Invasive Hemodynamic Characteristics in Patients With Mitral Annular Calcification Related Mitral Stenosis and Chest Radiation

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Quantification of invasive hemodynamics and mitral annular calcification-related mitral stenosis remains under-explored in patients exposed to chest radiation. We sought to explore invasive hemodynamic parameters via transseptal catheterization in patients with and without chest radiation who had a diagnosis of mitral annular calcification-related mitral stenosis. After excluding patients with more than moderate mitral regurgitation, we found that there was no difference in mitral valve area on hemodynamic testing in patients with and without radiation with an elevated baseline transmitral gradient on transthoracic echocardiography in the setting of mitral annular calcification-related mitral stenosis. There was a higher transmitral gradient and left atrial pressure in patients with prior radiation consistent with left atrial noncompliance, suggesting that treating mitral valve stenosis may not relieve symptoms in this cohort of patients.

Mitral annular calcification (MAC) that extends into the leaflets is associated with mitral stenosis (MS).¹ A definition of MAC-related MS was recently proposed as evidence of annular calcification with an elevated transmitral gradient (TMG).¹ However, an elevated TMG can be driven not only by mitral stenosis, but also mitral regurgitation, diastolic dysfunction, and left atrial noncompliance. Each of these conditions is prevalent in chest radiation (CR) heart disease, making accurate non-invasive evaluation of suspected MAC-related MS challenging.² Hemodynamic phenotypes in patients with MAC-related MS and CR remain poorly understood. We sought to explore the invasive hemodynamic parameters in patients with and without CR who had a diagnosis of MAC-related MS and underwent transseptal hemodynamic catheterization.

The cohort included consecutive adults (age ≥ 18 years) with MAC-related MS who underwent transseptal cardiac catheterization hemodynamic assessment of mitral inflow obstruction at Mayo Clinic (Rochester, MN or Jacksonville, FL) between January 2004 and February 2020. Noninvasive diagnosis of MAC-related MS as well as cardiac catheterization technique were previously described.³ Baseline demographic, echocardiographic, and invasive hemodynamic data were extracted from medical charts. Patients with at least moderate mitral valve regurgitation were excluded from the cohort. This study was approved by the Mayo Clinic Institutional Review Board, and informed consent was given by patients.

Continuous data were presented as mean ± standard deviation or median (25^th-75^th percentile), and nominal variables were presented as counts (%). Student’s t test and chi-square analysis were used for between-group comparisons. Statistical analysis was performed with SAS version 9.4. Statistical significance was defined as P less than .05.

Clinical and echocardiographic data are presented in the Table. There were 19 patients with prior CR (20.9%) and 72 without prior CR (79.1%). Patients with CR were younger (62.5 ± 10.4 vs 69.8 ± 10.3 years; P = .008) with lower body mass index (28.0 ± 6.8 vs 33.6 ± 8.0 kg/m²; P = .007). Patients with CR had lower prevalence of hypertension (57.9% vs 83.3%; P = .02) and diabetes mellitus (21.1% vs 47.2%; P =.04). There was no difference in left ventricular ejection fraction, mitral valve diastolic mean gradient, or computed tomography MAC score.

Transseptal invasive hemodynamics revealed no difference in mitral valve area (MVA) by Gorlin formula (1.9 ± 1.1 vs 2.2 ± 1.7 cm²; P = .52) but did show higher diastolic TMG (9.7 ± 4.1 vs 7.4 ± 3.6 mm Hg; P = .025), left atrial pressure (25.58 ± 7.65 vs 21.46 ± 6.21 mm Hg; P = .02), and left atrial (LA) v-wave (39.1 ± 13.7 vs 33.2 ± 11.7 mm Hg; P = .07) in the CR group compared to those without CR. There was no difference in cardiac index (2.45 ± 0.4 vs 2.68 ± 0.68 L/min/m²; P = .18), systemic vascular resistance (SVR) (1403.59 ± 554.13 vs 1193.0 ± 370.83 dynes/seconds/cm^-5; P = .075), nor left ventricular end diastolic pressure, which was elevated in both groups (19.21 ± 4.29 vs 17.18 ± 6.09 mm Hg; P = .18).

Our study demonstrated that in patients with and without CR with an elevated baseline TMG on TTE in the setting of MAC-related MS, invasive transseptal catheterization revealed no difference in the MVA. However, there was a higher TMG and left atrial pressure and LA v-wave in patients with prior CR consistent with LA noncompliance. Both groups had elevated, but not significantly different, left ventricular end-diastolic pressure (LVEDP) and all patients had less than moderate MR.

Often, elevated TMG is used as a surrogate of severity of MS in patients with MAC.¹ Our study findings suggest that the increased TMG in patients with CR is likely driven by left atrial noncompliance compared to patients with no CR. This supports the notion that TMG may not be the sole surrogate of severity of mitral stenosis in patients with MAC-related MS and prior CR. Moreover, noninvasive quantification of MAC-related MS remains complex and challenging. CR can cause endothelial proliferation of myofibroblasts leading to valvular, myocardial, and coronary artery damage. The resultant myocardial fibrotic changes can lead to stenotic and regurgitant valvular disease, restrictive cardiomyopathy, and left atrial noncompliance.⁴ Traditional parameters used to quantify rheumatic MS, including MVA by pressure half time, may not be accurate in this patient population due to the presence of such comorbidities like restrictive cardiomyopathy.⁴ Two-dimensional planimetry can also be difficult due to echogenic shadowing from MAC.

Our study also showed that there is a potential advantage of performing invasive hemodynamic assessment of the mitral valve in this patient population to better assess the severity of the mitral stenosis as well as the hemodynamic impact of concomitant left atrial and ventricular noncompliance. Per the American Society of Echocardiography guidelines, it is reasonable to consider evaluating invasive hemodynamics in symptomatic patients with a Doppler transmitral gradient on echocardiogram of at least 5 mm Hg to assess the contribution of true mitral valve stenosis to the invasive gradient.⁵ We recommend invasive mitral stenosis evaluation be performed in symptomatic patients with a history of chest radiation who are being considered for interventional cardiovascular procedures to help predict which patients may benefit from mitral valve or other interventions. Invasive evaluation may also be helpful in this cohort if their symptoms have been refractory to interventions and more investigation is needed.  Understanding the severity of mitral stenosis as well as LA and LV noncompliance may also have therapeutic implications, as patients with CR may continue to have symptoms driven by their myocardial disease despite treatment of their MS.

Among patients with MAC-related MS and CR, there is a higher prevalence of elevated noninvasive TMG compared to those with no CR. Invasive hemodynamic assessment did not show a difference in MVA or LVEDP, suggesting that the higher TMG is likely driven by left atrial noncompliance. Further studies are needed to validate these findings and assess their impact on patient outcomes.

From the ¹Department of Internal Medicine, Mayo Clinic, Jacksonville, FL, USA; ²Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, USA.

Disclosures: The authors report no financial relationships or conflicts of interest regarding the content herein.

Address for correspondence: Abdallah El Sabbagh, MD, 4500 San Pablo Road, Jacksonville, FL 32224, USA. Email: elsabbagh.abdallah@mayo.edu

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