Prognostic Implications of Left Atrial Stiffness Index in Heart Failure Patients With Preserved Ejection Fraction

BackgroundThe left atrium (LA) plays an important role in the pathophysiology and disease progression of heart failure with preserved ejection fraction (HFpEF).ObjectivesThis study sought to assess the prognostic potential of LA stiffness index in patients who have HFpEF.MethodsThis study retrospectively screened patients with elevated left ventricular end-diastolic pressure (≥16 mm Hg) and preserved ejection fraction (≥50%) between January 1, 2004, and December 31, 2019. All patients underwent left heart catheterization to measure left ventricular end-diastolic pressure. Among these, 307 patients who had suitable image quality for left peak atrial longitudinal strain (PALS) measurement were analyzed. The study population was classified into low LA stiffness (n = 178, early diastolic transmitral inflow velocity/mitral annulus early diastolic velocity [E/e′]/PALS ≤0.26) and high LA stiffness (n = 129, E/e′/PALS >0.26) according to the best LA stiffness index (E/e′/PALS) cutoff value. The primary outcome was a composite of mortality or hospitalization caused by heart failure during follow-up.ResultsLA stiffness index showed good correlations with E/e′ (r = 0.737; P < 0.001), LA volume index (r = 0.529; P < 0.001), right ventricular systolic pressure (r = 0.404; P < 0.001), and log N-terminal pro–B-type natriuretic peptide (r = 0.540; P < 0.001). LA stiffness index demonstrated better predictive performance than echocardiographic diastolic parameters did (P < 0.001). Patients with low LA stiffness had better clinical outcomes than those with high LA stiffness during a median follow-up of 6 years did (P < 0.001). In multivariable analysis, LA stiffness index was independently associated with increased risk of the composite endpoint of death or heart failure hospitalization (HR: 1.59 [95% CI: 1.01-2.51]; P = 0.044).ConclusionsIncreased LA stiffness was associated with increased risk for all-cause mortality and hospitalization caused by heart failure in patients who have HFpEF, and its prognostic role was more pronounced than that of indexes of left ventricular filling pressure.     

Sex Differences in LV Remodeling and Hemodynamics in Aortic Stenosis: Sex-Specific Criteria for Severe Stenosis?

BackgroundThe current criteria for aortic stenosis (AS) severity have not incorporated sex-related differences.ObjectivesThe authors investigated sex-related serial changes in left ventricular (LV) structure/function and hemodynamics in AS.MethodsSerial echocardiograms of patients with severe AS (time 0; aortic valve area [AVA] ≤1 cm²) and ≥1 previous echocardiogram were compared between sexes.ResultsOf 927 patients (time 0: AVA 0.87 ± 0.11 cm², peak velocity 4.03 ± 0.65 m/s, mean Doppler systolic pressure gradient [MG] 40.6 ± 13.1 mm Hg), 393 (42%) were women. Women had smaller body surface area (BSA) (1.77 ± 0.22 m² vs 2.03 ± 0.20 m²; P < 0.001), lower stroke volume (SV) (81.1 ± 17.2 mL vs 88.3 ± 18.6 mL; P < 0.001), and more frequent low-gradient severe AS (n = 196 [50%] vs n = 181 [34%]; P < 0.001). Women consistently had smaller AVA, indexed AVA (AVAi), peak velocity, and MG than men. The difference in aortic valve gradient lessened when AVAi ≤0.6 cm²/m² was applied as severe AS (n = 694, women 43%, AVA 0.95 ± 0.17 cm², AVAi 0.50 ± 0.07 cm²/m²). Peak velocity (3.83 ± 0.66 m/s) and MG (36.5 ± 13.2 mm Hg) were lower based on AVAi severity criteria compared to those based on AVA. Men had a lower left ventricular ejection fraction (LVEF) (55.8% ± 14.8% vs 61.1% ± 11.7%; P < 0.001) and greater reduction in SV (?13.3 ± 19.6 mL vs ?7.4 ± 16.4 mL; P < 0.001) as AS progressed from moderate to severe. Concentric LV hypertrophy was more common and E/e? higher in women (21.2 ± 10.9 vs 18.8 ± 9.1; P < 0.001). SV, LVEF, AVA, peak velocity, and MG became precipitously worse when AVA reached 1.2 cm² in both sexes.ConclusionsSmaller BSA in women yields lower SV, resulting in lower aortic valve gradient than men. Indexed parameters by BSA are thus important in sex-related differences of aortic valve hemodynamics, but AVAi ≤0.6 cm²/m² includes individuals with moderate AS. Elevated filling pressure is more common in women. Men experience a larger reduction in SV and LVEF as AS progresses. The definition of AS severity may require different criteria between sexes.     

Diagnostic Accuracy of the 2016 Guideline-Based Echocardiographic Algorithm to Estimate Invasively-Measured Left Atrial Pressure by Direct Atrial Cannulation

BackgroundAlthough estimation of left ventricular filling pressure (LVFP) using an integrated echocardiographic algorithm is recommended, the usefulness of this algorithm has not been fully validated.ObjectivesThe purpose of this study was to investigate the reliability of an algorithmic classification system using invasively measured left atrial pressure (LAP) in a large-scale cohort.MethodsThe authors enrolled 1,967 patients (age 68 ± 10 years) whose LAP was directly measured within the left atrium during catheter ablation for atrial fibrillation. Patients were classified into 3 groups based on the echocardiographic algorithm: normal (group N, n = 1,282), undetermined (group U, n = 160), and elevated (group E, n = 346) LAP groups. Invasively measured LAP and echocardiographic parameters estimating LVFP were compared among the groups.ResultsThe median LAP was 12.6 ± 5.7 mm Hg in the entire cohort. LAP was significantly higher in group E than that in the other groups (groups E vs U vs N, 14.2 ± 6.3 mm Hg vs 13.5 ± 5.9 mm Hg vs 12.0 ± 5.5 mm Hg; P < 0.001). Among group E patients, 43.1% had elevated LAP (≥15 mm Hg), whereas 56.9% had normal LAP (<15 mm Hg). Of the patients in group N, 69.0% had normal LAP, whereas 31% had elevated LAP. Although the correlation between invasively measured LAP and E/e′, peak tricuspid regurgitant velocity, and left atrial volume index was modest, the number of abnormal values correlated significantly with elevated LAP (P < 0.001).ConclusionsThe classification using combined echocardiographic parameters in the recommendations may be useful for detecting patients with normal LVFP but may be limited for detecting elevated LVFP.     

1-Year Outcomes of Cardioband Tricuspid Valve Reconstruction System Early Feasibility Study

BackgroundTricuspid regurgitation (TR) is prevalent and undertreated, with mortality and morbidity increasing with TR severity. Given poor outcomes with medical therapy and high in-hospital mortality for isolated tricuspid valve surgery, emerging transcatheter repair devices offer a promising alternative.ObjectivesThe Edwards Cardioband Tricuspid Valve Reconstruction System Early Feasibility study (NCT03382457) evaluates the treatment of functional TR via annular reduction with the Cardioband Tricuspid Valve Reconstruction System (Edwards Lifesciences).MethodsPatients with ≥ moderate functional TR were eligible for this prospective, single-arm multicenter study. At 1 year, patients were evaluated for echocardiographic parameters, clinical and quality-of-life measures, and major adverse events.ResultsThe 37 patients enrolled had a mean age of 78 years; 76% were female; and they had ≥ severe functional (97.3%) or mixed (2.7%) TR, atrial flutter/fibrillation (97%), and New York Heart Association functional class III/IV (65%). At 1 year, 73.0% achieved ≤ moderate TR (P < 0.0001), and 73.1% had ≥2 grade reductions. Echocardiography showed significant reductions in the tricuspid annulus diameter (P < 0.0001), mean vena contracta (P < 0.0001), proximal isovelocity surface area effective regurgitant orifice area (P < 0.0001), right ventricular end-diastolic diameter (P < 0.0001), and inferior vena contracta (P = 0.0006). New York Heart Association functional class improved significantly (P < 0.0001), with 92.3% achieving class I/II, and Kansas City Cardiomyopathy Questionnaire scores improved by 19.0 points (P < 0.0001). One-year cardiovascular mortality was 8.1%, reinterventions were necessary in 5.4%, major access site complications occurred in 8.1%, and severe bleeding was noted in 35.1% of patients. Kaplan-Meier estimates of survival and freedom from heart failure rehospitalization were 85.9% and 88.7%, respectively.ConclusionsOne-year experience using the Cardioband system for tricuspid valve repair shows high survival and low rehospitalization rates with durable outcomes in TR reduction and echocardiographic, clinical, and quality-of-life outcomes.     

Evolution of Myocardial Tissue Injury: A CMR Study Over a Decade After STEMI

BackgroundIn patients with a first ST-segment elevation myocardial infarction (STEMI), the multi-annual evolution of myocardial tissue injury parameters, as assessed by cardiac magnetic resonance (CMR), has not yet been described.ObjectivesThis study examined myocardial tissue injury dynamics over a decade after STEMI.MethodsSequential CMR examinations (within the first week after STEMI, and at 4, 12, months, and 9 years thereafter) were conducted in 74 patients with STEMI treated with primary percutaneous coronary intervention. Left ventricular function, infarct size (IS), and microvascular obstruction (MVO) were assessed at all time points. T21, T2, and T1 mapping (n = 59) were added at 9-year scan to evaluate the presence of iron and edema within the infarct core, respectively.ResultsIS decreased progressively and significantly between all CMR time points (all P < 0.001), with an average reduction rate of 5.8% per year (IQR: 3.5%-8.8%) and a relative reduction of 49% (IQR: 39%-76%) over a decade. MVO was present in 61% of patients at baseline, but was not present at the follow-up examinations. At 9-year CMR, 17 of 59 (29%) patients showed iron deposition within the infarct core, whereas 82% had persistent edema. Persistent iron and edema were associated with greater IS on any occasion (all P < 0.001), as well as the presence of MVO (P < 0.001). Patients with persistent iron and edema showed a lower relative regression of IS (P = 0.005 and P = 0.032, respectively) and greater end-systolic volumes over a decade (all P < 0.012 and P > 0.023, respectively). A T1 hypointense infarct core without evidence of T21 iron deposition (14 of 59 [24%] patients) was attributed to lipomatous metaplasia of the infarct.ConclusionsThe evolution of IS is a dynamic process that extends well beyond the first few months after STEMI. Persistence of iron and edema within the infarct core occurs up to a decade after STEMI and is associated with initial infarct severity and poor infarct healing.     

Pulmonary Artery 18F-Fluorodeoxyglucose Uptake by PET/CMR as a Marker of Pulmonary Hypertension in Sarcoidosis

ObjectivesThis study investigated whether pulmonary artery (PA) ¹⁸F-FDG uptake is associated with hypertension, and if it correlates to elevated pulmonary pressures.Background¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with computed tomography or cardiac magnetic resonance (CMR) has been used to assess inflammation mostly in large arteries of the systemic circulation. Much less is known about inflammation of the vasculature of the pulmonary system and its relationship to pulmonary hypertension (PH).MethodsIn a single-center cohort of 175 patients with suspected cardiac sarcoidosis, who underwent hybrid thoracic PET/CMR, ¹⁸F-FDG uptake in the PA was quantified according to maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) and compared with available results from right heart catheterization (RHC) or transthoracic echocardiography (TTE).ResultsThirty-three subjects demonstrated clear ¹⁸F-FDG uptake in the PA wall. In the subgroup of patients who underwent RHC (n = 10), the mean PA pressure was significantly higher in the group with PA ¹⁸F-FDG uptake compared with the group without uptake (34.4 ± 7.2 mm Hg vs 25.6 ± 9.3 mm Hg; P = 0.003), and 9 (90%) patients with PA ¹⁸F-FDG uptake had PH when a mean PA pressure cutoff of 25 mm Hg was used compared with 18 (45%) in the nonuptake group (P < 0.05). In the subgroup that underwent TTE, signs of PH were present in a significantly higher number of patients with PA ¹⁸F-FDG uptake (14 [51.9%] vs 37 [29.8%]; P < 0.05). Qualitative assessment of ¹⁸F-FDG uptake in the PA wall showed a sensitivity of 33% and specificity of 96% for separating patients with PH based on RHC-derived PA pressures. SUVmax and TBR in the PA wall correlated with PA pressure derived from RHC and/or TTE.ConclusionsWe demonstrate that ¹⁸F-FDG uptake by PET/CMR in the PA is associated with PH and that its intensity correlates with PA pressure.     

Structural Cardiac Remodeling in Atrial Fibrillation

ObjectivesThis study sought to evaluate preablation computed tomography angiography (CTA) for atrial and epicardial features to predict atrial fibrillation (AF) recurrence after ablation.BackgroundStructural atrial remodeling is a process associated with occurrence or persistence of AF. Different anatomical imaging features have been proposed to influence atrial remodeling both negatively and positively as substrate for AF.MethodsPatients with nonvalvular AF underwent cardiac CTA before pulmonary vein isolation at 2 high-volume centers. Left atrial (LA) and right atrial volumes, LA wall thickness (LAWT), and epicardial adipose tissue volume and attenuation were evaluated. Additional subanalyses of electroanatomical maps were made. Follow-up was performed for at least 12 months, including subanalysis of repeated cardiac CTA studies. Interrater variability was assessed.ResultsOf 732 patients, 270 (36.9%) had AF recurrence after a mean of 7 months. CT analysis revealed larger indexed LA volume (47.3 mL/m² vs 43.6 mL/m²; P = 0.0001) and higher mean anterior (1.91 mm vs 1.65 mm; P < 0.0001) and posterior (1.61 mm vs 1.39 mm; P = 0.001) LAWT in patients with AF recurrence. Epicardial adipose tissue volume in patients with AF recurrence was higher (144.5 mm³ vs 128.5 mm³; P < 0.0001) and further progressed significantly in a subset of 85 patients after 2 years (+11.8 mm² vs −3.5 mm²; P = 0.041). Attenuation levels were lower, indicating a higher lipid component associated with AF recurrence (−69.1 HU vs −67.5 HU; P = 0.001). A total of 103 atrial voltage maps were highly predictive of AF recurrence and showed good discriminatory power for patients with low voltage >50% and LAWT (1.55 ± 0.5 mm vs 1.81 ± 0.6 mm; P = 0.032). Net reclassification improvement (NRI) showed a significant incremental benefit (NRI = 0.279; P < 0.0001) when adding LAWT to established risk models.ConclusionsAtrial wall thickness, epicardial fat volume, and attenuation are associated with AF recurrence in patients undergoing ablation therapy.     

Aortic Stenosis Progression: A Systematic Review and Meta-Analysis

BackgroundAortic valve stenosis is a progressive disorder with variable progression rates. The factors affecting aortic stenosis (AS) progression remain largely unknown.ObjectivesThis systematic review and meta-analysis sought to determine AS progression rates and to assess the impact of baseline AS severity and sex on disease progression.MethodsThe authors searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to July 1, 2020, for prospective studies evaluating the progression of AS with the use of echocardiography (mean gradient [MG], peak velocity [PV], peak gradient [PG], or aortic valve area [AVA]) or computed tomography (calcium score [AVC]). Random-effects meta-analysis was performed to evaluate the rate of AS progression for each parameter stratified by baseline severity, and meta-regression was performed to determine the impact of baseline severity and of sex on AS progression rate.ResultsA total of 24 studies including 5,450 patients (40% female) met inclusion criteria. The pooled annualized progression of MG was +4.10 mm Hg (95% CI: 2.80-5.41 mm Hg), AVA −0.08 cm² (95% CI: 0.06-0.10 cm²), PV +0.19 m/s (95% CI: 0.13-0.24 m/s), PG +7.86 mm Hg (95% CI: 4.98-10.75 mm Hg), and AVC +158.5 AU (95% CI: 55.0-261.9 AU). Increasing baseline severity of AS was predictive of higher rates of progression for MG (P < 0.001), PV (P = 0.001), and AVC (P < 0.001), but not AVA (P = 0.34) or PG (P = 0.21). Only 4 studies reported AS progression stratified by sex, with only PV and AVC having 3 studies to perform a meta-analysis. No difference between sex was observed for PV (P = 0.397) or AVC (P = 0.572), but the level of confidence was low.ConclusionsThis study provides progression rates for both hemodynamic and anatomic parameters of AS and shows that increasing hemodynamic and anatomic baseline severity is associated with faster AS progression. More studies are needed to determine if sex differences affect AS progression. (Aortic Valve Stenosis Progression Rate: A Systematic Review and Meta-Analysis; CRD42021207726)     

Ventricular-Arterial Coupling Derived From Proximal Aortic Stiffness and Aerobic Capacity Across the Heart Failure Spectrum

BackgroundVentricular-arterial coupling (VAC) can be evaluated as the ratio between arterial stiffness (pulsed wave velocity [PWV]) and myocardial deformation (global longitudinal strain [GLS]).ObjectivesThis study aimed to evaluate VAC across the spectrum of heart failure (HF).MethodsThe authors introduced a Doppler-derived, single-beat technique to estimate aortic arch PWV (aa-PWV) in addition to tonometry-derived carotid-femoral PWV (cf-PWV). They measured PWVs and GLS in 155 healthy controls, 75 subjects at risk of developing HF (American College of Cardiology/American Heart Association stage A-B) and 236 patients in stage C heart failure with preserved ejection fraction (HFpEF) (n = 104) or heart failure with reduced ejection fraction (HFrEF) (n = 132). They evaluated peak oxygen consumption and peripheral extraction using combined cardiopulmonary-echocardiography exercise stress.Resultsaa-PWV was obtainable in all subjects and significantly lower than cf-PWV in all subgroups (P < 0.01). PWVs were directly related and increased with age (all P < 0.0001). cf-PWV/GLS was similarly compromised in HFrEF (1.09 ± 0.35) and HFpEF (1.05 ± 0.21), whereas aa-PWV/GLS was more impaired in HFpEF (0.70 ± 0.10) than HFrEF (0.61 ± 0.14; P < 0.01). Stage A-B had values of cf-PWV/GLS and aa-PWV/GLS (0.67 ± 0.27 and 0.48 ± 0.14, respectively) higher than controls (0.46 ± 0.11 and 0.39 ± 0.10, respectively) but lower than stage C (all P < 0.01). Peak arteriovenous oxygen difference (AVO₂diff) was inversely related with cf-PWV/GLS and aa-PWV/GLS (all P < 0.01). Although cf-PWV/GLS and aa-PWV/GLS independently predicted peak VO₂ in the overall population (adjusted R² = 0.33 and R²= 0.36; all P < 0.0001), only aa-PWV/GLS was independently associated with flow reserve during exercise (R² = 0.52; P < 0.0001).ConclusionsAbnormal VAC is directly correlated with greater severity of HF and worse functional capacity. HFpEF shows a worse VAC than HFrEF when expressed by aa-PWV/GLS.     

Transfemoral Tricuspid Valve Replacement in Patients With Tricuspid Regurgitation: TRISCEND Study 30-Day Results

ObjectivesThe TRISCEND study (Edwards EVOQUE Tricuspid Valve Replacement: Investigation of Safety and Clinical Efficacy after Replacement of Tricuspid Valve with Transcatheter Device) is evaluating the safety and performance of transfemoral transcatheter tricuspid valve replacement in patients with clinically significant tricuspid regurgitation (TR) and elevated surgical risk.BackgroundTranscatheter valve replacement could lead to a paradigm shift in treating TR and improving patient quality of life.MethodsIn the prospective, single-arm, multicenter TRISCEND study, patients with symptomatic moderate or greater TR, despite medical therapy, underwent percutaneous transcatheter tricuspid valve replacement with the EVOQUE system. A composite rate of major adverse events, echocardiographic parameters, and clinical, functional, and quality-of-life measures were assessed at 30 days.ResultsFifty-six patients (mean age of 79.3 years, 76.8% female, 91.1% TR severe or greater, 91.1% atrial fibrillation, and 87.5% New York Heart Association functional class III or IV) were treated. At 30 days, TR was reduced to mild or less in 98%. The composite major adverse events rate was 26.8% at 30 days caused by 1 cardiovascular death in a patient with a failed procedure, 2 reinterventions after device embolization, 1 major access site or vascular complication, and 15 severe bleeds, of which none were life-threatening or fatal. No myocardial infarction, stroke, renal failure, major cardiac structural complications, or device-related pulmonary embolism were observed. New York Heart Association significantly improved to functional class I or II (78.8%; P < 0.001), 6-minute walk distance improved 49.8 m (P < 0.001), and Kansas City Cardiomyopathy Questionnaire score improved 19 points (P < 0.001).ConclusionsEarly experience with the transfemoral EVOQUE system in patients with clinically significant TR demonstrated technical feasibility, acceptable safety, TR reduction, and symptomatic improvement at 30 days. The TRISCEND II randomized trial (NCT04482062) is underway.     

3-Dimensional Strain Analysis of Hypertrophic Cardiomyopathy: Insights From the NHLBI International HCM Registry

BackgroundAbnormal global longitudinal strain (GLS) has been independently associated with adverse cardiac outcomes in both obstructive and nonobstructive hypertrophic cardiomyopathy.ObjectivesThe goal of this study was to understand predictors of abnormal GLS from baseline data from the National Heart, Lung, and Blood Institute (NHLBI) Hypertrophic Cardiomyopathy Registry (HCMR).MethodsThe study evaluated comprehensive 3-dimensional left ventricular myocardial strain from cine cardiac magnetic resonance in 2,311 patients from HCMR using in-house validated feature-tracking software. These data were correlated with other imaging markers, serum biomarkers, and demographic variables.ResultsAbnormal median GLS (> –11.0%) was associated with higher left ventricular (LV) mass index (93.8 ± 29.2 g/m² vs 75.1 ± 19.7 g/m²; P < 0.0001) and maximal wall thickness (21.7 ± 5.2 mm vs 19.3 ± 4.1 mm; P < 0.0001), lower left (62% ± 9% vs 66% ± 7%; P < 0.0001) and right (68% ± 11% vs 69% ± 10%; P < 0.01) ventricular ejection fractions, lower left atrial emptying functions (P < 0.0001 for all), and higher presence and myocardial extent of late gadolinium enhancement (6 SD and visual quantification; P < 0.0001 for both). Elastic net regression showed that adjusted predictors of GLS included female sex, Black race, history of syncope, presence of systolic anterior motion of the mitral valve, reverse curvature and apical morphologies, LV ejection fraction, LV mass index, and both presence/extent of late gadolinium enhancement and baseline N-terminal pro–B-type natriuretic peptide and troponin levels.ConclusionsAbnormal strain in hypertrophic cardiomyopathy is associated with other imaging and serum biomarkers of increased risk. Further follow-up of the HCMR cohort is needed to understand the independent relationship between LV strain and adverse cardiac outcomes in hypertrophic cardiomyopathy.     

Mitral Annular Dynamics in AF Versus Sinus Rhythm: Novel Insights Into the Mechanism of AFMR

ObjectivesThis study aimed to investigate mitral annular dynamics in atrial fibrillation (AF) and after sinus rhythm restoration, and to assess the relationship between annular dynamics and mitral regurgitation (MR).BackgroundAF can be associated with MR that improves after sinus rhythm restoration. Mechanisms underlying this atrial functional MR (AFMR) are ill-understood and generally attributed to left atrial remodeling.MethodsFifty-three patients with persistent AF and normal left ventricular ejection fraction were prospectively examined by means of 3-dimensional transesophageal echocardiography before, immediately after, and 6 weeks after electric cardioversion to sinus rhythm. Annular motion was assessed during AF and in sinus rhythm with the use of 3-dimensional analysis software, and the relationship with MR severity was explored.ResultsDuring AF and immediately after sinus rhythm restoration, the mitral annulus behaved relatively adynamically, with an overall change in annular area of 10.3% (95% CI: 8.7%-11.8%) and 12.2% (95% CI: 10.6%-13.8%), respectively. At follow-up, a significant increase in annular dynamics (19.0%; 95% CI: 17.4%-20.6%; P < 0.001) was observed, owing predominantly to an increase in presystolic contraction (P < 0.001). The effective regurgitant orifice area decreased from 0.15 cm² (0.10-0.23 cm²) during AF to 0.09 cm² (0.05-0.12 cm²) at follow-up (P < 0.001) in the total cohort, and from 0.27 (0.23-0.33) to 0.16 (0.12-0.29) in the subgroup with effective regurgitant orifice area (EROA) ≥0.20 cm². The change in presystolic annular motion was the only independent determinant of the decrease in MR severity (P = 0.027), by optimizing annular-leaflet imbalance. Patients with more pronounced blunting of presystolic dynamics had a higher EROA (P < 0.001), because of a lower total-to-closed leaflet area ratio (P < 0.001) at each point in time. This ratio was the strongest independent determinant of AFMR severity (adjusted P = 0.003).ConclusionsMitral annular dynamics are impaired in AF, with blunted presystolic narrowing that contributes to AFMR. Sinus rhythm restoration allows gradual recovery of presystolic annular dynamics. Improved annular dynamics decrease AFMR severity by optimizing annular-leaflet imbalance, regardless of LA remodeling.     

Too Little of a Good Thing: Strong Associations Between Cardiac Size and Fitness Among Women

BackgroundCardiorespiratory fitness (CRF) is associated with functional impairment and cardiac events, particularly heart failure (HF). However, the factors predisposing women to low CRF and HF remain unclear.ObjectivesThis study sought to evaluate the association between CRF and measures of ventricular size and function and to examine the potential mechanism linking these factors.MethodsA total of 185 healthy women aged >30 years (51 ± 9 years) underwent assessment of CRF (peak volume of oxygen uptake [Vo₂peak]) and biventricular volumes at rest and during exercise by using cardiac magnetic resonance (CMR). The relationships among Vo₂peak, cardiac volumes, and echocardiographic measures of systolic and diastolic function were assessed using linear regression. The effect of cardiac size on cardiac reserve (change in cardiac function during exercise) was assessed by comparing quartiles of resting left ventricular end-diastolic volume (LVEDV).ResultsVo₂peak was strongly associated with resting measures of LVEDV and right ventricular end-diastolic volume (R² = 0.58-0.63; P < 0.0001), but weakly associated with measures of resting left ventricular (LV) systolic and diastolic function (R² = 0.01-0.06; P < 0.05). Increasing LVEDV quartiles were positively associated with cardiac reserve, with the smallest quartile showing the smallest reduction in LV end-systolic volume (quartile [Q]1: −4 mL vs Q4: −12 mL), smallest augmentation in LV stroke volume (Q1: +11 mL vs Q4: +20 mL) and cardiac output (Q1: +6.6 L/min vs Q4: +10.3 L/min) during exercise (interaction P < 0.001 for all).ConclusionsA small ventricle is strongly associated with low CRF because of the combined effect of a smaller resting stroke volume and an attenuated capacity to increase with exercise. The prognostic implications of low CRF in midlife highlight the need for further longitudinal studies to determine whether women with small ventricles are predisposed to functional impairment, exertional intolerance, and HF later in life.     

Hemodynamic Profiles and Clinical Response to Transcatheter Mitral Repair

BackgroundPrediction of the clinical response to transcatheter edge-to-edge repair (TEER) remains a vexing challenge.ObjectivesThis study sought to examine the relation between hemodynamic profiles and outcomes following mitral TEER.MethodsAmong 378 patients (median age 82 years; 43.9% women), 3 hemodynamic profiles using residual left atrial pressure (LAP) and mitral regurgitation (MR) were defined: type I (optimal), grade ≤1 MR and mean LAP (mLAP) ≤15 mm Hg; type II (mixed), MR grade >1 or mLAP >15 mm Hg; and type III (poor), MR grade >1 and mLAP >15 mm Hg. The discrimination of these profiles for predicting outcomes was examined. A positive clinical response to TEER was defined as improvement in New York Heart Association functional class ≥I grade at 1 year without heart failure rehospitalization or death.ResultsThere were 148 (39.0%) patients classified as optimal (type I), 187 (49.0%) patients as mixed (type II), and 43 (11.0%) patients as poor (type III). For all-cause mortality, survival at 1 year was 91.6%, 82.6%, and 67.9% for types I, II, and III, respectively (HR: 2.13; 95% CI: 1.44-3.15; P < 0.001). For the composite endpoint of all-cause mortality and rehospitalization for heart failure, event-free survival at 1 year was 84.1%, 70.7%, and 53.2% for types I, II, and III, respectively (HR: 1.93; 95% CI: 1.41-2.65; P < 0.001). Hemodynamic profiling was strongly associated with a positive response to TEER, occurring in 73.9%, 57.0%, 35.0%, for types I, II, and III, respectively (P < 0.001).ConclusionsIn patients undergoing mitral TEER, hemodynamic profiling is prognostic, with superior survival occurring among patients with optimal reduction in MR and normal postprocedural LAP.     

Association of Sex,Reduced Myocardial Flow Reserve,and Long-Term Mortality Across Spectrum of Atherosclerotic Disease

BackgroundCoronary vasomotor dysfunction (defined by reduced myocardial blood flow reserve [MBFR]) is associated with high cardiac risk in both men and women in absence of significant coexisting epicardial disease. Whether there is a sex-specific difference in prognostic value of reduced MBFR in patients with a greater burden of coexisting epicardial atherosclerotic disease is not well understood.ObjectivesThe purpose of this study was to examine the association of sex, MBFR, and mortality in consecutive patients with suspected or known coronary artery disease undergoing positron emission tomography myocardial perfusion imaging.MethodsUnique consecutive patients undergoing rubidium (Rb)-82 rest/stress positron emission tomography myocardial perfusion imaging from 2010-2016 were followed for a median of 3.2 years. Multivariable Cox models were built to describe the interaction of sex and MBFR on all-cause and cardiac death for the overall population and stratified by extent of calcified atherosclerosis (none: coronary artery calcium score = 0, subclinical: coronary artery calcium >0, clinical: prior myocardial infarction/percutaneous coronary intervention) and abnormal perfusion (no significant obstructive disease: summed stress score = 0, 1%-9.9%, and ≥10%) at baseline.ResultsAmong 12,594 patients, 52.8% were women. Compared with men, women had a lower prevalence of known coronary artery disease (16.5% vs 29.5%; P < 0.001) and were less likely to undergo revascularization after myocardial perfusion imaging (4.9% vs 9.7%; P < 0.001), but were more likely to have a reduced MBFR of <2 (56.2% vs 50.6%; P < 0.001). There were 1,699 (13.5%) all-cause and 490 (3.9%) cardiac deaths. In fully adjusted Cox models, reduced MBFR was independently associated with higher risk of death (HR per 0.1-U decrease: 1.09 [95% CI: 1.08-1.10]; P < 0.001), but female sex was not (HR: 0.95 [95% CI: 0.85-1.05]; P = 0.27). There was no significant interaction between sex and MBFR on death (P = 0.22) and cardiac death (P = 0.35) overall or in subgroups of patients with clinical, subclinical, and no atherosclerosis or across categories of perfusion abnormality at baseline.ConclusionsThe association between reduced MBFR and higher risk of all-cause and cardiac death did not differ by sex, regardless of extent of coexisting atherosclerosis or perfusion abnormality.     

Sex-Specific Stress Perfusion Cardiac Magnetic Resonance Imaging in Suspected Ischemic Heart Disease: Insights From SPINS Retrospective Registry

BackgroundCardiovascular disease (CVD) remains the leading cause of mortality in women, but current noninvasive cardiac imaging techniques have sex-specific limitations.ObjectivesIn this study, the authors sought to investigate the effect of sex on the prognostic utility and downstream invasive revascularization and costs of stress perfusion cardiac magnetic resonance (CMR) for suspected CVD.MethodsSex-specific prognostic performance was evaluated in a 2,349-patient multicenter SPINS (Stress CMR Perfusion Imaging in the United States [SPINS] Study) Registry. The primary outcome measure was a composite of cardiovascular death and nonfatal myocardial infarction; secondary outcomes were hospitalization for unstable angina or heart failure, and late unplanned coronary artery bypass grafting.ResultsSPINS included 1,104 women (47% of cohort); women had higher prevalence of chest pain (62% vs 50%; P < 0.0001) but lower use of medical therapies. At the 5.4-year median follow-up, women with normal stress CMR had a low annualized rate of primary composite outcome similar to men (0.54%/y vs 0.75%/y, respectively; P = NS). In contrast, women with abnormal CMR were at higher risk for both primary (3.74%/y vs 0.54%/y; P < 0.0001) and secondary (9.8%/y vs 1.6%/y; P < 0.0001) outcomes compared with women with normal CMR. Abnormal stress CMR was an independent predictor for the primary (HR: 2.64 [95% CI: 1.20-5.90]; P = 0.02) and secondary (HR: 2.09 [95% CI: 1.43-3.08]; P < 0.0001) outcome measures. There was no effect modification for sex. Women had lower rates of invasive coronary angiography (3.6% vs 7.3%; P = 0.0001) and downstream costs ($114 vs $171; P = 0.001) at 90 days following CMR. There was no effect of sex on diagnostic image quality.ConclusionsStress CMR demonstrated excellent prognostic performance with lower rates of invasive coronary angiography referral in women. Stress CMR should be considered as a first-line noninvasive imaging tool for the evaluation of women. (Stress CMR Perfusion Imaging in the United States [SPINS] Study [SPINS]; NCT03192891)     

Differential Effects of Newer-Generation Ultrathin-Strut Versus Thicker-Strut Drug-Eluting Stents in Chronic and Acute Coronary Syndromes

ObjectivesThe authors sought to compare the differential effects of ultrathin-strut and thicker-strut drug-eluting stents (DES) in patients with chronic (CCS) versus acute (ACS) coronary syndromes.BackgroundNewest-generation ultrathin-strut DES reduce target lesion failure (TLF) compared with thicker-strut second-generation DES in patients undergoing percutaneous coronary intervention.MethodsPubMed, Embase, and Cochrane Central Register of Controlled Trials were searched for randomized controlled trials comparing newer-generation ultrathin-strut (<70 μm) versus thicker-strut (≥70 μm) DES. Patients were divided based on baseline clinical presentation (CCS versus ACS). The primary endpoint was TLF, a composite of cardiac death, target vessel myocardial infarction, or clinically indicated target lesion revascularization (TLR).ResultsA total of 22,766 patients from 16 randomized controlled trials were included, of which 9 trials reported TLF rates in ACS patients. At a mean follow-up of 12.2 months, the risk of TLF was lower among patients treated with ultrathin-strut compared with thicker-strut DES (risk ratio [RR]: 0.85; 95% CI: 0.75-0.95; P = 0.006). The difference was driven by a lower risk of clinically-indicated TLR (RR: 0.75; 95% CI: 0.63-0.89; P < 0.001) among patients treated with ultrathin-strut DES. The treatment effect was consistent between patients presenting with CCS and ACS (relative RR: 0.97; 95% CI: 0.73-1.31; P for interaction = 0.854). In patients with ST-segment elevation myocardial infarction, TLF risk was lower among those treated with ultrathin- compared with thicker-strut DES (RR: 0.74; 95% CI: 0.54-0.99; P = 0.049).ConclusionsUltrathin-strut DES reduce the risk of TLF compared with thicker-strut second-generation DES in patients undergoing percutaneous coronary intervention, a difference caused by a lower risk of ischemia-driven TLR. The treatment effect was consistent among patients with CCS and ACS.     

Atrial Functional Tricuspid Regurgitation: Importance of Atrial Fibrillation and Right Atrial Remodeling and Prognostic Significance

BackgroundLittle is known about the determinants and outcomes of significant atrial functional tricuspid regurgitation (AFTR).ObjectivesThe authors aimed to identify risk factors for significant TR in relation to atrial fibrillation-flutter (AF-AFL) and assess its prognostic implications.MethodsThe authors retrospectively studied patients with mild TR with follow-up echocardiography examinations. Significant TR was defined as greater than or equal to moderate TR. AFTR was defined as TR, attributed to right atrial (RA) remodeling or isolated tricuspid annular dilatation, without other primary or secondary etiology, except for AF-AFL. The Mantel-Byar test was used to compare clinical outcomes by progression of AFTR.ResultsOf 833 patients with mild TR, 291 (34.9%) had AF-AFL. During the median 4.6 years, significant TR developed in 35 patients, including 33 AFTRs. Significant AFTR occurred in patients with AF-AFL more predominantly than in those patients without AF-AFL (10.3% vs 0.6%; P < 0.001). In Cox analysis, AF-AFL was a strong risk factor for AFTR (adjusted HR: 8.33 [95% CI: 2.34-29.69]; P = 0.001). Among patients with AF-AFL, those who developed significant AFTR had larger baseline RA areas (23.8 vs 19.4 cm²; P < 0.001) and RA area-to-right ventricle end-systolic area ratio (3.0 vs 2.3; P < 0.001) than those who did not. These parameters were independent predictors of AFTR progression. The 10-year major adverse cardiovascular event was significantly higher after progression of AFTR than before or without progression (79.8% vs 8.6%; Mantel-Byar P < 0.001).ConclusionsIn patients with mild TR, significant AFTR developed predominantly in patients with AF-AFL, conferring poor prognosis. RA enlargement, especially with increased RA area-to-right ventricle end-systolic area ratio, was a strong risk factor for progression of AFTR.     

First-Phase Ejection Fraction Predicts Response to Cardiac Resynchronization Therapy and Adverse Outcomes

ObjectivesThe aim of this study was to examine the value of first-phase ejection fraction (EF1), to predict response to cardiac resynchronization therapy (CRT) and clinical outcomes after CRT.BackgroundCRT is an important treatment for patients with chronic heart failure. However, even in carefully selected cases, up to 40% of patients fail to respond. EF1, the ejection fraction up to the time of maximal ventricular contraction, is a novel sensitive echocardiographic measure of early systolic function and might relate to response to CRT.MethodsAn initial retrospective study was performed in 197 patients who underwent CRT between 2009 and 2018 and were followed to determine clinical outcomes at King’s Health Partners in London. A validation study (n = 100) was performed in patients undergoing CRT at Barts Heart Centre in London.ResultsVolumetric response rate (reduction in end-systolic volume ≥15%) was 92.3% and 12.1% for those with EF1 in the highest and lowest tertiles (P < 0.001). A cutoff value of 11.9% for EF1 had >85% sensitivity and specificity for prediction of response to CRT; on multivariate binary logistic regression analysis incorporating previously defined predictors, EF1 was the strongest predictor of response (odds ratio [OR]: 1.56 per 1% change in EF1; 95% CI: 1.37-1.78; P < 0.001). EF1 was also the strongest predictor of improvement in clinical composite score (OR: 1.11; 95% CI: 1.04-1.19; P = 0.001). Improvement in EF1 at 6 months after CRT implantation (6.5% ± 5.8% vs 1.8% ± 4.3% in responders vs nonresponders; P < 0.001) was the best predictor of heart failure rehospitalization and death after median follow-up period of 20.3 months (HR: 0.81; 95% CI: 0.73-0.90; P < 0.001). In the validation cohort, EF1 was a similarly 1strong predictor of response (OR: 1.45; 95% CI: 1.23-1.70; P < 0.001) as in the original cohort.ConclusionsEF1 is a promising marker to identify patients likely to respond to CRT.     

Transvalvular Pressure Gradients and All-Cause Mortality Following TAVR: A Multicenter Echocardiographic and Invasive Registry

BackgroundLow ejection fraction (EF) and low flow as determined by an echocardiographic stroke volume index (SVi) <35 mL/m² are associated with low transvalvular gradients and increased mortality in both severe aortic stenosis (AS) and post–transcatheter aortic valve replacement (TAVR). Absence of an elevated echocardiographic transaortic gradient post-TAVR is considered a marker of procedural success despite the absence of data on its impact on mortality.ObjectivesThe authors sought to examine the association of invasive and echocardiographic gradients post-TAVR with all-cause mortality in relation to flow and EF.MethodsIn a multicenter retrospective registry of patients undergoing TAVR, Cox models with regression splines explored the relationship between invasive and echocardiographic gradients post-TAVR with 2-year mortality. An invasive gradient <5 mm Hg was considered low, between ≥5 and <10 mm Hg was considered intermediate, and ≥10 mm Hg was considered high. An echocardiographic gradient <10 mm Hg was considered low, ≥10 and <20 mm Hg was considered intermediate, and ≥20 mm Hg was considered high.ResultsHigher mortality occurred in low echocardiographic gradients at discharge relative to intermediate gradients (P < 0.001), and low gradient was associated with lower EF and echocardiographic SVi (P < 0.001 and P < 0.008, respectively). Lower mortality occurred in low invasive gradients relative to intermediate gradients (P = 0.012) with no difference in EF and echocardiographic SVi between groups (P = 0.089 and P = 0.947, respectively). There were insufficient observations to determine the impact of high echocardiographic and invasive gradients on mortality.ConclusionsIn this large retrospective analysis, the impact of transaortic gradients on mortality after TAVR was not linear and complex, showing opposite results among echocardiographic and invasive measurements in low-gradient patients.