Prognostic Significance of Elevated Left Ventricular Filling Pressures with Exercise: Insights from a Cohort of 14,338 Patients.

BACKGROUND: Exercise echocardiography can assess for cardiovascular causes of dyspnea other than coronary artery disease. However, the prevalence and prognostic significance of elevated left ventricular (LV) filling pressures with exercise is understudied. METHODS: We evaluated 14,338 patients referred for maximal symptom-limited treadmill echocardiography. In addition to assessment of LV regional wall motion abnormalities (RWMAs), we measured patients' early diastolic mitral inflow (E), septal mitral annulus relaxation (e'), and peak tricuspid regurgitation velocity before and immediately after exercise. RESULTS: Over a mean follow-up of 3.3 ± 3.4 years, patients with E/e' ≥15 with exercise (n = 1,323; 9.2%) had lower exercise capacity (7.3 ± 2.1 vs 9.1 ± 2.4 metabolic equivalents, P < .0001) and were more likely to have resting or inducible RWMAs (38% vs 18%, P < .0001). Approximately 6% (n = 837) had elevated LV filling pressures without RWMAs. Patients with a poststress E/e' ≥15 had a 2.71-fold increased mortality rate (2.28-3.21, P < .0001) compared with those with poststress E/e' ≤ 8. Those with an E/e' of 9 to 14, while at lower risk than the E/e' ≥15 cohort (hazard ratio [HR] = 0.58 [0.48-0.69]; P < .0001), had higher risk than if E/e' ≤8 (HR = 1.56 [1.37-1.78], P < .0001). On multivariable analysis, adjusting for age, sex, exercise capacity, LV ejection fraction, and presence of pulmonary hypertension with stress, patients with E/e' ≥15 had a 1.39-fold (95% CI, 1.18-1.65, P < .0001) increased risk of all-cause mortality compared with patients without elevated LV filling pressures. Compared with patients with E/e' ≤ 15 after exercise, patients with E/e' ≤15 at rest but elevated after exercise had a higher risk of cardiovascular death (HR = 8.99 [4.7-17.3], P < .0001). CONCLUSION: Patients with elevated LV filling pressures are at increased risk of death, irrespective of myocardial ischemia or LV systolic dysfunction. These findings support the routine incorporation of LV filling pressure assessment, both before and immediately following stress, into the evaluation of patients referred for exercise echocardiography.

Medium-Term Outcomes of the Different Antithrombotic Regimens After Transcatheter Aortic Valve Implantation.

Bioprosthetic valve thrombosis is associated with accelerated bioprosthesis degeneration and valve re-replacement. Whether 3-month warfarin use after transcatheter aortic valve implantation (TAVI) protects against such consequences is unknown. We aimed to investigate if 3-month warfarin treatment after TAVI is associated with better outcomes than dual antiplatelet therapy (DAPT) and single antiplatelet therapy (SAPT) at medium-term follow-up. Adults who underwent TAVI were identified retrospectively (n = 1,501) and classified into warfarin, DAPT, and SAPT groups based on antithrombotic regimen received. Patients with atrial fibrillation were excluded. Outcomes and valve hemodynamics were compared between the groups. Annualized change from baseline in mean gradients and effective orifice area at last follow-up echocardiography was calculated. Overall, 844 patients were included (mean age: 80 ± 9 years, 43% women; 633 receiving warfarin, 164 DAPT, and 47 SAPT). Median time to follow-up was 2.5 (interquartile range 1.2 to 3.9) years. There were no differences in the adjusted outcome end points of ischemic stroke, death, valve re-replacement/intervention, structural valve degeneration, or their composite end point at follow-up. Annualized change in aortic valve area was significantly higher in DAPT (-0.11 [0.19] cm2/year) than warfarin (-0.06 [0.25] cm2/y, p = 0.03), but annualized change in mean gradients was not different (p >0.05). In conclusion, antithrombotic regimen, including warfarin, after TAVI was associated with marginally lower decrease in aortic valve area but no difference in medium-term clinical outcomes compared with DAPT and SAPT.

Pulmonary artery pulsatility index in patients with tricuspid valve regurgitation: a simple non-invasive tool for risk stratification.

AIMS: Tricuspid valve regurgitation (TR) is a common valvular disease associated with increased mortality. There is a need for tools to assess the interaction between the pulmonary artery (PA) circulation and the right ventricle in patients with TR and to investigate their association with outcomes. The pulmonary artery pulsatility index (PAPi) has emerged as a haemodynamic risk predictor in left heart disease and pulmonary hypertension (PH). Whether PAPi discriminates risk in unselected patients with greater than or equal to moderate TR is unknown. METHODS AND RESULTS: In 5079 patients with greater than or equal to moderate TR (regardless of aetiology) and PA systolic and diastolic pressures measured on their first echocardiogram, we compared all-cause mortality at 5 years based on the presence or absence of PH and PAPi levels. A total of 2741 (54%) patients had PH. The median PAPi was 3.0 (IQR 1.9, 4.4). Both the presence of PH and decreasing levels of PAPi were associated with larger right ventricles, worse right ventricular systolic function, higher NT-pro BNP levels, greater degrees of right heart failure, and worse survival. In a subset of patients who had an echo and right heart catheterization within 24 h, the correlation of non-invasive to invasive PA pressures and PAPi levels was very good (r = 0.76). CONCLUSION: In patients with greater than or equal to moderate TR with and without PH, lower PAPi is associated with right ventricular dysfunction, right heart failure, and worse survival. Incorporating PA pressure and PAPi may help stratify disease severity in patients with greater than or equal to moderate TR regardless of aetiology.

The 5 Phenotypes of Tricuspid Regurgitation: Insight From Cluster Analysis of Clinical and Echocardiographic Variables.

BACKGROUND: The recent morphologic classification of tricuspid regurgitation (TR) (ie, atrial functional, ventricular functional, lead related, and primary) does not capture underlying comorbidities and clinical characteristics. OBJECTIVES: This study aimed to identify the different phenotypes of TR using unsupervised cluster analysis and to determine whether differences in clinical outcomes were associated with these phenotypes. METHODS: We included 13,611 patients with ≥moderate TR from January 2004 to April 2019 in the final analyses. Baseline demographic, clinical, and echocardiographic data were obtained from electronic medical records and echocardiography reports. Ward's minimum variance method was used to cluster patients based on 38 variables. The analysis of all-cause mortality was performed using the Kaplan-Meier method, and groups were compared using log-rank test. RESULTS: The mean age of patients was 72 ± 13 years, and 56% were women. Cluster analysis identified 5 distinct phenotypes: cluster 1 represented "low-risk TR" with less severe TR, a lower prevalence of right ventricular enlargement, atrial fibrillation, and comorbidities; cluster 2 represented "high-risk TR"; and clusters 3, 4, and 5 represented TR associated with lung disease, coronary artery disease, and chronic kidney disease, respectively. Cluster 1 had the lowest mortality followed by clusters 2 (HR: 2.22 [95% CI: 2.1-2.35]; P < 0.0001) and 4 (HR: 2.19 [95% CI: 2.04-2.35]; P < 0.0001); cluster 3 (HR: 2.45 [95% CI: 2.27-2.65]; P < 0.0001); and, lastly, cluster 5 (HR: 3.48 [95% CI: 3.07-3.95]; P < 0.0001). CONCLUSIONS: Cluster analysis identified 5 distinct novel subgroups of TR with differences in all-cause mortality. This phenotype-based classification improves our understanding of the interaction of comorbidities with this complex valve lesion and can inform clinical decision making.

Low Pulmonary Artery Pulsatility Index by Echocardiography Is Associated With Increased Mortality in Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a progressive pulmonary vascular disorder with elevated mortality risk. The pulmonary artery (PA) pulsatility index (PAPi) based on invasively acquired parameters has emerged as a hemodynamic risk predictor. Whether noninvasively derived PAPi (PA pulse pressure divided by right atrial pressure) is valuable is unclear. METHODS: Consecutive patients undergoing transthoracic echocardiography for known or suspected PH were included with conventional echocardiographic measures of PA systolic, PA diastolic, and estimated right atrial pressures. In those patients with PH (mean PA pressure > 20 mm Hg), PAPi was divided into 3 groups: <1.5, 1.5 to 3, and >3. Mortality was assessed over 5 years. RESULTS: Of 1,045 patients enrolled, 64% had PH. Patients with the lowest PAPi had higher N-terminal-pro hormone B-type natriuretic peptide levels, larger right ventricles (RVs), worse RV systolic function, and greater degrees of tricuspid regurgitation. In patients with PH, PAPi was inversely proportional to the risk of death, with PAPi <3 associated with a 1.96-fold increased risk of death (95% CI, 1.45-2.64, P < .0001). At multivariate analysis, RV longitudinal systolic strain (hazard ratio [HR] = 1.45, 1.24-1.71; P < .0001), PAPi <3 (HR = 1.76, 1.31-2.37; P = .0002), and the presence of a pericardial effusion (HR = 1.64, 1.20-2.26 P = .003) were independently associated with increased mortality. In age- and sex-adjusted models, PAPi was incremental to PA compliance. CONCLUSIONS: In patients with PH, low PAPi derived noninvasively by transthoracic echocardiography is associated with markers of right heart failure, RV dysfunction, and worse survival. PAPi could be incorporated into the conventional echo parameters reported in patients with PH and may be a useful predictor of outcome.

Prognostic Role of Cardiac Power in a Large Cohort of Patients with Normal Ejection Fraction Referred for Dobutamine Stress Echocardiography.

BACKGROUND: Cardiac power reflects cardiac performance in terms of energy transferred by the left ventricle to the aorta per unit time. Peak stress cardiac power has been shown to predict outcomes in patients with reduced left ventricular ejection fraction (LVEF) and, more recently, in patients with normal LVEF referred for exercise stress echocardiography. The aim of this study was to evaluate the prognostic significance of cardiac power in patients with normal LVEF referred for dobutamine stress echocardiography. METHODS: Data were studied from 15,576 patients with LVEF ≥ 50% and no significant valvular or right ventricular dysfunction who underwent dobutamine stress echocardiography. Cardiac power at rest and peak stress and power reserve (peak stress minus rest power) were calculated and normalized to left ventricular mass. Outcome end points were all-cause mortality and new-onset heart failure (HF). RESULTS: The mean age was 66 ± 13 years, and 49% patients were women. Resting and peak stress power/mass were 0.7 ± 0.2 and 1.6 ± 0.6 W/100 g left ventricular myocardium, respectively. During follow-up (median, 3.3 years; interquartile range, 0.7-7.3 years), 2,278 patients died and 2,137 developed HF. After adjusting for age, sex, comorbidities, and stress test results, lower peak stress power/mass was independently associated with mortality (adjusted hazard ratio, highest vs lowest quartile, 0.84; 95% CI, 0.74-0.95; P = .004) and HF at follow-up (adjusted hazard ratio, 0.67; 95% CI, 0.59-0.76; P < .0001). Power reserve showed similar associations with outcomes. CONCLUSIONS: Assessment of cardiac power during dobutamine stress echocardiography in patients with normal LVEF provides valuable prognostic information regarding risk for mortality and future HF, in addition to stress test results. It is an important research tool to study cardiac performance, and the development of risk scores incorporating this novel index could be considered after further validation in prospective studies.

Right Ventricular Enlargement and Dysfunction Are Associated With Increased All-Cause Mortality in Hypertrophic Cardiomyopathy.

OBJECTIVE: To assess whether right ventricular enlargement (RVE) and right ventricular dysfunction (RVD) adversely affect prognosis in hypertrophic cardiomyopathy (HCM). PATIENTS AND METHODS: Data were retrieved from Mayo Clinic's prospectively collected HCM registry between January 1, 2000, and September 30, 2012. Right ventricle (RV) size and function were semiquantitatively categorized via echocardiography as normal (RV-Norm) versus abnormal (RV-Abn) (RVE or RVD). All-cause mortality was the primary endpoint. RESULTS: Of 1878 HCM patients studied (mean age 53±15 years; 41.6% female), only 71 (3.8%) had RV-Abn (24 RVE, 28 RVD, 19 combined RVE and RVD). Compared with HCM patients with RV-Norm, RV-Abn patients were older (57±14 vs 53±15 years, P=.02), more symptomatic (New York Heart Association functional class III-IV in 62.0% vs 48.6%, P=.03), had more atrial fibrillation (53.5% vs 17.3%, P<.001), and more prior implantable cardioverter-defibrillator implantation (23.9% vs 11.3%, P=.02). Median follow-up was 9.4 years with 311 deaths. Patients who were RV-Abn had higher all-cause mortality compared with RV-Norm (log-rank P<.001); 24.1% (95% CI, 15.5% to 35.3%) vs 6.1% (95% CI, 5.1% to 7.3%) at 5 years. In multivariable Cox modeling, RV-Abn (hazard ratio, 1.89; 95% CI, 1.18 to 3.03; P=.008) was associated independently with all-cause mortality after adjusting for age, female sex, New York Heart Association functional class, atrial fibrillation, hypertension, coronary artery disease, implantable cardioverter-defibrillator implantation, beta blocker use, prior septal reduction therapy, resting LV outflow tract gradient, maximal LV wall thickness, and moderate or greater tricuspid regurgitation. CONCLUSION: Although perturbations in RV size and function were observed in fewer than 5% of patients with HCM, they were associated with nearly two-fold higher all-cause mortality at long-term follow-up.

Association of Postprocedural Left Atrial Volume and Reservoir Function with Outcomes in Patients with Atrial Fibrillation Undergoing Catheter Ablation.

BACKGROUND: The value of left atrial (LA) volume and reservoir function (ResF) after ablation for atrial fibrillation for predicting overall outcomes needs further investigation, particularly in large cohorts. The aim of this study was to test the hypothesis that abnormal LA volume and ResF after ablation are associated with adverse outcomes. METHODS: Patients who underwent primary atrial fibrillation ablation between 2007 and 2016 and had available measurements of maximum LA volume index (LAVImax) and minimum LA volume index (LAVImin) and LA ResF (LA emptying fraction and LA expansion index) at 3-month echocardiographic examination after ablation were included in this analysis. The primary endpoint was the composite of cardiac hospitalization for heart failure or acute ischemic events, stroke or transient ischemic attack, and all-cause death; secondary endpoints were cardiac hospitalization and all-cause death. RESULTS: A total of 792 patients were studied (mean age, 60 ± 10 years). Over a median of 7.5 years (interquartile range, 3.0-9.7 years) of follow-up, 96 patients experienced adverse events. After adjustment for several parameters, including age, comorbidities, and left ventricular structure and function, increased LA volumes and impaired ResF were each independently associated with the primary endpoint (LAVImax > 34 mL/m2: adjusted hazard ratio [HR], 2.37 [95% CI, 1.49-3.76; P = .0003]; LAVImin ≥ 20.5 mL/m2: adjusted HR, 3.21 [95% CI, 1.97-5.24; P < .0001]; LA emptying fraction < 40%: adjusted HR, 2.00 [95% CI, 1.29-3.10; P = .002]; LA expansion index < 66%: adjusted HR, 1.91 [95% CI, 1.22-2.98; P = .005]) as well as with the secondary endpoints of cardiac hospitalization (P < .05 for adjusted HR for all LA parameters) and all-cause death (P < .05 for adjusted HR for LAVImin, LA emptying fraction and LA expansion index). ResF measures were incremental to LAVImax (P < .05 for all), but not to LAVImin. In patients with normal LA (LAVImax ≤ 34 mL/m2; n = 403), those with higher LAVImin (≥17 mL/m2) were at 4 times higher risk for primary endpoint events (age-adjusted HR, 4.32; 95% CI, 1.90-9.81; P = .0005). All these findings were independent of atrial tachyarrhythmia recurrence. CONCLUSIONS: Enlarged left atrium and impaired ResF at 3 months after ablation for atrial fibrillation are strongly associated with long-term outcomes, independent of left ventricular function or cardiac rhythm at follow-up. LAVImin showed the strongest associations and even identified a high-risk subgroup among patients with nondilated left atria.

Performance of Echocardiographic Algorithms for Assessment of High Aortic Bioprosthetic Valve Gradients.

BACKGROUND: Bioprosthetic aortic valve dysfunction (BAVD) is a challenging diagnosis. Commonly used algorithms to classify high-gradient BAVD are the 2009 American Society of Echocardiography, 2014 Blauwet-Miller, and 2016 European Association of Cardiovascular Imaging algorithms. We sought (1) to evaluate the accuracy of existing algorithms against objectively proven BAVD and (2) to propose an improved algorithm. METHODS: This was a retrospective study of 266 patients with objectively proven BAVD (pathology of explanted valves, four-dimensional computed tomography prior to transcatheter valve-in-valve replacement, or therapeutically confirmed bioprosthetic thrombosis) who were treated. Of those, 191 had obstruction, 48 had regurgitation, 15 had mixed stenosis and regurgitation, and 12 had patient-prosthesis mismatch (PPM). Normal controls were matched 1:1 (age, prosthesis size, and type), of which 43 had high gradients (PPM in 30, high flow in nine, and normal prosthesis in nine). Algorithm assignment was based on the echocardiogram leading to BAVD diagnosis and the predischarge "fingerprint" echocardiogram after surgical or transcatheter aortic valve replacement. A novel algorithm (Mayo Clinic algorithm) incorporating valve appearance in addition to Doppler parameters was developed to improve observed deficiencies. RESULTS: The accuracy of existing algorithms was suboptimal (2009 American Society of Echocardiography, 62%; 2014 Blauwet-Miller, 62%; 2016 European Association of Cardiovascular Imaging, 57%). The most common overdiagnosis was PPM (22%-29% of patients and controls with high gradients). The novel Mayo Clinic algorithm correctly identified the mechanism in 256 of 307 patients and controls (83%). Recognition of regurgitation was substantially improved (42 of 47 patients, 89%), and the number of PPM misdiagnoses was significantly reduced (five patients). CONCLUSION: Currently recommended algorithms misclassify a significant number of BAVD patients. The accuracy was improved by a newly proposed algorithm.

Arrhythmia Recurrence After Atrial Fibrillation Ablation: Impact of Warfarin vs. Non-Vitamin K Antagonist Oral Anticoagulants.

PURPOSE: Both warfarin and non-vitamin K antagonist oral anticoagulants (NOACs) have pleiotropic effects including anti-inflammatory and anti-fibrotic properties. This study aims to explore whether arrhythmia recurrence after AF ablation is influenced by the choice of oral anticoagulant. METHODS: We retrospectively studied all patients who underwent primary AF ablation between 2011 and 2017 and divided them into two groups according to the anticoagulant used: Warfarin vs. NOACs. The primary endpoint was atrial tachyarrhythmia recurrence after ablation. RESULTS: Of the 1106 patients who underwent AF ablation in the study period (median age 62.5 years; 71.5% males, 48.2% persistent AF), 697 (63%) received warfarin and 409 (37%) received NOACs. After a median of 26.4 months follow-up, arrhythmia recurrence was noted in 368 patients in warfarin group and 173 patients in NOACs group, with a 1-year recurrence probability of 35% vs. 36% (log rank P = 0.81) and 5-year recurrence probability of 62% vs. 63% (Log rank P = 0.32). However, NOACs use was associated with a higher probability of recurrence (46% for 1 year, 68% for 5 years) in patients with persistent AF compared with those taking warfarin (34% for 1 year, 63% for 5 years; log rank P = 0.01 and P = 0.02 respectively). Multivariate analysis indicated that in patients with persistent AF, use of NOACs was an independent risk factor of atrial tachyarrhythmia recurrence after ablation (HR 1.39, 95% CI 1.07-1.81, P = 0.013). CONCLUSION: In this large contemporary cohort, overall AF recurrence after ablation was similar with NOACs or warfarin use. However, in patients with persistent AF, NOACs use was associated with a higher probability of arrhythmia recurrence and was an independent risk factor of recurrence at long-term follow-up.

Numerical wave speed sensitivity study for assessment of myocardial elasticity in a simplified linear elastic and isotropic left ventricle model.

Since tissue elasticity can change with pathology, noninvasive assessment of elasticity has received increasing attention. Emerging methods for assessing cardiac elasticity utilize either an external source to induce propagating shear waves or intrinsic longitudinal waves created by natural cardiac events such as left ventricle stretching that occurs due to atrial kick during late diastole. However, the effect of morphological variations that occur in diseased hearts on this longitudinal stretch wave and the corresponding estimate of elasticity is not well understood and is an active area of research. This study investigated the sensitivity of longitudinal wave speed to material properties and chamber geometry parameters through numerical simulations using a finite element model of a bullet-shaped chamber with homogeneous isotropic linear elastic material properties. A longitudinal impulse displacement was applied to the base edge of the model to investigate wave propagation from this boundary. Parametric studies were performed for variables of interest related to geometry and material properties. The wave speeds estimated from simulation results were used to determine wave speed sensitivity to each variable. Wave speed was found to be a strong function of material elasticity and a weak function of chamber geometry and viscous damping. Simulated wave speed as a function of elasticity was in good agreement with wave speeds determined from an analytical expression for longitudinal wave speed in elastic thin plates. These promising preliminary results increase our understanding of how these parameters affect intrinsic longitudinal wave speed and warrant future studies addressing the impact of patient-specific model geometry, material anisotropy and hyperelasticity, and boundary conditions on wave speed.

Cardiac remodeling in acute myocardial infarction: Prospective insights from multimodality ultrasound imaging.

BACKGROUND: The severity of MI declined markedly in the last decade, and contemporary patterns of cardiac remodeling after MI are not defined. METHODS: We prospectively enrolled community patients with first MI and performed comprehensive two- and three-dimensional echocardiography. Remodeling was defined as left ventricular (LV) end-systolic volume index (ESVI) above American Society of Echocardiography normal values. Remodeling patterns were characterized as an increase in LVESVI or LV end-diastolic volume index (LVEDVI), or both. RESULTS: Between 2014 and 2016, 213 patients (63±13 years; 34% women) were enrolled within 3 days after MI (77% non-ST-elevation MI). Acute remodeling was present in 51% of patients. Higher troponin and wall motion score index were associated with greater remodeling (p < 0.001). Atrial annular area, leaflet tenting and papillary muscle areas increased with greater remodeling (p < 0.001). The greater the cardiac remodeling, the lower the LV ejection fraction and global longitudinal strain (p < 0.001). This decrease in LV function was accompanied by stroke volume augmentation and maintenance of cardiac index at the expense of increased LVEDVI. Different remodeling patterns were identified. Cases showing increased LVEDVI and normal LVESVI had smallest infarct size and better hemodynamics compared to cases with augmented LVESVI and normal LVEDVI. CONCLUSION: Acute remodeling occurs in more than half of first MI cases and exhibits different patterns defined by cavity size and hemodynamic profile. Acute remodeling is a global phenomenon, which also involves the left atrium and the mitral apparatus.

Post Procedural Peak Left Atrial Contraction Strain Predicts Recurrence of Arrhythmia after Catheter Ablation of Atrial Fibrillation.

BACKGROUND: Left atrial (LA) function can be impaired by the atrial fibrillation (AF) ablation and might be associated with the risk of recurrence. We sought to determine whether the post-procedural changes in LA function impact the risk of recurrence following AF ablation. METHODS: We retrospectively reviewed patients who underwent AF ablation between 2009 and 2011 and underwent transthoracic echocardiography before ablation, 1-day and 3-month after ablation. Peak left atrial contraction strain (PACS) and left atrial emptying fraction (LAEF) were evaluated during sinus rhythm and compared across the three time points. The primary endpoint was atrial tachyarrhythmia recurrence after ablation. RESULTS: A total of 144 patients were enrolled (mean age 61 ± 11 years, 77% male, 46% persistent AF). PACS and LAEF initially decreased 1-day following ablation but partially recovered within 3 months in PAF patients, with a similar trend in the PerAF patients. After median 24 months follow-up, 68 (47%) patients had recurrence. Patients with recurrence had higher PACS1-day than that in non-recurrence subjects (-10.9 ± 5.0% vs. -13.4 ± 4.7%, p = 0.003). PACS1-day -12% distinguished recurrence cases with a sensitivity of 67.7% and specificity of 60.5%. The Kaplan-Meier curves showed significant difference in 5-year cumulative probability of recurrence between those with PACS ≥ -12% and PACS < -12% (log rank p < 0.0001). Multivariate regression showed that PACS1-day was an independent risk factor of arrhythmia recurrence. CONCLUSIONS: Left atrial function deteriorates immediately following AF ablation and partially recovers in 3 months but remains abnormal in the majority of patients. PACS1-day post procedure predicts arrhythmia recurrence at long-term follow-up.

Gradient changes in bioprosthetic valve thrombosis: duration of anticoagulation and strategies to improve detection.

OBJECTIVE: Bioprosthetic valve thrombosis (BPVT) is increasingly recognised as a major cause of prosthetic dysfunction in the first years postimplantation. How early abnormal gradients can be detected prior to diagnosis and how fast they normalise with anticoagulant therapy is unknown. We set forth to (1) evaluate patterns of increase in gradients prior to BPVT diagnosis and (2) characterise time-course of response to anticoagulation. METHODS: Patients treated with warfarin for BPVT (1999-2019) with clinically significant reduction of mean gradients (≥25%) were identified retrospectively. Recovery was defined as gradient decrease ≥50%, to postimplantation or to normal-range gradients per position, model and size. Time-to-BPVT (implantation-BPVT diagnosis), potential diagnostic delay (first abnormal gradient by position, model and size-BPVT diagnosis) and time-to-recovery (BPVT diagnosis-complete resolution) were recorded. RESULTS: 77 patients were identified; 32 (42%) aortic (23 surgical-12 porcine, 11 pericardial; 9 transcatheter); 24 (31%) mitral; 21 (27%) tricuspid. Median time-to-BPVT was 24, 21 and 10 months, respectively. Potential diagnostic delay was median 21 months for aortic, 4 months for mitral, but 0 for tricuspid. Recovery was significantly faster in mitral than aortic (median 2.5 vs 4.8 months, p=0.038) and tricuspid (median 5.9 months, p=0.025) positions. Porcine aortic valves responded faster than pericardial aortic valves (median 2.9 vs 20.3 months, p=0.004). CONCLUSION: Gradients start to increase months before the clinical BPVT diagnosis. Recovery is faster in mitral and surgical aortic porcine valves; a longer warfarin trial seems indicated in tricuspid and surgical aortic pericardial valves.

Atrial fibrillation is associated with large beat-to-beat variability in mitral and tricuspid annulus dimensions.

AIMS: Beat-to-beat variability in cycle length is well-known in atrial fibrillation (Afib); whether this also translates to variability in annulus size remains unknown. Defining annulus maximal size in Afib is critical for accurate selection of percutaneous devices given the frequent association with mitral and tricuspid valve diseases. METHODS AND RESULTS: Images were obtained from 170 patients undergoing 3D echocardiography [100 (50 sinus rhythm (SR) and 50 Afib) for mitral annulus (MA) and 70 (35 SR and 35 Afib) for tricuspid annulus (TA)]. Images were analysed for differences in annular dynamics with a commercially available software. Number of cardiac cycles analysed was 567 in mitral valve and 346 in tricuspid valve. Median absolute difference in maximal MA area over four to six cycles was 1.8 cm2 (range 0.5-5.2 cm2) in Afib vs. 0.8 cm2 (range 0.1-2.9 cm2) in SR, P < 0.001. Maximal MA area was observed within 30-70% of the R-R interval in 81% of cardiac cycles in SR and in 73% of cycles in Afib. Median absolute difference in maximal TA area over four to six cycles was 1.4 cm2 (range 0.5-3.6 cm2) in Afib vs. 0.7 cm2 (range 0.3-1.7 cm2) in SR, P < 0.001. Maximal TA area was observed within 60-100% of the R-R interval in 81% of cardiac cycles in SR, but only in 49% of cycles in Afib. CONCLUSION: MA and TA reach maximal size within a broad time interval centred around end-systole and end-diastole, respectively, with significant beat-to-beat variability. Afib leads to a larger beat-to-beat variability in both timing of occurrence and values of annulus size than in SR.