Nkomo, Vuyisile T.

Introduction: A significant portion of patients with aortic stenosis (AS) have low-gradient AS (LGAS) defined as aortic valve area ≤ 1.0 cm 2 and a trans-aortic mean systolic gradient and peak velocity < 40 mmHg and < 4 m/s, respectively. LGAS has been shown previously to have worse mortality compared to high-gradient AS (HGAS). Etiologies for LGAS include diastolic dysfunction, heart failure, other significant valvular disease, and atrial fibrillation (AF). AF is associated with worse outcomes compared to sinus rhythm (SR) in HGAS. AF is common in LGAS, but whether AF is associated with worse outcomes versus SR in LGAS has not been elucidated. Hypothesis: We hypothesize that AF is associated with higher mortality compared to SR in patients with LGAS. Methods: We retrospectively identified and reviewed charts of patients who were diagnosed with LGAS on transthoracic echocardiogram (TTE) from 2010-2020 at Mayo Clinic. Patient were classified according to rhythm at the time of TTE and history of AF was ascertained among those in SR. Patents were divided into 3 groups; SR without history of AF (group 1), SR with history of AF (group 2), and AF during TTE (group 3). Primary endpoints of overall mortality and cardiac mortality were ascertained. Results: A total of 3400 patients were included: n=2036 in group 1, n=519 in group 2, and n=845 in group 3. After adjusting for age, sex, and the Charlson index, group 2 and group 3 patient had significantly higher overall mortality (HR 1.22 and HR 1.52, respectively, p<0.0001 for both) and cardiac mortality (HR 1.37 and HR 2.05, respectively, p<0.0001 for both), Figure . Conclusions: In LGAS, AF is a significant prognostic indicator of overall mortality and cardiac mortality. LAGS associated with AF may need different management strategies given the higher mortality associated with the presence of AF.

Introduction: Acceleration time (AT) and Doppler Velocity Index (DVI) are critical parameters in assessment of bioprosthetic aortic valve dysfunction (BAVD). AT>100ms and DVI < 0.25 are highly suggestive of prosthetic obstruction and are incorporated in all triage algorithms. Little is known about their relationship with flow. Hypothesis: AT and DVI may be affected by transprosthetic flow in patients with significant bioprosthetic aortic valve dysfunction (BAVD). Methods: Single center, retrospective analysis of patients with severe BAVD (confirmed at surgical re-replacement, transcatheter valve-in-valve implantation, or successfully treated bioprosthetic valve thrombosis). Standard prosthetic parameters (AT, DVI, effective orifice area (EOA), mean gradient, presence and degree of regurgitation), flow (stroke volume index, Svi; transprosthetic flow rate, FR) were measured on the transthoracic echocardiogram at the time of diagnosis with severe BAVD. Results: A total of 266 patients with severe BAVD underwent treatment between 2008-2020. BAVD mechanism was obstruction (N=192, 72%), regurgitation (n=48, 18%) mixed stenosis and regurgitation (n=15, 6%) and patient-prosthetic mismatch (n=12, 5%). DVI was moderately correlated with FR (r=0.50, p<0.001); AT had a weak but significant inverse correlation with FR (r=0.24, p<0.001). SVi had a weaker influence on DVI (r=0.35, p<0.001) and no correlation with AT. Conclusions: AT and DVI are influenced by transprosthetic flow rate. This flow-dependency should be considered when assessing the mechanism of BAVD.

Introduction: Bioprosthetic valve thrombosis (BPVT) is a well-recognized cause of prosthetic dysfunction. Anticoagulation restores prosthetic valve gradients, but long term outcomes and complications from therapy are unknown. Objectives: To define the complications and long-term outcomes of anticoagulant therapy for BPVT. Methods: Retrospective matched cohort study of patients treated with warfarin for presumed BPVT at a single center from 1999 to 2016. Controls with normal bioprostheses by echocardiography were matched 2:1 for age at implantation, gender, prosthetic valve position, and type of prosthesis (porcine / pericardial). Results: A total of 83 presumed BPVT patients (40 aortic, 21 mitral, 18 tricuspid, and 4 pulmonary) and 166 controls were included. Age at BPVT diagnosis was 60±19 yrs (41±41 months post implantation); 45 (54%) were male. Transvalvular gradients returned to baseline in 63 (76%) of the patients, after 5±4 months of warfarin; 60 (72%) patients were maintained on warfarin indefinitely. Recurrent BPVT was seen in 13 (16%) patients, 33±31 months after initial therapy. When compared to controls, warfarin-treated BPVT patients had similar incidence of stroke [4(5%) vs 5 (3%), p=0.49], peripheral embolic events [4(5%) vs 10 (6%), p=0.78)], and death [12 (14%) vs 28 (17%), p= 0.72] (Figure, left panel), but more bleeding requiring transfusion [18 (22%) vs 3 (2%), p<0.0001]. Presumed BPVT patients more often required surgical or percutaneous valve re-replacement (Figure, center panel); this difference persisted even when comparing only patients with confirmed BPVT (those who responded to anticoagulant therapy) vs. their matched controls (Figure, right panel). Conclusion: Warfarin anticoagulation for presumed BPVT is successful in the majority of patients, without increase in stroke, peripheral embolism or death, but at the cost of excess bleeding. Recurrent BPVT occured in 16% of patients. Importantly, patients with BPVT required more often valve re-replacement. This finding suggests that anticoagulant therapy does not fully restore prosthetic valve durability, and that BPVT patients should be closely monitored.

Introduction: Atrial fibrillation (AF) is a serious complication, which occurs in 30% to 40% of patients after surgical aortic valve replacement (SAVR) and contributes to adverse outcomes. Advanced technology has enabled transcatheter aortic valve replacement (TAVR) in patients with High-risk Severe Aortic Stenosis (HRSAS). In these patients, the compliance of the systemic vasculature is an independent predictor of diastolic dysfunction, a known predictor of postoperative AF (POAF). We hypothesize that patients with HRSAS undergoing TAVR represent a population at increased risk for POAF. METHODS: The medical records of 195 TAVR patients at the Mayo Clinic from November 2008 to January 2013 were analyzed. All patient demographic, clinical, pre- and post-procedural outcomes were collected from the patients’ medical records, and reviewed to ascertain all cases of POAF (AF ≤30 days of surgery). Patients with a prior history of AF (n= 75 (38.5%)) were excluded. Logistic regression analysis was used to identify clinical predictors of POAF after TAVR. Results: The mean age of the study population was 80.8±7.8 years and 60.8% (n=73) were men. The mean STS risk score was 8.9±5.1. Of the 120 patients without prior AF, 20.8% (n=25) developed new-onset POAF after TAVR. Patients who developed POAF were more likely to have undergone a transapical or transaortic TAVR approach (OR 3.20; 95% CI (1.3-8.0), had a higher incidence of renal complications (52.0% vs 21.5%; p= 0.003), greater hospital length of stay (7.4±2.58 vs 5.0±2.6 days; p= 0.0003, and a trend toward higher 30-day mortality (28.0% vs 13.7%; p= 0.09) and pulmonary complications (16.0% vs 5.4%; p= 0.08) compared with those who did not develop POAF, respectively. Neurologic complications were not different between the 2 group (4.0% vs 3.2%; p= 0.85). Conclusions: Patients with High-risk Severe Aortic Stenosis undergoing TAVR have increased risk of POAF, primarily associated with a transapical or aortic surgical approach. Patients who develop POAF had higher incidence of post-procedural complications and longer hospitalizations. Therefore, perioperative strategies aimed at prevention of POAF are as important in TAVR patients as in those undergoing SAVR.

Background: Patients with severe aortic stenosis being considered for transcatheter aortic valve replacement (TAVR) undergo aortoiliac computed tomographic angiography (CTA) of the chest/abdomen/pelvis. Despite the increasing number of TAVR procedures worldwide, little is known regarding the clinical significance of non-cardiovascular incidental findings (IFs) on TAVR-CTA scans. Objective: To determine the frequency, clinical significance and impact on survival of non-cardiovascular IFs detected on TAVR-CTA scans. Methods: CTA studies for 424 consecutive patients being evaluated for TAVR were reviewed for non-cardiovascular IFs (62% male, median age 82±8.3 years). The electronic medical record was reviewed to assess for subsequent clinical management and survival. Results: An IF was present in nearly all patients (99%). The mean number of IFs per patient was 5.3 (±2.8; range 0-14). After excluding obviously benign IFs, 67% had at least one potentially pathologic IF (mean 1.1±1.0). Factors associated with higher numbers of IFs were age (p<0.0001) and use of IV contrast (p=0.03). IFs prompted clinical work-up in 39 patients (9.2%) and delayed or cancelled procedures in 7 patients (1.7%). The number needed to image to diagnose a new malignancy or medical condition was 19. The number of IFs was predictive of poor overall survival before (HR 1.09; 95% CI (1.02 to 1.70), p=0.02) and after adjustment for baseline clinical variables (HR 1.07; (1.0 to 1.15); p=0.04). Conclusions: This investigation demonstrates that IFs are present in nearly all TAVR-CTA scans, commonly require further clinical evaluation, and are associated with poorer survival. TAVR institutions should have mechanisms in place to ensure communication and follow-up of IFs.

Background: Non-cardiac surgery (NCS) in patients with severe aortic stenosis has traditionally been associated with high perioperative mortality. Aortic valve replacement is recommended prior to elective NCS, but the impact of this strategy has not been systematically assessed. Methods: A retrospective review was performed of all patients with severe aortic stenosis undergoing major NCS at Mayo Clinic between 2000 and 2013. Patients undergoing aortic valve intervention (AVI) prior to NCS were compared to those undergoing surgery without prior AVI (control). Patients undergoing emergency surgery were excluded. Primary endpoint was occurrence of major adverse cardiac events (MACE; combination of death, stroke, myocardial infarction, new/worsening heart failure, ventricular arrhythmia) within 30 days of NCS; secondary endpoints were mortality at 30 days and 1 year after NCS. Results: 180 patients (age 74.5 ± 10.5 years, 64% male) who underwent NCS within 12 months after AVI, were compared to 232 patients (age 76.6 ± 10.7 years, 56% male) in the control group. Patients undergoing AVI were more often symptomatic than controls (41% vs 26%, p = 0.002). MACE was significantly higher in the control group (21.6% vs 5.6%, p < 0.001), mainly due to the increased risk of heart failure in the postoperative period in this group (18.5% vs 2.2%, p < 0.001). There was no significant difference in the rate of myocardial infarction (1.7% vs 0.6%, p = 0.39), ventricular arrhythmia (0.9 % vs 0 %, p = 0.51) or stroke (0.9 % vs 0 %, p = 0.51). Kaplan-Meier assessment demonstrated no significant difference at 30 days but a reduction in 1 year mortality in the AVI group compared to the control group (Figure). Conclusions: Pre-operative AVI for severe aortic stenosis results in reduced heart failure and improved 1 year survival. However, other MACE and 30 day mortality appears unchanged. Pre-operative AVI should be considered in symptomatic patients, where the benefit of AVI is demonstrated to be greatest.

Introduction: Multiple Valvular Heart Disease (VHD), defined as at least moderate stenotic or regurgitant lesions in ≥2 valves, mixed VHD as combination of lesions in the same valve and mitral annular calcification (MAC) are common conditions. Association between multiple-mixed VHD (MMVHD), MAC and MACE in patients exposed to Radiation Therapy (RT) and/or chemotherapy (CT) who underwent Transcatheter Aortic Valve Replacement (TAVR) has not been studied. Aim: Assess the presence of MMVHD and MAC in cancer patients with prior RT and/or CT and their correlation with MACE (cardiovascular death, myocardial infarction, revascularization, stroke and hospitalization for heart failure) after TAVR. Methods: 544 patients were included and divided into 3 groups: 187 with prior chest RT and CT (RT/CT), 155 CT only, and 202 without CT/RT as controls (Table 1). Data was obtained from the pre-procedure echocardiogram and quantified in a 1-6 scale (none, mild, mild/moderate, moderate, moderate/severe and severe). Fisher’s exact test or chi-square were used to compare categorical. Multiple VHD-MACE correlation was evaluated through multivariable Cox analysis using a proportional hazards model. Results: The prevalence of Multiple VHD was 37.4% in RT/CT, 23.2% in CT, and 13.9% in controls p<0.001(Figure 1). The RT/CT group had a significantly higher prevalence of severe MAC. Multiple VHD predicted MACE at 18 months after TAVR in RT/CT (HR 3.42, CI 1.93-6.08, p<0.001) and in CT (HR 2.55, CI 1.39-4.66, p=0.002) (Table 2). In RT/CT, severe MAC also predicted MACE (HR 3.68, CI 2.13-6.37, p<0.001), while it was not a predictor in the other groups. Stenotic or regurgitant VHD was more prevalent in the RT/CT group (Figure 2). Conclusions: Multiple VHD was found higher in RT/CT and predicted MACE at 18 months post-TAVR, including CT only patients. Severe MAC was also a strong predictor of the outcome in RT/CT patients. Pre-TAVR evaluation of MMVHD lesions is crucial for optimal patient management.

Introduction: Rate of aortic stenosis (AS) progression in patients with concurrent atrial fibrillation (AF) has not been previously described. Objectives: To describe changes over time in aortic valve area (AVA) and associated hemodynamics during AS progression in patients in AF versus sinus rhythm (SR). Methods: Patients with AVA ≤ 1 cm 2 and preserved left ventricular ejection fraction ≥50% were identified from the Mayo Clinic Echocardiographic Laboratory Database. Serial echocardiograms prior to the development of AVA ≤ 1 cm 2 (Time 0) were examined. Inverse probability weighting was used for statistical analysis. Results: A total of 166 patients were included (SR=79 and AF=87), mean age 78.1 ± 7.8 years, females 31%. The rates of AVA reduction (-0.14±0.01 vs -0.12±0.01 cm2/year, p=0.31) and increase in trans-aortic peak velocity (+0.23 ± 0.02 vs +0.22 ± 0.02 m/sec, p=0.55) and mean gradient (MG) (3.9 ± 0.3 vs 3.8 ± 0.4 mmHg, p=0.83) did not differ between AF and SR (Figure 1). However, AF was associated with systematically lower forward stroke volume index (SVi), peak velocity and MG for the same AVA compared to SR (p<0.04 for all) throughout AS progression. When AVA reached 1 cm 2 , SVi (38.8±6.6 vs 45.7 ±8.9, p=0.02), peak velocity (3.9 ± 0.6 vs 4.1 ± 0.6 m/sec, p=0.04) and MG (36.6±10.9 vs 41±12.8 mmHg, p=0.03) were lower in AF compared to SR. Conclusions: The rate of AS progression was not different in AF versus SR. However, forward flow was systematically lower in AF resulting in discordant AS during AS progression and when AVA reached 1 cm 2 . Doppler velocity and MG criteria for severe AS appear to be lower in AF versus SR which has implications for timely diagnosis of severe AS and patient management.

Introduction: Doppler mean gradient (MG) can underestimate the severity of aortic stenosis (AS) in patients with atrial fibrillation (AF) compared to patients in sinus rhythm (SR). Patients with AF and severe AS may experience delayed diagnosis and more advanced disease at time of referral for transcatheter aortic valve replacement (TAVR). Methods: Patients who underwent TAVR from 2013 to 2017 for native valve severe AS were identified from an institutional database. MG and aortic valve calcium score (AVCS) at time of referral were compared in patients in AF and SR. Retrospective theoretical AVCS in AF patients were derived assuming an average progression of 152 AU/year (published data). Results: There were 820 patients included; mean age was 81.3+/- 8.2 years and 41.6% were female. AF was present in 356 patients at time of referral. 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) and a lower peak velocity (4.1 vs. 4.2, p = 0.010) with a similar indexed aortic valve area (0.4 vs. 0.4, p = 0.17). Stratified by sex, the median calcium score for AF patients was higher (by around 300 AU) among both males (AF 2850.0 vs. SR 2561.0, p = 0.044) and females (AF 1942.0 vs. 1610.5, p = 0.025) ( figure 1 ). A density plot of retrospective theoretical AVCS in AF patients (projected assuming referral to TAVR approximately two years prior) resulted in nearly identical median AVCS between the two cohorts ( figure 2 ). Conclusions: Older age and higher AVCS in patients with AF compared to SR suggests that AS was both underestimated and more advanced at time of referral to TAVR. Patients in AF may have severe AS as early as 2 years prior to TAVR referral.

Background: Clinically significant tricuspid regurgitation (TR) is an important contributor to morbidity and mortality. The Tricuspid Regurgitation Impact on Outcomes (TRIO) score based on 8 parameters (age, gender, chronic heart failure, chronic lung disease, heart rate, creatinine, aspartate transaminase level, and TR severity) is used for risk stratification. The performance of the TRIO score in patients with TR secondary to severe pulmonary hypertension (PH) is unknown. Research Questions: To evaluate whether the TRIO score can be applied in patients with TR and pulmonary hypertension (PH), and to identify other predictors of mortality. Methods: Retrospective study including patients with TR ≥ moderate. Severe PH was defined as right ventricular systolic pressure (RVSP) ≥50 mmHg. The impact of clinical, echocardiographic and laboratory variables on mortality was evaluated with the Cox proportional hazard method. Results: A total of 13,482 patients from the TRIO population were included; severe PH was present in 6,530 (48.4%); mean age 73.4 + 13.3, 55.7% females. TRIO score performance was modest (AUC 0.62) in risk stratification (Figure A). PH patients had significantly higher mortality than those without PH at all levels of TRIO score (Figure B); differences were progressively lower with increasing TRIO scores. At multivariate analysis, only TRIO score [HR = 1.54 (1.35-1.77) per unit change], presence of an elevated NT-proBNP [HR = 1.02 (1.02-1.03) per 1000 pg/ml change], RVSP (HR = 1.08 (1.02-1.16) per 10 mmHg change], presence of RV dysfunction [HR = 1.15, (1.05-1.26)] and pulmonary artery pulsatility index (PAPi) ≤ 4 [HR = 1.34 (1.07-1.67)] were significant predictors of mortality (model AUC 0.65). Conclusions: TRIO score allows risk stratification in PH patients, but performance is modest; incorporating additional factors marginally increased model performance. PH patients have higher mortality at all levels of TRIO score, more so at low scores.