Pislaru, Sorin V.

AbstractObjectivesWe aimed to investigate the invasive hemodynamic changes with transcatheter mitral valve replacement (TMVR) in patients with severe mitral stenosis due to severe mitral annular calcification.BackgroundThe hemodynamic response to TMVR in patients with mitral stenosis related to degenerative mitral annular calcification has not been fully elucidated.MethodsWe conducted retrospective review of patients who underwent successful transseptal TMVR with balloon‐expandable valves for symptomatic severe mitral stenosis due to mitral annular calcification at our institution between January 2014 and February 2020. Invasive hemodynamic measurements were obtained both before valve implantation (predeployment) and after (postdeployment).ResultsEighteen patients (age 72 ± 10 years, 44% female) were included for the analysis. There was a significant reduction in mean left atrial pressure (23.7 ± 5.6 mmHg versus 20.6 ± 4.8 mmHg; p = .01), left atrial v‐wave (mean 39.3 ± 10.2 mmHg versus 32.9 ± 9.9 mmHg; p = .01), and an increase in systemic mean blood pressure (72.6 mmHg ±11.2 versus 79.5 ± 9.9 mmHg; p = .02) postdeployment compared to predeployment. Patients who had symptom improvement at 30‐day follow‐up tended to have greater reduction in mean left atrial pressure (4.4 ± 4.4 mmHg versus 0.5 ± 5.2 mmHg; p = .16) and v‐wave (8.6 ± 9.0 mmHg versus 0.7 ± 8.4 mmHg; p = .10) compared to those who did not experience improvement of symptoms.ConclusionsTransseptal TMVR for severe mitral stenosis due to mitral annular calcification is associated with reductions in mean left atrial pressure and left atrial v‐wave, and an increase in systemic arterial pressure.

Abstract Aims Chronic volume-overload can impair systolic and diastolic myocardial properties. We tested the hypothesis that Intrinsic Cardiac Elastography may detect alterations in passive myocardial elasticity in patients with chronic severe mitral regurgitation (MR) and predict worsening left ventricular (LV) function after mitral valve repair (MVr). Methods and results Comprehensive transthoracic echocardiography and cardiac elastography were performed in 80 patients with primary MR (prolapse and/or flail leaflets) of varying severity and compared with 40 normal subjects. In patients who underwent MVr (n = 51), elastography measurements were related to changes in left ventricular ejection fraction (LVEF) at short-term (3–4 days post-op) and mid-term (1 year) follow-up. Most patients were asymptomatic or mildly symptomatic and had preserved LVEF (>60%). Intrinsic velocity propagation (iVP) of myocardial stretch, a direct measure of myocardial stiffness, was higher in patients with severe MR {median 2.0 [interquartile range (IQR) 1.5–2.2] m/s, range 1.1–3.4 m/s; n = 56} compared to normal subjects [median 1.7 (IQR 1.5–1.8) m/s; n = 40; P = 0.0005], but not in those with mild or moderate MR [median 1.7 (IQR 1.4–1.9) m/s; n = 24]. A higher iVP was associated with more severe LV volume-overload and LV and left atrial enlargement (P < 0.05 for all). In patients undergoing MVr, a higher iVP independently predicted a larger drop in LVEF post-intervention (short-term, P = 0.001; 1 year, P = 0.007), incrementally to pre-operative LVEF (P < 0.05). Conclusion Non-invasive measurements of myocardial stiffness were able to predict functional deterioration after MVr for chronic primary MR. Further studies should investigate the mechanisms and practical utility of this novel measurement.

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.

AbstractObjectivesWe sought to determine hemodynamic effects of aortic paravalvular leak (PVL) and predictors of clinical outcomes after aortic PVL closure.BackgroundThe significance of hemodynamic alterations in PVL and relation to severity, procedural success of percutaneous closure and clinical outcomes have not been defined.MethodsPatients undergoing percutaneous PVL closure between July 21, 2004 and September 10, 2018 were included. PVL severity was assessed by echocardiography and aortic angiography. Hemodynamics were assessed by intra‐arterial pressure tracings before and after PVL closure. The primary outcome was a composite of mortality, redo aortic valve replacement (AVR) and redo PVL closure.ResultsOne hundred and seventeen patients (mean age 70.3 ± 14.9 years, 79% surgical and 21% transcatheter prostheses) underwent PVL closure with 94% technical success. PVL was moderate or greater in 106 (91%) at baseline and 11 (11%) post‐procedure. Diastolic BP for those with moderate or greater PVL was lower than for those with less PVL (50.3 ± 11.7 vs. 56.5 ± 12.4 mmHg, p < .001). Pulse pressure was similar between these groups (69.9 ± 20.3 vs. 67.4 ± 21.2 mmHg, p = .39). 35 patients (34%) had 40 events during a mean follow‐up of 1.6 ± 1.9 years (23 deaths, 12 redo AVR, and five redo PVL closures). In a multivariate model, final diastolic BP <47 mmHg (HR 3.27 [1.45–7.36], p = .007) was a significant predictor of the composite endpoint.ConclusionsDiastolic BP was significantly associated with aortic PVL severity and clinical outcomes after PVL closure. In contrast, pulse pressure did not correlate with PVL severity or outcomes. These findings have implications for clinical management of patients with aortic PVL.

AbstractBackgroundTranscatheter edge‐to‐edge repair with MitraClip is only approved for treatment of mitral regurgitation but is increasingly used to treat concomitant tricuspid regurgitation (TR) due to its common coexistence and association with poor outcomes. This study aimed to describe the learning curve associated with the challenge of off‐label treatment of concomitant TR.MethodsThis is a retrospective review of initial and consecutive patients who underwent combined edge‐to‐edge repair of mitral and tricuspid valves (TVs) at our institution from August 2017 to October 2019.ResultsRepair of both valves with MitraClip was performed in 22 patients (median age 81.5 years, 32% female). Mean procedure time was 176 ± 47 min; mean fluoroscopy time was 65 ± 24 min. Procedure duration in the first tertile was significantly longer (223 ± 13 min) than in the third tertile (143 ± 23 min, p = .0003). Median number of total clips placed per case was 3; in 15 patients (68%), the anterior and septal leaflets of the TV were clipped. The average changes in mean right atrial (RA) and left atrial (LA) pressures were −1.7 ± 2.5 mmHg (p = .0080) and −3.2 ± 4.6 mmHg (p = .0045), respectively. The average changes in RA and LA V‐wave heights were −3.3 ± 4.0 mmHg (p = .0009) and −8.1 ± 9.9 mmHg (p = .038), respectively. There was a significant trend toward decreasing residual TR over the course of the series (p = .046). At 30 days, survival was 100% and mean NYHA class decreased from 2.8 to 1.8 (p < .0001).ConclusionsCombined edge‐to‐edge tricuspid and mitral valve repair is safe and feasible. With experience, procedure duration and residual TR decreased.

Objective To determine whether echocardiography-derived left ventricular filling pressure influences survival in patients with severe aortic stenosis (AS) undergoing aortic valve replacement (AVR). Methods We retrospectively reviewed 1383 consecutive patients with severe AS, normal ejection fraction and interpretable filling pressure undergoing AVR. Left ventricular filling pressure was determined according to current guidelines using mitral inflow, mitral annular tissue Doppler, estimated right ventricular systolic pressure and left atrial volume index. Cox proportional hazards regression was used to assess the influence of various parameters on mortality. Results Age was 75±10 years and 552 (40%) were female. Left ventricular filling pressure was normal in 325 (23%), indeterminate in 463 (33%) and increased in 595 (43%). Mean follow-up was 7.3±3.7 years, and mortality was 1.2%, 4.2% and 18.9% at 30 days and 1 and 5 years, respectively. Compared with patients with normal filling pressure, patients with increased filling pressure were older (78±9 vs 70±12, p<0.001), more often female (45% vs 35%, p=0.002) and were more likely to have New York Heart Association class III–IV symptoms (35% vs 24%, p=0.004), coronary artery disease (55% vs 42%, p<0.001) and concentric left ventricular hypertrophy (63% vs 37%, p<0.001). After correction for other factors, increased left ventricular filling pressure remained an independent predictor of mortality after successful AVR (adjusted HR 1.45 (95% CI 1.16 to 1.81), p=0.005). Conclusions Preoperative increased left ventricular filling pressure is common in patients with AS undergoing AVR and has important prognostic implications, regardless of symptom status. Future prospective studies should consider whether patients with increased filling pressure would benefit from earlier operation.

Abstract Aims Right ventricular dysfunction (RVD) is an important determinant of functional status and survival in various diseases states. Data are sparse on the epidemiology and outcome of patients with severe RVD. This study examined the characteristics, aetiology, and survival of patients with severe RVD. Methods and results Retrospective study of consecutive patients with severe RVD diagnosed by transthoracic echocardiography (TTE) between 2011 and 2015 in a single tertiary referral institution. Patients with prior cardiac surgery, mechanical assist devices, and congenital heart disease were excluded. Primary endpoint was all-cause mortality. In 64 728 patients undergoing TTE, the prevalence of ≥mild RVD was 21%. This study focused on the cohort of 1299 (4%) patients with severe RVD; age 64 ± 16 years; 61% male. The most common causes of severe RVD were left-sided heart diseases (46%), pulmonary thromboembolic disease (18%), chronic lung disease/hypoxia (CLD; 17%), and pulmonary arterial hypertension (PAH; 11%). After 2 ± 2 years of follow-up, 701 deaths occurred, 66% within the first year of diagnosis. The overall probability of survival at 1- and 5 years for the entire cohort were 61% [95% confidence interval (CI) 58–64%] and 35% (95% CI 31–38%), respectively. In left-sided heart diseases, 1- and 5-year survival rates were 61% (95% CI 57–65%) and 33% (95% CI 28–37%), respectively; vs. 76% (95% CI 68–82%) and 50% (95% CI 40–59%) in PAH, vs. 71% (95% CI 64–76%) and 49% (95% CI 41–58%) in thromboembolic diseases, vs. 42% (95% CI 35–49%) and 8% (95% CI 4–15%) in CLD (log-rank P &lt; 0.0001). Presence of ≥moderate tricuspid regurgitation portended worse survival in severe RVD. Conclusion One-year mortality of patients with severe RVD was high (∼40%) and dependent on the aetiology of RVD. Left-sided heart diseases is the most common cause of severe RVD but prognosis was worst in CLD.

Abstract Funding Acknowledgements Mayo Clinic Background Variability in Doppler signals is common in patients with atrial fibrillation (AF) and AF is common in low-gradient AS (LGAS). Presence of high single beat Doppler signals (peak velocity ≥4m/s or mean gradient ≥40mmHg) is not factored into decision-making in low-gradient aortic stenosis (LGAS). Objective Determine prevalence of at least one high Doppler signal in AF LGAS and its relationship to computed tomography aortic valve calcium score (AVCS) versus sinus rhythm (SR) high-gradient aortic stenosis (HGAS). Methods Consecutive patients with aortic valve area ≤1cm2 and left ventricular ejection fraction ≥50% during echo were identified (January 1, 2012-December 31, 2016). At least three consecutive Doppler signals were averaged in sinus rhythm (SR) and five in atrial fibrillation (AF). Results Of 1,854 patients, age 76± 11 years, male 52%, 301/1,854 (16%) were in AF and LGAS was present in 122/301 (41%). At least one high Doppler signal in AF LGAS was present in 43/122 (35%). AVCS within 1 year of echo was available for 36% of patient with SR HGAS and 34% of AS LGAS. Median AVCS was not different in SR HGAS 2424 (IQR 1623, 3445) vs AF LGAS with at least one high Doppler signal 2509 [IQR1547, 3119], p =0.10 AVCS threshold for severe AS (men &gt;2000 women &gt;1200) was met in 80% SR HGAS vs 86% AF LGAS with high signals. Conclusions High Doppler signals in AF LGAS are associated with high AVCS more frequently exceeding thresholds for severe AS. Single-beat high Doppler signals instead of the average correlate better with AVCS and classic HGAS.

Abstract Background: Aortic stenosis (AS) causes left ventricular (LV) pressure overload, leading to adverse LV remodeling and dysfunction. Identifying early subclinical markers of LV dysfunction in patients with significant AS is critical as this could provide support for earlier intervention, which may result in improved long-term outcomes. We therefore examined the impact of severe AS and its consequent increase in LV afterload on myocardial deformation and rotational mechanics by 2-dimensional (2D) and 3-dimensional (3D) speckle-tracking echocardiography. Methods: We prospectively measured various strain parameters in 168 patients (42% female, mean age 72±12 years) with severe AS and LV ejection fraction (EF) ≥50%, and compared them to normal values found in literature. 2D and 3D images were analyzed for global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), basal rotation, apical rotation, and peak systolic twist. We further assessed the degree of concordance between 2D and 3D strain, and examined their association with measures of LV preload and afterload. Results: Patients with severe AS exhibited significantly lower GLS and GRS but higher GCS, apical rotation, and twist by 2D and 3D echocardiography compared with published normal values (P=0.003 for 3D twist,P<0.001 for all others). Agreement between 2D- and 3D-GLS by concordance correlation coefficient was 0.49 (95% confidence interval: 0.39-0.57). GLS was correlated with valvulo-arterial impedance, a measure of LV afterload (r=0.34, p<0.001 and r=0.23, p=0.003, respectively). Conclusion: Patients with severe AS demonstrated lower-than-normal GLS and GRS but appear to compensate with higher-than-normal GCS, apical rotation, and twist in order to maintain a preserved LVEF. GLS showed a modest correlation with valvulo-arterial impedance.

ABSTRACT Aims Mild to moderate functional mitral regurgitation (MR) is common in patients with heart failure and preserved ejection fraction (HFpEF) where it is usually considered as an innocent bystander. We hypothesized that MR in HFpEF reflects greater left atrial (LA) myopathy, leading to more adverse haemodynamics and poorer exercise reserve. Methods and results Patients with HFpEF (n = 280) with and without MR underwent echocardiography, invasive haemodynamic exercise testing, and expired gas analysis. As compared to non-MR-HFpEF (n = 163), patients with MR-HFpEF (n = 117; 78 mild and 39 moderate, central jet in 90%) were older, more likely female, with lower body mass and higher prevalence of atrial fibrillation (AF). HFpEF patients with MR displayed greater LA volume, reduced LA strain and compliance, and greater mitral annular dilatation, which was strongly correlated with LA dilatation (r = 0.63, P &lt; 0.0001) but was only weakly related to left ventricular remodelling (r = 0.37). Patients with MR-HFpEF displayed worse biventricular function, more adverse pulmonary haemodynamics, impaired pulmonary vasodilatation, blunted right ventricular reserve, and reduced cardiac output with exercise as compared to non-MR-HFpEF. Importantly, these findings were maintained after excluding patients with HFpEF and AF, suggesting a role for LA myopathy in contributing to MR in HFpEF, independent of rhythm. Conclusions Functional MR in patients with HFpEF reflects LA myopathy, even in the absence of AF, and is associated with greater haemodynamic severity of disease and poorer functional capacity. Further study is required to better define causal mechanisms and potential treatments for MR and LA dysfunction in patients with HFpEF.