Mechanical or Biological Prosthesis for Aortic Valve Replacement in Patients Aged 45 to 74 Years.

OBJECTIVE: The selection of valve prostheses for patients undergoing surgical aortic valve replacement (SAVR) remains controversial. In this study, we compared the long-term outcomes of patients undergoing aortic valve replacement with biological or mechanical aortic valve prostheses. METHODS: We evaluated late results among 5,762 patients aged 45-74 years who underwent biological or mechanical aortic valve replacement with or without concomitant coronary artery bypass from 1989 to 2019 at four medical centers. The Cox proportional hazards model was used to compare late survival; the age-dependent effect of prosthesis type on long-term survival was evaluated by an interaction term between age and prosthesis type. Incidences of stroke, major bleeding, and reoperation on the aortic valve following the index procedure were compared between prosthesis groups. RESULTS: Overall, 61% (n=3,508) of patients received a bioprosthesis. The 30-day mortality rate was 1.7% (n=58) in the bioprosthesis group and 1.5% (n=34) in the mechanical group (P=0.75). During a mean follow-up of 9.0 years, the adjusted risk of mortality was higher in the bioprosthesis group (HR=1.30, P<0.001). The long-term survival benefit associated with mechanical prosthesis persisted until 70 years of age. Bioprosthesis (vs mechanical prosthesis) was associated with a similar risk of stroke (P=0.20), lower risk of major bleeding (P<0.001), and higher risk of reoperation (P<0.001). CONCLUSIONS: Compared to bioprostheses, mechanical aortic valves are associated with a lower adjusted risk of long-term mortality in patients aged 70 years or younger. Patients <70 years old undergoing SAVR should be informed of the potential survival benefit of mechanical valve substitutes.

Secondary tricuspid regurgitation: incidence, types, and outcomes in atrial fibrillation vs. sinus rhythm.

BACKGROUND AND AIMS: Incidence and types of secondary tricuspid regurgitation (TR) are not well defined in atrial fibrillation (AFib) and sinus rhythm (SR). Atrial secondary TR (A-STR) is associated with pre-existing AFib; however, close to 50% of patients with A-STR do not have AFib. The aim of this study was to assess incidence, types, and outcomes of ≥ moderate TR in AFib vs. SR. METHODS: Adults with and without new-onset AFib without structural heart disease or ≥ moderate TR at baseline were followed for the development of ≥ moderate TR. Tricuspid regurgitation types were pacemaker, left-sided valve disease, left ventricular (LV) dysfunction, pulmonary hypertension (PH), isolated ventricular, and A-STR. RESULTS: Among 1359 patients with AFib and 20 438 in SR, 109 and 378 patients developed ≥ moderate TR, respectively. The individual types of TR occurred more frequently in AFib related to the higher pacemaker implantation rates (1.12 vs. 0.19 per 100 person-years, P < .001), larger right atrial size (median 78 vs. 53 mL, P < .001), and higher pulmonary pressures (median 30 vs. 28 mmHg, P < .001). The most common TR types irrespective of rhythm were LV dysfunction-TR and A-STR. Among patients in SR, those with A-STR were older, predominantly women with more diastolic abnormalities and higher pulmonary pressures. All types of secondary TR were associated with all-cause mortality, highest in PH-TR and LV dysfunction-TR. CONCLUSIONS: New-onset AFib vs. SR conferred a higher risk of the individual TR types related to sequelae of AFib and higher pacemaker implantation rates, although the distribution of TR types was similar. Secondary TR was universally associated with increased mortality.

Prevalence and Prognostic Implications of Pulmonary Hypertension in Patients With Severe Aortic Regurgitation.

Background: Pulmonary hypertension (PH) has been shown to be associated with worse outcomes in patients with aortic regurgitation (AR) in small older studies. Objectives: The authors sought to evaluate the prevalence of PH in patients with severe AR, its impact on mortality and symptoms, and regression after aortic valve replacement (AVR). Methods: A total of 821 consecutive patients with chronic ≥ moderate-severe AR on echocardiography from 2004 to 2019 were retrospectively analyzed. PH was defined as right ventricular systolic pressure (RVSP) >40 mm Hg on transthoracic echocardiogram (mild-moderate PH: RVSP 40-59 mm Hg, severe PH: RVSP > 60 mm Hg). Clinical and echocardiographic data were extracted from the electronic medical record and echocardiographic reports. The diastolic function and filling pressures were manually assessed and checked, and the left ventricular (LV) volumes were traced by a level 3-trained echocardiographer. The primary objectives were prevalence of PH in patients with ≥ moderate-severe AR, its risk associations and impact on all-cause mortality as the primary outcome. Secondary outcomes were impact of PH on symptoms and change in RVSP at discharge post-AVR. Logistic and Cox proportional hazards regression were used to analyze these outcomes. Results: The mean age was 61.2 ± 17 years, and 162 (20%) were women. Mild-moderate PH was present in 91 (11%) patients and severe PH in 27 (3%). Larger LV size, elevated LV filling pressures, and ≥ moderate tricuspid regurgitation were associated with PH. During follow-up of 7.3 (6.3-7.9) years, 188 patients died. Compared to those without PH, risk of mortality was higher in mild-moderate PH (adjusted HR: 1.59 (95% CI: 1.07-2.36) (P = 0.021)) and severe PH (adjusted HR: 2.90 (95% CI: 1.63-5.15) (P < 0.001)). Symptoms were also more prevalent in those with PH (P = 0.004). Of 396 patients who underwent AVR during the study period, 57 had PH. AVR similarly improved survival in patients without and with PH (P for interaction = 0.23), and there was regression in RVSP (≥8 mm Hg drop) at discharge post-AVR in 35/57 (61%) patients with PH. Conclusions: PH was present in 14% of patients with AR and was associated with higher mortality and symptoms. The survival benefit of AVR was similar in patients without and with PH.

Cardiac function, haemodynamics, and valve competence with exercise in patients with heart failure with preserved ejection fraction and mild to moderate secondary mitral regurgitation.

AIMS: This study aimed to evaluate the clinical significance of secondary mitral regurgitation (MR) in patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: We conducted a prospective study enrolling consecutively evaluated patients with HFpEF undergoing invasive haemodynamic exercise testing with simultaneous echocardiography. Compared to HFpEF without MR (n = 145, 79.7%), those with mild or moderate MR (n = 37, 20.3%) were older, more likely to be women, had more left ventricular (LV) systolic dysfunction, and more likely to have left atrial (LA) myopathy reflected by greater burden of atrial fibrillation, more LA dilatation, and poorer LA function. Pulmonary artery (PA) wedge pressure was higher at rest in HFpEF with MR (17 ± 5 mmHg vs. 20 ± 5 mmHg, p = 0.005), but there was no difference with exercise. At rest, only 2 (1.1%) patients had moderate MR, and none developed severe MR. Pulmonary vascular resistance was higher, and right ventricular (RV)-PA coupling was more impaired in patients with HFpEF and MR at rest and exercise. LV and LA myocardial dysfunction remained more severe in patients with MR during stress compared to those without MR, characterized by greater LA dilatation during all stages of exertion, lower LA emptying fraction and compliance, steeper and rightward-shifted LA pressure-volume relationships, and reduced LV longitudinal contractile function. CONCLUSIONS: Patients with HFpEF and mild or moderate MR have more severe LV systolic dysfunction, LA myopathy, RV-PA uncoupling, and more severe pulmonary vascular disease. Mitral valve incompetence in this setting is a phenotypic marker of more advanced disease but is not a causal factor in development of HFpEF.

Prognostic Value of Aortic Valve Calcification in Nonsevere Aortic Stenosis with Preserved Ejection Fraction.

BACKGROUND: Aortic valve calcification(AVC) is prognostic in patients with aortic stenosis(AS). We assessed the AVC prognostic value in nonsevere AS patients. METHODS AND RESULTS: We conducted a retrospective study of 395 patients with nonsevere AS, LV ejection fraction ≥50%. The Agatston method was used for computed tomography AVC assessment. The log-rank test determined the best AVC cutoffs for survival under medical surveillance: 1185 AU in men and 850 in women, lower than the established-cutoffs for severe AS(2064AU in men and 1274 in women). Patients were divided into three AVC groups based on these cutoffs: low(<1185 AU men and <850 women), sub-severe(1185-2064AU men and 850-1274 women) and severe(>2064AU men and >1274 women). Of 395 patients(mean age 73 ± 12 years, 60.5% men, aortic valve area 1.23 ± 0.30cm2, mean pressure gradient 28 ± 8 mmHg), 218 underwent aortic valve intervention(AVI) and 158 deaths occurred during follow-up, 82 before AVI. Median survival time under medical surveillance was 2.1[0.7-4.9]years. Compared to the low AVC group, both sub-severe and severe AVC groups had higher risk for all-cause death under medical surveillance after comprehensive adjustment including echocardiographic AS severity and coronary artery calcium score(all p ≤ 0.006); while mortality risk was similar between sub-severe and severe AVC groups(all p ≥ 0.2). This mortality risk pattern persisted in the overall survival analysis after adjustment for AVI. AVI was protective of all-cause death in the sub-severe and severe AVC(all p ≤ 0.01), but not in the low AVC groups. CONCLUSIONS: Sub-severe AVC is a robust risk-stratification parameter in patients with nonsevere AS and may inform AVI timing.

Artificial intelligence-based classification of echocardiographic views.

Aims: Augmenting echocardiography with artificial intelligence would allow for automated assessment of routine parameters and identification of disease patterns not easily recognized otherwise. View classification is an essential first step before deep learning can be applied to the echocardiogram. Methods and results: We trained two- and three-dimensional convolutional neural networks (CNNs) using transthoracic echocardiographic (TTE) studies obtained from 909 patients to classify nine view categories (10 269 videos). Transthoracic echocardiographic studies from 229 patients were used in internal validation (2582 videos). Convolutional neural networks were tested on 100 patients with comprehensive TTE studies (where the two examples chosen by CNNs as most likely to represent a view were evaluated) and 408 patients with five view categories obtained via point-of-care ultrasound (POCUS). The overall accuracy of the two-dimensional CNN was 96.8%, and the averaged area under the curve (AUC) was 0.997 on the comprehensive TTE testing set; these numbers were 98.4% and 0.998, respectively, on the POCUS set. For the three-dimensional CNN, the accuracy and AUC were 96.3% and 0.998 for full TTE studies and 95.0% and 0.996 on POCUS videos, respectively. The positive predictive value, which defined correctly identified predicted views, was higher with two-dimensional rather than three-dimensional networks, exceeding 93% in apical, short-axis aortic valve, and parasternal long-axis left ventricle views. Conclusion: An automated view classifier utilizing CNNs was able to classify cardiac views obtained using TTE and POCUS with high accuracy. The view classifier will facilitate the application of deep learning to echocardiography.

New Approaches to Assessment and Management of Tricuspid Regurgitation Before Intervention.

Severe tricuspid regurgitation (TR) is a progressive condition associated with substantial morbidity, poor quality of life, and increased mortality. Patients with TR commonly have coexisting conditions including congestive heart failure, pulmonary hypertension, chronic lung disease, atrial fibrillation, and cardiovascular implantable electronic devices, which can increase the complexity of medical and surgical TR management. As such, the optimal timing of referral for isolated tricuspid valve (TV) intervention is undefined, and TV surgery has been associated with elevated risk of morbidity and mortality. More recently, an unprecedented growth in TR treatment options, namely the development of a wide range of transcatheter TV interventions (TTVI) is stimulating increased interest and referral for TV intervention across the entire medical community. However, there are no stepwise algorithms for the optimal management of symptomatic severe TR before TTVI. This article reviews the contemporary assessment and management of TR with addition of a medical framework to optimize TR before referral for TTVI.

Disproportionately High Aortic Valve Calcium Scores in Atrial Fibrillation: Implications for Transcatheter Aortic Valve Replacement.

AIMS: Doppler mean gradient (MG) can underestimate aortic stenosis (AS) severity in patients with atrial fibrillation (AF) compared to patients in sinus rhythm (SR), potentially delaying intervention in AF. This study compared outcomes in patients with AF and SR following transcatheter aortic valve replacement (TAVR) and investigated delay in TAVR based on computed tomography aortic valve calcium score (AVCS). METHODS AND RESULTS: Patients who underwent TAVR from 2013 to 2017 for native valve severe AS were identified from an institutional database. Baseline characteristics and overall survival were compared between those in SR and AF. There were 820 patients (mean age 81 years; 41.6% female) included. AF was present in 356 patients. Patients in AF were older (82.2 vs. 80.5, p = 0.003), had lower MG compared to SR patients (42.0 vs. 44.9, p = 0.002) with similar indexed aortic valve area (0.4 vs. 0.4, p = 0.17). Median AVCS was higher in AF (males: AF 2850.0 vs. SR 2561.0, p = 0.044; females: AF 1942.0 vs. SR 1610.5, p = 0.025). Projected AVCS assuming same age of diagnosis was similar between AF and SR. Median survival post-TAVR was worse in AF compared to SR (3.2 vs 5.4 years, log rank p < 0.001). AF, lower MG, higher RVSP, dialysis, diabetes, and significant TR were associated with higher mortality (p < 0.05 for all). CONCLUSION: Older age and higher AVCS in patients with AF compared to SR suggests that AS was both underestimated and more advanced at TAVR referral.

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.

Pulmonary Vein Flow Morphology After Transcatheter Mitral Valve Edge-to-Edge Repair as Predictor of Survival.

BACKGROUND: Data on the prognostic factors after mitral valve (MV) transcatheter edge-to-edge repair (TEER; MV-TEER) are limited. Pulsed-wave Doppler interrogation of pulmonary vein flow (PVF) is a convenient method to assess the hemodynamic burden of residual mitral regurgitation (MR), which could be of utility as a predictor of outcomes. METHODS: Patients that underwent MV-TEER between May 2014 and December 2021 at our institution were evaluated. Pulmonary vein flow patterns post-MV-TEER were reviewed on the procedural transesophageal echocardiogram and classified as normal (systolic dominant or codominant) or abnormal (systolic blunting or reversal). The PVF pattern was correlated with all-cause mortality at follow-up. RESULTS: Two-hundred sixty-five patients had diagnostic PVF post-MV-TEER, with 73 (27.5%) categorized as normal and 192 (72.5%) categorized as abnormal. Patients with abnormal PVF morphology were more likely to have atrial fibrillation (70% vs 42%, P < .001) and greater than moderate residual MR (16% vs 3%, P = .01) and had higher mean left atrial pressure (18.1 ± 5.0 vs 15.9 ± 4.2 mm Hg, P = .002) and left atrial V wave (26.6 ± 8.5 vs 21.4 ± 7.3 mm Hg, P < .001) postprocedure. In multivariable analysis, abnormal PVF morphology post-MV-TEER was independently associated with mortality at follow-up (hazard ratio = 1.70; 95% CI, 1.06-2.74; P = .03) after correction for end-stage renal disease, atrial fibrillation, and residual MR. Results were similar in subgroups of patients with moderate or less and those with mild or less residual MR. CONCLUSIONS: Pulmonary vein flow morphology is a simple and objective tool to assess MR severity immediately post-MV-TEER and offers important prognostic information to optimize procedural results. Additional studies are needed to determine whether patients with abnormal PVF pattern post-MV-TEER would benefit from more intensive goal-directed medical therapy postprocedure.

Mitral Annulus Calcium Score in Patients With Calcific Mitral Stenosis Undergoing Invasive Hemodynamic Assessment.

BACKGROUND: Aortic valve calcium score is associated with hemodynamic severity of aortic stenosis. Whether this association is present in calcific mitral stenosis remains unknown. METHODS AND RESULTS: This study was a retrospective analysis of consecutive patients with mitral stenosis secondary to mitral annular calcification (MAC) undergoing transseptal catheterization. All patients underwent invasive mitral valve assessment via direct left atrial and left ventricular pressure measurement. Computed tomography within 1 year of cardiac catheterization and with adequate visualization of the mitral annulus was included. MAC calcium score quantification by Agatston method was obtained offline using dedicated software (Aquarius, TeraRecon, V.4). Median patient age was 66.9±11.2 years, 47% of patients were women, 50% had coronary artery disease, 40% had atrial fibrillation, 47% had prior cardiac surgery, and 33% had prior chest radiation. Median diastolic mitral valve gradient was 9.4±3.4 mm Hg on echocardiography and 8.5±4 mm Hg invasively. Invasive median mitral valve area using the Gorlin formula was 1.87±0.9 cm2. Median MAC calcium score for the cohort was 7280±7937 Hounsfield units. MAC calcium score correlated with the presence of atrial fibrillation (P=0.02) but was not associated with other comorbidities. There was no correlation between MAC calcium score and mitral valve area (r=0.07; P=0.6) or mitral valve gradient (r=-0.03; P=0.8). CONCLUSIONS: MAC calcium score did not correlate with invasively measured mitral valve gradient and mitral valve area in patients with MAC-related mitral stenosis, suggesting that calcium score should not be used as a surrogate for invasive hemodynamic parameters.

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.

Biatrial myopathy in heart failure with preserved ejection fraction.

AIM: Left atrial (LA) myopathy is increasingly recognized as an important phenotypic trait in heart failure (HF) with preserved ejection fraction (HFpEF). Right atrial (RA) remodelling and dysfunction also develop in HFpEF, but little data are available regarding the clinical characteristics and pathophysiology among patients with isolated LA, RA, or biatrial myopathy. METHODS AND RESULTS: Patients with HFpEF underwent invasive haemodynamic exercise testing, comprehensive imaging including speckle tracking strain echocardiography, and clinical follow-up at Mayo Clinic between 2006 and 2018. LA myopathy was defined as LA volume index >34 ml/m2 and/or LA reservoir strain ≤24% and RA myopathy by RA volume index >39 ml/m2 in men and >33 ml/m2 in women and/or RA reservoir strain ≤19.8%. Of 476 consecutively evaluated patients with HFpEF defined by invasive exercise testing with evaluable atrial structure/function, 125 (26%) had no atrial myopathy, 147 (31%) had isolated LA myopathy, 184 (39%) had biatrial myopathy, and 20 (4%) had isolated RA myopathy. Patients with HFpEF and biatrial myopathy had more atrial fibrillation, poorer left ventricular systolic and diastolic function, more severe pulmonary vascular disease, tricuspid regurgitation, ventricular interdependence and right ventricular dysfunction, and poorer cardiac output reserve with exercise. There were 94 patients with events over a median follow-up of 2.9 (interquartile range 1.4-4.6) years. Individuals with biatrial myopathy had an 84% higher risk of HF hospitalization or death as compared to those with isolated LA myopathy (hazard ratio 1.84; 95% confidence interval 1.16-2.92, p = 0.01). CONCLUSIONS: Biatrial myopathy identifies patients with more advanced HFpEF characterized by more severe pulmonary vascular disease, right HF, poorer cardiac reserve, and a greater risk for adverse outcomes. Further study is required to define optimal strategies to treat and prevent biatrial myopathy in HFpEF.

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.