Shifts in Clinical Characteristics, Treatment, and Outcome for Rheumatic Mitral Stenosis: Insights From a 20-Year Multicentre Registry Study in Korea.

BACKGROUND: The rapid economic development of South Korea provides a unique model to study changes in the clinical characteristics, treatment approaches, and clinical outcomes of patients with rheumatic mitral stenosis (MS) relative to socioeconomic growth. METHODS: From the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, 2,337 patients diagnosed with moderate or severe rheumatic MS between January 2001 and December 2020 were analyzed. Patients were grouped into consecutive 5-year intervals based on their year of diagnosis. Clinical characteristics, echocardiographic data, and clinical outcomes were assessed. RESULTS: Over 20 years, the severity of mitral stenosis increased from 79.1% to 90.2%; similarly, the average age at diagnosis increased from 54.3 to 63.0 years (all P < 0.001). Comorbidities such as hypertension and atrial fibrillation increased (6.3% to 29.5% and 41.4% to 46.9%, respectively; all P for trend < 0.05). The rate of mitral intervention within five years after diagnosis increased from 31.2% to 47.4% (P for trend < 0.001). However, clinical outcomes of rheumatic mitral stenosis deteriorated over time in the composite outcomes (log-rank test, P < 0.001). Conversely, the incidence of stroke remained stable (60.6-73.7%; P < 0.001), which might be attributed to the increased use of anticoagulation therapy. CONCLUSION: This study observed an increase in patient age, comorbidities, and valve disease severity as the country transitioned from a developing to developed status. Despite a rise in mitral valve interventions, clinical outcomes deteriorated over 20 years, highlighting the need for modified treatment approaches to improve patient outcomes.

Transcatheter Therapy for Mitral Valve Stenosis.

Mitral valve stenosis remains highly prevalent among the US population although with dramatically shifting demographics. The significance of rheumatic mitral disease in developing nations persists, despite improvements in preventative measures and early detection, and its presence in developed countries is still evident as observed through international migration. In addition, the substantial growth in the aging population with a heightened occurrence of concurrent cardiovascular risk factors is leading to an increased prevalence of chronic calcific degeneration and degeneration of previously repaired or replaced valves. This article aims to review various transcatheter therapies in the treatment of mitral valve stenosis.

Impact of mitral stenosis on early and late outcomes of transcatheter aortic valve replacement for aortic stenosis: a single-center analysis.

OBJECTIVES: To assess the impact of concomitant mitral stenosis (MS) on early and late outcomes of transcatheter aortic valve replacement (TAVR) for aortic stenosis. METHODS: This study involved 952 patients undergoing TAVR for severe tricuspid aortic stenosis. The patients were classified into 3 groups: without MS, with progressive MS, and severe MS (mitral valve area ≤ 1.5 cm2). Clinical outcomes between these groups were compared. RESULTS: The median age of the overall cohort was 82 years, and patients in the progressive (n = 49) and severe (n = 24) MS groups were more likely to be female than those in the no-MS group (n = 879). Periprocedural mortality rate was lowest in the no-MS group (1.8%) compared with the progressive (4.1%) and severe (4.2%) MS groups, which were not significantly different (P = .20). During 5 years of follow-up (median: 27, range: 0-72 months), there was no significant difference in all-cause mortality (log-rank P = .99), a composite of all-cause mortality or rehospitalization for heart failure (log-rank P = .84), or cardiovascular death (log-rank P = .57) between groups. Although crude analysis showed a significant difference in rehospitalization for heart failure in the severe MS group compared with the no-MS group (P = .049), the difference was not significant in the multivariate analysis (adjusted hazard ratio: 1.36 [95% CI, 0.66-2.80], P = .41). CONCLUSIONS: TAVR can be safely performed in patients with severe tricuspid aortic stenosis and concomitant MS, with early and mid-term outcomes comparable to those in patients without MS.

Outcomes of Severe Mitral Stenosis With the Revised Severity Criteria: Mitral Valve Replacement vs Percutaneous Mitral Valvuloplasty.

BACKGROUND: This study aimed to compare the outcomes, according to percutaneous mitral valvuloplasty (PMV) vs mitral valve replacement (MVR), of severe mitral stenosis (MS) with the updated criteria (MVA ≤ 1.5 cm2). METHODS: From the Multicenter Mitral Stenosis With Rheumatic Etiology (MASTER) registry of 3140 patients, we included patients with severe MS who underwent PMV or MVR between January 2000 and December 2021 except for previous valvular surgery/intervention, at least moderate other valvular dysfunction, and thrombus at the left atrium/appendage. Moderately severe MS (MS-MS) and very severe MS (VS-MS) were defined as 1.0 cm2 < MVA ≤ 1.5 cm2 and MVA ≤ 1.0 cm2, respectively. Primary outcomes were a composite of cardiovascular (CV) death and heart failure (HF) hospitalization. Secondary outcomes were a composite of primary outcomes and redo intervention. RESULTS: Among 442 patients (mean 56.5 ±11.9 years, women 77.1%), the MVR group (n = 260) was older, had more comorbidities, higher echoscore, larger left chambers, and higher right ventricular systolic pressure than the PMV group (n = 182). During a mean follow-up of 6.9 ± 5.2 years with inverse probability-weighted matching, primary outcomes did not differ, but the MVR group experienced fewer secondary outcomes (P = 0.010). In subgroup analysis of patients with MS-MS and VS-MS, primary outcomes did not differ. However, the MVR group in patients with VS-MS showed better secondary outcomes (P = 0.012). CONCLUSIONS: PMV or MVR did not influence CV mortality or HF hospitalization in both MS-MS and VS-MS. However, because of increased early redo intervention in the PMV group in VS-MS, MVR would be the preferable option without clear evidence of suitable morphology for PMV.

Independent Clinical and Echocardiographic Predictors of Restenosis After Percutaneous Mitral Balloon Commissurotomy in a Large, Consecutive Cohort Followed for 24 Years.

OBJECTIVE: To enlighten preprocedural risk factors of mitral valve restenosis in a large, single-center cohort of patients submitted to percutaneous mitral balloon commissurotomy (PMBC) for the treatment of mitral stenosis (MS) secondary to rheumatic heart disease. METHODS: This is a database analysis of a single-center, high-volume tertiary institution involving all consecutive PMBC procedures performed in the mitral valve (MV). Restenosis was diagnosed when MV area was <1.5 cm² and/or loss of 50% or more of the immediate procedural result aligned with the return/worsened symptoms of heart failure. The primary endpoint was to determine the preprocedural independent predictors of restenosis after PMBC. RESULTS: Among a total of 1921 PMBC procedures, 1794 consecutive patients without previous intervention were treated between 1987 and 2010. Throughout 24 years of follow-up, MV restenosis was observed in 483 cases (26%). Mean age was 36 years and most (87%) were female. Median follow-up duration was 9.03 years (interquartile range, 0.33-23.38). Restenosis population, however, presented a significantly lower age at the procedure time as well as a higher Wilkins-Block score. At multivariate analysis, independent preprocedure predictors of restenosis were left atrium diameter (hazard risk [HR], 1.03; 95% confidence interval [CI], 1.02-1.05; P<.04), preprocedure maximum gradient (HR, 1.02; 95% CI, 1.00-1.03; P=.04), and higher Wilkins-Block score (>8) (HR, 1.38; 95% CI, 1.14-1.67; P<.01). CONCLUSIONS: At long-term follow-up, MV restenosis was observed in a quarter of the population undergoing PMBC. Preprocedure echocardiographic findings, including left atrial diameter, maximum MV gradient, and Wilkins-Block score were found to be the only independent predictors.

Independent clinical and echocardiographic predictors of restenosis after percutaneous mitral balloon commissurotomy in a large, consecutive cohort followed for 24 years

OBJECTIVES: to enlighten preprocedural risk factors of mitral valve restenosis in a large, single-center cohort of patients submitted to percutaneous mitral balloon commissurotomy (PMBC) for the treatment of mitral stenosis (MS) secondary to rheumatic heart disease. METHODS: this is a database analysis of a single-center, high-volume tertiary institution involving all consecutive PMBC procedures performed in the mitral valve (MV). Restenosis was diagnosed when MV area was <1.5 cm2 and/or loss of 50% or more of the immediate procedural result aligned with the return/worsened symptoms of heart failure. The primary endpoint was to determine the preprocedural independent predictors of restenosis after PMBC. Results: among a total of 1921 PMBC procedures, 1794 consecutive patients without previous intervention were treated between 1987 and 2010. Throughout 24 years of follow-up, MV restenosis was observed in 483 cases (26%). Mean age was 36 years and most (87%) were female. Median follow-up duration was 9.03 years (interquartile range, 0.33-23.38). Restenosis population, however, presented a significantly lower age at the procedure time as well as a higher Wilkins-Block score. At multivariate analysis, independent preprocedure predictors of restenosis were left atrium diameter (hazard risk [HR], 1.03; 95% confidence interval [CI], 1.02-1.05; P<.04), preprocedure maximum gradient (HR, 1.02; 95% CI, 1.00-1.03; P=.04), and higher Wilkins-Block score (>8) (HR, 1.38; 95% CI, 1.14-1.67; P<.01). CONCLUSIONS: at long-term follow-up, MV restenosis was observed in a quarter of the population undergoing PMBC. Preprocedure echocardiographic findings, including left atrial diameter, maximum MV gradient, and Wilkins-Block score were found to be the only independent predictors.

Use of Cardiopulmonary Exercise Testing to Assess Pulmonary Hypertension in Patients With Rheumatic Mitral Valve Disease: A Comparative Study With Echocardiography.

Rheumatic mitral stenosis (RMS) is still a significant public health problem in low- and middle-income countries. Pulmonary hypertension (PH) is a common consequence of RMS and may be used as a surrogate of disease severity. Cardiopulmonary exercise testing (CPET) provides a comprehensive assessment of the cardiorespiratory systems and can identify indirect signs of PH. To evaluate the relationship between CPET parameters and PH quantified by echocardiography in patients with RMS. This cross-sectional study retrospectively included thirty patients with RMS referred for CPET from 2012 to 2020. Two groups of patients were defined according to echocardiographic-derived pulmonary systolic arterial pressure (PASP): significant PH group (PSAP ≥ 50 mmHg); and non-significant PH group (PSAP < 50 mmHg). A decrease in peak oxygen consumption (VO2) and oxygen pulse predicted (O2PP) was observed in the PH group compared to the non-significant PH group (11.1±2.8 mL/kg/min vs 14.1±2.9 mL/kg/min; P = 0.02; 54±9% vs 67.8±15%; P = 0.02). The PH group exhibited a greater VE/VCO2 nadir rather than non-significant PH group (38±5 vs 32±3; P < 0.001). Receiver operating characteristic (ROC) analysis with O2PP <54% showed sensitivity and specificity of 67% and 90%, respectively. VE/VCO2 nadir ≥ 40 and VO2 peak < 10.8 mL/kg/min showed 44% and 56% of sensitivity and 100% and 90% of specificity respectively. CPET can improve the assessment of disease severity in patients with RMS with high specificity. The presence of higher O2PP, higher VO2 peak, and lower VE/VCO2 nadir highly suggests the absence of significant PH.

Physical activity and exercise recommendations for patients with valvular heart disease.

There is a paucity of studies looking at the natural history of valvular heart disease (VHD) in exercising individuals, and exercise recommendations are largely based on expert consensus. All individuals with VHD should be encouraged to avoid sedentary behaviour by engaging in at least 150 min of physical activity every week, including strength training. There are generally no exercise restrictions to individuals with mild VHD. Regurgitant lesions are better tolerated compared with stenotic lesions and as such the recommendations are more permissive for moderate-to-severe regurgitant VHD. Individuals with severe aortic regurgitation can still partake in moderate-intensity exercise provided the left ventricle (LV) and aorta are not significantly dilated and the ejection fraction (EF) remains >50%. Similarly, individuals with severe mitral regurgitation can partake in moderate-intensity exercise if the LV end-diastolic diameter <60 mm, the EF ≥60%, resting pulmonary artery pressure <50 mm Hg and there is an absence of arrhythmias on exercise testing. Conversely, individuals with severe aortic or mitral stenosis are advised to partake in low-intensity exercise. For individuals with bicuspid aortic valve, in the absence of aortopathy, the guidance for tricuspid aortic valve dysfunction applies. Mitral valve prolapse has several clinical, ECG and cardiac imaging markers of increased arrhythmic risk; and if any are present, individuals should refrain from high-intensity exercise.

Stroke risk prediction in patients with atrial fibrillation with and without rheumatic heart disease.

AIMS: Patients with atrial fibrillation (AF) and rheumatic heart disease (RHD), especially mitral stenosis, are assumed to be at high risk of stroke, irrespective of other factors. We aimed to re-evaluate stroke risk factors in a contemporary cohort of AF patients. METHODS AND RESULTS: We analysed data of 15 400 AF patients presenting to an emergency department and who were enrolled in the global RE-LY AF registry, representing 47 countries from all inhabited continents. Follow-up occurred at 1 year after enrolment. A total of 1788 (11.6%) patients had RHD. These patients were younger (51.4±15.7 vs. 67.8±13.6 years), more likely to be female (66.2% vs. 44.7%) and had a lower mean CHA2DS2-VASc score (2.1±1.7 vs. 3.7±2.2) as compared to patients without RHD (all P<0.001). Significant mitral stenosis (average mean transmitral gradient 11.5±6.5 mmHg) was the predominant valve lesion in those with RHD (59.6%). Patients with RHD had a higher baseline rate of anticoagulation use (60.4% vs. 45.2%, P<0.001). Unadjusted stroke rates at 1 year were 2.8% and 4.1% for patients with and without RHD, respectively. The performance of the CHA2DS2-VASc score was modest in both groups [stroke at 1 year, c-statistics 0.69, 95% confidence interval (CI) 0.60-0.78 and 0.63, 95% CI 0.61-0.66, respectively]. In the overall cohort, advanced age, female sex, prior stroke, tobacco use, and non-use of anticoagulation were predictors for stroke (all P<0.05). Mitral stenosis was not associated with stroke risk (adjusted odds ratio 1.07, 95% CI 0.67-1.72, P=0.764). CONCLUSION: The performance of the CHA2DS2-VASc score was modest in AF patients both with and without RHD. In this cohort, moderate-to-severe mitral stenosis was not an independent risk factor for stroke.

The Spectrum, Severity and Outcomes of Rheumatic Mitral Valve Disease in Pregnant Women in Australia and New Zealand.

BACKGROUND: Rheumatic heart disease (RHD) poses significant perinatal risks. We aimed to describe the spectrum, severity and outcomes of rheumatic mitral valve disease in pregnancy in Australia and New Zealand. METHODS: A prospective, population-based cohort study of pregnant women with RHD recruited 2013-14 through the hospital-based Australasian Maternity Outcomes Surveillance System. Outcome measures included maternal and perinatal morbidity and mortality. Univariable and multivariable logistic regression analyses were undertaken to test for predictors of adverse maternal and perinatal outcomes. RESULTS: Of 274 pregnant women identified with RHD, 124 (45.3%) had mitral stenosis (MS) and 150 (54.7%) had isolated mitral regurgitation (MR). One woman with mild MS/moderate MR died. There were six (2.2%) stillbirths and two (0.7%) neonatal deaths. Babies born to women with MS were twice as likely to be small-for-gestational-age (22.7% vs 11.4%, p=0.013). In women with MS, use of cardiac medication (AOR 7.42) and having severe stenosis (AOR 16.35) were independently associated with adverse cardiac outcomes, while New York Heart Association (NYHA) class >1 (AOR 3.94) was an independent predictor of adverse perinatal events. In women with isolated MR, use of cardiac medications (AOR 7.03) and use of anticoagulants (AOR 6.05) were independently associated with adverse cardiac outcomes. CONCLUSIONS: Careful monitoring and specialist care for women with RHD in pregnancy is required, particularly for women with severe MS, those on cardiac medication, and those on anticoagulation, as these are associated with increased risk of adverse maternal cardiac outcomes. In the context of pregnancy, contraception and preconception planning are important for young women diagnosed with RHD.

Effects of percutaneous balloon mitral valvuloplasty in patients with mitral stenosis and atrial fibrillation: a systematic review and meta-analysis.

OBJECTIVE: The study aimed to systematically review the existing literature and assess the effects of percutaneous balloon mitral valvuloplasty (PBMV) in patients with mitral stenosis and atrial fibrillation (AF) as opposed to sinus rhythm (SR). METHODS: Eligible studies were identified from six electronic databases before June 2021. The primary outcome was mitral valve area (MVA), and secondary outcomes were hemodynamic measurements, in-hospital complications, and long-term outcomes. Relative risks (RRs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs) were used as effect sizes. RESULTS: Fifteen studies were included involving 6351 patients. For the primary outcome, the AF group obtained less favourable changes in MVA (WMD: -0.10, 95%CI: -0.14, -0.06) and a significantly smaller postoperative and long-term MVA (WMD: -0.13, 95%CI: -0.18, -0.08 and WMD: -0.10, 95%CI: -0.17, -0.03, respectively) compared to the SR group. For secondary outcome, the AF group was associated with suboptimal outcomes as following (WMD/RR, [95%CI]): higher LAP (1.37, [0.86, 1.87]), more embolism (2.85, [1.44, 5.63]), lower event-free survival (0.89, [0.80, 1.00]), higher incidences of mitral valve replacement (2.20, [1.40, 3.46]), re-PBMV (2.28, [1.63, 3.19]), and mortality (3.28, [2.42, 4.44]). No significant differences were found in other outcomes. CONCLUSIONS: The currently available evidence suggests that PBMV may be less effective in patients with AF than in those with SR. However, early treatment and appropriate management of AF patients undergoing PBMV may benefit the immediate and long-term outcomes.

Management of mitral stenosis: a systematic review of clinical practice guidelines and recommendations.

A number of guidelines exist with recommendations for diagnosis and management of mitral stenosis (MS). We systematically reviewed existing guidelines for diagnosis and management of MS, highlighting their similarities and differences, in order to guide clinical decision-making. We searched national and international guidelines in MEDLINE and EMBASE (5/4/2011-5/9/2021), the Guidelines International Network, Guideline Library, National Guideline Clearinghouse, National Library for Health Guidelines Finder, Canadian Medical Association Clinical Practice Guidelines Infobase, and websites of relevant organizations. Two independent reviewers screened titles and abstracts, and the full text of potentially relevant articles where needed. Selected guidelines were assessed for rigor of development; only guidelines with Appraisal of Guidelines for Research and Evaluation II instrument score >50% were included in the final analysis. Four guidelines were retained for analysis. There was consensus for percutaneous mitral balloon commissurotomy as first-line treatment of symptomatic severe rheumatic MS with suitable anatomy. In patients with unfavourable anatomy, surgical intervention should be considered. Exercise testing is indicated if discrepancy exists between symptoms and echocardiographic measurements. There was no clear divide between rheumatic MS and degenerative MS for their respective diagnoses and management. Pregnancy in severe MS is discouraged and the stenosis should be treated before conception. Long-term antibiotic prophylaxis is recommended for patients with rheumatic MS. Recommendations for the management of patients with mixed valvular diseases are lacking.

Left atrial function by two-dimensional speckle tracking echocardiography in patients with severe rheumatic mitral stenosis and pulmonary hypertension.

We studied left atrial (LA) function in severe rheumatic mitral stenosis (MS) patients using two-dimensional speckle tracking echocardiography (STE). Eighty patients with isolated severe MS in sinus rhythm and 40 controls underwent comprehensive echocardiography including STE derived LA strain [reservoir strain (LASr), conduit strain (LAScd) and contractile strain (LASct)]. The mean MVA was 0.93 ± 0.21 cm2. The mean values of LASr (14.73 ± 8.59%), LAScd (-7.61 ± 4.47%) and LASct (-7.16 ± 5.15%) in patients were significantly lower (p < 0.001) vs. controls 44.11 ± 10.44%, -32.45 ± 7.63%, -11.85 ± 6.77% respectively and showed decreasing trend with increasing MS severity and higher NYHA class. In conclusion, LA dysfunction is prevalent in severe MS irrespective of NYHA functional class.