The Natural History of Atrial Functional Mitral Regurgitation.

BACKGROUND: The natural history of moderate/severe atrial functional mitral regurgitation (AFMR) is unknown. OBJECTIVES: The authors sought to study the incidence of left ventricular (LV) systolic dysfunction (LVSD), progression or regression of ≥mild-moderate AFMR, and impact on mortality. METHODS: Adults with left atrial (LA) volume index ≥40 mL/m2, ≥mild-moderate AFMR, and follow-up echocardiogram were followed for incident LVSD (ejection fraction <50% and ≥10% lower than baseline), progression of mild-moderate/moderate AFMR to severe, and persistent regression of AFMR to no/trivial. Relation of AFMR progression or regression as time-dependent covariates with all-cause mortality was studied. Incidence of LVSD was compared with patients with no/mild AFMR matched on age, sex, comorbidities and ejection fraction. Patients were followed until mitral intervention, myocardial infarction, or last follow-up. RESULTS: A total of 635 patients (median age 75 years, 51% female, 96% mild-moderate/moderate AFMR, 4% severe AFMR) were included. Over a median 2.2 years (Q1-Q3: 1.0-4.3 years), incidence rates per 100 person-years were 3.2 for LVSD (P = 0.52 vs patients with no/mild AFMR), 1.9 for progression of AFMR, and 3.9 for regression. Female sex and larger LA volume index were independently associated with progression, whereas younger age, male sex, absent atrial fibrillation, and higher LA emptying fraction were independently associated with regression. Neither AFMR progression nor regression was independently associated with mortality. Instead, independent risk factors for mortality included older age, concentric LV geometry, and higher estimated LV filling and pulmonary pressures. CONCLUSIONS: In patients with predominantly mild-moderate/moderate AFMR, regression of MR was more common than progression, but neither was associated with mortality. Instead, diastolic function abnormalities were more important. Over a median 2-year follow-up, LVSD risk was not increased.

[Summary: International consensus statement on nomenclature and classification of the congenital bicuspid aortic valve and its aortopathy, for clinical, surgical, interventional and research purposes]. / Resumen: Consenso internacional para la nomenclatura y clasificación de la válvula aórtica bicúspide congénita y su aortopatía, con fines clínicos, quirúrgicos, intervencionistas y de investigación.

This consensus of nomenclature and classification for congenital bicuspid aortic valve and its aortopathy is evidence-based and intended for universal use by physicians (both pediatricians and adults), echocardiographers, advanced cardiovascular imaging specialists, interventional cardiologists, cardiovascular surgeons, pathologists, geneticists, and researchers spanning these areas of clinical and basic research. In addition, as long as new key and reference research is available, this international consensus may be subject to change based on evidence-based data1.

Este consenso de nomenclatura y clasificación para la válvula aórtica bicúspide congénita y su aortopatía está basado en la evidencia y destinado a ser utilizado universalmente por médicos (tanto pediatras como de adultos), médicos ecocardiografistas, especialistas en imágenes avanzadas cardiovasculares, cardiólogos intervencionistas, cirujanos cardiovasculares, patólogos, genetistas e investigadores que abarcan estas áreas de investigación clínica y básica. Siempre y cuando se disponga de nueva investigación clave y de referencia, este consenso internacional puede estar sujeto a cambios de acuerdo con datos basados en la evidencia1.

Segmental analysis of aortic basal ring dimensions in normal and dilated tricuspid aortic roots.

OBJECTIVES: In patients with aortic root aneurysm, the aortic basal ring is frequently dilated. It has been speculated that the muscular part of the basal ring dilates most. The purpose of this study was to analyse the segmental dilatation of the basal ring, comparing normal and dilated roots in patients with tricuspid aortic valves. METHODS: Retrospective analysis of computed tomography studies in patients with normal and dilated aortic roots was performed. Lengths of segments of the basal ring corresponding to each of the 3 sinuses, and to the muscular and fibrous parts were measured. Fractions of these segments relative to the total basal ring perimeter were calculated. RESULTS: We analysed 152 normal and 126 dilated aortic roots and 86 propensity-matched pairs. Basal ring dilatation was present in all segments of dilated aortic roots with subtle differences between the segments corresponding to the 3 sinuses. The muscular part of the basal ring dilated proportionately to its fibrous part, with no difference in fractions of measured muscular part in normal and dilated roots [42.2% (interquartile range 4.3%) vs 42.1% (interquartile range 6.3%)]. CONCLUSIONS: Basal ring dilatation was present in all segments corresponding to the 3 sinuses in dilated aortic roots. Both muscular and fibrous parts dilated equally, supporting the need to stabilize the entire basal ring when performing aortic valve repair surgery.

Severe aortic stenosis: secular trends of incidence and outcomes.

BACKGROUND AND AIMS: Severe aortic stenosis (AS) is the guideline-based indication for aortic valve replacement (AVR), which has markedly increased with transcatheter approaches, suggesting possible increasing AS incidence. However, reported secular trends of AS incidence remain contradictory and lack quantitative Doppler echocardiographic ascertainment. METHODS: All adults residents in Olmsted County (MN, USA) diagnosed over 20 years (1997-2016) with incident severe AS (first diagnosis) based on quantitatively defined measures (aortic valve area ≤ 1 cm2, aortic valve area index ≤ 0.6 cm2/m2, mean gradient ≥ 40 mmHg, peak velocity ≥ 4 m/s, Doppler velocity index ≤ 0.25) were counted to define trends in incidence, presentation, treatment, and outcome. RESULTS: Incident severe AS was diagnosed in 1069 community residents. The incidence rate was 52.5 [49.4-55.8] per 100 000 patient-year, slightly higher in males vs. females and was almost unchanged after age and sex adjustment for the US population 53.8 [50.6-57.0] per 100 000 residents/year. Over 20 years, severe AS incidence remained stable (P = .2) but absolute burden of incident cases markedly increased (P = .0004) due to population growth. Incidence trend differed by sex, stable in men (incidence rate ratio 0.99, P = .7) but declining in women (incidence rate ratio 0.93, P = .02). Over the study, AS clinical characteristics remained remarkably stable and AVR performance grew and was more prompt (from 1.3 [0.1-3.3] years in 1997-2000 to 0.5 [0.2-2.1] years in 2013-16, P = .001) but undertreatment remained prominent (>40%). Early AVR was associated with survival benefit (adjusted hazard ratio 0.55 [0.42-0.71], P < .0001). Despite these improvements, overall mortality (3-month 8% and 3-year 36%), was swift, considerable and unabated (all P ≥ .4) throughout the study. CONCLUSIONS: Over 20 years, the population incidence of severe AS remained stable with increased absolute case burden related to population growth. Despite stable severe AS presentation, AVR performance grew notably, but while declining, undertreatment remained substantial and disease lethality did not yet decline. These population-based findings have important implications for improving AS management pathways.

Tricuspid Regurgitation: From Imaging to Clinical Trials to Resolving the Unmet Need for Treatment.

Tricuspid regurgitation (TR) is a highly prevalent and heterogeneous valvular disease, independently associated with excess mortality and high morbidity in all clinical contexts. TR is profoundly undertreated by surgery and is often discovered late in patients presenting with right-sided heart failure. To address the issue of undertreatment and poor clinical outcomes without intervention, numerous structural tricuspid interventional devices have been and are in development, a challenging process due to the unique anatomic and physiological characteristics of the tricuspid valve, and warranting well-designed clinical trials. The path from routine practice TR detection to appropriate TR evaluation, to conduction of clinical trials, to enriched therapeutic possibilities for improving TR access to treatment and outcomes in routine practice is complex. Therefore, this paper summarizes the key points and methods crucial to TR detection, quantitation, categorization, risk-scoring, intervention-monitoring, and outcomes evaluation, particularly of right-sided function, and to clinical trial development and conduct, for both interventional and surgical groups.

Computed tomography calcium scoring in aortic stenosis: bicuspid versus tricuspid morphology.

OBJECTIVE: CT aortic valve calcium score (AVCscore) and density (AVCdensity) thresholds have been recommended for aortic stenosis (AS) severity assessment in tricuspid aortic valve (TAV). We aimed to compare AVCscore and AVCdensity in bicuspid aortic valve (BAV) versus TAV. METHODS: Retrospective single-centre study of patients with echocardiographic AS-severity and CT-AVC assessments within 6 months, and left ventricular ejection fraction ≥50%, all referred for clinical AS evaluation.Severe AS was defined as aortic valve area (AVA) ≤1 cm2 or indexed AVA ≤0.6cm2/m2 plus mean gradient ≥40 mm Hg or peak velocity ≥4 m/s. AVC was assessed by Agatston method. RESULTS: Of the 1957 patients, 328 had BAV and 1629 had TAV, age 65±11 vs 80±9 years (p<0.001), men 65% vs 56% (p=0.006), respectively. BAV morphology was associated with higher AVCscore and AVCdensity independent of age, comorbidities and AS severity (p<0.001) in men only (sex and BAV interaction p<0.001). In patients with severe AS, mean AVCscore and AVCdensity were higher in BAV-men than that in TAV-men (both p<0.001), but similar in BAV-women and TAV-women (both p≥0.4). Such patterns remained the same after adjustment for clinical covariates and AS severity. Best thresholds for severe AS diagnosis in BAV-men were 2916 AU by AVCscore and 600 AU/cm2 by AVCdensity which were higher than the guideline-recommended thresholds, while thresholds in BAV-women (1036 AU and 282 AU/cm2) were similar to guideline-recommended ones. CONCLUSION: Valve calcification in AS differs according to valve morphology and sex. BAV-men with severe AS exhibit greater AVCscore and AVCdensity than TAV-men. This presents a diagnostic challenge to the current guidelines, which needs confirmation in larger studies.

Incidence of Severe Adverse Drug Reactions to Ultrasound Enhancement Agents in a Contemporary Echocardiography Practice.

OBJECTIVES: Prior data indicate a very rare risk of serious adverse drug reaction (ADR) to ultrasound enhancement agents (UEAs). We sought to evaluate the frequency of ADR to UEA administration in contemporary practice. METHODS: We retrospectively reviewed 4 US health systems to characterize the frequency and severity of ADR to UEA. Adverse drug reactions were considered severe when cardiopulmonary involvement was present and critical when there was loss of consciousness, loss of pulse, or ST-segment elevation. Rates of isolated back pain and headache were derived from the Mayo Clinic Rochester stress echocardiography database where systematic prospective reporting of ADR was performed. RESULTS: Among 26,539 Definity and 11,579 Lumason administrations in the Mayo Clinic Rochester stress echocardiography database, isolated back pain or headache was more frequent with Definity (0.49% vs 0.04%, P < .0001) but less common with Definity infusion versus bolus (0.08% vs 0.53%, P = .007). Among all sites there were 201,834 Definity and 84,943 Lumason administrations. Severe and critical ADR were more frequent with Lumason than with Definity (0.0848% vs 0.0114% and 0.0330% vs 0.0010%, respectively; P < .001 for each). Among the 3 health systems with >2,000 Lumason administrations, the frequency of severe ADR with Lumason ranged from 0.0755% to 0.1093% and the frequency of critical ADR ranged from 0.0293% to 0.0525%. Severe ADR rates with Definity were stable over time but increased in more recent years with Lumason (P = .02). Patients with an ADR to Lumason since the beginning of 2021 were more likely to have received a COVID-19 vaccination compared with matched controls (88% vs 75%; P = .05) and more likely to have received Moderna than Pfizer-Biotech (71% vs 26%, P < .001). CONCLUSION: Severe and critical ADR, while rare, were more frequent with Lumason, and the frequency has increased in more recent years. Additional work is needed to better understand factors, including associations with recently developed mRNA vaccines, which may be contributing to the increased rates of ADR to UEA since 2021.

Impact on Kidney Function and Medium-Term Outcomes of Transcatheter Aortic Valve Replacement in Patients With Chronic Kidney Disease.

Transcatheter aortic valve replacement (TAVR) is now widely approved for the treatment of aortic stenosis, regardless of the patients' surgical risk. However, the outcomes of TAVR and their determinants in patients with chronic kidney disease (CKD) beyond 1 year of follow-up are unknown. We aimed to assess the medium-term outcomes of TAVR in CKD, develop a risk score to estimate the 2-year mortality in patients with CKD, and evaluate the changes in kidney function at discharge after TAVR. Adults who underwent TAVR were retrospectively identified. The CKD stage was determined using the Chronic Kidney Disease Epidemiology 2021 creatinine formula. Improved kidney function was defined as post-TAVR creatinine ≤50% of pre-TAVR creatinine or decrease in creatinine of ≥0.3 mg/100 ml compared with pre-TAVR creatinine. Overall, 1,523 patients (median age 82 years; 59% men; 735 with CKD stage II or less, 661 with CKD III, 83 with CKD IV, and 44 with CKD V [of whom 40 were on dialysis]) were included. The all-cause mortality was higher in CKD stages IV and V on the multivariable analysis (p <0.001) at median follow-up of 2.9 (interquartile range 2.0 to 4.2) years. Moderate or severe tricuspid regurgitation, anemia, right ventricular systolic pressure >40 mm Hg and CKD stages IV and V were independent predictors of 2-year mortality and were used to develop a risk score. At hospital discharge, persisting acute kidney injury after TAVR occurred in 88 of 1,466 patients (6%), whereas improved kidney function occurred in 170 of 1,466 patients (12%). In conclusion, CKD stage was an independent determinant of mortality beyond 2 years after TAVR. Kidney function was more likely to improve than worsen at the time of hospital discharge after TAVR.

Characteristics and prognosis of isolated aortic valve infective endocarditis in patients with bicuspid aortic valves: a propensity matched study.

Introduction: Bicuspid aortic valve (BAV) is the most common congenital heart disease with an increased risk of infective endocarditis (IE). Few data are available on isolated native BAV-IE. The aim of this study was to compare patients with tricuspid aortic valve (TAV) IE and BAV-IE in terms of characteristics, management and prognosis. Material and methods: We included 728 consecutive patients with IE on isolated native aortic valve in 3 centres: Amiens and Marseille Hospitals in France and Salerno Hospital in Italy. We studied in hospital and long-term mortality before and after matching for age, sex and comorbidity index. Median follow-up was 67.2 [IQR: 19-120] months. Results: Of the 728 patients, 123 (16.9%) had BAV. Compared with patients with TAV-IE, patients with BAV-IE were younger, had fewer co-morbidities and were more likely to be male. They presented more major neurological events and perivalvular complications (both p < 0.05). Early surgery (<30 days) was performed in 52% of BAV-IE cases vs. 42.8% for TAV-IE (p = 0.061). The 10-year survival rate was 74 ± 5% in BAV-IE patients compared with 66 ± 2% in TAV-IE patients (p = 0.047). After propensity score matching (for age, gender and comorbidities), there was no difference in mortality between the two groups, with an estimated 10-year survival of 73 ± 5% vs. 76 ± 4% respectively (p = 0.91). Conclusion: BAV is a frequent finding in patients with isolated aortic valve IE and is associated with more perivalvular complications and neurological events. The differences in survival with TAV-IE are probably related to the age and comorbidity differences between these two populations.

Imaging Methods for Evaluation of Chronic Aortic Regurgitation in Adults: JACC State-of-the-Art Review.

A global multidisciplinary workshop was convened to discuss the multimodality diagnostic evaluation of aortic regurgitation (AR). Specifically, the focus was on assessment tools for AR severity and analyzing evolving data on the optimal timing of aortic valve intervention. The key concepts from this expert panel are summarized as: 1) echocardiography is the primary imaging modality for assessment of AR severity; however, when data is incongruent or incomplete, cardiac magnetic resonance may be helpful; 2) assessment of left ventricular size and function is crucial in determining the timing of intervention; 3) recent evidence suggests current cutpoints for intervention in asymptomatic severe AR patients requires further scrutiny; 4) left ventricular end-systolic volume index has emerged as an additional parameter that has promise in guiding timing of intervention; and 5) the role of additional factors (including global longitudinal strain, regurgitant fraction, and myocardial extracellular volume) is worthy of future investigation.

Bicuspid aortic valve: long-term morbidity and mortality.

BACKGROUND AND AIMS: Bicuspid aortic valve (BAV) is the most common congenital heart anomaly. Lifetime morbidity and whether long-term survival varies according to BAV patient-sub-groups are unknown. This study aimed to assess lifetime morbidity and long-term survival in BAV patients in the community. METHODS: The authors retrospectively identified all Olmsted County (Minnesota) residents with an echocardiographic diagnosis of BAV from 1 January 1980 to 31 December 2009, including patients with typical valvulo-aortopathy (BAV without accelerated valvulo-aortopathy or associated disorders), and those with complex valvulo-aortopathy (BAV with accelerated valvulo-aortopathy or associated disorders). RESULTS: 652 consecutive diagnosed BAV patients [median (IQR) age 37 (22-53) years; 525 (81%) adult and 127 (19%) paediatric] were followed for a median (IQR) of 19.1 (12.9-25.8) years. The total cumulative lifetime morbidity burden (from birth to age 90) was 86% (95% CI 82.5-89.7); cumulative lifetime progression to ≥ moderate aortic stenosis or regurgitation, aortic valve surgery, aortic aneurysm ≥45 mm or z-score ≥3, aorta surgery, infective endocarditis and aortic dissection was 80.3%, 68.5%, 75.4%, 27%, 6% and 1.6%, respectively. Survival of patients with typical valvulo-aortopathy [562 (86%), age 40 (28-55) years, 86% adults] was similar to age-sex-matched Minnesota population (P = .12). Conversely, survival of patients with complex valvulo-aortopathy [90 (14%), age 14 (3-26) years, 57% paediatric] was lower than expected, with a relative excess mortality risk of 2.25 (95% CI 1.21-4.19) (P = .01). CONCLUSION: The BAV condition exhibits a high lifetime morbidity burden where valvulo-aortopathy is close to unavoidable by age 90. The lifetime incidence of infective endocarditis is higher than that of aortic dissection. The most common BAV clinical presentation is the typical valvulo-aortopathy with preserved expected long-term survival, while the complex valvulo-aortopathy presentation incurs higher mortality.

Incidence, risk factors, and outcomes of atrial functional mitral regurgitation in patients with atrial fibrillation or sinus rhythm.

AIMS: Atrial functional mitral regurgitation (AFMR) has been associated with atrial fibrillation (AF) and heart failure with preserved ejection fraction. However, data on incident AFMR are scarce. We aimed to study the incidence, risk factors, and clinical significance of AFMR in AF or sinus rhythm (SR). METHODS AND RESULTS: Adults with new diagnosis of AF and adults in SR were identified. Patients with >mild MR at baseline, primary mitral disease, cardiomyopathy, left-sided valve disease, previous cardiac surgery, or with no follow-up echocardiogram were excluded. Diastolic dysfunction (DD) was indicated by ≥2/4 abnormal diastolic function parameters [mitral medial e', mitral medial E/e', tricuspid regurgitation velocity, left atrial volume index (LAVI)]. Overall, 1747 patients with AF and 29 623 in SR were included. Incidence rate of >mild AFMR was 2.6 per 100 person-year in new-onset AF and 0.7 per 100 person-year in SR, P < 0.001. AF remained associated with AFMR in a propensity score-matched analysis based on age, sex, and comorbidities between AF and SR [hazard ratio: 3.80 (95% confidence interval 3.04-4.76)]. Independent risk factors associated with incident AFMR were age ≥65 years, female sex, LAVI, and DD in both AF and SR, in addition to rate (vs. rhythm) control in AF. Incident AFMR was independently associated with all-cause death in both groups (both P < 0.001). CONCLUSIONS: AF conferred a three-fold increase in the risk of incident AFMR. DD, older age, left atrial size, and female sex were independent risk factors in both SR and AF, while rhythm control was protective. AFMR was universally associated with worse mortality.

Arrhythmic mitral valve prolapse and mitral annular disjunction: pathophysiology, risk stratification, and management.

Mitral valve prolapse (MVP) is the most frequent valve condition but remains a conundrum in many aspects, particularly in regard to the existence and frequency of an arrhythmic form (AMVP) and its link to sudden cardiac death. Furthermore, the presence, frequency, and significance of the anatomic functional feature called mitral annular disjunction (MAD) have remained widely disputed. Recent case series and cohorts have shattered the concept that MVP is most generally benign and have emphasized the various phenotypes associated with clinically significant ventricular arrhythmias, including AMVP. The definition, evaluation, follow-up, and management of AMVP represent the focus of the present review, strengthened by recent coherent studies defining an arrhythmic MVP phenotypic that would affect a small subset of patients with MVP at concentrated high risk. The role of MAD in this context is of particular importance, and this review highlights the characteristics of AMVP phenotypes and MAD, their clinical, multimodality imaging, and rhythmic evaluation. These seminal facts lead to proposing a risk stratification clinical pathway with consideration of medical, rhythmologic, and surgical management and have been objects of recent expert consensus statements and of proposals for new research directions.