Rheumatic mitral valve repair or replacement in the valve-in-valve era.

OBJECTIVE: For degenerative mitral disease, repair is superior to replacement; however, the best operative strategy for rheumatic mitral disease remains unclear. We evaluated the association between decision-making in choosing repair versus replacement and outcomes across 2 decades of rheumatic mitral surgery. METHODS: Patients undergoing isolated, first-time rheumatic mitral surgery were identified. Era 1 (1997-2008) and Era 2 (2009-2018) were distinguished by intraoperative assessment of anterior leaflet mobility/calcification (Era 2) in deciding between mitral repair versus replacement. Primary outcome was a composite of death, reoperation, and severe valve dysfunction. RESULTS: Among 180 patients, age was 59 ± 14 years, and ejection fraction was 58% ± 10%. A higher proportion in Era 1 (n = 56) compared with Era 2 (n = 124) had preoperative atrial fibrillation (68% vs 46%; P = .006); the groups were otherwise similar. Primary indication was mitral stenosis in 69% (124 out of 180; pure = 35, mixed = 89) and did not differ by era (P = .67). During Era 1, 70% (39 out of 56) underwent repair, compared with 33% (41 out of 124) during Era 2 (P < .001). Freedom from death, reoperation, or severe valve dysfunction at 5 years was higher in Era 2 (72% ± 9%) than Era 1 (54% ± 13%; P = .04). Five-year survival was higher in Era 2 than Era 1, but did not differ between repair versus replacement. Five-year cumulative incidence of reoperation with death as a competing risk did not differ by era, but was higher after repair than replacement. CONCLUSIONS: Careful assessment of anterior leaflet mobility/calcification to determine mitral repair or replacement was associated with improved outcomes. This decision-making strategy may alter the threshold for rheumatic mitral replacement in the current valve-in-valve era.

The relationship between plasma proadrenomedullin level and severity of the disease in patients with isolated rheumatic mitral stenosis.

OBJECTIVE: In this study, we aimed to determine the plasma proadrenomedullin (ProADM) levels in patients with rheumatic mitral stenosis (MS), to evaluate the relationship between ProADM levels and the echocardiographic parameters that represent the severity of stenosis and symptoms, and to compare the ProADM and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, which is a well-known marker for rheumatic MS. METHODS: Our study included 53 consecutive patients with isolated rheumatic MS and 45 volunteers with similar age and gender features. Patients with MS were divided into two groups based on the presence of an indication for intervention. Detailed echocardiographic examinations were performed on all participants, and blood samples were collected to detect the NT-proBNP and ProADM levels. RESULTS: NT-proBNP and ProADM levels were significantly higher in the rheumatic MS group compared with the control group. In rheumatic MS groups, patients with an indication for intervention had higher levels of NT-proBNP and ProADM compared with patients without an indication for intervention. Moreover, NT-proBNP and ProADM levels were found to be significantly correlated with echocardiographic parameters, which revealed the severity of stenosis in various degrees. Both parameters increased as the New York Heart Association (NYHA) class increased, and this increase had a statistical significance. Additionally, the cut-off values of both parameters (NT-proBNP: 119.9 pg/mL, ProADM: 6.15 nmol/L) could detect patients with an indication for intervention with high sensitivity and specificity rates. NT-proBNP was found to be slightly more effective in this regard. CONCLUSION: The increased NT-proBNP and ProADM levels in patients with isolated rheumatic MS can help clinicians in distinguishing patients with an indication for intervention by providing additional information to echocardiography.

Cardiac Complications in Pregnant Women With Isolated Mitral Stenosis and Their Association With Echocardiographic Changes During Pregnancy.

In women with mitral stenosis (MS), mitral valve gradients and right ventricular systolic pressure (RVSP) can increase in response to the physiologic stress of pregnancy. The prognostic significance of these echocardiographic changes has not been well studied. Pregnancy outcomes and serial echocardiograms were collected in women with MS prospectively recruited as part of a larger study on pregnancy outcomes. Third trimester echocardiograms were compared with baseline echocardiograms. Changes in mitral valve area (MVA), transmitral mean gradient (MG), and RVSP during pregnancy and their relationship to adverse cardiac events (CE) were examined. Fifty-six pregnancies in 47 women with MS were included. The MVA did not change during pregnancy (1.6 ± 0.6 cm2 at baseline vs 1.7 ± 0.6 cm2 in the third trimester, p = 0.46). There was an increase in the MG (8 ± 3 vs 11 ± 6 mm Hg, p <0.001) and the RVSP (39 ± 14 vs 47 ± 20 mm Hg, p <0.001) during the third trimester. Adverse CE occurred in 45% (25/56) of pregnancies. CE were associated with baseline MG>10 mm Hg, baseline RVSP >40 mm Hg, third-trimester MG>10 mm Hg, and RVSP >40 mm Hg. Women with mitral valve MG ≤10 mm Hg who had a normal RVSP at baseline and in the third trimester were at lowest risk for CE (11%) with a negative predictive value of 89%. In conclusion, baseline echocardiographic assessment of MS severity as well as changing echocardiographic parameters during pregnancy can help identify women at risk for cardiac complications during pregnancy.

Mid-term (up to 12 years) clinical and echocardiographic outcomes of percutaneous transvenous mitral commissurotomy in patients with rheumatic mitral stenosis.

BACKGROUND: Rheumatic heart disease (RHD) is still a concerning issue in developing countries. Among delayed RHD presentations, rheumatic mitral valve stenosis (MS) remains a prevalent finding. Percutaneous transvenous mitral commissurotomy (PTMC) is the intervention of choice for severe mitral stenosis (MS). We aimed to assess the mid-term outcome of PTMC in patients with immediate success. METHODS: In this retrospective cohort study, out of 220 patients who had undergone successful PTMC between 2006 and 2018, the clinical course of 186 patients could be successfully followed. Cardiac-related death, undergoing a second PTMC or mitral valve replacement (MVR) were considered adverse cardiac events for the purpose of this study. In order to find significant factors related to adverse cardiac outcomes, peri-procedural data for the studied patients were collected.The patients were also contacted to find out their current clinical status and whether they had continued secondary antibiotic prophylaxis regimen or not. Those who had not suffered from the adverse cardiac events were additionally asked to undergo echocardiographic imaging, in order to assess the prevalence of mitral valve restenosis, defined as mitral valve area (MVA) < 1.5 cm2 and loss of ≥ 50% of initial area gain. RESULTS: During the mean follow-up time of 5.69 ± 3.24 years, 31 patients (16.6% of patients) had suffered from adverse cardiac events. Atrial fibrillation rhythm (p = 0.003, HR = 3.659), Wilkins echocardiographic score > 8 (p = 0.028, HR = 2.320) and higher pre-procedural systolic pulmonary arterial pressure (p = 0.021, HR = 1.031) were three independent predictors of adverse events and immediate post-PTMC mitral valve area (IMVA) ≥ 2 cm2 (p < 0.001, HR = 0.06) was the significant predictor of event-free outcome. Additionally, follow-up echocardiographic imaging detected mitral restenosis in 44 patients (23.6% of all patients). The only statistically significant protective factor against restenosis was again IMVA ≥ 2 cm2 (p = 0.001, OR = 0.240). CONCLUSION: The mid-term results of PTMC are multifactorial and may be influenced by heterogeneous peri-procedural determinants. IMVA had a great impact on the long-term success of this procedure. Continuing secondary antibiotic prophylaxis was not a protective factor against adverse cardiac events in this study. (clinicaltrial.gov registration: NCT04112108).

Mitral valve diseases: Pathophysiology and interventions.

Valvular heart disease is common and increasingly prevalent among the elderly. The end result of valvular pathologies is cardiac failure and can lead to sudden death; thus, diagnosis and interventions are very important in the early stages of these diseases. The usual treatment methods of mitral regurgitation include percutaneous mitral valve repair, mitral valve replacement and minimally invasive surgery, whereas the treatment methods of mitral stenosis include percutaneous transluminal mitral commissurotomy and mitral commissurotomy as well as open surgical repair. Nonetheless, ongoing clinical trials are a clear indicator that the management of valve diseases is ever evolving. The focus of this paper is on the various pathologies of the mitral valve, their etiology and clinical management, offering a comprehensive view of mitral valve diseases.

Multimodal cardiovascular model for hemodynamic analysis: Simulation study on mitral valve disorders.

Valvular heart diseases are a prevalent cause of cardiovascular morbidity and mortality worldwide, affecting a wide spectrum of the population. In-silico modeling of the cardiovascular system has recently gained recognition as a useful tool in cardiovascular research and clinical applications. Here, we present an in-silico cardiac computational model to analyze the effect and severity of valvular disease on general hemodynamic parameters. We propose a multimodal and multiscale cardiovascular model to simulate and understand the progression of valvular disease associated with the mitral valve. The developed model integrates cardiac electrophysiology with hemodynamic modeling, thus giving a broader and holistic understanding of the effect of disease progression on various parameters like ejection fraction, cardiac output, blood pressure, etc., to assess the severity of mitral valve disorders, naming Mitral Stenosis and Mitral Regurgitation. The model mimics an adult cardiovascular system, comprising a four-chambered heart with systemic, pulmonic circulation. The simulation of the model output comprises regulated pressure, volume, and flow for each heart chamber, valve dynamics, and Photoplethysmogram signal for normal physiological as well as pathological conditions due to mitral valve disorders. The generated physiological parameters are in agreement with published data. Additionally, we have related the simulated left atrium and ventricle dimensions, with the enlargement and hypertrophy in the cardiac chambers of patients with mitral valve disorders, using their Electrocardiogram available in Physionet PTBI dataset. The model also helps to create 'what if' scenarios and relevant analysis to study the effect in different hemodynamic parameters for stress or exercise like conditions.

Energy loss associated with in-vitro modeling of mitral annular calcification.

INTRODUCTION: Study aims were to compare hemodynamics and viscous energy dissipation (VED) in 3D printed mitral valves-one replicating a normal valve and the other a valve with severe mitral annular calcification (MAC). Patients with severe MAC develop transmitral gradients, without the commissural fusion typifying rheumatic mitral stenosis (MS), and may have symptoms similar to classical MS. A proposed mechanism relates to VED due to disturbed blood flow through the diseased valve into the ventricle. METHODS: A silicone model of a normal mitral valve (MV) was created using a transesophageal echocardiography dataset. 3D printed calcium phantoms were incorporated into a second valve model to replicate severe MAC. The synthetic MVs were tested in a left heart duplicator under rest and exercise conditions. Fine particles were suspended in a water/glycerol blood analogue for particle image velocimetry calculation of VED. RESULTS: Catheter mean transmitral gradients were slightly higher in the MAC valve compared to the normal MV, both at rest (3.2 vs. 1.3 mm Hg) and with exercise (5.9 vs. 5.0 mm Hg); Doppler gradients were 2.7 vs. 2.1 mm Hg at rest and 9.9 vs 8.2 mm Hg with exercise. VED was similar between the two valves at rest. During exercise, VED increased to a greater extent for the MAC valve (240%) versus the normal valve (127%). CONCLUSION: MAC MS is associated with slightly increased transmitral gradients but markedly increased VED during exercise. These energy losses may contribute to the exercise intolerance and exertional dyspnea present in MAC patients.

Lessons from reoperations for mitral stenosis after mitral valve repair.

BACKGROUND: The durability of mitral valve repair (MVr) is usually defined by the absence of recurrent significant mitral regurgitation. Postrepair mitral stenosis (MS) is a less frequent and less studied mode of failure of MVr. We analyzed our experience in patients who underwent reoperation for postrepair MS to characterize mechanisms resulting in MS and to summarize reoperative surgical strategies and mid-term outcomes. METHODS: Using a prospective database, we retrospectively analyzed data on 35 consecutive patients who underwent reoperation for symptomatic moderate to severe MS between January 1, 2011, and February 1, 2020. RESULTS: The mean patient age was 61.4 ± 11.4 years, and 69% were female. The median annuloplasty ring size used at the initial repair was 28 mm (interquartile range, 26-30 mm). Additional repair techniques at the initial operation included leaflet resection in 12 patients (34%) and commissuroplasty or edge-to-edge repair in 6 patients (18%). At reoperation, the most common mechanism of MS was pannus ingrowth in 20 patients (57%), leaflet calcification in 12 (34%), commissural fusion in 5 (14%), and tunnel effect (functional MS) in 3 (9%). Twenty-two patients (63%) underwent valve replacement, and 13 (37%) underwent valve re-repair. In patients who underwent re-repair, annuloplasty revision was performed in all patients, with 6 patients (46%) converted from complete ring to band, 4 (11%) converted from ring to pericardial annuloplasty, 2 (6%) converted to no annuloplasty, and 1 (8%) with annuloplasty ring upsizing. There were no in-hospital or 1-year mortalities. Survival at the 5-year follow-up was 93.9%. CONCLUSIONS: MS causing late failure of MVr is frequently associated with smaller ring sizes and inflammatory or calcific changes in the valve. Highly selected patients may be good candidates for mitral valve re-repair.

TAVI in Patients with Mitral Annular Calcification and/or Mitral Stenosis.

BACKGROUND: We herein aimed for analysis of influence of mitral annular calcification (MAC) and mitral stenosis (MS) on outcomes in transcatheter aortic valve implantation (TAVI). METHODS: Between 11/2009 and 06/2017, 1,058 patients underwent TAVI in the presence of concomitant MAC or MS at our center. Subgroups were built and multivariate logistic regression, COX regression, Kaplan-Meier survival analyses, and receiver operating characteristics method were performed. RESULTS: Thirty-day mortality was 7.5% (79/1,058) with highest mortality in patients severe MS (MAC: 3.4% vs. mild MS: 5.9% vs. moderate MS: 15.0% vs. severe MS: 72.7%; p < 0.001). Moderate-to-severe MS (odds ratio [OR]: 7.75, confidence interval [CI]: 3.94-16.26, p < 0.001), impaired left ventricular ejection fraction (OR: 1.38, CI: 1.10-1.72, p < 0.01), and coronary artery disease (OR: 1.36, CI: 1.11-1.67, p < 0.01) were predictive of 30-day survival. Left ventricular systolic/end-diastolic pressure drop of <59.5 mm Hg / <19.5 mm Hg was associated with increased mortality. CONCLUSIONS: TAVI in the presence of MAC and mild MS is associated with acceptable acute outcomes but should be considered high-risk procedures in patients with moderate and especially those with severe MS. Our results suggest adverse hemodynamics after TAVI with concomitant MS, which may be caused by underfilling of the left ventricle leading to low-cardiac output.

Inhaled versus intravenous milrinone in mitral stenosis with pulmonary hypertension.

OBJECTIVE: To evaluate and compare the hemodynamic effects of intraoperative intravenous milrinone versus inhalational milrinone at two timepoints in patients with severe pulmonary hypertension undergoing mitral valve surgery. METHODS: A prospective observational study was performed in 100 patients with severe rheumatic mitral stenosis (with/without regurgitation) and right ventricular systolic pressure > 50 mm Hg. They were divided into two groups based on the strategy used to reduce pulmonary hypertension. Fifty patients had inhalational milrinone after sternotomy until initiation of cardiopulmonary bypass and after release of the aortic crossclamp until weaning off cardiopulmonary bypass. The other 50 patients received an intravenous loading dose of milrinone 50 µg·kg-1 over 10 min on release of the aortic crossclamp. Both groups received intravenous milrinone 0.5 µg·kg-1 during weaning from cardiopulmonary bypass. Hemodynamic data were evaluated at the 3 timepoints. RESULTS: Pulmonary artery pressures, central venous pressure, and pulmonary capillary wedge pressure decreased significantly in the inhalational milrinone group compared to the intravenous milrinone group. Systemic vascular resistance index and cardiac index were significantly higher and pulmonary vascular resistance index was significantly lower in the inhalational milrinone group. The mean arterial pressure-to-mean pulmonary artery pressure ratio was significantly lower in the intravenous milrinone group. Tricuspid annular plane systolic excursion and right ventricular fractional area change were increased significantly in the inhalational milrinone group. CONCLUSION: Intraoperative inhalational milrinone before and after cardiopulmonary bypass is safe, easy to administer, and results in significant improvements in right ventricular hemodynamics, right ventricular function, and systemic hemodynamics.

Long-term outcomes of rheumatic mitral valve repair: Is it worthwhile to do it?

AIM: This retrospective study was undertaken to evaluate the long-term outcomes of mitral valve repair in rheumatic patients. METHODS: From 2003 to 2019, 151 patients (mean age 26.5 ± 14.9 years; 68.9% female) underwent mitral valve repair. Fifty-three (35.1%) had atrial fibrillation, and 79 (52.3%) were in New York Heart Association class III/IV. Pure mitral regurgitation was present in 109 (72.2%) patients, pure stenosis in 9 (6%), and mixed regurgitation and stenosis in 33. RESULTS: Three (2%) patients died postoperatively and 4 (2.6%) were lost during follow-up. Mean follow-up was 90.5 ± 55.6 months. There were 22 (14.8%) late deaths. Actuarial survival at 5, 10, and 15 years was 90.7% ± 2.5%, 83.5% ± 3.6%, and 76.5 ± 6.1%, respectively. Twelve (8.5%) patients underwent reoperation. Freedom from reoperation at 5, 10, and 15 years was 96.1% ± 1.7%, 89.8% ± 3.2%, and 82.3% ± 6.1%, respectively. Forty-two (29.2%) patients developed recurrent mitral regurgitation. Freedom from recurrence of mitral regurgitation at 5, 10, and 15 years was 70.9% ± 4.3%, 56% ± 5.9%, and 53.3% ± 6.4%, respectively. Eighty-one (56.6%) patients were and free from all events during follow-up. Freedom from all events at 5, 10, and 15 years was 64.8% ± 4.1%, 48.6% ± 5.3%, and 43.7% ± 5.8%, respectively. CONCLUSIONS: Although rheumatic mitral valve repair is associated with late recurrence of mitral regurgitation, it has benefits in selected patients, especially children and young patients who want to avoid the lifelong risks of anticoagulation. Long-term follow-up is essential in these patients.

Three-dimensional transesophageal echocardiography measurement of mitral valve area in patients with rheumatic mitral stenosis: multiplanar reconstruction or 3D direct planimetry?

3D direct planimetry is increasingly used in clinical practice as a rapid way to measure the mitral valve area (MVA) in patients with rheumatic mitral stenosis (MS) who underwent three-dimensional transesophageal echocardiography (3D-TEE). However, data on its accuracy and reliability are scarce. This study aimed to compare the MVA measurements obtained by 3D direct planimetry to the conventional technique multiplanar reconstruction (MPR) in MS patients using 3D-TEE. We retrospectively included 49 patients with rheumatic MS undergoing clinically-indicated 3D-TEE in the study. We determined the 3D direct planimetry measurements of MVA from the left atria aspect (MVALA) and the left ventricle aspect (MVALV), and compared those with the MPR method (MVAMPR). We also assessed the major and minor diameters of the mitral valve orifice using MPR and 3D direct planimetry. We found an excellent agreement between the MVA measurements obtained by the MPR method and 3D direct planimetry (MVALA and MVALV) [intraclass correlation coefficients (ICC) = 0.951 and 0.950, respectively]. However, the MVAMPR measurements were significantly larger than the MVALA and MVALV (p < 0.001; mean difference: 0.12 ± 0.15 cm2 and 0.11 ± 0.16 cm2, respectively).The inter-observer and intra-observer variability ICC were 0.875 and 0.856 for MVAMPR, 0.982 and 0.984 for MVALA, and 0.988 and 0.986 for MVALV, respectively. The major diameter measured by MPR (1.90 ± 0.42 cm) was significantly larger than that obtained by 3D direct planimetry (1.72 ± 0.35 cm for the LA aspect, p < 0.001; 1.73 ± 0.36 cm for the LV aspect, p < 0.001). The minor diameter measured by MPR (0.96 ± 0.25 cm) did not differ from that derived by 3D direct planimetry (0.94 ± 0.25 cm for the LA aspect, p = 0.07; 0.95 ± 0.27 cm for the LV aspect, p = 0.32). 3D direct planimetry provides highly reproducible measurements of MVA and yields data in excellent agreement with those obtained by the MPR method. The discrepancy between the two techniques may be due to differences in major diameter measurements of the mitral valve orifice.

Long-term Clinical Impacts of Functional Mitral Stenosis After Mitral Valve Repair.

BACKGROUND: The relationship between functional mitral stenosis (MS) after mitral valve (MV) repair and long-term clinical outcomes is not fully understood. Therefore, we reviewed an institutional series to identify the determinants of functional MS and its effect on long-term clinical outcomes after MV repair for degenerative mitral regurgitation. METHODS: Between January 1990 and December 2015, 792 patients who underwent MV repair for degenerative mitral regurgitation were retrospectively enrolled and divided into 2 groups: functional MS (n = 192) (≥5 mm Hg mean diastolic pressure gradient across the MV) and nonfunctional MS (n = 600) (<5 mm Hg mean diastolic pressure gradient). Mean follow-up was 11.6 ± 5.8 years. RESULTS: After propensity-score matching, patients' characteristics were comparable between groups (n = 192/group). At 20 years, the functional MS group had significantly lower rates of freedom from new-onset atrial fibrillation (73.0% ± 5.6% versus 93.2% ± 2.3%; P = .003), overall survival (72.1% ± 4.6% versus 85.6% ± 4.3%; P = .010), and freedom from MV reoperation (82.8% ± 4.1% versus 92.5% ± 4.2%; P = .019) than the nonfunctional group. The functional MS group also had a significantly greater postoperative left atrial volume index and tricuspid regurgitation grade. A small left ventricular end-diastolic dimension (hazard ratio = 0.975; 95% confidence interval, 0.955-0.996; P = .022) and annuloplasty ring (hazard ratio = 0.757; 95% confidence interval, 0.685-0.837; P < .001) were independent risk factors for functional MS. CONCLUSIONS: A small left ventricle and annuloplasty ring increased the risk for functional MS after MV repair and was associated with progressive left atrial enlargement and tricuspid regurgitation exacerbation. As a result, functional MS increased the risk for new-onset atrial fibrillation, MV reoperation, and decreased long-term survival.

Left atrial structural and functional remodeling following balloon mitral valvuloplasty.

Mitral stenosis (MS) is associated with left atrial (LA) functional and morphological changes as a result of chronic increase in LA pressure. Relieving the mitral obstruction via balloon mitral valvuloplasty (BMV) might be associated with LA structural and functional remodeling. To study alterations of LA volume and functions 1 year following successful BMV in patients with isolated rheumatic severe mitral stenosis. Thirty patients (median age 33 years, 22 women) with severe rheumatic MS were included in the study. Using biplane method, trans-thoracic 2D echocardiography was used to estimate LA volume indexed to body surface area (BSA). Maximal, minimal and pre-A left atrial volumes were measured and indexed to BSA. LA volumetric functions were then assessed and the measurements were repeated 6 months and 1 year after successful valvuloplasty. At baseline, median mitral valve area (MVA) was 0.9 (0.6-1.3) cm2 measured by planimetry with a mean pressure gradient of 12.5 (8-24) mmHg. Following BMV, a significant regression of left atrial volume index was noticed at 6 months compared to baseline (51 vs. 60 ml/m2, p = 0.001) with a further decrease at 1 year (48 vs. 51 ml/m2, p = 0.03). At 6 months, volumetric assessment of left atrial functions showed a significant improvement in LA total emptying fraction (42% vs 30%, p = 0.001) as well as in LA passive emptying fraction (26% vs 14%, p = 0.033) and LA active emptying fraction (20% vs. 18%, p = 0.016). All these indices showed further improvement at 1 year [47% (P = 0.02), 29% (p = 0.03) and 31% (p = 0.001) respectively]. In patients with isolated rheumatic MS, mitral valvuloplasty was associated with a significant decline of LA volume accompanied by a significant improvement of its volumetric functions.

Comparison of Clinical Characteristics, Natural History and Predictors of Disease Progression in Patients With Degenerative Mitral Stenosis Versus Rheumatic Mitral Stenosis.

Mitral annular calcification (MAC) is a common echocardiographic finding and an increasingly recognized cause of degenerative mitral stenosis (DMS). However, little is known about the clinical characteristics and disease progression in DMS, particularly in comparison with rheumatic mitral stenosis (RMS). We retrospectively reviewed 203 consecutive patients with mitral stenosis (113 with DMS and 90 with RMS) who underwent echocardiography at our institution between January 2014 and December 2017. We compared the clinical characteristics and disease progression between the 2 groups. In addition, we analyzed the predictors of disease progression (defined as annual progression rate of a mean gradient >0 mm Hg/year) among patients with DMS. Patients with DMS were significantly older and had higher prevalence of atherosclerotic comorbidities than those with RMS. During the median follow-up period of 2.2 years, the annual progression rates were comparable (0.8 ± 0.8 mm Hg/year in DMS vs 1.0 ± 1.2 mm Hg/year in RMS; p = 0.32) and were highly variable (0.0 to 3.5 mm Hg/year in DMS and 0.0 to 5.5 mm Hg/year in RMS) within both groups among disease progression. In DMS patients, atherosclerotic comorbidities and lower initial mean gradient were significantly associated with disease progression even after adjustment by age and sex. There was no significant difference in the disease progression according to the circumferential MAC severity determined by echocardiography among DMS. In conclusion, DMS disease progression was slow but highly variable, similar to that of RMS. In patients with DMS, the baseline MAC severity did not correlate with disease progression, suggesting the importance of follow-up echocardiography regardless of the MAC severity.