Contemporary experience of mitral transcatheter edge-to-edge repair technology in patients with mitral annular calcification.

BACKGROUND: Mitral annular calcification (MAC) has been an exclusion for many of the earlier pivotal trials that were instrumental in gaining device approval and indications for mitral transcatheter edge-to-edge repair (M-TEER). AIMS: To evaluate the impact of MAC on the procedural durability and success of newer generation MitraClip® systems (G3 and G4 systems). METHODS: Data were collected from Northwell TEER registry. Patients that underwent M-TEER with third or fourth generation MitraClip device were included. Patients were divided into -MAC (none-mild) and +MAC (moderate-severe) groups. Procedural success was defined as ≤ grade 2 + mitral regurgitation (MR) postprocedure, and durability was defined as ≤ grade 2 + MR retention at 1 month and 1 year. Univariate analysis compared outcomes between groups. RESULTS: Of 260 M-TEER patients, 160 were -MAC and 100 were +MAC. Procedural success was comparable; however, there were three patients who required conversion to cardiac surgery during the index hospitalization in the +MAC group versus none in the -MAC group (though this was not statistically significant). At 1-month follow-up, there were no significant differences in MR severity. At 1-year follow-up, +MAC had higher moderate-severe MR (22.1% vs. 7.5%; p = 0.002) and higher mean transmitral gradients (5.3 vs. 4.0 mmHg; p = 0.001) with no differences in mortality, New York Heart Association functional class or ejection fraction. CONCLUSION: In selective patients with high burden of MAC, contemporary M-TEER is safe, and procedural success is similar to patients with none-mild MAC. However, a loss of procedural durability was seen in +MAC group at 1-year follow-up. Further studies with longer follow-ups are required to assess newer mTEER devices and their potential clinical implications in patients with a high burden of MAC.

Percutaneous balloon mitral valvuloplasty with shockwave lithotripsy for the treatment of calcific mitral valve stenosis.

BACKGROUND: Calcific mitral stenosis (calcific MS) presents a challenge for surgical treatment and is a contraindication for most contemporary transcatheter mitral valve replacement devices (TMVR), rendering patients with very limited therapeutic options. AIMS: This study aims to assess the clinical and hemodynamic follow-up after mitral valve lithotripsy (MVL). METHODS: All consecutive patients who underwent MVL to treat symptomatic calcific MS at St Michael's Hospital, Toronto, Canada, were included. Patients were deemed unsuitable for mitral surgery or TMVR after heart team assessment. Patients with rheumatic MS or ≥moderate mitral regurgitation (MR) were excluded. The primary endpoint was a reduction in the invasive mitral gradient by ≥50% without significant (≥moderate) MR. RESULTS: Fifteen patients underwent MVL between 2021 and 2023 with a mean age of 74 ± 9 years; 53% were female, with a mean STS score of 10% ± 0.1%. Following MVL, there was a reduction in the invasively measured mean trans-mitral gradient compared to baseline (14 mmHg vs. 6 mmHg; p < 0.05). The primary endpoint was achieved in 8 patients (53%) with no major procedural complications. At follow-up (median 90 days, IQR 58-115 days), 14 (93%) patients reported improved symptoms from New York Heart Association (NYHA) Class III-IV to NYHA Class I-II (p < 0.01) with stable echo-derived mean gradient (7.7 mmHg ± 2 mmHg vs. 8.4 mmHg ± 2.9 mmHg (p = 0.7). CONCLUSIONS: In selected patients with symptomatic inoperable calcific MS, MVL was safe and associated with significant short-term clinical and hemodynamic improvement. MVL may represent a new compassionate therapy for this challenging cohort. Further studies are needed to determine the long-term outcomes and help define the role of IVL technology in treating calcific valvular conditions.

Surgical treatment of caseous calcification of the mitral annulus causing mitral stenosis and mimicking the clinical picture of infective endocarditis: A case report.

Among masses involving the mitral valve and annulus, caseous calcification of the mitral annulus (CCMA) is a rare disease. CCMA accounts for .63% of all mitral annular calcification (MAC) cases. The pathophysiology is still unknown. The correct diagnosis and treatment of this disease is very important to prevent complications. We present a case of giant CCMA with advanced mitral stenosis and hypertrophic cardiomyopathy, presenting with symptoms of infection and therefore a preliminary diagnosis of infective endocarditis. Because of these features, we wanted to share our case as it is the 1st case in the literature.

Systolic anterior motion of a transatrial transcatheter mitral valve replacement causing left ventricular outflow tract obstruction.

Transatrial transcatheter mitral valve replacement is a hybrid strategy involving placing the patient on cardiopulmonary bypass and direct implantation of a transcatheter valve in a calcified annulus for mitral annular calcification. We report a rare phenomenon of systolic anterior motion of the leaflets of a transcatheter heart valve prosthesis used for mitral valve replacement causing left ventricular outflow tract obstruction. Although reported in transcatheter mitral valve replacement, we believe this is the first report of left ventricular outflow tract obstruction after transatrial mitral valve replacement and discuss the pre-disposing risk factors.

The impact of pulmonary hypertension on outcomes of transcatheter mitral valve replacement in mitral annular calcification.

OBJECTIVES: To assess the impact of pulmonary hypertension (PH) on outcomes of patients with severe mitral annular calcification (MAC) undergoing transcatheter mitral valve replacement (TMVR). BACKGROUND: PH is associated with poor outcomes after mitral valve surgery. Whether the presence of PH in patients with MAC undergoing (TMVR) is associated with poor outcomes, is unknown. METHODS: Retrospective evaluation of 116 patients from 51 centers in 11 countries who underwent TMVR with valve in mitral annular calcification (ViMAC) using balloon-expandable aortic transcatheter valves (THVs) from September 2012 to March 2017. Pulmonary artery systolic blood pressure (PASP) by echocardiogram was available in 90 patients. The subjects were stratified based on PASP: No PH = PASP ≤35 mmHg (n = 11); mild to moderate PH = PASP 36-49 mmHg (n = 21) and severe PH = PASP ≥50 mmHg (n = 58). Clinical, procedural, and echocardiographic outcomes were assessed. RESULTS: Mean age was 72.7 (±12.8) years, 59 (65.6%) were female, Society of Thoracic Surgeons score was 15.8 + 11.8% and 90.0% where in New York Heart Association (NYHA) class III-IV. There was no significant difference in all-cause mortality at 30 days (no PH = 27.3%, mild-moderate PH = 19.0%, severe PH = 31.6%; p = 0.55) or at 1 year (no PH = 54.5%, mild-moderate PH = 38.1%, severe PH = 56.1%; p = 0.36). No difference in adverse events, NYHA class or amount of residual mitral regurgitation at 1 year were observed between the groups. CONCLUSION: This study suggests that the presence of PH in patients with predominantly mitral stenosis with MAC undergoing TMVR does not impact mortality or adverse events. Further studies are needed to fully understand the effect of PH in this group of patients.

Atherogenic index of plasma is an independent predictor of mitral annular calcification.

BACKGROUND: In the latest reports, atherogenic indices have been related to acute coronary syndromes, stable coronary artery disease, heart failure and future cardiac events. Conventional atherosclerosis risk factors have been associated with mitral annular calcification (MAC), but data on the relationship between atherogenic indices and MAC are lacking. We aimed to investigate a possible relationship between MAC and atherogenic indices. METHODS: In total 741 patients (n = 427 with MAC and n = 314 without MAC) who were examined in our cardiology clinic from February 2016 to October 2021 were recruited in the study. Mitral annular calcification was diagnosed by transthoracic 2-dimensional echocardiography. The atherogenic coefficient (AC), Castelli risk index 1 (CRI-1), Castelli risk index 2 (CRI-2) and atherogenic index of plasma (AIP) were calculated by utilizing standard lipid test values. RESULTS: There was no statistically significant difference in sex, age, diabetes and hypertension status between the patient and the control groups. Serum triglyceride level, AIP, Hs-CRP, smoking and BMI were independently significantly associated with MAC in multiple regression analysis (p < 0.001). CONCLUSION: Higher AIP was related to the existence of MAC and also predict the presence of MAC independently. Studies evaluating the modification of these indices are needed.

Purposeful use of multimodality imaging in the diagnosis of caseous mitral annular calcification: a case series report.

BACKGROUND: Caseous mitral annular calcification (CMAC) is a rare liquefactive variant of mitral annular calcification (MAC) and superficially mimics a cardiac vegetation or abscess. CMAC is viewed as a benign condition of MAC, while MAC has clinical implications for patients' lives. Correctly diagnosing CMAC is essential in order to avoid unnecessary interventions, cardiac surgery or even psychological suffering for the patient. CASE PRESENTATION: We report on 6 patients with suspected intra-cardiac masses of the mitral annulus that were referred to our institution for further clarification. A definitive diagnosis of CMAC was achieved by combining echocardiography (Echo), cardiac magnetic resonance imaging (MRI) and cardiac computed tomography (CT) for these patients. Echo assessed the mass itself and possible interactions with the mitral valve. MRI was useful in differentiating the tissue from other benign or malign neoplasms. CT revealed the typical structure of CMAC with a "soft" liquefied centre and an outer capsule with calcification. CONCLUSION: CMAC is a rare condition, and most clinicians and even radiologists are not familiar with it. CMAC can be mistaken for an intra-cardiac tumour, thombus, vegetation, or abscess. Non-invasive multimodality imaging (i.e. Echo, MRI, and CT) helps to establish a definitive diagnosis of CMAC and avoid unnecessary interventions especially in uncertain cases.

Mitral annular calcification: The incremental diagnostic value of 3D transesophageal echocardiography.

Three-dimensional (3D) echocardiography is an important tool in the evaluation of mitral valve anatomy. We illustrate a case of a 67-year-old female who was admitted for non-ST-elevation myocardial infarction (NSTEMI) and underwent two-vessel coronary artery bypass grafting for surgical disease. Her two-dimensional (2D) echocardiographic images intraoperatively demonstrated a mass on the posterior mitral valve leaflet which created a diagnostic challenge; 3D transesophageal imaging was crucial in identifying the true nature of the pathology to be mitral annular calcification with supra-annular extension.

Partial ring annuloplasty in the management of mitral annular calcification.

Mitral annular calcification (MAC) complicates the management of mitral valve (MV) disease, regardless of its etiology. Strategies to address MV surgery in MAC include two main options with their own pros and cons; respect and resect strategy. Here, we present a case of minimally-invasive MV repair with partial annuloplasty in the management of noncircumferential MAC with respect to strategy. This technique may be an alternative option for rescuing high-risk patients without extensive decalcification.

Severe mixed mitral valve disease due to massive mitral annular calcification: A case report and literature review.

We present an unusual case of massive mitral annular calcification (MAC) leading to severe mixed mitral valve disease, viz severe mitral regurgitation and severe mitral stenosis. To our knowledge, severe mixed mitral valve disease secondary to MAC is extremely rare. The patient (a 65-year-old lady) presented with worsening shortness of breath and signs of congestive heart failure. Echocardiographic examination revealed massive mitral annular calcification. Despite the massive annular calcification, she had experienced neither embolism nor endocarditis in the past. Because of severe symptomatic mitral regurgitation and mitral stenosis, surgery was advised; however, the patient declined it.

Hybrid Surgery for Severe Mitral Valve Calcification: Limitations and Caveats for an Open Transcatheter Approach.

Background and Objectives: Mitral stenosis with extensive mitral annular calcification (MAC) remains surgically challenging in respect to clinical outcome. Prolonged surgery time with imminent ventricular rupture and systolic anterior motion can be considered as a complex of causal factors. The aim of our alternative hybrid approach was to reduce the risk of annual rupture and paravalvular leaks and to avoid obstruction of the outflow tract. A review of the current literature was also carried out. Materials and Methods: Six female patients (mean age 76 ± 9 years) with severe mitral valve stenosis and severely calcified annulus underwent an open implantation of an Edwards Sapien 3 prosthesis on cardiopulmonary bypass. Our hybrid approach involved resection of the anterior mitral leaflet, placement of anchor sutures and the deployment of a balloon expanded prosthesis under visual control. Concomitant procedures were carried out in three patients. Results: The mean duration of cross-clamping was 95 ± 31 min and cardiopulmonary bypass was 137 ± 60 min. The perioperative TEE showed in three patients an inconspicuous, heart valve-typical gradient on all implanted prostheses and a clinically irrelevant paravalvular leakage occurred in the anterior annulus. In the left ventricular outflow tract, mild to moderately elevated gradients were recorded. No adverse cerebrovascular events and pacemaker implantations were observed. All but one patient survived to discharge. Survival at one year was 83.3%. Conclusions: This "off label" implantation of the Edwards Sapien 3 prosthesis may be considered as a suitable bail-out approach for patients at high-risk for mitral valve surgery or deemed inoperable due to extensive MAC.

Temporal outcomes of transcatheter mitral valve replacement in native mitral valve disease with annular calcification.

BACKGROUND: Surgical intervention in patients with native mitral disease due to severe mitral annular calcification (MAC) carries significant risk. Transcatheter mitral valve replacement (TMVR) using balloon-expandable aortic transcatheter heart valve (THV) in MAC had emerged as alternative treatment. OBJECTIVES: We aim to study the temporal change in clinical outcomes of the procedure at a single center. METHODS: We retrospectively studied 23 patients who underwent TMVR in MAC at Mayo Clinic from January, 14, 2014 to March, 15, 2019. Cases were divided into early (n = 11) and late (n = 12) experience. The primary end point was 30-day all-cause mortality. The secondary end points were immediate technical success, 30-day procedural success, and 1-year all-cause mortality. RESULTS: Mean age of patients was 75.2 ± 8.9 years and 17 (74.0%) were female. Median STS score for 30-day mortality was 8 (Interquartile range 4.3-13.4) for the entire population. Immediate technical success was achieved in 21 out of 23 patients (two failures in the early experience were related to tamponade and procedural death). Thirty-day procedural success was higher in the late experience (10 out of 12 patients) compared to early experience (5 out of 11 patients, p = .06). Four deaths in the first 30-days were observed in the early experience while all patients survived to hospital discharge in the late experience (p = .01). CONCLUSIONS: Procedural success and 30-day survival of transcatheter mitral valve replacement in severe mitral annular calcification procedure using balloon-expandable aortic prosthesis had improved over the years. This is likely attributed to significant advancement in procedural planning, valve design, and techniques.

Prevalence of mitral annular calcification and its association with mitral valvular disease.

BACKGROUND: Mitral annular calcification (MAC) is increasingly observed in elderly population. The purpose of this study was to investigate incidence of MAC and its association with mitral valvular disease (MVD). METHODS: A total of 13,483 consecutive patients who underwent echocardiography were enrolled. MAC was defined as an echo-dense, shelf-like structure with an irregular, lumpy appearance involving the mitral valve annulus, with acoustic shadowing. Prevalence of MAC and its association with significant mitral stenosis (MS) or mitral regurgitation (MR) were studied. Significant (≥moderate) MS was defined as mean transmitral valvular pressure gradient > 5 mm Hg and significant MR was defined as ≥moderate MR based on quantitative or semi-quantitative Doppler methods. RESULTS: MAC was present in 1881 of 13,483 patients (14%). Patients with MAC (MAC group) was older and more female gender than those without MAC (non-MAC group). Significant MS was present in 2.2% of MAC and in .6% of the non-MAC group (p < 0.0001). Significant MR was present in 11.9% of MAC and in 5.0% of the non-MAC group (p < 0.0001). Co-existence of MAC and aortic valve replacement (AVR) was associated with increased prevalence of MVD (MS:11.4%, MR:17.2%, respectively). CONCLUSION: MAC was present in 14% of the patients and was associated with significant MVD. Co-existence of MAC and AVR may increase the risk of MVD.

Caseous calcification of the mitral annulus: An under recognized differential diagnosis of mitral annular mass.

A 55-year-old obese, diabetic and hypertensive female patient with history of cerebrovascular stroke 2 years ago was referred for echocardiography. Transthoracic echocardiography revealed a well-defined rounded mass located at the posterior mitral annulus. The mass had a sharp hyperechoic outer border and a central echolucency. Transesophageal and three-dimensional echocardiography confirmed these findings consistent with caseous calcification of the mitral annulus. This case presents a rare variant of mitral annular calcification considered in the differential diagnosis of cardiac masses that can be recognized by its characteristic appearance on echocardiography. As with mitral annular calcification, multiple cardiovascular risk factors are commonly associated.

How to Manage Mitral Stenosis Due to Mitral Annular Calcification.

PURPOSE OF REVIEW: Mitral annular calcification (MAC) is associated with cardiovascular comorbidities and events and in the presence of mitral stenosis (MS) represents a high-risk cohort with limited treatment options. Emerging hybrid, minimally invasive, and transcatheter therapies that use circumferential MAC as an anchor for mitral valve replacement are emerging, but none are consistently associated with ideal outcomes. RECENT FINDINGS: In patients with MAC and nonrheumatic calcific mitral stenosis who are severely symptomatic, mitral intervention may be indicated. Surgical decalcification and replacement of the mitral valve remains the conventional therapy. Surgical techniques to avoid decalcification are being described including a left atrium to left ventricular apex graft conduit. Transcatheter balloon-expandable valves designed for the aortic valve have been implanted in the mitral position in MAC with a surgical direct transatrial transcatheter approach or transseptal transcatheter approach. Left ventricular outflow tract (LVOT) obstruction remains prevalent and associated with increased mortality. Direct transatrial approach allows for surgical resection of the anterior leaflet to mitigate this risk, and percutaneous therapies to lacerate the anterior leaflet or to ablate the basal septum are being developed. Cardiac computed tomography has emerged as a requisite for patient selection and procedural planning and has powerful predictive value for LVOT obstruction and valve embolization in valve-in-MAC. Novel transcatheter valves designed specifically for the mitral space are being studied in patients with MAC. MAC with mitral stenosis remains a challenging disease. Advances in technique, technology, and imaging may create new and reproducible treatment options with low procedural mortality for this challenging disease entity.

Intraoperative repair of mitral paravalvular leak with Amplatzer plug.

BACKGROUND AND AIM OF THE STUDY: Significant paravalvular leaks may complicate mitral valve replacement (MVR), especially in the setting of mitral annular calcification. Correction has been accomplished postoperatively by endovascular delivery of Amplatzer plugs (Abbott Medical) with good results. Intraoperative delivery of Amplatzer plugs at the index operation may reduce postoperative paravalvular leaks. METHODS: A retrospective review of eight patients who underwent placement of Amplatzer plugs for treatment of paravalvular leak during MVR at a single institution is reported. RESULTS: Seven patients had ≤1+ residual mitral valve insufficiency and one patient had 1-2+ residual mitral valve insufficiency intraoperatively by transesophageal echocardiogram. At 222 days average follow-up, echocardiogram revealed ≤ 1+ residual mitral valve insufficiency in all surviving patients. CONCLUSION: Intraoperative delivery of Amplatzer plugs for treatment of paravalvular leaks during MVR appears to be safe and effective at reducing postoperative mitral valve insufficiency.

Editorial comment: "Plug-In Hybrid"-Are we ready for this in heart valve surgery?

If we think about plug-in hybrids, the treatment of paravalvular leaks in cardiac surgery may not be the first thing that comes to mind. Yet, there appears to be an attractive analogy between the plug in hybrid car and an interventional device that may be "plugged in" intra-operatively to treat a paravalvular leak. Both technologies provide additional degrees of freedom to the fields, combine different technologies but may also be criticized for their increase in cost, introduction of new problems and their questionable practical need. We address this analogy based on a case series presented in this issue of the Journal of Cardiac Surgery.

Giant caseous mitral annular calcification mimicking ventricular pseudoaneurysm.

An 82-year-old woman with precordial pain at rest was admitted to the Emergency Department for possible cardiac heart disease; electrocardiogram excluded ischemia and high-sensitive troponin was normal. Echocardiogram revealed a hyperechoic mass adjacent to the mitral annulus. Electrocardiography-gated computed tomography (CT) angiography exam confirmed the presence of the mass protruding into the atrioventricular groove, adjacent to the posterior mitral. On the precontrast images the lesion was hyperdense with some scattered central calcific spots. CT findings are typical of a giant caseous calcification of the mitral annulus and excluded the diagnoses of pseudoaneurysm (it does not show any communication with the left ventricular cavity), neoplasm/abscess (complete caseous/calcified content) or infected/abscessified mitral calcification (absence of internal hypodense core). This is a benign condition that can be easily misdiagnosed as ventricular aneurysm or pseudoaneurysm on the contrast-enhanced images, when the caseous content is isodense to the iodinated blood pool.

Anatomic classification of mitral annular calcification for surgical and transcatheter mitral valve replacement.

BACKGROUND AND AIM OF THE STUDY: A systematic approach to quantify mitral annular calcification (MAC) in all-comers by multidetector computed tomography (MDCT) is essential to guide treatment, but lacking. METHODS: From September 2015 to July 2019, 82 patients with MAC underwent MDCT at two institutions to evaluate for surgical mitral valve replacement (SMVR), transcatheter mitral valve replacement (TMVR), or medical management. Type 1 MAC was defined as <270° annular calcium and Type 2 as ≥270°. Absence/presence of predicted left ventricular outflow tract (LVOT) obstruction with virtual valve placement was used to further define Type 2 MAC into 2A/B for our treatment algorithm. RESULTS: Type 1 MAC was present in 51.2%, Type 2A in 18.3%, and Type 2B in 30.5%. Operable Type 1 patients (50.0%) underwent hybrid transatrial TMVR or SMVR. Type 2A underwent a variety of treatments, and Type 2B surgical candidates (40.0%) underwent hybrid transatrial TMVR secondary to difficult suture anchoring with significant MAC and predicted LVOT obstruction. At a follow-up of 29.6 ± 12.0 months, mortality was 42.7% with 46.3% in the intervention group and 39.0% in the medical group (p = 0.47). All percutaneous TMVR patients expired. This translated to a disproportionate number of Type 2A deaths (80.0% with intervention), but all were high/extreme surgical risk. The hybrid TMVR group consisted of 95.0% Type 1/2B patients and had a lower Society of Thoracic Surgeons predicted risk of operative mortality (7.4% vs. 9.2%, p = 0.43)/mortality. CONCLUSIONS: The highest mortality was seen in percutaneous TMVR Type 2A MAC patients, but they were at the greatest risk. Here we provide an objective MAC treatment algorithm for all-comers based on operability/anatomy.

Prognostic importance of the transmitral pressure gradient in mitral annular calcification with associated mitral valve dysfunction.

AIMS: The aim of this study was to define the natural history of patients with mitral annular calcification (MAC)-related mitral valve dysfunction and to assess the prognostic importance of mean transmitral pressure gradient (MG) and impact of concomitant mitral regurgitation (MR). METHODS AND RESULTS: The institutional echocardiography database was examined from 2001 to 2019 for all patients with MAC and MG ≥3 mmHg. A total of 5754 patients were stratified by MG in low (3-5 mmHg, n = 3927), mid (5-10 mmHg, n = 1476), and high (≥10 mmHg, n = 351) gradient. The mean age was 78 ± 11 years, and 67% were female. MR was none/trace in 32%, mild in 42%, moderate in 23%, and severe in 3%. Primary outcome was all-cause mortality, and outcome models were adjusted for age, sex, and MAC-related risk factors (hypertension, diabetes, coronary artery disease, chronic kidney disease). Survival at 1, 5, and 10 years was 77%, 42%, and 18% in the low-gradient group; 73%, 38%, and 17% in the mid-gradient group; and 67%, 25%, and 11% in the high-gradient group, respectively (log-rank P < 0.001 between groups). MG was independently associated with mortality (adjusted HR 1.064 per 1 mmHg increase, 95% CI 1.049-1.080). MR severity was associated with mortality at low gradients (P < 0.001) but not at higher gradients (P = 0.166 and 0.372 in the mid- and high-gradient groups, respectively). CONCLUSION: In MAC-related mitral valve dysfunction, mean transmitral gradient is associated with increased mortality after adjustment for age, sex, and MAC-related risk factors. Concomitant MR is associated with excess mortality in low-gradient ranges (3-5 mmHg) but gradually loses prognostic importance at higher gradients, indicating prognostic utility of transmitral gradient in MAC regardless of MR severity.