Mitral Valve Prolapse and out-of-hospital cardiac arrest: A case report and literature review.

We present the case of a 44-year-old woman who suffered an out of hospital cardiorespiratory arrest. After six direct current shocks and 10 minutes of cardiopulmonary resuscitation she had return of spontaneous circulation and regained consciousness. Transthoracic echocardiography showed normal left ventricular ejection fraction and a mildly dilated left atrium. The mitral valve was thickened with myxomatous degeneration (Barlow’s disease) and moderate regurgitation secondary to bi-leaflet prolapse. Cardiac catheterization showed no coronary artery disease while left ventriculography revealed a mildly dilated left ventricle with preserved systolic function and high-end diastolic pressures. Cardiac MRI revealed an enlarged left ventricle with mitral valve (MV) prolapse and moderate to severe mitral regurgitation (MR). There were no features suggestive of a specific cardiomyopathy other than her valvular heart disease. The patient had an uneventful hospitalization, received an implantable cardioverter defibrillator (ICD), and eventually had MV repair surgery. A genetic investigation revealed two DNA variants, one each in the MYPN and TMPO gene, substitutions of highly conserved aminoacid residues. Family segregation could not establish unequivocally their pathogenicity although the MYPN variant represents the same residue that was shown previously to be substituted by another aminoacid. In this article we also review the literature regarding similar cases and record important data for the epidemiology of the disease and the important research that has been carried out in the identification of prognostic imaging factors and the genetic background of these patients.

Acute Heart Failure in a Patient with Occult Barlow’s Disease Receiving Bevacizumab

Bevacizumab is a recombinant humanized monoclonal antibody and a key drug for treatment of various types of cancer. Bevacizumab is associated with the occurrence of heart failure, but its risk factors remain unknown. A 55-year-old woman was diagnosed with cervical cancer, which was completely treated by bevacizumab-incorporated chemotherapy. During the 9-month bevacizumab therapy, she suffered from hypertension requiring multiple antihypertensive agents. She was admitted to our hospital due to acute heart failure with afterload mismatch and severe mitral regurgitation. A transesophageal echocardiography showed Barlow’s disease with a degenerated and widely prolapsed mitral valve. She received a scheduled surgical mitral valve repair. Post-operative cause was uneventful, but metastatic dissemination developed later. The existence of mitral valve regurgitation, even when sub-clinical, might be a risk of worsening heart failure during bevacizumab therapy. Careful follow-up at an onco-cardiology clinic is highly encouraged particularly for such a cohort during bevacizumab therapy.

Transesophageal Echocardiographic Assessment of the Repaired Mitral Valve: A Proposed Decision Pathway

The indications for mitral valve repair extend across the entire spectrum of degenerative mitral valve disease, ranging from fibroelastic degeneration to Barlow’s disease. Collaboration between the surgeon and anesthesiologist is essential for ensuring optimal results. Echocardiographic assessment of the repair can be challenging but is essential to the success of the procedure, as even mild residual mitral regurgitation can portend poor patient outcomes. In addition to determining the severity of residual regurgitation, the anesthesiologist must elucidate the mechanism of disease in order to inform appropriate re-intervention measures. Finally, there are unique complications of mitral valve surgery for the anesthesiologist to understand and assess by echocardiography. This review describes a systematic pathway for a comprehensive intraoperative assessment of the mitral valve following surgical repair.

Characterization of the Electrophysiological Substrate in Patients with Barlow's Disease

BACKGROUND. Myxomatous mitral valve prolapse (MVP) and mitral-annular disjunction (Barlow disease) are at-risk for ventricular arrhythmias (VA). Fibrosis involving the papillary muscles and/or the infero-basal left ventricular (LV) wall was reported at autopsy in sudden cardiac death (SCD) patients with MVP. METHODS AND RESULTS: Twenty-three patients with VA were enrolled, including five with syncope and four with a history of SCD. Electrophysiological parameters were correlated with VA patterns, ECG inferior negative T wave (nTW), and late gadolinium enhancement (LGE) assessed by cardiac magnetic resonance. Premature ventricular complex (PVC) burden was 12061.9±12994.6 /24 hours with a papillary-muscle type (PM-PVC) in 18 patients (68%). Twelve-lead ECG showed nTW in 12 patients (43.5%). A large Uni<8.3mV area (62.4+/- 45.5 cm2) was detected in the basal infero-lateral LV region in 12 (73%) patients, and in the papillary muscles (2.2+/-2.9 cm2) in 5 (30%) of 15 patients undergoing EAM. A concomitant Bi<1.5 mV area (5.0±1.0 cm2) was identified in 2 patients. A history of SCD, and the presence of nTW, and LGE were associated with a greater Uni<8.3mV extension: (32.8+/-3.1 cm2 vs. 9.2+/-8.7 cm2), nTW (20.1+/-11.0vs.4.1+/-3.8cm2), and LGE (19.2 ± 11.7 cm2 vs. 1.0 ± 2.0 cm2, p=0.013), respectively. All patients with PM-PVC had a Uni<8.3mV area. CONCLUSIONS: Low unipolar low voltage areas can be identified with EAM in the basal infero-lateral LV region and in the papillary muscles as a potential electrophysiological substrate for VA and SCD in patients with MVP and Barlow disease phenotype

Influence of Annular Dynamics and Material Behavior in Finite Element Analysis of Barlow’s Mitral Valve Disease

Barlow’s disease affects the entire mitral valve apparatus, by altering several of the fundamental mechanisms in the mitral valve which ensures unidirectional blood flow between the left atrium and the left ventricle. In this paper, a finite element model of a patient diagnosed with Barlow’s disease with patient-specific geometry and boundary conditions is presented. The geometry and boundary conditions are extracted from the echocardiographic assessment of the patient prior to surgery. Material properties representing myxomatous, healthy human and animal mitral valves are implemented and computed response are compared with each other and the echocardiographic images of the patient. This study shows that the annular dilation observed in Barlow’s patients controls several aspects of the mitral valve behavior during ventricular systole. The coaptation of the leaflets is observed to be highly dependent on annular dilation, and the coaptation area reduces rapidly at the onset of mitral regurgitation. Furthermore, the leaflet material implementation is important to predict lack of closure in the FE model correctly. It was observed that using healthy human material parameters in the Barlow’s diseased FE geometry gave severe lack of closure from the onset of mitral regurgitation, while myxomatous material properties showed a more physiological leakage.

Mitral valve regurgitation

The prevalence of mitral regurgitation (MR) is increasing in Western countries, which results in making it the second most frequent valvular heart disease requiring surgery. MR can be classified as primary (organic) or secondary (functional). Causes of primary MR consist of leaflet lesions, either degenerative changes (Barlow’s disease, fibroelastic degeneration, and annular calcification), rheumatic disease, or infective endocarditis. Causes of secondary MR consist of those that produce geometrical distortion of the subvalvular apparatus due to dilatation and remodelling of the left ventricle such as ischaemic heart disease and cardiomyopathies. The implementation of mitral valve repair as well as the rise of new transcatheter techniques, provided that are performed in experienced, high volume centres with the contribution of a valvular heart team, have impressively changed the prognosis of patients with severe MR. This has set new frontiers in the management of MR and has upgraded the role of imaging, creating new responsibilities, since its presence in every step of the procedure either preoperatively (quantification of MR, determination of the underlying mechanisms, investigation of reparability, determination of prognosis) or intra- and postoperatively, has been declared as fundamental.

Electrophysiological Substrate in Patients with Barlow’s Disease

Mitral valve prolapse (MVP) is the most common valvular heart disease, affecting 2–3% of the general population. Barlow’s disease is a clinical syndrome characterised by MVP. Initially thought a benign condition, MVP is now recognised as a cause of sudden cardiac death and ventricular arrhythmias. The development of new imaging techniques has contributed recently to the identification of novel risk factors. Catheter ablation of ventricular arrhythmias in patients affected by MVP is traditionally considered challenging. In this review, the authors summarise the evidence on arrhythmogenesis in the context of MVP, along with risk stratification of sudden cardiac death and the available treatment options, including new catheter ablation techniques.

PASCAL mitral valve repair system versus MitraClip: comparison of transcatheter edge-to-edge strategies in complex primary mitral regurgitation

Background The PASCAL system is a novel device for edge-to-edge treatment of mitral regurgitation (MR). The aim of this study was to compare the safety and efficacy of the PASCAL to the MitraClip system in a highly selected group of patients with complex primary mitral regurgitation (PMR) defined as effective regurgitant orifice area (MR-EROA) ≥ 0.40 cm2, large flail gap (≥ 5 mm) or width (≥ 7 mm) or Barlow’s disease. Methods 38 patients with complex PMR undergoing mitral intervention using PASCAL (n = 22) or MitraClip (n = 16) were enrolled. Primary efficacy endpoints were procedural success and degree of residual MR at discharge. The rate of major adverse events (MAE) according to the Mitral Valve Academic Consortium (MVARC) criteria was chosen as the primary safety endpoint. Results Patient collectives did not differ relevantly regarding pertinent baseline parameters. Patients` median age was 83.0 [77.5–85.3] years (PASCAL) and 82.5 [76.5–86.5] years (MitraClip). MR-EROA at baseline was 0.70 [0.68–0.83] cm2 (PASCAL) and 0.70 [0.50–0.90] cm2 (MitraClip), respectively. 3D-echocardiographic morphometry of the mitral valve apparatus revealed no relevant differences between groups. Procedural success was achieved in 95.5% (PASCAL) and 87.5% (MitraClip), respectively. In 86.4% of the patients a residual MR grade ≤ 1 + was achieved with PASCAL whereas reduction to MR grade ≤ 1 + with MitraClip was achieved in 62.5%. Neither procedure time number of implanted devices, nor transmitral gradient differed significantly. No periprocedural MAE according to MVARC occured. Conclusion In this highly selected patient group with complex PMR both systems exhibited equal procedural safety. MitraClip and PASCAL reduced qualitative and semi-quantitative parameters of MR to an at least comparable extent. Graphic abstract

Minimally-invasive mitral valve repair of symmetric and asymmetric Barlow´s disease

Objectives Barlow´s disease represents a wide spectrum of mitral valve pathologies associated with regurgitation (MR), excess leaflet tissue, and prolapse. Repair strategies range from complex repairs with annuloplasty plus neochords through resection to annuloplasty-only. The latter requires symmetric prolapse patterns and central regurgitant jets. We aimed to assess repair success and durability, survival, and intraoperative outcomes with symmetric and asymmetric Barlow’s disease. Methods Between 09/10 and 03/20, 103 patients (of 1939 with mitral valve surgery) presented with Barlow´s disease. All received surgery through mini-thoracotomy with annuloplasty plus neochords (n = 71) or annuloplasty-only (n = 31). One valve was replaced for endocarditis (repair rate: 99%). Results Annuloplasty-only patients were older (64 ± 16 vs. 55 ± 11 years, p = 0.008) and presented with higher risk (EuroSCORE II: 4.2 ± 4.9 vs. 1.6 ± 1.7, p = 0.007). Annuloplasty-only patients had shorter cross-clamp times (53 ± 18 min vs. 76 ± 23 min, p < 0.001) and received more tricuspid annuloplasty (15.5% vs. 48.4%, p < 0.001). Operating times were similar (170 ± 41 min vs. 164 ± 35, p = 0.455). In three patients, annuloplasty-only caused intraoperative systolic anterior motion (SAM), which was fully resolved by neochords to the posterior leaflet. There were no conversions to sternotomy or deaths at 30-days. Three patients required reoperation for recurrent MR (at 25 days, 2.8 and 7.8 years). At the latest follow-up, there was no MR in 81.4%, mild in 14.7%, and moderate in 2.9%. Three patients died due to non-cardiac reasons. Surviving patients report the absence of relevant symptoms. Conclusions Minimally-invasive Barlow’s repair is safe with good durability. Annuloplasty-only may be a simple solution for complex but symmetric pathologies. However, it may carry an increased risk of intraoperative SAM.