Miranda, William R.

Abstract Aims Right atrial pressure (RAP) provides a composite measure of right ventricular diastolic dysfunction, right atrial compliance, and volume status, and these three variables are typically abnormal in adults with repaired tetralogy of Fallot (TOF). RAP is a well-established prognostic metric in patients with pulmonary hypertension, and recent data suggest that RAP is associated with clinical outcomes in TOF. The purpose of this study was to determine the role of inferior vena cava (IVC) haemodynamics (size and collapsibility) for the assessment of RAP and its potential application for risk stratification and prognostication in the TOF population. Methods and results Adult TOF patients with echocardiographic assessment of IVC haemodynamics were divided into patients with (derivation cohort, n = 256) and without (validation cohort, n = 492) cardiac catheterization data. We assessed the correlation between IVC haemodynamics, RAP, and disease severity indices [arrhythmias, peak oxygen consumption (VO2), and heart failure hospitalization] in derivation cohort and compared it with the correlations in the validation cohort. IVC haemodynamics correlated with RAP (r = 0.52, P < 0.001), with disease severity indices {atrial arrhythmias [area under the curve (AUC) 0.81], ventricular arrhythmias [AUC 0.67], heart failure hospitalizations [AUC 0.78], and peak VO2 [r = 0.53]}, and with transplant-free survival in the derivation cohort. Similar correlations between IVC haemodynamics, disease severity indices, and transplant-free survival were also observed in the validation cohort. Conclusions These findings suggest that IVC haemodynamics can potentially be used for risk stratification and prognostication in TOF patients and can complement the current risk models that are based predominately on right ventricular volumes and systolic function.

Abstract Aims Increased medial mitral annulus early diastolic velocity (e′) plays an important role in the echocardiographic diagnosis of constrictive pericarditis (CP) and mitral e′ velocity is also a marker of underlying myocardial disease. We assessed the prognostic implication of mitral e′ for long-term mortality after pericardiectomy in patients with CP. Methods and results We studied 104 surgically confirmed CP patients who underwent echocardiography and cardiac catheterization within 7 days between 2005 and 2013. Patients were classified as primary CP (n = 45) or mixed CP (n = 59) based on the clinical history of concomitant myocardial disease. On multivariable analysis, medial e′ velocity and mean pulmonary artery pressure were independently associated with long-term mortality post-pericardiectomy. There were significant differences in survival rates among the groups divided by cut-off values of 9.0 cm/s and 29 mmHg for medial e′ and mean pulmonary artery pressure, respectively (both P < 0.001). Ninety-two patients (88.5%) had elevated pulmonary artery wedge pressure (PAWP) (≥15 mmHg); there was no significant correlation between medial E/e′ and PAWP (r = 0.002, P = 0.998). However, despite the similar PAWP between primary CP and mixed CP groups (21.6 ± 5.4 vs. 21.2 ± 5.8, P = 0.774), all primary CP individuals with elevated PAWP had medial E/e′ <15 as opposed to 34 patients (57.6%) in the mixed CP group (P < 0.001). Conclusion Increased mitral e′ velocity is associated with better outcomes in patients with CP. A paradoxical distribution of the relationship between E/e′ and PAWP is present in these patients but there is no direct inverse correlation between them.

Background: Left ventricular global longitudinal strain (GLS) is associated with long-term outcomes of patients with severe aortic stenosis. However, its prognostic value in patients with moderate aortic stenosis remains unknown. Methods: Patients diagnosed with moderate aortic stenosis (1.0< aortic valve area ≤1.5 cm 2 ) and left ventricular ejection fraction ≥50% were identified. GLS was assessed by 2-dimensional strain imaging using speckle-tracking method. All-cause mortality was assessed according to the median GLS value. Results: Two hundred eighty-seven patients were included (median age 76 years; 47% male). Mean aortic valve area was 1.25 cm 2 , left ventricular ejection fraction 62%, and median GLS −15.2%. During a median follow-up of 3.9 years, there were 103 deaths (36%). Mortality was higher in patients with GLS>−15.2% (hazard ratio 2.62 [95% CI 1.69–4.06]) compared with patients with GLS ≤−15.2% even after adjusting for confounders. Mortality rates at 1, 3, 5 years were 21%, 35%, 48%, respectively, in patients with GLS >−15.2%, and 6%, 15%, 19% in those with GLS ≤−15.2%. Even among those with left ventricular ejection fraction ≥60%, GLS discriminated higher-risk patients ( P =0.0003). During follow-up, 106 (37%) patients underwent aortic valve replacement with median waiting-time of 2.4 years, and their survival was better than patients without aortic valve replacement. Among those patients undergoing aortic valve replacement, prognosis was still worse in patients with GLS >−15.2% ( P =0.04). Mortality rates at 1, 3, 5 years were 2%, 10%, 20%, respectively, in patients with GLS >-15.2% and 2%, 5%, 6% in those with GLS ≤−15.2%. Conclusions: Impaired GLS in moderate aortic stenosis patients is associated with higher mortality rates even among those undergoing aortic valve replacement.

Abstract Background Functional mitral regurgitation (MR) is expected to improve after aortic valve replacement (AVR) in patients with severe aortic stenosis (sAS) and MR. However, little is unknown about the impact of AVR on organic MR and whether concomitant mitral valve surgery (MVS) improves outcomes in patients with sAS and MR. Purpose We assessed the impact of AVR on MR severity according to MR mechanism. We also assessed the clinical outcomes in patients with sAS and MR that underwent AVR with vs without MVS. Methods We retrospectively investigated patients who received surgical AVR or transcatheter aortic valve implantation (TAVI) from 2008 to 2017. We identified patients with effective mitral regurgitant orifice area (ERO) ≥10 mm2 by the proximal isovelocity surface area method with transthoracic echocardiography. The change in MR after AVR was considered significant when there was at least one grade difference. We compared the all-cause mortality of patients with sAS and MR that underwent AVR with vs without MVS according to MR mechanism and patient age. Results We included 326 patients with sAS and MR (age 80 [Interquartile range 72–85] years, 53% male, 21% history of myocardial infarction). Organic and functional MR were present in 69% and 31%, respectively. Of these, 240 underwent AVR alone (AVR group) including TAVI in 112 while 86 underwent AVR and MVS (MVS group) including mitral valve replacement in 38 and mitral valve repair in 48. The median ERO at baseline was 17 (14–21) mm2 in AVR and 24 (19–33) mm2 in MVS (p<0.001). Improvement in MR was observed in 58% of AVR and 91% of MVS (p<0.001). In AVR group, organic MR improved as frequently as functional MR (58% vs. 59%, p=0.96). Predictors for improvement in organic MR were absence of atrial fibrillation and moderate or greater MR, and in functional MR, the only predictor was decrease in LV end-systolic diameter after AVR. During mean follow-up of 2.4±2.3 years, moderate or greater MR was observed in 23% of AVR and 7% of MVS (p=0.002). All-cause mortality was similar in AVR and MVS groups for organic and functional MR (hazard ratio for MVS group 0.68, 95% CI: 0.40–1.10, p=0.13 in organic MR and 0.62, 95% CI 0.29–1.22, p=0.68 in functional MR). All-cause mortality was lower in MVS group compared with AVR group in patients <80 years, and was similar in patients ≥80 years (Figure). Conclusion In patients with sAS and MR, MR improves after AVR, even in the majority of patients with organic MR. Compared with isolated AVR, concomitant MVS was associated with better prognosis in patients <80 years.

Abstract Background Currently data on the risk stratification of patients with moderate aortic stenosis (AS) are very limited. Method Patients diagnosed with moderate AS in 2012 (aortic valve area [AVA]: >1 and ≤1.5cm2) were identified. Patients were stratifying by LV diastolic function (normal vs high filling pressure), left ventricular ejection fraction (LVEF ≥50 vs <50%) and stroke volume index (SVI ≥35 vs <35 ml/m2). High filling pressure was defined as average E/e' ≥14 or septal E/e' ≥11 when atrial fibrillation was present. The prognosis was compared to age- and sex-matched general population. Results 898 patients were included (age 74 years, 58% male, AVA 1.25 cm2). During a median follow-up of 2.9 years, there were 346 deaths. In patients with moderate AS, mortality was higher than expected (P<0.001, Fig 1A). LV high filling pressure, LVEF<50% and SVI<35ml/m2 were present in 416 (55%), 140 (17%) and 81 (9%) patients, respectively. Those with normal filling pressure had similar prognosis when compared to controls (Fig 1C, P=0.35); whereas mortality rates remained higher than reference even when LVEF≥50% or SVI≥35ml/m2 (Fig 1E, 1G, P<0.001). Amongst all groups, mortality rates were the highest in patients with LVEF <50% or SVI <35 ml/m2 (Fig 1D, 1F, P<0.001); mortality ratios were 3.78 (95% CI 3.01–4.67) and 6.91 (95% CI 5.13–9.11), respectively. Noteworthy, high filling pressure allowed further risk stratification when LVEF or SVI was preserved (Fig 2, P<0.001). Figures 1 & 2 Conclusions Patients with moderate AS showed poor survival. A clinical trial examining role of aortic valve replacement would be beneficial not only in patients with reduced LVEF or SVI but also in those with high LV filling pressures.

Background: Mitral stenosis frequently coexists in patients with severe aortic stenosis. Mitral stenosis severity evaluation is challenging in the setting of combined aortic stenosis and mitral stenosis because of hemodynamic interactions between the 2 valve lesions. The impact of aortic valve replacement (AVR) for severe aortic stenosis on mitral stenosis is unknown. This study aimed to assess the effect of AVR on mitral stenosis hemodynamics and the clinical outcomes of patients with severe aortic stenosis with and without mitral stenosis. Methods: We retrospectively investigated patients who underwent surgical AVR or transcatheter AVR for severe aortic stenosis from 2008 to 2015. Mean transmitral gradient by Doppler echocardiography ≥4 mm Hg was identified as mitral stenosis; patients were then stratified according to mitral valve area (MVA, by continuity equation) as >2.0 cm 2 or ≤2.0 cm 2 . MVA before and after AVR in patients with mitral stenosis were evaluated. Clinical outcomes of patients with and without mitral stenosis were compared using 1:2 matching for age, sex, left ventricular ejection fraction, method of AVR (surgical AVR versus transcatheter AVR) and year of AVR. Results: Of 190 patients with severe aortic stenosis and mitral stenosis (age 76±9 years, 42% men), 184 were matched with 362 with severe aortic stenosis without mitral stenosis. Among all mitral stenosis patients, the mean MVA increased after AVR by 0.26±0.59 cm 2 (from 2.00±0.50 to 2.26±0.62 cm 2 , P <0.01). MVA increased in 105 (55%) and remained unchanged in 34 (18%). Indexed stroke volume ≤45 mL/m 2 (odds ratio [OR] 2.40; 95% CI, 1.15–5.01; P =0.020) and transcatheter AVR (OR, 2.36; 95% CI, 1.17–4.77; P =0.017) were independently associated with increase in MVA. Of 107 with significant mitral stenosis (MVA ≤2.0 cm 2 ), MVA increased to >2.0 cm 2 after AVR in 52 (49%, pseudo mitral stenosis) and remained ≤2.0 cm 2 in 55 (51%, true mitral stenosis). During follow-up of median 2.9 (0.7–4.9) years, true mitral stenosis was an independent predictor of all-cause mortality (adjusted hazard ratio, 1.88; 95% CI, 1.20–2.94; P <0.01). Conclusions: MVA improved after AVR in nearly half of patients with severe aortic stenosis and mitral stenosis. MVA remained ≤2.0 cm 2 (true mitral stenosis) in nearly half of patients with severe aortic stenosis and significant mitral stenosis; this was associated with worse survival among patients undergoing AVR for severe aortic stenosis.

Background The purpose of this study was to compare the incidence of pregnancy‐related adverse outcomes ( PRAO ) between patients with versus without hemodynamically significant right ventricle outflow tract ( RVOT) . Methods and Results This was a retrospective cohort study of all pregnant patients with isolated RVOT lesions undergoing evaluation at the Mayo Clinic, 1990 to 2017. Hemodynamic significance was defined as ≥moderate pulmonary/conduit stenosis (≥3 m/s) and/or ≥moderate regurgitation. Patients with concomitant significant left heart disease were excluded. PRAO was defined as cardiovascular, obstetric, and/or neonatal complications occurring during the pregnancy through 6 weeks postpartum. A total of 224 pregnancies in 114 patients with RVOT lesions were identified; 38 pregnancies occurred in 24 patients with hemodynamically significant RVOT . Forty‐eight (21%) pregnancies ended in spontaneous abortion. Of the 173 completed pregnancies, median gestational age at delivery was 38 (35–40) weeks and median birth weight 2965 (2065–4122) g. Seven pregnancies (4%) were complicated by cardiovascular events, 14 (8%) by obstetric complications, with adverse neonatal outcomes occurring in 38 (22%). There were no maternal deaths. The incidence of spontaneous abortion and PRAO were similar in both the RVOT and hemodynamically significant RVOT groups. As an isolated condition, Tetralogy of Fallot–pulmonary atresia was associated with spontaneous abortion and neonatal complications. Conclusions The risk of cardiovascular complications was low in patients with isolated RVOT lesions, and hemodynamically significant RVOT lesions were not associated with either cardiovascular complications or PRAO . Further studies are required to explore the factors responsible for PRAO in patients with Tetralogy of Fallot–pulmonary atresia.

AbstractObjectiveTo assess the association between elevated ventricular‐end diastolic pressures (VEDP) and pulmonary artery wedge pressure (PAWP) on long‐term survival in adult Fontan patients.BackgroundThe impact of ventricular filling pressures on long‐term survival in adults post‐Fontan palliation is unknown.MethodsWe included 148 adult Fontan patients (age ≥ 18 years) without atrioventricular valve prosthesis or pulmonary vein stenosis undergoing arterial and venous catheterization between December 1999 and November 2017. VEDP was defined as ≥12 mmHg and PAWP as >12 mmHg based on optimal cut‐offs for prediction of mortality on receiver‐operator curves (AUC 0.63 and 0.66, respectively).ResultsMean age was 31.3 ± 9.2 years and 48.6% of patients were females. Most common congenital defects were tricuspid atresia (36.4%) and double‐inlet left ventricle (28.3%); 59.5% patients had atriopulmonary Fontan connections. Mean VEDP was 11.5 ± 4.7 mmHg and PAWP 10.6 ± 4.5 mmHg (correlation coefficient .76). During a follow‐up of 6.0 ± 4.8 years (median 5.4, IQR 1.4–9.4), there were 45 deaths (30.4%). Overall survival was lower in patients with VEDP ≥ 12 compared to those with VEDP < 12 mmHg (p = .02). Similarly, survival was lower in patients with PAWP>12 compared to patients with PAWP ≤ 12 mmHg (p < .0001). In the multivariate model, PAWP was an independent predictor of death (HR 1.1 per mmHg, 95% CI 1.02–1.15, p = .009) whereas VEDP was not (HR 1.1 per mmHg, 95% CI 1.0–1.13; p = .08).ConclusionPAWP but not VEDP was independently associated with long‐term overall mortality in adult Fontan patients. Perhaps PAWP rather than VEDP should be used in the risk stratification of these patients.