Nkomo, Vuyisile T.

Objective: In patients with aortic stenosis (AS), the development of left ventricular (LV) systolic dysfunction adversely affects the natural history and is associated with poor outcomes following aortic valve replacement. However, the timing and possible reasons for transition from preserved to impaired LV ejection fraction (LVEF) in patients with AS have not been described. The aim of this study was to describe the time course of development of LV dysfunction and associated conditions in patients with severe AS. Methods & Results: Between 1/1/2009 and 12/31/2012, 667 (19%) of 3528 patients with severe AS (aortic valve area (AVA) ≤1 cm2) identified from the Mayo Clinic, Rochester, MN Echocardiographic Laboratory database; had LVEF ≤50%. Of those 667 patients, 263 (39%) had previous echocardiograms (median: 71.6 months, 25 IQR: 36.3, 75:118.2) before the development of severe AS, allowing an assessment of change in LVEF over time. Among these 263 patients, 8 (3%) had dilated cardiomyopathy (DCM), 225 (86%) had ischemic heart disease (IHD), 5 (2%) had other significant valve disease, and 25 (10%) had no concomitant heart disease before the development of severe AS. The evolution of development of reduced LVEF at several time points is shown in the Figure. The initial LVEF was 34±12 % in DCM patients, 51±13% in IHD patients and 61±9 % in AS patients without other heart diseases (p<0.001, ANOVA). Patients with AS alone or AS+DCM/IHD showed a gradual decline in LVEF before AS became severe, and a more rapid decline in LVEF once the AVA reached ≤ 1 cm2. Conclusion: In patients with severe AS, a majority of the patients (86%) with reduced EF had ischemic heart disease. Although there was a gradual decline in LVEF before development of severe AS, the decline was more rapid after AS became severe in almost all patients regardless of associated cardiac condition. More frequent monitoring may be indicated in AS patients especially when AVA reaches 1cm2 and concomitant IHD.

Introduction: Clinical predictive value of transient prolonged ventricular conduction and repolarization during right ventricular (RV) pacing have not been studied. Hypothesis: Ventricular conduction and repolarization prolongation during RV pacing predict risk of arrhythmic and mortality events. Methods: Electrophysiology studies in 501 patients with cardiomyopathy (CM) were reviewed. Duration changes of QRS and QT interval during pacing from the RV apex were measured. Subjects were followed up for a mean of 3.2 years for arrhythmic events and total mortality. Results: Participants had a mean age 65 yrs, 80% male, 74% funcional class II or III, and a mean EF of 33.1%. A paced QRS duration > 190 ms was associated with more severe CM and in multi-variable analysis it was associated with a 3.5 times higher risk of ventricular arrhythmias or appropriate defibrillator therapy (HR 3.5, 95% CI 2.3-5.4, p<0.01) and 2.6 times higher risk of total mortality or arrhythmic events (HR 2.6, 95% CI 2.3-3.4, p<0.01) compared to a paced QRS duration <190 ms, independent of baseline EF or baseline QRS duration, and after adjustment for electrophysiology study results, baseline functional class, type of cardiomyopathy and other relevant clinical factors. Similarly a QTc interval during RV pacing > 620 ms was associated with a 2.7 times higher risk of arrhythmic events compared to a QTc interval during RV pacing < 620 ms. Conclusions: Prolongation of ventricular conduction (QRS > 190 ms) and repolarization (QTc > 620 ms) observed during RV pacing in subjects with CM are associated with higher risk of arrhythmic events, defibrillator therapies and all-cause mortality.

Introduction: Excised aortic valve weight (AVW) correlates with severity of AS. There is some debate about the true severity of AS in low gradient AS (LGAS) compared to high gradient AS (HGAS). We sought to compare patient characteristics and operatively excised AVW in patients with LGAS vs HGAS vs moderate AS. Methods: 916 patients with EF ≥50% undergoing surgical aortic valve replacement for AS between 2010-2012 were included. Clinical and echocardiographic characteristics of LGAS patients (AVA≤1cm 2 , MnG<40mmHg; N=68) were compared to HGAS patients (AVA≤1cm 2 , MnG≥40mmHg; N=745) and operatively excised AVW were compared to moderate AS (AVA>1cm 2 , MnG<40mmHg; N=102). Results: Compared to HGAS, LGAS patients were older (mean age 77 ± 10 vs 73 ± 10 years; p=0.001), often female (56% vs 38%; p=0.006), but without differences in diabetes (26% vs 29%; p=0.78), hyperlipidemia (85% vs 86%, p=0.86), coronary artery disease (49% vs 44%; p=0.53), or hypertension (81% vs 76%; p=0.38). LGAS patients predominantly had trileaflet aortic valves (91% vs 71%; p<0.001), smaller LVOT diameter (2.16 ± 0.15 vs 2.25 ± 0.20 cm; p=0.002), lower stroke volume index (42.1 ± 7.3 vs 49.0 ± 8.8 cc/m 2 ; p<0.001), lower systemic compliance (0.77 ± 0.30 vs 0.93 ± 0.33 ; p<0.001), but no difference in valvulo-arterial impedance (3.96 ± 0.76 vs. 3.84 ± 0.80, p=0.24) compared to HGAS. Excised AVW were lower in patients with LGAS vs HGAS (1.77 ± 0.76 vs 2.69 ± 1.26 g, p<0.001), but not different from moderate AS (1.77 ± 0.76 vs 2.04 ± 0.94 g; p=0.1). This relationship held true when AVW was indexed to body surface area. Three-year mortality post-valve replacement was significantly higher in LGAS compared to HGAS (22% vs 11%, p=0.02). Conclusions: LGAS occurs mostly in older female patients with trileaflet aortic valves. Excised AVW in LGAS is similar to moderate AS but lower than HGAS. However, systemic compliance is higher in LGAS vs HGAS contributing to increased afterload. Poorer outcomes after surgery in LGAS patients may be attributed to noncompliant vasculature which is not corrected with valve replacement and evaluation of patients with LGAS should include assessment of peripheral resistance.

Background: Transcatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement in patients at high surgical risk. We investigated the impact of TAVR on left (LV) and right ventricular (RV) function using conventional echocardiography parameters. Methods and results: A total of 202 consecutive patients (age 80.6±8.0 years, aortic valve area 0.80±0.16cm 2 ) who underwent TAVR at Mayo Clinic between 2008 and 2013 were included in the study. LV ejection fraction (EF) and RV systolic function including tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC) and, systolic excursion velocity (S’) were compared before (median 33.5 days) and after TAVR procedure (median 30 days). Patients who underwent pacemaker implantation after TAVR were excluded. LV EF significantly improved following TAVR (55.3±12.6% pre vs 58.5±11.1% post; p<0.05). In contrast, RV systolic function significantly decreased after TAVR (pre vs post; TAPSE: 18.8±6.3 mm vs 17.4±6.3 mm, FAC: 42.6±9.8% vs 37.3±8.2%; S’: 10.7±2.6 cm/s vs 10.2±2.6 cm/s; p<0.05 for all). Stratifying RV functional change by TAVR approach site, patients undergoing trans-femoral TAVR (n=100) showed RV deterioration only by FAC (see Table). In contrast, RV systolic dysfunction was more prominent in trans-apical approach group (n=87) with significant decline in all parameters of RV systolic function (see Table). Conclusion: TAVR is associated with early enhancement in LV systolic function. However, there is evidence of worsening RV function in a significant number of patients. Further studies are necessary to determine whether this deterioration in RV function is related to anatomic access site or to other factors, and to evaluate its prognostic significance.

Introduction: Bioprosthetic valve thrombosis (BPVT) is increasingly being recognized as a cause of prosthetic valve dysfunction within the first years after surgical implantation. However, in the absence of changes in clinical status, current guidelines recommend cardiac imaging only after 10 years post bioprosthetic valve implantation . Hypothesis: We hypothesized that an increase in prosthetic valve gradient is detectable months before a formal diagnosis of symptomatic BPVT. Methods: Eighty-three patients diagnosed with BPVT and treated medically at our institution between 2002 and 2017 were retrospectively identified. Transvalvular gradients recorded on TTE immediately post implantation, at time of clinical BPVT diagnosis, and within a 12-month period prior to BPVT diagnosis were available in 45 patients: 18 for the aortic position, 11 for mitral, and 16 for tricuspid. When more than one study was conducted in the 12 months’ timeframe, the latest value was used in the analysis. Data are reported as mean (95% CI). Results: For all valve positions, an increased gradient was detectable within 12 months prior to formal BPVT diagnosis: mean increase vs. baseline of 17 (10-23) mmHg, p < 0.0001 for aortic prostheses; 5 (2-8) mmHg, p = 0.004 for mitral prostheses, and 2 mm Hg (1-3) mmHg, p = 0.003 for tricuspid prostheses. The figure presents the evolution of prosthetic valve gradients (normalized to the baseline, immediately post-implantation value) in patients with aortic (left), mitral (middle), and tricuspid (right) valve . Conclusions: Elevated gradients precede formal clinical diagnosis of BPVT. Closer monitoring of transvalvular gradients may prove useful for BPVT diagnosis before patients become symptomatic. With recent evidence supporting the efficacy of anticoagulant therapy in BPVT, earlier diagnosis may lead to an increased rate of response and better clinical outcomes.

Background Aortic stenosis (AS) affects, and is associated with significant comorbidity and mortality, including sudden cardiac death (SCD) from unknown mechanisms. However, it is difficult to predict which patients with AS will suffer a SCD event. Anemia and low iron are known risk factors for mortality in heart failure populations and AS. We hypothesized that anemia in patients with AS is associated with increased risk of SCD. Purpose Understand the relationship and prognostic implications between anemia and SCD in patients with severe AS. Methods and Results We selected 8,144 of 10,850 patients with severe AS (mean transvalvular gradient ≥40 mmHg or peak velocity ≥4 m/s or calculated valve area < 1 cm 2 ) from the Mayo Clinic Aortic Stenosis Registry, which includes all consecutive patients with severe AS over the time period January 1 st , 1983 to September 30 th , 2015. Subjects in this analysis (median age 76 years and 57% male) were diagnosed starting in 1995 and had hemoglobin (Hb) measurements within one year of diagnosis and prior to intervention. The mean Hb level was 12.8 (± 1.9) g/dL. The prevalence of anemia (Hb<13.0g/dL for men, <12.0g/dL for women) was 40%, 14% microcytic, 20% macrocytic, with the remainder normocytic. Of the 8,144 patients, a total of 4,440 died (10‐year survival 39%; and 240 were confirmed as SCD events [10 year cumulative incidence 4%]). Anemia was associated with increased all‐cause mortality (HR 1.87, 95% CI 1.76–1.99, P=<0.001) and increased SCD events (HR 1.58, 95% CI 1.22–2.06, P=<0.001) in patients with severe AS. Every SD decrease in Hb (1.9 g/dL) was associated with an increased risk of SCD (HR 1.42, 95% CI 1.24–1.62, P<0.001). Conclusions Anemia is highly prevalent in patients with severe aortic stenosis and is independently associated with increased all‐cause mortality, and more specifically with increased SCD risk. Possible mechanisms include anemia aggrevating myocardial hypoxia, increasing propensity for arrhythmia and abnormal Bezold‐Jarisch reflex mismatch. Anemia may be a useful prognostic marker and a potential therapeutic target in patients with severe AS. Support or Funding Information CAAC is supported by AHA17POST33400211 and NIH HL134885. This study was supported by a grant from the Department of Cardiovascular Medicine, Mayo Clinic Rochester. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

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.

Background: Warfarin is known to be effective in the treatment of bioprosthetic valve thrombosis (BPVT). However, the time-course of response to anticoagulation has not been fully characterized. Hypothesis: We hypothesized that response to warfarin can differ depending on valve position. Methods: We retrospectively identified 45 patients with BPVT diagnosis between 2002 and 2019 that involved either the mitral (MV) or the aortic valve (AV) prostheses, all with eventual echocardiographic resolution with warfarin. BPVT involved AV in 26 (57.8%) patients and MV in 19 (42.2%). Mean gradients (MGs) were tracked starting from BPVT diagnosis until recovery, which was defined as MGs decreasing to initial post-implantation MGs, to 50% below MGs at BPVT diagnosis, or to < 20 mmHg in AV and < 5 mmHg in MV. Kaplan Meier analysis was used to compare recovery time between MV and AV. Duration is reported relative to the time of BPVT diagnosis. Results: Recovery was faster in MV than in AV patients treated with warfarin, with median time of 3.8 months in the AV and 1.8 months in the MV group, p < 0.001 (Figure 1). At 1 month follow up, 15.4% recovered in AV group and 21.1% in MV, p = 0.605. At 3 months, 38.5% recovered in the AV and 78.9% in the MV, p = 0.009. At 6 months, 57.7% of AV group recovered while 100% recovered in the MV group, p = 0.001. The longest time for recovery was 30 months in 1 AV patient. Conclusion: Recovery using warfarin tended to be faster in BPVT involving the MV compared with the AV. In our study, all patients with MV BPVT recovered by 6 months, while this only happened in half the patients with AV BPVT. This suggests that a longer duration of warfarin trial may be needed in the case of AV disease. This might also suggest that the pathogenesis may differ between the two valves.

Background Transcatheter mitral valve repair (TMVr) is currently offered at selected centers that meet certain operator and institutional requirements. We sought to explore the hypothesis that the availability of TMVr is associated with improved outcomes of MV surgery. Methods and Results We used the Nationwide Readmissions Database to identify patients who underwent MV surgery at centers with or without TMVr capabilities between January 1 and December 31, 2017. The primary end point was in‐hospital mortality. Secondary end points were postoperative complications, resource use, and 30‐day readmissions. A total of 24 477 patients from 595 centers (446 TMVr, 149 non‐TMVr) were included. There were modest but statistically significant differences in the prevalence of comorbidities between the groups. Patients at non‐TMVr centers had higher unadjusted in‐hospital mortality than those at TMVr centers (5.6% versus 3.6%, P <0.001). They also had higher rates of postoperative complications, longer hospitalizations, higher cost, and fewer home discharges but similar 30‐day readmission rates. After propensity matching, mortality remained higher at non‐TMVr centers (5.5% versus 4.0%, P <0.001). Rates of postoperative complications, prolonged hospitalizations, and nonhome discharges also remained higher. Postoperative mortality was consistently higher at non‐TMVr centers in multiple risk‐adjustment analyses incrementally accounting for differences in risk factors, surgical volume, availability of surgical repair, and excluding concomitant procedures. In the most comprehensive model, surgery at non‐TMVr centers was associated with higher odds of death (odds ratio, 1.41; 95% CI, 1.14–1.73; P =0.002). Conclusions Mitral valve surgery at TMVr centers is associated with improved in‐hospital outcomes compared with non‐TMVr centers.