Contribution of Ventricular Diastolic Dysfunction to Pulmonary Hypertension Complicating Chronic Systolic Heart Failure

ObjectivesThe aim of the study is to clarify the clinical role of Doppler-echocardiographic parameters of left ventricular diastolic dysfunction (LVDD) as determinants of pulmonary hypertension in patients experiencing left ventricular systolic dysfunction (LVSD) with and without the presence of functional mitral valve regurgitation (FMR).BackgroundPulmonary hypertension (pulmonary venous or mixed pulmonary venous-arterial hypertension) complicating LVSD is associated with poor outcomes beyond that of LVSD alone. The view of the contribution of LVDD as a determinant of pulmonary hypertension is controversial and not well defined as a tool in clinical practice.MethodsData from patients with LVEF ≤40% undergoing Doppler-echocardiography evaluations during the period from August 2001 to December 2004 were analyzed. Pulmonary systolic pressure (PSP), parameters of diastolic function (mitral valve [MV] transmitral flow velocity [E]/mitral annular diastolic velocity [e′] ratio, MV deceleration time [DT]), quantitated effective regurgitant orifice area (EROA) of FMR, and clinical characteristics were evaluated. Pulmonary hypertension was defined as an estimated PSP ≥45 mm Hg.ResultsCriteria were met in 1,541 patients; one-third (n = 533) demonstrating PSP ≥45 mm Hg (58 ± 10 mm Hg, range 45 to 102 mm Hg). Patients with pulmonary hypertension were older with higher E/e′ ratio, EROA, and lower DT and LVEF. In multivariate analysis, pulmonary hypertension was independently predicted not only by severity of FMR (EROA ≥20 mm2, odds ratio: 3.8, p < 0.001) but also by parameters of LVDD (E/e′ ratio ≥15, odds ratio: 3.31, p < 0.001; DT ≤150 ms, odds ratio: 3.8, p < 0.001). Receiver-operating characteristics curve analysis showed that EROA, E/e′ ratio, and DT provided significant incremental value in predicting pulmonary hypertension (c-statistic 0.830, p < 0.001).ConclusionsPatients with LVSD commonly have secondary pulmonary hypertension, which is largely determined by the severity of LVDD even with adjustment for FMR and low LVEF. Thus, measures of LVDD in routine clinical practice where PSP may not be estimated are important physiologic descriptors of hemodynamic status and are cumulatively linked in the prediction of pulmonary hypertension

B-type natriuretic peptide clinical activation in aortic stenosis : impact on long-term survival

Objectives : This study was conducted to define the association between serum B-type natriuretic peptide (BNP) activation and survival after the diagnosis of aortic stenosis (AS).Background : In AS, the link between BNP levels and clinical outcome is in dispute. Failure to account for the normal shifting of BNP ranges with aging in men and women, not using hard endpoints (survival), and not enrolling large series of patients have contributed to the uncertainty.Methods : A program of prospective measurement of BNP levels with Doppler echocardiographic AS assessment during the same episode of care was conducted. BNP ratio (measured BNP/maximal normal BNP value specific to age and sex) >1 defined BNP clinical activation.Results : In 1,953 consecutive patients with at least moderate AS (aortic valve area 1.03 ± 0.26 cm2; mean gradient 36 ± 19 mm Hg), median BNP level was 252 pg/ml (interquartile range: 98 to 592 pg/ml); BNP ratio 2.46 (interquartile range 1.03 to 5.66); ejection fraction (EF) 57% ± 15%, and symptoms present in 60% of patients. After adjustment for all survival determinants, BNP clinical activation (BNP ratio >1) independently predicted mortality after diagnosis (p 2 (HR: 0.56; 95% CI: 0.47 to 0.66; p < 0.0001).Conclusions : In this large series of patients with AS, BNP clinical activation was associated with excess long-term mortality incrementally and independently of all baseline characteristics. Higher mortality with higher BNP clinical activation, even in asymptomatic patients, emphasizes the importance of appropriate clinical interpretation of BNP levels in managing patients with AS

Sex differences and survival in adults with bicuspid aortic valves : verification in 3 contemporary echocardiographic cohorts

Background-—Sex-related differences in morbidity and survival in bicuspid aortic valve (BAV) adults are fundamentally unknown. Contemporary studies portend excellent survival for BAV patients identified at early echocardiographic-clinical stages. Whether BAV adults incur a survival disadvantage throughout subsequent echocardiographic-clinical stages remains undetermined. Methods and Results-—Analysis was done of 3 different cohorts of consecutive patients with echocardiographic diagnosis of BAV identified retrospectively: (1) a community cohort of 416 patients with first BAV diagnosis (age 35 21 years, follow-up 16 7 years), (2) a tertiary clinical referral cohort of 2824 BAV adults (age 51 16 years, follow-up 9 6 years), and (3) a surgical referral cohort of 2242 BAV adults referred for aortic valve replacement (AVR) (age 62 14 years, follow-up 6 5 years). For the community cohort, 20-year risks of aortic regurgitation (AR), AVR, and infective endocarditis were higher in men (all P=0.04); for a total BAV-related morbidity risk of 52 4% vs 35 6% in women (P=0.01). The cohort’s 25-year survival was identical to that in the general population (P=0.98). AR independently predicted mortality in women (P=0.001). Baseline AR was more common in men (P=0.02) in the tertiary cohort, with 20-year survival lower than that in the general population (P<0.0001); age-adjusted relative death risk was 1.16 (95% confidence interval [CI] 1.05-1.29) for men versus 1.67 (95% CI 1.38-2.03) for women (P=0.001). AR independently predicted mortality in women (P=0.01). Baseline AR and infective endocarditis were higher in men (both =0.001) for the surgical referral cohort, with 15-year survival lower than that in the general population (P<0.0001); age-adjusted relative death risk was 1.34 (95% CI 1.22-1.47) for men versus 1.63 (95% CI 1.40-1.89) for women (P=0.026). AR and NYHA class independently predicted mortality in women (both P=0.04). Conclusions-—Within evolving echocardiographic-clinical stages, the long-term survival of adults with BAV is not benign, as both men and women incur excess mortality. Although BAV-related morbidity is higher in men in the community, and AR and infective endocarditis are more prevalent in men, women exhibit a significantly higher relative risk of death in tertiary and surgical referral cohorts, which is independently associated with A

Arrhythmic mitral valve prolapse in 2023: Evidence-based update

Patients with mitral valve prolapse (MVP) may develop ventricular arrhythmias, ranging from premature ventricular contractions through more complex non-sustained ventricular tachycardia to sustained life-threatening ventricular arrhythmias. The prevalence of MVP in autopsy series of young adults who died suddenly has been estimated to be between 4% and 7%. Thus, “arrhythmic MVP” has been reported as an underappreciated cause of sudden cardiac death, leading to a renewed interest in the study of this association. The term “arrhythmic MVP” refers to a small subset of patients who have, in the absence of any other arrhythmic substrate, MVP, with or without mitral annular disjunction, and frequent or complex ventricular arrhythmias. Our understanding of their coexistence in terms of contemporary management and prognosis is still incomplete. While literature regarding the arrhythmic MVP may be contrasting despite recent consensus document, the present review summarizes the relevant evidence concerning the diagnostic approach, prognostic implications, and targeted therapies for MVP-related ventricular arrhythmias. We also summarize recent data supporting left ventricular remodeling, which complicates the coexistence of MVP with ventricular arrhythmias. As the evidence for a putative link between MVP-associated ventricular arrhythmias and sudden cardiac death is scarce and based on scant and retrospective data, risk prediction remains a challenge. Thus, we aimed at listing potential risk factors from available seminal reports for further use in a more reliable prediction model that requires additional prospective data. Finally, we summarize evidence and guidelines on targeted therapies of ventricular arrhythmias in the setting of MVP, including implantable cardioverter defibrillators and catheter ablation. Our review highlights current knowledge gaps and provides an action plan for structured research on the pathophysiological genesis, diagnosis, prognostic impact, and optimal management of patients with arrhythmic MVP

Comparaison de deux méthodes de sélection classique avec l'haplodiploïdisation pour la résistance à la mouche de Hesse chez le blé tendre (Triticum aestivum)

L'efficacité des méthodes classiques et alternatives d'amélioration génétique repose sur l'évolution de la variabilité génétique des populations ségrégatives sous sélection. L'objectif de cette étude est de comparer l'évolution de la fréquence des gènes de résistance à la mouche de Hesse (Mayetiola destructor) sous deux méthodes classiques de sélection en comparaison avec la méthode de l'haplodiploïdisation. Les distributions et les proportions observées du caractère "résistance à la mouche de Hesse" ont été évaluées pour des lignées produites par la méthode de filiation unipare (FUP), la méthode " bulk " et l'haplodiploïdisation (DH) de quatre populations hybrides de blé tendre (Triticum aestivum). Ces populations sont issues des croisements entre des parents résistants à la mouche de Hesse marocaine et des parents sensibles mais adaptés aux conditions marocaines. Les résultats ont montré un effet marqué de la méthode d'amélioration génétique. En effet, malgré leur avancement à la génération F6, les lignées produites par les méthodes FUP et " bulk " présentent toujours un taux non négligeable d'hétérozygotie pour ce caractère alors que la méthode DH a abouti à une homozygotie parfaite. Les proportions de résistance observées chez les lignées FUP et haploïdes doublées sont approximativement les mêmes que celles théoriquement attendues. Cependant, la méthode " bulk " a permis une sélection naturelle au champ qui a favorisé le caractère résistant de manière significativeThe relative usefulness of conventional and alternative breeding methods relies on the evolution of genetic variability in segregating populations undergoing selection. The objective of this study was to compare the frequencies of genetic resistance to Hessian fly (Mayetiola destructor) in populations generated by two conventional breeding methods in comparison with lines advanced through doubled haploid method. Distribution and proportions of Hessian fly resistance were evaluated in four populations of bread wheat lines advanced through 'Single Seed Descent' (SSD), 'Bulk', and doubled-haploid (DH) methods. These populations were all derived from crosses involving resistant parents and susceptible lines adapted to Moroccan conditions. The results of this study have shown a clear effect of the breeding method. The Bulk and SSD (F6) derived lines have shown a substantial residual heterozygocity while DH method has produced completely homozygous material. The observed proportions of resistance did not deviate from expected in the populations of lines derived through SSD and DH methods while evidence of natural selection for resistance was significant in the lines derived through the Bulk method

Genome-wide association study reveals novel genetic loci:a new polygenic risk score for mitral valve prolapse

AIMS: Mitral valve prolapse (MVP) is a common valvular heart disease with a prevalence of >2% in the general adult population. Despite this high incidence, there is a limited understanding of the molecular mechanism of this disease, and no medical therapy is available for this disease. We aimed to elucidate the genetic basis of MVP in order to better understand this complex disorder. METHODS AND RESULTS: We performed a meta-analysis of six genome-wide association studies that included 4884 cases and 434 649 controls. We identified 14 loci associated with MVP in our primary analysis and 2 additional loci associated with a subset of the samples that additionally underwent mitral valve surgery. Integration of epigenetic, transcriptional, and proteomic data identified candidate MVP genes including LMCD1, SPTBN1, LTBP2, TGFB2, NMB, and ALPK3. We created a polygenic risk score (PRS) for MVP and showed an improved MVP risk prediction beyond age, sex, and clinical risk factors. CONCLUSION: We identified 14 genetic loci that are associated with MVP. Multiple analyses identified candidate genes including two transforming growth factor-beta signalling molecules and spectrin beta. We present the first PRS for MVP that could eventually aid risk stratification of patients for MVP screening in a clinical setting. These findings advance our understanding of this common valvular heart disease and may reveal novel therapeutic targets for intervention. KEY QUESTION: Expand our understanding of the genetic basis for mitral valve prolapse (MVP). Uncover relevant pathways and target genes for MVP pathophysiology. Leverage genetic data for MVP risk prediction. KEY FINDING: Sixteen genetic loci were significantly associated with MVP, including 13 novel loci. Interesting target genes at these loci included LTBP2, TGFB2, ALKP3, BAG3, RBM20, and SPTBN1. A risk score including clinical factors and a polygenic risk score, performed best at predicting MVP, with an area under the receiver operating characteristics curve of 0.677. TAKE-HOME MESSAGE: Mitral valve prolapse has a polygenic basis: many genetic variants cumulatively influence pre-disposition for disease. Disease risk may be modulated via changes to transforming growth factor-beta signalling, the cytoskeleton, as well as cardiomyopathy pathways. Polygenic risk scores could enhance the MVP risk prediction

International consensus statement on nomenclature and classification of the congenital bicuspid aortic valve and its aortopathy, for clinical, surgical, interventional and research purposes.

peer reviewedThis International Consensus Classification and Nomenclature for the congenital bicuspid aortic valve condition recognizes 3 types of bicuspid valves: 1. The fused type (right-left cusp fusion, right-non-coronary cusp fusion and left-non-coronary cusp fusion phenotypes); 2. The 2-sinus type (latero-lateral and antero-posterior phenotypes); and 3. The partial-fusion (forme fruste) type. The presence of raphe and the symmetry of the fused type phenotypes are critical aspects to describe. The International Consensus also recognizes 3 types of bicuspid valve-associated aortopathy: 1. The ascending phenotype; 2. The root phenotype; and 3. Extended phenotypes

Summary: International Consensus Statement on Nomenclature and Classification of the Congenital Bicuspid Aortic Valve and Its Aortopathy, for Clinical, Surgical, Interventional and Research Purposes.

peer reviewedThis International evidence-based nomenclature and classification consensus on the congenital bicuspid aortic valve and its aortopathy recognizes 3 types of bicuspid aortic valve: 1. Fused type, with 3 phenotypes: right-left cusp fusion, right-non cusp fusion and left-non cusp fusion; 2. 2-sinus type with 2 phenotypes: Latero-lateral and antero-posterior; and 3. Partial-fusion or forme fruste. This consensus recognizes 3 bicuspid-aortopathy types: 1. Ascending phenotype; root phenotype; and 3. extended phenotypes