Kato, Nahoko

AbstractObjectivesTo compare all‐cause mortality in patients with mitral annulus calcification (MAC) and severe mitral valve dysfunction (MVD) who received standard mitral intervention versus no intervention.BackgroundPatients with MAC often have high surgical risk due to advanced age, comorbidities, and technical challenges related to calcium. The impact of a mitral intervention on outcomes of patients with MAC and severe MVD is not well known.MethodsRetrospective review of patients with MAC by transthoracic echocardiography (TTE) in 2015 at a single institution. Patients with severe mitral stenosis (MS) or regurgitation (MR) were analyzed and stratified into two groups: surgical or transcatheter intervention performed <1 year after the index TTE, and no or later intervention. The primary endpoint was all‐cause mortality.ResultsOf 5502 patients with MAC, 357 had severe MVD (MS = 27%, MR = 73%). Of those, 108 underwent mitral intervention (surgery = 87; transcatheter = 21). They were younger (73 ± 11 vs. 76 ± 11 years, p < 0.01) and less frequently had cardiovascular diseases compared with no‐intervention. Frequency in women was similar (45% vs. 50%, p = 0.44). During median follow‐up of 3.2 years, the intervention group had higher estimated survival than those without intervention (80% vs. 72% at 1 year and 55% vs. 35% at 4 year, p < 0.01). Adjusted for age, eGFR, LVEF < 50%, and pulmonary hypertension, mitral intervention was an independent predictor of lower mortality (hazard ratio = 0.66, 95% confidence interval 0.43–0.99, p = 0.046).ConclusionPatients with MAC and severe MVD who underwent mitral intervention <1 year from index TTE had lower mortality than those without intervention. Mitral intervention was independently associated with lower mortality.

Abstract Aims Concurrent mitral regurgitation (MR) influences treatment considerations in patients with severe aortic stenosis (sAS). Limited information exists regarding haemodynamic effects of sAS on MR severity and outcome of these patients. We assessed the impact of aortic valve replacement (AVR) on MR according to mechanism in patients with sAS and MR. Methods and results In patients with sAS who received surgical or transcatheter AVR from 2008 to 2017, those with effective mitral regurgitant orifice area (ERO) ≥ 10 mm2 prior to AVR were evaluated. 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 and without improvement in MR. Of 234 patients with sAS and MR (age 80 ± 9 years, 52% male, ERO 19 ± 7 mm2), organic and functional MR were present in 166 (71%) and 68 (29%), respectively. MR improved in 136 (58%); improvement occurred with similar frequency in organic versus functional MR (59% and 57%, P = 0.88). Associated determinants were absence of atrial fibrillation in organic MR [odds ratio (OR) 2.09, 95% confidence interval (CI) 1.00–4.37; P = 0.049] and indexed aortic valve area (iAVA) ≤ 0.40 cm2 in functional MR (OR 3.28, 95% CI 1.13–9.47; P = 0.028). In the overall cohort, mitral annulus diameter &lt; 3 cm (OR 1.74, 95% CI 1.02–2.97; P = 0.041) and QRS duration &lt; 115 ms (OR 1.73, 95% CI 1.00–2.98; P = 0.049) were independently associated with improvement in MR. During median follow-up of 3.5 years, lack of improvement in MR was not associated with higher mortality in the overall cohort of patients with ERO ≥ 20 mm2 [adjusted hazard ratio (HR) 1.71, 95% CI 0.90–3.27; P = 0.10, adjusted for age, New York Heart Association III or IV, diabetes, and creatinine ≥ 2.0 mg/dL]. Lack of improvement in organic MR was associated with higher mortality (adjusted HR 3.36, 95% CI 1.40–8.05; P &lt; 0.01). In patients with functional MR, change in MR was not associated with mortality (HR 1.24, 95% CI 0.44–3.47; P = 0.68). Conclusions In nearly 60% of patients with sAS and MR, MR improved after AVR, even in the majority of patients with organic MR. Absence of atrial fibrillation in organic MR, iAVA ≤ 0.40 cm2 in functional MR, and mitral annulus diameter &lt; 3 cm and QRS duration &lt; 115 ms in the overall population were associated with MR improvement. Post-operative improvement in organic MR was associated with better survival.

Abstract Background There is a paucity of data about the prevalence and natural history of mitral annular calcification (MAC). Purposes In a large cohort of patients undergoing clinically-indicated echocardiography, we aimed to evaluate the prevalence and the natural history of MAC, and the frequency of associated mitral valve dysfunction (MVD). Methods Retrospective review of all patients who underwent echocardiographic evaluation at our institution between January 1st and December 31st 2015. The patients were stratified into 3 groups: MAC with MVD, MAC without MVD, no MAC. MVD was defined as moderate or greater mitral regurgitation (MR) or stenosis (MS). The 3 groups were compared for baseline clinical and echocardiographic characteristics and all-cause mortality during follow-up. Results Of 24,415 evaluated patients, 5478 (22%) had MAC. Patients with MAC were older (75±10 vs. 60±16 years, p&lt;0.01) and more often female (46% vs. 43%, p&lt;0.01). MVD was more frequently observed in patients with MAC (16% vs. 7%, p&lt;0.01); moderate or greater MR was found in 10% of patients with MAC vs. 6% without MAC (p&lt;0.01) and MS in 7% vs. 0.5% (p&lt;0.01). In patients with MAC, those with MVD were more often female and more frequently had creatinine ≥2mg/dl and moderate or greater aortic stenosis (AS) than those without MVD (Fig. A). Kaplan-Meier survivals at 1 year were 75% in patients with MAC and MVD, 87% in those with MAC without MVD, and 92% in those without MAC (Fig B). Adjusted for age, sex, diabetes, creatinine ≥2 mg/dl, coronary artery disease, left ventricular ejection fraction &lt;50%, and AS, MAC was associated with higher all-cause mortality (adjusted hazard ratio1.4, 95% confidence interval: 1.3–1.5, p&lt;0.01); combined MAC and MVD was associated with the highest mortality during follow-up of 2.5±1.8 years. Conclusion In a large cohort of patients undergoing echocardiographic evaluation, the prevalence of MAC was 22%. MV dysfunction was more than twice as prevalent in patients with MAC as without. Patients with MAC had higher all-cause mortality than patients without MAC. Among patients with MAC and mitral valvular dysfunction, adjusted mortality was two-fold higher compared to those without MAC. Funding Acknowledgement Type of funding source: None

Abstract Background Prevalence of calcific mitral stenosis (MS) increases with age. Mitral valve interventions for calcific MS are often delayed until symptoms are severely limiting because the natural history of calcific MS and its relation to cardiac symptoms or comorbidities have not been well assessed. Objectives We assessed the prevalence of symptoms, comorbidities and determinants of all-cause mortality in patients with severe calcific MS. Methods We retrospectively investigated adults with echocardiographic isolated severe MS, defined as mitral valve area (MVA by the continuity equation) ≤1.5 cm2, from July 2003 to December 2017. Among them, calcific MS was identified as obstruction of left ventricular inflow due to degenerative calcification of the mitral annulus using echocardiography and, whenever available, operative findings including histopathological examination. Inactivity was defined as requirement for assistance with activities of daily living. Follow up was obtained by review of medical records. Results Of 491 patients with isolated severe MS, calcific MS was present in 200 (41%; age 78±11 years, 18% men, 32% with atrial fibrillation). Charlson Comorbidity Index (CCI) was 5.1±1.7 and 14 (7%) were inactive. MVA and transmitral gradient (TMG) were 1.26±0.19 cm2 and 8.1±3.8 mmHg, respectively. Symptoms were present at baseline in 120 (60%) including dyspnea in 97, chest discomfort in 12, syncope in 3, lower extremity edema in 3, thrombosis in 3 and fatigue in 2. Of them, mitral valve interventions including surgical or transcatheter mitral valve replacement and mitral valve bypass were performed in 27 (23%): within 1 year after index TTE in 23 (19%) and at 2, 4, 5 and 6 years in 1 each. Of 80 patients without symptoms at index TTE, 20 (25%) developed symptoms at mean 2.9±3.2 years and interventions were performed in 5 (6%). Of 168 who did not receive interventions, 60 (36%) did not develop symptoms during follow up, 58 (35%) were considered to have moderate MS, 46 (27%) were not offered surgery because of high risk due to advanced age, multiple comorbidities or heavy calcification, and 2 (1%) declined interventions. During follow-up of 2.8±3.0 years, Kaplan-Meier survival at 1 and 3 years without intervention were 72% and 52%, respectively (Fig. A). Inactivity, CCI &gt;5, left ventricular ejection fraction (LVEF) &lt;50%, TMG ≥8 mmHg (the mean TMG) and right ventricular systolic pressure (RVSP) ≥50 mmHg were independently associated with mortality (Fig. B). Symptoms were associated with referral for interventions (OR 3.43, 95% CI 1.22–9.65; p=0.019), but not with mortality. Conclusion Patients with isolated severe calcific MS had a high burden of comorbidities and had high mortality without intervention. Symptoms were common (60%), but were not associated with mortality. TMG ≥8 mmHg, RVSP ≥50 mmHg, LVEF&lt;50%, CCI &gt;5 and inactivity were independently associated with mortality. Funding Acknowledgement Type of funding source: None

Abstract Background Transmitral gradient (TMG) is highly dependent on hemodynamic state, leading to discordance between TMG and mitral valve area (MVA). The effect of heart rate (HR) and stroke volume (SV) on TMG among patients with mitral stenosis (MS) is poorly understood. Purposes We aimed to (1) develop a formula for projected TMG (proTMG) for assessment of MS severity under varying hemodynamics; (2) assess the prognostic value of proTMG in patients with MS. Methods All patients evaluated for suspected MS without ≥moderate other valve disorder at our tertiary center between 2001 and 2017 were analyzed. Projected TMG is the expected gradient under normal flow (SV 80–94 ml and HR 60–79 bpm), and was modeled based on the observed impact of HR and SV on TMG by multiple regression analysis. The data were randomly split (2:1) into training and testing sets. The improvement in agreement between MVA and proTMG was evaluated. Composite cardiac events including all-cause death and mitral valve interventions were compared according to TMG grade using TMG and proTMG. Severe and moderate MS were defined as MVA ≤1.5 cm2 and 1.5–2.0 cm2 respectively, by the continuity equation. MVA ≤1.0 cm2 was considered as very severe MS. Results Of 4973 patients with suspected MS (age 73±12 years, 33% male), severe MS was present in 437 (9%, including 98 with very severe MS) and moderate MS in 934 (19%). In 838 patients with normal HR and SV, very severe, severe and moderate MS corresponded to TMG ≥12 mmHg, ≥6 mmHg and 4–6 mmHg, respectively. In the training set (n=3315), the median [interquartile range] of HR and SV were 70 [61–80] bpm and 97 [83–113] mL in men (n=1120), and 72 [63–82] bpm and 84 [71–97] mL in women (n=2195), respectively. The impact of HR and SV on TMG for men and women were 0.07 and 0.08 mmHg per 1 bpm increase in HR (95% confidence interval [CI] 0.06–0.07 and 0.07–0.08), and 0.03 and 0.05 mmHg per 1 mL increase in SV (95% CI 0.03–0.03 and 0.04–0.05), respectively. Therefore, the final formula to calculate proTMG was: proTMG=TMG-0.07(HR-70)-0.03(SV-97) in men and proTMG=TMG-0.08(HR-72)-0.05(SV-84) in women. In the testing set (n=1658), the proTMG (kappa=0.63, 95% CI 0.60–0.66) had better agreement with MS severity by MVA than TMG (kappa=0.28, 95% CI 0.24–0.32). To explore the prevalence of patients reclassified using proTMG, in 98 with TMG ≥12 mmHg, proTMG remained ≥6 mmHg. Of 657 with TMG 6–12 mmHg, proTMG remained ≥6 mmHg in 356 (54%), and decreased to &lt;6 mmHg in 301 (46%). In patients with TMG 6–12 mmHg, proTMG ≥6 mmHg was associated with higher probability of cardiac events compared with &lt;6 mmHg during follow-up of 2.8±3.1 years (Figure). Conclusion We propose a novel concept of projected TMG defined as the expected transmitral gradient at normal HR and SV levels. This improved the diagnostic yield of Doppler TMG measurements for MS severity assessment and identified a low-risk subset of patients with elevated TMG due to high HR or SV. Funding Acknowledgement Type of funding source: None

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.

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.