Effects of intensive blood pressure control on left ventricular hypertrophy in aortic valve disease.

BACKGROUND: Hypertension adds to the pressure overload on the left ventricle (LV) in combination with aortic valve (AV) disease, but the optimal blood pressure (BP) targets for patients with AV disease remain unclear. We tried to investigate whether intensive BP control reduces LV hypertrophy in asymptomatic patients with aortic stenosis (AS) or aortic regurgitation (AR). METHODS: A total of 128 hypertensive patients with mild to moderate AS (n = 93) or AR (n = 35) were randomly assigned to intensive therapy, targeting a systolic BP <130 mm Hg, or standard therapy, targeting a systolic BP <140 mm Hg. The primary end point was the change in LV mass from baseline to the 24-month follow-up. Secondary end points included changes in severity of AV disease, LV volumes, ejection fraction and global longitudinal strain (GLS). RESULTS: The treatment groups were generally well balanced regarding the baseline characteristics. The mean (±SD) age of the patients was 68 ± 8 years and 48% were men. The mean BP was 145 ± 12/81 ± 10 mm Hg at baseline. Medication at baseline was similar between the 2 groups. The 2 treatment strategies resulted in a rapid and sustained difference in systolic BP (P < .05). At 24-month, the mean systolic BP was 129 ± 12 mm Hg in the intensive therapy group and 135 ± 14 mm Hg in the standard therapy group. No patient died or underwent AV surgery during follow-up in either of the groups. LV mass was changed from 189.5 ± 41.3 to 185.6 ± 41.5 g in the intensive therapy group (P = .19) and from 183.8 ± 38.3 to 194.0 ± 46.4 g in the standard therapy group (P < .01). The primary end point of change in LV mass was significantly different between the intensive therapy and the standard therapy group (-3.9 ± 20.2 g vs 10.3 ± 20.4 g; P = .0007). The increase in LV mass index was also significantly greater in the standard therapy group (P = .01). No significant differences in secondary end points (changes in severity of AV disease, LV volumes, ejection fraction and GLS) were observed between the treatment groups. CONCLUSIONS: Among hypertensive patients with AV disease, intensive hypertensive therapy resulted in a significant reduction in LV hypertrophy, although progression of AV disease was similar between the treatment groups. CLINICAL TRIAL REGISTRATION: http://ClinicalTrials.gov (Number NCT03666351).

Data-driven mortality risk prediction of severe degenerative mitral regurgitation patients undergoing mitral valve surgery.

AIMS: The outcomes of mitral valve replacement/repair (MVR) in severe degenerative mitral regurgitation (MR) patients depend on various risk factors. We aimed to develop a risk prediction model for post-MVR mortality in severe degenerative MR patients using machine learning. METHODS AND RESULTS: Consecutive severe degenerative MR patients undergoing MVR were analysed (n = 1521; 70% training/30% test sets). A random survival forest (RSF) model was constructed, with 3-year post-MVR all-cause mortality as the outcome. Partial dependency plots were used to define the thresholds of each risk factor. A simple scoring system (MVR-score) was developed to stratify post-MVR mortality risk. At 3 years following MVR, 90 patients (5.9%) died in the entire cohort (59 and 31 deaths in the training and test sets). The most important predictors of mortality in order of importance were age, haemoglobin, valve replacement, glomerular filtration rate, left atrial dimension, and left ventricular (LV) end-systolic diameter. The final RSF model with these six variables demonstrated high predictive performance in the test set (3-year C-index 0.880, 95% confidence interval 0.834-0.925), with mortality risk increased strongly with left atrial dimension >55 mm, and LV end-systolic diameter >45 mm. MVR-score demonstrated effective risk stratification and had significantly higher predictability compared to the modified Mitral Regurgitation International Database score (3-year C-index 0.803 vs. 0.750, P = 0.034). CONCLUSION: A data-driven machine learning model provided accurate post-MVR mortality prediction in severe degenerative MR patients. The outcome following MVR in severe degenerative MR patients is governed by both clinical and echocardiographic factors.

Long-term outcomes in distinct phenogroups of patients with primary mitral regurgitation undergoing valve surgery.

OBJECTIVES: Patients with mitral regurgitation (MR) may be heterogeneous with different risk profiles. We aimed to identify distinct phenogroups of patients with severe primary MR and investigate their long-term prognosis after mitral valve (MV) surgery. METHODS: The retrospective cohort of patients with severe primary MR undergoing MV surgery (derivation, n=1629; validation, n=692) was analysed. Latent class analysis was used to classify patients into subgroups using 15 variables. The primary outcome was all-cause mortality after MV surgery. RESULTS: During follow-up (median 6.0 years), 149 patients (9.1%) died in the derivation cohort. In the univariable Cox analysis, age, female, atrial fibrillation, left ventricular (LV) end-systolic dimension/volumes, LV ejection fraction, left atrial dimension and tricuspid regurgitation peak velocity were significant predictors of mortality following MV surgery. Five distinct phenogroups were identified, three younger groups (group 1-3) and two older groups (group 4-5): group 1, least comorbidities; group 2, men with LV enlargement; group 3, predominantly women with rheumatic MR; group 4, low-risk older patients; and group 5, high-risk older patients. Cumulative survival was the lowest in group 5, followed by groups 3 and 4 (5-year survival for groups 1-5: 98.5%, 96.0%, 91.7%, 95.6% and 83.4%; p<0.001). Phenogroups had similar predictive performance compared with the Mitral Regurgitation International Database score in patients with degenerative MR (3-year C-index, 0.763 vs 0.750, p=0.602). These findings were reproduced in the validation cohort. CONCLUSION: Five phenogroups of patients with severe primary MR with different risk profiles and outcomes were identified. This phenogrouping strategy may improve risk stratification when optimising the timing and type of interventions for severe MR.

PRE-OPerative ECHOcardiograhy for prevention of cardiovascular events after non-cardiac surgery in intermediate- and high-risk patients: protocol for a low-interventional, mixed-cohort prospective study design (PREOP-ECHO).

BACKGROUND: Cardiac evaluation using transthoracic echocardiography before noncardiac surgery is common in real-world practice. However, evidence supporting preoperative echocardiography is lacking. This study aims to evaluate the additional benefit of preoperative echocardiography in predicting postoperative cardiovascular events (CVE) in noncardiac surgery. METHODS: This study is designed as a multicenter, prospective study to assess the utility of preoperative echocardiography in patients undergoing intermediate- or high-risk noncardiac surgery. This trial comprises two studies: (1) a randomized controlled trial (RCT) for patients undergoing intermediate-risk surgery with fewer than three clinical risk factors from the revised cardiac risk index (intermediate-risk group) and (2) a prospective cohort study for patients undergoing intermediate-risk surgery with three or more clinical risk factors, or who undergo high-risk surgery regardless of the number of clinical risk factors (high-risk group). We hypothesize that the use of preoperative echocardiography will reduce postoperative CVEs in patients undergoing intermediate- to high-risk surgery through discovery of and further intervention for unexpected cardiac abnormalities before elective surgery. A total of 2330 and 2184 patients will be enrolled in the two studies. The primary endpoint is a composite of all-cause death; aborted sudden cardiac arrest; type I acute myocardial infarction; clinically diagnosed unstable angina; stress-induced cardiomyopathy; lethal arrhythmia, such as sustained ventricular tachycardia or ventricular fibrillation; and/or newly diagnosed or acutely decompensated heart failure within 30 days after surgery. DISCUSSION: This study will be the first large-scale prospective study examining the benefit of preoperative echocardiography in predicting postoperative CVE. The PREOP-ECHO trial will help doctors identify patients at risk of postoperative CVE using echocardiography and thereby reduce postoperative CVEs. TRIAL REGISTRATION: The Clinical Research Information Service KCT0006279 for RCT and KCT0006280 for prospective cohort study. Registered on June 21, 2021.

Benefit of Sarcopenia Screening in Older Patients Undergoing Surgical Aortic Valve Replacement.

BACKGROUND: Sarcopenia, known as physical frailty, is highly prevalent in older patients and is related to adverse outcomes after cardiac surgery. However whether sarcopenia assessment can reclassify an individual patient's risk, which is estimated by Society of Thoracic Surgeons-predicted risk of mortality scores in patients who undergo surgical aortic valve replacement, is unclear. METHODS: This retrospective, single-center, cohort study comprised 874 patients aged ≥65 years who underwent surgical aortic valve replacement between 2009 and 2016. Total skeletal muscle area was calculated using height squared (cm2/m2) and was measured by preoperative computed tomography at the third lumbar vertebra inferior border using machine learning-based analysis. Sex-specific Z-scores were calculated, and patients in the lowest Z-score tertile were considered to have sarcopenia. The primary endpoint was 30-day mortality, and secondary endpoints were in-hospital events, 1-year mortality, and long-term mortality. RESULTS: Thirty-day mortality, 30-day in-hospital events, and 1-year mortality rates were 4.7%, 17.6%, and 8.0%, respectively. As the Z-score decreased, the odds of an early adverse event showed a stepwise increase. Sarcopenia was independently associated with higher 30-day mortality, 30-day in-hospital events, and 1-year mortality. Reclassification analyses showed improvements in the ability to predict early adverse events after adding the Z-scores over and above The Society of Thoracic Surgeons-predicted risk of mortality scores (all P < .005). CONCLUSIONS: Sarcopenic patients had significantly higher risks of early adverse events and long-term mortality after undergoing surgical aortic valve replacement than nonsarcopenic patients. Sarcopenia determined by preoperative computed tomography can enhance the prediction of postoperative outcome risk.

Timing of Intervention in Asymptomatic Aortic Stenosis.

The decision to perform an intervention for asymptomatic severe aortic stenosis (AS) requires careful weighing of the risks of early intervention against those of watchful observation, and the optimal timing of intervention remains controversial. With improvements in surgical and postoperative care, long-term survival after surgical aortic valve (AV) replacement (AVR) is excellent in low-risk patients, and the emergence of transcatheter AVR may change the thresholds for early preemptive intervention, although a durability issue has to be resolved. A watchful observation strategy also has a risk of sudden death, irreversible myocardial damage, and increase in operative risk while waiting for symptoms to develop. We have been waiting for a prospective randomized trial to solve the intense debate between early AVR and watchful observation, and the RECOVERY (Randomized Comparison of Early Surgery versus Conventional Treatment in Very Severe Aortic Stenosis) trial provides the evidence to support early AVR for asymptomatic severe AS. Risk assessment with severity of AS and staging classification may help to facilitate the identification of patients who may benefit from early intervention. Based on the results of the RECOVERY trial, early surgical AVR is reasonable for asymptomatic patients with very severe AS (aortic jet velocity ≥4.5 m/s) and low surgical risk. Further evidence is required to extend the indications of surgical AVR and to consider transcatheter AVR in asymptomatic patients with severe AS.

Different Clinical Features between Definite and Possible Takotsubo Syndrome in a Tertiary Referral Hospital.

BACKGROUND: Although imaging examination to exclude coronary artery disease (CAD) is an indispensable step for a definite diagnosis of takotsubo syndrome (TTS), this step may be overlooked in a substantial proportion of patients with secondary TTS admitted to a tertiary hospital. However, the clinical profiles and outcomes of these patients with "possible TTS" have rarely been investigated. METHODS: Among 420 consecutive TTS patients with characteristic transient ventricular ballooning on repeated echocardiography, 244 patients (58.1%) who underwent an imaging study for CAD were diagnosed with "definite TTS," whereas the remaining 176 were designated with "possible TTS." RESULTS: Overall, hypoxia (67.6%) and dyspnea (55.5%) were predominant presentations. The possible group was characterized by higher prevalence of male gender (46.6% vs. 35.2%, p = 0.019), secondary TTS (97.2% vs. 86.5%, p < 0.001), cancer (43.2% vs. 29.1%, p = 0.003), sepsis (46.0% vs. 32.0%, p = 0.003), and nonapical ballooning pattern (30.7% vs. 21.3%, p = 0.001) with less common ST-segment elevation on electrocardiogram (18.8% vs. 34.0%, p = 0.001). The possible group showed higher frequency of mechanical ventilation (56.2% vs. 40.2%, p = 0.001), pulmonary edema (72.2% vs. 61.5%, p = 0.023), and shock management (70.5% vs. 54.1%, p = 0.001) with similar in-hospital mortality (17.2% vs. 17.0%, p = 0.964). CONCLUSIONS: In real-world clinical practice, coronary evaluation for strict diagnosis of TTS is not frequently feasible. Addition of the possible group without coronary evaluation to the clinical spectrum of TTS would be helpful for fair estimation of clinical implication of TTS.

Effect of Neprilysin Inhibition for Ischemic Mitral Regurgitation after Myocardial Injury.

Angiotensin receptor neprilysin inhibitor (ARNI) treatment reduces functional mitral regurgitation (MR) to a greater extent than angiotensin receptor blocker (ARB) treatment alone, but the mechanism is unclear. We evaluated the mechanisms of how ARNI has an effect on functional MR. After inducing functional MR by left circumflex coronary artery occlusion, male Sprague Dawley rats (n = 31) were randomly assigned to receive the ARNI LCZ696, the ARB valsartan, or corn oil only (MR control). Excised mitral leaflets and left ventricle (LV) were analyzed, and valvular endothelial cells were evaluated focusing on molecular changes. LCZ696 significantly attenuated LV dilatation after 6 weeks when compared with the control group (LV end-diastolic volume, 461.3 ± 13.8 µL versus 525.1 ± 23.6 µL; p < 0.05), while valsartan did not (471.2 ± 8.9 µL; p > 0.05 to control). Histopathological analysis of mitral leaflets showed that LCZ696 strongly reduced fibrotic thickness compared to the control group (28.2 ± 2.7 µm vs. 48.8 ± 7.5 µm; p < 0.05). Transforming growth factor-ß and downstream phosphorylated extracellular-signal regulated kinase were also significantly lower in the LCZ696 group. Consequently, excessive endothelial-to-mesenchymal transition (EndoMT) was mitigated in the LCZ696 group compared to the control group and leaflet area was higher (11%) in the LCZ696 group than in the valsartan group. Finally, the MR extent was significantly lower in the LCZ696 group and functional improvement was observed. In conclusion, neprilysin inhibitor has positive effects on LV reverse remodeling and also attenuates fibrosis in MV leaflets and restores adaptive growth by directly modulating EndoMT.

Prognostic Implication of Right Ventricle Parameters Measured on Preoperative Cardiac MRI in Patients with Functional Tricuspid Regurgitation.

OBJECTIVE: To investigate the prognostic value of preoperative cardiac magnetic resonance imaging (MRI) for long-term major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing tricuspid valve (TV) surgery for functional tricuspid regurgitation (TR). MATERIALS AND METHODS: The preoperative cardiac MR images, New York Heart Association functional class, comorbidities, and clinical events of 78 patients (median [interquartile range], 59 [51-66.3] years, 28.2% male) who underwent TV surgery for functional TR were comprehensively reviewed. Cox proportional hazards analyses were performed to assess the associations of clinical and imaging parameters with MACCEs and all-cause mortality. RESULTS: For the median follow-up duration of 5.4 years (interquartile range, 1.2-6.6), MACCEs and all-cause mortality were 51.3% and 23.1%, respectively. The right ventricular (RV) end-systolic volume index (ESVI) and the systolic RV mass index (RVMI) were higher in patients with MACCEs than those without them (77 vs. 68 mL/m², p = 0.048; 23.5 vs. 18.0%, p = 0.011, respectively). A high RV ESVI was associated with all-cause mortality (hazard ratio [HR] per value of 10 higher ESVI = 1.10, p = 0.03). A high RVMI was also associated with all-cause mortality (HR per increase of 5 mL/m² RVMI = 1.75, p < 0.001). After adjusting for age and sex, only RVMI remained a significant predictor of MACCEs and all-cause mortality (p < 0.05 for both). After adjusting for multiple clinical variables, RVMI remained significantly associated with all-cause mortality (p = 0.005). CONCLUSION: RVMI measured on preoperative cardiac MRI was an independent predictor of long-term outcomes in patients who underwent TV surgery for functional TR.

Determinants of clinical outcomes of surgery for isolated severe tricuspid regurgitation.

OBJECTIVES: Although the incidence of patients with isolated tricuspid regurgitation (TR) is increasing, data regarding the clinical outcomes of isolated TR surgery are limited. This study sought to investigate the prognostic implications according to procedural types, and to identify preoperative predictors of clinical outcomes after isolated TR surgery. METHODS: Among consecutive 2610 patients receiving tricuspid valve (TV) procedure, we analysed 238 patients (age, 59.6 years; 143 females) who underwent stand-alone TV surgery (repair, 132; replacement, 106) for severe TR. Primary outcome was the composite of all-cause mortality and heart transplantation. Clinical outcomes between the repair and the replacement groups were compared after adjusting with the inverse probability of treatment weighting (IPTW) method. RESULTS: During follow-up (median, 4.1 years), 53 patients died and 4 received heart transplantation. Multivariable analysis revealed that age (p=0.001), haemoglobin level (p=0.003), total bilirubin (p=0.040), TR jet area (p=0.005) and right atrial (RA) pressure (p=0.022) were independent predictors of the primary outcome. After IPTW adjustment, there were no significant intergroup differences in the risk of primary outcome (HR 1.01; 95% CI 0.55 to 1.87). In the subgroup analysis, tricuspid annular diameter was identified as a significant effect modifier (p=0.012) in the comparison between repair versus replacement, showing a trend favouring replacement in patients with annular diameter >44 mm. CONCLUSIONS: The outcomes of stand-alone severe TR surgery were independently associated with the severity of TR and RA pressure. In selected patients with severe annular dilation >44 mm, replacement may become a feasible option.

Dipeptidyl peptidase-4 inhibition to prevent progression of calcific aortic stenosis.

OBJECTIVE: To evaluate whether the use of dipeptidyl peptidase-4 (DPP-4) inhibitors and their cardiac tissue distribution profile and anticalcification abilities are associated with risk of aortic stenosis (AS) progression. METHODS: Out of the five different classes of DPP-4 inhibitors, two had relatively favourable heart to plasma concentration ratios and anticalcification ability in murine and in vitro experiments and were thus categorised as 'favourable'. We reviewed the medical records of 212 patients (72±8 years, 111 men) with diabetes and mild-to-moderate AS who underwent echocardiographic follow-up and classified them into those who received favourable DPP-4 inhibitors (n=28, 13%), unfavourable DPP-4 inhibitors (n=69, 33%) and those who did not receive DPP-4 inhibitors (n=115, 54%). RESULTS: Maximal transaortic velocity (Vmax) increased from 2.9±0.3 to 3.5±0.7 m/s during follow-up (median, 3.7 years), and the changes were not different between DPP-4 users as a whole and non-users (p=0.143). However, the favourable group showed significantly lower Vmax increase than the unfavourable or non-user group (p=0.018). Severe AS progression was less frequent in the favourable group (7.1%) than in the unfavourable (29.0%; p=0.03) or the non-user (29.6%; p=0.01) group. In Cox regression analysis after adjusting for age, baseline renal function and AS severity, the favourable group showed a significantly lower risk of severe AS progression (HR 0.116, 95% CI 0.024 to 0.551, p=0.007). CONCLUSIONS: DPP-4 inhibitors with favourable pharmacokinetic and pharmacodynamic properties were associated with lower risk of AS progression. These results should be considered in the preparation of randomised clinical trials on the repositioning of DPP-4 inhibitors.

Clinical Situations Associated with Inappropriately Large Regurgitant Volumes in the Assessment of Mitral Regurgitation Severity Using the Proximal Flow Convergence Method in Patients with Chordae Rupture.

BACKGROUND: Regurgitant volume (RVol) calculated using the proximal flow convergence method (proximal isovelocity surface area [PISA]) has been accepted as a key quantitative parameter for the diagnosis of and clinical decision-making with regard to severe mitral regurgitation (MR). However, a recent prospective study showed a significant overestimation of RVol by the echocardiographic PISA method compared with the MR volume measured using magnetic resonance imaging. We aimed to evaluate the frequency of overestimation of RVol by the PISA method and the clinical conditions that require a different quantitative method to correct the overestimation. METHODS: We retrospectively enrolled 166 consecutive patients with degenerative MR and chordae rupture, in whom RVol was measured using both the PISA and two-dimensional Doppler volumetric methods. The volumetric method was used to measure total stroke volume using the two-dimensional Simpson biplane method, and forward stroke volume was measured using pulsed Doppler tracing at the left ventricular (LV) outflow tract. RVol by the volumetric method was calculated using total stroke volume - forward stroke volume. Severe MR was defined as an RVol >60 mL. RESULTS: All patients had severe MR based on RVol by the PISA method, but 68 (41.1%) showed RVol by the volumetric method values of <60 mL, resulting in discordant results. The patients with discordant results were characterized by a higher prevalence of female sex, lower body surface area, smaller LV diastolic and systolic dimensions and volumes, smaller left atrial volume, smaller PISA angle, and lower frequency of flail leaflets (39.7% vs 62.2%, P = .004). Multivariate analysis revealed that LV end-diastolic volume (LVEDV) and PISA angle were independent factors, with the best cutoff LVEDV and PISA angle being 173 mL and 103°, respectively. During follow-up (median, 3.4 years; interquartile range, 2.0-4.8 years), mitral valve repair and replacement were performed in 103 and six patients, respectively. The 2-year mitral valve surgery-free survival rate was higher in the discordant group (51.8% ± 0.06% vs 31.2% ± 0.05%, P < .001). CONCLUSIONS: Even in the patients with documented chordae rupture, the PISA method alone resulted in inappropriate overestimation of MR severity in a significant proportion of patients. Thus, an additive quantitative method is absolutely necessary in patients with a small LVEDV or narrow PISA angle.

Early Surgery or Conservative Care for Asymptomatic Aortic Stenosis.

BACKGROUND: The timing and indications for surgical intervention in asymptomatic patients with severe aortic stenosis remain controversial. METHODS: In a multicenter trial, we randomly assigned 145 asymptomatic patients with very severe aortic stenosis (defined as an aortic-valve area of ≤0.75 cm2 with either an aortic jet velocity of ≥4.5 m per second or a mean transaortic gradient of ≥50 mm Hg) to early surgery or to conservative care according to the recommendations of current guidelines. The primary end point was a composite of death during or within 30 days after surgery (often called operative mortality) or death from cardiovascular causes during the entire follow-up period. The major secondary end point was death from any cause during follow-up. RESULTS: In the early-surgery group, 69 of 73 patients (95%) underwent surgery within 2 months after randomization, and there was no operative mortality. In an intention-to-treat analysis, a primary end-point event occurred in 1 patient in the early-surgery group (1%) and in 11 of 72 patients in the conservative-care group (15%) (hazard ratio, 0.09; 95% confidence interval [CI], 0.01 to 0.67; P = 0.003). Death from any cause occurred in 5 patients in the early-surgery group (7%) and in 15 patients in the conservative-care group (21%) (hazard ratio, 0.33; 95% CI, 0.12 to 0.90). In the conservative-care group, the cumulative incidence of sudden death was 4% at 4 years and 14% at 8 years. CONCLUSIONS: Among asymptomatic patients with very severe aortic stenosis, the incidence of the composite of operative mortality or death from cardiovascular causes during the follow-up period was significantly lower among those who underwent early aortic-valve replacement surgery than among those who received conservative care. (Funded by the Korean Institute of Medicine; RECOVERY ClinicalTrials.gov number, NCT01161732.).

Mid-term Clinical Outcomes in a Cohort of Asymptomatic or Mildly Symptomatic Korean Patients with Bicuspid Aortic Valve in a Tertiary Referral Hospital.

BACKGROUND: Although bicuspid aortic valve (BAV) is one of the most common congenital heart diseases, clinical outcome data regarding BAV are still limited. We evaluated clinical characteristics and mid-term clinical outcomes of asymptomatic Korean patients with bicuspid aortic valve. METHODS: We initiated a prospective registry in 2014 at a tertiary referral hospital. To develop a cohort of asymptomatic patients, we excluded patients who previously underwent open heart surgery (OHS) or who had OHS within 6 months of referral. RESULTS: A total of 170 patients (117 male [69%], age 50 ± 13 years) were enrolled. More than 70% (n = 124, 73%) were incidentally diagnosed with BAV during routine health examinations or preoperative screening for non-cardiac surgery. At the time of enrollment, moderate to severe aortic stenosis (AS) or regurgitation (AR) was present in 77 patients (45%) and 98 (58%) showed aortic dilation: 42 (25%) had non-significant valvular dysfunction without aortic dilation. During a median follow-up of 4 years, AS severity increased significantly (p < 0.001), while there was no significant change in AR severity (p = 0.361). A total of 27 patients (16%) underwent OHS, including isolated aortic valve (AV) surgery (n = 11, 41%), AV with combined aortic surgery (n = 12, 44%), and isolated aortic surgery (n = 4, 15%): no patient developed aortic dissection. Moderate to severe AS (hazard ratio [HR] 4.61; 95% confidence interval [CI] 1.83-11.62; p = 0.001), NYHA class ≥ 2 (HR 2.53; 95% CI 1.01-6.35; p = 0.048) and aortic dilation (HR 2.13; 95% CI 0.87-5.21; p = 0.099) were associated with surgical events. CONCLUSIONS: Progression patterns of valvular dysfunction and impacts of BAV phenotype on OHS should be explored in future studies with longer follow-up durations.

Surgical Outcomes in Behcet's Disease Patients With Severe Aortic Regurgitation.

BACKGROUND: An optimal treatment for aortic regurgitation in Behcet's disease has not been established. We investigated the effect of operative technique, prosthetic material, and immunomodulation therapy on surgical outcomes. METHODS: In this study, 23 patients with Behcet's disease surgically treated for aortic regurgitation were assessed. Significant postoperative events were defined as death, aortic valve or graft-related problem(s), infective endocarditis, disabling stroke, and aortic valve or root reoperation. Surgical procedures were classified as isolated aortic valve replacement, bioprosthetic root replacement, and mechanical root replacement. Allograft root replacements were included in the bioprosthetic root replacement group. RESULTS: A total of 40 operations, including 39 aortic valve or root surgeries and 1 orthotopic heart transplantation, were performed on patients confirmed with Behcet's disease. However, the study only reviewed 35 of the 40 cases (4 cases with inadequately documented medical records and 1 heart transplantation case were excluded). Significant adverse events occurred in 8 of 11 (73%) isolated aortic valve replacement, 9 of 12 (75%) bioprosthetic root replacement (5 xenografts and 7 allografts), and 4 of 12 (33%) mechanical root replacement cases. Multivariate analysis revealed that the 1-month postdischarge C-reactive protein level and operative age were independent predictive factors for postoperative event-free survival. Mechanical root replacement was identified as the most significant predictive factor leading to positive outcomes (hazard ratio, 0.147; 95% confidence interval, 0.028 to 0.766; p = 0.023). CONCLUSIONS: The findings suggest that mechanical root replacement combined with a low postoperative C-reactive protein level maintained through adjunctive immunomodulation therapy may lead to optimal surgical outcomes in Behcet's disease associated with severe aortic regurgitation.

Angiotensin Receptor Neprilysin Inhibitor for Functional Mitral Regurgitation.

BACKGROUND: The morbidity and mortality of patients with functional mitral regurgitation (MR) remain high, but no pharmacological therapy has been proven effective. The hypothesis of this study was that sacubitril/valsartan would be superior to valsartan alone in improving functional MR via dual inhibition of the renin-angiotensin system and neprilysin. METHODS: In this double-blind trial, we randomly assigned 118 patients with heart failure with chronic functional MR secondary to left ventricular (LV) dysfunction to receive either sacubitril/valsartan or valsartan, in addition to standard medical therapy for heart failure. The primary end point was the change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, LV end-systolic volume, LV end-diastolic volume, and incomplete mitral leaflet closure area. RESULTS: The decrease in effective regurgitant orifice area was significantly greater in the sacubitril/valsartan group than in the valsartan group (-0.058±0.095 versus -0.018±0.105 cm2; P=0.032) in an intention-to-treat analysis including 117 (99%) patients. Regurgitant volume was also significantly decreased in the sacubitril/valsartan group in comparison with the valsartan group (mean difference, -7.3 mL; 95% CI, -12.6 to -1.9; P=0.009). There were no significant between-group differences regarding the changes in incomplete mitral leaflet closure area and LV volumes, with the exception of LV end-diastolic volume index ( P=0.044). We noted no significant difference in the change of blood pressure between the treatment groups, and 7 patients (12%) in the sacubitril/valsartan group and 9 (16%) in the valsartan group had ≥1 serious adverse events ( P=0.54). CONCLUSIONS: Among patients with secondary functional MR, sacubitril/valsartan reduced MR to a greater extent than did valsartan. Our findings suggest that an angiotensin receptor-neprilysin inhibitor might be considered for optimal medical therapy of patients with heart failure and functional MR. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02687932.