• Chamber assessment: Left atrial (LA) and LV volumes were calculated using images acquired in the apical four and apical two chamber views. Images were acquired in end-systole (LA volume and LV end-systolic volume) and end-diastole (LV end-diastolic volume). The Simpson's biplane method was used to calculate volumes and values were indexed to the Mosteller calculation of body surface area [5] . LA dilatation was defined as a left atrial volume > 34ml/m 2 after indexing to body surface area (LAVi) [6] . Left ventricular ejection fraction (LVEF) was calculated by the difference between LV end-diastolic and end-systolic volume, divided by the LV end-diastolic volume. • Mitral valve characteristics: Colour flow doppler echocardiographic images of the regurgitant jet in the parasternal long-axis, apical 4-,3-and 2-chamber views were analysed subjectively to obtain data regarding regurgitant jet direction. Information pertaining to the presence of mitral annular calcification and leaflet thickness were obtained from the echocardiographic reports.

Interventional treatment methods
All study patients underwent PCI and were treated according to European guidelines on the management of AMI [ 7 , 8 ]. This includes medical therapy with loading and maintenance doses of aspirin and P2Y12 receptor blocker, beta blockers, statins and angiotensin converting enzyme inhibitors [ 7 , 8 ]. Coronary lesions were graded by visual assessment of angiographic stenosis by the consultant interventional cardiologist treating the patient. Severe disease was defined as > 50% stenosis of the left main stem and > 75% stenosis of all other coronary vessels.

Statistical methods
Normal and non-normally distributed continuous variables are expressed as mean + standard deviation or median with interquartile range and compared using a Student's two-tailed T test or Mann-Whitney U test respectively. Categorical variables were compared using a chi squared test. A P value of < 0.05 was considered significant. Factors influencing survival were assessed by a univariate Cox regression model and analysed using SPSS software version 23.0 (SPSS, Inc, Chicago, IL, USA).

Ethics Statement
This study was a registered retrospective observational audit performed in compliance with local clinical and research governance principles.