Mitral regurgitation in patients with severe aortic stenosis: Diagnosis and management

Severe aortic stenosis (AS) and mitral regurgitation (MR) frequently coexist. Although some observational studies have reported that moderate or severe MR is associated with higher mortality, the optimal management of such patients is still unclear. Simultaneous replacement of both aortic and mitral valves is linked to significantly higher morbidity and mortality. Recent advances in minimally invasive surgical or transcatheter therapies for MR allow for staged procedures in which surgical or transcatheter aortic valve replacement (SAVR/TAVR) is done first and MR severity re-evaluated afterwards. Current evidence suggests MR severity improves in some patients after SAVR or TAVR, depending on several factors (MR aetiology, type of valve used for TAVR, presence/absence of atrial fibrillation, residual aortic regurgitation, etc). However, as of today, the absence of randomised clinical trials does not allow for evidence-based recommendations about whether or not MR should be addressed at the time of SAVR or TAVR. A careful patient evaluation and clinical judgement are recommended to distinguish patients who might benefit from a double valve intervention from those in which MR should be left alone. The aim of this review is to report and critique the available data on this subject in order to help guide the clinical decision making in this challenging subset of patients

Proportionate and Disproportionate Functional Mitral Regurgitation: A New Conceptual Framework That Reconciles the Results of the MITRA-FR and COAPT Trials

Traditional approaches to the characterization of secondary or functional mitral regurgitation (MR) have largely ignored the critical importance of the left ventricle (LV). We propose that patients with secondary MR represent a heterogenous group, which can be usefully subdivided based on understanding that the effective regurgitant orifice area (EROA) is dependent on left ventricular end-diastolic volume (LVEDV). According to the Gorlin hydraulic orifice equation, patients with heart failure, an LV ejection fraction of 30%, an LVEDV of 220 to 250 ml, and a regurgitant fraction of 50% would be expected to have an EROA of ≈0.3 cm2 independent of specific tethering abnormalities of the mitral valve leaflets. The MR in these patients is proportionate to the degree of LV dilatation and can respond to drugs and devices that reduce LVEDV. In contrast, patients with EROA of 0.3 to 0.4 cm2 but with LVEDV of only 160 to 200 ml exhibit degrees of MR that are disproportionately higher than predicted by LVEDV. These patients appear to preferentially benefit from interventions directed at the mitral valve. Our proposed conceptual framework explains the apparently discordant results from 2 recent randomized controlled trials of mitral valve repair. The MITRA-FR (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) trial enrolled patients who had MR that was proportionate to the degree of LV dilatation, and during long-term follow-up, the LVEDV and clinical outcomes of these patients did not differ from medically-treated control subjects. In comparison, the patients enrolled in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial had an EROA ≈30% higher but LV volumes that were ≈30% smaller, indicative of disproportionate MR. In these patients, transcatheter mitral valve repair reduced the risk of death and hospitalization for heart failure, and these benefits were paralleled by a meaningful decrease in LVEDV. Thus, characterization of MR as proportionate or disproportionate to LVEDV appears to be critical to the selection of an optimal treatment for patients with chronic heart failure and systolic dysfunction

Comparison of Baseline Characteristics and Outcomes in Men Versus Women With Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation

Female gender has been linked to increased risk of adverse events after surgical aortic valve replacement; however, the evidence regarding the role of gender differences on clinical outcomes in patients who underwent transcatheter aortic valve implantation (TAVI) is still debated. This retrospective study included 910 consecutive patients with severe, symptomatic aortic stenosis who underwent TAVI in 2 institutions from January 2012 to July 2016. The primary end point was all-cause mortality at 1 year after TAVI in women versus men. Women had a higher incidence of in-hospital vascular complications (7.8% vs 4.1%) and major or life-threatening bleeding (4.0% vs 1.6%) than men. At 1 year, women showed a lower mortality rate than men (7.0% vs 12.7%, adjusted hazard ratio [HR] 0.42, 95% confidence interval [CI] [0.23 to 0.76], p = 0.004). When stratifying by specific subgroups of interest, the survival benefit in women persisted in (1) patients with a Society of Thoracic Surgery risk score ≤ 8 (adjusted HR 0.35, 95% CI [0.14 to 0.88], p = 0.026); (2) patients treated with first-generation devices (adjusted HR 0.46, 95% CI [0.24 to 0.86], p = 0.016); and (3) patients treated with balloon-expandable valves (adjusted HR 0.40, 95% CI [0.19 to 0.86], p = 0.019). In conclusion, in this large patient cohort, women had lower 1-year mortality after TAVI than men, particularly with an STS score ≤ 8, or treated with first-generation and balloon-expandable devices

Complex Transitions Between C3 and C4 Photosynthesis During the Evolution of Paniceae: A Phylogenetic Case Study Emphasizing the Position of Steinchisma Hians (Poaceae), A C3-C4 Intermediate

A two-tiered, nested molecular phylogenetic study of panicoid grasses to explore character state transitions between the C3 and C4 adaptive syndromes is presented. A broad survey of 92 panicoid species was sampled for the grass-specific insert sequence in the chloroplast RNA polymerase locus (rpoC2), combining published and unpublished sequences. This portion of the study also included an intensive phylogenetic investigation of one clade of seven species that included Steinchisma hians, which is notable for exhibiting intermediacy between the C3 and C4 photosynthetic types. Both rpoC2 data and previously published sequences of the F subunit of an NADH-dependent dehydrogenase were analyzed together for this small group. A rigorous phylogenetic investigation of S. hians and 13 other species of Panicoideae included in the broad survey was then performed with sequences of both rpoC2 and the externally transcribed spacer region of the nuclear ribosomal repeat. These 14 species were selected to maximize representation among photosynthetic subtypes. Combined analysis resolved single origins of two photosynthetic subtypes. A reversion of C4 to C3 photosynthesis during the evolution of the lineage that includes S. hians is identified. These and other recent results indicate that repeated reversions from C4 to C3 have occurred. The C3 species Panicum laxum has a strongly supported sister group relationship to S. hians (C3-C4). The most parsimonious interpretation is that S. hians represents an incipient reversal from C3 to C4 photosynthesis, beginning with the capacity to compartmentalize photorespiratory metabolism in the bundle sheath tissue

Comparison of Efficacy and Safety of Transcatheter Aortic Valve Implantation in Patients With Bicuspid Versus Tricuspid Aortic Valves

Bicuspid aortic valve (BAV) stenosis has been considered a contraindication to transcatheter aortic valve implantation (TAVI). The aim of this study is to compare the efficacy and safety of TAVI in patients with BAV with those with tricuspid aortic valve (TAV) using balloon-expandable and self-expanding transcatheter heart valves. This retrospective study included 823 consecutive patients with severe, symptomatic aortic valve stenosis undergoing TAVI in 2 institutions, Baylor Heart and Vascular Hospital (Dallas, TX) and The Heart Hospital Baylor Plano (Plano, TX), from January 2012 to February 2016. Efficacy was evaluated by postprocedural valve function as mean gradient, peak velocity, effective orifice area, and ≥moderate paravalvular leak. Safety end points included all-cause 30-day and 1-year mortality, immediate postprocedural mortality and 30-day cardiovascular mortality, procedural success, pacemaker implantation, and procedural complications. Of the 823 included patients, 735 had TAV and 77 had BAV. Baseline characteristics were similar between the 2 groups. Procedural success was high in both BAV and TAV (98.7% vs 99.1%, p = ns). There were no significant differences between groups in valve hemodynamics after TAVI, pacemaker implantation rate, or procedural complications. There were no differences regarding immediate postprocedural mortality (BAV vs TAV, 1.1% vs 0.8%, p = ns), nor 30-day cardiovascular mortality (3.4% vs 2.3%, p = ns). All-cause mortality at 30 days (3.4% vs 3.1%, p = ns) and 1-year (8.5% vs 10.5%) were similar. Patients with BAV showed similar procedural and clinical outcomes to patients with TAV. Therefore, TAVI appears to be a safe and effective procedure for patients with BAVs as well as those with TAVs

2-year outcomes for transcatheter repair in patients with functional mitral regurgitation from the CLASP study

Background: Transcatheter mitral valve repair has emerged as a favourable option in patient care for treating functional mitral regurgitation (FMR) with a need for longer term data. We herein report two-year outcomes from the FMR group of the multicentre, prospective, single arm CLASP study with the PASCAL transcatheter valve repair system. Methods: Patients with symptomatic, clinically significant FMR ≥3+ as evaluated by the core laboratory and deemed candidates for transcatheter repair by the local heart team were eligible for the study. Follow-up was conducted at 30 days, one year, and two years with echocardiographic outcomes evaluated by the core laboratory at all timepoints and major adverse events (MAEs) evaluated by an independent clinical events committee to one year (site-reported thereafter). Results: Eighty-five FMR patients were treated with mean age 72 years, 55% male, 65% in NYHA Class III-IVa, 37% LVEF, and 100% MR grade ≥3+. Successful implantation was achieved in 96% of patients. MAEs included one cardiovascular mortality (1.2%) and one conversion tomitral valve replacement surgery (1.2%) at 30 days, and two reinterventions between 30 days and two years. Kaplan-Meier (KM) estimates for survival were 88% at one year and 72% at two years. Freedom from heart failure (HF) rehospitalization KM estimates were 81% at one year and 78% for two years. The reduction in annualized HF hospitalization rate was 81% at two years (p\u3c0.001). MR ≤1+ was achieved in 73% of patients at 30 days, 75% at one year, and 84% at two years; MR ≤2+ was achieved in 96% of patients at 30 days, 100% at one year, and 95% two years (all p\u3c0.001). Mean LVEDV of 199 mL at baseline decreased by 9 mL at 30 days (p=0.039), 29 mL at one year (p\u3c0.001), and 31 mL at two years (p\u3c0.001). NYHA class I/II was achieved in 87% of patients at 30 days, 86% at one year, and 88% at two years (all p\u3c0.001). Six-minute walk distance (6MWD) improved by 22 m at 30 days (p=0.004) and 40 m at one year (p=0.003). Kansas City Cardiomyopathy Questionnaire (KCCQ) score improved by 16 points at 30 days and one year (all p\u3c0.001). Conclusions: In the CLASP study, the PASCAL transcatheter valve repair system demonstrated sustained favourable outcomes at two years in patients with FMR. Results showed a high survival rate of 72% and freedom from HF rehospitalization of 78% at two years. An 81% reduction in annualized HF hospitalization rate was observed. At two years, sustained MR reduction of MR ≤2+ was achieved in 95% andMR ≤1+ in 84% of patients, with evidence of left ventricular reverse remodelling. Improvements in functional status were significant and sustained at two years. The CLASP IIF randomized pivotal trial is ongoing

Frequency of and Prognostic Significance of Atrial Fibrillation in Patients Undergoing Transcatheter Aortic Valve Implantation

The prognostic implications of preexisting atrial fibrillation (AF) and new-onset AF (NOAF) in transcatheter aortic valve implantation (TAVI) remain uncertain. This study assesses the epidemiology of AF in patients treated with TAVI and evaluates their outcomes according to the presence of preexisting AF or NOAF. A retrospective analysis of 708 patients undergoing TAVI from 2 heart hospitals was performed. Patients were divided into 3 study groups: sinus rhythm (n = 423), preexisting AF (n = 219), and NOAF (n = 66). Primary outcomes of interest were all-cause death and stroke both at 30-day and at 1-year follow-up. Preexisting AF was present in 30.9% of our study population, whereas NOAF was observed in 9.3% of patients after TAVI. AF and NOAF patients showed a higher rate of 1-year all-cause mortality compared with patients in sinus rhythm (14.6% vs 6.5% for preexisting AF and 16.3% vs 6.5% for NOAF, p = 0.007). No differences in 30-day mortality were observed between groups. In patients with AF (either preexisting and new-onset), those discharged with single antiplatelet therapy displayed higher mortality rates at 1 year (42.9% vs 11.7%, p = 0.006). Preexisting AF remained an independent predictor of mortality at 1-year follow-up (hazard ratio [HR] 2.34, 95% CI 1.22 to 4.48, p = 0.010). Independent predictors of NOAF were transapical and transaortic approach as well as balloon postdilatation (HR 3.48, 95% CI 1.66 to 7.29, p = 0.001; HR 5.08, 95% CI 2.08 to 12.39, p <0.001; HR 2.76, 95% CI 1.25 to 6.08, p = 0.012, respectively). In conclusion, preexisting AF is common in patients undergoing TAVI and is associated with a twofold increased risk of 1-year mortality. This negative effect is most pronounced in patients discharged with single antiplatelet therapy compared with other antithrombotic regimens

Penetration of left and right atrial wall and aortic root by an Amplatzer atrial septal occluder in a nine year old boy with Marfan syndrome: Case report

<p>Abstract</p> <p>Background</p> <p>To describe complications associated with Amplatzer septal occluders in a patient with Marfan syndrome</p> <p>Case presentation</p> <p>A nine-year-old boy with Marfan syndrome and a 22 mm atrial septal defect (ASD) was treated successfully by interventional closure of his ASD by placing a 24 mm Amplatzer septal occluder. Follow up examinations showed a good result but an increasing enlargement of aortic root, so the patient was scheduled for operation. Intraoperative findings showed a perforation of the left atrial roof and the non-coronary sinus by penetration of the occluder device as well as penetration into the right atrial wall. The occluder was resected, the ASD was closed and the aortic sinus was reconstructed using a Dacron patch.</p> <p>Conclusion</p> <p>We describe the first case of a patient with Marfan syndrome and an interventional closure of an ASD. Due to alterations of the connective tissue, as it is typical for patients with Marfan syndrome, the Amplatzer occluder probably perforated adjacent structures more easily as in non-affected individuals. Amplatzer occluders should be used with caution and follow up examinations should be performed in short intervals.</p

Baseline mitral regurgitation predicts outcome in patients referred for dobutamine stress echocardiography

Purpose: A number of parameters recorded during dobutamine stress echocardiography (DSE) are associated with worse outcome. However, the relative importance of baseline mitral regurgitation (MR) is unknown. The aim of this study was to assess the prevalence and associated implications of functional MR with long-term mortality in a large cohort of patients referred for DSE. Methods: 6745 patients (mean age 64.9±12.2 years) were studied. Demographic, baseline and peak DSE data were collected. All-cause mortality was retrospectively analyzed. DSE was successfully completed in all patients with no adverse outcomes. Results: MR was present in 1019 (15.1%) patients. During a mean follow up of 5.1±1.8 years, 1642 (24.3%) patients died and MR was significantly associated with increased all-cause mortality (p<0.001). With Kaplan-Meier analysis, survival was significantly worse for patients with moderate and severe MR (p<0.001). With multivariate Cox regression analysis, moderate and severe MR (HR 2.78; 95% CI 2.17 - 3.57; and HR 3.62; 95% CI 2.89 - 4.53, respectively) were independently associated with all-cause mortality. The addition of MR to C statistic models significantly improved discrimination. Conclusions: MR is associated with all-cause mortality and adds incremental prognostic information among patients referred for DSE. The presence of MR should be taken into account when evaluating the prognostic significance of DSE results

Risk of death in heart disease is associated with elevated urinary globotriaosylceramide

BACKGROUND: Elevated urinary globotriaosylceramide (Gb3) has been considered a hallmark of Fabry disease, an X-linked lysosomal disorder that is a risk factor for most types of heart disease. METHODS AND RESULTS: We screened 1421 consecutive patients with common forms of heart disease for Fabry disease by measuring urinary Gb3 in whole urine using tandem mass spectrometry, α-galactosidase A activity in dried blood spots, and we looked for GLA mutations by parallel sequencing of the whole gene (exons and introns) in pooled genomic DNA samples followed by Sanger sequencing verification. GLA variants were found in 13 patients. In the 1408 patients without GLA mutations, urinary Gb3 levels were significantly higher in heart disease patients compared to 116 apparently healthy controls (median difference=10.0 ng/mL and P<0.001). Urinary lipid profiling showed that levels of 5 other lipids significantly distinguished between urine of patients with Fabry disease (n=7) and heart disease patients with elevated urinary Gb3 (n=6). Sphingomyelin and Gb3 levels were abnormal in the left ventricular wall of patients with ischemic heart failure. Elevated levels of urinary Gb3 were independently associated with increased risk of death in the average follow-up of 17 months (hazard ratio=1.59 for increase in Gb3 of 200, 95% CI=1.36 and 1.87, and P<0.0001). CONCLUSIONS: In heart disease patients who do not have Fabry disease or GLA gene mutations, a higher level of urinary Gb3 is positively associated with near-term mortality. The elevation of urinary Gb3 and that of other lipids suggests that heart disease is associated with multiorgan lipid abnormalities. CLINICAL TRIAL REGISTRATION URL: clinicaltrials.gov. Unique Identifier: NCT01019629.Raphael Schiffmann, Sabrina Forni, Caren Swift, Nastry Brignol, Xiaoyang Wu, David J. Lockhart, Derek Blankenship, Xuan Wang, Paul A. Grayburn, Matthew R. G. Taylor, Brian D. Lowes, Maria Fuller, Elfrida R. Benjamin, Lawrence Sweetma