Degenerative Mitral Stenosis: From Pathophysiology to Challenging Interventional Treatment.

Mitral stenosis (MS) is characterized by obstruction of left ventricular inflow as a result of narrowing of the mitral valve orifice. Although its prevalence has declined over the last decade, especially in developed countries, it remains an important cause of morbidity and mortality.  The most often cause of MS worldwide is still postrheumatic mitral valve disease. However, in developed countries, degenerative or calcific changes cause MS in a siginificant proportion of patients. Although the range of treatment for mitral valve disease has grown over the years in parallel with transcatheter therapies for aortic valve disease, these improvements in mitral valve disease therapy have experienced slower development. This is mainly due to the more complex anatomy of the mitral valve and entire mitral apparatus, and the interplay of the mitral valve with the left ventricle which hinders the development of effective implantable mitral valve devices. This is especially the case with degenerative MS where percutaneous or surgical comissurotomy is rarely employed due to the presence of extensive annular calcification and at the base of leaflets, without associated commissural fusion. However, the last few years have witnessed innovations in transcatheter interventional procedures for degenerative MS which consequently hinted that in the future, transcatheter mitral valve replacement could be the treatment of choice for these patients.

Patient Disposition and Clinical Outcome After Referral to a Dedicated TAVI Clinic.

Introduction: Transcatheter aortic valve implantation (TAVI) is the standard of care for the majority of patients with severe symptomatic aortic stenosis (AS) at excessive-, high- and intermediate-surgical risk. A proportion of patients referred for TAVI do not undergo the procedure and proceed with an alternate treatment strategy. There is scarce data describing the final treatment allocation of such patients. Hence, we sought to evaluate the final treatment allocation of patients referred for TAVI in contemporary practice. Methods: We performed a single center prospective observational study, including all patients referred to our institution for treatment of severe aortic stenosis between February 2014 and August 2017. Baseline demographic and clinical data were recorded. Patients were categorized according to treatment allocation: TAVI, surgical aortic valve replacement (SAVR) or optimal medical therapy (OMT). Clinical outcomes were adjudicated according to VARC-2 definitions. All patients were discussed at a dedicated Heart Team meeting. Results: Total of 245 patients were referred for assessment to a dedicated TAVI clinic during the study period. Patients with moderate (N = 32; 13.1%) and asymptomatic (N = 31; 13.1%) AS were excluded. Subsequently, 53.9% (N = 132) received TAVI, 12.7% (N =31) were managed with OMT, and 7.3% (N =18) had SAVR. Reasons for OMT included primarily: patient's preference (N = 12; 38.7%); excessive surgical risk (N = 4; 12.9%) and severe frailty (N = 5; 16.1%). Reasons for surgical referral included low surgical risk (N = 11; 61.1%), excessive annulus size (N = 5; 27.8%), and aortic root dilatation (N = 2; 11.1%). Patients proceeding to SAVR had lower surgical risk than those in either the OMT or TAVI cohorts (P < 0.001). Mean STS score in SAVR group was 2.2 ± 1.3 vs. 4.5 ± 2.4 in OMT cohort and 6.1 ± 4.9 in TAVI cohort. Six-month all-cause mortality was 16.7, 19.4, and 9.3% among those receiving SAVR, OMT, and TAVI, respectively. Conclusions: Almost half of all patients with severe AS referred to a dedicated TAVI clinic did not receive a TAVI. A considerable proportion of patients were reclassified as moderate AS (13%), were asymptomatic (13%), or intervention was determined to be futile (13%) due to advanced frailty. Early detection and increased awareness of valvular heart disease are required to increase the number of patients that can benefit from TAVI.

A severe penetrating cardiac injury in the absence of cardiac tamponade.

Penetrating cardiac injury is rare and frequently not survivable. Significant haemorrhage resulting in cardiac tamponade commonly ensues. Such cardiac tamponade is a clear clinical, radiological and sonographic indicator of significant underlying injury. In the absence of cardiac tamponade, diagnosis can be more challenging. In this case of a 26-year old sailor stabbed at sea, a significant pericardial effusion and cardiac tamponade did not occur despite an injury transversing the pericardium. Instead, the pericardial haemorrhage drained into the left pleural cavity resulting in a haemothorax. This case is notable due to a favourable outcome despite a delay in diagnosis due to a lack of pericardial effusion, a concomitant cerebrovascular event and a long delay from injury to appropriate medical treatment in the presence of a penetrating cardiac wound deep enough to cause a muscular ventricular septal defect and lacerate a primary chordae of the anterior mitral leaflet.

Brief hypoxia conditions monocytes to protect reperfused cardiocytes against cell death via the CD11b receptor.

BACKGROUND: Traditionally leukocytes have been viewed as the mediators and effectors of cell injury after tissue ischemia and reperfusion through the indiscriminate release of toxic cytokines and oxygen free radicals. This can be detrimental to functioning of the transplanted heart when reperfused after implantation. Paradoxically, evidence now suggests that certain cytotoxic cytokines and even oxygen free radicals can be cytoprotective in smaller concentrations. This study sought to determine whether cultured human monocytes can be pre-conditioned by brief hypoxia to protect cardiomyocytes from cell death after hypoxia and re-oxygenation. METHODS: Cultured human monocytes were exposed to transient hypoxia (10 minutes), after which we determined CD11b expression using flow cytometry. The 3 control groups comprised immunoglobulin G-negative controls, fMLP-positive controls, and virgin monocyte (VM) controls. We studied chick embryonic ventricular myocytes in a flow-through chamber while controlling flow rate, pH, O(2), and CO2 tension. We quantified cardiomyocyte viability using propidium iodide (5 micromol/liter). Cell systems of cardiomyocytes alone, cardiomyocytes and VM, human monocytes exposed to transient hypoxia before coculture with cardiomyocytes (PCHM-cardiomyocyte), and PCHM cocultured with anti-CD11b antibodies for 30 minutes before coculture with cardiomyocytes (CDHM-cardiomyocyte) were subjected to 1 hour of hypoxia and 3 hours of re-oxygenation, and cell death was determined. The experiment was repeated and the cell systems fixed, stained, and examined for monocytes adhering to cardiomyocytes. RESULTS: CD11b expression increased significantly with both transient hypoxia and fMLP (18.39% +/- 4.116%, n = 5, and 37.04% +/- 7.783%, n = 5, respectively, p < 0.05 vs VM 100%, n = 5). Coculture of cardiomyocytes with VM had no effects on cardiocyte death (40.6% +/- 6.1%, n = 6) compared with controls (46.5% +/- 4.0%, n = 10). The PCHM cocultured with cardiomyocytes significantly decreased cardiomyocyte death (25.2% +/- 4.7%, n = 6, p < 0.05). This protection was abrogated by the addition of CD11b-blocking antibodies to PCHM before coculture with cardiomyocytes (51.0% +/- 6.1%, n = 6, p < 0.05). The PCHM showed increased adhesion to cardiomyocytes (5.4 +/- 0.38/high-power [HP] field vs 0.67 +/- 0.24/HP field in VM, p < 0.05). The increased adhesion was abolished by CD11b-blocking antibody (0.78 +/- 0.28 vs 0.67 +/- 0.24 cells/HP field, p < 0.05). CONCLUSIONS: These results suggest that monocytes activated by transient hypoxia protect cardiomyocytes during hypoxia and re-oxygenation through expression of CD11b receptors. These cells seem to adhere to myocytes through this receptor to achieve this effect. The exact mechanism is unclear and requires further study. Autologous recipient monocytes may be pre-conditioned to protect the donor heart during reperfusion.