Current methods to assess mitral annular calcification and its risk factors

Mitral Annulus Calcification

Background There is a paucity of data about the prevalence and natural history of mitral annular calcification (MAC). Purposes In a large cohort of patients undergoing clinically-indicated echocardiography, we aimed to evaluate the prevalence and the natural history of MAC, and the frequency of associated mitral valve dysfunction (MVD). Methods Retrospective review of all patients who underwent echocardiographic evaluation at our institution between January 1st and December 31st 2015. The patients were stratified into 3 groups: MAC with MVD, MAC without MVD, no MAC. MVD was defined as moderate or greater mitral regurgitation (MR) or stenosis (MS). The 3 groups were compared for baseline clinical and echocardiographic characteristics and all-cause mortality during follow-up. Results Of 24,415 evaluated patients, 5478 (22%) had MAC. Patients with MAC were older (75±10 vs. 60±16 years, p<0.01) and more often female (46% vs. 43%, p<0.01). MVD was more frequently observed in patients with MAC (16% vs. 7%, p<0.01); moderate or greater MR was found in 10% of patients with MAC vs. 6% without MAC (p<0.01) and MS in 7% vs. 0.5% (p<0.01). In patients with MAC, those with MVD were more often female and more frequently had creatinine ≥2mg/dl and moderate or greater aortic stenosis (AS) than those without MVD (Fig. A). Kaplan-Meier survivals at 1 year were 75% in patients with MAC and MVD, 87% in those with MAC without MVD, and 92% in those without MAC (Fig B). Adjusted for age, sex, diabetes, creatinine ≥2 mg/dl, coronary artery disease, left ventricular ejection fraction <50%, and AS, MAC was associated with higher all-cause mortality (adjusted hazard ratio1.4, 95% confidence interval: 1.3–1.5, p<0.01); combined MAC and MVD was associated with the highest mortality during follow-up of 2.5±1.8 years. Conclusion In a large cohort of patients undergoing echocardiographic evaluation, the prevalence of MAC was 22%. MV dysfunction was more than twice as prevalent in patients with MAC as without. Patients with MAC had higher all-cause mortality than patients without MAC. Among patients with MAC and mitral valvular dysfunction, adjusted mortality was two-fold higher compared to those without MAC. Funding Acknowledgement Type of funding source: None

To compare all-cause mortality in patients with mitral annulus calcification (MAC) and severe mitral valve dysfunction (MVD) who received standard mitral intervention versus no intervention. Patients with MAC often have high surgical risk due to advanced age, comorbidities, and technical challenges related to calcium. The impact of a mitral intervention on outcomes of patients with MAC and severe MVD is not well known. Retrospective review of patients with MAC by transthoracic echocardiography (TTE) in 2015 at a single institution. Patients with severe mitral stenosis (MS) or regurgitation (MR) were analyzed and stratified into two groups: surgical or transcatheter intervention performed <1 year after the index TTE, and no or later intervention. The primary endpoint was all-cause mortality. Of 5502 patients with MAC, 357 had severe MVD (MS = 27%, MR = 73%). Of those, 108 underwent mitral intervention (surgery = 87; transcatheter = 21). They were younger (73 ± 11 vs. 76 ± 11 years, p < 0.01) and less frequently had cardiovascular diseases compared with no-intervention. Frequency in women was similar (45% vs. 50%, p = 0.44). During median follow-up of 3.2 years, the intervention group had higher estimated survival than those without intervention (80% vs. 72% at 1 year and 55% vs. 35% at 4 year, p < 0.01). Adjusted for age, eGFR, LVEF < 50%, and pulmonary hypertension, mitral intervention was an independent predictor of lower mortality (hazard ratio = 0.66, 95% confidence interval 0.43-0.99, p = 0.046). Patients with MAC and severe MVD who underwent mitral intervention <1 year from index TTE had lower mortality than those without intervention. Mitral intervention was independently associated with lower mortality.

Breaking the Mold: Lithotripsy for Mitral Annular Calcification.

Background: Mitral annular calcification (MAC) is a chronic inflammatory condition that is associated with future cardiovascular events. There is limited data that explores how MAC impacts outcomes in patients with pre-existing mitral regurgitation (MR). Methods: This is a retrospective analysis using the TriNetX US Collaborative Network database. A database of hospitalized patients ≥50 years was queried using ICD-10 and TriNetX curated codes. We identified those given a discharge diagnosis of MR between 2020-2023, excluding patients with rheumatic mitral valve disease or ESRD. We then stratified by presence/absence of a new diagnosis of MAC (occurring after MR diagnosis). Cohorts were balanced for socio-demographics, body mass index, and common comorbidities including hypertension, hyperlipidemia, diabetes, and tobacco use, with a standard difference of &lt;0.1 considered to indicate adequate balancing. Hazard ratios were calculated for outcomes, with a P&lt;0.05 considered significant. Results: Our query yielded 11,462 patients in the MAC group and 450,474 patients in the no MAC group. Following propensity matching, each group had 11,462 patients. All targeted variables were adequately balanced. Average age was similar in both the MAC and no MAC groups (76 years vs 75.8 years). The populations were majority white (80.3% vs 81.2%) and female (56.8% vs 57.0%). BMI was also similar (29.2 vs 28.7). Among patients with pre-existing MR, subsequently diagnosed MAC was associated with increased 1-year risk of hospitalization (HR 1.22, 95%CI 1.180-1.262, p&lt;0.0001), ICU admission (HR 1.38, 95%CI 1.250-1.524, p&lt;0.0001), ischemic heart disease (HR 1.446, 95%CI 1.289-1.622, p&lt;0.0001), new onset HFpEF (HR 1.286, 95%CI 1.160-1.425, p&lt;0.0001), cerebrovascular disease (HR 1.341, 95%CI 1.190-1.512, p&lt;0.0001), prosthetic valve replacement (HR 2.126, 95%CI 1.786-2.530, p&lt;0.0001), and mitral stenosis (HR 3.16, 95%CI 2.490-5.234, p&lt;0.0001). There was not a significant difference between groups for HFrEF (HR 0.955, p=0.4377), cardiogenic shock (HR 1.188, p=0.1098), or cardiac arrest (HR 1.155, p=0.1979). Conclusions: In patients with previously diagnosed MR, a subsequent diagnosis of MAC was associated with increased 1-year risk of hospitalization, new onset ischemic heart disease or HFpEF, and a variety of other adverse cardiovascular outcomes.

Background Mitral Annular Calcification (MAC) is a significant predictor of cardiovascular events and mitral valve dysfunctions (MVD), including mitral regurgitation and mitral stenosis. This study investigates the prevalence of MAC and its severity across different age groups and genders, and examines its association with MVD in a single tertiary care center. Methods A retrospective analysis was conducted on an echocardiography database of 48,912 consecutive patients. The prevalence of MAC, including both any MAC and moderate to severe MAC was assessed. Patients were categorized into different age groups: &amp;lt;55 years, 55-65 years, 66-75 years, and &amp;gt;75 years. The study also analyzed the prevalence of MVD in these patients and examined gender differences. Chi-square tests were used to evaluate statistical significance in gender and age group differences in association with MVD. Results The overall prevalence of any MAC was 12.5% (6,104), while moderate or severe MAC was observed in 2.2% (1,104) of the patients. When stratified by age, the prevalence of any MAC was 3% in patients &amp;lt;55 years, 15.0% in patients 55-65 years, 28.6% in patients 66-75 years, and 40.9% in patients &amp;gt;75 years. The prevalence of moderate or severe MAC followed a similar trend, with 0.2%, 1.9%, 5.5%, and 10.7% in the respective age groups. Gender distribution analysis revealed a significant female predominance among patients with moderate or severe MAC (59.5% vs. 40.5%), p &amp;lt; 0.0001. Patients with moderate or severe mitral annular calcification (MAC) had a more than four-fold increased risk of mitral valve disease (MVD) compared to those with mild MAC (57.9% vs. 13.1%, p &amp;lt; 0.0001).Age group was not a significant factor in MVD prevalence. Conclusion The age-related prevalence of mitral annular calcification (MAC), especially in older women, represents a significant clinical concern given its association with increased risk of mitral valve disease (MVD). This highlights the importance of vigilant MAC screening and proactive MVD management in this population. Future research should focus on identifying modifiable risk factors and developing effective screening strategies to mitigate the progression of MAC and its associated valvular complications.

Introduction: Mitral annular calcification (MAC) has been associated with age, hemodialysis (HD) status, coronary disease, and mortality. While MAC is seen frequently in pts undergoing percutaneous edge-to-edge repair of mitral regurgitation (MR) its impact on survival is unknown. Hypothesis: MAC is not associated with mortality after percutaneous MR repair. Methods: Pts who underwent MitraClip repair of MR between Apr 2009 and May 2014 were included. Kaplan-Meier survival was plotted between pts with no MAC and pts with MAC. A multivariate Cox regression of all-cause mortality was performed simultaneously adjusting for MAC, age, HD status, and prior myocardial infarction (MI). Results: 173 pts were included. Mean age at percutaneous repair was 76.9 ± 12.6 yrs and 40.8% were females. MAC was present in 86/173 (49.7%) of pts, and was mild in 61/86 (70.9%) cases and moderate or severe in the remaining cases. In pts with MAC prevalence of prior MI was higher 28/86 (32.6%) vs. 16/87 (18.4%) p=0.037 but ejection fraction was similar 51.8 ± 17.1 vs. 50.4 ± 18.6 % p=0.603. Age was increased in pts with MAC 79.9 ± 10.1 vs. 74.3 ± 14.0 yrs p=0.003. MR was moderate-to-severe in 35/173 (20.2%) of pts and severe in 138/173 (79.8%) of pts. MR improved by 2 grades or more in 165/173 (95.4%) of pts after repair. Survival was decreased in pts with MAC as compared to pts with no MAC by Log Rank p=0.049 (Figure 1A). However, in a multivariate Cox regression model of all-cause mortality, MAC, after adjusting for age, HD status, and prior MI, was not associated with mortality with a hazard ratio of 1.166 (95% CI 0.707 - 1.922) p=0.548 (Figure 1B). In this model age and prior MI were associated with mortality with hazard ratios of 1.048 (95% CI 1.021 - 1.077) p=0.001 and 1.798 (95% CI 1.052 - 3.075) p=0.032, respectively. Conclusions: The presence of MAC was not associated with mortality after adjusting for age, HD status, and prior MI and should not preclude the MitraClip procedure. Procedural success was equally high.

Background Patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) have frequently severe mitral annulus calcification (MAC) that can cause mitral stenosis. However, the left ventricular (LV) pressure overload caused by the aortic stenosis may reduce the transmitral pressure gradient and the severity of mitral stenosis may be underestimated. Purpose To evaluate the frequency of severe MAC in patients undergoing TAVI and describe the changes in transmitral pressure gradient after TAVI according to the severity of the MAC. Methods Patients with severe aortic stenosis undergoing TAVI who had cardiac computed tomography data to analyse the severity of MAC and a transthoracic echocardiogram prior to the intervention and at hospital discharge were included. The severity of MAC was defined as mild MAC (3 points or less), moderate MAC (4 to 6 points), and severe MAC (7 points or more) based on the distribution of the calcification of the mitral valve (thickness, circumferential distribution, involvement of the trigones and leaflets). The changes in transmitral pressure gradient were evaluated with linear multivariate regression adjusting for age and sex. Results A total of 203 patients (median age 81 years, 40% male) with severe AS who successfully underwent TAVI were included. According to the classification of MAC severity by cardiac CT, 55 (27%) patients had no MAC, 57 (28%) mild MAC, 55 (27%) moderate MAC, and 36 (18%) severe MAC. The groups were comparable in terms of demographics and clinical characteristic. The NT-proBNP increased progressively with the severity of MAC. Transthoracic echocardiography was performed at a median of 43 days before TAVI and 3 days after TAVI. In terms of echocardiographic characteristics at baseline, there were no statistically significant differences across theg roups except from transmitral pressure gradient, which was significantly higher as the severity of MAC increased on CT . After TAVI, there was no significant change in mean transmitral pressure gradient in patients without MAC. In contrast, patients with mild, moderate and severe MAC had significant increases in trasmitral pressure gradient following TAVI, with greater changes associated with increasing severity of MAC (mild p&amp;lt;0.0001, moderate p&amp;lt; 0.0007, severe p&amp;lt;0.0060) Conclusions In patients with severe aortic stenosis and severe MAC, the transmitral pressure gradient increases significantly after TAVI. Therefore, TAVI may unmask significant mitral stenosis that may impact the results of TAVI at mid term follow-up.

Minimally invasive treatment of mitral valve disease with severe mitral annular calcification: Meeting paper for Mitral Conclave 2022.

Mitral annular calcification in hypertrophic cardiomyopathy

Mitral Annular Calcification in Obstructive Hypertrophic Cardiomyopathy: Prevalence and Outcomes

We evaluated the relationship between the mitral inflow velocities by pulsed Doppler echocardiography and mitral annular motion velocities by pulsed Doppler tissue imaging in patients with mitral annular calcification. Fifty-three patients with mitral annular calcification were divided into two groups: severe mitral annular calcification (n=15, mitral annular calcification bigger than or equal 5mm in width) and mild mitral annular calcification (n=38, mitral annular calcification <5mm in width). In addition, 20 patients with hypertensive heart disease (HHD group) and mild left ventricular hypertrophy but no mitral annular calcification and 30 normal individuals (normal group) were studied. The early diastolic mitral inflow velocity (E) was higher in the severe mitral annular calcification group (0.75+/-0.26 m/s) than in the HHD and normal groups (mild mitral annular calcification, 0.65+/-0.21; HHD, 0.57+/-0.24; normal, 0.55+/-0.15m/s), and the late diastolic mitral inflow velocity (A) was higher in the severe mitral annular calcification group (1.24+/-0.23 m/s) than in the other three groups (mild mitral annular calcification, 0.96+/-0.20; HHD, 0.84+/-0.23; normal, 0.75+/-0.13 m/s). In contrast, the early and late diastolic annular velocities (Ea, Aa) were lower in the severe mitral annular calcification group (Ea: 5.7+/-2.2; Aa: 11.9+/-4.4 cm/s) than in the other three groups (Ea: mild mitral annular calcification, 8.3+/-2.5; HHD, 7.7+/-2.2; normal, 9.0+/-1.8 cm/s; Aa: mild mitral annular calcification, 14.2+/-4.1; HHD, 14.3+/-2.8; normal, 14.2+/-2.1cm/s). Mitral valve area was smaller in the severe mitral annular calcification group (2.6+/-1.0 cm(2)) than in the other three groups (mild mitral annular calcification, 3.1+/-0.7; HHD, 4.1+/-0.7; normal, 4.2+/-0.9 cm(2)). In the mitral annular calcification and normal groups, the A correlated inversely with mitral valve area (r=-0.67, P<0.01) and directly with severity of mitral annular calcification (r=0.65, P<0.01), and the Ea correlated inversely with left ventricular wall thickness (r=-0.37, P<0.01) and severity of mitral annular calcification (r=-0.45, P<0.01). Patients with severe mitral annular calcification have higher mitral inflow velocities due to mitral annular restriction and lower mitral annular velocities caused by decreased mitral annular motion and abnormal left ventricular relaxation.

BackgroundMany previous studies have evaluated the impact of mitral valve (MV) deformity scores on the percutaneous transvenous mitral commissurotomy (PTMC) outcome in patients with mitral stenosis; however, the relationship between mitral annulus calcification (MAC) and the PTMC result has not yet been established. The current study aimed to investigate whether MAC could independently influence the immediate result of PTMC.MethodsOf all patients undergoing PTMC in our institution between April 2005 and November 2009, we included 87 patients (28.7%male, mean ± SD age = 42.8 ± 12.6 years) with rheumatic mitral stenosis who had additional data on the echocardiographic evaluation of MAC along with MV leaflets morphology. Echocardiographic assessments were repeated up to six weeks after PTMC to evaluate the immediate PTMC outcome. The frequency of the optimal PTMC result (secondary MV area > = 1.5 cm2 with > = 25% increase and without final mitral regurgitation grade > 2) was compared between two groups of patients with MAC (n = 17) and those without MAC (n = 70).ResultsThe optimal result was obtained in 55 (63.2%) patients, whereas the result was suboptimal in 32 (36.8%) patients due to insufficient MV area increase in 31(96.9%) subjects and post-procedure mitral regurgitation grade > 2 in 1(3.1%). The rate of optimal PTMC results was less in patients with MAC in comparison to those without MAC (29.4% vs.71.4%). After adjustments for possible confounders such as age and leaflets morphological subcomponents (thickening, mobility, calcification, and subvalvular thickening), MAC remained a significant negative predictor of a suboptimal PTMC result (odds ratio = 0.154; 95%CI = 0.038-0.626, p value = 0.009) together with leaflet thickening (odds ratio = 0.214; 95%CI = 0.060-0.770, p value = 0.018).ConclusionsMAC appeared to independently influence the immediate result of PTMC; therefore, mitral annulus evaluation may be considered in the echocardiographic assessment of the mitral apparatus prior to PTMC.

BackgroundCalcified amorphous tumor (CAT) of the heart is a rare, non-neoplastic cardiac mass with mitral valves and annuli being the most common sites. The presence of mitral annular calcification (MAC) is associated with an increased risk of stroke or other systemic embolisms. Here, we report a case of CAT showing rapid growth with MAC and investigate the link between the two.Case presentationA 71-year-old man presented at our hospital with dyspnea and had been undergoing hemodialysis for 26 years for chronic glomerulonephritis. Transthoracic echocardiography (TTE) revealed moderate mitral stenosis with bulky MAC. Two months later, the patient developed progressive dyspnea, and follow-up TTE revealed a highly mobile mass (8 × 5 mm) attached to the left ventricular (LV) side of the posterior MAC. He underwent surgery because of congestive heart failure and a high risk of embolization. Surgical inspection revealed that the tumor was attached beneath the P3 segment of the mitral valve on the LV side and was removed. When removing the MAC, toothpaste-like contents drained from the encapsulated mass inside the MAC at the P3 segment, where the tumor was located. After reconstructing the posterior mitral annulus defect with a bovine pericardial patch, mitral valve replacement with a mechanical prosthesis, a maze procedure, and left appendage closure were performed. Histopathological examination revealed that the excised tumor contained fibrin and calcium deposits. The mass was diagnosed as a CAT.ConclusionsCAT may be one of the causes of stroke induced by MAC. Routine follow-up echocardiography should be recommended for patients with MAC, especially those undergoing hemodialysis.

Background: Mitral annular calcification (MAC) is associated with systemic atherosclerosis and cardiometabolic risk factors. Although hematologic inflammatory indices have been reported to be correlated with MAC, whether these associations persist after accounting for the cardiometabolic context in which MAC occurs remains unclear. Methods: In a prospective, cross-sectional study of consecutive adults, patients with mild MAC were compared to those without MAC. Individuals with major inflammatory conditions, advanced chronic kidney disease, cirrhosis, malignancy, autoimmune/acute inflammatory disorders, significant valvular disease, prosthetic valves/pacing devices, psychiatric disorders, or moderate-severe MAC were excluded. C-reactive protein (CRP) and hematological inflammatory indices including neutrophil-to-lymphocyte ratio (NLR), Systemic Inflammatory Response Index (SIRI), and lymphocyte-to-leukocyte ratio (LLR) were analyzed in relation to MAC status. Results: Among 205 patients, 134 had mild MAC and 71 had no MAC. Patients with MAC were older and displayed higher cardiometabolic burden, including more frequent dysglycemia, higher blood pressure and greater adiposity. In unadjusted comparisons inflammatory markers differed by MAC status: CRP (0.31 mg/dL vs. 0.18 mg/dL, p = 0.002), NLR (2.52 vs. 1.99, p = 0.032) and SIRI (1.27 vs. 1.04, p = 0.039), and LLR (0.26 vs. 0.29, p = 0.032). In multivariable logistic regression models, none of the inflammatory markers remained independently associated with MAC. In contrast, age (ORs 1.056 - 1.063 per year increase, p ≤ 0.001), prediabetes (ORs 2.43 - 3.63, p ≤ 0.001) and type 2 diabetes (OR 5.91 and 6.19, p ≤ 0.001) demonstrate consistent independent associations with MAC across all models. Conclusions: In this cardiometabolic population with mild MAC, inflammatory indices showed unadjusted differences but no independent associations with MAC after comprehensive cardiometabolic adjustment. These findings are most compatible with inflammatory markers primarily reflecting the cardiometabolic milieu in which MAC occurs rather than representing MAC-specific processes. Age and glucose metabolism abnormalities emerged as the dominant independent factors associated with mild MAC reinforcing the central role of metabolic disfunction in MAC pathogenesis.