Fractional Flow Reserve to Assess Coronary Artery Disease in Patients with Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation: Long-Term Outcomes.

Background: The long-term outcomes of patients undergoing functional assessment of coronary lesions with fractional flow reserve (FFR) while awaiting transcatheter aortic valve implantation (TAVI) are unknown. Data on the safety of intracoronary adenosine use in this setting are scarce. The objectives of this study were to describe (1) the long-term outcomes based on the coronary artery disease (CAD) assessment strategy used and (2) the safety of intracoronary adenosine in patients with severe aortic stenosis (AS). Methods: 1023 patients with severe AS awaiting TAVI were included. Patients were classified according to their CAD assessment strategy: angiography guided or FFR guided. Patients were further subdivided according to the decision to proceed with percutaneous coronary intervention (PCI): angiography-guided PCI (375/1023), angiography-guided no-PCI (549/1023), FFR-guided PCI (50/1023), and FFR-guided no-PCI (49/1023). Patients were followed up for the occurrence of major adverse cardiac and cerebrovascular events (MACCEs). Results: At a mean follow-up of 33.7 months, we observed no significant differences in terms of major adverse cardiovascular and cerebrovascular events (MACCE) in the angiography-guided group (42.4%) compared with the FFR-guided group (37.4%) (p = 0.333). When comparing outcomes of the FFR-guided no-PCI group (32.7%) with the angiography-guided PCI group (46.4%), no significant difference was noted (p = 0.999). Following intracoronary adenosine, a single adverse event occurred. Conclusions: In this population, intracoronary adenosine is safe and well tolerated. We found no significant benefit to an FFR-guided strategy compared with an angiography-guided strategy with respect to MACCEs. Although clinically compelling, avoiding the procedural risks of PCI by deferring the intervention in functionally insignificant lesions failed to show a statistically significant benefit.

Effects of Cyproheptadine on Mitral Valve Remodeling and Regurgitation After Myocardial Infarction.

BACKGROUND: Ischemic mitral regurgitation (MR) is primarily caused by left ventricle deformation, but leaflet thickening with fibrotic changes are also observed in the valve. Increased levels of 5-hydroxytryptamine (5-HT; ie, serotonin) are described after myocardial infarction (MI); 5-HT can induce valve fibrosis through the 5-HT type 2B receptor (5-HT2BR). OBJECTIVES: This study aims to test the hypothesis that post-MI treatment with cyproheptadine (5-HT2BR antagonist) can prevent ischemic MR by reducing the effect of serotonin on mitral biology. METHODS: Thirty-six sheep were divided into 2 groups: inferior MI and inferior MI treated with cyproheptadine (0.5 mg/kg/d). Animals were followed for 90 days. Blood 5-HT, infarct size, left ventricular volume and function, MR fraction and mitral leaflet size were assessed. In a complementary in vitro study, valvular interstitial cells were exposed to pre-MI and post-MI serum collected from the experimental animals. RESULTS: Increased 5-HT levels were observed after MI in nontreated animals, but not in the group treated with cyproheptadine. Infarct size was similar in both groups (11 ± 3 g vs 9 ± 5 g; P = 0.414). At 90 days, MR fraction was 16% ± 7% in the MI group vs 2% ± 6% in the cyproheptadine group (P = 0.0001). The increase in leaflet size following MI was larger in the cyproheptadine group (+40% ± 9% vs +22% ± 12%; P = 0.001). Mitral interstitial cells overexpressed extracellular matrix genes when treated with post-MI serum, but not when exposed to post-MI serum collected from treated animals. CONCLUSIONS: Cyproheptadine given after inferior MI reduces post-MI 5-HT levels, prevents valvular fibrotic remodeling, is associated with larger increase in mitral valve size and less MR.

Progression of aortic stenosis after an acute myocardial infarction.

BACKGROUND: Myocardial infarction (MI) has been shown to induce fibrotic remodelling of the mitral and tricuspid valves. It is unknown whether MI also induces pathological remodelling of the aortic valve and alters aortic stenosis (AS) progression. We thus compared AS progression after an acute MI and in patients with/without history of MI, and assessed post-MI pathobiological changes within the aortic valve leaflets in a sheep model. METHODS: Serial echocardiograms in human patients with AS were retrospectively analysed and compared between 3 groups: (1) acute MI at baseline (n=68), (2) prior history of MI (n=45) and (3) controls without MI (n=101). Annualised progression rates of AS severity were compared between these 3 groups. In addition, aortic valves were harvested from 15 sheep: (1) induced inferior MI (n=10) and (2) controls without MI (n=5), for biological and histological analyses. RESULTS: In humans, the acute MI, previous MI and control groups had comparable baseline AS severity. Indexed aortic valve area (AVAi) declined faster in the acute MI group compared with controls (-0.07±0.06 vs -0.04±0.04 cm2/m2/year; p=0.004). After adjustment, acute MI status was significantly associated with faster AVAi progression (mean difference: -0.013 (95% CI -0.023 to -0.003) cm2/m2/year, p=0.008). In the post-MI experimental animal model, aortic valve thickness and qualitative/quantitative expression of collagen were significantly increased compared with controls. CONCLUSIONS: The results of this study suggest that AS progression is accelerated following acute MI, which could be caused by increased collagen production and thickening of the aortic valve after the ischaemic event.

Echocardiographic Variables Associated with Transvalvular Gradient After a Transcatheter Edge-To-Edge Mitral Valve Repair.

BACKGROUND: Transcatheter edge-to-edge mitral valve repair may lead to a reduction in mitral valve area (MVA) and elevated mean transmitral gradient (TMG). The objectives of this study were to assess the value of baseline MVA by different imaging methods and to explore the associations between MVA indexed to body surface area or left ventricular forward stroke volume and postprocedural TMG. METHODS: Preprocedural echocardiographic images from 76 consecutive patients were retrospectively reviewed. MVA planimetry from two-dimensional (2D) transthoracic echocardiography (MVATTE), 2D transesophageal echocardiography in the transgastric view (MVA2D TEE), and three-dimensional (3D) transesophageal echocardiography (MVA3D) were measured. Postprocedural TMGs were assessed at 1 to 3 months and all-cause mortality at 1 year. RESULTS: Postprocedural mean TMG > 5 mm Hg was associated with a 3.42-fold (95% confidence interval [CI], 1.08-10.87; P = .04) increased risk for 1-year all-cause mortality. Patients with postprocedural TMG > 5 mm Hg (25% [19 of 76]) had significantly smaller preprocedural MVA3D (3.9 ± 0.8 vs 5.2 ± 1.3 cm2, P < .01) and MVATTE (4.9 ± 1.1 vs 5.8 ± 1.5 cm2, P = .01) compared with patients without elevated TMG. No significant difference was found for MVA2D TEE (P = .20). The best threshold values for MVA3D and MVATTE to be associated with postprocedural TMG > 5 mm Hg were, respectively, 3.9 cm2 (area under the curve [AUC] = 0.80; 95% CI, 0.66-0.94; sensitivity 62%, specificity 87%) and 4.6 cm2 (AUC = 0.68; 95% CI, 0.54-0.82; sensitivity 53%, specificity 80%). MVA3D indexed to body surface area and to stroke volume showed overall the best associations with postprocedural mean TMG > 5 mm Hg, with optimal thresholds, respectively, of 2.5 cm2/m2 (AUC = 0.88; 95% CI, 0.77-0.98; sensitivity 92%, specificity 74%) and 95 cm2/L (AUC = 0.87; 95% CI, 0.77-0.97; sensitivity 85%, specificity 82%). CONCLUSIONS: Elevated TMG following transcatheter edge-to-edge mitral valve repair was associated with increased mortality. The present results indicate that MVA3D, MVA3D indexed to body surface area, and MVA3D indexed to stroke volume may be considered potential predictors of postprocedural TMG > 5 mm Hg and could help optimize patient selection, while the use of 2D methods for valve area were poorly associated with TMG.

To Take One's Breath Away: Echocardiography-Guided Aspiration of an Air Embolism During a MitraClip Procedure.

An air embolism (AE) is a rare but dreaded complication during endovascular procedures. Current guidance recommends hyperbaric oxygen therapy and aspiration for the management of a venous AE. However, the management of an arterial AE is much less described. We report a case of a 79-year-old man with symptomatic mitral regurgitation who underwent a MitraClip procedure. During the intervention, a massive AE was detected in the ascending aorta on transesophageal echocardiography. The AE was successfully aspirated while the patient remained hemodynamically stable. This report demonstrates the efficacy of an arterial AE's aspiration with a real-time echocardiography recording of the technique.

Une embolie gazeuse (EG) est une complication rare mais redoutée lors des interventions endovasculaires. Les directives actuelles recommandent l'oxygénothérapie hyperbare et l'aspiration pour la prise en charge d'une EG veineuse. Cependant, la prise en charge d'une EG artérielle est beaucoup moins bien décrite. Nous rapportons le cas d'un homme de 79 ans présentant une insuffisance mitrale symptomatique et ayant subi une procédure MitraClip. Au cours de l'intervention, une EG massive a été détectée dans l'aorte ascendante à l'échocardiographie transoesophagienne. L'EG a été aspirée avec succès alors que le patient est resté stable sur le plan hémodynamique. Ce rapport démontre l'efficacité de l'aspiration d'une EG artérielle avec un enregistrement en temps réel de la technique par échocardiographie.

Pathophysiology, Diagnosis, and New Therapeutic Approaches for Ischemic Mitral Regurgitation.

Ischemic mitral regurgitation (MR) is a valvular complication frequently seen in patients with coronary artery disease and is associated with increased mortality and morbidity. Ischemic mitral regurgitation has a complex, heterogeneous, and still incompletely understood pathophysiology involving both the mitral valve and the left ventricle. The occurrence of valve regurgitation in patients with ischemic cardiomyopathy in return accelerates left ventricular remodelling and dysfunction, ultimately leading to irreversible heart failure. Diagnostic evaluation of ischemic MR is unique and different from the other causes of MR. The severity thresholds associated with outcomes are different from primary MR, and specific imaging characteristics are potentially useful to guide therapy. The use of imaging modalities such as 3-dimensional echocardiography and cardiac magnetic resonance imaging can refine the diagnostic evaluation and help in choosing the correct management. Although multiple treatments are available to improve ischemic MR, each therapeutic option is associated with limitations and incomplete success. Therapy has therefore to be individualised for each patient. Current options include optimal medical therapy, cardiac resynchronisation therapy, percutaneous or surgical revascularisation, surgical mitral repair or replacement, and new percutaneous interventions. This review aims to discuss the latest insights regarding the pathophysiology, diagnosis, and treatment of ischemic MR.

Characteristics and Outcomes of Patients Who Are Denied From a Percutaneous Edge-to-Edge Mitral Valve Repair After Being Referred to a Transcatheter Mitral Valve Program: Impact of a Dedicated Multidisciplinary Mitral Heart Team Approach.

BACKGROUND: Many patients referred for a MitraClip intervention are finally refused for this intervention, and data are very scarce on their outcomes. Our study sought to determine the characteristics and outcomes of patients who are referred to a mitral valve clinic and are finally denied from a percutaneous mitral edge-to-edge repair. METHODS: A total of 210 patients referred to our clinic for severe mitral regurgitation were retrospectively analyzed. Fifty-seven patients underwent a MitraClip procedure. For exploratory purposes, a propensity-matched cohort comparing the patients accepted for a MitraClip procedure and those refused for any mitral intervention was analyzed. RESULTS: Among the 153 patients who were refused for MitraClip, 46% had functional MR, 42% had degenerative MR, and 11% had mixed disease. Reasons for denial included unfavorable anatomy, patient refusal, mitral valve surgery referral, cardiac resynchronization therapy, other advanced heart failure therapies, and palliative care. After a mean follow-up of 13 months, 50% were in New York Heart Association class I or II, 63% had less than severe MR, and mortality rate was 29%. In the propensity-matched cohort, there was no difference in symptoms improvement, but there was less overall mortality (P=.01), cardiovascular mortality (P<.01) and severe MR (P<.01) in the MitraClip group. CONCLUSIONS: A multidisciplinary heart team evaluation for complex MR patients can be useful not solely for selecting the ideal MitraClip eligible patients, but also to select the best treatment strategy in each individualized context.

Attenuated Mitral Leaflet Enlargement Contributes to Functional Mitral Regurgitation After Myocardial Infarction.

BACKGROUND: Mitral leaflet enlargement has been identified as an adaptive mechanism to prevent mitral regurgitation in dilated left ventricles (LVs) caused by chronic aortic regurgitation (AR). This enlargement is deficient in patients with functional mitral regurgitation, which remains frequent in the population with ischemic cardiomyopathy. Maladaptive fibrotic changes have been identified in post-myocardial infarction (MI) mitral valves. It is unknown if these changes can interfere with valve growth and whether they are present in other valves. OBJECTIVES: This study sought to test the hypothesis that MI impairs leaflet growth, seen in AR, and induces fibrotic changes in mitral and tricuspid valves. METHODS: Sheep models of AR, AR + MI, and controls were followed for 90 days. Cardiac magnetic resonance, echocardiography, and computed tomography were performed at baseline and 90 days to assess LV volume, LV function, mitral regurgitation and mitral leaflet size. Histopathology and molecular analyses were performed in excised valves. RESULTS: Both experimental groups developed similar LV dilatation and dysfunction. At 90 days, mitral valve leaflet size was smaller in the AR + MI group (12.8 ± 1.3 cm2 vs. 15.1 ± 1.6 cm2, p = 0.03). Mitral regurgitant fraction was 4% ± 7% in the AR group versus 19% ± 10% in the AR + MI group (p = 0.02). AR + MI leaflets were thicker compared with AR and control valves. Increased expression of extracellular matrix remodeling genes was found in both the mitral and tricuspid leaflets in the AR + MI group. CONCLUSIONS: In these animal models of AR, the presence of MI was associated with impaired adaptive valve growth and more functional mitral regurgitation, despite similar LV size and function. More pronounced extracellular remodeling was observed in mitral and tricuspid leaflets, suggesting systemic valvular remodeling after MI.