Enriquez‐Sarano, Maurice

AbstractBackgroundThe severity of MI declined markedly in the last decade, and contemporary patterns of cardiac remodeling after MI are not defined.MethodsWe prospectively enrolled community patients with first MI and performed comprehensive two‐ and three‐dimensional echocardiography. Remodeling was defined as left ventricular (LV) end‐systolic volume index (ESVI) above American Society of Echocardiography normal values. Remodeling patterns were characterized as an increase in LVESVI or LV end‐diastolic volume index (LVEDVI), or both.ResultsBetween 2014 and 2016, 213 patients (63±13 years; 34% women) were enrolled within 3 days after MI (77% non‐ST‐elevation MI). Acute remodeling was present in 51% of patients. Higher troponin and wall motion score index were associated with greater remodeling (p < 0.001). Atrial annular area, leaflet tenting and papillary muscle areas increased with greater remodeling (p < 0.001). The greater the cardiac remodeling, the lower the LV ejection fraction and global longitudinal strain (p < 0.001). This decrease in LV function was accompanied by stroke volume augmentation and maintenance of cardiac index at the expense of increased LVEDVI. Different remodeling patterns were identified. Cases showing increased LVEDVI and normal LVESVI had smallest infarct size and better hemodynamics compared to cases with augmented LVESVI and normal LVEDVI.ConclusionAcute remodeling occurs in more than half of first MI cases and exhibits different patterns defined by cavity size and hemodynamic profile. Acute remodeling is a global phenomenon, which also involves the left atrium and the mitral apparatus.

Abstract Background Intracranial aneurysm (IA) has been associated with bicuspid aortic valve (BAV) with prevalence of 6–10% which has led some to recommend routine surveillance for IA in BAV patients. Higher incidence of IA in BAV could signal towards systemic arteriopathy beyond the thoracic aorta. With CoA as an independent risk factor for IA formation, it is currently uncertain if the association between IA and BAV reflects the association of BAV and CoA, or the result of BAV-related systemic arterial changes. Purpose Despite this association, 2 small studies suggest no increased risk of the most important patient outcome: aneurysmal sub-arachnoid hemorrhage (aSAH). Our primary aim was identifying the prevalence of BAV in aSAH patients and compare it with that of a control group without aSAH. Secondary aims included neurologic outcomes of aSAH and anatomical characteristics of IA in BAV, and final disposition and outcome. Methods Patients (&gt;18 years age) with an accurate diagnosis of aSAH and at least one echocardiogram in the system between January 2000-December 2019 were identified from a prospectively maintained registry of aSAH admissions. Controls, without a diagnosis of SAH ever, were age- and gender-matched (1:2 cases:controls). BAV prevalence was echocardiographically-confirmed in all patients. Severity of aSAH was categorized using the modified Fisher (mFisher) and the World Federation of Neurological Scale (WFNS). Results A total of 488 aSAH cases and 990 controls were included in the final analysis with confirmed aortic valve status. The prevalence of BAV in aSAH patients was 1.2% (6/488) vs 3.5% (35/990) in controls, p=0.01. None of the aSAH cases were noted to have CoA, whereas 3 (0.3%; p=0.12) control patients had presence of both BAV and CoA. Within aSAH patients, BAV+aSAH were noted to be younger than tricuspid aortic valve (TAV)+aSAH (56±11 vs 68±14; p=0.03). Aneurysm size was smaller in the BAV+aSAH group (5±2 vs 7±4 in TAV+aSAH; p=0.31). The severity of the bleed was lesser in BAV+aSAH than TAV+aSAH (mFisher grade &gt;2 50% vs 74%; p=0.19, WFNS grade &gt;3 17% vs 36%; p=0.43) which is clinically significant. The BAV+aSAH group had higher disposition rate to home (67% vs 39%; p=0.21) with no difference in in-hospital mortality rates (17% vs 18%; p=0.93). BAV had lower odds on univariate and multivariate analyses adjusted for age/sex/body mass index (OR 0.33 [CI 0.14–0.81]; p=0.01, OR 0.23 [CI 0.08–0.65]; p=0.01) of presenting with aSAH. Conclusion Within a large prospective registry with accurate aSAH diagnoses, we found 3-times lower prevalence of echocardiographically-confirmed BAV as compared to non-aSAH controls. We observed 3-times higher prevalence of BAV in controls than among aSAH cases. In addition, size of intracranial aneurysms was clinically smaller in BAV patients, and the severity of SAH was significantly lesser in BAV from a clinical standpoint. Our findings argue against routine surveillance for IA in BAV patients without CoA. Funding Acknowledgement Type of funding sources: None.

Abstract Background The Mitral Regurgitation International Database (MIDA) score is a validated tool for Degenerative Mitral Regurgitation (DMR) management, being able to position a given patient within a continuous spectrum of short and long term mortality. However, whether this score may be applicable and incremental in the entire span of Floppy Mitral Valves (FMV), regardless of DMR severity, remains unsubstantiated. Methods The MIDA-Quantitative (MIDA-Q) unprecedented registries include 8187 consecutive patients (age 64±17 years, 45% women, follow-up 5.5±3.4 years) with isolated degenerative mitral valve disease diagnosed at tertiary (European/ North-American/ Middle Eastern) centers in whom DMR severity used both integrative and quantitative grading. The MIDA-Q Score ranged from 0 to 15 depending on accumulating risk factors. Long-term survival overall, under medical management and post-mitral surgery was analysed. Results By quantitative grading, MR was no/trivial in 1938 (24%), mild in 1423 (17%), moderate in 2027 (25%) and severe in 2799 (34%), with ERO 0.24±24cm2, RVol 37±35mL, and posterior leaflet prolapse in 49%. MIDA-Q Scores stratified in 8 categories were 0 (score 0, n=851), 1 (score 1–2, n=1301), 2 (score 3–4, n=2043), 3 (score 5–6, n=1581), 4 (score 7–8, n=1273), 5 (score 9–10, n=718), 6 (score 11–12, n=331) and 7 (score 13–15, n=89). In the whole MIDA-Q population (n=8187 patients), 5-year survival under medical management with Scores categories 0–1, 2–4, and 5–7 was 96±1%, 73±1%, and 61±3% respectively (P&lt;0.0001). Five-year mortality ranged from 3% with MIDA Q-score 0 to 95% with MIDA Q-score 13–15 (P&lt;0.0001). After mitral surgery, 1-year mortality with Scores categories 0–1, 2–4, and 5–7 was 0%, 1%, and 6% respectively and 5-year post-operative survival was 99±1%, 94±1%, and 82±2% (all P&lt;0.0001). In models including age, sex and all guideline-provided prognostic markers, the EuroScoreII and the MIDA Score without DMR severity, the MIDA-Q Score provided incremental prognostic information (P&lt;0.001). Conclusion This unheard international cohort of patients with FMV and prospective mitral severity quantitative grading, enables for the first time the calculation of a MIDA-Q Score, highly determinant of survival after diagnosis of FMV with any degree of DMR, that may be very useful for mitral valve prolapse management. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Mayo Fundation Figure 1

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.

Background: We conducted this study to assess the safety of symptom-limited cardiopulmonary exercise testing (CPX) in patients with varying severity of aortic stenosis (AS). We hypothesized that exercise testing would be safe, as defined by a rates for all-cause death of <0.01% and rate of nonfatal major cardiovascular (CV) events <0.1% within 24 hours of CPX. Secondary purpose of this study was to determine the frequency of complications during CPX. Methods: This cohort study was carried out with 308 consecutive patients with varying degree of AS (as determined by standard echocardiographic criteria) with no or equivocal symptoms who were referred for clinically indicated cardiopulmonary testing between 1994 and 2009. We did not include patients with pending or completed heart transplant, or ventricular assist device implantation. These patients underwent standard symptom limited CPX, and continuous monitoring of heart rate, blood pressure, and electrocardiogram was performed. Complications recorded included death, non-fatal major CV events (cardiac arrest, symptomatic and sustained ventricular or atrial tachycardia, and syncope), and minor events such as hypotension, non-sustained atrial and ventricular arrhythmias, positive exercise ECG and anginal pain. Results: The mean age of patients was 66 ± 14 years, and 252 (82%) were males. The number of patients with mild, moderate and severe AS were 44 (14%), 138 (49%), and 126 (41%) respectively. No death or major CV event occurred during or within 24 hours of CPX. Eleven patients developed supraventricular arrhythmias without compromising hemodynamic status, and one had asymptomatic non-sustained ventricular tachycardia. Detailed description of complications is presented in the Table 1 . Conclusion: Our results show that symptom-limited CPX is safe among AS patients with no or equivocal symptoms based on no deaths or major CV events in our cohort. Minor complications occurred in 110 patients (36%). Table 1 Mild AS (n=44) Moderate AS (n=138) Severe AS (n=126) Age 61.7 ± 15.3 66.5 ± 13.86 67.89 ± 12.74 Males 36 (81%) 128 (83%) 96 (85%) Test protocol O2 protocol 39 (86%) 123 (89%) 104 (82%) Other 5 15 22 Reason for termination Symptom-limited 41 (93%) 114 (82%) 96 (76%) Other 3 24 30 Chest pain None 41 (93%) 122 (88%) 117 (93%) Non-cardiac 0 2 0 Non-anginal 0 2 0 Anginal 2 14 9 Treadmill ECG interpretation Negative 27 (61%) 67 (49%) 45 (37%) Non-diagnostic 14 48 58 Positive 3 23 23 Ventricular arrhythmia None 42 (95%) 134 (97%) 122 (97%) 3-5 beats VT 2 3 4 NSVT 0 1 0 Supraventricular arrhythmia None 42 (95%) 135 (97%) 120 (95%) SVT ≤ 30 sec 2 3 4 SVT > 30 sec 0 0 1 Afib 0 0 1 BP response Normal 41 (93%) 117 (85%) 93 (74%) Hypotensive 3 21 33 AS = Aortic Stenosis, ECG = Electrocardiogram, VT = Ventricular tachycardia, NSVT = Non-sustained ventricular tachycardia, SVT = Supraventricular tachycardia, Afib = Atrial fibrillation, BP = Blood pressure

Introduction: Left ventricular longitudinal strain (LV-LS) 1) predicts mortality in patients with aortic stenosis (AS) and 2) is highly correlated to type-B natriuretic peptide (BNP) values. The BNP ratio (measured BNP/maximal expected BNP value specific for age and sex) is a powerful independent predictor of death in patients with AS. Hypothesis: we hypothesize that BNP activation (i.e. BNP ratio >1) affects the association between LV-LS and mortality in patients with asymptomatic AS and preserved LV ejection fraction (EF ≥50%). Methods: 315 patients (age 74±12 years, 56% men and mean aortic valve area = 1.02±0.15cm2) underwent simultaneous Doppler echocardiographic and BNP measurements. LV-LS was calculated as the average of 12 LV segments from apical 2- and 4-chamber views using Velocity Vector Imaging. Results: Mean LV-LS was -16.8±3.2%, LV EF 66±7%, median BNP level 121 (interquartile 48-320) pg/ml. 58% of patients had BNP activation. Better LV-LS was associated with lower log BNPratio (regression coefficient 0.10, p<0.001). After a median follow-up of 6.5 yrs (interquartile: 3.6-8.2), 119 deaths occurred. After adjustment for age, sex, Charlson score index, hemoglobin level, aortic valve replacement (as a time dependent variable), LV-LS and log BNPratio were separately associated with increased risk for death (all p<0.01). Further adjustment for predictors of mortality, LV-LS and log-BNP ratio remained associated with increased risk for death (hazard ratio HR [95%CI]: 1.09 [1.03-1.15]; p=0.003 and 1.82 [1.52-2.19]; p<0.0001 respectively). In patients without BNP activation (i.e. normal BNP), LV-LS was associated with mortality (HR: 1.22 [1.04-1.43]; p=0.01) while it was not in patients with BNP activation (p=0.22). Conclusions: In patients with asymptomatic AS, without clinically obvious myocardial impairment (i.e. normal LVEF), a notable proportion of patients present with myocardial alterations detected by an elevated BNPratio or reduced LV-LS. These signs of myocardial alterations were predictive of mortality after diagnosis. Thus both BNP and LV-LS should be assessed in the clinical setting to provide complementary information on prognosis in patients with asymptomatic AS and preserved LV EF.

Background Mitral regurgitation (MR) due to mitral valve prolapse (MVP) is often treatable by surgical repair. However, the very long-term (>10-year) durability of repair in both anterior leaflet prolapse (AL-MVP) and posterior leaflet prolapse (PL-MVP) is unknown. Methods and Results In 917 patients (aged 65±13 years, 68% male), surgical correction of severe isolated MR due to MVP (679 repairs and 238 replacements [MVRs]) was performed between 1980 and 1995. Survival after repair was better than survival after MVR for both PL-MVP (at 15 years, 41±5% versus 31±6%, respectively; P =0.0003) and AL-MVP (at 14 years, 42±8% versus 31±5%, respectively; P =0.003). In multivariate analysis adjusting for predictors of survival, repair was independently associated with lower mortality in PL-MVP (adjusted risk ratio [RR] 0.61, 95% CI 0.44 to 0.85; P =0.0034) and in AL-MVP (adjusted RR 0.67, 95% CI 0.47 to 0.96; P =0.028). The reoperation rate was not different after repair or MVR overall (at 19 years, 20±5% for repair versus 23±5% for MVR; P =0.4) or separately in PL-MVP ( P =0.3) or AL-MVP ( P =0.3). However, the reoperation rate was higher after repair of AL-MVP than after repair of PL-MVP (at 15 years, 28±7% versus 11±3%, respectively; P =0.0006). From the 1980s to the 1990s, the RR of reoperation after repair of AL-MVP versus PL-MVP did not change (RR 2.5 versus 2.7, respectively; P =0.58), but the absolute rate of reoperation decreased similarly in PL-MVP and AL-MVP (at 10 years, from 10±3% to 5±2% and from 24±6% to 10±2%, respectively; P =0.04). Conclusions In severe MR due to MVP, mitral valve repair compared with MVR provides improved very long-term survival after surgery for both AL-MVP and PL-MVP. Reoperation is similarly required after repair or replacement but is more frequent after repair of AL-MVP. Recent improvement in long-term durability of repair suggests that it should be the preferred mode of surgical correction of MVP whether it affects anterior or posterior leaflets and is an additional incentive for early surgery of severe MR due to MVP.

Background: Little is known about the association between coronary artery disease (CAD) and the risk of heart failure (HF) after myocardial infarction (MI), and whether it differs by reduced (HFrEF) or preserved (HFpEF) ejection fraction (EF) has yet to be determined. Subjects and Methods: Olmsted County, Minnesota residents (n=1,924; mean age, 64 years; 66% male) with first MI diagnosed in 1990-2010 and no prior HF were followed through 2013. Framingham Heart Study criteria were used to define HF, which was further classified according to EF (applying a 50% cutoff). The extent of angiographic CAD was defined at index MI according to the number of major epicardial coronary arteries with ≥50% lumen diameter obstruction. Fine & Gray and Cox proportional hazards regression models were used to assess the association of CAD categories with incidence of HF, and multiple imputation methodology was applied to account for the 19% with missing EF data. Results: During a mean (SD) follow-up of 6.7 (5.9) years, 594 patients developed HF. Adjusted for age and sex, with death considered a competing risk, the cumulative incidence rates of HF among patients with 1- (n=581), 2- (n=622), and 3-vessel disease (n=721) were 11.2%, 14.6% and 20.5% at 30 days; and 18.1%, 22.3% and 29.4% at 5 years after MI, respectively. The increased risk of HF with greater number of occluded vessels was only modestly attenuated after further adjustment for patient and MI characteristics, and did not differ materially by EF (Table). Conclusions: The extent of angiographic CAD expressed by the number of diseased vessels is independently associated with HF incidence after MI. The association is evident promptly after MI and applies to both HFrEF and HFpEF.