RNA sequencing provides novel insights into the pathogenesis of naturally occurring myxomatous mitral valve disease stage B1 in beagle dogs.

Myxomatous mitral valve disease (MMVD) is the most common cardiovascular disorder in dogs with a high prevalence, accounting for approximately 75% of all canine heart disease cases. MMVD is a complex disease and shows variable progression from mild valve leakage to severe regurgitation, potentially leading to heart failure. However, the molecular mechanisms and age-related changes that govern disease progression, especially at the early stage (B1) before the development of discernable clinical signs, remain poorly understood. In this prospective study, we aimed to compare gene expression differences between blood samples of aged beagle dogs with stage B1 MMVD and those of healthy controls using RNA sequencing. Clinical evaluation was also conducted, which revealed minimal differences in radiographic and echocardiographic measurements despite distinct biomarker variations between the two groups. Comparative transcriptomics revealed differentially expressed genes associated with extracellular matrix remodeling, prostaglandin metabolism, immune modulation, and interferon-related pathways, which bear functional relevance for MMVD. In particular, the top 10 over- and under-expressed genes represent promising candidates for influencing pathogenic changes in MMVD stage B1. Our research findings, which include identified variations in clinical markers and gene expression, enhance our understanding of MMVD. Furthermore, they underscore the need for further research into early diagnosis and treatment strategies, as, to the best of our knowledge, no prior studies have explored the precise molecular mechanisms of stage B1 in MMVD through total RNA sequencing.

Anomalous circumflex artery encircling the aortic annulus: implications for mitral valve repair.

Injury to coronary arteries during mitral surgery is a rare but life-threatening procedural complication, an anomalous origin and course of the left circumflex artery (LCx) increase this risk. Recognizing the anomaly by the characteristic angiographic pattern and identifying its relationship with the surrounding anatomical structure using imaging techniques, mainly transesophageal echocardiography (TOE) or coronary computed tomography angiography (CCTA), is of crucial importance in setting up the best surgical strategy. We report a case of anomalous origin of a circumflex artery (LCx) from the proximal portion of the right coronary artery (RCA) with a pathway running retroaortically through the mitro-aortic space. An integrated diagnostic approach using a multidisciplinary team with a cardiologist and an imaging radiologist allowed us to decide the surgical strategy. We successfully performed a mitral valvular repair using a minimally invasive minithoracotomic approach and implanting a complete semirigid ring.

Delayed Diagnosis of Pulmonary Artery Thrombosis in a Patient Undergoing Mitral Valve Replacement.

ABSTRACT: The occurrence of pulmonary artery thrombus in association with rheumatic mitral stenosis is a rare complication. Pulmonary artery thrombus formation may worsen pulmonary artery pressures, and this may precipitate acute right heart failure. The possible mechanisms behind pulmonary artery thrombus formation during mitral valve replacement surgery could be acute coagulopathy following surgery, the presence of chronic pulmonary thromboembolism, or chronic atrial fibrillation. We report an unusual case of pulmonary artery thrombus in a patient with rheumatic MS which was diagnosed with transoesophageal echocardiography after MVR.

Congenital Sub-Mitral Aneurysm: Anesthetics and Surgical Management.

ABSTRACT: A sub-mitral left ventricular aneurysm is a rare condition. It is a congenital outpouching of the left ventricular wall, invariably occurring adjacent to the posterior mitral leaflet. Sub-mitral aneurysm (SMA) has usually been reported as a consequence of myocardial ischemia (MI), rheumatic heart disease, tuberculosis, and infective endocarditis. Nevertheless, there have been few case reports of congenital SMA in India. It usually presents with symptoms of heart failure. We report a rare case of congenital SMA in a 27-year-old young Indian and its successful management through a trans-aneurysmal approach.

[Redo Mitral Valve Replacement for Prosthetic Valve Endocarditis in a Patient with End Stage Colon Cancer:Report of a Case].

Prosthetic valve endocarditis (PVE) is rare but devastating. A 69-year old man admitted for active endocarditis caused by Streptococcus pasteurianus. Antibiotic therapy was started, but the patient developed bowel obstruction owing to cancer with multiple liver metastases, and underwent transverse colectomy. Following colectomy, antibiotic agent was given continued for 4 weeks after and mitral valve replacement( MVR) using a bioprosthesis was performed. Oral antibiotic therapy was continued for six months after MVR to avoid infection recurrence. One year after MVR, the size of multiple liver metastases increased despite oral anticancer drugs administration. A totally implantable central venous access port( CV port) was placed and intravenous chemotherapy was started for progressive metastatic colorectal cancer. But the CV port was removed due to device infection caused by multiple drug resistant Staphyrococcus lugdunensis one month later, but the patient developed prosthetic valve endocarditits( PVE) due to the same bacterium, that caused valve stenosis. Redo MVR was indicated because of progressive dyspnea and uncontrollable fever. The patient was discharged one month after redo MVR, but suffered carcinomatous peritonitis, and eventually died eight months post-discharge. Chemotherapy needs caution because of potential risk of PVE in patients with prosthetic valves, especially for those with a history of infectious endocarditis.

Phosphoproteomics analysis of serum from dogs affected with pulmonary hypertension secondary to degenerative mitral valve disease.

Pulmonary hypertension (PH), a common complication in dogs affected by degenerative mitral valve disease (DMVD), is a progressive disorder characterized by increased pulmonary arterial pressure (PAP) and pulmonary vascular remodeling. Phosphorylation of proteins, impacting vascular function and cell proliferation, might play a role in the development and progression of PH. Unlike gene or protein studies, phosphoproteomic focuses on active proteins that function as end-target proteins within signaling cascades. Studying phosphorylated proteins can reveal active contributors to PH development. Early diagnosis of PH is crucial for effective management and improved clinical outcomes. This study aimed to identify potential serum biomarkers for diagnosing PH in dogs affected with DMVD using a phosphoproteomic approach. Serum samples were collected from healthy control dogs (n = 28), dogs with DMVD (n = 24), and dogs with DMVD and PH (n = 29). Phosphoproteins were enriched from the serum samples and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Data analysis was performed to identify uniquely expressed phosphoproteins in each group and differentially expressed phosphoproteins among groups. Phosphoproteomic analysis revealed nine uniquely expressed phosphoproteins in the serum of dogs in the DMVD+PH group and 15 differentially upregulated phosphoproteins in the DMVD+PH group compared to the DMVD group. The phosphoproteins previously implicated in PH and associated with pulmonary arterial remodeling, including small nuclear ribonucleoprotein G (SNRPG), alpha-2-macroglobulin (A2M), zinc finger and BTB domain containing 42 (ZBTB42), hemopexin (HPX), serotransferrin (TRF) and complement C3 (C3), were focused on. Their unique expression and differential upregulation in the serum of DMVD dogs with PH suggest their potential as biomarkers for PH diagnosis. In conclusion, this phosphoproteomic study identified uniquely expressed and differentially upregulated phosphoproteins in the serum of DMVD dogs with PH. Further studies are warranted to validate the diagnostic utility of these phosphoproteins.

Transcatheter Mitral Valve Repair With the MitraClip Device for Prior Mitral Valve Repair Failure: Insights From the GIOTTO-FAILS Study.

BACKGROUND: Minimally invasive mitral valve repair has a favorable risk-benefit profile in patients with significant de novo mitral regurgitation. Its role in patients with prior mitral valve repair is uncertain. We aimed to appraise the outcome of patients undergoing transcatheter edge-to-edge repair (TEER) with prior transcatheter or surgical mitral valve repair (SMVR). METHODS AND RESULTS: We queried the Italian multicenter registry on TEER with MitraClip, distinguishing naïve patients from those with prior TEER or (SMVR). Inhospital and long-term clinical/echocardiographic outcomes were appraised. The primary outcome was the occurrence of death or rehospitalization for heart failure. A total of 2238 patients were included, with 2169 (96.9%) who were naïve to any mitral intervention, 29 (1.3%) with prior TEER, and 40 (1.8%) with prior SMVR. Several significant differences were found in baseline clinical and imaging features. Respectively, device success was obtained in 2120 (97.7%), 28 (96.6%), and 38 (95.0%, P=0.261) patients; procedural success in 2080 (95.9%), 25 (86.2%), and 38 (95.0%; P=0.047); and inhospital death in 61 (2.8%), 1 (3.5%), and no (P=0.558) patients. Clinical follow-up after a mean of 14 months showed similar rates of death, cardiac death, rehospitalization, rehospitalization for heart failure, and their composite (all P>0.05). Propensity score-adjusted analysis confirmed unadjusted analysis, with lower procedural success for the prior TEER group (odds ratio, 0.28 [95% CI, 0.09-0.81]; P=0.019) but similar odds ratios and hazard ratios for all other outcomes in the naïve, TEER, and SMVR groups (all P>0.05). CONCLUSIONS: In carefully selected patients, TEER can be performed using the MitraClip device even after prior TEER or SMVR.

Iron parameters analysis in dogs with myxomatous mitral valve disease.

BACKGROUND: Myxomatous mitral valve disease (MMVD) is the most common acquired cardiovascular disease in small breed dogs. In contrast to human patients with heart failure (HF), iron deficiency (ID) prevalence in dogs with MMVD is weakly known. The study aimed to assess the usability of ID markers in serum and reticulocyte parameters from whole blood of dogs with MMVD to evaluate early ID symptoms. RESULTS: Sixty-eight dogs (43 male and 25 female) were included in the study. MMVD dogs were assigned according to the 2019 ACVIM guidelines for groups B1 (n = 9), B2 (n = 10), C (n = 27) and D (n = 10). Groups were also combined into B1 and B2 as non-symptomatic HF and C with D as symptomatic HF. Healthy controls were 12 dogs. Serum iron concentration below the reference range in dogs with MMVD was 12.5%. Other ID indices, such as %SAT, UIBC, and TIBC were similar in the MMVD groups and healthy controls (p > 0.05 for all parameters). Statistical comparison between control group and 4 groups of different stages of MMVD showed that significant differences occur only in serum transferrin. The assessment of ferritin and soluble transferrin receptors using Western Blotting did not show differences between control (n = 7) and MMVD (n = 33) dogs. Study has shown positive correlation between ID parameters and echocardiographic indices such as LA/Ao and LVIDdN, and some biochemical parameters. A significant increase in reticulocytes percentage, assessed manually, was observed in the HF group of animals (p = 0.027) compared to the control group. CONCLUSIONS: Studies have shown that ID parameters in serum are not significantly different in dogs with MMVD compared to healthy dogs. However, there is a clear correlation between atrial size and normalised left ventricular size to body size and some biochemical parameters, including ID parameters and therefore the severity of MMVD.

Computer-Assisted Transcatheter Mitral Valve Implantation for Valve-in-Valve Procedures.

Transcatheter mitral valve-in-valve is an alternative to high-risk reoperation on a failing bioprosthesis. It entails specific challenges such as left ventricular outflow tract obstruction. We propose a patient-specific augmented imaging based on preoperative planning to assist the procedure. Valve-in-valve simulation was performed to represent the optimal level of implantation and the neo-left ventricular outflow tract. These data were combined with intraoperative images through a real-time 3D/2D registration tool. All data were collected retrospectively on one case (pre and per-procedure imaging). We present for the first time an intraoperative guidance tool in transcatheter mitral valve-in-valve procedure.

Model for predicting the recurrence of atrial fibrillation after monopolar or bipolar radiofrequency ablation in patients with AF and mitral valve disease.

OBJECTIVES: This study aimed to identify the risk factors for postoperative atrial fibrillation in patients with valvular atrial fibrillation, and establish predictive models of atrial fibrillation recurrence. METHODS: Overall, 224 patients who underwent radiofrequency ablation of atrial fibrillation from November 2014 to November 2020 were included. The statistical package for social sciences, X-tile, and R-studio were used for statistical analysis. RESULTS: Patients were divided into training and validation sets according to a ratio of 3:1. The training set was analysed using univariate and multivariate Cox regression analysis and showed that preoperative uric acid > 401 µmol/L (P = 0.006), B-type natriuretic peptide > 202 ng/L (P = 0.042), hypersensitivity C-reactive protein > 6.1 mg/L (P = 0.026), erythrocyte sedimentation rate > 7.0 mm/h (P = 0.016), preoperative left atrial diameter > 48 mm (P = 0.031) were significantly correlated with the recurrence of atrial fibrillation after radiofrequency ablation in patients with valvular atrial fibrillation. In the training set, a Cox regression model of the five related factors was established using the R language. The C-index of the model was 0.82, and the area under the receiver operating characteristic curve was 0.831 (P < 0.001). Internal and external verification was performed in the training and validation sets, respectively, and both showed that the fit of the verification curve was relatively good at 3 months, 6 months, 1 year, and 3 years postoperatively. After calculating the weight of each related factor using the nomogram, a new risk predictive model (BLUCE) for postoperative atrial fibrillation was established. CONCLUSIONS: In patients with atrial fibrillation, preoperative uric acid, B-type natriuretic peptide, hypersensitivity C-reactive protein, erythrocyte sedimentation rate, and left atrial diameter are risk factors for atrial fibrillation or atrial flutter recurrence after radiofrequency ablation. The BLUCE predictive model can distinguish high-risk groups of postoperative atrial fibrillation. High-risk patients in the BLUCE model were more likely to experience recurrence of atrial fibrillation after radiofrequency ablation and a low possibility of maintaining sinus rhythm.

Blending three repair techniques in a case of complex mitral valve endocarditis.

In a 39-year-old male with mitral valve endocarditis, after 6 weeks of intravenous antibiotics, echocardiography confirmed multiple vegetations on both leaflets, a flail posterior leaflet flail and contained perforation of the anterior leaflet in a windsock-like morphology. All vegetations, diseased and ruptured chords and the windsock-like contained rupture of the anterior leaflet were carefully resected via a right minithoracotomy and with femoral cannulation. Three repair techniques were blended to reconstruct the valve: (1) A large, infected portion of the prolapsing posterior leaflet was resected in a triangular fashion, and the edges were re-approximated using continuous 5-0 polypropylene sutures. (2) The anterior leaflet defect was repaired with a circular autologous pericardial patch that had been soaked in glutaraldehyde. (3) A set of artificial chords for P2 was created using CV-4 polytetrafluoroethylene sutures and adjusted under repeated saline inflation. A 38-mm Edwards Physio-I annuloplasty ring was implanted. The artificial chords were adjusted again after annuloplasty and then tied. Transoesophageal echocardiography (TEE) confirmed the absence of residual mitral regurgitation and systolic anterior motion and a mean pressure gradient of 3 mmHg. The patient was discharged after 5 days with a peripherally inserted central catheter to complete an additional 4 weeks of intravenous antibiotics and had an uneventful recovery.

Complications of transcatheter paravalvular leak device closure of mitral valve: An updated review of the literature and a rare case presentation.

Paravalvular leak (PVL) is an uncommon complication of prosthetic valve implantation, which can lead to infective endocarditis, heart failure, and hemolytic anemia. Surgical reintervention of PVLs is associated with high mortality rates. Transcatheter PVL closure (TPVLc) has emerged as an alternative to surgical reoperation. This method provides a high success rate with a low rate of complications. This article reviews the pathogenesis, clinical manifestation, diagnosis, and management of PVL and complications following TPVLc. Besides, we presented a case of a patient with severe PVL following mitral valve replacement, who experienced complete heart block (CHB) during TPVLc. The first TPVLc procedure failed in our patient due to possible AV-node insult during catheterization. After 1 week of persistent CHB, a permanent pacemaker was implanted. The defect was successfully passed using the previous attempt. Considering the advantages of TPVLc, procedure failure should be regarded as a concern. TPVLc should be performed by experienced medical teams in carefully selected patients.

In vivo mitral valve repair for the transplanted donor heart in orthotopic heart transplantation.

A 53-year-old woman with the dilated phase of hypertrophic cardiomyopathy underwent orthotopic heart transplantation. The donor heart was evaluated as normal preoperatively without mitral regurgitation or the left atrium dilation, transplanted using the modified bicaval technique. Although the heart beat satisfactorily after aortic declamping, massive mitral regurgitation was observed without any prolapse or annular dilation. Because of the difficulty in weaning from cardiopulmonary bypass, a second aortic cross-clamp was applied, and we detached the inferior vena cava and the right side of the left atrial anastomosis to approach the mitral valve, obtaining a satisfactory exposure. No abnormalities were observed in the mitral valve leaflets, annulus or subvalvular apparatus. Subsequent in vivo mitral annuloplasty using prosthetic full ring successfully controlled the regurgitation, and the patient was easily weaned from cardiopulmonary bypass. She discharged to home with good mitral valve and cardiac functions. And the patient has been doing well without any recurrence of MR or heart failure for over a year after surgery.

Contemporary 1-Year Outcomes of Mitral Valve-in-Ring With Balloon-Expandable Aortic Transcatheter Valves in the U.S.

BACKGROUND: Adequate valve performance after surgical mitral valve repair with an annuloplasty ring is not always sustained over time. The risk of repeat mitral valve surgery may be high in these patients. Transcatheter mitral valve-in-ring (MViR) is emerging as an alternative for high-risk patients. OBJECTIVES: The authors sought to assess contemporary outcomes of MViR using third-generation balloon-expandable aortic transcatheter heart valves. METHODS: Patients who underwent MViR and were enrolled in the STDS/ACC TVT (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy) Registry between August 2015 and December 2022 were analyzed. RESULTS: A total of 820 patients underwent MViR at 236 sites, mean age was 72.2 ± 10.4 years, 50.9% were female, mean STS score was 8.2% ± 6.9%, and most (78%) were in NYHA functional class III to IV. Mean left ventricular ejection fraction was 47.8% ± 14.2%, mean mitral gradient was 8.9 ± 7.0 mm Hg, and 75.5% had ≥ moderate mitral regurgitation. Access was transseptal in 93.9% with 88% technical success. All-cause mortality at 30 days was 8.3%, and at 1 year, 22.4%, with a reintervention rate of 9.1%. At 1-year follow-up, 75.6% were NYHA functional class I to II, Kansas City Cardiomyopathy Questionnaire score increased by 25.9 ± 29.1 points, mean mitral valve gradient was 8.4 ± 3.4 mm Hg, and 91.7% had ≤ mild mitral regurgitation. CONCLUSIONS: MViR with third-generation balloon-expandable aortic transcatheter heart valves is associated with a significant reduction in mitral regurgitation and improvement in symptoms at 1 year, but with elevated valvular gradients and a high reintervention rate. MViR is a reasonable alternative for high-risk patients unable undergo surgery who have appropriate anatomy for the procedure. (STS/ACC TVT Registry Mitral Module [TMVR]; NCT02245763).

Mitral Valve Transcatheter Edge-to-Edge Repair: 1-Year Outcomes From the MiCLASP Study.

BACKGROUND: Mitral transcatheter edge-to-edge repair (M-TEER) is a guideline-recommended treatment option for patients with severe symptomatic mitral regurgitation (MR). Outcomes with the PASCAL system in a post-market setting have not been established. OBJECTIVES: The authors report 30-day and 1-year outcomes from the MiCLASP (Transcatheter Repair of Mitral Regurgitation with Edwards PASCAL Transcatheter Valve Repair System) European post-market clinical follow-up study. METHODS: Patients with symptomatic, clinically significant MR were prospectively enrolled. The primary safety endpoint was clinical events committee-adjudicated 30-day composite major adverse event rate and the primary effectiveness endpoint was echocardiographic core laboratory-assessed MR severity at discharge compared with baseline. Clinical, echocardiographic, functional, and quality-of-life outcomes were assessed at 1 year. RESULTS: A total of 544 patients were enrolled (59% functional MR, 30% degenerative MR). The 30-day composite major adverse event rate was 6.8%. MR reduction was significant from baseline to discharge and sustained at 1 year with 98% of patients achieving MR ≤2+ and 82.6% MR ≤1+ (all P < 0.001 vs baseline). One-year Kaplan-Meier estimate for survival was 87.3%, and freedom from heart failure hospitalization was 84.3%. Significant functional and quality-of-life improvements were observed at 1 year, including 71.6% in NYHA functional class I/II, 14.4-point increase in Kansas City Cardiomyopathy Questionnaire score, and 24.2-m improvement in 6-minute walk distance (all P < 0.001 vs baseline). CONCLUSIONS: One-year outcomes of this large cohort from the MiCLASP study demonstrate continued safety and effectiveness of M-TEER with the PASCAL system in a post-market setting. Results demonstrate high survival and freedom from heart failure hospitalization, significant and sustained MR reduction, and improvements in symptoms, functional capacity, and quality of life.